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Mammalian urea transporters are facilitated membrane transport proteins belonging to two families, UT-A and UT-B. They are best known for their role of maintaining the renal inner medullary urinary concentrating gradient. Urea transporters have also been identified in tissues not typically associated with urea metabolism. The purpose of this study was to survey the major organs in rat to determine the distribution of UT-A and UT-B mRNA transcripts and protein forms and determine their cellular localization. Five kidney subregions and 17 extrarenal tissues were screened by Northern blot analysis using two UT-A and three UT-B probes and by Western blot analysis using polyclonal COOH-terminal UT-A and UT-B antibodies. Immunohistochemistry was performed on 16 extrarenal tissues using the same antibodies. In kidney, we detected mRNA transcripts and protein bands consistent with previously-identified UT-A and UT-B isoforms, as well as novel forms. We found that UT-A mRNA and protein are widely expressed in extrarenal tissues in various forms that are different from the known isoforms. We determined the cellular localization of UT-A and UT-B in these tissues. We found that both UT-A and UT-B are ubiquitously expressed as numerous tissue-specific mRNA transcripts and protein forms that are localized to cell membranes, cytoplasm, or nuclei.

Rationale: Bupropion reduces discomfort and craving associated with smoking cessation. This study determined whether a rat model of nicotine dependence could detect such nicotine abstinence-alleviating effects., Objectives: Experiments determined whether the abstinence-alleviating effects of bupropion were detectable by (1) behavioral abstinence signs precipitated by the nicotinic antagonist mecamylamine, (2) place aversion conditioned to mecamylamine-precipitated nicotine abstinence, and (3) spontaneous behavioral abstinence signs after abrupt nicotine withdrawal., Methods: In experiments 1 and 2, nicotine-dependent rats were coinfused for 7 days with 3.15 mg/kg/day nicotine and 20 mg/kg/day bupropion or with nicotine alone. They were then challenged with 1 mg/kg mecamylamine and observed for behavioral abstinence signs (experiment 1) or place aversion conditioned to precipitated abstinence (experiment 2). In experiment 3, rats were nicotine-infused for 7 days as above. A day after termination of nicotine infusion, rats were observed for spontaneous nicotine abstinence signs before and after injection with saline or bupropion., Results: In experiment 1, rats coinfused with nicotine and bupropion had significantly fewer mecamylamine-precipitated abstinence signs than rats infused with nicotine alone but similar numbers to rats infused with saline alone. In experiment 2, bupropion pretreatment significantly reduced the aversiveness of mecamylamine-precipitated nicotine abstinence. In experiment 3, a single bupropion injection dose-dependently alleviated spontaneous nicotine abstinence syndrome., Conclusions: These results suggest that these rat models of nicotine dependence and abstinence syndrome may be useful in detecting nicotine abstinence-alleviating effects of potential medications for smoking cessation. The effects of acute bupropion administration raise interesting questions regarding bupropion's mechanism of action.

The Harderian gland is a poorly understood anterior ocular gland that occurs in most terrestrial vertebrates. Numerous extraorbital functions have been ascribed to the Harderian gland, principally based on its association with the nasolacrimal duct. Few studies have centered on archosaurs and the majority of those available focused solely on the Harderian gland of birds. Little is known about the lacrimal apparatus of the crocodilians. We examined the lacrimal apparatus of several specimens of Alligator mississippiensis anatomically, histologically, and histochemically and studied the embryogenesis of this system. The nasolacrimal duct possesses a distal secretory area, which is more convoluted than that of typical mammals or lepidosaurs. The alligator Harderian gland possesses a unique combination of characteristics found in lepidosaurs, birds, and mammals. Like that of both mammals and lepidosaurs, it is a large, tuboloacinar gland that appears to secrete both mucoprotein and lipids. However, the presence of blood vessels and immune cells is reminiscent of that of the avian Harderian gland. The immunogenesis of the alligator Harderian gland appears to be tied to the development of the vascular system. The presence of a distinct palpebral gland in the anterior aspect of the ventral eyelid is a feature unique to alligators. Based on position, this gland does not appear to be homologous to the anterior lacrimal gland of lepidosaurs. Lymphatic aggregations were also found in the palpebral gland. The presence of interstitial immune cells in the orbital glands of alligators suggests that the alligator lacrimal apparatus, like that of birds, may play a role in the head-associated lymphatic tissue system., (Copyright 2005 Wiley-Liss, Inc.)

The paranasal sinuses remain elusive both in terms of function and in the proximate mechanism of their development. The present study sought to describe the maxillary sinuses (MSs) in three species of callitrichid primates at birth, a time when secondary pneumatization occurs rapidly in humans. The MSs were examined in serially sectioned and stained slides from the heads of two Callithrix jacchus, one Leontopithecus rosalia, and two Saguinus geoffroyi. Specimens were examined microscopically regarding the distribution of osteoclasts and osteoblasts along the osseous boundaries of the MS and other parts of the maxillary bone. Selected sections were immunohistochemically evaluated for the distribution of osteopontin (OPN), which facilitates osteoclast binding. Taken together, OPN immunoreactivity and bone cell distribution suggested trends of bone resorption/deposition that were consistent among species for the superior (roof) and inferior (floor) boundaries of the MS. Expansion at the roof and floor of the MS appeared to correspond to overall vertical midfacial growth in callitrichids. Much more variability was noted for the lateral (alveolar) and medial (nasal walls) of the MS. Unlike the other species, the nasal wall of Saguinus was static and mostly composed of inferior portions of the nasal capsule that were undergoing endochondral ossification. The variation seen in the alveolar walls may relate to the presence or absence of adjacent structures, although it was noted that adjacency of deciduous molars influenced medial drift of the alveolar wall in Saguinus but not Leontopithecus. The results of this study are largely consistent with the "structural" or "architectural" hypothesis of sinus formation with respect to vertical MS enlargement, and the variable cellular/OPN distribution found along the nasal and alveolar walls was evocative of Witmer's (J Vert Paleontol 1997;17:1-73) epithelial hypothesis in revealing that most expansion occurred in regions unopposed by adjacent structures., ((c) 2005 Wiley-Liss, Inc.)

Euclidean distance matrix analysis (EDMA) of three-dimensional data is used here to examine mandibular morphology between two species of galagos. Otolemur crassicaudatus consumes primarily exudates, while O. garnettii is more frugivorous. Acquisition of exudates involves either gouging or scraping tree bark, and may involve different forces at the mandible than incising fruits. Previous studies of mandibular morphology in exudate-feeding primates produced mixed results, some suggesting that morphological specializations reflect adaptations for greater force at the anterior dentition, while others suggest specializations for producing a large gape. This study addresses these controversies by testing predictions associated with O. crassicaudatus generating greater force at the anterior dentition or producing a larger gape relative to O. garnettii. In addition, this study tests predictions associated with specializations of the anterior dentition in O. crassicaudatus as related to exudate-feeding. Crania and mandibles from 28 O. crassicaudatus and 17 O. garnettii were digitized in three dimensions, using 18 landmarks that summarize the shape of the jaw. Two-dimensional measurements were taken to assess incisor robusticity. All three-dimensional data were analyzed using EDMA, and bootstrap tests were executed to identify specific interlandmark differences that were driving any significant (P < 0.05) overall shape differences. Two-dimensional data were analyzed using Student's t-test for independent measures. Results revealed that there was a significant shape difference in mandibles between species, and that mandibles of O. crassicaudatus showed higher condyles, longer mandibles, decreased incisor procumbency, and greater incisor robusticity relative to O. garnettii. It is suggested that the results of the present study reflect adaptations for scraping in O. crassicaudatus rather than gouging., (2004 Wiley-Liss, Inc.)

The main and accessory olfactory systems of certain mammals (e.g., rodents, ungulates, and carnivores) have been investigated using lectin histochemistry to probe for sugar residues that may reflect physiological aspects of signal transduction or development. Morphologically, the vomeronasal organs (VNOs) of strepsirrhine primates (lemurs and lorises) are typical of functional VNOs in other mammals, whereas in humans and chimpanzees the VNOs appear vestigial. However, the human VNO is considered functional by some authors. To elucidate the cellular nature of the VNO in human and chimpanzees, a panel of six lectins (Con-A, ECL, PNA, RCA, s-WGA, and UEA-1) was applied to the VNO in eight species of primates, including humans and chimpanzees. The results indicated that there were few, if any, lectin-reactive cells in the human or chimpanzee VNO that resembled those seen in the vomeronasal neuroepithelium in other primates. The overall pattern of lectin reactivity in the human and chimpanzee VNO is unlike that seen in mammals with chemosensory VNOs, suggesting that the VNO of these hominoids does not function similarly to that of other primates.

