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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

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

Expression of transforming growth factor-beta s and their receptors by human retinal glial cells.

PURPOSE: To help test the hypothesis that transforming growth factor beta (TGF-beta) may serve an autocrine function in the retina, we asked whether human Müller (glial) cells in culture express TGF-beta receptors, contain transcripts for various isoforms of this cytokine, and release TGF-beta s into the medium. METHODS: Using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique with specific primers for TGF-beta 1, -beta 2 and -beta 3 precursors and for TGF-beta type I and type II receptors, we searched for mRNA transcripts expressed by cultured human Müller cells. Also, an ELISA assay allowed quantification of the levels of various TGF-beta s in medium exposed to these glial cells. RESULTS: Human Müller cells in culture express transcripts for both type I and type II TGF-beta receptors and also for TGF-beta 1 and TGF-beta 2. In conditioned medium, the concentration of TGF-beta 1 in the mature form was below detectable levels, and the total TGF-beta 1 was relatively low (mean = 252 pg/ml in confluent cultures). In contrast, the mean levels of mature (55 pg/ml) and total (2530 pg/ml) TGF-beta 2 were markedly higher. CONCLUSIONS: Our observations that cultured Müller cells contain mRNA coding for the TGF-beta 2 precursor, release TGF-beta 2 into the medium and express transcripts for both type I and type II TGF-beta receptors are consistent with the idea that this cytokine serves an autocrine function for these glia in the retina.

Cells, Cultured↗
PubMed1998

Predictability of conventional tests for the assessment of bladder outlet obstruction in benign prostatic hyperplasia.

BACKGROUND: The degree of bladder outlet obstruction (BOO) in benign prostatic hyperplasia (BPH) is most accurately quantified by pressure flow studies (PFS), although these studies are more invasive and complicated than conventional tests. We examined how precisely conventional tests predicted the PFS-assessed degree of BOO. METHODS: The study population consisted of 232 BPH patients who had undergone routine conventional tests and PFS. Correlation of the conventional test results with the degree of BOO assessed by PFS was examined by Spearman's correlation coefficients. Regression and subgroup analyses were performed to predict the degree of BOO using the conventional test results as the explanatory variables. RESULTS: The degree of BOO correlated with prostate volume, the degree of endoscopic obstruction, and to a lesser extent, with the maximum flow rate (Qmax) and age. The predictability of conventional tests alone, or in combination, for BOO, was approximately 60% to 70%, which is not acceptable for investigational use. However, almost all patients with a prostate volume larger than 30 mL, or with severe obstruction on urethroscopic findings, had an obstructed bladder outlet. CONCLUSION: PFS is mandatory when the precise evaluation of the degree of BOO is required, and patients are highly likely to have an outlet obstruction when they have a prostate larger than 30 mL, or severely obstructed posterior urethra on endoscopy.

Aged↗
PubMed1998

Urologic morbidity and its influence on global satisfaction with treatment outcome after radical prostatectomy for prostate cancer.

BACKGROUND: This cross-sectional observational study examined urologic morbidity and its effects on Japanese patients' global satisfaction with their treatment outcome. METHODS: A questionnaire was mailed to 44 men who had undergone radical prostatectomy for prostate cancer at a mean age of 65.5 years and were free from recurrent symptoms at a mean follow-up of 3.3 years. Most (70%) had pathologic stage C or D1 disease and many (86%) had received adjuvant endocrine therapy. After reporting urinary symptoms, the patients estimated their overall urinary, sexual, physical, psychological, and social functioning, and global satisfaction level with their treatment outcome. Regression analysis was performed to detect significant factors in predicting overall urinary conditions or satisfaction. RESULTS: Daily urinary leakage and forceless urinary stream was noted in 30% and 23% of patients, respectively. Overall urinary conditions were evaluated as good or very good in 61 % of patients, and were most significantly associated with the patient's satisfaction with their force of urinary flow (P < 0.001). Global satisfaction with treatment outcome was estimated as good or very good in 80% of patients, and it was predicted by physical functions (P= 0.013) and psychological distress (P= 0.036), and to a lesser extent by urinary conditions (P= 0.195). CONCLUSION: A forceless urinary stream was the most significant determinant for overall urinary conditions in patients who had a radical prostatectomy. Global satisfaction with treatment outcome was only marginally affected by urinary conditions. Physical function and psychological distress were major factors affecting the satisfaction level in this population.

