Search PubMed⌕ Search

Biomedical subjects

R Gama

Publications and source records attributed to R Gama.

At least 55 records · Page 3Linked to original sources

t-complex-associated embryonic surface antigen homologous to mLAMP-1. II. Expression and distribution analyses.

We have previously demonstrated that a mouse t-complex-associated antigen (ESGp) is present on the cell surface, specifically at areas of cell-cell contact, of cleavage stage embryos and embryonal carcinoma cell lines. In the accompanying paper, we document isolation, purification, and partial sequencing of this molecule. Amino-terminal and internal peptide fragments are highly homologous to the mouse lysosomal-associated membrane protein-1 (mLAMP-1). We also demonstrate considerable similarity, though not necessarily identity, between these two antigens through both biochemical and molecular analyses. In this report we use immunological techniques to compare the expression and distribution of these antigens in various cell lines as well as mouse tissues and preimplantation stage embryos. The data presented indicate that there are: (1) different antigenic forms of the ESGp/ mLAMP-1 homologues and (2) changes in the molecular composition and expression of these forms during embryogenesis and differentiation. It is obvious from these studies that mLAMP-1 is not strictly a static molecule whose sole function is to protect the lumenal side of the lysosomal membrane but rather is a dynamic molecule of potential import in many other cellular and organismal functions.

Animals↗

Elevated post-prandial gastric inhibitory polypeptide concentrations in hypertriglyceridaemic subjects.

1. We investigated whether abnormalities of gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1) contribute to the hypertriglyceridaemia and hyperinsulinaemia in hypertriglyceridaemic subjects. Serum triglycerides and plasma glucose GIP, GLP-1 and immunoreactive insulin (IRI) concentrations were measured before and after a mixed meal in 15 hypertriglyceridaemic patients and in eight healthy normotriglyceridaemic control subjects. 2. Integrated post-prandial GIP concentrations were greater than in controls (P < 0.05) and correlated positively with both fasting and integrated post-prandial triglyceride concentrations (P < 0.05 for both). Fasting and integrated post-prandial IRI levels were higher in hypertriglyceridaemic subjects than in controls (P < 0.02 and P < 0.05 respectively) and correlated positively with fasting triglycerides (P < 0.02 and P < 0.001 respectively) and integrated post-prandial triglycerides (P < 0.005 and P < 0.05 respectively). There was no correlation between GIP concentrations and either fasting or post-prandial IRI levels. Fasting and post-prandial concentrations of GLP-1 were similar in patients and controls. 3. Hypertriglyceridaemic subjects have post-prandial hyperGIPaemia in addition to the well-documented hyperinsulinaemia. We found no association between GIP and insulin. There is, however, clear evidence for an association between post-prandial GIP concentrations and triglyceride levels. We suggest that this association may depend on changes in lipoprotein lipase activity and that there may be a feedback loop between GIP and triglyceride lipolysis.

Adult↗

Hyperproinsulinaemia in acromegaly: evidence for abnormal pancreatic beta-cell function?

We investigated whether pancreatic beta-cell dysfunction has a role in the pathogenesis of glucose intolerance in acromegaly by comparing plasma intact proinsulin, immunoreactive insulin, C-peptide and glucose concentrations during a 75 g oral glucose load in six patients with active acromegaly and eight healthy volunteers. Only acromegalic patients with normal glucose tolerance were studied. Glucose concentrations were similar in acromegalic patients and controls. Acromegalic patients had higher fasting insulin (P < 0.005) and fasting C-peptide (P < 0.005) concentrations than controls. Although fasting proinsulin levels were higher in acromegalic patients than controls, this did not achieve statistical significance. Integrated insulin (P < 0.05), C-peptide (P < 0.05) and proinsulin (P < 0.005) concentrations were greater in acromegalic patients than control subjects. Integrated (P < 0.05) proinsulin:insulin molar ratios were higher in acromegalic patients than controls. Fasting and integrated insulin:C-peptide molar ratios were similar in acromegalic patients and controls. These results indicate that hyperproinsulinaemia contributes to the hyperinsulinaemia which characterizes active acromegaly. The disproportionate hyperproinsulinaemia in acromegaly suggests that prolonged and excessive growth hormone secretion may result in pancreatic beta-cell dysfunction which may predispose acromegalic subjects to glucose intolerance.

Acromegaly↗

The entero-insular axis in polycystic ovarian syndrome.

