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Biomedical subjects

T Kakihara

Publications and source records attributed to T Kakihara.

At least 19 recordsLinked to original sources
PubMed2001

Morphological differences between glomerular epithelial cells (GEC) excreted during chemotherapy with antineoplastic drugs and GEC excreted in renal diseases.

BACKGROUND: To better understand the mechanisms of glomerular epithelial cell (GEC) injuries in various diseases, we compared GEC excreted during chemotherapy (antineoplastic drugs) and GEC excreted in renal diseases. METHODS: For 19 patients undergoing chemotherapy (85 courses), 69 patients with IgA nephropathy and 16 patients with Henoch-Schölein purpura nephritis, the number of excreted GEC and GEC casts were counted by an immunofluorescent study. The morphological features of GEC were also studied in an immunofluorescent study combined with Hoechst stain. RESULTS: Glomerular epithelial cells were detected in 78% of the chemotherapy courses and in 94% of the patients with renal diseases. The GEC casts were observed in 2% of chemotherapy courses, while in renal diseases GEC casts were observed in 60% of the patients. Proteinuria (>30 mg/dL) and hematuria were not identified in any of the chemotherapy courses. The morphology and size of GEC were more variable than that in patients with nephropathy. Furthermore, GEC in patients undergoing chemotherapy often showed small nuclei and fragmented nuclei, which were rarely observed in patients with nephropathy. CONCLUSIONS: These results showed that the detachment of podocytes was not directly associated with proteinuria or hematuria. The findings also suggest that GEC are damaged via an apoptotic process by chemotherapy. On the contrary, GEC may be detached through a non-apoptotic process in renal diseases.

Adolescent↗
PubMed2001

[Analysis of chimerism in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation].

Serial monitoring of chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) can be performed easily and rapidly using PCR-based assays analyzing informative tandem repeat genetic markers. Sequential analysis of individual chimerism status was performed in 34 patients who underwent myeloablative allo-HSCT using a commercial multiplex short tandem repeat (STR) kit. Mixed chimerism (MC) was found in 14 of the patients for more than one month. The incidence of MC seemed to be dependent on the type of disease or pretransplantation regimen. There was no significant difference in relapse rates between MC and complete donor chimerism (CC) in all patients. However, the relapse rate was significantly higher in MC than in CC among patients with acute leukemia. The severity of acute graft-versus-host disease (aGVHD) was significantly reduced in the patients with MC. Most of the MC patients with hematologic malignancies had transient mixed T-lymphoid chimerism, and CC was achieved within 6 months after HSCT in such cases. Patients with MC beyond 6 months after HSCT and patients with reappearance of autologous signals (MC after CC) may have an enhanced risk of relapse.

Adolescent↗
PubMed2000

Utility of blasts with a clear halo around the nucleolus as a predictive indicator for disease progression in patients with myelodysplastic syndromes and aplastic anemia.

This study was designed to evaluate the utility of blasts with a clear halo around their nucleoli (BCHN) as a predictive indicator of disease progression in myelodysplastic syndromes (MDSs) and aplastic anemia (AA). Bone marrow aspirates from 75 patients with MDSs and 18 with AA were fixed in 95% ethanol solution or 10% neutral formalin and stained with the Papanicolaou method. BCHNs were detected in 57 of 75 patients with MDSs and in 10 of 18 AA patients. Disease progression was restrictedly observed in 17 patients with MDSs who had BCHNs at onset and in 1 patient with AA. The proportion of BCHNs increased with disease progression in these 16 of 17 patients with MDSs. The presence of BCHNs at onset and the increase in proportion of BCHNs during the clinical course of MDSs were significant indications for predicting disease progression.

Anemia, Aplastic↗
PubMed2000

Clear cell sarcoma arising in the transverse colon.

A case of clear cell sarcoma (CCS) arising in the transverse colon is presented. The tumor consisted of sheets or small nests of epithelioid malignant cells possessing pleomorphic nuclei with one or more prominent nucleoli and ample clear or slightly eosinophilic cytoplasm. Some of the tumor cells contained various amounts of melanin pigments that were confirmed by histochemical and ultrastructural examinations. Immunohistochemical examination showed a positive immunoreactivity for HMB45 and S-100 protein. A metastatic nodule, which was found 9 months after surgery, showed similar histological findings to those of the primary one but lacked melanin pigments. Reverse transcriptase- polymerase chain reaction using total ribonucleic acid obtained from metastatic nodule demonstrated the presence of EWS-ATF-1 fusion gene. Based on these findings, the present case tumor is a CCS of the colon.