Aged↗
PubMed1998

Optimal conditions to induce rat adrenal medullary changes, such as pheochromocytoma, by nicotine.

BACKGROUND: Nicotine-induced adrenal medullary hypertrophy in rats has been suggested to be a model for pheochromocytoma. Study conditions for proving such an assertion, however, have not been optimized. METHODS: Studies on strain difference, dose dependency, and the time course of catecholamine metabolism in response to nicotine treatment were conducted. Under the putative optimal experimental conditions, metabolic and histologic changes in the adrenal medulla were investigated. RESULTS: Male Wistar rats treated with a maximum dose of 4 mg/kg per day of nicotine for 9 weeks, including a 2-week lead-in period, developed highly consistent changes in the adrenal medulla. Concerning metabolic indices, the norepinephrine content of the adrenal and the urinary excretion of epinephrine and metanephrine were significantly elevated. Hyperplastic and hyperactive states of the adrenal medulla were also indicated by a morphometric analysis on electron microscopic figures. These showed an enlarged cytoplasmic area, the development of a rough-surfaced endoplasmic reticulum, and an increased number and density of intracellular catecholamine granules. The metabolic changes were found to reverse 3 weeks after the cessation of nicotine administration. CONCLUSION: These results provide better-defined experimental conditions for an animal model of pheochromocytoma.

Adrenal Medulla↗
PubMed1998

Expression of epidermal growth factor and epidermal growth factor receptor immunoreactivity in the asthmatic human airway.

Chronic airway inflammation, one of the pathophysiologic features of bronchial asthma, is suspected to be responsible for irreversible pathological changes of airways, called airway remodeling. To examine the mechanisms of airway remodeling in asthma, we investigated the expression of epidermal growth factor (EGF) and its receptor immunohistochemically in asthmatic human airways. Airway specimens from seven patients with asthma were obtained from autopsied and surgically resected lungs. Control specimens were obtained from lungs of eight subjects without asthma and other pulmonary complications at autopsy. We stained those specimens by the avidin-biotin-peroxidase complex (ABC) method with anti-human polyclonal EGF antibody and monoclonal EGF receptor antibodies. Three different portions of airways-large bronchi (about 1 cm in diameter), small bronchi (about 3 mm in diameter), and peripheral airways (less than 2 mm in diameter)-were examined. The thickness of the bronchial smooth muscle and basement membrane was significantly greater in the asthmatic airways than in controls. Clear immunoreactivities of EGF were widely observed on bronchial epithelium, glands, and smooth muscle in asthmatic airways. In the controls, the bronchial epithelium and the bronchial glands partially expressed faint EGF immunoreactivity. For the EGF receptor, clear immunoreactivities were also observed on bronchial epithelium, glands, smooth muscle, and basement membrane in asthmatic airways. In control airways, only part of the bronchial epithelium and smooth muscle weakly expressed EGF receptor immunoreactivity. These results suggest a possible contribution of EGF to the pathophysiology of bronchial asthma, including airway remodeling.

Adult↗
PubMed1998

[An analysis of the status of surgical transfusion in Sapporo Medical University Hospital].

To evaluate the present status of blood transfusion during operation in our hospital, we retrospectively analyzed the amount of preoperative preparation & intraoperative use of homologous blood and the circumstances of autologous blood transfusions. The amount of prepared blood was 4,505 units of which 1,187 units were transfused; the mean cross matched-to-transfused (C/T) ratio was 3.8. A trial of maximum surgical blood order schedule (MSBOS, C/T = 1.5) revealed that we could save over 70% of the homologous blood presently prepared. Preoperative blood donation (PBD) and intraoperative autologous blood transfusion (IAT) were performed in 74 cases (47.4%) and 55 cases (35.3%), respectively, of all 156 blood-transfused cases, and the operations were performed without homologous blood transfusion in 88.0% of PBD cases and 67.3% of IAT cases respectively. We are sure that the introduction of MSBOS will lead to a more efficient use of autologous blood, and that we should use homologous blood transfusion techniques so far as is possible to avoid autologous blood transfusion.

