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Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1994

Inhibition of human immunodeficiency virus type 1 replication by SDZ NIM 811, a nonimmunosuppressive cyclosporine analog.

(Me-Ile-4)cyclosporin (SDZ NIM 811) is a 4-substituted cyclosporin which is devoid of immunosuppressive activity but retains full capacity for binding to cyclophilin and exhibits potent anti-human immunodeficiency virus type 1 (HIV-1) activity. SDZ NIM 811 selectively inhibits HIV-1 replication in T4 lymphocyte cell lines, in a monocytic cell line, and in HeLa T4 cells. Furthermore, its antiviral activity against laboratory strains and against clinical isolates from geographically distinct regions in primary T4 lymphocytes and in primary monocytes (50% inhibitory concentration = 0.011 to 0.057 micrograms/ml) was demonstrated. SDZ NIM 811 does not inhibit proviral gene expression or virus-specific enzyme functions, either free or bound to cyclophilin. The compound does not influence CD4 expression or inhibit fusion between virus-infected and uninfected cells. SDZ NIM 811 was, however, found to block formation of infectious particles from chronically infected cells. Oral administration to mice, rats, dogs, and monkeys resulted in levels in blood considerably exceeding the drug concentration, which completely blocked virus replication in primary cells. SDZ NIM 811 caused changes of toxicity parameters in rats to a smaller degree than cyclosporine (formerly cyclosporin A). Thus, the potent and selective anti-HIV-1 activity of SDZ NIM 811 and its favorable pharmacokinetic behavior together with its lower nephrotoxicity than that of cyclosporine make this compound a promising candidate for development as an anti-HIV drug.

Amino Acid Isomerases↗
PubMed1994

Isolated glycerol kinase deficiency in a neonate.

Glycerol kinase deficiency occurs either as a relatively benign isolated enzyme deficiency, or as part of a syndrome resulting from a microdeletion in the p21 region of the X chromosome associated with congenital adrenal hypoplasia and/or Duchenne muscular dystrophy. Developmental delay is a consistent feature of the microdeletion syndrome but not of the isolated enzyme defect. We report a case of isolated glycerol kinase deficiency in a neonate presenting with hypotonia, apnea, mild developmental delay, and glyceroluria, without evidence of adrenal insufficiency or myopathy. A mild communicating hydrocephalus was noted on magnetic resonance imaging brain scan. It is important, therefore, to exclude glyceroluria in infants being investigated for apnea and hypotonia.

Apnea↗
PubMed1994

Selective inner hair cell ototoxicity induced by carboplatin.

Carboplatin is a second-generation platinum antineoplastic agent. It has biological activity similar to cisplatin and is currently recommended for the treatment of ovarian cancer. In clinical use, carboplatin appears less ototoxic than cisplatin. This paper reports the ototoxic effects of carboplatin, in doses equivalent to the clinical use of the drug, in the chinchilla. Intravenous carboplatin 200 to 400 mg/m2 by bolus injection caused significant ototoxicity in this model as revealed by brainstem evoked responses (ABR audiometry). The cochlear pathology as seen by scanning electron microscopy revealed predominantly inner hair cell (IHC) stereocilia damage. Furthermore, the extent (grade) of the morphological lesions appears to be well correlated with the auditory brainstem response pattern of threshold elevation.

Animals↗
PubMed1993

RANTES is a chemotactic and activating factor for human eosinophils.

