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Biomedical subjects

R James

Publications and source records attributed to R James.

At least 271 records · Page 15Linked to original sources

Role of testosterone and of its metabolites in regulating gonadotrophin secretion in the Japanese quail.

In the Japanese quail gonadal steroids can depress plasma levels of LH and FSH. Since it is now accepted that testosterone metabolites may be metabolized to the tissue-active forms of the hormone, the in-vitro tissue incubation has been combined with steroid replaement therapy in vivo to investigate the physiological roles of various testosterone metabolites as inhibitory feedback agents on gonadtorophin secretion in quail. After the incubation of quail pituitary glands for 3 h with labelled testosterone four metabolites could be identified; androst-4-ene-3,17-dione, 5 beta-dihydrotestosterone (5 beta-DHT), 5 beta-androstane-3 alpha, 17 beta-diol and 5 alpha-DHT. No 5 alpha-androstane-3 alpha, 17 beta-diol was found. Quantitatively, androstenedione was the major metabolite and converison of testosterone to 5 beta-metabolites was significantly greater than to 5 alpha-androgens. Hypothalamic and hyperstriatal tissues converted testosterone than to 5 alpha-androgens. Hypothalamic and hyperstriatal tissues converted testosterone to androstendione, 5 beta-DHT and 5 beta-androstane-3 alpha, 17 beta-diol but not to 5 alpha-DHT or 5 alpha-androstane-3 alpha, 17 beta-diol. Gonadotrophin secretion was studied in castrated quail after chronic s.c. implantation of steroid-containing silicone elastomer capsules or acute injection i.m. of steroid in ethanol: saline. Irrespecive of the route of administration seven androgens, listed in descending order of potency, reduced the increased levels of plasma LH: testosterone: 5 alpha-DHT; androstenedione; 5 alpha-androstane-3, 17-dione; 5 alpha-androstane-3 alpha, 17 beta-diol; 5 alpha-androstan-3 alpha-ol-17-one; 5 alpha-androstan-3 beta-ol-17-one. No changes in levels of plasma LH were observed after the administration of 5 beta-DHT, 5 alpha-androstane-3 beta,17 beta-diol, 5 beta-androstante-3 alpha, 17 beta-diol, 5 beta-androstane-3, 17-dione, androst-5-ene-3 beta, 17 beta-diol or androst-5-en-3 beta-ol-17-one. Testosterone and oestradiol-17 beta were effective in inhibiting secretion of both LH and FSH in young photostimulated quail and completely blocked testicular growth: 5 alpha-DHT inhibited only the release of LH and testicular growth was unaffected.

Androgens↗

Cheilitis granulomatosa. Successful treatment with combined local triamcinolone injections and surgery.

Cheilitis granulomatosa is a rare condition that has traditionally proved difficult to treat satisfactorily. Excellent results were obtained in our case with local triamcinolone acetonide injections and surgery. Histopathologic features of the classic, untreated condition were reviewed and compared to the histopathologic features of labial tissues after a seris of triamcinolone injections. It was found that the injected medication was effective in achieving some reduction of labial volume, apparently through a necrotizing effect of granulomas with subsequent replacement by fibrous scars. Discontinuation of local injections after initial surgery apparently contributed to an exacerbation, as shown by the histopathology of a second cheiloplastic procedure. We therefore recommended that patients with chelitis granulomatosa who are receiving combinaed triamcinolone-surgical therapy continue to receive local triamcinolone injections after surgery in order to minimize the tendency for recurrence.

Cheilitis↗

Urological applications of computerized axial tomography: a preliminary report.

Computerized tomography scanning of the chest and abdomen has been used as a diagnostic technique in more than 4,500 patients since 1974, 190 of whom had histologically proved disorders of the genitourinary system and retroperitoneum. On the basis of this experience computerized tomography scanning has been found to be safe and effective, and offers certain advantages over conventional techniques. The number, extent and content of renal mass lesions can be determined with relatively great accuracy. The presence and extent of metastases into the retroperitoneum, liver and chest can often be shown by computerized tomography scanning when other tests are negative. Placement of needles for aspiration, biopsy, injection of contrast medium or insertion of drainage tubes can be done more accurately under computerized tomography control. Computerized tomography in itself is non-invasive, carries a low radiation exposure comparable to other radiographic procedures and therefore, can be valuable in following the course of patients with various diseases during and after therapy. While scanning will not replace other diagnostic procedures it should lead to a more judicious selection of potentially hazardous tests in selected cases, such as angiography, aspiration and open biopsy.

Adrenal Gland Neoplasms↗

The anthelmintic efficacy of fenbendazole in the control of Moniezia expansa and Trichuris ovis in sheep.

The anthelmintic efficacy of fenbendazole (methyl 5-(phenyl-thio)-2-benzimidazole-carbamate) against Moniezia expansa and Trichuris ovis was tested. At dose rates of 5 mg per kg and above, efficacies were found to be greater than 91 percent against M expansa and greater than 92 per cent against T ovis. At these dose rates efficacy on egg suppression was 100 per cent for Moniezia and greater than 97 per cent for Trichuris.