Blood Loss, Surgical↗
PubMed1998

[Two cases of clipping surgery of cerebral aneurysm under profound hypothermia with closed-chest extracorporeal circulation].

A 68-year-old female and a 47-year-old male patients underwent clipping surgery for giant basilar arterial and thrombotic internal carotid arterial aneurysms respectively with closed-chest extracorporeal circulation (femoro-femoral bypass). Profound hypothermia and continuous infusion of thiamylal were used to prevent brain damage. Blood outflow via the femoral vein was sufficient to induce profound hypothermia down to 20 degrees C. Hemodynamics were controllable without catecholamines during closed-chest extracorporeal circulation. Preoperative symptoms significantly improved and no neurological complication was observed in either case postoperatively. Right femoral phlebothrombosis was, however, observed in one case. In conclusion, profound hypothermia with closed-chest extracorporeal circulation is a safe technique to reduce the complications induced by open-chest technique, but special attention should be given to postoperative phlebothrombosis.

Aged↗
PubMed1998

[Evaluation of risks for postoperative pulmonary complications using a preoperative consultation system].

We retrospectively investigated the perioperative management and postoperative pulmonary complications of patients who had preoperative respiratory problems and consultations with anesthesiologists. These patients numbered eight hundred, 23.7% of all patients who had preoperative consultations, and 40.9% and 62.0% of the 800 had preoperative and postoperative respiratory management, respectively. Forty eight patients (6.0%) received postoperative artificial respiration. One hundred and twenty four patients (15.5%) had some respiratory complications post-operatively, and 5 patients (0.7%) died mainly because of the complications. In an evaluation of these patients with the modified predicted risk factors of Okutsu including the obesity factor and smoking history, there was no respiratory complication in patients under 14 points. Patients with high points of more than 20 included almost all of the patients (114 patients, 91.9%) who had postoperative respiratory complications. We conclude that our preoperative consultation system works well and that the modified predicted-risk factors for postoperative pulmonary complications is useful for the standardization and objectivity of preoperative patient evaluation.

Humans↗
PubMed1998

[Neoadjuvant androgen deprivation preceding to radical prostatectomy--its role in short-term and long-term outcomes].

Neoadjuvant androgen deprivation has been demonstrated to reduce the risk of surgical margin positivity and lymphnode metastasis, and facilitate a thorough prostatectomy. On the contrary, no long-term studies have proved the beneficial effects of preoperative therapy on patients' survival. A multicenter randomized study in Japan comparing neoadjuvant therapy and immediate surgery (control) was conducted. All the patients were to receive hormonal therapy for 2 years. The results confirmed the short-term efficacy of neoadjuvent hormonal treatment, and no significant difference in clinical relapse rate (5.6% (5/90) in neoadjuvant group versus 11.6% (10/86) in control group), nor PSA relapse rate (13.3% versus 17.4%) at 2 years posttreatment; however in stage C cancer there was a tendency of a lower clinical relapse rate in neoadjuvant group (9.5%: 2/21) than the control (30.4%: 7/23). These data provide no obvious evidence for favorable long-term outcomes in neoadjuvant group, although a possibility that stage C cancer benefits from the treatment remains to be explored.

Androgen Antagonists↗
PubMed1998

Evaluation of glomerular filtration rate by camera-based method in both children and adults.

UNLABELLED: We describe a method to evaluate glomerular filtration rate (GFR) in both children and adults using 99mTc-diethylenetriamine pentaacetic acid (DTPA) and a gamma camera. METHODS: Renal scintigraphy with 99mTc-DTPA was performed in 40 children and 92 adults with various degrees of renal function. The percent renal uptake at 2-2.5 min after tracer arrival in the kidney was determined with background subtraction and correction for soft-tissue attenuation and was correlated by linear regression analysis with GFR measured from two blood samples. A perirenal region of interest was used for background subtraction. Renal depth was computed using the equations determined or validated on the basis of CT measurements, and the attenuation coefficient was set at 0.12. The obtained regression equation was used to predict GFR. Renal function was also assessed by the Gates' method. RESULTS: Percent renal uptake was closely correlated with GFR normalized for body surface area in all patients (y = 15.958x - 2.94; r = 0.939). GFR was successfully predicted using the regression equation in both children and adults. Gates' method severely overestimated GFR in children and provided less accurate values even in adults than our method. CONCLUSION: The method presented here requires neither blood sampling nor additional imaging and allows estimation of GFR in both children and adults.

