Biomedical subjects

Y Kodera

Publications and source records attributed to Y Kodera.

At least 19 recordsLinked to original sources

PubMed2003

Lymphoid blast crisis of chronic myelogenous leukemia occurring more than 11 years after receiving an allogeneic bone marrow transplant for chronic myelogenous leukemia in myeloid blast crisis at onset.

A 25-year-old male developed lymphoid blast crisis (BC) of chronic myelogenous leukemia (CML) more than 11 years after receiving an allogeneic bone marrow transplant (alloBMT) for CML with myeloid BC at presentation from his HLA-identical brother. The lymphoid BC of CML probably occurred without a preceding chronic phase of CML. This case illustrates the difficulties involved in determining the appropriate length of follow-up after alloBMT.

Adult↗

PubMed2002

Polymorphisms in TNFA and TNFR2 affect outcome of unrelated bone marrow transplantation.

Effects of polymorphisms in TNFA and TNFR2 on the outcome of 462 cases of unrelated bone marrow transplantation (uBMT) were studied retrospectively. Four alleles of TNFA (U01-U04) distinguished by polymorphism in the upstream region, -1031 (T/C), -863 (C/A) and -857 (C/T), and two alleles of TNFR2 (196M/196R) distinguished by polymorphism at codon 196 were determined. Transplantation involving TNFA-U02- and/or U03-positive donors and/or recipients resulted in a higher incidence of graft-versus-host disease (GVHD) of grade III-IV (P < 0.05 for donor type, P < 0.01 for recipient type) and a lower relapse rate than that involving TNFA-U01 homozygous recipients and/or donors (P < 0.025 for donor type, P < 0.01 for recipient type). These results include the HLA mismatching effect due to linkage disequilibirium of TNFA with HLA loci. However, the effects were also observed in HLA-A, -B and -DRB1 allele-matched transplantation. Transplantation from TNFR2-196R-positive donors exhibited a higher incidence of severe GVHD (P < 0.05) and tendency for a lower relapse rate than that from TNFR2-196M homozygous donors. TNFR2-196R of recipient origin had no effect on GVHD but increased the relapse rate (P < 0.025). These results suggest that TNFA and TNFR2 typings are helpful for predicting uBMT outcome and for preventing severe complications at an early stage.

Adult↗

PubMed2002

Prognostic significance of the null genotype of glutathione S-transferase-T1 in patients with acute myeloid leukemia: increased early death after chemotherapy.

We investigated the prognostic significance of genetic polymorphism in glutathione-S transferase mu 1 (GSTM1), glutathione-S transferase theta 1 (GSTT1), NAD(P)H:quinone oxidoreductase (NQO1) and myeloperoxidase (MPO), the products of which are associated with drug metabolism as well as with detoxication, in 193 patients with de novo acute myeloid leukemia (AML) other than M3. Of the patients, 64.2% were either homozygous or heterozygous for GSTT1 (GSTT1(+)), while 35.8% showed homozygous deletions of GSTT1 (GSTT1(-)). The GSTT1(-) group had a worse prognosis than the GSTT1(+) group (P = 0.04), whereas other genotypes did not affect the outcome. Multivariate analysis revealed that GSTT1(-) was an independent prognostic factor for overall survival (relative risk: 1.53; P = 0.026) but not for disease-free survival of 140 patients who achieved complete remission (CR). The rate of early death after the initiation of chemotherapy was higher in the GSTT1(-) group than the GSTT1(+) group (within 45 days after initial chemotherapy, P = 0.073; within 120 days, P = 0.028), whereas CR rates and relapse frequencies were similar. The null genotype of GSTT1 might be associated with increased toxicity after chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies.

