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Biomedical subjects

N Kamada

Publications and source records attributed to N Kamada.

At least 199 records · Page 11Linked to original sources
PubMed1994

Estimation of chronic phase duration in Ph-positive chronic myelocytic leukemia treated with busulfan: statistical analysis on Japanese patients.

Chronic phase duration was analyzed in 148 Japanese patients with Ph-positive chronic myelocytic leukemia (CML) treated only with busulfan, and multivariate proportional hazard models were constructed to infer the prognosis of a given patient, and to evaluate the prognostic importance of the clinical findings. To make an accurate estimation of an individual patient's prognosis, we introduced a piecewise linear model for describing a hazard function in each prognostic variable. Of the 11 prognostic variables initially analyzed, the absolute count of peripheral basophils was revealed as the most important prognostic factor. A high basophil count was clearly a factor in cases with poor prognosis. The statistical model selection based on the criteria of model approximation finally suggested a model with three covariates; absolute count of peripheral basophils, platelet count, and presence or absence of additional chromosome abnormalities superimposed on the translocation of 9;22. By analyses based on the above model, we estimated that the median of the chronic phase duration for the patients with poor and good prognosis was 12 and 75 months, respectively. The piecewise linear model was well suited for an accurate estimation of an individual patient's prognosis. Thus, the model constructed here would become a reliable control to evaluate investigational approaches, such as hydroxyurea, interferons, and/or bone marrow transplantation.

Adolescent↗
PubMed1994

Cancer incidence in atomic bomb survivors. Part III. Leukemia, lymphoma and multiple myeloma, 1950-1987.

This paper presents an analysis of data on the incidence of leukemia, lymphoma and myeloma in the Life Span Study cohort of atomic bomb survivors during the period from late 1950 through the end of 1987 (93,696 survivors accounting for 2,778,000 person-years). These analyses add 9 additional years of follow-up for leukemia and 12 for myeloma to that in the last comprehensive reports on these diseases. This is the first analysis of the lymphoma incidence data in the cohort. Using both the Leukemia Registry and the Hiroshima and Nagasaki tumor registries, a total of 290 leukemia, 229 lymphoma and 73 myeloma cases were identified. The primary analyses were restricted to first primary tumors diagnosed among residents of the cities or surrounding areas with Dosimetry System 1986 dose estimates between 0 and 4 Gy kerma (231 leukemias, 208 lymphomas and 62 myelomas). Analyses focused on time-dependent models for the excess absolute risk. Separate analyses were carried out for acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelocytic leukemia (CML) and adult T-cell leukemia (ATL). There were few cases of chronic lymphocytic leukemia in this population. There was strong evidence of radiation-induced risks for all subtypes except ATL, and there were significant subtype differences with respect to the effects of age at exposure and sex and in the temporal pattern of risk. The AML dose-response function was nonlinear, whereas there was no evidence against linearity for the other subtypes. When averaged over the follow-up period, the excess absolute risk (EAR) estimates (in cases per 10(4) PY Sv) for the leukemia subtypes were 0.6, 1.1 and 0.9 for ALL, AML and CML, respectively. The corresponding estimated average excess relative risks at 1 Sv are 9.1, 3.3 and 6.2 respectively. There was some evidence of an increased risk of lymphoma in males (EAR = 0.6 cases per 10(4) PY Sv) but no evidence of any excess in females. There was no evidence of an excess risk for multiple myeloma in our standard analyses.

Adolescent↗
PubMed1994

Identification of illegitimate recombination hot spot of the retinoic acid receptor alpha gene involved in 15;17 chromosomal translocation of acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) has been characterized by 15;17 chromosomal translocation, which involves the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. The breakpoints have been mapped to three cluster regions in the PML gene, and to RARA gene intron 2. We have examined the distribution of breakpoints within RARA gene intron 2. An extremely restricted region (ERR) of 50 bp within RARA gene intron 2 was identified as the cluster region of breakpoints by polymerase chain reaction and sequence analysis of DNA from APL patients. To study experimentally the mechanism involved in the translocation, ERR was tested in NIH3T3 cells by in vitro transfection-recombination assay, in which target sequences were placed either downstream of the SV40 promoter or upstream of the neo gene. Cells were conferred resistance to G418 only when the promoter was fused to the neo gene by recombination of two target sequences during transfection. The molecular junctions were analysed in five clones, and all of them were shown to be confined within a 20 bp region in a 148 bp DNA fragment containing ERR. This suggests that ERR might be the illegitimate recombination hot spot in mammalian cells.

