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Biomedical subjects

K Yasuda

Publications and source records attributed to K Yasuda.

At least 253 records · Page 14Linked to original sources
PubMed2000

Role of endothelium and vasoconstrictor prostanoids in norepinephrine-induced vasoconstriction in isolated rat common carotid arteries.

We investigated the role of endothelium and vasoconstrictor prostanoids in the norepinephrine (NE)-induced vasoconstriction of isolated rat common carotid arteries (CCAs). Isolated CCAs were cannulated with stainless steel cannulae by the cannula inserting method. NE was administered intra- or extraluminally by a single microinjection. For denudation of endothelium, the intimal surface was gently rubbed with a cotton pellet. NE produced dose-related vasoconstricting responses in isolated arteries with intact endothelium. These responses were attenuated by pretreatment with denudation, OKY046, a thromboxane A2 synthesis inhibitor or indomethacin. The residual responses after denudation were further blocked by OKY046 or indomethacin. All NE-induced responses were blocked by a single injection of prazosin. There were no significant differences in responses between intra- and extraluminal administration of NE. These results show that most vasoconstriction induced by NE via alpha1-adrenoceptors in CCAs is dependent on vasoconstrictor prostanoids distributed both in endothelium and vascular smooth muscle.

Animals↗
PubMed2000

Expression of interleukin-15 in human endometrium and decidua.

In human endometrium, cytokines and growth factors that vary periodically during the menstrual cycles have been suggested to play various roles in uterine function. In the present study, differential gene expression in human endometrium between the proliferative and the secretory phases was investigated by using a human cDNA expression array system. Human interleukin (IL)-15 was identified as an up-regulated transcription product during the secretory phase, in comparison with the proliferative phase, and therefore its expression in human uterus was examined by Northern blot analysis. In human endometrium, expression of IL-15 mRNA significantly increased during the secretory phase compared with the proliferative phase (P < 0.01). The most abundant expression of IL-15 mRNA during the menstrual cycle was observed in the midsecretory phase. In the first trimester pregnancy, the expression of IL-15 mRNA in the decidua was significantly higher than that in the chorionic villi (P < 0.01). By using an in-vitro decidualization with human endometrial stromal cells, it was demonstrated that the expression of IL-15 mRNA is up-regulated during progesterone-induced decidualization. These results suggest that IL-15 plays a role in uterine function during pregnancy, as well as during the menstrual cycle.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Progression of joint arthrosis 10 to 15 years after high tibial osteotomy.

Forty-eight knees in 44 patients who had a high tibial osteotomy performed for medial compartment osteoarthritis were reevaluated twice, once at 1 year after surgery and again at 10 to 15 years after the high tibial osteotomy, to determine the effects of high tibial osteotomy on progression of medial and lateral joint arthrosis. Radiologically, although arthrosis significantly increased in the medial and the lateral joint compartment, there was no significant difference in the degree of progression between the two compartments. There was a significant correlation between the progression of medial joint arthrosis evaluated at 10 years or more after surgery and the femorotibial angle measured at 1 year. There was no significant correlation between the progression of lateral joint arthrosis in 10 to 15 years and the femorotibial angle measured at 1 year. The average knee function score improved significantly from 59.1 +/- 5.5 points before surgery to 85.1 +/- 6.1 points at the 1-year followup. At the final followup, the clinical score (80.7 +/- 5.4) had deteriorated relative to the 1-year results but still was significantly better than the preoperative score. The current results indicate that the greater the surgical valgus correction, the slower the progression of medial joint arthrosis. Lateral joint arthrosis did not progress more quickly after high tibial osteotomy, even if an overcorrection was performed.

Aged↗
PubMed2000

Seroepidemiological investigation of feline chlamydiosis in cats and humans in Japan.

The prevalence of chlamydia antibodies in Japan was investigated in 215 cat sera, consisting of 88 sera of stray cats and 127 sera of pet cats, and 2,184 human sera, taken from 2,003 general persons and 181 small animal clinic veterinarians, by microimmunofluorescence (MIF) testing with Chlamydia psittaci Fe/Pn1 of feline origin and Prk/6BC of avian origin as antigens. The prevalence rates of anti-Fe/Pn1 antibodies were 45.5% in stray cats, 17.3% in pet cats, 1.7% in general persons and 8.8% in small animal clinic veterinarians. The prevalence rates of anti-Prk/6BC antibodies were 51.1% in stray cats, 15.0% in pet cats, 3.1% in general persons and 5.0% in small animal clinic veterinarians. These results suggested that feline chlamydia infection is widely spread in cats especially in stray cats in Japan, and suggested that feline chlamydiosis could be transmitted to people who are in close contact with infected cats.

