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K Takekawa

Publications and source records attributed to K Takekawa.

At least 37 records · Page 2Linked to original sources
PubMed1995

Identification of a new susceptibility locus for insulin-dependent diabetes mellitus by ancestral haplotype congenic mapping.

The number and exact locations of the major histocompatibility complex (MHC)-linked diabetogenic genes (Idd-1) are unknown because of strong linkage disequilibrium within the MHC. By using a congenic NOD mouse strain that possesses a recombinant MHC from a diabetes-resistant sister strain, we have now shown that Idd-1 consists of at least two components, one in and one outside the class II A and E regions. A new susceptibility gene (Idd-16) was mapped to the < 11-centiMorgan segment of chromosome 17 adjacent to, but distinct from, previously known Idd-1 candidates, class II A, E, and Tap genes. The coding sequences and splicing donor and acceptor sequences of the Tnfa gene, a candidate gene for Idd-16, were identical in the NOD, CTS, and BALB/c alleles, ruling out amino acid changes in the TNF molecule as a determinant of insulin-dependent diabetes mellitus susceptibility. Our results not only map a new MHC-linked diabetogenic gene(s) but also suggest a new way to fine map disease susceptibility genes within a region where strong linkage disequilibrium exists.

Animals↗
PubMed1995

Insulin receptor gene polymorphism and hyperinsulinemia in hypertensive patients.

Although insulin resistance often occurs in association with hypertension, considerable variation is observed in the degree of insulin resistance among hypertensive patients. Since there is evidence of a genetic basis in the development of insulin resistance in hypertension, we analyzed the contribution of genetic factors to insulin resistance in hypertensive patients. Sixty-six Japanese hypertensive patients were studied. These patients were divided into two groups (hyperinsulinemia group and normoinsulinemia group) according to plasma insulin response during a 75-g oral glucose tolerance test (75g-OGTT). Insulin receptor gene (INSR) was studied for association with insulin resistance in hypertensive patients. A microsatellite polymorphism in intron-2 of the insulin receptor gene was analyzed by the polymerase chain reaction method. Five alleles were detected in the INSR microsatellite. The frequency of C/C genotype in the hyperinsulinemia group was significantly higher than that in the normoinsulinemia group (73% vs. 43%, p = 0.02). There was no difference in genotype frequency of INSR between hypertensive patients and control subjects. When the hypertensive patients were divided into two groups, the frequency of C/C genotype in the hyperinsulinemia group was significantly higher than that in the control group (73% vs. 45%, p = 0.014). There was no significant difference between the normoinsulinemia group and control group. These data suggest that the insulin receptor gene may contribute to insulin resistance in hypertensive patients with hyperinsulinemia.

Alleles↗
PubMed1995

Angiotensin I-converting enzyme gene polymorphism is associated with myocardial infarction, but not with retinopathy or nephropathy, in NIDDM.

OBJECTIVE: To clarify the relationship between the angiotensin I-converting enzyme (ACE) gene polymorphism and diabetic micro- and macroangiopathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We examined 267 NIDDM patients with various stages of diabetic retinopathy, 61 patients with myocardial infarction (MI), and 136 patients without MI. An insertion/deletion polymorphism of the ACE gene was typed by polymerase chain reaction. RESULTS: Although no association was found between ACE gene polymorphism and diabetic retinopathy or nephropathy, this polymorphism was associated with MI in the patients with NIDDM. Homozygotes for the deletion polymorphism (DD genotype) were found more frequently in diabetic patients with MI (31.1%) than in diabetic patients without ischemic heart disease (16.9%), with a relative risk of 2.22 (95% confidence interval 1.11-4.46, P = 0.024). CONCLUSION: These data indicate that ACE gene polymorphism is associated with MI, but not with retinopathy or nephropathy, in patients with NIDDM and suggest that the ACE gene confers susceptibility to diabetic macroangiopathy but not to microangiopathy.

Alleles↗
PubMed1994

Absence of association of TAP and LMP genes with type 1 (insulin-dependent) diabetes mellitus.

