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Biomedical subjects

S Araki

Publications and source records attributed to S Araki.

At least 109 records · Page 6Linked to original sources
PubMed1999

[Syndromes of severe insulin resistance].

The syndromes of extreme severe insulin resistance are mainly caused by genetic defects of the insulin receptor gene (Type A syndrome, Leprechaunism, and Rabson-Mendenhall syndrome) or by the presence of circulating autoantibodies that disrupt the normal functions of the insulin receptor (Type B syndrome). These syndromes are characterized by the hyperinsulinemia and severe insulin resistance and in most cases accompanied by impaired glucose tolerance and diabetes mellitus. The clinical features common to these syndromes are acanthosis nigricans, hyperandrogenism and ovarian dysfunction. On the other hand, an important distinguishing typical feature in type B syndrome is evidence of other autoimmune disorders. [These syndromes can be a contributory causes of insulin resistance in a subpopulation with NIDDM.]

Autoantibodies↗
PubMed1999

Effect of manoalide on apoptosis induced by deprivation of growth factors in vascular endothelial cells.

AIM: To study effect of manoalide on apoptosis induced by deprivation of acidic fibroblast growth factor (aFGF) and serum in vascular endothelial cells (VEC). METHODS: Morphologic changes were observed by light microscopy. Viability was determined by counting the cells that attached to dishes after treatments. DNA fragmentation was analyzed by agarose gel electrophoresis and fluorescence microscopy. RESULTS: The cells deprived of aFGF and serum were exposed to manoalide 1-4 mumol. L-1 for 48 h, detachment and DNA fragmentation of these cells were suppressed. At 7 mumol. L-1, manoalide promoted detachment and DNA fragmentation of VEC. CONCLUSION: manoalide 2 mumol.L-1 inhibited, but 7 mumol.L-1 promoted, apoptosis of VEC.

Apoptosis↗
PubMed1999

[Multiple chemical sensitivities: case definition, etiology and relations to allergy, poisoning, psychogenic illness etc].

Multiple Chemical Sensitivities (MCS) have been defined as an acquired disorder characterized by recurrent symptoms, referable to multiple organ systems, occurring in response to demonstrable exposure to many chemically unrelated compounds at doses far below those established in the general population to cause harmful effects; no single widely accepted test of physiologic function can be shown to correlate with symptoms (Cullen MR, 1987). The etiology of MCS is hypothesized as a toxicant-induced loss of tolerance to multiple chemicals with subsequent manifestation of multiple-organ symptoms triggered by low-level exposure to such chemicals. The involvement of multiple organs might be attributed to a neurogenic switching mechanism. The final diagnosis of MCS is to rely on provocation of symptoms in a exposure chamber by a double-blind method. Relations of MCS to allergy, poisoning, psychogenic illness, chemical sensitivity, idiopathic environmental intolerances etc. are discussed in terms of case definition and etiology of these disorders.

Diagnosis, Differential↗
PubMed1998

Inhibition of insulin-induced GLUT4 translocation by Munc18c through interaction with syntaxin4 in 3T3-L1 adipocytes.

Insulin induces the translocation of vesicles containing the glucose transporter GLUT4 from an intracellular compartment to the plasma membrane in adipocytes. SNARE proteins have been implicated in the docking and fusion of these vesicles with the cell membrane. The role of Munc18c, previously identified as an n-Sec1/Munc18 homolog in 3T3-L1 adipocytes, in insulin-regulated GLUT4 trafficking has now been investigated in 3T3-L1 adipocytes. In these cells, Munc18c was predominantly associated with syntaxin4, although it bound both syntaxin2 and syntaxin4 to similar extents in vitro. In addition, SNAP-23, an adipocyte homolog of SNAP-25, associated with both syntaxins 2 and 4 in 3T3-L1 adipocytes. Overexpression of Munc18c in 3T3-L1 adipocytes by adenovirus-mediated gene transfer resulted in inhibition of insulin-stimulated glucose transport in a virus dose-dependent manner (maximal effect, approximately 50%) as well as in inhibition of sorbitol-induced glucose transport (by approximately 35%), which is mediated by a pathway different from that used by insulin. In contrast, Munc18b, which is also expressed in adipocytes but which did not bind to syntaxin4, had no effect on glucose transport. Furthermore, overexpression of Munc18c resulted in inhibition of insulin-induced translocation of GLUT4, but not of that of GLUT1, to the plasma membrane. These results suggest that Munc18c is involved in the insulin-dependent trafficking of GLUT4 from the intracellular storage compartment to the plasma membrane in 3T3-L1 adipocytes by modulating the formation of a SNARE complex that includes syntaxin4.

