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The stink bugs Acrosternum arabicumWagner and Brachynema germariKolenati (Hemiptera: Pentatomidae) damage developing pistachio nuts in Iran. Ooencyrtus egeriaHuang and Noyes (Hymenoptera: Encyrtidae) parasitizes eggs of both species, alternating between them seasonally. We compared the biological and life history attributes of O. egeriareared for 3 generations on each host species with those that had been transferred to the alternate host for 2 generations. We also tested female responses to host egg density. Eggs of B. germariwere parasitized at higher rates and yielded faster wasp development, heavier female progeny with greater fecundity, and a more female-biased sex ratio, than eggs of A. arabicum. Rearing on A. arabicumdid not diminish wasp fitness on B. germari, and the F1 progeny of wasps switched to A. arabicuminherited some beneficial parental effects from rearing on B. germari. Regardless of host species, females parasitized fewer eggs in 8 h as density increased from 10 to 30 eggs, but progeny sex ratio (% female) increased. The anomalous response to host density appears to arise from a combination of behavioral and egg load constraints. Females mature only 10–12 eggs per day. Carefully inspect egg clusters before selecting the most suitable eggs for oviposition, a more time-consuming process for large clusters. Our results indicate that rearing O. egeriaon eggs of A. arabicum, which are more convenient and cost-effective to produce than those of B. germari, will not diminish its performance on B. germarifollowing augmentative release, beyond a slight reduction in female fecundity.

The carob moth, Ectomyelois ceratoniae(Zeller) (Lepidoptera: Pyralidae), is an important pest of pistachio causing direct damage to nuts during ripening, and in storage. We examined the tritrophic effects of 5 pistachio cultivars, representing the full range of kernel suitability for E. ceratoniae, on 2 larval parasitoids, Habrobracon hebetor(Say) (Hymenoptera: Braconidae), a gregarious, synovigenic, idiobiont, ectoparasitoid, and Venturia canescensGravenhorst (Hymenoptera: Ichneumonidae), a solitary, pro-ovigenic, koinobiont, endoparasitoid. The suitability of pistachio cultivars for development and reproduction of the 2 parasitoids was closely correlated, despite their divergent lifestyles and developmental patterns, and paralleled variation in kernel suitability for host larvae. Although kernels of the most resistant cultivar reduced demographic parameters of the parasitoids, the potential impact on numerical responses was minor. Successful biological control of carob moth within the vulnerable period of nut ripening will likely depend on the functional responses of earlier generations of adult parasitoids emerging from other fruit and nut crops, or those released in an augmentation program.

The nutritional status of host plants can have direct impacts on herbivore physiology and insect–plant interactions. We investigated the effect of micronutrients, including manganese, iron, zinc, and copper, on cucumber plant physiology, and on the biology and physiology of a strain of Aphis gossypiiGlover selected over 12 generations to be resistant to pirimicarb. The micronutrient treatment increased the activity of superoxide dismutase, ascorbate peroxidase, guaiacol peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase in cucumber plants, and also increased levels of total phenolics, hydrogen peroxide, salicylic acid, and total chlorophyl, whereas malondialdehyde levels were unaffected. Pirimicarb-resistant cotton aphids that fed on micronutritient-amended cucumber plants expressed significantly decreased levels of acetylcholinesterase and detoxifying enzymes, specifically glutathione S-transferase, and carboxylesterase. Analysis of energy reserves in resistant A. gossypiifed on micronutritient-amended plants revealed decreases in the lipid and protein contents of aphids, whereas glycogen and carbohydrate contents showed no response. Resistant cotton aphids fed on micronutritient-amended plants showed significantly reduced fecundity, longevity, and reproductive periods, and a 1.7-fold reduction in pirimicarb LC50compared with those fed on control plants. We conclude that micronutrient amendment negatively impacts the biological performance of insecticide-resistant cotton aphids, and diminishes their resistance to pirimicarb. Both direct effects on plant health, such as enhanced inducible defenses, and indirect effects on aphid fitness, such as reduced biological performance and detoxification abilities, were implicated. Therefore, optimization of micronutrient amendments could be a useful complement to other tactics for managing insecticide-resistant A. gossypiion cucumbers, and warrants exploration in other contexts.