Animals↗
PubMed2000

Relations of insulin resistance and serum concentrations of estradiol and sex hormone-binding globulin to potential breast cancer risk factors.

There is a hypothesis that hyperinsulinemia or insulin resistance may be a mediator for breast cancer risk factors. On the other hand, some, but not all, of the well-known risk factors of breast cancer have been associated with serum estrogen concentrations. We assessed the relationships of potential breast cancer risk factors to indicators of insulin resistance, fasting plasma insulin concentration and homeostasis model assessment insulin resistance (HOMA-R), in 88 postmenopausal Japanese women. We also examined whether insulin resistance would explain the association of breast cancer risk factors with serum estradiol and sex hormone-binding globulin (SHBG). Information on potential breast cancer risk factors, such as demographic characteristics, smoking and drinking habits, diet, exercise, menstrual and reproductive factors, was obtained by self-administered health questionnaire including a validated semiquantitative food frequency questionnaire. Body mass index (BMI) was significantly correlated with the ratio of estradiol to SHBG (Spearman r = 0.30, P = 0.0004), fasting plasma insulin (r = 0.45) and HOMA-R (r = 0.43, P = 0.0001) after controlling for age. The correlations were still significant between BMI and estradiol / SHBG ratio (r = 0.21, P = 0.047) after controlling for fasting plasma insulin and between BMI and fasting plasma insulin (r = 0.40, P = 0. 0001) as well as HOMA-R (r = 0.38, P = 0.0003) after controlling for estradiol / SHBG ratio. There is a possibility that effect of BMI on breast cancer risk is mediated by both insulin resistance and estrogen metabolism.

Aged↗
PubMed2000

Emergence of the precore mutant late in chronic hepatitis B infection correlates with the severity of liver injury and mutations in the core region.

OBJECTIVE: The reason that precore negative mutants (e-minus DNA) gradually become predominant in some patients during chronic hepatitis B virus infection is not clear. Theoretically, as long as both e-plus and e-minus DNA share the same epitopes in the core region, HBcAg-specific cytotoxic T lymphocytes (CTLs) cannot distinguish between the target peptides expressed by e-plus and e-minus DNA. Therefore, e-minus DNA may be accompanied by additional mutations in the core region, which may affect cytotoxic T lymphocyte recognition. To examine this possibility, the sequences of the precore and the entire core region of the hepatitis B virus genome were analyzed from paired serum samples in CH-B patients who experienced HBeAg to anti-HBe seroconversion (SC). METHODS: Patients were divided into two groups. Group A patients (n = 17) genome-converted to e-minus DNA in the precore region, which abolished HBeAg secretion within 3-4 yr after SC. Group B patients (n = 16) retained precore wild-type DNA for more than 3-4 yr after SC. To investigate the impact of the emergence of precore mutant type DNA on liver injury, alanine aminotransferase (ALT) levels were also examined. RESULTS: ALT flares were more severe among patients in group A than in group B. The average mean ALT level during the HBeAg negative phase of chronic infection was 54 +/- 38 in group A and 28 +/- 24 in group B. The average maximal ALT level during the HBeAg negative phase was 235 +/- 249 in group A and 83 +/- 106 in group B. Furthermore, all 17 patients in group A developed new core mutants during genome conversion. The average number of mutations in the core gene was 0.9 +/- 1.2 before genome conversion (e-plus DNA dominant phase) and increased to 2.8 +/- 1.3 for the 3-4 yr during genome conversion (e-minus DNA dominant phase). In contrast, only 56% (nine of 16) of patients in group B developed new core mutations after the loss of HBeAg. The average number of mutations in the core gene was 1.8 +/- 1.3 before SC (HBeAg-positive and e-plus DNA dominant phase), and decreased to 1.1 +/- 1.1 for 3-4 yr after seroconversion (anti-HBe-positive and e-plus DNA dominant phase). CONCLUSIONS: These data indicate that the emergence of a predominant precore negative genotype late in chronic hepatitis B virus infection is associated with the selection of additional mutations in the core gene, as well as with liver injury.

