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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 181 records · Page 10Linked to original sources

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↗

Drug targeting efficacy to underlying muscle following topical application. I. Evaluation based on a physiological pharmacokinetic model.

A physiological pharmacokinetic model describing the absorption and disposition of topically applied drugs was proposed, and the effect of various pharmacokinetic and physiological parameters on the drug delivery into the targeted muscle was simulated. The proposed model consists of vehicle, and stratum corneum, viable epidermis and muscle below the application and reference sites, and plasma, each joined with transfer clearance and plasma flow. Indomethacin concentrations in tissues and plasma after topical application to rats could be explained by the model. Most indomethacin delivered into the underlying muscle was via direct penetration. The model simulation showed that the increase in plasma clearance and clearance between viable skin and muscle, and the decrease in application area and plasma flow rate into viable skin and muscle would promote the targeting efficacy of topically applied drugs to the underlying muscle.

Administration, Topical↗

A new pentanorlanostane derivative, cladosporide A, as a characteristic antifungal agent against Aspergillus fumigatus, isolated from Cladosporium sp.

In the course of searching for new antifungal agents, a new pentanorlanostane derivative, cladosporide A (1), was isolated along with ergosterol, ergosterol peroxide and 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) from Cladosporium sp. as a characteristic antifungal agent against the human pathogenic filamentous fungus Aspergillus fumigatus. The structure of 1 was established as 3beta,22-dihydroxy-23,24,25,26,27-pentanorlanostane-29-al by spectroscopic and chemical investigation and X-ray crystallographic analysis. Inhibitory activity against A. fumigatus (IC80 0.5-4.0 microg/ml) was observed for cladosporide A (1), but no activity was observed against pathogenic yeasts, Candida albicans and Cryptococcus neoformans, and other pathogenic filamentous fungi, Aspergillus niger and A. flavus. The 4beta-aldehyde residue in 1 might be essential for the antifungal activity, since 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) showed no inhibition against the above four fungi.

Antifungal Agents↗

A simple and rapid extraction of high molecular weight chromosomal DNA from Bacillus subtilis protoplasts for cosmid cloning and interspecific transformation.

After conversion of Bacillus subtilis vegetative cells to protoplasts, a simple and rapid method for extracting high-molecular-weight chromosomal DNA was devised with the inclusion of bovine serum albumin and phenol-chloroform treatments. The DNA sample thus prepared was the size of 100-450 kb and could be used for cosmid cloning and interspecific transformation.

Animals↗

Control of blood pressure and prevention of end-organ damage in patients with accelerated hypertension by combination with arotinolol and extended release nifedipine.

In patients with accelerated (malignant) hypertension, end-organ damage is the determinant factor for prognosis. Although recent advances in antihypertensive therapy have improved the outcome of patients with accelerated hypertension, the effectiveness of antihypertensive therapy still remains less convinced. In this study, we followed 13 patients clinically diagnosed with accelerated hypertension (defined as diastolic blood pressure > 130 mmHg, retinopathy with K-W IV and accelerated renal impairment) for 3 yr. One patient died due to acute myocardial infarction arising from poor compliance with antihypertensive therapy. One patient was maintained on hemodialysis for 3 yr. One patient was introduced for continuous ambulatory peritoneal dialysis (CAPD) for a year and then lived without dialysis therapy. The remaining 10 patients were followed for 3 yr. All patients were initially treated with intravenous administration of calcium antagonist for reduction of blood pressure, followed by hemodialysis therapy if needed. After stabilization of blood pressure, combination therapy with extended release nifedipine (40 to 80 mg daily) and arotinolol (20 mg daily) was started. The targets for blood pressure control were a systolic pressure of 135 mmHg and a diastolic pressure of 80 mmHg. If blood pressure control was unsatisfactory, guanabenz (2 to 4 mg before bedtime), a central acting drug, was added. At presentation, the mean diastolic blood pressure (mDBP) among the 10 remaining patients was 134 +/- 2 mmHg, the mean serum creatinine (mScr) was 4.5 +/- 0.7 mg/dl and the left ventricular mass index (LVMi) as measured by echocardiography was 150 +/- 9 g/m2. At 1 yr, the mDBP was reduced to 90 +/- 3 mmHg, the mScr to 2.9 +/- 0.9 mg/dl and the LVMi to 140 +/- 9 g/m2. At 3 yr, the mDBP was stabilized at 79 +/- 3 mmHg, the mScr maintained at 2.2 +/- 0.4 mg/dl, and the LVMi reduced to 128 +/- 9 g/m2. These results indicate that appropriate blood pressure control is important for improvement of renal impairment and cardiac damage in patients with accelerated hypertension. Moreover, combination therapy with arotinolol and extended release nifedipine may be beneficial for this purpose.

