Biomedical subjects

K Dohi

Publications and source records attributed to K Dohi.

At least 271 records · Page 15Linked to original sources

PubMed1996

Postoperative adjuvant randomised trial comparing chemoendocrine therapy, chemotherapy and immunotherapy for patients with stage II breast cancer: 5-year results from the Nishinihon Cooperative Study Group of Adjuvant Chemoendocrine Therapy for Breast Cancer (ACETBC) of Japan.

Between 1985 and 1988, the effect of using ftorafur (FT) or PSK (an immunotherapy agent) in combination with the conventional postoperative adjuvant therapy using mitomycin (MMC) plus tamoxifen (TAM) was assessed in stage II, oestrogen receptor-positive (ER+) breast cancer patients. Furthermore, in ER- breast cancer stage II patients, the effects of postoperative adjuvant therapy using MMC plus FT were compared with the effects of postoperative adjuvant therapy using MMC plus PSK. Patients had primary stage II breast cancer and had undergone total mastectomy plus axillary dissection or more radical surgery. On the day of surgery, MMC (13 mg/m2) was administered intravenously. Then, ER+ patients received one of three regimens of drug therapy, starting 2 weeks after surgery: regimen A (daily oral treatment with 30 mg of TAM), regimen B (daily oral treatment with 30 mg of TAM and 600 mg of FT) or regimen C (daily oral treatment with 30 mg of TAM and 3 g of PSK) [corrected]. ER- patients received either regimen D (daily oral treatment with 600 mg of FT) or regimen E (daily oral treatment with 3 g of PSK), starting 2 weeks after surgery. Of the 540 ER+ patients registered, 525 were evaluated. The 5-year overall survival rate for ER+ patients was higher for patients who received regimen B (94.2%) than for those who received regimen A (86.9%) or regimen C (89.9%) (P = 0.063). The 5-year relapse-free survival rate was higher for regimen B (88.9%) than for regimen A (78.6%) and regimen C (77.2%) (P = 0.010). Stratified analysis revealed better results with the FT-combined therapy in patients positive for lymph node metastasis and premenopausal patients. These results indicate the effectiveness of using FT in combination with TAM. Of the 376 ER- patients registered, 364 were evaluated. The 5-year overall and relapse-free survival rate for ER- patients did not differ significantly between patients who received regimen D and those who received regimen E.

Adult↗

PubMed1996

Isolation and characterization of a TATA-less promoter for the human RAG-1 gene.

Human recombination activating gene-1 (RAG-1) genomic DNA clones containing the first exon coding for the 5' untranslated region and the second exon coding for the remaining 5' untranslated region, coding region, and 3' untranslated region were cloned. Primer extension analysis and RNase protection analysis demonstrated the multiple RAG-1 transcription start sites, clustered in a 31 nucleotide (nt) region. Sequence analysis showed that the RAG-1 promoter lacked a TATA box as well as an initiator sequence. Transient expression assays using a luciferase reporter gene with truncated promoter fragments and substitution mutants, showed that the 5' promoter region containing the CCAAT box between -110 and -86, is indispensable for its basal promoter activity in RAG-1 expressing Nalm 6 cell line. Comparative transient expression assays in various cell lines revealed that the 854 nt upstream promoter region was active, not only in RAG-1 expressing cell lines but also in RAG-1 non-expressing cell lines. These data indicate that the 854 nt upstream region of RAG-1 gene confer basal promoter activity, and that the tissue- and stage-specific expression of RAG-1 is controlled by elements present outside of the promoter region and/or differential chromatin structure(s) of the individual cells.

Base Sequence↗

PubMed1996

Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis.