Adolescent↗
PubMed2000

Extrinsic cell infiltration and revascularization accelerate mechanical deterioration of the patellar tendon after fibroblast necrosis.

This study was performed to determine the contribution of extrinsic cell infiltration and revascularization into the patellar tendon in alteration of the mechanical properties of the patellar tendon after intrinsic fibroblast necrosis using 77 rabbits. In Group I, after the patellar tendon underwent the in situ freeze-thaw treatment, a wrapping treatment was performed to inhibit any extrinsic cell infiltration into the tendon. In Group II, the patellar tendon underwent the freeze-thaw treatment without any of the wrapping treatment. In Group III, the patellar tendon underwent the same wrapping treatment but without any freeze-thaw treatment. The cell culture study demonstrated that the in situ freeze-thaw treatment killed from 97 to 100 percent of the cells in the patellar tendon. Histologically, no cells were found in the midsubstance of the patellar tendon in Group I at 1, 3, and 6 weeks. In Group II, a number of cells and some vessels were found scattered in the tendon at 3 and 6 weeks. Mechanically, the elastic modulus and the tensile strength of the patellar tendon of Group II were significantly lower than those of Groups I and III at 3 and 6 weeks. These facts suggest that extrinsic cell infiltration and revascularization from the surrounding tissues accelerate the deterioration of the mechanical properties of the patellar tendon matrix after intrinsic fibroblast necrosis.

Animals↗
PubMed2000

Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX.

Malformations in the eye can be caused by either an excess or deficiency of retinoids. An early target gene of the retinoid metabolite, retinoic acid (RA), is that encoding one of its own receptors, the retinoic acid receptor beta (RARbeta). To better understand the mechanisms underlying this autologous regulation, we characterized the chick RARbeta2 promoter. The region surrounding the transcription start site of the avian RARbeta2 promoter is over 90% conserved with the corresponding region in mammals and confers strong RA-dependent transactivation in primary cultured embryonic retina cells. This response is selective for RAR but not retinoid X receptor-specific agonists, demonstrating a principal role for RAR(s) in retina cells. Retina cells exhibit a far higher sensitivity to RA than do fibroblasts or osteoblasts, a property we found likely due to expression of the orphan nuclear receptor TLX. Ectopic expression of TLX in fibroblasts resulted in increased sensitivity to RA induction, an effect that is conserved between chick and mammals. We have identified a cis element, the silencing element relieved by TLX (SET), within the RARbeta2 promoter region which confers TLX- and RA-dependent transactivation. These results indicate an important role for TLX in autologous regulation of the RARbeta gene in the eye.

Amino Acid Sequence↗
PubMed2000

Effective treatment with topical cyclosporin A of a patient with Cogan syndrome.

The purpose of this report is to describe the effective treatment of severe anterior segment inflammation due to Cogan syndrome through the use of topical administration of cyclosporin A. A 47-year-old female patient had been experiencing headaches and difficulties with her vision. Subsequent examination revealed the sudden onset of bilateral conjunctival injection and swelling of bilateral auricles. Despite the multiple treatment (systemic and topical corticosteroid and antibiotic therapy), necrotizing scleritis had appeared bilaterally and the scleral wall was thinning. Topical administration of 1% cyclosporin A was applied to both eyes 4 times a day. After 2 months of this therapy, the epithelial tissue covered the necrotizing tissue and her symptom of ocular pain was relieved and her corrected visual acuity was improved. This is the first case exhibiting that topical cyclosporin A is an effective treatment for severe anterior segment inflammation associated with Cogan syndrome.

Administration, Topical↗
PubMed2000

Pyridoxine-induced photosensitivity and hypophosphatasia.

We describe a case of photosensitivity due to pyridoxine hydrochloride (vitamin B(6)) in a heterozygote of hypophosphatasia. Photopatch tests using pyridoxine hydrochloride and pyridoxal 5'-phosphate, compounds referred to as vitamin B(6), with ultraviolet light A irradiation were positive. Laboratory examination showed low serum alkaline phosphatase. Tissue-nonspecific alkaline phosphatase exon amplification from DNA of the patient's lymphocytes detected deletion 1154-1156 hypophosphatasia mutation, indicating that this patient was diagnosed to be a heterozygote of hypophosphatasia. The seric pyridoxal 5'-phosphate level of this patient with hypophosphatasia was higher than in normals. Furthermore, after oral administration of vitamin B(6) this level increased greatly and long-lastingly, and this might be related to the low level of alkaline phosphatase in this patient. Photosensitivity in this patient may have been caused by abnormal metabolism of vitamin B(6) under the hypophosphatic condition.

