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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 19 recordsLinked to original sources
PubMed1996

Purification and characterization of the phosphatidylinositol-3,4,5-trisphosphate phosphatase in bovine thymus.

Using phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] prepared from phosphatidylinositol 4,5-bisphosphate and inositolphospholipid 3-kinase, we identified in bovine thymus extracts the enzyme activity which catalyzed dephosphorylation of PtdIns(3,4,5)P3, to produce phosphatidylinositol biphosphate. Since bovine thymus exhibited the highest level of activity among tissues screened, we tried to purify this enzyme PtdINs(3,4,5)P3 phosphatase from bovine thymus. After sequential chromatographies using S-Sepharose, heparin-Sepharose, blue Sepharose, and Toyopearl HW55, the enzyme was purified 1875-fold with a yield of 10%. SDS/PAGE analysis revealed that a 120-kDA protein band copurified with the enzyme activity. The apparent molecular mass of the active protein was 120 kDa on size-exclusion chromatography, suggesting that the 120-kDa band on SDS/PAGE is the PtdIns(3,4,5)P3 phosphatase. Since PtdIns(3,4,5)P3 phosphatase seemed to be the only activity that metabolized PtdIns(3,4,5)P3, and the enzyme did not hydrolyze phosphatidylinositol 4,5-biphosphate, the enzyme may play a critical role in the inositolphospholipid 3-kinase signalling.

Animals↗
PubMed1996

Characterization of the interaction between RhoA and the amino-terminal region of PKN.

The yeast two-hybrid system and in vitro binding assay were carried out to characterize the interaction between PKN and a small GTP-binding protein, RhoA. It was revealed that the region corresponding to the amino acid residues 33-111 in the amino-terminal region of PKN was sufficient to confer the ability to associate with RhoA. Each synthetic peptide fragment corresponding to the amino acid residues 74-93 and 94-113 of PKN inhibited the interaction between PKN and RhoA in the in vitro binding assay, suggesting that this region is important in the association with RhoA. The endogenous and the GAP-stimulated GTPase activity of RhoA was inhibited by the interaction with PKN, suggesting the presence of a regulatory mechanism that sustains the GTP-bound active form of RhoA.

Binding Sites↗
PubMed1996

Cooperation of tyrosine kinases p72syk and p53/56lyn regulates calcium mobilization in chicken B cell oxidant stress signaling.

A chicken B cell line DT40 and its syk-negative or lyn-negative mutants were used to investigate the roles of protein-tyrosine kinases in oxidant stress signaling. The data presented here for wild-type cells demonstrate that hydrogen peroxide stimulates p53/56lyn-dependent tyrosine phosphorylation and activation of p72syk, and induces a rapid and prolonged elevation of intracellular calcium, which consists of calcium release from intracellular stores and influx from the extracellular space. Hydrogen-peroxide-triggered calcium mobilization was impaired in both syk-negative and lyn-negative cells, which was mainly due to the loss of calcium release from intracellular stores. Further studies indicated that inositol trisphosphate production was also abolished in both syk-negative and lyn-negative cells, which is consistent with the loss of calcium release. Taken together, these observations suggest that the defect of p72syk or p53/56lyn was responsible for the abnormality of calcium mobilization in both lyn-negative and syk-negative cells, and that both p72syk and p53/56lyn might regulate calcium mobilization through the phosphatidylinositol pathway in B cell oxidant stress signaling.

Animals↗
PubMed1996

Injection of glutaraldehyde cross-linked collagen for urinary incontinence: two-year efficacy by self-assessment.

BACKGROUND: Glutaraldehyde cross-linked (GAX) collagen has recently become available as injection material for treatment of urinary incontinence and should be evaluated for its long-term efficacy. METHODS: The subjects included 78 females with genuine stress incontinence (GSI) and 19 male or female patients with intrinsic sphincter deficiency (ISD: urinary incontinence due to urethral sphincter damage). GAX collagen was injected transperineally or transurethrally through an injection needle under direct endoscopic observation. The efficacy was evaluated by the patients' overall assessment at two years post-treatment. RESULTS: Under local or regional anesthesia, GAX collagen was injected 1.9 times on average (total injection volume: 23.5 mL) in GSI patients and 2.2 times (40.1 mL) in ISD patients. Improvement at two years post-treatment by patients' assessment was observed in 71.7% of GSI patients and 53.3% in ISD patients. Side effects were urinary retention and difficulty in voiding after 48 of the total of 188 injections (25.5%), a large amount of residual urine in four (2.1%) and miscellaneous in 19 (10.1%), for a short period after injection and were not serious. CONCLUSION: Our study indicates that GAX collagen injection is an effective, safe and easy non-medical treatment for urinary incontinent patients.

