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Biomedical subjects

H A Peters

Publications and source records attributed to H A Peters.

At least 37 records · Page 2Linked to original sources
PubMed1991

Finger tremor after carbon disulfide-based pesticide exposures.

Index finger tremor accompanying voluntary movement was studied in 19 age-matched control subjects and in 19 grain industry employees chronically exposed to carbon disulfide-based fumigants. Visual judgments of tremor amplitude made by neurologists during clinical examinations equaled the sensitivity of computerized tremor amplitude measurements. Tremor frequency variations detectable only with computerized measurement were present in grain workers with and without increased tremor amplitudes. Frequency differences discriminated between normal subjects and 74% of the grain workers. The distribution of tremor frequency power in the grain workers was often sequestered at 5 to 7 Hz, reminiscent of tremor in idiopathic Parkinson's disease. These findings suggest that the measurement of subtle tremor frequency changes may provide an early indication of chronic carbon disulfide poisoning.

Adult↗
PubMed1990

Growth factor-receptor pathway interfering treatment by somatostatin analogs and suramin: preclinical and clinical studies.

UNLABELLED: Interference in growth factor mediated pathways is a new strategy in the treatment of cancer. Somatostatin analogs can inhibit hormone and growth factor secretion, while suramin can block the binding of several growth factors to their receptors. In addition, somatostatin analogs can cause direct growth inhibitory effects after binding to tumoral somatostatin receptors. We tested the efficacy and endocrine effects of chronic treatment with three somatostatin analogs (Sandostatin, R RC-160 and CGP 15-425) or suramin in several tumor models and in patients with various types of cancer. Treatment with somatostatin analogs caused growth inhibition of breast cancer cells (MCF-7) in vitro, and of rat transplantable pancreatic (50-70% inhibition) and prostatic Dunning tumors (12% inhibition). No tumor growth inhibition was observed with respect to DMBA-induced rat mammary tumors, a transplantable colon tumor and a rhabdomyosarcoma in rats. In 34 patients with metastatic pancreatic or gastrointestinal adenocarcinomas chronic Sandostatin treatment caused stable disease in 27% of the patients, but no objective remissions. Somatostatin receptors were found in the responding MCF-7 mammary tumor cells, rat pancreatic tumors and in 20-45% of human breast cancer specimens [J. Steroid Biochem. Molec. Biol. 37 (1990) 1073-1077], but not in rat DMBA-mammary tumors or in 10 human pancreatic adenocarcinomas. Suramin caused significant dose-dependent growth inhibition of human breast cancer cells in vitro and of rat pancreatic tumors in vivo in the presence of plasma levels up to 150 micrograms/ml. In a preliminary clinical study concerning 11 patients with various tumor types we observed significant hematological, biochemical, endocrine and clinical side effects, but no objective remissions in spite of relevant peak plasma suramin concentrations of 270-330 micrograms/ml. IN CONCLUSION: somatostatin analogs and suramin can cause growth inhibition of various experimental tumors in vitro and in vivo, but the clinical value has to be established for several types of cancer, especially with respect to suramin and suramin-like compounds.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Manipulation of cell cycle kinetics: influence on the cytotoxicity of doxorubicin in human breast cancer cells.

In vitro exposure of estrogen receptor-negative (ER-) EVSA-T human breast cancer cells to insulin and/or estradiol had no effect on cell cycle distribution, in contrast to a 3-5-fold increase in the percentages of cells in the S-phase of the cell cycle in the ER+ MCF-7 cell line. Estrogen pretreatment of MCF-7 cells followed by incubation with doxorubicin resulted in an augmented inhibition of cell growth compared to unstimulated controls. This delay in growth was accompanied by a decrease in the percentages of cells actively synthesizing DNA, and by an augmented percentage of cells exhibiting a G2M-amount of DNA at the end of a 6-9 day period of culture in complete growth medium.

Breast Neoplasms↗
PubMed1989

Prognostic value of estrogen and progesterone receptors measured by enzyme immunoassays in human breast tumor cytosols.