Adult↗
PubMed2000

Heart rate recovery after exercise and cardiac autonomic nervous activity in children.

To investigate the difference in heart rate (HR) recovery after exercise between children and young adults, we administered a constant load of light exercise intensity and progressive treadmill exercise tests to nine children (aged 9 to 12 y, group A) and eight young adults (six male and two female, aged 17 to 21 y, group B) who had a history of Kawasaki disease without significant coronary arterial lesions. HR after both exercise protocols was analyzed. The low-frequency (LF) and high-frequency (HF) components of HR variability were measured, and LF/HF was calculated (log LF, log HF, log L/H). Arterial baroreflex sensitivity was assessed by the phenylephrine method. There were no differences between groups A and B in resting HR, peak HR, peak oxygen uptake, and decreases in systolic blood pressure during the recovery period. HR 1 and 2 min after peak exercise and 1 min after constant-load exercise was significantly lower in group A than in group B (p < 0.05), and the changes in HR from peak values after both exercise tests were also greater in group A than in group B (p < 0.05-0.01). Although no difference in arterial baroreflex sensitivity was observed, log HF was significantly higher in group A than in group B (p < 0.01), and log L/H was significantly lower in group A than in group B (p < 0.05). The value of log HF correlated inversely with the decrease in HR immediately after both exercise protocols (p < 0.05-0.01). Although log L/H correlated with the decrease in HR after peak exercise (p < 0.05-0.0005), the early decline in HR after constant-load exercise did not correlate with log L/H. Arterial baroreflex sensitivity did not correlate with the decrease in HR at any recovery time. These data suggest that the early phase of HR recovery after light to severe exercise is influenced by the cardiac parasympathetic nervous activity at rest and that the greater central cholinergic modulation of HR in children than in young adults may be responsible in part for children's faster HR recovery after exercise.

Adolescent↗
PubMed2000

Progesterone enhances interleukin-15 production in human endometrial stromal cells in vitro.

Interleukin-15 (IL-15) is a novel cytokine that stimulates lymphocyte proliferation and migration via a trimeric receptor sharing the ss and gamma signal-transducing chains with the IL-2 receptor. It is suggested that IL-15 is involved in regulating the proliferation and differentiation of uterine natural killer cells. In the human endometrium, we have recently reported that IL-15 messenger ribonucleic acid (mRNA) levels significantly increased during the secretory phase compared with those during the proliferative phase. In this study we investigated whether the female sex steroids progesterone (P) and estradiol (E(2)) regulate IL-15 messenger RNA (mRNA) and the secretion in human endometrial stromal cells (ESC) in vitro. Northern blot analyses revealed a significant increase in IL-15 mRNA levels in ESC treated with P alone or E(2) plus P compared with vehicle. Furthermore, P is a potent inducer of IL-15 mRNA expression in ESC in a dose-dependent manner. On the other hand, E(2) alone did not increase IL-15 mRNA expression. By enzyme-linked immunosorbent assay, IL-15 protein secretion was stimulated by P and further enhanced by combined treatment with E(2) and P, whereas E(2) alone was ineffective. It is suggested that IL-15 is deeply involved in the hormonal control of the human endometrium by P and E(2).

Blotting, Northern↗
PubMed2000

Antihyperglycemic effect of T-1095 via inhibition of renal Na+-glucose cotransporters in streptozotocin-induced diabetic rats.

T-1095, a derivative of phlorizin, is an orally active inhibitor of Na+-glucose cotransporter (SGLT). We investigated the acute antihyperglycemic effect of T-1095 in streptozotocin-induced diabetic rats (STZ rats). T-1095 and its metabolite T-1095A inhibited the SGLT activity in brush border membranes prepared from kidneys of both normal and STZ rats, but the latter agent was approximately 10 times more potent than the former. Single oral administration of T-1095 (30-100 mg/kg) dose-dependently induced glycosuria in normal rats. The fed glucose levels in STZ rats were dose-dependently suppressed by single oral administration of T-1095 (3-100 mg/kg), whereas there was only marginal hypoglycemic effect in normal rats. Since there was no effect on blood glucose in nephrectomized STZ rats, inhibition of renal glucose reabsorption rather than intestinal glucose absorption mainly contributes to the antihyperglycemic effect of T-1095. In conclusion, T-1095 is the first orally active agent which has an acute antihyperglycemic action in the absence of endogenous insulin secretion with a low risk of hypoglycemia and has therapeutic potential for treatment of diabetes mellitus.

