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Biomedical subjects

R Green

Publications and source records attributed to R Green.

At least 343 records · Page 19Linked to original sources
PubMed1987

Activation of blood coagulation in Crohn's disease. Increased plasma fibrinopeptide A levels and enhanced generation of monocyte tissue factor activity.

We have examined the relationships among activation of blood coagulation, generation of monocyte procoagulant activity, and clinical activity in patients with Crohn's disease. Subclinical activation of blood coagulation was measured using a radioimmunoassay for fibrinopeptide A. Fibrinopeptide A levels were strongly correlated with the level of disease activity as measured by the Crohn's disease activity index. Patients with active disease who were successfully treated either medically or surgically demonstrated a reduction of fibrinopeptide A levels. Failure of fibrinopeptide A to return to the normal range predicted an early relapse. Monocyte tissue factor generation was assessed in both unstimulated and lipopolysaccharide-stimulated mononuclear cell cultures obtained from the peripheral blood of patients with Crohn's disease. A strong correlation (r = 0.89) was observed between plasma fibrinopeptide A levels and monocyte tissue factor generation. These results suggest that monocyte procoagulant generation may contribute to the activation of blood coagulation in this inflammatory bowel disease. Moreover, fibrinopeptide A levels in Crohn's disease may provide a useful quantitative measure of inflammatory activity.

Adolescent↗
PubMed1986

Infusional cisplatin plus cyclophosphamide in advanced ovarian cancer.

Twenty-one patients with previously untreated advanced ovarian cancer received a two-drug regimen of cisplatin delivered as a systemic infusion at 20 mg/m2/d for 5 days concomitant with oral cyclophosphamide 150 mg/d in divided doses. Courses were repeated at 3- to 4-week intervals. Responses were observed in 14 of 19 evaluable patients (74%) with three complete responses (one pathologically confirmed at second-look laparotomy) and 11 partial responses. Median time to disease progression in the responders was 12 months (range, 4 to 24 months with four patients maintaining remission at 11, 13, 14, and 19 months). The median survival for the entire group was 12 months (range, 1 to 64 months). A higher-than-expected frequency of nephrotoxicity (38%) and neurotoxicity (24%) was observed, suggesting that infusional cisplatin may lead to cumulative adverse effects and necessitate limiting the number of courses delivered in this fashion. Forty-three percent of patients received less than four courses of therapy related to these two categories of toxicity. The therapeutic effect of infusional cisplatin may be comparable to previous reports of bolus schedules in ovarian cancer when employed in combination with cyclophosphamide but the non-hematologic toxicities are substantial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Secretion of somatostatin by Saccharomyces cerevisiae. Correct processing of an alpha-factor-somatostatin hybrid.

Somatostatin is a 14-amino acid peptide hormone that is proteolytically processed from its precursor, prosomatostatin, by a paired-basic-specific protease localized in the Golgi apparatus and secretory vesicles. Yeast (Saccharomyces cerevisiae MAT alpha) synthesize an analogous peptide hormone precursor, pro-alpha-factor, that contains tandem repeats of alpha factor (13 amino acids) flanked by spacers that include paired basic residues. To investigate the role of these two pro regions in mediating intracellular transport and processing, cloned genes specific for preprosomatostatin and prepro-alpha-factor were used to generate recombinants encoding hybrids between the alpha-factor pro region (amino-terminal) and somatostatin (carboxyl-terminal). These recombinants were inserted into yeast expression vectors under control of either the native alpha-factor promoter or the inducible yeast PHO5 (acid phosphatase) promoter. Yeast transformed with these plasmids expressed the hybrid messenger RNAs constitutively (alpha-factor promoter) or when induced in phosphate-deficient medium (PHO5 promoter). Radioimmunoassay of culture media revealed the secretion of up to 200 ng of immunoreactive somatostatin/10(7) cells. Metabolic labeling with [35S]cysteine, followed by immunoprecipitation with anti-somatostatin antibodies revealed two forms of hybrid precursor intracellularly, one of Mr 25,000, containing core carbohydrates, and a second of Mr 11,000, which was unglycosylated. Translation of mRNA extracted from these transformants in the wheat germ cell-free system revealed that the Mr 11,000 form was the primary translation product, whereas the Mr 25,000 species could be generated in vitro by inclusion of mammalian rough microsomes. The secreted immunoreactive material was shown to be authentic somatostatin by high pressure liquid chromatography analysis and protein sequencing. These results demonstrate that the yeast processing enzymes recognize these chimeric precursors, resulting in the secretion of the mature peptide hormone.

Chromatography, High Pressure Liquid↗
PubMed1986

Visualization of the receptor for transferrin on K562 cells by a rosette-forming assay.

