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Biomedical subjects

R Kishi

Publications and source records attributed to R Kishi.

At least 19 recordsLinked to original sources

Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects.

Genetic susceptibility to tobacco smoke might have relation to adverse pregnancy outcomes. To estimate the effects of maternal smoking and genetic polymorphisms on infant birth weight and length, we conducted a prospective cohort study of 293 women who delivered singleton live births in Sapporo, Japan. Birth weight and length were significantly lower among infants born to continuously smoking women having the aryl hydrocarbon receptor (AhR) wild type genotype (Arg/Arg; 211 g +/- 76 g; 1.2 cm +/- 0.4 cm, p < 0.01 and p < 0.01, respectively), the CYP1A1 variant genotype (m1/m2 + m2/m2; 170 g +/- 64 g, 0.8 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively), or the GSTM1 null genotype (171 g +/- 58 g, 0.6 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively). When combinations of these genotypes were considered, birth weight and length were significantly lower for infants of continuously smoking women in the AhR wild type + CYP1A1 variant group (315 g +/- 116 g; 1.7 cm +/- 0.6 cm, p < 0.01 and p < 0.01, respectively) and in the CYP1A1 variant + GSTM1 null group (237 g +/- 92 g; 1.3 cm +/- 0.5 cm, p < 0.05 and p < 0.01, respectively). These genotypes did not confer adverse effects among women who had never smoked; therefore, maternal smoking in combination with maternal AhR, CYP1A1 and GSTM1 genetic polymorphisms may adversely affect infant birth size.

Adult↗

Relationships of C-reactive protein, uric acid, and glomerular filtration rate to arterial stiffness in Japanese subjects.

The relationships between C-reactive protein (CRP), uric acid (UA), glomerular filtration rate (GFR), and arterial stiffness have not been fully investigated. The aim of this study was to clarify whether CRP, UA, and estimated GFR are related to arterial stiffness estimated using brachial-ankle pulse wave velocity (baPWV). The subjects were local government employees (3412 men and 854 women). baPWV, CRP, UA, GFR, and conventional risk factors were evaluated. Multiple linear regression analyses revealed that CRP and UA were significantly related to an elevation of PWV in male and female subjects, and that the estimated GFR was significantly related to an elevation of PWV in male subjects. Significant progressive increases in baPWV were observed across the quartiles of CRP in male subjects and for UA in male and female subjects. In female subjects, the relationship of quartile CRP to baPWV had marginal significance (P = 0.055). But, in male and female subjects, quartile of estimated GFR had no significant association with PWV. These results suggest that CRP and UA are associated with an increase of arterial stiffness in male and female subjects, and that estimated GFR is possibly related to arterial stiffness in male subjects.

Adult↗

Effect of the blockade of mu1-opioid and 5HT2A-serotonergic/alpha1-noradrenergic receptors on sweet-substance-induced analgesia.

RATIONALE: Sweet-substance-induced analgesia has been widely studied, and the investigation of the neurotransmitters involved in this antinociceptive process is an important way for understanding the involvement of the neural system controlling this kind of antinociception. OBJECTIVE: The aim of this study was to investigate the involvement of opioid and monoaminergic systems in sweet-substance-induced analgesia. METHODS: The present work was carried out in an animal model with the aim of investigating whether acute (24 h) or chronic (14 days) intake of a sweet substance, such as sucrose (250 g/l), is followed by antinociception. Tail withdrawal latencies in the tail-flick test were measured before and immediately after this treatment. Immediately after the recording of baseline values, independent groups of rats were submitted to sucrose or tap-water intake and, after chronic treatment, they were pretreated with intraperitoneal administration of (1) naltrexone at 0.5, 1, 2 or 3 mg/kg; (2) naloxonazine at 5, 10, 20 or 30 mg/kg; (3) methysergide at 0.5, 1, 2 or 3 mg/kg; (4) ketanserin at 0.5, 1, 2 or 3 mg/kg; or (5) physiological saline. RESULTS: Naltrexone and methysergide at two major doses decreased sweet-substance-induced analgesia after chronic intake of a sweet substance. These effects were corroborated by peripheral administration of naloxonazine and ketanserin. CONCLUSIONS: These data give further evidence for: (a) the involvement of endogenous opioids and a mu1-opioid receptor in the sweet-substance-induced antinociception; (b) the involvement of monoamines and 5HT2A serotonergic/alpha1-noradrenergic receptors in the central regulation of the sweet-substance-produced analgesia.

