Search PubMed⌕ Search

Biomedical subjects

B Cooper

Publications and source records attributed to B Cooper.

At least 181 records · Page 10Linked to original sources
PubMed1977

Continuous subcutaneous administration of deferoxamine in patients with iron overload.

Since deferoxamine B, when administered as a single daily intramuscular injection of 0.75 g, is unable to promote sufficient urinary iron excretion to achieve net negative iron balance in siderosis, we evaluated its administration as a constant infusion over 24 hours. We compared intravenous and subcutaneous routes in 24 siderotic patients who had excreted 420 to 630 mg (mean, 480 mg) of iron per month on intramuscular therapy. With the intravenous route urinary iron excretions increased to 570 to 3690 mg (mean, 1595 mg) per month. Constant subcutaneous delivery was 90 per cent as effective as intravenous administration on a dose-for-dose basis. Noteworthy net cumulative urinary iron excretions (urinary iron excretions minus transfused iron), often in excess of 1 g per month, have been maintained in all patients. Constant subcutaneous deferoxamine administration may prove to be an effective and practical means of eliminating large quantities of iron in siderosis.

Administration, Oral↗
PubMed1977

Treatment of iron overload in adults with continuous parenteral desferrioxamine.

Adult patients with transfusional hemosiderosis were given ascorbic acid and treated with the iron chelator, desferrioxamine B. The drug was administered by continuous subcutaneous or intravenous infusions using a light weight portable constant infusion device. On this regimen, four of the five patients studied were able to excrete significant amounts of iron (greater than 35 mg/da) when receiving a daily desferrioxamine dose of 1.5 to 2.2 g. Continuous subcutaneous infusion was well tolerated and about 80 per cent as effective as intravenous therapy in chelating iron. The number of prior transfusions, the hepatic iron content and the serum ferritin levels appear to be useful in predicting which patients will respond to iron chelation therapy, especially if there is little bone marrow erythropoietic activity. One patient with ineffective erythropoiesis did not have significantly increased hepatic iron stores but responded to the administration of desferrioxamine. Continuous subcutaneously administered desferrioxamine may prove to be adaptable for long-term outpatient therapy, allowing patients with ongoing transfusion requirements to go into negative iron balance. Long-term studies will be needed to demonstrate reversal of endocrine, hepatic and cardiac dysfunction secondary to iron deposition in these patients.

Adult↗
PubMed1977

Psychiatric illness, maladjustment and juvenile delinquency: an ecological study in a London borough.

Patterns of adult psychiatric referral, of child guidance referral and of juvenile delinquency in a metropolitan borough were examined. The 3 sets of rates showed parallel trends among the 20 electoral wards of the borough, all 3 being similarly related to socio-demographic indices. A cluster analysis technique was used to combine the 450 enumeration districts of the borough into 22 clusters defined by social characteristics rather than by geographical boundaries. Ecological correlates of treated psychiatric disorder and of delinquency, based on these clusters, were found to be similar to those derived from the electoral ward data. The findings suggest that it may be possible to demarcate relatively small urban areas with high concentrations of psychiatric disorder, maladjustment and delinquency.

Adolescent↗
PubMed1977

Enhanced activity of hormone-sensitive adenylate cyclase during dietary restriction in the rat: dependence on age and relation to cell size.

