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Biomedical subjects

P Seligman

Publications and source records attributed to P Seligman.

17 recordsLinked to original sources
PubMed1999

Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American Clinical Trial.

A new intravenous (i.v.) iron compound, sodium ferric gluconate complex in sucrose (Ferrlecit, R&D Laboratories, Inc, Marina Del Rey, CA), was administered over 8 consecutive dialysis days in equally divided doses to a total of either 0.5 or 1.0 g in a controlled, open, multicenter, randomized clinical study of anemic, iron-deficient hemodialysis patients receiving recombinant human erythropoietin (rHuEPO). Effectiveness was assessed by increase in hemoglobin and hematocrit and changes of iron parameters. Results were compared with historically matched controls on oral iron. High-dose i.v. treatment with 1.0 g sodium ferric gluconate complex in sucrose resulted in significantly greater improvement in hemoglobin, hematocrit, iron saturation, and serum ferritin at all time points, as compared with low-dose i.v. (0.5 g) or oral iron treatment. Despite an initial improvement in mean serum ferritin and transferrin saturation, 500 mg i.v. therapy did not result in a significant improvement in hemoglobin at any time. Eighty-three of 88 patients completed treatment with sodium ferric gluconate complex in sucrose: 44 in the high-dose and 39 in the low-dose group. Two patients discontinued for personal reasons. The other three discontinued because of a rash, nausea and rash, and chest pain with pruritus, respectively. In comparison with 25 matched control patients, adverse events could not be linked to drug therapy, nor was there a dose effect. In conclusion, sodium ferric gluconate complex in sucrose is safe and effective in the management of iron-deficiency anemia in severely iron-deficient and anemic hemodialysis patients receiving rHuEPO. This study confirms the concepts regarding iron therapy expressed in the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) that hemodialysis patients with serum ferritin below 100 ng/mL or transferrin saturations below 18% need supplementation with parenteral iron in excess of 1.0 g to achieve optimal response in hemoglobin and hematocrit levels.

Adult↗
PubMed1994

Activated THP-1 cells depress mitochondrial respiration in Hep G2 cells infected with influenza B virus.

Influenza B virus has been aetiologically linked to Reye Syndrome (RS), but the mechanism(s) by which this pathogen could disrupt liver metabolism and produce the hepatic mitochondrial injury characteristic of the syndrome are unknown. In this study, two mechanisms by which infection of hepatocytes with influenza B virus could disrupt cellular metabolism were investigated. (1) virus-induced increase in pro-oxidant iron with subsequent iron-induced lipid peroxidation (LP) and (2) increased membrane permeability. Hep G2 cells, a well-differentiated continuous human liver cell line derived from a hepatoblastoma, were infected with allantoic-fluid derived influenza B Lee/40 virus (AFDV) at a multiplicity of infection of 10 for 24 h; productive infection was confirmed by both haemagglutination of chick erythrocytes and by plaque assay. Infection of Hep G2 cells preloaded with 59Fe-transferrin resulted in increased release of 59Fe (153 +/- 17% of controls, P < 0.03). However, the iron released did not result in increased LP (assessed by thiobarituric acid reactive substances; TBARS). To confirm that this lack of of increase in TBARS was not due to insensitivity of the cell line to pro-oxidant iron, cells were exposed to 15 microM iron ascorbate for 60 min. Production of TBARS was increased (122 +/- 4% of controls, P < 0.0003). Release of 51Cr from infected cells was also increased (128 +/- 12% of controls, P < 0.05); thus the infected cells exhibited a generalized increase in membrane permeability. However, infection did not depress mitochondrial respiration (as assessed by the formation of MTT-f3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan. To determine if the combination of viral infection and soluble products of activated macrophages would affect mitochondrial respiration, infected hepatocytes were exposed to the supernatant fluid from THP-1 cells which had previously been incubated with lipopolysaccharide at 100 ng ml-1 for 18 h. This supernate did depress the formation of MTT-f (81 +/- 5% of controls, P < 0.03). We conclude that influenza B virus does productively infect Hep G2 cells, and does increase hepatocyte membrane permeability. This effect does not impair mitochondrial respiration directly. However, infection does act in concert with soluble products of activated macrophages to depress hepatic mitochondrial respiration. Whether this interaction can be explained by virus-induced permeability changes and/or other effects of infection deserves further investigation.