3T3 Cells↗
PubMed1998

Behavior of heavy metals in human urine and blood following calcium disodium ethylenediamine tetraacetate injection: observations in metal workers.

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the behavior of 8 heavy metals in human urine and blood, CaEDTA was administered for 1 h by intravenous injection to 18 male metal foundry workers, whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) microg/dl. Significant increases were found in urinary excretion of manganese, chromium, lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium excretion reached a maximal level within 1 h after the start of injection, while urinary manganese, lead, and zinc excretion reached their highest concentrations between 1 and 2 h. Urinary copper excretion reached the highest level between 2 and 4 h. The rapid increases in urinary excretion of five metals were different from the "circadian rhythms," which are the normal, daily variations in renal glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead concentrations were highest 1.5 h after the start of the 1-h injection, while plasma zinc concentration became lowest 5 h after the start of CaEDTA injection. Data suggest that manganese and chromium absorbed in human tissues might be mobilized by CaEDTA.

Adult↗
PubMed1998

A new isoform of human myosin phosphatase targeting/regulatory subunit (MYPT2): cDNA cloning, tissue expression, and chromosomal mapping.

Myosin phosphatase target subunit 1 (MYPT1), a subunit of myosin phosphatase, plays a pivotal role in the regulation of myosin phosphatase activity. Here we have cloned a novel isoform of MYPT1, termed MYPT2, from a human brain cDNA library screened with a cDNA fragment of rat MYPT1. Overlapping clones indicated an open reading frame of 3763 nucleotides and a predicted polypeptide of mass 110,398. Ankyrin repeats and leucine zipper motifs were identified for the sequences 57-316 and 956-982, respectively. Overall, the deduced amino acid sequence of MYPT2 was 61% identical to MYPT1. MYPT2 gene is transcribed abundantly in heart and skeletal muscle, while Western blots using an antibody specific for MYPT2 showed exclusive expression of MYPT2 in heart and brain. A recombinant of the N-terminal two-thirds of MYPT2 bound to the catalytic subunit of type 1 phosphatase (delta isoform) and increased activity toward phosphorylated myosin light chain. In situ hybridization localized the human MYPT2 gene on chromosome 1q32.1, compared to the chromosomal location 12q15-q21-2 for MYPT1. It is suggested that the products of the two gene families of myosin phosphatase target subunit may be localized differently among various tissues.

Amino Acid Sequence↗
PubMed1998

Two vascular apoptosis-inducing proteins from snake venom are members of the metalloprotease/disintegrin family.

Hemorrhagic snake venom induces apoptosis in vascular endothelial cells. In a previous report, we described the purification of a vascular apoptosis-inducing protein (VAP) from Crotalus atrox [Masuda, S., Araki, S., Kaji, K. & Hayashi, H. (1997) Biochem. Biophys. Res. Commun. 235, 59-63]. We report here the identification of a second vascular apoptosis-inducing protein, VAP2, in venom from C. atrox. When we fractionated crude venom from C. atrox by isoelectric focusing, we found two proteins with apoptosis-inducing activity, one was basic and the other acidic. The basic protein corresponded to VAP, and we named the acidic protein VAP2. VAP2 was a monomeric protein with molecular mass of 55 kDa and an isoelectric point of 4.5. VAP2 killed vascular endothelial cells in culture, and the death of cells exhibited the characteristic features of apoptotic activity of VAP2 seemed to be specific to endothelial cells, as reported for VAP. The half-lethal doses of VAP and VAP2 were 0.3 microg/ml and 0.1 microg/ml, respectively. Analysis of the partial amino acid sequences of VAP and VAP2 revealed similarities to members of the metalloprotease/disintegrin family. The sensitivity of VAP2 to changes in pH and temperature was distinct from that of VAP. Our results suggest that VAP and VAP2 are members of the metalloprotease/disintegrin family.

Amino Acid Sequence↗
PubMed1998

Stimulatory effects of neopterin on hematopoiesis in vitro are mediated by activation of stromal cell function.

