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Biomedical subjects

Y Seino

Publications and source records attributed to Y Seino.

At least 55 records · Page 3Linked to original sources
PubMed2001

Transdermal estrogen replacement therapy and vasomotor response.

Previous studies have shown that acute administration of estrogen improves endothelial function in postmenopausal women, but there has been little investigation of the chronic effects of transdermal estrogen replacement therapy. The present study assessed the effect of transdermal estrogen replacement therapy (0.025 mg / day for 4 weeks, the normally applied dosage in Japan) on flow-mediated endothelium-dependent vasodilation of the brachial artery (B-mode ultrasound) and forearm cutaneous blood flow (laser Doppler flowmetry), and plasma hormonal and lipid levels in 12 normolipidemic postmenopausal women. Neither resting vascular diameter, flow-mediated vasodilation, nor time to peak vasodilation, showed significant changes after the estrogen therapy. In contrast, resting forearm cutaneous blood flow decreased significantly after the estrogen therapy. The time to the peak reactive hyperemia in the forearm skin was slightly shortened, and the % change in reactive hyperemia decreased slightly after the therapy. These findings seemed to reflect the inhibition of hot-flush symptoms associated with vasomotor abnormalities in cutaneous tissue. The lack of improvement in flow-mediated vasodilation of the brachial artery despite the inhibitory effect on cutaneous vasomotor abnormalities may be related to the low plasma estradiol concentration obtained with the present transdermal therapy (42.4+/-15.2 pg / ml), a finding which supports the estrogen threshold hypothesis in hormone replacement therapy.

Administration, Cutaneous↗
PubMed2001

Plasma natriuretic peptide levels and daily physical activity in patients with pacemaker implantation.

To determine whether plasma ANP and/or BNP levels can be used to detect limitations in daily physical activity after pacemaker implantation, we measured plasma ANP and BNP levels at a pacemaker follow-up clinic in 56 patients (62+/-15 yrs, 2AAI, 9VVI, 34DDD, 7VDD and 4 rate-responsive modes), daily physical activity evaluated by a specific activity scale questionnaire (METs) and VO2 max obtained by expired gas analysis during ergometer exercise. A very close correlation (n=6, r=0.89, p<0.05) was obseved between. ANP in patients with daily physical activity class III (2-4 METs, n=21) was significantly higher than class II (5-6 METs, n=23, p<0.01) and class I (>7 METs, n=8, p<0.01), while BNP in class III patients was significantly higher than in class II (p<0.0001) and class I (p<0.0001) patients. Significant correlations between daily physical activity and BNP (r=-0.64, p<0.0001) and ANP (r=-0.43, p<0.001) were observed. Physiological pacing mode did not necessarily offer a better profile for BNP levels compared with non-physiological pacing modes. Patients with ventricular pacing (wide QRS: VDD, RR-VVI and VVI) showed significantly high ANP (p<0.01) and BNP (p<0.01) levels compared with those in patients with atrial pacing (narrow QRS: AAI and RR-AAI). During exercise, plasma catecholamines and ANP levels were significantly elevated, however, BNP levels, which were already elevated at rest, did not change significantly, and reflected a limitation of daily physical activity. The present study revealed that 37.5% of the patients displayed an elevation in BNP and this was judged to be a limitation of physical activity class III being equivalent to NYHA II or more. Elevated resting BNP levels reflected a limitation in daily physical activity in these patients. These findings suggested a third condition for physiological pacing--synchronization of ventricular contraction (narrow QRS pacing)--in addition to the two conventional conditions of atrioventricular synchrony and rate-responsiveness.

Aged↗
PubMed2001

A Utstein-style analysis of prognostic factors related to survival in out-of-hospital cardiac arrests in Akita-City, Japan.

