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The Drosophila Fused (Fu) kinase is an integral component of the Hedgehog (Hh) pathway that helps promote Hh-dependent gene transcription. Vertebrate homologues of Fu function in the Hh pathway in vitro, suggesting that Fu is evolutionarily conserved. We have generated fused (stk36) knockout mice to address the in vivo function of the mouse Fu (mFu) homologue. fused knockouts develop normally, being born in Mendelian ratios, but fail to thrive within 2 weeks, displaying profound growth retardation with communicating hydrocephalus and early mortality. The fused gene is expressed highly in ependymal cells and the choroid plexus, tissues involved in the production and circulation of cerebral spinal fluid (CSF), suggesting that loss of mFu disrupts CSF homeostasis. Similarly, fused is highly expressed in the nasal epithelium, where fused knockouts display bilateral suppurative rhinitis. No obvious defects were observed in the development of organs where Hh signaling is required (limbs, face, bones, etc.). Specification of neuronal cell fates by Hh in the neural tube was normal in fused knockouts, and induction of Hh target genes in numerous tissues is not affected by the loss of mFu. Furthermore, stimulation of fused knockout cerebellar granule cells to proliferate with Sonic Hh revealed no defect in Hh signal transmission. These results show that the mFu homologue is not required for Hh signaling during embryonic development but is required for proper postnatal development, possibly by regulating the CSF homeostasis or ciliary function.

Nephrogenic fibrosing dermopathy (NFD) is a rare and recently recognized sclerosing skin disorder of unknown etiology. Reported cases have occurred in patients with chronic renal failure, with or without renal replacement therapy. All previous cases have been reported in older adult patients. We describe two pediatric patients who recently developed this condition and review the existing literature for NFD. Our patients included an 8-year-old boy on peritoneal dialysis with no prior renal transplant and a 19-year-old boy on hemodialysis with a history of previous failed renal transplants. We speculate that the recent emergence of this condition and occurrence in patients with chronic renal failure suggest an association with some newer pharmacological agent that has recently come into wide use. Since both our patients also had previously experienced large vessel thrombosis, hypercoagulable states may also be implicated.

Several techniques for treatment of atrial fibrillation (AF) have been developed, including the direct placement of radiofrequency for lesions at open heart surgery. Detailed evaluation of left atrial (LA) function has not been performed after these procedures and has not been compared in patients with chronic AF. We compared the atrial function of patients with sustained sinus rhythm (SR) after linear ablation with a group who underwent direct-current cardioversion and a group of normal controls to investigate the measurable deleterious effects, if any, on atrial function after the surgical procedure. Twenty-one consecutive patients who had maintained SR for >6 months after a linear radiofrequency ablation (LRFA) procedure were studied. As control subjects, we examined 33 patients with chronic AF successfully restored to SR by cardioversion who maintained SR for >6 months and 42 age-matched normal subjects. LA function was decreased in both the LRFA and cardioverted AF groups compared with normal controls. The parameters of LA function, atrial fraction, LA ejection fraction, and the A' velocity were lowest in the LRFA group, intermediate in the cardioverted AF group, and highest in the normal controls (LA function: 15.8 +/- 10%, 26 +/- 10%, 33 +/- 7%; p = 0.0001; LA ejection fraction: 31 +13%, 41 +/- 12%, 51 +/- 9%; p = 0.0001; A' velocity: 4.2 +/- 1.4, 7.6 +/- 2.2, 9.5 +/- 1.9 cm/s; p = 0.0001). LA volumes were increased in the LRFA and cardioverted AF groups compared with normals (62.8 +/- 22 vs 70.6 +/- 17 vs 38.7 +/- 9.8 ml; p = 0.0001). Thus, although LA function is restored and maintained after LRFA has been performed during open heart surgery, LRFA use is associated with a measurable decrease in LA function over and above that found after conventional cardioversion.