Monocytes/macrophages (M phi) have been implicated in the pathogenesis of lupus nephritis (LN), but the precise molecular mechanism of recruitment and activation of M phi in LN remains unclear. To clarify the involvement of chemotactic cytokines (chemokines) in those events, we measured levels of monocyte chemotactic and activating factor (MCAF, also termed monocyte chemoattractant protein-1, MCP-1) in urines and sera derived from 42 patients with LN. Both urinary and serum MCAF levels were significantly higher in patients with LN as compared with 22 healthy volunteers (10.3 +/- 3.2 vs. 1.0 +/- 0.1 pg/ml . creatinine, 212.2 +/- 75.8 vs. 66.1 +/- 15.5 pg/ml, respectively, P < 0.05, mean +/- SEM). Histological examination of renal lesions from 41 patients classified 19 as active according to the WHO-defined classes IIIb, IVb and IVc, and 22 as inactive by the WHO-defined classes I, II, IIIc, IVd and V. Urinary MCAF levels in the patients with active lesions were significantly higher than those with inactive lesions (20.3 +/- 6.4 vs. 1.7 +/- 0.3 pg/ml . creatinine, P < 0.01). Moreover, elevated urinary MCAF levels were dramatically decreased during steroid therapy-induced convalescence in 29 patients examined serially (13.9 +/- 4.5 vs. 5.3 +/- 1.7 pg/ml . creatinine, P < 0.001), whereas serum MCAF levels did not change significantly. Endothelial cells, renal epithelial cells and infiltrating mononuclear cells in the tubulointerstitial regions were MCAF-positive in immunohistochemical as well as in situ hybridization analysis. These observations suggest that MCAF is probably involved in the pathogenesis of LN with active lesions, possibly through the recruitment and activation of M phi, and that measurement of urinary MCAF levels may be a useful clinical tool for monitoring the disease activity of LN.

Adolescent↗

PubMed1996

Quantification of glomerular TGF-beta 1 mRNA in patients with diabetes mellitus.

Transforming growth factor-beta 1 (TGF-beta 1) is a primary determinant of the mesangial expansion observed in diabetic nephropathy. In this study, we quantitated the levels of intraglomerular TGF-beta 1 mRNA in patients with diabetes mellitus using a competitive polymerase chain reaction (PCR) method. Renal biopsy specimens were obtained from 29 patients with non-insulin-dependent diabetes mellitus. Total RNA was extracted from the glomeruli and reverse transcribed into cDNA with reverse transcriptase. To prepare samples containing identical amounts of beta-actin cDNA (8 pg), we performed competitive PCR by co-amplifying mutant templates of beta-actin with a unique EcoRI site. We also used this competitive PCR method to measure TGF-beta 1 cDNA by co-amplifying mutant templates of TGF-beta 1. We observed higher expression of TGF-beta 1 mRNA in glomeruli of patients with diabetic nephropathy as compared with normal glomeruli. Intraglomerular TGF-beta 1 mRNA was elevated, even in the early stage of diabetic nephropathy. Moreover, levels of intraglomerular TGF-beta 1 mRNA correlated with values of HbA1c. These data suggest that hyperglycemia induces intraglomerular TGF-beta 1 mRNA expression in vivo, and that TGF-beta 1 overproduction may be associated with the progression of diabetic nephropathy.

Aged↗

PubMed1996

IL-6 mRNA synthesis by peripheral blood mononuclear cells (PBMC) in patients with chronic renal failure.

We measured levels of IL-6 mRNA in PBMC obtained from patients with chronic renal failure, using polymerase chain reaction (PCR). PBMC were isolated from 45 patients on haemodialysis (HD) at the start of HD. PBMC were also isolated from 35 patients on HD at the end of HD, 23 patients on continuous ambulatory peritoneal dialysis (CAPD), 24 undialysed patients with chronic renal failure (CRF), and 19 healthy controls. Total RNA was extracted from PBMC with RNA zol and reverse transcribed into cDNA. To prepare samples containing identical amounts of beta-actin cDNA, we performed competitive PCR by co-amplifying serial dilutions of mutant templates containing a single point mutation which generated a unique Eco RI site. Next, to measure IL-6 cDNA semiquantitatively in the samples containing identical amounts of beta-actin (100 pg), we performed PCR amplification using 2 fg of the IL-6 mutant template containing a unique Eco RI site. Higher levels of IL-6 mRNA in the PBMC were observed in the HD patients than in the CAPD patients and healthy controls. The levels of IL-6 mRNA in the PBMC at the end of HD were not significantly higher than those at the start of HD. These results suggest that the dialysis session itself did not significantly affect IL-6 mRNA levels in the PBMC, but that chronic stimulation by maintenance HD may be associated with higher levels of IL-6 mRNA observed in HD patients.

