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Biomedical subjects

M Asaka

Publications and source records attributed to M Asaka.

At least 181 records · Page 10Linked to original sources
PubMed1997

Low levels of serum soluble c-kit relates to delayed engraftment after bone marrow transplantation.

Serum soluble c-kit concentrations were measured in 28 patients undergoing bone marrow transplantation (BMT). The c-kit levels in patients with delayed engraftment (time to leukocyte recovery > 1.0 x 10(9)/L being more than 20 days after BMT) were significantly lower than those in patients with early engraftment (time to leukocyte recovery being less than 19 days after BMT) from the start of conditioning until day 100 after BMT. The data from this study indicates that the measurement of serum soluble c-kit concentrations may be a useful indicator of engraftment.

Adolescent↗
PubMed1997

Phorbol ester enhancement of IL-3-dependent proliferation of primitive hematopoietic progenitors of mice in culture.

Protein kinase C (PKC) is a Ca++- and phospholipid-dependent protein kinase activated by diacylglycerol that is either released from cell membranes in response to certain growth factors or mimicked by 12-O-tetradecanoyl phorbol-13-acetate (TPA). We studied the effects of TPA on interleukin-3 (IL-3)-dependent colony formation of mouse bone marrow cells from mice injected with 5-fluorouracil 2 days before examination in order to clarify the significance of PKC in the proliferation of primitive hematopoietic progenitors. Although TPA alone did not support colony formation, TPA in combination with IL-3 increased colony numbers from 1.5 to 2 times that formed with IL-3 and vehicle. TPA increased not only the granulocyte/macrophage colonies, but also the multilineage colonies. A sequential colony count showed that TPA, unlike IL-6, did not hasten the appearance of colonies. Because TPA enhanced IL-3-dependent colony formation derived from lineage-negative marrow cells obtained from mice that received 5-FU 2 days before, it is possible that it might act directly on primitive progenitors. Prolonged pretreatment of marrow cells with TPA prevented TPA-augmented colony growth. Calphostin C, a specific PKC inhibitor, and certain specific tyrosine kinase inhibitors, such as genistein and herbimycin A, abrogated the enhancing effects of TPA on IL-3-dependent colony formation. These data suggest that TPA had a direct effect on the primitive progenitors and enhanced IL-3-dependent colony formation via activation of PKC and certain tyrosine kinases.

Animals↗
PubMed1997

Differential flotation centrifugation study of hepatitis C virus and response to interferon therapy.

Hepatitis C virus (HCV) appears to circulate in various forms such as native virion, immune complexes, and nucleocapsids during chronic infections. To determine the association of the physicochemical properties of HCV and its response to interferon therapy in patients with chronic hepatitis C, we examined pretreatment serum samples from 43 patients with HCV RNA who had received interferon therapy, using differential flotation centrifugation in a NaCl solution with a density of 1.063 g/ml. After centrifugation, the ratio of HCV RNA in the top and bottom fractions was determined by the polymerase chain reaction and expressed as T/B. Patients with a sustained response to IFN therapy were found to have higher T/B ratios than transient responders who relapsed after treatment (P < 0.01) and nonresponders (P < 0.01). With regards to HCV genotypes, patients with genotype 1b had higher T/B ratios in the sustained response group than in the nonsustained response groups (P = 0.001), but patients with genotype 2 had a similar distribution of T/B among the 3 response groups (not significant). These findings indicate that the physicochemical properties of HCV affect the effectiveness of interferon therapy, particularly in patients with genotype 1b.

Adult↗
PubMed1996

An effect of K-ras gene mutation on epidermal growth factor receptor signal transduction in PANC-1 pancreatic carcinoma cells.