Human natural killer antigen-1 (HNK-1) is a carbohydrate epitope associated with sulfoglucuronylglycolipids and glycoproteins. Biochemical analyses have demonstrated associations between the HNK-1 epitope and isoforms of the neural cell adhesion molecule (N-CAM) family. In the cerebellum, HNK-1 is prominently expressed in Purkinje cell dendrites and Golgi cells. Purkinje cell expression of HNK-1 reveals an array of parasagittal stripes and transverse zones. Interestingly, the parasagittal expression pattern of HNK-1 is different from those reported with several other markers such as zebrin II/aldolase C and the small heat shock protein HSP25. N-CAM null knockout mice were used to explore the possible role of the HNK-1/N-CAM interaction during the topographical organization of the cerebellar cortex. N-CAM null mice have no N-CAM immunoreactivity but otherwise the cerebellum appears morphologically normal. Further, in the N-CAM null HNK-1 immunoreactivity is abolished from Purkinje cell dendrites but is retained on Golgi cells and neurons of the cerebellar nuclei. Despite the absence of N-CAM/HNK-1, parasagittal stripes and transverse zones in the cerebellum as revealed by using zebrin II immunocytochemistry appear normal.

A recognized disadvantage of power-assisted adenoidectomy (PAA) is the increased patient charge associated with the disposable instrumentation. The elimination of pathological review of routine adenoid specimens may provide a means of offsetting the increased charge, as 1) unsuspected findings are rare, and 2) PAA specimens are too traumatized to provide the microscopic detail necessary to make an unsuspected diagnosis. The pathology reports of all adenoidectomy specimens removed over a 10-year period were reviewed and combined with previously published reviews in order to estimate the prevalence of unsuspected disease. The estimated prevalence of unsuspected diagnoses found by routine pathological review of adenoid specimens is 37 per 100,000 cases (95% confidence interval, 26-51). In a separate analysis, a pathologist blinded to the technique of adenoid removal assessed the tissue effects of curette adenoidectomy versus PAA. Significant tissue damage at the microscopic level was identified in 6 of 11 specimens removed with the power-assisted technique as compared to 0 of 11 specimens removed by curette (p = .03). Eliminating histopathologic review of routine adenoidectomy specimens can potentially offset the increased patient charge of PAA by 62%. Power-assisted adenoidectomy, however, should be avoided in nonroutine cases in which the potential for occult disease exists.

Insulin secretion is controlled by the beta cell's metabolic state, and the ability of the secretory granules to undergo exocytosis increases during glucose stimulation in a membrane potential-independent fashion. Here, we demonstrate that exocytosis of insulin-containing secretory granules depends on phosphatidylinositol 4-kinase (PI 4-kinase) activity and that inhibition of this enzyme suppresses glucose-stimulated insulin secretion. Intracellular application of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] stimulated exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in a readily releasable pool. Reducing the cytoplasmic ADP concentration in a way mimicking the effects of glucose stimulation activated PI 4-kinase and increased exocytosis whereas changes of the ATP concentration in the physiological range had little effect. The PI(4,5)P(2)-binding protein Ca(2+)-dependent activator protein for secretion (CAPS) is present in beta cells, and neutralization of the protein abolished both Ca(2+)- and PI(4,5)P(2)-induced exocytosis. We conclude that ADP-induced changes in PI 4-kinase activity, via generation of PI(4,5)P(2), represents a metabolic sensor in the beta cell by virtue of its capacity to regulate the release competence of the secretory granules.

The ATP-sensitive potassium channel is a key molecular complex for glucose-stimulated insulin secretion in pancreatic beta cells. In humans, mutations in either of the two subunits for this channel, the sulfonylurea type 1 receptor (Sur1) or Kir6.2, cause persistent hyperinsulinemic hypoglycemia of infancy. We have generated and characterized Sur1 null mice. Interestingly, these animals remain euglycemic for a large portion of their life despite constant depolarization of membrane, elevated cytoplasmic free Ca(2+) concentrations, and intact sensitivity of the exocytotic machinery to Ca(2+). A comparison of glucose- and meal-stimulated insulin secretion showed that, although Sur1 null mice do not secrete insulin in response to glucose, they secrete nearly normal amounts of insulin in response to feeding. Because Sur1 null mice lack an insulin secretory response to GLP-1, even though their islets exhibit a normal rise in cAMP by GLP-1, we tested their response to cholinergic stimulation. We found that perfused Sur1 null pancreata secreted insulin in response to the cholinergic agonist carbachol in a glucose-dependent manner. Together, these findings suggest that cholinergic stimulation is one of the mechanisms that compensate for the severely impaired response to glucose and GLP-1 brought on by the absence of Sur1, thereby allowing euglycemia to be maintained.

