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Biomedical subjects

H Ikegami

Publications and source records attributed to H Ikegami.

At least 91 records · Page 5Linked to original sources
PubMed1998

[A case of mild-type myotonic dystrophy with dementia and severe arteriosclerosis obliterans].

A 70-year-old man, with mild-type myotonic dystrophy (MyD) diagnosed by molecular genetic analysis when he was 68 years old, complained of worsening intermittent claudication during the past 2 years. Doppler examination revealed severe stenosis and obstruction in his leg arteries, which we diagnosed as arteriosclerosis obliterans (ASO). We then found him to be suffering from dementia, which was confirmed by dementia scale tests (Mini Mental State, 20/30; Hasegawas' Dementia Scale-Revision, 15/30). Even in mild-type MyD, as MyD is one of the progeria syndromes, the abnormal genes of MyD may accelerate the aging processes.

Aged↗
PubMed1998

[Positional cloning of susceptibility genes for non-insulin-dependent diabetes mellitus].

Although studies of families and twin studies have demonstrated that non-insulin-dependent diabetes mellitus (NIDDM) has a strong genetic component, the genes responsible for the common forms of NIDDM are largely unknown, due to the complex and heterogeneous nature of the disease. To study the genetics of NIDDM, we used an inbred animal model of NIDDM, the NSY mouse, in which NIDDM spontaneously develops in an age-dependent manner. The inheritance pattern of glucose tolerance, fasting insulin levels, insulin response to glucose, body mass index, and epididymal fat pad weight in F 1 hybrids of NSY with control C3H/He mice suggested the different modes of inheritance in these phenotypes. Multipoint linkage analysis of glucose tolerance in F2 mice with microsatellite markers throughout the genome mapped at least three loci on different chromosomes. Positional cloning of susceptibility genes for NIDDM in NSY mice may increase our understanding of the genetics and etiology of human NIDDM and may lead to more effective methods for prevention and intervention.

Animals↗
PubMed1998

[Cardiac sympathetic denervation after aortic surgery in a patient with thoracic dissecting aneurysm: a case report].

We experienced a case of a 60 year-old man with cardiac sympathetic denervation after aortic graft replacement of ascending aorta for a dissecting aneurysm (Debakey type II). Fourteen years after pheochromocytomectomy (paraganglioma), the patient developed a severe chest pain, and admitted to the hospital for the diagnosis of dissecting aneurysm. CT scan with contrast enhancement revealed thrombosed dissecting aneurysm in the region of ascending aorta to aortic arch. Graft replacement was undergone on the same day. 123I-MIBG imaging 20 days after the operation showed severely attenuated myocardial uptake (heart to mediastinum ratio 1.19), although the MIBG imaging before the operation showed normal myocardial uptake (heart to mediastinum ratio 1.55). Heart rate variability analysis in Holter ECG showed that the power of the low frequency (LF), that of the high frequency (HF) and L/H ratio were severely decreased. MIBG and heart rate variability analysis indicated that cardiac sympathetic and parasympathetic nerve were denervated. This is the first report of cardiac sympathetic denervation after aortic vascular surgery. Clinical significance of cardiac sympathetic denervation after aortic vascular surgery is uncertain, and further investigation will be required.

3-Iodobenzylguanidine↗
PubMed1998

[Clinical utility of pulmonary 99mTc-Tetrofosmin uptake measurement by the exercise myocardial scintigraphy in patients with ischemic heart disease].

Increased pulmonary 201TlCl (Tl) uptake during exercise has been used as a marker of multivessel critical stenosis. We studied whether pulmonary 99mTc-Tetrofosmin (TF) uptake measurement during exercise is useful as an additional indicator for the detection of coronary artery disease. Pulmonary to myocardial uptake ratio (P/M) measured by TF scintigraphy during exercise were compared with findings of coronary angiography in eighty one patients with ischemic heart disease and also P/M measured with Tl in twenty one cases. TF P/M level in the patients with triple vessel disease was higher than that in the patients with no coronary stenosis, single vessel disease and double vessel disease. However, there was no significant correlation between TF P/M and the severity of coronary artery stenosis. Inverse correlation was observed between TF P/M and left ventricular ejection fraction (LVEF) (r = 0.29, p < 0.01). TF P/M in the patients less than 50% of LVEF was significantly higher than that in the patients over 50% of LVEF (p = 0.05). TF P/M was well correlated with Tl P/M (r = 0.86). In conclusion, quantitative TF P/M during exercise was thought to be useful indicator for the evaluation of coronary artery disease.

