AIDS: a guide to suicide assessment.
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Biomedical subjects
Publications and source records attributed to J M Hall.
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The presence of patients with AIDS and AIDS-related complex (ARC) on a psychiatric unit requires education of and adaptation by staff and other patients as well as changes in the psychiatric milieu. The authors describe their experiences with 36 AIDS and ARC patients admitted to a psychiatric unit over an 18-month period. They address issues related to staff reactions to terminal illness and to increased demands to provide physical care, milieu management that takes into account the limitations of AIDS patients suffering from dementia, diagnostic complications arising from mixed psychopathology in some AIDS patients, and the increased susceptibility of AIDS patients to side effects and toxicity from psychotropic medication. Other issues relating to infection control, ethical concerns, needs of friends and family, and disposition planning are also discussed.
The experiments described were undertaken to determine which cells of guinea pigs immunized by different ocular routes produce the IgG1 and IgG2 antibodies detected in the serum. Guinea pigs were immunized intravitreally, topically, or by intravitreal immunization followed by topical conjunctival challenge. An indirect plaque assay was used to detect antibody producing cells in the cervical lymph nodes and ocular tissues. Passive hemagglutination, passive cutaneous anaphylaxis and ELISA assays were used to detect serum antibody. Both the topical and intravitreal methods initiated a primary antibody response. The guinea pigs developed IgG1 and IgG2 serum antibodies, but IgE and IgA antibodies were not detected. IgG1 and IgG2 plaque forming cells (PFC) were found in the lymph node and uveal tissues of the intravitreally immunized guinea pigs, and in the lymph node and conjunctival tissues of the topically immunized animals. IgA plaque forming cells were not detected in topically immunized animals. No antibody producing cells were found in intravitreally immunized guinea pigs sacrificed after the first conjunctival challenge (two months after sensitization). The highest numbers of lymph node and conjunctival PFC were found in the animals sacrificed three days after the second or third topical challenge. The numbers of IgG1 antibody producing cells in this group of guinea pigs were usually higher than the numbers of IgG2 PFC. Serum antibody levels, undetectable before challenge, increased after the second challenge. We conclude that both lymph node and ocular cells produce antibody in guinea pigs immunized by ocular routes.
The accumulation of histone H1o in mouse NIE-115 neuroblastoma cells was measured during the course of three treatments that block cell division. Over the course of 12 days, these treatments, 5 mM butyrate, 2% dimethyl sulfoxide, and serum withdrawal, all resulted in decreased levels of DNA synthesis and increased levels of H1o (in absolute terms and relative to the other H1 histones, H1abc). However, the increase in H1o differed comparing butyrate treatment, where there was a 6-fold increase in the H1o/H1abc ratio, with the other two treatments which both had only 3-fold increases in the H1o/H1abc ratio. The mechanism for increasing H1o differed for each of the three treatments and involved differential changes in both synthesis and degradation of the H1 subfractions to favor H1o accumulation on the chromatin. Despite the obvious correlation of the increase in H1o levels with the inhibition of DNA replication, we also showed that increases in H1o can occur without any change in DNA synthesis when cells are switched from media containing dimethyl sulfoxide to media with butyrate as the blocking agent. Finally, there was no correlation between the production of neurites in this cell line and H1o accumulation, arguing against simple, direct involvement of H1o in differentiation.
The phosphorylation of H1 histone subfractions was measured in mouse neuroblastoma cells stopped from dividing by three treatments that block cell division: 5 mM butyrate, 2% dimethyl sulfoxide, and serum withdrawal. H1 histone phosphorylation decreased in response to all three treatments, but the response differed in its timing and its extent for the different H 1 subfractions. The different decreases in phosphorylation correlated well with the differential decreases in biosynthesis of the individual H1 subfractions; however, an exception to this parallel decrease in synthesis and phosphorylation was observed in the case of histone H1(0). Phosphorylation of H1(0) was absent in each of the three treatments after 2 days, despite the continued synthesis and deposit of H1(0) on the chromatin. Thus, despite the fact that H1(0) was being synthesized and that the other newly synthesized H1 subfractions were phosphorylated at this time, the phosphorylation of H1(0) became uncoupled from its synthesis after prolonged treatments blocking cell division.
The advent of totally implantable venous access devices (TIVADs) is changing the method of treatment for those chronically ill patients who require long-term chemotherapy or narcotic infusion. TIVADs eliminate the problem of limited peripheral vein access with little risk of complication. At Good Samaritan Hospital in Cincinnati, Ohio, we have implanted 30 TIVADs (3 Infuse-A-Ports and 27 Port-a-Caths) for a total of 4,502 patient days. This report documents our experience with the implantation and utilization of TIVAD systems.