A new microsporidian species is described from the predatory mite Metaseiulus (formerly Typhlodromus or Galendromus) occidentalis (Nesbitt) (Acari, Phytoseiidae). The ultrastructure of this new species is presented together with the first molecular characterization for a microsporidium of mites. All stages of this new microsporidium are haplokaryotic and develop in direct contact with the host-cell cytoplasm. Sporogony is disporoblastic and spores are formed in eggs, immature stages, and adults of M. occidentalis. There are two morphological classes of spores, one with a short polar filament (3-5 coils) that measured 2.53 x 1.68 microm and one with a longer polar filament (8-9 coils) that measured 3.14 x 1.77 microm. Horizontal transmission of this new species occurs by cannibalism of eggs and other stages and perhaps involves the spores with the long polar filament. Spores with the short polar filament may play a role in autoinfection and vertical (transovarial) transmission that is highly efficient in transferring the microsporidium from adults to progeny. Analysis of the small subunit ribosomal DNA indicated that this species from M. occidentalis is most closely related to the Nosema/Vairimorpha clade of microsporidia. A conflict between the morphological and molecular data is discussed. The species is compared to previously described microsporidia of arachnids resulting in creation of Oligosporidium occidentalis n. sp. in the family Unikaryonidae., (Copyright 2002 Elsevier Science B.V.)

Objective: To assess the validity of four models for the role of quantitative ultrasound (QUS) in the management of osteoporosis., Design: Cross-sectional survey and review of literature., Settings: Nuclear medicine departments of three teaching hospitals in Sydney., Subjects: 1000 women aged 22 to 88 years (mean, 59 years) referred for assessment of osteoporotic fracture risk., Main Outcome Measures: BMD categories as defined by dual-energy x-ray absorptiometry (DEXA) of the lumbar spine and proximal femur, and QUS category as defined by calcaneal ultrasound stiffness; prevalence of DEXA-defined osteoporosis in the different QUS categories., Results: In women with QUS Achilles stiffness < or = 70 the prevalence of axial osteoporosis was 51%, whereas in the group with stiffness > 70 the prevalence of axial osteoporosis was 8%. In women 65 years and over the corresponding values were 59% and 17%., Conclusions: Of the four possible models for QUS, the use of QUS for the estimation of BMD, or in a "standalone" model, can not be recommended at the current time. The model of QUS as a "prescreening" modality may be acceptable assuming adequate education of clinicians and patients of its limitations, particularly the risk of false negatives. The model of QUS as one factor in a composite risk factor assessment of patients is promising but more data are required.

Potentially selective and integrated pest management (IPM)-compatible pesticides for the citrus leafminer Phyllocnistis citrella Stainton and its parasitoid Ageniaspis citricola Logvinovskaya were compared under nursery field conditions at Gainesville, FL. In 1996, replicated blocks of young grapefruit trees were treated with 2% petroleum oil and 1 x the lowest recommended field rate (LRFR) of diflubenzuron + oil (0.4%). Untreated and treated controls (avermectin at 1 x the LRFR + oil) were included. In 1997, blocks were treated with oil (3%), 1 x the LRFR of azadirachtin + oil, 1 x the LRFR of diflubenzuron + oil and 0.1 x the LRFR of avermectin + oil. Untreated and treated controls were again included. Oil at 3%, azadirachtin at 1 x the LRFR + 0.4% of oil, and diflubenzuron at 1 x the LRFR + 0.4% of oil were shown to be IPM-compatible pesticides. In 1997, these blocks had fewer mines per leaf and P. citrella pupae parasitized by A. citricola per total leaves sampled compared with the untreated control but more than the treated control (alpha = 0.05). Avermectin at 0.1 x the LRFR + 0.4% of oil was not considered an IPM-compatible pesticide because, while it reduced the number of P. citrella mines per leaf, it reduced the number of A. citricola to levels as low as the treated control. Actual P. citrella infestation levels had no detectable effect on tree growth and vigor. Pesticide applications were not justified when P. citrella infestations were < 1 mine per leaf and the biological control agent A. citricola was present.

