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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cutting edge: essential role of phospholipase C-gamma 2 in B cell development and function.

Cross-linking of the B cell Ag receptor (BCR) induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-gamma 2, which is involved in the activation of the phosphatidylinositol pathway. To assess the importance of PLC-gamma 2 in murine lymphopoiesis, the PLC-gamma 2 gene was inducibly ablated by using IFN-regulated Cre recombinase. Mice with a neonatally induced loss of PLC-gamma 2 function displayed reduced numbers of mature conventional B cells and peritoneal B1 cells and defective responses in vitro to BCR stimulation and in vivo to immunization with thymus-independent type II Ags. In contrast, T cell development and TCR-mediated proliferation were normal. Taken together, PLC-gamma 2 is a critical component of BCR signaling pathways and is required to promote B cell development.

Animals↗
PubMed2000

Cadmium-induced acute hepatic injury is exacerbated in human interleukin-8 transgenic mice.

It is reported repeatedly that severe hepatocellular necrosis along with infiltration of neutrophils occurs after acute cadmium exposure. Neutrophils, which migrate by the gradient of chemoattractants such as interleukin-8, are believed to play an important role in inflammation at the damaged sites. To investigate whether neutrophils aggravate or repair the liver injury induced by cadmium, we checked the hepatotoxic effects of cadmium on human interleukin-8 transgenic mice (hIL-8Tg), which overexpressed IL-8 and displayed an inability of neutrophil migration resulting from both the lack of chemotactic gradient and the downregulation of l-selectin on the surface of neutrophils. A significantly lower survival rate was observed in hIL-8Tg compared with wild-type mice after subcutaneous administration of cadmium. Evident liver injury characterized by abrupt increases in plasma GOT and GPT levels was found in hIL-8Tg at 18 h after cadmium administration. Histological examinations, including H & E staining and esterase staining, revealed the infiltration of numerous neutrophils into the damaged liver tissues in wild-type mice, and the inhibition of the neutrophil migration into the liver as well as enhanced hepatocellular necrosis in hIL-8Tg. Peripheral white blood cell and polymorphonuclear cell counts increased and reached their peaks at 12 h after cadmium administration in wild-type mice, whereas the increase in blood leukocyte counts was delayed in hIL-8Tg. There was no significant difference in the amounts of cadmium accumulated in liver and kidneys between wild-type mice and hIL-8Tg. In conclusion, an acute cadmium hepatotoxic effect was exacerbated in hIL-8Tg resulting from inhibited neutrophil migration, suggesting that migrated neutrophils can prevent aggravation of liver injury by acute cadmium administration.

Alanine Transaminase↗
PubMed2000

Preclinical evaluation of [11C]SA4503: radiation dosimetry, in vivo selectivity and PET imaging of sigma1 receptors in the cat brain.

Our previous in vivo study with rats has demonstrated that 11C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([11C]SA4503) is a potential radioligand for mapping CNS sigmal receptors by positron emission tomography (PET). In the present study, we further characterized this ligand. The radiation absorbed-dose of [11C]SA4503 in humans estimated with the tissue distribution in mice, was higher in the liver, kidney and pancreas than in other organs studied, but was low enough for clinical use. The brain uptake of [11C]SA4503 in mice was reduced to approximately 60-70% by co-injection of carrier SA4503 and haloperidol, but not by co-injection of any of six ligands for sigma2 or other receptors, for which SA4503 showed in vitro >100 times weaker affinity than for signal receptor. In the cat brain, the uptake in the cortex was higher than that in the cerebellum. The radioactivity in the cortex and cerebellum accumulated for the first 10 min and then gradually decreased until 81.5 min in the baseline measurement, but rapidly decreased in the carrier-loading condition. The receptor-mediated uptake was estimated to be approximately 60-65% of the total radioactivity in the cortex and cerebellum at 76 min after tracer injection. We have concluded that [11C]SA4503 has the potential for mapping sigma1 receptor by PET.

Animals↗
PubMed2000

Effect of overexpression of very low density lipoprotein receptor on cell growth.

