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Biomedical subjects

S Araki

Publications and source records attributed to S Araki.

At least 127 records · Page 7Linked to original sources
PubMed1998

Assessment of mutations of Ha- and Ki-ras oncogenes and the p53 suppressor gene in seven malignant mesothelioma patients exposed to asbestos--PCR-SSCP and sequencing analyses of paraffin-embedded primary tumors.

To examine whether malignant mesothelioma due to asbestos has genetic alterations in the Ha- and Ki-ras oncogenes or in the p53 suppressor gene, we analyzed the point mutations of these genes in paraffin-embedded autopsy samples of the primary tumors of malignant mesothelioma in seven asbestos patients who died from malignant mesothelioma. The genetic analysis was conducted by the polymerase chain reaction-single strand comformation polymorphysms (PCR-SSCP) method in all patients, and through the sequencing of deoxyribonucleic acid (DNA) bases in one patient. No genetic alterations were found in exons 1 or 2 of Ha- and Ki-ras oncogenes, or in exons 5 to 9 of the p53 gene, in any of the patients. Further studies on a larger number of patients are required to reach a definite conclusion concerning the genetic effects of asbestos on malignant mesothelioma.

Aged↗
PubMed1998

Increase in the helper inducer (CD4+CD29+) T lymphocytes in smokers.

Previously, we reported an increase in the number of CD4+ T lymphocytes in the peripheral blood of smokers. In the present study, subpopulations of CD4+ T lymphocytes together with CD8+ T lymphocytes, total (CD3+) T lymphocytes, B (CD19+) lymphocytes, natural killer (CD16+) cells and total lymphocytes were examined by two-color staining using anti-2H4 (CD45RA) and anti-4B4 (CD29) monoclonal antibodies in 8 male smokers and 22 age-matched male non-smokers. The number of CD4+CD29+ T lymphocytes in smokers was significantly higher than that in non-smokers. The total number of CD4+ T lymphocytes in smokers was also significantly higher. No significant differences in CD8+ T, CD19+ B lymphocytes and CD16+ NK cells were found between smokers and non-smokers. Thus, it is suggested that the increase in the number of CD4+CD29+ (helper inducer) T lymphocytes is responsible for the increase in total CD4+ T lymphocytes in smokers.

Adult↗
PubMed1998

The human poly(ADP-ribose) glycohydrolase maps to chromosome 10q11.23-21.1 by fluorescence in situ hybridization.

Poly(ADP-ribose) glycohydrolase (PARG) digests poly(ADP-ribose), which is synthesized by poly(ADP-ribose) polymerase (PARP) after DNA damage. We mapped the human poly(ADP-ribose) glycohydrolase gene to chromosome 10q11.23-21.1 by fluorescence in situ hybridization analysis. Since chromosomal rearrangements in thyroid papillary carcinoma and loss of heterozygosity in glioblastoma are frequently observed in this region, genetic alteration of PARG could be implicated in these diseases.

Base Sequence↗
PubMed1998

Enhanced engraftment of intravenously transplanted hematopoietic stem cells into bone marrow of irradiated mice treated with AcSDKP.

The effect of the tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) on intravenously transplanted hematopoietic stem cell engraftment into the bone marrow (BM) of irradiated mice was studied. When 5 x 10(4) marrow cells were transplanted into lethally irradiated mice given 10 microg AcSDKP, the survival of these animals 4 weeks posttransplantation increased markedly from 20.0 +/- 4.4% to 86.1 +/- 4.8%, the same result as that obtained from mice transplanted with 5 x 10(5) cells without AcSDKP treatment. Increased numbers of hematopoietic stem cells, including spleen colony-forming unit and colony-forming unit granulocyte-macrophage, were observed in the BM of AcSDKP-treated mice 1 and 8 days after transplantation. This finding suggested that AcSDKP influenced homing of hematopoietic stem cells into the BM of lethally irradiated animals. This enhancing activity of AcSDKP was neutralized by the simultaneous administration of an anti-AcSDKP polyclonal antibody. Furthermore, recovery of leukocytes in peripheral blood occurred faster in AcSDKP-treated than in untreated transplanted mice. These findings may provide a basis for the clinical use of AcSDKP in BM transplantation patients.

Animals↗
PubMed1998

[Chemotherapy of gastric cancer].