The ability to genetically engineer arthropods using recombinant DNA methods opens new opportunities for improving pest management programs but also creates new responsibilities, including evaluation of the potential risks of releasing transgenic arthropods into the environment. It is now becoming easier to transform diverse species of arthropods by a variety of recombinant DNA methods. Useful genes and genetic regulatory elements are being identified for pest arthropods, but less effort is being expended to identify genes that could improve the efficacy of beneficial arthropods. A transgenic strain of the natural enemy Metaseiulus (= Typhlodromus or Galendromus) occidentalis (Acari: Phytoseiidae) was developed using a method termed maternal microinjection. This transgenic strain was released into an experimental site on the campus of the University of Florida in 1996 after extensive reviews by the University of Florida Biosafety Committee, Florida Department of Agriculture and Consumer Services, United States Department of Agriculture Animal and Plant Health Inspection Service, and the United States Fish and Wildlife Service. The short term releases established a precedent for releasing a transgenic arthropod but, at present, no guidelines are available that would allow transgenic arthropods to be released permanently into the environment. Several scientific, environmental, and policy issues must be resolved before transgenic pests or beneficial arthropods can be deployed in practical pest management programs.

Objective: To characterize chondrocytes in normal and arthritic joints and compare their phenotype to that of synovial macrophages present in rheumatoid joints., Methods: Using an immunoperoxidase staining technique, we examined the presence and distribution of a number of leukocyte activation and differentiation antigens on samples of cartilage obtained from resected joints of normal controls and subjects with rheumatoid arthritis or osteoarthritis., Results: Chondrocytes in each group were CD14+, CD68+, Thy-1+, CD11a+, CD18+, MAX.3-, and MAX.24-. Staining was variable for MAX.1 and CD45. HLA-DR and CD71 were expressed only on cells located in the superficial layer of rheumatoid cartilage. We found lower levels of expression of CD14 on chondrocytes in arthritic joints, whereas CD58 was expressed at higher levels. Surface expression of CD14 was confirmed on normal chondrocytes using flow cytometry and further supported by the detection of CD14 mRNA by polymerase chain reaction., Conclusion: Our findings demonstrate that chondrocytes express several antigens that are also found on monocytes and macrophages.

Weight loss in obese subjects ingesting very-low-energy (VLE; < 2510 kJ/d), low-fat (< or = 1 g/d) formula diets is associated with liver-function-test abnormalities and gallstone formation. It is unknown whether these abnormalities develop during treatment with diets higher in energy and fat. We prospectively studied liver-function tests and gallstone formation in 73 obese patients ingesting approximately 3500 kJ and 15-25 g fat daily for 10 wk. Two of 53 patients completing the protocol developed ultrasonographic gallstones during weight loss, a rate substantially lower than that observed with VLE diets. Trend analysis demonstrated significant increases in AST and ALT activities, but changes were less than those observed with VLE diets. Patients who developed gallstones had a significantly greater weight loss rate and larger increases in AST and ALT than did nonstone-forming patients. These results suggest that the risk of developing hepatobiliary abnormalities with dieting is lowered when subjects ingest greater amounts of energy and fat than that administered in earlier VLE-diet studies. Our results also highlight potential risk factors and markers of new gallstone formation.

