Stable mineral isotopes in nutritional and related research.
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Humans↗
Biomedical subjects
R Schwartz
Publications and source records attributed to R Schwartz.
Shared idiotypes and restricted immunoglobulin variable region heavy chain genes characterize murine autoantibodies of various specificities.
The study of the Ig variable region heavy chain (VH) genes used to encode antibodies specific for self-epitopes from murine hybridomas showed that three VH families are primarily utilized: VH J558, the largest family, and VH QPC52 and VH 7183, the families most proximal to the Ig joining region heavy chain genes. These monoclonal autoantibodies express cross-reactive idiotopes shared by rheumatoid factors and antibodies specific for Sm. The expression of these idiotypes is independent of major histocompatibility complex and Ig constant region heavy chain haplotypes, self-antigen specificity, and even the VH gene family utilized. Though the experiments described here are limited to murine autoantibodies, similarities exist between murine and human autoimmune diseases. Studies that aim to investigate the relationship between VH gene expression and the presence of cross-reactive idiotypes among human autoantibodies should enable us to better understand the mechanisms of autoimmunity and self-tolerance.
Animals↗
Temporal response of immunoreactive erythropoietin to acute hypoxemia in fetal sheep.
Acute hypoxemia was produced in chronically catheterized sheep fetuses to determine the response time necessary to increase plasma immunoreactive erythropoietin (Ep) concentration. Sodium nitrite (0.2 mM) was infused via a fetal vein to induce fetal hypoxemia. The resultant fetal methemoglobinemia was associated with a predictable, incremental decrease in arterial oxygen content. Twelve nitrite infusions were performed in eight fetal sheep preparations (gestational ages 115-146 days). Mean methemoglobin level increased to 33% of total Hb after 1-2 h of NaNO2 infusion. These results were compared to those obtained in nine control studies in eight fetuses in which no change was observed for plasma Ep, arterial oxygen content, PaO2, pHa, or whole blood lactate. In the nitrite infused group, however, a significant and progressive increase in mean plasma Ep level over baseline levels was observed during the 4th and 5th h of hypoxemia (p less than 0.01). This change in Ep was significantly greater compared to the control group. These results, however, were confounded by the concomitant development of a lactic acidemia secondary to the fetal hypoxemia. To examine the theoretic possibility that lactic acidemia may primarily affect fetal Ep levels, an additional group of five fetuses was infused with L-lactic acid for the same time period. Although the decrements in pHa and whole blood lactate levels achieved in these fetuses were in excess of those observed during the nitrite infusions, this possibility was ruled out since no change in fetal plasma Ep levels occurred. We conclude that during the 4th h of acute fetal hypoxemia a predictable, progressive increase in plasma Ep level is observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Acidosis↗
Preserved fetal plasma amino acid concentrations in the presence of maternal hypoaminoacidemia.
The effects on the conceptus of persistently decreased maternal plasma amino acid concentrations were studied in pregnant rats by the infusion of glucagon (0.21 mg/day) to the mother from day 14 to 20 of gestation with a subcutaneous, osmotically driven minipump. Controls received diluent. The experimental animals either had normal caloric intake and weight gain, or diminished caloric intake with no weight gain. Both experimental groups exhibited a decrease in plasma total amino acid concentration of approximately 50%. Maternal plasma glucose and insulin concentrations were unaffected except for slight decreases in the low weight gain group. At cesarean section on day 20, fetal weight was unaffected in the normal weight gain group, while the low weight gain animals exhibited intrauterine growth retardation. Fetal plasma glucose and insulin concentrations were unaffected. Despite the marked decrease in maternal plasma total amino acid concentration, fetal plasma total amino acid concentration was unaffected. Individual plasma amino acid concentrations in the normal weight gain mothers and fetuses revealed a spectrum of changes. Some maternal amino acids were decreased by more than 60% (alpha-aminobutyric acid, asparagine, threonine, glutamine, alanine) while others were unaffected (tyrosine, tryptophan, phenylalanine, histidine). In general, amino acids that were decreased in the mother exhibited no change or a lesser decrease in fetal plasma concentration, while those that were unaffected in the mothers showed increased fetal concentrations. Fetuses from the low weight gain mothers had plasma amino acid profiles that were similar to those of the normal weight gain mothers.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
A linkage study of cystic fibrosis in extended multigenerational pedigrees.
