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Biomedical subjects

B Clark

Publications and source records attributed to B Clark.

At least 91 records · Page 5Linked to original sources
PubMed1989

Protein-related abnormalities in keratoconus.

Two-dimensional electrophoretic maps of extracts from eleven normal and eleven keratoconus corneas were compared. Of the eleven corneas analyzed, eight were pooled and the remaining three were analyzed individually. Several differences were demonstrated between electrophoretic patterns of normal and keratoconus corneas. In keratoconus corneas, 1) two abnormal components (MW 54kD and 26kD) were observed; 2) three normal corneal components (MW 12kD, 14kD, and 39kD) were present in significantly higher amounts; and 3) three normal corneal proteins (MW 66kD, 55kD, and 13kD) were present in reduced amounts. The molecular weight and isoelectric point of one of the normal corneal proteins that we found to be reduced in keratoconus corneas were close to that of a subunit of prolyl-4-hydroxylase, an enzyme required for hydroxylation of proline residues of collagen. The possibility the abnormal proteins detected in the keratoconus corneas were derived from those normal corneal proteins which were absent or were present in reduced amounts in the keratoconus corneas remains to be established. This study may provide protein markers for elucidation of the biochemical abnormality in keratoconus.

Adult↗
PubMed1988

Pharmacodynamic profile of CQP 201-403, a novel 8 alpha-amino-ergoline.

The profile of action in animals of CQP 201-403, a novel 8 alpha-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and be more potent than bromocriptine (Parlodel).

Animals↗
PubMed1988

A clinical, histopathologic, and molecular biologic investigation of vulvar intraepithelial neoplasia.

The spectrum of vulvar intraepithelial neoplasia (VIN) was investigated with human papillomavirus (HPV) DNA probes by Southern blot hybridization technique. The results of vulvar tissue examinations from 25 patients were compared to prior genital and systemic diseases, clinical presentation, and histopathologic manifestations. The presence of HPV DNA in these lesions was largely associated with multifocality of the lesions, the presence of synchronous and metachronous multicentric genital neoplasia, and depressed immunocompetence. These findings indicate that VIN is associated with HPV and may have an infectious etiology.

Adult↗
PubMed1988

Myristylation of rotavirus proteins.

After labelling with [3H]myristic acid during replication the structural proteins VP6 and VP2 of purified rotavirus particles were found to be myristylated in an amide bond. [3H]Palmitic acid was converted to myristic acid before bonding to the viral proteins. Possible functions of rotavirus protein myristylation are discussed.

Capsid↗
PubMed1987

7S IgM in the sera of patients with arthritis.

Using radial immunodiffusion in 7% agarose, 7S IgM was quantified in the sera of 45 normal individuals, 37 patients with rheumatoid arthritis (RA), 18 patients with psoriatic arthritis and 11 patients with ankylosing spondylitis. 7S IgM was only found in the sera of patients with RA, 43% of whom had detectable levels of 7S IgM (median 47.5 micrograms/ml). The patients with 7S IgM had significantly higher IgM rheumatoid factor (IgM RF) and C-reactive protein levels in their sera (p less than 0.005). There was a strong correlation between 7S IgM and IgM RF levels in the sera of these patients. These data demonstrate that patients with more active and severe disease have 7S IgM present in their sera but the absence of 7S IgM from the sera of some patients with high levels of IgM RF and CRP suggest that additional factors may influence the synthesis and secretion of 7S IgM by B cells in RA.

Arthritis↗
PubMed1987

Heterogeneity of genome rearrangements in rotaviruses isolated from a chronically infected immunodeficient child.

Rotaviruses with genome rearrangements, isolated from a chronically infected immunodeficient child, were adapted to growth in BSC-1 cells. Preparations of viral RNA from fecal extracts showed a mixed atypical rotavirus RNA profile, which was due to the presence of at least 12 subpopulations of viruses grossly differing in genotype. Besides various forms of genome rearrangements involving segment 8-, 10-, and 11-specific sequences, reassortment in vivo was likely to have occurred during the emergence of these viruses. The protein products of viral genomes with various forms of segmental rearrangements seemed to be largely unaltered. Genome rearrangement is proposed to be a third mechanism directing the evolution of rotaviruses.

Animals↗
PubMed1987

Antineoplastic effects of tumor necrosis factor alone and in combination with gamma-interferon on tumor biopsies in clonogenic assay.

