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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 181 records · Page 10Linked to original sources

Aberrant phosphoinositide metabolism in Alzheimer's disease.

Since phosphoinositide-specific phospholipase C (PLC) is one of the key molecules in signal transduction, its involvement was assessed in Alzheimer's disease (AD). The phosphatidyl-inositol (PI)-specific PLC activity in the Alzheimer cytosolic and particulate fractions was not significantly different from that in the control fractions. The PI-specific PLC activity as a function of the free Ca2+ concentration was also similar between control and Alzheimer brains. These results suggest that the PI-specific PLC activity is not altered in AD. Immunostaining of a specific antibody against the PLC isozyme, PLC-delta, demonstrated that this enzyme was abnormally accumulated in neurofibrillary tangles (NFT), the neurites surrounding senile plaque (SP) cores, and neuropil threads in AD brains. Western blot analysis confirmed that PLC-delta was concentrated in the paired helical filament (PHF)-rich fraction of AD brains. PLC-delta marked the same neurons containing tau immunoreactivity and yet tau and PLC-delta often marked different structures within the same neuron, with tau more clearly on NFT and PLC-delta covering it superficially. The double stain with PLC-delta and basic fibroblast growth factor (bFGF) binding suggest that PLC-delta is an intracellular marker, showing little overlap with bFGF binding, an extracellular marker. All of this was consistent with the electron microscopy, with PLC-delta being NFT associated. Antibodies to other PLC isozymes did not produce positive immunostaining of these pathologic structures. Moreover, diffuse and amorphous deposits of PLC-delta were found to precede the accumulation of fibrillary deposits. These results suggest that PLC-delta accumulation plays a possible role in the formation of intraneuronal inclusions in AD.

Alzheimer Disease↗

Synthetic boundary cell in an analytical ultracentrifuge to determine the flotation coefficient of human serum lipoproteins.

Human serum lipoproteins were analyzed by a new modified synthetic boundary cell using an analytical ultracentrifuge. This cell allows the formation of the synthetic boundary at the bottom level of the cell with self-adjusting meniscus and baseline. Thus, the total amount of lipoproteins was seen as a single peak at first. During centrifugation, each component of the lipoproteins was separated according to its flotation characteristics. It was, therefore, possible to determine precisely all lipoprotein components, especially high-density lipoproteins, in the presence of a more rapidly migrating species and to calculate the flotation coefficient of each lipoprotein using the formula for sedimentation coefficient reported by Svedberg (Svedberg, T. (1925) Kolloid-Z. 36, 53-64.

Humans↗

Phospholipase C-gamma 1 associates with viral and cellular src kinases.

A tyrosine kinase inhibitor, genistein, caused the subcellular translocation of phosphoinositide-specific phospholipase C (PLC) activity from membrane fractions to cytosolic fractions in rat 3Y1 fibroblasts and their transformants by Rous sarcoma virus, SR-3Y1. The ratio of PLC activities associated with the membrane fractions to those of the homogenate fractions was greater in SR-3Y1 (32.6%) than in 3Y1 (20.8%) whereas membrane-associated PLC activities were strikingly reduced to the same levels in both cells by treatment with genistein. Moreover, it was found by immunoblotting analyses of membrane fractions that the amounts of PLC-gamma 1 isozyme were reduced to 20.4% of initial level in SR-3Y1 and to 30.2% of that in 3Y1 cells. While the levels of PLC-delta, another detectable PLC isozyme, were not altered by genistein suggesting that tyrosine kinase plays an important role in the association of PLC-gamma 1 with membranes. PLC-gamma 1 molecules were detected in anti-p60arc antibody immunoprecipitates of both 3Y1 and SR-3Y1 cells. The amounts of PLC-gamma 1 co-immunoprecipitating with src kinases were higher in SR-3Y1 than 3Y1 cells and were reduced in both cell types by treatment with genistein. In addition, it was confirmed that PLC-gamma 1 purified from rat liver was phosphorylated at a tyrosine residue and associated with viral src kinase and that src kinases associated with the recombinant SH2 region of PLC-gamma 1, expressed in Escherichia coli, depending upon phosphorylation of tyrosine residues. These findings suggest that both viral and cellular src kinases associate with PLC-gamma 1 and may mediate cellular signaling in normal and transformant cell growth.

Animals↗

[Effect of lipiodol on MR images evaluation by dynamic MR imaging with intraarterial lipiodol injection in the rabbit VX-2 tumor].

