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K Iwamoto

Publications and source records attributed to K Iwamoto.

At least 73 records · Page 4Linked to original sources

Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats.

Troglitazone (CS-045) is one of the thiazolidinediones that activate the peroxisome proliferator-activated receptor gamma (PPARgamma), which is expressed primarily in adipose tissues. To elucidate the mechanism by which troglitazone relieves insulin resistance in vivo, we studied its effects on the white adipose tissues of an obese animal model (obese Zucker rat). Administration of troglitazone for 15 d normalized mild hyperglycemia and marked hyperinsulinemia in these rats. Plasma triglyceride level was decreased by troglitazone in both obese and lean rats. Troglitazone did not change the total weight of white adipose tissues but increased the number of small adipocytes (< 2,500 micron2) approximately fourfold in both retroperitoneal and subcutaneous adipose tissues of obese rats. It also decreased the number of large adipocytes (> 5,000 micron2) by approximately 50%. In fact, the percentage of apoptotic nuclei was approximately 2.5-fold higher in the troglitazone-treated retroperitoneal white adipose tissue than control. Concomitantly, troglitazone normalized the expression levels of TNF-alpha which were elevated by 2- and 1.4-fold in the retroperitoneal and mesenteric white adipose tissues of the obese rats, respectively. Troglitazone also caused a dramatic decrease in the expression levels of leptin, which were increased by 4-10-fold in the white adipose tissues of obese rats. These results suggest that the primary action of troglitazone may be to increase the number of small adipocytes in white adipose tissues, presumably via PPARgamma. The increased number of small adipocytes and the decreased number of large adipocytes in white adipose tissues of troglitazone-treated obese rats appear to be an important mechanism by which increased expression levels of TNF-alpha and higher levels of plasma lipids are normalized, leading to alleviation of insulin resistance.

Adipocytes↗

Quantitation of acetazolamide in rat plasma, brain tissue and cerebrospinal fluid by high-performance liquid chromatography.

A simple and sensitive high-performance liquid chromatographic method for the analysis of acetazolamide (AZ) in rat blood (plasma/serum, whole blood and serum ultrafiltrate), brain tissue and cerebrospinal fluid (CSF) was described. Quantitative extraction of AZ with ethyl acetate from both buffered plasma and brain tissue homogenate (pH 8.0) was achieved. Each extract was evaporated to dryness and the residue was chromatographed on a reversed-phase column. CSF was directly analysed without extraction step. The limits of detection were 0.05 microgram ml-1 for plasma, 0.02 microgram g-1 for brain tissue and 0.004 microgram ml-1 for CSF. Calibration curves were linear over the working ranges of 0.1-100 micrograms ml-1 for plasma, 0.05-50 micrograms g-1 for brain tissue and 0.025-50 micrograms ml-1 for CSF. The reproducibility of AZ assay in the rat biologic media indicated very low relative standard deviations (RSDs). The recoveries of AZ added to plasma and brain tissue were more than 96% with an RSD of less than 5%. The present method was applied to studies of plasma concentration profiles of the drug after administration and its distribution into central nervous system.

Acetazolamide↗

Effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of tolbutamide in rats.

Although Sho-saiko-to (Xiao Chai Hu Tang), a major Chinese traditional medicine, is frequently prescribed with other synthetic or biotechnological drugs for the treatment of various chronic diseases, there is a dearth of information about interactions between sho-saiko-to and co-administered drugs. This paper reports the effects of Sho-saiko-to on the pharmacokinetics and glucose responses of a sulphonylurea hypoglycaemic agent, tolbutamide, after their oral administration in rats. After oral administration of tolbutamide (50 mg kg(-1)) with or without Sho-saiko-to extract powder (300 mg kg(-1)) to male Sprague-Dawley rats cannulated in the jugular vein, plasma tolbutamide and glucose levels were periodically measured. Co-administration of Sho-saiko-to tended to elevate the plasma tolbutamide concentration in the absorption phase. A two-compartment lag-time model was found to describe the plasma tolbutamide concentration-time data. The maximum concentration of tolbutamide was significantly increased and time to reach the maximum concentration was reduced to about 70% by co-administration with Sho-saiko-to. There was no significant change in area under the curve or in the elimination half-life of tolbutamide. The extent of the lowering effect of tolbutamide on plasma glucose levels was increased up to 0.75 h and decreased after 5 h after co-administration of Sho-saiko-to. In conclusion, these studies suggest that sho-saiko-to slightly hastens the gastrointestinal absorption of tolbutamide. Furthermore, it is considered that elevation of the gastrointestinal absorption rate by Sho-saiko-to might potentiate the hypoglycaemic effect of this sulphonylurea in the early period after oral administration.

