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K Yoshioka

Publications and source records attributed to K Yoshioka.

At least 199 records · Page 11Linked to original sources
PubMed1997

Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C.

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male:female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5-2.0 to 2.0-3.0 and 3.0-4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 +/- 82 to 62 +/- 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic hepatitis C, although an antiviral effect was not noted.

Administration, Oral↗
PubMed1997

Earlier loss of hepatitis C virus RNA in interferon therapy can predict a long-term response in chronic hepatitis C.

To distinguish responders from non-responders early in interferon (IFN) treatment would be beneficial in patients with chronic hepatitis C. Those patients unlikely to respond would be spared the cost and hazard of prolonged treatment. Forty-three chronic hepatitis C patients who had received IFN-alpha therapy (6-9 MU; six times weekly for 2 weeks followed by thrice weekly for 22 additional weeks) were randomly enrolled into the present study. Serially obtained sera were retrospectively tested for HCV-RNA by reverse transcription-polymerase chain reaction (Amplicor HCV) with a low limit detection of approximately 10(2) copies/mL. Genotypes were determined by type-specific primers. Sixteen subjects were defined as sustained responders (SR), who showed sustained loss of viraemia with normalized alanine aminotransferase values for at least 6 months of follow-up after completion of therapy. The other 27 subjects were non-responders (NR), whose viraemia persisted during follow-up. Pretreatment serum HCV-RNA levels (P < 0.0001) and the genotype (P < 0.01) were significant predictors for sustained response to IFN therapy. Hepatitis C virus RNA was detectable in only one (6%) SR and in 23 (85%) NR at the second week of therapy (P < 0.0001) and was detected in none of the SR subjects and in 18 (67%) NR at the fourth week of therapy (P < 0.0001). Pretreatment viral load was correlated with the time until loss of viraemia. Multivariate analysis revealed that loss of viraemia at the second week of therapy was the strongest predictor for a long-term response, followed by the initial viral load and loss of viraemia at the fourth week of therapy. These findings suggest that it is possible to predict a long-term response to IFN as early as at the second and fourth weeks after the start of therapy by identifying the presence or absence of HCV-RNA with a sensitive assay.

Adult↗
PubMed1997

In vitro cytotoxicity of imidazolyl-1,3,5-triazine derivatives.

We examined in vitro cytotoxic activity of imidazolyl-1,3,5-triazine derivatives using human breast cancer cell lines (MCF-7, R-27, T-47D and ZR-75-1) and murine leukemia cell line (P388). The percentage of viable cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazorium bromide (MTT) assay. Hexamethylmelamine (HMM), a 1,3,5-triazine derivative has previously been recognized as an antitumor agent effective against lung, ovarian and breast cancer, but failed to show a significant cytotoxic activity in the present study. In contrast, four imidazolyl-1,3,5-triazine derivatives, 2-(1-imidazolyl)-4,6-bis(morpholino)-1,3,5-triazine, 2-(1-imidazolyl)-4-morpholino-6-(3-thiazolidinyl)-1,3,5-triazine, 2-(4-cyano-4-phenylpiperidino)-4-(1-imidazolyl)-6-morpholino-1,3,5-triaz ine and 2-(1-imidazolyl)-4-(N-methyl-N-phenylamino)-6-morpholino-1,3,5-triazine showed cytotoxic activity for most cell lines, which was significantly greater than the activity of hydroxymethylpentamethylmelamine (HMPMM), a major metabolite of HMM.

Altretamine↗
PubMed1997

Pyogenic clavicular osteomyelitis associated with disseminated intravascular coagulation and acute renal failure in a patient with non-insulin-dependent diabetes mellitus.

Pyogenic osteomyelitis is often accompanied by diabetes, but the disease in the clavicula has rarely been reported. We describe an unusual case of a 53-year-old man with poorly controlled non-insulin-dependent diabetes mellitus who presented with pyogenic clavicular osteomyelitis and developed DIC and acute renal failure. A 67Ga scintigram revealed an abnormal accumulation of the isotope in the right clavicula, where magnetic resonance imaging (MRI) showed inflammatory changes. This suggests that a 67Ga scintigram and MRI are of clinical value for the early diagnosis of the disease. Antibiotic chemotherapy with gamma-globulin and gebexate mesilate, and hemodialysis almost cured his serious condition.

Acute Kidney Injury↗
PubMed1997

Beta 3-adrenoreceptor gene polymorphism: a newly identified risk factor for proliferative retinopathy in NIDDM patients.