The linkage of polymorphic DNA markers on chromosome 7 to cystic fibrosis (CF) was examined in two pedigrees and a number of smaller nuclear families. The pedigrees are multigenerational and together consist of more than 300 members including 30 affected individuals, while the nuclear families each have two generations and either two or three children with CF. Tight linkage was observed between the CF locus and the met oncogene locus theta = 0, zeta = 15.45), pJ3.11 (theta = 0, zeta = 10.07), and 7C22 (theta = 0, zeta = 6.64) in both the pedigrees and nuclear families with no evidence for recombination between CF and any of the DNA markers. Weaker linkage between the CF locus and the locus for the serum enzyme activity marker paraoxonase (PON) was detected, theta = 0.18, zeta = 0.76. The two pedigrees were sufficiently informative to detect significant linkage between CF and each of the three DNA markers previously shown to be tightly linked to the CF locus. These results establish a locus for CF in these pedigrees in the region of chromosome 7 nearest the three DNA markers met, pJ3.11, and 7C22 and are consistent with locus homogeneity for the defect causing CF in these populations and others that have been examined to date.
Chromosomes, Human, Pair 7↗
Phase I clinical investigation of 7-con-O-methylnogaril, a new anthracycline antibiotic.
7-con-O-Methylnogaril (menogaril, NSC-269148) is a new anthracycline antibiotic that has been evaluated in a Phase I clinical trial. The drug was administered in a single i.v. infusion over a period of 60 min given every 3 weeks. Twenty-four patients received 64 courses of the drug in a dose range of 16 to 256 mg/m2. Granulocytopenia was dose limiting and prolonged, requiring treatment delay in 5 of 9 patients treated at doses greater than or equal to 192 mg/m2. Concentration dependent phlebitis occurred in 12 patients, and was of minimal severity when the menogaril concentration was less than 1 mg/ml. Hair loss was experienced by 8 patients but was generally mild with only one patient developing total alopecia. Possible acute cardiac toxicity was noted in one patient who had a transient episode of atrial fibrillation following his fifth course of menogaril. Phase II studies of 7-con-O-methylnogaril are planned at a starting dose of 160 mg/m2 for patients with prior chemotherapy or radiotherapy, and 200 mg/m2 for those without prior therapy given at 28-day intervals.
Antineoplastic Agents↗
Effect of periocularly administered gentamicin on serum aminoglycoside concentrations.
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Aged↗
Constitutive production of colony-stimulating factor by mouse lymphoma cell lines is correlated with granulocytosis in vivo.
The mouse lymphoma cell line Eb, its highly metastasizing variant ESb, and an unrelated metastasizing tumor MDAY-D2, were shown to produce colony-stimulating factor (CSF) constitutively both in vitro and in vivo in ascites. For each tumor, the amounts of CSF produced on a per-cell basis in vitro and in vivo were similar. The findings were substantiated using two different methods for CSF determination, a colony assay and an isotope incorporation test. Elevated levels of CSF in serum of mice with tumors were also found. Examination of blood from tumor-bearing mice revealed that whereas total leukocyte counts remained within the normal range, all three tumors caused a reversal of the normal neutrophil-lymphocyte ratio. The severity of the reversal correlated with the propensity of the tumor to elevate serum CSF rather than with in vitro CSF-producing capacity. Thus, whereas production of CSF in vivo was not related to the ability of the tumors to metastasize, it could be causative in creating an imbalance in normal hematopoiesis.
Animals↗
Pharmacokinetics of the bipyridines amrinone and milrinone.
The pharmacokinetics of milrinone were studied in sequential ascending doses in New York Heart Association Class III and IV patients receiving oral and intravenous medication. The parameters determined after parenteral administration were estimated by fitting the plasma concentration data to an open two-compartment body model. After oral medication, regression-independent parameters were determined. After either oral or parenteral administration of milrinone, plasma levels were dose dependent and the drug had an apparent first-order terminal elimination half-life of approximately 2 hr. The apparent volume of distribution was approximately 400 to 500 ml/kg, and total body clearance was approximately 130 ml/kg/hr. These values obtained in patients receiving milrinone were compared with those obtained for milrinone in volunteers, as well as those noted with the other inotropic bipyridine, amrinone. Milrinone's elimination from the blood stream patients was slower that that in normal healthy subjects and faster than amrinone's elimination in patients with congestive heart failure. Milrinone's pharmacokinetic parameters in these patients were unchanged after approximately 30 days of continuous oral medication.
Administration, Oral↗
Glycoconjugates of murine tumor lines with different metastatic capacities. II. Diversity of glycolipid composition.