Clinically significant cut-off values to discriminate between receptor-positive and -negative, and the prognostic value of estrogen receptors (ER) and progesterone receptors (PgR) measured by enzyme immunoassay (EIA) have not yet been established. We have therefore measured ER and PgR by EIA in cytosols from 205 primary breast cancer biopsies. Clinically significant cut-off values (30 fmol/mg protein for ER; 27 fmol/mg protein for PgR), as related to tumor recurrence (median follow-up, 47 months), have been established by isotonic regression analysis. These data were compared to those obtained by simultaneously performed dextran-coated charcoal (DCC) assays (cut-off values: 18 fmol/mg protein for ER, and 26 fmol/mg protein for PgR) on the same cytosols, and to DCC assays performed previously (up to 10 years ago) on cytosols prepared from other parts of the tissue biopsies (cut-off values: 18 fmol/mg protein for ER, and 23 fmol/mg protein for PgR). Using the cut-off values for the EIA and the DCC assays performed on the same cytosols, the discrepancies between receptor status appeared less than 10% both for ER and for PgR. Furthermore, the concentrations of ER or PgR detected with the EIA or DCC assay were highly and significantly correlated (Spearman rank correlations: for ER, Rs = 0.94; for PgR, Rs = 0.88; P less than 0.0001). After classification in different phenotypes with respect to ER/PgR status (+/+, +/-, -/+, and -/-), analysis for relapse-free survival and overall survival showed equal prognostic power in the comparable groups in the order, from favorable to unfavorable, of +/+ greater than +/-(-/+) greater than -/- (chi2: P less than 0.0001), irrespective of the assay which has been used for quantification of the receptor. It is concluded that both the conventionally used DCC and the newly available EIA methods are equally useful for assessing ER and PgR status.

Biomarkers, Tumor↗
PubMed1989

Preparatory processes in a case of hemi-parkinsonism.

Reaction times and movement times were recorded in a subject with parkinsonian symptoms confined largely to the left side of the body. Advance information concerning the movement was varied, being with complete, partial or no preparation. The results suggest that processing of preparation for the movement is not qualitatively different for the more affected side, but is substantially slowed.

Female↗
PubMed1989

Effect of hormonal manipulation and doxorubicin administration on cell cycle kinetics of human breast cancer cells.

Dual-parameter flow cytometry, following bromodeoxyuridine (BrdUrd) incorporation and propidium iodide (PI) uptake into DNA, was used to study the effects of oestradiol and/or insulin on cell cycle kinetics of human breast cancer cells in vitro. After a lag-period of 6-12 h, an optimum in the percentage of S-phase cells was reached between 18 and 24 h after hormone administration. A 1 h pulse of oestradiol was as effective as the continuous presence of oestradiol in pushing the cells from quiescent growing cultures into the cell cycle. A 1 h pulse of insulin was less effective than continuous administration. The addition of doxorubicin resulted in an accumulation of the cells in the late S/G2M-phases. It is concluded that dual-parameter flow cytometry allows accurate assessment of the effects of hormones and chemotherapy on the cell cycle. Therefore this method is very suitable for studying the interaction of hormones and chemotherapy on cell growth.

Breast Neoplasms↗
PubMed1989

Hexachlorobenzene episode in Turkey.

During the period 1955-1959, approximately 4000 people in southeast Anatolia developed porphyria due to the ingestion of hexachlorobenzene (HCB), a fungicide added to wheat seedlings. These HCB exposures subsequently led to the development of bullae on sun-exposed areas, hyperpigmentation, hypertrichosis, and porphyrinuria. The condition was called kara yara or "black sore." Many of the breast-fed children under the age of 2 years whose mothers had ingested HCB-treated grain died from a disease known as pembe yara or "pink sore." In this follow-up study of 252 patients, 20-30 years postexposure, there were 162 males and 90 females, with an average current age of 35.7 years, an average of onset of 7.6 years, and a duration of 2.2 years. Many patients had dermatologic, neurologic, and orthopedic symptoms and signs. The observed clinical findings include scarring of the face and hands (83.7%), hyperpigmentation (65%), hypertrichosis (44.8%), pinched facies (40.1%), painless arthritis (70.2%), small hands (66.6%), sensory shading (60.6%), myotonia (37.9%), cogwheeling (41.9%), enlarged thyroid (34.9%), and enlarged liver (4.8%). Urine and stool porphyrin levels were determined in all patients, and 17 have at least one of the porphyrins elevated. A total of 56 specimens of human milk obtained from mothers with porphyria were analyzed for HCB. The average value was 0.51 ppm in HCB-exposed patients compared to 0.07 ppm in unexposed controls. Offspring of mothers with three decades of HCB-induced porphyria appear normal.

Adolescent↗
PubMed1988

Extrapyramidal and other neurologic manifestations associated with carbon disulfide fumigant exposure.

