Dose Response to Ethanol-Containing Liquid Diets for Use in a Murine Model for Studies of Biological Effects due to Ethanol Consumption

Dose-response experiments were performed to establish an optimum concentration of ethanol (EtOH) in liquid diet formulations for use with a murine model (C57BL/6) of potential biological effects attributable to EtOH consumption. An optimum condon was predetermined to be the highest EtOH concentration consumed by mice without resulting in a loss of body weight Feeding trials were performed using EtOH concentrations that ranged from 25 to 36% ethanol-derived calories (EDC) during 7-day experiments, or 10 to 30% EDC fed during 21-day experiments. The parameters studied included body weight changes, diet consumptions, daily g EtOH kg^?1 body weight, as well as differences in mononuclear cell numbers from the spleen, thymus, and bone marrow. Diet consumptions by the EtOH groups and pair-fed (PF) groups were monitored by weight rather than by volume. During either 7-day or 21-day trials, diet consumptions were lower by groups receiving diets of higher EtOH concentrations; however, daily EtOH intake was maximal by groups fed diets of 25% EDC in all experiments. These mice also gained weight, whereas mice maintained on 30% EM: did not gain weight, and mice maintained on diets of 33 or 36% EDC lost significant body weight Body weight changes in PF groups were similar to their respective EtOH group. Changes in mononudear cell numbers of the spleen and thymus paralleled the changes seen in body weights. In the 7-day trials, cell counts declined progressively in groups maintained on diets of high EDC (≥30% EDC) or their PF controls. From the 21-day trials, cell counts of both the 30% EDC group and their PF controls declined, compared with all other groups. Together, the conclusion drawn from these findings was that nutritional stress was principally responsible for the mononuclear cell depletions. This contradicts previous reports and highlights the need for strict attention to the pair-feeding paradigm to avoid masking a nutritional component of such studies through overfeeding of the PF controls. Liquid diets of 25% EDC were determined to be optimal for immunological studies using a murine model, because this concentration maximizes EtOH consumption and maintains body weight of the experimental animals.     

Human BMP sequences can confer normal dorsal-ventral patterning in the Drosophila embryo.

The type beta transforming growth factor family is composed of a series of processed, secreted growth factors, several of which have been implicated in important regulatory roles in cell determination, inductive interactions, and tissue differentiation. Among these factors, the sequence of the DPP protein from Drosophila is most similar to two of the vertebrate bone morphogenetic proteins, BMP2 and BMP4. Here we report that the human BMP4 ligand sequences can function in lieu of DPP in Drosophila embryos. We introduced the ligand region from human BMP4 into a genomic fragment of the dpp gene in place of the Drosophila ligand sequences and recovered transgenic flies by P-element transformation. We find that this chimeric dpp-BMP4 transgene can completely rescue the embryonic dorsal-ventral patterning defect of null dpp mutant genotypes. We infer that the chimeric DPP-BMP4 protein can be processed properly and, by analogy with the action of other family members, can activate the endogenous DPP receptor to carry out the events necessary for dorsal-ventral patterning. Our evidence suggests that the DPP-BMP4 signal transduction pathway has been functionally conserved for at least 600 million years.     

The prevalence of suicidal behaviours in a group of HIV-positive men

We studied a convenience sample of 54 HIV-positive men, recruited from HIV/AIDS community based service organizations. Data were collected on HIV risk factors and suicidal behaviours. Fifty-nine percent of the sample reported ever thinking about suicide, and 50% of those individuals reported attempting suicide at some point in their lives. Suicide ideation and attempts were more common among white participants. Suicidal behaviours were prevalent in this sample suggesting a need for mental health and suicide interventions targeted for this population.     

Mink as a predictive model in toxicology.

This paper reviewed the biomedical and toxicological database concerning the use of mink as a predictive model of human responses. It is concluded that substantial information exists on the mink genetics, physiology, metabolism, nutritional requirements, and susceptibility to infectious disease; and provides a foundation upon which interspecies extrapolation may be considered. In addition, information on the response of mink to several dozen toxic substances revealed that mink respond in a qualitatively and quantitatively similar manner to other more commonly employed species as well as humans. Our conclusion does not infer that mink should be used routinely in toxicological testing for estimation of human responses. However, it indicates that toxicological data from this species may be a useful complement in risk assessment processes based upon data obtained from traditionally employed models such as rats and dogs.     

