Search PubMed⌕ Search

Biomedical subjects

K Kawaguchi

Publications and source records attributed to K Kawaguchi.

At least 91 records · Page 5Linked to original sources
PubMed1997

[The mechanism of increased thyroidal function caused by (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence, administration in rats].

A study was conducted to elucidate the mechanism of the increased thyroidal function caused by oral administration of (+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, in rats. Rats were given 500 mg/kg of NS-21 orally for 13 weeks. Rats were also given 500 mg/kg of the drug and 15 micrograms/animal of thyroxine (T4) in order to assess the influence of T4 treatment. NS-21 caused decreases in both total and free T4 and increases in TSH and thyroxine uridine diphosphate glucuronyltransferase (T4UDP-GT). Morphological examination of thyroid gland revealed stimulated follicles indicating heightened thyroidal function. The treatment of T4 inhibited the stimulating effect of NS-21 on thyroid gland. These results show that the administration of NS-21 caused induction of T4UDP-GT, which resulted in a compensatory stimulation of the thyroidal function by the increased secretion of pituitary TSH in response to increased blood thyroid hormone metabolism.

Animals↗
PubMed1997

[Indication for percutaneous transluminal coronary angioplasty based on quality of life of patients with angina pectoris].

The changes in quality of life (QOL) before and after percutaneous transluminal coronary angioplasty (PTCA) were investigated to establish criteria for determining whether patients with angina pectoris should undergo PTCA. The QOL was surveyed twice by self-completed questionnaire for QOL by Iida and Kohashi (QUIK) before and about 4 months after PTCA in 84 patients (mean age 62.8 +/- 10.1 years) with angina pectoris. High QUIK score reflects a poor QOL, of which the internal consistency was 0.86, demonstrating high reliability. The subjects were classified into three groups according to the changes of total QUIK score before and after PTCA (I: QOL improved 31.0%, II: QOL unchanged 48.8%, III: QOL worsened 20.2%). Age, gender, total QUIK score prior to PTCA, presence of anginal pain, complications extent and degree of coronary artery stenosis, and left ventricular ejection fraction were compared between the three groups. The total QUIK score prior to PTCA in the improved QOL group was higher than that in the worsened QOL group (11.6 vs 5.1, p < 0.01). Most patients showing a poor QOL prior to PTCA demonstrated an improvement in their QOL after PTCA. The number of patients with anginal pain prior to PTCA was high in the improved QOL group (35.8%, p < 0.05). Percutaneous transluminal coronary angioplasty might not aggravate QOL (12.1%, p = 0.1) in patients with single-vessel disease. In patients with multivessel disease, PTCA might not improve (35.3%) but also might aggravate QOL (25.5%). Multivariate analysis showed that PTCA improved QOL in male or sixty-ager patients and in patients with a total QUIK score of 10 or more prior to PTCA (p < 0.01). The total QUIK score, presence of anginal pain and extent of coronary artery stenosis prior to PTCA, gender and age are factors predicting QOL after PTCA. The adaptation of PTCA for those patients should be prudently and inclusively taken into consideration to extend their QOL.

Adult↗
PubMed1997

Lethal drug interactions of sorivudine, a new antiviral drug, with oral 5-fluorouracil prodrugs.

Rats were orally co-administered sorivudine (SRV: 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil), a new oral antiviral drug for herpes zoster, with the oral anticancer drug tegafur (FT: 1-(2-tetrahydrofuryl)-5-fluorouracil) as a prodrug of 5-flourouracil (5-FU) once daily to investigate a toxicokinetic mechanism of 15 Japanese patients' deaths recently caused within a brief period by the drug interaction of these drugs. All the rats showed extremely elevated levels of 5-FU in plasma and tissues, including bone marrow and small intestine, and died within 10 days, whereas the animals given the same dose of SRV or FT alone were still alive over 20 days without any appreciable toxic symptom. Before their death, there was marked damage of bone marrow, marked atrophy of intestinal membrane mucosa, marked decreases in white blood cells and platelets, diarrhea with bloody flux, and severe anorexia as reported with the Japanese patients. Data obtained by in vivo and in vitro studies strongly suggested that (E)-5-(2-bromovinyl)uracil generated from SRV by gut flora was reduced in the presense of NADPH to a reactive form by hepatic dihydropyrimidine dehydrogenase (DPD), a key enzyme determining the tissue 5-FU levels, bound covalently to DPD as a suicide inhibitor, and markedly retarded the catabolism of 5-FU.