We examined the ability of Coleomegilla maculataDeGeer and Hippodamia convergensGuerin-Meneville to regenerate, during pupation, a foreleg amputated in the fourth instar. Leg regeneration was complete for 80.7% of amputated H. convergenslarvae, with 12.5% regenerating partially, and 6.8% showing no regeneration. Regeneration in C. maculatawas 72.2% complete, 20.5% partial, and 7.2% none, but mortality following ablation was slightly higher than for H. convergens(7.4 vs. 0.6%). Ablation/regeneration caused a slight delay in pupation, but pupation time, fresh mass at emergence, and reproductive performance remained unaffected in either species. Reciprocal crosses were made between regenerated and unoperated beetles, and 12 progeny reared from the second clutch of each female in all treatments. Mating treatment affected eclosion time in H. convergens, whereas in C. maculata, larval development and pupation time were also affected. Considering all treatments, larval mortality was higher in H. convergensthan in C. maculata, but lower when both H. convergensparents regenerated. Parental mating treatment did not affect adult weight in either species, but development of C. maculataprogeny was faster when only the sire regenerated, and slower when the only the dame regenerated, whereas progeny of regenerated sires completed pupated faster than those sired by controls. We infer that genes activated during regeneration have pleiotropic effects with subtle, gender-specific, epigenetic consequences. If these pleiotropic effects are genetically linked to important traits, regenerative genetic elements could be conserved in coccinellids via natural selection acting on these traits, rather than on regenerative ability per se.

Cotton bollworm, Helicoverpa armigeraHubner, is a cosmopolitan polyphagous pest of many crops. Habrobracon hebetorSay and Helicoverpa armigera nucleopolyhedrovirus (HearNPV) are two important biocontrol agents used to manage this pest, sometimes in combination. We evaluated the sublethal effects of HearNPV on H. hebetorlife table parameters under laboratory conditions when its host (second instar H. armigera) was treated with HearNPV, and tested H. hebetorfemales for their ability to discriminate against inoculated hosts. Emergence of adults reared as solitary larvae was reduced by half on LC30-inoculated larvae compared to controls, but not on LC5or LC15-inoculated hosts. Low concentrations (LC5, LC15, and LC30) of HearNPV had no effects on overall parasitoid developmental time, but longevity and lifetime fecundity was reduced for females emerging from hosts receiving the LC30treatment. Net reproductive rate (R0), intrinsic rate of increase (rm), and finite rate of increase (λ) were all decreased in a concentration-dependent manner in the LC15and LC30treatments, as were female life expectancy, age-specific survivorship (lx), and age-specific fecundity (mx), whereas population doubling time (DT) increased. Parasitoids did not discriminate against LC15-inoculated larvae in choice or no-choice tests, but parasitized more LC50-inoculated hosts than controls in the choice test, with no significant differences in total numbers of eggs laid in either case. Although parasitoids suffered some loss of fitness in HearNPV-inoculated hosts under these laboratory conditions, these agents still appear compatible for joint application against H. armigeraunder field conditions, provided parasitoid releases are made 2 d after NPV application.

The egg parasitoid Trissolcus vassilievi(Mayr) is a key natural enemy of sunn pest, Eurygaster integricepsPuton (Hemiptera: Scutelleridae). This laboratory study examined how the aggregation of parasitoids varied in response to host density and numbers of foraging conspecifics. Five host densities (1, 2, 4, 8, and 15 clutches of E. integricepseggs), were offered simultaneously to 1, 2, 4, 8, or 16 female wasps in a standardized arena (30 cm diameter) and patch residence times were recorded. Patch residence time was strongly correlated with parasitism, and increased as the number of host clutches increased up to eight, but declined when more clutches were offered. Wasps displayed low mobility and tended to remain in the patch initially encountered, even when it contained few egg masses. At higher wasp densities, patches were occupied more quickly, host exploitation began sooner, and per capita handling time was reduced. However, total patch residence times were similar across all densities. Thus, females responded to conspecifics with increased movement, which increased dispersal and resulted in a more homogeneous distribution of wasps among patches. Pseudo-interference, resulting from wasps remaining in some patches and neglecting others, had greater impact on final levels of host exploitation than did actual interference (patch abandonment following conspecific encounters). These phenomena resulted in decreased parasitoid searching rates and a 2-fold increase in host survival at higher wasp densities.