Animals↗

Evidence of the involvement of an outer membrane protein in DNA initiation.

Protein D of molecular weight 80,000 is incorporated into the membrane of Escherichia coli B/r for a brief fraction of the cell cycle. The protein is incorporated into the outer membrane; its incorporation seems to reflect de novo synthesis and, once incorporated, it is stable. In synchronous acetate-grown cultures a 10-fold increase in the rate of protein D synthesis occurs toward the end of the cell cycle, near the end of one round of DNA synthesis and the start of the next. In synchronous glucose-grown cultures the protein appears approximately halfway through the cell cycle, shortly before DNA synthesis begins. The observed correlation between protein D synthesis and DNA initiation, approximately 15 min later, is strengthened by experiments with inhibitors and mutants. Inhibition of protein synthesis at any time during DNA synthesis delays the subsequent appearance of protein D and the initiation of the next round of DNA synthesis. The synthesis of both protein D and DNA is prevented by nalidixic acid; after its removal a sharp spike of protein D synthesis is followed by a wave of DNA synthesis. Experiments with DNA and DNAB mutants, with amino acid starvation of an auxotroph and with nutritional shift-up, all supported the coupling of protein D synthesis with the initiation of DNA synthesis. The addition of beta-lactam antibiotics which affect murein metabolism dramatically increases the amount of protein D. The cells are prevented from terminating protein D synthesis; different antibiotics have different kinetics of action. Protein D preferentially binds to double-stranded DNA in vitro. We suggest that this protein provides a metabolic link between murein synthesis, protein synthesis, and DNA initiation, and that it acts at a specific time in the cell cycle as an attachment site for DNA to the cell envelope.

Acetates↗

The ectopic secretion of calcitonin by lung and breast carcinomas.

Many patients with advanced non-thyroid malignancies have elevated plasma immunoreactive calcitonin concentrations. Breast and bronchial carcinomas contain immunoreactive calcitonin and an epidermoid bronchial carcinoma has been shown to produce immunoreactive calcitonin in vitro. We have established monolayer cultures of breast carcinomas and eight out of fifteen consecutive carcinomas released immunoreactive calcitonin; some released HCG (human chorionic gonadotrophin) or CEA (carcinoembryonic antigen). In addition, a primary human breast carcinoma has been shown to release and contain calcitonin after being passaged in 'nude' mice over 1 year. Chromatography of extracts and culture media of a bronchical carcinoma demonstrated that, in contrast with the other tumours, it secreted a form or forms of calcitonin having size, charge and immunological differences when compared to calcitonin M. Preliminary evaluation of plasma immunoreactive calcitonin estimations in patients with breast carcinoma showed that twenty-three out of twenty-eight patients with metastatic disease had elevated plasma calcitonin concentrations, whereas only one out of thirteen with localized disease had high levels.

Animals↗

Decomposition of N-(2-chloroethyl)-N-nitrosoureas in aqueous media.

A reinvestigation of the aqueous decomposition of N-(2-chloroethyl)-N-nitrosoureas has shown that their mode of decomposition is dependent upon whether or not the solution is buffered at or near physiological pH. In distilled water, the 2-chloroethyl compounds decompose with the loss of 1 mol, or slightly less, of chloride ion per mole in nitrosourea and the formation of acetaldehyde and 3-4% of 2-chloroethanol. In buffer, the yield of 2-chloroethanol increases to 0.3-0.6 mol per mole of nitrosourea, the yield of chloride ion decreases to 0.5 mol per mole of nitrosourea, and the yield of acetaldehyde decreases to 0.1-0.4 mol per mole of nitrosourea. Evidence for the formation of the vinyl cation, a possible precursor of acetaldehyde, in these reactions is presented. In contrast to the results obtained with the N-(2-chloroethyl)-N-nitrosoureas, the decomposition of N,N'-bis(2-fluoroethy)-N-nitrosourea in distilled water gave almost 1 mol of 2-fluoroethanol per mole of nitrosourea and only 0.04 mol of acetaldehyde per mole of nitrosourea.

Carmustine↗

Inhibition of an early event in the cell division cycle of Escherichia coli by FL1060, an amidinopenicillanic acid.

