Biomedical subjects

K Nagashima

Publications and source records attributed to K Nagashima.

At least 271 records · Page 15Linked to original sources

PubMed1995

Protective effects of KW-3902, an adenosine A1-receptor antagonist, against cisplatin-induced acute renal failure in rats.

We investigated possible renal protective and therapeutic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel and potent adenosine A1-receptor antagonist, on cisplatin-induced acute renal failure (ARF). ARF was induced in rats by a single injection of cisplatin-induced acute renal failure (ARF). ARF was induced in rats by a single injection of cisplatin (5 mg/kg, i.v.). Prophylactic treatment with KW-3902 (0.01-1 mg/kg, p.o., twice a day) significantly attenuated the increases of serum creatinine (S-CRE) and urea nitrogen (S-UN) induced by cisplatin. On the other hand, neither furosemide nor trichlormethiazide showed any ameliorating effects against the cisplatin-induced ARF. In the clearance study, the cisplatin-treatment induced marked decreases of glomerular filtration rate (GFR), renal plasma flow (RPF), and reabsorptions of water, sodium and potassium at tubular sites, in comparison with those in untreated normal rats. KW-3902 (0.1 mg/kg, p.o., twice a day) significantly improved these deteriorated glomerular and tubular functions. In the rats with established cisplatin-induced ARF, KW-3902 ameliorated the cisplatin-induced reductions of GFR, RPF, and reabsorptions of water, sodium and potassium at tubular sites. These results suggest that activation of adenosine A1-receptors is involved in the pathogenesis of cisplatin-induced ARF. The adenosine A1-receptor antagonist may be useful for the treatment of cisplatin-induced ARF.

Absorption↗

PubMed1995

Effects of KW-3902, an adenosine A1-receptor antagonist, on ascites volume in puromycin aminonucleoside (PAN)-induced nephrotic rats.

We investigated the effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a potent adenosine A1-receptor antagonist, on the nephrotic edema induced by puromycin aminonucleoside (PAN; 100 mg/kg, i.v.) in rats. The treatment with PAN decreased urine volume and urinary excretions of sodium and potassium, resulting in the ascites formation in 7 days. In rats with the nephrosis, KW-3902 (0.01-1 mg/kg/day for 3 days, p.o.) showed diuretic effects and reduced the volume of ascites, as was the case with furosemide (30 mg/kg/day) and trichlormethiazide (1 mg/kg/day). These results suggest that even in the nephrotic state, the adenosine A1-receptor antagonist can be an effective diuretic to ameliorate edema.

Animals↗

PubMed1995

Antihypertensive effects of KW-3902, an adenosine A1-receptor antagonist, in Dahl salt-sensitive rats.

We determined the effects of KW-3902 (8-(noradamantan-3-yl)-1,3- dipropylxanthine), a novel adenosine A1-receptor antagonist, on the development of hypertension in Dahl salt-sensitive (Dahl-S) rats. KW-3902 (0.00017% w/w-0.017% w/w), fed with the diet, prevented the development of hypertension at 2-6 weeks in response to the high (8% w/w) NaCl diet. KW-3902 increased urine volume and sodium excretion and attenuated cardiac hypertrophy. In another series of the experiments employing the clearance method, KW-3902 (0.1 mg/kg, i.v.) increased urine volume, sodium excretion and lithium clearance in anesthetized Dahl-S rats. These results suggest that the antihypertensive effect of KW-3902 in Dahl-S rats is mediated via its natriuretic effect, the site of action being, at least partly, the proximal tubule. The adenosine A1-receptor antagonist may be effective for the treatment of salt-sensitive hypertension.

Animals↗

PubMed1995

Effects of alpha-adrenergic activation on the shift of electrolytes and fluid after hemorrhage in rats.