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human malignancy. An internal tandem duplication (ITD) of the juxtamembrane (JM) domain-coding sequence of the FLT3 gene (FLT3/ITD) is found in 20% of patients with acute myeloid leukemia (AML) and is strongly associated with leukocytosis and a poor prognosis. On the other hand, mutations of the c-KIT gene, which have been found in mast cell leukemia and AML, are clustered in 2 distinct regions, the JM domain and D816 within the activation loop. This study was designed to analyze the mutation of D835 of FLT3, which corresponds to D816 of c-KIT, in a large series of human hematologic malignancies. Several kinds of missense mutations were found in 30 of the 429 (7.0%) AML cases, 1 of the 29 (3.4%) myelodysplastic syndrome (MDS) cases, and 1 of the 36 (2.8%) acute lymphocytic leukemia patients. The D835Y mutation was most frequently found (22 of the 32 D835 mutations), followed by the D835V (5), and D835H (1), D835E (1), and D835N (1) mutations. Of note is that D835 mutations occurred independently of FLT3/ITD. An analysis in the 201 patients newly diagnosed with AML (excluding M3) revealed that, in contrast to the FLT3/ITD mutation (n = 46), D835 mutations (n = 8) were not significantly related to the leukocytosis, but tended to worsen disease-free survival. All D835-mutant FLT3 were constitutively tyrosine-phosphorylated and transformed 32D cells, suggesting these mutations were constitutively active. These results demonstrate that the FLT3 gene is the target most frequently mutated to become constitutively active in AML.

Acute Disease↗

PubMed2001

A novel hydrophobic diheme c-type cytochrome. Purification from Corynebacterium glutamicum and analysis of the QcrCBA operon encoding three subunit proteins of a putative cytochrome reductase complex.

Electrophoresis of a Corynebacterium glutamicum membrane preparation in the presence of sodium dodecyl sulfate, followed by staining for peroxidase activity (heme staining), showed only one band at about 28 kDa. This 28 kDa protein was purified from C. glutamicum membranes by chromatography in the presence of decylglucoside using DEAE-Toyopearl and hydroxylapatite columns, as the sole c-type cytochrome in the bacterium. The cytochrome showed an alpha band at 551 nm, and its E(m, 7) was about 210 mV. A QcrCAB operon encoding the subunits of a putative quinol cytochrome c reductase was found 3'-downstream of ctaE encoding subunit III of cytochrome aa(3) in the C. glutamicum genome. The deduced amino acid sequence of qcrC, composed of 283 amino acid residues, contained two heme C-binding motifs and was in agreement with partial peptide sequences obtained from the 28 kDa protein after V8 protease digestion. We propose to name this protein cytochrome cc. The presence of cytochrome cc is a common feature of high G+C content Gram-positive bacteria, since we could confirm this protein by electrophoresis; homologous QcrCAB operons are also known in Mycobacterium and Streptomyces. QcrA and qcrB of C. glutamicum encode the Rieske Fe-S protein and cytochrome b, respectively, although these proteins were not co-purified with cytochrome cc. The phylogenetic tree of cytochromes b and b(6) show that C. glutamicum cytochrome b, along with those of other bacteria in the high G+C group, is rather different from the Bacillus counterparts, but highly similar to the Deinococci and Thermus cytochromes. This indicates that there is a fourth group of bacteria in addition to the three clades: proteobacterial cytochrome b, cyanobacterial b(6) and green sulfur-low G+C Gram-positive bacteria.

Amino Acid Sequence↗

PubMed2001

Glutamate synthesis via photoreduction of NADP+ by photostable chlorophyllide coupled with polyethylene-glycol.

Chlorophyllide a was coupled with alpha-(3-aminopropyl)-omega-methoxypoly(oxyethylene) (PEG-NH2) to form a PEG-chlorophyllide conjugate through an acid-amide bond. The conjugate catalyzed the reduction of methylviologen in the presence of 2-mercaptoethanol. It also catalyzed the photoreduction of NADP+ or NAD+ in the presence of ascorbate as an electron donor and ferredoxin-NADP+ reductase as the coupling enzyme. Utilizing the reducing power of NADPH generated by PEG-chlorophyllide conjugate under illumination, glutamate was synthesized from 2-oxoglutarate and NH4+ in the presence of glutamate dehydrogenase. PEG-chlorophyllide conjugate was quite stable toward light illumination compared with chlorophyll a. The increase in the molecular weight of PEG in the PEG-chlorophyllide conjugates was accompanied by the enhancement of photostability of the conjugate and also by the increased solubility in the aqueous solution.