Coevolutionary interactions between pathogens and their insect vectors can dramatically impact the fitness of herbivorous insects and patterns of plant disease transmission. Soybean mosaic virus (SMV) is a common disease in soybean production worldwide. Infected seed is the primary source of inoculum in fields and the virus is secondarily spread among plants by the soybean aphid, Aphis glycinesMatsumura (Hemiptera: Aphididae), in a nonpersistent manner. In this study, we compared the biological fitness of A. glycinescolonizing both SMV-infected and uninfected soybean plants. Aphids feeding on SMV-infected soybean seedlings were significantly smaller and lighter than those feeding on uninfected plants across life stages. SMV infection caused delayed development of aphid nymphs on soybean seedlings, but this was more than compensated by a reduction in the pre-reproductive period of apterous adults. The fecundity of A. glycineswas reduced when feeding on SMV-infected seedlings, resulting in a lower reproductive rate, a longer generation time, and a slower population doubling time. A smaller proportion of aphid offspring developed into alatae when feeding on SMV-infected soybean seedling, and these took longer to mature than their counterparts on uninfected plants. We infer that SMV infection has significantly negative effects on the biological performance of A. glycines, which may be consistent with the long-term coevolution of SMV, soybean, and A. glycinesin the transmission cycle of SMV.

Nitrogen (N) fertilization is a common agricultural practice, which, by increasing the quality of plants, also enhances their nutritional suitability for insect herbivores, creating the possibility of a cascade of N across trophic levels, from plant to herbivore to predator. We manipulated the quality of cucumber plants by fertilizing them with three different N rates (110, 160, and 210 ppm), which represented low, medium, and high N levels, respectively. Colonies of Aphis gossypiiGlover (Hemiptera: Aphididae) were then reared on these plants and used as prey for adult Hippodamia variegata(Goeze) (Coleoptera: Coccinellidae) in experiments that characterized the predator’s foraging behavior and functional response to different aphid densities. The nutritional content of plants and aphids was also measured. As N fertilization increased, so did the nutrient content (total energy) of aphids and this resulted in declining rates of aphid consumption by beetles at higher aphid densities. Females in the 110 N treatment, and males in all treatments, responded to aphids with a type II functional response (decelerating consumption at higher densities), but females in the 160 and 210 ppm N treatments exhibited a type III response (consuming a declining proportion of available aphids at high densities). Beetles fed aphids from the 110 N treatment consumed more prey in both assays than did those fed aphids from the 210 N treatment. Beetle searching time, handling time, and duration of digestive pauses all increased at high levels of N fertilization, especially for females. The results indicate that heavy N fertilization can increase prey nutritional quality to the point where it alters predator foraging and feeding behavior, resulting in slower rates of prey consumption and longer prey handling times.

Augmentation biological control has successfully replaced a lot of insecticide use in ‘closed system’ agriculture (e.g., greenhouses). The profitable commercialization of biocontrol agents in greenhouses has created an incentive to expand markets for mass-reared beneficial insects into open agricultural systems, often without sufficient scientific justification. However, the semi-contained nature of greenhouse culture is often critical to the success of augmentation and can serve to mask potential pitfalls and intrinsic limitations of this approach in open systems. Factors contributing to greenhouse successes include the reduced biological diversity of contained agroecosystems, the prevention of agent dispersal, the ability to maintain environmental conditions within a range favorable for the agent, the exclusion of competitors and natural enemies of the agent that might otherwise diminish its efficacy, and the absence of alternative prey/hosts that could divert predation/parasitism from the target pest. There are also problems arising from collection of source material from locally adapted populations, and the inadvertent imposition of artificial selection in the course of laboratory rearing. Besides highlighting these pitfalls, this paper aims to encourage more consideration of conservation approaches prior to investment in augmentation programs which entice farmers into perpetual cycles of ‘rear and release.’ I argue that although augmentation can benefit agriculture whenever it replaces pesticide applications, it does not constitute an ecologically sustainable solution because it requires continued inputs, and it can distract research attention away from more sustainable objectives. Sustainable biological control is best achieved through modifications to cultural practices that increasingly ‘naturalize’ agroecosystems, thus facilitating the natural recruitment and persistence of beneficial arthropod fauna, combined with habitat management geared to increasing overall plant and arthropod diversity in the agroecosystem.

We present numerical and experimental results demonstrating the slow light effect induced by the sharp resonance of the Raman gain on a spatial Raman soliton in a Kerr planar waveguide.

