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Biomedical subjects

M Thornton

Publications and source records attributed to M Thornton.

At least 37 records · Page 2Linked to original sources
PubMed1998

Reduction of the viral load of HIV-1 after the intraperitoneal administration of dextrin 2-sulphate in patients with AIDS.

OBJECTIVE: To determine the safety and efficacy of the sulphated polysaccharide, dextrin 2-sulphate, when delivered to the lymphatic circulation by the peritoneal route. DESIGN: An open Phase I/II dose-escalation clinical study in which six patients with AIDS were treated with seven courses of dextrin 2-sulphate each lasting 1 month. METHODS: During each course of treatment, the drug was administered daily for 28 days using an intraperitoneal catheter. Viral load was measured at frequent intervals using a plasma tissue culture infectious dose (TCID) assay, a cellular TCID assay, p24 antigenaemia, HIV-1 RNA and HIV-1 DNA. Plasma beta-chemokine levels were also measured. RESULTS: Dose escalation was completed without toxicity. A total of 7 patient-months of treatment were completed. With increasing doses of dextrin 2-sulphate, the infectious plasma viraemia, cellular viraemia and p24 antigenaemia all fell during the period of drug administration, but with no significant change in HIV-1 RNA. This was associated with increased plasma levels of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta. Dextrin 2-sulphate accumulated in peritoneal macrophages and induced the release of MIP-1alpha and MIP-1beta from these cells in vitro. These beta-chemokines could have augmented the cell surface-mediated anti-HIV-1 effect of dextrin 2-sulphate in vivo by binding to and blocking the CC-chemokine receptor-5. A second fall in infectious plasma viraemia, cellular viraemia, p24 antigenaemia and HIV-1 RNA was seen at day 100 which was then sustained for several months. A clinical improvement in Kaposi's sarcoma was also seen. CONCLUSIONS: Our results suggest that the intraperitoneal administration of dextrin 2-sulphate can reduce the replication of HIV-1 in patients with AIDS. With increasing doses of dextrin 2-sulphate, the fall in viral load was seen during the period of drug administration and again 2 months after completing treatment.

AIDS-Related Opportunistic Infections↗
PubMed1998

Nasotemporal directional bias of V1 neurons in young infant monkeys.

PURPOSE: Optokinetic nystagmus (OKN) in young infants typically shows a temporal-to-nasal asymmetry under monocular viewing conditions. The neural basis for this asymmetry has been a matter of debate. One idea is that the OKN asymmetry reflects a similar asymmetry in the directional sensitivity of primary visual cortical (V1) neurons. An alternative hypothesis is that the OKN asymmetry is due to an immaturity in the ability of cortical neurons to influence the activity of subcortical structures that directly control OKN. We addressed this issue by studying the directional sensitivity of V1 neurons in young infant monkeys. METHODS: The neuronal activity of V1 units was recorded from anesthetized and paralyzed rhesus monkeys ranging in age from 6 days to 8 weeks using standard extracellular single-unit recording methods. For comparison, V1 units from normal adult monkeys were also studied. Using drifting sinusoidal gratings of the optimal spatial frequency and a moderate contrast, we measured the responsiveness of individual units to 24 directions of stimulus movement. The preferred stimulus direction and the magnitude of the directional response bias were determined by a vector summation method. RESULTS: No clear signs of nasotemporal asymmetries in direction tuning were found in our cell population from infant monkeys. However, the overall directional sensitivity and the peak monocular response amplitudes of these units were significantly lower, and binocular suppression was greater during the first 4 weeks of life than in adults. CONCLUSIONS: The OKN asymmetry in young infants may be more closely associated with the lower overall directional sensitivity and the subnormal responsiveness of V1 neurons rather than with an obvious asymmetry in the directional properties of V1 neurons.

Action Potentials↗
PubMed1997

Replication and segregation of a miniF plasmid during the division cycle of Escherichia coli.

Replication of the miniF plasmid pML31 was examined during the division cycle of Escherichia coli growing with doubling times between 40 and 90 min at 37 degrees C and compared to the replication of plasmid pBR322 and the minichromosome pAL70. The replication pattern of pML31 was indistinguishable from that of pBR322 at all growth rates and very different from the cell-cycle-specific replication of the minichromosome. It is concluded that both pML31 and pBR322 plasmids can replicate at all stages of the division cycle, with a probability of replication that increases gradually, but perhaps not exponentially, during the cycle. In contrast, the modes of segregation of pML31 and pBR322 plasmids into daughter cells at division appeared to differ, raising the possibility that pML31 may segregate in a nonrandom fashion similar to that of chromosomes and minichromosomes.

Cell Division↗
PubMed1995

Perioperative low-molecular-weight heparin. Is it effective and safe.