Proliferative diabetic retinopathy is an important cause of visual impairment. We investigated whether the polymorphism of the beta 3-adrenoreceptor (beta 3-AR) gene, which is associated with insulin resistance and an earlier onset of NIDDM, was associated with proliferative diabetic retinopathy (PDR) in 215 Japanese NIDDM patients with a duration of diabetes of > or = 10 years. The polymorphism of the beta 3-AR gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The Trp64Arg allele of the beta 3-AR gene was significantly more frequent in the NIDDM patients with PDR (P = 0.002), but not in those with non-PDR (P = 0.151), than in NIDDM patients without diabetic retinopathy. Those with the mutation had an earlier onset of diabetes, a longer duration of diabetes, and higher current and maximal BMI values, compared with those without the mutation. Moreover, this mutation was also associated with higher serum triglyceride and decreased HDL-cholesterol levels. When adjustment was made for age, age at diagnosis, duration of diabetes, current BMI, systolic blood pressure, HbA1e, and serum lipids in a multiple regression analysis, a significant association was found between the Trp64Arg allele and diabetic retinopathy (P = 0.039). The Arg/Arg or Arg/Trp genotype was significantly associated with PDR, compared with the Trp/Trp genotype, with an odds ratio of 2.55 (95% CI 1.25-5.16). We concluded that the beta 3-AR gene polymorphism is a newly identified risk factor for PDR.

Aged↗
PubMed1997

Serial quantitation of serum core protein and viral RNA of hepatitis C virus after interferon therapy: increase in viral loads in biochemical responders.

OBJECTIVES: Interferon (IFN) therapy is often ineffective in eradicating hepatitis C virus (HCV). Some patients show normal serum ALT levels for a long time after IFN therapy despite the presence of HCV. These patients are considered not virological responders but biochemical responders. We investigated the changes in the amount of HCV after IFN therapy in biochemical responders. METHODS: Nine biochemical responders and 11 nonresponders were studied. Serum HCV amount was measured by fluorescence enzyme immunoassay for HCV core (pg/ml) and Amplicor HCV Monitor test for HCV RNA (logarithms of copy numbers per milliliter). RESULTS: In biochemical responders, core protein and HCV RNA were increased significantly at 1 month after IFN therapy (291 +/- 191 pg/ml and 5.4 +/- 0.9, respectively; p < 0.05 for both) and at 1 yr (324 +/- 189 pg/ml and 5.6 +/- 0.7, respectively; p < 0.01 for both) compared with pretreatment values (122 +/- 114 pg/ml and 4.8 +/- 0.9, respectively). The change ratios of core protein at 1 month and 6 months after therapy to the pretreatment values were significantly higher in biochemical responders (3.2 +/- 2.4 and 2.9 +/- 2.3, respectively) than in nonresponders (0.9 +/- 0.7 and 1.1 +/- 0.8, respectively) (p < 0.05 for both). Similarly, the change ratios of HCV RNA at 1 month and 1 yr after IFN therapy were significantly higher in biochemical responders (9.9 +/- 14.6 and 12.8 +/- 15.1) than in nonresponders (0.6 +/- 0.5 and 1.2 +/- 1.2) (p < 0.05 for both). CONCLUSIONS: HCV amount increased significantly after IFN therapy in biochemical responders, whereas it did not change notably in nonresponders.

Alanine Transaminase↗
PubMed1997

[Influence for cultured renal cell growth ability by toxins of Escherichia coli].

There have been many reports indicating that Escherichia coli from pyelonephritis may exhibit several specific phenotypes. The purpose of the present study was to examine the effects of various toxins from Escherichia coli on cultured renal cell growth. alpha-hemolysin suppressed growth of Mardin Darby canine kidney (MDCK) cells in a dose-dependent manner. A low dose of O-antigen suppressed MDCK cell growth, while a high dose of the antigen increased the cell growth slightly. K:1-antigen had no effect on MDCK cell growth. Mesangial cell growth was not affected by alpha-hemolysin. A significant increase in mesangial cell growth was recognized by the O- or K:1-antigen. From these results it can be speculated that alpha-hemolysin from Escherichia coli may play a leading role, and O- or K-antigen may play a supporting role in the pathogenesis of pyelonephritis.

Animals↗
PubMed1997

Mechanism of decreased albuminuria caused by angiotensin converting enzyme inhibitor in early diabetic nephropathy.