We investigated the contributions made by the entero-insular axis, proinsulin and the fractional hepatic extraction of insulin to the hyperinsulinaemia characteristic of polycystic ovarian syndrome (PCOS). We measured plasma glucose, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (7-36 amide) (GLP-1(7-36) amide), immunoreactive insulin (IRI), intact proinsulin (IPI), and C-peptide concentrations during a 75 g oral glucose tolerance test in seven normal weight women with PCOS and eight healthy women. Women with PCOS had higher fasting (P = 0.05) and integrated (P < 0.01) IRI concentrations than controls. Fasting C-peptide levels were similar in both groups but integrated C-peptide (P < 0.05) concentrations were greater in PCOS subjects than controls. Fasting and integrated concentrations of glucose, GIP and GLP-1(7-36) amide were similar in subjects with PCOS and controls. Although fasting IPI concentrations were similar in both groups, integrated IPI concentrations were higher (P = 0.05) in patients with PCOS. Women with PCOS had similar fasting but higher (P < 0.05) integrated IRI:C-peptide molar ratios than controls. Fasting and integrated IPI:IRI molar ratios were similar in both groups. These results confirm that lean women with PCOS have peripheral hyperinsulinaemia. The mild fasting hyperinsulinaemia is due to increased pancreatic secretion, whereas the stimulated hyperinsulinaemia is due to both pancreatic hypersecretion and reduced fractional hepatic extraction of insulin. Hyperproinsulinaemia is modest and appropriate in PCOS, GIP and GLP-1(7-36) amide do not contribute to the stimulated hyperinsulinaemia in PCOS.

Adult↗

Octreotide exacerbated fasting hypoglycaemia in a patient with a proinsulinoma; the glucostatic importance of pancreatic glucagon.

Octreotide, a long-acting somatostatin analogue, has been used to alleviate hypoglycaemia in patients with insulinomas. Transient worsening of fasting hypoglycaemia following octreotide has also been described (Stehouwer et al., 1989). We describe a patient with a 'proinsulinoma' in whom octreotide caused rapid and prolonged symptomatic worsening of fasting hypoglycaemia. Catecholamine and cortisol counterregulatory hormonal responses were normal but those of glucagon and GH were impaired. Acute neuroglycopaenic symptoms were present during octreotide induced hypoglycaemia, which was accompanied by and attributed to an acute reduction in pancreatic glucagon secretion in the presence of persistent and unsuppressed hyperproinsulinaemia. This suggests that glucagon may be important in maintaining glucose homeostasis in chronic hypoglycaemia due to endogenous hyperinsulinism even though its concentration in the peripheral blood is not raised.

Blood Glucose↗

Hyperinsulinaemia of hypertriglyceridaemia: a reappraisal.

The peripheral hyperinsulinaemia of hypertriglyceridaemic subjects has only been defined using insulin immunoassays in which proinsulin and proinsulin fragments cross-react. Relative contributions of pancreatic secretion and hepatic extraction of insulin to this hyperinsulinaemia have not been studied. We, therefore, reassessed the hyperinsulinaemia of hypertriglyceridaemia by measuring fasting plasma concentrations of intact proinsulin, glucose, insulin, and C-peptide in 24 hypertriglyceridaemic subjects with normal glucose tolerance (n = 14) and with impaired glucose intolerance (n = 10) and in normal subjects (n = 14). Hypertriglyceridaemic subjects had higher (p < 0.01) fasting concentrations of insulin and C-peptide and greater (p < 0.01) fasting insulin: C-peptide molar ratios than in control subjects. Fasting intact proinsulin concentrations were similar in hypertriglyceridaemic subjects with normal glucose tolerance and control subjects but these were lower (p < 0.01) than in hypertriglyceridaemic subjects with impaired glucose tolerance. These results suggest that the fasting peripheral hyperinsulinaemia of hypertriglyceridaemic subjects is due to increased pancreatic secretion and reduced hepatic fractional extraction of insulin. The peripheral hyperinsulinaemia of hypertriglyceridaemia appears to reflect peripheral insulin resistance and is not attributable to elevated proinsulin concentrations which are characteristic of impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus.

Adult↗

Modifying the request behaviour of clinicians.

AIM: To evaluate whether the feedback of laboratory use and cost data to clinicians modifies their request behaviour. METHODS: Over two years the effect of monthly feedback of clinical chemistry test use and revenue expenditure to three consultant physicians on their clinical chemistry and haematology requesting patterns was evaluated. Two physicians who received no information served as controls. RESULTS: Feedback over one year led to an immediate and sustained decrease of 15%, 27%, and 21% in clinical chemistry requests (p less than 0.01), tests (p less than 0.001), and revenue expenditure (p less than 0.001), respectively, and a 10% reduction in haematology tests (p less than 0.05) per outpatient visit. These changes persisted in the six months after the feedback was stopped. CONCLUSIONS: These results suggest that feedback of laboratory data to clinicians modifies their request behaviour and that supplying clinicians with information on what they do can influence the way they make decisions.

