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T McHugh

Publications and source records attributed to T McHugh.

30 records · Page 2Linked to original sources
PubMed1991

Increased catalytic activity of cytochrome P-450IIE1 in pericentral hepatocytes compared to periportal hepatocytes isolated from pyrazole-treated rats.

Cytochrome P-450IIE1 is induced by a variety of agents, including acetone, ethanol and pyrazole. Recent studies employing immunohistochemical methods have shown that P-450IIE1 was expressed primarily in the pericentral zone of the liver. In order to evaluate whether catalytic activity of P-450IIE1 is preferentially localized in the pericentral zone of the liver acinus, the oxidation of aniline and p-nitrophenol, two effective substrates for P-450IIE1, by periportal and pericentral hepatocytes isolated from pyrazole-treated rats was determined. Periportal and pericentral hepatocytes were prepared by a digitonin-collagenase procedure; the marker enzymes glutamine synthetase and gamma-glutamyl transpeptidase indicated reasonable separation of the two cell populations. Viability, yield and total cytochrome P-450 content were similar for the periportal and pericentral hepatocytes. Pericentral hepatocytes oxidized aniline and p-nitrophenol at rates that were 2-4-fold greater than periportal hepatocytes under a variety of conditions. Carbon monoxide inhibited the oxidation of the substrates with both preparations and abolished the increased oxidation found with the pericentral hepatocytes. Pyrazole or 4-methylpyrazole, added in vitro, effectively inhibited the oxidation of aniline and p-nitrophenol and prevented the augmented rate of oxidation by the pericentral hepatocytes. Western blots carried out using isolated microsomes revealed a more than 2-fold increase in immunochemical staining with microsomes isolated from the pericentral hepatocytes, which correlated to the 2-4-fold increase in the rate of oxidation of aniline or p-nitrophenol by the pericentral hepatocytes. These results suggest that functional catalytic activity of cytochrome P-450IIE1 is preferentially localized in the pericentral zone of the liver acinus, and that most of the induction by pyrazole of P-450IIE1 appears to occur within the pericentral zone.

Aniline Compounds↗
PubMed1990

Increased oxidation of p-nitrophenol and aniline by intact hepatocytes isolated from pyrazole-treated rats.

Induction of cytochrome P-450 IIE1 by pyrazole has been shown in a variety of studies with isolated microsomes or reconstituted systems containing the purified P-450 isozyme. Experiments were conducted to document induction by pyrazole in intact hepatocytes by studying the oxidation of p-nitrophenol to 4-nitrocatechol or of aniline to p-aminophenol. Hepatocytes prepared from rats treated with pyrazole for 2 days oxidized p-nitrophenol or aniline at rates which were 3- to 4-fold higher than saline controls. To observe maximal induction in hepatocytes, it was necessary to add metabolic substrates such as pyruvate, sorbitol or xylitol, which suggests that availability of the NADPH cofactor may be rate-limiting in the hepatocytes from the pyrazole-treated rats. Carbon monoxide inhibited the oxidation of p-nitrophenol and aniline by hepatocytes from the pyrazole-treated rats and controls, demonstrating the requirement for cytochrome P-450. The oxidation of both substrates by the hepatocyte preparations was inhibited by a variety of agents that interact with and are effective substrates for oxidation by P-450 IIE1 such as ethanol, dimethylnitrosamine, pyrazole and 4-methylpyrazole. Microsomes isolated from pyrazole-treated rats oxidized aniline and p-nitrophenol at elevated rats compared to saline controls. These results indicate that induction by pyrazole of the oxidation of drugs which are effective substrates for P-450 IIE1 can be observed in intact hepatocytes. The extent of induction and many of the characteristics of aniline or p-nitrophenol oxidation observed with isolated microsomes from pyrazole-treated rats can also be found in the intact hepatocytes.

Aniline Compounds↗
PubMed1988

Effects of interleukin 2 and large envelope glycoprotein (gp 120) of human immunodeficiency virus (HIV) on lymphocyte proliferative responses to cytomegalovirus.

Lymphocytes from many HIV-infected asymptomatic individuals or patients with AIDS-related conditions (ARC) and from all AIDS patients were unable to proliferate in vitro in response to UV-inactivated cytomegalovirus (CMV). The addition of recombinant IL2 (rIL2) restored proliferative responses of lymphocytes from most HIV-infected asymptomatic individuals and ARC patients to levels similar to those of HIV-seronegative (HIV-) CMV-seropositive (CMV+) individuals. In contrast, rIL2 augmented CMV-specific lymphocyte proliferation of only 33% (6/18) of AIDS patients. Proliferative responses to CMV with or without rIL2 did not correlate well with the levels of CD4+ lymphocytes, HIV antigen levels or ratios of CD4+ and CD8+ lymphocytes. Proliferative responses to CMV were inhibited by relatively high concentrations (greater than or equal to 10 micrograms/ml) of recombinant HIV envelope glycoprotein (rgp120) and this immunosuppression was completely overcome by rIL2. These results indicate that defects in antigen-driven lymphocyte responses of HIV-infected individuals are not simply the result of reduced numbers of CD4+ lymphocytes but are influenced by defects in IL2 pathways and by immunosuppressive effects of HIV gp120.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Human immunodeficiency virus can productively infect cultured human glial cells.

