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Biomedical subjects

A J Cooper

Publications and source records attributed to A J Cooper.

At least 217 records · Page 12Linked to original sources
PubMed1984

Strategies for the drug treatment of depression.

Antidepressants are a useful addition to a physician's therapeutic armamentarium, but because they are used to treat disorders of diverse and largely unknown cause, there is a much greater element of chance associated with their use than with the use of many other types of drugs (e.g., antibiotics and analgesics). Nevertheless, empirically derived treatment schemes, applied systematically, increase the odds of a favourable response and are preferred to haphazard prescribing. To date, no one antidepressant has been shown to be more effective than any other, although the newer agents are alleged to be faster acting, more specific and less toxic than the established drugs. However, generally, such claims have not been proven clinically. Unless there are overwhelming contraindications (e.g., intolerable side effects, an idiosyncratic response or coexisting cardiac disease) the established agents, with their proven efficacy, are preferred initially.

Antidepressive Agents↗
PubMed1984

Prognostic factors and in vitro cytotoxic sensitivity in colorectal cancer.

The poor response rates to chemotherapy for colorectal cancer justify attempts to rationalize selection of patients for treatment, and the development of systems to evaluate new cytotoxic agents. Refinement of prognostic indices may identify colorectal cancer patients at a higher risk of recurrence who merit more aggressive treatment. We report our experience with the stem cell assay and pulse thymidine labelling in 43 primary colorectal cancers. Thirty-six tumours were evaluable, and clonogenic growth was obtained in 30 (83 per cent). In 24 tumours (67 per cent) growth was adequate for meaningful interpretation of a cytotoxic drug assay. Frequency of growth and colony forming efficiency did not correlate with histopathological grade, Dukes' stage or tumour cell kinetic indices. Thymidine labelling indices correlated with Dukes' stage (A and B versus C and D, P less than 0.01, Mann-Whitney U test). Cytotoxic assays with 5-fluorouracil and 5'-deoxy-5-fluorouridine were undertaken in 18 cases (14 primary carcinomas, 4 malignant ascites), of which 14 were evaluable and 3/14 (21.5 per cent) were chemosensitive in vitro. Both drugs were equally effective in vitro at clinically attainable plasma concentrations. This is in accordance with the response rates observed clinically with 5-FU chemotherapy in colorectal cancer.

Antineoplastic Agents↗
PubMed1984

Oxime formation between alpha-keto acids and L-canaline.

Canaline reacts rapidly with glyoxylate, but more slowly with other alpha-keto acids, to form stable oximes. Oxidation of L-canaline with L-amino acid oxidase yields the cyclic, internal oxime, isoxazoline-3-carboxylate. L-Canaline-alpha-keto acid oximes are also substrates of L-amino acid oxidase, yielding isoxazoline-3-carboxylate, alpha-keto acid, and ammonia.

Amino Acid Oxidoreductases↗
PubMed1984

A clinical trial of the beta blocker propranolol in premature ejaculation.

Twelve male patients, with a primary complaint of premature ejaculation in a setting of chronic anxiety with prominent somatic manifestations, participated in a double-blind trial: propranolol against placebo. The study consisted of 5 X 4 week phases: run-in, propranolol or placebo--120 mg/day allocated randomly, wash-out; placebo or propranolol and run-out, in a balanced design. Anxiety was rated initially, and every 2 weeks, throughout the trial using the Hamilton Rating Scale. Sitting blood pressure and pulse were also noted. The time to coital ejaculation (every 3 days) was recorded using a stopwatch, and subjects were also required to rate "overall coital satisfaction" and "quality of erection". Neither prematurity nor other signs/symptoms of anxiety improved on the preparations, which were statistically equivalent. Moderate beta-blockade was achieved with propranolol as evidenced by a median reduction in pulse rate of 5 beats/min.

Adolescent↗
PubMed1984

Sister Mary Joseph's nodule: a clinical and histologic study.

The clinical and histologic findings in eighty-five cases of tumors metastatic to the umbilicus were studied. Clinically, the lesions were seen as firm, indurated nodules, sometimes with fissuring or ulceration. In twelve cases, the initial presentation of the internal primary malignancy was an umbilical nodule. Histologic material from the metastatic umbilical tumor was studied in all cases but was diagnostic of the primary carcinoma in only twenty-one. In seventeen cases, the primary site was never reliably determined, while stomach, large bowel, ovary, and pancreas were the most frequent primary sites in the other cases. Most patients died within months after the appearance of the umbilical tumors, thus emphasizing the ominous significance of this sign of metastatic, usually intra-abdominal, malignant disease.

