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F W Sunderman

Publications and source records attributed to F W Sunderman.

At least 271 records · Page 15Linked to original sources
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Investigation of exposure to nickel and lung cancer mortality: case control study at aircraft engine factory.

A case-control mortality study was performed at an aircraft engine factory to assess the possible association between exposure to nickel-containing compounds and death from lung cancer. Forty-two non-salaried male workers who died of lung cancer from 1966 to 1976 were identified from a chronological registry of death certificates that has been maintained by the company's medical department. Each of the decedents was matched with the next two non-salaried decedents in the registry who were of the same sex and comparable age (+/- 10 years), and who died of causes other than cancer. Without knowledge of the workmen's identities or causes of death, one of the authors classified the deceased workmen as exposed or non-exposed to nickel compounds during their employment. The proportion of workmen who died of lung cancer and were exposed to nickel (11/42) was found to be equal to the proportion of workmen who died of non-cancerous causes and were exposed to nickel (22/84). This study indicates that workers in an aircraft engine factory who were chronically exposed to low atmospheric concentrations of presumably weakly carcinogenic nickel compounds did not have any apparent increase in the relative risk of mortality from lung cancer prior to treatment.

Age Factors↗
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Rapid analysis of nickel in serum and whole blood by electrothermal atomic absorption spectrophotometry.

A method is described for analysis of nickel in serum and heparinized blood. After the sample has been subjected to protein precipitation with nitric acid and heat, nickel in the protein-free extract is measured by electrothermal atomic absorption with Zeeman background correction. The method is more sensitive, rapid, and convenient than previous techniques, and less subject to nickel contamination. Nickel concentrations in serums from New Zealand rabbits (mean +/- SD) average 4.0 +/- 2.5 micrograms per L, range = 0.9 to 11.9, N = 30; these results agree with measurements by the International Union of Pure and Applied Chemistry (IUPAC) reference procedure ( corr . coef . = 0.98). The following values are reported for nickel concentrations in serum and whole blood from healthy adult persons living in central Connecticut: serum, 0.46 +/- 0.26 micrograms per L, range = 0.1 to 1.3, N = 39; whole blood, 1.26 +/- 0.33 micrograms per L, range = 0.6 to 1.8, N = 30. This method is suitable for routine use in clinical and industrial laboratories.

Adult↗
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Effects of cobalt chloride, nickel chloride, and nickel subsulfide upon erythropoiesis in rats.

The erythropoietic effects of sustained intraperitoneal (i.p.) administration of CoCl2 and NiCl2 were compared with the effects of a single intrarenal (i.r.) injection of alpha Ni3S2 in female Fischer-344 rats. Infusion of NiCl2 by osmotic minipumps (0.85 mg Ni per day, i.p., for 24 days; total dose = 20 mg Ni per rat) did not alter the blood hematocrit or reticulocyte count during six weeks of observation. Under identical conditions, i.p. infusion of CoCl2 (0.85 mg Co per day, i.p., for 24 days; total dose = 20 mg Co per rat) caused significant erythrocytosis (hematocrit at six weeks = 62 +/- 4 percent, P less than 0.001 versus 50 +/- 3 percent in controls) and reticulocytosis (reticulocyte count at three weeks = 2.5 +/- 1.5 percent, P less than 0.005 versus 0.8 +/- 0.7 percent in controls). Administration of alpha Ni3S2 to rats as a single i.r. injection (7 mg Ni per rat) caused pronounced erythrocytosis (hematocrit at six weeks = 79 +/- 2 percent, P less than 0.001 versus controls) and reticulocytosis (reticulocyte count at three weeks = 2.8 +/- 1.2 percent, P less than 0.005 versus controls). This study demonstrates that i.p. infusion of Ni[II] is ineffective in stimulating erythropoiesis in rats, and that salient differences exist between the enhanced erythropoiesis that occurs in rats following i.p. infusion of Co[II] and that produced by i.r. injection of alpha Ni3S2.

Animals↗
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63Nickel-constituents in renal cytosol of rats after injection of 63nickel chloride.

