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Biomedical subjects

K Amano

Publications and source records attributed to K Amano.

At least 91 records · Page 5Linked to original sources
PubMed1998

Marginal benefit/disadvantage of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in children: results of a prospective randomized trial. The Japanese Cooperative Study Group of PBSCT.

In this prospective trial, a total of 74 children who were scheduled to undergo high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) were prospectively randomized at diagnosis to evaluate the effectiveness of exogenous granulocyte colony-stimulating factor (G-CSF) treatment in accelerating hematopoietic recovery after PBSCT. The diagnosis included acute lymphoblastic leukemia (ALL) (n = 27), neuroblastoma (n = 29), and miscellaneous solid tumors (n = 18). Eligibility criteria included (1) primary PBSCT, (2) chemotherapy-responsive disease, and (3) collected cell number >1 x 10(5) colony-forming unit-granulocyte-macrophage (CFU-GM)/kg and >1 x 10(6) CD34(+) cells/kg patient's body weight. After applying the above criteria, 11 patients were excluded due to disease progression before PBSCT (n = 6) or a low number of harvested cells (n = 5), leaving 63 patients for analysis; 32 patients in the treatment group (300 microg/m2 of G-CSF intravenously over 1 hour from day 1 of PBSCT) and 31 in the control group without treatment. Two distinct disease-oriented high-dose regimens without total body irradiation consisted of the MCVAC regimen using ranimustine (MCNU, 450 mg/m2), cytosine arabinoside (16 g/m2), etoposide (1.6 g/m2), and cyclophosphamide (100 mg/kg) for patients with ALL, and the Hi-MEC regimen using melphalan (180 mg/m2), etoposide (1.6 g/m2), and carboplatinum (1.6 g/m2) for those with solid tumors. Five patients (two in the treatment group and three in the control group) were subsequently removed due to protocol violations. All patients survived PBSCT. The median numbers of transfused mononuclear cells (MNC), CD34(+) cells, and CFU-GM were, respectively, 4.5 (range, 1 to 19) x 10(8)/kg, 8.0 (1.1 to 25) x 10(6)/kg, and 3.7 (1.2 to 23) x 10(5)/kg in the treatment group (n = 30) and 2.9 (0.8 to 21) x 10(8)/kg, 6.3 (1.1 to 34) x 10(6)/kg, and 5.5 (1.3 to 37) x 10(5)/kg, respectively, in the control group (n = 28), with no significant difference. After PBSCT, the time to achieve an absolute neutrophil count (ANC) of >0.5 x 10(9)/L in the treatment group was less than that in the control group (median, 11 v 12 days; the log-rank test, P =.046), although the last day of red blood cell (RBC) transfusion (day 11 v day 10) and the duration of febrile days (>38 degrees C) after PBSCT (4 v 4 days) were identical in both groups. However, platelet recovery to >20 x 10(9)/L was significantly longer in treatment group than control group (26 v 16 days; P =.009) and >50 x 10(9)/L tended to take longer in the treatment group (29 v 26 days; P =.126), with significantly more platelet transfusion-dependent days (27 v 13 days; t-test, P =.037). When patients were divided into two different disease cohorts, ALL patients showed no difference in engraftment kinetics between the G-CSF treatment and control groups, while differences were seen in those with solid tumors. We concluded that the marginal clinical benefit of 1 day earlier recovery of granulocytes could be offset by the delayed recovery of platelets. We recommend that the routine application of costly G-CSF therapy in children undergoing PBSCT should be seriously reconsidered.

Adolescent↗
PubMed1998

Effect of the Kobe earthquake on stress and glycemic control in patients with diabetes mellitus.

OBJECTIVE: To examine the effects of the Kobe, Japan, earthquake, a life-threatening event, on stress and glycemic control in diabetic patients. PATIENTS AND METHODS: Hemoglobin A1c levels before and after the earthquake were evaluated in diabetic patients in Kobe (N = 157; magnitude, 7.2) and in Osaka, Japan, as a control (N = 277; magnitude, 4.2), where little damage to houses and traffic facilities occurred. Glycosylated hemoglobin levels were also compared with those of 2 years before and 1 year after the earthquake. The General Health Questionnaire (GHQ) and a self-administered questionnaire regarding damage to houses and relatives killed or injured were used to assess psychological and mental stresses on earthquake survivors. RESULTS: Glycemic control was aggravated in diabetic patients after the earthquake in Kobe but not in Osaka. THe GHQ scores were significantly higher in the patients in Kobe than those in Osaka. Increased hemoglobin A1c concentrations and high scores on the GHQ were especially evident in diabetic patients with severe damage to houses and/or with relatives killed or injured. CONCLUSION: These results suggest an association between chronic, life-threatening stress and the worsening of metabolic control in patients with diabetes mellitus.

