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Biomedical subjects

L Forman

Publications and source records attributed to L Forman.

At least 37 records · Page 2Linked to original sources
PubMed1989

Functional analysis of lymphocytes subpopulations in experimental cocaine abuse. I. Dose-dependent activation of lymphocyte subsets.

The potential role of substance abuse, especially cocaine and alcohol as co-factor in HIV infection and in the development and expression of AIDS has been suggested, but the possible biological role of substance abuse in the development of AIDS is not known. In order to better understand immune system function in chronic cocaine abuse, we have assessed primary B cell responses to helper T-cell independent (TI) and dependent (TD) antigens in inbred Fisher male rats injected with 1.25-5 mg cocaine/kg body weight for 10 days. The ability of cocaine-exposed animals to mount primary in vivo splenic plaque-forming cell (PFC) and serum antibody responses to the TI antigen, pneumococcal polysaccharide type III (SIII), was elevated several-fold when compared with controls. The degree of elevation of humoral antibody responses seemed to be directly related to the dose of cocaine. Primary in vivo B cell responses to the TD antigen, sheep red blood cells (SRBC), was elevated at lower concentrations of cocaine (1.25-2.5 mg/kg) and was found to be significantly suppressed after chronic exposure to the higher concentration (5.0 mg/kg). The elevated primary splenic immunostimulation to TI (SIII) may be attributed to a combination of loss of T suppressor cell control and direct B cell stimulation. Elevated immune responses to SRBC at lower concentrations were attributed to stimulation of T helper cells as well as loss of T suppressor cells. Immunosuppression to SRBC observed in response to 5.0 mg/kg of cocaine was most probably due to loss of T helper cell subset functions. These findings were further tested by in vitro methods, where splenic lymphocytes from cocaine-exposed animals were examined for their ability to respond to concanavalin A (Con A) in terms of the induction of antigen non-specific suppressor T cells. The addition of Con A-stimulated splenic lymphocytes from cocaine-treated animals did not inhibit the primary antibody responses of SRBC as compared with saline-treated controls, indicating that suppressor T cells malfunction after cocaine exposure. Lymphocyte subpopulation analysis using fluorescein-labelled monoclonal antibodies showed a significant increase in the B cell populations at doses of 1.25-5 mg/kg. A reciprocal change in T cell populations also took place. No significant numerical change in macrophage (NSE+) and T cell subset, T helper and T suppressor was noticed, suggesting that cocaine probably directly effects mature T cell subset functions but does not affect their differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Mechanism of improved maintenance of 2,3-diphosphoglycerate in stored blood by the xanthone compound 2-(2-hydroxyethoxy)-6-(1-H-tetrazole-5-yl)xanthen-9-one (BW A440C).

The effect of the xanthone derivative 2-(2-hydroxyethoxy)-6-(1-H-tetrazole-5-yl)xanthen-9-one (BW A440C) on red cells was studied. When added to stored red cells at a concentration of 6 mM, greatly improved preservation of 2,3-diphosphoglycerate (2,3-DPG) was observed. There was no effect on internal pH of the erythrocyte. At a concentration 0.500 mM, many red cell enzyme activities were inhibited completely. At a 0.500 mM concentration, however, inhibition of pyruvate kinase and diphosphoglycerate phosphatase was most striking. Inhibition of either of these enzymes could result in elevation of 2,3-DPG levels. BW A440C in concentrations which elevated 2,3-DPG levels in humans caused a decrease in 2,3-DPG levels in rabbits and markedly impaired the viability of 21-day stored rabbit erythrocytes.

2,3-Diphosphoglycerate↗
PubMed1988

Enzymatic diagnosis in non-spherocytic hemolytic anemia.

Blood samples from 722 unrelated patients with anemia and/or reticulocytosis were submitted to our laboratory for red cell enzyme assay during the past 7 years. Among these 722 cases, we found 82 cases of 7 different red cell enzyme deficiencies and 2 of unstable hemoglobin. Abnormalities of pyruvate kinase (PK) were found to cause hemolysis in 55 patients. Although their average PK activity was about 35% of the normal level, 5 showed normal and 2 demonstrated high PK activity. Among 17 patients in whom pyruvate kinase assays or screening tests had been carried out in routine laboratories, the correct diagnoses had been made in only 4. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was found in 15 patients, pyrimidine 5'-nucleotidase deficiency in 5, glucose phosphate isomerase deficiency in 3, adenylate kinase deficiency in 2, phosphoglycerate kinase deficiency in 1, and glutathione synthetase deficiency in 1 patient. Even after we performed a panel of over 20 different red cell enzyme assays, 519 patients still remained undiagnosed.