The present study examined interspecies, intersexual, and age-related changes in size of the vomeronasal neuroepithelium (VNNE) of two species of greater bushbabies (genus Otolemur, Infraorder Lorisiformes, Suborder Strepsirrhini). Tissue blocks containing the vomeronasal organs of nine O. crassicaudatus (8 adults, 1 neonate) and ten O. garnettii (9 adults, 1 neonate) were studied by means of serial paraffin sectioning and computer-based reconstruction of VNNE volume. In addition, the immunoreactivity of the VNNE to two neuronal markers, neuron-specific beta tubulin (BT) and olfactory marker protein (OMP) was compared between species, sexes, and ages. Results indicated that a clear VNNE is present at birth in both species, and OMP immunoreactivity was verified in O. garnettii at birth. Male and female adults of both species showed OMP-immunoreactive and BT-immunoreactive neurons in the VNNE. Immunohistochemical findings indicated that all males and the youngest females had the thickest VNNE, especially at the marginal junctions with the receptor-free epithelium. Results of a 2-way Analysis of Variance (ANOVA, species x sex) revealed no significant differences in VNNE length or volume between species, but O. crassicaudatus had significantly (p < 0.05) greater palatal length. Significant (p < 0.05) differences also were found between sexes in VNNE volume, but no significant differences in palatal length or VNNE length. The distribution of VNNE volume against age indicated that the sex differences were more pronounced in O. crassicaudatus than O. garnettii. For both species and sexes, distribution of VNNE volume against age suggested an age-related reduction in volume. These findings demonstrate postnatal plasticity in VNNE size in Otolemur that is reminiscent of that found for olfactory structures in some rodents. Bushbabies or other strepsirrhine primates may offer an opportunity for further understanding of behavioral correlates of VNNE postnatal plasticity, which may represent primitive functional characteristics of the order Primates.

The present study describes seasonal changes in delta5 3beta hydroxysteroid dehydrogenase (3beta-HSD), glusose-6 phosphates dehydrogenase (G-6-PD), and lipids in the ovary of a vespertilionid bat, Scotophilus heathi. Total lipids and 3beta-HSD activity are restricted to thecal and interstitial cells of the ovary. The total lipids, 3beta-HSD, and G-6-PD significantly increase during recrudescence, and remain high during winter dormancy and breeding as compared to the other reproductive phases. High incidence of lipids and enzyme activity in interstitial cells during the breeding period and at the time of ovulation clearly suggests that these cells are actively involved in steroidogenesis. A decline in enzymes and lipid activity during winter dormancy, which correlates with the declining levels of steroidogenesis, might be the factors responsible for prolonged survival of the Graafian follicle in the ovary of S. heathi.

This study explored the correlations of scores on the Wechsler Intelligence Scale for Children-III in screening language problems and scores on the three Comprehensive Receptive and Expressive Vocabulary Test subscales. Participants were 243 students ages 6 to 17 years in Grades K-11 who were identified as learning disabled, learning disabled with speech impairment, mentally retarded, and speech impaired. Analysis indicated strong correlations between the two measures, particularly between the CREVT General Vocabulary and WISC-III Verbal IQ (r = .80), WISC-III Verbal Comprehension Index (r =.83), and the Vocabulary subtest (r =.76). These results held across the grades. Supporting earlier studies of relationships of Verbal IQ and Receptive Vocabulary, correlations were lower between participants in Grades K through 2 than those in higher grades on the WISC-III Verbal IQ and the Receptive Vocabulary subtest. An analysis of the accuracy of the WISC-III for classifying students with language problems indicated improvement in classification over chance. These findings suggest that the WISC-III may be an effective screen for language problems.

Although hyperthyroidism has many signs and symptoms, right heart failure can occasionally be the main presenting symptom. We describe the case of a previously healthy 42-year-old woman whose chief complaint was progressive bilateral lower extremity edema. The echocardiogram revealed right atrial dilatation and moderate-to-severe tricuspid regurgitation. Results of laboratory studies were consistent with hyperthyroidism. Thyroid ablation resulted in permanent resolution of symptoms and resolution of tricuspid incompetence on echocardiography. In a case of isolated, unexplained tricuspid regurgitation, it is important to consider indolent hyperthyroidism in the differential diagnosis.

The present special issue of The Anatomical Record is the result of a symposium entitled Evolution of the Special Senses in Primates. Considered together, the special senses of primates are remarkable because they constitute a singular and definitive suite of mammalian characteristics. Examining their evolution is pivotal for understanding the origin and present-day variation of primate behavior and ecology. Accordingly, the 14 articles assembled here consider the different constraints and opportunities associated with the uptake and use of physical and chemical stimuli. The present issue brings together experts on different primate sensory modalities and stresses events at the sensory periphery, where the organism is exposed to and comes into contact with its environment. Key topics include color vision, the genetics of olfaction, the morphological basis and significance of chemical communication, and the neural organization and scaling of primate sensory systems. The result is a special issue that both reflects our current understanding of primate sensory modalities and challenges certain fundamental assumptions concerning their evolution., ((c) 2004 Wiley-Liss, Inc.)

Vomeronasal organ (VNO) morphology varies markedly across primate taxa. Old World monkeys display no postnatal VNO. Humans and at least some apes retain a vestigial VNO during postnatal life, whereas the strepsirrhines and New World Monkeys present a morphologically well-defined VNO that, in many species, is presumed to function as an olfactory organ. Available microanatomical and behavioral studies suggest that VNO function in these species does not precisely duplicate that described in other mammalian taxa. The questions of which species retain a functional VNO and what functions they serve require inquiry along diverse lines but, to be functional, the vomeronasal epithelium must be neuronal and olfactory. We used immunohistochemistry to establish these criteria in six primate species. We compared the expression of two neuronal markers, neuron-specific beta-tubulin (BT) and protein gene product 9.5, and olfactory marker protein (OMP), a marker of mature olfactory sensory neurons, in paraffin-embedded VNO sections from two strepsirrhine and four haplorhine species, all of which retain morphologically well-defined VNOs during postnatal life. The infant Eulemur mongoz, adult Otolemur crassicaudatus, neonatal Leontopithicus rosalia, and adult Callithrix jacchus express all three proteins in their well-defined vomeronasal neuroepithelia. The infant Tarsius syrichta showed some BT and OMP immunoreactivity. We establish that two strepsirrhine species and at least some New World haplorhines have mature sensory neurons in the VNO. In contrast, at all ages examined, Saguinus geoffroyi VNO expresses these markers in only a few cells., ((c) 2004 Wiley-Liss, Inc.)

The terms "microsmatic" and "macrosmatic" are used to compare species with greater versus lesser olfactory capabilities, such as carnivores compared to certain primates. These categories have been morphologically defined based on the size of olfactory bulb and surface area of olfactory epithelium in the nasal fossa. The present study examines assumptions regarding the morphological relationship of bony elements to the olfactory mucosa, the utility of olfactory epithelial surface area as a comparative measurement, and the utility of the microsmatic concept. We examined the distribution of olfactory neuroepithelium (OE) across the anteroposterior length of the nasal fossa (from the first completely enclosed cross-section of the nasal fossa to the choanae) in the microsmatic marmoset (Callithrix jacchus) compared to four species of nocturnal strepsirrhines (Otolemur crassicaudatus, O. garnetti, Microcebus murinus, and Cheirogaleus medius). Adults of all species were examined and infant C. jacchus, O. crassicaudatus, M. murinus, and C. medius were also examined. All specimens were serially sectioned in the coronal plane and prepared for light microscopic study. Distribution of OE across all the turbinals, nasal septal surfaces, and accessory spaces of the nasal chamber was recorded for each specimen. The right nasal fossae of one adult C. jacchus and one neonatal M. murinus were also three-dimensionally reconstructed using Scion Image software to reveal OE distribution. Findings showed OE to be distributed relatively more anteriorly in adult C. jacchus compared to strepsirrhines. It was also distributed more anteriorly along the nasal septal walls and recesses in neonates than adults. Our findings also showed that OE surface area was not a reliable proxy for receptor neuron numbers due to differing OE thickness among species. Such results indicate that nasal cavity morphology must be carefully reconsidered regarding traditional functional roles (olfaction versus air conditioning) assigned to various nasal cavity structures. At present, the microsmatic concept itself lacks a basis in nasal chamber morphology, since OE may have varying patterns of distribution among different primates., ((c) 2004 Wiley-Liss, Inc.)

