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Biologic effects of airborne particulate lead on continuously exposed rats and rhesus monkeys.

The biological effects of airborne particulate lead were studied in rats and rhesus monkeys (Macaca mulatta) exposed nearly continuously (22 hours per day) at a concentration of 21.5 mug Pb/cubic meter of air. The year-long exposure elicited an increase in the concentration of lead in the blood to 28 mug/100 ml in the rats and 17 mug/100 ml in the monkeys. Levels of lead in control animals were about 5 mug/100 and 4 mug/100 ml, respectively, in the rats and monkeys. The elevated blood-lead levels reached a maximum during the first few months of exposure and did not increase significantly after that time. Elevated concentrations of lead were also detected in lung, liver, kidney and bone of both species. While concentrations of lead were nearly always less than 1 mug/g in control animals, they rose to 2-3 mug/g in soft tissues of exposed animals and up to 6 mug/g in bone. Differences between lead levels in animals exposed six months or twelve months were very small. The concentration of lead decreased in the soft tissues of animals removed from the chamber after one year's exposure but remained elevated in bone. The activity of the enzyme delta-amino-levulinic acid dehydrase (ALAD) in circulating erythrocytes was inhibited about 70% in rats exposed to the airborne lead. No reduction of the enzyme activity occurred in brain or liver tissue of either the rats or monkeys. Normal levels of ALAD in erythrocytes of the monkeys were too low to permit meaningful measurements. In spite of the reduced ALAD activity in rat erythrocytes, there was no concomitant alteration in the excretion of heme precursors. In all other respects, there appeared to be no deleterious effects on the animals from exposure to the airborne particulate lead. No changes were detected in serum chemistry or hematology nor were there any gross, microscopic or ultrastructural pathologic changes observed.

Aerosols↗

[Appraisal of the feasibility of the accepted Bulgarian MPEL for lead in the air of the working environment using modern criteria].

The MAC for lead in the workplace atmosphere adopted in Bulgaria, amounting to 0.01 mg/m3, appears to be much lower than abroad. Upon investigation of groups of workers employed in the lead mining and processing industry, working under conditions of lead exposure up to 0.10 mg/m3 and exceeding 0.11 mg/m3, no changes were found in the delta-amino-levulinic acid and coproporphyrin level in the urine--the early signs of lead damage--nor in plumburia mong the workers exposed to lead concentrations up to 0.10 mg/m3 which is a concentration exceeding ten times the MAC accepted in this country. A reassessment of the later on the basis of up-to-date biochemical criteria is deemed necessary.

Air Pollutants↗

[Multifocal axonal motor neuropathy associated with anti-ganglioside antibodies].

We report a patient with asymmetrical patchy weakness of the limbs, and with autoantibodies against gangliosides GM1, GD1b, asialo GM1. Although electrophysiological studies did not reveal conduction block, treatment with prednisolone resulted in clinical improvement. A 52-year-old man was admitted to Kyoto University Hospital, because of gait disturbance. Neurological examination revealed a patchy distribution of weakness in the limbs. Deep tendon reflex was normal at the right knee, and was depressed at the right biceps. Other deep tendon reflexes were absent. There was a slight decrease in vibratory sensation in the distal portions of the lower extremities. Routine laboratory studies, heavy metal screen, vitamin, cryoglobulin, coproporphyrin and delta-amino levulinic acid in urine, and the protein value of the cerebrospinal fluid were normal. Head and neck MRI, and myelography were normal. Immunofixation electrophoresis showed IgM lambda M-protein in serum. Thin-layer chromatography with immunostaining showed his serum IgM reacted with GM1, GD1b, and asialo GM1. ELISA (Enzyme Linked Immunosorbent Assay) demonstrated high titers of anti GM1, GD1b and low titer of anti asialo GM1. Motor conduction studies showed no demonstrable conduction block, normal conduction velocities and the low amplitudes of CMAP. Sensory conduction studies showed no abnormalities except for slightly decreased amplitude of SNAP in sural nerve. Electromyography showed active denervation in extensor digitorum communis muscle, tibialis anterior muscle and left biceps brachii muscle. Muscle biopsy specimen revealed large and small group atrophy and there was perivascular mononuclear infiltration at one point.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

[Toxicokinetic and toxicodynamic indices in persons exposed to lead and manganese].