Adrenergic alpha-1 Receptor Antagonists↗

Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias.

Hypospadias is one of the most common congenital anomalies. Increased exposure to environmental factors (endocrine-disrupting chemicals and smoking) or maternal endogenous estrogen may cause hypospadias because male sexual differentiation is dependent on normal androgen homeostasis. Moreover, interactions between genetic factors and cigarette smoking and other chemicals have been suggested. It has been demonstrated that the CYP1A1 metabolizes not only environmental chemicals but also estrogens, and glutathione-S-transferases (GSTs) are detoxification enzymes that protect cells from toxicants by conjugation with glutathione. In this study, to investigate the association of CYP1A1 (MspI), GSTM1 and GSTT1 polymorphisms with hypospadias, a case-control study of 31 case mothers who had boys with hypospadias and 64 control mothers was performed in Japan. These polymorphisms were investigated by PCR-based methods using DNA from peripheral lymphocytes. We found that the heterozygous CYP1A1 and heterozygous and homozygous CYP1A1 were less frequent in the case mothers than in the control mothers [adjusted odds ratio (OR)=0.17, 95% confidence interval (CI)=0.04-0.74, OR = 0.28, 95% CI = 0.08-0.97, respectively]. We found no effect of maternal smoking on the hypospadias risks among the gene polymorphisms. The results suggest that mothers with the CYP1A1 MspI variant allele may have a decreased risk for hypospadias.

Adult↗

Symptoms in relation to chemicals and dampness in newly built dwellings.

OBJECTIVES: As the airtightness of dwellings has recently increased, problems associated with indoor air pollution and dampness have become important environmental health issues. The aim of this study was to clarify whether symptoms in residents living in newly built dwellings were related to chemicals and dampness. METHODS: Symptoms of 317 residents were surveyed by standardized questionnaires, and the concentrations of formaldehyde, acetaldehyde, and 17 volatile organic compounds (VOCs) in their homes were measured. Dampness (condensation on window panes and/or walls, and mold growth) was identified by questionnaires given to the householders or their partners. RESULTS: Some VOCs (toluene, butyl acetate, ethylbenzene, alpha-pinene, p-dichlorobenzene, nonanal, and xylene) were significantly related to the symptoms, and the sum of all VOCs (all identified VOCs) was significantly related to throat and respiratory symptoms [odds ratio (OR) for eye symptoms =2.4; 95% confidence interval (CI) 1.0-5.5], although the concentrations of VOCs were relatively low. As for the dampness index, condensation on window panes and/or walls was related to all symptoms, and mold growth was related to all symptoms except skin, throat and respiratory and general symptoms. As the number of dampness signs increased, the ORs increased for the symptoms except general symptoms (OR for nose symptoms = 4.4, 95% CI 1.6-11.9). CONCLUSION: Both VOCs and dampness were significantly related to symptoms. We should take measures to reduce the concentrations of VOCs, dampness and microbial growth in dwellings.

Acetaldehyde↗

Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss.

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.

Abortion, Habitual↗

Relationship between C-reactive protein and visceral adipose tissue in healthy Japanese subjects.

AIM: Recent studies have suggested that the elevated C-reactive protein (CRP) levels are associated with body fat, especially visceral adipose tissue, but most of them were investigated in Westerners who had higher body mass index (BMI) than Asians. To investigate the association between CRP concentrations, parameters of visceral obesity, the insulin resistance syndrome and carotid atherosclerosis in healthy Japanese who had a lower BMI than Westerners. METHODS: We explored the relationships between fatness and visceral obesity parameters [by anthropometry, bioelectrical impedance analysis and abdominal computed tomography (CT)] and CRP (high sensitivity) and examined their associations with components of insulin resistance syndrome, interleukin-6 (IL-6), tissue necrosis factor-alpha (TNF-alpha) and intima-media thickness (IMT) of common carotid arteries (CCAs) by ultrasonograms in 116 healthy Japanese subjects. RESULTS: In crude regression analyses, CRP was significantly associated with measures of obesity. After adjustment for age, gender and smoking, the association with CRP was stronger for parameters of visceral obesity (waist circumference, waist-to-hip ratio and visceral adipose tissue accumulation) than for other parameters of obesity. IL-6 and TNF-alpha were not associated with CRP. Blood pressure (BP), metabolic variables and CCA-IMT were also significantly associated with CRP. But, after being adjusted for age, gender, smoking and BMI, BP and high-density lipoprotein cholesterol (HDLc) were significantly associated. CONCLUSION: CRP level is associated with visceral adipose tissue and is significantly associated with the components of insulin resistance syndrome in healthy Japanese subjects. These data support a possible role of visceral adipose tissue in inflammation component of atherosclerosis, and further studies are needed to study the mechanism of CRP elevation caused by visceral adipose tissue.