Animals↗
PubMed2000

Inhibitory effect of human immunodeficiency virus protease inhibitors on multidrug resistance transporter P-glycoproteins.

The objective of this study was to determine whether human immunodeficiency virus (HIV) protease inhibitors (saquinavir, ritonavir and nelfinavir) interact with other HIV protease inhibitors and/or HIV reverse transcriptase inhibitors (zidovudine, didanosine, lamivudine, zalcitabine and sanilvudine). We measured transport of nelfinavir, an HIV protease inhibitor which is known as a substrate for the multidrug resistance transporter P-glycoprotein (P-gp), in an epithelial monolayer model and Ki for P-gp of some drugs by a calcein flux assay. Transport in a basal to apical direction was 2-fold greater than apical to basal flux for nelfinavir, Ki for P-gp of a potent P-gp inhibitor cyclosporin A was 1.09 microM and those of ritonavir and nelfinavir were 111 microM and 28.6 microM, whereas all HIV reverse transcriptase inhibitors gave high K1 values. These data show that nelfinavir, which is a substrate for P-gp, inhibits a P-gp function as a drug efflux pump and that HIV reverse transcriptase inhibitors do not inhibit P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Correction of hyperglycemia and insulin sensitivity by T-1095, an inhibitor of renal Na+-glucose cotransporters, in streptozotocin-induced diabetic rats.

We investigated the effects of T-1095 (3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl)-beta-D-glucopyranoside), an orally active inhibitor of Na+-glucose cotransporter, on hyperglycemia and insulin resistance in skeletal muscle of streptozotocin (STZ)-induced diabetic rats. Chronic (4 weeks) administration of T-1095 as food admixture (0.01 -0.1% wt/wt) suppressed the blood glucose level without affecting the food intake and body weight. In addition, the reduced 2-deoxyglucose uptake and lactate release in the soleus muscle of STZ rat was ameliorated by chronic treatment of T-1095. These data suggest that T-1095 improves insulin sensitivity in skeletal muscle through correction of hyperglycemia and has novel therapeutic potential for treatment of diabetes mellitus through removing glucose toxicity.

Animals↗
PubMed2000

Focal extraction of surface-bound DNA from a microchip using photo-thermal denaturation.

High-throughput, selective extraction of a particular DNA fragment from a mixture of DNA before PCR amplification is becoming increasingly important in the DNA analysis field. Although the latest microchip technology has enabled real-time DNA expression analysis using hybridization between surface-bound probe DNA and sample DNA, the potential of this technology in purification of a small amount of DNA has not been demonstrated. We report here a method for area-selective release and collection of specific DNA, in which an IR laser beam is focused onto surface-bound sample DNA at the target-spotted area to denature hybridized DNA. First, sample DNA labeled with a fluorescent dye was hybridized to a probe DNA immobilized on a chromium-coated chip. A 1053-nm IR laser beam with an intensity of 10-100 mW was then focused on the target area with a spatial resolution of 10 microns, causing the release of the fluorophore-labeled sample DNA as a result of photo-thermal denaturation. Confirmation of the amount of eluted DNA by PCR amplification after collection indicated that more than 10(-20) mol DNA/micron 2 area was eluted from the microchip, representing more than 70% of the chip-bound sample DNA. These results indicate that this method can be applied to the highly sensitive purification of DNA in microchip technology.

Chromium↗
PubMed2000

Antibody-mediated insulin resistance treated by cessation of insulin administration.

A 45-year-old Japanese man was referred to our hospital because of hyperglycemia despite the administration of as much as 120 U/day of human insulin. He had no history of injecting animal insulin. Free insulin was below 5 microU/ml, but a high titer of total insulin (about 3,000 microU/ml) was observed, suggesting the presence of antibodies against human insulin. Scatchard analysis showed an increased insulin binding capacity in the plasma characterized by a higher affinity for insulin. He was successfully treated by cessation of insulin administration. A Scatchard analysis series showed that a reduction in the insulin binding capacity of antibodies paralleled the improvement in glycemic control.

Blood Glucose↗