To assess the effects of alpha-adrenergic activation on hemorrhage-induced shifts of K+, Na+ and fluid between the intravascular and extravascular spaces, we continuously measured changes in plasma concentrations of K+ and Na+ (delta[K+]p, delta[Na+]p) and blood volume (delta BV) over 60 min after hemorrhage in nephrectomized rats. Hemorrhage was conducted over 5 min at the level of 0.5, 1.0 and 1.5% of body weight (H0.5, H1.0, H1.5), and the result was compared with hemorrhage of 1.0% body weight after administration of alpha 1-adrenoreceptor antagonist prazosin (0.2 mg/kg, H1.0P). delta[K+]p increased significantly (p < 0.05) after hemorrhage, and the peak value was proportional to the level of hemorrhage (0.18 +/- 0.08, 0.62 +/- 0.22 and 1.64 +/- 0.19 meq/l in H0.5, H1.0 and H1.5, respectively). delta[Na+]p decreased significantly (p < 0.05) after hemorrhage, and the decrease was sustained until the end of the experiment (-0.8 +/- 0.6, -1.0 +/- 0.5 and -2.2 +/- 0.5 meq/l in H0.5, H1.0 and H1.5, respectively). In H1.0P, the increase in delta[K+]p (0.25 +/- 0.09 meq/l at the peak) and the decrease in delta[Na+]p (-0.2 +/- 0.1 meq/l at the bottom) were suppressed significantly (p < 0.05) compared to H1.0. Although delta BV was greater in H1.0P than H1.0, plasma K+ content was not different between the groups. In H1.0, the calculated concentrations of K+ and Na+ in the fluid which shifted into the intravascular space ([K+]sf, [Na+]sf) in the first 30 min after hemorrhage were higher in [K+]sf (6.25 +/- 0.70 meq/l) and lower in [Na+]sf (128.0 +/- 3.2 meq/l) than the pre-hemorrhage plasma level. With regard to H1.0P, [K+]sf and [Na+]sf were not different from the pre-hemorrhage level of plasma. These results suggest that alpha-adrenergic activation after hemorrhage induces K+ movement into plasma to increase [K+]p, which might be related to the fluid shift from the intracellular to the extracellular space.

Adrenergic alpha-Agonists↗

PubMed1995

[A case of incarceration of a right femoral hernia in a very old female with a intriguing clinical course].

The patient was a 94-year-old woman. She was admitted on our hospital for ileus due to incarceration of a right femoral hernia on October 29, 1993. Although an emergency operation was necessary she refused, therefore we continued to have conservative therapy. After repeated persuasion, she agreed the operation which was performed under spinal anesthesia on November 17. The peritoneal cavity was opened through a transverse incision of the lower abdomen. Some bloody ascites was encountered. Part of the jejunum was incarcerated through right femoral canal and was completely obstructed, with ischemic but no necrotic changes. It was excised. She resumed oral intake on the 7th postoperative day and was discharged on the 77th postoperative day. Initially due to her opposition we could not perform the operation, but after persistent persuasion she agreed and survived. Good communications between the doctor and the patient, and of course informed consent, was very important in such cases.

Aged↗

PubMed1995

[Perceived quality of life and social factors in elderly hypertensive patients].

We conducted a cross-sectional study of elderly outpatients with hypertension to examine the relationship between quality of life (QOL) scores and social background factors. The subjects consisted of 516 outpatients (267 females), age of 60 or over, at nine clinics of major hospitals which participated in the National Cardiovascular Center Research Project. The perceived QOL was evaluated by the QOL scale originally based on Japanese patients with cardiovascular diseases. The scale consisted of the following 5 subscales; difficulty due to disease, psychological stability, independence, satisfaction in daily living and vitality. The background factors included family structure, socioeconomic factors and work status, and physical activity of daily living (ADL). After adjusting for age, sex, administered drugs and complicating conditions such as ischemic heart disease and/or apoplexy, a significant odds ratio of a low score of difficulty due to disease, psychological stability, satisfaction in daily living and vitality was found in the impaired physical ADL group with low socioeconomic class, and a significant odds ratio of low score of independence were found in the impaired physical ADL group who had lost jobs due to illness and had no children.