The very low density lipoprotein (VLDL) receptor is a member of the LDL receptor gene family and binds only apoE-containing lipoproteins. Although the VLDL receptor has been shown to play an important role in the proliferation of vascular smooth muscle cells and the formation of foam cells as primary responses of atherogenesis, its actual functions are still unclear. To understand the biological roles of the VLDL receptor in foam cell formation and cell growth, we tried to overexpress VLDL receptors in various cells. When COS-7 cells were transfected with an expression plasmid containing VLDL receptor cDNA, cell growth was inhibited by overexpression of the receptor and this growth inhibition was ligand-independent. The O-linked glycosylation region, but not the cytoplasmic domain, of the receptor appeared to be responsible for this growth inhibition. On the other hand, VLDL receptor expression induced enhanced incorporation of lipids and cytoplasmic enlargement. These changes were dependent on the exogenous ligand and the cytoplasmic domain of the receptor. These results suggest that the VLDL receptor functions as a regulator of cell growth and differentiation, which may be distinct from its lipid-incorporating function.

Animals↗
PubMed2000

Nocturia in the adult: classification on the basis of largest voided volume and nocturnal urine production.

PURPOSE: We propose a criterion to clarify the underlying etiologies of nocturia. MATERIALS AND METHODS: Frequency-volume charts were recorded for 24 hours by 35 men and 32 women who were subjectively free of lower urinary tract symptoms and had no evidence of voiding disorders. At least 5 subjects were included in each of 5 age groups of 20 to 49, 50 to 59, 60 to 69, 70 to 79, 80 to 89 years for both genders. The charts were used to make a tentative criterion, which was validated in 39 elderly individuals with nocturnal frequency. RESULTS: Correlation and regression analyses indicated that the quotients of nocturnal urine output divided by body weight (U(N)/BW) and largest voided volume divided by body weight (V(L)/BW) were useful classification factors. Cutoffs, which were set close to worst quartiles, were 10 ml./kg. for U(N)/BW and 4 ml./kg. for V(L)/BW, respectively. Correction by body weight made the same criterion applicable irrespective of weight. Symptomatic elderly patients were classified into 3 mutually exclusive groups of nocturnal polyuria (U(N)/BW greater than 10 ml./kg.), low bladder capacity (V(L)/BW less than 4 ml./kg.) and combined nocturia. Of 20 subjects who voided 2 times a night 11 (55%) were classified as having nocturnal polyuria and 15 of 19 who voided 3 or 4 times (79%) were classified as having low bladder capacity or combined nocturia. CONCLUSIONS: The criterion provides a reasonable distinction of etiologies of nocturia, and may be usefulness in examination and treatment.

Adult↗
PubMed2000

Efficient HPLC separation of [11C]beta-CFT or [11C]beta-CIT from an N-desmethyl precursor on a semipreparative reversed phase ODS column.

HPLC separation of either [11C]beta-CFT or [11C]beta-CIT from the N-desmethyl precursor greatly depended on the ODS column used and the pH of the phosphate buffer in the mobile phase. The separation was accomplished on the semipreparative reversed phase ODS column without end-capping treatment over a pH ranging from 6.4 to 9.2, but failed on the end-capped ODS column. This suggests that the presence of residual silanol groups on the ODS is an important factor for the separation.

Carbon Radioisotopes↗
PubMed2000

In vivo evaluation of [(11)C]SA4503 as a PET ligand for mapping CNS sigma(1) receptors.

The potential of the (11)C-labeled selective sigma(1) receptor ligand 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([(11)C]SA4503) was evaluated in vivo as a positron emission tomography (PET) ligand for mapping sigma(1) receptors in rats. SA4503 is known to have a high affinity (IC(50) = 17.4 nM) and a higher selectivity (sigma(1)/sigma(2) = 103) for the sigma(1) receptor. A high and increasing brain uptake of [(11)C]SA4503 was found. Pre-, co- and postinjection of cold SA4503 significantly decreased uptake of [(11)C]SA4503 in the brain, spleen, heart, lung, and kidney in which sigma receptors are present as well as in the skeletal muscle. In the blocking study with one of four sigma receptor ligands including haloperidol, (+)-pentazocine, SA4503, and (-)-pentazocine (in the order of their affinity for sigma(1) receptor subtype), SA4503 and haloperidol significantly reduced the brain uptake of [(11)C]SA4503 to approximately 30% of the control, but the other two benzomorphans did not. A high specific uptake of [(11)C]SA4503 by the brain was also confirmed by ex vivo autoradiography (ARG) and PET. Ex vivo ARG showed a higher uptake in the vestibular nucleus, temporal cortex, cingulate cortex, inferior colliculus, thalamus, and frontal cortex, and a moderate uptake in the parietal cortex and caudate putamen. Peripherally, the blocking effects of the four ligands depended on their affinity for sigma(1) receptors. No (11)C-labeled metabolite was detected in the brain 30 min postinjection, whereas approximately 20% of the radioactivity was found as (11)C-labeled metabolites in plasma. These results have demonstrated that the (11)C-labeled sigma(1) receptor ligand [(11)C]SA4503 has a potential for mapping sigma(1) receptors in the central nervous system and peripheral organs.

