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Biomedical subjects

I Okazaki

Publications and source records attributed to I Okazaki.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Reproductive and developmental toxicity studies of prulifloxacin (NM441)(4)--A perinatal and postnatal study in rats by oral administration].

A peri- and postnatal study of prulifloxacin, a new antibacterial agent, was conducted in Sprague-Dawley rats. Female rats were given prulifloxacin orally at dose levels of 0 (control), 30, 100 and 300 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. Food consumption in the period of pregnancy decreased in the dams given 100 and 300 mg/kg, and food and water consumption during lactational period increased in the dams given 300 mg/kg. The weight of the cecum of the dams increased in 100 and 300 mg/kg groups, and these doses caused enlargement of the cecum. Prulifloxacin had no effects on general sign, delivery, nursing, body weight gain, and kidney. Prulifloxacin also did not affect the number of live newborns and birth index, and have any adverse effects on the postnatal development of the first generation offspring (F1) such as differentiation, functional development, emotionality, motor ability, learning ability and reproductive performance. Prulifloxacin also had no adverse effects on the second generation offspring (F2). These results show that the NOAEL of prulifloxacin are 30 mg/kg for general toxicity in mother animals, 300 mg/kg for pregnancy and delivery of mother animals and development of their offspring.

Administration, Oral↗
PubMed1996

Effects of ethyl alcohol administration to THA rat dams during their gestation period on learning behavior and on levels of monoamines and metabolites in the brain of pups after birth.

Children born from chronic alcoholic mothers have shown behavioral teratogenic effects more frequently than morphological malformations. To investigate the possible mechanisms and evaluate maternal alcohol dosage levels to induce behavioral dysfunctions, we gave pregnant Tokai High Avoider (THA) rats 0, 5, 10, and 20% ethanol (EtOH) as drinking water during the gestation period. We evaluated the brain function of pups born of alcohol-administered dams. Sidman avoidance behavior test and the levels of monoamines (nor-adrenalin, dopamine, and serotonin) and metabolites (3, 4-dihydroxyphenyl acetic acid, homovanillic acid, and 5-hydroxyindole acetic acid) in whole brain were examined for neurobehavioral and neurochemical effects. EtOH-exposed THA offsprings showed high pre- and postnatal mortality, growth deficits, and brain weight reductions. Compared with the results of the same conditioning experiment using Wistar rats, the THA rat may have higher susceptibility to the effects of in utero EtOH exposure than Wistar rats. EtOH-exposed THA pups exhibited deficits in avoidance operant learning that were not shown in Wistar rats. We also observed the increased levels of all monoamines that were assumed to be related with the deficit of learning, the decreased levels of 3, 4-dihydroxyphenyl acetic acid and homovanillic acid, and the unchanged levels of 5-hydroxyindole acetic acid in pups from dams administered 10 and 20% EtOH. However, contrary alteration of monoamines and their metabolites were shown in pups from 5% EtOH-administered dams.

Animals↗
PubMed1995

cAMP-independent effects of cholera toxin on B cell activation. III. Cholera toxin A subunit-mediated ADP-ribosylation acts synergistically with ionomycin or IL-4 to induce B cell proliferation.

To investigate whether ADP-ribosylation of proteins by cholera toxin could influence B cell activation, B cells were incubated with the A subunit of cholera toxin. Ionomycin acted synergistically to induce B cell proliferation with the A subunit of cholera toxin but not with cAMP-enhancing agents or with the B subunit of cholera toxin, suggesting that the synergistic effect of the A subunit was mediated via ADP-ribosylation and not via cAMP elevations or ganglioside GM1 binding. Indeed, inhibitors of ADP-ribosylation blocked the synergistic effect. Unlike anti-Ig, B cell proliferation stimulated by LPS or by the combination of the A subunit and ionomycin was observed in protein kinase C (PKC)-depleted B cells. However, neither the A subunit nor ionomycin enhanced B cell proliferation stimulated by low dose LPS, suggesting that the A subunit plus ionomycin stimulated an activation pathway distinct from the LPS-stimulated pathway. Additionally, unlike LPS, the A subunit plus ionomycin did not stimulate B cells in vitro to secrete Ig. IL-4 acted synergistically with the A subunit to induce B cell proliferation to the same extent as it did with anti-Ig; unlike the anti-Ig plus IL-4 synergy, however, the A subunit plus IL-4-mediated synergy persisted in PKC-depleted B cells. Taken together, our data suggest that cholera toxin A subunit-catalyzed ADP-ribosylation modifies a non-Gs protein involved in the activation of B cells, either through a novel pathway or at a point distal to the activation of PKC along the anti-Ig-stimulated pathway.

