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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 199 records · Page 11Linked to original sources

Phospholipase C activation in the cytotoxic response of human natural killer cells requires protein-tyrosine kinase activity.

Treatment of highly purified natural killer (NK) cells with the protein-tyrosine kinase (PTK) inhibitors, genistein and herbimycin A, diminished their ability to lyse K562 target cells by as much as 100%. The ability of NK cells to bind to K562 cells was not affected by PTK inhibition. However, activation of phospholipase C (PLC) in response to K562 cell binding (as measured by inositol phosphate turnover) was decreased by as much as 75% when PTK activity was inhibited. Furthermore, there was an increase in tyrosine phosphorylation of NK cell PLC gamma 2 after exposure to K562 target cells. These data indicate that a PTK is involved in the activation of NK PLC by tumour target cells in the cytotoxic response.

Benzoquinones↗

[Atherosclerotic and hemodynamic effects of obesity].

Obesity is a risk factor of atherosclerosis. The TG content of a fat cell is determined by the balance of lipogenesis from plasma FFA and glucose and lipolysis by hormone-sensitive lipase (HSL). Plasma FFA is produced by TG lipolysis by lipoprotein lipase (LPL). Insulin stimulates LPL activity and inhibits HSL activity. Therefore, hyperinsulinemia stimulates TG accumulation in fat cells. Insulin also stimulates fat cell proliferation. Hyperinsulinemia is a major factor for obesity. Portal FFA stimulates VLDL synthesis and gluconeogenesis and inhibits insulin degradation in the liver. Therefore, visceral obesity is important as a risk factor of atherosclerosis. However the increase of total adipose tissue mass is more important for blood pressure and cardiac performance.

Adipose Tissue↗

Decrease of plasma large, light LDL (LDL1), HDL2 and HDL3 levels with concomitant increase of cholesteryl ester transfer protein (CETP) activity by probucol in type II hyperlipoproteinemia.

The effects of 12 week probucol treatment on plasma lipoprotein subfraction levels and on lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities in type II hyperlipoproteinemia were investigated. Plasma VLDL-TG, VLDL-apoB, VLDL-apoCII and VLDL-apoCIII concentrations were not changed by probucol, but VLDL-TC and VLDL-PL levels were slightly reduced. Probucol slightly reduced plasma IDL-TC, but not IDL-TG, IDL-PL and IDL-apoB levels. Plasma large, light LDL (LDL1)-TC, LDL1-PL, LDL1-apoB levels were decreased significantly by 28.5 +/- 20.1% (p < 0.001), 18.1 +/- 18.8% (p < 0.01) and 23.3 +/- 19.1% (p < 0.001) by probucol treatment while LDL1-TG concentration was unchanged. Absolute amounts of plasma small, heavy LDL(LDL2)-TC, LDL2-TG, LDL2-PL and LDL2-apoB levels remained unchanged but percent increases of LDL2-TC and LDL2-apoB were statistically significant (p < 0.05). 2-16% gradient polyacrylamide gel electrophoresis demonstrated the diminution of LDL of large size by probucol treatment. Probucol markedly reduced plasma high density lipoprotein levels. The reductions of HDL2-TC, HDL2-TG, HDL2-PL and HDL2-apoAI concentrations were 36.2 +/- 25.4% (p < 0.001), 25.8 +/- 36.9% (p < 0.01), 34.4 +/- 23.8% (p < 0.001) and 35.6 +/- 28.4% (p < 0.001). Probucol significantly decreased plasma HDL3-TC, HDL3-PL and HDL3-apoAI amounts by 17.4 +/- 22.9% (p < 0.01), 18.3 +/- 20.8% (p < 0.01) and 19.8 +/- 27.9% (p < 0.01) without change of HDL3-TG level. The decrease of HDL2 level was more marked than that of HDL3 level. Probucol did not change LCAT activities. Probucol significantly stimulated CETP activities from 126.6 +/- 50.6 units to 172.8 +/- 40.2 units by 12 week treatment (p < 0.001). We concluded that probucol decreased plasma LDL1, HDL2 and HDL3 amounts and made them triglyceride-rich with the concomitant increase of CETP activities.