Subject to examination are 161 workers (118 men and 43 women) in professional contact with manganese and lead of the agglomeration production of Kremikovtsi. A complex of toxicokinetic (content of manganese in blood, urine and hair) and toxicodynamic indices is applied. Increased levels of manganese are established in the examined biological media. No plumbemia above 2.88 mumol/l is registered. The excretion of 5-amino-levulinic acid in urine is increased at a low rate. There are no considerable deviations in the clinic and chemical indices.

Adult↗

[Porphyria and inappropriate antidiuretic hormone syndrome].

We report the case of a 37-years-old woman with inappropriate antidiuretic hormone syndrome due to an attack of acute porphyria. The patient was admitted to our hospital for abdominal pain, sleepiness and pink urine. Family and personal history were normal. Seven days before the admission the patient had a laparoscopy operation for endometriosis in her left ovary. The patient had had two normal pregnancies. The physical examination was normal, the skin turgor was good and no edema was present, the blood pressure was 140/90 mmHg. Her serum sodium was 114 mEq/L, serum osmolality 243 mOsm/kg, urine sodium 146 mEq/L and urine osmolality 457 mOsm/kg. Values from laboratory examination revealed a normal peripheral haematogram, a normal kidney function, normal liver, adrenal and thyroid function. The urine tested for amino-levulinic acid, coproporphyrin and uroporphyrin was strongly positive. These findings are compatible with Porphyria Variegata or Coproporphyria Hereditary. A diagnosis of Porphyria acute with SIADH was made, and water fluid restriction, i.v. hypertonic saline infusion and furosemide to correct the hyponatremia was begun. In 1966, lesions of the median eminence of the hypothalamus and both hypothalamic -hypophyseal tracts were described in a patient with Porphyria acute intermittent and SIADH. It was suggested that SIADH occurred because of damage to these areas of the brain from excessive exposure to porphyrins.

Abdominal Pain↗

Glutamyl-tRNA reductase from Escherichia coli and Synechocystis 6803. Gene structure and expression.

In the cyanobacterium Synechocystis sp. PCC 6803 and in the enterobacterium Escherichia coli delta-amino-levulinic acid (ALA) is formed from glutamyl-tRNA by the sequential action of two enzymes, glutamyl-tRNA reductase (GluTR) and glutamate-1-semialdehyde aminotransferase. E. coli has two GluTR proteins with sizes of 45 kDa (GluTR45) and 85 kDa (GluTR85) (Jahn, D., Michelsen, U., and Söll, D. (1991) J. Biol. Chem. 266, 2542-2548). The hemA gene, isolated from E. coli and several other eubacteria, has been proposed to encode a structural component of GluTR. Because of the inability to overexpress this gene in E. coli, we demonstrate directly GluTR function for the E. coli hemA gene product by its expression and functional analysis in yeast, which does not form ALA from Glu-tRNA. Gel filtration experiments demonstrated definitively that the yeast-expressed HemA protein corresponded to GluTR45. Furthermore, analysis of GluTR activity in an E. coli strain with a disrupted hemA gene displayed GluTR85, but not GluTR45 activity. The hemA gene from Synechocystis 6803 was cloned by functional complementation in E. coli. DNA sequence analysis revealed an open reading frame capable of encoding a 427-amino acid polypeptide (molecular mass of 47,525 Da). The Synechocystis 6803 amino acid sequence shows significant similarity upon alignment with HemA sequences from E. coli, Bacillus subtilis, Salmonella typhimurium, and Chlorobium vibrioforme but does not contain the amino acid sequence derived from the N terminus of the previously purified GluTR protein (Rieble, S., and Beale, S. I. (1991) J. Biol. Chem. 266, 9740-9745). These experiments are the first direct demonstration of GluTR activity of the HemA protein and provide further evidence for two pathways of ALA formation in prokaryotes.

Aldehyde Oxidoreductases↗

Cytochrome c1 of bakers' yeast. I. Isolation and properties.