Chromatographic and electrophoretic fractionations of 63Ni-constituents were performed upon renal cytosol samples from rats that were killed following administration of 63NiCl2. At 0.5 to one hr after i.v. injection of 63NiCl2 (0.1 to 0.5 mumole per kg body wt., N = 6), renal cytosol contained 11 percent (SE +/- 2 percent) of the 63Ni-dose. An average of 68 percent (SE +/- 4 percent) of 63Ni in these cytosol samples was associated with low molecular weight components (mol. wt. less than 2,000). The remainder was bound to five macromolecular constituents, with molecular weights of greater than 130,000 (Peak A), approximately 70,000 (Peak B), approximately 55,000 (Peak C), approximately 30,000 (Peak D), and approximately 10,000 (Peak E), based upon column chromatography on Sephadex G-200. The 63Ni that was present in Peaks A to E averaged, respectively, 1.8 percent, 10.7 percent, 7.5 percent, 10.0 percent and 1.6 percent of total 63Ni in renal cytosol. At one to fours hrs after i.m. injection of 63NiCl2 (100 mumol per kg body wt., N = 17), renal cytosol contained 2.2 percent (SE +/- 0.1 percent) of the 63Ni-dose; ultrafiltrable 63Ni averaged 57 percent (SE +/- 3 percent) of total 63Ni in renal cytosol. Macromolecular 63Ni-constituents in these samples were separated by electrophoresis in agarose gel and visualized by autoradiography. Peak D (mol. wt. approximately 30,000) was the most prominent of the five 63Ni-constituents. This study demonstrates that renal cytosol of 63NiCl2-treated rats contains five macromolecular 63Ni-constituents that may be involved in renal uptake, transport, storage, and excretion of 63Ni(II).

Animals↗
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Fluctuations of nickel concentrations in urine of electroplating workers.

Nickel analyses were performed by electrothermal atomic absorption spectrometry upon urine specimens obtained from electroplating workers at the beginning, middle and end of the work-shift. The means (+/- S.D.) for nickel concentrations in urine specimens from seven electroplating workers on three regular workdays were: 34 +/- 32 micrograms/L (pre-shift); 64 +/- 63 micrograms/L (mid-shift) and 46 +/- 32 micrograms/L (end-shift), compared to 2.7 +/- 1.6 micrograms/L (pre-shift) in 19 controls (hospital workers). Nickel concentrations in urine specimens from six electroplating workers on the first workday after a two-week vactation averaged: 5 +/- 3 micrograms/L (pre-shift); 9 +/- 6 micrograms/L (mid-shift), and 12 +/- 6 micrograms/L (end-shift). Nickel concentrations in personal air samples (seven hours) collected from the breathing zones of five electroplating workers on three regular workdays averaging 9.3 +/- 4.4 micrograms/m3. Nickel concentrations in the air samples were correlated with nickel concentrations in end-shift urine specimens (corr. coef. = 0.70; P less than 0.05), but were not correlated with nickel concentrations in pre-shift or mid-shift urine specimens. In view of the fluctuations of urine nickel concentrations that occur during the work-shift, the authors recommend that nickel analyses of eight hour urine specimens be used routinely to monitor occupational exposures to nickel. In situations where timed urine collections are impractical, analyses of end-shift urine specimens are the best alternative.

Adult↗
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Effects of intrarenal injection of nickel subsulfide in rodents.

After intrarenal (i.r.1 administration of 5 mg of nickel subsulfide (alpha Ni3S2) to Fischer rats, blood hematocrit became increased within one week and reached 76 +/- 1 percent at eight weeks (p less than 0.001 versus mean hematocrit of 46 +/- 1 percent in control rats). The alpha Ni3S2-induced erythrocytosis was attended by intense stimulation of erythropoiesis, with reticulocytosis, increased 59Fe-uptake into erythrocytes and erythroid hyperplasia in bone marrow and spleen. The half-life of 51Cr-labeled erythrocytes from alpha Ni3S2-treated rats was prolonged, consistent with increased proportion of circulating juvenile erythrocytes. Histological examination of rat kidneys after i.r. injection of alpha Ni3S2 showed mild inflmmation at one and two weeks. Dense black particles of alpha Ni3S2 were visible in histological sections of rat kidneys for eight weeks. 5'-Nucleotidase activity in rat kidney microsomes was inhibited at one to seven days after i.r. injection of alpha Ni3S2. Erythrocytosis did not occur in rats after (a) i.r. implantation of semi-permeable cellulose tubules containing alpha Ni3S2, (b) repeated i.m. injections of alpha Ni3S2, or (c) intrahepatic injection of alpha Ni3S2 after partial hepatectomy. Erythrocytosis did not occur in male BALB/c mice or ground squirrels after i.r. injection of alpha Ni3S2.

Animals↗
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Effects of nickel chloride and nickel carbonyl upon glucose metabolism in rats.

Hyperglycemia, hyperglucagonemia and hyperinsulinemia were observed in fasting rats at 0.5 hr after ip injection of NiCl2 (68 mumole per kg). Infusion of somatostatin iv (0.5 mg per rat) did not prevent Ni(II)-mediated hyperglycemia, hyperglucagonemia or hyperinsulinemia. Exposure of rats to inhalation of Ni(CO)4 (1.2 to 6.4 mumole per liter of air per 15 min) caused acute hyperglycemia, similar to that observed after ip injection of NiCl2. Hyperglycemia induced by NiCl2 and Ni(CO)4 was not associated with inhibition of erythrocyte glycolysis measured in vitro by erythrocyte uptake of 1-14C-glucose and release of 14CO2. These findings indicate that Ni-induced hyperglycemia may be mediated by increased pancreatic release of glucagon, but that Ni stimulation of glucagon release differs from stimulation of glucagon release by arginine or epinephrine, since the Ni effect is not antagonized by somatostatin.

