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Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 865 records · Page 48Linked to original sources
PubMed1988

Cysteine protease and its inhibitor in experimentally produced squamous cell carcinomas in hairless mouse skin.

Squamous cell carcinomas (SCC) were experimentally produced in hairless mouse skin, and cysteine protease and its inhibitor were simultaneously purified from extracts of 1 g of tissue of SCC and normal skin. Activity of cysteine proteinases, Mr greater than 50,000 and Mr 28,000, increased in SCC compared to those in normal skin. SCC also showed elevation of cysteine proteinase inhibitor activity and Mr 13,000 and Mr 82,000 inhibitors were purified. Mr 13,000 inhibitor was found to have biochemical properties which were the same as those of the inhibitor present in normal skin. Mr 82,000 inhibitor was not detectable in normal skin and it differed from a serum inhibitor with a similar Mr in terms of activity and stability at acidic pH. The findings suggest that the increased activity of both cysteine proteases and endogenous inhibitors may be involved in the regulatory mechanisms of malignant cell metabolism and tissue remodeling associated with SCC development.

Animals↗
PubMed1988

Secretion in yeast of human lysozymes with different specific activities created by replacing valine-110 with proline by site-directed mutagenesis.

Computer graphics indicate that a steric hindrance exists between valine-110 side chain of human lysozyme (EC 3.2.1.17) and an acetyl group of a modified substrate that contains N6,O-diacetylmuramic acid. To alter the substrate specificity of human lysozyme to be effective on the modified substrate, we replaced the valine-110 residue with various amino acids by site-directed mutagenesis. One of the mutant proteins (valine residue replaced with proline:P110) was secreted in Saccharomyces cerevisiae as at least four components (P110-A, P110-B, P110-C, and P110-D) with different specific activities. Two components, P110-B and P110-D, were isolated in a pure form and structurally characterized. The results suggest that this mutation lowered the lytic activity against Micrococcus lysodeikticus by changing a local conformation of the catalytic site while keeping almost the same substrate binding sites. Our results also indicate that cis/trans isomerization of prolyl peptide bonds probably occurs in vivo and that the conformational change of protein as well as point mutations in genes might influence the molecular evolution of the protein.

Amino Acid Sequence↗
PubMed1988

Limited proteolysis of high molecular weight histidine-rich protein of rat epidermis by epidermal proteinases.

Epidermal proteinases, which may be involved in proteolysis of Mr greater than 300k histidine-rich protein in epidermis, were studied by SDS-PAGE analysis. Mr greater than 300k histidine-rich protein was extracted from granular cells of 2-day-old rats in citric acid-sucrose solution and separated from proteinases and smaller Mr proteins by Sephacryl S-300 column chromatography. The proteinase-free histidine-rich protein was stable in pH 3.5-9 at 37 degrees C for 12 h. Proteinases were partially purified from rat epidermis and inhibitor spectrum determined for each enzyme. Limited hydrolysis of Mr greater than 300k histidine-rich protein yielded a derivative of Mr 56k with cathepsin D at pH 3.5-7.5 and a serine proteinase at pH 7-9. Further proteolysis of Mr 56k protein to Mr 44k and a doublet of Mr 45k and 47k also was detected with cathepsin D at pH 3.5 and 7.5, respectively, while the serine proteinase degraded Mr 56k protein to a number of protein bands. Cathepsins B and L degraded Mr greater than 300k protein but no specific predominant product was identified. We suggest that cathepsin D and the serine proteinase may play a role in in situ processing of histidine-rich protein during cornification.

Animals↗
PubMed1988

Histiocytic necrotizing lymphadenitis.

Eleven cases of histiocytic necrotizing lymphadenitis were studied. Originally four were misdiagnosed as cervical tuberculous lymphadenitis. The characteristic symptoms and signs were local tenderness, fever, leucocytopenia and good prognosis. Antibody to Epstein-Barr virus was elevated in 2 of 3 cases. Biopsy of the affected lymph node was necessary when the differential diagnosis from lymph node tuberculosis or malignant lymphoma could not be made. The characteristic histological feature was focal necrosis without neutrophil infiltration in cortical or subcortical areas. Ultrastructurally, we found characteristic inclusions ('tubulo-reticular structures') in histiocytes and lymphocytes.

Adolescent↗
PubMed1988

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M.

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia.

Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Residual B cell function in patients with long-standing NIDDM and its relation to metabolic control and diabetic complications.

We have evaluated the residual pancreatic B cell function by glucagon load test in 28 patients with non-insulin-dependent diabetes mellitus (NIDDM) of a duration of 20 years or more. The increase in serum C-peptide at 6 minutes after glucagon administration (delta C-peptide) was used as an index of residual B cell function. There was much less delta C-peptide in patients treated with insulin than in those treated with sulfonylurea (p less than 0.05), and it was significantly correlated with the body mass index (r = 0.40, p less than 0.05). Long term metabolic control assessed by the average annual mean fasting blood glucose for the observation period (mean, 21 years) was not correlated with delta C-peptide (r = -0.13). The prevalence of retinopathy which needed photocoagulation therapy and of neuropathy in patients with poor residual B cell function (delta C-peptide less than or equal to 0.3 ng/ml) was the same as that in those with good residual B cell function (delta C-peptide greater than or equal to 1.0 ng/ml). The present study shows that the residual B cell function is not correlated with long term glycemic control and the prevalence of diabetic complications in long-standing NIDDM patients.

Adult↗
PubMed1988

[Improved survival rates in Hodgkin's disease].

Results of treatment of 25 Hodgkin's disease patients at Kyushu University Hospital from 1981 to 1985 were reviewed. Total nodal irradiation or MOPP chemotherapy was used mainly. The actuarial 5-year survival rate, 87.2%, was significantly better than the 41.0% of 61 patients treated between 1966 and 1980 (P less than 0.01). However, 12 of the 24 patients in remission eventually relapsed. To further improve the survival rates of patients with Hodgkin's disease, technical improvements in total nodal irradiation and altering Adriamycin-containing chemotherapy protocol from MOPP chemotherapy are advisable.

Adult↗
PubMed1988

[A case of signet-ring cell type cancer of the colon].

A rare case of a primary signet-ring cell carcinoma of the sigmoid colon in a 66-year-old man is reported. Endoscopically, a sessile polyp, 2 cm in diameter, was found in sigmoid colon, consisting mainly of a well differentiated adenocarcinoma and, partially of a signet-ring cell carcinoma. A residual polyp was found at the same site in the sigmoid colon, sixth months after surgery. The resected polyp was histologically confirmed as being a signet-ring cell carcinoma, which had infiltrated into submucosal space by scirrhous invasion. After a polypectomy, a partial colectomy was performed and no carcinoma cells have been identified in the resected colon. We have speculated that this signet-ring cell polyp could develop into Borrmann type 4 advanced colon cancer.

Adenocarcinoma↗