Aged↗
PubMed1995

Requirement of phospholipase C-gamma 2 activation in surface immunoglobulin M-induced B cell apoptosis.

Surface IgM (sIgM) stimulation induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-gamma 2, which is involved in the activation of phosphatidylinositol pathway. DT40 B cells underwent apoptotic cell death when activated through sIgM, a phenomenon that is related to elimination of self-reactive B cells. To examine the roles of PLC-gamma 2 in sIgM signaling, we have generated DT40 cells deficient in PLC-gamma 2 Cross-linking of sIgM on PLC-gamma 2-deficient cells evoked neither inositol 1,4,5-trisphosphate nor calcium mobilization. In PLC-gamma 2- or Syk-deficient DT40 cells, the induction of apoptosis was blocked, but was still observed in Lyn-deficient cells. Src homology 2 domains of PLC-gamma 2 were essential for both its activation and sIgM-induced apoptosis. Since tyrosine phosphorylation of PLC-gamma 2 is mediated by Syk, these results indicate that activation of PLC-gamma 2 through Syk is required for sIgM-induced apoptosis.

Animals↗
PubMed1995

Effects of simvastatin on plasma lipoprotein subfractions, cholesterol esterification rate, and cholesteryl ester transfer protein in type II hyperlipoproteinemia.

We investigated the effects of simvastatin on plasma levels of lipoprotein subfractions, cholesterol esterification rates and activities of cholesteryl ester transfer protein in 28 patients with type II hyperlipoproteinemia (i.e., nonfamilial hyperlipoproteinemia type IIa and type IIb, and heterozygous familial hypercholesterolemia (FH)). Plasma levels of VLDL-cholesterol (C) and VLDL-triglyceride (TG) were significantly reduced overall by 12.9 +/- 58.0% (mean +/- S.D.; P < 0.05) and 4.2 +/- 54.2% (P < 0.05) respectively, but not in FH. Plasma levels of IDL-C and IDLT-G were decreased overall by 23.2 +/- 47.5% (P < 0.001) and 12.3 +/- 49.7% (P < 0.05), respectively, again mainly due to decreases seen in nonfamilial type II hyperlipoproteinemia. Plasma levels of LDL1 (1.019 < d < 1.045)-C and LDL1-TG were significantly reduced by 33.1 +/- 12.9% (P < 0.001) and 23.3 +/- 24.7% (P < 0.001), respectively. Plasma levels of LDL2 (1.045 < d < 1.063)-C were significantly reduced by 22.9 +/- 18.1% (P < 0.001) overall but not in FH. Gradient PAGE showed no consistent changes in the distribution of LDL particles. Thus, plasma levels of all apo B-containing lipoprotein subfractions were reduced by simvastatin, but its effects varied among the three subgroups. Cholesterol esterification rates were suppressed by 9.3 +/- 19.7% (P < 0.01) and activities of cholesteryl ester transfer protein were reduced by 30.6 +/- 21.5% (P < 0.001). Changes in CETP activity and in plasma levels of cholesterol in lipoprotein subfractions were not correlated. Thus, the changes in distribution of lipoprotein subfractions were not due mainly to CETP suppression.

Adult↗
PubMed1995

Potentiation of Gi-mediated phospholipase C activation by retinoic acid in HL-60 cells. Possible role of G gamma 2.