Adult↗
PubMed1998

Gene arrangement in the upstream region of Clostridium botulinum type E and Clostridium butyricum BL6340 progenitor toxin genes is different from that of other types.

The cluster of genes encoding the botulinum progenitor toxin and the upstream region including p21 and p47 were divided into three different gene arrangements (class I-III). To determine the gene similarity of the type E neurotoxin (BoNT/E) complex to other types, the gene organization in the upstream region of the nontoxic-nonhemagglutinin gene (ntnh) was investigated in chromosomal DNA from Clostridium botulinum type E strain Iwanai and C. butyricum strain BL6340. The gene cluster of type E progenitor toxin (Iwanai and BL6340) was similar to those of type F and type A (from infant botulism in Japan), but not to those of types A, B, and C. Though genes for the hemagglutinin component and P21 were not discovered, genes encoding P47, NTNH, and BoNT were found in type E strain Iwanai and C. butyricum strain BL6340. However, the genes of ORF-X1 (435 bp) and ORF-X2 (partially sequenced) were present just upstream of that of P47. The orientation of these genes was in inverted direction to that of p47. The gene cluster of type E progenitor toxin (Iwanai and BL6340) is, therefore, a specific arrangement (class IV) among the genes encoding components of the BoNT complex.

Botulinum Toxins↗
PubMed1998

The molecular basis for cross-reacting material-positive hemophilia A due to missense mutations within the A2-domain of factor VIII.

Factor VIII (FVIII) is the protein defective in the bleeding disorder hemophilia A. Approximately 5% of hemophilia A patients have normal amounts of a dysfunctional FVIII protein and are termed cross-reacting material (CRM)-positive. The majority of genetic alterations that result in CRM-positive hemophilia A are missense mutations within the A2-domain. To determine the mechanistic basis of the genetic defects within the A2-domain for FVIII function we constructed six mutations within the FVIII cDNA that were previously found in five CRM-positive hemophilia A patients (R527W, S558F, I566T, V634A, and V634M) and one CRM-reduced hemophilia A patient (DeltaF652/3). The specific activity for each mutant secreted into the conditioned medium from transiently transfected COS-1 cells correlated with published data for the patients plasma-derived FVIII, confirming the basis of the genetic defect. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitated FVIII protein radiolabeled in COS-1 cells showed that all CRM-positive mutant proteins were synthesized and secreted into the medium at rates similar to wild-type FVIII. The majority of the DeltaF652/3 mutant was defective in secretion and was degraded within the cell. All mutant FVIII proteins were susceptible to thrombin cleavage, and the A2-domain fragment from the I566T mutant had a reduced mobility because of use of an introduced potential N-linked glycosylation site that was confirmed by N-glycanase digestion. To evaluate interaction of FVIII with factor IXa, we performed an inhibition assay using a synthetic peptide corresponding to FVIII residues 558 to 565, previously shown to be a factor IXa interaction site. The concentration of peptide required for 50% inhibition of FVIII activity (IC50) was reduced for the I566T (800 mumol/L) and the S558F (960 mumol/L) mutants compared with wild-type FVIII (> 2,000 mumol/L). N-glycanase digestion increased I566T mutant FVIII activity and increased its IC50 for the peptide (1,400 mumol/L). In comparison to S558F, a more conservative mutant (S558A) had a sixfold increased specific activity that also correlated with an increased IC50 for the peptide. These results provided support that the defects in the I566T and S558F FVIII molecules are caused by steric hindrance for interaction with factor IXa.

Animals↗
PubMed1998

Up-regulation of alphaEbeta7, a novel integrin adhesion molecule, on T cells from systemic lupus erythematosus patients with specific epithelial involvement.