Carboxylic Ester Hydrolases↗

PubMed2001

Is Borrmann type IV gastric carcinoma a surgical disease? An old problem revisited with reference to the result of peritoneal washing cytology.

BACKGROUND AND OBJECTIVES: Borrmann type IV gastric carcinoma (B-4) remains a disease with poor prognosis despite an aggressive surgical approach. Cytology examination of the peritoneal washes is an established prognostic factor for gastric carcinoma in general, and may be useful for identifying adequate treatment strategy for B-4. METHODS: Pathologic data from 70 patients with B-4 who underwent laparotomy and peritoneal washing cytology during the recent 6 years were retrieved from a prospective computer database and reviewed. Prognostic significance of the cytology examination along with other known clinicopathologic variables was evaluated by univariate and multivariate analyses. RESULTS: Long-term survivors were observed only among the patients who were treated with curative R0 resection. Prognosis of the patients with positive cytology and no other residual disease (R1) was extremely poor and was equivalent to that of the patients undergoing noncurative R2 resection. No difference in survival, either, was observed between the patients treated by R2 resection and those who did not undergo resection. Multivariate analysis identified cytology examination as an independent prognostic factor. CONCLUSIONS: Peritoneal washing cytology plays an important role in staging B4. Positive cytology findings as well as other evidence of disseminated disease may indicate that gastrectomy should be avoided.

Demography↗

PubMed2001

Use of a segment of transverse colon as a gastric substitute after total gastrectomy: an audit of 18 patients.

BACKGROUND: Various types of reconstruction have been employed in attempts to improve the quality of life after total gastrectomy. The use of a jejunal pouch has been the most common approach, and preservation of the duodenal passage has been recommended in several related studies. The aim of the present study was to investigate the benefit of the use of a segment of transverse colon as a gastric substitute. METHODS: Isoperistaltic interposition with a segment of transverse colon was performed after total gastrectomy in 18 patients with gastric malignancies. To clarify the benefits and disadvantages of this technique, a comparison was made between these patients and another 17 patients who underwent jejunal interposition without a pouch. The parameters to be compared included operation time, amount of blood loss, incidence of postoperative complications, and changes in body weight. RESULTS: Postoperative complications were more frequent in the patients reconstructed with the transverse colon, despite a lower incidence of extended lymphadenectomies in this group of patients. No advantage over those treated by the jejunal interposition, in terms of postoperative body weight, was evident during 2 years of follow-up. CONCLUSION: Although it may be too early to draw definite conclusions, there seems to be little benefit in the use of the transverse colon as a gastric substitute.

Carcinoma↗

PubMed2001

Expression of Cdx1 and Cdx2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa--with special emphasis on participation in intestinal metaplasia of the human stomach.