Although one of the major genes which cause type 1 (insulin-dependent) diabetes mellitus is located in the class II HLA region in humans, its precise location is still unknown. In order to investigate whether TAP (Transporter associated with Antigen Processing) and LMP (Low Molecular Weight Polypeptide) genes, which are located in the class II HLA region, are HLA-linked diabetogenic genes, the association of TAP1, TAP2 and LMP2 genes with type 1 diabetes was analyzed in the Japanese population. No difference in allele frequencies of these genes was detected between diabetic patients and control subjects. On the other hand, DQA1 and DQB1 genes showed significant association with type 1 diabetes. These data suggest that the diabetogenic gene in the class II HLA region may be located near the DQA1 and DQB1 loci, rather than the TAP and LMP loci.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Early-onset type 2 (non-insulin-dependent) diabetes mellitus is associated with glucokinase locus, but not with adenosine deaminase locus, in the Japanese population.

To investigate the possible contribution of glucokinase (GCK) and adenosine deaminase (ADA) loci to the genetic susceptibility to type 2 (non-insulin-dependent) diabetes mellitus, we studied the association of these loci with type 2 diabetes in the Japanese population. Fifty patients with type 2 diabetes and 50 control subjects were analyzed for microsatellite polymorphism 3' to the GCK gene and PstI polymorphism in the ADA gene by polymerase chain reaction. The frequency of the most common GCK allele (Z) was significantly lower in type 2 diabetic patients than that in control subjects and a longer Z + 2 allele was more common in type 2 diabetic patients (26% vs. 15%, P = 0.053), particularly in those with younger age of onset (33% vs. 15%, younger onset type 2 diabetes vs. control, P = 0.014). The frequency of genotypes containing at least one Z + 2 allele was significantly more common in type 2 diabetic patients (46% vs. 28%, P < 0.05), particularly in those with younger age of onset (61% vs. 28%, relative risk 4.00, P < 0.01). In contrast, there was no difference in allelic or genotypic frequencies of PstI polymorphism in the ADA gene between the two groups. Despite the association between the GCK locus and type 2 diabetes, none of the patients had known mutations (Glu265-->AM265, Glu279-->AM279, Gly299-->Arg299, Glu300-->Gln300, Leu309-->Pro309). These results suggest that the GCK locus, but not the ADA locus, contributes to the genetic susceptibility to type 2 diabetes in Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗
PubMed1994

[Extramedullary blastic crisis of chronic myelogenous leukemia--a case with various additional chromosomal appearance].

We describe a characteristic case of chromosomal abnormalities in a 47-year-old man with chronic myelogenous leukemia (CML). He had been diagnosed with the chronic phase of CML on May 1990, but he refused treatment. He was readmitted in October 1991 because of peripheral lymphadenopathy. Hematologic studies showed that he remained in the chronic phase of CML. There were no additional chromosomal findings in the bone marrow, but cervical lymph node biopsy revealed complete replacement with blastoid cells. The blasts were positive for CD13 and CD33. DNA analysis for the breakpoint cluster region gene showed rearrangement pattern, but immunoglobulin heavy chain joining region genes and T-cell antigen receptor gene rearrangement were not observed. The karyotype of lymph node cells showed various additional chromosomal abnormalities. Therefore, we concluded that the patient had an extramedullary blastic crisis in his peripheral lymph nodes. Abnormal clones were composed of one main clone and three subclones, with the latter occupying more than 10% of the volume each other. Considering the types of the additional chromosomal abnormalities, all four types of clones were thought to have evolved through independent pathways.

Blast Crisis↗
PubMed1994

Detection of microplatelet formation using an electroimpedance cell counter.

Changes in the platelet size distribution curves during the process of ADP-induced aggregation were observed using a particle distribution analyzer (PDA) based on electronic impedance. The maximum primary aggregation was seen at a final ADP concentration of 3 microM. After stimulation, the platelet distribution curve changed rapidly from a log normal curve to a curve skewed to the left. When the changes were evaluated at 1 min after the addition of ADP, the peak height was increased, and the median and total volume were decreased significantly. These findings indicate that microplatelets are formed by membrane stimulation and this formation can be monitored with the use of this automated instrument.

Adenosine Diphosphate↗
PubMed1993

[Two cases of bladder cancer in patients with chronic renal failure].