Adenosine Diphosphate Ribose↗
PubMed1995

Anal atresia: effect of smoking and drinking habits during pregnancy.

Using data compiled from 216,707 births from the population-based Kanagawa Birth Defects Monitoring Program (KAMP), we conducted a case-control study to evaluate the effect of maternal smoking and/or drinking during pregnancy on the risk of infants' anal atresia in 1989-1994. The frequency of maternal smoking (including passive smoking) and/or maternal drinking during pregnancy among 84 infants with anal atresia was compared with 174 matched controls. The 84 anal atresias include 49 cases of isolated anal atresia and 35 cases of syndromal anal atresia. Our findings suggest that maternal drinking during early pregnancy is associated with an increased risk of isolated anal atresia (OR = 4.8, 95% CI 1.2 to 19.1, p < 0.05). A slightly increased trend was also observed in the association of maternal smoking during pregnancy with both in the pooled groups of anal atresia (OR = 1.4, 95% CI 0.5 to 3.6).

Adult↗
PubMed1995

Wound healing of acetic acid-induced gastric ulcer in rats and the effects of cimetidine and calcitonin, with special reference to prolylhydroxylase and collagenase enzyme activity.

The healing of acetic acid-induced gastric ulcer in rats and the effects of cimetidine and calcitonin were investigated with reference to the enzyme activity of both prolylhydroxylase and collagenase as related to histological findings. The rats were observed by endoscopy on the 3rd day after the subserosal injection of acetic acid; rats with ulcers were divided into three groups: non-treated, and cimetidine- and calcitonin-treated. The latter two groups were treated for 7 days. Prolylhydroxylase activity in active ulcers in the non-treated group was slightly higher on the 3rd day and significantly higher on the 10th day than the activity in control rats that had received subserosal injections of physiological saline solution on the respective days. In non-treated rats, the healed ulcer on the 10th day showed lower prolylhydroxylase activity than that in the active ulcer on the same day. Cimetidine did not affect prolylhydroxylase activity, but, with calcitonin, there was higher prolylhydroxylase activity in the healed than in the active ulcer, although the difference was not significant. Interstitial collagenase showed the highest activity on the 3rd day and decreased on the 10th day in non-treated rats. Collagenase activity was higher in the cimetidine-treated group, than that in the non-treated group, and numerous peroxidase-positive granulocytes were seen in the mucosa and submucosa. Calcitonin did not affect collagenase activity. The participation of both enzymes is indispensable in the healing process and the effects of anti-ulcer agents on these enzymes must be considered.

Acetates↗
PubMed1995

Acute hepatitis in an adult with acquired rubella infection.

We report a case of acute hepatitis in a 28-year-old male with acquired rubella infection. Serological tests revealed acute rubella virus infection and ruled out infection by other common viruses, including type A and type B hepatitis viruses. The patient showed not only marked increase of lactate dehydrogenase (LDH) activity, with only slight liver dysfunction, but also platelet and kidney injury, suggesting systemic rubella virus infection. Because the liver dysfunction was slight, liver biopsy was not performed. When a patient has mild, transient hepatitis accompanied by high LDH activity in comparison with both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, we should take a common viral infection such as rubella into consideration when making a diagnosis.

Acute Disease↗
PubMed1995

Serum concentrations of basement membrane proteins in NIDDM as a prognostic marker for nephropathy.

Metabolic changes of basement membrane proteins, collagenous and non-collagenous, will be followed by morphological changes and develop into diabetic microangiopathy. In this study, serum concentrations of laminin and type IV collagen were measured in 87 cases o f non-insulin-dependent diabetes mellitus (NIDDM) and examined with the development of diabetic nephropathy and retinopathy. Serum type IV collagen was measured by two methods, assays of the 7S portion (7S-RIA) and of both the 7S and central triple helical domain (IV-EIA). IV-EIA showed more significant elevation with development of diabetic microangiopathy than 7S-RIA and laminin. After measurement of basement membrane proteins, 66 cases were followed clinically for 3 or 4 years. In 45 cases without worsening of diabetic nephropathy, IV-EIA and laminin concentrations in serum were significantly lower than those in 21 cases who showed worsening of diabetic nephropathy in the same period, Multivariate analysis revealed a good model including three dependent variables of serum values of laminin, IV-EIA and mean blood pressure for discriminating between the worsened group and the non-worsened group. High values of IV-EIA and laminin in serum may be useful in predicting the worsening of diabetic nephropathy.