Carrier Proteins↗

[Transurethral resection of papillary tumor in the lower end of the ureter: report of two cases].

Two cases of papillary ureteral end tumors, treated by transurethral resection are presented. Case 1: A 71-year-old female visited us for asymptomatic macroscopic hematuria. Cystoscopy revealed a papillary pedunculated tumor in the bladder protruding from the right ureteral orifice. Under a diagnosis of superficial tumor at the right ureteral end, transurethral resection was performed using a rigid ureteral resectoscope. Pathological examination revealed transitional cell carcinoma, grade 2 without muscular invasion. There is no evidence of recurrence after 25 months of follow up postoperatively. Case 2: On a routine cystoscopy after transurethral resection of bladder tumor in a 68-year-old male, papillary pedunculated tumors protruding from the right ureteral orifice were found. Under a diagnosis of superficial tumor at the right lower ureter, transurethral resection was performed using cold cup forceps and loop electrocoagulation. The tumor was transitional cell carcinoma, grade 1 without invasion. No evidence of recurrence was detected 15 months postoperatively. Transurethral resection of the ureteral tumor at the lower end appeared to be useful for the selected cases. The indications, complications and follow up for this procedure were discussed.

Aged↗

Inhibitory effect of src homology (SH) 2/SH3 fragments of phospholipase C-gamma on the catalytic activity of phospholipase C isoforms. Identification of a novel phospholipase C inhibitor region.

In order to study the regulatory mechanisms of phospholipase C-gamma (PLC-gamma) via the intrinsic SH2/SH3 region (Z region), two recombinant Z proteins, rP45Z and rP38Z, derived from rat PLC-gamma 1 and PLC-gamma 2, respectively, were purified from the inclusion bodies of Escherichia coli. We examined their direct effects on phosphoinositide hydrolysis induced by four different PLC isoforms purified from bovine brain and thymus, and found that both of these Z proteins suppress the enzyme activity of all four PLC isoforms in a dose-dependent manner. This suppressive effect is very potent and stoichiometric. The kinetics studies indicate that the suppression is non-competitive. This suppression is eliminated by treatment with proteases but is not affected by heat treatment at 95 degrees C for 15 min, indicating that the primary structure might be important for the action of Z proteins. Comparative studies suggested that two Z proteins but not Src and phosphatidylinositol 3-kinase possess, adjacent to their SH2 and SH3 motifs, a phospholipase C inhibitor (PCI) region that strongly suppresses their phosphatidylinositol 4,5-bisphosphate (PIP2)-hydrolyzing activity. A series of synthetic peptides identical with the sequence of the proposed PCI region, including an octamer, YRKMRLRY, inhibited PIP2 hydrolysis induced by four different phospholipase C isoforms. These results demonstrate that both types of phospholipase C-gamma contain the PCI sequence which is responsible for the inhibition of PIP2 hydrolysis, indicating that phospholipase C-gamma is a self-regulating enzyme.

Amino Acid Sequence↗

Enhancement of phospholipase C delta 1 activity in the aortas of spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR), which develop hypertension approximately 10 weeks after birth, are considered to provide a good animal model for human essential hypertension. We report here that the abnormal activation of phospholipase C delta 1 (PLC-delta 1) may be one of the main causes of hypertension. Levels of the second messengers inositol 1,4,5-trisphosphate and diacylglycerol are found to be higher in the aortas of 12-week-old SHR than in age-matched normotensive Wistar-Kyoto rats (WKY), although the levels in the aortas of 7-week-old SHR, which have normal blood pressure, are the same as in WKY. Moreover, PLC activity is also higher in the aortas of 12-week-old SHR. Judging from Western blot analysis and immunoabsorption of PLCs, this activation is found to be due to that of PLC-delta 1. PLC-delta 1 from rat aorta is expressed significantly from 7 to 12 weeks, which correlates with the development of hypertension in SHR. The activity of PLC-delta 1 in the aortas of 12-week-old SHR is more markedly activated at low Ca2+ concentration than that of age-matched WKY. These results suggest that the abnormal enhancement of PLC-delta 1 activity is responsible for accumulation of inositol 1,4,5-trisphosphate and diacylglycerol, leading to continuous hypertonicity of vascular smooth muscle in SHR. The activity of PLC-delta 1 in the aortas of 12-week-old SHR is significantly higher at low Ca2+ concentration than that of normotensive WKY.

