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Biomedical subjects

H Kuroda

Publications and source records attributed to H Kuroda.

At least 73 records · Page 4Linked to original sources
PubMed2000

HLA-DRB genotypes in Japanese patients with renal cell carcinoma.

OBJECTIVES: Several clinical features, such as the spontaneous regression of some renal cell carcinoma (RCC) metastases after nephrectomy, suggest immune involvement in tumor destruction. PATIENTS AND METHODS: We investigated the role of genetic variation at the HLA class II loci in RCC by analyzing the HLA-DR antigen and HLA-DRB1, DRB3, DRB4 and DRB5 alleles in 55 patients using the polymerase chain rection. RESULTS: No statistically significant differences were observed in the frequency of the HLA-DR antigen or HLA-DRB3, DRB4, or DRB5 genes between the patients and a healthy control group. On the other hand, the HLA-DRB1*0403 and *1202 alleles were significantly more frequent in the patients than in the controls (p < 0.001 and p < 0.01, respectively). CONCLUSION: RCC might be linked to these two alleles in Japanese patients.

Adult↗
PubMed2000

A role of pituitary adenylate cyclase activating polypeptide (PACAP) as a regulator of paracrine interactions between folliculo-stellate cells and gonadotropes through the control of activin-follistatin interactions.

Pituitary folliculo-stellate (FS) cells were able to modify the effect of activin-A on gonadotropes through the paracrine factor, follistatin. The present study was aimed to examine whether a hypothalamic peptide, pituitary adenylate cyclase activating polypeptide (PACAP), could be a regulator of this paracrine interaction. Co-culture of FS cell-originated cell line TtT/GF cells with rat anterior pituitary cells showed faint inhibitory effect on the stimulatory action of activin-A on FSH secretion. When PACAP was added to the culture during the co-culture period, however, the presence of TtT/GF cells caused significant suppression of the effect of activin-A on FSH secretion. Conditioned-media (CM) from TtT/GF cells, obtained by incubation of TtT/GF cells in the presence or absence of PACAP, were next added to the cultures of anterior pituitary cells alone. CM from TtT/GF cells without PACAP treatment revealed slight, but not significant, suppressive effect on activin-induced increases in FSH secretion and the percentage of FSH cells. Meanwhile, CM from PACAP-treated TtT/GF cells attenuated both effects of activin-A. Furthermore, the inhibitory effect of the CM was neutralized when follistatin antibody was present in the culture. These results suggest that PACAP is able to regulate the paracrine action of FS cells on pituitary gonadotropes. Besides expressing direct actions on pituitary endocrine cells, PACAP may have roles as a regulator of cell-to-cell interactions within the pituitary gland.

Activins↗
PubMed2000

Induction of unseasonable hibernation and involvement of serotonin in entrance into and maintenance of its hibernation of chipmunks T. asiaticus.

Chipmunks that had been housed at 22 degrees C under a light-dark cycle of 14L:10D for at least one year were exposed to a short photoperiod (10L:14D) and low temperature to induce unseasonable hibernation. We were able to induce hibernation at any time of year and there was no significant difference in the duration of the hibernation bout, the duration of interbout euthermia and duration of bouts of torpor throughout the year; however entrance into hibernation took about 60 days in summer but only about 30 days in any other seasons. In addition, interbout euthermia predominantly occurred during the light phase in winter, whereas in spring interbout euthermia occurred equally in the light and dark phases. These results suggest that both the circadian and circannual systems are linked to hibernation in chipmunks. Subcutaneous infusion of a serotonin antagonist, para-chlorophenylalanine (PCPA), facilitated entrance into and interrupted hibernation in aroused and hibernating chipmunks in summer, respectively. On the other hand, opioid antagonist, naloxone, did not affect hibernation, but extended the period of interbout euthermia. These results suggest that the role of serotonin in entrance into and maintenance of hibernation in chipmunks is independent of the circannual system, and that opioid system may not be involved in hibernation in chipmunks.

Animals↗
PubMed2000

Involvement of distinct signaling pathways in activin-induced increases in FSH secretion and enlargement of FSH cell population in the rat pituitary.