BACKGROUND: The caudal-type homeobox genes, Cdx1 and Cdx2, are candidates for directing intestinal development, differentiation, and maintenance of the intestinal phenotype. The aims of this study were: (1) to assess the normal tissue expression patterns of Cdx1 and Cdx2 in the human gastrointestinal tract and (2) to ascertain levels in intestinal metaplasia (IM) of the stomach associated with gastritis. METHODS: Fresh human tissues were collected by surgical resection from 39 patients after informed consent had been received. RNAs were extracted from 11 distinct sites in the gastrointestinal mucosa (gastric body, gastric antrum, duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum), and Northern hybridization was performed for Cdr1 and Cdx2 mRNAs. In addition, RNAs were also extracted from normal gastric mucosa, and gastric mucosa with mild to severe IM, confirmed histopathologically. Reverse-transcriptase polymerase chain reaction (RT-PCR) was then carried out for Cdx1 and Cdx2. RESULTS: The expression of Cdx1 mRNA increased gradually from the duodenum to the distal colon, with no expression detected in the stomach. Compared with the distribution of Cdx1 mRNA in the mouse gastrointestinal tract, the expression of Cdr1 mRNA in the human gastrointestinal tract showed greater predominance in the jejunum and ileum. The expression of Cdx2 mRNA increased gradually from the duodenum to the proximal colon and decreased from the ascending colon to the rectum. Compared with the expression pattern of Cdx2 mRNA in the mouse gastrointestinal tract, the expression of Cdx2 mRNA in the human gastrointestinal tract showed greater predominance in the ileum. By RT-PCR, both Cdx1 and Cdx2 mRNAs were detected in the mild and severe types of IM. However, neither of these mRNAs was identified in normal gastric mucosa without IM. CONCLUSIONS: Cdr1 and Cdx2 mRNAs are widely present in the human intestinal and colonic mucosae, but not in the gastric mucosa, suggesting that their expression may contribute to the intestinal phenotype. The high levels of these mRNAs in IM mucosa associated with chronic atrophic gastritis point to an association with this phenotypic shift in the gastric mucosa.

Adult↗

PubMed2001

Early and late elevation of plasma atrial and brain natriuretic peptides in patients after bone marrow transplantation.

Clinical usefulness of bone marrow transplantation (BMT) remains limited by myocardial damage during the post-transplantation period. Measurements of plasma atrial and brain natriuretic peptides (ANP, BNP) during the acute post-transplantation period could serve to monitor cardiac complications since these peptides are known to increase in heart failure depending on its severity. We prospectively analyzed ANP and BNP levels from 14 days before to 100 days after BMT in 46 consecutive patients undergoing allogeneic (n=42) and autologous (n=4) transplantation. Cardiac performance was assessed by echocardiography and radionuclide ventriculography. BNP and ANP levels of the patients on admission (baseline: day-14) were 16.3+/-13.3 pg/ml and 14.4+/-8.8 pg/ml, respectively. There were two different types of changes in the BNP and ANP levels. The 21 patients in group I showed dual peaks of elevation on day 1 (BNP=164.4+/-136.0 pg/ml, P<0.01; ANP=44.5+/-35.4 pg/ml, NS) and day 14 (BNP=233.9+/-106.2 pg/ml, P<0.01; ANP=142.7+/-154.6 pg/ml, P<0.05), whereas the remaining 25 patients in group II had a single peak on day 1 (BNP=124.5+/-124.9 pg/ml, P<0.05; ANP=45.2+/-42.4 pg/ml, NS). The left ventricular ejection fraction on day 63 was unchanged in both groups of patients from the baselines. The time to peak filling rate, a parameter of diastolic function in the radionuclide ventriculography, was significantly prolonged in group I patients (by 30+/-53%), whereas unaffected in group II patients. These results suggest that plasma BNP monitoring for 2 weeks after BMT may be useful for early detection of patients at high risk for cardiac dysfunction in the post-transplantation period.

Adult↗

PubMed2001

Small incisional esophagectomy with endoscopic assistance: evaluation of a new technique.

Laparoscopic surgery now can be performed safely and efficiently for various types of cancer; however, reconstruction of the gastric tube may be technically demanding. We attempted to make a breakthrough by designing and employing a new technique for performing a small incisional operation with endoscopic assistance. A midline incision, 10cm in length, was made in the upper abdomen. Some procedures were performed through the incision under direct vision, while other procedures required in the lateral extremes of the abdominal cavity, that are inaccessible by direct vision, were performed by laparoscopic-assisted surgery. Similarly, intrathoracic procedures were essentially performed through a minithoracotomy, 10-15cm in length, made without dissection of the dorsal latissmus or anterior serratus muscles. The postoperative courses of 20 consecutive patients who underwent this procedure were generally uneventful, and significant improvements in terms of intensive care and analgesic requirements were observed.

Aged↗

PubMed2001

Lymph node metastasis in cancer of the middle-third stomach: criteria for treatment with a pylorus-preserving gastrectomy.