Animals↗
PubMed2000

Effects of castration on contraction and alpha(1)-adrenoceptor expression in rat prostate.

1. The prostate function is regulated by androgens and alpha-adrenergic activity. Clinically, antiandrogens and/or alpha(1)-adrenergic antagonists are commonly used to treat symptomatic prostatic hypertrophy. To elucidate the effects of androgen deprivation on prostate contractility via alpha(1)-adrenoceptor, the characteristics and expression of alpha(1)-adrenoceptors were examined in castrated rats. 2. Isolated prostate strips from intact and castrated rats were subjected to a phenylephrine stimulated contraction. Prazosin (10 nM), [(3)H]-prazosin and phenoxybenzamine (3 - 300 nM) were used for inhibition assay, receptor characterization and partial alkylation of alpha-adrenoceptor, respectively. The mRNA content of three subtypes of alpha-adrenoceptors was determined by reverse transcription combined with polymerase chain reaction (RT - PCR). 3. Contractile response to phenylephrine increased in castrated rats, which could be explained by a relative increase of the stromal component. A lowered contraction potency was also noted in castrated rats. Receptor binding assay indicated minimal changes in the affinity or density of alpha(1)-adrenoceptor. Escalating alkylation of the alpha(1)-adrenoceptor population resulted in a rightward shift in the contraction-response curves before depressing maximal contractile force, and the suppression was detected at lower doses in castrated rats. RT - PCR study confirmed the expression of three types of alpha(1)-adrenoceptor, alpha(1a), alpha(1b) and alpha(1d)-adrenoceptors, in intact rat prostate, and revealed that alpha(1a)-adrenoceptor, but not alpha(1b) or alpha(1d)-adrenoceptors, was down-regulated in castrates. 4. The results show that androgen deprivation suppressed alpha(1)-adrenergic contractility of rat prostate strips, and the suppression was associated with down-regulation of receptor reserve for the alpha(1a)-adreneroceptor population expressed in intact rat prostate.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2000

Early results of LH-RH agonist treatment with or without chlormadinone acetate for hormone therapy of naive localized or locally advanced prostate cancer: a prospective and randomized study. The Prostate Cancer Study Group.

BACKGROUND: The majority of patients with localized and some cases of locally advanced prostate cancer undergo radical prostatectomy. However, radical prostatectomy cannot always be selected for those patients. In this situation, primary hormone therapy is an alternative treatment option. We have designed a prospective randomized study of the effects of primary hormone therapy for such patients. METHODS: A total of 151 patients with T1b, T1c, T2a, T2b or T3a prostate cancer who were not scheduled for radical prostatectomy were enrolled into this study. Patients were randomly allocated into two groups; Group I received luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy (leuprorelin acetate depot, 3.75 mg monthly) and Group II received LH-RH agonist in combination with chlormadinone acetate (100 mg/day). Effects on serum prostate-specific antigen level, progression-free survival and survival were observed for 2 years. RESULTS: The reasons why radical prostatectomy was not scheduled were poor risk for surgery (38%), patient's wish (32%) and physician's recommendation (30%). After 12 weeks of treatment, 49% of the patients in both groups showed a complete response (CR). Of the patients showing a partial response (PR) after 12 weeks of treatment, 25% in Group I and 52% in Group II improved to CR 1 year later (p<0.05). Group II showed a longer progression-free survival (p <0.05). Progression-free survival rates were 62% (Group I) and 91% (Group II) in T2b patients and 43% (Group I) and 73% (Group II) in T3 patients. Only one patient in each group died from prostate cancer. CONCLUSIONS: Early primary hormone therapy is a reasonable treatment option for localized or locally advanced prostate cancer patients if radical prostatectomy was not scheduled. Chlormadinone acetate showed an additive effect with LH-RH agonist, at least in 2 years' observation.