To analyze the epidemiology of out-of-hospital cardiac arrests and to elucidate modifiable factors affecting survival, we conducted a prospective cohort study in a middle-sized urban city served by a single emergency medical service (EMS) system in which emergency medical technicians use an automated external defibrillator. Data were collected from out-of-hospital cardiac arrests occurring between 1 January, 1994 and 31 December, 1998 by applying the Utstein style. The main outcome measure was survival at 1 year after hospital discharge. The overall incidence of out-of-hospital cardiac arrest was 71.7/100 000 inhabitants/year. Resuscitations were attempted in 762 of 1118 patients with confirmed cardiac arrest. Of the 762 patients, 37 (4.86%) survived. The cause of cardiac arrest was presumed to be cardiac in 340 (44.6%). Of the 340 cardiac arrests, 180 (52.9%) were witnessed by bystanders. Ventricular fibrillation (VF) was recorded as an initial rhythm in 56 (31.1%) of the 180 patients, and cardiopulmonary resuscitation (CPR) was performed by bystanders in 89 (49.4%). The survival rate was 39.2% (22/56) when cardiac arrest was bystander-witnessed and of cardiac origin with VF as an initial rhythm. VF as an initial rhythm, age of the patients and intervals of call-to-first CPR attempt and collapse-to-arrival at patient's side were major factors relating to survival in the witnessed cardiac arrests of cardiac origin. The age, and gender of the patients, place of collapse and intervals of collapse-to-first CPR and collapse-to-arrival at patient's side were representative factors affecting the incidence of VF as an initial rhythm. The survival rate in Akita-City from bystander-witnessed cardiac arrests of cardiac origin with VF as an initial rhythm was comparable to those in other regions with advanced EMS systems. However, the incidence of VF as an initial rhythm is extremely low. Reduction of intervals of call (collapse)-to-first CPR attempt and collapse-to-arrival at patient's side or authorization of use of automated external defibrillator in basic life support may increase the incidence of VF as an initial rhythm and improve the survival from witnessed cardiac arrests with cardiac origin.

Cardiopulmonary Resuscitation↗
PubMed2001

Nephrin is an important component of the barrier system in the testis.

Nephrin, a gene product of the congenital nephrotic syndrome of the Finnish type (NPHS1), is a 1242-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules. The expression of this gene is localized in rat and human glomerular epithelial cells. Here we report the expression of nephrin in various tissues other than the kidneys in mice. The expression of nephrin mRNA in various tissues of mice, including the kidneys, testes, spleen, thymus and brain, were first investigated by the RT-PCR method, and it was shown that a high level of nephrin mRNA could be detected in the testes of mice 1-6 weeks old. In situ hybridization revealed the expression of the nephrin gene in the Sertoli cells. Additionally, immunofluorescent staining studies indicated that nephrin was colocalized with anchoring protein ZO-1 in the mouse testis. From these results, it is inferred that nephrin is an important component of the barrier system in testes.

Animals↗
PubMed2001

Human TSC-22 gene: no association with type 2 diabetes.

OBJECTIVE: In order to elucidate whether or not genetic variations of TSC-22 (TGF [transforming growth factor]-beta-stimulated clone 22), which was originally identified as a TGF-beta-responsive leucine zipper protein in murine osteoblastic cells, are associated with type 2 diabetes, the genomic organization of the human TSC-22 gene was determined and the association between its polymorphisms and type 2 diabetes was examined. RESULTS: The human TSC-22 gene spans approximately 5 kilobase pairs and is encoded in three exons. Two single nucleotide polymorphisms (SNPs) were identified in the coding region of the first exon, two other SNPs in the first intron, and one SNP in the putative promoter region. There were, however, no significant differences in the frequency of these polymorphisms between patients with type 2 diabetes and non-diabetic control subjects. CONCLUSION: It is unlikely that the TSC-22 gene is a locus responsible for type 2 diabetes.

Aged↗
PubMed2001

The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes.

The allele frequencies for a Pro12-->Ala substitution in peroxisome proliferator-activated receptor-gamma differ among ethnic groups, and its relationship with diabetes and associated diseases is controversial. The prevalence of this polymorphism and its effects on clinical characteristics have now been evaluated with a large number of Japanese individuals with type 2 diabetes (n = 2,201) and normal control subjects (n = 1,212) recruited by 10 institutions located in seven different cities in Japan. The allele frequency for the Ala12 variant was significantly lower in the type 2 diabetic group than in the control group (2.39 vs. 4.13%, P = 0.000054). However, compared with subjects without the Ala12 variant, the diabetic subjects with this variant exhibited a significantly higher serum concentration of total cholesterol (P = 0.001), manifested a reduced capacity for insulin secretion as evaluated by homeostasis model assessment (P = 0.007), and tended to possess a higher level of HbA1c. These data suggest that the Ala12 variant is associated with a reduced risk for the development of diabetes in the general population, but that it may be also a risk factor for insulin deficiency and disease severity in individuals with type 2 diabetes.

