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Biomedical subjects

S Krantz

Publications and source records attributed to S Krantz.

At least 37 records · Page 2Linked to original sources

The anemia of primary autonomic failure and its reversal with recombinant erythropoietin.

OBJECTIVE: To determine if chronic sympathetic deprivation is associated with anemia and a low erythropoietin response. DESIGN: Survey of the prevalence and characteristics of anemia in patients with severe primary autonomic failure. SETTING: A referral service for autonomic failure in a tertiary teaching hospital. PATIENTS: 84 patients with primary autonomic failure who had symptomatic orthostatic hypotension. INTERVENTION: Open-label trial with human recombinant erythropoietin. RESULTS: Anemia was present in 32 of 84 patients (38%; 95% Cl, 27% to 50%). Plasma norepinephrine levels, measured in patients standing upright, were lower in the patient group with lower hemoglobin levels. Mean values in 22 patients with a hemoglobin level of less than 120 g/L were as follows: hemoglobin, 108 g/L (range, 87 to 118 g/L); hematocrit, 0.33; corrected reticulocyte counts, 0.008; mean corpuscular volume, 89 fL (89 microns 3); serum iron, 16.5 mumol/L (92 micrograms/dL); total iron binding capacity, 43.3 mumol/L (242 micrograms/dL); ferritin, 184 micrograms/L; serum vitamin B12, 410 pmol/L (556 pg/mL); and serum folate, 22.7 nmol/L (10 ng/mL). No relation was found between serum erythropoietin and blood hemoglobin levels. In seven of nine patients with autonomic failure who had hemoglobin levels less than 120 g/L, serum erythropoietin levels decreased below the 95% confidence interval corresponding to patients with iron deficiency anemia. Therapy with recombinant erythropoietin improved mean hemoglobin levels (from 108 to 133 g/L) in all patients treated (n = 5) at relatively low doses (25 to 50 units/kg body weight, subcutaneously, three times a week). CONCLUSIONS: Our data support the hypothesis that the sympathetic nervous system stimulates erythropoiesis in humans because anemia is a frequent occurrence in patients with severe autonomic failure and is associated with a blunted erythropoietin response.

Aged↗

Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin.

We treated myelodysplastic syndrome patients (MDS) with both recombinant human granulocyte colony-stimulating factor (G-CSF) and recombinant human erythropoietin (EPO) to determine whether such combination therapy resulted in improvement of their anemias. Twenty-four of 28 patients begun on study completed the protocol and were evaluable for erythroid responses. Therapy was initiated with G-CSF at 1 micrograms/kg administered by daily subcutaneous injection and adjusted to either normalize or double the neutrophil count. EPO was then administered by daily subcutaneous injection at a dose of 100 U/kg and dose-escalated to 150 and 300 U/kg every 4 weeks while continuing the G-CSF. Changes in absolute reticulocyte count, hematocrit level, and need for RBC transfusions were compared with pretreatment values as well as other blood cell counts. Ten of 24 patients (42%) had erythroid responses, whereas all patients had neutrophil responses. Six previously transfused patients no longer required RBC transfusions during the treatment period. Erythroid responses were found to be independent of patient age, French-American-British subtype, duration of disease, prior RBC transfusion requirements, or cytogenetic abnormalities at presentation. Pretreatment serum EPO levels were lower in erythroid-responding as compared with nonresponding patients (median 157 v 600 U/L; P = .05). The combined treatment modality was generally well tolerated. We conclude that a substantial percentage of MDS patients had both erythroid and myeloid responses when treated with the combination of G-CSF and EPO.

Adult↗

Binding sites for short-term glycated albumin on peritoneal cells of the rat.

The interaction of in vitro short-term glycated rat serum albumin with rat peritoneal cells (40% macrophages) was investigated. Using 125I-labeled albumins the following results were obtained. Glycated albumins showed a binding reaction at 4 degrees C, which appeared to reach equilibrium within 2 h. The concentration-dependent binding of glycated albumin showed saturation. Binding data evaluated for glycated albumin using the Sips equation are: average association constant Ko = 3.15 x 10(7) M-1 with a heterogeneity index of a = 0.8 and 1.12 x 10(4) binding sites per cell. Such binding sites were identified in 40% of the peritoneal cell preparations studied. Native albumins, maleylated albumin, chondroitinsulfates, polylysine, lysine, fructose, glucose and hexitol-lysine could not compete with radio-labeled glycated rat albumin for its binding site on peritoneal cells. Effective competitors were glycated human serum albumin, glycated polylysine and fructose-lysine. Although the contamination with minute amounts of advanced glycosylation end products (AGE) could not be excluded, short-term glycated albumin was found to be bound to membranes of peritoneal phagocytotic cells by fructose-lysine specific proteins, whose approximately defined molecular masses of 290 kDa are distinct from hitherto described binding proteins for AGE- and aldehyde-modified proteins or for the scavenger receptors.