Animals↗
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Nephrotoxicity of nickel carbonyl in rats.

Urinary excretions of protein and amino acids were measured before and after exposure of rats to inhalation of nickel carbonyl in LD40 dosage. Urinary excretion of total protein was increased by an average of 2.4-fold on the first day after exposure and remained elevated (2.0-fold and 1.9-fold) on the second and third days. Urinary excretions of 16 neutral or basic amino acids were all increased on the third day. In comparison to pre-exposure values, the increased excretion of neutral or basic amino acids averaged 3.0-fold, and ranged from 1.2-fold (ornithine) to 7.3-fold (valine). Among the acidic amino acids and amides, only the excretion of glutamic acid was increased (4.6-fold), and the excretions of glutamine, aspartic acid and asparagine were reduced, respectively, to 3.8 percent, 64 percent, and 52 percent of the pre-exposure values. Urinary excretion of ammonia was greatly increased after exposure to nickel carbonyl. The alterations of urinary excretions of amino acids were apparently mediated by nephrotoxicity rather than by mobilization of amino acids from tissues, since plasma concentrations of amino acids were not significantly affected by exposure to nickel carbonyl. The pronounced diminution of glutamine excretion and the marked increase of ammonia excretion were consistent with enhanced renal production of ammonia from glutamine by action of glutaminase.

Amino Acids↗
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The influence of zinc on apoptosis.

This review summarizes the evidence that apoptosis is modulated by intracellular excess or deficiency of Zn2+, considers mechanisms whereby Zn2+ may influence apoptosis, and delineates gaps in current knowledge and opportunities for research. The experimental evidence supports four major conclusions: [1] Zinc deficiency, resulting from dietary deprivation of mice, or exposure of cultured cells to membrane-permeable Zn(2+)-chelators, can induce apoptosis; [2] Zinc supplementation, either by pretreating mice with ZnSO4, or adding Zn2+ to the media of cell cultures, can prevent apoptotic death. Zn2+ protects against the apoptosis induced by diverse physical, chemical, or immunologic stimuli in cultured cells of lymphoid, hepatic, or neoplastic origin; [3] Zn2+ does not affect the triggering events or earliest signs of apoptosis, but acts later in the apoptotic pathway, preventing endonucleosomal fragmentation and subsequent cytolysis; and [4] An intracellular pool of chelatable Zn2+ plays a critical role in apoptosis, possibly by modulating the activation or activity of endonuclease(s). These conclusions should alert pharmacologists and physicians to the potential therapeutic applications of zinc compounds and zinc chelators in clinical disorders and diseases that involve apoptosis, and to the relevance of zinc nutrition in such conditions.

Animals↗
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Ocular malformations of Xenopus laevis exposed to nickel during embryogenesis.

The pathogenesis of eye anomalies induced by exposure to Ni2+ (as nickel chloride) during embryogenesis was studied in the frog, Xenopus laevis. Eyes of control and Ni(2+)-exposed tadpoles were examined without staining using a dissecting microscope, by light microscopy of histological sections, and by electron microscopy. The ocular abnormalities of Ni(2+)-exposed tadpoles included (a) microphthalmia, (b) hypopigmentation, (c) hernias and cysts of the choroid and retina, and (d) iris coloboma; cataracts were uncommon. The pathogenesis of the ocular lesions appears to involve diffuse or focal dysplasia and loss of the retinal pigment epithelium, with dystrophy of photoreceptor outer segments and protrusion of neuroretina through gaps in the pigment epithelium. This study confirms that Ni2+ is a potent ocular teratogen for Xenopus embryos and points to the retinal pigment epithelium as a primary cellular target for Ni(2+)-induced embryotoxicity.

Abnormalities, Drug-Induced↗
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Dose-response and time-response study of erythrocytosis in rats after intrarenal injection of nickel subsulfide.

Erythrocytosis was induced in Fischer rats by intrarenal (ir) injection of nickel subsulfide (Ni3S2) in dosages ranging from 0.6 to 10 mg per rat. Measurements of blood packed cell volume (PCV) became increased by one month after ir injection of Ni3S2; reached maximum values at approximately two months; and gradually returned to control values by seven months. The duration and magnitude of erythrocytosis were related to the dosage of Ni3S2. Increases in hemoglobin concentrations and erythrocyte counts (RBC) in Ni3S2-treated rats were consistently proportional to blood PCV values. Blood hemoglobin concentration was 24.9 +/- 1.2 g per dl at two months after bilateral ir injection of Ni3S2 (10 MG PER RAT), VERSUs 15.8 +/- 0.5 g per dl in saline-injected controls (P less than 0.001). No significant changes occurred in leukocyte or platelet counts of Ni3S2-treated rats. Autopsy of rats killed two months after ir injection of Ni3S2 showed marked erythroid hyperplasia of bone marrow and fibrotic needle tracts in renal parenchyma with localized deposits of particles of Ni3S2. In contrast to the erythrocytosis induced by ir injection of Ni3S2, administration of Ni3S2 by intramuscular (im) injection (10 mg per rat) had no significant effect upon blood PCV, RBC or hemoglobin values or upon morphology of bone marrow.