Aged↗
PubMed2000

Control of island formation on silicon surfaces using ultra-high-vacuum scanning electron microscopy

In situ scanning electron microscopy has been used to control Au island formation on a patterned Si(111) surface with a periodic array of atomic-step bunches and holes. Liquid phase Au-Si islands were observed to redistribute on the patterned surface by annealing. The islands accumulate at a particular position of the step bunch in each pattern unit. This phenomenon is interpreted in terms of the energetic stability of a droplet on a patterned surface.

Journal Article↗
PubMed2000

Reproducibility of cystometry in overactive detrusor.

OBJECTIVE: To examine the reproducibility of cystometry in the overactive detrusor. METHODS: The study sample involved 30 patients of the placebo arm in double-blind clinical trials for an overactive detrusor. They had demonstrated detrusor overactivity and underwent the second cystometry after 2-4 weeks. Nonparametric tests for paired data were used to examine the reproducibility of four variables: volume at first desire to void, volume at first involuntary contraction, cystometric capacity, and the maximum pressure of involuntary contraction. Percent change and within-subject standard deviation were calculated to assess intraindividual variability. RESULTS: The second test results showed a significant and systematic change for the better. Volume variables increased by 10-13% (p<0.01), involuntary contraction was not elicited in 3 cases (10%), and the maximum contraction pressure decreased by 18% in the remaining cases. Intraindividual variability was not small. Seventeen patients (57%) demonstrated > or = 25% change in one or more variables, and the 95% confidence interval of cystometric capacity, for example, was calculated as (x -57, x +57), where x is a test result. No specific patients' demographics were found related to variability. CONCLUSION: Repeat cystometry in the overactive detrusor is not highly reproducible and may be subject to a systematic effect for the 'better'. Whether this is due to the placebo effect or the learning effect could not be determined.

Double-Blind Method↗
PubMed2000

Serum KL-6 concentrations in dairy farmers.

STUDY OBJECTIVES: Serum KL-6 (Krebs von den Lungen-6) has been recognized to be a marker for the activity of diffuse interstitial lung diseases. The purpose of the study is to evaluate serum KL-6 measurement as a marker for farmer's lung disease (FLD). DESIGN: A cross-sectional survey of a cohort of dairy farmers. Retrospective measurement of KL-6 stored serum samples from those dairy farmers previously screened for FLD. SETTING: University hospital screening project for FLD within a dairy-farming community in Japan. PARTICIPANTS: Four hundred seventy-two dairy farmers were invited to attend a local clinic. MEASUREMENTS AND RESULTS: We examined serum KL-6 concentrations in 272 farmers. Subjects were classified into three groups: (1) 5 farmers with FLD, (2) 30 farmers with positive serum precipitating antibodies to Saccharopolyspora rectivirgula and/or Thermoactinomyces vulgaris without FLD (Ab(+)), and (3) 237 farmers without these antibodies (Ab(-)). Serum KL-6 concentrations in the FLD group were significantly higher than those in the Ab(+) and the Ab(-) groups (1,263 +/- 288 [SEM], 328 +/- 57, and 207 +/- 6 U/mL, respectively, p < 0.001). Serum KL-6 concentrations in those with FLD were significantly higher than KL-6 concentrations from stored screening samples from the same individual when FLD was not diagnosed (1,263 +/- 288 and 419 +/- 209 U/mL, respectively, p < 0.05). Serum KL-6 concentrations of the Ab(+) group were significantly higher than those of the Ab(-) group (p < 0.001). In the Ab(+) group, farmers with high serum KL-6 concentrations had lower permeability coefficients than farmers with normal serum KL-6 concentrations (p < 0.05). These results may suggest that subclinical FLD can be detected in farmers with high KL-6 concentrations and precipitating antibodies. CONCLUSION: Serum KL-6 concentration can be a useful marker for assessing the activity of FLD and may be able to be used to detect subclinical disease.

Actinomycetales↗
PubMed2000

CT-Guided acetic acid injection therapy for aldosterone-producing adrenocortical adenoma: a preliminary report of three cases.

We reported the preliminary outcomes of CT-guided percutaneous injection therapy for aldosterone-producing adrenocortical adenoma (APA). Five sessions of injection therapy, 4 percutaneous acetic acid injections (PAI) and 1 percutaneous ethanol injection (PEI) were performed in 3 patients with APA. A small amount of acetic acid or ethanol solution was injected via a needle placed precisely inside the tumor. The procedure was frequently monitored by repetitive CT scanning. The follow-up period ranged from 5 to 27 months. After the treatment, hypertension was normalized or controlled by a low dose of conventional anti-hypertensive drug. In 2 of 3 cases the plasma aldosterone levels were normalized. Although temporary symptoms of alcoholic intoxication were observed in the single session of PEI, the 4 sessions of PAI were associated with no adverse symptoms or complications. Although this study covers only short-term results in 3 patients, CT-guided PAI appears to be a safe and effective treatment and may be a promising alternative as a simple and far less invasive therapy for APA.