We conditioned colonies of Melanaphis sacchari(Zehntner, Hemiptera: Aphididae) to three different temperature regimes over a period of 2 mo: 30°C, 25°C, and a cycle of 18/8°C (L:D), all under a diurnal photoperiod of 12:12 (L:D). Plants of susceptible sorghum, 85Y40, were grown to the five-leaf stage in 4-liter pots, 2 per pot, and then infested with mixtures of second-fourth instar M. saccharinymphs, either 50 (18/8°C treatment) or 100 (25 and 30°C treatments) aphids per plant. In each run of the experiment, a series of two to four plants of each treatment group were lowered to the desired cold temperature (4.0, 2.0, 0.0, −2.0, and −4.0°C) in a climate-controlled chamber and then evaluated for aphid survival after 12 h in complete darkness. Results revealed substantial survival of aphids from the 18/8 and 25°C conditioned treatments, even at −4.0°C, a temperature sufficient to kill the plants, and >90 and 60% survival, respectively, at 0.0°C. In contrast, aphids conditioned to 30°C experienced about 50% mortality at 4.0°C, and complete mortality at 0.0°C. Our results indicate that M. sacchariis able to survive periods of sub-freezing temperatures quite easily and will not suffer ‘cold-shock’ mortality unless subjected to a rapid drop in temperature from very warm conditions (e.g., 30°C or higher). Therefore, only temperatures that are cold enough to kill sorghum plants are likely to kill all apterous virginoparae of M. sacchari.

We present numerical and experimental results demonstrating the slow light effect induced by the sharp resonance of the Raman gain on a spatial Raman soliton in a Kerr planar waveguide.

Biotype 2 of the Russian wheat aphid, Diuraphis noxia(Mordvilko), is virulent to both sources of resistance presently available in commercial wheat, Triticum aestivumL. The performance of biotype 2 was compared with that of biotype 1 on eight wheat cultivars at two constant temperatures, and the plants were evaluated for overall damage and leaf rolling. Colonies of biotype 2 grew an average of 2.3 and 24.9 times faster in the first and second generation, respectively, than did their biotype 1 counterparts at 20°C, reaching 80 to 125 aphids per plant after 20 d, compared with 10 to 31. The no. of aphids per plant at 10 and 20 d after infestation displayed a significant biotype–temperature interaction. There was also a biotype–temperature interaction for plant damage at 10 d, and for damage and leaf rolling at 30 d. After 20 d at 24°C, damage ratings ranged from 7.3 to 8.6 on a scale of 1.0 to 9.0, and leaf rolling ranged from 2.4 to 2.9 on a scale of 1.0 to 3.0 for biotype 2, whereas values for biotype 1 ranged from 2.8 to 5.1 and 1.4 to 2.2, respectively. There were no differences among cultivars in plant damage or leaf rolling induced by biotype 2, and ratings of both were higher than for biotype 1 in all cultivar–temperature combinations. Biotype 2 D. noxiahas overcome both Dn4‐ and Dny‐based sources of resistance, was more virulent than biotype 1 to all the cultivars tested, and induced plant injury more rapidly than biotype 1, especially at higher temperatures.

Abstract: The SmartCut process was first developed to obtain silicon-on-insulator (SOI) materials. Now an industrial process, the main Unibond SOI-structure trends are reported in this paper. Many material combinations can be achieved by this process, because it appears to enable the generic development of new structures. Several of the new structures combining different materials and different bonding layers are described. These include SiGe and strained-Si films onto an oxidized Si wafer, silicon-on-insulating multilayer (SOIM) structures, and InP or 4H-SiC film transfers onto low-cost substrates via metallic or even refractory conductive-film bonding layers. More recently, an original bonding process based on mark patterning, wafer bonding, and layer transfer has been proposed to obtain structures in which the relative crystalline-axis orientations of both the film and the substrate can be controlled accurately. In this case, a SmartCut process that includes a mark-patterning step appears well suited for precise control of axis orientations. A procedure is described to obtain an ultra-thin Si film bonded onto a Si wafer. An example of a pure screw-dislocation network achieved by the mark patterning, bonding, and layer-transfer process is reported in this paper. The results have important implications for nanostructure development.

Objective To compare the preservative effects of Celsior solution and modified blood Wallwork solution in lung transplantation.Methods From 1989 to 2000, 44 lung transplantations for cystic fibrosis were performed: 26 grafts were preserved with modified blood Wallwork solution and 18 with Celsior solution.Results Preoperative status of the 2 groups was similar. The ratio of arterial oxygen to fraction of inspired oxygen and the pulmonary vascular resistance on the first postoperative day did not differ significantly between the 2 groups. Early death was 4% (SD, 20%) in the Wallwork group versus 11% (SD, 32%) in the Celsior group (not significant). No death was related to graft failure. The forced expiratory volume in 1 second during the first month after transplantation was 63% (SD, 19%) in the Wallwork group versus 63% (SD, 16%) in the Celsior group (not significant).Conclusion Because the solution does not need to be prepared on site and does not require blood from the donor, Celsior seems better than Wallwork solution for preserving lung grafts.