The terms "microsmatic" and "macrosmatic" refer to species with lesser or greater levels, respectively, of olfactory function. Historically, primates are considered microsmats (olfactory sense reduced) with a concomitant increased emphasis on vision. The olfactory bulbs (forebrain centers that receive peripheral olfactory input) are proportionately smaller in primates compared to most other mammals. Similarly, the regions of the nasal cavity that are covered with olfactory epithelium (containing receptor cells) have proportionately less surface area in primates than other mammals. Thus, the generalization that primates are microsmatic is most frequently stated in terms of the proportional rather than absolute size of olfactory structures. Yet the importance of scaling to body size is unclear in regard to the chemical senses such as the olfactory or vomeronasal systems-do chemosensory structures such as olfactory bulbs and olfactory epithelium exhibit the same neural relationship to body mass that is seen for neural tissues that supply innervation to musculature or the skin? Previous studies examining neuronal density, volume, and/or surface area of the olfactory epithelium illustrate that different conclusions may be supported based on the parameter used. Plots of olfactory bulb volume versus body mass that generated for large-scale taxonomic studies or growth studies benefit from body mass (or total brain volume) with a comparative perspective. However, our examination of proportional versus absolute measurements implies that in comparisons within taxa, body size adjustments needlessly distort the data. As a final consideration, another embryonic derivative of the nasal placode, the vomeronasal organ, may warrant consideration regarding a definition of microsomia versus macrosomia.

Callitrichid primates (tamarins, marmosets) have extreme variation in the vomeronasal organ (VNO), including ontogenetic differences in the neuroepithelium and vomeronasal duct (VND) patency at birth. Such differences render the timing and extent of VNO maturation debatable in callitrichids, but no studies have used neuron-specific immunohistochemical markers to address this question. The present study compared the number of VNO epithelial cells that express immunoreactivity to neuron-specific beta-tubulin III (BT), VNO length, and VNO cross-sectional area between two species of tamarins (Leontopithecus rosalia and Saguinus geoffroyi) that differed in perinatal VND patency. Neonatal lemurs and adult marmosets and bushbabies were also examined for a comparison to species previously shown to have a relatively large amount of VNO neuroepithelium and patent VNDs. The head of each specimen was serially sectioned in the coronal plane. Based on known rostrocaudal start/stop points of the VNO, selected unstained sections were used for BT protocols and area measurement at three percentiles (25th, 50th, 75th) in each specimen. Each section was photographed and enlarged for cell counts and measurement of cross-sectional epithelial area. In each specimen, the number of BT(+) cells in the VNO was counted at each percentile and expressed as a number per mm(2). Results indicated that lemur VNOs had a dense population of BT(+) cells at birth, but the VNO was more varied in the tamarin species. S. geoffroyi had few or no BT(+) cells in VNOs of neonates, which had fused VNDs, but had an increased BT(+) population by 1 and 2 months postnatal age, when the VND was patent. Of the species with patent VNDs at birth, neonatal L. rosalia had a denser population of BT(+) cells compared to S. geoffroyi, though not to the degree seen in neonatal lemurs or adult marmosets and bushbabies. These findings show that BT immunohistochemistry is a useful comparative method for the study of VNOs in subadult primates. Since the quantity of nonsensory VNO epithelium varies substantially between species, epithelial area measurements may be misleading, and BT(+) cell counts appeared to be the best quantitative method for comparing receptor neuron numbers among primates. It is suggested that the greater BT(+) cell population in L. rosalia at all subadult stages examined reveals an earlier maturation of the neuroepithelium compared to S. geoffroyi. Further investigation should consider whether this may relate to a comparatively brief subadult ontogeny and early onset of adult behaviors in L. rosalia compared to other tamarins studied to date., (Copyright 2004 Wiley-Liss, Inc.)

Adult primates have at least five known phenotypes of vomeronasal organ (VNO), ranging from the typical morphology seen in most other mammals to complete absence. With such morphological disparity, the phylogenetic value and any inferences on ancestral VNO morphology of the primate VNO are left uncertain. The present study investigated the VNO of embryonic and fetal Tarsius bancanus borneanus (n = 4) in comparison with prenatal specimens from four other species of primates in an effort to clarify adult morphological variations. In all except one of the fetal primates, the VNO communicated to the nasopalatine duct. One exception occurred in the largest fetal Tarsius (25 mm crown-rump length), in which the VNO communicated with the nasal cavity alone. The vomeronasal neuroepithelium was well differentiated from a thinner, non-sensory epithelium in all Tarsius and New World monkeys studied, as well as late embryonic and fetal Microcebus myoxinus. In anterior sections, this neuroepithelium was found in a more superior location in Tarsius and New World monkeys compared with Microcebus myoxinus. In all primates, masses of cell bodies were found superior to the VNO, intermingled with nerve fibres. These morphologically resembled luteinizing hormone-releasing hormone neurons described in other mammals, including humans, suggesting that a primitive association of these neurons with the VNO may exist in all primate taxa. The present study revealed that prenatal similarities exist in Tarsius and New World primates in VNO epithelial morphology. However, these are transient stages of morphology. If tarsiers and anthropoids do represent a clade (Haplorhini), then the atypical morphology seen in adult tarsiers and New World monkeys probably represents the adult VNO morphology of a haplorhine common ancestor.

Ecological explanations have been put forward to account for the precocious or delayed development of patency in ducts leading to the vomeronasal organ (VNO) in certain mammals. Perinatal function may be related, in part, to the patency or fusion of the vomeronasal and nasopalatine (NPD) ducts. However, few studies have focused on NPD development in primates, which generally have a prolonged period of dependence during infancy. In this study we examined 24 prenatal primates and 13 neonatal primates, and a comparative sample of fetal mice and insectivores. In embryonic and early fetal Microcebus murinus, the NPD was completely fused, whereas in fetuses of later stages the duct was partially fused or completely patent. M. myoxinus of all stages demonstrated some degree of NPD fusion. In all other prenatal primates, the NPD was fused to some extent. Four prenatal insectivores (Tenrec ecaudatus) showed some degree of NPD fusion. In Mus musculus at 19 days gestation, the NPD was patent, although the anatomically separate VNO duct was fused. T. ecaudatus and most of the neonatal primates revealed complete NPD patency. An exception was Saguinus geoffroyi, which exhibited fusion of the NPD near the VNO opening. These observations may relate to differences in perinatal VNO function. The differences noted in our study suggest that M. murinus and M. myoxinus may differ in perinatal VNO functionality and perhaps in related behavior. Observations of neonatal primates suggest that NPD patency may be relatively common at birth and could serve other purposes in addition to being an access route for VNO stimuli., (Copyright 2003 Wiley-Liss, Inc.)

Gross and histologic aspects of facial expression muscles are presented here for Otolemur spp. (suborder Prosimii, family Lorisidae) and are compared with those of lemuroids. Muscles of facial expression are involved in social signaling among primates, and are a primary means by which close-proximity nonverbal communication is achieved. These muscles have been well described in catarrhines and many of the lemuroids; however, their arrangement is not well known in the lorisids. In the present study we examined muscles of facial expression in Otolemur by dissecting preserved faces. The arrangement and appearance of the muscles were noted, and samples were gathered from each muscle for histologic processing. The results showed 17 muscles of facial expression in Otolemur, as compared to seven reported in previous studies. Histologically, muscles of the ear region were arranged in tight, dense fascicles, while muscles of the orbital region were arranged more loosely. Grossly, the facial expression muscles in Otolemur were very similar in morphology and attachments to those in the lemuroids, with some differences in the ear region. Otolemur garnettii had several muscles that appeared to be more robust than in the larger O. crassicaudatus. This may be due to dietary and/or social differences between the species. In previous studies it was concluded that, relative to lemuroids, Otolemur has a primitive arrangement of facial expression muscles. The current results do not support that conclusion, and in fact support a far greater similarity between Otolemur and lemuroids in general. These results underscore the need for a reexamination of facial musculature in prosimians in general, and may have taxonomic value as regards the position of Otolemur with lemuroids and other galagos., (Copyright 2003 Wiley-Liss, Inc.)