In previous randomised clinical trials of thromboprophylaxis after total hip replacement, low-molecular-weight heparin has been given for an arbitrary 7 to 14 days. The risk factors are mainly perioperative and it is possible that a shorter course may be adequate. We assessed the safety and effectiveness of a three-day course. We assessed 156 primary THR patients after randomisation to either a control group or to receive enoxaparin at 12 hours preoperatively and 12 and 36 hours postoperatively. Thrombosis was diagnosed by routine venography. Haemorrhagic side-effects were assessed by measurement of blood loss, and soft-tissue side-effects by descriptive scores for wound discharge and bruising of the leg. The prevalence of calf thrombosis was 15.4% in the enoxaparin group and 32.1% in the control group (p = 0.01); the prevalence of proximal thrombosis was 15.4% and 17.9% respectively (not significant). There was no difference in haemorrhagic side-effects or wound discharge, but there was more bruising in the enoxaparin group.

Anticoagulants↗
PubMed1994

Immunogold localization of GyrA and GyrB proteins in Escherichia coli.

Immunogold preparations of Escherichia coli, using anti-GyrA and anti-GyrB antibodies to the subunits of DNA gyrase, showed clear labelling with both secondary antibody and protein A-gold conjugates. Both proteins were located mainly in the cytoplasm, with typically less than 10% in the nucleoid. This partitioning of gyrase proteins between nucleoid and cytoplasm was nonrandom and was consistently observed for a range of different cell preparations. Total gold particle counts were highly variable but suggested levels of at least 1000-3000 molecules per cell for both GyrA and GyrB. Sequential treatment with both anti-GyrA and anti-GyrB monoclonal antibodies resulted in simultaneous labelling of both proteins and revealed no clear association between the two groups of molecules. Treatment of cells with chloramphenicol caused marked changes in nucleoid conformation, but no reduction in cytoplasmic labelling of gyrase proteins. On the assumption that gyrase complexes within the nucleoid are not differentially masked from the monoclonal antibodies, the results obtained in this study suggest that most of the gyrase proteins are not associated with either central nucleoid DNA or cytoplasmic loops of peripheral single-stranded DNA, but are distributed randomly throughout the cytoplasm.

Antibodies, Monoclonal↗
PubMed1994

Donor recruitment.

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Blood Donors↗
PubMed1989

Modifying influence of dehydroepiandrosterone or butylated hydroxytoluene treatment on initiation and development stages of azaserine-induced acinar pancreatic preneoplastic lesions in the rat.

Dietary administration of dehydroepiandrosterone (DHEA) (0.6%) or butylated hydroxytoluene (BHT) (1%) during or subsequent to two i.p. injections of azaserine (30 mg/kg body wt) resulted in significant alteration of yield of preneoplastic lesions in both pancreas and liver. While concomitant application appeared not to have any effect on subsequent development of glutathione S-transferase P form (GST-P) positive hepatocellular lesions in either case, BHT and to a lesser extent also DHEA reduced initiation of pancreatic acinar carcinogenesis. Both BHT and DHEA were associated with significant increase in GST-A form positive pancreatic foci when administered after cessation of carcinogen treatment while clearly inhibiting liver lesion development. The results point to a marked differential in the response of the liver and pancreas to external stimulus with regard to preneoplastic focal lesions while demonstrating significant second stage promotion of pancreatic acinar carcinogenesis by BHT and DHEA.

Animals↗
PubMed1988

Sex-dependent, tissue-specific opposing effects of dehydroepiandrosterone on initiation and modulation stages of liver and lung carcinogenesis induced by dihydroxy-di-n-propylnitrosamine in F344 rats.

Administration of the hormone dehydroepiandrosterone (DHEA) (0.6% in the diet) during or subsequent to injections of the carcinogen dihydroxy-di-n-propylnitrosamine (DHPN) (2 X 1000 mg/kg body weight, i.p.) brought about alteration in the yield of preneoplastic lesions in liver and lung of both male and female F344 rats. Concomitant treatment with DHEA was associated with decrease in the numbers and size of glutathione S-transferase (GST-P)-positive hepatocellular foci while effecting a significant increase in development of lung lesions, especially in females. Long-term treatment with the hormone subsequent to carcinogen exposure brought about a reduction in numbers of liver foci in both sexes but in males was also associated with the development of large GST-P-negative foci and nodules of amphophilic/tigroid cell character. DHEA itself did not induce any focal lesions in the lungs or livers of either sex. Thus the hormone increased sensitivity to 'initiation' in the lung while decreasing that in the liver and exerted a sex-dependent pronounced modulation of the phenotype of a proportion of hepatocellular lesions.