RANTES is a member of the 8-kDa cytokine family that has been shown to possess chemotactic activity for monocytes and CD4 T cells. In this study, we investigated whether RANTES could affect eosinophil chemotaxis and function. Peripheral blood eosinophils from blood donors were isolated on Percoll gradients to > 98% purity and then used for chemotaxis, flow cytometry, eosinophil cationic protein release assay, and survival assay. We found that RANTES is chemotactic for eosinophils at 10(-9) to 10(-8) M concentrations. RANTES elicited 65% of the chemotactic response to 10(-7) M platelet-activating factor in all experiments. The mechanism of chemotaxis was investigated by studying the expression of adhesion molecules on eosinophils by flow cytometry. We found that RANTES up-regulated the expression of CD11b/CD18 on eosinophils in a dose-dependent manner. In another set of experiments, purified eosinophils incubated with various concentrations of RANTES released eosinophil cationic protein as measured by a RIA. We also investigated the effect of RANTES on eosinophil density. Leukocytes were incubated in the presence or absence of RANTES, and the distribution of eosinophils on discontinuous Percoll gradients was then examined. We found that eosinophils became hypodense (< 1.085) when incubated in RANTES. However, unlike IL-3, RANTES did not affect the survival of eosinophils in a 4-day culture system. Thus, we established that RANTES is a chemotactic and activating factor for eosinophils.

Chemokine CCL5↗
PubMed1993

Argon laser trabeculoplasty in pigmentary glaucoma.

PURPOSE: To evaluate the long-term effect of argon laser trabeculoplasty (ALT) in pigmentary glaucoma. METHODS: The authors retrospectively analyzed results of ALT in 32 eyes of 32 patients with medically uncontrolled pigmentary glaucoma. Data were longitudinally adjusted to normalize the disparity in time of follow-up and evaluated by life-table analysis. RESULTS: Mean age (+/- standard deviation) was 45.1 +/- 13.1 years (range, 23-72 years) (males, 46.3 +/- 13.7 years; females, 42.9 +/- 12.2 years). Mean baseline intraocular pressure (IOP) was 27.8 +/- 5.3 mmHg. Mean follow-up time was 33.0 +/- 5.0 months (range, 1 week [immediate failures] to 96 months). Three eyes were lost to follow-up at 3 months. Eleven eyes required trabeculectomy between 1 week (2 eyes) and 37 months after laser treatment. Life-table analysis indicated a cumulative success for all eyes of 80% at 1 year, 62% at 2 years, and 45% at 6 years. Mean IOP was significantly reduced (P < 0.001; paired Student's t test) for male and female eyes at all intervals calculated. Age was a significant factor in determining time to failure. CONCLUSION: Argon laser trabeculoplasty is effective in pigmentary glaucoma. Younger patients had a greater chance of success than older patients at all intervals. This became highly significant (P < 0.001) after 3 years.

Adult↗
PubMed1993

Carboplatin ototoxicity: an animal model.

A new animal model of ototoxicity is presented using intravenous carboplatin in adult chinchillas. A range of physiological and morphological effects was produced using doses calculated from the recommended therapeutic range (200-400 mg/m2). Auditory thresholds to tone pips stimuli were monitored using brain stem evoked responses (ABR). Cochlear histopathology was studied by light microscopy (LM) and ultrastructural hair cell abnormalities investigated with scanning electronmicroscopy (SEM). Carboplatin in this animal model predominantly affected the inner hair cells. This may provide an important model for the study of selective loss of the main afferent input in the auditory system.

Animals↗
PubMed1993

Hepatitis C virus antibody positive blood donors.

In an analysis of 15 blood donors referred from the Blood Transfusion Service to the Queen Elizabeth Hospital, Birmingham, more than 50% of anti-hepatitis C virus (HCV) positive patients had a parenteral risk factor. Most were serum HCV-RNA positive, and all were liver HCV-RNA positive. Although no physical signs of liver disease were apparent, all anti-HCV positive donors had abnormal liver histology.

Adult↗
PubMed1992

Helical model of nucleation and propagation to account for the growth of type I collagen fibrils from symmetrical pointed tips: a special example of self-assembly of rod-like monomers.

A model was developed to account for the recent observations indicating that type I collagen fibrils assembled in vivo grow from symmetrical pointed tips. The essential features of the model are (i) a distinctive structural nucleus forms at each end of a growing fibril and growth of the fibril then proceeds by propagation of the two structural nuclei, (ii) the two structural nuclei have similar spiral or helical conformations, and (iii) assembly of each structural nucleus requires two kinds of specific binding steps defined as 3.4 D-period and 0.4 D-period overlaps, but propagation of the nucleus requires only the 3.4 D-period binding step.

Collagen↗