Animals↗
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Evolution of clinical science. An overview.

An overview is presented of immortals, institutions, and discoveries of past ages which have contributed to the furtherance of clinical science. The presentation is divided into two parts: I. Noteworthy contributions to the development of clinical science--1500 to 1700 A.D. II. Noteworthy contributions to the development of clinical science--1700 to 1949 A.D. The time has come for a transformation and rejuvenation of clinical laboratories in hospitals and medical institutions in our country. In recent years, the clinical investigative mission of hospital laboratories has been grossly neglected owing, in large measure, to the increased work loads for analytical service that are required for patient care. However, commercial corporations have now gradually invaded the field of clinical laboratory services, so that in the foreseeable future clinical laboratories will be afforded more time and opportunities for fulfillment of the investigative mission. The objectives of clinical science are to conserve health and to cure disease. By promoting the investigative point of view, clinical science will be destined to contribute to the furtherance of its objectives.

Chemistry, Clinical↗
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Embryotoxicity and teratogenicity of Cu2+ and Zn2+ for Xenopus laevis, assayed by the FETAX procedure.

Cupric chloride (CuCl2) and zinc chloride (ZnCl2) were tested by the FETAX (Frog Embryo Teratogenesis Assay: Xenopus) procedure in the South African frog, Xenopus laevis. The median teratogenic concentrations (EC50) of Cu2+ and Zn2+ were 2.5 and 40 mumol per L. The median embryolethal concentrations (LC50) of Cu2+ and Zn2+ were 22 and 850 mumol per L. The teratogenic indices (TI = LC50/EC50) were 8.8 for Cu2+ and 21 for Zn2+. Both metal ions were shown to be potent teratogens for Xenopus, causing concentration-related increases of eye, gut, facial, notochord, and cardiac anomalies.

Abnormalities, Drug-Induced↗
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Mg(2+)-deprivation enhances and Mg(2+)-supplementation diminishes the embryotoxic and teratogenic effects of Ni2+, Co2+, Zn2+, and Cd2+ for frog embryos in the FETAX assay.

The influence of Mg2+ on the embryotoxicity and teratogenicity of Ni2+, Co2+, Zn2+, and Cd2+ for Xenopus embryos was studied by an adaptation of the FETAX protocol. In seven assays, 25 groups of embryos were grown from 5 to 101 hours post-fertilization in FETAX media that contained five graded MgCl2 concentrations (0, 6.2, 62, 620, or 6,200 mumol per L), with or without added NiCl2 (56 mumol per L), CoCl2 (1,800 mumol per L), ZnCl2 (300 mumol per L), or CdCl2 (18 mumol per L). In FETAX assays performed with the standard Mg2+ concentration (620 mumol per L), the incidence of malformations in control embryos averaged 5.4 (SD +/- 1.3) percent; the incidence of malformations in the controls was increased at low Mg2+ concentrations (32 +/- 7 percent at 62 mumol per L; 100 percent at greater than or equal to 6.2 mumol per L). The specified additions of Ni2+, Co2+, Zn2+, or Cd2+ caused death in < 10 under standard conditions (620 mumol Mg2+ per L). Mg(2+)-deprivation greatly enhanced and Mg(2+)-supplementation significantly reduced the incidence and severity of the teratogenic and embryotoxic effects of Ni2+, Co2+, Zn2+, and Cd2+ (p < 0.0001 by analysis of variance [ANOVA]). To explain these findings, the authors speculate that Mg2+ competes with the other divalent metal ions for a carrier mechanism involved in metal absorption or cellular uptake, or for binding to critical molecular targets.

Abnormalities, Drug-Induced↗
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Nickel concentrations in human parotid saliva.

Measurements of nickel were performed by electrothermal atomic absorption spectrometry upon specimens of parotid saliva from 38 healthy adults. The mean concentration of nickel in saliva was 1.9 +/- 1.0 microng Ni per liter (range = 0.8 to 4.5). There was no significant correlation between the concentrations of salivary nickel and protein. No significant differences were observed between the mean concentrations of nickel in saliva samples from (1) men vs women; (2) health center employees vs naval recruits; (3) caries-free subjects vs caries-prone subjects; or (4) non-smokers vs cigarette smokers.

Adolescent↗