Aged↗
PubMed1997

Purification and characterization of the human interleukin-18 receptor.

Interleukin (IL)-18 was identified as a molecule that induces IFN-gamma production and enhances NK cell cytotoxicity. In this paper, we report upon the purification and characterization of human IL-18 receptor (hIL-18R). We selected the Hodgkin's disease cell line, L428, as the most strongly hIL-18R-expressing cell line based on the results of binding assays. This binding was inhibited by IL-18 but not by IL-1beta. The dissociation constant (Kd) of 125I-IL-18 binding to L428 cells was about 18.5 nM, with 18,000 binding sites/cell. After immunizing mice with L428 cells and cloning, a single monoclonal antibody (mAb) against hIL-18R was obtained (mAb 117-10C). Sequentially, hIL-18R was purified from 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS)-extracted L428 cells by wheat germ lectin-Sepharose 4B chromatography and mAb 117-10C-Sepharose chromatography. The internal amino acid sequences of hIL-18R all matched those of human IL-1 receptor-related protein (IL-1Rrp), the ligand of which was unknown to date. When expressed in COS-1 cells, the cDNA of IL-1Rrp conferred IL-18 binding properties on the cells and the capacity for signal transduction. From these results, we conclude that a functional IL-18 receptor component is IL-1Rrp.

Amino Acid Sequence↗
PubMed1997

Prolactin stimulates mitogen-activated protein kinase in human leiomyoma cells.

The effects of prolactin (PRL) on proliferation of cultured human uterine leiomyoma-derived smooth muscle cells (SMC) and its mechanism of action were investigated. PRL stimulated DNA synthesis and the expression of PRL receptor was identified by ribonuclease protection assay. Moreover, the regulation of mitogen-activated protein (MAP) kinase by PRL in leiomyoma-derived SMC was investigated. PRL stimulated MAP kinase activity, as detected by 32P incorporation into MAP-2, in a dose-dependent manner. PRL also rapidly stimulated MAP kinase phosphorylation as detected by in vivo phosphorylation using 32P labeling and phosphotyrosine immunoblotting. These results suggest that PRL stimulates the proliferation of human leiomyoma cells via the MAP kinase cascade.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

Insulin gene region contributes to genetic susceptibility to, but may not to low incidence of, insulin-dependent diabetes mellitus in Japanese.

In the Caucasian population, it has been demonstrated that the insulin gene (INS) region contains the insulin-dependent diabetes mellitus locus (IDDM2). In the Japanese population, however, there has been no report demonstrating the contribution of IDDM2 to the pathogenesis of IDDM. We conducted an association study of IDDM in a large number of Japanese subjects with multiple polymorphisms in INS region. We found a significant association of the INS region with IDDM. Alleles positively associated with IDDM in INS region were the same as those positively-associated with IDDM in Caucasian population, although positively-associated alleles are very common (allele frequencies > 0.9) in the Japanese general population. These data suggest that IDDM2 is involved in the genetic susceptibility to IDDM in Japanese. The high frequencies of disease-associated alleles in the general population suggest that IDDM2 locus is not responsible for the low incidence of IDDM in Japanese.

DNA, Satellite↗
PubMed1997

Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population.

The Werner syndrome (WS) is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus (NIDDM), ocular cataracts and osteoporosis [Epstein et al., 1966]. The major cause of death (at a median age of 47) is myocardial infarction (MI) [Epstein et al., 1966]. The WS mutation involves a member (WRN) of the RecQ family of helicases and may perturb DNA replication, repair, recombination, transcription, or chromosomal segregation [Yu et al., 1996]. We now report data on 149 MI cases and age-matched controls suggesting that a polymorphic WRN variant is associated with increased risk for MI. Based on our data, homozygosity for a cysteine at amino acid 1367 (the most prevalent genotype) predicts a 2.78 times greater risk of MI (95% confidence intervals: 1.23 to 6.86). The variant was not significantly associated with NIDDM. The two alleles (cysteine vs. arginine) could influence helicase activity, turnover, macromolecular interactions or, alternatively, could be markers for haplotypes influencing WRN regulation or reflecting gene action at linked loci. However, given the caveats implicit in genetic association studies, it is imperative that the present results be replicated in independent populations.