Adult↗
PubMed1997

Inhibition of rat prostate carcinogenesis by a 5alpha-reductase inhibitor, FK143.

BACKGROUND: Androgen levels in the prostate may influence carcinogenesis in this organ. Inhibitors of the enzyme 5alpha-reductase block conversion of testosterone to the more active androgen dihydrotestosterone. The use of a 5alpha-reductase inhibitor, finasteride, in the chemoprevention of prostate cancer is being evaluated in a clinical trial. PURPOSE: This study was conducted to determine if a 5alpha-reductase inhibitor, FK143, inhibits the development of prostate cancer in rats. METHODS: Male ACI/Seg rats, which spontaneously develop prostate cancer, were randomly assigned at 80 weeks of age to receive one of three diets (n = 35/group) containing 0 (i.e., control group), 20, or 200 ppm FK143. At 140 weeks of age, the animals were killed, and the prostates were removed and examined for histopathologic features in addition to being assayed for androgen concentrations. Two-sided statistical tests were used to calculate all P values. RESULTS: The incidence of prostate carcinoma in the control group was 62.9% (22 of 35 rats); in the group fed the 20 ppm FK143-containing diet, it was 45.7% (16 of 35); and in the group fed the 200 ppm FK143-containing diet, it was 67.6% (23 of 34) (overall, P = .153). The corresponding incidences of macroscopic lesions were 17.1% (six of 35 rats), 0% (none of 35), and 23.5% (eight of 34), respectively (overall, P = .004). The incidence of macroscopic lesions in the prostates of rats in the 20-ppm diet group was significantly lower than that in the control group (P = .029) or that in the 200-ppm diet group (P = .003). Intraprostatic dihydrotestosterone content was significantly lower in rats in the groups fed diets containing 20 or 200 ppm FK143 (mean values: 4.51 and 4.33 pg/mg wet weight of prostate tissue, respectively) than in the control group (6.10 pg/mg) (overall, P<.001); by contrast, testosterone was higher in the 200-ppm diet group (2.09 pg/mg) than in the control group (1.08 pg/mg) or the 20-ppm diet group (1.21 pg/mg) (overall, P<.001). CONCLUSIONS: FK143, when fed to rats at 20 or 200 ppm, significantly reduced the level of dihydrotestosterone in their prostate tissue. However, the incidence of macroscopic cancer in the prostate was suppressed in rats consuming the 20 ppm FK143-containing diet but not in those consuming the 200-ppm diet. The lack of dose dependence for the chemopreventive activity of FK143 may be explained by the reciprocal increase of tissue testosterone in the 200-ppm diet group. IMPLICATIONS: The 5alpha-reductase inhibitor FK143 may, at specific doses, reduce the incidence of spontaneously developing prostate cancer; however, whether these findings in rats will apply to humans remains to be determined.

5-alpha Reductase Inhibitors↗
PubMed1997

Specific reduction of plasma large, light low-density lipoprotein by a bile acid sequestering resin, cholebine (MCI-196) in type II hyperlipoproteinemia.