3T3 Cells↗
PubMed1994

[Clinical study of the hypogastric plexus preserving operation for Y-prosthesis replacement for abdominal aneurysm--operative technique for avoiding postoperative sexual disorders].

We studied the effect of the hypogastric plexus preserving operation for Y-prosthesis replacement in abdominal aneurysm. The hypogastric plexus preserving operation was performed for avoiding postoperative sexual disorders such as the impotence and the abnormalities of ejaculation. With wide abrasion of retroperitoneum as usually, postoperative abnormalities of ejaculation occurred in 70% and postoperative impotence occurred in 50% of cases undergoing Y-prosthesis replacement. More reliable nerve preserving operation was the minimum abrasion of retroperitoneum and the aorta had not to he abrased at the origin of the inferior mesenteric artery, bifurcation of the aorta and the common iliac artery. Then with this nerve preserving operation, abnormalities of ejaculation occurred in 30% (p < 0.05) of cases and impotence occurred in 20% of cases. The results indicate that sexual dysfunction may he prevented to minimize by the nerve preserving operation.

Aged↗
PubMed1993

Influence of M-BCR breakpoint sites on the duration of chronic phase in 100 patients with chronic myelocytic leukemia.

Rearrangements of the bcr (M-BCR) gene were studied in 100 patients with chronic myelocytic leukemia (CML). To determine the significance of a chimeric gene expression in the progression of CML, we analyzed 43 patients for bcr-ABL chimeric mRNA expression. Both DNA and RNA analyses revealed a possible influence of breakpoint sites in the bcr region on the duration of the chronic phase. Patients with the breakpoint located at about the 1-kb region between BamHI and HindIII in bcr exon 3 (region C2) had a significantly shorter chronic phase (31 months) (p = 0.028) than patients in whom the breakpoint was located in other regions. When the bcr locus was divided into 5' and 3' regions as for the BamHI cleavage site located near the 5' region of bcr exon 3, the chronic phase duration in patients with the 5' site (HindIII-BamHI) and 3' site (BamHI-EcoRI site) was 75 and 38 months, respectively. However, the difference was not statistically significant (p = 0.128). These results suggest that only the breakpoint site at C2 on the bcr locus, rather than breakpoint sites in other regions, has an important role in the progression of CML.

Chromosome Mapping↗
PubMed1993

Junctions of the AML1/MTG8(ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction.

The chromosomal translocation, t(8;21), is found frequently in acute myeloid leukemia (AML) with maturation (FAB-M2). We have previously mapped the translocation breakpoints of t(8;21) in a specific intron of the AML1 gene on chromosome 21. In this study, we cloned cDNAs synthesized from a cell line carrying t(8;21) by reverse transcription polymerase chain reaction (RT-PCR) using an AML1-specific primer. The analysis of the cDNAs structure has led to the identification of the fusion of AML1 with a gene named MTG8 on chromosome 8, which seems to be identical to ETO. Northern analysis using MTG8 (ETO) probes detected 7.8-kb and 6.2-kb RNAs and several minor RNAs in the cell line with t(8;21), but failed to detect any transcripts in a cell line without t(8;21). A set of primers were designed to detect the AML1/MTG8(ETO) fusion by PCR. The PCR amplified identical products in all 6 patients and one cell line with t(8;21), suggesting that the AML1/MTG8(ETO) fusion is a constant feature associated with t(8;21) and the junctions of the AML1/MTG8(ETO) fusion are restricted in a unique site. Because the PCR detection of the AML1/MTG8(ETO) fusion at the RNA level is highly sensitive, it can be used as a sensitive method for diagnosis and detection of minimal residual disease in t(8;21) leukemia.

Amino Acid Sequence↗
PubMed1993

Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs.