We evaluated the effect of lipiodol on the MR image by using dynamic MR imaging (MRI) with an intraarterial lipiodol injection in the VX-2 tumor. The signal intensity of the tumor had been risen gradually during the dynamic MRI, using T 1-weighted Spin Echo techniques. The high intensity areas on the dynamic MRI nearly corresponded with the lipiodol accumulated areas on CT. On the micrograph, no necrosis or degeneration of the tumor cell was visible. We conclude that the presence of lipiodol will affect the signal intensity of T 1-weighted MR images.

Animals↗

Evidence for involvement of phospholipase C-gamma 2 in signal transduction of platelet-derived growth factor in vascular smooth-muscle cells.

In order to examine the mechanisms underlying smooth-muscle cell proliferation, we investigated effect of platelet-derived growth factor (PDGF) dimers on proliferation of rabbit vascular smooth-muscle cells (VSMCs) and also involvement of phospholipase C (PLC) isoforms in the signal transduction. PDGF-BB and -AB, but not -AA, stimulated cell proliferation and intracellular production of inositol trisphosphate. Northern and Western analyses demonstrated that VSMCs mainly expressed PLC-gamma 2 and PLC-delta 1 among four PLC isoforms tested. A number of cellular proteins, including PLC-gamma 2, but not PLC-delta 1, were phosphorylated on a tyrosine residue by the stimulation of either PDGF-BB or -AB. These results suggest a functional association of PDGF receptor and PLC-gamma 2 that might be responsible for PDGF-dependent VSMC growth. In addition, the expression of PLC-gamma 2 was extremely low in the primary VSMC cultures and was induced during further cultivation of the primary cultures, indicating that an acquisition of PDGF-signal-transducing components, including PLC-gamma 2, may be an important step for proliferation of smooth-muscle cells.

Animals↗

[Evaluation of early MR imaging of the liver in rabbits after ethanol injection].

Seven days after ethanol injection, MR images of the liver in 5 rabbits were evaluated by T1, T2-weighted SE and TURBO-FLASH dynamic images. Necrotic area was visualized as low-intensity on T1-weighted images and high-intensity on T2-weighted images. These findings were similar to the tumor that was not treated, so it is necessary to be careful for evaluation of therapeutic efficacy. Necrotic area was not meanwhile enhanced on TURBO-FLASH dynamic images, therefore, dynamic study seemed to be useful for therapeutic efficacy after ethanol injection.

Animals↗

Transurethral microwave thermotherapy for benign prostatic hyperplasia: a 2-year follow-up study.

The authors studied the long-term effect of transurethral microwave thermotherapy (TUMT) using the Prostratron device on 30 patients with symptomatic benign prostatic hyperplasia (BPH). The maximum power output was 45 W, and the temperature within the prostate was expected to rise above 45 degrees C. The efficacy was evaluated using a specially designed scoring system based on both subjective symptoms and objective findings. Assuming that more than a 25% reduction of the total score indicates "effective," 80%, 70%, 63%, and 57% of the treatments remained effective at 8 weeks, 6 months, 1 year, and 2 years after TUMT, respectively. There were no major complications associated with TUMT during the follow-up period. Our results indicate that TUMT is an effective and long-lasting (at least 2 years) nonsurgical treatment in approximately 60% of patients.

Aged↗

Influence of age on the signal transduction of T cells in mice.

A 5- to 10-fold decline was observed in the proliferative activity of T cells stimulated with anti-CD3 mAb between young and old mice. However, the number of CD3 molecules on the T cell surface was almost comparable between young and old T cells. The formation of the second messenger such as inositol triphosphate (IP3) and diacylglycerol (DAG) after mitogenic stimulation decreased in old T cells as compared with young ones. The activity of phospholipase C (PLC), which is responsible for the liberation of IP3 and DAG from phosphatidylinositol-4,5-bisphosphate (PIP2) was not different between young and old T cells. The content of PIP2 in the membrane was also comparable between young and old T cells. These findings have suggested that the age-related decline in the proliferative activity of T cells could be due to impairment of intracellular signal transduction, probably in the pathway somewhere between TCR and PLC.

Aging↗

Effect of high hydrostatic pressure on the conversion of alpha-connectin to beta-connectin.