Cytochrome c1 has been purified from mitochondria of the yeast Saccharomyces cerevisiae. The procedure involves solubilization withcholate, ammonium sulfate fractionation, disruption of the dytochrome b-c1 complex with mercaptoethanol and detergents, and chromatography on DEAE-cellulose. The final product is psectrally pure, contains up to 62 nmol of covalently bound heme per mg of protein and does not react with oxygen or carbon monoxide. Sodium dodecyl sulfate disaggregates the purified cytochrome into a single 31,000 dalton subunit carrying the covalently attached heme group. Many cytochrome c1 preparations contain in addition an 18,500 dalton polypeptide which is devoid of covalently bound heme. Since this polypeptide can be removed from the heme-carrying polypeptide by relatively mild procedures, it is probably not an essential subunit of cytochrome c1. Cytochrome c1 is extremely sensitive to proteolysis. If it si purified in the absence of protease inhibitors, a family of heme polypeptides with molecular weights of 29,000, 27,000, and 25,000 daltons is obtained. In the presence of the protease inhibitor phenylmethylsulfonylfluoride the purification yields predominantly a 31,000 dalton heme protein with only little contamination by a 29,000 dalton degradation product. In order to show that only the 31,000 dalton heme-polypeptide is the native species, yeast cells were labeled with the heme-precursor delta-amino[3H]levulinic acid, converted to protoplasts and directly lysed with dodecyl sulfate in the presence of protease inhibitors. Subsequent electrophoresis of the lysate in the presence of dodecyl sulfate reveals the covalently bound heme of cytochrome c1 as a single symmetrical peak at 31,000 daltons.

Amino Acids↗

Endogenous bilirubin excretion in Bolivian squirrel monkeys with a Gilbert's-like syndrome.

Fasted Bolivian squirrel monkeys (BoSM) exhibit a marked hyperbilirubinemia when compared to fed BoSM. This fasting hyperbilirubinemia (FH) is similar to that in human patients with Gilbert's syndrome. Endogenous bilirubin (BR) excretion (production) into bile was elevated two-fold in BoSM upon fasting. The fraction of injected dose of 3 H-amino-levulinic acid (ALA) incorporated into biliary BR in fasted monkeys was of less magnitude than in fed monkeys and was associated with lower specific activities of 3 H-BR. Both the lower incorporation of ALA and lower specific activities of 3H-BR in fasted BoSM suggest that increased BR excreted may have arisen from pre-existing non-labeled pools of either heme or BR.

Aminolevulinic Acid↗

[Benefits of ecogenetics in Hungary].

Five enzymes and one protein were studied in 10 ethnical and two reference groups involving 1370 persons. The frequency of atypical heterozygotes of plasma cholinesterase was 2.7%. Aldehyde dehydrogenase I isozyme deficiency was found in four persons including two gypsies. The low paraoxonase activity was found in 48.7% of persons examined. The proportion of gene frequencies of sigma-ALADH-1 and sigma-ALADH-2 in the locus of sigma-amino-levulinic acid dehydratase was 9:1. The percentage of slow acetylators was 56.9% in the total study sample. The rate of heterozygotes in Pi alleles of alpha 1-antitrypsin (protease-inhibitor) was 3.7% and one Pi ZZ phenotype could be observed.

Aldehyde Dehydrogenase↗

[Anemia in chronic lead poisoning. Apropos of 2 cases].

The authors report two cases of lead poisoning in which the diagnosis was made following anemia. They recall the clinical, laboratory and physiopathological characteristics of the blood signs of chronic lead poisoning. Anemia is the result of more rapid aging of the red cells, and of the effect of lead on erythropoiesis. The diagnosis is based on the finding of stippled red cells, on the rise in urinary delta-levulinic acid and on urinary lead after chelation.

Adult↗

[Examination medicine in the industrial health--aspects of biological monitoring].

