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Biomedical subjects

K Kawabata

Publications and source records attributed to K Kawabata.

At least 37 records · Page 2Linked to original sources
PubMed2001

The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor.

Environmental factors essential for the first stages of B lymphopoiesis remain elusive. Here, we report that immediately after commitment to B lineage, precursors become dependent on a chemokine SDF-1 and its receptor CXCR4 using mutant and radiation chimeric mice. In bone marrow, generation of the earliest identifiable B cell precursor populations requires CXCR4. In fetal liver, we identified Lin(-)CD19(-)c-kit(+)IL-7Ralpha(+)AA4.1(+), the earliest unipotent B cell precursor population, and found that its development was severely affected in SDF-1(-/-) embryos but not in IL-7(-/-) embryos. Lin(-) T cell progenitors appeared normal in SDF-1(-/-) embryos. Moreover, SDF-1 exhibited specific biologic activities on the earliest B cell precursors. SDF-1 provides the first example of a cytokine responsible for the earliest B lineage stages.

Animals↗
PubMed2001

Ca2+-antagonists inhibit the N-methyltransferase-dependent synthesis of phosphatidylcholine in the heart.

Evidence indicates that, in addition to the L-type Ca2+ channel blockade, Ca2+-antagonists target other functions including the Ca2+-pumps. This study was conducted to test the possibility that the reported inhibition of heart sarcolemmal (SL) and sarcoplasmic reticular (SR) Ca2+-pumps by verapamil and diltiazem could be due to drug-induced depression of phosphatidylethanolamine (PE) N-methylation which modulates these Ca2+-transport systems. Three catalytic sites individually responsible for the synthesis of PE monomethyl (site I), dimethyl (site II) and trimethyl (phosphatidylcholine (PC), site III) derivates were examined in SL and SR membranes by employing different concentrations of S-adenosyl-L-methionine (AdoMet). Total methyl group incorporation into SL PE, in vitro, was significantly depressed by 10(-6)-10(-3) M verapamil or diltiazem at site III. The catalytic activity of site I was inhibited by 10(-3) M verapamil only, whereas the site II activity was not affected by these drugs. The inhibition induced by verapamil or diltiazem (10(-5) M) was associated with a depression of the Vmax value without any change in the apparent affinity for AdoMet. Both drugs decreased the SR as well as mitochondrial PE N-methylation at site III. A selective depression of site III activity was also observed in SL isolated from hearts of rats treated with verapamil in vivo. Furthermore, administration of [3H-methyl]-methionine following the treatment of animals with verapamil, reduced the synthesis of PC by N-methyltransferase. Verapamil also depressed the N-methylation-dependent positive inotropic effect induced by methionine in the isolated Langendorff heart. Both agents depressed the SL Ca2+-pump and although diltiazem also inhibited the SR Ca2+-pump, verapamil exerted a stimulatory effect. In addition, verapamil decreased SR Ca2+-release. These results suggest that verapamil and diltiazem alter the cardiac PE N-methyltransferase system. This action is apparently additional to the drugs' effect on L-type Ca2+ channels and may serve as a biochemical mechanism for the drugs' inhibition of the cardiac Ca2+-pumps and altered cardiac function.

Animals↗
PubMed2001

CD31 expression on leukocytes is downregulated in vivo during hemodialysis.

BACKGROUND/AIM: CD31 on leukocytes is the adhesion molecule involved in the leukocyte extravasation in inflammatory conditions. During hemodialysis with cellulosic membranes, it is considered that activated leukocytes adhere to endothelium, but do not show extravasation. However, it is not elucidated why activated leukocytes do not show endothelial transmigration during hemodialysis with cellulosic membranes. METHODS: In the present study, changes in the expressions of Mac-1 and CD31 on granulocytes and monocytes were analyzed by flow cytometry during hemodialysis in 7 patients treated with regenerated-cellulose (RC) membranes and next with polysulfone (PS) membranes. RESULTS: During dialysis with RC, Mac-1 expressions on granulocytes and monocytes both significantly increased as compared with predialysis values and across the dialyzer. During dialysis with RC, the CD31 expression on granulocytes and monocytes significantly decreased as compared with predialysis values. During dialysis with PS, changes in Mac-1 and CD31 expressions on granulocytes and monocytes were smaller than those during dialysis with RC. CONCLUSIONS: Decreased CD31 expression on leukocytes may affect leukocyte function more in patients chronically hemodialyzed with RC than in those hemodialyzed with PS, since CD31 is important in leukocyte transendothelial migration in inflammatory conditions.

