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Biomedical subjects

K Kurokawa

Publications and source records attributed to K Kurokawa.

At least 19 recordsLinked to original sources
PubMed1995

Effects of long-term omeprazole treatment on adult rat gastric mucosa--enhancement of the epithelial cell proliferation and suppression of its differentiation.

Effects of long-term omeprazole treatment on the process of epithelial cell proliferation and differentiation in the adult rat gastric mucosa were investigated. Animals were treated with omeprazole (25 mg/kg body weight/day) for 28 days to induce anacidity in the stomach. The treatment induced a marked decrease in the number of chief cells in the gastric mucosa and at the same time an increase in that of immature pepsinogen-producing cells expressing class III mucin. This was accompanied by a decrease to 60% and 10% of the control values in the mucosal levels of pepsinogen and its mRNA, respectively. Moreover, the expression of cathepsin E in surface mucous cells was reduced. Cell proliferation studies revealed that the rate of bromodeoxyuridine-labeled cells was increased by omeprazole. The above-described changes were reversed by cessation of the treatment and they were not caused by the omeprazole-treatment at a dose which does not induce anacidity in the stomach. These results suggest that long-term omeprazole treatment reversibly increases the epithelial cell proliferation and suppresses its differentiation in the adult rate gastric mucosa probably by altering the acidic environment specific for the stomach.

Animals↗
PubMed1995

Clinical efficacy of fluvastatin for hyperlipidemia in Japanese patients.

The objective of the study was to evaluate the efficacy and safety of fluvastatin in patients with hypercholesterolemia, including heterozygous familial hypercholesterolemia, in a 1-year study (a 12-week open assessment, followed by 40 weeks of active treatment). Of the 337 patients enrolled in the study, the effects of fluvastatin were analyzed in 296 patients at baseline and at 12 weeks. Of these, 265 were receiving 20 mg/day fluvastatin at week 12 and in 20 patients the dose had been increased to 30 mg/day; 11 patients violated the dosing protocol. A total of 229 patients continued into the 40-week, long-term phase, and 212 patients were analyzed at baseline and after 24 and 52 weeks. At the end of treatment, 153 evaluable patients were still taking 20 mg/day fluvastatin, 1 was taking 10 mg/day, and 48 patients were taking 30 mg/day, and 10 were taking 40 mg/day. In the 20 mg/day fluvastatin group, low density lipoprotein cholesterol (LDL-C) levels decreased by 24.1% at week 12 and by 29.3% at week 52. In those patients requiring the higher doses, the corresponding reductions in LDL-C were 20.2% (week 12) and 26.7% (week 52). Total cholesterol was also reduced at week 12 by 17.0% (20 mg/day) and 15.7% (20-30 mg/day), and at week 52 by 20.4% (< or = 20 mg/day) and 19.2% (> or = 30 mg/day). Throughout the study, fluvastatin was generally well tolerated and no serious clinical adverse events were observed. In conclusion, long-term treatment of hypercholesterolemia with fluvastatin at dosages of 20-40 mg daily can be considered both safe and effective.

Anticholesteremic Agents↗
PubMed1995

Involvement of rho in GTP gamma S-induced enhancement of phosphorylation of 20 kDa myosin light chain in vascular smooth muscle cells: inhibition of phosphatase activity.

In beta-escin-permeabilized cultured pig aortic smooth muscle cells GTP gamma S dose-dependently enhances Ca(2+)-induced, wortmannin-sensitive phosphorylation of 20 kDa myosin light chain (MLC20). GTP gamma S does not potentiate thiophosphorylation of MLC20, but does inhibit its dephosphorylation. Pretreatment with C. botulinum exotoxin C3, which specifically ADP-ribosylates and inactivates the rho family of the small molecular weight G proteins, completely abolishes the effects of GTP gamma S. These results indicate that rho is involved in the GTP gamma S-induced enhancement of Ca(2+)-dependent MLC20 phosphorylation in aortic smooth muscle cells, and strongly suggest that this effect of rho is due to inhibition of protein phosphatase activity toward MLC20.

Animals↗
PubMed1995

A possible role of vitamin D receptors in regulating vitamin D activation in the kidney.