Activin-A induces increases in FSH secretion, as well as the number of immunoreactive FSH cells, in cultured rat pituitary cells. In this study, we examined whether mechanisms involved in these two actions of activin-A are identical or not, with respect to the involvement of cellular proliferation and of Ca2+-dependent signaling pathways. Treatment with activin-A (25 ng/ml) for 48 h caused increases in the number of cultured rat anterior pituitary cells that incorporated BrdU, a thymidine analog. The stimulatory effects of activin-A on FSH secretion and on the percentage of immunoreactive FSH cells were, however, not inhibited by the presence of the mitotic inhibitor cytosine arabinoside. On the other hand, the stimulatory effect of activin-A on the percentage of immunoreactive FSH cells was completely blocked in the presence of the Ca2+/calmodulin kinase inhibitor KN-62 or the L-type Ca2+ channel blocker nicardipine. Neither of these inhibitors, however, revealed significant influence on the effect of activin-A on FSH secretion. These results suggest that activin-A exhibits its dual effect on FSH cells without causing cellular proliferation. Furthermore, activin-A appears to induce increases in FSH secretion and enlargement of FSH cell population through distinct intracellular signaling pathways, the former through Ca2+-independent and the latter through Ca2+-dependent mechanisms.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

[Coronary artery bypass grafting for a patient with bronchial asthma seceeded from cardiopulmonary bypass by additional bypass for spasm of radial artery graft: a case report].

A 78-year-old male who had a bronchial asthma underwent coronary artery bypass grafting (CABG) using the left internal thoracic artery and the radial artery. The patient could not be weaned from the cardiopulmonary bypass because the radial artery which anastomosed to the obtuse marginal artery (OM) had a spasm after CABG. An additional bypass using a long saphenous vein to OM was carried out immediately. It brought a weaning from cardiopulmonary bypass. If the cardiac function after CABG is insufficient in patients with bronchial asthma, CABG must be re-done immediately, considering that they cause the arterial spasm more than patients without bronchial asthma.

Aged↗
PubMed2000

Permanent cardiac pacing following surgery for acquired valvular disease.

Between January 1980 and January 1998, implantation of a permanent pacemaker (PP) was performed in 22 patients (6.7%) following 327 acquired valvular surgeries. The indications for implantation of a PP were bradycardia with atrial fibrillation in 12 cases, sick sinus syndrome in 7 cases and complete atrioventricular block in 3 cases. These patients received an implantation after surgery for mitral valvular disease in 14 cases, aortic valvular disease in 3 cases and combined valvular disease in 5 cases. These cases were also concomitant with a tricuspid valve annuloplasty in 6 cases for secondary regurgitation and with a maze procedure in 4 cases. For the purpose of this study, these patients were compared to patients who did not require implantation of a PP after surgery. Univariate analysis showed the significant factors to be female gender (p = 0. 041), preoperative atrial fibrillation (p = 0.013), redo cardiac surgery (p < 0.0001), and the use of blood cardioplegia (p = 0.003). There were no differences in valvular disease, age at the last valvular operation, addition of tricuspid valve annuloplasty, extracorporeal circulation times, or aortic cross-clamp times between those patients with and those without PP. Among these factors, logistic regression analysis showed female gender, redo surgery and the use of blood cardioplegia to be more significant predictors for the requirement of PP after acquired valvular disease operation. Maze procedure was not a significant predictor for the requirement of PP after surgery.

Adult↗
PubMed2000

[Retardation of platelet recovery after autologous stem cell transplantation in a patient with acute lymphoblastic leukemia: possible role of decreased thrombopoietin production by bone marrow stromal cells].