Differentiated HL-60 cells acquire responsiveness to fMet-Leu-Phe (fMLP), which activates phospholipase C and O2- generation in a pertussis toxin-sensitive manner. Addition of retinoic acid (RA) for the last 24 h during dimethyl sulfoxide (Me2SO)-induced differentiation enhanced fMLP-dependent signals and interaction between fMLP receptor and G(i). RA modifies both the function and subunit composition of G(i)2, the predominant G(i) of HL-60 membranes, as shown by comparing purified G(i)2 from membranes of Me2SO-treated cells (D-G(i)2) to G(i)2 from membranes of cells treated with both Me2SO and RA (DR-G(i)2). As compared to D-G(i)2, DR-G(i)2 induced more fMLP binding when added to membranes of pertussis toxin-treated HL-60 cells and, in the presence of GTP gamma S, stimulated beta gamma-sensitive phospholipase C in extracts of HL-60 cells to a much greater extent at a lower concentrations. Immunoblasts revealed that RA induced expression of the gamma 2 subunit, which was otherwise undetectable in G(i)2 purified from HL-60 cells or in HL-60 membranes. Possibly by inducing expression of gamma 2, RA alters two functions of the G(i) beta gamma subunit, modulation of fMLP receptor-G(i)2 coupling and activation of the effector, Phospholipase C.

Cell Differentiation↗
PubMed1995

A lysophosphoinositide-specific phospholipase C distinct from other phospholipase C families in rat brain.

Distinct phospholipase C activities capable of hydrolyzing lysophosphatidylinositol (lysoPI-PLC) or phosphatidylinositol (PI-PLC) have been demonstrated in rat brain membranes. Treatment of brain membranes with 1 M NaCl or 1% sodium cholate solubilized a majority of PI-PLC activity from the membranes, whereas a significant level of lysoPI-PLC activity still remained membrane-associated. Most of the lysoPI-PLC activity was recovered in a 0.5% sodium deoxycholate-0.25 M NaCl extract which contained only low levels of PI-PLC activity. Using the separated fractions, differences between lysoPI-PLC and the known PI-PLC isoforms were examined. A specific peptide inhibitor of PI-PLC, which was previously shown to interact with active site regions common to known PI-PLC activity. Immunoblot analysis of both the lysoPI-PLC-rich and PI-PLC-rich fractions revealed that an antiserum against PI-PLC delta 1 cross-reacted with other PI-PLC isoforms, but not significantly with lysoPI-PLC. Furthermore, lysoPI-PLC was more resistant to sulfhydryl reagents than was PI-PLC. Our results indicate that lysoPI-PLC is an enzyme distinct from PI-PLC and that lysoPI-PLC possesses a different active site than known PI-PLC isoforms.

Amino Acid Sequence↗
PubMed1995

A dual functional signal mediator showing RhoGAP and phospholipase C-delta stimulating activities.

We have cloned a novel regulator protein, p122, in the PLC-delta signalling pathway by screening a rat brain expression library with antiserum raised against purified phospholipase C-delta 1 (PLC-delta 1). This novel p122-RhoGAP binds to PLC-delta 1 and activates the phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolyzing activity of PLC-delta 1. As suggested by the deduced amino acid sequence, this regulator protein shows a similarity to the GTPase activating protein (GAP) homology region of Bcr and possesses GAP activity for RhoA, but not for Rac1; no guanine nucleotide exchange activity for RhoA and Rac1 was detected. These findings suggest that this novel RhoGAP is involved in the Rho signalling pathway, probably downstream of Rho activation, and mediates the stimulation of PLC-delta, which leads to actin-related cytoskeletal changes through the hydrolysis of PIP2, which binds to actin binding proteins such as gelsolin and profilin.

Amino Acid Sequence↗
PubMed1995

Three cases of idiopathic interstitial pneumonia with bullae seen in schoolteachers.

We encountered three patients with chronic interstitial pneumonia with many bullae in the lower lung fields whose lifetime occupation was teaching school. Pathological examination of autopsy lungs of these patients revealed interstitial pneumonia and multiple bullae throughout the lungs, including the lower lobe. Since blackboard chalk has been used as a popular writing material among teachers in Japan, the mineral contents in the lungs of two of the three cases and four control cases with idiopathic interstitial pneumonia (IIP) (whose occupations were not teaching) were analyzed. The amount of deposition of total dust, inorganic dust, non-SiO2 inorganic dust, and calcium was significantly higher in the lungs of two schoolteachers compared with those of the control lungs. The amount of free silica in case 1 and alpha-quartz in case 3 were also significantly higher than in the controls. Two thirds of the chalk produced in Japan is still made from gypsum and involves small amounts of silica and other minerals, in addition to calcium. These findings indicated the deposition of chalk in the lungs of these patients with interstitial pneumonia and multiple bullae.

Blister↗
PubMed1995

Increased incidental detection and reduced mortality in renal cancer--recent retrospective analysis at eight institutions.

