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Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 109 records · Page 6Linked to original sources
PubMed1996

Genotypic analysis of infant macaques infected transplacentally and orally.

The SIV-infected macaque provides an excellent model to study factors involved in maternal-fetal transmission of HIV. In our prenatal transmission studies, female macaques were inoculated intravenously during midgestation with either SIV/DeltaB670 or a combination of SIV/ DeltaB670 and the macrophage-tropic molecular clone SIV/17E-Fr. The females harbored a genetically diverse virus population at parturition, whereas a single genotype from the maternal quasispecies was identified in the infants. One of two variants was transplacentally transmitted to the infants, SIV/17E-Fr or B670-Cl 12, a genotype contained within the SIV/ DeltaB670 inoculum. Both of these variants have been identified in the central nervous system of macaques that have developed encephalitis and they replicate in vitro on primary rhesus macrophages. These results suggest a critical role for macrophages in fetal infection in utero. In our perinatal transmission studies we have evaluated the viral genotypes found in two newborn macaques infected orally with SIV/DeltaB670 and in one infant infected via amniotic inoculation in late gestation. More than one viral genotype was identified in each infant, moreover, each infant harbored different genotypes. These results suggest different mechanisms are responsible for viral infection via these routes.

Amino Acid Sequence↗
PubMed1996

Risk factors for liver rejection: evidence to suggest enhanced allograft tolerance in infancy.

After liver transplantation, a relatively low intensity immunosuppressive regimen is employed in our unit: after initial triple therapy (prednisolone, azathioprine, cyclosporin), prednisolone is discontinued at three months and azathioprine at one year. A retrospective study was therefore performed to determine the incidence of rejection, and to identify risk factors for rejection in our patient population. Over a 10 year period, 135 transplants were performed on 109 children. Thirty four (25%) were on infants less than 1 year old. Incidences of acute rejection and irreversible chronic rejection were calculated for grafts surviving more than one and four weeks respectively. Acute rejection occurred in 51 of 101 allografts (50%), and irreversible chronic rejection in 11 of 91 allografts (12%). The immunosuppression strategy was not associated with an increased incidence of rejection. Acute rejection occurred in only eight of 28 allografts (29%) in those transplanted during their first year, compared with 43 of 73 (59%) in older children. Logistic and Cox regression analysis supported age at transplantation as a significant risk factor for acute rejection. Irreversible chronic rejection did not occur in any of 24 grafts in patients transplanted before one year, compared with 11 of 67 (16%) in older recipients. This suggests possible enhanced allograft tolerance with transplantation during the first year of life. This unexpected and potentially important finding now requires confirmation in other large patient series, with blind interpretation of post-transplant liver biopsies.

Adolescent↗
PubMed1996

Increased expression of cytokine-induced neutrophil chemoattractant in septic rat liver.

Hepatocellular dysfunction in sepsis may be neutrophil mediated. We therefore tested the hypothesis that sepsis-induced neutrophil accumulation is associated with increased expression of the chemokine, cytokine-induced neutrophil chemoattractant (CINC). In Sprague-Dawley rats made septic by cecal ligation and puncture, we demonstrate a time-dependent increase in CINC mRNA, which returns to baseline by 48 h. By in situ hybridization, this mRNA is present in hepatocytes and nonparenchymal cells. CINC protein levels in septic animals parallel mRNA levels and resolve by 48 h. Because CINC expression is induced by cytokines including tumor necrosis factor-alpha (TNF- alpha), we show, by immunohistochemistry, that sepsis elevates intrahepatic TNF-alpha. Finally, because the CINC promoter is transactivated by the transcription factor, nuclear factor kappa B (NF-kappa B), we determined that hepatic NF-kappa B DNA binding increases dramatically, peaking 16 h after cecal ligation and puncture. Thus activated NF-kappa B may mediate CINC induction in sepsis. This constellation of findings suggests a mechanism by which sepsis may induce neutrophil accumulation in the liver and may have implications regarding sepsis-induced hepatic dysfunction.

Animals↗
PubMed1996

The future role of telemedicine at the interface between primary and secondary care.

Telemedicine has been in existence for 25 years. Owing to the primitive state of technological development and poor telecommunications, early projects could not be sustained. Recent improvements in technology and communications, together with a convergence of political and economic trends, has led to a massive surge in development. In the UK one promising application is to link GPs with hospital specialists. This offers the potential for improved quality of communication, more effective use of expensive resources, and more convenient delivery of medical services to the patient.

Evaluation Studies as Topic↗
PubMed1996

Motor evoked potential monitoring during spinal surgery: responses of distal limb muscles to transcranial cortical stimulation with pulse trains.