Aged↗

PubMed1995

Salfredins, new aldose reductase inhibitors produced by Crucibulum sp. RF-3817. I. Fermentation, isolation and structures of salfredins.

New inhibitors of aldose reductase, designated salfredins A3, A4, A7, C1, C2, C3 and B11, were isolated from the fermentation broth of Crucibulum sp. RF-3817 by successive purification procedures of solvent extraction, silica gel column chromatographies and reverse-phase HPLC. Their structures were established by spectroscopic methods, including UV, SI-MS and NMR. The structures of salfredins A4 and B11 were confirmed by X-ray crystallographic analysis.

Aldehyde Reductase↗

PubMed1995

The validity of intraoperative frozen section diagnosis based on video-microscopy (telepathology).

The validity of intraoperative frozen section diagnosis (IFSD) via telepathology between Hokkaido University School of Medicine (HUSM) and a remote hospital was evaluated. Video-microscopic images of hematoxylin-eosin (HE)-stained frozen sections were transmitted by a cytoscreener via the Pathtran 1,000 system and a telephone line to a color monitor at HUSM (120 km from the submitting hospital) with a resolution of 512 x 480 pixel matrix. The pathologists at HUSM made diagnoses on the received images. Of the 59 cases, there was diagnostic concordance between telepathology and permanent paraffin sections in 19 malignant, 36 benign, and one borderline case. The latter was a case of atypical ductal hyperplasia of the breast. The telepathology diagnostic modality was inconclusive in three cases, two of which were benign and one malignant by paraffin section examination. These results provide evidence for the diagnostic adequacy of video-microscopic images, the interpretation of which compared favorably with that of conventional frozen sections. Although the need for IFSD is increasing, the proportion of hospital pathologists accepting this modality is not. For the appropriate use of telepathology, it is necessary that more pertinent personnel, especially cytoscreeners and pathologists receive a thorough training and become familiar with the system. Telepathology offers pathologists a diagnostic modality that responds to the needs of physicians and serves to enhance the pathologist's position in health care services.

Adult↗

PubMed1994

[The measurement of insulin antibodies and insulin autoantibodies by enzyme-linked immunosorbent assay using recombinant human insulin antigen and its clinical application].

Insulin antibodies (IA) are detectable in the sera of most insulin-treated patients with diabetes mellitus. Antibodies to exogenous insulin sometimes cause clinical symptoms of insulin resistance, allergy, and local lipoatrophy. Although the frequency of these complications has diminished with the use of highly purified porcine insulin or recombinant human insulin, there are some patients with high titer of IA. Autoantibodies to insulin (IAA) are also described. IAA has been reported to be in association with both insulin-dependent diabetes mellitus (IDDM) and polyendocrine autoimmune disease. For many years these antibodies have been measured by radiobinding assay (RBA) in which the complexes are precipitated non-specifically by polyethylene glycol. In the present study we developed a rapid and quantitative enzyme-linked immunosorbent assay (ELISA) method for measuring IA and IAA using recombinant human insulin antigen. We applied this method to the samples obtained from patients with diabetes mellitus and autoimmune thyroid disease and then compared the results with those obtained from the RBA method. The calibration curve for ELISA was derived from the dilution curve of a single serum from a patient positive for insulin antibody, and the results were expressed arbitrarily as ELISA UNIT. The calibration curve was approximately linear on the log-log scale within the range of 0.1-2.0 at optical density (OD)450nm, (6.25-200 ELISA UNIT). The intra-assay (CV = 2.3-3.1%) and inter-assay (CV = 2.8-7.2%) precisions were acceptable. Recovery rate varied from 74.5% to 118.5% and dilution experiments showed good linearity. Specificity was demonstrated by substituting purified human IgG for the test serum and glucagon for insulin. Except for hemoglobin, coexisting substances in serum had almost no effect on ELISA. The range of ELISA UNIT (Mean +/- SD) of 83 normal sera was 12.7 +/- 4.6. Positivity for IA by ELISA (> normal Mean + 3SD) was 11 out of 58 (19.0%) and 26 out of 55 (47.3%) in patients with IDDM and with non-insulin-dependent diabetes mellitus (NIDDM) who were treated with insulin, respectively. Positivity for IAA by ELISA was 5 out of 173 (2.8%) and 1 out of 20 (5.0%) in patients with NIDDM without insulin therapy and hyperthyroidism due to Graves' disease, respectively. However, by RBA, we detected 4 other cases positive for IAA in NIDDM without insulin therapy and one case in Graves' disease. The present study demonstrates that the newly developed method of ELISA using recombinant human insulin antigen is clinically useful for measuring IA and IAA.

