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Biomedical subjects

R Walker

Publications and source records attributed to R Walker.

At least 289 records · Page 16Linked to original sources
PubMed1989

Infection of monocyte-derived macrophages with human immunodeficiency virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types.

To characterize the host range of different strains of HIV-1, we have used four types of cells, primary monocyte-derived macrophages (MDM), primary PBL, a promonocyte cell line (U937), and a CD4+ T cell line (SUP-T1). These cells were infected with three prototype strains of HIV-1, a putative lymphocyte-tropic strain (IIIB), and two putative monocyte-tropic strains (SF162 and DV). Infections were monitored by assays for infectious virus, for cell-free and cell-associated viral antigen (p24), and for the proportion of cells infected by immunohistochemical staining. It was concluded that: (a) the use of four different cell types provides a useful biological matrix for distinguishing the tropism of different strains of HIV-1; this matrix yields more information than the infection of any single cell type. (b) A monocyte-tropic strain of HIV-1, such as strain SF162, shows a reciprocal host range when compared with a lymphocyte-tropic strain such as IIIB; strain SF162 replicates well in primary MDM but not in U937 or SUP-T1 cells, while strain IIIB replicates well in both U937 and SUP-T1 cells but not in MDM. (c) Both lymphocyte-tropic and monocyte-tropic strains of HIV-1 replicate well in PBL. (d) The promonocyte cell line, U937, and the T cell line, SUP-T1, differ markedly from primary cells, such as MDM and PBL, in their ability to support the replication of different strains of HIV-1; these cell lines cannot be used as surrogates for primary cells in host range studies of HIV-1 strains.

Antibodies, Monoclonal↗
PubMed1989

Preferential induction of the rat hepatic P450 I proteins by the food carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline.

1. Administration of the food carcinogen, 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) to rats gave rise to significant dose-dependent increases in the microsomal O-deethylations of ethoxycoumarin and ethoxyresorufin but had no effect on the O-dealkylation of pentoxyresorufin and the NADPH-dependent reduction of cytochrome c, and decreased the N-demethylation of dimethylnitrosamine. Microsomal cytochrome b5 and total cytochrome P-450 levels decreased following the administration of the carcinogen. 2. Hepatic microsomal preparations from IQ-treated animals were much more efficient than control in activating the premutagen 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole to mutagenic intermediates in the Ames test. 3. Immunoquantification of two of the major families of cytochrome P-450, namely P450 I and P450 II B, using ELISA techniques showed that treatment with IQ induced the apoprotein levels of the P450 I family but not of P450 II B. 4. Immunoblot analysis employing polyclonal antibodies against P450 I revealed that IQ induced both isoenzymes of this family, namely P450 I A1 and A2. 5. It is concluded that IQ is an inducer of the rat hepatic monooxygenases, selectively inducing the P450 I family as predicted by a computer-graphic analysis of its dimensions which showed that it is a large, essentially planar, molecule.

Animals↗
PubMed1989

Patterns of gliosis in Alzheimer's disease and aging cerebrum.

The distribution of astrocytic gliosis in Alzheimer's disease (AD) and aging cerebrum, as marked by immunoperoxidase staining for glial fibrillary acidic protein (GFAP), was examined in whole-hemisphere coronal sections. Cortical gliosis in AD had an obvious laminar pattern. There were two heavy bands of staining, one in layers II-III and another in layer V. Normal aging cases sometimes displayed considerable cortical gliosis, but no specific patterns were apparent. Most AD cases, and some normal aging cases, displayed hypertrophy of immunoreactive astrocytes at grey matter-white matter interfaces, especially the cortico-medullary junction. Subcortical grey matter gliosis was common in both normal aging and AD, but there was no consistent pattern in either group. The deep cerebral white matter, which is stained evenly and heavily in young, healthy individuals, showed uneven staining in both normal elderly and AD brains. In both AD and aging, perivascular gliosis was prominent throughout the cerebrum and especially in the putamen. In conclusion, both AD and aging cerebri show extensive gliosis: AD cortical gliosis has a specific laminar pattern, but there does not appear to be an AD-specific pattern of subcortical gliosis.

Adult↗
PubMed1989

Influence of dietary protein and gut microflora on endogenous synthesis of nitrate and N-nitrosamines in the rat.