Adipose Tissue↗

Glutathione S-transferase M1 and T1 polymorphisms and the risk of recurrent pregnancy loss.

The aetiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in two genes, glutathione S-transferases (GST) M1 and T1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. A case-control study of 115 cases with RPL and 160 controls was conducted. All cases and controls were women resident in Sapporo, Japan and the surrounding area. They were genotyped for polymorphisms of GSTM1 and GSTT1 using PCR-based methods. We found that 65.2% of the cases with RPL and 45.6% of the controls had the GSTM1 null genotype [odds ratio (OR) = 2.23, 95% confidence interval (CI) = 1.36-3.66]. On the other hand, 47.0% of the cases and 49.4% of the controls had the GSTT1 null genotype (OR = 0.95; 95% CI = 0.58-1.55). The results suggest that women with GSTM1 null polymorphism may therefore have an increased risk of RPL.

Abortion, Habitual↗

A polymorphism in the CYP17 gene relates to the risk of recurrent pregnancy loss.

The CYP17 gene encodes the enzyme cytochrome P450c17alpha, which mediates both 17alpha-hydroxylase and 17,20-lyase activity in the steroid biosynthesis pathway. A T-->C polymorphism in the 5' promoter region of CYP17 has been described. To examine the association between recurrent pregnancy loss (RPL) and a polymorphism in CYP17, a case-control study of 117 cases with RPL and 164 controls was conducted. This polymorphism was investigated by PCR/restriction fragment length polymorphism using DNA from peripheral lymphocytes. The T-->C transition in the variant allele (A2) creates a new recognition site for the restriction enzyme MspA1, which permits designation of the wildtype allele (A1) and A2. Women with the A2 allele of CYP17 had an increased risk of RPL [A1/A1 genotype (reference); A1/A2 genotype: odds ratio (OR), 1.68; 95% confidence interval (CI), 0.94-3.01; A2/A2 genotype: OR, 2.37; 95% CI, 1.16-4.83; P trend, 0.016]. Additionally, there was a similar tendency for the increased risk of primary RPL [A1/A1 genotype (reference); A1/A2 genotype: OR, 2.14; 95% CI, 1.14-4.01; A2/A2 genotype: OR, 2.50; 95% CI, 1.16-5.41; P trend, 0.015]. These results suggest that possession of the A2 variant of CYP17 may predispose to an increased risk of RPL with a gene dosage effect.

Abortion, Habitual↗

Relation between colour vision loss and occupational styrene exposure level.

AIMS: To investigate the relation between colour vision loss and the exposure level of styrene. Exposure level included the current exposure concentration, past cumulative exposure, and the maximum exposure level in the past. METHODS: Colour vision was examined by the Lanthony desaturated panel D-15 test for 76 subjects exposed to styrene in a fibreglass reinforced plastics boat plant (as an exposed group) and 102 non-exposed subjects (as a control group). The current exposure level was expressed by the concentration of atmospheric styrene and end shift urinary mandelic acid (MA) and phenylglyoxylic acid (PGA) levels. The individual cumulative exposure index (CEI) was calculated, based on the exposure frequency and urinary MA concentrations measured for the past eight years. RESULTS: The Colour Confusion Index (CCI) of the exposed group showed a significant difference from the age matched controls. However, only a slight significant relation was found between CCI and the concentration of urinary MA plus PGA. In this study, the exposed group was further divided into two subgroups (as sub-MA+PGA groups) by the median of urinary MA plus PGA of each subject. The dividing line between the subgroups was 0.24 g/g creatinine, which was equivalent to an atmospheric concentration of styrene of about 10 ppm. The CCI values of both the sub-MA+PGA groups were significantly higher than that of the control group. The relation between CCI value and the maximum exposure concentration in the past eight years was examined. It was found that the CCI values of the group with the maximum exposure concentration of styrene over 50 ppm were significantly higher than that of the other groups. CONCLUSIONS: Exposure to styrene would impair colour vision even if the exposure concentration was lower than 10 ppm. Furthermore, if the maximum concentration of styrene exposure transiently exceeded 50 ppm in the past, the styrene related damage might remain. Thus, the safe limit of exposure to styrene and the relation between exposure to styrene and the degree of damage to ocular structure, retina, optic nerve, and brain need to be re-examined.