Adult↗
PubMed2001

Microvascular angina in a patient with aortic stenosis.

A 39-year-old woman had exercise-induced ST segment depression associated with chest pain. Cardiac evaluation revealed moderate aortic stenosis (AS), related to the bicuspid valves, with an aortic mean pressure gradient of 22 mmHg, a calculated aortic valve area of 1.3 cm2 and normal left ventricular (LV) peak systolic and end-diastolic pressures, but no LV hypertrophy, resulting in normal LV wall stress. Although the coronary arteries were angiographically normal, rapid atrial pacing and an intracoronary papaverine injection revealed a significantly decreased coronary flow reserve (CFR), which may have played an important role in the pathogenesis of angina pectoris in this patient. Though the CFR is usually decreased in patients with AS, as well as in microvascular angina, in this particular case, it appeared to have decreased as a consequence of microvascular dysfunction rather than of AS-related mechanisms.

Adult↗
PubMed2001

Massive subchorionic hematoma (Breus' mole) complicated by intrauterine growth retardation.

We present here a case of massive subchorionic hematoma complicated by intrauterine growth retardation and oligohydramnios diagnosed at 22 weeks' gestation. The patient was managed with the following medications: (1) tocolysis with ritodrine infusion, (2) 10%maltose infusion therapy (1500mL/day), (3) antibiotic infusion (cefotaxim sodium, 2 g/dayx7) and (4) kampo therapy with Sairei-to until delivery. At 33 weeks and 0 days' gestation, a female baby weighing 1,342 g was delivered without complication by caesarean section. During surgery, an escape of about 500~600 g of dark brown blood with no clots was noted from the subchorionic space of the placenta. Examination of the placenta showed a large fibrosis with well-defined margins on the fetal surface.

Adult↗
PubMed2001

[Memory function in patients with Parkinson's disease: in relation to neuropsychological tests and cerebral blood flow].

We conducted a neuropsychological comparison between Parkinson's disease (PD; n = 24) and healthy control subjects (n = 12) using Rey's auditory-verbal learning test (RAVLT) and the Rey-Osterrieth complex figure test (RCFT) assessing memory function. In addition, to determine the function of cortical and subcortical areas, we measured the regional cerebral blood flow (rCBF) using N-isopropyl-p[123I]-iodoamhetamine (123I-IMP) and single photon emission computed tomography (SPECT) and analyzed the relationships between brain regions and memory function. On the RAVLT, significant group differences in recall words were found on all learning trials between patients with PD and control subjects, whereas recognition, learning rate and forgetting rate were basically the same. In addition, the primacy/recency effect was statistically equal for both groups. Results suggest faulty retrieval mechanisms in PD, whereas encoding and retention procesess did not prove to be affected. There were significant correlations between perfusion of the prefrontal and parietal cortices and total number of free recall in five trials. On the RCFT, recalls after 30 sec and 30 min were impaired in patients with PD although no significant difference in accuracy scores obtained in copy was noted. A percent recall score calculated using the formula 100 x [1 - (copy-recall)/copy] was also decreased in patients with PD. There were significant correlations between perfusion of the occipital and parietal cortices and percent recall score. Our data suggest that auditory memory deficits based on the RAVLT in PD may be mainly related to frontal and parietal cortical dysfunction, while visual recall deficits based on the RCFT may be related to the parieto-occipital cortical dysfunction.

Aged↗
PubMed2001

Drug interaction between simvastatin and itraconazole in male and female rats.

Taking into account the species and sex differences in drug interactions based on the inhibition of cytochrome P450 (P450)-mediated drug metabolism, we examined whether the interaction between simvastatin and itraconazole observed in humans could also occur in rats, the most commonly used animal species for pharmacokinetic studies. Itraconazole inhibited the in vitro metabolism of simvastatin in female rat liver microsomes, but not in male rat liver microsomes. Using anti-P450 antisera, the main P450 isozyme responsible for the metabolism of simvastatin was identified as CYP3A in female rats and CYP2C11 in male rats. Therefore, the sex difference in the inhibition of simvastatin metabolism by itraconazole seems to be caused by a difference in the P450 isozymes responsible for the metabolism of simvastatin in male and female rats and the different ability of itraconazole to inhibit CYP3A and CYP2C11. In addition, the effect of itraconazole on the pharmacokinetics of simvastatin in rats was also investigated. The area under the curve value of simvastatin was increased approximately 1.6-fold by the concomitant use of itraconazole (50 mg/kg) in female rats, whereas in male rats, itraconazole had no effect. In conclusion, it was found that the results obtained in male rats did not reflect the results in humans as far as the inhibition of simvastatin metabolism by itraconazole was concerned. The P450 isozymes involved in the metabolism of drugs should be taken into consideration when rats are used as a model animal for humans in the investigation of drug interactions.