Animals↗
PubMed1994

Lymphocyte lines under iron-depriving conditions: transferrin receptor expression related to various growth responses.

The relation of expression of cell surface transferrin receptors to growth responses under defined iron-depriving conditions was studied in mouse B-cell line PLV-01, human T-cell line Jurkat, and human B-cell line Raji. Iron chelator deferoxamine at a concentration of 150 microM, which inhibited completely growth of the cell lines cultured in a serum-free transferrin-containing (5 micrograms/ml) medium, stimulated the surface transferrin receptor number to increase to 150-250% within a 24-h incubation period. The increased number (300%) of transferrin receptors on PLV-01 cells was associated with complete growth inhibition of these cells in counterpart serum-free transferrin-free medium. Only a slight increase in transferrin receptor number on Raji cells corresponded with unaffected growth of these cells in the transferrin-free medium. Jurkat cells increased the number of transferrin receptors to 150-200% and decreased the number of cells grown in the transferrin-free medium to about 60%. The data show that, under limited availability of iron, a significant increase of transferrin receptor expression on lymphoid cells was found only when the growth of the cells was inhibited. However, complete inhibition of growth achieved under different iron-depriving conditions is accompanied by different degrees of increase in transferrin receptor number.

Animals↗
PubMed1994

The prevalence of back pain, hand discomfort, and dermatitis in the US working population.

OBJECTIVES: The purpose of the study was to provide the health care and public health communities with national prevalence estimates of selected conditions in the US working population. METHODS: National prevalence estimates of self-reported conditions among working people were calculated from data collected for the 1988 Occupational Health Supplement to the National Health Interview Survey. RESULTS: The highest prevalence estimates were found among occupational groups. For example, the prevalence of back pain due to an injury at work among truck drivers was 6.7%; back pain due to repeated activities at work among mechanics and repairers of heavy equipment and machinery was 10.5%; hand discomfort among operators of machines that process metal, plastic, stone, and glass was 23.5%; and dermatitis due to contact with substances at work among physicians, dentists, nurses, pharmacists, and dietitians was 5.6%. CONCLUSIONS: A substantial proportion of these conditions among occupational groups with the highest prevalence estimates are occupational in origin. These prevalence estimates identify occupations in which efforts are needed to prevent these conditions.

Adult↗
PubMed1993

Neuroblastoma sensitivity to growth inhibition by deferrioxamine: evidence for a block in G1 phase of the cell cycle.

Iron (Fe) is known to be necessary for cellular proliferation. Previous studies have suggested that neuroblastoma cells appear to be relatively sensitive to growth inhibition by a specific Fe chelator, deferrioxamine (DFO), in vitro. Also, DFO has been recently used for the treatment of neuroblastoma patients. In this paper we demonstrate that neuroblastoma cell proliferation in vitro is extremely sensitive to inhibition by DFO as compared to another cell line with almost identical growth kinetics. Neuroblastoma cells treated with DFO adapt appropriately to Fe chelation as measured by marked upregulation of transferrin receptor mRNA, increased functional transferrin receptor, and decreased cellular ferritin concentration. Further studies that quantitated cellular incorporation of 59Fe from added transferrin-59Fe in the presence of DFO indicated that neuroblastoma cells were more sensitive to inhibition of Fe incorporation by the chelator as compared to the other cell line. Neuroblastoma cells treated with DFO showed a consistent arrest in the G1 phase of the cell cycle. For cells taken from the "resting" state this block occurred before the vast majority of cells had entered S or G2-M phases of the cell cycle. Further evidence that neuroblastoma cells were arrested before the G1-S interface was provided when cells inhibited by DFO and released into aphidicolin exhibit arrest at the G1-S interface, whereas release from aphidicolin into DFO resulted in entry into S phase. Also, DFO-treated cells exhibited a decrease in both p34cdc2 immunoreactive protein as well as kinase activity. The results of these latter studies strongly indicate evidence for a Fe requirement for malignant cell proliferation before the onset of DNA synthesis. Our results also provide a basis for further studies that will better define a therapeutic approach to patients with neuroblastoma utilizing DFO treatment.