A method is described to visualize the receptor for transferrin by a rosette-forming assay. K562 cells, a human pre-erythroid leukemia cell line, were used as a source of receptor-positive cells. Bovine erythrocytes coated with human transferrin by the CrCl3 method were used as indicator cells. Rosette formation occurred at 37 degrees C but not at 4 degrees C, and was inhibited by soluble transferrin in a dose-dependent manner. Human lactoferrin, which is known to have considerable amino acid sequence homology with transferrin, did not inhibit rosette formation with transferrin-coated bovine erythrocytes. A variety of blocking and non-blocking monoclonal antibodies against the human transferrin receptor (42/6, B3/25 and OKT9) inhibited rosette formation. Rosettes are able to withstand low-speed centrifugation (130 X g, 2 min) making this method potentially useful for cytochemical identification of receptor-positive or receptor-negative cells. Also, it was possible to enrich receptor-positive cells by separation of rosette-forming from non-rosette-forming cells using a density gradient centrifugation technique.

Animals↗
PubMed1986

Lesbian mothers and their children: a comparison with solo parent heterosexual mothers and their children.

Two types of single-parent households and their effects on children ages 3-11 years were compared. One type comprised 50 homosexual mothers and their 56 children, and the other was a group of 40 heterosexual mothers and their 48 children. There were 30 daughters and 26 sons of homosexual mothers and 28 daughters and 20 sons of heterosexual mothers. The sexual identity and social relationships of the children were assessed in relation to the sexual orientation of the mothers. The samples consisted of families from rural and urban areas in 10 American states. All have lived without adult males (18 years or older) in the household for a minimum of 2 years (average 4). Families with heterosexual mothers were matched to families with homosexual mothers on age and race of mother; length of mother and child separation from father; educational level and income of mother; and number, age, and sex of children. Data are reported from childrens' tests designed to provide information on general intelligence, core-morphologic sexual identity, gender-role preferences, family and peer group relationships, and adjustment to the single-parent family. No significant differences were found between the two types of households for boys and few significant differences for girls. Concerns that being raised by a homosexual mother might produce sexual identity conflict and peer group stigmatization were not supported by the research findings. Data also revealed more similarities than differences in parenting experiences, marital history, and present living situations of the two groups of mothers. The postulated compromised parental fitness of lesbian mothers, commonly asserted in child custody cases, is not supported by these data.

Adult↗
PubMed1986

On the expression of H-Y antigen in transsexuals.

Histocompatibility-Y (H-Y) antigen, the presumptive inducer of the mammalian testis, is present in the cells of normal males and not in the cells of normal females. Recent reports have implied that patients with transsexualism exhibit H-Y antigen phenotypes at variance with those of normal males and females and, thus, that H-Y serology might provide a tool for the diagnosis and study of the transsexual condition. We therefore evaluated blood and testicular cells from 21 male-to-female transsexuals using conventional and monoclonal H-Y antibodies. We found no evidence of abnormal H-Y phenotype. Five of the patients were interviewed postoperatively by two examiners and rated for the diagnosis of transsexualism. Three of the five were rated primary transsexual by one or both examiners, and two were rated secondary transsexual.

Adult↗
PubMed1986

Vitamin B12 neuropathy is not due to failure to methylate myelin basic protein.

It has been proposed that the biochemical lesion in subacute combined degeneration of the cord due to vitamin B12 deficiency, is impaired methylation of residue 107 (arginine) in myelin basic protein. We have examined myelin basic protein in brains of rats in which vitamin B12 was inactivated by exposure to nitrous oxide for up to 7 days. In addition brains of fruit bats in which vitamin B12 neuropathy had been produced by feeding washed, and hence vitamin B12-free fruit, were examined. There was no difference in the methylation of arginine 107 in myelin basic protein in these animals as compared to healthy control animals. Rats given an inhibitor of transmethylation reactions (cycloleucine) showed the expected fall in methylation of myelin basic protein.

Animals↗
PubMed1986

Bearing illness: study of couples where the husband awaits coronary graft surgery.

This paper reports findings from the first of a series of interviews with men treated by coronary grafting, and with their wives. Seen immediately after angiography, these couples were asked about their social and conjugal roles, attitudes to the men's illness, and changes to their circumstances. Clustering the couples on these responses yielded four groups: strained relationships in which husbands who had given up work had become withdrawn but were supported by wives who had increased the burden of their responsibilities; strained relationships in which husbands forced to give up outside engagements took on household duties from wives who were less concerned about their spouses' activity levels; where husbands who had modified their activities, and wives who showed most concern, together made mutual adjustments in relation to the illness; where husbands had experienced little need for change and, together with their wives, had largely maintained a 'normal' life. A measure of adjustment to illness showed that there were parallels between the relationship of patient to illness, and of husband to wife in each group. A theoretical proposal is offered integrating these two forms of relationship, and inferences are drawn regarding the counselling of patients and wives in the period prior to graft surgery.