Clinical Laboratory Techniques↗

Cytogenetic analysis of a multinodular thyroid goiter.

Short-term cultures of a collagenase disaggregated multinodular goiter was shown by cytogenetic analysis to have the mosaic karyotype 47,XX, +7/48,XX, +7, +17/49,XX, +7, +10, +17. No cytogenetic data on goiter are available for comparison with the present case.

Adult↗

Feedback of laboratory usage and cost data to clinicians: does it alter requesting behaviour?

In a 1 year prospective study we evaluated the effect of feedback of laboratory data on the requesting behaviour of physicians in general medicine. Data on within-hours and out-of-hours clinical chemistry laboratory usage and revenue expenditure for inpatients and outpatients, expressed in terms of clinical workload, were supplied monthly to a group of three consultant physicians in general medicine. With these data the physician could monitor his performance over a period of time and compare it with that of his peers. Two consultants in general medicine who received no information served as controls. Over a period of 6 months, there was a 25%, 13% and 18% decrease in tests (P less than 0.01), requests (P less than 0.05) and revenue expenditure (P less than 0.01) per outpatient visit, respectively, in the intervention group of physicians following the introduction of feedback when compared to their baseline period and to the control group. The decrease (P less than 0.01) was in the commonly requested and 'seemingly cheap' tests. There was no significant change in laboratory use and expenditure on inpatients. The feedback of laboratory data was acceptable to the physicians, raised their awareness of laboratory usage and costs and decreased laboratory workload and expenditure.

Feedback↗

The effect of synthetic very low calorie diets on the GH-IGF-1 axis in obese subjects.

IGF-1 concentrations were measured in plasma from 20 obese patients and 20 age- and sex-matched control subjects all of whom were fasting. Plasma IGF-1 concentrations were lower (p less than 0.05) in the obese individuals than in the controls. Plasma GH and insulin responses to stimulation with oral glucose were measured in 7 healthy normal weight individuals and both before and after energy restriction in 7 obese individuals. Before treatment the obese individuals were hyperinsulinaemic (fasting and integrated stimulated concentrations p less than 0.05) and showed attenuation of the plasma GH response to stimulation (peak and integrated stimulated values p less than 0.05 and less than 0.005, respectively) following oral glucose when compared to normal weight controls. Plasma insulin levels fell (both fasting and integrated concentrations p less than 0.05 and less than 0.005, respectively) and stimulated plasma GH responses increased (both peak and integrated values p less than 0.01 and less than 0.05, respectively) in the obese individuals following 3 wk treatment with a synthetic very low energy diet. Plasma IGF-1 concentrations remained unchanged during energy restriction. These results fail to support an endocrine IGF-1 mediated feedback inhibition on the hypothalamic-pituitary axis as the cause of the attenuated release of GH in obesity.

Adult↗

Cardiac enzyme changes in elderly fallers.

The pattern of enzyme changes in elderly fallers admitted to an acute geriatric unit was investigated. Creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activities were measured daily for 3 days after admission in all patients in whom a fall preceded admission. Of 270 patients, 52 (19%) had fallen prior to admission, of whom five (10%) had an acute myocardial infarction (AMI). In fallers without an AMI in whom a history was available, CK and AST activities were significantly higher (p less than 0.05) in patients who had spent more than 1 hour on the floor than in those who had spent less than 1 hour. No other clinical factor affected enzyme activities. CK and AST activities were raised in 66% and 40%, respectively, of fallers without an AMI. Elevation of CK and AST activities in elderly fallers is likely to be a result of the fall itself rather than of an AMI.

Accidental Falls↗

The effective use of cardiac enzymes and electrocardiograms in the diagnosis of acute myocardial infarction in the elderly.

The diagnosis of acute myocardial infarction (AMI) in the elderly is difficult and often depends on the results of investigations. In a 3-month prospective study, 270 patients admitted to an acute geriatric unit were studied to determine the most effective diagnostic strategy for the diagnosis of AMI, and to assess the value of screening acute geriatric admissions for AMI. Patients were assessed clinically and investigated with serial electrocardiograms and measurements of serum creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase activities on three consecutive days after admission. Measurement of serum activity of CK and AST had a diagnostic sensitivity of 100% and specificity of 86.8% for AMI. This was the optimum combination of cardiac enzymes in the diagnosis of AMI. Although electrocardiograms on the first two days of admission had a low diagnostic sensitivity (33.3%) their usefulness was their high positive predictive value (100%) when characteristic of an AMI. AMI was considered in the differential diagnosis of 79 patients (29%). All 25 patients (9%) who had an AMI were in this group, and therefore screening all geriatric admissions for AMI is not clinically justified.

Aged↗