A syngeneic tumor system in DBA/2 mice consisting of a methyl-cholanthrene-induced, weakly metastatic lymphoma, L5178YE (= Eb), its spontaneous strongly metastatic variant, L5178YES (= ESb), and an unrelated, methylcholanthrene-induced, metastasizing tumor, MDAY-D2, were used to study the relationship between metastatic behavior and composition of GSLs. The D-1-14C galactose and D-1-14C glucosamine-labelled neutral GSL and gangliosides of these tumor cells, and additionally ConA-stimulated spleen T cells from normal mice, were analysed by thin-layer chromatography. Unlabelled GSLs of the tumors were also characterized by (HPLC) after perbenzoylation. Results obtained with the radioactively labelled GSLs correlated with those of the HPLC analysis of unlabelled GSLs. All tumors contained neutral GSL of the ganglio-series. Weakly metastatic tumor Eb showed neutral GSL patterns comparable to those from ConA-stimulated spleen cells, whereas strongly metastatic tumors ESb and MDAY-D2 had an enhanced expression of lactosylceramide. Gangliosides of metastatic ESb and MDAY-D2 had a higher degree of polarity than those of weakly metastatic Eb. Eb cells expressed primarily GM1. Metastasizing ESb and MDAY-D2 had significantly higher amounts of GM3, GM2 and GD1a. An unusual ganglioside, IV3GalNAc-GM1, was found in MDAY-D2 cells and ConA blasts. When the extent of label was compared in neutral GSLs and gangliosides, metastasizing ESb and MDAY-D2 were more heavily labelled in the ganglioside fraction (62%, 58%) than Eb (39%). ESb and MDAY-D2 also contained larger amounts of gangliosides than Eb.
Animals↗
Induction of HLA class-II antigen expression on human carcinoma cell lines by IFN-Gamma.
The effects of recombinant interferon gamma (IFN-gamma) on HLA antigen expression were examined in various human carcinoma cell lines: carcinomas of the lung (ChaGo, Oat 75, SK-LC-LL), colon (HT-29, WiDr), larynx (HEp-2), cervix (ME-180) and mammary gland (AlAb). Surface expression of HLA antigens was determined using monoclonal antibodies directed against monomorphic determinants of HLA class II (HD II, 2.06) and HLA class I (W6/32) by several techniques including indirect immunofluorescence, immunoperoxidase assay, radioimmunoassay of cells, and immunoprecipitation of radioiodinated cells. Without previous exposure to IFN-gamma, HLA class-II antigen was surface-expressed on a small subpopulation of HEp-2 only. All cell lines examined, except AlAb, could be induced to cell-surface expression of HLA class-II antigen after 48 hr incubation in the presence of IFN-gamma (10 units/ml). HLA class-I antigen was present on all cell lines even without treatment, and it was increased after IFN-exposure. Incorporation of 3H-thymidine and 3H-leucine and expression of the transferrin receptor were not significantly altered by IFN-gamma application, indicating a specific regulatory effect of IFN-gamma on HLA antigen expression. Our data demonstrate that HLA class-II surface expression is inducible by IFN-gamma in a variety of epithelial tumor lines. This may have implications for the host immune system defense mechanisms against tumors.
Breast Neoplasms↗
Assay for the determination of human carcinoma cells in circulating blood.
Methods have been developed in an in vitro system (1) of assessing the number of disseminated tumor cells in peripheral blood and (2) of enriching tumor cells from peripheral blood samples for further characterization. Cells from three human carcinoma lines (E 14, ChaGo, and LEDWiDr) were mixed with leukocytes from normal individuals in various ratios. The proportions of tumor cells were determined by a quantitative assay using 3H-thymidine, 3H-leucine, and 3H-galactose incorporation. Determination of tumor cell proportions with this method was most accurate in the range of 5 X 10(4) to 5 X 10(3) tumor cells mixed with a constant number (5 X 10(5] of lymphocytes. It was possible to separate 75Se-labeled tumor cells from 51Cr-labeled blood leukocytes by centrifugation in isopyknic Percoll density gradients. These cells were mixed at different ratios and subjected to Percoll gradient centrifugation. By this approach as few as 5 X 10(3) tumor cells could by identified in the presence of 5 X 10(7) leukocytes, representing a ratio of 1: 10,000. Percoll centrifugation did not damage the tumor cells. In blood cells from two lung cancer patients with lung metastases the incorporation of 3H-thymidine and 3H-galactose was significantly enhanced compared with that in blood cells from patients with primary lung tumors and in cells from normal individuals. This difference became even more apparent when metabolically-labeled blood cells were subsequently separated by Percoll gradient centrifugation.