Adaptation, Psychological↗
PubMed1986

Effect of posture on plasma immunoreactive atrial natriuretic peptide concentrations in man.

The effect of changes of posture on plasma atrial natriuretic peptide concentrations and renal function was studied in normal human volunteers. Plasma atrial natriuretic peptide concentrations increased in the supine posture, reached a maximum value after 30-60 min, remained elevated for 4 h and decreased to baseline values on return to the upright posture. Inflation of antishock trousers, which apply positive pressure to the legs and lower abdomen, attenuated the fall in plasma atrial natriuretic peptide concentration in the upright position. In the supine posture there were increases in urine flow rate, sodium, lithium, fractional sodium and fractional lithium clearances. Fractional distal water and sodium excretion, and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, also increased. Heart rate and systolic and diastolic blood pressures decreased in the supine and increased on return to the upright posture. Inflation of antishock trousers prevented the increase in heart rate in the upright posture. The contribution of haemodynamic factors to the increase in plasma atrial natriuretic peptide concentrations in the supine position and the relationship between this increase and the associated changes in renal function are discussed. However, the contribution of atrial natriuretic peptide to these changes is uncertain.

Adult↗
PubMed1986

Monocyte ferritin in idiopathic haemochromatosis, thalassaemia and liver disease.

Monocyte ferritin (MF) content was measured in normal subjects and patients with a variety of disorders of iron storage. MF was above the normal range in 4 patients with idiopathic haemochromatosis (IHC). However, in 4 patients with transfusion siderosis (TS), secondary to aplastic anaemia, who had similar elevations in serum ferritin, MF was highly elevated. 10 patients with thalassaemia intermedia and thalassaemia major with no previous history of transfusions, but with elevated serum ferritin, also had significantly elevated MF. Disproportionately low MF in IHC could reflect defective ferritin metabolism in reticuloendothelial cells in this disorder. Finally, in 3 patients with acute rises in serum ferritin caused by acute hepatitis, MF was not increased. This suggests that MF is not directly affected by high circulating levels of serum ferritin raised acutely, but rather reflects iron storage status in conditions not associated with primary disorders of iron metabolism.

Acute Disease↗
PubMed1986

Morphological, biochemical and secretory studies on rat pancreatic ducts maintained in tissue culture.

Interlobular ducts were isolated from the pancrease of copper-deficient rats and maintained in culture on polycarbonate filter rafts. Within 8 h the ends of the ducts had sealed. This was followed by a marked dilatation of the lumen, a flattening of the epithelium against the surrounding connective tissue layer and an over-all swelling of the duct. Apart from a reduction in their height, a fall in the number of intracellular fat droplets and a widening of intercellular spaces, epithelial cells within the cultured ducts retained all the ultrastructural characteristics of those in freshly isolated preparations. The basal concentration of adenosine 3',5'-phosphate (cyclic AMP) in the cultured ducts was 43.3 +/- 6.8 mumol.1-1 duct epithelium (n = 5) and was increased to 188.9 +/- 55.2 mumol.l-1 duct epithelium (n = 5) in the presence of 10(-8) M secretin. The basal rate of fluid secretion, measured using micropuncture techniques, was 0.16 +/- 0.03 nl.h-1.nl-1 duct epithelium (n = 12). This was increased 14-fold by 10(-8) M secretin while the dose of the hormone required for half-maximal secretion was about 2 X 10(-11) mol.l-1. The concentration of chloride ions in secreted fluid and perifusion buffer were similar. Variation in culture time up to 52 h had no effect on fluid secretion, and the response to secretin was dependent on the presence of bicarbonate ions in the perifusion fluid. N6,O2-dibutyryl adenosine 3',5'-phosphate (dibutyryl cyclic AMP) also increased fluid secretion but caerulein had no effect. We suggest that isolated ducts secrete fluid at comparable rates to ducts in situ within the pancrease of copper-replete rats.

Animals↗
PubMed1986

Fluid reabsorption by the proximal convoluted tubule of the kidney in lactating rats.