Adrenergic beta-Antagonists↗

The characteristics of fatigue symptoms and their association with the life style and the health status in school children.

In order to evaluate the characteristics of fatigue symptoms and their association with the life style and the health status, we examined using data accumulated by the longitudinal surveys from 1992 to 1998, in 118 six-year primary school children and 129 second-year junior high school children. The complaints of "drowsiness and dullness", such as "become drowsy" (71%), "give a yawn" (59%) and "want to lie down" (51%), respectively, were most frequently observed. The proportion of these complaints was high before the first morning class, but decreased when the children leave school. Notably, the complaints of "difficulty in concentration" annually have increased. Children with undesirable eating habits, particularly those who often eat salty foods, or poor life style, such as staying up late at night tended to have more complaints of fatigue symptoms. By correlation analysis, these complaints were significantly related to the obesity degree, blood pressure, HDL cholesterol and atherogenic index. These results support the hypothesis that fatigue symptoms increase or are associated with life style and health status. Consequently, it is necessary to improve the life style such as dietary habits and rhythm of life for the reduction of fatigue symptom.

Child↗

Dream-recall frequency and waking imagery.

The purpose was to investigate the relationship between dream-recall frequency and waking imagery, so 323 undergraduates completed four imagery tests: (1) Sheehan's modified version of Betts' Questionnaire on Mental Imagery, (2) Marks' Vividness of Visual Imagery Questionnaire, (3) the Gordon Test of Visual Imagery Control, (4) Richardson's Verbalizer Visualizer Questionnaire, and a dream-recall questionnaire which contained a question about dream-recall frequency. When scores on the four imagery tests and the seven sensory subscales of the Questionnaire on Mental Imagery were compared for the n = 82 frequent and n = 80 infrequent dream recallers, higher recall was associated with more vivid voluntary images and more frequent use of visual imagery; however, control visual imagery as measured by the Test of Visual Imagery Control was not associated with dream-recall frequency. Scores for frequent use of visual imagery on dream-recall frequency might have been due to the two items of the Verbalizer-Visualizer Questionnaire which asked about dream experiences. The results for the seven sensory subscales of the Betts' questionnaire indicated that the frequency of dream recall was significantly related to scores on visual, cutaneous, and organic but not on auditory, gustatory, kinaesthetic, and olfactory subscales. No significant differences were found between males and females. Present findings indicated that forming vivid mental images in the waking state is related to frequency of dream recall and support Cohen's salience theory of dream recall, i.e., that evoking vivid waking mental images voluntarily may play an important role in retrieving dream images or saving them during wakefulness. All sensory modalities should be considered in study of dream recall.

Adult↗

Methionine imbalance and toxicity in calves.

The occurrence of methionine imbalance and toxicity was examined using 70- and 100-kg Holstein bull calves. The animals had been trained to maintain reflex closure of the reticular groove after weaning at 5 wk of age, and Trials 1 (n = 30) and 2 (n = 24) were conducted on animals at 7 and 12 wk of age, respectively. Calves received a corn-soybean meal diet in Trial 1 and a corn-corn gluten meal diet in Trial 2. In Trial 1, postruminal administration of 6 g of DL-methionine/d increased ADG, feed intake, gain/feed, and N retention compared with a control group receiving N-free supplement. However, the administration of 12 g of DL-methionine/d did not improve these variables, whereas both 18 and 24 g/d resulted in BW loss and decreased gain/feed and N utilization efficiency. In Trial 2, postruminal administration of 16 g/d of L-lysine from L-lysine monohydrochloride increased ADG, gain/feed, and N utilization efficiency compared with a control group receiving a N-free supplement. The administration of 8 g of DL-methionine/d in addition to L-lysine did not exert an adverse effect on these variables. However, the additional supplementation of 16 and 24 g of DLmethionine/d negated the improvement, whereas 32 g/d resulted in BW loss and decreased gain/feed and N utilization efficiency. These results showed that a methionine imbalance and toxicity occurred in calves with even a modest excess of DL-methionine, and 70-kg calves were more susceptible to methionine toxicity than 100-kg calves. Plasma concentrations of branched-chain amino acids and phenylalanine linearly decreased with increasing amounts of additional DL-methionine from 0 to 32 g/d in Trial 2. However, such a decrease occurred mainly within the range from 0 to 12 g/d in Trial 1. This decrease was suggested to occur in relation to methionine metabolism via the transsulfuration pathway.