A retrospective survey of renal cell carcinoma between 1975 and 1993 at eight collaborating institutions was conducted with special reference to the incidental detection and mortality of renal cancer. The analysis demonstrated a recent dramatic increase in the frequency of incidental renal cancer, which now comprises two-thirds of all renal cancers, and a simultaneous recession in non-incidental or suspected renal cancer. Incidental renal cancer has remained unchanged during the last decade as far as patient demographics, occasion and method of detection, and the degree of tumor extension are concerned. On the other hand, the annual number of deaths from renal cancer has significantly decreased, and kidney-sparing surgery has been more frequently performed. These results indicate that incidental renal cancers are now in the majority, and earlier detection may contribute to improving the mortality and morbidity from the disease as a whole.

Aged↗
PubMed1995

Treatment of benign prostatic hyperplasia with high intensity focused ultrasound: an initial clinical trial in Japan with magnetic resonance imaging of the treated area.

BACKGROUND: High intensity focused ultrasound (HIFU) is a method of delivering acoustic energy to a focal point and is expected to induce tissue thermal ablation. Transrectal HIFU was applied to symptomatic benign prostatic hyperplasia (BPH) for relief of intravesical obstruction without injury to surrounding tissue. The clinical effectiveness and safety of transrectal HIFU were investigated. METHODS: Thirty-seven Japanese men with symptomatic BPH were treated with HIFU. The treatment was minimally invasive; operating time was less than 40 minutes, and a posttreatment indwelling catheter was left in place for 3-4 days. RESULTS: The maximum urinary flow rate (ml. per second) increased from 7.6 +/- 0.6 to 9.3 +/- 0.6 at three months in 37 patients (P < 0.05). During the same period the International Prostatic Symptom Score and Quality of Life score (points) decreased from 23.6 +/- 1.4 to 10.5 +/- 0.3, 5.2 +/- 0.3 to 2.6 +/- 0.1 (P < 0.001), respectively. Overall response estimated by these three individual parameters were as follows; excellent 18.9%, good 48.6%, fair 10.8% and poor 21.6% at three months. Magnetic resonance imaging using an endorectal coil showed coagulative necrosis defined in the therapy zone at one month after treatment. Side effects were transient urinary retention in six patients (16.2%), gross hematuria in four patients (10.8%) and hematospermia in four patients (10.8%). There was almost no intraoperative blood loss. CONCLUSIONS: Transrectal HIFU treatment of symptomatic BPH is safe, reduces symptoms significantly, and leads to a slight increase in uroflow.

Aged↗
PubMed1995

Response criteria for the therapeutic efficacy of treatment for benign prostatic hyperplasia.

Response criteria for the therapeutic efficacy of treatments for benign prostatic hyperplasia (BPH) were proposed following the International Consultation on BPH held in 1993. In the present study, we validated the criteria and proposed a simplified form, which consists of the responses of three parameters: symptom score and quality of life assessed by the international prostate symptom score and the maximum flow rate. Each of the three individual parameters is evaluated as one of four response grades: excellent, good, fair or poor, and the number of response grade of the three parameters determines the overall response. Excellent and Good responses are regarded as effective, and fair and poor are regarded as not effective. The validity of the response criteria was assessed by comparing the responses determined by these criteria with those made by physicians in charge using a group of 225 patients receiving various treatments. The agreement rates on effectiveness of overall responses between the response criteria and physicians were 77% for a multicenter trial of medical treatment (n = 94), 100% for TURP (n = 23), 92% for laser treatment (n = 47), 80% for thermal treatment (n = 26) and 78% for alpha-blockers (n = 35), respectively. Altogether, 88% (198 of 225 cases) were evaluated accurately regarding effectiveness. Addition of prostate volume to the battery of response parameters made little contribution to diagnostic accuracy. Deletion of any of the other three parameters, however, significantly compromised the quality of assessment. These results suggest that the proposed criteria may be useful as the standard method for the assessment of the clinical efficacy of BPH treatment.

Aged↗
PubMed1995

Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma.