Groups of four germ-free (GF) and conventional (CV) rats were given purified diets containing either 50 or 200 g lactalbumin/kg for 2 wk and their urinary excretion of nitrate was measured. Urinary excretion of N-nitrosoproline was also measured in one of the three experiments. Both GF and CV rats given the high-protein diet excreted significantly more nitrate and N-nitrosoproline than those given the low-protein diet. On both diets GF rats excreted more nitrate than their CV counterparts but N-nitrosoproline excretion was not affected by environment. Groups of 11 GF and CV rats given diets containing sesame meal with or without a supplement of lysine-HCl for 2 wk, excreted similar amounts of nitrate on both diets, but more nitrate was excreted by GF rats than by their CV counterparts. N-nitrosoproline excretion by rats given the lysine supplement was higher in both environments. It is concluded that endogenous synthesis of nitrate is mediated by mammalian tissues rather than microflora and that dietary protein is an important source of nitrogen for the synthesis, although surplus amino acids from an imbalanced protein source do not act as precursors of endogenously formed nitrate. Some of the synthesized nitrate or its precursors appears to be metabolized by the microflora in the CV rat.

Animals↗
PubMed1989

Modeling and guided practice as components within a comprehensive testicular self-examination cancer education program.

This study sought to assess the effects of modeling and guided practice as components within a comprehensive testicular self-examination education program for college-aged men. We studied three treatment groups (N = 161) at two Arkansas universities. The variables investigated were knowledge of testicular cancer, attitudes toward testicular cancer, and frequency of self-reported testicular self-examination. A summary of the major findings revealed a significant difference in knowledge of testicular cancer and attitudes toward testicular cancer and a significant difference in frequency of testicular self-examination for all treatment groups. Modeling and guided practice yielded no significant differences in knowledge of testicular cancer or frequency of self-reported testicular self-examination but some significant attitudinal differences. Results indicated that subjects were not knowledgeable about testicular cancer and that most (91.7%) were not practicing testicular self-examination. Three months after participation in one of three education programs, 78.9% of the subjects indicated they had performed testicular self-examination. Modeling and guided practice as components of one education approach used appear to be an essential strategy to increase the practice of regular testicular self-examination.

Adolescent↗
PubMed1989

The food pyrolysis product IQ enhances its own activation.

The metabolic activation of the food pyrolysis product 2-amino-3-methylimidazo (4,5-f) quinoline (IQ) to mutagenic intermediates in the Ames test was studied using hepatic activation systems from control and IQ-treated rats. Hepatic S9 preparations from IQ-treated rats were more efficient than control in converting IQ to mutagens. An increase was also seen when isolated microsomes were employed as activation systems but this was less pronounced. The microsome-mediated mutagenicity of IQ was potentiated by addition of the cytosolic fraction from control and IQ-treated rats, the latter being more effective. It is concluded that IQ, at the doses employed in the present study, enhances its own bioactivation to genotoxic metabolites by stimulating both its microsomal and cytosolic metabolism.

Animals↗
PubMed1989

Mutagenicity, metabolism and DNA adduct formation of 6-nitrochrysene in Salmonella typhimurium.

The mutagenic activities of 6-nitrochrysene (6-NC) and its previously identified metabolites were evaluated in Salmonella typhimurium TA100 and TA98 in the presence and absence of metabolic activation by 9000 g supernatant from the livers of rats treated with Aroclor. 6-Aminochrysene (6-AC) and trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene (1,2-DHD-6-AC) were the most active mutagens in TA100 upon metabolic activation. 6-NC and 6-AC were the most active mutagens in TA100 in the absence of metabolic activation. Upon metabolic activation, 6-AC was the most active in TA98; the other compounds were weak or inactive depending on the conditions of the assay. In the absence of metabolic activation, the mutagenic activities of 6-NC and its metabolites in TA98 were comparable to those observed in TA100. The major metabolite formed upon incubation of [3H]6-NC with S.typhimurium TA100 and 9000 g supernatant from the livers of Aroclor-induced rats was identified as trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene (1,2-DHD-6-NC); trans-9,10-dihydro-9,10-dihydroxy-6-nitrochrysene and 1,2-dihydroxy-6-nitrochrysene were also identified. The major DNA adduct formed in TA100 under these conditions was chromatographically identical to that previously detected in vivo in the liver and lungs of newborn mice treated with 6-NC, as well as to that obtained upon incubation of 1,2-DHD-6-AC with calf thymus DNA in the presence of rat liver microsomes. The DNA adducts derived from 6-NC in S.typhimurium TA100 without activation were identical to those adducts previously identified after incubation of 6-hydroxylaminochrysene with calf thymus DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Patient experience with a jet injector.