The factors affecting the conversion of alpha-connectin to beta-connectin induced by pressurization of muscle were investigated over a pressure range from 100 to 400 MPa by using SDS-PAGE and immunoblot analysis. When muscles were exposed to high pressures, the conversion of alpha-connectin to beta-connectin was the most pronounced at a pressure of 300 MPa, and the appearance of 1,200-kDa peptide accompanied by conversion of alpha- to beta-connectin was observed. Connectin was relatively resistant to degradation under a pressure of 400 MPa. The degradative products of beta-connectin reactive with mAb 2D4 were not observed. The effect of high pressure on connectin in isolated myofibrils was similar to that on connectin in muscle. Addition of leupeptin and E-64 to the isolated myofibrils resulted in the prevention of the degradation of connectin at each stage of the pressurization. The ability of calcium-activated protease (calpain) to hydrolyze connectin from alpha to beta gradually declined with increasing pressure. The results indicate that calpain is responsible for the pressure-induced conversion of alpha- to beta-connectin. The rate of this conversion is probably regulated by the pressure-dependent structural change of alpha-connectin and inactivation of calpain.

Animals↗

Two-year follow up on the protective value of dust masks against farmer's lung disease.

Some advocate moving away from the farm environment for farmers affected with farmer's lung disease (FLD), but most affected farmers still live on farms. In this study, we evaluated the practicality of dust masks and their effectiveness in prevention of FLD. The dust masks we chose were practically used and no new severe episodes of FLD developed in 20 of 21 farmers with FLD using the masks during a 2-year period. When the farmers took off the dust masks in a farming environmental provocation test, statistically significant reductions in FVC (mean 3.43 to 3.351, p < 0.01), DLco (mean 19.6 to 18.2 ml/torr/min, p < 0.01), and DL/VA (mean 5.1 to 4.8 (x10(-3)) 1/torr/min, p < 0.01) were observed several hours after exposure. These findings suggest that the dust masks were used practically during routine dairy farming and were effective in protection against FLD.

Adult↗

[Recent advances and trends in the therapies for benign prostatic hyperplasia].

A number of new treatment modalities for benign prostatic hyperplasia (BPH) have been introduced in these days: for example, laser ablation, alpha-adrenergic blocker, antiandrogens, hyperthermia, stenting and balloon dilation. The author basically mentioned the personal experiences in some of these modalities, and gave a general review on their effectiveness and safety. Also pointed out were a variety of problems, important but sometimes ignored, in the evaluation of treatments for BPH, including severity grading of BPH, response criteria of effectiveness, method for proper selection of treatment.

Adrenergic alpha-Antagonists↗

[Clinical observations of advanced renal cell carcinomas--the chronological change between 1975 and 1991].

An analysis has been undertaken to determine chronological changes that have occurred in the clinical features and treatments of advanced renal cell carcinomas. To accomplish this, 96 renal cell carcinoma cases, handled by the authors' department and at the branch hospital, were divided into two groups: 48 patients treated between 1975 and 1983 (group 1) and 48 patients treated between 1984 and 1991 (group 2). Between the two groups, no differences were seen in the sex ratio, the mean age, and the ratio of those who were found to be advanced cases at the time of diagnosis and those whose cancers had advanced after undergoing a nephrectomy. Concerning treatment, interferon (IFN) and UFT were more frequently used in treating group 2 than group 1, and chemotherapy, radiotherapy, and endocrine therapy less frequently used. No differences were seen in the prognosis between the two groups; however, in those who had advanced after nephrectomy, group 2 cases survived for a significantly longer period than did group 1 cases. Patients who survived for 5 years or longer accounted for two cases in group 1 and 5 cases in group 2 and combination therapies involving surgery, IFN, UFT, or similar medications were used for their treatments. These results suggest that adjuvant therapies, such as surgery, IFN, and UFT, have possibly contributed to prolonging survival, especially for cases that advanced after nephrectomy.

Carcinoma, Renal Cell↗

[A clinical study on renal pelvic and ureteral tumor associated with bladder tumor].