The vitamin D endocrine system is regulated reciprocally by renal 25-hydroxyvitamin D3 1 alpha- and 24-hydroxylases. Previously, we reported that renal proximal convoluted tubules, the major site of 1 alpha, 25-dihydroxyvitamin D3 production, have vitamin D receptors. In the presence of vitamin D receptors, renal proximal convoluted tubules cannot maintain the state of enhanced production of 1 alpha, 25-dihydroxyvitamin D3. To clarify this discrepancy, we proposed a working hypothesis for the reciprocal control of renal 25-hydroxyvitamin D3 1 alpha- and 24-hydroxylase activities. In rat models of enhanced renal production of 1 alpha, 25-dihydroxyvitamin D3, expression of vitamin D receptors and 25-hydroxyvitamin D3 24-hydroxylase mRNAs was strikingly suppressed in renal proximal convoluted tubules but not in the cortical collecting ducts. In vitamin D-deficient rats with up-regulated renal 25-hydroxyvitamin D3 1 alpha-hydroxylase activity, expression of vitamin D receptor mRNA in renal proximal convoluted tubules was also down-regulated, indicating that the down-regulation of vitamin D receptor mRNA is not the result of the enhanced production of 1 alpha, 25-dihydroxyvitamin D3. In Japanese quail models with up-regulated renal 25-hydroxyvitamin D3 1 alpha-hydroxylase activity by sex steroids, expression of vitamin D receptor mRNA was also down-regulated in the kidney but not in the duodenum. These results suggest that the down-regulation of vitamin D receptors plays a critical role in production of 1 alpha, 25-dihydroxyvitamin D3 in renal proximal convoluted tubules.

Animals↗
PubMed1995

Effect of CCK-B/gastrin receptor antagonist on pepsinogen-producing cells during omeprazole treatment.

The present study investigated the effect of long-term treatment with omeprazole on pepsinogen-producing cells and examined whether the selective CCK-B/gastrin receptor antagonist was able to prevent the omeprazole-induced changes, if occurred, in rat stomach. Rats were treated with omeprazole and/or the CCK-B/gastrin receptor antagonist for 28 days. As a result, omeprazole markedly reduced mucosal pepsinogen activity and its mRNA concentration in rat stomach. Morphologically, in fundic glands omeprazole drastically decreased the proportion of mature chief cells and reciprocally increased that of immature chief cells which were positive for class III mucin. These effects of omeprazole were attenuated by an addition of the CCK-B/gastrin receptor antagonist. Our results suggest that omeprazole retards the differentiation of chief cells in fundic mucosa probably through hypergastrinemia in adult rat.

Animals↗
PubMed1995

Prostaglandin F2 alpha stimulates formation of p21ras-GTP complex and mitogen-activated protein kinase in NIH-3T3 cells via Gq-protein-coupled pathway.

Prostaglandin (PG) F2 alpha activated mitogen-activated protein (MAP) kinase and MAP kinase kinase in NIH-3T3 cells by a mechanism that was completely inhibited by protein kinase inhibitors, staurosporine (20 nM) or H-7 (20 microM), but was insensitive to pretreatment with islet-activating protein (100 ng/ml; 24 h) or 12-O-tetradecanoylphorbol 13-acetate (2.5 microM; 24 h). PGF2 alpha stimulation also led to a significant increase in Ras.GTP complex. Transfection of a cDNA encoding a constitutively active mutant of Gq alpha-subunit (Q209L) mimicked PGF2 alpha-induced MAP kinase activation, increase in Ras.GTP complex, and DNA synthesis in these cells, suggesting that activation of Gq mediates the PGF2 alpha-activation of Ras-MAP kinase pathway and mitogenesis in NIH-3T3 cells. These data provide a new insight into regulatory mechanisms of Ras-MAP kinase pathway through heterotrimeric G-protein-mediated pathways.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Reliability of maximum number of simultaneously open channels as an estimator for the number of channels in single-channel recordings.

The single-channel recording technique has revolutionized the electrophysiological study of the ion channels. Interpretation of single-channel recordings often requires the exact number of channels present in a given patch--for example, derivation of the probability of a channel being open--and most theories handling gating kinetics assume that there is only one channel in the patch. Most investigators have estimated the number of channels as the number of maximal simultaneously open channels observed. Although this method is easy to understand and apply, examination of the validity of such estimation has not been much conducted before. As an attempt for such an examination, we have applied computer simulation method in order to obtain practically useful aids in judging the reliability of such estimates. Results show that (i) large estimated values (for example, larger than 10) are likely to be incorrect, and (ii) when the estimated value is small and the derived probability of a channel being open is within a certain range, the estimated number of channels is most likely to be correct.