Administration, Oral↗
PubMed1997

[Clinical evaluation of tamsulosin hydrochloride on bladder outlet obstruction associated with benign prostatic hyperplasia: effect on urethral pressure profile and cystometrogram].

The efficacy and safety of tamsulosin hydrochloride were evaluated in 54 patients with bladder outlet obstruction associated with benign prostatic hyperplasia. Oral tamsulosin hydrochloride 0.2 mg was administered once daily for 7 weeks. The international prostate symptom score, residual urine, uroflowmetrogram, urethral pressure profile and cystometrogram were obtained before and after treatment. The international prostate symptom score improved significantly, and the residual urine volume and ratio of residual urine decreased significantly. In uroflometry, voided volume, maximum flow rate and average flow rate increased significantly. In urethral pressure profile, prostatic urethral pressure decreased significantly. In cystometry, bladder capacity at the first sensation increased significantly. No adverse reactions except for slight elevation in laboratory data in 3 patients were observed. In conclusion, tamsulosin hydrochloride is a useful drug in the treatment of bladder outlet obstruction associated with benign prostatic hyperplasia.

Administration, Oral↗
PubMed1996

Focal ischemia induces expression of the DNA damage-inducible gene GADD45 in the rat brain.

GADD45 is a DNA damage-inducible gene that accelerates DNA excision repair and can be induced by a variety of DNA-damaging stimuli in mammalian cells. We investigated the expression of GADD45 mRNA and protein using in situ hybridization and immunocytochemistry in rat brains after 2 h of temporal focal ischemia. The expression of GADD45 mRNA was induced in neurons throughout ischemic cortex 4 h after the onset of ischemia but was restricted to ischemic penumbra regions at 24 h after ischemia. The expression of GADD45 protein was increased only in sublethally injured neurons in the penumbra regions at both 4 h and 24 h following ischemia. These results suggest that GADD45 could have a protective role in ischemic neurons.

Animals↗
PubMed1996

Structural studies of synthetic peptides dissected from the voltage-gated sodium channel.

Peptides representing transmembrane regions of the alpha-subunit of the voltage-gated sodium channel were synthesised and their structures analysed, using 1H NMR and CD, in trifluoroethanol and in dodecylphosphocholine micelles. Sequence analysis suggests that the channel has six regions, S1 to S6, predicted to span the membrane in four homologous domains, designated, I, II, III and IV. Presented here are studies of representatives examples of possible single spanning segments (IS2, IS4, IVS4) and a double spanning segment, IS34, composed of segments IS3 and IS4. In addition, we investigated ISlink56, the putative linker region between segments IS5 and IS6. All of the peptides were found to have predominantly alpha-helical structures in both solvent systems. There was some evidence for bending of the longer helices but there was no discernible evidence for well-defined tertiary structure.

Amino Acid Sequence↗
PubMed1996

Pure Rotational Spectra of SO: Rare Isotopomers in the 80-GHz to 1.1-THz Region

Pure rotational spectra of rare isotopomers of sulfur monoxide, SO, have been recorded with the Cologne Terahertz Spectrometer, Germany, and the millimeter- and submillimeter-wave spectrometer at Nobeyama, Japan. In total, 176 new transitions have been measured in the X3Sigma- electronic ground state, including the first laboratory detection of the rare isotopomer 36SO. New lines are also reported for 33SO and S17O in their vibrational ground states, and for 33SO and S18O in the first excited vibrational state. A simultaneous fit of 451 transitions has led to an improved set of isotopically invariant parameters for rotation and fine structure. Hyperfine structure constants for 33SO and S17O have been obtained also from the global fit, including first values for the magnetic nuclear spin-rotation interaction. These are compared to other molecules. The isotopically invariant parameters allow precise frequency predictions for the submillimeter-wave region far beyond 1 THz for all SO isotopomers, of importance to astrophysical applica- tions.