Vascular responses to activated leukocytes after regression of atherosclerosis.

Activation of leukocytes in vivo produces marked constriction of large arteries in atherosclerotic, but not in normal, monkeys. We tested the hypotheses that vasoconstrictor responses to activated leukocytes in vivo may be abnormal during hypercholesterolemia before the development of atherosclerotic lesions and that responses may return to normal after the regression of atherosclerosis. Leukocytes were activated by injection of the chemotactic peptide formyl-methionine-leucine-phenylalanine (fMLP) into the blood-perfused hind limb of four groups of cynomolgus monkeys: monkeys fed a normal diet (normal group, n = 18), monkeys fed an atherogenic diet for 3-4 months (hypercholesterolemic group, n = 6), monkeys fed an atherogenic diet for 20 months (atherosclerotic group, n = 19), and monkeys fed an atherogenic diet for 18 months, followed by a normal diet for 20 months (regression group, n = 14). Baseline resistance of large arteries was 1.5 +/- 0.2 (mean +/- SEM), 2.0 +/- 0.6, 3.5 +/- 0.4 (p less than 0.05 versus normal), and 1.7 +/- 0.2 mm Hg/ml/min per 100 g tissue for the normal, hypercholesterolemic, atherosclerotic, and regression groups, respectively. Injection of fMLP did not change resistance of large arteries in normal or hypercholesterolemic monkeys. Injection of fMLP increased resistance of large arteries by 3.0 +/- 0.7 mm Hg/ml/min per 100 g tissue in atherosclerotic monkeys and by 1.3 +/- 0.4 mm Hg/ml/min per 100 g tissue in regression monkeys (p less than 0.05 versus atherosclerotic and normal). Thus, abnormal vasoconstriction in response to activation of leukocytes persists, but to a lesser extent, after regression. In contrast, vasoconstrictor responses to serotonin, which were potentiated in atherosclerotic monkeys, were normal after regression.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of nonintegrated DNA from JC papovavirus in organs of patients with progressive multifocal leukoencephalopathy

Tissues from 10 patients with progressive multifocal leukoencephalopathy (PML) and 14 patients without PML who were serologically positive for JC papovavirus were examined by molecular hybridization for human polyomavirus DNA sequences. Although viral proteins were not identified by fluorescent antibody methods, viral DNA was found in the kidneys of seven of nine patients with PML by hybridization, at 0.2-10 viral genome copies per cell genome equivalent, compared with 0.6-4 X 10(3) copies per cell in diseased areas of the brain. Examination of viral DNA from brains and kidneys of patients with PML by blot hybridization yielded no evidence of integration into the host cell genome. In three of the patients with PML, viral DNA was also found in liver, lung, lymph node, and spleen. Two of these patients, with widely disseminated JC virus, were children. In tissues from patients without PML, no evidence of JC virus infection was found, but BK papovavirus DNA was detected in two of 14 kidneys tested.     

I. Comparing Use of Public and Private Mental Health Services: The Enduring Barriers of Race and Age

Data from the NIMH-Epidemiologic Catchment AreaProject were used to predict differential use of privateversus public outpatient mental health services, asalient concern in integrating public and private services in market-based health care reformefforts. Having a recent psychiatric disorder, being age25-44, female, white, of higher educational level, andunmarried increase the odds of any mental health service use. However, odds of treatment in thepublic sector are increased for males, AfricanAmericans, those with low educational and income levels,and odds are mark edly decreased for the elderly,suggesting significant barriers to care for these mentallyill subpopulations.     

Use of neuroleptics after an episode of neuroleptic malignant syndrome

The authors report a case of unequivocal Neuroleptic Malignant Syndrome, in which the patient was successfully rechallenged with a different potent neuroleptic in substantial dosage during the recovery phase. The Neuroleptic Malignant Syndrome did not recur and the patient's psychosis cleared. Reference is made to the relevant world literature.