Animals↗
PubMed1995

Dominant replication of either virus in dual infection with hepatitis viruses B and C.

To characterize the state of dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), HBV-DNA and HCV-RNA levels were determined by spot hybridization or polymerase chain reaction in the sera of patients who were positive for both hepatitis B surface antigen and HCV antibody. Among 27 patients who showed evidence of double infection, 21 (77.8%) had detectable levels of only either HBV or HCV genome in their sera, 2 (7.4%) showed none of the viral genomes, and 4 (14.8%) had both HBV-DNA and HCV-RNA. In the 4 patients with both HBV-DNA and HCV-RNA, the titers of HCV-RNA or HBV-DNA were lower than those in the patients with HCV-RNA or HBV-DNA alone. In some patients with chronic hepatitis, the viruses appeared to replicate in turn in the course of the disease. These results indicate that the viruses show alternating dominance in replication in most of the patients who have dual infection with HBV and HCV, probably due to interference of the viruses.

Adolescent↗
PubMed1995

C1q-binding immunoglobulin G in MRL/l mice consists of immune complexes containing antibodies to DNA.

Previous studies have shown that the majority of C1q-binding IgG in patients with systemic lupus erythematosus (SLE) is composed of autoantibodies to the collagen-like region of C1q. Mice of the MRL/l strain are considered as a murine model of human SLE and possess autoantibodies to nuclear antigens as well as IgM and IgG rheumatoid factors (RF). This study was undertaken to characterize the C1q-binding IgG in MRL/l mice. In contrast to human SLE, C1q-binding IgG in MRL/l mice showed immunochemical characteristics of immune complexes rather than those of autoantibodies to C1q. Namely, C1q-binding IgG in MRL/l mice was large-sized upon HPLC gel filtration and abolished by digestion with pepsin or by high salt concentration, and bound to the globular region of C1q. The C1q-binding activity in MRL/l mice was absorbed by double-stranded DNA- or single-stranded DNA-cellulose. The medium-sized immune complexes containing RF have been well documented in MRL/l mice. In this study, however, mouse IgG-Sepharose failed to absorb fully C1q-binding IgG. We conclude that the majority of C1q-binding IgG in MRL/l mice consists of large-sized immune complexes containing antibodies to DNA.

Animals↗
PubMed1995

Activation of the basolateral Cl- conductance by cAMP in rabbit renal proximal tubule S3 segments.

The regulatory mechanism of basolateral Cl- conductance in rabbit renal proximal tubule S3 segments was investigated with conventional and Cl- sensitive microelectrodes. After the basolateral Cl-/HCO3- exchanger was blocked by 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) we increased the bath K+ concentration from 5 mmol/l to 20 mmol/l, which depolarized the cells and thereby increased intracellular Cl- activity ([Cl-]i). This [Cl-]i response was enhanced by +63% in the presence of forskolin (20 mumol/l), by +40% in the presence of dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) (1 mmol/l) and by +44% in the presence of parathyroid hormone (PTH, 10 nmol/l), whereas it was inhibited by a Cl- channel blocker, indanyl-oxyacetic acid (IAA-94, 0.3 mmol/l). In addition, forskolin, PTH and chlorophenylthio-cAMP enhanced the electrogenic response to removal of bath Cl- after the blockade of K+ conductance, and this activation was also sensitive to IAA-94. On the other hand, 2 mumol/l ionomycin and 0.5 mumol/l phorbol myristate failed to activate the [Cl-]i response to elevation of bath K+ concentration and the electrogenic response to Cl- removal, and ionomycin had no effect even in the absence of DIDS. These results indicate that this basolateral Cl- conductance can be activated by cAMP, while neither the increase in cytosolic Ca2+ nor the activation of protein kinase C has direct effects on this conductance.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Occurrence of antibody against rat hepatic sinusoidal endothelial cells in sera of patients with autoimmune hepatitis.

