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Biomedical subjects

B Glaser

Publications and source records attributed to B Glaser.

At least 127 records · Page 7Linked to original sources

Basement membrane collagen: degradation by migrating endothelial cells.

One of the first steps in neovascularization is dissolution of the basement membrane at the point of endothelial outgrowth. An assay was developed to determine whether basement membrane collagens (types IV and V) are degraded by endothelial cells migrating toward a chemotactic stimulus. Fetal bovine endothelial cells were placed on one side of a filter containing the collagen substrate, and a chemoattractant derived from retinal extracts was placed on the opposite side. Degradation of both type IV and type V collagens was observed when the retinal factor was placed on the side of the filter opposite the endothelial cells. Metalloproteinases that cleaved type IV and type V collagens could be extracted from the endothelial cells with detergents. Such endothelial cell-associated (possibly membrane-bound) proteinases may locally disrupt the basement membrane and facilitate the outgrowth of capillary sprouts toward the angiogenic stimulus.

Animals↗

Secretion of pancreatic polypeptide in man in response to beef ingestion is mediated in part by an extravagal cholinergic mechanism.

The effect of atropine, a muscarinic cholinergic blocking agent, on the response of plasma pancreatic polypeptide (hPP) to the ingestion of beef was investigated. Six healthy subjects ingested 250 g broiled ground beef on three occasions. After beef ingestion alone, the expected biphasic plasma hPP response was observed. On the two other occasions atropine (intravenous bolus followed by infusion) was begun either at 4 or 60 min after the beginning of beef ingestion so as to coincide with the early (first) and late (second) phases of hPP response to beef ingestion. On both occasions plasma hPP concentrations returned rapidly to baseline. Mean integrated incremental hPP responses in the absence of atropine were 9.1 +/- 3.4 ng min ml-1 for the first phase (0-40 min) and 29.7 +/- 5.7 ng min ml-1 for the second phase (60-180 min); with atropine at 4 min, respective responses were 0.8 +/- 0.9 and -1.0 +/- 1.3 ng min ml,-1 and with atropine at 60 min they were 10.6 +/- 5.0 and 1.3 +/- 1.6 ng min ml.-1 After atropine administration, the half-time of disappearance of hPP from the circulation was 4-6 min, suggesting the complete cessation of stimulated hPP secretion. We conclude that the mechanisms of both the early and late phases of beef meal-stimulated release of hPP involve muscarinic cholinergic-neural transmission. The portion of the second (late) phase response which has been shown to persist after truncal vagotomy must be mediated by a cholinergic mechanism which is extravagal in character.

Adult↗

A spot sample test for the estimation of urinary or nephrogenous cAMP in the evaluation of parathyroid function.

The measurement of urinary or nephrogenous cAMP is considered to be a reliable index of parathyroid function. This test usually involves timed urine collections which renders it logistically burdensome. We have therefore assessed the validity of using spot urine samples for this purpose, 2-hour urine collections were compared to spot samples for the estimation of urinary and nephrogenous cAMP in 10 patients with hypercalcemic primary hyperparathyroidism and 22 control subjects. The results demonstrated: (1) a considerable overlap between the primary hyperparathyroid and control groups when the urinary and nephrogenous cAMP values were expressed as a function of creatinine excretion. (2) A satisfactory separation between the two groups when the 2-hour urine and spot sample levels of urinary cAMP--and even more so nephrogenous cAMP--were expressed as a function of glomerular filtrate (i.e. nmol cAMP/100 ml glomerular filtrate). (3) An excellent correlation (r = 0.91, p less than 0.001, n = 32) between 2-hour urine collections and spot samples for both urinary and nephrogenous cAMP levels. The feasibility of using a spot sample for measuring urinary or nephrogenous cAMP without impairing its diagnostic efficacy considerably simplifies the logistics of the test. This is of particular importance for ambulatory patients.

Adult↗

Sex difference in the sensitivity of the human pancreatic polypeptide cell to autonomic nervous stimulation in man.

