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Biomedical subjects

J Alexander

Publications and source records attributed to J Alexander.

At least 505 records · Page 28Linked to original sources

Effect of exercise training and diet modification on serum lipids and lipoproteins in coronary artery disease patients treated with thiazides.

The effects of chronic exercise training and diet modification on serum lipids and lipoproteins were measured in 17 hypertensive males and 41 normotensive males with documented coronary artery disease (CAD). Exercise consisted of aerobic activities which were performed at approximately 75-85% of the symptom-limited maximum heart rate for 30-40 minutes, three times weekly for 3 months. Each participant's diet was also controlled, the recommended daily intake of fat and cholesterol was no more than 40 g/day and 200 mg/day, respectively. Significant increases in estimated VO2max and total cholesterol/high density lipoprotein (HDL) and a significant decrease in serum triglycerides were documented after training. Significant differences in serum cholesterol and triglycerides between the nondiuretic and diuretic patients were also noted. No significant changes were found in low density lipoprotein (LDL), HDL, or body weight. Vigorous aerobic training and diet modification can favorably modify the deleterious effects of diuretic medications on serum triglycerides and total cholesterol/HDL in patients with documented CAD.

Adult↗

Sunburn and malignant melanoma.

We investigated the relationship between cutaneous malignant melanoma and multiple sunburns in the Queensland population. Interview data were gathered from 236 case-control pairs concerning their lifetime experience of severe sunburns, their occupational and recreational sun exposure, and their skin type. Excluding the lentigo maligna melanoma subtype, an association between multiple sunburns and melanoma was evident. After controlling for other major risk factors there was a significant dose-response relationship (P less than 0.05): the estimated relative risk associated with 2-5 sunburns in life was 1.5, and with 6 or more was 2.4. This observation extends the hitherto circumstantial evidence of a causal relationship between exposure to solar ultraviolet radiation and melanoma, and suggests that precautionary measures could prevent the development of this disease in a proportion of cases in fair-skinned populations.

Adolescent↗

Myocardial necrosis in a patient with mixed connective tissue disease.

A 23-year-old black woman with mixed connective tissue disease developed acute onset of shortness of breath and evidence of pulmonary edema. Cardiac isoenzymes, electrocardiograms and radionuclide myocardial scintigraphy were consistent with focal myocardial necrosis. The patient has had no further myocardial complication since initiation of therapy with steroids.

Adult↗

Immunoregulatory pathways in murine leishmaniasis: different regulatory control during Leishmania mexicana mexicana and Leishmania major infections.

The effect of whole body sublethal gamma irradiation on the subsequent growth of Leishmania mexicana mexicana and Leishmania major was studied in CBA/Ca and BALB/c mice. Whereas BALB/c mice are highly susceptible to both parasites developing non healing progressively growing lesions at the site of cutaneous infection, CBA/Ca mice develop small healing cutaneous ulcers following subcutaneous infection with L. major but non healing lesions following subcutaneous infection with L.m. mexicana. Prior whole body sublethal irradiation of CBA/Ca mice, but not BALB/c mice, resulted in strong resistance against infection with L.m. mexicana: no lesions developed at the site of cutaneous infection. Irradiated BALB/c mice did, however, develop small lesions which healed when infected with L. major. The protective effects of irradiation coincided with the development of delayed type hypersensitivity. Both naive and sensitized nylon wool purified lymphocytes could restore susceptibility to L. major in irradiated BALB/c mice but only lymphocytes from long term infected donor mice adoptively transferred a non healing response to irradiated CBA/Ca mice infected with L.m. mexicana. Non-irradiated, L. major infected, CBA/Ca mice, but not similarly treated BALB/c mice, were found to be resistant to subsequent infection with L.m. mexicana. On the other hand, irradiated BALB/c mice infected with L. major were resistant to subsequent infectious challenge with L.m. mexicana. We suggest that the susceptibility of CBA/Ca mice to L.m. mexicana is under the control of an as yet unidentified gene which is not dependent on the generation of T suppressor cells and is bypassed by previous infection with L. major. Therefore, BALB/c mice immunized against L. major by prior sublethal irradiation are also resistant to L.m. mexicana.

Animals↗

Evidence for two trans-acting genes regulating HLA class II antigen expression.