Adult↗

Opioid neurotransmission in the post-ictal analgesia: involvement of mu(1)-opioid receptor.

Pentylenetetrazol (PTZ), a non-competitive antagonist that blocks GABA-mediated Cl(-) flux, was used in the present work to induce seizures in animals. The aim of this work is to study the neurochemical basis of the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test, in eight rats per group. Convulsions were followed by significative increase in the tail-flick latencies (TFL), for at least 120 min of the post-ictal period. Peripheral administration of naltrexone (5 mg/kg, 10 mg/kg and 20 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls. These data were corroborated with peripheral administration of naloxonazine (10 mg/kg and 20 mg/kg), a mu(1)-opioid blocker, in the same doses used for non-specific antagonist. These results indicate that endogenous opioids may be involved in the post-ictal analgesia. The involvement of mu(1)-opioid receptor was also considered.

Analgesia↗

Psychopharmacological evidences for the involvement of muscarinic and nicotinic cholinergic receptors on sweet substance-induced analgesia in Rattus norvegicus.

In order to investigate the effects of sweet substance intake on pain modulation, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l) for 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex) were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The index (mean +/- SEM, N = 8) for the groups receiving sucrose solution plus saline (NaCl; 0.9%) for 14 days was 0.70 +/- 0.01. Atropine (1 and 2 mg/kg)-treated rats (N = 8) after intake of sucrose exhibited an analgesia index of 0.39 +/- 0.09 and 0.39 +/- 0.08, respectively, while mecamylamine (1 and 2 mg/kg)-treated rats (N = 10) after intake of sucrose had an index of -0.02 +/- 0.07 and 0.03 +/- 0.07, respectively. These results indicate that the effect of sucrose intake on nociceptive thresholds is controlled by neurotransmission of acetylcholine and depends on the nicotinic cholinergic receptors for its major analgesic effect, although muscarinic receptors were also involved in this antinociceptive process.

Acetylcholine↗

Effect of rigidity on the crystallization processes of short polymer melts.

Order formation in crystallization processes of the dense melts of chain molecules has been studied by the coarse-grained molecular dynamics method. For semirigid molecules, the parallel orientation and elongation of chains take place simultaneously. However, for semiflexible molecules, long induction periods are observed. Time evolution studies of local order parameters indicated that two different processes occur, which implies that a precondition exists. For flexible molecules, the structures become mostly amorphous at certain sharp threshold conditions of chain rigidity. It was determined that the rigidity of the main chains strongly influences the dynamic behavior of crystallization for dense melts, particularly in the early stage.

Journal Article↗

Effects of prenatal styrene exposure on postnatal development and brain serotonin and catecholamine levels in rats.

Maternal reproductive effects in Wistar rats exposed to 0, 50, or 300 ppm styrene for 6 h/day during gestational days 6 to 20 were evaluated. Their offspring were observed postnatally for neurochemical changes, growth, and physical landmarks of development. Mothers exposed to styrene were compared with pair-fed and ad-lib-fed controls in order to adjust nutrient conditions. Prolongation of the gestational period, food intake, and the number of neonatal deaths or stillbirths in 300-ppm-exposed dams showed evidence of styrene-related effects. Other reproductive parameters, such as litter size, birth weight, and sex ratio, were found to exhibit no effects within the variation range studied. A neurochemical effect was observed in that the 5-HT and HVA concentrations in cerebrum were significantly decreased. Incisor eruption (mandible), eye opening, and the air-righting reflex were delayed in rat pups born to dams receiving 300 ppm styrene exposure compared with the pair-fed and ad lib control groups. Pups born to dams exposed to 50 ppm styrene also had a significantly delayed air-righting reflex compared with ad lib controls. These results suggest that the offspring were susceptible to the effects of styrene on a few developmental landmarks even when nutritional effects were controlled.

Animals↗

Effects of low-level occupational exposure to styrene on color vision: dose relation with a urinary metabolite.