Animals↗
PubMed2001

[Aneurysm-like wall motion abnormality in hibernating myocardium detected by stress thallium scintigraphy].

A 70-year-old female patient presented and ECG with QS patterns and ST elevation in V1-3. Left ventriculography showed severely abnormal wall motion of the anteroseptal similar to a left ventricular aneurysm. Based on previous experience that 201Tl myocardial scintigraphy revealed possible myocardial viability in a patient with left ventricular aneurysm suspected of having apparently no myocardial viability, percutaneous transluminal coronary angioplasty (PTCA) was performed for severe stenosis of the left anterior descending artery. Follow-up images 3 months later showed a remarkable improvement in parietal motility of the left ventricle and recovery of almost normal cardiac function. This case demonstrates that exercise myocardial scintigraphy is useful for diagnosing hibernating myocardium associated with severely abnormal parietal motility, such as left ventricular aneurysm.

Aged↗
PubMed2001

[Collateral blood flow showing dissection-like filling defect on coronary arteriography: a case report].

A 51-year-old man presented under a diagnosis of angina pectoris manifesting as exertional chest pain. First coronary angiography showed severe stenosis with ulceration and spontaneous dissection at the proximal right coronary artery and linear dissection-like filling defects extending to the distal right coronary artery. After about 3 months, repeat coronary angiography showed the previously observed stenosis with unclear dissection, and better developed collaterals from the left coronary artery to the right coronary artery showing the linear dissection-like filling defects. The bilateral coronary angiography did not clearly show filling defects. This phenomenon suggested that the collateral flows were related to filling of the defects. Intravascular ultrasonic imaging demonstrated severe atherosclerotic lesions at the proximal right coronary artery, but no dissection in the distal right coronary artery. Percutaneous transluminal coronary angioplasty for the stenosis was performed successfully with a stent. Coronary angiography after the angioplasty showed no collaterals, and the right ventricular branch appeared, suggesting that the linear dissection-like filling defects extending to the distal right coronary artery were due to the collateral flows. Filling defects extending distal to a severe stenosis must be distinguished carefully from coronary dissection.

Angioplasty, Balloon, Coronary↗
PubMed2000

Nitric oxide synthase is induced in tumor promoter-sensitive, but not tumor promoter-resistant, JB6 mouse epidermal cells cocultured with interferon-gamma-stimulated RAW 264.7 cells: the role of tumor necrosis factor-alpha.

Expression of inducible nitric oxide synthase (iNOS) has been reported to be involved in certain organs of potential tumorigenesis, including the stomach and colon. The mechanisms for iNOS expression in epithelial cells, however, are not fully understood. In the present study, we investigated the role of macrophages in epithelial iNOS expression by coculturing a stimulated murine macrophage-like cell line, RAW 264.7, with either tumor promoter-sensitive (P+) or promoter-resistant (P-) JB6 murine epidermal cells. After monoculture, treatment of RAW 264.7 cells with IFN-gamma for 24 h generated a large amount of nitrite (NO2-), as reported previously, whereas no increase in NO2- concentration was observed in the IFN-gamma-treated P+ or P-subclones. Interestingly, when IFN-gamma-treated RAW 264.7 cells were cocultured with P+ but not P- cells, we observed a marked increase in NO2- concentration (30.8+/-3.6 microM), which significantly exceeded (P < 0.01) the sum of the concentrations (20.0+/-2.3 microM) added from each cell line monoculture. Western blotting analysis revealed that, after coculture, iNOS protein was up-regulated 55-fold more than the control in JB6 P+ but not in P- cells. IFN-gamma-treated RAW 264.7 cells secreted proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. The addition of IFN-gamma-treated RAW 264.7 cell-conditioned media to P+ subclones led to a significant enhancement of NO2- formation that was diminished by the TNF-alpha-specific but not IL-1beta-specific antibody. When combined with IFN-gamma, the recombinant TNF-alpha (1-100 ng/ml) enhanced NO2- formation in JB6 P+ cells, whereas IL-1beta (1-100 ng/ml) did not. These results led us to conclude that IFN-gamma-treated RAW 264.7 cells release TNF-alpha to induce iNOS expression in promoter-sensitive JB6 cells. Thus, we propose the hypothesis that macrophages stimulate neoplastic cells with TNF-alpha via a paracrine loop to induce epithelial iNOS protein expression.