Adenocarcinoma↗
PubMed1983

Inhibition of glutamate-aspartate transaminase by beta-methylene-DL-aspartate.

beta-Methylene-DL-aspartate, a new beta, gamma-unsaturated amino acid, is an irreversible inhibitor of soluble pig heart glutamate-aspartate transaminase (Ki approximately 3 mM with respect to the L-form; limiting rate constant for inactivation approximately 0.4 min-1). The new amino acid is the most specific inhibitor of glutamate-aspartate transaminase thus far studied. It does not inactivate pig heart glutamate-alanine transaminase, soluble rat kidney glutamine transaminase K, gamma-aminobutyrate transaminase (from Pseudomonas fluorescens), glutamate decarboxylase (Escherichia coli), snake venom L-amino acid oxidase, or hog kidney D-amino acid oxidase. In addition, the following enzymes were not inhibited by beta-methylene-DL-aspartate in rat tissue homogenates: gamma-aminobutyrate transaminase (brain), tyrosine transaminase (liver), glutamine transaminase L (liver), asparagine, transaminase (liver), ornithine transaminase (liver) or branch-chain transaminase(s) (kidney). Intraperitoneal injection of beta-methylene-DL-aspartate into mice decreased kidney and liver glutamate-aspartate transaminase activities but had no effect on liver glutamate-alanine transaminase activity.

Amino Acid Oxidoreductases↗
PubMed1983

Cyclophosphamide pretreatment in tumor cryotherapy: a comparison with alternative drugs.

The method of Turk and Lagrange for modulating immune responses in favor of the cell-mediated effector arm by using single high doses of cyclophosphamide 3 days before antigen has previously been shown to cause decreased rates of local tumor recurrence when adapted as an adjunctive therapy to cryosurgery in a murine model. This series of experiments compares cyclophosphamide, azathioprine, and methotrexate against cryosurgery alone in the same therapeutic protocol. Only cyclophosphamide gave enhanced numbers of cures; azathioprine caused an increase in metastases arising concurrently with local tumor recrudescence.

Animals↗
PubMed1983

Use of beta-methylene-D,L-aspartate to assess the role of aspartate aminotransferase in cerebral oxidative metabolism.

Several inhibitors of aspartate aminotransferase, a key enzyme of the malate-aspartate shuttle, were investigated for their effects on cerebral oxidative metabolism in vitro. beta-Methylene-D,L-aspartate (2 mM), aminooxyacetate (0.1 mM), and D,L-vinylglycine (20 mM) all significantly reduced the activity of aspartate aminotransferase and the rate of oxygen consumption of rat cerebral cortex slices respiring on glucose. In the presence of beta-methyleneaspartate, a one-to-one correlation was found between the degree of inhibition of tissue respiration and the degree of inhibition of transaminase activity. Slices of rat liver incubated in the presence of glucose and beta-methyleneaspartate showed a similar one-to-one relationship between inhibition of oxygen comsumption and inhibition of aspartate aminotransferase activity, whereas with rat kidney cortex slices, the inhibition of aspartate aminotransferase activity was greater than the inhibition of oxygen consumption. Structural analogs of beta-methyleneaspartate (D,L-beta-methyl-D,L-aspartate, gamma-methyl-D,L-glutamate, and alpha-methyl-D,L-didehydroglutamate) that did not inhibit the activity of aspartate aminotransferase similarly did not inhibit the rate of oxygen consumption by cerebral cortex slices. In the presence of beta-methyleneaspartate, pyruvate oxidation by cerebral cortex slices was inhibited to almost the same extent as was glucose oxidation, and the oxidation of succinate was decreased by approximately 20%. The artificial electron acceptor phenazine methosulfate (0.1 mM) only partially overcame the beta-methyleneaspartate-mediated inhibition of respiration with glucose as substrate. The content of ATP and phosphocreatine declined steadily in slices incubated with glucose and beta-methyleneaspartate. At 1 h the concentration of lactate and the lactate/pyruvate ratio, an indicator of the cytoplasmic redox state, increased threefold, whereas the concentrations of malate, citrate, and aspartate decreased. The findings are interpreted in the context of the hypothesis that enzymes common to the malate-aspartate shuttle and the tricarboxylic acid cycle are physically complexed in brain, so that inhibition of aspartate aminotransferase, a component of the complex, impedes the flow of carbon through both metabolic pathways.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminooxyacetic Acid↗
PubMed1983

Biochemistry of sulfur-containing amino acids.

The literature on sulfur amino acid metabolism is too vast for a short chapter to cover in great depth. I attempt here a brief overview with references to many specialized review articles. This review emphasizes aspects of sulfur amino acid metabolism elucidated in the last ten years, in particular aspects not generally covered in biochemistry texts, e.g. transaminative pathways of methionine metabolism. A selected list of reviews is given in references 1-15. References to reviews on glutathione are covered in the chapter by A. Meister in this volume (1a).

Adenosine↗
PubMed1983

A comparative study of bupropion and amitriptyline in depressed outpatients.