Previous studies have shown that a trans-acting regulatory factor is required for expression of HLA class II molecules in B-LCL, and that a trans-active factor derived from B-LCL induces de novo synthesis of T-LCL-encoded class II antigens in hybrids of T-LCL and B-LCL. To further examine the genetics of class II antigen regulation, we have now fused two different T-LCL with the class II antigen negative B-LCL 6.1.6, a regulatory mutant that does not synthesize a trans-acting factor necessary for transcription of class II genes. Northern blot analysis and cell surface immunofluorescence studies indicate that the hybrids express class II antigens encoded by both 6.1.6 and T-LCL parent cell lines. Thus, expression of class II antigens in these hybrids is controlled by a minimum of two trans-acting regulatory genes. One of these genes is inactivated in the 6.1.6 mutant and is provided by the T-LCL fusion partner. The second regulatory gene may still be active in 6.1.6, but it alone is insufficient for maintenance of class II antigen expression.

Antigens, Surface↗

Multi-institutional arrangements: relationships between governing boards and hospital chief executive officers.

This investigation focuses on the impact of multi-institutional arrangements on the role of governing boards in limiting or enhancing the managerial autonomy of individual hospitals. Data from a 1979 Special Survey by the American Hospital Association (N = 4213) are used to examine governing board-administrator relationships as a function of the degree of autonomy and scope of responsibility of the hospital governing board. It is hypothesized that governing boards responsible for multiple hospitals or for multiple nonhospital organizations and those boards accountable to a higher organizational authority will exercise more formal control over hospital chief executive officers (CEOs) than will boards of single or autonomous hospitals. The analysis assumes that formal control by the governing board over the management function of the individual hospital is exercised partly through soliciting or limiting participation by hospital administrators in key policy decisions and through the evaluation of administrative performance. Therefore, it is anticipated that hospitals governed by boards with multiple responsibilities as well as hospitals governed by boards accountable to a higher authority will be (1) less likely to have CEOs who are members of the governing board executive committee, (2) more likely to have annual performance reviews of the CEO by the governing board, and (3) more likely to have such reviews conducted according to preestablished criteria. Study results provide general support for the hypotheses with respect to hospital boards with multiple responsibilities: the data suggest that such boards do exercise greater control over hospital administrators and these effects do appear to be stronger for hospitals in the private sector. Hospitals governed by boards accountable to a higher authority, however, are more likely to have CEOs who are members of the governing board executive committee--a pattern in direct opposition to that hypothesized. Furthermore, these boards are no more likely to conduct annual CEO performance reviews than are boards with more autonomy. Boards accountable to higher authorities are more likely, however, to use preestablished criteria when such reviews are conducted. This general pattern is similar whether hospital boards are accountable to religious authorities, to investor-owned corporate boards, or to the boards of not-for-profit multi-institutional systems. A different pattern emerges, however, for boards accountable to a state, county, or local government authority.(ABSTRACT TRUNCATED AT 400 WORDS)

Employee Performance Appraisal↗

Inhibitory action of hexavalent chromium (Cr(VI)) on the mitochondrial respiration and a possible coupling to the reduction of Cr(VI).

The reduction of hexavalent chromium (Cr(VI] in isolated liver mitochondria was studied under different redox conditions in the respiratory chain. With 25 microM Na2CrO4 the rates were 1.6 +/- 0.7, 13.9 +/- 0.6 and 12.7 +/- 0.7 nmole Cr(VI) reduced 15 min/mg protein with the electron transport chain oxidized, reduced and only complex 1 reduced respectively. Electrons from succinate, bypassing complex 1, were apparently unavailable for Cr(VI)-reduction. The kinetics of chromate reduction was studied with only complex 1 in a reduced state. A rapid and a slow phase were found, probably corresponding to different electron donors in the mitochondria. Blocking the free thiols with N-ethylmaleimide lead to less than 10% decrease in the rapid initial Cr(VI)-reduction and to about 20% decrease during the whole incubation period (15 min). The amounts of free thiols were moderately decreased (15%) in chromate treated mitochondria during the slow reduction of Cr(VI) only. SH-groups may thus participate as reductants during the slow reduction phase. The respiration rate was inhibited about 50% by 25 microM Na2CrO4 when the mitochondria oxidized NAD-linked substrates. In contrast, succinate stimulated respiration was inhibited 50% by 3.6 mM Na2CrO4. The observed inhibition was Na2CrO4 in the micromolar range was therefore probably localized at complex 1 and may be coupled to the reduction of Cr(VI) at the same place. The respiration of isolated hepatocytes was also affected by Na2CrO4. Five micromolar chromate caused 5-10% inhibition. The inhibitory action of chromate on the mitochondrial respiration may thus constitute an important cytotoxic mechanism.

