Search PubMed⌕ Search

Biomedical subjects

J M Martin

Publications and source records attributed to J M Martin.

At least 145 records · Page 8Linked to original sources

Activities of gamma-glutamyl transferase, 5'-nucleotidase and alkaline phosphatase in human duodenal aspirate.

Duodenal aspirates were obtained before, during, and after stimulation with secretin-cholecystokinin in 26 patients whose pancreatic function was classified as normal, moderately reduced, or severely reduced. The activities of gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and 5'-nucleotidase (5NT) in the aggregated duodenal aspirate collected 10-40 min after stimulation showed marked overlap between the functional groups and lacked diagnostic value. For all three enzymes, the peak response occurred later in the severely impaired group than in those with normal pancreatic function. The three enzymes showed significant positive correlations with each other, and were negatively correlated with the output of trypsin and chymotrypsin and, in contrast with these proteolytic enzymes which were reduced in pancreatic disease, GGT, ALP, and 5NT all tended to increase with pancreatic disease. Contrary to a previous report, GGT did not serve as a useful index of pancreatic cancer in this study.

5'-Nucleotidase↗

Insulinotropic activity in the serum of obese and nonobese infants and children.

The ability of a serum fraction, mol wt 1000-5000, to stimulate insulin release in vitro was studied in 123 obese and normal weight children aged 0-17 yr. The sera were fractionated by serial molecular filtration after treatment with urea. Stimulation of insulin release was determined with a bioassay using isolated rat islets in perifusion. The islet-stimulating activity was found in all obese children less than the age of 10 yr and in the majority of the obese children older than 10 yr of age. In normal weight children the activity was also found in the majority of infants, but was infrequent in older children. The serum islet-stimulating activity was positively correlated with the duration and degree of obesity and with linear growth rate. The molecular structure and origin of the insulinogenic activity in the serum is still unknown. In high-performance liquid chromatography it has the same elution characteristics as the hypothalamic insulin-glucagon liberin. The present results suggest a role for the serum islet-stimulating activity in the pathogenesis of obesity.

Adolescent↗

Serum insulin-releasing activity and the Prader-Willi syndrome.

Pathogenesis and etiology of the various clinical features of the Prader-Willi syndrome (PWS) are not completely understood. There is evidence suggesting a hypothalamic abnormality leading to hypogonadism in this syndrome. To test the possible hypothalamic involvement in the pathogenesis of obesity in these patients we studied the sera of 5 patients with PWS for insulin-releasing activity of possible hypothalamic origin. In addition 4 patients with a PWS-like syndrome and 6 obese patients with signs of central nervous system damage were studied. All five patients with PWS showed significant insulin-releasing activity in their sera. Of the four patients with PWS-like symptoms three showed similar activity while three of the obese patients with central nervous system damage had this activity in their sera. Serum insulin-releasing activity has been shown earlier to be associated with childhood obesity and it could play a role in the pathogenesis of obesity in PWS.

Adolescent↗

Effects of retained fetal membranes on milk yield and reproductive performance.

Effects of retained fetal membranes on subsequent productive and reproductive performance were measured in a single Florida Holstein dairy herd (n = 216 retained fetal membranes and 208 normal cases). Mean performance was peak daily milk yield, 31.9 kg; 305-d milk yield, 6317 kg; days to first service, 60; days open, 115; and services per conception, 2.3. Yield was unaffected by retained fetal membranes; however, retention resulted in an increase of 4 d to first service, 19 d open, and .2 services per conception. Detrimental effects of parturitions in hot weather (July through September) compared with cool (December through February) were peak daily milk yield, 5.5 kg; 305-d milk yield, 512 kg; days to first service, 3; days open 39; and services per conception, .9. Interactions could not be detected between diagnosis (retained or normal) and season for any response. Sex of calf effects could not be detected for any response. Continued research to reduce occurrence of retained fetal membranes or to obviate its effects should lead to improved reproductive performance.

Animals↗

Cervical thymoma.

A 45-year-old woman presented with a five-year history of neck swelling and occasional difficulty in swallowing. The clinical impression was of a thyroid nodule, and fine-needle aspiration biopsy cytology revealed a monotonous lymphoid population, raising the suspicion of Hashimoto's thyroiditis. At surgery, the mass was identified at the level of the cricoid cartilage, displacing the right lobe of the thyroid gland superiorly and extending posteriorly to the prevertebral fascia. Although a frozen-section diagnosis of malignant lymphoma had been suggested at the time of surgery, permanent sections favored a diagnosis of thymoma. Surface marker studies showed the majority of cells to be of thymic T-cell phenotype, and ultrastructural examination demonstrated a dual population of lymphoid and epithelial cells, thus confirming the presence of thymoma. Cervical thymomas are extremely rare and this case report illustrates the difficulties in diagnosis; we speculate that cervical thymoma may be an underdiagnosed entity.

Female↗

Breast pathology in MRI. First results.