Journal Article↗
PubMed1996

Therapeutic effect of secretin in patients with jaundice; double-blind placebo-controlled multicentric trial.

Secretin, a gastrointestinal hormone, has been shown to have a potent choleretic effect. Having already obtained some beneficial effects with secretin in patients with intrahepatic cholestasis, we sought to confirm its effects in a double-blind placebo-controlled study in patients with mild jaundice after acute or during chronic hepatitis, where total bilirubin level was in excess of 4.0 mg/dl for 3 days or more. Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and familiar hyperbilirubinemia were excluded from the study. Ninety-three patients were included in this analysis, but the final evaluation covered 69 of them. No statistically significant differences were found in the reduction of serum bilirubin levels between secretin and placebo groups. As a number of patients with liver cirrhosis had been included, the subjects were subdivided into one group with cholestasis in hepatitis and one with liver cirrhosis. In the subgroup of cirrhotic patients who received secretin, serum levels of AST were significantly increased compared with the placebo group. However, since the choleretic effect of secretin is unique, further studies seem to be warranted.

Adolescent↗
PubMed1996

Biotransformation of digitoxigenin by cultured ginseng cells.

Nine compounds, including a new compound (digitoxigenin beta-D-glucoside malonyl ester), were isolated as biotransformation products of digitoxigenin by cell suspension cultures of Panax ginseng (Pg-3 cell line). At the same time, two known products were identified by TLC and HPLC.

Carbohydrate Sequence↗
PubMed1996

Myelodysplastic changes in three cases within 100 days after allogeneic bone marrow transplantation.

Three patients with severe aplastic anemia, acute promyelocytic leukemia (M3) and chronic myelogenous leukemia, developed myelodysplastic changes with trilineage morphological abnormalities in a few months following allogenic bone marrow transplantation (BMT). Morphologically dysplastic changes associated with moderate-severe anemia, leukopenia and/or thrombocytopenia appeared on day 40, day 62 and day 68 after BMT. A ferrokinetics study clearly showed ineffective erythropoiesis in one patient. Hematopoietic cells were shown to be of donor-origin in all three cases. The levels of vitamin B12 and folic acid were normal. Laboratory tests showed no signs of hemolysis or fragmentation of red blood cells. Although the cause of aberrant hematopoiesis compatible with MDS within 100 days post-BMT remains to be determined, cytomegalovirus infection, ganciclovir and/or graft-versus host disease (GVHD) might be associated with this myelodysplasia following allogeneic BMT.

Adolescent↗
PubMed1996

Second transplantation with CD34+ bone marrow cells selected from a two-loci HLA-mismatched sibling for a patient with chronic myeloid leukaemia.

A 43-year-old man with chronic myeloid leukaemia underwent a second transplant with CD34+ bone marrow cells selected from his two-loci HLA-mismatched sibling after rejection of the first graft from an HLA-matched unrelated donor. By immunomagnetic positive selection, CD34+ marrow cells at 0.95 x 10(6)/kg with 97% purity and CD3+ T lymphocytes at 1.3 x 10(4)/kg were collected and transplanted. Engraftment was confirmed to be of CD34+ cell-donor origin. The patient developed only grade I acute graft-versus-host disease (GVHD) and no chronic GVHD to date. These observations suggest that allogeneic CD34+ bone marrow cells are capable of reconstituting haemopoiesis and that CD34+ selection could be applicable to T-cell depletion.

Adult↗
PubMed1996

A novel tetrasaccharide, with a structure similar to the terminal sequence of an arabinogalactan-protein, accumulates in rice anthers in a stage-specific manner.

Analysis of free sugars in developing rice anthers by high-performance anion-exchange chromatography (HPAEC) showed that a very high concentration of a novel oligosaccharide accumulated specifically during microsporogenesis. Structural analysis of the purified oligosaccharide by methylation analysis, mass spectrometry/mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) spectroscopy revealed its structure to be beta-L- Ara(f)-(1-->3)-alpha-L-Ara(f)-(1-->3)-beta-D-Gal(p)-(1-->6)-D-Gal, which is closely related to a tetrasaccharide unit found in the glycan chain of a plant cell surface proteoglycan, the arabinogalactan-protein (AGP). Chilling treatment (12 degrees C, 4 days), which injures rice anthers during microsporogenesis, decreased the concentration of the tetrasaccharide, but the sucrose level increased. This effect was especially evident in a chilling-sensitive mutant line, YM56-1. These results suggest that this unique tetrasaccharide may play an important role in both the development of the rice anther and its response to chilling.