The data of the health examinations for workers during the last few decades show two changes on the health level of labor. One is the reincrease of the prevalence rate of the detected diseases in the periodic health examinations (PHE) after once decrease, the other is the continuous decrease of the prevalence rate of the clinical findings owing to harmful work in the special health examinations (SHE). The first change requires us to consider the PHE as not only the mass screening method of the adult diseases but also the health-check to collect the information provided for the preparation and the evaluation of the health instruction by which the worker tries to promote his own health. The second change suggests that the SHE for the workers employed for harmful work should not be regarded hereafter as the screening method for the occupational diseases but as the biological monitoring for the exposure and the effect of the low level of the harmful compounds to workers. In the case of lead workers, for instance, the lead concentration in blood (B-Pb) and in urine (U-Pb) and the delta-amino levulinic acid in urine (U-ALA) are employed in SHE as the biological monitoring, and these have been considered to correlate well with the lead level in the air (A-Pb). However, A-Pb in workshops B-Pb, U-Pb and U-ALA level in the lead workers are decreasing year by year.(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental Monitoring↗

[Turnover of microsomal hemeproteins in the guinea pig liver during food sensitization].

A phase-dependent type of microsomal hemoproteins turnover in liver tissue, estimated by incorporation of 14C-amino-levulinic acid, was detected in guinea pig males in dynamics of alimentary sensitization (1, 7, 14 and 21 days) with ovalbumin and bovine blood serum albumin (BSA). The first phase was expressed as elevated catabolism of microsomal cytochromes simultaneously with a decrease in their turnover; the second phase involved an increase in the hemoproteins biosynthesis. Less distinct sensitization with BSA exhibited the shortened period of the first phase, while activation of aminopyrine N-demethylase and aniline p-hydroxylase as well as considerably increased rate of microsomal cytochromes turnover were found during the second phase in liver tissue.

Animals↗

Synergistic effect of allyl isopropyl acetamide with cadmium on hepatic heme synthesis in chick embryo.

The effect of cadmium along with a porphyrogenic drug, allyl isopropyl acetamide, on the induction of 5-amino levulinic acid (ALA) synthetase, ALA dehydratase and heme level was studied. The interaction of cadmium with allyl isopropyl acetamide indicated that the decrease in hepatic heme level by cadmium or allyl isopropyl acetamide may occur in a synergistic manner, whereas the induction of ALA synthetase by cadmium or allyl isopropyl acetamide may not take place in the same manner. Further, neither allyl isopropyl acetamide treatment alone nor allyl isopropyl acetamide-cadmium treatment had any effect on ALA dehydratase activity.

5-Aminolevulinate Synthetase↗

[An unusual mechanism of lead poisoning. Presentation of a case].

A case is described, that came to our attention for suspected acute intermittent porphyria, with abdominal pain and ascending tetraplegia. The patient (HIV positive and with a HBsAg positive chronic aggressive hepatitis) was a heroin addict. In urine: high porphyrins with extremely increased delta amino-levulinic acid (ALA) and normal porphobilinogen. High protoporphyrin was present in blood red cells. The lead poisoning was confirmed by a very low ALA-dehydratase activity in erythrocytes and a high content of lead in urine and plasma. With Ca-versenate and penicillamine the abdominal and neurological symptoms rapidly disappeared. The possibility of contact with lead, professional or environmental, was ruled out. It was found however, that shortly before the appearance of symptoms, the patient had used a batch of unrefined brown sugar heroin, which was probably mixed with lead salts. It is noteworthy that during the same period, other young heroin addicts died with similar symptoms.

Adult↗

Effect of exogenous heme on sulfide-induced changes in rat heme metabolism.

Intraperitoneal heme treatment (5 mg/kg body wt) reversed the effects of a preceding (2 h) intraperitoneally injected Na2 S (150 mumol/kg body wt) dose on blood delta-amino levulinic acid synthase and heme synthase activities. The sulfide dosing caused decreased activity of both enzymes of which that of heme synthase was overcorrected above controls by the heme treatment 25 h after the sulfide dose. Heme alone caused a transient induction in the heme oxygenase activity in liver 23 h after the injection. The effects on heme synthesis in the sulphide-dosed rats support the role of the inactivation of the heme-controlled translational inhibitor of protein synthesis by the supply of exogenous heme.

5-Aminolevulinate Synthetase↗