To determine whether an antibody against hepatic sinusoidal endothelial cells was present in sera of patients with autoimmune hepatitis (AIH) type 1, we measured the serum IgG bound to the glutaraldehyde-fixed cultured rat sinusoidal endothelial cells by enzyme-linked immunosorbent assay. IgG bound to the cells was detected significantly more in patients with autoimmune hepatitis type 1 (97.1%) than in those with primary biliary cirrhosis (13.0%), chronic hepatitis C (5.9%) or B (7.9%), or healthy controls (0%). IgG-F(ab')2 fragments from autoimmune hepatitis patients also bound to the cells, and this binding was observed after absorption of the fragments with rat hepatoma cells, but not after absorption with bovine carotid endothelial cells. Culture of sinusoidal endothelial cells in the presence of IgG from AIH patients significantly reduced the number of viable attached cells. In conclusion, anti-sinusoidal endothelial cell antibody occurred in the sera from patients with autoimmune hepatitis type 1.

Animals↗
PubMed1995

Insulin nonattenuation of vasoactive agent-induced responses in mesangial cells from spontaneously hypertensive rats.

We recently found that insulin attenuates intracellular calcium transients and cell contraction caused by vasoactive agents in cultured rat mesangial cells. Because altered glomerular function may be causally related to the evolution of hypertension, we examined in the present study the effects of insulin on the functions of mesangial cells derived from spontaneously hypertensive rats (SHR) of 4- and 8-weeks of age. Age-matched Wistar Kyoto rats (WKY) were used as controls. Intracellular calcium concentration ([Ca2+]i) was measured with Fura-2 method in suspended mesangial cells. Pretreatment of mesangial cells with 5 micrograms/ml insulin for 120 minutes did not affect basal [Ca2+]i in either WKY or SHR mesangial cells. However, insulin pretreatment significantly attenuated [Ca2+]i transients to vasoactive agents in WKY mesangial cells. In contrast, [Ca2+]i transients to these agents were not attenuated by insulin in SHR mesangial cells. Additionally, SHR mesangial cell contraction in response to angiotensin II (Ang II) was not altered by insulin, while WKY mesangial cell contraction to Ang II was, as in normal Wistar rats, significantly reduced by insulin. Since we previously showed the possibility that the attenuation of calcium signal by insulin is via insulin-like growth factor I (IGF-I) receptor, we also examined the effect of IGF-I. In contrast to WKY mesangial cells, IGF-I-induced attenuation of [Ca2+]i responses to platelet activating factor was absent in SHR mesangial cells. [125I]-IGF-I binding in SHR mesangial cells was not significantly different from that in WKY mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Highly efficient adenovirus-mediated gene transfer into renal cells in culture.

In summary, we have shown that adenovirus vector efficiently introduced foreign gene into cultured renal cells both of mesangial and tubular origin. Genes transferred were properly expressed to produce the molecules of expected function. It was possible to introduce the gene into nearly 100% of the cells treated. Expression of the gene began as early as 12 hours after the infection, increased until 48 hours and persisted at least up to eight days. Finally, the vector was non-toxic to the cells, as judged from simple toxicity tests. Successful application of adenovirus vector enables for us to study function of pertinent molecules in suitable host cells and opens a new way for examining renal cellular physiology and pathophysiology.

Adenoviruses, Human↗
PubMed1995

Increased levels of soluble CD8 and CD4 in patients with infectious mononucleosis.

Plasma levels of soluble CD8 (sCD8) and soluble CD4 (sCD4) in 44 patients with infectious mononucleosis (IM) were studied. A marked increase in sCD8 (22366 +/- 2702 U/ml; control: 219 +/- 10 U/ml; P < 0.0001) and significant increase in sCD4 (19.3 +/- 0.9; control: 8.1 +/- 0.2, P < 0.0001) strongly suggest activation of both CD8+ and CD4+ lymphocytes, which is important in restraining Epstein-Barr virus-infected B lymphocytes. Levels of sCD8 strongly correlated with the percentage and the absolute number of both CD8+ and CD8(+)-HLA-DR+ lymphocytes. In addition, we showed increased release of sCD8 from lymphocytes in vitro and increased ratio between plasma sCD8 and the number of CD8+ lymphocytes in blood, indicating that elevation of plasma sCD8 is due to expansion of CD8+ subset as well as increased sCD8 release from each CD8+ cell. Increased sCD4 release from CD4+ lymphocytes, the number of which is not increased in the blood during IM, was also seen. Patients with more severe fever had higher levels of sCD8 and sCD4. During convalescence sCD8 and sCD4 levels showed progressive decrease; however, even at 60-119 d after onset the levels of sCD8 and sCD4 remained higher than normal, suggesting prolonged lymphocyte activation. These results suggest that sCD8 and sCD4 are useful in monitoring immune activation during IM.