The pteridine neopterin (NP) was shown to be produced by monocytes and is known to be a useful marker of immunological activation, although, its biological activity is still unclear. Recently, we found that intravenous administration of NP increased the numbers of blood leukocytes, and granulocyte-macrophage progenitor cells (CFU-GM) in the bone marrow and spleens of mice. In order to elucidate the mechanism whereby NP stimulates hematopoiesis, the effects of NP on hematopoietic stem cell proliferation and differentiation in vitro were studied using a long-term bone marrow culture (LTMC) system with cloned stromal cell line, MS-5. Adding NP to the LTMC increased the numbers of cells in total, CFU-GM and colony-forming unit in spleen (CFU-S). NP also increased the number of CFU-GM in a soft agar culture system, but it did not enhance CFU-GM colony formation when target bone marrow cells were semi-purified (T, B and adherent cell-depleted bone marrow cells) and cultured in this system, suggesting that NP did not directly affect the proliferation of hematopoietic progenitors. Conditioned medium obtained from NP-treated stromal cells had much greater colony-stimulating activity than that obtained from untreated stromal cells. Furthermore, NP treatment stimulated the production of IL-6 and GM-CSF by stromal cells. All these findings suggest that NP stimulates hematopoietic cell proliferation and differentiation in vitro by activating stromal cell function.

Animals↗
PubMed1998

Changes in T cell subpopulations in lead workers.

To investigate the effects of lead on the human immune system, we analyzed T cell subpopulations and B (CD19+) cells in peripheral blood in 71 male lead workers. They were engaged in manufacturing lead stearate in a chemical factory, aged 20 to 74 (mean 48) years. Their blood lead concentrations (PbB) were between 7 and 50 (mean 19) micrograms/dl. The control group consisted of 28 "healthy" male volunteers without a history of occupational exposure to lead or other hazardous substances, aged 33 to 67 (mean 55) years. In comparison with the controls, a significant reduction in the number of CD3+CD45RO+ (memory T) cells and a significant expansion in the percentage of CD8+ cells in the lead workers were found. There was a significant positive correlation between the percentage of CD3+CD45RA+ (naive T) cells and PbB in the lead workers. It is suggested that CD45RO+ memory T cells may be most susceptible to the effects of lead on T cell subpopulations.

Adult↗
PubMed1998

Effects of smoking, aromatic amines, and chromates on CD4+ and CD8+ T lymphocytes in male workers.

To investigate effects of smoking, aromatic amines (AAs), and chromates (CRs) on T lymphocyte subpopulations, we measured CD3+, CD4+, and CD8+ T lymphocytes in the peripheral blood of 33 nonexposed workers, 25 AA-use workers, 27 AA-production workers, and 19 CR workers (all subjects were males). The number of CD4+ T lymphocytes in smokers of nonexposed workers was significantly larger than that of the nonsmokers; also, the numbers of CD4+ and CD3+ T lymphocytes in smokers of each group of AA-production and AA-use workers were significantly larger than those in nonsmokers. Number of CD4+ and CD3+ T lymphocytes in nonsmokers of AA-production and CR workers were significantly smaller than those in nonsmokers of nonexposed workers; the number of CD8+ T lymphocytes in nonsmokers of CR workers was significantly smaller than that in nonsmokers of nonexposed workers. The cross-sectional study suggests that (1) smoking increases CD4+ (and CD3+) T lymphocytes in all categories of workers except for CR workers; (2) exposure to CRs and AAs decreases CD4+ (and CD3+) T lymphocytes; (3) the magnitude of decrease in CD4+ T lymphocytes is large among CR workers, intermediate among AA-production workers, and small among AA-use workers regardless of smoking status; and (4) exposure to CRs also decreases CD8+ T lymphocytes.

Adult↗
PubMed1998

Job strain and arterial blood pressure, serum cholesterol, and smoking as risk factors for coronary heart disease in Japan.

OBJECTIVE: To determine the effects of the job demands-control model on arterial blood pressure, serum total cholesterol, and smoking in male daytime and rotating-shift workers in Japan. METHODS: The survey was conducted for all employees of an electrical factory in Japan using a mailed questionnaire concerning three job stressors, i.e., job overload, work-pace control, and work-site social support. A blood sample was taken at the same time. Data on 1703 male daytime workers and 1 173 male rotating-shift workers were analyzed. Multiple logistic regression or analysis of covariance (ANCOVA) were employed to determine the effects of the job stressors on systolic and diastolic blood pressure, serum total cholesterol, and smoking with control for other covariates. RESULTS: Among daytime workers, systolic and diastolic blood pressures were highest in the "high-strain" (i.e., higher job overload + lower work-pace control) group; ANCOVA indicated that a two-way interaction between job overload and work-pace control was significant (P < 0.01). This tendency was not observed among rotating-shift workers. The number of cigarettes smoked per day was greater in groups with lower work-pace control and lower work-site social support among daytime workers (two-way interaction between these two job stressors, P < 0.05); it was greater in groups with lower work-site social support among rotating-shift workers (main effect of work-site social support, P < 0.05). CONCLUSIONS: Our study suggest that job strain as defined in the job demands-control model is associated with increased systolic and diastolic blood pressures in male daytime workers in Japan. Smoking might be affected by lower work-site social support.