To investigate the threshold effects of chronic low-level occupational exposure to styrene on color vision, we examined color discrimination in 105 male workers exposed to styrene (mean age 37.7 years; mean length of exposure 6.2 years; mean urinary concentration of mandelic acid 0.21 g/L) and in 117 referents (mean age 37.7 years). We also assessed the effects of styrene by examination of the nature of the relation between disorders of nervous function and age, alcohol consumption, and other variables. A standardized questionnaire was adopted to collect information about work history, occupational or nonoccupational solvent exposure, alcohol consumption, and drug use. Color vision was evaluated by the Lanthony desaturated panel D-15 test. The results of the test were expressed as the color confusion index (CCI). There was a dose-dependent relationship between the urinary concentration of mandelic acid and color vision loss. The CCIs of the subgroups whose urinary mandelic acid levels were 0.1-0.2 and >0.2 g/L were significantly higher than those of each referent group (P<0.05 and P<0.01, respectively), but not in the subgroup whose urinary mandelic acid level was lower than 0.1 g/L. Our study suggests that a low level of styrene, presumably 0.1-0.2 g/L, involves the risk of inducing adverse effects on color vision. After confounding factors were adjusted for, the urinary mandelic acid level had a significant positive relationship with color vision.

Adult↗

Risk factors for human alveolar echinococcosis: a case-control study in Hokkaido, Japan.

A case-control study to determine the risk factors for human alveolar echinococcosis (AE) was conducted in Hokkaido, Japan. The 134 cases were either patients clinically diagnosed as having AE (N =61) or other individuals found to be seropositive for Echinococcus multilocularis although showing no abnormalities in ultrasound scans (N = 73). Two groups of case-matched controls were employed: one of 670 individuals selected from a list of residents of Hokkaido (group A) and the other of 650 subjects selected from a list of individuals who had been found seronegative in earlier investigations (group B). Because of the long latency of AE, potential risk factors were studied over two different periods: for the 0-10 and 11-20 years before the year of diagnosis/recorded seropositivity. The results of multivariate analyses, in which the cases were compared with each control group, indicated that the rearing of cattle and pigs and the use of well water were significant risk factors and that the use of tap water significantly decreased the risk of an individual having AE. Extension of the piped water supply and health education on improving the disposal of household rubbish (to keep foxes away from houses) should help reduce the risk of AE infection in the study area.

Animal Husbandry↗

Long-term blood pressure variability and cerebrovascular changes on CT in a community-based elderly population.

The effects of long-term blood pressure (BP) levels on cerebrovascular changes were analyzed in a community-based healthy elderly population. Cranial computed tomography (CT) was performed for 300 residents aged 69 years and older. Long-term BP during the ten years prior to CT was assessed, and the cerebrovascular changes were compared among different patterns of long-term blood pressure variability. White matter lesions (WML) and/or silent infarctions (SI) were found in 73 subjects (23.6%). Multiple logistic regression analysis showed that subjects with long-term diastolic hypertension (DHT) had the highest risk of cerebrovascular changes (adjusted odds ratio (OR), 95% confidence interval (CI); 7.1, 2.4-21.6, for WML; 7.2, 2.7-19.4, for SI), and that long-term isolated systolic hypertension (ISHT) was significantly associated with SI (adjusted OR, 95%CI, 2.3, 1.1-4.9), but not with WML (adjusted OR, 95%CI, 1.3, 0.5-3.3). Efforts to prevent both DHT and ISHT would be beneficial, though different underlying mechanisms for WML and SI were suggested.

Aged↗

[The epidemiology of prostate cancer--recent trends in prostate cancer incidence and mortality].

Prostate cancer is one of the major malignant diseases in Western countries. In Japan, the incidence and mortality of prostate cancer is not so high, but is continuously increasing. The recent drastic increase in incidence has been attributed to the growth of the elderly population, a westernized diet in daily life, widespread environmental contamination, and improved screening techniques such as the serum PSA test. The epidemiology of prostate cancer hints that its etiology is both environmental and genetic. Androgenic stimulation over time, perhaps due to a high fat diet, has been suggested as a cause of prostate cancer. Dietary factors such as phytoestrogens, vitamins and trace elements are suggested to have a protective effect against prostate cancer, and encourage us to search for means of prevention. Some have suggested that certain polymorphisms increase the risk of prostate cancer, whereas others are searching for genetic mutations that may also increase prostate cancer risk. The cause of prostate cancer is likely to be a combination of environmental and genetic factors.

Adult↗