Characterization of HIV-1 neutralization escape mutants

Infection by molecularly cloned HIV-1, in the presence of a high-titre neutralizing monoclonal antibody (MAb), resulted in the selection of plaques in MT4 cells releasing HIV resistant to neutralization by the same MAb. The epitope recognized by the MAb was mapped to the V3 neutralization epitope at amino acids 305-321. The HIV-1 variants showed a reduced binding capacity for the selecting MAb as determined by immunofluorescence. Polymerase chain reaction (PCR) amplification of complementary DNA derived from viral RNA, cloning and sequencing identified a base pair (bp) change C----G at position 6663 in variant 110.5/1, predicting a change at amino acid 308 Arg----Gly. No other changes in the epitope were observed by sequencing three other variants. Differential hybridization of PCR amplified viral RNA and DNA, with oligonucleotides specific for the observed bp change or the 'wild type' sequence, indicated that the variants 110.5/1 and 110.5/7 were genotypically mixed for 308Gly/Arg. Subsequent screening of biologically 'recloned' variants 110.5/1 and 110.5/7 identified two subclones homozygous for the 308Gly change. The Arg----Gly change appears to affect the binding of the antibody to the epitope, since the linear peptide substituting 308Gly for 'wild type' 308Arg was 100 times less potent in blocking the neutralization of parental HIV. Amino-acid residue 308 thus appears to be crucial for antibody binding to the epitope. In addition, mutations distant from the monoclonal antibody binding site may also affect neutralization by antibodies recognizing the V3 loop.     

Carbohydrate studies in tropical sprue

Summary The lactose tolerance test is useful for detecting malabsorption in tropical sprue. For this purpose it is superior to a number of other oral tolerance tests. The generalized disaccharidase deficiency found in tropical sprue appears to be a secondary phenomenon resulting from injury to the intestinal mucosa.     

A comparison of simultaneous longitudinal and radial recordings of anal canal pressures

A new anal manometry perfusion catheter is described that offers the capability of simultaneous linear longitudinal pressure measurements. The authors studied 20 control subjects with this catheter and with a four-quadrant perfusion catheter. An asymmetry of basal, squeeze, and relaxation pressures was found. The highest basal pressures were in the middle of the anal canal, regardless of quadrant orientation. Using the radial perfusion catheter, the squeeze pressure profile was consistent with a double-loop external sphincter mechanism. Using the linear perfusion catheter, the internal sphincter relaxation pressures show a greater negative deflection at the proximal portions of the sphincter, which was not achieved at points distally in the same quadrant. This implies that during reflex relaxation, pressure is maintained in the distal anal canal so that patients remain continent during sensory sampling of rectal contents. The authors believe this is the first time this same-quadrant longitudinal asymmetry of relaxation has been shown with a single rectal balloon stimulus.     

Intensive cytotoxic therapy followed by autologous bone marrow transplantation for non-Hodgkin's lymphoma of high-grade malignancy

Fourteen patients with non-Hodgkin's lymphoma (NHL) of high-grade malignancy were treated with cyclophosphamide and total body irradiation followed by autologous bone marrow transplantation (ABMT). All patients were pretreated with conventional chemotherapy. Three of four patients with drug-resistant disease achieved complete remission (CR), but relapse occurred within six months. Four patients in partial remission (PR) achieved CR; one died because of sepsis, two relapsed within six months, and one is still in CR 28+ months later. Six were treated in CR, five in first CR, and one in second CR. From these six patients (who received this treatment as consolidation therapy), five are in unmaintained CR seven to 31+ months after ABMT (one patient died of a secondary illness). There were two therapy-related deaths, both in patients with a poor clinical condition. Toxicity of this treatment was mild for those receiving transplants who were in better condition. These preliminary results suggest that intensive cytoreductive therapy followed by ABMT may improve disease-free survival in patients in NHL of high-grade malignancy in CR.     

Effect of Short-term Psychiatric Intervention in Amputees

A total of 40 patients with limb amputations were included in the present study aimed at evaluating the psychological status of amputees. All patients filled a specially designed proforma and the following psychological questionnaires: General Health Questionnaire, Carroll Rating Scale for Depression, State-Trait Anxiety Inventory, Michigan Alcoholism Screening Test and Disability Assessment Questionnaire. Analysis of the results showed that 29 (72.5%) of the amputees had psychiatric disorders and this number had reduced to 20 (50%) after therapy. The difference was statistically significant. Psychiatric treatment also resulted in a statistically significant reduction in level of depression as measured by Carroll Rating scale for Depression. The amputees had the highest score on vocational subscale of Dysfunction Analysis Questionnaire. Short term psychiatric treatment was found to be very useful in treating psychiatric morbidity and depression in amputees.Key Words: Amputees, Depression, Psychiatric morbidity     

Unhealthy landscapes: Policy recommendations on land use change and infectious disease emergence

Anthropogenic land use changes drive a range of infectious disease outbreaks and emergence events and modify the transmission of endemic infections. These drivers include agricultural encroachment, deforestation, road construction, dam building, irrigation, wetland modification, mining, the concentration or expansion of urban environments, coastal zone degradation, and other activities. These changes in turn cause a cascade of factors that exacerbate infectious disease emergence, such as forest fragmentation, disease introduction, pollution, poverty, and human migration. The Working Group on Land Use Change and Disease Emergence grew out of a special colloquium that convened international experts in infectious diseases, ecology, and environmental health to assess the current state of knowledge and to develop recommendations for addressing these environmental health challenges. The group established a systems model approach and priority lists of infectious diseases affected by ecologic degradation. Policy-relevant levels of the model include specific health risk factors, landscape or habitat change, and institutional (economic and behavioral) levels. The group recommended creating Centers of Excellence in Ecology and Health Research and Training, based at regional universities and/or research institutes with close links to the surrounding communities. The centers' objectives would be 3-fold: a) to provide information to local communities about the links between environmental change and public health; b) to facilitate fully interdisciplinary research from a variety of natural, social, and health sciences and train professionals who can conduct interdisciplinary research; and c) to engage in science-based communication and assessment for policy making toward sustainable health and ecosystems.