It has been suggested that the variability of the primate vomeronasal organ (VNO) may be greater than previously thought, especially among New World monkeys. It is not clear to what extent VNO variation reflects ontogenetic, functional, or phylogenetic differences among primates. The present study investigated VNO anatomy in an ontogenetic series of two genera of callitrichid primates, in order to assess recent attempts to develop VNO character states and to examine the evidence for VNO functionality at different life stages. A sample of six Leontopithecus rosalia, one L. chrysomelas, and six Saguinus geoffroyi was serially sectioned and stained using various methods. Two adult Callithrix jacchus were also sectioned for comparative purposes. The VNO of each primate was examined by light microscopy along its entire rostrocaudal extent. VNOs of the tamarins were described to determine whether they fit into 1 of 3 character states recently attributed to various New World monkeys. At birth, the two species of tamarins differed in the nature of communication between the VNO and nasopalatine duct (NPD). Two of 3 neonatal S. geoffroyi exhibited a fused VNO duct in a more dorsal position (adjacent to the nasal cavity) compared to that of L. rosalia. The VNO duct communicated with the NPD and was patent in neonatal L. rosalia. Both species appeared to have an age-related increase in the amount of sensory epithelium in the VNO. Subadult L. rosalia had caudal regions of the VNO that were exceptionally well-developed, similar to those of strepsirhine primates. Compared to subadults, all adult callitrichids appeared to have more ventral communications of the VNO duct directly into the NPD. Adult S. geoffroyi and L. chrysomelas both had VNO sensory epithelium separated by multiple patches of nonsensory epithelium. This contrasted with the VNOs of C. jacchus, which had a nearly continuous distribution of receptors on all surfaces of the VNO. The findings indicate that tamarins have delayed maturation of the VNO epithelium, and that some species have little or no perinatal function. These results also suggest that ontogenetic changes in craniofacial form may alter the position of the VNO in tamarins. The present study supports the use of at least two character states to categorize the VNO of various callitrichids, but it is suggested that one of these, previously called "reduced sensory epithelium" should be instead termed "interrupted sensory epithelium." The distribution of VNO sensory epithelium does not appear to reflect phylogenetic influences; it is more likely a functional characteristic that varies throughout postnatal life. Therefore, this chemosensory system has a high degree of plasticity relating to age and function, which in some instances can confound the use of characteristics as phylogenetic traits. Further study is needed to quantify VNO receptors in various species to determine if functional differences exist and if some species have more precocious VNO function than others., (Copyright 2002 Wiley-Liss, Inc.)

Most studies on mammalian vomeronasal organ (VNO) have been on laboratory-bred animals. Our present study examines the VNO in wild-caught meadow voles (Microtus pennsylvanicus: n=16) and prairie voles (M. ochrogaster: n=15). These species vary in their mating strategies and degree of parental care by males. M. ochrogaster exhibits pair bonding and more paternal care compared to M. pennsylvanicus, a promiscuous species. We hypothesize that sexual dimorphism will occur in the promiscuous species based on previous studies which suggest that those who exhibit more aggressive or masculine behavior have larger VNOs. Our results support our original finding that VNOs are not different in size in wild Microtus spp. that vary in male parental tendencies. However, the present study also indicates that M. pennsylvanicus, the species exhibiting more disparate parental tendencies, exhibited larger VNOs in females than males. This is the reverse of previous findings on rats, and we hypothesize that this difference may be due to mate selectivity and/or maternal aggression.

The vomeronasal organs (VNOs) of mammals are highly variable epithelial structures found bilaterally in the mucosa of the nasal septum. Whereas the discovery of the human VNO is traditionally ascribed to Frederick Ruysch (1703, 1724), the organ is named after Ludwig Levin Jacobson (1811, 1813) who described it in nonhuman mammals. We recently have pointed out controversies surrounding the incidence and structure of the enigmatic human VNO, and herein, we provide a historical analysis of its discovery. We present evidence that the honor of discovering the human VNO truly belongs to Kölliker (1877), and not to Ruysch. Ruysch illustrated the lateral view of a 2-year-old infant's nasal septum, and it is unclear whether the right nasal passage, the tubular VNO or its opening, or an unrelated duct is being indicated. Jacobson reported the VNO to be missing in humans. Its discovery in the human embryo can be related in part to later authors, such as Dursy (1869). Our reappraisal of the literature confirms that Kölliker was actually the first among these 18th-689th century investigators to provide evidence of the human VNO as a histologically identifiable structure in the fetus and the adult.

Background: Previous reports on the human vomeronasal organ (VNO) have been inconsistent. Observations of fossae on the nasal septum have been reported as the VNO., Methods: Adult human subjects (210) and cadavers (31) were examined using rigid nasal endoscopy, serial histology, and biopsy ultrastructure (5)., Results: The nasopalatine fossa (NPF) and the nasopalatine recess (NPR) are discrete, but variable, structures located adjacent to the VNO region. The NPF is not a vomeronasal pit. A septal mucosal pit could hide the vomeronasal duct opening. The VNO is a submucosal structure located 2-8 mm superior to the NPR and cannot be positively identified either macroscopically or endoscopically., Conclusion: The VNO has long been mistaken for the NPF and septal mucosal pits. We show that serial histology is the correct method for identifying the VNO.

Cowpox virus (Brighton Red strain) possesses one of the largest genomes in the Orthopoxvirus genus. Sequence analysis of a region of the genome that is type-specific for cowpox virus identified a gene, vCD30, encoding a soluble, secreted protein that is the fifth member of the tumor necrosis factor receptor family known to be encoded by cowpox virus. The vCD30 protein contains 110 aa, including a 21-residue signal peptide, a potential O-linked glycosylation site, and a 58-aa sequence sharing 51-59% identity with highly conserved extracellular segments of both mouse and human CD30. A vCD30Fc fusion protein binds CD153 (CD30 ligand) specifically, and it completely inhibits CD153/CD30 interactions. Although the functions of CD30 are not well understood, the existence of vCD30 suggests that the cellular receptor plays a significant role in normal immune responses. Viral inhibition of CD30 also lends support to the potential therapeutic value of targeting CD30 in human inflammatory and autoimmune diseases.

The vomeronasal organ (VNO) is a chemosensory structure that has morphological indications of functionality in strepsirhine and New World primates examined to date. In these species, it is thought to mediate certain socio-sexual behaviors. The functionality and even existence of the VNO in Old World primates has been debated. Most modern texts state that the VNO is absent in Old World monkeys, apes, and humans. A recent study on the VNO in the chimpanzee (Smith et al., 2001b) challenged this notion, demonstrating the need for further comparative studies of primates. In particular, there is a need to establish how the human/chimpanzee VNO differs from that of other primates and even nonhomologous mucosal ducts. Histochemical and microscopic morphological characteristics of the VNO and nasopalatine duct (NPD) were examined in 51 peri- and postnatal primates, including humans, chimpanzees, five species of New World monkeys, and seven strepsirhine species. The nasal septum was removed from each primate and histologically processed for coronal sectioning. Selected anteroposterior intervals of the VNO were variously stained with alcian blue (AB)-periodic acid-Schiff (PAS), PAS only, Gomori trichrome, or hematoxylin-eosin procedures. All strepsirhine species had well developed VNOs, with a prominent neuroepithelium and vomeronasal cartilages that nearly surrounded the VNO. New World monkeys had variable amounts of neuroepithelia, whereas Pan troglodytes and Homo sapiens had no recognizable neuroepithelium or vomeronasal nerves (VNNs). Certain unidentified cell types of the human/chimpanzee VNO require further examination (immunohistochemical and electron microscopic). The VNOs of P. troglodytes, H. sapiens, and New World monkeys exhibited different histochemistry of mucins compared to strepsirhine species. The nasopalatine region showed great variation among species. It is a blind-ended pit in P. troglodytes, a glandular recess in H. sapiens, a mucous-producing duct in Otolemur crassicaudatus, and a stratified squamous passageway in all other species. This study also revealed remarkable morphological/histochemical variability in the VNO and nasopalatine regions among the primate species examined. The VNOs of humans and chimpanzees had some structural similarities to nonhomologous ciliated gland ducts seen in other primates. However, certain distinctions from the VNOs of other primates or nonhomologous epithelial structures characterize the human/chimpanzee VNO: 1) bilateral epithelial tubes; 2) a superiorly displaced position in the same plane as the paraseptal cartilages; 3) a homogeneous, pseudostratified columnar morphology with ciliated regions; and 4) mucous-producing structures in the epithelium itself., (Copyright 2002 Wiley-Liss, Inc.)