Adult↗

PubMed1996

Assessment of microchimerism in rat liver transplantation by polymerase chain reaction.

Mixed chimerism has been demonstrated in organ transplant recipients surviving over a long period. However, little is known about the fate and movements of donor cells following liver transplantation. In this study, using rat male-to-female liver transplantation, we assessed microchimerism by semiquantitative polymerase chain reaction (PCR). A PCR specific for the Y-chromosome (sex-determining region Y [Sry]) allowed the distinction of small amounts of male cells in a large excess of female cells. Nonimmunosuppressed Lewis recipients of Lewis liver grafts survived >60 days, and donor cells were detected in peripheral blood up to day 60 in four of six recipients. All immunosuppressed Lewis recipients survived for 60 days, and the donor cells were detected up to day 60. Semiquantitative PCR demonstrated that in immunosuppressed Lewis recipients surviving >60 days with no acute rejection episode, the donor-to-recipient cell ratio remained >1:1,000. In nonimmunosuppressed Lewis recipients of ACI liver allografts, donor cells in peripheral blood decreased rapidly by day 7. In immunosuppressed Lewis recipients of ACI liver allografts, donor cells were detected for longer periods, in proportion to the amount and duration of FK506 (Fujisawa Pharmaceutical Co., Osaka, Japan) administered. However, in recipients with deteriorating function due to ongoing rejection, small amounts (0.01 percent) of donor cells were detected. Our results indicate that the Sry-specific PCR is useful for assessing microchimerism following rat liver transplantation, and demonstrate correlation between microchimerism and graft outcome; high-level microchimerism (>O.l percent) correlated well with graft acceptance, whereas low-level microchimerism (<O.01 percent) did not.

Animals↗

PubMed1996

Hepatoblastoma in an adult associated with c-met proto-oncogene imbalance.

A rare case of hepatoblastoma in a 61-year-old Japanese housewife is described. This liver tumor mainly consisted of two tissue components: embryonal hepatocytes and primitive mesenchymal tissue. Fetal hepatocytes with alpha-fetoprotein production, gland formation, cartilage and osteoid were also found in a small portion. Molecular analysis by slot blot method revealed increased copy numbers of c-met and K-sam proto-oncogenes and cyclin D1 genes. These findings suggest that alterations of these oncogenes might play a role in the development of adult hepatoblastoma.

Cyclin D1↗

PubMed1996

Diet-induced hypercholesterolemia increases endothelin-1 release by aortic endothelial cells.

Our previous studies demonstrated the morphological heterogeneity of endothelial cells (ECs) and the emergence of large multinucleated ECs in human and animal atherosclerotic lesions. To investigate the functional alteration of ECs in diet-induced atherosclerosis, immunoreactive endothelin-1 (irET-1) release by ECs of the rabbit aorta was correlated with scanning electron microscopy. Rabbits were fed a cholesterol diet for 12 weeks: by scanning electron microscopy, the area of ECs in the aorta increased in the hypercholesterolemic (HC) group as atherosclerosis progressed. Cultured ECs of the HC group released significantly more irET-1 than ECs of the control. The plasma irET-1 level was also elevated in the HC group. The results obtained suggest that accelerated secretion of ET-1 by ECs contributes to the development of atherosclerotic vascular lesions.

Animals↗

PubMed1996

[An autopsy case of systemic lupus erythematosus complicating leukocytosis, amegakaryocytic thrombocytopenia, interstitial pneumonitis, and pleulitis].