Animals↗
PubMed1987

Interleukin 1 and interleukin 2 production in the acquired immune deficiency syndrome (AIDS) and AIDS-related complex.

Interleukin 1 (IL-1) production by freshly isolated and lipopolysaccharide (LPS)-stimulated adherent monocytes-macrophages and IL-2 production by unstimulated and phytohemagglutinin (PHA)-activated T cells were examined in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). Spontaneous IL-1 production was significantly increased in patients with ARC, whereas IL-1 production by LPS-activated monocytes-macrophages was significantly decreased in patients with AIDS. Spontaneous IL-2 production by unstimulated T cells was significantly decreased in AIDS and IL-2 produced by PHA-activated T cells was significantly decreased in AIDS and ARC. This study shows abnormality of both monocyte and T-cell functions in AIDS and ARC. These abnormalities appear to play a role in the immunopathogenesis of AIDS.

AIDS-Related Complex↗
PubMed1985

Autologous mixed lymphocyte reaction in man. XIII. Characterization of the T-T autologous mixed lymphocyte reaction.

In this study we have demonstrated that in the T-TA autologous mixed lymphocyte reaction (AMLR), OKT4+ T cells are the major responders; however, in the presence of additional interleukin-2 (IL-2), OKT8+ T cells also respond by proliferation. Both OKT4+ and OKT8+ T cells, activated in the T-non-T AMLR, act as stimulators in the T-TA AMLR. OKT4+ T cells activated in the T-TA AMLR suppress the proliferative response of the fresh T-non-T AMLR; control OKT4+ cells show no immunoregulatory activity in this system. In contrast, control OKT8+ T cells spontaneously suppress the proliferation of the T-non-T AMLR, but activation of OKT8+ T cells in the T-TA AMLR does not result in a further increase in the suppressor activity of OKT8+ T cells. In summary, in the T-non-T and T-TA AMLR phenotypically similar T-cell subpopulations proliferate but express distinct immunoregulatory functions and perhaps regulate the tempo of the AMLR.

Antibodies, Monoclonal↗
PubMed1985

Collagen and the proliferation and differentiation of rat ventral prostate epithelial cells.

The purpose of this study was to determine if a cause-and-effect relationship exists between androgen-induced changes in collagen and epithelial cell proliferation and/or differentiation in rat ventral prostate. Analyses of the temporal relationship between dihydrotestosterone (DHT)-induced changes in the synthesis and levels of collagen in the regressed ventral prostates of adult castrates demonstrated that, during the first 7 days of restoration of prostatic growth, androgen increased the synthesis as well as the degradation of collagen. Cis-hydroxyproline (CHP) treatment (2-200 mg/kg) during the first 7 days of androgen-stimulated prostatic growth, combined with maintenance of animals on a proline-free diet, produced a dose-dependent reduction in prostate weight and DNA content to a maximum of 50%. The epithelium was characterized by numerous disorganized layers of irregularly shaped and tightly packed cells, many of which had no contact with the basal lamina. There was a loss of epithelial lamina lucida and the development of a ragged lamina densa. Cis-hydroxyproline effects were reversible in that, following cessation of CHP treatment, the perturbed morphology, DNA content, and organ weight returned to the range of DHT-treated controls. Collagenous components seem to be important in supporting the normal androgen-dependent proliferation and differentiation of prostatic epithelial cells.

Animals↗
PubMed1984

Autologous mixed lymphocyte reaction in man. XIV. Deficiency of the autologous mixed lymphocyte reaction in acquired immune deficiency syndrome (AIDS) and AIDS related complex (ARC). In vitro effect of purified interleukin-1 and interleukin-2.

Peripheral blood mononuclear cells from male homosexuals with acquired immune deficiency syndrome (AIDS) and with AIDS related complex (ARC) were examined for the autologous mixed lymphocyte reaction (AMLR) between responder T and irradiated autologous non-T cells and in vitro influence of purified human interleukin-1 (IL-1) and -2 (IL-2) on the AMLR. The AMLR was significantly (P less than 0.001) deficient in both ARC and AIDS; the deficiency of the AMLR was of the similar magnitude in two groups when compared to asymptomatic homosexuals and healthy heterosexuals. In vitro addition of IL-2 enhanced the AMLR to the baseline levels of control subjects in most patients in ARC group (P less than 0.01) and in four of 15 patients in AIDS group (P less than 0.01). Addition of IL-1 to IL-2 containing cultures resulted in no further increase in the AMLR response over those with IL-2 alone. This study demonstrates deficiency of the AMLR in patients with ARC and AIDS that is corrected by purified IL-2 in the majority of cases with ARC but only a subset of patients with AIDS. The significance of these findings is discussed.

Acquired Immunodeficiency Syndrome↗