The authors present the first results of the assessment of MRI (0.35 T) with adapted surface reel in the exploration of mammary pathology in 90 cases. On a morphological level, MRI permits a new analysis of signs of dystrophy. As far as MRI is concerned, no specific sign of mammary neoplasia seems to exist. A classification is suggested, taking into account morphology and parameters of relaxation.

Adenofibroma↗

Distribution of the Mr 52,000 estrogen-regulated protein in benign breast diseases and other tissues by immunohistochemistry.

A secreted glycoprotein with a molecular weight of 52,000 is induced by estrogen in breast cancer cells and has been purified to prepare monoclonal antibodies. The protein has been detected in some breast cancers but not in normal breast and uterus. In order to study its potential value as a marker, we have tested by immunohistochemistry frozen sections of several normal and malignant tissues and of benign mastopathies. Among different tissues tested, the Mr 52,000 protein was detected only in liver, sweat glands, and some sebaceous glands, and in malignant melanomas and some breast tumors. Other estrogen-responsive tissues (ovary, placenta, endometrium, etc.) gave negative results. Immunoradiometric assay of the Mr 52,000 protein in biological fluid revealed an elevated concentration in cyst fluid (0.5 to 7.4 micrograms/ml), pleural effusions of certain metastatic breast cancer, and sweat. By immunohistochemistry, the Mr 52,000 antigen was also detected in 42% of 129 benign mastopathies. Gynecomastia, fibrous disease, fibroadenoma, and adenosis were mainly negative, whereas ductal hyperplasia and cysts were positive. The Mr 52,000 protein was found mostly in proliferative ducts and in cysts but not in lobular hyperplasia and nonproliferative lesions without cyst. More Mr 52,000 protein was found in postmenopausal patients than in premenopausal patients. We conclude that the Mr 52,000 protein is a marker associated with mammary cysts and proliferative ducts. On the basis of the increased risk of breast cancer in proliferative mastopathies, we suggest that the Mr 52,000 protein is useful for predicting high-risk mastopathies acting as a marker associated with the proliferation of ductal tissue.

Age Factors↗

Islet activating protein inhibits physiological responses evoked by cardiac muscarinic acetylcholine receptors. Role of guanosine triphosphate binding proteins in regulation of potassium permeability.

The involvement of GTP binding proteins in muscarinic acetylcholine receptor (mAChR) mediated responses of cultured chick embryonic cardiac muscle cells was studied by using islet activating protein (IAP) from Bordetella pertussis. Incubation of cells for 24 h with IAP resulted in inhibition of subsequent IAP-catalyzed incorporation of [alpha-32P]ADP-ribose into membrane proteins of Mr 39 000 (No alpha) and 41 000 (Ni alpha); treatment of cultures with 5 ng/mL IAP was sufficient to ADP-ribosylate all available No alpha and Ni alpha. Inhibition of forskolin-stimulated cAMP accumulation by the muscarinic agonist carbachol was abolished in cultures pretreated with IAP. The affinity of carbachol for the mAChR in membranes from IAP-treated cells was considerably decreased compared to control membranes and was not further decreased by addition of guanyl-5'-yl imidodiphosphate. In contrast, the affinity of carbachol for the mAChR on intact cells was not affected by pretreatment with IAP. To investigate the involvement of No and/or Ni in mAChR-mediated increases in K+ permeability, the effect of IAP treatment on mAChR stimulation of 86Rb+ efflux was determined. Treatment of cultures with 5 ng/mL IAP for 24 h completely blocked the stimulation of 86Rb+ efflux evoked by carbachol. Because previous work has shown that mAChR regulation of K+ permeability is independent of changes in cAMP levels, these results suggest a role for No and/or Ni in coupling the mAChR directly to K+ channels in the heart.

Animals↗

Endogenous release of hepoxilin A3 from isolated perifused pancreatic islets of Langerhans.

Pancreatic islets of Langerhans were perifused with Krebs-bicarbonate solution containing glucose (5 and 10 mM). The perifusate was spiked with tetradeuterated hepoxilin A3 and was extracted and analysed by gas chromatography-mass spectrometry using NICI detection. Evidence is presented showing the presence of hepoxilin A3 as the hydrolysis product trioxilin A3. These results demonstrate for the first time that this pathway is active in intact cells; this finding, taken together with our previous evidence that hepoxilins possess insulin secretagogue properties further supports our hypothesis that these products could play a role as endogenous mediators of insulin release.

8,11,14-Eicosatrienoic Acid↗

Giant lymph node hyperplasia (Castleman's disease) of hyaline vascular type. Clinical heterogeneity with immunohistologic uniformity.

Of three patients with giant lymph node hyperplasia (GLNH) of hyaline vascular type, one had multicentric involvement and systemic symptoms, and had the nephrotic syndrome develop. The two others had localized adenopathy and were asymptomatic. Immunohistochemistry carried out on frozen and paraffin-embedded tissue was uniform in all cases. For the most part this revealed a polyclonal B-cell population and a reactive T-cell population in keeping with reactive follicular hyperplasia. In contrast to the latter, however, was a total absence of Leu-7 (natural killer cell) activity. The significance of this is unclear but may represent an abnormal immunologic response in the face of overwhelming antigenic stimulation. GLNH is a clinically and pathologically heterogeneous disorder, the management of which is dependent on both the clinical presentation of the patient and the histologic appearances of the involved lymph nodes.