Tumor colony-forming cells were grown from fresh biopsy specimens from 102 patients with a variety of nonhematologic malignant neoplasms and exposed in vitro to pharmacologically achievable doses of recombinant human tumor necrosis factor (rTNF). In 68 instances, the tumor specimens were also tested against recombinant human gamma-interferon (rIFN-gamma), as well as the combination of rTNF and rIFN-gamma. rTNF exhibited dose-dependent and tumor-type-dependent antitumor effects. Sensitivity to rTNF at doses of less than 100 U was observed in 28% of the tumors tested. A higher than average frequency of sensitivity was observed in colorectal and lung cancer. Resistance to rTNF was observed in 42% of the tumors, including 52% of the ovarian cancer specimens tested. In paired experiments, exposure of tumor specimens to rTNF and rIFN-gamma in combination often resulted in a greater antitumor effect than was observed with either agent alone, with at least subadditive effects seen in 62% of the specimens tested against the combination. Antagonism between rTNF and rIFN-gamma was observed in 18% of the studies. Overall, exposure to the combination of rTNF and rIFN-gamma reduced the dose of rTNF required for significant antitumor activity by about threefold. Normal bone marrow granulocyte-macrophage colony-forming cells were also tested against both rTNF and rIFN-gamma and the combination. The bone marrow progenitors were more sensitive to rTNF and the combination with rIFN-gamma than were the tumor cells; however, the significance of this comparison between two different in vitro assay systems is indeterminate. Based on our observations, rTNF warrants phase II clinical trials in selected solid tumors with definite emphasis on colorectal and lung cancer. Additionally, studies of the combination of rTNF and rIFN-gamma are indicated and will be of particular interest in endometrial and breast cancer.

Antineoplastic Agents↗
PubMed1986

Control of biliary phospholipid secretion. Effect of continuous and discontinuous infusion of taurocholate on biliary phospholipid secretion.

A major determinant of biliary lipid secretion is bile-salt secretion. Taurocholate (TC), a micelle-forming bile salt, was infused continuously at different rates in both isolated perfused livers and biliary-fistula rats. In both of these systems, infusion of TC brought about an elevated secretion of phosphatidylcholine for the duration of the TC infusion period. Initial phospholipid/bile-salt ratios in the bile were higher in the whole-animal model than in isolated livers, but at the higher infusion rates both secreted approx. 6 mol of phospholipid for every 100 mol of bile salt. The secretion of phospholipid, which was maintained even at high rates of bile-salt infusion, suggest a continuous and regulated phospholipid supply and secretion mechanism. In contrast, however, multiple short pulses of TC to the perfused liver, which brought about relatively equal biliary bile-salt output pulses, did not bring about equal phospholipid outputs, since the phospholipid peak size declined with each bile-salt pulse. These experiments taken together suggest either that a threshold (intracellular) bile-salt concentration may be required to 'switch-on' the phospholipid supply and that it may need to be maintained for continuous biliary phospholipid supply to the canalicular membrane.

Animals↗
PubMed1986

Pilot study of phenytoin in rheumatoid arthritis.

The anticonvulsant drug phenytoin has several interesting immunological properties which could theoretically be of benefit in the treatment of rheumatoid arthritis. For this reason a pilot study has been carried out on 11 patients with active classical or definite disease. Seven patients completed a 20 week course of treatment and showed continuous improvement at 12 and 20 weeks and some deterioration eight weeks after the drug was stopped. Laboratory and clinical measurements of disease activity responded favourably during the treatment period, suggesting that phenytoin may have second line activity.

Adult↗
PubMed1986

Potency of natural and synthetic canine gastrin-releasing decapeptide on canine antral muscle.

The carboxyl terminal decapeptide of gastrin-releasing peptide (GRP-10), a small, naturally occurring bombesin-like peptide, has been isolated from canine antral muscle, synthesized, and its bioactivity compared with other synthetic and natural gastrin-releasing peptides on stimulation of spontaneously occurring contractions of canine circular antral muscle in vitro. Concentrations of peptides were verified by amino acid analysis and radioimmunoassay. In this system three forms of natural canine GRP, synthetic GRP-10, synthetic porcine gastrin-releasing heptacosapeptide (GRP-27), [Gln3]GRP-10, and [Arg3]GRP-10 all were similar in potency to synthetic amphibian bombesin. These results differ from the low activity of GRP-10 previously reported in rat brain. The full biological potency on canine antral motility and the presence of GRP-10 in nerve fibers in the gut and in the spinal cord suggest a possible role for this peptide as a neurotransmitter or neuromodulator in regulation of smooth muscle contraction.

Amino Acids↗
PubMed1986

Nedocromil sodium preclinical safety evaluation studies: a preliminary report.

The preclinical safety evaluation programme for nedocromil sodium was conducted to examine the toxicity potential of the compound in animals and to support its chronic use in man by the inhalation route. Tests, from single-dose to 'lifetime' studies, were conducted in mouse, rat, rabbit and dog at high doses and by various routes of administration. This programme evaluated nedocromil sodium in terms of its general and reproductive toxicology, mutagenic and carcinogenic potential and other areas of interest. Nedocromil sodium proved to be safe, with a low order of toxicity and high safety margins. The results of the preclinical safety programme support the chronic use of nedocromil sodium in humans.

Animals↗
PubMed1985

An assessment of a toxicological incident in a drug development program and its implications.

In an exceptionally thorough program of preclinical toxicity testing in laboratory animals of the anti-allergy drug FPL 52757 (6,8-diethyl-5-hydroxy-4-oxo-4H-1-benzopyran-2-carboxylic acid), no significant hepatotoxic potential was detected. Despite this evidence of safety in a wide range of laboratory animals, the drug produced mild reversible hepatotoxicity in some patients in some clinical trials. Extensive toxicity and investigational studies are described, and the importance of the correct choice of species for toxicology evaluations based on sound pharmacokinetic principles is highlighted. This paper reviews this incident and the lessons to be learned from it in light of current regulatory requirements.

Animals↗