Adult↗
PubMed1998

Calcium disodium ethylenediaminetetraacetate-chelated lead as a predictor for subclinical lead neurotoxicity: follow-up study on gun-metal foundry workers.

OBJECTIVES: To examine if chelated lead was a more predictive indicator of the subclinical effect of lead on conduction velocities of faster or slower nerve fibers as compared with blood lead (BPb). METHODS: Distribution of conduction velocities (DCV) in large myelinated fibers of the sensory median nerve was measured twice at a 1-year interval in 17 male gun-metal foundry workers with BPb concentrations of 22-59 (mean 40.2) microg/dl and a mobilization yield of lead into urine (MPb) by calcium disodium ethylenediaminetetraacetate of 0.15-2.09 (mean 1.19) mg/24 h for the 1st year and in 20 healthy males (controls). RESULTS: Yearly changes in the conduction velocities of faster fibers were significantly correlated with the corresponding change in MPb (P < 0.05) but not with that in BPb (P > 0.05). In ten workers showing an increase in MPb during the 1-year period (0.44 mg/24 h on average) the conduction velocities of faster fibers were decreased significantly, resulting in the values being significantly lower in all the workers combined than in the controls (P < 0.05). On the other hand, in the remaining workers, who showed a lesser extent of reduction in MPb (0.08 mg/24 h on average), the DCV did not change (P > 0.05). CONCLUSION: Chelated lead might be a more predictive indicator of the effect of lead on the conduction velocities of faster fibers than blood lead.

Adult↗
PubMed1998

Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation.

The present study was carried out to examine the chemopreventive effects of carotenoids such as fucoxanthin, lycopene and lutein as well as curcumin and its derivative, tetrahydrocurcumin (THC), on development of putative preneoplastic aberrant crypt foci (ACF) in colons of mice initiated with 1,2-dimethylhydrazine dihydrochloride (DMH). Influence on proliferation of colonic crypt epithelial cells was also assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Five-week-old B6C3F1 male mice were divided into three groups, groups 1 and 2 being given DMH (20 mg/kg body wt, s.c.) twice a week for 3 weeks. Animals of group 1 were then treated with one of the test compounds, lycopene (0.005% and 0.0025%) or fucoxanthin (0.01%) in the drinking water and lutein (0.05%), curcumin (0.5%) or THC (0.5% and 0.2%) in the diet from weeks 5-12. Group 2 served as a carcinogen alone control and group 3 mice were given test compounds alone. All animals were killed at week 12. Numbers of ACF/mouse in the group 1 treated with fucoxanthin (47.1 +/- 13.7), lutein (42.6 +/- 19.6) or 0.5% THC (46.6 +/- 17.7) were significantly decreased as compared to the control group 2 value (63.3 +/- 19.4) (P < 0.01). Numbers of aberrant crypts (ACs)/mouse were also significantly lower after treatment with lutein (79.9 +/- 34.7) or 0.5% THC (81.8 +/- 32.5) than in the control group (115.1 +/- 37.1) (P < 0.01). BrdU labeling indices (LI) in mice treated with lutein and 0.5% THC were significantly decreased in both upper and lower half compartments of colonic crypts as compared to the controls (P < 0.05 and 0.01, respectively), especially the upper half data corresponding to reduction of ACs/mouse. The results thus suggest that fucoxanthin, lutein, and THC may have potential as chemopreventive agents against colon carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1998

Lower risks of adverse outcome in twins conceived by artificial reproductive techniques compared with spontaneously conceived twins.