Animals↗

Stress and coping among Missouri rural and urban children.

A cross-sectional survey using a convenience sample of 157 Missouri rural and urban children (ages 8-13 years) yielded no significant differences in perceptions of stressors or use of coping strategies for dealing with those stressors between rural and urban children. The Feel Bad Scale and the Schoolagers' Coping Strategies Inventory measured the children's perceptions of stressors and use of coping strategies. Rural children experienced stressor levels equivalent to urban children, yet they were underserved in mental and physical health needs. The children studied reported self-care through coping strategies for management of their stressors. Longitudinal research is needed to identify the impact of stress and interventions on the health and behavior of children in rural settings.

Adaptation, Psychological↗

Vanadate mimics the effect of stem cell factor on highly purified human erythroid burst-forming units in vitro, but not the effect of erythropoietin.

When orthovanadate, an inhibitor of protein tyrosine phosphatase activity, was added to highly purified human blood erythroid burst-forming units (BFU-E) a marked increase in the number and size of erythroid bursts was evident at an optimum concentration of 4 microM. Because BFU-E are stimulated by stem cell factor (SCF), interleukin 3 (IL-3), and erythropoietin (EP), this effect could occur through an enhancement of any one of these pathways. However, no effect was observed on human erythroid colony-forming units (CFU-E), indicating that vanadate was not potentiating the effect of EP. The time course of decline in BFU-E, when vanadate was added in vitro on successive days, followed the time course produced by delayed addition of SCF but not IL-3. In addition, vanadate markedly enhanced the effect of an optimal concentration of IL-3, but it could only enhance the effect of SCF when SCF concentrations were less than optimum. These experiments demonstrate that vanadate markedly stimulates the number and size of human BFU-E in vitro and that it mimics the effect of SCF. Vanadate may be acting as a phosphatase inhibitor that potentiates the kinase activity induced by SCF, but elucidation of its specific biochemical effects on these cells awaits further investigation.

Cells, Cultured↗

Mechanisms of the cardioprotective actions of WEB-2170, bepafant, a platelet activating factor antagonist, in myocardial ischemia and reperfusion.

The cardioprotective effects of WEB-2170, a specific platelet activating factor (PAF) receptor antagonist, were investigated in a feline model of myocardial ischemia (MI) and reperfusion. Either WEB-2170 (1-mg/kg bolus plus 2 mg/kg/hr) or its vehicle (0.9% NaCl) was administered 1 hr after left anterior descending coronary artery occlusion (i.e., 30 min before reperfusion). The cardiac area-at-risk (AAR) was similar in MI-reperfused (MI + R) cats given either WEB-2170 (31.5 +/- 3.6%) or vehicle (27.8 +/- 2.8%). However, in cats receiving only the vehicle, 1.5 hr of ischemia plus 4.5 hr of reperfusion resulted in significant myocardial injury (necrotic tissue/AAR, 37.7 +/- 4.5%), high plasma creatine kinase activity (29.4 +/- 4.1 I.U./micrograms of protein) and a marked decrease in endothelium-dependent relaxation in isolated left anterior descending coronary arteries to acetylcholine (33 +/- 4% of U-46619-induced vasocontraction) with no change in endothelium-independent relaxation to NaNO2 (91 +/- 1%). In contrast, MI + R cats treated with WEB-2170 developed significantly less myocardial necrosis (necrotic tissue/AAR, 12.0 +/- 2.8%, P less than .001), lower plasma creatine kinase activity (16.5 +/- 4.1 I.U./micrograms of protein, P less than .01) and enhanced vascular relaxation to acetylcholine (53 +/- 4.1%, P less than .01) compared to MI + R cats given only the vehicle. Furthermore, the addition of WEB-2170 to PMN suspensions in vitro significantly inhibited (P less than .01) PAF-induced polymorphonuclear leukocyte (PMN) adherence to endothelial cells (12 +/- 2.4 cells/field vs. 27 +/- 2.6 in the control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Occupational implications of the chlorofluorocarbon ban in Sweden.

Limitations on the use of full halogenated chlorofluorocarbons (CFCs) may create occupational environmental problems. These are currently largely unknown, because the toxicology of most CFC substitutes is unknown. Therefore, toxicity testing of CFC substitutes is necessary, and this can best be done before their use commences. Destruction of CFC and materials containing CFC could generate new chemical compounds, especially during incineration. In addition, problems with higher noise and vibration levels may occur when CFC substitutes are employed, and we should keep in mind that occupational environment problems could also develop when new routines are introduced for transporting, storing, and handling new materials.