Amino Acids↗

Interleukin-2: developing additional cytokine gene therapies using fibroblasts or dendritic cells to enhance tumor immunity.

PURPOSE: Recombinant interleukin (IL)-2 administration can mediate regression of solid tumors in patients with melanoma and renal cell carcinoma. A better understanding of the mechanisms of IL-2-mediated antitumor effects has led to the investigation of novel immunotherapeutic approaches. The rationale for these immunotherapeutic approaches and the results of preliminary clinical studies are presented. PATIENTS AND METHODS: The therapeutic potential of dendritic cells and the role of FLT3 ligand, a potent hematopoietic growth factor, was investigated in a variety of preclinical models. In addition, a clinical study with autologous dendritic cells pulsed with synthetic melanoma peptides derived from the MART1/ Melan A, gp100, and tyrosinase proteins was conducted. Twenty-eight human leukocyte antigen (HLA)-A2+ melanoma patients received an average of 106 dendritic cells a week for 4 weeks. RESULTS: In a murine liver metastases model, FLT3 ligand administration alone or in combination with IL-12 or IL-2 had significant antitumor effects and resulted in significant infiltration of the tumor border by lymphocytes and dendritic cells, which was associated with an increased number of apoptotic figures. Administration of melanoma peptide-pulsed dendritic cells to 28 patients with advanced metastatic melanoma produced a complete response in two patients and a partial response in one. Significant infiltration of T cells and dendritic cells into melanoma lesions was observed. CONCLUSION: These studies confirm the feasibility of immunotherapeutic approaches using dendritic cells and FLT3 ligand and demonstrate their potential antitumor activity. These approaches may be effective for patients with metastatic melanoma and other solid tumors and will likely be used to improve the efficacy of IL-2-based immunotherapy.

Cancer Vaccines↗

XYY male with essential thrombocythemia in childhood.

We describe a boy with XYY male accompanied with essential thrombocythemia. This is, to our knowledge, the first complete case report of the kind in the pediatric literature. The patient was asymptomatic, but at age 5 his platelet count had increased to 145.5 x 10(4)/microL, and he was diagnosed as having essential thrombocythemia based on the diagnostic criteria of the Polycythemia Vera Study Group. At that time, it was discovered by chromosome analysis of both bone marrow and peripheral blood cells that he was XYY male. At times during the clinical course when his platelet count was 94.1 x 10(4)/microL, his serum thrombopoietin (measured by enzyme-linked immunosorbent assay) was 1.09 fmol/mL, which was normal for his age. Aspirin was administered, and he remained asymptomatic throughout the course. After 2 years, he underwent a spontaneous remission. Because of the small number of reported cases, we have been unable to determine the relation between XYY males and essential thrombocythemia.

Aspirin↗

Changes in calcium metabolism and bone demineralization after orthotopic intestinal neobladder creation.

PURPOSE: We evaluated calcium metabolism and bone demineralization by measuring specific markers for bone reabsorption and bone mineral density in patients with an intestinal neobladder. MATERIALS AND METHODS: We studied 33 men 55 to 72 years old who underwent creation of an orthotopic sigmoid (23), ileocolic (8) or ascending colon (2) neobladder after cystectomy. Mean followup plus or minus standard deviation (SD) was 28.4+/-30.1 months (range 4 to 114). Serum electrolytes and arterial blood gases were measured. As markers of bone absorption we assayed urinary pyridinoline, deoxypyridinoline and N-terminal pyridinoline cross-linked telopeptides, and serum pyridinoline cross-linked C-terminal telopeptide of type I collagen. Bone mineral density of the spine and femur was determined by dual x-ray absorptiometry. RESULTS: Mean blood pH plus or minus SD was 7.38+/-0.04 (range 7.29 to 7.43). Mean plasma bicarbonate was 22.9+/-3.4 mmol./l. and mean base excess was -1.63+/-3.61 mmol./l. Serum sodium, potassium, calcium, alkaline phosphatase and phosphate were normal in most patients. Mean serum chloride was 108.0+/-3.5 mEq./l., and was elevated in 9 of the 33 patients (27.3%). Serum intact parathyroid hormone was normal in all patients, osteocalcin was increased in 2 and 1alpha, 25-dihydroxyvitamin D3 was decreased in 2. Pyridinoline cross-linked C-terminal telopeptide of type I collagen was higher in 19 of 33 cases (57.6%) and N-terminal pyridinoline cross-linked telopeptides were elevated in 6 (18.2%). Pyridinoline and deoxypyridinoline were higher than normal in 19 (57.6%) and 7 (21.2%) patients, respectively. C-terminal telopeptide of type I collagen and deoxypyridinoline significantly correlated with serum pH (p = 0.017 and 0.0418, respectively). Z score for the bone mineral density of L2 to L4, the femoral neck and Ward's triangle was -0.350+/-1.031, -0.82+/-0.99 and -0.94+/-1.01, respectively. CONCLUSIONS: In patients with a neobladder of intestinal segments metabolic acidosis results in increased bone absorption and decreased bone mass. Thus, attention should be given to bone metabolism in patients with even mild acidosis after orthotopic neobladder creation.