The mechanism of decreased albuminuria caused by an inhibitor of angiotensin converting enzyme (ACE) was investigated in patients with early diabetic nephropathy. The subjects were 10 patients with non-insulin-dependent diabetes mellitus without azotemia but with albuminuria (less than 650 mg/day). First, a two-week study was done: one week with a diet with ordinary sodium levels and one week with a sodium-restricted diet, in random order. The systemic blood pressure and urinary excretion of sodium and albumin were measured daily. Intrarenal hemodynamics, in terms of the resistance of afferent and efferent arterioles (RA and RE) and glomerular capillary pressure (PGC), were calculated from renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Results obtained before and two weeks after starting the ACE inhibitor cilazapril (2 mg/day) were compared. Urinary excretion of albumin was decreased by cilazapril in 8 of the 10 patients. Cilazapril decreased the RE [6830 (3680, 14,750) to 4660 (1750, 10,790) dynes.sec.cm-5, P < 0.05, mean (minimum, maximum)] and PGC (53 +/- 5 to 43 +/- 9 mm Hg, P < 0.02, mean +/- SD) in these 8 patients, but not in the two other patients. The RA was not significantly changed in any patient. The percent change caused by cilazapril in the urinary excretion of albumin was significantly correlated with the change in PGC (N = 10, r = 0.875, P < 0.01), but not with changes in the systemic blood pressure. In conclusion, the mechanism by which an ACE inhibitor caused a short-term decrease in albuminuria in early diabetic nephropathy involved a glomerular hemodynamic change, namely, a decrease in PGC.

Aged↗
PubMed1997

[Radiology information system using HTML, JavaScript, and Web server].

We have developed a radiology information system using intranet techniques, including hypertext markup language, JavaScript, and Web server. JavaScript made it possible to develop an easy-to-use application, as well as to reduce network traffic and load on the server. The system we have developed is inexpensive and flexible, and its development and maintenance are much easier than with the previous system.

Local Area Networks↗
PubMed1997

[The drug sensitivity of enterohemorragic Escherichia coli and antibiotics treatment for hemorrhagic enterocolitis--from an outbreak of enterocolitis in Sakai city].

In July, 1996, a massive outbreak of hemorrhagic enterocolitis involving more than 5,000 people was caused by enterohemorragic Escherichia coli (EHEC) O157:H7 occurred mainly among elementary school children of Sakai City, Japan. The antibacterial activities in vitro against EHEC from stool specimens were determined. Norfloxacin showed the highest antibacterial activity, and fosfomycin, kanamycin, ampicillin, cefaclor were considered as effective drugs. But doxycycline showed lower antibacterial activities compared to other examined drugs, and it appears necessary to take antibiotic resistance of Escherichia coli into consideration when a treatment regimen is determined. As a result of the oral administration of fosfomycin to 95 patients of hemorrhagic enterocolitis and carrier, no patients developed complications with hemolytic uremic syndrome (HUS). However, a study of 17 patients with HUS demonstrated the fact that most of them were subjected to intravenous administration of fosfomycin. It may be needed to consider oral administration route of effective antibiotics in the treatment of enterocolitis in order to maintain high concentrations of a drug in the intestine.

Administration, Oral↗
PubMed1996

The tumor promoter arsenite stimulates AP-1 activity by inhibiting a JNK phosphatase.

Trivalent arsenic (As3+) is highly carcinogenic, but devoid of known mutagenic activity. Therefore, it is likely to act as a tumor promoter. To understand the molecular basis for the tumor-promoting activity of As3+, we examined its effect on transcription factor AP-1, whose activity is stimulated by several other tumor promoters. We found that As3+, but not As5+, which is toxic but not carcinogenic, is a potent stimulator of AP-1 transcriptional activity and an efficient inducer of c-fos and c-jun gene expression. Induction of c-jun and c-fos transcription by As3+ correlates with activation of Jun kinases (JNKs) and p38/Mpk2, which phosphorylate transcription factors that activate these immediate early genes. No effect on ERK activity was observed. As5+, on the other hand, had a negligible effect on JNK or p38/Mpk2 activity. Biochemical analysis and co-transfection experiments strongly suggest that the primary mechanism by which As3+ stimulates JNK activity involves the inhibition of a constitutive dual-specificity JNK phosphatase. This phosphatase activity appears to be responsible for maintaining low basal JNK activity in non-stimulated cells and its inhibition may lead to tumor promotion through induction of proto-oncogenes such as c-jun and c-fos, and stimulation of AP-1 activity. The same phosphatase may also regulate p38/Mpk2 activity.