Acetic Acid↗
PubMed2000

Tubelactomicin A, a novel 16-membered lactone antibiotic, from Nocardia sp. I. Taxonomy, production, isolation and biological properties.

A novel 16-membered lactone antibiotic named tubelactomicin A was isolated from the culture broth of an actinomycete strain. The producing organism, designated MK703-102F1, was identified as a member of Nocardia. Tubelactomicin A was isolated from the culture broth by Diaion HP20 absorption, ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies and centrifugal liquid-liquid partition chromatography (CPC). Tubelactomicin A showed strong activity against acid-fast bacteria including the drug-resistant strains.

Anti-Bacterial Agents↗
PubMed2000

Migrastatin, a new inhibitor of tumor cell migration from Streptomyces sp. MK929-43F1. Taxonomy, fermentation, isolation and biological activities.

A new compound, migrastatin, was isolated from a cultured broth of Streptomyces sp. MK929-43F1, as an inhibitor of tumor cell migration. It was purified by column chromatographies on silica gel and Sephadex LH-20 and HPLC. Migrastatin has the molecular formula of C27H39NO7 consisting of 14-membered macrolide and glutarimide moiety. It inhibited spontaneous migration of human esophageal cancer EC17 cells. Migration inhibitory activity of migrastatin was not dependent on cytotoxicity or inhibition of protein synthesis.

Animals↗
PubMed2000

MK800-62F1, a new inhibitor of apoptotic cell death, from Streptomyces diastatochromogenes MK800-62F1. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity.

A new compound, MK800-62F1, was isolated from a cultured broth of Streptomyces diastatochromogenes MK800-62F1. It inhibited H2O2-induced apoptosis in human small cell lung carcinoma Ms-1 cells as well as in human T-cell leukemia Jurkat cells. In addition, MK800-62F1 also inhibited camptothecin-induced apoptosis in Jurkat cells, which was mediated by intracellular H2O2 generation. MK800-62F1 did not exhibit antioxidative activity in vitro, suggesting that inhibition of apoptosis by MK800-62F1 was not due to the scavenging of H2O2, rather it was due to the modulation of the downstream event of H2O2 generation.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Chronic hepatitis C beta-interferon-induced severe hypertriglyceridaemia with apolipoprotein E phenotype E3/2.

The mechanisms of hypertriglyceridaemia and changes in plasma lipoprotein subfractions by beta-interferon treatment were studied in a hepatitis C patient with apo E phenotype E3/2. Plasma levels of triglyceride (TG) were increased by treatment with 6 x 10(6) beta-interferon and reached 8.06 mmol/l at 4 weeks of treatment. Low energy and low fat diet reduced them to half the maximal level. Plasma levels of LDL1 (1.019 < d < 1.045)-C, LDL2 (1.045 < d < 1.063)-C, HDL2-C and HDL3-C were 0.39, 0.31, 0.21 and 0.28 mmol/l, respectively, which are low, but the plasma levels of IDL, which is a remnant of TG-rich lipoproteins, was normal at 7 weeks of treatment. The distribution of plasma lipoprotein subfractions returned to normal after interferon treatment was discontinued. The mass and activity of lipoprotein lipase (LPL) were reduced to half the baseline level by interferon treatment. The activity of hepatic triglyceride lipase (HTGL) which transforms IDL to LDL was normal. The patient's apo E phenotype was E3/2; with that phenotype the removal of TG-rich lipoproteins and IDL through the receptors of the remnant and LDL is impaired. But the IDL plasma level was normal, probably because of normal HTGL activity and high LDL-receptor activity. Lymphocyte LDL-receptor activity was double that of the control. We conclude that interferon caused the low mass and activity of LPL which in turn caused the hypertriglyceridaemia. And no retention of the remnant of TG-rich lipoproteins in this patient with apo E3/2 and low levels of LDL subfractions was due to the active removal of them through LDL-receptors as well as the impaired production of them by suppression of LPL by interferon.

Adult↗