At present curative resection is the only radical treatment for gastric cancer, although recently developed combination chemotherapy shows increased activity in treating locally advanced and metastatic disease. Among several combination regimens, those based on biochemical modulation, such as sequential methotrexate/5-fluorouracil or low-dose CDDP/5-fluorouracil, are thought to provide increased efficacy with decreasing adverse reactions in unresectable gastric cancer. Therefore, a prospective randomized clinical trial comparing the prognosis of patients receiving adjuvant multi-agent chemotherapy with those treated only surgically should be pursued for estimation of the clinical benefit of these agents.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Beraprost sodium, an analogue of prostacyclin, induces the expression of mitogen-activated protein kinase phosphatase and inhibits the proliferation of cultured mesangial cells.

Beraprost sodium, an analogue of prostacyclin, increases intracellular cyclic adenosine monophosphate (cAMP) in cultured glomerular mesangial cells. We examined the effect of beraprost on mesangial cell proliferation. Beraprost was able to inhibit fetal bovine serum-stimulated proliferation of mesangial cells in concentrations enough to increase cellular cAMP. By northern blot analysis, beraprost induced the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in a dose- and time-dependent manner, similarly to dibutyryl cAMP and adrenomedullin. These results indicate that beraprost inhibits the proliferation of mesangial cells and one of the mechanisms might be cAMP-dependent induction of MKP-1.

Animals↗
PubMed1997

Purification of a vascular apoptosis-inducing factor from hemorrhagic snake venom.

Hemorrhagic snake venom induces apoptosis in vascular endothelial cells specifically. We report here the purification of an apoptosis-inducing factor from the venom of the rattlesnake Crotalus atrox. The purified factor was a homodimeric protein with a molecular mass of 110 kD and an isoelectric point of 8.5. When exposed to the factor, vascular endothelial cells in culture died, with the characteristic features of apoptosis, such as fragmentation of cells and cleavage of DNA into fragments that yielded a characteristic ladder pattern upon electrophoresis. The activity seemed to be specific to endothelial cells. This factor may prove to be a useful tool for studies of the molecular mechanisms of vascular apoptosis.

Animals↗
PubMed1997

Inhibition of the binding of SNAP-23 to syntaxin 4 by Munc18c.

SNARE proteins have been implicated in the insulin-induced translocation of vesicles containing the GLUT4 glucose transporter to the plasma membrane of adipocytes. The role of the target SNARE SNAP-25 or its homologs in this process was investigated by screening a mouse adipocyte cDNA library with rat SNAP-25 and human SNAP-23 cDNA probes. Both positive clones isolated encoded a protein with 87% sequence identity to human SNAP-23, and which was therefore designated mouse SNAP-23. Immunoblot and immunofluorescence analyses revealed that SNAP-23 is located predominantly in the plasma membrane of 3T3-L1 adipocytes incubated in the absence or presence of insulin. Of syntaxins 1 to 5, SNAP-23 bound with the highest affinity to syntaxins 1 and 4 in the yeast two-hybrid system. Expression of SNAP-23, syntaxin 4, and the syntaxin-binding protein Munc 18c in COS cells revealed that Munc18c reduced the amount of SNAP-23 bound to syntaxin 4 in a concentration-dependent manner. These results suggest that the binding of SNAP-23 to syntaxin 4 is inhibited by Munc18c in adipocytes.

Adipocytes↗
PubMed1997

Integrin beta4 is involved in apoptotic signal transduction in endothelial cells.

To clarify the signal transduction in vascular endothelial cells (VEC) apoptosis induced by deprivation of FGF and serum, we investigated the function of integrin beta4 by using the monoclonal antibody (mAb) of this integrin. We added anti-beta 4 integrin mAb at the concentration of 5 microg/ml to the cells deprived of FGF and serum, apoptosis of these cells were completely inhibited 24 h after the treatment. Furthermore we plated the cells onto untreated bacterial culture plates on which the cells cannot adhere and spread in MCDB medium without FGF and serum; however, when anti-beta 4 integrin mAb was present at 5 microg/ml in the seeding medium, the cells rapidly adhered and spread. Our results first demonstrated that integrin beta4 participated in apoptotic signaling in VEC, and our findings indicate that hemidesmosome structures and keratin filament system might be important in regulation of apoptotic signaling.

Antibodies, Monoclonal↗
PubMed1997

Immunological effects of CaEDTA injection: observations in two lead workers.