Antibodies from the serum of patients with the autoimmune disease scleroderma CREST were used to investigate the association and distribution of kinetochores in mouse cells during meiosis and spermiogenesis. The pattern of indirect immunofluorescent staining in pachytene nuclei indicated that each autosomal bivalent contains one fluorescent spot. Throughout pachytene, the kinetochores were arranged non-randomly into several clusters and distributed around the periphery of the nucleus. In subsequent stages of meiotic prophase I, distribution was random and the number of fluorescent spots increased from 21 to 40 corresponding to the diploid chromosome number and the number of halfbivalents oriented to the spindle poles at the metaphase I. Twenty pairs of kinetochores were observed at metaphase II. During spermiogenesis, the number of kinetochores correlated with the haploid chromosome number in early spermatids but tandem association of centromeres and clustering into a conspicuous chromocenter corresponded to a significant reduction in the number of fluorescent foci in mid-spermatid nuclei. The number of stained sites per nucleus continued to decrease during sperm maturation and total absence of staining was apparent in mature spermatozoa. Immunoblotting of proteins extracted from mature sperm however, indicated that a kinetochore antigen of Mr 80,000 was still present. Therefore, the absence of kinetochore staining in mature spermatozoa is probably due to the blockage of epitopes during chromatin condensation.
The effect of individual vitamins and minerals on esophageal carcinogenesis was assessed by supplementing a diet (based on corn) that was marginally deficient in many micronutrients. The test diets were fed to weanling inbred BD IX rats for 45 days; they were then given five subcutaneous doses (3 mg/kg body wt) N-nitrosomethylbenzylamine (MBN) over two and one-half weeks. The diets were continued until termination: 150 days later; at that time all rats were still clinically normal. Marked reductions in the number of tumors and tumor-bearing rats were recorded in groups of rats given supplements of riboflavin, nicotinic acid, zinc, magnesium, selenium, and molybdenum. Various combinations of nutrients did not distinctly reduce the tumor yield further; however, tissue analyses suggest that individual supplements could enhance the status of other marginally deficient nutrients. When the experiment was repeated, but was varied by commencing the supplements only well after the cessation of MBN exposure, inhibitory effects on tumorigenesis were still exerted by most nutrients. We emphasized that these nutritional effects along with the epidemiological evidence in humans are relevant to early prevention; also, the treatment of premalignant esophageal changes by high doses of these nutrients may be unwise. The merits of food supplementation schemes are discussed.
Thrombotic thrombocytopenic purpura (TTP) is characterized by widespread occluding and persistent microthrombotic lesions. Evidence for both endothelial damage and primary platelet aggregation as possible pathogenetic mechanisms has been produced. Persistence of microthrombi has not been explained satisfactorily. In patients with TTP we studied plasma fibrinolysis and protein C. Tissue plasminogen activator (t-PA) activity levels, measured functionally, were low or unmeasurable in 11 of 12 patients; t-PA antigen levels, measured immunochemically, were normal in all six observed. The level of potent inhibitor of plasminogen activation directed against both t-PA and urokinase was elevated significantly in all 12, whereas the alpha 2-antiplasmin level was elevated in only two. Protein C antigen levels were low in three of six patients observed. Fibrinolysis levels in patients in remission did not differ from those in patients with acute disease. Plasma exchange resulted in temporary reversal of the abnormalities, but achievement of clinical remission was not associated with permanent normalization of fibrinolysis. Inasmuch as all 12 patients had severely depressed fibrinolytic mechanisms it is possible that a defect in the fibrin-clearing system permits thrombus formation to occur and proceed in an unchallenged fashion, thereby contributing to the complex events leading to arterial ischemia in vital organs.
Mouse neuroblastoma cells treated with millimolar concentrations of butyrate adjusted their recipe of histone H1 subfractions over the course of several days, eventually attaining an enrichment of about 5-fold in H1(0). This adjustment in the proportions of the H1's, which was essentially complete by 4 days, was brought about by changes in synthesis and turnover that were different for each of the three H1 subfractions. As the cells stopped dividing, the synthesis of all histones slowed substantially, but core histones were affected more than the H1's. Transiently, therefore, there was an overproduction of H1's relative to core histones, but the excess H1 was eventually removed by turnover. The very slow turnover of H1(0) and the rapid turnover of H1c were not substantially affected by butyrate treatment, but the turnover of H1ab was greatly accelerated by butyrate. Acetylation of the core histones was not necessary for maintenance of elevated H1(0) levels in the nondividing cells, although we did not rule out its involvement in the initial accumulation of H1(0).