Arsenites↗
PubMed1996

Functional localization of sensorimotor cortex by somatosensory evoked potentials produced by femoral nerve stimulation.

Cortical somatosensory evoked potentials (SSEPs) can be used to localize the central sulcus during a craniotomy. In particular, contralateral median nerve stimulation producing SSEPs can disclose the location of the central sulcus around the sensorimotor hand representation area. However, the median nerve cannot be stimulated in patients who undergo craniotomy at locations other than the hand representation area. The present study attempts to localize the central sulcus in the lateral surface of the brain near the interhemispheric fissure by stimulating the contralateral femoral nerve to produce SSEPs. Somatosensory evoked potentials were recorded between the superior lip of the interhemispheric fissure and 1.5 to 2 cm laterally in the cortex. Only seven of the 12 patients studied showed a phase reversal of the initial component across the central sulcus. The polarity was negative in the postcentral gyrus and positive in the precentral gyrus. The other five patients did not show a phase reversal of the initial component across the central sulcus. The amplitude was highest in the postcentral gyrus and the polarity was positive. Based on these results, the authors hypothesize that stimulating the contralateral femoral nerve to produce SSEPs and then analyzing the distribution of the SSEPs may provide a method for functional localization of the sensorimotor cortex around the interhemispheric fissure during craniotomy.

Journal Article↗
PubMed1996

The burst firing in the layer III and V pyramidal neurons of the cat sensorimotor cortex in vitro.

We identified the burst and single-spiking cells, and the repetitive bursting cells in layers III and V of the cat sensorimotor cortex with intracellular recording and staining techniques. Both types of the bursting cells were found in 22.7% of the recorded layer V neurons and in 23.1% of the recorded neurons in layer III. The bursting cells were characterized by the prominent afterdepolarization (ADP) which was usually reaching the threshold depolarization. Intracellular staining revealed that the morphology of the bursting cells was not so different from that of the regular-spiking cells in the cat.

Adenosine Diphosphate↗
PubMed1996

Immunosuppressant FK506 induces interleukin-6 production through the activation of transcription factor nuclear factor (NF)-kappa(B). Implications for FK506 nephropathy.

FK506 is a powerful immunosuppressive drug currently in use that inhibits the activation of several transcription factors (nuclear factor (NF)-AT and NF-kappaB) critical for T cell activation. We show here that, contrary to the situation in T cells, FK506 activates transcription factor NF-kappaB in nonlymphoid cells such as fibroblasts and renal mesangial cells. We further show that FK506 induces NF-kappaB-regulated IL-6 production in vitro and in vivo, in particular in kidney. IL-6 has been shown previously to produce renal abnormalities in vivo, such as mesangioproliferative glomerulonephritis. Similar renal abnormalities were also observed in FK506-treated animals. These results thus suggest a causal relationship between FK506-induced NF-kappaB activation/IL-6 production and some of FK506-induced renal abnormalities.

Animals↗
PubMed1996

rho-Mediated protein tyrosine phosphorylation in lysophosphatidic-acid-induced tumor-cell invasion.

Rat ascites hepatoma cell (MM1) invade a mesothelial cell monolayer in vitro in assay medium containing serum, but not in serum-free medium. Serum could be completely replaced by 1-oleoyl lysophosphatidic acid (LPA) in inducing invasion. LPA-induced invasion was inhibited by genistein, a tyrosine-kinase inhibitor. Protein tyrosine phosphorylation in response to LPA was thus analyzed in order to determine the molecular mechanism of invasion. LPA of invasion-inducible concentrations evoked a transient increase in tyrosine phosphorylation, mainly of 110- to 130-kDa proteins in MM1 cells but not in mesothelial cells. These concentrations of LPA were over 10 times higher (10 to 25 micron) than those necessary to produce a variety of biological actions, such as tyrosine phosphorylation in fibroblasts, neurite retraction and platelet aggregation. Protein tyrosine phosphorylation and invasion by MM1 cells induced by LPA are largely regulated by rho p21, because both were inhibited by Clostridium botulinum C3 exo-enzyme, which is known to specifically inactivate rho p21. Invasion of MCL by MM1 cells induced by serum and that by B16FE7 cells induced by LPA were inhibited by genistein or C3 as well. By immunoprecipitation, we detected p 125 focal adhesion kinase (FAK) as a major protein of 110- to 130-kDa tyrosine phosphorylated in response to LPA. Tyrosine phosphorylation of paxillin by LPA was also detected.

Animals↗