Animals↗
PubMed2000

Synthesis and association behavior of butadiyne-bridged

Butadiyne-bridged [4(4)](2,6)pyridinophane and [4(6)](2, 6)pyridinophane derivatives were synthesized, and their heteroassociations with the corresponding metacyclophanes and complexations with organic cations were investigated.

Journal Article↗
PubMed2000

Shocks and curvature dynamics: A test of global kinetic faceting in crystals

We investigate the microscopic mechanisms underlying the dynamical faceting of crystals. Partially faceted crystal shapes of CCl4 are formed from a melt contained in a Bridgman apparatus and pressure is used to control growth which is observed using optical microscopy. In contrast to predictions of models in which the local interfacial motion is greatest where the step density is the highest, the loss of rough orientations is observed to occur via a local decrease in curvature which results in the formation of discontinuities-shocks-in the surface of the growth forms, a feature predicted by a recent theory of kinetic faceting.

Journal Article↗
PubMed2000

Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats.

The modifying effects of dietary administration of ferulic acid (FA) on azoxymethane (AOM)-induced colon carcinogenesis were examined in three experiments with male 344 rats. In the first experiment, the modifying effect of FA on AOM (15 mg/kg body weight, once a week, for 3 weeks)-induced formation of aberrant crypt foci (ACF) was examined in five groups. Numbers of ACF/colon of groups 2 (AOM+250 ppm FA) and 3 (AOM+500 ppm FA) at the termination (5 weeks after the start) were smaller than of group 1 (AOM alone). Those of ACF/cm(2) of group 3 were also smaller than of group 1 (P<0.05). In the second experiment, a long-term assay for the effects of FA was conducted with seven groups. At the termination (35 weeks), groups 2 and 3 which were given FA during the initiation phase at doses of 250 and 500 ppm, respectively, had lower incidences of colonic carcinomas (23 and 27%, respectively) than group 1 which was given AOM alone (59%; P<0.05). In the third experiment, to determine whether FA could modify the activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR) in liver and colon, 60 rats were gavaged with FA at four doses (0, 25, 50, 100 mg/kg body weight). Dosing of 100 mg/kg significantly elevated GST activity in liver (P<0.03), and QR activities in liver and colonic mucosa (P<0.01 and P<0.02, respectively), suggesting that detoxifying enzymes are related to the blocking effect of FA on AOM-induced colon carcinogenesis.

Animals↗
PubMed2000

Frequent beta-catenin gene mutations and accumulations of the protein in the putative preneoplastic lesions lacking macroscopic aberrant crypt foci appearance, in rat colon carcinogenesis.

Activating mutations in the beta-catenin gene is thought to be responsible for the excessive beta-catenin signaling involved in the majority of carcinogen-induced colonic carcinomas. To determine whether beta-catenin signaling is involved in the initial stage of colon carcinogenesis, mutational analysis of the gene and immunohistochemistry for beta-catenin protein were performed in the early appearing lesions, including aberrant crypt foci (ACF), of colonic mucosa in rats given azoxymethane. Male F344 rats received s.c. injections of azoxymethane at a dose of 15 mg/kg body weight, once weekly for 3 weeks, and they were sacrificed 10 weeks after the carcinogen treatment. The colonic mucosa was examined in en face preparations and in serial sections after the observation in whole mount preparations. Microscopical observations in the cross sections have shown two populations of histologically altered crypts. The first type had a macroscopic feature resembling ACF [histologically altered crypts with ACF appearance (HACAs)]. The second type of altered crypts did not have the ACF-like appearance and could not be clearly distinguished from adjacent normal crypts in whole mount preparations [histologically altered crypts with macroscopically normal-like appearance (HACNs)]. The beta-catenin gene mutations were recognized in 10 of 15 HACNs (67%) and 3 of 15 HACAs (20%). Frequent immunoreactivity of beta-catenin protein was seen in the cytoplasm of HACNs (13 of 15 cases), whereas apparent accumulation was not confirmed in any HACAs analyzed. These results suggest that (a) there are two types of putative preneoplastic lesions in cancer-predisposed colonic mucosa, and beta-catenin signaling may contribute to the initial stage of colon carcinogenesis; and (b) HACNs are more likely to be direct precursors of colon tumors than HACAs in the rat colon carcinogenesis.