The acceptability of a jet injector compared with disposable syringes for insulin injections was assessed in 10 people with Type 1 diabetes. The majority considered disposable syringes easier to use and either less painful or no more painful than jet injections. Given the choice only 1 of the 8 people completing the study would continue using the jet injector.

Adult↗
PubMed1989

Rate-related electrophysiologic effects of long-term administration of amiodarone on canine ventricular myocardium in vivo.

The electrophysiologic effects of amiodarone were examined in 13 dogs that received 30 g amiodarone orally during 3 weeks and compared with 13 control dogs that did not receive amiodarone. Longitudinal and transverse epicardial conduction velocities were estimated with a square array of 64 closely spaced electrodes and a computer-assisted acquisition and analysis system. Amiodarone caused a rate-dependent decrease in conduction velocity with a slightly greater effect in the longitudinal direction of propagation. Rate-related depression of conduction velocity developed rapidly after abrupt shortening of the pacing cycle length; 67% of the change occurred between the first two beats of the rapid train, and little change occurred after the 10th beat. Recovery from use-dependent depression of conduction velocity was exponential with a mean time constant of 447 +/- 172 msec in the longitudinal direction and 452 +/- 265 msec in the transverse direction. Repolarization intervals, defined as the interval between the activation time and the repolarization time in the unipolar electrograms, correlated highly with refractory period determinations in the absence and presence of amiodarone at each cycle length tested. The increase in repolarization intervals and refractory periods resulting from amiodarone treatment did not vary with cycle length. Amiodarone treatment also resulted in a significant rate-related reduction in systolic blood pressure. The systolic blood pressure in the group that received amiodarone decreased by a mean of 50 +/- 23% between steady-state pacing cycle lengths of 1,000 and 200 msec, whereas the corresponding decrease in the control group was 21 +/- 32% (p less than 0.05). Plasma and myocardial amiodarone and desethylamiodarone levels were comparable to those observed clinically. We conclude that long-term amiodarone administration causes rate-dependent reductions in conduction velocity and blood pressure and causes rate-independent increases in repolarization intervals.

Amiodarone↗
PubMed1989

An electrode montage for electrocardiographic monitoring.

An electrocardiographic electrode montage is described using electrodes mounted on the manubrium sterni (RA), xiphisternum (LA) and V5 position (LL). The lead II setting on the monitor, equivalent to CM5, offers optimal ischaemia detection, while lead I, now a vertical lead, manubrium to xiphisternum, results in maximal P wave amplitude. The montage has been evaluated in sixty-two intensive care patients with electrocardiographic abnormalities and has been used extensively in intensive care, the operating theatres and in shock wave lithotripsy. The 'Prince Henry' montage offers advantages over the standard bipolar leads in P wave amplitude, arrhythmia diagnosis and artefact rejection.

Arrhythmias, Cardiac↗
PubMed1989

The hormonal environment of post-natal depression.

The incidence of post-natal depression is high, and dramatic changes in steroid hormones and prolactin occur in the post-partum period. In an attempt to correlate these events, 147 mothers, six to eight weeks after delivery of a healthy infant, completed standard psychological tests, including the Edinburgh, Montgomery-Asberg, and Raskin scales. They also provided matched samples of plasma for assay of cortisol, oestradiol, progesterone and prolactin, and saliva for assay of cortisol and progesterone. All steroid concentrations were within the appropriate normal ranges. Of the mothers, 14.9% were depressed on all three scales. Significant correlations were seen between depression ratings and salivary progesterone and prolactin. In bottle-feeders, salivary progesterone was positively associated with depression, whereas in breast-feeders it was negatively associated. Plasma prolactin levels were inappropriately low in depressed breast-feeders. These data indicate that differing therapies may be appropriate for depression in breast- and bottle-feeders.

Adolescent↗
PubMed1989

Hunting for a headhunter. How to select a physician search firm.