Six isolates of the human immunodeficiency virus (HIV) showed differences in their ability to productively infect glioma-derived cell lines and early-passage human brain cell cultures. Susceptibility to HIV infection correlated well with the expression of the astrocyte marker glial fibrillary acidic protein. The CD4 molecule was expressed on some, but not all, of the brain-derived cells; however, no correlation was observed between CD4 protein expression and susceptibility to virus infection. The results show that HIV can productively infect human brain cells, particularly those of glial origin, and suggest that these cell types in the brain can harbor the virus.

Antigens↗
PubMed1985

AIDS-associated retroviruses (ARV) can productively infect other cells besides human T helper cells.

We have examined the host range of AIDS-associated retroviruses (ARV) that are known to infect human T cells of the helper subset. We have observed that the virus cannot infect fibroblast and epithelial cell lines of many different animal species. It is infectious and replicates efficiently in peripheral mononuclear cells (PMC) of chimpanzee and at low levels in baboon and rhesus monkey PMC. Most importantly, it has been found to replicate in established lines of human B cells, monocytes, and promyelocytes. This ability to infect these other cell types appears to be associated, in most cases, with the presence of the Leu 3 T helper cell antigen on the cell surface. Other mechanisms for virus infection, however, may be involved. The results suggest that ARV will be found in other cells of AIDS patients, besides T cells, and that these cells could be the reservoir for continual virus spread in the host. Variations in the replicative ability of ARV isolates in human cells have also been noted; they could reflect potentially important pathogenic differences among these human retroviruses.

Animals↗
PubMed1985

High prevalence of antibodies to acquired immune deficiency syndrome (AIDS)-associated retrovirus (ARV) in AIDS and related conditions but not in other disease states.

A rapid, sensitive indirect immunofluorescence assay has been developed for detection of antibodies to the acquired immune deficiency syndrome (AIDS)-associated retrovirus (ARV). The human T-cell line HUT-78 was chronically infected with ARV-2 and used to detect antibodies to virus-specific cytoplasmic antigens. Because the helper T-cell marker Leu-3 is substantially reduced in this cell line after ARV infection, it appears to be an important receptor for virus infection. Nearly all patients with AIDS and most cases with related conditions showed antibodies against ARV. Some healthy individuals in risk groups for developing AIDS also had antibodies to the agent. In contrast, no antibodies to the virus were found in any individuals outside the risk groups for developing AIDS or with diseases other than those associated with AIDS. The titers of antibodies to ARV and to Epstein-Barr virus varied independently from each other. The level of anti-ARV antibodies in a patient's serum was found to reflect the severity of the disease; it was lower in individuals with more severe manifestations. Taken together, these data support the role of ARV in AIDS and its related disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1979

Intermittent catheterization in children less than 6 years old.

Neurogenic bladder dysfunction often requires treatment early in life. Intermittent catheterization is an accepted means of treatment in older children and adults but its use in young children and infants has been limited because of fear of urethral injury. The results of managing 42 patients less than 6 years old by intermittent catheterization are presented. Excellent results were achieved even in small infants.

Child, Preschool↗
PubMedDate not supplied

Therapeutic efficacy of timentin and augmentin versus silvadene in burn wound infections.

Successful closure of thermal injuries, by either skin graft or delayed wound closure, largely depends on the ability to control the number of bacteria in the wound. The purpose of this study was to investigate the efficacy of two new antimicrobial agents, ticarcillin and clavulanate (Timentin) and amoxicillin and clavulanate (Augmentin), in the infected thermal injury. The therapeutic results were compared with the model treated with the standard topical silver sulfadiazine (Silvadene). Seventy-six Sprague-Dawley rats received a 20% full-thickness thermal injury and were then divided into six treatment groups. Three of the groups were inoculated topically with 10(8) Pseudomonas aeruginosa/ml, and three of the groups received topical inoculation of 10(8) Staphylococcus aureus/ml. The groups inoculated with P. aeruginosa received either intraperitoneal Timentin, topical Silvadene, or placebo treatment. The groups inoculated with S. aureus were treated with either enteral Augmentin, topical Silvadene, or placebo. The animals received 10 days of therapy and underwent tissue biopsies on alternate days. Statistical analysis showed that the level of bacteria in the wounds compared with the control group was significantly (p less than 0.05) decreased for both antibiotics tested as measured by quantitative wound biopsies. These studies demonstrate the efficacy of systemic Timentin and Augmentin in the infected thermal injury.

Amoxicillin↗