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) injection on human immune system in relation to exposure to lead, we administered CaEDTA by intravenous injection for 1 hr three times (three consecutive days) a week to two male lead workers. They had been engaged in recycling lead for 31 and 22 years, aged 61 and 53 years (workers 1 and 2), respectively. Before the treatment of CaEDTA, their blood lead concentrations (PbB) were 81 and 68 micrograms/dl, respectively. The administration of CaEDTA had been carried out to worker 1 for 10 weeks and to worker 2 for 6 weeks. A significant decrease in PbB between before and after three-times CaEDTA injection was found in both workers. Significant increases in IgG, IgA, IgM, CD8+, and CD57+ cells were found in worker 1. A significant increase in IgD was found in worker 2. During the study period, IgG in worker 1 and CD4+ cells in worker 2 were gradually increasing. There was a significant negative correlation between IgG and PbB in worker 1. It is suggested that the immunological function such as antibody formation in lead workers might be improved by CaEDTA injection.

Antibody Formation↗
PubMed1997

Neurophysiological methods in occupational and environmental health: methodology and recent findings.

Neurophysiological measurement, a promising technique for assessment of the subclinical effects of occupational and environmental factors, is rapidly progressing following development of computer technology. The methods include measurement of evoked and event-related potentials, nerve conduction velocity, distribution of nerve conduction velocities, electrocardiographic R-R interval variability, and computerized static posturography. This paper provides an overview of these methods, except for evoked and event-related potentials, which have been reviewed previously by the authors, to evaluate the effects of occupational and environmental factors on the peripheral, autonomic, and cerebellar nervous systems. The available data indicate that these methods are sensitive, reliable, and easily applied in a field study. When conducting these measurements, controlling for confounding factors such as age, sex, height, skin temperature, alcohol ingestion, and neurologic diseases is necessary.

Electrophysiology↗
PubMed1997

Postural sway frequency analysis in workers exposed to n-hexane, xylene, and toluene: assessment of subclinical cerebellar dysfunction.

To clarify the effects of organic solvents on the postural balance system, 29 male sandal, shoe, and leather factory workers exposed to n-hexane, xylene, and toluene (solvent workers) were examined by computerized static posturography with sway frequency analysis. Concentrations of metabolites of solvents in urine samples taken from the workers in the morning before work ranged from 0.41 to 3.06 (mean, 1.20) mg/g creatinine (Cn) for 2,5-hexanedione, from 0.10 to 0.43 (mean, 0.19) g/g Cn for methylhippuric acid, and from 0.05 to 2.53 (mean, 0.37) g/g Cn for hippuric acid; estimated concentrations of n-hexane in workplace air ranged from 13 to 100 (mean, 40) ppm. Control subjects were 22 healthy males without exposure to solvents. With eyes open, postural sway with a frequency of 2-4 Hz in solvent workers was significantly larger than that in controls in the anteroposterior direction. With eyes closed, sway with a frequency of 0-1 Hz was significantly larger in solvent workers in the mediolateral and anteroposterior directions. Results of multiple regression analysis showed that with eyes open the 1- to 2-Hz and 2- to 4-Hz sways were related positively to 2,5-hexanedione and inversely with methylhippuric acid. The pattern of changes suggests that the vestibulocerebellar and spinocerebellar afferent systems are asymptomatically affected by n-hexane; the effect of n-hexane on the vestibulocerebellar system is possibly inhibited by xylene.

Cerebellum↗
PubMed1997

Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack.

Six to eight months after the Tokyo subway attack in March 1995, the neurophysiological effects of acute sarin poisoning were investigated in 18 passengers exposed to sarin (sarin cases) in the subways to ascertain the focal or functional brain deficits induced by sarin. The event-related and visual evoked potentials (P300 and VEP), brainstem auditory evoked potential, and electrocardiographic R-R interval variability (CVRR), together with the score on the posttraumatic stress disorder (PTSD) checklist, were measured in the sarin cases and the same number of control subjects matched for sex and age. None of the sarin cases had any obvious clinical abnormalities at the time of testing. The P300 and VEP (P100) latencies in the sarin cases were significantly prolonged compared with the matched controls. In the sarin cases, the CVRR was significantly related to serum cholinesterase (ChE) levels determined immediately after exposure; the PTSD score was not significantly associated with any neurophysiological data despite the high PTSD score in the sarin cases. These findings suggest that asymptomatic sequelae to sarin exposure, rather than PTSD, persist in the higher and visual nervous systems beyond the turnover period of ChE; sarin may have neurotoxic actions in addition to the inhibitory action on brain ChE.