Adult↗

Insulin and central regulation of spontaneous fattening and weight loss.

Insulin binding to receptors in a partially purified hypothalamic membrane preparation is altered by prolonged starvation. To define further the relationship between hypothalamic insulin binding and energy balance, we studied the Richardson's ground squirrel, a hibernator that exhibits spontaneous 6- to 8-mo body weight cycles when kept in constant conditions. Isolated pancreatic islets from squirrels killed during the weight gain phase had greater glucose-stimulated insulin secretion than those from weight loss phase animals, and adipocytes showed significantly greater glucose incorporation into total lipid in response to insulin. Differences in lipogenesis were not attributable to changes in insulin-binding capacity. Hypothalamic tissue from weight gain phase animals bound more insulin than that from weight loss phase animals. Maximal binding was correlated with pancreatic islet responsiveness and maximal insulin-stimulated lipogenesis. The strong positive correlation between peripheral metabolic events associated with spontaneous alterations in energy balance and the binding kinetics of hypothalamic insulin receptors suggests that insulin may play an important role in the central regulation of body weight.

Adipose Tissue↗

Neurohumoral stimulation of lipogenesis during altered states of energy balance.

Acid extracts of bovine hypothalamus stimulate lipogenic activity in adipose tissue. We employed a rat fat cell bioassay system to determine whether tissue concentrations of the active material vary as a function of spontaneous alterations in energy balance in hibernators and/or the obesity resulting from bilateral electrolytic lesions of the ventromedial area of the hypothalamus in rats. When hypothalamic extracts and partially purified plasma were fractionated using reverse-phase high-pressure liquid chromatography, both the void volume and material eluting 17 min after the start of a 25-min linear methanol gradient enhanced glucose incorporation into total lipid. Activities eluting with these two fractions were positively correlated with one another and were independent of insulin. The results indicate that a hypothalamic lipogenic factor (LHF) is detectable in plasma, that hypothalamic and circulating LHF concentrations vary in a reciprocal manner, and that elevations in plasma LHF concentration are associated with insulin resistance. The data suggest that the central regulation of lipogenesis is at least partially mediated by a hypothalamic humoral factor reaching fat depots via the circulation.

Adipose Tissue↗

Cortisone fails to affect levels of islet cell surface antibodies and incidence of diabetes in the BB rat.

Cortisone acetate (250 micrograms/kg X day) was given by im injections to 40 21-day-old diabetes-prone BB rats. The animals were followed longitudinally to determine islet cell surface antibodies (ICSA), as an expression of an abnormal immune reaction against the pancreatic islet cells and plasma glucose to estimate the degree of metabolic control. ICSA were detected 10-150 days before the diagnosis of diabetes. In the cortisone-treated group the diabetic rats showed significantly higher ICSA values compared to the nondiabetic ones, both in frequency of positive tests (P less than 0.05) and in mean binding values (P less than 0.02). In the control group, no difference in ICSA levels were seen between diabetic and nondiabetic rats. The cortisone regimen also failed to influence the degree of insulitis, commonly associated with diabetes in these rats. These experiments in well defined animals which spontaneously develop diabetes do not support the use of low dose cortisone treatment in attempts to improve or prevent insulin-dependent diabetes in human subjects.

Animals↗

Growth hormone binding to specific receptors stimulates growth and function of cloned insulin-producing rat insulinoma RIN-5AH cells.

Binding of 125I-labeled human GH (hGH) to a cloned rat insulin-producing cell line RIN-5AH in monolayer culture was studied along with some physiological effects of the hormone on these cells. Binding was time and temperature dependent, and steady state binding was observed in 60 min at 37 C with [125I]hGH at 4.2 pM, whereas at 24 C, binding had not reached a steady state after 120 min. The binding was largely reversible, since 80% of initially bound [125I]hGH dissociated from the cells upon incubation in hGH-free buffer for 120 min. Half-maximal binding was obtained when cells were incubated in the presence of 3.0 X 10(-10) M unlabeled hGH. Rat GH as well as human placental lactogen were able to compete for binding sites, but with less affinity. Other non-GH peptides at 6.7 micrograms/ml did not affect [125I]hGH binding. Scatchard analysis revealed curvilinear plots, and approximately 2700 high affinity binding sites were calculated. Culture of RIN-5AH in the presence of 1 microgram/ml hGH for 4 days resulted in an 80% increase in insulin content as well as an 18% increase in cell number and DNA and protein content compared to those in cells cultured in the absence of hGH. The dose dependence of the insulinotropic effect showed that half-maximal and maximal stimulation were observed in cells cultured in the presence of 10 and 100 ng/ml, respectively. Insulin release to the medium during the 4-day culture period was not affected by hGH. These data suggest that GH, through binding to specific receptors in the cell membrane, directly stimulates proliferation and function of pancreatic beta-cells.

Adenoma, Islet Cell↗