Community based, effective, low cost approach to the treatment of severe malnutrition in rural Jamaica

Moderate and severe malnutrition are endemic in much of the developing world and in association with pockets of deprivation in the developed world. The cost in terms of individual and social development is high. The principles of effective management are clearly documented. A low cost, community based treatment programme for moderately and severely malnourished children under 3 years of age was established at a health centre in rural Jamaica. Children were followed up monthly and defaulters were rigorously recalled. Management consisted of carefully delivered dietary advice, antibiotics, anthelminthics, and vitamin supplements. All children improved and the response of 36 children, who were treated in the first year, showed an accelerated weight gain, with catch-up growth and the maintenance of length gain. There was a significant increase in the weight for age, at 1.9% per month over six months, which exceeds the rate reported with food supplementation programmes and nutrition rehabilitation centres.     

Pituitary neoplasia induced by expression of human neurotropic polyomavirus, JCV, early genome in transgenic mice

In recent years, there has been mounting evidence pointing to the association of polyomaviruses with a wide range of human cancers. The human neurotropic polyomavirus, JCV, infecting greater than 75% of the human population produces a regulatory protein named T-antigen which is expressed at the early phase of viral lytic infection and plays a critical role in completion of the viral life cycle. Furthermore, this protein has the ability to transform neural cells in vitro and its expression has been detected in several human neural-origin tumors. To further investigate the oncogenic potential of the JCV early protein in vivo, transgenic mice expressing JCV T-antigen under the control of its own promoter were generated. Nearly 50% of the animals developed large, solid masses within the base of the skull by 1 year of age. Evaluation of the location as well as histological and immunohistochemical data suggest that the tumors arise from the pituitary gland. As T-antigen is known to interact with several cell cycle regulators, the neoplasms were analysed for the presence of the tumor suppressor protein, p53. Immunoprecipitation/Western blot analysis demonstrated overexpression of wild-type, but not mutant p53 within tumor tissue. In addition, co-immunoprecipitation established an interaction between p53 and T-antigen and overexpression of p53 downstream target protein, p21/WAF1. This report describes the analysis of inheritable pituitary adenomas induced by expression of the human polyomavirus, JCV T-antigen in transgenic mice where T-antigen disrupts the p53 pathway by binding to and sequestering wild-type p53. This animal model may serve as a useful tool to further evaluate mechanisms of tumorigenesis by JCV T-antigen.     

The impact of a very high purity factor VIII concentrate on the immune system of human immunodeficiency virus-infected hemophiliacs: a randomized, prospective, two-year comparison with an intermediate purity concentrate [see comments]

Pathophysiologic considerations as well as non-comparative clinical results suggest that very high purity concentrates may slow immunologic deterioration in human immunodeficiency virus (HIV)-infected hemophiliacs. In an attempt to evaluate this hypothesis, we prospectively compared CD4 cell counts, skin testing responses, and changes of the clinical status in 20 asymptomatic HIV-positive hemophiliacs, randomly assigned to continue the treatment with an intermediate purity concentrate or to receive a very high purity product, purified by immunoaffinity chromatography with monoclonal antibodies. In the group switched to the very high purity concentrate there was no significant change of the CD4 cell counts over the 96-week follow-up period, whereas in the group continued on the intermediate purity concentrate, a highly significant decline was detected (P less than .013). Furthermore, in the very high purity group, four of six anergic patients at entry acquired reactivity to skin testing. The results of this study clearly support the use of very high purity concentrates for the replacement therapy of HIV-infected hemophiliacs.     

Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.     

Direct demonstration of transsynaptic degeneration in the human visual system: a comparison of retrograde and anterograde changes

Transneuronal degeneration of retinal ganglion cells was directly demonstrated in a patient who had unilateral removal of the striate cortex forty years prior to necropsy. For comparison, another case is presented showing anterograde transneuronal atrophy forty years after enucleation of one eye.     

Picrotoxin accelerates relaxation of GABAC receptors

Picrotoxin is a plant alkaloid that is often used to block the activity of neuronal GABA and glycine receptors. However, the mechanism by which picrotoxin inhibits these receptors is still in debate. In this study, we investigated the picrotoxin inhibition on perch-rho subunits expressed heterologously in Xenopus laevis oocytes, and on native GABA(C) receptors of perch bipolar cells. Both competitive and noncompetitive mechanisms were observed for picrotoxin inhibition of the GABA(C) receptor. In oocytes expressing the rho1A subunit, terminating simultaneously the coapplication of GABA and picrotoxin induced a large rebound of membrane current. In addition, picrotoxin significantly accelerated the kinetics of GABA responses, particularly in the relaxation (offset) phase of GABA currents. Both current rebound and the large acceleration of GABA relaxation were unique to picrotoxin inhibition and were not observed with the competitive antagonist (1,2,5,6-tetrahydropyridin-4-yl)-methylphosphinic acid or the allosteric modulator zinc. The change in kinetics induced by picrotoxin was also observed on receptors formed by other GABA rho subunits, as well as on the GABA(C) receptors of retinal bipolar cells. Based on these observations, we proposed a model in which picrotoxin binds to the GABA(C) receptor in both channel open and closed states. Overall, this model provides a remarkably good approximation of the experimental findings we observed for picrotoxin inhibition of GABA(C) receptors. These results support an allosteric mechanism of picrotoxin inhibition of ligand-gated chloride channels.     

Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma

BACKGROUND: The human polyomavirus JC virus (JCV) causes progressive multifocal leukoencephalopathy. Subclinical infection with JCV occurs in 85-90% of the population worldwide. The virus usually remains latent but can reactivate under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy. JCV is oncogenic in experimental animals and is associated with human brain tumors. JCV is found in normal mucosa of the gastrointestinal tract, and some colon carcinomas express the oncogenic JCV T-antigen protein. The objective of this study was to examine the presence of JCV DNA sequences and JCV protein expression in normal and malignant human esophageal tissues. METHODS: The authors examined the presence of JCV DNA sequences and protein expression in normal and malignant human esophageal tissues. Seventy well characterized biopsy specimens from patients with a spectrum of esophageal disorders were studied by immunohistochemistry, and 18 specimens were analyzed further by polymerase chain reaction amplification. RESULTS: JC viral DNA was isolated from 11 of 13 normal esophageal biopsy specimens (85%) and from 5 of 5 esophageal carcinomas (100%). Using immunohistochemistry, JCV T antigen was detected in 10 of 19 carcinomas (53%), agnoprotein was detected in 8 carcinomas (42%), p53 tumor suppressor was detected in 11 carcinomas (58%), and beta-catenin was detected in 4 carcinomas (21%). Zero of 51 normal, benign, and premalignant esophageal samples expressed viral proteins. Laser-capture microdissection verified the presence and specificity of JCV DNA sequences. beta-Catenin and p53 were colocalized with JCV T-antigen in the nuclei of neoplastic cells. CONCLUSIONS: The results provide evidence for infection of gastrointestinal tract cells by JCV and suggest a potential role of JCV in the development of upper digestive tract carcinomas.