Adult↗
Effects of ischemia on capillary density and flow velocity in nailfolds of human toes.
The purpose of this study was to investigate reactive hyperemia in the capillary network of human skin in terms of the flow per capillary and the density of flow-active capillaries. Seventeen male subjects 20 to 40 years of age were seated with their right foot placed on the stage of a Leitz epi-ilumination microscope such that the nailfold capillary field in their large toes could be viewed. These vessels were video taped while flow velocity in the right posterior tibial artery was recorded via Doppler ultrasound at rest, then following a 45-sec period of arterial occlusion to the foot. Subsequent to experimentation flow velocity in single nailfold capillaries was measured via video densitometry and the number of flow-active capillaries in the field of view were counted. Following the release of arterial occlusion arterial flow velocity increased 142% above rest, the velocity in single capillaries increased by 54%, and the density of flow-active capillaries, as identified by the presence of red cells, decreased by 37%. The fact that capillary flow velocity increased to a lesser degree than arterial velocity during reactive hyperemia vis-a-vis a decrease in the number of flow-active capillaries indicates that ischemia to the foot elicits a smaller dilatory effect in vascular elements controlling blood flow to the superficial cutaneous region of the toe as compared to other regional vascular networks.
Adult↗
Quality assurance, standards and criteria in health education: a review.
The necessity for health-education program development and implementation to follow principles of quality assurance is discussed. Sound principles of health education practice need to be followed for delivery of quality health education services. The integration of health education and quality assurance in medical care is promoted as an example of activities that may be interdependent with greater relevance together than either approach alone. Examples of standards and criteria for health education are provided. A case is made for the promotion of quality assurance activities for health education practice.
Health Education↗
Correlation of the interpretation of fetal heart rate records with cord plasma erythropoietin levels.
On the basis that fetal levels of plasma erythropoietin (Ep) may reflect fetal oxygenation the primary purpose of the present study was to assess the relation between Ep measured in cord plasma at delivery and the intrapartum fetal heart rate (FHR) record. A scoring system for interpreting FHR recordings blindly was prospectively utilized in 41 selected human pregnancies during the 4 h immediately preceding birth. The correlation of the overall mean FHR score for each individual patient with cord plasma Ep was significant such that the highest Ep levels were observed in those infants with the most abnormal FHR scores. Furthermore, when the birthweights of the infants were adjusted for gestational age, sex, and birth order, birthweight centile was negatively correlated with cord plasma Ep. When both FHR score and birthweight were simultaneously correlated with cord plasma Ep using multiple regression, the combined effect of these two factors improved the association of either alone with both contributing approximately equally.
Birth Weight↗
Near-total pancreatectomy for hyperinsulinism. Spontaneous remission of resultant diabetes.
Persistent hyperinsulinism in the newborn may warrant surgical intervention to prevent neurologic sequelae. Subtotal pancreatectomy may not be adequate, necessitating near-total pancreatectomy with subsequent development of diabetes mellitus. We report an infant with hyperinsulinemic hypoglycemia who underwent near-total pancreatectomy. The postoperative period was characterized by insulin-dependency and extreme insulin sensitivity. Clinical follow-up and C-peptide determinations showed a return of insulin secretory capacity permitting the discontinuation of insulin therapy after five months. This experience reaffirms the potential for a favorable outcome after near-total pancreatectomy in the newborn period for severe hyperinsulinism.
Blood Glucose↗
Induction in utero of hepatic glucose-6-phosphatase by fetal hypoinsulinemia.
The effect of fetal hypoglycemia and hypoinsulinemia on fetal rat hepatic glucose-6-phosphatase activity was studied. Fetal hypoglycemia and hypoinsulinemia were produced by inducing maternal hyperinsulinemia and hypoglycemia secondary to the exogenous administration of insulin via implantation of osmotically driven minipumps on day 15 of gestation into 15 experimental animals. 13 animals served as sham-operated controls. Cesarean sections were performed on day 20 or 21 of gestation under pentobarbital anesthesia. Liver glucose-6-phosphatase activity was increased in the hypoinsulinemic fetuses. In contrast, the hyperinsulinemic mothers had suppressed hepatic glucose-6-phosphatase activity. Hypoinsulinemia would appear to be the primary stimulus for enhanced fetal glucose-6-phosphatase in this model.
Animals↗
Third party reimbursement for diabetes care. I. The prospective payment system: implications for diabetes patient education.
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Diabetes Mellitus↗