The persistence of DNA injected into two species of adult female phytoseiids and its transmission to serial eggs deposited by them was assessed by the polymerase chain reaction (PCR). The effect of DNA concentration on persistence and transmission was examined in Metaseiulus occidentalis. M. occidentalis females were microinjected with plasmid DNA at three different concentrations (250, 500, 750 ng microL-1) and allowed to deposit one to five eggs before the females and their last eggs were analyzed. Plasmid DNA was found in 82% of the females assayed and in 70% of all the eggs analyzed (including the fifth eggs produced after microinjection). Transmission of DNA to multiple eggs was also examined in Amblyseius finlandicus. Females of this species are less traumatized by microinjection allowing analysis of transmission over a more extended number of eggs. Females were microinjected and allowed to deposit eggs until their death. DNA from every fifth egg was analyzed by the PCR. PCR products were amplified from 51% of the eggs and from all egg classes except the 30th egg. The persistence and presence of plasmid DNA in both eggs and females suggests that (1) maternal microinjection is a more efficient method for DNA delivery than traditional egg microinjection, (2) it may be possible to isolate transformants from fewer maternally-microinjected females than originally expected, and (3) maternal microinjection could be useful as a DNA delivery system in other phytoseiids.

The Drosophila melanogaster heat shock 70 promoter (hsp70) was used to regulate expression of the Escherichia coli beta-galactosidase gene (lacZ) in transiently-transformed predatory mite larvae. A construct containing the hsp70 promoter upstream of the D. melanogaster alcohol dehydrogenase (adh) translational start site and Escherichia coli lacZ gene fusion (adh/lacZ) was injected into larvae of Metaseiulus occidentalis and Amblyseius finlandicus. LacZ expression was compared to expression of a similar construct lacking any upstream regulatory sequence. Expression from the hsp70 promoter was strong and heat shock-dependent in both species. The Drosophila hsp70 promoter therefore appears useful for regulating expression of exogenous DNA in both phytoseiid species and may be broadly applicable in the Phytoseiidae. Furthermore, the lacZ gene is a useful gene for analysis of expression in both species. Larval microinjection provides a method of assessing transient expression and of examining native regulatory sequences in these two phytoseiids and will likely be useful in other phytoseiid mites with only minor modifications.

This report documents the presence of an expanded population of dual CD45RA, CD45RO positive T cells (up to 91% of T cells) in the rheumatoid joint. Cells from peripheral blood (PB) and synovial fluid (SF) were analysed by dual immunofluorescence labelling. Synovium from a separate patient population was analysed by single and dual immunoenzyme staining of serial sections. Dual CD45RA, CD45RO positive T cells were found in PB (up to 74%), SF (up to 91%) and synovium. This was associated with a lack of early activation antigens (4F2, interleukin-2 receptor, transferrin receptor) but increased HLA-Class II antigens (HLA-DR, -DP, -DQ) in SF compared with PB. This intermediate activation phenotype may support the hypothesis that T cell activation or reactivation occurs within the rheumatoid joint.

The most common class of activation domains, the so-called acidic activators, has been proposed either to adopt an amphipathic alpha-helical structure or to exist as unstructured "acid blobs." However, genetic analysis of an acidic activation domain in the yeast GAL4 protein has suggested that the structure of the activation region is a beta sheet. To distinguish between these models, we conducted a biophysical analysis of peptides corresponding to the yeast GAL4 and GCN4 acidic activation domains. Circular dichroism spectroscopy shows that the peptides are not alpha helical, but that they can undergo a transition to a structure that is almost 100% beta sheet in character in slightly acidic solution. We also show that the artificial acidic activator AH has structural properties that are markedly different from the natural GAL4 and GCN4 domains and does not adopt a beta-rich structure at reduced pH.