Using free-flow micropuncture techniques, the rate of reabsorption from the proximal convoluted tubules was measured in virgin, 19-day-pregnant and 6- to 7-day-lactating Sprague-Dawley rats. In separate groups of animals proximal convoluted tubules were filled with silicone rubber, dissected out and their lengths measured. Single nephron glomerular rate was increased in pregnant and lactating animals. The rate of reabsorption per unit length of the proximal convoluted tubule was decreased in pregnant animals but similar in virgins and lactating rats. The proximal convoluted tubule was increased in length in pregnant and lactating animals. As a result the total reabsorption by the proximal convoluted tubule was similar in virgin and pregnant animals but increased in lactating animals. The amount reabsorbed by the loop of Henle and distal parts of the nephron is greater in pregnant and lactating animals than in virgins.

Absorption↗
PubMed1986

Clinical evaluation of amoscanate in healthy male volunteers.

Single oral doses of amoscanate (4-isothiocyanato-4'-nitrodiphenylamine), an experimental antiparasitic agent, are highly effective in animals against the four major species of schistosomes which infect humans. Two prospective, randomized, double blinded, placebo controlled Phase I studies were designed to evaluate the tolerance and safety of the 5% aqueous suspension of 2-mu particles of amoscanate administered to healthy male volunteers. In addition to routine safety monitoring, particular attention was directed toward detecting hepatic, neurological, cardiovascular or ocular toxicity. Three of four men who received 3.5 mg/kg of amoscanate developed mild, reversible hepatotoxicity, which could not be unequivocably attributed to the drug. In the second study, of 1 mg/kg amoscanate, there was no statistically significant evidence of hepatotoxicity, although 1 of 12 drug recipients developed transient liver chemistry changes. Despite intensive monitoring, there was no evidence in either study of significant symptomatic complaints, or of neurological, cardiovascular or ocular toxicity. No mutagenic activity attributable to amoscanate was detectable in the urine. These results suggest that this formulation of amoscanate, at 1 mg/kg, is sufficiently well tolerated and safe to justify evaluation for efficacy in patients with schistosomiasis.

Adult↗
PubMed1985

Ocular anterior segment disease in northern fur seals.

Eyes of 1,716 wild northern fur seals (Callorhinus ursinus; 1,501 subadults and 215 adults) were examined for the prevalence of ocular anterior segment disease; 4.6% of the seals had clinically recognizable eye lesions. Six seals had bilateral eye lesions. Corneal scars were the most frequently observed lesion, followed by prominent lens sutures, cataracts, and iris depigmentations. Corneal edema, active corneal ulceration, or inflammation was not observed. Examination of normal corneas indicated an epithelial structure similar to that of the California sea lion, with 11 to 14 layers of nucleated superficial stratified squamous cells that lacked keratohyaline granules. The seal corneal endothelium had less hexagonality than do human corneal endothelial cells, with mean endothelial cell areas of 331 to 396 micron2, similar to that found in primates.

Animal Population Groups↗
PubMed1985

5-Fluorouracil and methotrexate administered simultaneously as a continuous infusion. A phase I study.

Infusion delivery systems have been evaluated for administration of many individual chemotherapeutic agents including 5-fluorouracil (5-FU) and methotrexate (MTX). This study combined the two drugs as an admixture, and in a Phase I trial design established a useful dose schedule for each of the component drugs. 5-FU at a fixed dose rate of 300 mg/M2/day was delivered with methotrexate (MTX) at four different dose rates (0.75, 1.0, 1.5, or 2.0 mg/M2/day, respectively). The drug solution was delivered via a subclavian venous access with a portable infusion pump in an ambulatory setting. Twenty-nine patients received a total of 38 courses of the two-drug infusion: 21 courses were delivered with the two agents admixed constantly throughout treatment (Schedule A) and 17 were administered the treatment with 5-FU delivered continuously and MTX added to the 5-FU for alternate 14-day cycles (Schedule B). For the former schedule, dose-rate-limiting toxicity was related to MTX and included stomatitis developing at days 8 to 14 (median, day 8) with the higher dose rates (1.5-2.0 mg/M2/day) and thrombocytopenia developing at days 11 to 56 (median, day 14) at the lowest dose rates (1.0 mg/M2/day). For Schedule B, dose-rate-limiting toxicity was similarly due to the MTX with thrombocytopenia and/or chemical hepatitis developing in six of seven courses of MTX at 1.0 mg/M2/day and in five of ten courses delivered at 0.75 mg/M2/day. On Schedule B the MTX-associated toxicities were reversed when the MTX administration was interrupted and in the face of continued 5-FU infusion. A reasonable dose rate and schedule for continuous infusion of 5-FU combined with MTX is: 5-FU 300 mg/M2/day X 28 days and MTX 0.75 mg/M2/day for days 1 to 14, with cycles administered consecutively each 28 days.

Adult↗