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Biomedical subjects

R Schwartz

Publications and source records attributed to R Schwartz.

At least 343 records · Page 19Linked to original sources

Rapid fluctuations in glycohemoglobin (hemoglobin Alc) related to acute changes in glucose.

Since glycohemoglobin (Hb Alc) has been observed to change acutely, Hb Alc was studied in both human and monkey subjects to determine whether acute changes occurred with rapid changes in plasma glucose concentration. A marked increase in Hb Alc was observed over 2 days in a 3 1/2-year-old boy who developed steroid-induced diabetes mellitus. In addition, a significant fall in Hb Alc was observed over 7 days in a pregnant woman recovering from hyperglycemia and ketoacidosis. During marked acute hyperglycemia and its recovery, three normal rhesus monkeys were studied for changes in plasma glucose and Hb Alc over 1 day. Hb Alc more than doubled in each study by the time plasma glucose reached approximately 90 mmol/L and then declined by 12 hr. While maintained at their usual stable glucose concentrations, human and monkey subjects showed little differences in Hb Alc levels for dialyzed and nondialyzed hemolysates. With acute changes in blood glucose, however, the dialysis for 48 hr yielded lower Hb Alc values. Hb Alc increased when hemolysates were dialyzed against high glucose concentrations. Thus the effect of dialysis in sample preparation may be an important factor in correlating glycohemoglobin with acute and chronic changes in glucose status.

Adult↗

A computerized tube leukocyte adherence inhibition assay to detect antitumor immunity in early human cancer: a review of two years' experience.

A 2-year experience with a computerized in vitro assay of leukocyte adherence inhibition (LAI) indicated that patients with cancer of either the colorectum, stomach, pancreas, breast, or lung expressed antitumor immunity to an organ-type specific neoantigen. About 1% of the 1,299 control subjects with benign or malignant disease had a positive LAI assay and 2.5% of patients with inflammatory disease of the colorectum, stomach, pancreas, or lung had a positive LAI assay when tested against tumor extracts of the same organ. Of the 351 patients with cancer of either the colorectum (111), stomach (40), pancreas (28), lung (57), or breast (116) who harbored a microfocus of cancer, 80% or more were LAI positive. As the stage of the cancer advanced, fewer patients were LAI positive. Nine of 45 patients (20%) with colon adenomas had a positive LAI response to colon cancer antigen and 17 of 204 patients (8%) with benign breast disease reacted to the breast cancer antigen. Our results suggested that the leukocytes of some of the LAI-positive patients with either colon adenomas or benign breast disease were responding to an organ-specific neoantigen. Whether the acquisition of a cell surface tumor antigen by the colon adenomas and the dysplastic lesions of the breast implies an irretrievable step to ultimate malignancy is unknown. Most patients exhibit a vigorous antitumor immune response when the cancer exists as a microfocus, and some even before the neoplasm has acquired the capacity to invade.

Antigens, Neoplasm↗

Mass spectrometry of a volatile Mg chelate in the measurement of stable 26Mg when used as a tracer.

A method for the detection of 26Mg enrichment of natural Mg was developed based on mass spectrometry (MS) of a Mg chelate made by complexing Mg to 2,2',6,6'-tetramethylheptanedione (THD). The chelate [Mg(THD)2] was extracted at pH greater than 9 from dilute aqueous solutions into ethyl ether, recovered by sublimation at room temperature, and introduced by solid probe into a Finnigan 3300 mass spectrometer. The chelate was ionized by electron impact. Samples were heated to a maximum temperature of 200 degrees C at a rate of 700 degrees C/h. Each analysis required 1--5 micrograms Mg(THD)2. Enrichment levels as low as 5% above natural abundance could be detected satisfactorily. Precision was best at 26Mg enrichment levels of 8--40% above natural abundance, the levels most likely to be encountered in analysis of plasma, urine and fecal samples from experimental subjects who had received 26Mg as a tracer. The method was compared to neutron activation (NA) analysis and judged superior.

Chelating Agents↗

The nasopharyngeal culture in acute otitis media. A reappraisal of its usefulness.