Carbohydrate Conformation↗
PubMed1996

Expression of the apoptosis-effector gene, Bax, is up-regulated in vulnerable hippocampal CA1 neurons following global ischemia.

The observation that delayed death of CA1 neurons after global ischemia is inhibited by protein synthesis inhibitors suggests that the delayed death of these neurons is an active process that requires new gene expression. Delayed death in CA1 has some of the characteristics of apoptotic death; however, candidate proapoptotic proteins have not been identified in the CA1 after ischemia. We studied the expression of Bax protein and mRNA, a member of the bcl-2 family that is an effector of apoptotic cell death, after global ischemia in the four-vessel global ischemia model in the rat and compared these results with the expression of the antiapoptotic gene bcl-2. Bax mRNA and protein are both expressed in CA1 before delayed death, whereas bcl-2 protein is not expressed. Bcl-2 protein expression, but not that of Bax, is increased in CA3, a region that is ischemic but less susceptible to ischemic injury. In the dentate gyrus, both Bax and bcl-2 proteins are expressed. The selective expression of Bax in Ca1 supports the hypothesis that Bax could contribute to delayed neuronal death in these vulnerable neurons by an independent mechanism or by forming heterodimers with gene family members other than bcl-2.

Animals↗
PubMed1996

Dimethylarsenics reveal DNA damage induced by superoxide anion radicals.

We previously reported that DNA single-strand breaks (ssb) induced by exposure to dimethylarsinic acid (DMAA) were enhanced by the presence of paraquat (PQ), a superoxide anion radical 0 -(2)-producing agent, in cultured human alveolar type II (L-132) cells in vitro. In the present study, we examined the effect of sequential exposure of the cells to PQ and then DMAA under conditions causing no ssb by each alone, and observed a remarkable occurrence of ssb. The result suggests that 0 -(2) caused DNA damage, which became detectable as ssb by the treatment using DMAA. The DNA damage induced by the exposure to PQ alone was different from that by DMAA; PQ-induced damage was fully repaired after 24 h, while DMAA-induced damage was repaired only partially, and aphidicolin, an inhibitor of repair-serving DNA polymerases alpha, delta and/or epsilon, inhibited only the latter repair but not the former. These findings indicate that the DMAA treatment may be an effective tool to reveal DNA damage induced by 0 -(2), which to date has not been sufficiently clarified.

Aphidicolin↗
PubMed1996

Differential effect of UV-B and UV-C on DNA damage in L-132 cells.

Ultraviolet radiation is known to induce skin cancer. The induction of DNA damage caused by UV-B and UV-C was investigated using cultured L-132 cells. DNA strand breaks assayed by the alkaline elution procedure occurred in a dose-dependent manner, the extent of the strand breaks were inversely well correlated with the number of viable L-132 cells after 24 h incubation. About a 10-fold dose of UV-B irradiation was required to induce a similar degree of strand breaking to that induced by UV-C. Similarly about a 10-fold dose of UV-B was required to produce a similar amount of pyrimidine dimers, such as cyclobutane-type dimers and pyrimidine-(6-4)-pyrimidone photoproducts, which were determined by ELISA using the specific monoclonal antibody, to that produced by UV-C. Strand breaks induced by UV-B, however, were not fully repaired in viable cells remaining after incubation of cells for a longer period of time, although UV-C-induced strand breaks were repaired in a time-dependent manner. Furthermore, an experiment with a cell-free system, where the induction of strand breaks by repair enzymes did not take place, indicated that UV-B caused significantly more direct DNA strand breaks than that caused by one-tenth the dose of UV-C. The data shown here suggest that UV-B-induced DNA damage is mediated, at least in part, via a different mechanism from the UV-C induced one.

Antibodies, Monoclonal↗