Nonsyndromic coronal suture synostosis produces predictable and well-documented morphologies of the cranial vault with anteroposterior growth restrictions and mediolateral compensatory growth. The potential effects of nonsyndromic coronal suture synostosis on mandibular form are not as clear, however. This study was designed to evaluate whether coronal suture synostosis is associated with alterations in mandibular form by using a familial rabbit model of coronal suture synostosis. To assess this potential relation, the following hypothesis was tested: mandibular form in rabbits with coronal suture synostosis is significantly (P < 0.05) different from that seen in normal rabbits. The cleaned and dried mandibles of 33 adult New Zealand white rabbits were used (12 from normal rabbits, 13 from rabbits with delayed-onset synostosis, and 8 from rabbits with complete coronal suture synostosis). Seven anatomical landmarks on the mandible were located and digitized in three dimensions: anterior molar on the alveolus, posterior molar on the alveolus, coronoid process, anterior pole of the condyle, condylar process, angular process, and mandibular angle. To describe the mandibular condyle, the distance from the anterior pole to the posterior pole of the condyle was measured with digital sliding calipers, as was the distance between the medial and lateral poles. A shape ratio was then created using the dividend of these sums. Statistical analyses of mean form differences between mandibles were executed using Euclidean distance matrix analysis. Statistical analyses of the mandibular condyle linear and shape measurements were analyzed using one-way ANOVA in the three groups. Results showed that complete coronal suture synostosis is associated with significant (P < 0.05) differences in mandibular form compared with that of normal rabbits but that mandibular form in rabbits with delayed-onset synostosis does not differ from that of normal rabbits (P > 0.05). In particular, distances involving the coronoid process in rabbits with coronal suture synostosis were significantly different, paralleling previous work in human patients with coronal synostosis. There are no intrinsic condylar linear or shape differences between any of these groups, however. The form difference noted is most likely secondary to the synostosed coronal suture and may reflect alterations in the cranial base or masticatory musculature in this rabbit model.

Approximately 300 to 500 infants per 1,000,000 have prematurely fused cranial sutures (craniosynostosis). Craniosynostosis can result in increased intracranial pressure and craniofacial deformities, which often require extensive and costly craniofacial surgery. Because the neurocranium and basicranium are developmentally interrelated, understanding their influence on one another is important for surgical planning. Although surgery has been found to have long-term effects on the cranial bases of craniosynostotic human beings and rabbits, the biological mechanisms behind these effects remain uncertain. Some researchers have suggested that the surgical release of synostosed sutures alters long-term growth patterns, resulting in cranial base differences between craniosynostotic individuals who undergo surgery and those who do not. Additionally, some investigators have proposed that an acute and surgically related displacement of basicranial elements may contribute to the observed differences. The current study examines acute postoperative changes in four lengths, three angles, and three triangles between cranial base landmarks in a sample of seven New Zealand white rabbits with familial nonsyndromic craniosynostosis. Results indicate that suturectomy caused no statistically significant (P < 0.05) acute length, angular, or shape differences in the cranial base. Thus, previous long-term cranial base differences found between rabbits that were operated on and those that were not were probably not caused by an acute displacement of skeletal elements as a result of surgery. These findings suggest that postoperative cranial base changes may be related more to chronically altered growth patterns than to acutely altered changes in intracranial pressure or dural tension.

Objective: The present radiographic study describes the size and shape of the cranial base from the sagittal aspect for a sample of 77 second-trimester "normal" control fetuses (n = 61) and fetuses (n = 16) exhibiting isolated, unilateral clefts of the lip (CL), ranging in fertilization age from 10 to 22 weeks., Methods: Fetuses were placed in a cephalostat, and standardized, lateral head radiographs were taken. The radiographs were traced, and 15 cephalometric landmarks were identified and digitized for analysis. Growth curves for cranial base lengths, angles, and areas were compared between control and CL groups. Also, cranial base triangles were constructed and shape comparisons were made using tensor biometric analysis., Results: No significant differences (p >.05) in regression line slopes were noted for any comparisons between the control and CL samples. Tensor biometric analysis also revealed no significant differences in the shapes of various cranial base triangles between the control and CL samples., Conclusion: This report presents second-trimester baseline growth curves for various cranial base components in CL human fetal specimens, and these data suggest that CL fetuses may also be used as an appropriate control sample for prenatal growth comparison studies of cleft lip and palate and cleft palate.

Objective: The present study investigates the potential relationship between craniosynostosis and any changes in endocranial vasculature. The hypothesis that crania from rabbits with familial, nonsyndromic coronal suture synostosis and crania from rabbits with experimental immobilization of the coronal suture are associated with altered form of the middle meningeal vessels and dural venous sinuses is tested., Design: Silicone rubber endocasts from 14 adult New Zealand white rabbits (Oryctolagus cuniculus) with familial nonsyndromic coronal suture synostosis (five with bilateral coronal suture synostosis and nine with unilateral coronal suture synostosis) were made to assess middle meningeal vessel and dural venous sinus form. For comparative purposes, endocasts were made from 25 rabbits with normal, patent coronal sutures and 10 rabbits with experimental immobilization of the coronal suture. Impressions of the dural venous sinuses were assessed for depth and width. The area of the confluens of sinuses was also assessed. Impressions of the middle meningeal vessels were assessed for depth, width, and degree of convolution. For width of the dural venous sinuses and area of the confluens of sinuses, comparisons among groups were made with a one-way analysis of variance (ANOVA). For depth of the dural venous sinuses and impressions of the middle meningeal vessels, comparisons among groups were made using a Kruskal-Wallis one-way ANOVA., Results: Crania with familial coronal suture synostosis had significantly (p <.05) reduced posterior dural venous sinus dimensions when compared with both crania from rabbits with experimental immobilization of the coronal suture and rabbits with normal coronal sutures. Crania with both coronal suture synostosis and experimental immobilization had significant increases in dimensions of the middle meningeal vessels relative to normal crania. In addition, casts from rabbits with unicoronal suture synostosis showed marked asymmetry in the dural venous sinuses., Conclusions: These results support the hypothesis that craniosynostosis is associated with alterations in endocranial vasculature. These changes are most likely a secondary response to synostosis rather than a causal factor and may reflect increased intracranial pressure, decreased intracranial volume, and local accumulations and reductions of cerebrospinal fluid in the posterior region of the skull and immediately deep to the coronal suture.

In the last decade or so, there has been a renewed interest in the adult human vomeronasal organ (VNO). Studies have yielded sometimes disparate findings about the microscopic structure of the organ and its supporting tissues. Such varied descriptions may be due to examination of different regions of the VNO, individual variation of VNOs among humans, or the presence of multiple, non-homologous structures that bear false resemblance to the human VNO. A histological description of the spatial relationship of the human VNO to other nasal septal elements is needed to ensure that all investigators are examining the same regions and homologous structures. Histologically sectioned nasal septa from, 22 human cadavers (1 child, 21 adults) were examined grossly and by light microscopy for the VNO. Using histological sections, the position of the VNO relative to other structures was estimated. Sections containing the VNO were retrospectively compared to scaled photographic slides of the unsectioned septa to identify surface landmarks. Human VNOs varied in anteroposterior and superoinferior position relative to the anterior nasal spine and the nasal cavity floor. In the absence of a visible duct opening, the only reliable surface marker, no consistent surface markings were noted for precise location. VNOs were frequently found superior to swellings associated with the paraseptal and/or septal cartilages. Such findings demonstrate that the human VNO is positionally variable, which may have contributed to previous conflicting findings on presence versus absence. Furthermore, our findings support recent suggestions that the VNO may have been misidentified by some investigators, and that its opening can be easily confused with other structures.

The large literature on the human vomeronasal organ (VNO) offers little consensus as to its persistence in the adult. We have already documented the existence of the VNO from embryonic day 33 through the neonatal stages. This has now been extended to human adults: 27 cadaver nasal septa, aged 2-86 y, were either dissected or decalcified, serially sectioned, stained and examined. The consistent presence of the VNO is reported as a homologue, in the form of a duct-like structure on the nasal septum at all ages. Also reported are size variability, pronounced bilateral asymmetry, a nonchemosensory pseudostratified ciliated epithelium with considerable structural variation and generally without medial-lateral differentiation, nasal septal glands opening into the VNO lumen, a lack of correlation between postnatal age and VNO size, visualisation of the human VNO with certainty by histological means alone, and a minute opening as its only visible surface feature. The human VNO is a discrete structure that should not be confused with the nasopalatine fossa, the septal mucosal pits or VNO openings.