Adolescent↗
PubMed1988

Erythrocyte glutathione S-transferase deficiency and hemolytic anemia.

A patient with unexplained erythrocyte glutathione-S-transferase (GST) deficiency has been detected among 513 unrelated persons with hemolytic anemia. An otherwise healthy adult male, the deficient individual had a mild hemolytic anemia with splenomegaly, indirect hyperbilirubinemia, and cholelithiasis. Because he was adopted and childless, the hereditary nature of the defect could not be established. The residual enzyme activity was only about 15% of mean normal. Depletion of glutathione (GSH) from the cells by 1-chloro-2,4-dinitrobenzene (CDNB), a substrate for GST, was somewhat decreased in the red cells from the patient, suggesting that a functional defect existed. The kinetic properties of the residual enzyme and the ratio of activity to antigenicity were normal. Modest decreases in leukocyte and platelet GST activities were documented. Although a cause-and-effect relationship between the GST deficiency and hemolysis may exist, this cannot be proven in the absence of affected family members.

Adolescent↗
PubMed1987

Elevated pyruvate kinase activity in patients with hemolytic anemia due to red cell pyruvate kinase "deficiency".

Two patients with non-spherocytic hemolytic anemia were found to have elevated red blood cell pyruvate kinase activities commensurate with the decreased mean red cell age, but the residual pyruvate kinase had marked kinetic abnormalities. Accumulation of metabolic intermediates before pyruvate kinase and reduced levels of activity of the red blood cells of the parents of both patients supported the diagnosis of an inherited abnormal pyruvate kinase causing hemolytic anemia. Although it was observed in two unrelated persons, review of enzyme assays performed on the red blood cells of 651 patients with hereditary non-spherocytic hemolytic anemia suggests that this occurrence is rare.

Adolescent↗
PubMed1987

Effect of oxalate and malonate on red cell metabolism.

The addition of oxalate to blood stored in Citrate-phosphate-dextrose (CPD) produces a marked improvement in 2,3-diphosphoglycerate (2,3-DPG) preservation; an increase in 2,3-DPG levels can also be documented in short-term incubation studies. Oxalate is a potent in vitro inhibitor of red cell lactate dehydrogenase, monophosphoglycerate mutase, and pyruvate kinase (PK). In the presence of fructose 1,6-diphosphate the latter inhibitory effect is competitive with phospho(enol)pyruvate (PEP). Determination of the levels of intermediate compounds in red cells incubated with oxalate suggest the presence of inhibition at the PK step, indicating that this is the site of oxalate action. Apparent inhibition at the glyceraldehyde phosphate dehydrogenase step is apparently due to an increase in the NADH/NAD ratio. Oxalate had no effect on the in vivo viability of rabbit red cells stored in CPD preservatives for 21 days. Greater understanding of the toxicity of oxalate is required before it can be considered suitable as a component of preservative media, but appreciation of the mechanism by which it affects 2,3-DPG levels may be important in design of other blood additives. Malonate, the 3-carbon dicarboxylic acid analogue of oxalate late did not inhibit pyruvate kinase nor affect 2,3-DPG levels.

2,3-Diphosphoglycerate↗
PubMed1986

G-6-PD Walter Reed: possible insight into "structural" NADP in G-6-PD.

A new G-6-PD variant, G-6-PD Walter Reed, causing hereditary nonspherocytic hemolytic anemia is characterized. This variant is unusual in that its stability requires the presence of high concentrations of NADP, while its Km for NADP is normal. This finding is consistent with the suggestion that G-6-PD has two separate binding sites, a high affinity "structural" site and a lower affinity catalytic site. The mutation in G-6-PD Walter Reed, like that of the previously described variant, G-6-PD Torrance, may be due to a mutation of the "structural" site for NADP.

Anemia, Hemolytic, Congenital↗
PubMed1986

Genetic variation within and among lion tamarins.