Humans↗

[Some problems in standardization of fructosamine tests].

The degree of nonenzymatic glycation of serum proteins was estimated in 500 nondiabetic subjects and in 124 Type 2 diabetic out-patients. The values were evaluated in relation to a DMF calibration curve, a secondary glycated protein standard and to serum protein concentrations. Neglecting the evaluation with respect to the protein concentration 0.4% of the samples from nondiabetics and 9% from diabetic patients would have been incorrectly interpreted. The fructosamine values from nondiabetic subjects showed a Gaussian distribution. The use of secondary protein standards is a premise to a widespread application of the fructosamine assay in diabetic care. The calibration of such secondary glycated protein standards results in some problems when using DMF protein mixtures as primary standards, because albumin preparations from the same or different suppliers gave variable standardization curves.

Adult↗

Complement component 3 (C3) genetics and diabetes mellitus.

Complement component 3 (C3) phenotype and allele frequencies were defined in 312 patients with type-1 diabetes (insulin-dependent diabetes mellitus), 256 patients with type-2 diabetes (non-insulin-dependent diabetes mellitus), 114 apparently non-diabetic first-degree relatives of type-1 diabetics, in 10 families (29 members) with a familial history of type-1 or type-2 diabetes, in 181 patients with coronary heart disease and 255 subjects with arterial hypertension. 512 blood donors served as controls. All persons investigated were Europeans. There is no evidence that genes linked to C3 influence susceptibility to type-1 and type-2 diabetes and to their late complications as well as to atherosclerosis and essential hypertension. The distribution of apolipoprotein E phenotypes in patients and controls was likewise not significantly different. The combined evaluation of data from linked genes (C3 and apo E) could not improve the results. Deductions of C3 as a genetic disease marker have to be interpreted with caution.

Alleles↗

[Methodologic studies of the isolation of VLDL using the lipoprotein precipitation reaction in the preparation of apolipoprotein E (Apo E)].

Several lipoprotein precipitation reactions were examined in the isolation of VLDL for apo E phenotyping in comparison to ultracentrifugation. MgCl2-Heparin- and phosphotungstic acid precipitation revealed the best results, although an apo E phenotyping was possible in only 40% of the samples. Ultracentrifugation was unequivocally superior to lipoprotein precipitation reactions.

Apolipoproteins E↗

ATPase and acetylcholinesterase activities in erythrocyte membranes after incubation with glucose and in streptozotocin diabetic rats.

Enzyme activities of ATPases and acetylcholinesterase from isolated erythrocyte membranes (ghosts) were investigated before and after incubation with 50 mM glucose. Glucose incubation caused a time dependent loss of ATPase and acetylcholinesterase activities. Ghost enzyme activities in steptozotocin diabetic rats were found only insignificantly diminished.

Acetylcholinesterase↗

Diminished adhesion of endothelial aortic cells on fibronectin and collagen layers after nonenzymatic glycation.

Adhesion of bovine endothelial cells on fibronectin and collagen before and after nonenzymatic glycation in vitro has been studied. Nonenzymatic glycation of these proteins reduced their ability to bind endothelial cells. Furthermore, nonenzymatically glycated fibronectin failed to bind to normal and nonenzymatically glycated gelatin and to fibrin. So gelatin and fibrin Sepharoses can be used to separate highly glycated fibronectins from fibronectins with a low degree of nonenzymatic glucose substitution. Sodium dodecylsulfate polyacrylamide gel electrophoresis did not demonstrate a covalent cross-link between nonenzymatically glycated fibronectins. These results present further evidences for the role of nonenzymatic glycation of proteins in the development of vascular complications in long-term diabetes and of atherosclerosis.

Animals↗

Complement component 3 (C 3) and diabetes mellitus.

Complement factor 3 (C3) phenotype and allele frequencies were defined in 312 patients with Type 1 diabetes (IDDM), 256 patients with Type 2 diabetes mellitus (NIDDM), 114 apparently healthy first-degree relatives of Type 1 diabetics, in 10 families (29 members) with a familial history of Type 1 or Type 2 diabetes, and 512 controls (blood donors). All persons investigated were Europeans. There is no evidence to suggest that genes linked to C3 influence susceptibility to Type 1 and Type 2 diabetes and to their late complications. C3 levels in blood plasma were found to be slightly elevated in both types of diabetes. But the C3 concentrations varied considerably within the groups. C3 split products were demonstrable in a high percentage in the blood plasma of freshly manifested Type 1 diabetic persons as well as in Type 1 diabetics with a duration of the disease of 1 to 3 years. C3 proteolysis could also be found in plasma of Type 2 diabetics (26%).

Adolescent↗