Adult↗
PubMed2000

A novel glucokinase regulator in pancreatic beta cells: precursor of propionyl-CoA carboxylase beta subunit interacts with glucokinase and augments its activity.

A glucokinase regulatory protein has been reported to exist in the liver, which suppresses enzyme activity in a complex with fructose 6-phosphate, whereas no corresponding protein has been found in pancreatic beta cells. To search for such a protein in pancreatic beta cells, we screened for a cDNA library of the HIT-T15 cell line with the cDNA of glucokinase from rat islet by the yeast two hybrid system. We detected a cDNA encoding the precursor of propionyl-CoA carboxylase beta subunit (pbetaPCCase), and glutathione S-transferase pull-down assay illustrated that pbetaPCCase interacted with recombinant rat islet glucokinase and with glucokinase in rat liver and islet extracts. Functional analysis indicated that pbetaPCCase decreased the K(m) value of recombinant islet glucokinase for glucose by 18% and increased V(max) value by 23%. We concluded that pbetaPCCase might be a novel activator of glucokinase in pancreatic beta cells.

Animals↗
PubMed2000

Rapid screening method to detect mutations in CYP21, the gene for 21-hydroxylase.

To facilitate a rapid and practical molecular diagnosis of 21-hydroxylase deficiency (21-OHD), we developed a polymerase chain reaction (PCR) test in which only the 21-OH gene (CYP21) is amplified. We applied the test to diagnose 23 patients with salt-wasting type of 21-OHD. The upstream and downstream sequences of CYP21 have been specifically amplified by using a primer set containing the 8-bp deletion sequence of exon 3, which is distinct from its pseudogene CYP21P. The amplified PCR products were further subjected to mutation detection by restriction analysis: E1PL by AciI, I2g by PstI, E63a by DraIII, E7VL by ApaLI, E8non by PstI, and E8RW by AciI. To detect delections and/or gene conversions occurring on exon 3, we used the method described by Rumsby and Honour [1990: J Med Genet 27:676-678]. Our method is able to elucidate 8 common CYP21 mutations by using only 3 primer pairs and 4 restriction enzymes. The overall detection ratio of abnormal haplotypes by this method was over 95%, indicating that our method is practical and useful, particularly for carrier detection.

Adrenal Hyperplasia, Congenital↗
PubMed2000

Sustained enhancement of Ca(2+) influx by glibenclamide induces apoptosis in RINm5F cells.

Cytosolic Ca(2+) elevations are known to be involved in triggering apoptosis in many tissues, but the effect of sustained enhancement of Ca(2+) influx on apoptosis in beta cells remains unknown. We have found that the viability of RINm5F cells is decreased dose-dependently by continuous exposure to glibenclamide at concentrations from 10(-7) to 10(-4) M, and that this effect is partially ameliorated by pretreatment with cycloheximide. Electrophoresis of the cells exposed to glibenclamide revealed ladder-like fragmentation characteristic of apoptosis, and which also is suppressed by cycloheximide pretreatment. By using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, we detected increased DNA fragmentation in the nuclei of the cells exposed to glibenclamide, and staining with Hoechst 33342 and propidium iodide showed a dose-dependent increase in the number of cells with the chromatin condensation and fragmentation in their nuclei that is characteristic of apoptosis. The effects of glibenclamide on cell viability and apoptotic cell death were partially inhibited by treatment with Ca(2+) channel blocker, and by reducing the extracellular Ca(2+) concentration during glibenclamide exposure, suggesting that they may be derived from increased Ca(2+) influx. Furthermore, only the percentage of apoptotic cells, and not that of necrotic cells, increased with the increasing intracellular Ca(2+) concentration during glibenclamide exposure. In conclusion, we have demonstrated that the sustained enhancement of Ca(2+) influx caused by glibenclamide exposure can induce apoptotic cell death in a pure beta cell line.

