Ligand interactions by activating and inhibitory Ly-49 receptors

Summary: Natural killer (NK) cells express families of homologous receptors, members of which either activate or inhibit NK cells. We demonstrate that mouse Ly-49D is an activating receptor for the MHC antigen H2-D^d, which is also a ligand for the related inhibitory receptor Ly-49A. To compare and contrast their interactions with class I MHC ligand, we studied each of these receptors expressed in a rat NK-cell line, RNK-16, for their capacity to recognize wild-type or mutated H2-D^d. Our studies with Ly-49A reveal that functional interaction with H2-D^d depends on residues in the floor of the H2-D^d peptide-binding groove. The recent co-crystal of Ly-49A with H2-D^d indicates that these are not contact residues, thus they may contribute to allelic specificity through conformational changes in H2-D^d. We found that structural requirements for functional recognition of H2-D^d by Ly-49D differ markedly from those for recognition by Ly-49A. We note that H2-D^d expression on certain target cells is not sufficient to activate lysis mediated by Ly-49D, though the additional requirements for functional interaction are not yet identified. Here we review recent studies of Ly-49 receptor ligand specificities and their molecular basis. The functions of these related receptors with opposing functions and shared allospecificity remains unclear.
This work was supported by the Veterans Administration. M.C.N. is also supported by the Arthritis Foundation and the American Cancer Society. W.E.S. received NIH grant RO1 CA69299. We thank J.C. Ryan for communication of unpublished results. We thank H. Houtkooper and T. Ferrin for the molecular graphics image in Fig. 3 , which was created with the MidasPlus modeling system, supported by the NIH grant P41-RR-01081.     

Nutritional problems in urban slum children

Nutritional problems like protein energy malnutrition (PEM), anemia and vitamin A deficiency continue to plague a large proportion of Indian children. The diets and nutritional status of urban slum children in India is far away from being satisfactory. The nutritional status of slum children is worst amongst all urban groups and is even poorer than the rural average. Urban migration has not provided them salvation from poverty and undernutrition. Another distressing feature is the lack of any significant improvement over the years in this population. Most common causes of malnutrition include faulty infant feeding practices, impaired utilization of nutrients due to infections and parasites, inadequate food and health security, poor environmental conditions and lack of proper child care practices. High prevalence of malnutrition among young children is also due to lack of awareness and knowledge regarding their food requirements and absence of a responsible adult care giver. With increasing urban migration in the years ahead, the problem of malnutrition in urban slums will also acquire increasing dimension unless special efforts are initiated to mitigate the health and nutrition problems of the urban poor. Improving nutritional status of urban poor requires a more direct, more focused, and more integrated strategy.     

Patterns of Substance Abuse Treatment Seeking Following Cocaine-Related Emergency Department Visits

Chest pain is the most common medical complaint among cocaine-using emergency department (ED) patients. Correlates of substance abuse treatment seeking were examined using 3-month post-discharge surveys from 170 ED patients admitted with cocaine-related chest pain. Four treatment categories were specified as the dependent variable in an ordered logistic regression: no treatment (74.7%), informal treatment only (7.1%), formal treatment only (5.9%), and both formal and informal treatment (12.4%). The following variables were found to be positively associated with a higher treatment category: frequency of cocaine use (OR = 1.07, CI₉₅ = 1.01–1.15, p = 0.03), global severity index (OR = 2.26, CI₉₅ = 1.04–4.90, p = 0.04), number of endorsed stigma barriers (OR = 4.40, CI₉₅ = 1.41–13.78, p = 0.01), interpersonal consequences (OR = 1.41, CI₉₅ = 1.01–1.88, p = 0.02), and pre-baseline informal treatment (OR = 6.69, CI₉₅ = 1.58–28.36, p = 0.01). Physical consequences were found to be negatively associated with a higher treatment category (OR = 0.63, CI₉₅ = 0.47–0.85, p < 0.01). ED visits for cocaine-related chest pain represent missed opportunities to link patients to substance abuse treatment, and interventions are needed to motivate patients to seek care.     

“We have to ask and only then do”: Unpacking agency and autonomy in women's reproductive health in urban India

The limited autonomy and agency of women in developing countries is recognized as a key barrier to improving their reproductive health. Using an existing perinatal cohort in urban South India, we interviewed 36 women who had recently been through childbirth, and we carried out observations of family life and clinic encounters. Critical domains involved in women's agency and autonomy were women's participation in employment and group action and their mobility. Household decision making was considered a joint rather than individual responsibility. We call for a more nuanced understanding of these domains and their relationship to women's reproductive health, particularly for urban populations.     