1-Phosphatidylinositol 4-Kinase↗

Isolation and characterization of rat 3Y1 fibroblast clones overexpressing the src homology region of phospholipase C-gamma 2.

To examine the regulatory function of the src-related SH2 and SH3 (SH2/SH3) region of phospholipase C-gamma 2 (PLC-gamma 2), we expressed this region of rat PLC-gamma 2 cDNA in rat 3Y1 fibroblasts and isolated and characterized a number of clones (approximately 20 clones). An increase of endogenous tyrosine kinase activity was observed in all cell clones that highly expressed a translational product of the SH2/SH3 domain. Moreover, endogenous phosphatidylinositol 4,5-bisphosphate hydrolyzing activity was also enhanced in these clones, and PLC-gamma 1 seemed to be preferentially activated among endogenous PLC isozymes. Genistein, an inhibitor of tyrosine kinase, inhibited this activation of PLC-gamma 1, and tyrosine phosphorylation was observed on PLC-gamma 1 molecules, indicating the involvement of tyrosine kinases in the PLC-gamma 1 activation. These results suggest that the SH2/SH3 region of PLC-gamma would function as a multidirectional regulator which controls at least two major signaling pathways: tyrosine kinase and phosphatidylinositol 4,5-bisphosphate hydrolysis.

Animals↗

Purification of recombinant SH2/SH3 proteins of phospholipase C-gamma 1 and -gamma 2 and their inhibitory effect on PIP2-hydrolysis induced by both types of phospholipase C-gamma.

In order to examine physiological function of the SH2/SH3 region of phospholipase C-gamma (Z region), we independently expressed cDNA fragments corresponding to the SH2/SH3 region of PLC-gamma 1 and PLC-gamma 2 in Escherichia coli. Although these recombinant proteins were recovered in particulate fractions by centrifugation of cell extracts, they were successfully solubilized by guanidium hydrochloride and then purified to homogeneity by heparin column chromatography. The molecular mass of the proteins was 45 kDa (derived from PLC-gamma 1 and designated as rP45Z) and 38 kDa (derived from PLC-gamma 2 and designated as rP38Z), which was consistent with that as expected from inserted cDNA. We determined the effect of purified rP45Z or rP38Z on PIP2-hydrolyzing activity of either PLC-gamma 1 or PLC-gamma 2 and found that these proteins strongly suppressed the rate of PLC-dependent PIP2-hydrolysis. Furthermore, both rP45Z and rP38Z were phosphorylated at tyrosine residue by epidermal growth factor receptors and their inhibitory effect on PIP2-hydrolysis was significantly decreased by this phosphorylation. These results indicate that the Z region might be involved in autoregulation of PLC-gamma as intrinsic negative regulator.

Animals↗

[Detection of intrahepatic lipids by 1H-MRS--studies by breath-holding & 1 cm3 VOI].

The authors performed 1H-MR spectroscopy (MRS) to depict lipids in the liver of 10 healthy volunteers. Spectra were obtained by a 1.5 T-MR unit, with STEAM from 1 x 1 x 1 cm3 VOI. Lipid peaks were depicted in 7 of the 10 volunteers by breath-holding 1H-MRS study, while in only 4 on normal breathing. The existence of lipids could not be depicted through chemical shift imaging adopting in-phase & opposed images. This suggests a clinical utility of 1H-MRS, particularly through breath-holding studies, in depicting lipids from 1 x 1 x 1 cm3 VOI in the liver in vivo.