A 16-year-old boy was diagnosed as having acute lymphoblastic leukemia and underwent autologous stem cell transplantation at the time of his second complete remission. Retardation of platelet recovery was evident at day 90 (< 5 x 10(4)/microliter), and at day 660 after transplantation the platelet count was 8.5 x 10(4)/microliter. Neutrophils and RBCs showed only slightly retarded recovery. Bone marrow stromal cells, which are thought to play an integral role in megakaryopoiesis, were examined. Although TPO mRNA expression per cell was normal, CFU-F was significantly decreased, resulting in a decrease of total TPO mRNA expression. In contrast, expression of G-CSF mRNA per cell was increased. It was thought that chemotherapy before bone marrow transplantation may have reduced the number of stromal cells, leading to retardation of platelet recovery because of low TPO expression.

Adolescent↗
PubMed2000

Evaluation of speech function after mesopharyngeal reconstruction with radial forearm flap.

This study examined postoperative speech function in ten patients who underwent mesopharyngeal resection and reconstruction using radial forearm flap. Patient age ranged from 49 to 71 years (mean 60 years) with 9 males and 1 female. Speech function was assessed by articulatory and velopharyngeal function. Articulatory function was judged by intelligibility of monosyllables and sentences. The percentage of 100 Japanese monosyllables perceived as correct in each case were scored. Intelligibility of sentences was evaluated using the Hirose standard. Velopharyngeal function was fiberoptically examined both in soft-blowing and at rest, and visual information about velopharyngeal closure was obtained. Correlation between the extent of resection and the speech function was then analysed. In order to maintain over 50% speech intelligibility and an excellent state in the Hirose standard, the extent of resection in the soft palate is particularly important. This result has to be explained in correlation with the resected range of the levator muscle, which is important for velopharyngeal closure. Surgically treated mesopharyngeal cancer patients face several functional problems. In order to counsel patients more meaningfully before surgical intervention, information about the postoperative speech function should be made available. The goal of reconstruction is to achieve acceptable speech in order to maintain the patients' quality of life. The results in this study reveal that resection which doesn't extend to the opposit side of the soft palate, can achieve the goal by utilization of the foream flap, because its pliable nature brings out the residual function of the levator.

Aged↗
PubMed1999

Transforming growth factor-beta1 (TGF-beta1) induces thrombopoietin from bone marrow stromal cells, which stimulates the expression of TGF-beta receptor on megakaryocytes and, in turn, renders them susceptible to suppression by TGF-beta itself with high specificity.

The present study was designed to test the concept that platelets release a humoral factor that plays a regulatory role in megakaryopoiesis. The results showed that, among various hematoregulatory cytokines examined, transforming growth factor-beta1 (TGF-beta1) was by far the most potent enhancer of mRNA expression of bone marrow stromal thrombopoietin (TPO), a commitment of lineage specificity. The TPO, in turn, induced TGF-beta receptors I and II on megakaryoblasts at the midmegakaryopoietic stage; at this stage, TGF-beta1 was able to arrest the maturation of megakaryocyte colony-forming units (CFU-Meg). This effect was relatively specific when compared with its effect on burst-forming unit-erythroid (BFU-E) or colony-forming unit-granulocyte-macrophage (CFU-GM). In patients with idiopathic thrombocytopenic purpura (ITP), the levels of both TGF-beta1 and stromal TPO mRNA were correlatively increased and an arrest of megakaryocyte maturation was observed. These in vivo findings are in accord with the aforementioned in vitro results. Thus, the results of the present investigation suggest that TGF-beta1 is one of the pathophysiological feedback regulators of megakaryopoiesis.

Bone Marrow↗
PubMed1999

Regression of hepatocellular carcinoma in vitro and in vivo by radiosensitizing suicide gene therapy under the inducible and spatial control of radiation.