OBJECTIVE: To determine the possible role of a novel integrin, alphaEbeta7, in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: Expression of alphaEbeta7 was examined on peripheral blood lymphocytes (PBL) from normal subjects (n = 25) and patients with SLE (n = 31), primary Sjogren's syndrome (n = 7), or polymyositis/dermatomyositis (n = 8) by cytofluorometry and/or immunoprecipitation. Adhesion of alphaEbeta7+ T cells to HSG epithelial cells was investigated using a confocal image analyzer. RESULTS: After phytohemagglutinin stimulation, expression of alphaEbeta7 on PBL, especially on CD8+ T cells, was significantly higher in SLE patients than in normal subjects (P<0.01). Elevated alphaEbeta7 expression was associated with the presence of oral ulcers or serositis (P<0.05). Activated SLE T cells with enhanced alphaEbeta7 expression strongly adhered to HSG; this adhesion was partially blocked by anti-alphaEbeta7. CONCLUSION: Expression and adhesion of alphaEbeta7 on activated PBL was significantly increased in patients with SLE with epithelial involvement. This suggests a role of this novel integrin in tissue-specific retention of activated PBL, due to increased alphaEbeta7-E-cadherin interaction, which may contribute to epithelial inflammation.

Adult↗
PubMed1998

Mapping the genetic determinants of human immunodeficiency virus type 2 for cell tropism and replication efficiency.

Two distinct infectious molecular clones of human immunodeficiency type 2 (HIV-2) were analyzed for their biological properties in six cell lines. Fourteen chimeric and ten mutant viruses were constructed from these two viral genomes to localize the genetic determinants responsible for the phenotypes. Growth property of the viruses in the cell lines, together with the biochemical data, showed that a major determinant for the viral tropism resides in the env gene. In addition, in some cell lines, the accessory genes vif and nef affected the efficiency of virus replication. Thus, like HIV-1, mutations in the auxiliary and env genes of HIV-2 contributed much to the differences in virological characteristics.

Base Sequence↗
PubMed1998

Primary low-grade, B-cell, mucosa-associated lymphoid tissue lymphoma of the colorectum: clinical and colonoscopic features in six cases.

BACKGROUND: Unlike gastric lymphoma, the endoscopic features of low-grade, mucosa-associated lymphoid tissue (MALT) lymphoma of the colorectum have not been defined. METHODS: We analyzed colonoscopy, endoscopic ultrasonography, and histologic findings in six patients with MALT lymphoma restricted to the colorectum. Histologic confirmation of the proliferation of centrocyte-like cells with lymphoepithelial lesions formed the criteria for the selection of patients. RESULTS: Based on endoscopic findings, the patients were divided into cases of solitary (4 patients) or multifocal (2 patients) involvement. Endoscopic findings in cases of solitary involvement were uniform in that the lesions were either smooth or nodular protrusions, demonstrated by a hypoechoic mass under endoscopic ultrasonography. Multifocal involvement was endoscopically recognized as protrusions, dilated vasculature, or small ulcers. CONCLUSIONS: Protruding lesions are the main pattern of involvement in MALT lymphoma of the colorectum, although variable and multifocal involvement is also possible in this type of lymphoma.

Aged↗
PubMed1998

Antiepileptic effects of topiramate on amygdaloid kindling in rats.

We examined the antiepileptic properties of topiramate (TPM) in amygdaloid (AM) kindling in rats. Electrodes were implanted into the left AM of adult male Wistar rats. The animals were kindled at the after-discharge (AD) threshold. After the completion of kindling, the generalized seizure triggering threshold was determined. The drugs were administered intraperitoneally in animals which showed stable generalized convulsions at near-threshold stimulation. Intraperitoneal administration of TPM at doses of 25 mg/kg or more produced an anticonvulsive effect, but did not readily suppress limbic seizures. Complete suppression of AD was observed in only 3/8 rats at the highest dose of 200 mg/kg, which was not statistically significant. On the other hand, TPM at 100 and 200 mg/kg significantly delayed AM kindling. Thus, TPM showed modest therapeutic properties of conventional antiepileptic drugs in kindling model, those of TPM more closely resemble those of phenobarbital and the benzodiazepines than those of phenytoin and carbamazepine.

Amygdala↗
PubMed1998

Gag-Pol region determines the tropism of SIVagm for human cells.

Simian immunodeficiency virus isolated from African green monkeys (SIVagm) does not grow in many of human cell lines such as CEM x 174, H9, and MT-4, but could replicate in some human cell lines. Sequence of SIVagm responsible for its narrow host range was determined by making and monitoring growth potential of chimeric clones between SIVagm and human immunodeficiency virus type 1 (HIV-1). The results obtained indicated that the gag-pol region determines the observed narrow host range. By monitoring virus DNA synthesis and progeny virion production, the defect(s) of SIVagm in the replication in the restricted cells was demonstrated to be located at early phase.