The Ras protein is involved in tyrosine kinase signal transduction pathway steps such as EGFR signalling. Most human pancreatic carcinomas harbor a point mutation of K-ras oncogene and overexpress transforming TGF-alpha. We studied how K-ras gene mutation could influence the EGFR signal transduction mechanism and the autonomous proliferation of pancreatic carcinoma cells, using PANC-1 human pancreatic carcinoma line and W1-38 normal human fibroblast cell line as a control. PANC-1 cells responded to neither EGF nor exogenous TGF-alpha, although anti-TGF-alpha MAb suppressed their growth. Expression of TGF-alpha mRNA was detected only in PANC-1 cells, which confirmed EGFR being within an autocrine loop. Ras protein and MAP kinase were constitutively activated in PANC-1 cells so that the cells did not respond to treatment with staurosporine or herbimycin A, and exhibited slight response to EGF stimulation. PANC-1 cells harbored K-ras gene mutation in codon 12. In contrast, EGF stimulation induced an elevation of GTP-bound ratio to Ras protein and an activation of MAP kinase with accelerated growth in W1-38 cells. From these findings, we concluded that K-ras gene mutation possibly plays an important role in the autonomous proliferation of PANC-1 pancreatic carcinoma cells, and that an autocrine loop represented by TGF-alpha and EGFR may further accelerate the growth of PANC-1 cells.

Antibodies, Monoclonal↗
PubMed1996

Nucleotide sequences of the hepatitis C virus core region in patients without anti-core antibody.

Second-generation assays for detection of hepatitis C virus (HCV) infection that include reactivity of antibodies to core, NS3, NS4 are used because of their high sensitivity. Among these antibodies, anti-core antibody seems to be the most sensitive. However, there are some patients without anti-core antibodies, although HCV RNA is detectable by reverse transcription-polymerase chain reaction and branched DNA assay. The mechanism for the absence of anti-core antibody on its own is unclear. We therefore determined the nucleotide and deduced amino acid sequences of the core region obtained from two anti-core antibody-negative patients with HCV RNA (genotype 1b) and compared them with those of four anti-core antibody-positive patients and a previously reported sequence. Amino acids spanning 1-47, which seemed to exist in major B cell epitopes, were found to be completely conserved among these patients. Furthermore, the predictive binding motif to HLA DR4 (a.a 81-90) was completely conserved in both of the anti-core antibody-negative patients. There were various mutations in the residual amino acids spanning 49-108, but specific mutations could not be found in anti-core antibody-negative patients. These data indicate that the absence of anti-core antibody in two patients is not due to the presence of some formerly unknown viral variants, but due to a possible defect in the host's immune system.

Amino Acid Sequence↗
PubMed1996

Changes in hepatitis C virus quasispecies and density populations in patients before and after interferon therapy.

Some chronic hepatitis C patients show sustained response to interferon (IFN) therapy despite viremia. This condition seems to be related to the density populations of hepatitis C virus (HCV) [Kanto et al. (1995): J Med Virol 46:230-237]. To investigate further the relationship between alanine aminotransferase (ALT) levels after IFN therapy and the HCV density populations, we undertook differential flotation centrifugation of HCV and single strand conformation polymorphism targeted the hypervariable region (HVR) of E2 glycoprotein, which seems to be related to the density populations. Sera were obtained serially from 12 patients who had undergone IFN therapy (six sustained responders with viremia, six nonresponders). During the follow-up after interferon therapy, the HVR heterogeneities changed in 9 of the 12 patients. The remaining three patients whose heterogeneities did not changed persistently showed normal ALT. The changes in HVR heterogeneities were less pronounced in the sustained responders with viremia than in nonresponders; however, their density populations were prominently high in both responders. In two cases, changes in HVR heterogeneities and increase in low-density virion were observed before the hepatitis flare-up. These data indicate that HVR quasispecies show more relation to ALT levels after IFN therapy than HCV density populations and that the changes in the HVR sequences and HCV density populations may be associated with ALT elevation in some patients.

Adult↗
PubMed1996

Reversal effect of itraconazole on adriamycin and etoposide resistance in human leukemia cells.