Chromosome translocations involving band 11q23 are associated with human acute leukemias. These translocations fuse the ALL-1 gene, homolog of Drosophila trithorax and located at chromosome band 11q23, to genes from a variety of chromosomes. We cloned and sequenced cDNAs derived from transcripts of the AF-4 and AF-9 genes involved in the most common chromosome abnormalities, t(4:11)(q21:q23) and t(9:11)(p22:q23), respectively. Sequence analysis indicates high homology between the AF-9 gene protein product and the protein encoded by the ENL gene fused to ALL-1 in (11:19) chromosome translocations. AF-4, AF-9, and ENL proteins contain nuclear targeting sequences as well as serine-rich and proline-rich regions. Stretches abundant in basic amino acids are also present in the three proteins. These results suggest that the different proteins fused to ALL-1 polypeptide(s) provide similar functional domains.

Acute Disease↗
PubMed1993

Establishment and characterization of a human gastric scirrhous carcinoma cell line in serum-free chemically defined medium.

We have established a human gastric scirrhous carcinoma cell line (designated as HSC-43) in a serum-free chemically defined medium (CDM) without any polypeptide growth factor, from a primary tumor of a 56-year-old male patient. HSC-43 cells grew in vitro in adherence with a population doubling time of 55 hr, and had the cytological properties of mucinous epithelial tumor cells. Cytogenetic analysis of the cells revealed pseudotetraploidy, with structural abnormalities of deletion at chromosome Iq25 and with 3 marker chromosomes. Some cells had retained features of signet-ring cells and caused fibroblastic proliferation when transplanted into athymic nude mice. The possible involvement of transforming growth factor-alpha (TGF-alpha), and its receptor, the epidermal-growth-factor receptor (EGFR), on the growth of HSC-43 cells was studied. Synthesis and secretion of TGF-alpha by HSC-43 cells were confirmed by biological assay and enzyme-linked immunosorbent assay. Radioreceptor analysis showed the presence of receptors for EGF in HSC-43 cells. Proliferation of HSC-43 cells was inhibited by antibodies against TGF-alpha and/or the EGFR. However, neither TGF-alpha nor epidermal growth factor (EGF) was effective in stimulating the cell growth of HSC-43 cells, irrespective of the cell density when supplemented exogenously. Our data suggest that TGF-alpha and EGFR play a role in the autocrine growth of HSC-43 cells. This may be another example of growth regulation of gastric carcinoma.

Adenocarcinoma, Scirrhous↗
PubMed1993

The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript.

The t(8;21) translocation is one of the most frequent chromosome abnormalities in acute myeloid leukemia. It has been shown that the t(8;21) breakpoints on chromosome 21 cluster within a single specific intron of the AML1 gene, which is highly homologous to the Drosophila segmentation gene runt. Here we report that this translocation juxtaposes the AML1 gene with a novel gene, named MTG8, on chromosome 8, resulting in the synthesis of an AML1-MTG8 fusion transcript. The fusion protein predicted by the AML1-MTG8 transcript consists of the runt homology region of AML1 and the most part of MTG8, which contains putative zinc finger DNA binding motifs and proline-rich regions constituting a characteristic feature of transcription factors. The MTG8 gene is not expressed in normal hematopoietic cells, whereas AML1 is expressed at high levels. Our results indicate that the production of chimeric AML1-MTG8 protein, probably a chimeric transcription factor, may contribute to myeloid leukemogenesis.

Acute Disease↗
PubMed1993

Retransplantation of the liver in the rat.

A successful technique of liver retransplantation in the rat is described. Heterotopic nonauxiliary liver engraftment of a whole liver using cuffed anastomoses is the primary transplant procedure. The graft is implanted in the right hypochondrium and is revascularized by a portal end-to-end anastomosis. Venous drainage is via an end-to-side anastomosis between the donor infrahepatic vena cava and recipient right renal vein. The graft suprahepatic vena cava is ligated. Biliary drainage is achieved by a double stent anastomosis of the biliary ducts. Total parenchymectomy of the recipient's liver is completed leaving intact the intrahepatic and suprahepatic vena cava. Retransplantation in the orthotopic position can thus be attempted, after removal of the first graft, by cuffed anastomoses between the donor and recipient portal veins, infrahepatic vena cava and a double stent anastomosis of the common bile ducts. Anastomosis between the donor and recipient suprahepatic vena cava is completed with a 7/0 Prolene running suture. In the first group of operations (n = 6), a three week survival rate of 50% after retransplantation was obtained. Using the technical lessons of these preliminary cases, 80% of the second group of operations (n = 5), were successful in the long term. Utilization of this new technique may allow further investigations in different fields of research dealing with liver surgery and transplantation.