Adult↗
PubMed1995

[The study of the relation between the working conditions and the prevalences of obesity, liver disorder and hyperlipidemia: evaluation of physiological examination data during the terms of car manufacturing work and car sales work].

To evaluate the relation between the working conditions and the workers' health, particularly the prevalences of obesity, liver disorder and hyperlipidemia, we analyzed physiological examination data and the questionnaire survey about life behaviors and working conditions during the terms of car manufacturing work and car sales work among 61 male subjects. In the physiological examination data, compared with the term of car manufacturing work, the values of body weight, body mass index (BMI), GOT, GPT, gamma-GTP, TG and T-CHO elevated and the prevalences of obesity and liver disorder increased during the term of car sales work. During the term of car sales work, the prevalences of alcohol drinkers and cigarette smokers increased and the changes of food intake behaviors were noted. It was estimated that the changes of food intake behaviors associated with the differences of working conditions contributed increasing number of obesity and liver disorder that was based on fatty liver caused by hyperlipidemia. These results of this study suggested that working conditions associated with the prevalences of obesity, liver disorder and hyperlipidemia were important to conduct the effective health education in the present occupational health administration.

Adult↗
PubMed1995

[Alteration of drinking pattern after the entrance of university].

Three hundred fifty-nine freshmen and freshwomen of Tokai University and Tamagawa University were examined for alcohol habituelle using questionnaires on life style and club activity as well as the established questionnaires of the Adolescent Alcohol Involvement scale (AAIS). The scores of AAIS of the male and female students were 30.6 and 27.7, respectively. About 10% of the subjects were revealed to be alcohol misusers. In both sexes, the drinking patterns remarkably changed after the entrance of university. Even in females, the drinking pattern markedly changed. The grade of club activity is one of factors influencing the drinking pattern of students. Especially big changes were observed in the students of cultural clubs.

Adult↗
PubMed1995

Urinary concentrations of heavy metals in healthy Japanese under 20 years of age: a comparison between concentrations expressed in terms of creatinine and of selenium.

Voided urine samples from 575 young Japanese under 20 years of age (297 males and 278 females including infants) and from 380 subjects (20-29 years old, 193 males and 187 females) were analyzed for levels of creatinine, selenium, zinc, cadmium and mercury. This investigation presents data regarding the normal urinary levels of these substances in age groups of 0-4, 5-9, 10-14, 15-19, and 20-29 years. Urinary levels of creatinine and cadmium showed remarkable increases with the age of the subjects, whereas that of selenium was constant at all ages under 20. Urinary concentrations of heavy metals were represented by creatinine and selenium ratios. Comparisons between these ratios revealed that selenium is an excellent index for representing the levels of the substances contained in a voided urine sample. Creatinine was not useful as an index for younger subjects, because the urinary concentration of this compound increased almost threefold as the subjects became older, up to 15 years of age.

Adolescent↗
PubMed1994

Gene expression of interstitial collagenase (matrix metalloproteinase 1) in gastrointestinal tract cancers.

Collagenolytic proteinases play an important pathological role in the invasion and metastasis of cancer cells. However, little is known about the role of interstitial collagenase (matrix metalloproteinase-1; MMP-1) in this process. To investigate the expression of the MMP-1 gene in cancer tissues, an in situ hybridization study was carried out in gastrointestinal tract cancers (one esophageal cancer, five gastric cancers, and four colorectal cancers), using a 35S-labeled MMP-1 cDNA probe. The MMP-1 gene was expressed in the stromal cells of fibrous tissue around cancer nests, especially at the margin of invasion and/or within the cancer nest; however, no definite expression within cancer cells was observed. Expression of the MMP-1 gene in the stromal cells was more common in well differentiated gastric adenocarcinoma than in poorly differentiated adenocarcinomas. These findings indicate that expression of the MMP-1 gene is greater in stromal cells that are closely associated with cancer cells, suggesting a pathophysiological role of MMP-1 in the invasion and metastasis of cancer cells.

Adenocarcinoma↗
PubMed1994

[Effects of aging on urinary secretion of 3-hydroxyproline and its importance for cancer screening in the elderly with ROC analysis].