A retrospective study was conducted to establish the criteria for performing a pylorus-preserving gastrectomy. This study was performed on 491 patients who had cancer of the middle-third stomach and had been curatively treated with a distal gastrectomy. The incidence of node metastasis for each lymph node station (the group of regional lymph nodes which have been anatomically defined and classified by the Japanese Classification of Gastric Carcinoma) was evaluated with reference to the depth of invasion, tumor size, and circumferential location, to show any significant correlations with an increase in tumor diameter or in the depth of tumor invasion. The benefits of resecting each station was then evaluated based on the incidence of metastasis to each station and the rate of long-term survivors among those with metastasis to each station. The benefit was substantial for the lymph nodes along the lesser curvature, along the right gastroepiploic artery, and at the base of the left gastric artery, while the advantages were almost negligible for the suprapyloric nodes and right paracardial nodes. In conclusion, carcinoma that fulfills either of the following conditions may thus be indicated to undergo a pylorus-preserving gastrectomy: (i) restricted to a depth of m or sml, (ii) a depth of sm2 or mp with a diameter of less than 2cm, (ii) a depth of sm2 or mp and located in the greater curvature.

Adult↗

PubMed2001

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation.

Adult T cell leukemia/lymphoma (ATL) is a poor prognosis T cell malignancy. In order to improve the outcome, we employed allogeneic stem cell transplantation (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings and one from an unrelated donor. Conditioning regimens varied among the patients except that all received total body irradiation. The patients tolerated the regimens well with mild, if any toxicity, and engraftment occurred in all cases. Median leukemia-free survival after allo-SCT was 17.5+ months (range 3.7-34.4+). Six of the 10 patients developed acute GVHD (one case each with grade I, III or IV, and three cases with grade II) and three patients developed extensive chronic GVHD. Four patients died after allo-SCT during the study period from either acute GVHD (grade IV), pneumonitis, gastrointestinal bleeding or renal insufficiency. Two of the 10 cases with no symptoms of GVHD relapsed with clinical ATL. These results strongly suggest that allo-SCT may improve the survival in ATL if a controlled degree of GVHD develops.

Adult↗

PubMed2001

Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation.

We report the results of a phase III trial comparing tacrolimus (FK506) with cyclosporine for GVHD prophylaxis after allogeneic BMT. From February 1995 to July 1996, 136 patients were enrolled and followed up to September 1997. During the first 100 days post-transplant the incidence of grade II-IV acute GVHD (the primary end-point) was lower in the tacrolimus group (17.5%) compared with the cyclosporine group (48.0%, P < 0.0001). A significant difference was observed between the tacrolimus and cyclosporine groups when subset analyses were performed based on recipients from HLA-matched siblings (13.3% vs 41.3%, P = 0.015) or donors other than HLA-matched siblings (21.4% vs 53.8%, P= 0.0029). The incidence of chronic GVHD (47.3% and 47.8%) and Kaplan-Meier estimate of overall survival (62.9% and 65.2%) were similar between the tacrolimus and cyclosporine groups, respectively. The overall leukemia relapse rate was not significantly different between the tacrolimus and cyclosporine groups (19.6% and 11.4%, respectively). However, the relapse rate among recipients from HLA-matched siblings was significantly higher in the tacrolimus group (30.9%) compared with the cyclosporine group (3.6%, P = 0.013). These results suggest the merit of tacrolimus for the prophylaxis of acute GVHD, but a lack of merit for a graft-versus-leukemia effect among recipients from HLA-matched sibling donors.

Adolescent↗

PubMed2001

Polymorphisms in the coding region of mtDNA and effects on clinical outcome of unrelated bone marrow transplantation.