Administration, Oral↗

Ratio of motor nerve conduction velocity to F-wave conduction velocity in diabetic neuropathy.

OBJECTIVE: To investigate the usefulness of a new parameter, the ratio of motor nerve conduction velocity to F-wave conduction velocity (M/F ratio), for the differential diagnosis of diabetic neuropathy. RESEARCH DESIGN AND METHODS: Nerve conduction studies were conducted in 95 patients with diabetic neuropathy, 44 nondiabetic patients with peripheral neuropathy, and 24 normal control subjects. Nondiabetic patients with neuropathy were grouped by clinical diagnosis as follows: segmental demyelination (n = 15), axonal neuropathy (n = 11), alcoholic polyneuropathy (n = 4), and other polyneuropathy (n = 14). Motor nerve conduction velocity (MCV) of post-tibial nerves, sensory nerve conduction velocity (SCV) of sural nerves, and F-wave conduction velocity (FWCV) of post-tibial nerves were measured by standardized techniques. The M/F ratio was calculated from these measurements. RESULTS: The MCV and SCV of diabetic patients were significantly slower and the M/F ratio was significantly lower than those of normal subjects: MCV, 43.7 +/- 5.4 vs. 47.1 +/- 2.9 m/s, P < 0.001; SCV, 44.7 +/- 11.1 vs. 48.3 +/- 5.7 m/s, P < 0.05; M/F ratio, 0.84 +/- 0.09 vs. 0.90 +/- 0.06, P < 0.001. The FWCV of nondiabetic patients with neuropathy was significantly slower (40.0 +/- 6.3 vs. 48.3 +/- 4.0 m/s, P < 0.001) and the M/F ratio was significantly higher (1.04 +/- 0.12, P < 0.001) than that of normal subjects, respectively. Although MCV, SCV, and FWCV were correlated with age in normal control subjects, the M/F ratio was independent of age in the diabetic as well as the nondiabetic patients with neuropathy. CONCLUSIONS: Results suggest that the M/F ratio, which is influenced by the neuronal damages in the distal segment of peripheral nerves, is useful in the differential diagnosis of diabetic neuropathy.

Diabetic Neuropathies↗

[Prevalence of dementia and its subtypes in a rural area in Japan].

The prevalence of dementia in Japan in 1985 for people aged 65 years or older was 4.8%. Vascular dementia (VD) has been reported to be the commonest subtype A report from Tokyo in 1970 showed that it was 2.8 times more frequent than Alzheimer type dementia (SDAT). We assessed the prevalence of dementia in a rural area (population: 12,931, 25.3% were 65 years or older in 1994) in Kyoko. First, we questioned subjects about their demographic circumstances, memory disturbance, apraxia (agnosia) and daily activities. Our questionnaire was answered by 3.132 (95.8%) subjects, and 2,280 of them agreed to be examined by neurologists. Those who met the appropriate criteria of the DSM-III-R and NINCDS-ADRDA were diagnosed with dementia. By use of the Hachinski ischemic score (HIS), we distinguished VD from non-vascular dementia. In this study patients with non-vascular dementia were diagnosed with SDAT by the neurologists. Analysis of the data revealed that 4.8% of the study population was demented. According to the HIS results, only 3 of 15 had vascular dementia. The prevalence of dementia was the same as the average prevalence in Japan even though the elderly population of this town was twice as high as the average. It is hard to determine the prevalence of dementia in any community. Many factors must be taken into consideration: the coverage rate, the criteria for dementia, and whether to include institutionalized residents. The prevalence of dementia will increase with the aging of the population, and we must collect accurate data in order to plan efficiently.