Animals↗
PubMed2000

Antioxidant alpha-tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes.

We have shown recently that oxidative stress by chronic hyperglycemia damages the pancreatic beta-cells of GK rats, a model of non-obese type 2 diabetes, which may worsen diabetic condition and suggested the administration of antioxidants as a supportive therapy. To determine if natural antioxidant alpha-tocopherol (vitamin E) has beneficial effects on the glycemic control of type 2 diabetes, GK rats were fed a diet containing 0, 20 or 500 mg/kg diet alpha-tocopherol. Intraperitoneal glucose tolerance test revealed a significant increment of insulin secretion at 30 min and a significant decrement of blood glucose levels at 30 and 120 min after glucose loading in the GK rats fed with high alpha-tocopherol diet. The levels of glycated hemoglobin A1c, an indicator of glycemic control, were also reduced. Vitamin E supplementation clearly ameliorated diabetic control of GK rats, suggesting the importance of not only dietary supplementation of natural antioxidants but also other antioxidative intervention as a supportive therapy of type 2 diabetic patients.

Animals↗
PubMed2000

Wortmannin, a PI3-kinase inhibitor: promoting effect on insulin secretion from pancreatic beta cells through a cAMP-dependent pathway.

To determine the role of phosphatidylinositol 3-kinase (PI3-kinase) in the regulation of insulin secretion, we examined the effect of wortmannin, a PI3-kinase inhibitor, on insulin secretion using the isolated perfused rat pancreas and freshly isolated islets. In the perfused pancreas, 10(-8) M wortmannin significantly enhanced the insulin secretion induced by the combination of 8.3 mM glucose and 10(-5) M forskolin. In isolated islets, cyclic AMP (cAMP) content was significantly increased by wortmannin in the presence of 3.3 mM, 8.3 mM, and 16.7 mM glucose with or without forskolin. In the presence of 16.7 mM glucose with or without forskolin, wortmannin promoted insulin secretion significantly. On the other hand, in the presence of 8.3 mM glucose with forskolin, wortmannin augmented insulin secretion significantly; although wortmannin tended to promote insulin secretion in the presence of glucose alone, it was not significant. To determine if wortmannin increases cAMP content by promoting cAMP production or by inhibiting cAMP reduction, we examined the effects of wortmannin on 10(-4) M 3-isobutyl-1-methylxantine (IBMX)-induced insulin secretion and cAMP content. In contrast to the effect on forskolin-induced secretion, wortmannin had no effect on IBMX-induced insulin secretion or cAMP content. Moreover, wortmannin had no effect on nonhydrolyzable cAMP analog-induced insulin secretion in the perfusion study. These data indicate that wortmannin induces insulin secretion by inhibiting phosphodiesterase to increase cAMP content, and suggest that PI3-kinase inhibits insulin secretion by activating phosphodiesterase to reduce cAMP content.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Effects of lowering ambient temperature on pain-related behaviors in a rat model of neuropathic pain.

To clarify the mechanism by which changes in chronic pain are induced by cold environments, rats rendered neuropathic by a chronic constriction injury (CCI) to the sciatic nerve were exposed to low ambient temperature (LT; 7 degrees C decrease from 22 degrees C) in a climate-controlled room. LT exposure aggravated pain-related behaviors in CCI rats, i.e., decreased the threshold to von Frey hair and paw pressure stimulation, prolonged the duration of foot withdrawal to pinprick stimulation, and increased the cumulative duration of guarding posture. Lumbar sympathectomy (SYX) did not inhibit LT-induced augmentations of pain-related behaviors in CCI rats. LT exposure decreased the skin temperatures of both hind paws to the same degree in the sham-operated control and SYX rats, while in the CCI and SYX+CCI rats it caused a larger temperature decrease in the injured paw than in the uninjured one. These results indicate that LT exposure augments abnormalities in pain-related behaviors of neuropathic rats, and also suggest that sympathetic nervous activity is not a predominant factor in the augmenting mechanism.

Animals↗
PubMed2000

Correlations between bone mineral density and circulating bone metabolic markers in diabetic patients.