Acute Disease↗
PubMed1997

Changes in natural killer cell subpopulations in lead workers.

To investigate the effects of lead on human immune system, we analyzed T cell subpopulations (CD4+, CD8+ and CD3+ cells), natural killer (NK) cell subpopulations (CD16+ and CD57+ cells) and B (CD19+) cells in peripheral blood in 29 male lead workers. All were engaged in manufacturing lead stearate in a chemical factory. They were aged 23-74 (mean 49) years. Their blood lead concentrations (PbB) were between 7 and 35 (mean 18) micrograms/dl. They were divided into two groups according to their PbB: a high-PbB group (> or = 20 micrograms/dl), and a low-PbB group (< 20 micrograms/dl). The control group consisted of 19 "healthy" male workers without a history of occupational exposure to lead or to other hazardous substances, aged 48-67 (mean 58) years. The number and percentage of CD16+ cells in the high-PbB group were significantly lower than those in the controls and in the low-PbB group. There was significant negative correlation between the number of CD16+ cells and PbB in the lead workers. The percentage of CD8+ cells in the high-PbB group was larger than that in the controls and in the low-PbB group. It is suggested that the CD16+ NK cell should be a major site of the effects of lead on lymphocyte subpopulations.

Adult↗
PubMed1997

Effects of occupational use of vibrating tools in the autonomic, central and peripheral nervous system.

OBJECTIVES: The objective of this study was to clarify the autonomic, central and peripheral nervous effects of vibrating-tool operation. METHODS: The ECG R-R interval variability (CVRR), including the C-CVHF, C-CVLF (two component CVs of the CVRR reflecting parasympathetic and sympathetic activities, respectively) and the power spectral densities (PSDHF and PSDLF) after autoregressive analysis, short-latency somatosensory evoked potentials (SSEP), distribution of nerve conduction velocities (DCV), and median and radial nerve conduction velocities (NCVs) were measured in 17 vibrating-tool operators and the same number of age-matched control subjects. Some of the operators complained of white finger even in summer as soon as they arrived at the cold workplace. DESIGN: The significance of the differences in neurophysiological data between the exposed and unexposed groups and the associations between these data in the former were investigated. RESULTS: The CVRR, C-CVHF and PSDHF were significantly lower in the vibrating-tool operators than in the matched controls. The N9-N13 interpeak latency of the SSEP, i.e., conduction time of the cervico-spinobulbar pathway, in the operators was significantly prolonged as compared with the controls; the faster velocities of the DCV and the NCVs were significantly slowed in the operators. The N9-N13 interpeak latency in the operators was significantly correlated with the C-CVHF. CONCLUSION: Complex stressors of local vibration, cold, noise and heavy work, seem to affect the cervico-spinobulbar, parasympathetic and peripheral nerve functions. Also, parasympathetic hypofunction may imply a consequence in brainstem pathology induced by cold exposure in addition to vibration.

Adult↗
PubMed1997

Nicotinamide adenine dinucleotide synthetase activity in erythrocytes as a tool for the biological monitoring of lead exposure.

OBJECTIVE: The objective of this study was to evaluate the usefulness of nicotinamide adenine dinucleotide synthetase (NADS) activity for the biological monitoring of lead exposure. METHODS: The subjects were 76 male lead workers and 13 normal volunteers (7 males and 6 females). NADS activity and blood lead concentration (Pb-B) was determined in each subject. Delta-aminolevulinic acid dehydratase (ALAD) activity was determined in 58 lead workers out of 76 subjects. RESULTS: NADS activity in the lead workers ranged from 0.08 to 1.1 mumol/h per g of hemoglobin (gHb) and decreased linearly (r = -0.867) as Pb-B increased up to 81.6 micrograms/dl. The pattern of depressed activity of NADS was different from that of ALAD activity, which decreased rapidly and reached a plateau at the Pb-B level between 40 and 60 micrograms/dl. The Pb-B levels inducing 50% inhibition of the enzyme activities were calculated to be 43 micrograms/dl and 20 micrograms/dl for NADS and ALAD, respectively. At the Pb-B level of 40 micrograms/dl, NADS activity showed high validity (1.77) with predictivity of 0.92 at the cut-off level of 0.4 mumol/h per gHb, which were higher than those of ALAD activity. CONCLUSIONS: These results show an apparent dose-effect relationship of NADS activity versus Pb-B. NADS activity can be used for the biological monitoring of lead exposure.

Adult↗