OBJECTIVE: to observe the influence of aging on urinary secretion of 3-hydroxyproline (3-Hyp) in normal subjects and in cancer patients and study the effects of aging on the accuracy of urinary 3-Hyp as a general-purpose cancer screening test. DESIGN: We reanalyzed, from the aspect of gerontology, the amounts of 3-Hyp in the urine samples of the 211 healthy persons and 94 patients with cancer reported earlier. The two groups were divided in 3 age subgroups: adult, 30 to 44 years, middle-aged, 45 to 64 years, and aged, 65 years and older. The cancer stage was separated into 3 categories: stage 1, the early stage without any invasion, stage 2, locally invasive with no distant metastasis, and stage 3, advanced cancer. The correlation of age and urinary 3-Hyp was analyzed in normal subjects and cancer patients. Sensitivity and specificity were calculated for different cutoff points in the diverse groups to construct the receiver operating characteristic (ROC) curves. MAIN RESULTS: We observed that aging decreases the urinary secretion of 3-Hyp in normal subjects, with a correlation coefficient of -0.250 (p < 0.001). The mean levels of urinary 3-Hyp in patients with cancer were significantly higher than in the normal subjects, p = 0.005. The correlation coefficient of urinary 3-Hyp and age was not significant (0.100) in cancer patients. The cutoff points of 0.800 mg/g creatinine of urinary 3-Hyp for persons under 65 years of age and 0.600 mg/g creatinine for persons 65 years or older were the best thresholds for cancer screening. In the ROC analyses, we observed that 3-Hyp has higher accuracy for cancer screening in the aged group for all stages together and in the aged and middle-aged for early stages of cancer. CONCLUSIONS: The urinary 3-Hyp test was more effective for cancer screening in old persons (65 years or older), where cancer is more frequent and more difficult to discover. The authors stress the necessity and importance of verifying the effectiveness of urinary 3-Hyp for general cancer screening in a larger population and in a community set.

Adult↗
PubMed1994

[Maternal drinking and smoking and the risk of birth defects].

Maternal drinking or smoking and the risk of birth defects was studied in a case-control study, performed on 1,789 babies, born between 1990 and 1992 in the Tokai University hospital, and their mothers. The findings were as follows: The proportion of maternal drinking before or during pregnancy was higher in the mothers of children with birth defects (odds ratio 2.2; 95% confidence intervals 0.5-8.9). However, this difference was not statistically significant. Maternal smoking, defined as 11 or more cigarettes per day before pregnancy, was 13.5% in the mothers of children with birth defects, compared to 6.7% in the mothers of controls (odds ratio 2.2; 95% CI 0.6-7.4). This difference was not statistically significant. A total of 78 classified deformities were reported in the 52 children with birth defects, of which 24.4% were associated with maternal drinking and 16.7% were associated with maternal smoking, respectively. A significant association was found between premature birth and mothers who reported drinking during pregnancy (odds ratio 3.3 95% CI 1.1-10.9). The frequency of spontaneous abortion was higher among mothers who reported both drinking and smoking during pregnancy. In addition the frequency of complications during pregnancy was higher. Analysis of factors related to birth defects showed that the risk for birth defective infants was higher for mothers above 35 years of age than for those under 35 (p < 0.05). This study supports an association between maternal drinking during pregnancy and infant birth defects, but does not implicate maternal smoking because the number of mothers who smoked during pregnancy was too small to be of significance.

Adult↗
PubMed1993

[Gene expression of MMPs and TIMPs in the process of hepatic fibrosis].

The matrix metalloproteinases (MMPs) gene family includes MMP-1 (interstitial collagenase), MMP-2 (72 kD type IV collagenase/gelatinase), MMP-3 (stromelysin/transin), MMP-7 (putative MMP; pump-1), MMP-8 (granulocyte collagenase) and MMP-9 (92 kD type IV collagenase/gelatinase). This gene family has the common characteristics in the gene structure as follows: All of MMPs have the active site metal ion-binding domain. All six enzymes are activated with the concomitant removal of N-terminal segment of the latent enzyme. The removed segment contains an unpaired cystein residue within the conserved amino acid sequence PRCGVPDV, located immediately adjacent to the proenzyme cleavage site. The authors showed the gene expression of MMP-1 in the process of hepatic fibrosis. The remarkable expression was noted on fibroblasts and macrophages within the newly-formed fibrous bands with lots of infiltrated lymphocytes. Liver cirrhosis did not showed the positive dots of MMP-1 mRNA. On the other hands, the expression of TIMP reported by Takahara et al., revealed the high level of expression in the advanced fibrosis.

Amino Acid Sequence↗
PubMed1993

[An epidemiological study of allergic conjunctivitis].