Simultaneous cultures of the nasopharynx and middle ear exudate (obtained by tympanocentesis) were obtained from 225 children (mean age, 34 months; median age, 41 months) with suppurative otitis media. A 72% prediction rate for middle ear pathogens was obtained by examining the nasopharyngeal cultures after the strict observance of two essential prerequisites: (1) the nasopharyngeal culture was immediately plated on appropriate solid agar and (2) a semiquantitative method for bacterial enumeration was employed in the reading of the nasopharyngeal culture plates. The technique was most valuable where 2+ (greater than 25% up to 50% of total number of colonies was a single pathogen) or greater of a single pathogen was recovered from the nasopharynx. In only one instance, the semiquantitative nasopharyngeal culture incorrectly predicted the middle ear pathogen if one was recovered. Quantitative nasopharyngeal cultures were particularly useful in predicting the presence of ampicillin-resistant Haemophilus influenzae and group A streptococci as causative agents in otitis media.

Acute Disease↗

Serologic diagnosis of human infections with lymphocytic choriomeningitis virus: comparative evaluation of seven methods.

The aim of this work was to compare different procedures for the serodiagnosis of human infections with the lymphocytic choriomeningitis (LCM) virus and to single out those which are both reliable and practicable. By the use of 46 sera from as many persons who had undergone infection with this virus either some time in the past or very recently and of 26 control sera, seven methods were evaluated. For making a rapid diagnosis soon after infection, determination of antibody by the immunofluorescence procedure appears to be the method of choice. Of equal reliability, though less easy to perform, is demonstration of sensitizing antibody by a plaque reduction assay, this procedure having the additional advantage of detecting antibody many years after infection, probably for life. For the demonstration of neutralizing antibody, three of four methods which were analyzed in this study gave the expected information, two employing mice, one employing cell cultures for the determination of residual infectivity. Neutralizing antibody was found to appear relatively late after infection and cannot, therefore, be recommended for the demonstration of seroconversion early in covalescence. This antibody, however, persists for many years, presumably lifelong, and is well suited to detect infections with this virus if they have occurred in the more distant past. Based on previous observations by ourselves and others, as well as on the work reported here, the complement fixation test appears to be of little value for the serological diagnosis of infection with LCM virus.

Animals↗

Influence of magnesium depletion on matrix-induced endochondral bone formation.

The effect of magnesium deficiency on bone cell differentiation and bone formation was investigated using in vivo matrix-induced endochondral ossification as a test system. Demineralized bone matrix was implanted subcutaneously in young (35-day-old) male Long-Evans rats that had been fed a semisynthetic Mg-deficient diet (50 ppm Mg) for 7 days. Plasma Mg levels were reduced to 25-30% of control values at that time. Control rats were paired the same diet, supplemented to contain 1000 ppm Mg. The implants were harvested 7, 9, 11, 15, and 20 days after implantation and analyzed for Mg and Ca content, 45Ca incorporation, and alkaline phosphatase levels. At each stage, plaques (implants) removed from Mg-deficient rats showed retardation in cartilage and bone differentiation and matrix calcification. Magnesium content was markedly reduced when compared to the control plaques. Histological appearance of the matrix-induced plaques confirmed the retardation in bone development and mineralization suggested by the chemical indicators. Most marked was the virtual absence of bone marrow in 20-day-old plaques in Mg-depleted rats. These data show that bone cell differentiation can occur in a severely Mg-depleted environment, although the onset of mineralization and bone remodeling was delayed and bone marrow differentiation was impaired.

Alkaline Phosphatase↗

'Minor hemoglobins': an alternative approach for evaluating glucose control in pregnancy.

'Minor hemoglobins' (Hb AI) were measured in 178 women during pregnancy and immediately postpartum by a thiobarbituric acid spectrophotometric method. The patients were classified according to an oral glucose tolerance test (GTT) and an assessment of risk factors for diabetes in normal (n = 75), probably normal (n = 72) and chemical diabetics (n = 26). 5 pregnant insulin-dependent diabetics were also studied. Hb AI was unchanged during the second and third trimesters of pregnancy and immediately postpartum (less than 6 days) in women with normal glucose tolerance. Moreover, no difference of Hb AI level was found when compared with a separate group of nonpregnant individuals (n = 15). Chemical diabetics had significantly higher mean third trimester and postpartum Hb AI than normals (p less than 0.001). The highest Hb AI levels during pregnancy were found in the insulin-dependent diabetics, although these were lower compared to a separate group of nonpregnant insulin-dependent diabetics (n = 10; p less than 0.05). During pregnancy, a significant correlation was found between Hb AI and the 2-hour value of the GTT (p less than 0.001). A positive correlation was also found between third trimester maternal Hb AI and infant birth weight (p less than 0.001). Hb AI may complement other parameters in evaluating maternal glucose tolerance during pregnancy.