To improve the efficacy and selectivity of gene therapy for hepatocellular carcinoma (HCC), we designed a strategy for suicide gene therapy in conjunction with radiation therapy using an HVJ-liposome vector system. The radio-inducible suicide gene was constructed by insertion of the early growth response gene 1 (Egr-1) promoter upstream of the HSV-tk gene (EGF-tk). First, to test the tumor specificity of Egr-1, RT-PCR and immunohistochemistry were performed. The Egr-1 gene was highly expressed in HCC compared with normal liver, where expression was barely detectable. Next, radiation-inducible activity of the Egr-1 promoter was examined in primary cultured normal hepatocytes and human hepatoma cell lines Huh7, HepG2, and PLC/PRF/5 by luciferase assay as a reporter gene system. Egr-1 promoter activity was markedly increased in hepatoma cell lines in a radiation dose-dependent manner, with maximum activation (15- to 28-fold) 12 hr after irradiation. In contrast, only a twofold increase in activation was noted in normal hepatocytes. An in vitro gene therapy experiment showed that EGR-tk-transduced hepatoma cells became highly sensitive to ganciclovir (GCV) after irradiation, but not without irradiation. GCV with or without irradiation did not show any cytotoxic effects against control gene-transfected cells. In addition, a "radiosensitization effect" was also demonstrated by combination therapy with the HSV-tk/GCV system and irradiation. To examine the efficacy of this EGR-tk/GCV gene therapy in vivo, xenografted liver tumors in nude mice were targeted using the HVJ-liposome vector system. EGR-tk-transfected tumors regressed significantly after a combination therapy of irradiation and GCV in all mice (n = 8), and almost disappeared in 3 weeks without any side effects. In comparison, tumors continued to grow in all mice (n = 8 in each group) treated by transfer of EGR-tk followed by either irradiation without GCV or GCV without irradiation. Our data indicate that HSV-tk gene therapy under the control of a radioinducible promoter is effective, and might be selective for hepatoma cells because of its inducible and radiosensitive capacity after radiation exposure as well as its tumor-specific activation.

Aged↗
PubMed1999

Cloning and characterization of a novel Rab-family gene, Rab36, within the region at 22q11.2 that is homozygously deleted in malignant rhabdoid tumors.

Malignant rhabdoid tumors (MRTs) are rare, pediatric soft-tissue tumors. Homozygous deletions at chromosome 22q11.2 are a recurrent cytogenetic characteristic of MRTs, an indication that this locus may harbor one or more genes conferring tumor-suppressor activity. We constructed a deletion map of the relevant part of 22q11.2 from a panel of seven MRT cell lines, and isolated a novel gene from the center of the region. As it showed a high degree of sequence homology to genes of the Rab family, we designated it Rab36. The protein encoded by Rab36 was localized at the Golgi body. Sequencing of Rab36 cDNAs from three cell lines that retained at least one allele of this gene revealed no nonsense or frameshift mutations. Experiments to induce over-expression of Rab36 by transfection to an MRT cell line similarly failed to justify designation of this gene as a tumor suppressor that would contribute to tumorigenesis by a loss-of-function mechanism.

Amino Acid Sequence↗
PubMed1999

The advantages of normocalcemic continuous warm cardioplegia over low calcemic cardioplegia in myocardial protection.

The effects of changing the calcium content of a continuous warm hyperkalemic crystalloid cardioplegia (CWCP) were investigated in an isolated rat heart preparation. The hearts were divided into eight groups of six each. A control group consisted of fresh nonarrested hearts and the remaining seven groups consisted of hearts perfused with continuous hyperkalemic (20 mM) modified Krebs-Henseleit bicarbonate buffer solution with calcium concentrations of 0.1, 0.3, 0.5, 1.0, 1.5, 2.0, or 2.5 mM, for either 180 or 240 min at 37 degrees C. In the hearts arrested for 180 min, there were no significant differences in postarrest cardiac functions between the control group and any of the groups perfused with calcium concentrations of 0.5 mM or more. With a calcium concentration of 0.1 mM, the calcium paradox was provoked. The change in the calcium content of CWCP perfused for 240 min significantly affected myocardial protection. Maximum aortic flow recovery, of 74.7% +/- 2.7%, and minimum CK release, of 15.7 +/- 2.4 IU/15 min/g dry weight, were observed in hearts perfused with a calcium concentration of 1.5 mM. The calcium paradox occurred even at a calcium concentration of 0.3 mM; therefore, normal calcium concentrations should be maintained in cardiac surgery to prevent cardiac injury.

Animals↗
PubMed1999

Expression of Brachyury-like T-box transcription factor, Xbra3 in Xenopus embryo.