An epidemiological study focusing on the home environment and lifestyle was conducted in order to analyze the differences between a group of patients with allergic conjunctivitis only and a group with other allergic diseases associated with allergic conjunctivitis. Subjects were five hundred and sixty-four patients who visited the Ophthalmologic Clinic of Tokai University Hospital during 1990, and for controls 200 households were randomly selected from an elementary school list in Yokohama city. RAST score was measured in 102 patients. A mailed questionnaire was sent to 240 patients chosen at random and to 200 controls. Sixty patients and 139 controls responded to the questionnaire. RAST score showed no statistical difference between patients with allergic conjunctivitis only and patients with other allergic diseases associated with allergic conjunctivitis. Analysis of associations between RAST score and seasonal symptoms, showed very strong positive reactions to pollens in patients with seasonal symptoms. On the other hand, in patients with constant symptoms during the year, reaction was very strong to house dust and mite. Epidemiological factors causally associated with allergic conjunctivitis were compared among the controls, patients with allergic conjunctivitis only (Group I), patients with other allergic diseases (Group II) and all patients (Group III). Compared to controls, Groups II and III had significantly higher prevalence of past history of skin itching and inflammatory symptoms (p < 0.05 and p < 0.01, respectively). Group II subjects showed more frequent use of carpets, when compared to the controls (p < 0.05). The use of Japanese mattress (futon) was more frequent in Group II and III than controls (p < 0.05 for both comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Purification and characterization of an 85 kDa sialoglycoprotein in rat liver lysosomal membranes.

Sialoglycoprotein with a molecular mass of 85 kDa (LGP85) was purified from rat liver lysosomal membranes with a 0.9% recovery to apparent homogeneity, as determined from the pattern on polyacrylamide gel electrophoresis in the presence and in the absence of SDS. The purification procedures included: preparation of lysosomal membranes, elimination of LGP107 and LGP96 with immunoaffinity columns, WGA-Sepharose affinity chromatography, hydroxylapatite chromatography, and preparative polyacrylamide gel electrophoresis. LGP85 contains about 22.8% carbohydrate and the carbohydrate moiety is composed of mannose, galactose, fucose, glucosamine, galactosamine, and neuraminic acid, in a molar ratio of 40:20:2:23:3:13. Susceptibility to neuraminidase and immunoreactivity of the protein in intact tritosomes were examined to study the topology of the protein in tritosomal membranes. Neuraminidase susceptibility and immunoreactivity of the protein were not observed in intact tritosomes until the tritosomes had been disrupted by osmotic shock. These observations suggest that both oligosaccharide chains and the main protein portion of the protein are located on the interior surface of the tritosomal membranes. Subcellular localization of LGP85 was determined using enzyme immunoassay. The lysosomes seem to be the major location. LGP85 in the lysosomes was divided into the membrane bound form (90%) and the soluble form (10%). Immunoelectron microscopy clearly confirmed that the localization of LGP85 is mainly confined to lysosomes.

Animals↗
PubMed1992

Endogenous urinary 3-hydroxyproline has 96% specificity and 44% sensitivity for cancer screening.

A method for determining the endogenous urinary excretion levels of both 3-hydroxyproline and 4-hydroxyproline that may be useful for cancer screening of the general population and at the workplace is evaluated in this report. The excretion levels of 3-hydroxyproline and 4-hydroxproline were estimated in 97 patients with cancer and in 99 patients with various nonmalignant diseases and were compared with those of 211 healthy persons. Measurable 3-hydroxyproline peaks (by amino acid autoanalyzer) were absent from 93 samples from 211 healthy persons (44%), 50 of 99 patients with nonmalignant disease (50%), and 10 of 96 patients with cancer (10%). The levels of both 3-hydroxyproline and 4-hydroxyproline in cancer patients were significantly higher than those in healthy persons (p < 0.001 and p < 0.01, respectively) and those in patients with nonmalignant diseases (p < 0.05 and p < 0.01, respectively). Cancer patients were classified into three groups according to grade of cancer growth and invasion. The sensitivity of 3-hydroxyproline was 44% and higher than that of 4-hydroxyproline for the detection of stage II cancers (no distant metastasis); the sensitivities of both hydroxyprolines for the detection of stage I (very early cancer) were low. The specificity of these assays for healthy persons and patients with nonmalignant disease was 96% and 92% for 3-hydroxyproline, and 97% and 79% for 4-hydroxyproline, respectively. Urinary 3-hydroxyproline level should be further investigated as a cancer screening method for healthy persons in the community or the workplace, but appears unlikely to detect many cancers in the earliest stages.

Adult↗