Aged↗

[Auditory evoked magnetic fields in patients of pure word deafness].

Auditory evoked magnetic fields (AEF) were recorded in 2 cases with pure word deafness. AEF examination were performed with a novel 129-channel vector neuromagnetic imaging system (SBI 100). The latency and the location of equivalent current dipole (ECD) of N100 m after 1,000 Hz tone burst stimulation, one of the most prominent peak of AEF, were evaluated. One patient, 59-year-old man, suffered from left putaminal hemorrhage and the other, 59-year-old man, had a history of bilateral putaminal hemorrhage. There was no N100 m detected in the left temporal lobe with the right ear stimulation in both patients. However normal N100 m was obtained in the right hemisphere with the left ear stimulation in both cases. And the position of ECD of N100 m in the right hemisphere were correctly superimposed on the Heschl gyrus in brain MRI. The pathophysiology of pure word deafness has been postulated that a disconnection between Wernicke area and bilateral auditory inputs played one of important roles in progression of pure word deafness. Because there was no pathological lesion in temporal lobe verified by MRI study in both patients, N100 m in the left could not be evoked due to interception of the auditory pathway to the Heschl gyrus, but not due to destruction of Heschl gyrus. AEF test is one of the most useful tools in order to estimate central auditory function in patients with pure word deafness.

Aphasia, Wernicke↗

Excretion of ofloxacin into saliva in rats with renal failure.

To clarify effects of renal failure on salivary distribution of ofloxacin (OFLX), a quinolone antibiotics, blood, parotid and mandibular saliva were collected from the single-step 5/6th-nephrectomized and sham-operated (control) rats after bolus i. v. administration of OFLX (5 mg/kg). The concentrations of OFLX in these samples were determined by high-performance liquid chromatography. Renal failure induced by the partial nephrectomy significantly elevated plasma levels and cumulative salivary excretion of OFLX when compared to control rats. Total body clearance was significantly decreased by the renal failure, although salivary clearance of the partially nephrectomized rats was about three times larger than that of the control. At the terminal phase, the saliva/plasma concentration ratios of OFLX for parotid and mandibular saliva in control rats was 0.249 +/- 0.180 and 0.136 +/- 0.024, respectively, and there was a significant difference between both salivary glands. The saliva/plasma concentration ratios in the rats with renal failure were significantly greater than those in the control group in both parotid (about 3.2 times) and mandibular (about 2.5 times) saliva. The results of this study suggest that the salivary excretion of OFLX is significantly increased by renal failure and a glandular difference in the salivary excretion of OFLX exists in both rats with normal and impaired renal function.

Animals↗

[Abnormalities of electrocardiographic P wave morphology and the relationship to electrophysiological parameters of the atrium in patients with idiopathic paroxysmal atrial fibrillation].

In 39 patients with idiopathic paroxysmal atrial fibrillation (PAF group), the incidence of the abnormal P wave morphology (prolonged P wave and mitral P in lead II and increased P terminal force in lead V1: PTF V1) was examined, and the relationships to the electrophysiologic findings of the atrial muscle were investigated. The control group consisted of 42 patients with various cardiac arrhythmias other than sick sinus syndrome. P wave duration was significantly longer in the PAF group than in the control group (112 +/- 12 vs 98 +/- 10 msec, p < 0.0001). PTF V1 was greater in the PAF group than in the control group (0.051 +/- 0.018 vs 0.028 +/- 0.010 msec, p < 0.0001). P mitrale occurred in only 5 patients (12%) in the control group as compared to 25 patients in the PAF group (64%, p < 0.0001). The longest duration of the right atrial electrograms was longer in the PAF group than in the control group (101 +/- 17 vs 85 +/- 10 msec, p < 0.0001), as was the maximal number of the fragmented deflections (8.0 +/- 2.5 vs 5.8 +/- 1.4, p < 0.0001). Repetitive atrial firing zone and also fragmented atrial activity zone were longer in the PAF group than in the control group (34 +/- 24 vs 12 +/- 19 msec, p < 0.02 and 47 +/- 27 vs 24 +/- 19 msec, p < 0.001, respectively). Interatrial conduction delay zone was longer in the PAF group than in the control group (55 +/- 25 vs 38 +/- 18 msec, p < 0.001). P wave duration and PTF V1 had significant and/or borderline correlations with the longest duration of the right atrial electrocardiograms (r = 0.75, p < 0.0001 and r = 0.68, p < 0.0001, respectively), and the maximal number of its fragmented defections (r = 0.50, p < 0.002 and r = 0.40, p < 0.05, respectively). Furthermore, P wave duration had a correlation with the repetitive atrial firing zone (r = 0.55, p < 0.01). Prolonged P wave duration and increased PTF V1 are electrocardiographic indicators for the coexistence of electrophysiologic abnormalities in patients with idiopathic paroxysmal atrial fibrillation.