The golden lion tamarin Leontopithecus rosalia rosalia, one of the rarest and most endangered of New World primates, has been the focus of an intensive research and conservation effort for two decades. During that period, managed breeding from 44 founders has brought the captive population to over 400 individuals, a number that equals or exceeds the estimated number of free-ranging golden lion tamarins. The extent of genetic variation among golden lion tamarins was estimated with an electrophoretic survey of 47 allozyme loci from 67 captive and 73 free-ranging individuals. The amount of variation was low, compared to 15 other primate species, with 4% of the loci being polymorphic (P), and with an average heterozygosity H estimate of 0.01 in these callitrichids. Electrophoretic analyses of captive and free-ranging animals (N = 31) of two allopatric morphotypes, Leontopithecus rosalia chrysopygus and L. r. chrysomelas, were similar to the L. r. rosalia findings insofar as they also revealed limited genetic polymorphism. Computation of the Nei-genetic distance measurements showed that the three morphotypes were genetically very similar, although discernible differentiation had occurred at two loci. These data are consistent with the occurrence of recent reproductive isolations of these subspecies.

Animals↗
PubMed1983

Coexistence of alpha-thalassemia and a new pyruvate kinase variant: PK Fukien.

A 12-year-old male of Chinese ancestry had life-long hemolytic anemia attributed to alpha-thalassemia. Restriction endonuclease mapping of his DNA revealed that in reality, he had three alpha-globin loci, but he was homozygous for pyruvate kinase deficiency. The new pyruvate kinase variant carried by this patient was characterized and designated PK Fukien.

Blood Protein Electrophoresis↗
PubMed1983

Metabolic compensation for profound erythrocyte adenylate kinase deficiency. A hereditary enzyme defect without hemolytic anemia.

A child with hemolytic anemia was found to have severe erythrocyte adenylate kinase (AK) deficiency, but an equally enzyme-deficient sibling had no evidence of hemolysis. No residual enzyme activity was found in erythrocytes by spectrophotometric methods that could easily have detected 0.1% of normal activity. However, concentrated hemolysates were shown to have the capacity to generate small amounts of ATP and AMP from ADP after prolonged incubation. Hemolysates could also catalyze the transfer of labeled gamma-phosphate from ATP to ADP. Intact erythrocytes were able to transfer phosphate from the gamma-position of ATP to the beta-position, albeit at a rate substantially slower than normal. They could also incorporate 14C-labeled adenine into ADP and ATP. Thus, a small amount of residual AK-like activity representing about 1/2,000 of the activity normally present could be documented in the deficient erythrocytes. The residual activity was not inhibited by N-ethylmaleimide, which completely abolishes the activity of the normal AK1 isozyme of erythrocytes. The minute amount of residual activity in erythrocytes could represent a small amount of the AK2 isozyme, which has not been thought to be present in erythrocytes, or the activity of erythrocyte guanylate kinase with AMP substituting as substrate for GMP. Peripheral blood leukocytes, cultured skin fibroblasts, and transformed lymphoblasts from the deficient subject manifested about 17, 24, and 74%, respectively, of the activity of the concurrent controls. This residual activity is consistent with the existence of genetically independent AK isozyme, AK2, which is known to exist in these tissues. The cause of hemolysis in the proband was not identified. Possibilities include an unrelated enzyme deficiency or other erythrocyte enzyme defect and intraction of another unidentified defect with AK deficiency.

Adenine↗
PubMed1982

Polymorphonuclear cell chemotaxis to secretions of pathogenic and nonpathogenic Trichomonas vaginalis.

Polymorphonuclear cell chemotaxis to secretions of pathogenic and nonpathogenic strains of Trichomonas vaginalis were investigated. Cells from three groups, laboratory workers, patients with urogenital symptoms, and asymptomatic patients attending an antenatal clinic, all showed greater response to secretions of pathogenic strains, when the secretion was dilute. At higher concentrations of secretion, responses to both strains were similar, except in the pregnant group, where increased chemotaxis to pathogenic strains was still evident.

Animals↗
PubMed1980

In vitro attraction of polymorphonuclear leucocytes by Trichomonas vaginalis.

Boyden chambers were used to investigate the attraction of polymorphonuclear leucocytes to T. vaginalis. Chemotaxis to live organisms was demonstrated, and chemotaxis to T. vaginalis supernatant was shown to be concentration dependent. Both chemokinesis and true chemotaxis characterized the response to supernatants. There was no chemotaxis to the supernatant after it had been heated to 60 C for 1 hr, or to the supernatant from formalin-fixed T. vaginalis. The chemotactic factor in the supernatant did not pass through a dialysis membrane. Protein was found in the supernatant of T. vaginalis suspensions.

Adult↗