The effect of a bile acid sequestrant, cholebine (3 g/day), on plasma lipoprotein subfractions was investigated in 16 patients with type II hyperlipoproteinemia. Activities of low density lipoprotein (LDL)-receptor and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) were assayed to address the mechanism of cholebine-induced changes in plasma lipoprotein subfractions. Twelve weeks of treatment with cholebine reduced plasma levels of total cholesterol (TC) and LDL-cholesterol (C) by 8.3 +/- 8.1% (mean +/- S.D.) and 14.4 +/- 11.9%, respectively (P < 0.001), but did not affect plasma levels of high density lipoprotein (HDL)-C. Cholebine significantly reduced plasma levels of LDL1-C (1.019 < d < 1.045) by 22.9 +/- 18.9% (P < 0.001) but did not affect plasma levels of very low density lipoprotein (VLDL)-C, intermediate density lipoprotein (IDL)-C, LDL2-C (1.045 < d < 1.063), HDL2-C, and HDL3-C (d > 1.125). Gradient polyacrylamide gel electrophoresis (PAGE) revealed that cholebine reduced large LDL in plasma but had almost no effects on small LDL and HDL subfractions. Cholebine did not alter the activities of LCAT and CETP. LDL-receptor activities of cultured lymphocytes negatively correlated with the reduction in plasma levels of LDL-C (r = -0.500, P < 0.05), IDL-C (r = -0.581, P < 0.02), and LDL1-C (r = -0.610, P < 0.01), respectively. Thus, cholebine seems to reduce further the plasma levels of IDL and large, light LDL in patients with lower LDL-receptor activities. We conclude that cholebine only reduces plasma levels of large, light LDL. This may be due to the stimulation of hepatic LDL-receptor activity.

Anticholesteremic Agents↗
PubMed1997

Combined analysis with Bcl-2 and P53 immunostaining predicts poorer prognosis in prostatic carcinoma.

PURPOSE: The objective of the current study is to investigate the relationship between bcl-2 and p53 expression and prognosis in prostatic carcinoma. MATERIALS AND METHODS: One hundred and forty-six needle core biopsy specimens obtained before any treatment were used for immunohistochemical detection of bcl-2 and p53 positivity. The relationship between these proteins was assessed by serial sections. Associations with Gleason score, clinical stage and patient survival were studied. Additionally, multivariate analysis by Cox proportional hazard model was used to determine the prognostic significance of these proteins. RESULTS: Bcl-2 positivity was found in 20% and p53 in 27% of 146 prostatic carcinomas. Both bcl-2 and p53 positivity were found only in 5%. They were expressed almost reciprocally in the tumors. P53 positivity correlated with high Gleason grade tumors. Bcl-2 positivity correlated with high T stage. Both bcl-2 and p53 positivity correlated with poor survival and short progression-free period. Multivariate analysis revealed that bcl-2 positivity was an independent prognostic indicator (p = 0.001). CONCLUSIONS: Bcl-2 and p53 were almost independently expressed in prostatic cancer. Both correlated with malignant phenotypes of prostatic cancer. The combined data from this staining further improved the ability to predict the patient prognosis.

Disease Progression↗
PubMed1997

Inhibition of phosphoinositide hydrolysis and cell growth of Swiss 3T3 cells by myristoylated phospholipase C inhibitor peptides.

It has been demonstrated that the phospholipase C-gamma (PLC-gamma) molecule contains within it a phospholipase C inhibitor (PCI) region and that synthetic peptides based on the sequence of this region (PCI peptides) suppress the enzymatic activity of PLC isoforms [Y. Homma and T. Takenawa (1992) J. Biol. Chem. 267, 21884-21889]. In order to improve the permeability of the plasma membrane to PCI peptides, we synthesized myristoylated PCI peptides, myr-GLYRKAMRLRYPV [myr-PCI(Y)] and myr-GLFRKAMRLRFPV [myr-PCI(F)], which are identical except for the replacement of the two tyrosine residues in myr-PCI(Y) by phenylalanines in myr-PCI(F), and examined their inhibitory activity on PLC enzymes in vitro and in vivo. This fatty acid modification potentiated the inhibitory activity of the original PCI peptides and both myr-PCI(Y) and myr-PCI(F) suppressed the PIP2-hydrolyzing activity of purified PLC isoforms in vitro. The Ki values of myr-PCI(Y) and myr-PCI(F) for purified PLC-gamma1 were 3.5 and 55 microM, respectively. Myr-PCI(Y) at concentrations in the sub-micromolar range significantly suppressed IP3 formation induced by EGF, PDGF, bombesin, or serum in Swiss 3T3 cells. Furthermore, myr-PCI(Y) also strongly inhibited cell proliferation induced by these stimuli. The inhibitory effect on IP3 formation and proliferation of myr-PCI(F) was much less potent than that of myr-PCI(Y). These results suggest that myristoylated PCI peptides could be applied to living cells as specific inhibitors of PLC signaling pathways and that PLC pathways are at least in part required for growth in Swiss 3T3 cells.