We have examined the plasma human pancreatic polypeptide (hPP) response to beta-adrenergic (infusion of epinephrine-phentolamine), vagal cholinergic, (insulin-hypoglycemia), and extravagal cholinergic (secretion infusion) stimulation in healthy, nonobese, age-matched males and females. beta-Adrenergic stimulation caused a rise in plasma hPP concentration in males that was 6 times that of females, whereas there were no differences between the sexes in the mean responses of pulse rate, systolic and diastolic blood pressure, or in plasma concentrations of glucose, insulin, and glucagon. Extravagal cholinergic stimulation caused increases of hPP secretion that were similar in males and females. Insulin-induced hypoglycemia was the most efficacious stimulus, and caused a similar rise in hPP response in males and females. Thus, in males there is greater sensitivity of the hPP cell to beta-adrenergic stimulation than females. The plasma hPP responses appear to be a more sensitive, discriminating index of adrenergic autonomic function than cardiovascular and other pancreatic hormonal responses.

Autonomic Nervous System↗

A new syndrome of symptomatic cutaneous mastocytoma producing vasoactive intestinal polypeptide.

An 8-mo-old male child presented with generalized flushing and apnea which followed irritation of a 1.5 x 0.5 cm cutaneous mastocytoma on the left upper arm. Peripheral venous blood samples were drawn before and after manipulation of the tumor, immediately after excision, and again 30 days later. The plasma vasoactive intestinal polypeptide level before excision was high (345 pg/ml) and was accompanied by low acid secretion (15.4 mEq/L) and hypergastrinemia (209 pg/ml), all of which returned to normal after excision of the tumor (50 pg/ml, 35.7 mEq/L, and 131 pg/ml, respectively). Serum histamine levels were undetectable. Histology of the tumor showed only mast cells and no enterochromaffin tissue. The immunoreactive vasoactive intestinal polypeptide content of the tumor was 28 ng/g wet wt and the extracted vasoactive intestinal polypeptide was immunologically indistinguishable from natural porcine vasoactive intestinal polypeptide. The child has remained asymptomatic postoperatively. We conclude that the symptoms associated with this mastocytoma may have been produced by oversecretion of vasoactive intestinal polypeptide and not histamine.

Apnea↗

Gastrointestinal/pancreatic hormone concentrations in the portal venous system of nine patients with organic hyperinsulinism.

Percutaneous transhepatic sampling of blood in the portal venous system (TPVS) was used to; (1) localize hormone secreting tumors and help in differentiating tumors from diffuse disease (nesideoblastosis and hyperplasia with adenomata) in 9 patients with fasting hypoglycemia and hyperinsulinism, and (2) study the concentration an distribution of the immunoreactive peptides: insulin (IRI), gastrin (IG), glucagon (IRG), pancreatic polypeptide (hPP), and somatostatin (SRIF-LI), in the venous drainage of the uninvolved portion of the pancreas and GI tract. Localized elevations of IRI (64-920 microunits/ml) predicted tumor localization in 6 patients with single tumors that were not demonstrable angiographically. In one patient with nesideoblastosis and another with islet cell hyperplasia with adenoma, elevated IRI concentrations at multiple locations suggested a diffuse or multicentric process. Elevations of SRIF-LI in the same region as IRI elevations in one patient and of IRG in another patient suggested that these tumor produced two hormones. Some problems in the interpretation of portal venous insulin concentrations are discussed. The locations of maximum portal venous system plasma concentrations and portal-arterial gradients (mean +/- SE pg/ml) in five patients with small single insulinomas were: IG, gastrocolic trunk (126 +/- 27, 46 +/- 22); IRG, proximal splenic vein (130 +/- 30, 47 +/- 13) and gastrocolic trunk (131 +/- 23, 60 +/- 13); hPP, portal vein (164 +/- 48, 49 +/- 22); SRIF-LI, superior mesenteric vein (186 +/- 50, 57 +/- 20) and gastrocolic trunk (178 +/- 59, 55 +/- 21). It is concluded; (1) TPVS can be used successfully to localize single insulin-secreting tumors of the pancreas and to help distinguish them from diffuse disease but problems in such differentiation do occur, (2) circulating SRIF-LI and IRG are derived from both the pancreas and the gut, IG predominantly from the proximal gut and hPP from the head of the pancreas, and (3) The data provide new information for the interpretation of portal insulin concentrations in patients with organic hyperinsulinism and of hormone concentrations for localization of peptide-producing tumors of the pancreas other than insulinomas.