Many healthcare facilities in search of a physician are bombarded with offers from physician search firms to drum up potential candidates. Determining which firm has the right stuff for the job takes considerable time and skill. More than 60 companies belong to the National Association of Physician Recruiters, and their methods, policies, and results may vary widely. Administrators can begin getting basic information by contacting firms and requesting written material. During the initial telephone call, the administrator in charge of the search should speak with a consultant or principal of the firm (whoever would be doing the search) and find out what experience that person has had with searches for facilities in similar geographical areas, his or her success in placing physicians who specialize in the specialty needed, how many searches the consultant undertakes at one time, whether the firm guarantees its services, and an outline of its fee structure. After evaluating written material, the administrator should choose two or three search firms to make personal presentations. These presentations should follow a logical sequence and include statistics, completion times, ratios, and specific deadlines for various parts of the search process.

Consultants↗
PubMed1988

Anti-retroviral effects of interferon-alpha in AIDS-associated Kaposi's sarcoma.

21 patients with AIDS and Kaposi's sarcoma were enrolled in an open therapeutic trial to determine the in vivo anti-retroviral activity of recombinant interferon-alpha (IFN-alpha). 8 (38%) showed a complete or partial anti-tumour response. The mean pretreatment CD4 count for the responders was 399 cells/microliter vs 154 cells/microliter for the non-responders. All 5 of the patients with more than 400 CD4 cells/microliter pretreatment showed a significant reduction in tumour, whereas none of the 7 patients with under 150 CD4 cells/microliter had any response. 5 of the 6 complete or partial responders with greater than 50 pg/ml of human immunodeficiency virus (HIV) p24 before IFN therapy showed a 75% or greater reduction by 12 weeks of therapy, with 3 patients having persistently negative HIV cultures. The anti-viral effects were also most pronounced in the patients with the highest CD4 counts. These data demonstrate the potential benefits, both anti-tumour and anti-retroviral, of treatment with IFN-alpha in the early stages of HIV infection and Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Streptozotocin-induced diabetes modulates the metabolic activation of chemical carcinogens.

The effect of chemically-induced diabetes on the hepatic microsomal mixed-function oxidase system and the activation of chemical carcinogens was investigated in animals treated with streptozotocin (STZ). In order to distinguish between the effects of the diabetogenic chemical per se and that of the diabetic state, groups of STZ-treated animals received either nicotinamide simultaneously with STZ to prevent the onset of diabetes, or daily treatment with insulin in order to reverse the effects of diabetes. STZ-treated animals exhibited higher pentoxyresorufin O-dealkylase, ethoxy-resorufin O-deethylase, ethoxycoumarin O-deethylase, aniline p-hydroxylase and NADPH-cytochrome c reductase activities; similarly, increases were seen in cytochrome P-450 and b5 levels. All of these effects were prevented by nicotinamide and, at least partly, antagonised by insulin therapy. Treatment of animals with STZ markedly increased the activation, by liver microsomes in vitro, of Trp-P-1 and Trp-P-2 to mutagens, the effect being totally preventable by nicotinamide and successfully antagonised with insulin therapy. The diabetic animals were similarly more efficient in activating MeIQ but the effect was not preventable by nicotinamide or reversed by insulin. In contrast no changes were seen in the activation of IQ and only a modest increase in the case of MeIQx. It is concluded that diabetes may modulate the metabolic activation of some chemical carcinogens, presumably by changing the ratio of the various cytochrome P-450 isoenzymes.

Animals↗
PubMed1988

Immunological and pharmacological heterogeneity of alpha-bungarotoxin binding sites extracted from TE671 cells.

A proportion of the acetylcholine receptors (AChR) extracted from the human medulloblastoma cell line, TE671, differed pharmacologically and immunologically from AChR extracted from ischaemic human calf muscle (HCM). 29.6% (mean value) of the total 125I-alpha-bungarotoxin (alpha-BuTx) binding sites in the TE671 extracts was not inhibited by d-tubocurarine (dTC). Three of five monoclonal antibodies (m.abs), all of which precipitated greater than 80% of HCM AChRs, precipitated less than 55% of the total TE671 AChR. However, myasthenia gravis sera bound to TE671, and TE671 cell surface AChRs appeared to be similar to that of HCM.

Antibodies, Monoclonal↗