The Xenopus Brachyury-like Xbra3 gene is a novel T-box gene that is closely associated with Xenopus Brachyury. The expression pattern of Xbra3 during development is similar to that of Xbra. During gastrulation Xbra3 is expressed in the marginal zone, with a gradient of increasing expression from ventral to dorsal. In the early neurula stage Xbra3 is expressed in the notochord and posterior mesoderm, but by the tailbud stage its expression is restricted to the forming tailbud and the posterior portion of the notochord.

Amino Acid Sequence↗
PubMed1999

Expression of Xenopus T-box transcription factor, tbx2 in Xenopus embryo.

We report here the cloning and expression of the Xenopus orthologue of the T-box transcription factor gene Tbx2 (optomotor-blind in Drosophila). Tbx2 is first detected in the ventral mesodermal cells just above the yolk plug at late gastrula. At the neurula stage it is strongly expressed in the cement gland, dorsal root ganglia, and otic vesicle region. At the tailbud stage strong Tbx2 expression is observed in the dorsal part of the optic cup and trigeminal ganglia, and it is also expressed in the branchial arches, heart anlage, nasal pit, proctodeum, and the region around the pronephros.

Amino Acid Sequence↗
PubMed1999

Overexpression of insulin-like growth factor-1 (IGF-I) receptor and the invasiveness of cultured keloid fibroblasts.

Keloid is a dermal fibroproliferative tissue of unknown etiology. Protein tyrosine kinases (PTKs) play an important role in the regulation of cell growth and differentiation. Activation of PTK cascades in keloid fibroblasts is thought to be closely linked to abnormal cell proliferation and migration. We determined the expression profile of PTK genes in normal skin and keloid fibroblasts using the homology cloning method with a degenerated primer. Eight PTK genes were expressed among a total of 46 receptor-type clones. The most abundant type of PTK receptors was the platelet-derived growth factor receptor in both fibroblasts. However, insulin-like growth factor-I receptor (IGF-IR) was overexpressed only in keloid-derived fibroblasts (9 of 24). Immunohistochemical analysis confirmed the high expression of IGF-IR in keloid fibroblasts, but not in normal fibroblasts. To examine the functional properties of the IGF-I/IGF-IR pathway, we investigated cell proliferation and invasion activities of both types of fibroblasts. The mitogenic effect of IGF-I on both fibroblasts was very weak compared with serum stimulation. In contrast, the invasive activity of keloid fibroblasts was markedly increased in the presence of IGF-I, and inhibited by a neutralizing antibody against IGF-IR. Our results indicate the involvement of activated IGF-I/IGF-IR in the pathogenesis of keloid by enhancing the invasive activity of fibroblasts.

Adolescent↗
PubMed1999

Risk of low calcium and high magnesium in continuous warm hyperkalemic cardioplegia.

BACKGROUND: The recent introduction of operations on a warm heart has prompted clinical reports on the usefulness of continuous blood cardioplegia, but no in-depth basic evaluation of continuous cardioplegia has been done. The cardioprotective effects of magnesium (Mg) and calcium (Ca) in continuous warm hyperkalemic crystalloid cardioplegic solutions were investigated in an isolated rat heart model. METHODS: Isolated rat hearts were arrested for 180 minutes at 37 degrees C with a continuous warm hyperkalemic (20 mmol/L) modified Krebs-Henseleit bicarbonate buffer solution containing 1.2, 8.0, or 16.0 mmol/L of Mg and 0.1 to 2.5 mmol/L of Ca in different concentrations. Recovery of cardiac function and tissue damage were estimated. RESULTS: For each Mg concentration, the percentage recovery of aortic flow generated dose-response curves depending on Ca concentration. However, as Mg concentration increased, the recovery of aortic flow decreased in the groups with 0.5 mmol/L of Ca or less. CONCLUSIONS: In continuous warm cardioplegia the combination of low Ca and high Mg concentration caused severe cardiac injury, and normal Ca concentration avoids cardiac injury regardless of Mg concentrations.

Animals↗