[Show abstract][Hide abstract] ABSTRACT: Although lead exposure has, in the absence of mathematical modelling, been believed to elevate blood pressure in females, it is necessary to clarify the relation between lead and blood pressure by eliminating confounding factors in the analysis.
Blood lead was measured in 193 female workers, including 123 lead exposed workers. Possible confounding factors were controlled by multiple regression analyses.
Blood lead above 40 micro g/dl was found to be the most potent factor for elevating systolic/diastolic blood pressure. Aging, urine protein, and plasma triglyceride also contributed to systolic/diastolic/pulse pressure increase, but hypertensive heredity did not. Data suggested that lead induced changes in lipoprotein metabolism may play an important role in the lead induced blood pressure increase in female workers.
Occupational and Environmental Medicine 12/2002; 59(11):734-8. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: By computerized static posturography with sway frequency analysis, subclinical effects of lead on postural balance was examined in 29 female workers (lead workers) employed at a glass factory for 3-17 (mean 7.9) years in Beijing, China, in relation to brainstem function assessed by brainstem auditory evoked potential (BAEP). Their blood lead concentrations ranged from 26 to 79 (mean 55.7) microg/dl; ages were 21-30 (mean 28) years. Control subjects, aged 22-29 (mean 27.0) years, were 14 healthy female workers at a textile factory located in the same district. With eyes closed, power of the sway of high (2-4 Hz) and low (1 Hz or less) frequencies in lead workers was significantly larger than that in controls; with eyes open, their power of the sway of low frequency was significantly larger (p<0.05). The multiple regression analysis showed that the power of high frequency sway with eyes closed and of low and high frequencies with eyes open were significantly related to blood lead concentrations in lead workers (p<0.05). On the other hand, no significant differences in BAEP latencies between lead workers and controls were observed. The low frequency sway with eyes open was significantly correlated with the high frequency sway with eyes closed in the lead workers. The pattern of changes in postural balance suggested that the anterior cerebellar lobe, vestibulo-cerebellar and spinocerebellar afferent systems were affected asymptomatically in female lead workers; the sway of vestibulo-cerebellar and anterior cerebellar lobe types were simultaneously affected by lead. It appears that a computerized static posturography with sway frequency analysis is useful technique for assessment of subclinical lead neurotoxicity.
Industrial Health 07/2002; 40(3):245-53. DOI:10.2486/indhealth.40.245 · 1.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recombinant adeno-associated virus (AAV) has attracted tremendous interest as a promising vector for gene delivery. In this study we have developed an HIV-1 vaccine, using an AAV vector expressing HIV-1 env, tat, and rev genes (AAV-HIV vector). A single injection of the AAV-HIV vector induced strong production of HIV-1-specific serum IgG and fecal secretory IgA antibodies as well as MHC class I-restricted CTL activity in BALB/c mice. The titer of HIV-1-specific serum IgG remained stable for 10 months. When AAV-HIV vector was coadministered with AAV-IL2 vector, the HIV-specific cell-mediated immunity (CMI) was significantly enhanced. Boosting with AAV-HIV vector strongly enhanced the humoral response. Furthermore, the mouse antisera neutralized an HIV-1 homologous strain, and BALB/c mice immunized via the intranasal route with an AAV vector expressing the influenza virus hemagglutinin (HA) gene showed protective immunity against homologous influenza virus challenge. These results demonstrate that AAV-HIV vector immunization may provide a novel and promising HIV vaccination strategy.
Human Gene Therapy 07/2001; 12(9):1047-61. DOI:10.1089/104303401750214276 · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, the role of delta-aminolevulinic acid dehydratase (ALAD) variants in lead susceptibility was examined. The study subjects comprised 223 male workers, and the relationship between their blood lead level and erythrocyte ALAD activity or plasma/urine delta-aminolevulinic acid level was studied. Leukocyte specimens from 11 workers, whose erythrocyte ALAD activities were as low as one-fifth that of the other normal workers, were subjected to analyses of their ALAD and ALAD alleles. Further, the entire exon fragment of the ALAD gene was analyzed by polymerase chain reaction, and the reaction product was used as a target for direct DNA sequencing. Genomic DNA analysis revealed that all 11 workers had the ALAD allele, whereas the entire ALAD gene analysis failed to indicate other variants, except for the Rsa I site. The depletion in erythrocyte ALAD activity was not found to be caused by the ALAD allele.