Aged↗

Sigmoid neobladder in women after radical cystectomy.

PURPOSE: Neobladder reconstruction using an intestinal segment is the common procedure of choice in men after cystectomy. Recently this procedure has been extended to women. We present our surgical and functional experience with the sigmoid neobladder in women. MATERIALS AND METHODS: A total of 11 women 49 to 74 years old (mean age plus or minus standard deviation 60 +/- 8.5) with transitional cell carcinoma of the bladder underwent lower urinary tract reconstruction with a modified sigmoid neobladder after nerve and urethral support sparing cystectomy. After at least 3 months voiding pattern and continence status were evaluated. Pressure flow studies and uroflowmetry were performed, the urethral pressure profile and neocystourethral angle were measured, and blood chemistry was analyzed. RESULTS: After at least 3 months complete daytime continence was achieved in 2 patients, while 8 had mild stress incontinence. At night 8 of the 11 women (72.7%) were continent with or without voiding at regular intervals. All except 1 patient voided to completion. Of the 2 patients with complete continence 1 needed clean intermittent catheterization 4 months postoperatively. Mean maximal urinary flow was 19.9 +/- 10.5 ml. per second. Excluding the woman who required catheterization mean residual urine volume was 15 +/- 13.7 ml. Postoperatively maximal urethral pressure was slightly lower and functional urethral length was about 10 mm. shorter than preoperatively. The mean neocystourethral angle was 131.9 +/- 21.7 degrees. Mean pH, bicarbonate and base excess were 7.38 +/- 0.03, 23. 48 +/- 2.34 mmol./l. and -0.92 +/- 2.50, respectively. CONCLUSIONS: After nerve and urethral support sparing cystectomy a modified sigmoid neobladder may be constructed in women to obtain satisfactory continence and voiding results.

Aged↗

[Multi-vasospastic angina refractory to medical therapy caused by hyperthyroid stage of chronic thyroiditis and hypereosinophilia: a case report].

A 49-year-old woman with bronchial asthma was followed up at our hospital. After 3 years, she experienced an attack of chest pain with ST elevation in the precordal leads of electrocardiography. After admission, the chest pain and ST elevation disappeared, but the chest pain recurred after 6 days. Coronary angiography revealed no significant stenosis in the coronary arteries. After discharge, she had the chest pain repeatedly. ST elevation in the II, III, aVF leads was recorded. The diagnosis was coronary multispasm. The chest pain was refractory to medical therapy. Hypereosinophilia developed and bronchial asthma worsened. After steroid administration, the angina and bronchial asthma ceased. She has lost about 15 kg during 1 year. Laboratory data revealed low thyroid-stimulating hormone, high thyroid hormone, positive thyroglobulin antibody, and negative thyroid-stimulating hormone receptor antibody. The diagnosis was chronic thyroiditis. The multi-vasospastic angina refractory to medical therapy was caused by the hyperthyroid stage of chronic thyroiditis and hypereosinophilia.

Angina Pectoris↗

Immunohistochemistry for parathyroid hormone-related protein (PTHrP) in benign and malignant mammary mixed tumors of dogs with and without hypercalcemia.

We evaluated the expression of parathyroid hormone-related protein (PTHrP) by immunohistochemistry in eight benign and malignant mammary mixed tumors of dogs with (n = 4) and without (n = 4) hypercalcemia. Positive immunoreactive staining for PTHrP was observed in all four tumors from hypercalcemic dogs. The mammary tumors from 2 of the 4 normocalcemic dogs stained positively for PTHrP, but the numbers of immunoreactive cells and intensity of the immunoreaction were less than in the hypercalcemic dogs. In the other 2 tumors without hypercalcemia, the tissue samples were negative for PTHrP.