Aged↗
PubMed1999

Expression of multidrug resistance-related genes does not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia.

BACKGROUND: The present study was designed to evaluate the association of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP) gene and lung resistance protein (LRP) gene expression (mRNA levels) with risk factors such as phenotype, age and leukocyte count in newly diagnosed childhood acute lymphoblastic leukemia, because biological mechanisms contributing to risk factors were not known. METHODS: Expression of the MDR1, MRP and LRP genes in leukemic cells from 40 pediatric patients was quantitated using the reverse transcriptase polymerase chain reaction method. The associations of expression of these genes with age and leukocyte count, which are known as risk factors for acute lymphoblastic leukemia (ALL), were analyzed. Moreover, the associations with clinically classified risk-related groups (high-risk ALL and low-risk ALL) were also investigated. RESULTS: No positive correlations between expression of these genes and age or leukocyte count were found. The expression of these genes was not different among clinically classified risk-related groups. CONCLUSIONS: Expression (mRNA levels) of the MDR1, MRP and LRP genes did not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia.

Adolescent↗
PubMed1998

Proportion of blasts with a clear halo around nucleoli at the end of induction therapy of acute myeloid leukemia correlates with achievement of complete remission, remission duration and relapse.

Bone marrow aspirates from 60 patients with acute myeloid leukemia (AML) were investigated using 95% ethanol fixation Papanicolaou stained preparations. The blasts were grouped into those with a clear halo around nucleoli (BCHN) and those without a clear halo. The patients were classified into three groups according to the degree of persistent BCHN at the end of induction therapy: group 1, no BCHN; group 2, less than 1% BCHN; and group 3, 1% or more BCHN. All patients in groups 1 (17 cases) and 2 (12 cases), and 12 of 31 cases in group 3 achieved complete remission (CR). Of 17 patients in group 1, two underwent bone marrow transplantation and two died from infection. Of the 37 patients who achieved CR, relapse was observed in two of 13 patients in group 1, and in all patients in groups 2 and 3. As to the patients treated with N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine + daunorubicin + 6-mercaptopurine + prednisolone (BHAC-DMP) protocol, the percentages and number of BCHN at the diagnosis of AML in group 1 were significantly lower than those of groups 2 and 3. The percentage and number of BCHN at the diagnosis of AML were significant factors for the achievement of CR and for the prediction of long-term outcome. The reduction of BCHN to less than 1% at the end of induction therapy is a good indicator for the achievement of CR, and the disappearance of BCHN is a useful target for a long-lasting first CR; conversely, the persistence of BCHN is a major adverse factor for relapse.

Acute Disease↗
PubMed1998

Glomerular injuries--excretion of glomerular epithelial cells-- induced by chemotherapy (antineoplastic drugs) independent of tubular damage.

For the purpose of studying glomerular injuries induced by antineoplastic drugs, the excretion of glomerular epithelial cells (GEC) was evaluated. In 13 children who received antineoplastic drugs, the excretion of GEC in urine samples was examined with an immunofluorescent study using a monoclonal antibody directed against podocalyxin, which was expressed on glomerular epithelial cells. GEC were detected in 20 of 25 chemotherapy courses. The excretion of GEC persisted until the next chemotherapy course in some cases. After an initiation of chemotherapy an increased urinary albumin-creatinine ratio (more than 2-fold) was found in 6 patients. A significant increase of N-acetylglucosaminidase was observed in 2 patients. Proteinuria and hematuria were not observed in all patients. These results indicate that glomerular injuries are frequently induced by chemotherapy independent of the tubular damage. Repeated glomerular injuries may result in late renal dysfunction.

Acetylglucosaminidase↗
PubMed1998

Expression of deoxycytidine kinase (dCK) gene in leukemic cells in childhood: decreased expression of dCK gene in relapsed leukemia.