Three groups of pesticide-exposed grain workers from three different work facilities experienced chronic central and peripheral nervous system dysfunction that appeared to be exposure related. The grain inspectors, malt laboratory workers, and grain elevator workers displayed higher prevalence rates of atypical parkinsonism, cerebellar signs, hearing loss, and sensory changes than would be expected in a nonneurologic control population. The 21 self-selected patients included in this report exhibited cogwheel rigidity in 80% (17/21), decreased associated movements in 71% (15/21), distal sensory shading in 62% (13/21), intention tremulousness in 52% (11/21), resting tremulousness in 48% (10/21), and nerve conduction abnormalities in 44% (7/16). Carbon disulfide, a major component of the fumigant mixtures used, has been associated in the rayon industry, since the 1930s, with similar neurologic symptoms.

Adult↗
PubMed1987

Lectin-enzyme immunoassay of transferrin sialovariants using immobilized antitransferrin and enzyme-labeled galactose-binding lectin from Ricinus communis.

A heterologous lectin-enzyme immunoassay is described. Microtiter plate wells were coated with affinity-purified antibodies to human transferrin. After incubation with transferrin sialovariants, prepared by limited neuraminidase treatment and separated with chromatofocusing, a lectin-enzyme-streptavidin complex was added. A good correlation was obtained between the number of terminal galactose groups on transferrin and the response in the lectin-enzyme immunoassay using Ricinus communis agglutinin as the galactose-binding lectin. The results indicate that characterization of glycosylation is possible with less than a microgram of the glycoprotein available, using lectin-enzyme immunoassays.

Enzyme-Linked Immunosorbent Assay↗
PubMed1987

The effects of post-exercise glucose and alanine ingestion on plasma carnitine and ketosis in humans.

1. Several studies have hypothesized that alanine decreases plasma ketone body levels by increasing availability of oxaloacetate, thus allowing acetyl groups to enter the tricarboxylic acid cycle and releasing co-enzyme A (CoA). 2. Four, fasted adult males exercised at 50% of their maximal oxygen consumption for 1.5 h, then ingested 100 g of either glucose or alanine 2 h into recovery. 3. Post-exercise ketosis had developed at 2 h into recovery, as shown by a significantly elevated concentration of beta-hydroxybutyrate in the plasma. At this time plasma free fatty acids were elevated above resting levels while plasma free carnitine concentrations had fallen below resting values. 4. After either alanine or glucose ingestion beta-hydroxybutyrate concentrations fell to the same extent. After the alanine load free carnitine increased above that seen in the glucose trial. Following either alanine or glucose ingestion free fatty acid levels fell; they remained at resting levels in the alanine trial but decreased below rest in the glucose trial. 5. We assume that plasma carnitine concentrations largely reflect the hepatic carnitine pools; therefore, elevations in the plasma free carnitine are probably the result of an increased utilization of acetyl CoA. The significant elevation in plasma free carnitine concentration found after alanine ingestion is consistent with the hypothesis that alanine increases the oxidation of acetyl CoA by providing oxaloacetate for the tricarboxylic acid cycle.

3-Hydroxybutyric Acid↗
PubMed1986

Synergistic neurotoxicity of carbon tetrachloride/carbon disulfide (80/20 fumigants) and other pesticides in grain storage workers.

Neurophysiologic, neurobehavioral, and neuropsychologic profiles in 17 grain storage workers, 1 grain inspector, and 4 malting laboratory workers are described. The effects of CS2 toxicity as seen in viscose rayon workers as well as in experimental animals is remarkably similar to the clinical profile of our grain storage workers. CS2 use explains the dysfunction of peripheral axons, auditory nerve, the optic nerve, and the extrapyramidal system, as well as altered behavior and cognition changes. The signs and symptoms in these workers seem to be dose-related and we note that workers separated out from the areas where fumigation took place reported improvement not seen by fellow workers who continued the fumigant treatment routine. Likewise, malting laboratory workers exposed only to the grain dust from 3 to 7 years showed only minimal symptoms. Though a number of mechanism have been suggested for the alteration of neuropsychological function, the chelating ability of DDC derived from CS2 and its ability to markedly increase copper and zinc within the central nervous system suggests a mechanism of toxicity analogous to copper intoxication as in Wilson's Disease and may explain the production of extrapyramidal symptoms in these patients. Chelation of copper might prove therapeutic in CS2 poisoning. It is obvious that both basic and clinical research will be necessary to sort out the questions raised. We applaud the EPA's decision to ban the use of 80/20 fumigants and also methyl bromide, and trust that similar toxic substances be carefully studied before their selection for replacing these previous toxic agents. We further decry the technique of re-introducing grain dust into the food chain rather than destroying it, since the dust contains very high residues of fumigant material. We speculate on the possible role of CS2 and other pesticides in the food chain and the incidence of Parkinsonian symptoms in these patients and the general public.

Adult↗