Adult↗

Type Ia supernovae: their origin and possible applications in cosmology.

Spectroscopic and photometric evidence indicates that Type Ia supernovae (SNe Ia) are the thermonuclear explosions of accreting white dwarfs. However, the progenitor binary systems and hydrodynamical models for SNe Ia are still controversial. The relatively uniform light curves and spectral evolution of SNe Ia have led to their use as a standard candle for determining cosmological parameters, such as the Hubble constant, the density parameter, and the cosmological constant. Recent progress includes the calibration of the absolute maximum brightness of SNe Ia with the Hubble Space Telescope, the reduction of the dispersion in the Hubble diagram through the use of the relation between the light curve shape and the maximum brightness of SNe Ia, and the discovery of many SNe Ia with high red shifts.

Astronomical Phenomena↗

Caffeine induces S-phase apoptosis in cis-diamminedichloroplatinum-treated cells, whereas cis-diamminedichloroplatinum induces a block in G2/M.

Caffeine overrides checkpoints in the G2 phase of the cell cycle by inhibiting DNA repair at this phase and increases the cytotoxicity of antitumor drugs, such as cis-diamminedichloroplatinum (CDDP). The enhanced cell death induced by caffeine is characterized by apoptosis. In this paper, we demonstrate that this apoptotic event occurs in S phase of the cell cycle, whereas CDDP induces a block in G2/M. DNA histogram analysis revealed that caffeine reduced G2 arrest in CDDP-treated EL-4 cells. In a synchronous population, the ratio of cyclin B:p34cdc2 was upregulated just before the cells went into the apoptotic pathway. A rapid increase in DNA fragmentation was detected at 12-24 h, when marked regression of G2/M phase was observed. Moreover, the degree of DNA fragmentation in CDDP + caffeine-treated cells was not reduced when the cell cycle was arrested at metaphase by exposure to the spindle-inhibitor nocodazole. It is possible that execution of the apoptotic program after treatment with caffeine did not require the EL-4 cells to reenter G1 phase. The apoptotic cell fraction in the group of CDDP + caffeine was recognized as an S population by bivariate analysis of apoptosis and DNA content. These results suggest that enhancement of the apoptotic activity of CDDP-treated cells by caffeine is not a G1-phase event but an S-phase-specific event, whereas cells were arrested in G2/M phase, and that it is regulated by G2 checkpoint-related proteins.

Animals↗

Development of non-insulin-dependent diabetes mellitus in the double knockout mice with disruption of insulin receptor substrate-1 and beta cell glucokinase genes. Genetic reconstitution of diabetes as a polygenic disease.