BACKGROUND: Beta 2 adrenergic dysfunction may be one of the underlying mechanisms responsible for atopy and bronchial asthma. The gene encoding the human beta 2 adrenergic receptor (beta 2ADR) has recently been isolated and sequenced. In addition, a two allele polymorphism of this receptor gene has been identified in white people. A study was carried out to determine whether this polymorphism is functionally important and has any relation to airways responsiveness, atopy, or asthma. METHODS: The subjects studied were 58 family members of four patients with atopic asthma. Restriction fragment length polymorphism (RFLP) with Ban-I digestion of the beta 2ADR gene was detected by a specific DNA probe with Southern blot analysis. Airways responses to inhaled methacholine and the beta 2 agonist salbutamol, the skin prick test, and serum IgE levels were also examined and correlated to the beta 2ADR gene RFLP. In addition, measurements of cAMP responses to isoproterenol in peripheral mononuclear cells were performed in 22 healthy subjects whose genotype for beta 2ADR was known. RESULTS: A two allele polymorphism (2.3 kb and 2.1 kb) of the beta 2ADR gene was detected in the Japanese population. Family members without allele 2.3 kb (homozygote of allele 2.1 kb) had lower airways responses to inhaled salbutamol than those with allele 2.3 kb. The incidence of asthma was higher in those without allele 2.3 kb than in those with allele 2.3 kb. The beta 2ADR gene RFLP had no relation to airways responses to methacholine and atopic status. cAMP responses in peripheral mononuclear cells of the subjects without allele 2.3 kb tended to be lower than those of the subjects with allele 2.3 kb. CONCLUSIONS: These results suggest that Ban-I RFLP of the beta 2ADR gene may have some association with the airways responses to beta 2 agonists and the incidence of bronchial asthma.

Adolescent↗
PubMed1995

Can interstitial pneumonia as the sole presentation of collagen vascular diseases be differentiated from idiopathic interstitial pneumonia?

We prospectively followed 68 patients diagnosed as idiopathic interstitial pneumonia (IIP) over a period of 1-11 years. Thirteen patients (19%) subsequently developed systemic manifestations of collagen vascular diseases (CVD) and were diagnosed as having had interstitial pneumonia as the sole presentation of CVD (CVD-IP). Compared with the 55 IIP patients, the 13 CVD-IP patients were relatively younger, predominantly female, and had a lower incidence of dust inhalation in their history. They also had a higher erythrocyte sedimentation rate, higher incidence of the x-ray finding of discoid atelectasis in the lower lung fields, and a better prognosis than the IIP patients. However, these features did not clearly distinguish the two groups. We conclude that the patients clinically and/or histologically defined as suffering from IIP cannot be distinguished from CVD-IP patients before systemic signs of CVD appear in the latter group.

Adult↗
PubMed1995

Dairy farmers have increased methacholine bronchial responsiveness independent of sensitization to mold antigens.

Patients with farmer's lung disease (FLD) and dairy farmers have nonspecific bronchial hyperresponsiveness. To examine the factors determining bronchial hyperresponsiveness among dairy farmers, we studied airway functions, airway responses to inhaled methacholine, serum total IgE levels, and antigen-specific IgE levels in 37 dairy farmers and 11 local control subjects. The 37 dairy farmers consisted of three groups; 12 farmers with episodes of FLD (FLD group), 13 farmers with serum antibody to Micropolyspora faeni (MF) and/or Thermoactinomyces vulgaris (TV) but without episodes of FLD (Ab(+) group), and 12 farmers without serum antibodies to MF and TV and without episodes of FLD (Ab(-) group). Pulmonary function tests showed small airways disorders among farmers (each of the three groups versus control subjects; p < 0.05). Methacholine provocation test, utilizing PD35Grs (a cumulative dose of methacholine that induces 35% reduction in respiratory conductance [Grs]), showed bronchial hyperresponsiveness in each group of dairy farmers compared with that in control subjects (Log PD35Grs, mean +/- SEM: 1.22 +/- 0.18, 1.00 +/- 0.17, and 1.20 +/- 0.20, respectively, versus 2.10 +/- 0.09; p < 0.001). However, there was no statistically significant difference in bronchial responsiveness among the three groups of dairy farmers. In addition, there was no significant difference in serum total IgE levels and specific IgE antibodies among the four groups. These results suggest that the bronchial hyperresponsiveness to methacholine among dairy farmers is not due to past episodes of FLD or sensitization to MF and/or TV, but is possibly due to the occupational environment of dairy farming.

Antibodies, Bacterial↗