Aphidicolin↗
PubMed1993

Inhibition of growth of the lymphocyte lines by deferoxamine under various iron-supply conditions.

Inhibition of growth of the lymphocyte lines by iron-binding agent deferoxamine under various iron-supply conditions was studied. Three different defined culture media, representing three different iron-supply conditions, were used: (1) ferric citrate (500 microM) medium, (2) transferrin (5 micrograms/ml) medium, and (3) low-iron medium (this medium without any iron compound added contains 0.6 microM contaminative non-transferrin iron). Mouse B cell line PLV-01, human T cell line Jurkat, and human B cell lines Raji and HSCE- were employed. Raji and HSCE- cells are able to grow in low-iron medium but PLV-01 and Jurkat cells do not grow in the medium. For all cell lines tested in ferric citrate medium, a 50% growth inhibition was achieved with 440-500 microM deferoxamine. In transferrin medium, deferoxamine concentrations of 4.4-5.5 microM were required for a 50% inhibition of PLV-01, Jurkat and HSCE- cells. For the same degree of inhibition of Raji cells, 39 microM deferoxamine was required. In the case of low-iron medium, a 50% inhibition of Raji and HSCE- cells was achieved with about 1.4-2.1 microM deferoxamine. The data demonstrate that the sensitivity of the lymphocyte lines to deferoxamine depends on iron-supply conditions. Under the same iron-supply conditions, individual cell lines can exhibit different sensitivity. However, the sensitivity does not correlate with the ability of the cell lines to grow in low-iron medium.

Animals↗
PubMed1990

Imaging of non-small cell lung cancers with a monoclonal antibody, KC-4G3, which recognizes a human milk fat globule antigen.

To determine the role of lung cancer tumor imaging with monoclonal antibodies directed against high molecular weight human milk fat globule antigens, we administered i.v. 111In-KC-4G3 to 24 patients with advanced non-small cell lung cancer. One mg of 111In-KC-4G3 was mixed with 0, 9, 49, 99, or 499 mg of unlabeled KC-4G3 and infused i.v. over 1 to 5 h. The mean 111In-KC-4G3 radiochemical purity was greater than 97% and the resultant immunoreactivity averaged 62%. Successful imaging of cancer sites was accomplished in 92% of 24 patients, and 57% of 91 total lesions were visualized. Successful localization of tumor sites related to size (P less than 0.001), with 81% of lesions greater than 3.0 cm in diameter, 50% of lesions 1.5 to 3 cm, and 6% of lesions less than 1.5 cm successfully imaging, and to location (P less than 0.05), with 69% of pulmonary lesions, 80% of soft tissue lesions, and only 32% of bone metastases being visualized. Nonspecific reticulo-endothelial uptake of radioactivity was a major problem. Approximately 35% of 111In was chelated to serum transferrin by 24 and 48 h after infusion. The mean t 1/2 beta for plasma radioisotope and immunoreactive KC-4G3 was 29 and 27 h, respectively. There was no correlation between total infused antibody dose and imaging success or between total dose and effect on 111In and KC-4G3 kinetics. Circulating free KC-4 antigen was measurable in all but one patient before study. Tumor biopsy following infusion could demonstrate antibody presence but not saturable antigen binding. We conclude that (a) 111In-KC-4G3 demonstrates successful tumor localization in non-small cell lung cancers bearing generally high expression of its antigen and (b) further investigations to diminish nonspecific radioactivity for imaging and utilization of high dose radiolabeled antibody for therapeutic intent are warranted.