A 52-year-old female was admitted to our hospital in August 1988, for evaluation of purpura and gingival bleeding. Hematologic examination showed mild leukocytosis (12,400/microliter) and severe thrombocytopenia (1,000/microliter). On bone marrow examination, megakaryocyte count was normal and the number of myeloblasts was increased (7.2%). Serological examination was positive for anti-nuclear antibody and anti-DNA antibody. She was diagnosed as having idiopathic or autoimmune thrombocytopenia, and received thrombocyte transfusion and gamma-globulin administration. Hematologic values improved temporarily, but leukocytosis and thrombocytopenia recurred. On the 22nd hospital day, leukocytes increased to 49,300/microliter and thrombocytes decreased to 10,000/microliter. Bone marrow myeloblasts were also increased to 18.8%, and she was suspected of having myelodysplastic syndrome. Then, hematologic values improved simultaneously, and she was discharged in November 1988. After the discharge, leukocyte count ranged from 6,000 to 16,500/microliter, but the number of bone marrow myeloblasts was normal. However, transient thrombocytopenia appeared in association with decrease or absence of bone marrow megakaryocytes and rise of platelet associated-IgG, (PA-IgG) to 99.6 ng/10(7) cells. From September to December 1989, she complained of fever, morning stiffness, multiple arthralgia, and oral ulcer. On serological findings, she was positive for LE cell. Therefore, she was diagnosed as having systemic lupus erythematosus (SLE). In January 1990, she had a high grade fever and dyspnea. Bilateral pleuritis and interstitial pneumonitis were shown on the chest roentgenogram. She received gamma-globulin administration, methylprednisolone pulse therapy, and mechanical ventilation. However, hypoxia developed rapidly, and she died of respiratory failure. Autopsy revealed severe interstitial pneumonitis, fibrinous pleuritis, fibrinous pericarditis, and vasculitis in the arcuate artery of the kidney. This is the first report of SLE complicating thrombocytopenia associated with decrease of megakaryocytes and rise of the PA-IgG, and severe leukocytosis associated with increased bone marrow myeloblasts.

Fatal Outcome↗

PubMed1996

[Clinicopathological study of diabetic nephropathy in the elderly].

We studied the relationship between clinical characteristics and renal structural changes in 29 elderly patients in whom non-insulin-dependent diabetes mellitus was diagnosed when they were 60 years of age or older. The clinical stage of nephropathy was graded according to the criteria of the Ministry of Health and Welfare of Japan: stage 1 (12 patients), normoalbuminuria; stage 2 (11 patients), microalbuminuria; stage 3 (1 patient), persistent proteinuria; stage 4 (5 patients), chronic renal failure. Renal biopsy specimens were semiquantitatively evaluated with regard to diffuse glomerular lesions, nodular lesions, and vascular lesions. In patients at stage 1, minimal-to-moderate diffuse lesions were observed, and vascular lesions were already present. In patients at stage 2, various alterations in diffuse lesions were observed and were associated with prominent changes in the vascular lesions. More advanced changes in the diffuse and vascular lesions were noted in patients at stages 3 and 4, but nodular lesions were found in only one patient. These patients had a high incidence of hypertension and ischemic heart disease. We conclude that elderly diabetic patients with nephropathy of different clinical stages have different underlying diabetic renal lesions.

Aged↗

PubMed1996

HLA-A and -B genotyping in living related one haploidentical kidney.

Sixty-five haplo-identical living-related renal transplant pairs were subjected to comparative studies for HLA class-I typing suitability between the DNA and serological methods. Our HLA-A genotyping method was highly resolutive and allowed assigning 33 serologically blank specificities and subdividing some HLA-A serological specificities, of which A2 discrimination was considered to be indispensable for the matching analysis because of its high frequency among Japanese. Our HLA-B genotyping method made it possible to identify the 17 serologically blank specificities despite their "low resolutive" capacities. Analysis of 14 DRB1-compatible pairs suggested that HLA-A and -B compatibilities had beneficial effects on the long term graft survival. It was concluded that HLA-A and -B should be genotyped for the matching analysis of the kidney transplant pairs to obtain satisfactory graft outcome.

Alleles↗

PubMed1996