Of 65 cases of renal pelvic and/or ureteral tumor treated at Department of Urology, The University of Tokyo, during the period from January 1975 through December 1991, 26 had bladder tumors as well. These cases were divided into three groups; 1) bladder tumor preceding upper urinary tract tumor, 2) bladder tumor found simultaneously with upper urinary tract tumor, and 3) bladder tumor following upper urinary tract tumor. In group 1 (nine cases), the last bladder tumor preceded renal pelvic and/or ureteral tumors by 3 to 42 months (mean 14.6 months), and in seven cases, bladder tumor recurred 3 to 29 months (mean 9.0 months) after nephroureterectomy. The interval between the diagnosis of preceding bladder tumor and upper urinary tract tumor was highly correlated with the latent period of postoperative recurrence of bladder tumor (r = 0.948). Highly malignant pathological grade of bladder tumor featured seven cases of group 2, with the survival rate being significantly (p < 0.01) lower than that of other groups. In the group 3 consisting of ten cases, bladder tumors subsequently developed 6 to 37 months (mean 15.0 months). The latent period of bladder tumor was significantly (p < 0.01) longer than that in group 1. These results indicated that the bladder tumors associated with renal pelvic and/or ureteral tumors have distinct characteristics depending on the sequence of association.

Adult↗

[A clinical classification of severity of benign prostatic hyperplasia].

The grading of severity of benign prostatic hyperplasia (BPH) was attempted by scoring clinical manifestations associated with the disease. The total score (0 to 100 points) is the sum total of subjective and objective one, each of which is 50 points at its maximum. Subjective score is composed of symptom score (0 to 25 points) evaluating 5 each obstructive and irritative symptoms and quality of life (QOL) score (0 to 25 points). Objective score consists of functional and anatomical scores. Functional score (0 to 25 points) is calculated by scoring maximum flow rate and residual urine. Anatomical score (0 to 25 points) is calculated by the score of prostatic volume. Seventy-seven BPH patients have been evaluated by this scoring system. The mean values of 4 kinds of scores (symptom, QOL, functional and anatomical scores) were about 8-9 points and thus comparable each other. The total score was 35.4 +/- 12.3 in the average and divided into 6 grades: Grade 0; < 10, Grade 1; > or = 10, Grade 2; > or = 20, Grade 3; > or = 30, Grade 4; > or = 40, Grade 5; > or = 50. The present scoring and grading systems appear to be appropriately formulated to estimate the global severity of BPH patients. Further studies to apply the system to evaluation of therapeutic responses would be mandatory to examine its validity.

Humans↗

[A survey of postoperative steroid replacement in 40 patients with Cushing's syndrome].

Adrenalectomy for Cushing's syndrome due to adrenocortical adenoma was performed on 40 patients at Tokyo University Hospital between 1960 and 1990. There were 32 women and 8 men aged 2 to 59 (mean 35.7) years. Three different operative approaches to the adrenal gland were employed: lumbar approach in 24 cases, dorsal in 8, and transabdominal in 8 of whom 7 patients were operated before 1970 without definite preoperative localization of the lesions. Postoperative administration of cortisone and hydrocortisone as a steroid replacement has been reduced in duration and dosage in recent 10 years. Average treatment period was 3 years and 1 month in the 1970's, and 9.5 months in the 1980's, respectively. The mean daily dosage of steroid hormone was 517.5 mg (mean) on the operative day and 43.1 mg after three weeks in the 1970's, while 187.5 mg and 18.4 mg in the recent five years, respectively. Nonetheless, even in the recent 6 patients, metabolic alkalosis and hypopotassemia because of steroid excess were observed in a few days after the surgery. These observations indicate that period and dosage of steroid replacement have been reduced in these years and could be further shortened by means of rapid tapering in the early postoperative phase.

Adenoma↗

[Causes of idiopathic interstitial pneumonia (IIP): inhaled dust as environmental problem].

We have reported that patients with IIP can be roentgenologically grouped into two subtypes, typical (type-A) and atypical (type-B). The characteristic feature of X-ray findings in type-A is marked restriction of the lung, especially of the lower lobes, and in type-B is emphysematous changes in addition to the findings of type-A. In this study, to clarify the pathological findings of these two subtypes, 60 IIP patients in whom open lung biopsy and/or autopsy were performed were studied both clinically and pathologically. The following results were obtained. 1) Pathological features of type-A were alveolitis, marked restriction of the lung secondary to atelectasis and fibrosis of lung parenchyma, and honeycombing as a result of remodeling. 2) The features of type-B were intra-alveolar organization and secondary emphysema after intra-alveolar inflammation (pneumonia) overlapped the pathological changes of type-A. 3) Patients with a history of dust inhalation were much more frequently observed in type-B than in type-A (p < 0.01). These results suggest that inhaled dust may be a causative factor of IIP, especially of type-B.

Dust↗