Antibodies, Monoclonal↗
PubMed1990

Differential growth-inhibitory effects of gallium on B-lymphocyte lines in high versus low iron concentrations.

The growth inhibitory effects of gallium on a murine and human B-cell line were studied using two different serum-free culture systems: (a) ferric citrate medium containing 500 microM iron and (b) transferrin medium containing 5 micrograms/ml of iron-saturated transferrin (0.125 microM iron). For the human cell line in ferric citrate medium, 50% growth inhibition achieved in the presence of transferrin-gallium represented a gallium concentration 80-fold lower than the concentration required when gallium nitrate was added. In the transferrin system, significantly higher transferrin-gallium concentrations were required to achieve the same inhibitory effects. Monoclonal antibody to the transferrin receptor significantly decreased the growth inhibiting effect of transferrin-gallium in the mouse ferric citrate system. Thus, under very different culture conditions, gallium and iron appear to compete via the transferrin-transferrin receptor pathway for cellular uptake. The growth inhibitory effects of gallium are markedly potentiated when the metal is taken up by functional transferrin receptors even in cells continuously cultured in transferrin-free medium.

Animals↗
PubMed1988

Use of workers' compensation claims data for surveillance of cumulative trauma disorders.

Workers' compensation claims in Ohio were evaluated as a source of surveillance data for identifying workplaces at high risk of cumulative trauma disorders (CTDs) and analyzed for their demographic and industrial characteristics. During a 5-year period (1980 to 1984), 6,849 workers' compensation claims met the case criteria for CTDs. Tenosynovitis due to continuous motion was the most frequently reported condition (58%), and the wrist was the body part most frequently affected (48%). The highest case rate was observed for female workers in the 36 to 45 age group. Incidence rates for individual companies were determined and those with the highest rates for CTDs were identified. The employer-specific rates for CTDs based on workers' compensation claims data can be used as an effective surveillance tool in locating high-risk operations where ergonomic interventions can be implemented to reduce CTD hazards.

Adolescent↗
PubMed1986

A brief family intervention with an adolescent referred for drug taking.

This paper is a description of three family sessions with parents and their 19 year old and 17 year old sons. Their GP had referred the older son to the Family Institute, Cardiff as an "urgent" case saying that the son was taking LSD and cannabis and spending periods of time away from home. The paper argues in favour of a "non-pathological" approach to some adolescents who are on the brink of receiving serious psychiatric labels.

Adolescent↗
PubMed1983

Chromosome 3q (22-ter) encodes the human transferrin receptor.

The human transferrin receptor is an integral membrane glycoprotein of 180,000 molecular weight (mol. wt.) formed from two subunits of 90,000 mol. wt. A clone panel of Chinese hamster-human somatic cell hybrids was screened using a single cell plating cytotoxicity assay and rabbit antiserum raised to purified human transferrin receptor. Chromosome 3 displayed the highest rate of concordance with the presence of human transferrin receptor, as assayed by cytotoxicity. Antitransferrin receptor serum-resistant segregants of chromosome 3 positive, receptor-positive hybrids were selected, using antiserum and complement. The segregants consistently lost chromosome 3. 125I human transferrin binding studies confirmed synteny between the functional human transferrin receptor and chromosome 3. Examination of hybrids with either translocated or deleted chromosome 3's allows regional mapping to 3q(22-ter).

Animals↗
PubMedDate not supplied

Training in the radiation sciences: opportunities in the United States and internationally.

The need to improve the scientific bases for recommendations and regulations to protect human health from ionizing radiation and associated hazards has resulted in the creation by the U.S. Department of Energy (DOE) of a training program for radiation scientists at the University of Pittsburgh. In addition, the DOE's Office of International Health Programs (IHP), together with other national and international agencies, supports international meetings focused on health effects of radiation exposures. The IHP also provides fellowships to scientists from other countries, making it possible for them to attend relevant meetings of the American Association for the Advancement of Science. These and other international collaborative efforts, in particular those focusing on research in conjunction with Russian scientists, are described.

Fellowships and Scholarships↗