The yeast GAL4 protein, a transcriptional activator of genes involved in galactose metabolism, binds as a dimer to several closely related seventeen base pair upstream activation sequences (UASGs) that are nearly symmetric about a central dT-dA base pair. A previous study of a GAL4-UASG complex (Carey, M., Kakidani, H., Leatherwood, J., Mostashari, F. and Ptashne, M. (1989) J. Mol. Biol. 209, 423-432) elucidated a pattern of contacts consistent with the protein partially wrapping itself around the helical cylinder, assuming a B-form conformation for the DNA. Alternatively, both monomers could sit on one face of the cylinder if the DNA exists in an underwound conformation such as A-form. Spectroscopic studies that distinguish between these models are reported here. Oligonucleotides containing the consensus UASG or a nine base pair "half site" both exhibit circular dichroism (CD) spectra characteristic of B-form DNA. Two-dimensional NMR studies of the half-site also indicate a B-form conformation. When a GAL4 protein fragment containing the entire DNA-binding and dimerization domains (amino acids 1-140) is bound to the UASG, the CD spectrum above 240 nm changes only slightly, and not in a manner consistent with DNA unwinding. Our studies suggest that the UASG does not adopt an unusual underwound conformation in the absence or presence of the GAL4 protein, and favor the model in which the dimer partially wraps around the helix cylinder.

Intersegmental limb dynamics and muscle activities were analyzed for consecutive cycles of paw-shake responses from chronic-spinalized cats to investigate how hindlimb trajectories organize into a pattern with regular oscillations, a steady-state response, or alternatively, into a pattern with irregular oscillations, a nonsteady-state response. In the spinalized preparation, steady-state and nonsteady-state responses have an equal likelihood of emerging from the initial cycles of a paw-shake response, suggesting that regular coupling of joint oscillations is not planned by pattern-generating networks within lumbosacral segments. To examine the characteristics of coupled and uncoupled limb oscillations during paw-shake responses, we assessed patterns of muscle activity and hindlimb kinematics of six adult chronic-spinalized cats. Additionally, we used inverse-dynamics techniques to quantify the intersegmental dynamics of the paw, leg, and thigh. Our data indicate that by the second cycle of both steady-state and nonsteady-state responses, the basic pattern of interaction between muscle and motion-dependent torques at the ankle and knee joints was established. During subsequent cycles of steady-state responses, a consistent sequence of timing changes occurred, such that, just prior to steady-state oscillations, torque maximums peaked simultaneously at each joint and joint reversals occurred simultaneously. Although nonsteady-state responses showed a similar sequence during beginning cycles, increased ankle muscle and net torques during middle cycles created larger inertial torques at the knee joint that were not counteracted and resulted in irregular and uncoupled knee oscillations. It is likely that neither steady-state nor nonsteady-state oscillations are planned by pattern-generating networks within lumbosacral segments, but that patterns of interjoint coordination emerge from the coupling among oscillators. For paw-shake responses in the spinalized preparation, coupling may depend on interactions between central circuits and motion-dependent feedback that is necessary to stabilize inertial effects due to large ankle joint accelerations.

We have developed a model of the human lower extremity to study how surgical changes in musculoskeletal geometry and musculotendon parameters affect muscle force and its moment about the joints. The lines of action of 43 musculotendon actuators were defined based on their anatomical relationships to three-dimensional bone surface representations. A model for each actuator was formulated to compute its isometric force-length relation. The kinematics of the lower extremity were defined by modeling the hip, knee, ankle, subtalar, and metatarsophalangeal joints. Thus, the force and joint moment that each musculotendon actuator develops can be computed for any body position. The joint moments calculated with the model compare well with experimentally measured isometric joint moments. We developed a graphical interface to the model that allows the user to visualize the musculoskeletal geometry and to manipulate the model parameters to study the biomechanical consequences of orthopaedic surgical procedures. For example, tendon transfer and lengthening procedures can be simulated by adjusting the model parameters according to various surgical techniques. Results of the simulated surgeries can be analyzed quickly in terms of postsurgery muscle forces and other biomechanical variables. Just as interactive graphics have enhanced engineering design and analysis, we have found that graphics-based musculoskeletal models are effective tools for designing and analyzing surgical procedures.