Journal of Occupational and Environmental Medicine 09/1999; 41(8):662-8. DOI:10.1097/00043764-199908000-00008 · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rats of Long-Evans Cinnamon (LEC) strain were used as a hepatorenal syndrome model of fulminant Wilson's disease. Copper levels in the kidneys increased markedly from 16 to 126 microg Cu/g from 12 to 16 weeks, and remained at the same level at 16 and 19 weeks when the rats suffered from severe renal dysfunction and also at 20 weeks in some other normal rats. The above findings imply that the renal dysfunction may have been induced independently of the copper level in the kidneys. The present study suggested the following mechanism: immediately after copper-induced hepatic dysfunction, plasma copper-metallothionein (CuMT), which was released from the liver, became elevated. The elevation was closely related to the increases in alkaline phosphatase, glucose and amino acids, all in the urine. The above findings suggest that plasma CuMT, which was released from the liver into the blood upon copper-induced hepatic dysfunction, was subsequently filtered at the glomeruli due to its smaller molecular weight, and then caused dysfunction of the brush border membrane of the renal proximal tubules probably after splitting into radical copper and amino acids in acidic vesicles close to the membrane. The critical concentration of plasma CuMT required to induce renal dysfunction was estimated as 1 microg Cu/l.
[Show abstract][Hide abstract] ABSTRACT: Thirteen rabbits were given subcutaneous cadmium (0.3 mg Cd/kg) daily. The plasma cadmium-metallothionein (CdMT) and the Cd-induced hepatic and renal functions were determined at 0, 5, 8, 11, 12, 13 and 14 weeks. Hepatic dysfunction, an elevated plasma CdMT and renal dysfunction were detected mostly between 12 and 14 weeks. The hepatic dysfunction parameters were closely related with the plasma CdMT, which was then found to correlate with the renal dysfunction parameters. All the above findings suggest the following mechanism for the Cd-induced renal dysfunction: hepatic CdMT is released into the plasma upon the Cd-induced hepatic dysfunction, and then excess plasma CdMT, whose concentration is proportional to the CdMT in the renal proximal tubular lumen, induces renal dysfunction. The critical concentration of plasma CdMT to induce renal dysfunction was estimated as 80 microg Cd/l. The plasma CdMT is proposed therefore as a biological exposure index for the Cd-induced renal dysfunction, based on the mechanism of its action.
[Show abstract][Hide abstract] ABSTRACT: A fluorometric high-performance liquid chromatographic (HPLC) method was developed for the highly sensitive measurement of delta-aminolevulinic acid (ALA) in biological materials. By using this method, we determined ALA in the plasma and urine of 418 workers occupationally exposed to lead and in the plasma and urine of 227 controls. The concentrations of ALA in the plasma and urine of lead workers were significantly elevated as compared with those of the controls. The concentration of ALA in plasma and urine was highly correlated with that of lead in blood in lead workers. It was found that the correlation (r = 0.742) between log of plasma ALA concentrations and blood lead concentrations in lead workers was similar to that (r = 0.711) between log of urine ALA concentrations and blood lead concentrations. These results demonstrated that the measurement of ALA in plasma or in urine using a fluorometric HPLC method was useful for the biological monitoring of lead workers.
[Show abstract][Hide abstract] ABSTRACT: To elucidate the sex difference in porphyrin metabolic disorders induced by lead exposure, we determined plasma delta-aminolevulinic acid (ALA), urinary ALA, and urinary coproporphyrin (CP) in 298 lead-exposed workers (160 males and 138 females), and compared the data thus obtained. The use of fluorometric high-performance liquid chromatography (HPLC) method which is highly sensitive and specific made possible the measurement of ALA in a small volume (50 microliters) of plasma. The concentrations (mean +/- SD) of lead in blood (males: 55.1 +/- 12.9 micrograms/dl; females: 54.7 +/- 13.5 micrograms/dl) indicated that the intensity of occupational exposure to lead was almost equal in the two groups. However, the elevation of plasma ALA concentration and the increased urine ALA and CP excretion among these lead workers were much higher in females than in males, confirming the finding of a sex difference in the biological effect of human exposure. The difference in urine CP excretion was especially pronounced, the mean concentration of urinary CP in the female workers being 3.5-5 times higher than that in the male workers.