Non-insulin-dependent diabetes mellitus (NIDDM) is considered a polygenic disorder in which insulin resistance and insulin secretory defect are the major etiologic factors. Homozygous mice with insulin receptor substrate-1 (IRS-1) gene knockout showed normal glucose tolerance associated with insulin resistance and compensatory hyperinsulinemia. Heterozygous mice with beta cell glucokinase (GK) gene knockout showed impaired glucose tolerance due to decreased insulin secretion to glucose. To elucidate the interplay between insulin resistance and insulin secretory defect for the development of NIDDM, we generated double knockout mice with disruption of IRS-1 and beta cell GK genes by crossing the mice with each of the single gene knockout. The double knockout mice developed overt diabetes. Blood glucose levels 120 min after intraperitoneal glucose load (1.5 mg/g body wt) were 108 +/- 24 (wild type), 95 +/- 26 (IRS-1 knockout), 159 +/- 68 (GK knockout), and 210 +/- 38 (double knockout) mg/dl (mean +/- SD) (double versus wild type, IRS-1, or GK; P < 0.01). The double knockout mice showed fasting hyperinsulinemia and selective hyperplasia of the beta cells as the IRS-1 knockout mice (fasting insulin levels: 0.38 +/- 0.30 [double knockout], 0.35 +/- 0.27 [IRS-1 knockout] versus 0.25 +/- 0.12 [wild type] ng/ml) (proportion of areas of insulin-positive cells to the pancreas: 1.18 +/- 0.68%; P < 0.01 [double knockout], 1.20 +/- 0.93%; P < 0.05 [IRS-1 knockout] versus 0.54 +/- 0.26% [wild type]), but impaired insulin secretion to glucose (the ratio of increment of insulin to that of glucose during the first 30 min after load: 31 [double knockout] versus 163 [wild type] or 183 [IRS-1 knockout] ng insulin/mg glucose x 10(3)). In conclusion, the genetic abnormalities, each of which is nondiabetogenic by itself, cause overt diabetes if they coexist. This report provides the first genetic reconstitution of NIDDM as a polygenic disorder in mice.

Animals↗

Evidence of three clinical subgroups in patients with dual atrioventricular nodal pathways.

We attempted to test the hypothesis that dual atrioventricular (A-V) nodal pathways with second-degree atrioventricular block (2nd A-V block) present as a different clinical entity from those with A-V nodal reentranttachycardia (AVNRT). By evaluation with Holter monitoring (2.9 +/- 2.5 recordings/patient) and 12-lead electrocardiogram (11.9 +/- 11.6), 177 patients with dual A-V nodal pathways could be divided into three subgroups. Thirty-two patients had 2nd A-V block only (2nd A-V block group), 57 had AVNRT only (AVNRT group), 88 had neither 2nd A-V block nor AVNRT (silent group), and none had 2nd A-V block and AVNRT both. Electrophysiologic studies showed that the atrio-His interval was significantly greater (P < 0.0001) and the maximal 1:1 atrioventricular conduction rate was lower (P < 0.0001) in the 2nd A-V block group than in the other two groups. These differences were nullified after the administration of atropine. These results suggest that patients with dual A-V nodal pathways can be classified into three clinical subgroups based on the presence of either 2nd A-V block or AVNRT. We suggest also that patients of the 2nd A-V block group may have a more augmented vagal tone on the A-V node than the other two groups.

Adolescent↗

Partial purification and characterization of manganese-oxidizing factors of Pseudomonas fluorescens GB-1.

The Mn(2+)-oxidizing bacterium Pseudomonas fluorescens GB-1 deposits Mn oxide around the cell. During growth of a culture, the Mn(2+)-oxidizing activity of the cells first appeared in the early stationary growth phase. It depended on the O2 concentration in the culture during the late logarithmic growth phase. Maximal activity was observed at an oxygen concentration of 26% saturation. The activity could be recovered in cell extracts and was proportional to the protein concentration in the cell extracts. The specific activity was increased 125-fold by ammonium sulfate precipitation followed by reversed-phase and gel filtration column chromatographies. The activity of the partly purified Mn(2+)-oxidizing preparation had a pH optimum of circa 7 and a temperature optimum of 35 degrees C and was lost by heating. The Mn(2+)-oxidizing activity was sensitive to NaN3 and HgCl2. It was inhibited by KCN, EDTA, Tris, and o-phenanthroline. Although most data indicated the involvement of protein in Mn2+ oxidation, the activity was slightly stimulated by sodium dodecyl sulfate at a low concentration and by treatment with pronase and V8 protease. By polyacrylamide gel electrophoresis, two Mn(2+)-oxidizing factors with estimated molecular weights of 180,000 and 250,000 were detected.