Itraconazole is a triazole antifungal agent that inhibits cell membrane serol biosynthesis. Currently, itraconazole is a potent candidate for in vivo use to revert multidrug resistance in acute leukemias, with the added benefit of its antifungal effect. As previously reported, itraconazole, as well as verapamil, reversed adriamycin-resistant K562 cells (K562/ADR) and HL60 cells (HL60/ADR) in dosages compatible to the plasma levels achieved by the therapeutic dosages used for the treatment of fungal infections. By RT-PCR analysis of mdr1, mdr3, and mrp mRNA, these adriamycin-resistant cells showed a higher expression of the transcript of these genes than those of the parent cells. By FACS analysis, both the adriamycin-resistant cells showed a higher expression of P-glycoprotein on their cell surfaces. These results suggested the involvement of itraconazole in the mdr gene and/or mrp gene product-associated resistance. Furthermore, itraconazole partially reversed etoposide resistance in both the K562 and K562/ADR cells. The present study suggests that itraconazole may reverse multidrug resistance, at least in part, via a classical MDR-associated mechanism.

Antibiotics, Antineoplastic↗
PubMed1996

Transformation of severe aplastic anemia into acute myeloblastic leukemia with monosomy 7.

A cytogenetically normal man with severe aplastic anemia was treated with granulocyte colonystimulating factor (G-CSF), erythropoietin (EPO), cyclosporin A, anti-thymocyte globulin, and interleukin-6 (IL-6), which resulted in a gradual improvement in his neutrophil count and hemoglobin level. After 2 years of the therapy, monosomy 7 was detected during cytogenetic analysis of his bone marrow, which evolved during a period of 5 months into acute myeloblastic leukemia. An in vitro proliferation assay of cytokine responses showed that leukemic blasts were sensitive only to G-CSF, and not to EPO or IL-6. Although allogeneic bone marrow transplantation from an HLA-matched unrelated donor was carried out in the non-remission stage, the patient died of systemic fungal infection on day 25, without any evidence of hematological engraftment. As long-term use of cytokines and immunomo-suppressants in patients with severe aplastic anemia may induce or hasten the onset of a malignant transformation, careful attention must be paid to clonal evolution. Due to the poor prognosis of secondary myelodysplasia and leukemia, allogeneic bone marrow transplantation for such patients must be carried out early in the course of the disease.

Adult↗
PubMed1996

High incidence of common bile duct dilatation in autosomal dominant polycystic kidney disease patients.

Two autosomal dominant kidney disease (ADPKD) patients with cholecystitis or communicating extrahepatic dilatation of the common bile duct accompanied by tiny common bile duct stones prompted us to examine the incidence of gall stone disease and dilatation of the common bile duct in ADPKD patients. Computed tomography scans were examined retrospectively in 55 ADPKD patients and 55 age-, gender-, and duration of dialysis-matched non-ADPKD patients. The incidence of calcium-containing gall stones found on tomography scans was the same: eight of the 55 ADPKD patients and nine of the 55 non-ADPKD patients. However, common bile duct dilatation, defined as measuring more than 7 mm in diameter at the pancreatic head on CT scans, was found more frequently in the ADPKD patients (22 patients; 40.0%) than in the non-ADPKD patients (5 patients; 9.1%) (P = 0.0002). These results suggest that the high incidence of intrapancreatic common bile duct dilatation in ADPKD is a previously undescribed sign of extracellular matrix remodeling in ADPKD.

Adult↗
PubMed1996

Effects of lansoprazole plus amoxycillin on the cure of Helicobacter pylori infection in Japanese peptic ulcer patients.