Adult↗
PubMed1997

Respiratory variability in R-R interval during sinusoidal exercise.

The R-R interval varies with the cycles of respiration. The response of the variability in the R-R interval with respiration was examined during sinusoidal cycle exercise in 12 healthy young male subjects. Work rate varied sinusoidally between 30 W and 60% maximal oxygen uptake for an 8-min period. The higher the heart rate (HR), the smaller was the magnitude of the variation in R-R interval with respiration (delta RR). When HR increased with an increase in exercise intensity, however, delta RR tended to decrease more markedly at lower HR. On the other hand, since delta RR generally increased linearly during the decrease in HR with a reduction in exercise intensity, delta RR was greater during decreases in HR than during increases in HR at a similar HR. These results suggest that the contribution of the withdrawal of cardiac parasympathetic activity to increases in HR with increases in exercise intensity during sinusoidal exercise were greater at lower HR, and that the cardiac parasympathetic system was more activated during HR decreases than during HR increases at the same HR. From our findings it would seem that such complex parasympathetic HR regulaltion during sinusoidal exercise, which depends on the level of HR and the direction of the change in HR, may be influenced by factors other than the parasympathetic system, such as the cardiac sympathetic system.

Adolescent↗
PubMed1997

Trp64Arg mutation of beta3-adrenergic receptor in essential hypertension: insulin resistance and the adrenergic system.

A putative pathogenic mutation in the beta3-adrenergic receptor gene (Trp64Arg) has been reported to be associated with higher diastolic blood pressure as well as clinical features of the insulin resistance syndrome and an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians and Finns. Because essential hypertension is reported to be associated with insulin resistance, we studied the mutation in Japanese patients with essential hypertension to clarify associations of this mutation with hypertension, insulin resistance, and basal adrenergic state in hypertensive subjects. The allele frequency of the mutation (Arg) in patients with essential hypertension was similar to that in control subjects (35 of 202 alleles [17.3%] v 27 of 146 [18.5%], respectively, P > .7). Insulin sensitivity measured by hyperinsulinemic euglycemic glucose clamp and plasma norepinephrine and epinephrine levels were also similar in hypertensive subjects with and without the mutation. These data suggest that Trp64Arg mutation in the beta3-adrenergic receptor gene does not play a major role in susceptibility to essential hypertension or in insulin resistance and basal adrenergic state in hypertension.

Adult↗
PubMed1997

Effects of fructose-induced hypertriglyceridemia on hepatorenal toxicity of acetaminophen in rats: role of pharmacokinetics and metabolism of acetaminophen.

Fructose-induced hypertriglyceridemic rats become resistant to hepatotoxicity and susceptible to nephrotoxicity of acetaminophen (APAP), as compared with normal ones. The present study was designed to test the hypothesis that alterations in the distribution of APAP and in the intrinsic susceptibility to toxicants are responsible for the alteration in hepatorenal toxicity of APAP in fructose-induced hypertriglyceridemic rats. Following APAP-administration (750 mg/kg, i.p.), fructose-pretreated rats (25% fructose in drinking water for 5 weeks) showed nephrotoxicity of APAP more promptly and more severely than normal ones. Renal APAP-concentrations at the early phase (15 and 30 min. after APAP-administration) were significantly greater in fructose-pretreated rats than those in normal ones. Plasma and hepatic APAP concentrations in fructose-pretreated rats were greater than those in normal ones only at the later phase (plasma; 6 hr, liver; 6 and 12 hr after APAP-administration). There were no significant differences in the APAP-induced depletion of hepatic and renal glutathione and in the basal hepatic and renal cytochrome P-450 contents between these rats. Fructose-pretreated rats were also more susceptible to p-aminophenol (PAP), a nephrotoxic metabolite of APAP, than normal rats. Therefore, enhanced susceptibility to APAP-nephrotoxicity in fructose-pretreated rats may be due, at least in part, to increased renal APAP concentration and increased intrinsic susceptibility to the metabolic nephrotoxicant.