Competitive RT-PCR was used to determine the quantitative variation in the expression of deoxycytidine kinase (dCK) gene in childhood leukemic cells. The degree of dCK gene expression varied over a 50-fold range. In two cases in which both primary and relapsed leukemic cells were analysed, decreased expression of dCK gene was found in relapsed leukemic cells. The sequence variation analysis using bisbenzimide/polyethylene glycol electrophoresis demonstrated no sequence alteration of dCK cDNA in all cases. These results indicate that the expression of dCK gene varies in patients and suggests decreased expression of the dCK gene as one of the mechanisms responsible for clinical resistance to ara-C.

Adolescent↗
PubMed1997

High incidence of angiotensin I converting enzyme genotype II in Kawasaki disease patients with coronary aneurysm.

UNLABELLED: A 287 base pair insertion/deletion polymorphism in intron 16 of the angiotensin I converting enzyme (ACE) gene was examined by polymerase chain reaction in 36 Kawasaki disease patients (16 without coronary aneurysm, 20 with coronary aneurysm). A polymorphism in the ACE gene was characterized by three genotypes: two D alleles (genotype DD), two I alleles (genotype II), and heterozygous allele (genotype DI). Genotype II was found in 65% of the patients with aneurysm and 12.5% of those without aneurysm (P < 0.01, odds ratio 13.0, 95% confidence intervals). CONCLUSION: Patients with Kawasaki disease and coronary aneurysm more often than expected had the genotype II suggesting that reactions induced by the type of ACE polymorphism predispose to coronary aneurysm formation.

Age of Onset↗
PubMed1997

Reactivity of antibody YU-311 in formalin-fixed, paraffin-embedded specimens of normal organs, non-hematopoietic tumors, and mast cell tumors.

YU-311 is a monoclonal antibody that reacts with a human leukemia cell line resistant for cytosine arabinoside and that identifies a 92 kDa membrane protein. The reactivity of YU-311 in normal organs, various non-hematopoietic tumors and in mast cell tumors in formalin-fixed, paraffin-embedded specimens was examined using immunohistochemical methods. In normal organs, YU-311 reacted with fundic glands of the stomach, the intercalated duct of the pancreas, the distal portion and the loop of Henle of renal tubules and tissue mast cells. Benign neoplasms of various organs showed no immunoreaction with YU-311, except for mast cell tumors. Some types of malignant neoplasms were occasionally positive against YU-311, suggesting neoplasms arising from or differentiating along normal YU-311-positive counterparts. Some other types of malignancies were rarely positive for YU-311, although their normal counterparts showed no immunoreactivity with YU-311. None of the non-epithelial tumors reacted with YU-311, except for one case of malignant melanoma. In contrast, normal tissue mast cells and their related tumors, such as urticaria pigmentosa or solitary mastocytoma, were constantly positive for YU-311. None of the non-hematopoietic human tumor cell lines examined in the present study was reactive with YU-311. These findings indicate that YU-311 is a good marker of some types of tumors and mast cell tumors and that an aberrant expression of YU-311 rarely occurs.

Adenoma↗
PubMed1997

High reactivity of monoclonal antibody (TO73) with human malignant tumor cell line.

The biological characteristics of a new monoclonal antibody (TO73) reacting with a vincristine-resistant human leukemic cell line (KY-VCR) were evaluated. Immunological and electron-immunological studies showed that TO73 reacted with the surface glycoprotein of KY-VCR. TO73 was found to have no effect on cell growth and intracellular uptake of vincristine. In human neoplastic cell lines, TO73 was found to react with 11 of 27 (41%) cell lines. With regard to de novo primary tumor with one exception, TO73 did not react with any of the examined primary tumor cells. The patient with TO73-positive leukemia died of induction failure due to drug resistance. Complete remission was achieved in the other leukemic patients. These results indicate that TO73 antigen may be associated with immortalization of tumor cells and poor prognosis in some cases.

Antibodies, Monoclonal↗
PubMed1997

Serum level and gene polymorphism of angiotensin I converting enzyme in Japanese children.

The aim of the present study was to determine the distribution of the insertion/deletion polymorphism of angiotensin I converting enzyme (ACE) gene in Japanese children. In addition, the relationship between this polymorphism and serum ACE levels in the same population were analyzed. Insertion/deletion polymorphism located in intron 16 of the ACE gene was examined by polymerase chain reaction in Japanese children aged 10-15 years. Allele frequencies were 0.64 for the insertion allele and 0.36 for the deletion allele in 122 subjects. No association was found between genotypes in this polymorphism and the level of systolic or diastolic blood pressure. A significant relationship between this polymorphism and serum ACE activity was observed. These results suggest that interindividual variability of serum ACE level is strongly influenced by the ACE genotype as early as in childhood.