AIM: The effect of lansoprazole plus amoxycillin on curing Helicobacter pylori infection and peptic ulcer recurrence was evaluated. METHOD: The study group was composed of 68 patients with gastric ulcers and 51 with duodenal ulcers, all were H. pylori-positive. The participants were assigned at random to the lansoprazole alone group (lansoprazole 30 mg o.m. for 6 or 8 weeks) or the lansoprazole plus amoxycillin group (lansoprazole alone regimen plus amoxycillin at 500 mg q.d.s. concomitantly for the first 2 weeks). Healed patients were not given maintenance treatment with acid secretion inhibitors. The cure rate for H. pylori infection and the ulcer recurrence rate after 1 year were investigated. RESULT: The cure rate for H. pylori infection was 4.2% in patients receiving lansoprazole alone and 38.5% in patients receiving lansoprazole plus amoxycillin (P < 0.01) for gastric ulcers, and 0% in patients receiving lansoprazole alone and 61.9% in patients receiving lansoprazole plus amoxycillin (P < 0.001) for duodenal ulcers. The recurrence rate was 42.3% in patients receiving lansoprazole alone and 28.6% in patients receiving lansoprazole plus amoxycillin for gastric ulcers, and 66.7% for patients receiving lansoprazole alone and 11.1% for patients receiving lansoprazole plus amoxycillin (P < 0.001) for duodenal ulcers. None of the patients with gastric or duodenal ulcers cured of H. pylori infection had a recurrence. CONCLUSION: Concomitant use of lansoprazole and amoxycillin increased the curative effects on H. pylori infection. However, the cure rates with this regimen remained inadequate.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Atrophic changes of gastric mucosa are caused by Helicobacter pylori infection rather than aging: studies in asymptomatic Japanese adults.

BACKGROUND: The current study was designed to evaluate the effect of aging and Helicobacter pylori infection on the gastric mucosa in asymptomatic Japanese adults. MATERIALS AND METHODS: Eighty-five asymptomatic healthy adults were recruited from a health-screening center in Sapporo. All subjects underwent endoscopy and gastric biopsy, and serum was obtained for IgG antibodies to H. pylori, serum gastrin, and pepsinogen levels. RESULTS: The prevalence of atrophic change of the gastric mucosa assessed by pathological findings increased with age (49% in the 30- to 39-year-old group compared to 89% in those 60 years and older, p < .001). The frequency of intestinal metaplasia also increased with age (38% in the 30- to 39-year-old group compared to 82% in those 60 years and older, p < .001). In contrast, the frequency of atrophic gastritis and intestinal metaplasia was extremely low in the H. pylori seronegative group regardless of age. Mean serum gastrin level in H. pylori-positive adults was significantly greater than in those who were H. pylori-negative (114.3 +/- 11.2 compared to 65.8 +/- 6.5 pg/ml, p < .03). The serum pepsinogen I-II ratio was significantly lower in those with H. pylori infection than in those without (3.1 compared to 6.6, p < .0001). CONCLUSIONS: These results suggest that the chronological changes in the gastric mucosa in Japanese individuals are either entirely related to H. pylori infection or the process is greatly accelerated by H. pylori infection.

Adult↗
PubMed1996

Antitumor effect in cyclosporine A- or FK506-treated mice after syngeneic bone marrow transplantation.

We investigated the possibility for induction of graft-versus-tumor (GVT) effects in cyclosporine A (CsA)- or FK506 (FK)-treated DBA/2 mice after syngeneic bone marrow transplantation (BMT). For in vitro assays of spleen cells, the CsA-treated mice had more enhanced cytotoxic activity against YAC1 and P388, while the FK-treated animals had more against P815, YAC1, and P388. IL-4 mRNA expression was detected in spleen cells of the FK-treated mice and IL-6 mRNA expression was clearly detected in both the treated groups. Concerning GVT effects, FK had more pronounced immunostimulatory potential than CsA in this experimental setting using DBA/2 mice. In tumor-loading in vivo experiments, we could not show any antitumor effect on survival. However, this immunostimulation could be expected to eradicate the minimal residual disease after autologous BMT and autologous peripheral blood stem cell transplantation.

Actins↗