The vomeronasal organ (VNO) is a chemosensory organ that functions in sociosexual communication in many vertebrates. In strepsirhine primates and New World monkeys, the bilateral VNOs are traditionally understood to exist as a well-developed chemosensory epithelial unit. In contrast, the VNOs of catarrhine primates are thought to be absent or exist only as reduced epithelial tubes of uncertain function. However, the VNO of New World monkeys shows substantial variation in the extent of sensory epithelium. Recent findings that the chimpanzee (Pan troglodytes) possesses a VNO similar to humans suggest the variability of the VNO among haplorhine primates may be more extensive than previously thought, and perhaps more at par with that observed in chiropterans. The atypical histologic structure and location of the human/chimpanzee VNO suggest accessory glandular secretion and transport functions. Other catarrhine primates (e.g., Macaca spp.), may truly be characterized by VNO absence. Unique aspects of facial growth and development in catarrhine primates may influence the position or even presence of the VNO in adults. These recent findings demonstrate that previous investigations on some catarrhine primates may have missed the VNO and underestimated the extent of variability. As an understanding of this variation increases, our view of VNO functionality and associated terminology is changing. Further investigations are needed to consider phylogenetic implications of VNO variability and the association of craniofacial form and VNO anatomic position in primates., (Copyright 2001 Wiley-Liss, Inc.)

Objective: Resynostosis following surgical correction of craniosynostosis is a common clinical correlate. Recent studies suggest that the dura mater is necessary to maintain suture patency. It has also been hypothesized that dura mater from synostotic individuals may provide aberrant biochemical signals to the osteogenic fronts of the calvaria, which result in premature suture fusion and subsequent resynostosis following surgery. This study was designed to test this hypothesis by surgically manipulating the coronal suture and dura mater in rabbits with familial craniosynostosis to prevent postsurgical resynostosis., Design: Craniofacial growth and histomorphometric data were collected from 129 rabbits: 72 normal controls and 57 rabbits with bilateral coronal suture synostosis (15 unoperated on controls; 13 surgical controls; 9 dura mater transplant only; 10 suture transplant only; and 10 suture and dura mater transplant). At 10 days of age, all rabbits had radiopaque amalgam markers placed on either side of the coronal, frontonasal, and anterior lambdoidal sutures. At 25 days of age, 42 synostosed rabbits had a 3 to 5-mm wide coronal suturectomy. Coronal sutures and/or underlying dura mater allografts were harvested from same-aged, wild-type, isohistogenic control rabbits and transplanted onto the dura mater of synostosed host rabbits. Serial radiographs were taken at 10, 25, 42, and 84 days of age, and the suturectomy sites were harvested at 84 days of age in 44 rabbits and serially sectioned for histomorphometric examination., Results: Results revealed that cranial vault growth was significantly (p < .05) improved following surgical release of the fused coronal suture compared with synostosed rabbits who were not operated on but was still significantly different (p < .05) from that of normal control rabbits. By 84 days of age, significant (p < .05) differences were noted in calvarial suture marker separation, cranial vault shape indices, and cranial base angles between rabbits with and without dura mater allografts, probably as a result of resynostosis of the suturectomy site or suture-only allografts. Qualitative histological examination revealed that at 84 days of age rabbits with suture and dura allografts had patent coronal sutures, suture-only allografts had fused coronal sutures with extensive endosteal hyperostosis, dura mater-only allografts had some new bone in the suturectomy site that resembled rudimentary osteogenic fronts, and suturectomy controls had extensive endosteal bone formation and resynostosis of the suturectomy site. Significantly (p < .05) more bone was found in the suturectomy sites of rabbits without dura mater allografts compared with rabbits with dura mater allografts., Conclusions: Results support the initial hypothesis that normal dura mater allografts will maintain suture or suturectomy site patency and allow unrestricted craniofacial growth. However, it is still unclear whether the dura mater from normal rabbits was providing biochemical signals to the transplanted sutures or suturectomy sites or simply acting as a barrier to prevent abnormal biochemical signals from the dura mater of synostosed rabbits from reaching the calvaria. The clinical and therapeutic implications of these procedures are discussed.

Hippocampal N-methyl-D-Aspartate (NMDA) receptors mediate mechanisms of cellular plasticity critical for spatial learning in rats. The present study examined the relationship between spatial learning and NMDA receptor expression in discrete neuronal populations, as well as the degree to which putative age-related changes in NMDA receptors are coupled to the effects of normal aging on spatial learning. Young and aged Long-Evans rats were tested in a Morris water maze task that depends on the integrity of the hippocampus. Levels of NR1, the obligatory subunit for a functional NMDA receptor, were subsequently quantified both biochemically by Western blot in whole homogenized hippocampus, and immunocytochemically by using a high-resolution confocal laser scanning microscopy method. The latter approach allowed comprehensive, regional analysis of discrete elements of excitatory hippocampal circuitry. Neither method revealed global changes, nor were there region-specific differences in hippocampal NR1 levels between young and aged animals. However, across all subjects, individual differences in spatial learning ability correlated with NR1 immunofluorescence levels selectively in CA3 neurons of the hippocampus. Parallel confocal microscopic analysis of the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor failed to reveal reliable differences as a function of age or spatial learning ability. This analysis linking age, performance, and NR1 levels demonstrates that although dendritic NR1 is generally preserved in the aged rat hippocampus, levels of this receptor subunit in selective elements of hippocampal circuitry are linked to spatial learning. These findings suggest that NMDA receptor abundance in CA3 bears a critical relationship to learning mediated by the hippocampus throughout the life span., (Copyright 2001 Wiley-Liss, Inc.)

It is currently thought that New World monkeys, prosimians, and humans are the only primates to possess vomeronasal organs (VNOs) as adults. Recent studies of the human VNO suggest that previous investigations on Old World primates may have missed the VNO. We examined nasal septa from the chimpanzee (Pan troglodytes) grossly and histologically for comparison with nasal septa from humans, Old World monkeys (Macaca fascicularis, M. nemistrina) and prosimian primates (Microcebus murinus, Otolemur garnettii). Grossly, chimpanzees had depressions on the nasal septum similar to fossae reported anterior to the VNO openings in humans. Histologically, chimpanzees and humans had bilateral epithelial tubes which were above the superior margin of the paraseptal cartilages (vomeronasal cartilage homologue). The epithelial tubes had a homogeneous ciliated epithelium. These structures were thus positionally and structurally identical to the human VNO and unlike the well-developed prosimian VNOs which were surrounded by vomeronasal cartilage. Macaques had no structures which resembled the VNO of either the prosimians or humans. The results demonstrate that the VNO is present postnatally in the chimpanzee and is almost identical to the human VNO in its anatomical position and histological structure. This in turn suggests that the reported absence of the VNO in at least some adult Old World primates is artifactual, and that further study may provide evidence for its existence in other species.

Fluoxetine (FLU) rapidly enhances extracellular (EC) serotonin (5-HT) in rodent brain, whereas the antidepressant effects of this drug in humans are typically not observed for 2-3 weeks. Thus, the effects of chronic oral FLU administration on neocortical and hippocampal EC 5-HT, and on caudate EC 5-HT and dopamine (DA), were examined in awake monkeys (Macaca fascicularis) using in vivo microdialysis (10.0 mg/kg; 3, 7, 14, and 21 days). On day 3, 5-HT was significantly increased above baseline levels in hippocampus (HC) and caudate. There was a trend for an increase in neocortex EC 5-HT levels. However, by day 7 5-HT remained significantly elevated only in HC, although 5-HT levels elsewhere had not completely returned to baseline. In contrast, levels of the 5-HT metabolite, 5-HIAA, were significantly reduced in all brain regions at all time points. Caudate DA levels tended to be decreased throughout FLU treatment. Local FLU and K(+) infusion were also used at various times during chronic systemic FLU administration to evaluate changes in functional synaptic regulation. In general, these results, along with the significant decrease in 5-HIAA levels and the tendency for basal EC 5-HT levels to remain modestly elevated only in HC during sustained FLU administration, suggest a reduction in releasable pools of 5-HT. Taken together with the trend for a decrease in caudate EC DA levels, these results do not appear to support the current hypothesis regarding the mechanism of action of SSRI antidepressants-that monoaminergic neurotransmission is progressively augmented during chronic treatment., (Copyright 2000 Wiley-Liss, Inc.)