Antigens↗

PubMed1994

Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novel Helicobacter species.

BACKGROUND: In the autumn of 1992, a novel form of chronic, active hepatitis of unknown etiology was discovered in mice at the National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), Frederick, Md. A high incidence of hepatocellular tumors occurred in affected animals. The disease entity was originally identified in A/JCr mice that were untreated controls in a long-term toxicologic study. PURPOSE: Our original purpose was to determine the origin and etiology of the chronic hepatitis and to quantify its association with hepatocellular tumors in mice of low liver tumor incidence strains. After a helical microorganism was discovered in hepatic parenchyma of diseased mice, we undertook characterization of the organism and investigation of its relationship to the disease process. METHODS: Hepatic histopathology of many strains of mice and rats, as well as guinea pigs and Syrian hamsters, in our research and animal production facilities was reviewed. Steiner's modification of the Warthin-Starry stain and transmission electron microscopy were used to identify bacteria in the liver. We transmitted the hepatitis with liver suspensions from affected mice and by inoculation with bacterial cultures. Bacteria were cultivated on blood agar plates maintained under anaerobic or microaerophilic conditions and characterized morphologically, biochemically, and by 16S rRNA sequence. RESULTS: We report here the isolation of a new species of Helicobacter (provisionally designated Helicobacter hepaticus sp. nov.) that selectively and persistently colonizes the hepatic bile canaliculi of mice (and possibly the intrahepatic biliary system and large bowel), causing a morphologically distinctive pattern of chronic, active hepatitis and associated with a high incidence of hepatocellular neoplasms in infected animals. CONCLUSIONS: The novel Helicobacter is a likely candidate for the etiology of hepatocellular tumors in our mice. The Helicobacter-associated chronic active hepatitis represents a new model to study mechanisms of carcinogenesis by this genus of bacteria. IMPLICATIONS: Adenocarcinoma of the stomach, the second most prevalent of all human malignancies world-wide, is associated with infection at an early age with Helicobacter pylori. Infection leads to several distinctive forms of gastritis, including chronic atrophic gastritis, which is a precursor of adenocarcinoma. H. hepaticus infection in mice constitutes the only other parallel association between a persistent bacterial infection and tumor development known to exist naturally. Study of the H. hepaticus syndrome of chronic active hepatitis and liver tumors in mice may yield insights into the role of H. pylori in human stomach cancer and gastric lymphoma.

Adenoma, Liver Cell↗

PubMed1994

High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice.

We have generated TCR transgenic mice (T/R+) specific for myelin basic protein (MBP) and crossed them to RAG-1-deficient mice to obtain mice (T/R-) that have T cells expressing the transgenic TCR but no other lymphocytes. Both T/R+ and T/R- mice carry, in the lymph nodes and spleen, large numbers of the potentially encephalitogenic CD4+ anti-MBP T cells. These cells respond to MBP in vitro but show no signs of activation in vivo. Nevertheless, approximately 14% of H-2u T/R+ and 100% of H-2u T/R- mice developed spontaneous experimental autoimmune encephalomyelitis (EAE) within 12 months. These data indicate that EAE can be mediated by CD4+ anti-MBP T cells in the absence of any other lymphocytes and that nontransgenic lymphocytes that are present in T/R+ but absent in T/R- mice have a protective effect. The data also suggest that spontaneous EAE may be triggered by an in situ activation of CD4+ anti-MBP cells in the nervous system.