Adolescent↗
PubMed1997

High-dose dexamethasone therapy for a 14-month-old boy with refractory idiopathic thrombocytopenic purpura.

A 14-month-old boy with refractory idiopathic thrombocytopenic purpura (ITP), who was successfully treated with pulsed high-dose oral dexamethasone therapy is reported. The platelet count increased after six scheduled courses of treatment (10 mg/day x 4 days, six courses). Twenty-four months later, the platelet count remained over 10.0 x 10(4)/microL. No obvious side effects were observed during or after the therapy. This treatment could be taken into consideration not only for adults but also for young children with refractory ITP. It is effective, safe, easy to administer, patient comfort is taken into consideration, and hospitalization duration and costs are minimized.

Anti-Inflammatory Agents↗
PubMed1997

Resistance to apoptosis induced by serum depletion and all-trans retinoic acid in drug-resistant leukemic cell lines.

The relation between resistance to anticancer drugs and resistance to apoptosis has been investigated in the human leukemic cell line(KY-821) and its drug-resistant sublines. Under serum depletion conditions, drug-resistant cell lines showed apoptotic resistance when compared with the parental cell line. Drug resistant cell lines also showed resistance to apoptosis when treated with all-trans retinoic acid. DNA fragmentation was low in drug resistant cell lines under both stimulations. Flowcytometry analysis did not show any alterations of the Fas antigen, p53, bcl-2 and c-myc protein expression toward inhibition of apoptotic response in drug-resistant sublines. These results indicate that drug-resistant leukemic cells still show resistance to apoptosis-inducing stimulation such as poor nutrition and differentiation-inducing agents.

Antineoplastic Agents↗
PubMed1996

Identification of drug-resistant myeloid leukemic cells by measurement of DNA content, nuclear area, and detection of P-glycoprotein.

BACKGROUND: This study was designed to evaluate the significance of aneuploidy in DNA ploidy, nuclear area, and expression of P-glycoprotein (P-GP) in differentiating drug-resistant myeloid leukemic cells (DRMLC) from drug-sensitive myeloid leukemic cells. METHODS: Bone marrow aspirates from 28 myeloid leukemic patients were fixed in 95% ethanol solution and stained using the Papanicolaou method. The nuclear area and DNA content were measured. An immunohistochemical study was performed using monoclonal antibody (JSB-1) directed against P-GP. RESULTS: Leukemic cell morphology changed once or twice after the diagnosis of acute myeloid leukemia (AML), blastic crisis (BC) of chronic myeloid leukemia, or chronic neutrophilic leukemia. DRMLC showed severe atypia and were morphologically distinguishable from normal myeloblasts, promyelocytes, and drug-sensitive leukemic cells at the diagnosis of AML or BC. The mean nuclear index (NI) and DNA index (DI) of DRMLC were significantly larger than those of drug-sensitive leukemic cells of AML or BC. The frequency of aneuploidy and P-GP expression was 9.1% and 4.5%, respectively, at the diagnosis of AML or BC, and 92.8% and 28.5%, respectively, for resistant disease. The incidence of heterogeneity in DNA ploidy was 86.3%. CONCLUSIONS: DI and NI values larger than 1.2 and the expression of P-GP are significant indications of DRMLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Differentiation induction therapy with all-trans retinoic acid (ATRA) in a patient with secondary 11q23 leukemia.

PURPOSE: Frequently recurrent leukemia is encountered in childhood and is usually resistant to multidrug therapy. We evaluated the efficacy of differentiation induction therapy in a child with leukemia. PATIENT AND METHODS: We administered all-trans retinoic acid (ATRA) alone, and then a combination of low-dose 1-beta-D-arabinofuranosylcytosine (Ara-C), to a 7-year-old boy who had leukemia secondary to etoposide with chromosomal abnormality 11q23. RESULTS: The patient exhibited a good response to ATRA and had a complete remission after combination therapy of ATRA and low-dose Ara-C. CONCLUSION: Differentiation induction therapy with ATRA was effective in treating a patient with recurrence of leukemia without t(15;17) translocation, and which is resistant to conventional cytotoxic treatment.

Antineoplastic Combined Chemotherapy Protocols↗