Age-related decreases of hormone-sensitive adenylate cyclase activities of rat fat cell plasma membranes (ghosts) have been recently described. Glucagon-sensitive activity was completely lost between 1 and 6 mo, an interval in which fat cell size increases rapidly, while decreased activation by ACTH was gradual over the entire life span of the animal (24 mo), and epinephrine-sensitive enzyme diminished modestly and only during senescence. In the present studies an attempt was made by restricting food intake to assess the importance of changing cell size in the age-related alterations of hormone-sensitive enzyme activities. Enzyme activities were determined before restriction and at monthly intervals for 3 mo for the unstimulated enzyme (basal) and in the presence of maximally stimulating concentrations of glucagon, ACTH, epinephrine, and fluoride. Activities were calculated per milligram ghost protein or per cell. Restriction of food intake for 3 mo starting at 1 or 12 mo produced fat cells equal in size to those of 5-wk-old animals fed ad lib. In young animals restricted for 1 mo, hormone-stimulated activity expressed as fold increase (stimulated/basal) was not merely maintained as the cells were prevented from enlarging, but was enhanced two to three times over the initial values with all three hormones. With continued restriction epinephrine-sensitive activity remained two times increased. Glucagon and ACTH responses subsequently decreased, but even by 3 mo of restriction, responses to the latter hormones, although declining, were still 1.5-3 times greater than the unrestricted controls, regardless of whether activity was expressed as total activity per milligram ghost protein or per cell, or as fold-increase. In the young animals, basal and fluoride-sensitive activities after a 3-mo restriction were unchanged or had decreased only slightly, depending on the base line used. Dietary restriction of adult animals for 3 mo, in contrast to the results in the young, did not increase total hormone-stimulated activity but rather produced either 0% (per milligram protein) or 25% decrease (per cell) for epinephrine-sensitive enzyme, 25 or 50% decrease of ACTH response, and 40 or 60% decreases of basal- and fluoride-stimulated activities. Expression of activities of restricted adults as fold-increase (stimulate/basal) showed an "increase of responsiveness" for all three hormones, but this was a reflection of the marked decrease of basal activity. Nonetheless, the restricted adults showed significant restoration of a small amount of glucagon-sensitive activity (1.8-fold over basal). These results indicate that cell size, per se, is not a dominant factor affecting hormone-responsive adenylate cyclase under conditions of dietary restriction...

Adenylyl Cyclases↗
PubMed1976

Human fat cell adenylate cyclase. Enzyme characterization and guanine nucleotide effects on epinephrine responsiveness in cell membranes.

Human adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) has been studied in preparations of fat cell membranes ("ghosts"). As reported earlier, under ordinary assay conditions (1.0 mM ATP, 5 mM Mg2+, 30 degrees C, 10 min incubation) the enzyme was activated 6-fold by epinephrine in the presence of the GTP analog, 5'-guanylyl-imidodiphosphate [GMP-P(NH)P] (Cooper, B. et al. (1975) J. Clin. Invest. 56, 1350-1353). Basal activity was highest during the first 2 min of incubation then slowed and was linear for at least the next 18 min. Epinephrine, added alone, was often without effect. but sometimes maintained the initial high rate of basal activity. GMP-P(NH)P alone produced inhibition ("lag") of basal enzyme early in the incubation periods. Augmentation of epinephrine effect by GMP-P(NH)P, which also proceeded after a brief (2 min) lag period, was noted over a wide range of substrate (ATP) concentrations. GTP inhibited basal levels of the enzyme by about 50%. GTP also allowed expression of an epinephrine effect, but only in the sense that the hormone abolished the inhibition by GTP. Occasionally a slight stimulatory effect on epinephrine action was seen with GTP. At high Mg2+ concentration (greater than 10 mM) or elevated temperatures (greater than 30 degrees C) GMP-P(NH)P alone activated the enzyme. Maximal activity of human fat cell adenylate cyclase was seen at 50 mM Mg2+, 1.0 mM ATP, pH 8.2, and 37 degrees C in the presence of 10(-4) M GMP-P(NH)P; under these conditions addition of epinephrine did not further enhance activity. Human fat cell adenylate cyclase of adults was insensitive to ACTH and glucagon even in the presence of GMP-P(NH)P.