Acetaminophen↗
PubMed1997

Effects of fructose-induced hypertriglyceridemia on hepatorenal toxicity of acetaminophen in rats. II. Role of enhancement of fructose metabolism and overproduction of triglyceride in the liver and kidney on hepatorenal toxicity of acetaminophen.

Fructose-induced hypertriglyceridemic rats are resistant to hepatoxicity and susceptible to nephrotoxicity of acetaminophen (APAP) as compared with normal ones. The present studied were designed to evaluate how fructose-treatment affects the developmental mode of hepatorenal toxicity of APAP. First, following fructose-pretreatment for various durations (1 day, 1 week or 3 weeks), 1-day-fructose-pretreatment induced hypertriglyceridemia and enhancement of APAP-nephrectoxicity simultaneously. However, it took at least 3 weeks for fructose-pretreatment to reduce APAP-hepatotoxicity. Second, following fructose, sucrose or glucose-pretreatment for 3 weeks, fructose-pretreated rats showed marked hypertriglyceridemia and modification of APAP-hepatorenal toxicity. Sucrose-pretreated rats showed less effects than fructose-pretreated rats. Glucose-pretreated rats showed no changes in plasma triglyceride and APAP-hepatorenal toxicity. Third, rats with hypertriglyceridemia induced by olive oil or Triton WR-1339 which did not produce enhanced metabolism and triglyceride-overproduction in the liver and kidney showed no modification of APAP-hepatorenal toxicity. Pretreatment of glycerol which was metabolized in liver and kidney and induced an overproduction of triglyceride resulted in an enhancement of APAP-nephrotoxicity. These results indicate that an enhancement of fructose metabolism and an overproduction of triglyceride in liver and kidney are responsible for the modification of APAP-hepatorenal toxicity in fructose-induced hypertriglyceridemic rats.

Acetaminophen↗
PubMed1997

Enhanced nephrotoxicity of acetaminophen in fructose-induced hypertriglyceridemic rats: contribution of oxidation and deacetylation of acetaminophen to an enhancement of nephrotoxicity.

Fructose-induced hypertriglyceridemic Sprague-Dawley (SD) rats become resistant to hepatotoxicity and susceptible to nephrotoxicity of acetaminophen (APAP) as compared with normal SD rats. Fischer-344 rats, which are susceptible to APAP nephrotoxicity, have two toxic metabolic pathways involving cytochrome P450-dependent oxidation of APAP to N-acetyl-p-benzoquinone imine (NAPQI) and P450-independent deacetylation of APAP to p-aminophenol (PAP). SD rats, however, have only the former pathway. This study was undertaken to investigate whether alterations in the metabolic pathways of APAP and in the intrinsic susceptibility to toxic metabolites are responsible for an enhancement of APAP nephrotoxicity in the fructose-pretreated SD-rats. In the non-pretreated rats, the inhibition of APAP oxidation by the MFO inhibitor, piperonyl butoxide, and deacetylation by carboxyesterase inhibitor, bis(p-nitrophenyl)phosphate, did not alter APAP-induced renal lesions. In contrast, these inhibitors protected the fructose-pretreated rats from APAP-induced renal lesions. Since there were no differences in the severity of gentamicin-, chloroform, and 45 min-ischemia/reperfusion-induced renal lesions between the non-pretreated and the fructose-pretreated rats, it is unlikely that the increased intrinsic susceptibility to chemicals and their metabolites in the fructose-pretreated rats is a major factor in the enhancement of APAP nephrotoxicity. These results indicate that the enhancement of APAP nephrotoxicity in the fructose-pretreated rats is due, at least in part, to an alteration in metabolic pathways of APAP.

Acetaminophen↗
PubMed1997

Enhanced nephrotoxicity of acetaminophen in fructose-induced hypertriglyceridemic rats: effect of partial hepatectomy.