International Archives of Occupational and Environmental Health 02/1996; 68(5):298-304. DOI:10.1007/BF00409414 · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify the effects of lead on autonomic and central nervous system functions, electrocardiographic R-R interval variability (CVRR) as well as visual and brainstem auditory evoked potentials (VEP and BAEP) were measured in 36 female workers exposed to lead (exposed group) and in 15 female textile workers (unexposed group). The C-CVLF, C-CVHF (two component CVs of the CVRR reflecting sympathetic and parasympathetic activities, respectively), and LF/HF ratio (indicator of sympatho-vagal balance) were also computed from component spectral powers by means of autoregressive spectral and component analyses. The exposed group had engaged in glass work for 2-17 (mean 7.8) years. Blood lead (BPb) concentrations were 25.8-79.3 (mean 55.6) micrograms/dl in the exposed group and 4.7-8.6 (mean 6.3) micrograms/dl in the unexposed group. The CVRR, C-CVLF, C-CVHF, and LF/HF ratio in the exposed group were significantly lower than those in the unexposed group. Also, the exposed group had more complaints of subjective symptoms and signs than did the unexposed group. On the other hand, no significant differences in either VEP or BAEP latencies were found between the two groups. It is suggested that autonomic nervous function is more susceptible to lead than visual and auditory nervous functions; lead affects sympathetic activity more strongly than parasympathetic activity.
American Journal of Industrial Medicine 08/1995; 28(2):233-44. DOI:10.1002/ajim.4700280208 · 1.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of long-term (9 y) po administration of daily low doses of cadmium on blood pressure, heart rate, electrocardiogram and plasma cholesterol and triglyceride concentrations were examined in rhesus monkeys. Thirty-five male rhesus monkeys were divided into 5 groups and fed pelleted food containing cadmium chloride at dosages of 0, 3, 10, 30 or 100 micrograms cadmium/g food (= ppm). The 100 ppm group had increased blood pressure during the initial 1 1/2 y. Thereafter, the expected increase in blood pressure that occurred due to aging in the control and 3 ppm groups was not evident in the 100 ppm group. No changes attributable to cadmium were detected in pulse rates or in electrocardiograms. Plasma cholesterol in the 2 highest dosage groups and triglyceride in the 100 ppm group were slightly lower than in controls after 2 1/2 y. Long-term exposure to cadmium contributed to the development of elevated blood pressure during the first and second years and then inhibited the hypertension expected due to aging.
Veterinary and human toxicology 09/1994; 36(4):290-4.
[Show abstract][Hide abstract] ABSTRACT: Thirty-five male rhesus monkeys (Macaca mulatta) 2-5 y-of-age were separated into 5 groups and fed 200 g solid food daily which contained 0, 3, 10, 30 or 100 micrograms cadmium/g (ppm) as cadmium chloride for 462 w (9 y). The control feed (0 ppm) contained 0.27 micrograms cadmium/g. Dietary zinc intake was limited to the minimum requirement of 6 mg zinc/day (control food concentration was 3 mg zinc/100 g) to avoid impacting cadmium toxicity due to excessive zinc intake. Urine was collected at 3-w intervals. Decreased development (reduced body weight and body length) was observed in groups that received 10 ppm cadmium or more. The 100 ppm group had glucose in the urine after 48 w, elevated urine protein at 98 w, and markedly increased urine volume after the 102nd week. No abnormalities in renal functions were noted in the 3 or 10 ppm groups. Despite the development of these clinical signs of renal dysfunction, none of the 100 ppm group had aggravated renal dysfunction or renal failure during the 9 y of study.
Veterinary and human toxicology 07/1994; 36(3):189-94.