Animals↗

The mouse beta h1 gene codes for the z chain of embryonic hemoglobin.

Beta h0 and beta h1 are two beta-like globin genes in the mouse beta-globin gene cluster whose functions have not previously been established. Transcripts of both beta h0 and beta h1 are found in yolk sac-derived erythroid cells from mouse embryos and in the murine erythroleukemic cell line GM979. S1 nuclease analysis shows that beta h1 is the more abundant of the two transcripts in both embryonic erythroid cells and the cell line GM979. Hybridization of a beta h1-specific probe to RNA from erythroid cells of 10-, 11-, 12-, 13-, and 14-day-old mouse embryos indicates that levels of beta h1 mRNA are high at 10 and 11 days and then decline during further fetal development. The in vitro translation product of hybrid-selected beta h1 mRNA was analyzed by acid/urea polyacrylamide gel electrophoresis. The beta h1 translation product has the electrophoretic mobility expected for the z chain. We conclude that beta h1 is a fully functional gene which codes for the embryonic z chain.

Animals↗

Relationship between inositol polyphosphate production and the increase of cytosolic free Ca2+ induced by vasopressin in isolated hepatocytes.

Addition of vasopressin to rat hepatocytes prelabeled with myo-[2-3H]inositol resulted in a very rapid decrease [3H]phosphatidylinositol 4,5-bisphosphate (Ptd-Ins-4,5-P2) which was paralleled by increases of up to 3-fold in the levels of [3H]inositol trisphosphate (Ins-P3) and [3H]inositol bisphosphate (Ins-P2). Increases of [3H]inositol phosphate (Ins-P) were not detected until about 5 min after hormone addition. These data indicate that the major pathway for hormone-induced lipid breakdown in liver is through a phosphodiesterase for PtdIns-4,5-P2 and that decreases of phosphatidylinositol are a secondary result of increased PtdIns-4,5-P2 resynthesis. Using the fluorescent Ca2+ indicator Quin 2, cytosolic free Ca2+ increased from 160 nM to about 400 nM after vasopressin addition to hepatocytes and preceded the conversion of phosphorylase b to a. Half-maximal and maximal increases of cytosolic free Ca2+ and phosphorylase a activity were observed at 0.2 and 1 nM vasopressin, respectively. The dose-response curve for the initial rate of cytosolic free Ca2+ increase was very similar to those obtained for the initial rates of Ins-P3 production and PtdIns-4,5-P2 breakdown. Pretreatment of hepatocytes with Li+ caused a 3--4-fold potentiation of vasopressin-induced elevations of Ins-P, Ins-P2, and Ins-P3, with half-maximal effects at 0.5, 1, and 5 mM, respectively. The calculated maximal concentrations of Ins-P3 in cells treated with 20 nM vasopressin were 10 and 30 microM, respectively, without and with Li+. Lithium did not affect the initial rate of inositol polyphosphate production or Ca2+ mobilization. The increase of Ins-P3 which correlated with peak cytosolic free Ca2+ elevation was about 0.6 microM. In a saponin-permeabilized hepatocyte preparation, Ins-P3 (1 microM) caused Ca2+ release from a vesicular, ATP-dependent Ca2+ pool. The data presented here suggest that Ins-P3 may be a second messenger for the mobilization of intracellular Ca2+ by hormones in liver.

Animals↗

One-trial reward learning in the snail Lymnea stagnalis.

We present evidence that the pond snail Lymnaea stagnalis is capable of aquisition and extensive retention of an appetitively reinforced feeding response after only a single training trial. Food-deprived snails presented with a single pairing of a phagostimulant (a mixture of sucrose and casein digest) and a novel, non-food chemostimulus (amyl acetate) subsequently made feeding responses to the amyl acetate and retained the association for at least 19 days. This demonstration of one-trial, non-aversive classical conditioning enhances the utility of Lymnaea stagnalis as a model system for the detailed analysis of neural mechanisms underlying plasticity.

Animals↗