Fructose-induced hypertriglyceridemic rats become resistant to hepatotoxicity and susceptible to nephrotoxicity of acetaminophen (APAP). Enhanced susceptibility to APAP nephrotoxicity in fructose-pretreated rats is due, at least in part, to increased renal APAP concentration at the early phase (15 and 30 min after APAP administration). However, the mechanism of an increase in renal APAP concentration is still obscure. The present study was designed to test the hypothesis that a decrease in capacity of hepatic APAP metabolism is responsible for an increase in renal APAP concentration in fructose-pretreated rats. Non-pretreated rats and fructose-pretreated rats (25% fructose in drinking water for 3 weeks) received 70% or 90% partial hepatectomy (PH) or sham operation at 1 hr before APAP administration (600 or 750 mg/kg, i.p.). PH did not potentiate APAP nephrotoxicity and renal APAP concentration, and fructose-pretreated rats showed server renal lesions and greater renal APAP concentration than non-pretreated rats irrespective of PH. The result indicates that an increase in renal APAP concentration in the fructose-pretreated rats has no relation to an alteration in hepatic metabolic capacity of APAP.

Acetaminophen↗
PubMed1997

An age-related change in susceptibility of rat brain to encephalomyocarditis virus infection.

Rats were inoculated intraperitoneally (i.p.) or intracerebrally (i.c.) with 1 x 10(4) plaque forming units (PFU)/animal of the D variant of encephalomyocarditis virus (EMC-D) at 2, 4, 7, 14, 28 or 56 days of age for virological and histopathological examination. In the i.p.-inoculation study, neither viral replication nor lesions were detected in the animals inoculated at 28 and 56 days of age. In the animals inoculated when younger than 14 days of age, lesions were restricted to the brain although viral replication was detected in the brain, heart and pancreas. The brain lesions were characterized by acute meningoencephalitis with neuronal necrosis in the cerebral cortex, hippocampus and thalamus, and viral RNA was detected in degenerated and/or intact neurons. In the i.c.-inoculation study, similar age-related changes in susceptibility of rat brain to EMC-D infection were observed, but a minor difference was that viral replication and lesions were still detected in the hippocampus of some animals inoculated at 28 days of age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC virus infection may reflect an age-related change in the susceptibility of neurons themselves as well as in maturation of the immune system.

Aging↗
PubMed1997

Dynamics of respiratory response to sinusoidal work load in humans.

The present study was undertaken to investigate possible distortion in responses of respiratory variables including O2 uptake (VO2), CO2 output (VCO2), and ventilation (VE) to sinusoidal work load, and to find out whether the conventional transfer models were applicable to analyze the dynamics of these variables. Six healthy subjects performed exercise for 32 min on a bicycle ergometer with electro-magnetic braking. The work load was varied sinusoidally between 30 W and 60% of maximum O2 uptake (VO2max) during periods from 1 to 16 min. The respiratory variables were measured on a breath-by-breath basis with a mass spectrometer and a computer system. The responses of VO2, VCO2, and VE to sinusoidal work load were not completely sinusoidal in form but were somewhat distorted, forming saw-tooth waves with steeper down-slopes during periods of 4-16 min, but this distortion was not observed at 1 min or 2 min periods. However, the results could be approximately described by a first-order model without or with time delay. Time constants of the first-order model without time delay were 46 sec for VO2, 62 sec for VCO2, and 73 sec for VE, respectively. We also found a close relationship between the time constants of VO2 and VCO2 and VO2max. These results suggested that exponential functions may be applied and are expected to yield valid results in assessing physical fitness, although the control of ventilatory and gas exchange in exercise does show non-linear characteristics.

Adult↗
PubMed1997

Tissue-specific and glucose-dependent expression of receptor genes for glucagon and glucagon-like peptide-1 (GLP-1).

Both glucagon and glucagon-like peptide-1 (GLP-1) play an important role in the regulation of nutrient homeostasis. In this study, the tissue distributions of the expression of receptor genes for glucagon and GLP-1 were examined. Expression of glucagon receptor gene was detected in liver, kidney, ileum and pancreatic islets but not in brain. In contrast, expression of GLP-1 receptor gene was detected in brain, pancreas and pancreatic islets but not in liver, kidney, or ileum. To investigate the existence and characteristics of glucagon and GLP-1 receptors on pancreatic beta cells, expression of the receptor genes and translational regulation of the expression of the receptor genes by glucose were analyzed in a mouse pancreatic beta cell line, MIN6 cells. In the cDNA pool of MIN6 cells, both glucagon and GLP-1 receptor genes were identified and showed higher expression level in MIN6 cells cultured under high glucose condition than in those cultured under low glucose condition. These results suggest that glucagon and GLP-1 receptor genes are expressed in pancreatic beta cells and their expression is upregulated by glucose.

Animals↗