Study Design: A masked, single-factor, posttest-only control group design., Objective: To explore the relationship between reported oral contraceptive use and peripheral joint laxity., Background: Studies have found an association between increased ligamentous laxity and changes in serum levels of hormones such as estrogen, progesterone, and relaxin. Two of these hormones, estrogen and progesterone, are present in most oral contraceptives. Oral contraceptive users, therefore, provide a population for studying the effects of these hormones on the degree of ligamentous laxity., Methods and Measures: Fifty-five women between the ages of 20 and 25 years participated in this study. Thirty users of oral contraceptives were a test group and 25 nonusers of oral contraceptives were controls. The KT-1000 Arthrometer was used to measure passive anterior translation of the tibia in relation to the femur in both knees. Passive abduction and adduction of the proximal interphalangeal (PIP) joint of the second digit of the nondominant hand and distal interphalangeal (DIP) joint hyperextension of the fifth digit of the nondominant hand were measured using a goniometer. A subjective measurement of passive second PIP joint motion was also assessed and a value of minimum, moderate, or maximum laxity was assigned. Independent sample t tests were performed to compare the measurements of the oral contraceptive user and nonuser groups for each joint. A chi-square test compared the subjective PIP joint data between the 2 groups., Results: No significant differences in laxity measurements at the knee or hand were found between the 2 groups. Average knee laxity varied between 5.7-7.9 mm of anterior displacement for both groups. Average PIP abduction and adduction varied between 6.5-6.7 degrees for both groups and DIP hyperextension was 28.6-29.9 degrees., Conclusions: Results of this study indicate that self-reported oral contraceptive use was not associated with peripheral joint laxity.

Previous studies from our laboratory have characterized the craniofacial morphology and growth patterns of an inbred strain of rabbits with autosomal dominant coronal suture synostosis. A number of rabbit perinates from this colony have been collected sporadically over a 5-year period with premature interfrontal suture synostosis. The present study describes the very early onset of craniofacial dysmorphology of these rabbits and compares them to similar-aged normal control rabbits. A total of 40 perinatal New Zealand White rabbits were used in the present study. Twenty-one comprised the sample with interfrontal suture synostosis and ranged in age from 27 to 38 days postconception (term = 31 days) with a mean age of 33.53 days (+/-2.84 days). Nineteen rabbits served as age-matched, normal controls (mean age = 33.05 days +/-2.79 days). Lateral and dorsoventral radiographs were collected from each rabbit. The radiographs were traced, computer digitized, and 12 craniofacial measurements, angles, and indices were obtained. Mean measures were compared using an unpaired Student's t-test. All synostosed rabbits were stillborn or died shortly after birth. Grossly, these rabbits exhibited extreme frontal bossing, trigonocephaly with sagittal keeling, and midfacial shortening. No somatic anomalies were noted. Radiographically, rabbits with interfrontal suture synostosis had significantly (P < 0.05) narrower bifrontal widths, shorter cranial vault lengths, kyphotic cranial base angles, and different cranial vault indices (shapes) compared to controls. Results reveal severe and early pathological and compensatory cranial vault changes associated with premature interfrontal suture synostosis in this rabbit model. The 100% mortality rate noted in this condition may be related to the inheritance of a lethal genetic mutation or to neural compression from reduced intracranial volume. Results are discussed in light of current pathogenic hypotheses for human infants with premature metopic suture synostosis., (Copyright 2000 Wiley-Liss, Inc.)

Opioid and alpha-adrenergic receptor activation protect the heart from ischemic damage. One possible intracellular mechanism to explain this is that an improvement in ATP availability contributes to cardioprotection. We tested this hypothesis by correlating postischemic left ventricular developed pressure (LVDP) and myofibrillar Ca(2+)-dependent actomyosin Mg(2+)-ATPase from isolated rat hearts treated with the kappa-opioid receptor agonist U-50488H (1 microM) or the alpha-adrenergic receptor agonist phenylephrine (10 microM) + propranolol (3 microM). Preischemic treatment with U-50488H or phenylephrine + propranolol improved postischemic LVDP recovery by 25-30% over control hearts. Ca(2+)-dependent actomyosin Mg(2+)-ATPase was found to be 20% lower in both U-50488H- and phenylephrine + propranolol-treated hearts compared with control hearts. The kappa-opioid receptor antagonist nor-binaltorphimine (1 microM) abolished the effects of U-50488H on postischemic LVDP and actomyosin Mg(2+)-ATPase activity. Reduced actomyosin ATP utilization was also suggested in single ventricular myocytes treated with either U-50488H or the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), because U-50488H and PMA lowered maximum velocity of unloaded shortening by 15-25% in myocytes. U-50488H and phenylephrine + propranolol treatment both resulted in increased phosphorylation of troponin I and C protein. These findings are consistent with the hypothesis that kappa-opioid and alpha-adrenergic receptors decrease actin-myosin cycling rate, leading to a conservation of ATP and cardioprotection during ischemia.

During the 20th century, the human vomeronasal organ (VNO) has been controversial regarding its structure, function, and even identity. Despite reports that provide evidence for its presence throughout prenatal and postnatal ontogeny, some studies and numerous textbooks declare its absence in late fetal and postnatal humans. To that end, the present study was designed to establish firmly whether the human VNO is homologous with that of other mammals and whether it degenerates (partially or completely) or persists throughout prenatal development. Fifty human embryos and fetuses (33 d to 32 wk fertilisation age) and 2 neonates were examined by light microscopy. Four embryonic primates (mouse lemurs) were examined for a comparison of VNO embryogenesis. The presence or absence and structural characteristics of the VNO and supporting tissues are described. The first appearance of the VNO was in the form of bilateral epithelial thickenings of the nasal septum, the vomeronasal primordium. The primordia invaginated between 37 and 43 d of age and formed the tubular VNO. The tubular VNO was located dorsally at a variable distance from, but was always spatially separated from the paraseptal cartilages. The mouse lemurs examined in this study and other reports from the literature indicate that the human VNO resembles that of primates having functional VNOs until just after a tubular VNO is formed. Examination of the VNO and adjacent tissues suggested that the VNO may lose receptor cells and corresponding vomeronasal nerves and become a ciliated, pseudostratified epithelium between approximately 12 and 14 wk of age. Our findings indicate the prenatal human VNO goes through 3 successive stages: early morphogenesis, transformation (of the epithelium), and growth. These observations indicated that (1) all embryonic humans develop a vomeronasal organ which is homologous with the VNOs of other mammals, but which has become displaced and highly variable in relative location during embryogenesis; (2) the human vomeronasal organ does not degenerate prenatally, but very likely loses the functional components of the vomeronasal complex of other mammals; and (3) the remnant of the human VNO persists until birth and beyond.

Purpose: To compare the sensitivity and specificity of four approaches to glaucoma screening., Methods: Case patients were persons with possible, probable, or definite glaucomatous optic nerve damage, as judged by a glaucoma specialist using Humphrey 24-2 threshold findings and clinical assessment of disc and nerve fiber layer, identified in the population-based Baltimore Eye Survey Follow-up Study. Control patients were participants in the same study, frequency-matched for age, without evidence of glaucomatous optic nerve damage. Participants underwent optic disc photography (Topcon ImageNet), disc imaging (GlaucomaScope), scanning laser polarimetry (Nerve Fiber Analyzer), and suprathreshold field testing (Dicon)., Results: A total of 100 case patients with open-angle glaucoma and 149 control patients were included. Objective imaging had the best screening performance. For the GlaucomaScope, a criterion of cup-to-disc ratio of -0.68 had a sensitivity of 72% and specificity of 82% for detecting eyes with definite or probable glaucomatous optic nerve damage. For the nerve fiber layer, a criterion of The Number as > or = 20 had a sensitivity of 69% and specificity of 77% for detecting eyes with definite or probable glaucomatous optic nerve damage. Usable data could be obtained in 93% of participants with the Dicon and the Nerve Fiber Analyzer and in 82% and 87% of participants with the GlaucomaScope and Topcon instruments, respectively., Conclusions: Vertical cup-to-disc ratio, as measured by the GlaucomaScope or Topcon instruments, and the Nerve Fiber Layer neural network Number had the best combination of sensitivity and specificity among the instruments tested. The Nerve Fiber Analyzer had the highest percentage of participants with usable data.