The outcomes of twins conceived by 136 women after medical assistance (MA) such as ovulation induction with or without assisted reproductive techniques, and twins conceived spontaneously (SP) by 72 women were compared. All 208 women were monitored from < 20 weeks gestation; they all delivered at > or = 24 weeks gestation. The chorionicity of the placenta was diagnosed antenatally and confirmed after delivery. There were 10 perinatal deaths; the physical and neurological status of the remaining 406 infants was assessed at 1 year of corrected age. There were no differences in gestational age at birth, the birth weights of the larger and smaller twins, the birth weight discordance, or the incidence of life-threatening major malformations between groups. Adverse infant outcomes, such as death, cerebral palsy and mental retardation occurred in nine (3.3%) of 272 MA twins compared with 12 (8.3%) of 144 SP twins (P < 0.05). The placenta was monochorionic in only three (2.2%) of 136 MA twin pregnancies compared with 41 (57%) of 72 SP twin pregnancies (P < 0.001). Of the 21 infants with adverse outcomes, nine had monochorionic placentas. Thus, the risk of an adverse outcome was 2.8-fold higher (95% confidence interval (CI) 1.2-6.4) in monochorionic twins than in dichorionic twins (10 versus 3.7%; P < 0.05). There was no difference in the incidence of adverse infant outcomes between SP (4.8%) and MA (3.4%) twins with dichorionic placentas. These findings suggest that ovulation induction in itself was not associated with an adverse outcome of twin pregnancies. The lower frequency of monochorionic placentas in MA twins may have been responsible for the lower risk of an adverse outcome in MA twins.

Birth Weight↗
PubMed1998

Relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ.

BACKGROUND: No one has previously examined the relation of serum total cholesterol, serum triglycerides and fasting plasma glucose to colorectal carcinoma in situ. METHODS: A case-control study was performed with 129 cases of colorectal carcinoma in situ and 258 matched controls among examinees undergoing a health check-up in Tokyo from January 1991 to March 1993. RESULTS: There was a significant, positive association between serum total cholesterol levels and the risk of colorectal carcinoma in situ after adjustment for age, sex, body mass index, smoking status and alcohol consumption. Serum triglyceride levels were significantly and positively associated with colorectal carcinoma in situ risk regardless of adjustment for the above covariates. Although there was no clear relation between colorectal carcinoma in situ and fasting plasma glucose levels, a modest increase of colorectal carcinoma in situ risk was observed in the highest category (> or =116 mg/dl) of fasting plasma glucose levels. CONCLUSIONS: The findings suggest a positive association between serum total cholesterol levels and the risk of colorectal cancer, rather than an inverse relation. The strong association with serum triglyceride levels and the weak association with fasting plasma glucose levels support the hypothesis that hyperinsulinaemia may play an important role in colorectal carcinogenesis.

Adult↗
PubMed1998

Effects of chronic electrical stimulation on spiral ganglion neuron survival and size in deafened kittens.

We have studied spiral ganglion cell (SGC) survival and soma size in neonatally pharmacologically deafened kittens. They were implanted with a four-electrode array in the left cochlea at 100 to 180 or more days of age. Eight animals were chronically stimulated approximately 1000 hours over approximately 60 days with charge-balanced, biphasic current pulses; three were unstimulated controls. Using three-dimensional computer-aided reconstruction of the cochlea, the SGC position and cross-sectional area were stored. SGC position was mapped to the organ of Corti by perpendicular projections, starting from the basal end. The basal region of the cochlea was divided into three 4-mm segments. SGC survival (number per 0.1 mm of the length of the organ of Corti) and soma size for stimulated cochleae were compared statistically with implanted but unstimulated cochleae. There was no evidence of an effect of electrical stimulation on SGC survival under this protocol and with this duration. On the other hand, the cell size on the stimulated side was significantly larger than the control side in the middle segment (4 to 8 mm from the basal end). SGCs undergo a reduction in size after prolonged auditory deprivation; however, these changes may be partially moderated after chronic intracochlear electrical stimulation.

Animals↗
PubMed1998

A preliminary study on delayed vestibulo-cerebellar effects of Tokyo Subway Sarin Poisoning in relation to gender difference: frequency analysis of postural sway.

To evaluate delayed (long-term) effects of acute sarin poisoning on postural balance, nine male and nine female victims of the Tokyo Subway Sarin Poisoning in Japan (sarin cases) were examined by computerized posturography 6-8 months after the poisoning. Their plasma cholinesterase activities (ChE) on the day of the poisoning (March 20, 1995) were 13-95 (mean 68.2) IU/l for females and 19-131 (mean 75.9) IU/l for males, which were not significantly different between the two sexes. In females, the postural sway of low frequency (0-1 Hz) in the anterior-posterior direction and area of sway with eyes open was significantly larger in the cases than in the controls. Romberg quotients for the low-frequency sway in the anterior-posterior direction for females and low-frequency sway and length of sway in the medio-lateral direction for males were significantly related to log ChE. It is suggested that a delayed effect on the vestibulo-cerebellar system was induced by acute sarin poisoning; females might be more sensitive than males.

Adult↗