Analysis of exponential and synchronous cultures of Escherichia coli B/r after the addition of FL1060 indicates a block point for division by this agent some 15 to 20 min before the end of the preceding cell division cycle, a time corresponding to the beginning of the C period of the cell division cycle. Morphological examination of FL1060-treated synchronous cultures of E. coli /r was consistent with inhibition by FL1060 of a very early event in the cell division cycle. This event appears to be essential for normal cell surface elongation in a rod configuration. Temporary treatment of synchronous cultures of E. coli B/r with FL1060 resulted in division delay, the extent of which was a function of the duration of exposure to FL1060. However, even after relatively long times of FL1060 treatment the delayed divisions were still synchronous. Although FL1060 had no direct effect on deoxyribonucleic acid (DNA) synthesis, the synchronous delayed division occuring after temporary treatment with FL1060 were accompanied by a delay in the attainment of resistance of cell division to inhibitors of DNA, ribonucleic acid, and protein synthesis. These results suggest aht an FL1060-sensitive event initiates at the beginning of the C period of the cell division cycle of E. coli and is responsible for normal cell elongation. This cell elongation pathway procedes independently of DNA synthesis, but there is an interaction between this pathway and termination of a round of DNA replication in which a normal rod configuration is necessary to allow a signal for cell division to be generated upon completion of DNA replication.

Cell Division↗

Identification of an outer membrane protein of Escherichia coli, with a role in the coordination of deoxyribonucleic acid replication and cell elongation.

Protein G of molecular weight 15,000 is the fourth commonest protein in the outer membrane of Escherichia coli B/r. From experiments described here on the relationship of protein G production to cell elongation and septation, the hypothesis is proposed that protein G is a structural protein of cell elongation. Furthermore, a surplus of protein G is produced when deoxyribonucleic acid synthesis is arrested and septation is thereby prevented. Thus protein G may be an important coordination protein in E. coli for integration of deoxyribonucleic acid synthesis, cell envelope elongation, and septation. Inhibition of normal cell elongation in a rod configuration in E. coli B/r by the novel amidinopenicillanic acid FL1060 was accompanied by changes in the rate of appearance of protein G and several other outer membrane proteins. The rate of appearance of protein G decreased some 70% within 60 min, in parallel with termination of rounds of normal cell elongation. Filament-inducing concentrations of nalidixic acid increased dramatically the rate of appearance of protein G. After 30 min a plateau level some 250% higher than the control value was reached. Similar kinetics were observed in parallel with filament formation induced by incubation of a dnaB mutant of E. coli at the nonpermissive temperature. No change in the rate of appearance of protein G was observed during cephalexin- or benzylpenicillin-induced filament formation, indicating that increased protein G production was not a secondary consequence of filamentation. Cells treated with FL1060 lost their ability to be induced for protein G formation, with nalidixic acid, in parallel with their loss of ability to initiate rounds of normal cell elongation. A pulse-chase experiment demonstrated that the protein G appearing in the outer membrane as a consequence of inhibition of deoxyribonucleic acid synthesis was the result of de novo synthesis rather than of interconversion from previously synthesized protein species. A preliminary characterization of protein G revealed several similarities with the well-characterized lipoprotein of the outer membrane of E. coli. A comparison of the incorporation of several 14C-labeled amino acids into protein G and the lipoprotein revealed substantial differences, however, perhaps ruling out a simple relationship between these two proteins.

Bacterial Proteins↗

Isolation and partial characterization of macromolecular urinary aggregates containing carcinoembryonic antigen-like activity.

Carcinoembryonic antigen-like substances in the urine of patients with bladder carcinoma and of healthy male subjects occur in a wide range of average molecular sizes. Some of these substances are glycoproteins giving reactions of antigenic identity with carcinoembryonic antigen (CEA) derived from colorectal carcinoma and occur in aggregation with proteins showing antigen specificities of albumin, haptoglobin and the heavy chains of immunoglobulins G, A and M. Recoveries of CEA-like activities, following Sepharose 4B chromatography of urinary materials of molecular size > 3 × 10(4), varied from 40 to 1530%. Treatment with 1 mol/1 HClO(4) caused an apparent solubilization of 85% of the CEA-like activity of such materials from the urine of a patient with bladder carcinoma and raised the specific CEA-like activity of the solubilized product to 379% of that of the untreated materials.

Albumins↗

Immunological study of carcinoembryonic antigen (CEA) and a related glycoprotein.

A comparison has been made of the immunological properties of CEA (carcinoembryonic antigen) and another perchloric acid-soluble macromolecule which occurs in colonic and certain other carcinomata and which is here termed CEX. By using a variety of antisera it was shown that the two substances share common antigenic groups as well as having characteristic ones of their own. These latter groups have enabled the preparation of (a) antisera which give a gel diffusion line only with CEA and (b) and antiserum which gives a line only with CEX. No immunological difference could be found between CEX and the NGP of Mach or the NCA of von Kleist and Burtin. CEX was found in foetal gut, in plasma and associated with CEA in virtually all the tissues and fluids in which the latter occurs; the two appear to go hand-in-hand and no proof was found that CEX is either less or more cancer specific than CEA-it is merely found in greater quantity; neither substance showed absolute cancer specificity. The usefulness of a radioimmunoassay for CEX is discussed, and also the possibility of interference by CEX in the radioimmunoassay for CEA. Evidence of two molecular species of CEA has been found.

Absorption↗