Birth Weight↗

Evidence for the existence of phosphoenolpyruvate carboxykinase ferroactivator activity in adult and fetal guinea pigs.

Newborn (24--72 h) guinea pig liver cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity is increased by incubation of the cytosol with the metal salts FeCl2, MnCl2, CoCl2 and CdCl2. FeCl2 at 30 micromol/l concentration is the most effective activator causing a 3.5-fold increase in activity. Purified rat liver cytosolic PEPCK is activated by 30 mumol/l FeCl2 in the presence of liver cytosol of fetal and newborn guinea pigs. These results confirm the existence of PEPCK ferroactivator in the guinea pig which has properties similar to the one found in rat liver. The tissue distribution of ferroactivator activity parallels that of cytosolic PEPCK, being highest in the gluconeogenic organs liver and kidney. Hepatic PEPCK ferroactivator activity can be demonstrated by day 45 of gestation, increasing linearly in specific activity to adult levels at term (65 days). The distribution and development of the ferroactivator is consistent with the hypothesis that it may play a role in the physiologic control of PEPCK.

Animals↗

Phosphoenolpyruvate carboxykinase in experimental intrauterine growth retardation in rats.

This study examines the role of impaired gluconeogenesis in the pathogenesis of neonatal hypoglycemia in intrauterine growth retardation (IUGR). IUGR was produced experimentally in eight pregnant rats by ligation of uterine arteries at the 17th day of gestation. Delivery occurred spontaneously at term. Sham operations were performed in five pregnant rats at the same gestational age and the fetuses delivered at term served as controls. The body weights of newborn rats with IUGR were significantly lower than the controls (5.32 +/- 0.12 vs. 6.22 +/- 0.06 g, mean +/- SE, P less than 0.001). The fetal liver weights were also significantly smaller in IUGR than in the control animals (0.224 +/- 0.14 vs. 0.340 +/- 0.12 g, P less than 0.001). The activity of phosphoenolpyruvate carboxykinase (PEPCK) (the rate-limiting enzyme of gluconeogenesis) in liver cytosols was significantly lower in rats with IUGR (0.06 +/- 0.01 vs. 0.11 +/- 0.02 microM phosphoenolpyruvate/g liver/min when compared with controls (P less than 0.05). A direct relationship between this enzyme and the birth weight was observed, suggesting a close relationship between intrauterine nutrition and the status of gluconeogenesis. The blood glucose level was also lower in growth-retarted fetuses (36.6 +/- 4.7 vs. 69.6 +/- 4.3 mg/dl, p less than 0.001) when compared with controls. The data suggest that gluconeogenesis is impaired in IUGR and is partly responsible for the increase in the incidence of neonatal hypoglycemia in this group of subjects.

Animals↗

Chronic hyperinsulinemia in the fetal rhesus monkey: effects on hepatic enzymes active in lipogenesis and carbohydrate metabolism.

Hyperinsulinemia was produced in fetal rhesus monkeys for 21 days in the last third of gestation by subcutaneous pork insulin injected at 19 U a day. Plasma insulin concentrations in treated fetuses (N = 4) were 3525 microU/ml. There was no difference in paired pre- and post-treatment fetal plasma glucose concentration. Activity of the hepatic enzymes that promote glucose utilization (glucokinase and hexokinase) and glycolysis (phosphofructokinase, pyruvate kinase, and pyruvate dehydrogenase) was unaffected. Similarly, glycogen metabolism enzymes (active and inactive synthase and phosphorylase) were unaltered. Two gluconeogenic enzymes (PEPCK and glucose-6-phosphatase) were diminished in the treated group compared with controls. Fetal hyperinsulinemia enhanced lipogenic and NADPH-producing enzyme activities, as evidenced by a twofold increase in fatty acid synthase and in citrate cleavage enzyme activity. Malic enzyme was absent. Hyperinsulinemia with euglycemia (1) increases the activity of enzymes that participate in lipogenesis, (2) decreases some of those controlling gluconeogenesis, and (3) has no effect on the enzymes of glycolysis.

Animals↗