During spinal surgery, motor evoked potentials (MEPs) were recorded from distal upper and lower limb muscles following multipulse transcranial electrical stimulation of the cortex. Twenty-two patients, 9 of them myelopathic, were anaesthetised with propofol +/- nitrous oxide. Using trains of 3-6 pulses separated by 2 ms, consistent responses generally measuring more than 100 microV were obtained from every patient except one, and persisted with nitrous oxide concentrations as high as 74%. Responses could usually be elicited from 3 or more limbs simultaneously, although the location of the stimulating anode was sometimes critical. The lower limb responses of one patient disappeared transiently during excision of an intramedullary tumour; his leg weakness was increased for a few days after surgery. Three other patients experienced increased weakness or spasticity, two without concomitant MEP changes and one with no recordable responses. Although other methods may be preferable in some circumstances, we believe this represents an advance over previously reported non-invasive techniques for peroperative MEP monitoring, and may be particularly useful for monitoring patients with myelopathy in the thoracic region.

Adult↗
PubMed1995

Molecular activation-deactivation of xanthine oxidase in human milk.

Enzymic activity and protein levels of xanthine oxidase were measured in serial samples of breast milk donated by each of 14 mothers, starting, in all but two cases, within 7 days following parturition. Enzyme activity varied widely, usually reaching peak values during the first 15 days and falling thereafter, by as much as 98%, to basal levels that were subsequently largely maintained. Corresponding changes in xanthine oxidase protein levels were not observed and, consequently, the specific activity of xanthine oxidase followed the above pattern. The capacity of human xanthine oxidase to undergo activation-deactivation cycles at the molecular level has important implications, not only for its role in breast milk, but also for its potential as a source of reactive oxygen species in other human tissues.

Enzyme Activation↗
PubMed1995

Outbreak of Salmonella enteritidis phage type 4 infection associated with cheese and onion quiche.

Twelve people developed gastrointestinal symptoms suggestive of food poisoning after a party attended by between 60 and 80 people. The outbreak went unrecognised, however, until general practitioners admitted three patients to hospital, where faecal specimens were examined. An epidemiological investigation identified 12 cases, and a case control study showed a significant association between illness and eating a cheese and onion quiche at the party. Salmonella enteritidis phage type 4 was cultured from three out of seven faecal specimens obtained from cases. Consultants in communicable disease control should continue to encourage general practitioners to investigate and notify suspected cases of food poisoning.

Adult↗
PubMed1995

Magnetization transfer and T2 relaxation components in tissue.

T2 relaxation makes an important contribution to tissue contrast in magnetic resonance (MR) imaging. Many tissues are known to exhibit multicomponent T2 relaxation that suggests some compartmental segregation of mobile protons on a T2 timescale. Magnetization transfer (MT) is another relaxation mechanism that can be used to produce tissue contrast in MR imaging. The MT process depends strongly on water-macromolecular interactions. To investigate the relationship between multicomponent T2 relaxation and the MT process, multiecho T2 measurements have been combined with MT measurements for freshly excised samples of cardiac muscle, striated muscle, and white matter. For muscle, short T2 components show greater MT than long T2 components, consistent with the belief that they represent distinct water environments. For white matter, quantitative MT measurements were identical for the two major T2 components, apparently because of exchange between the T2 compartments on a time-scale characteristic of the MT experiment. Implications for accurate modeling of MT in tissue and the use of MT for MR image contrast are discussed.

Animals↗
PubMed1995

Use of a Gammarus pulex bioassay to measure the effects of transient carbofuran runoff from farmland.

There is now much information on the presence of pesticides in surface waters, but very little about their actual effects on aquatic life. This paper reports on the transient concentrations of a carbamate insecticide carbofuran, which were observed in a head-water stream draining treated farmland, and describes the resulting effects on a bioassay organism. One month after an application of 3 kg carbofuran/ha as broadcast granules to an oilseed rape crop, carbofuran concentrations of up to 26 micrograms/liter were measured in a nearby headwater stream after heavy rainfall. The majority of the carbofuran was translocated via field drains (where concentrations up to 264 micrograms/liter were detected), although the possibility of some surface runoff cannot be ruled out. Peak carbofuran concentrations only persisted for about 24 hr after the rainfall event, although measurable levels could be detected for at least 4 days. An in situ bioassay of streamwater which monitored the feeding rate of the gammarid amphipod crustacean Gammarus pulex showed that feeding stopped completely during the rainfall event, and was rapidly followed by death of all the caged organisms. Subsequent laboratory studies of toxicity showed that the peak concentrations of carbofuran had exceeded the G. pulex 24-hr LC50 of 21 micrograms/liter, and that concentrations as low as 4 micrograms/liter could reduce feeding rate. These findings are discussed with reference to regulatory risk evaluation procedures.

Agrochemicals↗
PubMed1995

Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus type 1 (HIV-1): interference with early and late events in HIV-1 replication.