Subcutaneous Dissemination from an Orbital Diffuse Large B Cell Lymphoma

Secondary cutaneous dissemination from an orbital diffuse large B cell lymphoma has not been described before. The authors report an unusual case of anaplastic variant of diffuse large B cell lymphoma which primarily presented in the orbit and during the course of disease had subcutaneous dissemination.     

Rat liver metabolism and toxicity of 2,2,2-trifluoroethanol.

2,2,2-Trifluoroethanol (TFE) is a metabolite of anesthetic agents and chlorofluorocarbon alternatives. Its toxicity in rats is a consequence of its metabolism to 2,2,2-trifluoroacetaldehyde (TFAld) and then to trifluoroacetic acid (TFAA). The enzymes involved in the toxic metabolic pathway have been investigated in this study. For the reaction of TFE to TFAld, the major hepatic metabolism associated with toxicity (as assessed by pyrazole-inhibitability) was NADPH dependent and occurred in the microsomes, whereas for TFAld conversion to TFAA, NADPH-dependent microsomal metabolism was significant, but mitochondrial and cytosolic metabolism in the presence of NADPH were also major contributors. NADPH-dependent hepatic microsomal metabolism of TFE to TFAld and TFAld to TFAA was inhibited by carbon monoxide, 2-allyl-2-isopropylacetamide, SKF-525A, metyrapone, imidazole, and pyrazole, and both reactions were oxygen dependent. The metabolism of TFE to TFAld was inhibited by diethyldithiocarbamate, a specific inhibitor of cytochrome P450E1, and by a monoclonal antibody to P4502E1, whereas the metabolism of TFAld was inhibited by neither. Ethanol pretreatment of rats enhanced the Vmax for hepatic microsomal metabolism of TFE to TFAld from 5.3 to 9.7 nmol/mg protein/min, while for TFAld to TFAA the Vmax was increased from 4.3 to 6.5 and the Km was unaffected for both reactions. Phenobarbital pretreatment of the rats did not affect any of these kinetic parameters. Coadministration of ethanol and a lethal dose of TFE very markedly decreased the lethality. Both the lethality (LD50 0.21 to 0.44 g/kg) and the metabolic kinetic parameters [(Vmax/Km)H(Vmax/Km)D = 4.2] were affected markedly when deuterated TFE replaced TFE. In contrast, deuteration of TFAld did not affect its lethality or rates of metabolism, but did affect its Km. Taken together these results indicate that P4502E1 catalyzed toxicity-associated hepatic metabolism of TFE to TFAld, while TFAld metabolism was catalyzed by a P450 which was not P4502E1. The hepatic metabolism of TFAld was not associated with its toxicity, which has been determined previously to be associated with its intestinal metabolism.     

Current Zinc Intake and Risk of Diabetes and Coronary Artery Disease and Factors Associated with Insulin Resistance in Rural and Urban Populations of North India

Objective: To determine the association between current zinc intake and prevalence of coronary artery disease (CAD) and diabetes as well as factors associated with insulin resistance.

Design, Subjects and Methods: In this cross sectional survey, 3575 subjects, aged 25 to 64 years, including 1769 rural (894 men, 875 women) and 1806 urban (904 men, 902 women) subjects were studied. The survey methods included questionnaires for 7-day food intake record, physical examination, and electrocardiography using World Health Organization criteria.

Results: The prevalence of CAD, diabetes and glucose intolerance was significantly higher among subjects consuming lower intakes of dietary zinc. There was a higher prevalence of hypertension, hypertriglyceridemia and low high-density lipoprotein cholesterol levels which showed significant upward trend with lower zinc intakes. Serum lipoprotein (a) and 2-hour plasma insulin levels also were associated with low zinc intake. Multivariate logistic regression analysis after adjustment for age showed that zinc intake and CAD were inversely associated. Serum zinc (odds ratio:men 0.77, women 0.57), serum triglycerides (men 0.86, women 0.81), blood pressure (0.83 men, women 0.76), diabetes mellitus (men 0.90, women 0.85), central obesity (men 0.88, women 0.87), glucose intolerance (men 0.66, women 0.57) and low high-density lipoprotein cholesterol (men 0.72, women 0.70) were significant risk factors for CAD (explained by tertiles of zinc status) in urban subjects. These associations were not observed in rural subjects.

Conclusion: Lower consumption of dietary zinc and low serum zinc levels were associated with an increased prevalence of CAD and diabetes and several of their associated risk factors including hypertension, hypertriglyceridemia and other factors suggestive of mild insulin resistance in urban subjects.     

Method to record evoked potentials from the frog eighth nerve

A method for recording evoked potentials from the eighth nerve of frogs is described. A prominent bipolar wave with latency of 3-6 ms recorded in response to auditory stimuli in Rana catesbeiana is attributable to eighth-nerve activity. The evoked potential provides an integrated response for study of inner ear and peripheral neural activity which complements responses obtained by other recording methods.