Objective—To compare the preservative effects of Celsior solution and modified blood Wallwork solution in lung transplantation.Methods—From 1989 to 2000, 44 lung transplantations for cystic fibrosis were performed: 26 grafts were preserved with modified blood Wallwork solution and 18 with Celsior solution.Results—Preoperative status of the 2 groups was similar. The ratio of arterial oxygen to fraction of inspired oxygen and the pulmonary vascular resistance on the first postoperative day did not differ significantly between the 2 groups. Early death was 4% (SD, 20%) in the Wallwork group versus 11% (SD, 32%) in the Celsior group (not significant). No death was related to graft failure. The forced expiratory volume in 1 second during the first month after transplantation was 63% (SD, 19%) in the Wallwork group versus 63% (SD, 16%) in the Celsior group (not significant).Conclusion—Because the solution does not need to be prepared on site and does not require blood from the donor, Celsior seems better than Wallwork solution for preserving lung grafts.

It has been established that leptin displays a number of effects on peripheral tissues. We have investigated the effect of the hormone on lipid synthesis, apolipoprotein biogenesis and lipoprotein secretion in Caco‐2 cells. Immunocytochemistry revealed the presence of leptin receptors (Ob‐Rb) on the basolateral membrane. Incubation of cells with 200 nM leptin resulted in a decreased export of triglycerides in the basolateral medium without affecting monoglyceride, diglyceride and cholesterol ester lipid classes. It also significantly reduced the output of de novo‐synthesized apolipoprotein (Apo)B‐100 and ApoB‐48 as well as that of newly formed chylomicrons and of low‐density lipoproteins. It also enhanced that of ApoA‐I, ApoA‐IV and ApoE. Our results support the hypothesis that leptin can affect energy balance at the gut level by reducing lipid release into the circulation.

To clarify the clinical features and pathologic manifestations of isolated angiitis of the CNS (IACNS) in children.

It has been established that leptin displays a number of effects on peripheral tissues. We have investigated the effect of the hormone on lipid synthesis, apolipoprotein biogenesis and lipoprotein secretion in Caco-2 cells. Immunocytochemistry revealed the presence of leptin receptors (Ob-Rb) on the basolateral membrane. Incubation of cells with 200 nM leptin resulted in a decreased export of triglycerides in the basolateral medium without affecting monoglyceride, diglyceride and cholesterol ester lipid classes. It also significantly reduced the output of de novo-synthesized apolipoprotein (Apo)B-100 and ApoB-48 as well as that of newly formed chylomicrons and of low-density lipoproteins. It also enhanced that of ApoA-I, ApoA-IV and ApoE. Our results support the hypothesis that leptin can affect energy balance at the gut level by reducing lipid release into the circulation.

The secreted protein sonic hedgehog (Shh) is required to establish patterns of cellular growth and differentiation within ventral regions of the developing CNS. The expression of Shh in the two tissue sources responsible for this activity, the axial mesoderm and the ventral midline of the neural tube, is regulated along the anteroposterior neuraxis. Separate cis-acting regulatory sequences have been identified which direct Shh expression to distinct regions of the neural tube, supporting the view that multiple genes are involved in activating Shh transcription along the length of the CNS. We show here that the activity of one Shh enhancer, which directs reporter expression to portions of the ventral midbrain and diencephalon, overlaps both temporally and spatially with the expression of Sim2. Sim2 encodes a basic helix-loop-helix (bHLH-PAS) PAS domain containing transcriptional regulator whose Drosophila homolog, single-minded, is a master regulator of ventral midline development. Both vertebrate and invertebrate Sim family members were found sufficient for the activation of the Shh reporter as well as endogenous Shh mRNA. Although Shh expression is maintained in Sim2(-)(/)(-) embryos, it was determined to be absent from the rostral midbrain and caudal diencephalon of embryos carrying a dominant-negative transgene that disrupts the function of bHLH-PAS proteins. Together, these results suggest that bHLH-PAS family members are required for the regulation of Shh transcription within aspects of the ventral midbrain and diencephalon.