A double-blind controlled trial comparing a standard antidepressant drug, amitriptyline, with a new compound, bupropion, was conducted at six centers. There was a placebo washout, after which patients were assigned in a randomized fashion to one of the two treatments. No significant difference was found in therapeutic response to the two drugs after 4 weeks of treatment. Anticholinergic and cardiovascular side effects were less common in the bupropion-treated patients.

Adolescent↗
PubMed1982

On the chemistry and biochemistry of 3-mercaptopyruvic acid, the alpha-keto acid analog of cysteine.

3-Mercaptopyruvate, generally believed to be formed by enzymatic transamination of L-cysteine and by the oxidative deamination of L-cysteine, has been found to exist in solution, in equilibrium with the cyclic dimer, 2,5-dihydroxy-1,4-dithiane-2,5-dicarboxylic acid; the equilibrium markedly favors the cyclic dimer in aqueous solution at pH 5-7. However, in neutral solutions, and especially in alkaline solution, 3-mercaptopyruvate undergoes very rapid and irreversible conversion to an acyclic aldol dimer. The rate of aldol dimerization is about 100 times greater than that of pyruvate dimerization under comparable conditions. Thus, 10 mM solutions of 3-mercaptopyruvate at pH 7.2 lose about 75% of their lactate dehydrogenase reactivity in 90 min at 25 degrees C. The present findings explain the previous observation that 3-mercaptopyruvate exhibits anomalous behavior in transamination with glutamine. Oxidative deamination of L-cysteine by L-amino acid oxidase yields the highly reactive imine, 2-imino-3-mercaptopropionic acid, which can be quantitatively trapped with semicarbazide. In the absence of semicarbazide, almost quantitative formation of ammonia from L-cysteine occurs with only a 10-20% yield of alpha-keto acid, none of which is 3-mercaptopyruvate; however, 3-mercaptopyruvate may be trapped as 3-mercaptolactate when the oxidase reaction is carried out in the presence of lactate dehydrogenase and NADH. One of the physiological functions of glutamine transaminase may be to convert 3-mercaptopyruvate to L-cysteine, thus preventing its loss through further transformations. In the course of this work it was found that hemithioketals (formed by reaction of cysteine with alpha-keto acids) are substrates of L-amino acid oxidase. Evidence for the cyclic dimer in the solid and vapor states of 3-mercaptopyruvate has been found through infrared and mass spectroscopic observations.

Amino Acid Oxidoreductases↗
PubMed1982

Does lofepramine have fewer side effects than amitriptyline? Results of a comparative trial.

A double blind trial was carried out comparing the tricyclic antidepressant lofepramine with amitriptyline in the treatment of patients suffering from moderate to markedly severe depression. No difference was demonstrated between the two drugs in terms of their antidepressant effect, but patients treated with lofepramine suffered from significantly less side effects than patients treated with amitriptyline. Both groups of patients had a high drop out rate but this was less marked in the groups of patients treated with lofepramine.

Adolescent↗
PubMed1982

Hematologic malignancies occurring in patients with urticaria pigmentosa.

Six patients had hematologic malignancies and coincident urticaria pigmentosa, five with the disseminated maculopapular form and one with the plaque form. Two patients had the juvenile-onset variety; the remainder had the adult eruptive variety. None of the patients complained of symptoms that could be attributed to liberation of histamine. In the two patients with juvenile-onset urticaria pigmentosa, the hematologic malignancies developed at the age of 17 years; one had Hodgkin's disease, and the other had acute myelomonocytic leukemia. In three patients with adult eruptive urticaria pigmentosa, the cutaneous lesions developed within 12 months of the diagnoses of lymphocytic lymphoma (two patients) and evolving myelomonocytic leukemia (one patient). In the remaining patient, cutaneous lesions developed many years before chronic lymphocytic leukemia was diagnosed. None of the patients had systemic mastocytosis. Skin biopsy specimens from all six patients showed an increase in dermal and perivascular round cells, and mast cells were seen in specimens from five of the six patients. In patients who received cytotoxic drugs for the hematologic malignancy, there was no change in the urticaria pigmentosa.

Adolescent↗
PubMed1982

Epidermoid hidradenoma. A clinicopathologic study.

Clinical and histopathologic data in 8 cases of epidermoid hidradenoma are presented. Most of the tumors were in the head and neck, and most of the patients were middle-aged and older adults. Generally, the lesions were asymptomatic nodules that sometimes showed ulceration or rapid growth. Despite having some histologic atypia or focal mitotic activity, the tumors were found to be benign on long-term evaluation. This epidermoid variant should not be otherwise differentiated from the benign group of solid-cystic hydradenomas, because cytologic variability did not predict a significant change in prognosis.

Adenoma, Sweat Gland↗