Animals↗
PubMed1993

Protocol for the technique of orthotopic liver transplantation in the rat.

Orthotopic rat liver transplantation (OLT) has been generally accepted as an excellent model for the analysis of pathological, physiological, and immunological aspects related to organ transplantation. However, many researchers require a long training period to achieve a high success rate using this major surgical procedure on small animals. We therefore developed a protocol for learning rat OLT. It is recommended, initially, that the heterotopic heart transplantation (HHT) model be used to master the cuff technique, since this technique is similar to that in OLT and leads to an understanding of another organ transplantation technique. For beginners who advance beyond the HHT step to OLT but cannot finish the anhepatic phase within 30 min, we recommend the use of portosystemic-shunted rats as recipients. These animals have had their spleens transposed subcutaneously more than 3 weeks before use. The use of these modifications and this training program makes it possible to master the techniques and to achieve a high success rate with a short training period.

Animals↗
PubMed1993

The effect of a prostaglandin I2 analogue (OP-41483) on energy metabolism in liver preservation and its relation to lipid peroxidative reperfusion injury in rats.

The effect of the stable prostacyclin (PGI2) analogue OP-41483 (OP) on liver preservation was investigated in the rat liver transplant model. In a 1-week survival study, 33 orthotopic liver transplants were performed using Wistar rats. In group A, untreated livers were stored with modified UW (mUW) solution at 4 degrees C. In group B, livers from OP-pretreated donors (2 micrograms/kg, i.v.) were stored with mUW solution containing OP (1 microgram/ml) at 4 degrees C. After 24 h storage, the donor grafts in each group were transplanted to untreated recipients. OP treatment (group B) significantly improved 1-week survival (62.5%, 10/16, P < 0.01 versus group A; 11.8%, 2/17). For the measurement of adenine nucleotides and lipid peroxidation (malondialdehyde, MDA) in liver tissue before preservation, after preservation, and 3 h after transplantation, 20 rat livers in groups A and B were studied. In both groups, the levels of adenosine triphosphate (ATP) declined 6 h after cold preservation, but this degradation of ATP was significantly halted at the level of adenosine monophosphate (AMP) in the OP-treated livers after 24 h of storage. However, OP treatment showed no significant difference in the degree of ATP recovery after transplantation. On the other hand, OP treatment resulted in suppression of the increase in MDA levels and histological amelioration of microcirculatory disturbance 3 h after transplantation. Our data suggested that the combined use of the stable PGI2 analog (OP-41483) and UW solution is beneficial in liver preservation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1993

Small bowel transplantation in rats: endoscopic and histological evaluation of graft rejection.

Heterotopic small bowel transplantation was performed using the cuff technique in DA(RT1a) to PVG(RT1c) rat fully allogeneic combination. In this model, the rejection course of the grafted intestine was evaluated endoscopically via double stomata and was classified into four stages. Early changes appeared on postoperative day 3. Stage I: The mucosa of the grafted intestine showed patchy paleness and loss of the capillary fine network patterns, accompanied by microerosions. Closer examination revealed irregularity of the epithelial height and arrangement. Stage II: The damage spread progressively over the entire mucosa on day 4-5. Stage III: On day 6-7, the necrotic epithelium became detached, showing multiple ulcers which provoked hemorrhagic enteritis. Stage IV: Graft rejection was completed with total necrosis and white scar tissue formation by day 10-14. These endoscopic findings of the mucosa of the grafted intestine corresponded closely to the time course of pathological examinations. We conclude that endoscopic examination of grafted intestine may be an effective diagnostic tool to detect the rejection phenomenon at an early stage, as well as a simple tool to use for postoperative follow-up in combination with pathological examination.

Animals↗