Animals↗

[Gradually enhancing breast cancer on dynamic MRI].

PURPOSE: The aim of our study was to evaluate the frequency and the radiologic and pathologic features of gradually enhancing breast cancers on contrast enhanced dynamic MRI. MATERIAL AND METHODS: 83 patients with pathologically proven breast cancer underwent contrast enhanced dynamic MRI. Breast cancers that showed a gradually enhancing pattern were selected, and their pathological features and the findings in other imaging modalities were retrospectively analyzed. RESULTS: Of 83 lesions, 8 lesions (10%) showed a gradually enhancing pattern on dynamic MRI. The lesions included 3 papillotubular carcinomas, 3 scirrhous carcinomas, one solid-tubular carcinoma, and one mucinous carcinoma. All of them had imaging features suggesting malignancy on mammography and ultrasonography. Histopathologically, all 7 invasive ductal carcinomas showed prominent fibrosis in the stroma, and one showed many dilated ducts. One mucinous carcinoma showed large mucinous pools. CONCLUSION: Some breast cancers may show a gradually enhancing pattern on dynamic MRI. Other imaging features should be taken into account in the differential diagnosis of breast tumors.

Adult↗

Impact of introduction of continuous ambulatory peritoneal dialysis on blood pressure: analysis of 24-hour ambulatory blood pressure.

Introduction of continuous ambulatory peritoneal dialysis (CAPD) induces a variety of hemodynamic changes in patients with end-stage renal failure. Among them, blood pressure (BP) control is likely to be the most important in determining long-term survival. The aim of our study was to use 24-hour ambulatory blood pressure monitoring (24 ABPM) to evaluate the previous and present BP status of patients on CAPD. We studied 18 non diabetic hypertensive patients who were introduced onto CAPD. At least 3-6 months before the introduction of CAPD, recordings of 24 ABPM were obtained. These recordings were then compared to others obtained 2-3 months after the introduction of CAPD. The average BP was higher before CAPD than after (160/91 +/- 10/5 mmHg vs 154/88 +/- 6/3 mmHg, p < 0.01). In addition, the doses and number of antihypertensive drugs used by the patients were reduced. Analysis of 24 ABPM revealed BP reduction predominantly in the daytime and less in the nighttime after introduction of CAPD. These results indicate that introduction of CAPD cannot reduce susceptibility of cardiovascular events, because nocturnal elevation of BP remains unchanged. We are therefore reminded that, after introduction of CAPD, casual BP measurements confined to the daytime may underestimate cardiovascular risk.

Adult↗

Glucocorticoid restores the deterioration of water transport in the peritoneum through increment in aquaporin.

This study was carried out to investigate the role of aquaporin (AQP) in the peritoneum undergoing continuous ambulatory peritoneal dialysis (CAPD). Furthermore, we examined the effects of treatment with prednisolone (PSL) in a rat model of peritoneal sclerosis. We modelled peritoneal sclerosis by using dialysis solution with the addition of 0.1% chlorhexidine gluconate (CHG) for 10 days. Twenty male Wistar Kyoto (WKY) rats were divided into four groups and dialyzed with various solutions: (1) saline (NS group, n = 5); (2) 10% glucose (TZ group, n = 5); (3) 0.1% CHG (CHG group, n = 5); and (4) 0.1% CHG plus PSL (CHG + PSL group, n = 5). Expression of mRNA of AQPs (AQP-1-AQP-4) was studied by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR). Expression of AQP-4 was also measured by Western blot analysis. Ultrafiltration volume and peritoneal function were measured by the peritoneal equilibration test. In the TZ group, expression of AQP-1 and AQP-4 were significantly enhanced, in parallel with an increment in ultrafiltration volume. On the other hand, in the CHG group, expression of AQP-1 and AQP-4 were significantly suppressed, and ultrafiltration volume was lost. The use of PSL with CHG completely restored the expression of AQP-1 and AQP-4, and peritoneal function improved. No expression of AQP-2 and AQP-3 was seen in the peritoneum. Our results suggest that AQP-1 and AQP-4 may be important factors in water transport in patients undergoing CAPD. PSL might be an effective treatment to prevent the progress of peritoneal sclerosis in patients undergoing CAPD.

Animals↗