The entire protein-coding region was divided into 45 fragments, separately amplified and analyzed for polymorphism by the PCR-SSCP (single-strand conformation polymorphism) method. The effect of polymorphism mismatching on the clinical outcome of unrelated bone marrow transplantation was studied to clarify whether products from mtDNA become minor antigens. Variability in PCR-SSCP pattern combinations of the 45 fragments suggests that each individual has a different polymorphism combination in the protein-coding region if all the coding regions were compared at the nucleotide sequence level. Nonsynonymous polymorphisms were found at relatively high frequency in MTATP8 and MTND3. Both the polymorphisms with and without substitution matched the peptide-binding motifs of HLA-A*0201. The effects of the polymorphism matching were retrospectively analyzed in 340 recipients transplanted with HLA-A, -B, -DRB1 allele-matched bone marrow from unrelated donors. There were no effects of polymorphism matching on the incidence of acute GVHD and cumulative disease-free survival. These results suggest that polymorphisms which generate peptides, with and without substitutions, that bind the same HLA molecule hardly influence GVHD because the difference between the HLA-peptide complexes is minute.

Bone Marrow Transplantation↗

PubMed2001

Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: indications and dose escalation.

To clarify the role of dose escalation of donor leukocyte infusion (DLI) in the treatment of relapsed leukemia after allogeneic bone marrow transplant (BMT), data from 100 patients were collected from 46 facilities in Japan and analyzed with respect to indications and infused cell dose. Complete remission (CR) was achieved in 11 of 12 (91%) patients with relapsed chronic myelogenous leukemia (CML) in the chronic phase, 3 of 11 (27%) with CML in the acute phase, 8 of 21 (38%) with acute myelogenous leukemia (AML), 6 of 23 (25%) with acute lymphoblastic leukemia (ALL), and 5 of 11 (45%) with myelodysplastic syndrome (MDS). The probability of remaining in CR at 3 years was 82% in CML patients in the chronic phase, but 0% in those with CML in the acute phase, 7% in those with AML, 0% with ALL, and 33% with MDS. Acute graft-versus-host disease (GVHD) (> or = 2) developed in 31 of 89 (34%) patients with human leukocyte antigen identical related donors and was fatal for 7 (7%). A leukocyte dose of 1 x 10(7)/kg of recipient body weight with CML in the chronic phase, 3 x 10(7)/kg of recipient body weight with MDS, and 1 x 10(8)/kg of recipient body weight with acute leukemia appeared to be optimal as an initial dose of DLI. However, the minimal dose of leukocyte developing fatal GVHD was 7 x 10(7)/kg of recipient body weight. These suggest that a relatively small dose of DLI ranging from 1 x 10(7)/kg to 5 x 10(7)/kg of recipient body weight should be administered initially then the infused escalating dose 2 or 3 months later in patients with CML in the chronic phase and MDS. However, a large number of leukocytes around 1 x 10(8)/kg are needed to induce graft versus leukemia effects in patients with acute leukemia despite a 7% fatality in GVHD.

Adolescent↗

PubMed2001

Osteonecrosis of the femoral head after allogeneic bone marrow transplantation.

A comparative retrospective analysis of 100 consecutive patients after bone marrow transplantation was performed with magnetic resonance imaging in addition to plain radiography for the development of osteonecrosis of the femoral head. The incidence and risk factors for osteonecrosis of the femoral head were identified, comparing various parameters concerning bone marrow transplantation between the groups with and without evidence of osteonecrosis. Nineteen (19%) of 100 patients had osteonecrosis of the femoral head develop. Four factors were found to be statistically significantly different between patients who had osteonecrosis develop and those who did not: younger age at the time of bone marrow transplantation, chronic graft-versus-host disease, cumulative dose of steroid, and intravenous pulse therapy with methylprednisolone. It was concluded that a low rate of complications and low dose steroid administration would reduce the incidence of osteonecrosis after bone marrow transplantation.

Adolescent↗

PubMed2001

Allixin induction and accumulation by light irradiation.

Allixin, a phytoalexin isolated from garlic, was induced by irradiating fresh garlic cloves with sunlight or UV light. Induced allixin was analyzed by HPLC, and the accumulated amounts of allixin were 3.1-6.3 microg/g under experimental conditions.

Antineoplastic Agents, Phytogenic↗