Humans↗

A survey on incidental renal cell carcinoma in Japan.

A survey of renal cell carcinoma detected incidentally (incidental renal cancer) in 116 collaborating institutions was conducted nationwide in Japan between 1980 and 1988. The analysis of 1,428 cases demonstrated a dramatic increase in the frequency of incidental renal cancer from 20 cases in 1980 to 338 cases in 1988. Detection occurred at routine health examinations in 32.8% of the cases and during examinations for unrelated diseases in the remainder. The chief method of detection was ultrasonography (68.2%), followed by computerized tomography (21.8%) and excretory urography (6.4%). Tumor extension was within the renal capsule in 76.5% of the cases and the mean tumor diameter was 5.4 cm. The 5-year survival rate was 76.5% but it was better in cases detected by ultrasonography compared with other methods. These results were compatible with previous reports and suggest that incidental renal cancer detection may improve the prognosis of renal cancer as a whole.

Carcinoma, Renal Cell↗

Advantage of a smaller caliber fiberscope and learning curve on transurethral lithotripsy.

Transurethral lithotripsy was performed in 63 patients with ureteral calculi between September 1987 and March 1991. Three types of flexible nephroureteroscopes with diameters of 12.8F, 10.5F and 9.3F were used in groups 1, 2 and 3, respectively. The rate of successful stone disintegration and the stone-free rate 3 months after lithotripsy were 73% (11 of 15 patients) and 67% (10 of 15), respectively, in group 1, 93% (26 of 28) and 82% (23 of 28), respectively, in group 2, and 95% (19 of 20) and 85% (17 of 20), respectively, in group 3. Four complications were encountered in the patients treated with the 12.8F device (group 1). Our results clearly show that use of a slimmer fiberscope and the effect of learning to perform techniques with the flexible nephroureteroscope improved the success rate and decreased the complication rate in transurethral lithotripsy.

Adult↗

A survey on incidental adrenal tumors in Japan.

A nationwide Japanese survey of 210 cases from 116 collaborating institutions demonstrated a dramatic increase in incidentally detected adrenal tumor from 4 cases in 1980 to 54 in 1988. The most common diagnosis was nonfunctioning cortical adenoma (69 cases), followed by pheochromocytoma (49). A total of 14 malignant tumors (6.7%) and 16 functioning benign cortical lesions was also found. Histological study revealed that functioning tumors were small and found in relatively young female patients, nonfunctioning cortical adenomas were of similar size but found in older patients, and all malignant tumors were larger than 6.5 cm. in diameter and occurred in patients 58 years or younger. These results indicate an increase in the occurrence of incidental adrenal tumor and the complexity of pathology.

Adrenal Gland Neoplasms↗

Percutaneous reduction of cyst volume of polycystic kidney disease: effects on renal function.

Percutaneous reduction of cyst volume was performed in 10 patients with autosomal dominant polycystic kidney disease and its effects on renal function were studied. Although creatinine clearance, urinary excretion of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase, and renal uptake of 99mtechnetium-dimercaptosuccinic acid did not change significantly, a transient increase in urinary protein and a decrease in inulin clearance were observed. Complications, such as hematuria, fever and decreases in hematocrit, were slight and transient in most patients. This procedure holds little promise for altering the course of polycystic kidney disease.

Adult↗

[A case report of laparoscopic adrenalectomy].

Laparoscopic left adrenalectomy was performed on a 47 years old male patient with primary aldosteronism. Subcutaneous steel traction method was utilized in addition to intraperitoneal CO2 insufflation method. The combined use of steel traction method reduced CO2 insufflation pressure below 12 mmHg and might reduce possibility of CO2-related complications. A left adrenal gland was approached by a resection of phrenic colic ligament and a traction of a transverse and descending colon. Laparoscopic adrenalectomy has distinct advantages over open adrenalectomy in terms of avoidance of skin and muscle incision and rib resection, and early convalescence. This less invasive method might prevail in near future.