We report here two cases of bladder cancer in patients with chronic renal failure who had been treated with hemodialysis. Case 1: A 58-year-old male on hemodialysis for 3 years visited with a complaint of gross hematuria. Transurethral resection of the bladder tumor (TUR-Bt) was performed and histopathological examination showed grade 1, stage pTa transitional cell carcinoma (TCC). The patient was followed for 4 years postoperatively without recurrence. Case 2: A 64-year-old male with hemodialysis for 1 week was referred to our department with a gross hematuria. TUR-Bt was conducted and histopathological findings showed grade 2, stage pT1b TCC. In April, 1992, he revisited our hospital with bladder tamponade due to massive hematuria, and TUR-Bt was performed. Histopathologically, the tumors were grade 2, stage pT2 TCC. He was followed for 1 year without recurrence.

Carcinoma, Transitional Cell↗
PubMed1993

[Isospora belli infection in a patient with adult T cell leukemia].

A 53-year-old man was hospitalized for the development of watery diarrhea associated with decreased appetite and progressive weight loss and was found to have leukocytosis. The white blood cell count was 14,600/microliters with 66 percent abnormal lymphocytes. Serum anti-HTLV-I was positive and monoclonal insertion of HTLV-I provirus into the atypical cell genome was confirmed with the southern blotting hybridization technique. A diagnosis of ATL was made. Examination of fresh stool specimens revealed Isospora belli (I. belli) oocysts. Initial treatment for I. belli consisted of oral trimethoprim 160mg and sulfamethoxazole 400mg given twice daily for nine days. Diarrhea ceased within 2 days of the start of treatment, but I. belli oocysts were again detected after 20 days. Trimethoprim 160mg and sulfamethoxazole 400mg were reinstituted four times daily for 10 days, and then twice daily for 21 days. The clinical response was again dramatic, with rapid clearance of oocysts from the stool. There has been no recurrence of diarrhea. The patient's leukemia was refractory to chemotherapy; the white blood cell count continued to rise, pneumonia developed, and the patient died. I. belli is a previously unrecognized opportunistic pathogen that must be considered in the clinical setting of chronic diarrhea in patients with ATL.

Animals↗
PubMed1993

[Adult T cell leukemia/lymphoma effectively treated with chronic oral etoposide].

A 52-year-old man, who complained of tarry stool and systemic lymphadenopathy, was admitted to our hospital on July 2, 1992. Biopsy showed diffuse large cell lymphoma. Leukocytosis with atypical lymphocytes was not shown in the peripheral blood, but there was an elevated serum LDH level. The man was found to have both HTLV-I antibody and the monoclonal integration of proviral DNA in malignant lymph node cells obtained at biopsy. The diagnosis was lymphoma-type adult T-cell leukemia (ATLL). The chemotherapy regimens of MI-FP, CHOP and modified DHAP were used for the treatment, but were not effective. So, he was treated with etoposide 75 mg orally for 25 days (chronic oral etoposide therapy) and achieved partial remission. This chemotherapy induced myelosuppression with neutropenia, but there was no documented infection. Chronic oral etoposide therapy is an effective regimen for patients with relapse or refractory lymphoma.

Administration, Oral↗
PubMed1991

[Incidental renal cell carcinoma].

We reviewed the cases of incidental renal cell carcinoma that had been treated at the Kitasato University Hospital between July, 1971 and December, 1989. Forty one of the 170 (24.1%) cases were found without any direct signs of renal cell carcinoma. The patients were between 30 and 78 years old (mean 55.0 years) and consisted of 29 males and 12 females. Fifteen cases were detected at the general health check-up and the remaining 26 during the postoperative follow-up for other malignant tumors or other diseases. Twenty three cases were identified by ultrasonography followed by computed tomography (CT) and excretory pyelography in 4 cases each. Especially, the number of patients incidentally found by ultrasonography had increased in the recent 8 years. Urinalysis did not show any microhematuria in 31 of the 37 cases (83.7%), and no tumor mass could be detected by excretory pyelography in 3 cases. We believe that ultrasonography may be valuable as a screening modality for early detection of renal cell carcinoma and should be used as a screening method at the routine health check-up.

Adult↗