3T3 Cells↗
PubMed1997

Pulmonary dysanapsis, methacholine airway responsiveness and sensitization to airborne antigen.

Whether the disproportional growth of airways relative to lung parenchyma (dysanapsis) has any relationship to the development of non-specific bronchial hyperresponsiveness and atopy was investigated in 45 family members of the patients with atopic asthma. As indices of pulmonary dysanapsis, forced expiratory flow25-75/forced vital capacity (FEF25-75/FVC) and the tracheal cross sectional area divided by the forced expiratory volume (X-SA/FVC) were examined. As an index of non-specific airway responsiveness, the cumulative dose of inhaled methacholine needed to induce 35% reduction of respiratory conductance (PD35) was determined by continuous respiratory resistance measurement. For examination of atopy, skin prick tests were conducted, and total serum IgE and IgE specific to common inhaled antigens were measured. FEF25-75/FVC showed no significant correlation to FVC but showed a significant correlation to log(PD35). When the analysis was done in the subjects whose FEV1/FVC was more than 0.8, FEF25-75/FVC showed a significant negative correlation to FVC but lost its correlation to log(PD35). X-SA/FVC showed a significant negative correlation to FVC but had no significant correlation to log(PD35). These relations were conserved when the analysis was done in subjects without airway obstruction. In addition, FEV1/FVC had a significant correlation to log(PD35) and FEF25-75/FVC. However, subjects who had a positive IgE(MAST) had a significantly smaller X-SA/FVC than those with a negative IgE(MAST) (0.60 +/- 0.14[SD] and 0.72 +/- 0.18, respectively, P < 0.02). These results suggest that although pulmonary dysanapsis does not have a significant relation to airway responsiveness to inhaled methacholine, it may be associated with sensitization to airborne antigens.

Adolescent↗
PubMed1997

Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score.

BACKGROUND: The prevalence of lower urinary tract symptoms was determined by survey as an initial step in estimating the significance of benign prostatic hyperplasia (BPH) in Asia and Australia. METHODS: The symptom index (0 to 35) and quality-of-life (QOL) index (0 to 6) of the international prostate symptom score were measured in 7588 men in 9 Asian countries and 146 men in Australia. RESULTS: The percentages of Asian men considered to be symptomatic (symptom index > or = 8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, respectively. For Australian men, these figures were 36%, 33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups, respectively. CONCLUSIONS: Our estimates indicate that the prevalences of symptomatic men in Asia and Australia are similar to or greater than those in Europe and America, and suggest BPH is similarly common in these areas.

Adult↗
PubMed1997

Preoperative endocrine therapy for clinical stage A2, B, and C prostate cancer: an interim report on short-term effects. Prostate Cancer Study Group.

BACKGROUND: Preoperative endocrine therapy has been suggested to improve surgical radicality and/or patient prognosis in prostate cancer. METHODS: Patients with clinical stage A2, B, and C prostate cancer were randomized to either group I (n = 113) or group II (n = 111). Group I patients were to receive preoperative endocrine therapy consisting of leuprolide and chlormadinone for 3 months, followed by radical prostatectomy with lymph node dissection. Group II patients were to undergo the surgery before endocrine therapy. RESULTS: Group I patients showed a remarkable decrease in prostate-specific antigen (PSA) (mean +/- SE: 41.8 +/- 8.6 ng/mL to 2.7 +/- 0.7 ng/mL) and prostate volume (29.8 +/- 1.7 mL to 21.2 +/- 1.6 mL) during the preoperative therapy. Histopathologic analysis showed a significant difference in the rates of down-staging (19.1% in group I versus 3.3% in group II), positive surgical margins (63.8% versus 81.3%) and positive lymph node metastasis (20.7% versus 36.5%). No significant difference was detected in operating features. Subgroup analyses indicated that beneficial effects were correlated positively with degree of histologic differentiation and negatively with the basal PSA level. CONCLUSIONS: Preoperative endocrine therapy reduced local extension of prostate cancer, and the effects depended on histologic differentiation and PSA level. Long-term follow-up data are needed to determine the effects on the patient prognosis.

Aged↗