Bacterial Proteins↗

Preventive effect of whey hydrolysate formulas for mothers and infants against allergy development in infants for the first 2 years.

We studied the preventive effect against allergies in infants who and whose mothers consumed hypoallergenic formulas until 6 months after birth. Mother and infant pairs were divided into three groups, and the infants were monitored for the development of allergies for the first 2 years. In the MD group (n = 102; n = number of infants), the mothers were given a hypoallergenic formula for mothers (MOM HA), which contained hydrolyzed whey protein as the only protein source, as a substitution for cow's milk during late pregnancy and lactation. In the CD group (n = 127), the mothers were given cow's milk during the corresponding period. All infants in the MD and CD groups were exclusively breast-fed or mixed-fed with breast milk and hypoallergenic infant formula (NAN HA), which contains the same hydrolyzed protein as MOM HA. In the AF group (n = 54), the mothers consumed MOM HA and their infants were mixed-fed with breast milk and a cow's milk-based adopted infant formula during the corresponding period. In the MD group, no infants were positive to cow's milk-specific immunoglobulin E (RAST) at 4 months of age, in contrast to 6% and 3% of infants in the CD and AF groups, respectively. The infants in the MD group showed low incidence of various allergies, especially of eczema, as compared to the CD and AF groups. These results suggest that consumption of cow's milk by mothers and cow's milk-based formula feeding to infants elevate the risk of allergies in infants, and that consumption of hypoallergenic formula for pregnant and lactating women and for infants could be helpful in preventing allergy development in infants.

Dairy Products↗

[Smoking behavior, knowledge and attitudes of freshmen students].

A questionnaire on smoking behavior, knowledge of smoking-related diseases and attitudes toward the passive exposure to smoking was administered and results analyzed for differences in (1) region, (2) major area of study in the university, (3) grade and (4) date of survey on smoking behavior, knowledge and attitude of the freshmen students. (1) 294 urban and 217 provincial university students, (2) 138 freshmen at the Department of Pharmacology and 156 freshmen at the Department of Technology, (3) 136 freshmen of Y. University and 158 freshmen in senior high school of Yamaguchi prefecture, and (4) 217 freshmen surveyed in 1990 and 136 freshmen surveyed in 1995 were the subjects. The results were as follows; 1) The percentage who had smoked once ranged from 0 to 3% among the senior high school girls and female students at minor universities. However, the percentage for male students ranged from 26% to 44% in each survey. There were clear gender differences in smoking behavior. 2) The proportion of students who admitted that they had smoked cigarettes was 30.9% for urban students and 38.6% for provincial university students, but was not a significant difference. There were no significant differences between urban and provincial students regarding knowledge of smoking-related diseases or attitudes toward passive smoke. 3) The proportion of students who admitted that they had smoked cigarettes was 44.0% for the Department of Pharmacology and 26.2% for the Department of Technology, a significant difference. There were no significant differences between pharmaceutical and engineering students in knowledge of smoking-related diseases or attitudes toward passive smoke. 4) The proportion of students who admitted that they had smoked cigarettes was 27.4% for university freshmen and 1.6% for senior high school freshmen. There was a significant difference between the two. The percentage who replied that the smoker must be considerate to non-smokers tended to be higher in the senior high school students than the university students. However, there was no significant differences between the two groups of students in knowledge of smoking-related diseases or attitudes toward passive smoke. 5) Although the proportion of students who admitted that they had smoked cigarettes was 38.6% in the 1990 survey and 27.4% in the 1995 survey, this was not a significant difference. The percentage of students in the 1990 survey who indicated an awareness of the relationship between smoking and coronary heart diseases was significantly greater than the percentage of students who indicated a similar awareness in the 1995 survey. These results suggest that the differences in the grade and the department of the university (or the nature of school) must be considered when surveying smoking behavior. It does not appear to be necessary, however, to consider regional differences or the date of survey, if students were surveyed relatively recently, concerning smoking behavior, knowledge of smoking-related diseases and attitudes toward the effect of passive exposure to smoking.

Adolescent↗