Histone H1(0) is an H1 subfraction whose level on the chromatin is inversely correlated with the mitotic index of the cell. We investigated the increase in H1(0) in 6 cell lines when cell division was blocked by 4 methods: 5 mM butyrate, 2% DMSO, serum withdrawal or density inhibition. The 6 cell lines (HeLa S1 and S3, CHO, 3T6, NIE-115 and Vero) responded differently to the treatments as regards the amount of increase in H1(0) and comparisons among the lines reveal no obvious similarities between the lines in the differential effects of the various treatments on H1(0) levels.
Previous epidemiologic studies associated large differences of esophageal cancer risk with the nature of the staple diet. In this study, various cereals and dietary staples were fed to inbred BD IX rats for 7 months or longer. N-Nitrosomethylbenzylamine [(MBN) CAS:937-40-6] was given five times subcutaneously between the 45th and 58th day. The percentage of rats with tumors and the mean number of tumors per esophagus were similar when corn, wheat, commercial bird-resistant sorghum, bananas, and polished rice were fed but were strikingly lower when the basis of the diets was millet, red sorghum, brown rice, or potatoes. The number of esophageal tumors was significantly related to the dietary concentration of some minerals and vitamins. Supplementing marginally deficient corn or wheat diets with various combinations of nicotinic acid, riboflavin, zinc, magnesium, molybdenum, and selenium significantly reduced the numbers of esophageal tumors. When the feeding of protective cereals or nutrients was commenced only 150 days after MBN was given, a marked inhibitory effect on the progression of tumors was still observed.
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We have screened 173 wild caught mice (Mus musculus) from multiple sites in Europe for variation in the activity of 14 enzymes and found 8 different mutants with low enzyme activity; an incidence of 3.69/1000. This compares with the incidence of 3.26/1000 found for low enzyme activity variants in man (Mohrenweiser, 1981).
The stable prostacyclin analogue [3H]iloprost has been used for labelling prostacyclin-binding sites on human platelets and NCB-20 neuronal hybrid cells. The ligand-binding properties of the sites have been determined and correlate well with stimulation of cAMP synthesis in NCB-20 cells and inhibition of aggregation in human platelets.
A series of detergents of varying chemical properties has been tested for solubilisation of bovine caudate nucleus D2 dopamine receptors using [3H]spiperone binding to assay the solubilised sites. The properties of the lysophosphatidylcholine (LPC)- and 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulphonate (CHAPS)-solubilised preparations are described in detail. The preparations are truly solubilised, and sucrose density gradient and gel filtration data are reported. Specific [3H]spiperone binding in the LPC-solubilised preparation assayed at 4 degrees C is solely to D2 dopamine receptors. If the assay temperature is raised to 25 degrees C, the amount of specific [3H]spiperone binding is largely unchanged, but it forms a greater proportion of the total [3H]spiperone binding owing to a reduction in nonstereospecific (spirodecanone) [3H]spiperone binding at the higher temperature. The effect of raising the assay temperature is important as it enables more precise determinations of specific [3H]spiperone binding to be made. Part of the specific [3H]spiperone binding at 25 degrees C is to solubilised S2 serotonin receptors in addition to D2 dopamine receptors. Good correlations are observed between the affinities for binding of ligands to the solubilised D2 receptors and corresponding data obtained on membrane-bound receptors. Agonist binding in LPC-solubilised preparations is insensitive to guanine nucleotides. It is speculated that the spirodecanone sites represent, in part, proteolysed or damaged D2 dopamine, or S2 serotonin, receptors. In the CHAPS-solubilised preparation the pharmacological profile of [3H]spiperone binding is unclear when assayed at 4 degrees C, but in assays at 25 degrees C a clear serotonin S2 receptor component of specific [3H]spiperone binding can be discerned.(ABSTRACT TRUNCATED AT 250 WORDS)
The right eyes of guinea pigs were injected with 1.5 mg sterile ovalbumin. Two months later, one drop of ovalbumin (approximately 0.6 mg) was applied to the conjunctiva of both eyes. All challenged eyes developed an immediate hypersensitivity reaction within 5 min. The reaction subsided within 2 hrs. Prechallenge antibody titers, as determined by passive hemagglutination, passive cutaneous anaphylaxis, and by an ELISA test were low. Titers rose rapidly after two conjunctival applications at weekly intervals. The hypersensitivity reaction was elicited each time antigen was applied to the conjunctiva of the intravitreally sensitized guinea pigs. Control guinea pigs received weekly conjunctival application of ovalbumin, without prior intravitreal sensitization. Most animals developed an immediate hypersensitivity reaction following the fourth application of the antigen. There was no detectable hemagglutinating or ELISA (IgG1, IgG2) antibody at the time the conjunctival reaction was first elicited. These experiments demonstrated that high circulating IgG1 or IgG2 antibody is apparently not necessary to initiate an immediate hypersensitivity reaction in the guinea pig conjunctiva. The authors also demonstrated that weekly topical application of ovalbumin sensitized guinea pigs for immediate hypersensitivity.