Animals↗
PubMed1998

Complete inhibition of SIVmac replication by its capsid mutants.

Mutations were introduced into a genomic region encoding the C-terminal portion of Gag capsid protein of pathogenic simian immunodeficiency virus (SIVmac239). All the mutants generated were defective for virion production and were non-infectious for monkey cells. They all efficiently suppressed the replication of wild type SIVmac in monkey cells. These results were in good agreement with those obtained for human immunodeficiency virus type 1, showing the importance of SIV/monkey model system for studies on Gag.

Animals↗
PubMed1998

Anticonvulsant effects of dipotassium clorazepate on hippocampal kindled seizures in rats.

We examined the anticonvulsant properties of dipotassium clorazepate (DC) against hippocampal kindled seizures in rats. Adult male Wistar rats were subjected to kindling 1 week after the implantation of electrodes. After five stage 5 seizures were induced, the generalized convulsion triggering threshold (GST) was determined. Dipotassium clorazepate was administered intraperitoneally in rats that showed two stable stage 5 seizures induced at the GST current intensity. Dipotassium clorazepate at doses of 1 mg/kg or more produced an anticonvulsant effect, but did not readily suppress limbic seizures. Dipotassium clorazepate did not completely suppress after-discharges (AD) even at the highest dose, which was 5 mg/kg. Moreover, raised stimulus intensity failed to affect its efficacy as an anticonvulsant. The results of the present study suggest that DC has a modest anticonvulsant potency. It is reasonable to assume that its anticonvulsant efficacy is primarily due to attenuation of AD propagation rather than the raising of the seizure triggering threshold at the kindling focus.

Animals↗
PubMed1998

An assessment of local curability of endoscopic surgery in early gastric cancer without satisfaction of current therapeutic indications.

BACKGROUND AND STUDY AIMS: Therapeutic endoscopy for early gastric cancer has been established with strict criteria for indications. In the present study, we evaluated the efficacy of endoscopic treatment in cases that did not fulfil the standard therapeutic criteria, consisting of well differentiating mucosal adenocarcinomas less than 2 cm in size and without an ulcer or a scar. PATIENTS AND METHODS: Sixty nine early gastric cancers in 64 patients that did not fulfil the standard criteria were treated endoscopically, and a rate of cure was retrospectively assessed during a mean follow-up of 5.2 years. Endoscopic treatment consisted of mucosal resection or thermal methods, or both. RESULTS: Curative resection was achieved in 19/20 (95%) of cases which came into one of the following categories, all being well differentiated adenocarcinomas, less than 3.0 cm in size, without ulcer or the scar of an ulcer, with invasion limited to mucosal layer (depth m); tumors less than 2.0 cm, with an ulcer or scar, depth m; tumors less than 2.0 cm, without ulcer or scar, invading the submucosa but in which invasion was limited to the superficial portion (depth sm-1); and poorly differentiated tumors less than 1.0 cm in size, without an ulcer or scar, depth m. The rate of cure in this group was statistically similar to the cure rate of cases that fulfilled the standard criteria (98%). CONCLUSIONS: Our retrospective results suggest that the indications for curative treatment of early gastric cancer could be expanded. Prospective studies are required.

Adenocarcinoma↗
PubMed1998

Improvement in nerve regeneration by monoclonal antibodies to ICAM-1 and LFA-1 in allogeneic mice.

We examined whether giving monoclonal antibodies (MoAb) to intercellular adhesion molecule 1 (ICAM-1) and leucocyte function associated antigen (LFA-1), which have important roles in the initial stage of rejection after allografts, can improve nerve regeneration in allogeneic mice. Fresh sciatic nerves were grafted using BALB/c mice as donors and C3H/He mice as recipients. Nerve regeneration at six weeks was significantly better in the mice given MoAbs at one and five days than in those given none (n = 5 in each group), although nerve regeneration even in the five-day group was significantly inferior to that in the syngeneic nerve graft group (n = 5). The survival time of the nerve donor skin graft at 12 weeks was not prolonged by treatment with MoAbs, indicating a failure to induce immunological tolerance. However, at 10 months after nerve grafting there were fewer Mac-1, Lyt-1, and Thy-1 positive cells in the five-day group and they showed less immunoreactivity than the untreated group. We conclude that giving MoAbs could effectively improve nerve regeneration in grafted allogeneic nerve segments, although it did not induce immunological tolerance.

Animals↗
PubMed1998

TCR zeta chain lacking exon 7 in two patients with systemic lupus erythematosus.