We have developed a musculoskeletal model of the human lower extremity for computer simulation studies of musculotendon function and muscle coordination during movement. This model incorporates the salient features of muscle and tendon, specifies the musculoskeletal geometry and musculotendon parameters of 18 musculotendon actuators, and defines the active isometric moment of these actuators about the hip, knee, and ankle joints in the sagittal plane. We found that tendon slack length, optimal muscle-fiber length, and moment arm are different for each actuator, thus each actuator develops peak isometric moment at a different joint angle. The joint angle where an actuator produces peak moment does not necessarily coincide with the joint angle where: (1) muscle force peaks, (2) moment arm peaks, or (3) the in vivo moment developed by maximum voluntary contractions peaks. We conclude that when tendon is neglected in analyses of musculotendon force or moment about joints, erroneous predictions of human musculotendon function may be stated, not only in static situations as studied here, but during movement as well.

Ground reaction forces and center of pressure (CP) were studied during gait in children with unilateral lower extremity amputations. Five children, three with knee disarticulations and two with above-knee amputations, walked at slow, normal, and fast speeds, while wearing a conventional SACH prosthetic foot and again, while wearing an experimental CAPP prosthetic foot. Fore-aft (F-A) and vertical force (VF) components and CP patterns were examined for a total of 90 trials. Walking speed had a significant effect on both F-A and VF amplitudes. No differences, however, were found between the force amplitudes of the SACH foot and CAPP foot. Significant asymmetries were found in the force and amplitudes of a child's natural limb versus the prosthetic limb; the retarding and propelling F-A forces in the prosthetic limb were significantly less than the corresponding forces in a child's natural limb. The CP patterns during stance phase were markedly different for a child's natural limb, prosthetic limb with the SACH foot, and prosthetic limb with the CAPP foot. With the CAPP foot, the CP remained in the forefoot region during stance. In contrast with the CAPP foot, the SACH foot had a potential for producing a flexor moment at the knee joint at the initiation of the foot-ground contact. Stability in the prosthetic knee was enhanced when the children wore a CAPP prosthetic foot.

Embryogenic mitoses, mitoses in females and spermatogenesis are described in the predatory mite Metaseiulus occidentalis (Nesbitt). At 22 degrees C, egg development lasts approximately 4 days. Six chromosomes are seen in mitotic metaphases and anaphases of 0--24 h eggs. Toward the end of this period some embryo squashes have patches of cells containing nuclei which are partially heteropycnotic. These patches of cells apparently increase in size with the age of the embryo. In approximately 1/2 of all 24--48 h-old eggs they encompass all or most cells of the embryo. In these embryos metaphases involved 6 chromosomes, anaphases 3. Either prior to, or following metaphase, a pairing of chromosomes appeared to take place to form 3 units which resembled meiotic diplotene chromosomes where there is opening out between homologues. At metaphase, two sets of 3 chromosomes were slightly differentially stained. One, designated the H set, was darker and slightly more contracted than the other, the E set. At anaphase, 3H and 3E chromosomes segregated in a reductional division retaining the differential contraction until telophase. No cytokinesis appeared. The H set appeared to remain contracted while the E set decontracted to assume the appearance of an interphase nucleus. Both of these entities, side-by-side, created the partially heteropycnotic nucleus mentioned above. The H set then appeared to be excluded from the cell. Mitotic meta- and anaphases involving 6 chromosomes were noted in female deutonymphs. Spermatogenesis appeared to encompass an equational division of 3 chromosomes, which the formation of a binucleate spermatid. Two tail structures appeared juxtaposed at the edge of each spermatid and thereafter a separation into two individual sperms occurred.--While mitosis was not studied in known males, we believe that the embryos exhibiting heterochromatinization and elimination of chromosomes in most or all cells were in fact demonstrating parahaploidization.

By genetic selection a gypsy moth strain was obtained within eight generations that could be reared continuously in the insectary without its normal "obligatory" diapause. This strain should be useful for making physiological and genetical comparisons with normal diapausing gypsy moths. It could also be used in a genetic control program. However, caution should be exercised, for its release could create a new environmental hazard.