Amino Acid Sequence↗

PubMed1994

C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins.

CRK protein, together with GRB2/ASH and Nck proteins, belongs to the adaptor-type Src homology (SH)2-containing molecules, which transduce signals from tyrosine kinases. Here another guanine nucleotide-releasing protein (GNRP), C3G, has been identified as a CRK SH3-binding protein. The nucleotide sequence of a 4.1-kb C3G cDNA contains a 3.2-kb open reading frame encoding a 121-kDa protein, and antibodies against C3G have been shown to detect a protein of 130-140 kDa. The carboxyl terminus of C3G has a peptide sequence homologous to GNRPs for Ras, and the expression of this carboxyl terminus region suppresses the loss of CDC25 function in the yeast Saccharomyces cerevisiae. The C3G protein expressed in Escherichia coli binds to CRK and GRB2/ASH proteins. Mutational analysis of C3G assigns the SH3 binding region to a 50-amino acid region containing a proline-rich sequence. The mRNAs of both the C3G and CRK proteins are expressed ubiquitously in human adult and fetal tissues. The results of these studies suggest that the complex of CRK and C3G, or GRB2/ASH and C3G, may transduce the signals from tyrosine kinases to Ras in a number of different tissues.

Adaptor Proteins, Signal Transducing↗

PubMed1994

Distribution of angiotensinogen in diseased human hearts.

Extrahepatic synthesis and localization of angiotensinogen (ATN) have been described in animals, thus establishing the tissue renin-angiotensin (RA) system. However, there had been no reports of tissue RA systems in human organs, including the heart. In earlier, we have reported the possibility of ATN synthesis in the human heart using ribonuclease protection assay system. ATN mRNA was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that ATN is synthesized in the human heart. In this report, we looked for the distribution of ATN in diseased human heart. Northern blot hybridization of cDNA with total RNA extracted from human liver, brain, kidney, atrial and ventricular tissues revealed that ATN mRNA exists in cardiac ventricule. Immunohistochemical studies using a specific antibody to ATN revealed a stronger reaction in the endocardial layer of the human left ventricle, than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. This distribution pattern was similar to that of human atrial natriuretic peptide (hANP), which functions a smooth muscle relaxant. Double immunostaining of ATN and hANP demonstrated that all myocytes in the right atrium had immunopositive reactions to ATN, hANP or both of ATN and hANP. Double immunoelectron staining enabled us to show more detailed localization of ATN and hANP; hANP only existed in the specific granules and ATN existed in the myofibril, but not in the granule. Furthermore, our experiments provide evidence of ATN in healthy human hearts and also reveal a widespread immunopositive reaction for ATN in the left ventricle of diseased hearts.

Angiotensinogen↗

PubMed1994

Cyclosporin A sensitive peptidyl-prolyl cis-trans isomerase in a halophilic archaeum, Halobacterium cutirubrum.

A cyclophilin type peptidyl-prolyl cis-trans isomerase was purified from a halophilic archaeum, Halobacterium cutirubrum DSM 669. The activity increased with an increase in KCl concentration up to 4 M. Sensitivity to cyclosporin A was comparable to that of eukaryotic cyclophilin and was also affected by KCl. IC50 for Cyclosporin A was 1.5 x 10(-8) M in 2.9 M KCl but 1.4 x 10(-7) M in 1.4 M KCl. The apparent molecular weight was 31 K by SDS-PAGE and 22 K in 2.9 M KCl and 150 K in 0 M KCl by gel filtration chromatography. The N-terminal amino acid sequence (33 residues) sheared 4 completely and 5 highly conserved amino acid residues with other reported cyclophilin family PPIases.