Adrenal Gland Neoplasms↗

[A survey on urinary incontinence in the institutionalized elderly].

A survey on urinary incontinence in 161 (41 male, 120 female) institutionalized elderly was independently performed by urologists and attending nurses. Urinary incontinence was found in 107 cases (66%), with 76 cases (47%) suffering from severe leakage (more than 5 times a day and needs diaper). The prevalences of incontinence and severe leakage were 63% and 52% at geriatric hospitals, 59% and 29% at intermediate care centers and 78% and 63% at nursing homes, respectively. The risk factors for incontinence were consciousness disturbance, urinary urgency, impaired mobility and dementia, and those for severe leakage were apathy, loss of urinary sensation, dementia and impaired mobility. The type of incontinence was considered functional one in 81% of cases. The agreement of the incontinence type evaluated by urologists and that by nurses was found in 90% of incontinent cases. Incontinence was estimated "incurable" in 54% of cases by attending nurses. These observations indicate a high prevalence of severe and "incurable" incontinence in the institutionalized elderly, urgently warranting an effective remedy for the increasing aged society.

Aged↗

[A single session of transurethral microwave thermotherapy for benign prostatic hyperplasia].

A single session of transurethral microwave thermotherapy using Prostatron (Technomed International, France) was performed in 20 patients with benign prostatic hyperplasia, and the clinical efficacy of this modality was evaluated by analysing the subjective and objective responses following the treatment. 1,296 MHz microwaves are delivered to the prostate by an antenna placed in a 20 Fr urethral balloon catheter equipped with a cooling system for preservation of the urethral mucosa. The treatment was performed in a single session for an hour on an outpatient basis. The clinical efficacy was evaluated by a total score of subjective symptoms and objective findings including residual urine and average flow rate, 8 weeks after the treatment. Reduction of subjective symptom score was observed in 26 cases (86.7%), and that of objective findings in 21 (70%). When 25% or more decrease of the total score was defined as good, the overall good result including subjective and objective responses was seen in 24 cases (80%). During the treatment and follow-up period, no severe adverse effect was detected. In conclusion, a single session of thermotherapy by Prostatron is a safe and useful modality as a non-surgical treatment performed on an outpatient basis for benign prostatic hyperplasia.

Aged↗

[The distribution and localization of alpha 1-adrenoceptor agonist on the bladder and urethra of female rats].

The distribution of selective alpha 1-adrenoceptor agonist 1-(2',5'-dimethoxyphenyl)-2-glycinamidoethanol hydrochloride, midodrine, and its active metabolite 1-(2',5'-dimethoxyphenyl)-2-aminoethanol, DMAE, was evaluated on bladder and urethra of 8-weeks and 52-weeks old female rats. Prior to the intravenous injection of 14C-labeled midodrine and DMAE, bilateral ureters were ligated to prevent drug uptake from the urinary tract. In 8-weeks rats, 14C-midodrine activity was significantly (p less than 0.01) higher in the bladder than in the femoral muscle, which served as a control for drug distribution. Similarly, higher uptake of 14C-DMAE was observed in the bladder than in the femoral muscle (p less than 0.01) and the urethra (p less than 0.05). In 52-weeks rats, there was no significant difference of midodrine uptake among these tissues. However, significantly higher uptake of 14C-DMAE was observed in the urethra than in the femoral muscle (p less than 0.05). Compared with midodrine, the concentration of DMAE was significantly increased in the bladder of 8-weeks rat and in the urethra of 52-weeks rats (respectively, p less than 0.05). In autoradiogram, the grains corresponding to midodrine and DMAE were diffusely distributed on the smooth muscles of bladder (mainly bladder neck and trigone) and urethra. The grains were also recognized on the vessels and perivascular areas of these tissues. These findings support that midodrine and DMAE could be effective for stress incontinence, because these drugs are known to bind specifically to alpha 1-adrenoceptor.

Adrenergic alpha-Agonists↗