A hospital pharmacy's efforts to advance clinical pharmacy practice and reduce pharmacy costs as part of a hospitalwide re-engineering program are described. In 1995, a 321-bed community hospital in Wisconsin undertook a three-year re-engineering program aimed at reducing operating expenses, primarily labor costs. The pharmacy department focused its efforts within the program on improving the efficiency of product-related functions, mainly through automation, and redeploying staff to value-added clinical functions. This involved installation of a hospitalwide pneumatic-tube system, use of unit-based automated medication dispensing devices, and implementation of a dedicated clinical pharmacy services program. Implementation of this program was to occur incrementally, with the first 12 months to be used primarily in developing a service model, initiating a staff-development program, and hiring additional clinical staff. Services added under the program included i.v. to oral conversion, dosage adjustments for patients with renal impairment, advanced patient counseling, development of care plans, and rounds in all areas of the hospital. After the first full year of implementation of the program, a cost-benefit analysis was undertaken; costs were composed primarily of pharmacists' salaries and benefits, and benefits were composed primarily of drug cost savings. A benefit to cost ratio of 2.61:1 and a net saving of $217,551 were calculated. The introduction of clinical pharmacy services as part of a hospitalwide re-engineering program was associated with a positive benefit to cost ratio and a substantial net cost saving.

Development of the neuroendocrine hypothalamus is characterized by a precise series of morphogenetic milestones culminating in terminal differentiation of neurosecretory cell lineages. The homeobox-containing gene Orthopedia (Otp) is expressed in neurons giving rise to the paraventricular (PVN), supraoptic (SON), anterior periventricular (aPV), and arcuate (ARN) nuclei throughout their development. Homozygous Otp(-/-) mice die soon after birth and display progressive impairment of crucial neuroendocrine developmental events such as reduced cell proliferation, abnormal cell migration, and failure in terminal differentiation of the parvocellular and magnocellular neurons of the aPV, PVN, SON, and ARN. Moreover, our data provide evidence that Otp and Sim1, a bHLH-PAS transcription factor that directs terminal differentiation of the PVN, SON, and aPV, act in parallel and are both required to maintain Brn2 expression which, in turn, is required for neuronal cell lineages secreting oxytocin (OT), arginine vasopressin (AVP), and corticotropin-releasing hormone (CRH).

Objectives: To determine the incidence of various causes of sudden unexpected death (SUD) within an entire population and to assess the relative importance of an expert autopsy, as well as age of demise, in predicting the likelihood of finding a cause of death. Methods: We reviewed all cases of SUD in infants aged 1 week to 18 months that occurred in the province of Quebec (Canada) between 1987 and 1996. Results: We identified 623 cases of SUD; in 80% the diagnosis was sudden infant death syndrome (SIDS). Infection was the most common non-SIDS diagnosis (7.1% of all SUDs), followed by cardiovascular anomalies (2.7%), child abuse or negligence (2.6%), and metabolic or genetic disorders (2.1%). The percentage of non-SIDS deaths was much higher for autopsies performed in centers with expertise in pediatric pathology (18% vs 6%, P < .005). The likelihood of a non-SIDS diagnosis was much higher at age ranges atypical, as compared with typical, for SIDS (33% at 7 to 27 days, 19% at 6 to 12 months, and 64% at 12 to 18 months [atypical] vs 15% at 1 to 6 months [typical]; P = .003). Conclusion: The study of an entire population provides more reliable data regarding causes of SUDs than does the study of small groups. We recommend that in addition to a thorough investigation of each SUD, autopsies be performed in centers with expertise in pediatric pathology. This recommendation takes on added significance in this era of decreasing SIDS rates. (J Pediatr 1999;135:437-43)

Bronchopleural fistula after pneumonectomy is a very serious complication, occurring in 1-4% of cases, regardless of the bronchial stump closure technique adopted. The objective of this study was to report a bronchial stump closure technique in pneumonectomy by manual suture (polypropylene running suture) and to study the incidence of bronchopleural fistula.

Agenesis of the cerebellar vermis with fusion of the dentate nuclei and cerebellar hemispheres (rhombencephalosynapsis) is a rare cerebral malformation. We report the case of a 7-h-old girl whose mother had taken the drug phencyclidine during the first 6 weeks of pregnancy. Absence of the septum pellucidum, hypoplasia of the commissural system, optic nerves, chiasm and tracts, moderate hydrocephalus, and agenesis of the posterior lobe of the pituitary were also found. Extracranial congenital anomalies involved the cardiovascular, respiratory, urinary, and musculoskeletal systems. Death was secondary to severe respiratory distress and bradycardia. The literature concerning this rare form of cerebellar malformation is reviewed.