Amino Acid Substitution↗
PubMed2000

Sarcoplasmic reticulum Ca(2+)/Calmodulin-dependent protein kinase is altered in heart failure.

Although Ca(2+)/calmodulin-dependent protein kinase-II (CaMK) is known to phosphorylate different Ca(2+) cycling proteins in the cardiac sarcoplasmic reticulum (SR) and regulate its function, the status of CaMK in heart failure has not been investigated previously. In this study, we examined the hypothesis that changes in the CaMK-mediated phosphorylation of the SR Ca(2+) cycling proteins are associated with heart failure. For this purpose, heart failure in rats was induced by occluding the coronary artery for 8 weeks, and animals with >30% infarct of the left ventricle wall plus septum mass were used. Noninfarcted left ventricle was used for biochemical assessment; sham-operated animals served as control. A significant depression in SR Ca(2+) uptake and release activities was associated with a decrease in SR CaMK phosphorylation of the SR proteins, ryanodine receptor (RyR), Ca(2+) pump ATPase (SR/endoplasmic reticulum Ca(2+) ATPase [SERCA2a]), and phospholamban (PLB) in the failing heart. The SR protein contents for RyR, SERCA2a, and PLB were decreased in the failing hearts. Although the SR Ca(2+)/calmodulin-dependent CaMK activity, CaMK content, and CaMK autophosphorylation were depressed, the SR phosphatase activity was enhanced in the failing heart. On the other hand, the cAMP-dependent protein kinase-mediated phosphorylation of RyR and PLB was not affected in the failing heart. On the basis of these results, we conclude that alterations in SR CaMK-mediated phosphorylation may be partly responsible for impaired SR function in heart failure.

Animals↗
PubMed2000

Chemopreventive effects of coffee bean and rice constituents on colorectal carcinogenesis.

Polyphenolic compound chlorogenic acid (CGA) known to be much contained in coffee beans was found to have a regressive effect on induced aberrant crypt foci (ACF) as well as on development of ACF in azoxymethane (AOM)-induced colorectal carcinogenesis in rats. Rice germ and gamma-aminobutyric acid-enriched defatted rice germ inhibited AOM-induced ACF formation and colorectal carcinogenesis in rats. Ferulic acid (FA) also known to be contained in coffee beans and rice prevented AOM-induced ACF formation and intestinal carcinogenesis in rats. Both of food factors, coffee and rice may be of benefit to prevention of human colorectal cancers.

Animals↗
PubMed2000

Neuronal components of the superior and inferior tentacles in the terrestrial slug, Limax marginatus.

To identify the types of neurons and to infer the patterns of connectivity in slug tentacles, we stained the neurons in the superior and inferior tentacles in the terrestrial slug, Limax marginatus, by backfilling of the tentacular nerves with Lucifer yellow. Four types of stained neurons, '(1) sensory neurons', '(2) gamma cells', '(3) ganglion cells', '(4) lateral cells', were identified both in the superior and inferior tentacles. Three subtypes of the sensory neurons, '(1a) round sensory neurons', '(1b) spindle-shaped sensory neurons', and '(1c) small sensory neurons', were found in the digits. The gamma cells and the ganglion cells were interneurons. Three subtypes of gamma cells, '(2a) round monopolar gamma cells', '(2b) round bipolar gamma cells', and '(2c) large gamma cells', were present in the digits. The ganglion cells were composed of '(3a) monopolar ganglion cells', '(3b) bipolar ganglion cells', and '(3c) elongated ganglion cells'. The monopolar and bipolar types were located both in the tentacular ganglia and digits, whereas the elongated type was present only in the tentacular ganglia. The lateral cells, whose function is unknown, were found in the dermo-muscular sheaths of the tentacles. Our study provides the first description of the neuronal map of inferior tentacles in gastropods. The results showed no differences in the morphological features of stained neurons between the superior and inferior tentacles in L. marginatus.

Animals↗