Diabetic osteopenia, a known chronic complication of diabetes, has been demonstrated with alterations in the calcium-vitamin D endocrine system. In order to investigate the relationship between the decrease of bone density and the altered mineral metabolism in non-insulin-dependent diabetes mellitus (NIDDM), 104 male clinical-proven NIDDM patients were studied. All patients were examined on metacarpal bone mineral density (m-BMD) by means of computed X-ray densitometry (CXD) methods. The values of the Z-score of m-BMD were significantly lower than those of age-matched controls (P<0.01). There was a positive correlation between m-BMD and serum calcium levels (P<0.01), but a negative correlation was conversely observed between m-BMD and serum intact parathyroid hormone (PTH) (P<0.01), indicating that the negative calcium balance under diabetic conditions could cause the decrease of m-BMD in NIDDM. Interestingly, since a significantly positive correlation was found between circulating levels of calcium and parathyroid hormone-related peptide (PTHrP) (P<0.05) but not PTH, it seems likely that PTHrP plays a more compensatory role on the maintenance of calcium homeostasis than PTH under diabetic conditions. Based on these observations, the CXD method would be useful in measuring the mineral density of cortical bone, and would also be beneficial to investigate underlying pathogenetic mechanism of diabetic osteopenia.

Absorptiometry, Photon↗
PubMed2000

Altered biochemical markers of bone turnover in humans during 120 days of bed rest.

Microgravity induces significant and progressive bone loss in both humans and animals. This is the consequence of disturbed bone remodeling. We performed a bed rest experiment to simulate microgravity and tried to clarify bone metabolism by measuring biochemical markers of bone turnover. Six healthy volunteers participated in 120 days of bed rest. The parameters of calcium homeostasis, calcitropic hormones, and biochemical markers of bone turnover were examined. After ambulatory control evaluation, all subjects underwent 120 days of bed rest. Metabolic evaluation was performed in a baseline period, and on days 7, 16, 50, 72, 92, and 108 during bed rest, and on days 10 and 25 during a recovery period. Bed rest induced an increase in urinary calcium (Ca) excretion and serum Ca and bone resorption markers. Urine pyridinoline, deoxypyridinoline, and type I collagen cross-linked N-telopeptide increased more rapidly than urinary Ca excretion and serum Ca. Tartrate-resistant acid phosphatase (TRAP) increased even in the recovery period. Carboxy-terminal propeptide of type I collagen, a bone formation marker, significantly decreased on days 50, 92, and 108 of bed rest. These changes of biochemical markers of bone metabolism, except for TRAP, rapidly returned toward control levels in the recovery period. Immunoreactive parathyroid hormone showed a modest decrease during bed rest and a significant increase in the recovery period. Insulin-like growth factor I (IGF-I) and its binding protein, insulin-like growth factor binding protein-3, increased during bed rest, indicating the possibility of resistance to IGF-I in bones under reduced mechanical stress and strain. Bone loss from unloading results from the combination of acceleration of bone resorption and subsequent retardation of bone formation.

Adult↗
PubMed2000

A novel mutation (296 del G) of the SOX90 gene in a patient with campomelic syndrome and sex reversal.

The human SOX9 gene is responsible for the campomelic syndrome (CMPS) and sex reversal. This gene encodes a transcription factor containing a DNA binding domain homologous to the SRY high mobility group (HMG) domain. A novel mutation of SOX9, i.e. a single G deletion in one allele at nt 296 from A of the first ATG in the open reading frame, was identified in a patient with CMPS with sex reversal. The deletion resulted in a frameshift mutation upstream of the HMG box and a stop codon 30 bp downstream of the HMG box. The predicted truncated SOX9 protein contained 108 amino acids instead of the 509 amino acids of the normal SOX9 protein, removing nearly 80% of the SOX9 protein, including the HMG and the C-terminal transactivation domain. Most patients with CMPS reported previously died within the neonatal period. Our findings that the patient has survived, although has been in daily need of mechanical ventilation support for 5 years and 3 months despite a severely impaired SOX9 protein, do not support a linear relationship between the type of mutation and severity of the clinical outcome.

Abnormalities, Multiple↗