Amino Acid Isomerases↗

PubMed1994

Propagation of JC virus in human neuroblastoma cell line IMR-32.

JC virus (JCV), the causative agent of a human demyelinating disease, progressive multifocal leukoencephalopathy, has a very narrow host range. Cells permissive for infection by JCV have been essentially limited to primary human fetal glial cells, which are difficult to obtain and maintain. In pilot studies, it was found that JCV can multiply in an established cell line of human neuroblastoma. JCV strains Mad-1 and Tokyo-1 were inoculated, respectively, into two cell lines, IMR-32 (neuroblastoma) and A-172 (glioblastoma). Viral infection with cytopathic effect was observed only in IMR-32 cells, and the most efficient viral proliferation was obtained in cells cultured in medium containing 2% fetal calf serum (FCS). Both Mad-1 and Tokyo-1 strains propagated well, with the former being more efficient than the latter. Viral replication was confirmed by immunofluorescence, electron microscopy, and a hemagglutination assay. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and Western blot analysis of the purified virus revealed the characteristic JCV protein profile. Thus, IMR-32 cells have been found to be permissive for JCV, which should provide a useful system for further studies of virus proliferation and viral tissue tropism.

Blotting, Western↗

PubMed1994

Effect of naftopidil on urethral obstruction in benign prostatic hyperplasia: assessment by urodynamic studies.

Thirty-two patients with voiding dysfunction attributable to symptomatic benign prostatic hyperplasia were treated with naftopidil, an alpha 1-blocker, at doses of 25-75 mg/day for 4-6 weeks. The efficacy of the drug was assessed from the changes in urinary symptoms and urodynamic data. Total symptom scores were significantly reduced after treatment (P < 0.001). Average flow rate and maximum flow rate were significantly increased (P < 0.001 and P < 0.001, respectively), and residual urine volume, residual urine rate (ratio of residual urine volume/sum of voided volume and residual urine volume), and maximum urethral closure pressure were significantly (P < 0.05, P < 0.01, and P < 0.05, respectively) reduced, and at bladder capacity, the first desire to void was significantly (P < 0.05) increased. The pressure/flow study demonstrated no changes in intravesical pressure at maximum flow, but a significant (P < 0.05) reduction in minimum urethral resistance. A mild side effect (dizziness) was noted in one patient (3.3%), which soon disappeared after the dose was decreased. The efficacy was good or excellent in 21 of 30 patients (70.0%). The drug was evaluated to be promising in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗

PubMed1994

Case report 869. Benign metastasizing giant cell tumor of bone.

We presented a case of giant cell tumor of the sacrum with multiple pulmonary metastases in an 11-year-old girl. To the best of our knowledge, our patient is the youngest reported patient with a giant cell tumor with pulmonary metastases. Although giant cell tumor of bone with pulmonary metastases is extremely rare, this entity must be considered in the differential diagnosis of bone tumors.

Child↗

PubMed1994

Investigation of DNA synthesis in experimentally induced Long-Evans rat myeloschisis by the BrdU/antiBrdU technique.

The volume and DNA synthesis of the neuroepithelium in induced myeloschisis in Long-Evans rats as shown by hematoxylin-eosin and BrdU/antiBrdU immunohistochemical staining patterns were examined at different stages of embryonal development. On day 14 of gestation, control animals contained BrdU-incorporating cells mainly at the alar plate of the closed neural tube. On the same day, the everted neural plate of rats with myeloschisis showed active, diffuse uptake of BrdU in the cells of the matrix layer, although an increase in the volume of the everted neural plate was not yet identifiable. On day 21 of gestation, rats with myeloschisis showed a marked increase in the volume of the neuroepithelium compared with controls. Our investigations suggest that, in myeloschisis, more neuroepithelial cells than normal retain their capability for DNA synthesis on day 14 of gestation, and the overgrowth of the neuroepithelium found on day 21 is possibly a secondary effect of failure of neural tube closure.

Animals↗