To address the molecular mechanism underlying the functional defects of peripheral T cells in systemic lupus erythematosus (SLE), we focused on early signaling events. We demonstrated that protein expression of the TCR zeta chain was significantly decreased in peripheral T cells from patients with SLE compared to normal controls and patients with systemic sclerosis (SSc). Among those patients showing decreased TCR zeta chain expression, we found two patients with pronounced TCR zeta chain abnormalities, including an aberrant 14 kDa form in one and only trace expression in the other. RT-PCR, SSCP and subsequent cloning of the transcripts revealed that bases 468503, corresponding to exon 7, were deleted in both patients. Since exon 7 spans the GTP/GDP binding site and N-terminal tyrosine in the third ITAM domain of TCR zeta chain, the transcript lacking exon 7 may be responsible for altered signal transduction via TCR in these SLE patients.

Adult↗
PubMed1998

Antigenic characteristics of polypeptides of Coxiella burnetii isolates.

Eighteen Coxiella burnetii strains from a variety of clinical and geographical sources were screened for antigenic variation of polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) coupled with Coomassie brilliant blue (CBB) staining or immunoblotting. These polypeptide profiles showed the greatest variability in the region from 33 to 8.1 kDa. Such differences in the antigenicity of the polypeptides were also recognized by immunoblotting with 15 various mouse anti-C. burnetii antisera. In addition, we detected a polypeptide at about 28 kDa which was immunodominant in strains from human cases of acute Q fever, milk and ticks but not immunogenic in strains from human cases of chronic Q fever. These findings suggest that this polypeptide is a marker to distinguish between acute and chronic strains.

Animals↗
PubMed1998

Utilization of proteinase K-treated cells as lipopolysaccharide antigens for the serodiagnosis of Helicobacter pylori infections.

We have evaluated the use of proteinase K (PK)-treated cells isolated from Helicobacter pylori as lipopolysaccharide (LPS) antigens in an immunoblot assay and an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of H. pylori infection. The sera from patients with chronic gastritis, gastric ulcer, duodenal ulcer or gastric cancer, and from healthy adults with or without H. pylori infection were assayed with three commercial serodiagnostic kits (HM-CAP, Helico-G, and G.A.P. II) and novel methods relying on the use of PK-treated cells. The PK-treated cells used in these assays were selected on the basis of their possibility to possess a common epitope in the O-polysaccharides of H. pylori, which is known to be highly immunogenic in humans. Of the sera from these patients, 71-94% were positive with the commercial kits, 97% with immunoblot assay, and 90% with ELISA. On the other hand, of the healthy adults infected with H. pylori, 72-97% were positive with the commercial kits, 86% with immunoblot assay, and 72% with ELISA. PK-treated cells that did not contain the common epitope were unsuitable as an antigen for immunoblot assay or ELISA. Furthermore, the reactivity of these sera reacted specifically with H. pylori PK-treated cells but not with LPSs from other gram-negative bacteria, such as Campylobacter, Proteus, Bordetella, and Salmonella. These results demonstrate that the serological assays relying on the use of H. pylori PK-treated cells possessing a highly antigenic epitope are potentially useful as a serodiagnostic test for H. pylori infection.

Adult↗
PubMed1998

Serological studies of an acid-labile O-polysaccharide of Proteus vulgaris OX19 lipopolysaccharide using human and rabbit antibodies.

In a Weil-Felix test, sera from patients infected with Rickettsia sp. agglutinate Proteus OX types of bacteria and Proteus lipopolysaccharide (LPS) are responsible for the cross-reaction. Data on the character of LPS of one of the OX group strains, Proteus vulgaris OX19, are contradictory, and it remained unclear whether it has an O-polysaccharide (OPS) and is thus LPS of the smooth type (S) or not (rough-type LPS). Our studies showed that P. vulgaris OX19 (strain PZH-24) produces a smooth-type LPS that contains a long-chain OPS, but it undergoes depolymerization during mild acid hydrolysis conventionally used for LPS delipidation and loses the serological activity. An elucidation of the complete structure of OPS demonstrated the presence of a glycosyl phosphate linkage responsible for the acid-lability of the polysaccharide chain. In ELISA, both IgM type antibodies in a Weil-Felix test with human anti-Rickettsia typhi sera and rabbit anti-P. vulgaris OX19 antibodies reacted with OPS. Rabbit antibodies did not inhibit the cross-reaction with human antibodies and thus bind to different epitopes.

Animals↗