Summary HTLV-III was searched for in frozen sections of peripheral blood lymphocytes obtained from AIDS patients by an immunofluorescence technique. Human IgG against HTLV-III/LAV and monoclonal antibodies against HTLV-III/LAV P24 antigen, yielded a strong cytoplasmic fluorescence in frozen sections of the lymphocytes. Some cells containing HTLV-III antigens displayed multinucleated giant forms. They also reacted with monoclonal antibodies against helper/inducer T-cells (OKT 4+), as demonstrated by direct double staining immunofluorescence. Similarly, complexes of immunoglobulins and C3 component of complement were also detected on HTLV-III/LAV Ag expressing lymphocytes.

It is now well documented that human immunodeficiency virus type 1 (HIV-1) induces encephalopathy in patients with AIDS. In vitro studies have implicated the envelope protein (gp120) as a factor which causes neuronal death. To better evaluate the role and elucidate the mechanisms of gp120 neurotoxicity, we have developed transgenic mice carrying a segment of the HIV-1 genome that expresses the viral gp160 protein under the control of the human neurofilament light gene promoter. In two separate lines of transgenic mice, the Env protein was found to be expressed in several nuclei of the brain stem and in the anterior horns of the spinal cord. The two lines showed identical patterns of Env expression. Neuropathological evaluation revealed numerous abnormal dendritic swellings in the immunostained motor neuron structures. Large and numerous neuritic swellings were also prominent in the nucleus gracilis and in the gracilis and cuneate fascicles. In addition, reactive astrocytosis was observed in several immunoreactive areas of the central nervous system. These transgenic mice offer a unique model to further investigate the role of HIV-1 Env protein in neuronal toxicity and to help elucidate the mechanisms that are involved.

Five human glioblastomas maintained in an organ culture system were studied by autoradiography to determine, after 8 days in vitro, the growth fraction (GF) of the explants, their total cell cycle time (TC) and cell cycle phase durations (TS,TG1,TG2 andTM), and their potential doubling time (Tpot) after pulse-labeling with [3H] TdR for 1 h. These parameters were derived from computer analysis of fraction of labeled mitoses (FLM) curves. The results fell into two groups.

An 18-year-old girl died following a slowly progressive neurodegenerative disease of nine years duration. At 9 years of age, she developed intellectual deterioration associated with speach difficulty, pseudobulbar palsy and ataxia. The progression included spastic quadriplegia, anarthria, severe dysphagia, ophthalmoplegia, and pes cavus. There was no family history. The brain was uniformly small and the substantia nigra was not pigmented. Neuronal loss and gliosis involving globus pallidus, subthalamic nucleus, thalamic nuclei, brain stem, cerebellum, and spinal cord gave the picture of multisystem atrophy. Intranuclear hyaline inclusions were observed in numerous neurons of the central and peripheral nervous system. These were auto-fluorescent and were made up of intermingled straight filaments (8–9 nm in diameter).

The history, theory, statistics, and development of mathematical models that assess biological responses to combinations of chemicals are well represented in the literature. A relative paucity of literature focuses on the actual application of methods and experimental guidelines for assessing toxic interactions. The wide variety of methods in use - some complicated, many nonideal - confounds the comparison of results from different laboratories. This communication is not a comprehensive exposition of the methods appropriate for the study of toxic or pharmacologic interactions of combinations of chemical agents. The modular approach presented here is intended to offer a unifying framework for such studies and to provide a simple yet versatile procedure for new investigators in this area. This approach is modular in that the components, such as experimental designs and mathematical models, can be (re)selected to suit specific research questions and to test the generality of conclusions without altering the overall structure of the approach. A brief background is given with references to some of the most rigorous and recent theoretical developments and reviews of this topic. The strategy and steps of the modular approach are outlined, followed by a more detailed description of these steps, general considerations, and suggested guidelines. Each step (such as experimental design, data analysis) is illustrated by an example. Advantages and disadvantages as well as assumptions and limitations of selected methods are discussed. Also addressed are aspects of in vitro systems that make them particularly conducive to investigations of toxic interactions.

When it first appears at stage HH16, the wing bud is already polarized along the dorsoventral axis. To study the mechanisms leading to the establishment of its dorsoventral polarity, we decided to focus our attention on an earlier stage (HH13). Using the quail-chick chimera system, we first show that the presumptive wing mesoderm occupies the medial half of the somatopleure at the level of somites 15-20. The corresponding ectodermal area, however, will only give rise to the apical ectodermal ridge. The rest of the limb bud ectoderm originates from the ectoderm overlying the paraxial and the intermediate mesoderms for its dorsal aspect and the lateral somatopleural mesoderm for its ventral aspect. We next used five experimental paradigms to show that the dorsoventral polarity of the presumptive limb is determined by its environment. Thus, presumptive limb regions flanked on two sides by rows of somites give rise to bidorsal limb buds, indicating that the somites produce a dorsalizing factor. In addition, insertion of filters laterally to the presumptive limb region also results in bidorsal limb buds, suggesting that the lateral somatopleure produces a ventralizing factor. We propose a model in which the polarizing activity of these two signals is mediated by the morphogenetic movements of the presumptive dorsal and ventral ectoderms, which carry the dorsoventral information over the limb bud mesenchyme.