SDZ NIM 811 is a cyclosporin A analog that is completely devoid of immunosuppressive capacity but exhibits potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity. The mechanism of action of SDZ NIM 811 is clearly different from those of all other anti-HIV agents described so far. In cell-free assays, it is not an inhibitor of reverse transcriptase, protease, integrase, and it does not interfere with Rev or Tat function. SDZ NIM 811 does not down-regulate CD4 or inhibit fusion between infected and uninfected, CD4-expressing cells. p24 production from chronically HIV-infected cells is not impaired either. To elucidate the mode of action of SDZ NIM 811, we performed DNA PCR analysis in HIV-1 IIIB-infected MT4 cells in one cycle of virus replication. The effects of SDZ NIM 811 on the kinetics of viral DNA synthesis, appearance of two-long terminal repeat circles (2-LTR circles), and integration of DNA were studied. SDZ NIM 811 inhibited 2-LTR circle formation in a concentration-dependent manner, which is indicative of nuclear localization of preintegration complexes. Half-maximal inhibition was achieved at 0.17 microgram/ml; this concentration is close to the 50% inhibitory concentrations (0.01 to 0.2 microgram/ml) for viral growth inhibition. As expected, integration of proviral DNA into cellular DNA was also inhibited by SDZ NIM 811. Analysis of the viral particles produced by SDZ NIM 811-treated, chronically infected cells revealed amounts of capsid proteins, reverse transcriptase activity, and viral RNA comparable to those of the untreated control. However, these particles showed a dose-dependent reduction in infectivity (50% inhibitory concentration of 0.028 microgram/ml) which indicates that the assembly process is also impaired by SDZ NIM 811. Gag proteins are postulated to play a role not only in assembly but also in early steps of viral replication, e.g., nuclear localization of the preintegration complex. Recently, it was reported that HIV-1 Gag protein binds to cyclophilin A, the intracellular receptor for cyclosporin A. Interference with Gag-cyclophilin interaction may be the molecular basis for the antiviral activity of cyclosporin A and its analogs.

Antiviral Agents↗
PubMed1995

Fulminant hepatic failure caused by tuberculosis.

A 54 year old Asian woman developed fulminant hepatic failure followed by renal failure. Because of a past history of possible tuberculosis, she was given antituberculous drugs. The chest x ray was normal. A transjugular liver biopsy showed caseating necrosis, granulomas, and acid fast bacilli indicative of miliary tuberculosis. Despite full supportive therapy, her condition deteriorated and she died. Postmortem examination showed widespread miliary tuberculosis; culture confirmed the presence of Mycobacterium tuberculosis. Tuberculosis causes fulminant hepatic failure rarely and only three cases have been described. In this, as with the other cases, hyponatraemia and hepatomegaly were features at presentation. This is the first report of treatment being given before death.

Acute Kidney Injury↗
PubMed1994

Molecular cloning, tissue expression of human xanthine dehydrogenase.

Xanthine dehydrogenase (XDH, EC 1.1.1.204) is a molybdenum iron-sulphur flavin hydroxylase which oxidizes a variety of purines, pterins and other heterogenic nitrogen compounds, serving as a rate-limiting enzyme in nucleic acid degradation. In this work, we have isolated and sequenced cDNA clones of human liver XDH. The obtained cDNA covers 4577 bases of human liver XDH mRNA with a 63 bp 5'-end untranslated region and a 515 bp 3'-end untranslated region. A termination codon TGA and a polyadenylation signal AATAAA were identified. An open reading frame encodes 1333 amino acid residues. The assignment of the N-terminal was confirmed by directly sequencing that region of purified human milk XDH. Northern blot analysis shows that the human XDH gene is widely expressed in human tissues.

Amino Acid Sequence↗
PubMed1994

Does patient semen quality alter during an in vitro fertilization (IVF) program in a manner that is clinically significant when specific counseling is in operation?

PURPOSE: It has been shown that the stress of infertility may impair semen quality. Whether counseling can attenuate this affect is unproven. This study examines, in an IVF program setting, where specific counseling is in operation, whether semen collected on the day of oocyte recovery is significantly different from that obtained during the prior clinical suitability assessment of the couple. RESULTS: In the 125 consecutive couples examined, there were no significant overall differences in semen volume or sperm density. There was a significant increase in sperm motility on the day of oocyte retrieval (P < 0.001). Twenty-three patients (18.4%) showed an increase in quality, and 21 (16.8%) a decrease, on the day of oocyte recovery. The environment of production appeared to exert no influence. Fertilization failure occurred in seven couples, three (14%) of whom presented for the first time with decreased semen parameters on the day of IVF. This compares with 1 of 23 (4%) fertilization failure in those whose parameters increased. CONCLUSION: The semen quality of the vast majority of the patients studied in this highly counseled program does not appear to be significantly affected by the superstress of participation in the day of oocyte recovery.

Adult↗