The vomeronasal organ (VNO) is a chemosensory structure of the vertebrate nasal septum that has been recently shown to exist in nearly all adult humans. Although its link to reproductive behaviors has been shown in some primates, its functionality in humans is still debated. Some authors have suggested that the human VNO has the capacity to detect pheromones, while others described it as little more than a glandular pit. However, no studies have utilized histochemical techniques that would reveal whether the human VNO functions as a generalized gland duct or a specialized chemosensory organ. Nasal septal tissue from 13 humans (2-86 years old) were compared to that of two adult lemurs (Microcebus murinus) and eight adult voles (four Microtus pennsylvanicus and four Microtus ochrogaster). Sections at selected intervals of the VNO were stained with periodic acid-Schiff (PAS), alcian blue (AB), AB-PAS, and PAS-hematoxylin procedures. Results revealed typical well-developed VNOs with tubuloacinar glands in Microtus and Microcebus. VNO glands were AB-negative and PAS-positive in voles and mouse lemurs. Homo differed from Microtus and Microcebus in having more branched, AB and PAS-positive glands that emptied into the VNO lumen. Furthermore, the human VNO epithelium had unicellular mucous glands (AB and PAS-positive) and cilia, similar to respiratory epithelia. These results demonstrate unique characteristics of the human VNO which at once differs from glandular ducts (e.g., cilia) and also from the VNOs of mammals possessing demonstrably functional VNO., (Copyright 2000 Wiley-Liss, Inc.)

The present study examined the long-standing concept that changes in hippocampal circuitry contribute to age-related learning impairment. Individual differences in spatial learning were documented in young and aged Long-Evans rats by using a hippocampal-dependent version of the Morris water maze. Postmortem analysis used a confocal laser-scanning microscopy method to quantify changes in immunofluorescence staining for the presynaptic vesicle glycoprotein, synaptophysin (SYN), in the principal relays of hippocampal circuitry. Comparisons based on chronological age alone failed to reveal a reliable difference in the intensity of SYN staining in any region that was examined. In contrast, aged subjects with spatial learning deficits displayed significant reductions in SYN immunoreactivity in CA3 lacunosum-moleculare (LM) relative to either young controls or age-matched rats with preserved learning. SYN intensity values for the latter groups were indistinguishable. In addition, individual differences in spatial learning capacity among the aged rats correlated with levels of SYN staining selectively in three regions: outer and middle portions of the dentate gyrus molecular layer and CA3-LM. The cross-sectional area of SYN labeling, by comparison, was not reliably affected in relation cognitive status. These findings are the first to demonstrate that a circuit-specific pattern of variability in the connectional organization of the hippocampus is coupled to individual differences in the cognitive outcome of normal aging. The regional specificity of these effects suggests that a decline in the fidelity of input to the hippocampus from the entorhinal cortex may play a critical role.

Objective: Chronic, elevated intracranial pressure (ICP) in craniosynostotic infants may result in ocular and neurocapsular problems; however, not all infants exhibit elevated ICP. Clinical ICP studies are further confounded by small and heterogeneic samples, multiple-suture involvement, and varying surgical management protocols. The present study was designed to describe longitudinal changes in ICP in a large, homogenous sample of rabbits with uncorrected familial, nonsyndromic coronal suture synostosis., Methods: Ninety-one rabbits were divided into four groups: (1) normal rabbits (n = 28), (2) rabbits with delayed-onset coronal suture synostosis (DOCS; n = 25), (3) rabbits with unilateral coronal suture synostosis (UCS; n = 12), and (4) rabbits with bilateral coronal suture synostosis (BCS; n = 26). ICP was measured at 24 and 42 days of age using a Codman epidural microtransducer., Results: Rabbits with BCS had a significantly (p < .05) higher mean ICP at 25 days of age than rabbits in the other three groups by approximately 146%. However, by 42 days of age, mean ICP in normal control rabbits and rabbits with DOCS was significantly (p < .01) increased compared with their mean ICP values seen at 25 days of age, while mean ICP in BCS rabbits significantly (p < .01) decreased (by 32%) over the same time period. ICP in rabbits with UCS was between that seen in normal control rabbits and rabbits with BCS and did not significantly (p > .05) change over time., Conclusions: These findings suggest that the degree of suture involvement may be related to early increases in ICP. Possible multifactorial explanations for intracranial decompression and compensation in the craniosynostotic rabbit model are discussed.

Unlabelled: We evaluated 99mTc-labeled anti-CD15 immunoglobulin M monoclonal antibody (LeuTech) for diagnosing acute appendicitis in patients with an equivocal clinical presentation. LeuTech avidly binds to circulating and sequestered human polymorphonuclear neutrophils in vivo, eliminating in vitro cell labeling and blood handling., Methods: We studied 49 patients to evaluate the safety and efficacy of LeuTech imaging. 99mTc-labeled LeuTech was prepared on site using a lyophilized kit, 99mTc-labeled pertechnetate, and 2 different incubation techniques, 1 at room temperature and the other at 37 degrees C. The abdomen was serially imaged for up to 3 h after the intravenous administration of 370-740 MBq 99mTc-labeled LeuTech. Scans were read as positive or negative for acute appendicitis or other intraabdominal infection. The institutional diagnosis was established by surgery, other diagnostic studies, or 1-mo clinical follow-up., Results: Scans were positive for appendicitis in all 26 patients with appendicitis, for a sensitivity of 100%, and negative for appendicitis in 19 of 23 patients without appendicitis, for a specificity of 83%. Accuracy, positive predictive value, and negative predictive value were 92%, 87%, and 100%, respectively. Results were not different between the LeuTech preparations. The rate of laparotomies with negative findings in patients who underwent surgery was 10%. The average time from injection to LeuTech visualization in the appendix for cases positive for appendicitis was 9 min. No serious adverse reactions occurred., Conclusion: LeuTech imaging is safe, rapid, and sensitive for diagnosis of appendicitis in equivocal cases. The potential advantages of LeuTech over currently available radiopharmaceuticals for infection imaging are ease of preparation, absence of blood handling, excellent image quality, no requirement for SPECT, and rapid diagnostic uptake.

Paraseptal cartilages (PCs) have been the subject of controversy, in that some authors believe them to be absent or rarely present, while others have described them to exist at predictable locations in adult human tissue specimens. This study seeks to determine the presence or absence of PCs in humans and describe their morphology and size. Nasal septal tissue from 19 adults and 1 child were paraffin embedded, coronally sectioned, placed on slides, and stained for microscopic observation. For all specimens, PCs were identified and lengths were calculated. Selected PCs were also digitized in order to calculate volume. Results demonstrated that PCs were present in all 20 tissue specimens and assumed a common morphology. In each, PCs were found to begin as hyaline cartilage lobes that extend projections in a superolateral direction as an anteroposterior course is followed. The projections were found to rotate inferiorly until each PC was found to assume a position that extended below the nasal septum. Length measures in adults ranged from 8,725 to 19,000 microm (x = 14,188.9 microm) and volumes ranged from 7.7 to 24.2 (x = 13.2) x 10(-3) ml. A quantitative comparison to foetal data from a previous study suggests prenatal and/or postnatal growth of PCs. Results from this study support the presence of PCs in adult humans as well as prenatal/postnatal growth of PCs.

Objective: It has been suggested that abnormal brain morphology or growth rates may be a primary causal factor of craniosynostosis due, in part, to a lack of normal growth stretch and tension at the sutural margins. The purpose of the present study was to quantify cerebral hemisphere morphology and growth in a rabbit model of nonsyndromic coronal suture synostosis to determine whether cerebral dysmorphology is primary or secondary to synostosis in this model., Design: Fifty-seven brains (114 hemispheres) were examined from 40 normal control rabbits and 17 rabbits with bilateral coronal suture synostosis ranging in age from 25 to 450 days postconception (synostosis occurs at approximately 23 days postconception in this model). The calvariae were removed, the brains were fixed in 10% paraformaldehyde, and in situ bilateral measurements of cerebral hemisphere length and cerebral hemisphere width were obtained using a Wild microscope with a camera lucida attachment and digital caliper. Regression analysis was used to compare cerebral cortex growth rates by age between the two groups., Results: Cerebral hemisphere width and cerebral index regression line slopes had similar y intercepts (23 day postconception) with significantly (p < .05) diverging slopes over time. Normal rabbits increased more rapidly than synostosed rabbits. No significant (p > .05) differences were noted in regression line slopes between groups for cerebral hemisphere length by age or length by width., Conclusions: Cerebral dysmorphologies are probably a compensatory, secondary (postsynostotic) event and not a primary causal factor of craniosynostosis in this rabbit model of human familial, nonsyndromic coronal suture synostosis.