The correct patterning of vertebrate skeletal elements is controlled by inductive interactions. Two vertebrate hedgehog proteins, Sonic hedgehog and Indian hedgehog, have been implicated in skeletal development. During somite differentiation and limb development, Sonic hedgehog functions as an inductive signal from the notochord, floor plate and zone of polarizing activity. Later in skeletogenesis, Indian hedgehog functions as a regulator of chondrogenesis during endochondral ossification. The vertebrate Gli zinc finger proteins are putative transcription factors that respond to Hedgehog signaling. In Drosophila, the Gli homolog cubitus interruptus is required for the activation of hedgehog targets and also functions as a repressor of hedgehog expression. We show here that Gli2 mutant mice exhibit severe skeletal abnormalities including cleft palate, tooth defects, absence of vertebral body and intervertebral discs, and shortened limbs and sternum. Interestingly, Gli2 and Gli3 (C.-c. Hui and A. L. Joyner (1993). Nature Genet. 3, 241-246) mutant mice exhibit different subsets of skeletal defects indicating that they implement specific functions in the development of the neural crest, somite and lateral plate mesoderm derivatives. Although Gli2 and Gli3 are not functionally equivalent, double mutant analysis indicates that, in addition to their specific roles, they also serve redundant functions during skeletal development. The role of Gli2 and Gli3 in Hedgehog signaling during skeletal development is discussed.

The bHLH-PAS transcription factor SIM1 is expressed during the development of the hypothalamic-pituitary axis in three hypothalamic nuclei: the paraventricular nucleus (PVN), the anterior periventricular nucleus (aPV), and the supraoptic nucleus (SON). To investigate Sim1 function in the hypothalamus, we produced mice carrying a null allele of Sim1 by gene targeting. Homozygous mutant mice die shortly after birth. Histological analysis shows that the PVN and the SON of these mice are hypocellular. At least five distinct types of secretory neurons, identified by the expression of oxytocin, vasopressin, thyrotropin-releasing hormone, corticotropin-releasing hormone, and somatostatin, are absent in the mutant PVN, aPV, and SON. Moreover, we show that SIM1 controls the development of these secretory neurons at the final stages of their differentiation. A subset of these neuronal lineages in the PVN/SON are also missing in mice bearing a mutation in the POU transcription factor BRN2. We provide evidence that, during development of the Sim1 mutant hypothalamus, the prospective PVN/SON region fails to express Brn2. Our results strongly indicate that SIM1 functions upstream to maintain Brn2 expression, which in turn directs the terminal differentiation of specific neuroendocrine lineages within the PVN/SON.

A study of Calypso, Cephalanthera, Corallorhizaand Epipactisseeds suggests that morphometric analysis can be useful as a taxonomic tool and an indicator of developmental patterns.

Between 1986 and 1994, 19 patients underwent pulmonary resection for metastatic colorectal carcinoma. The mean interval between colon resection and appearance of pulmonary metastasis was 41 +/- 21 months. All the patients had no more than two metastases. Wedge resection alone or associated with lobectomy was performed in four patients, lobectomy in ten, and pneumonectomy in five. One patient died within the month after surgery. Mean follow-up was 35 +/- 26 months. The 5-year survival rate was 38.7%. Repeat thoracotomy for recurrent metastases was performed in one patient. The disease-free interval, the size of metastases, the type of pulmonary resection, and the location and the stage of primary cancer had no apparent influence on survival, but the survival rate at 4 years was 25% for patients with high carcinoembryonic antigen (CEA) level versus 80% for those with low CEA level. We conclude that, at least when the number of metastases is less than two, resection of colorectal lung metastasis is safe and effective.

A 33-year-old man, an immunosuppressed renal allograft recipient, developed fever of unknown etiology, multiple pulmonary densities, space-occupying lesions in the liver, confusion, disorientation, and seizures with cerebral infarcts. At autopsy, changes classical of active lymphomatoid granulomatosis (LYG) were found in the brain but those studied in the lungs and liver were in the healing phase.