Acute Disease↗
PubMed1995

Transurethral balloon laser hyperthermia for chronic non-bacterial prostatitis: a clinical trial.

Transurethral balloon laser hyperthermia (TUBAL-H) was performed on five patients with chronic non-bacterial prostatitis who failed to respond to conventional treatment administered for more than two years. The prostatic interstitial temperature during treatment was measured and the safety and efficacy of this treatment was assessed. TUBAL-H was performed at a target temperature of 43 degrees C (5 mm depth) and at a laser power of 30 watts with urethral cooling for 20 min in the first three patients and for 30 min in the remaining two patients. The prostatic interstitial temperature at a depth of about 5 mm from the urethral surface ranged from 40.5 to 43.0 degrees C during treatment. The temperature of the urethra ranged from 31.5 to 39 degrees C and that of the rectum remained below 39.5 degrees C. After treatment, no abnormal findings were noted in any of the hematological and biological tests carried out, including prostatic specific antigen. The leukocyte count in expressed prostatic secretions fell to less than five cells per high-power field in four of the five patients after three months. A complete improvement in symptoms was observed in one patient, partial improvement in three, and no improvement in one. Based on these results, TUBAL-H was considered to be safe and a suitable treatment for patients with chronic prostatitis.

Adult↗
PubMed1995

Changes in prostatic thickness and the location of ejaculatory ducts in autopsy prostates.

OBJECTIVE: To measure prostatic thickness and the depth of ejaculatory ducts from the urethral surface to prevent ejaculatory duct damage during transurethral balloon laser thermotherapy. MATERIALS AND METHODS: In 47 prostates obtained at autopsy, the prostatic thickness and the depth of ejaculatory ducts from the urethral surface were measured in eight directions from the centre of the urethra. RESULTS: The depth of ejaculatory ducts was approximately 6 mm from the urethral surface regardless of prostatic weight. Increase in prostatic weight was associated with increase in the thickness in all directions except the posterior one; the thickness ranged from 9 to 20 mm. The posterior thickness at the level of the transition zone was 10 mm regardless of prostatic weight. CONCLUSION: When benign prostatic hypertrophy is treated transurethrally, using laser or microwave equipment, care should be taken to avoid heating the posterior region of the prostate.

Adult↗
PubMed1995

Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent.

Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative disease of humans caused by an unidentified infectious agent, the prion. To determine whether there was an involvement of the host-encoded prion protein (PrPc) in CJD development and prion propagation, mice heterozygous (PrP+/-) or homozygous (PrP-/-) for a disrupted PrP gene were established and inoculated with the mouse-adapted CJD agent. In keeping with findings of previous studies using other lines of PrP-less mice inoculated with scrapie agents, no PrP-/- mice showed any sign of the disease for 460 days after inoculation, while all of the PrP+/- and control PrP+/+ mice developed CJD-like symptoms and died. The incubation period for PrP+/- mice, 259 +/- 27 days, was much longer than that for PrP+/+ mice, 138 +/- 12 days. Propagation of the prion was barely detectable in the brains of PrP-/- mice and was estimated to be at a level at least 4 orders of magnitude lower than that in PrP+/+ mice. These findings indicate that PrPc is necessary for both the development of the disease and propagation of the prion in the inoculated mice. The proteinase-resistant PrP (PrPres) was undetectable in the brain tissues of the inoculated PrP-/- mice, while it accumulated in the affected brains of PrP+/+ and PrP+/- mice. Interestingly, the maximum level of PrPres in the brains of PrP+/- mice was about half of the level in the similarly affected brains of PrP+/+ mice, indicating that PrPres accumulation is restricted by the level of PrPc.

Animals↗