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Biomedical subjects

S Manley

Publications and source records attributed to S Manley.

31 records · Page 2Linked to original sources
PubMed1997

Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect.

Maturity-onset diabetes of the young (MODY) type 3 is a dominantly inherited form of diabetes, which is often misdiagnosed as non-insulin-dependent diabetes mellitus (NIDDM) or insulin-dependent diabetes mellitus (IDDM). Phenotypic analysis of members from four large Finnish MODY3 kindreds (linked to chromosome 12q with a maximum lod score of 15) revealed a severe impairment in insulin secretion, which was present also in those normoglycemic family members who had inherited the MODY3 gene. In contrast to patients with NIDDM, MODY3 patients did not show any features of the insulin resistance syndrome. They could be discriminated from patients with IDDM by lack of glutamic acid decarboxylase antibodies (GAD-Ab). Taken together with our recent findings of linkage between this region on chromosome 12 and an insulin-deficient form of NIDDM (NIDDM2), the data suggest that mutations at the MODY3/NIDDM2 gene(s) result in a reduced insulin secretory response, that subsequently progresses to diabetes and underlines the importance of subphenotypic classification in studies of diabetes.

Adult↗
PubMed1996

Thermodynamics of transfer of cholesterol from gel to fluid phases of phospholipid bilayers.

The partitioning of cholesterol between gel and fluid phases of model membrane bilayers has been studied by differential scanning calorimetry. The partition coefficients and thermodynamics of transfer between phases of dimyristoyl-, dipalmitoyl-, distearoyl- and diarachidoylphosphatidylcholines were determined using a regular solution model for the partitioning process. The partition coefficient, which is the ratio of cholesterol in fluid to gel phase lipid, varies from 2.3 to 8.4 as the acyl chain length increases from the C14 to the C20 bilayer and determined at the phase transition temperature. The enthalpies of transfer increase from -46 to +32 kcal/mol as the chain length increases, and there is a compensating increase in the entropy of transfer. The results are interpreted in terms of a disruption of gel phase lipid by the cholesterol, which for the thinner bilayers is increased because the cholesterol molecule spans across the two leafs of the bilayer. At bilayer thicknesses between 18 and 19 carbons, the cholesterol can fit into one-half of the gel phase bilayer, and the enthalpy becomes positive, suggesting less disruption in the gel phase relative to the thinner bilayers. The data support the interpretation that cholesterol does mediate fluidity by acting to disrupt gel domains of lipid.

Calorimetry, Differential Scanning↗
PubMed1995

Preoperative pregnancy testing in ambulatory surgery. Incidence and impact of positive results.

BACKGROUND: The incidence of unrecognized early pregnancy and its influence on the surgical and anesthetic course in patients presenting for elective ambulatory surgery have not been previously determined. The current study was designed to determine the incidence of unrecognized pregnancy in women presenting for ambulatory surgery. In addition, it examined how discovery of the pregnancy altered the anesthetic or surgical course. METHODS: In a prospective study over a 1-yr period, all women of childbearing potential (defined as menstruating women without prior hysterectomy or tubal ligation) were preoperatively evaluated and tested for urine or serum human chorionic gonadotropin, to determine unrecognized pregnancy. If a pregnancy was detected, the disposition of the surgical procedure and the effect on the surgical and anesthetic management was recorded. RESULTS: Of 2,056 women of childbearing potential presenting for ambulatory surgery, testing revealed 7 previously unrecognized pregnancies, an incidence of 0.3%. Included among these patients were two patients scheduled to undergo fertility procedures. On learning the test result and even before being advised of available options, all patients elected to cancel or postpone the surgical procedure. CONCLUSIONS: The incidence of previously unrecognized pregnancy in menstruating women presenting for ambulatory, nonobstetric surgery was 0.3%. The knowledge of a positive test resulted in cancellation or postponement of the operative procedure. Patient desire for cancellation was the main determining factor in each case.

Ambulatory Surgical Procedures↗
PubMed1983

Alterations of renal cortex and medullary glycosaminoglycans in aging dog kidney.

Age-related changes in renal function have been attributed to alterations in the chemical composition of the kidney tissues. Hence, the glycosaminoglycan composition of the renal cortex and medulla at varying age intervals was investigated. Glycosaminoglycans were isolated from the tissues by means of digestion with collagenase and pronase and purified by ethanol precipitation. Subsequent separation of various polyanions was accomplished by ion exchange chromatography on a Dowex 1-X2 column, using sodium chloride buffers of increasing ionic strengths. The glycosaminoglycans in each fraction were identified and quantitated by digestion with specific enzymes, including hyaluronidase, chondroitinase AC and ABC. The enzyme resistant material was separated and further digested with nitrous acid to quantitate the proportion of heparon sulfate. The results indicate that the glycosaminoglycan content of the renal medulla was much higher than the cortex at all the age intervals studied, and age-induced reduction was mainly cortical. There was a significant reduction in the heparan sulfate content of the cortex in aging. Interestingly, the major glycosaminoglycan content of the medulla was hyaluronic acid, which showed a sharp increase during aging, whereas heparan sulfate declined. Chondroitin sulfate was not altered due to age in either tissue. The molecular weight of hyaluronic acid was determined by column chromatography. Results indicate that the size of hyaluronate in the cortex was small and did not vary with age. In the medulla of the younger age group, a considerable amount of large size hyaluronate was observed. As age increased, the size decreased. The results strongly suggest that alteration in the renal glycosaminoglycans may be partly responsible for the age related protinuria and ionic imbalance.

Aging↗
PubMed1974

The effect of nickel on secretory systems. Studies on the release of amylase, insulin and growth hormone.

The effects of Ni(2+) on the release of amylase from rat parotids, insulin from mouse pancreatic islets and growth hormone from bovine pituitary slices were investigated. In all these secretory systems, Ni(2+) was shown to inhibit release evoked by a variety of stimuli both physiological and pharmacological. Measurements of rates of substrate oxidation and tissue concentrations of ATP and 3':5'-cyclic AMP suggest that this inhibitory action of Ni(2+) does not arise through an effect on energy metabolism or cyclic AMP metabolism. It is concluded that although some effects of Ni(2+) may involve antagonism between Ni(2+) and Ca(2+) in stimulus-secretion coupling, others appear to be independent of Ca(2+). It is suggested that Ni(2+) may block exocytosis by interfering with either secretory-granule migration or membrane fusion and microvillus formation. The possible mode of action of Ni(2+) and its potential use as a tool in the study of exocytosis are discussed.

Adenosine Triphosphate↗