Adenoma↗

Truncal vagotomy abolishes the somatostatin response to insulin-induced hypoglycemia in man.

The mechanism whereby insulin-induced hypoglycemia stimulates release of immunoreactive somatostatin (SRIF-LI) into the peripheral circulation in man is unknown. We have measured the plasma SRIF-LI response to insulin-induced hypoglycemia in 16 healthy subjects and five subjects with prior truncal vagotomy. Mean nadir of plasma glucose was similar in the two groups (37 +/- 5 and 34 +/- 2 mg/dl in the control group). Hypoglycemia induced a brisk rise in plasma pancreatic polypeptide (hPP) concentrations in healthy subjects (maximum concentration 1563 +/- 245 pg/ml) whereas in none of the postvagotomy subjects was there a significant change in hPP concentrations, indicative of completeness of the truncal vagotomy. In healthy subjects SRIF-LI concentrations rose for a basal of 168 +/- 19 pg/ml to a maximum of 254 +/- 30 at 39 +/- 4 minutes (p less than 0.005) with an incremental area of 2.8 +/- 1 ng . min/ml above basel. In vagotomized subjects, the mean basal SRIF-LI concentration of 166 +/- 22 pg/ml was not significantly different from that in healthy subjects. After insulin injection, SRIF-LI concentration fell with a net decrement of -3.2 +/- 1 ng . min /ml below the basal. It is concluded that the SRIF-LI response to insulin-induced hypoglycemia is dependent upon vagal integrity. Section of the vagus unmasks a suppressive effect of insulin action or its metabolic or hormonal consequences on the concentration of SRIF-LI in plasma.

Adult↗

Design of a study to evaluate drug therapy of serious ventricular rhythm disturbances after an acute myocardial infarction.

A study was designed to investigate whether long-term use of aprindine can prevent sudden death from primary ventricular fibrillation. Patients with a proven recent myocardial infarction and malignant ventricular arrhythmias occurring late after the acute episode were asked to participate in a 1-yr, double-blind, randomized, placebo-controlled trial to suppress the rhythm disturbances observed on an ambulatory electrocardiogram. Particular care was taken to monitor drug adherence. Arrhythmia detection by ambulatory electrocardiography was used to assess drug efficacy; side-effects establish the maximum tollerated dose for each individual patient. Aprindine was therefore used under optimal circumstances. An interactive computer system served as a data base and provided the investigators and the monitoring committee with all the information required for a proper evaluation of the progress of the study.

Aprindine↗

Increased uterine activity and fetal deterioration during maternal hyperthermia.

The role of hyperthermia in the absence of infection has been investigated in the pregnant baboon. Twenty-three near term animals were used. Catheters were placed in maternal and fetal arteries and thermocouples implanted in maternal colon and fetal esophagus. Maternal temperature was raised to between 41 and 42 degrees Centigrade (C.), by applying external heat. The temperature gradient between fetus and mother (delta T F-M) was 0.47 degree C. under steady-state conditions with maternal temperature at 38 degrees C. and rose to 0.75 degree C. at 42 degrees C. Hyperthermia caused a twofold increase in uterine activity; a metabolic acidosis developed in the mother and a profound acidosis and hypoxia developed in the fetus. There was also a marked fall in blood pressure and an increase in heart rate in both mother and fetus; late deceleration of the fetal heart rate occurred at a higher oxygen level and pHa than has been observed under normothermic conditions.

Acidosis↗