Adenosine Triphosphate↗
PubMed1976

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

The possibility has been explored that decreases of adenylate cyclase may explain diminished hormone sensitivity of adipose tissue with aging. Isolated cells were prepared from epididymal fat pads of rats 1-, 2-, 6-, 12-, and 24-mo old, fixed in OSO4, and sized and counted with a Coulter apparatus. Adenylate cyclase was assayed in cell membranes (ghosts) using [alpha-32P] ATP as substrate and expressed as cyclic [32P] AMP/10 min per mg protein or per 10(6) cells. Enzyme activity was determined for the basal state and in the presence of varying concentrations of glucagon, ACTH, epinephrine, and fluoride. Basal activity per cell increased in threefold between 1 and 2 mo with a comparable increase in cell surface area, suggesting synthesis of enzyme along with new cell membrane. Although epinephrine stimulated adenylate cyclase 8-fold and fluoride 12-fold throughout the life-span of the rat, stimulated activity paralleled basal levels, decreasing 60% between 2 and 24 mo per mg protein and 40% between 6 and 24 mo per cell. Glucagon stimulated adenylate cyclase 4.5-fold relative to basal in the 1-mo-old rat, but its effect then rapidly decreased and was absent by 12 mo. The fourfold stimulation by ACTH noted in the 1-mo-old animals decreased gradually with age but was still twice basal at 24 mo. Since no significant change of cell size occurred after 6 mo, diminished hormone sensitivity with senescence cannot be related to cell size. Similar age-related patterns of hormonal activation were evoked by 5'-guanylyl-imidodiphosphate [GMP-P(NH)P], a nucleotide analogue which increased both basal- and hormone-activated enzyme at all ages studied. Dose-response curves to hormones, fluoride, and GMP-P (NH)P were not affected by age. High Mg++ (50 mM) in the presence of GMP-P-(NH)P stimulated adenylate cyclase to levels greater than with fluoride, but a similar loss of activity with aging was still observed. Loss of hormone receptors may partially explain the age-related decreases of glucagon and ACTH-sensitive adenylate cyclase, but decreased basal-, epinephrine-, fluoride-, and GMP-P-(NH) P-stimulated responses suggest loss of the catalytic component of the adenylate cyclase enzyme complex in the aging fat cell membranes.

Adenylyl Cyclases↗
PubMed1976

The health of clients of a social service department.

A survey was undertaken of the health problems and current medical care of new clients making contact with the Social Service Department of an outer London borough. The findings indicated that social-service clients represent a high-morbidity group of the population: 47 per cent of the survey sample showed evidence of major physical illness or disability, and 16 per cent of major mental illness. A sub-group was identified, corresponding to about 300 new clients annually, who suffered from serious ill-health or disability, but were at the time not under medical care.These findings support the argument for closer liaison between medical and social services in the community and, in particular, for more social-worker attachments in general practice.

Adolescent↗
PubMed1975

Mental health care in the community: an evaluative study.

A study was designed to assess the therapeutic value of attaching a social worker to a metropolitan group practice in the management of chronic neurotic illness. The psychiatric and social status of a group of patients before treatment and after one year was compared with the status of a control group treated more conventionally over the same period. The results indicate that the experimental service conferred some benefit on the patient population.

Adult↗
PubMed1975

Adenylate cyclase of human fat cells. Expression of epinephrrine-sensitive activation revealed by 5'guanylyl-imidodiphosphate.

Although catecholamines stimulate lipolysis in human fat cells, activation by epinephrine of adenylate cyclase in human fat cell membranes is not readily observed. The possible role of guanine nucleotides in this reaction has now been examined with human material. Fat cell ghosts were prepared from subcutaneous fat obtained from patients undergoing elective surgery. Adenylate cyclase was assayed with [alpha-32P]ATP as substrate. Fluoride ion stimulated the enzyme 8.3-fold relative to basal levels, but epinephrine activation of cyclase was not statistically significant. GTP did not allow expression of an epinephrine effect. However, the addition of the GTP analogue, 5'-guanylyl-imidodiphosphate [GMP-P(NH)P], along with epinephrine produced 5.7-fold activation of the enzyme (P less than 0.001). GMP-P(NH)P alone was without stimulatory effect. Comparable augmentation by GMP-P (NH) P of adenylate cyclase activity was seen with isoproterenol, norepinephrine, and epinephrine. Propranolol blocked catecholamine-GMP-P (NH) P stimulation of the enzyme, suggesting that the nucleotide-dependent activation of catecholamine-sensitive adenylate cyclase is mediated by beta-receptors. GMP-P(NH)P may prove useful in allowing in vitro demonstration of additional hormone-sensitive adenylate cyclase systems.

Adenylyl Cyclases↗