As a few quantitative data exist characterizing the gait of child lower extremity amputee (CLEA), this study provides such data by examining selected kinematic and kinetic variables during locomotion. Five unilateral CLEA were analyzed in an experimental design which comprised 3 different speeds of walking, 2 types of prosthetic feet (SACH-foot and an experimental CAPP-foot), and normal versus prosthetic limbs for a total of 104 trials. Cinematographic data and footprint information where used to quantify walking speed and uniplanar lower extremity angles. A rigid-body, linked model was used to evaluate the extent and range to thigh and leg motion and moments of force at the knee joint. The kinematic and kinetic characteristics of CLEA gait were affected significantly by variations in walking speed. Stride length, step length, and walking velocity decreased and stride width increased when the children used the experimental foot component; as speed of walking increased, stride length and step length increased with both prosthetic feet. Foot angles increased with walking velocity except for fast walking with the experimental foot component. Joint angles were significantly different between the normal and prosthetic limb. The only significant limb angle differences between the 2 prosthetic feet were in maximum hip flexion and the total range of thigh movement; the experimental foot elicited less hip flexion and and smaller range of thigh movement.

The convention of using medical certificates to assess benefit claims has grown over the years to a complex situation. The certificate serves as written testimony of the patient's state of health (be it illness, fitness or a need which is based on those grounds). While the practitioner is presumed to be serving only his patient, this study suggests that he is required to act as arbitrator in many situations that are unnecessarily defined as medical.

A method was presented for quantifying cat (Felis catus) hind limb dynamics during swing phase of locomotion using a two-link rigid body model of leg and paw, which highlighted the dynamic interactions between segments. Comprehensive determination was made of cat segment parameters necessary for dynamic analysis, and regression equations were formulated to predict the inertial parameters of any comparable cat. Modulations in muscle and non-muscle components of knee and ankle joint moments were examined at two treadmill speeds using three gaits: (a) pace-like walk and trot-like walk, at 1.0 ms-1, and (b) gallop, at 2.1 ms-1. Results showed that muscle and segment interactive moments significantly effected limb trajectories during swing. Some moment components were greater in galloping than in walking, but net joint maxima were not significantly different between speeds. Moment magnitudes typically were greater for pace-like walking than for trot-like walking at the same speed. Generally, across gaits, the net and muscle moments were in phase with the direction of distal joint motion, and these same moments were out of phase with proximal joint motion. Intersegmental dynamics were not modulated exclusively by speed of locomotion, but interactive moments were also influenced significantly by gait mode.

The interactive dynamic effects of muscular, inertial and gravitational moments on rapid, multi-segmented limb oscillations were studied. Using three-segment, rigid-body equations of motion, hip, knee and ankle intersegmental dynamics were calculated for the steady-state cycles of the paw-shake response in adult spinal cats. Hindlimb trajectories were filmed to obtain segmental kinematics, and myopotentials of flexors and extensors at each of the three joints were recorded synchronously with the ciné film. The segmental oscillations that emerged during the paw-shake response were a consequence of an interplay between active and passive musculotendinous forces, inertial forces, and gravity. During steady-state oscillations, the amplitudes of joint excursions, peak angular velocities, and peak angular accelerations increased monotonically and significantly in magnitude from the proximal joint (hip) to the most distal joint (ankle). In contrast to these kinematic relationships, the maximal values of net moments at the hip and knee were equal in magnitude, but of significantly lower magnitude than the large net moment at the ankle joint. At both the ankle and the knee, the flexor and extensor muscle moments were equal, but at the hip the magnitude of the peak flexor muscle moment was significantly greater than the extensor muscle moment. Muscle moments at the hip not only acted to counterbalance accelerations of the more distal segments, but also acted to maintain the postural orientation of the hindlimb. Large muscle moments at the knee functioned to counterbalance the large inertial moments generated by the large angular accelerations of the paw. At the ankle, the muscle moments dominated the generation of the paw accelerations. At the ankle and the knee, muscle moments controlled limb dynamics by slowing and reversing joint motions, and the active muscle forces contributing to ankle and knee moments were derived from lengthening of active musculotendinous units. In contrast to the more distal joints, the active muscles crossing the hip predominantly shortened as a result of the interplay among inertial forces and gravitational moments. The muscle function and kinetic data explain key features of the complex interactions that occur between central control mechanisms and multi-segmented, oscillating limb segments during the paw-shake response.