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Biomedical subjects

K Marumo

Publications and source records attributed to K Marumo.

At least 73 records · Page 4Linked to original sources
PubMed1989

[An attempt at clinical applications of adhesive protein from the marine mussel, Mytilus edulis L].

Polyphenolic or adhesive protein (PPP, Mr = 125,000) from the marine mussel Mytilus edulis consists largely of tandemly repeated decapeptide sequence, ala-lys-pro/hyp-ser-tyr/dopa-hyp-hyp-thr-dopa-lys. Because of our interest in better understanding of the mechanism of under water adhesion by this protein, we have attempted to ascertain the adhesiveness of PPP to a cultured chondrocyte. About 90% of the chondrocyte were rapidly attached to the dish coated by PPP within 60 minutes. A protein with 216 amino acids and molecular weight of 24,000 has 20 repeats of decapeptide sequence (20 mer), which designed as a synthetic analogue of proto-PPP. Nearly 44% of tyrosyl group in the 20 mer were converted to dopa which is thought to play an essential role in the adhesive and cohesive properties of the protein by mushroom tyrosinase. The dopa conversion ratios of tyr-5 (-ser-tyr-pro-) and tyr-9 (-thr-tyr-lys) in the decapeptide sequence of the 20 mer were very similar to those of PPP. These findings may contribute to design a new type of adhesives for living tissues.

Adhesiveness↗
PubMed1988

[Anti-tumor effects of interleukin 2 against genitourinary cancer--basic study and clinical application].

In order to establish an optimum mode for systemic administration of recombinant interleukin 2 (rIL-2), the effects of rIL-2 (Biogen, Switzerland) on lymphocyte-mediated cytotoxicity against established renal carcinoma cell line Caki 1. KU-2 and freshly prepared renal carcinoma cells were studied. Augmentation of cell-mediated cytotoxicity by rIL-2 was dose- and time-dependent. The results indicated that the optimal dose of rIL-2 was 100 to 500 units (Jurkat units)/ml, and that cytotoxicity increased significantly even at a low concentration such as 4 units/ml. We thus chose daily administration of multiple repeated dose for inpatients. To prevent withdrawal from the therapy as a result of un-tolerable adverse effects, the daily dose was set at 1 x 10(6) units, and rIL-2 was given to 17 patients with advanced genitourinary cancer. Two-hour intravenous drip infusions containing 5 x 10(5) units of rIL-2 was given daily two times to inpatients and after at least 28 days of this mode of administration, subcutaneous injection at a dose of 1 x 10(6) units was given 6 days a week to outpatients. In 12 patients with renal cell carcinoma, 2 patients showed complete response; 1 patient partial response; 7 patients no change, and 2 patients progressive disease. In patients with carcinoma of the prostate or bladder carcinoma, all patients were no change from criteria of Japan Society for Cancer Therapy, however, marked decrease in serum acid-phosphatase and improvement of performance status in 1 patient with carcinoma of the prostate, and massive necrosis of tumor accompanied by disappearance of severe leg edema in a patient with bladder carcinoma were observed.

Adult↗
PubMed1987

Prolyl 4-hydroxylase in the foot of the marine mussel Mytilus edulis L.: purification and characterization.

The mussel foot secretes a variety of unusual hydroxyproline-containing collagenous and noncollagenous proteins. Prolyl 4-hydroxylase acting on one or more of the secreted proteins was isolated from the foot by using conventional gel filtration and ion exchange chromatography. Mr of the intact enzyme was 230,000 (alpha 2 beta 2) composed of two subunits with Mr of 60,000 (alpha) and 57,000 (beta) as estimated by HPLC gel filtration and SDS-PAGE. The enzyme utilized (Pro-Pro-Gly)10 as a substrate with an apparent Km value of 0.17 mM. Cofactors and inhibitors were very similar to animal, plant, and microbial prolyl hydroxylases previously described. The enzyme had a relatively sharp pH optimum in the range of 7.8-8.3 and the hydroxyproline formed increased in proportion to the rise in the temperature between 5 and 20 degrees C. No detectable hydroxylation occurred with poly-L-proline or the unhydroxylated decapeptide analog (Ala-Lys-Pro-Ser-Tyr-Pro-Pro-Thr-Tyr-Lys) of the polyphenolic protein. Kinetic studies, however, revealed that the mussel prolyl 4-hydroxylase was competitively inhibited by poly-L-proline and uncompetitively inhibited by the decapeptide. These results suggest that the decapeptide binds the enzyme-substrate i.e. (Pro-Pro-Gly)10 complex. It is not yet clear whether this enzyme acts exclusively on collagenous substrates or whether its catalytic purview extends as well to the polyphenolic protein.

Animals↗
PubMed1987

Augmentation of cell-mediated cytotoxicity against renal carcinoma cells by recombinant interleukin 2.

The effects of recombinant interleukin 2 (IL-2) on natural killer (NK) cell activity against established renal carcinoma cell lines CaKi 1, KU-2, and freshly prepared renal carcinoma cells were studied. Augmentation of NK cell activity by IL-2 was dose- and time-dependent. The results indicate that the optimal dose of IL-2 was 100 to 500 U/mL, and that cytotoxicity increased significantly even at a low concentration such as 4 U/mL. IL-2 induced significantly higher levels of cytotoxicity against renal carcinoma cells than did gamma-interferon. The influence of IL-2 on lymphocyte subpopulations was then examined using flow cytometry with monoclonal antibodies OKT3, OKT4, OKT8, Leu 7, and Leu 11. The results showed that IL-2 increased the number of cells positive to Leu 11, the so-called active NK cells. We concluded that IL-2 has an important role in the treatment of renal carcinoma.

Carcinoma, Renal Cell↗
PubMed1987

[Comparative study of the activating effects of recombinant human interleukin 2 and interferon-gamma on cell-mediated cytotoxicity against renal cell carcinoma in vitro].

The effects of recombinant interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) on lymphocyte-mediated cytotoxicity against established human renal carcinoma cell lines KU-2 and Caki 1, and freshly prepared human renal carcinoma cells were compared in vitro. After incubation of peripheral blood lymphocytes from normal adult volunteers with IL-2 and IFN-gamma over a range of concentrations, cytotoxicity was determined by 4-h 51Cr-release assay. Augmentation of cytotoxicity by IL-2 and IFN-gamma was dose-and time-dependent. IL-2 induced significantly greater cytotoxicity against renal carcinoma cells than did IFN-gamma. The optimal dose of IL-2 was 100 to 500 units/ml, and cytotoxicity was increased even at concentrations as low as 4 units/ml. The results indicated that the systemic administration of IL-2 to patients will be effective for treatment of renal cell carcinoma which is resistant to interferon therapy. A continuous infusion or multiple repeated bolus doses over a period of one day, however, should be considered in order to maintain high levels of IL-2 in the serum.

Adult↗
PubMed1986

Optimization of hydroxylation of tyrosine and tyrosine-containing peptides by mushroom tyrosinase.

Free tyrosine and tyrosine residues in various peptides and proteins are converted into dopa and dopa residues by tyrosinase (monophenol,L-dopa:oxygen oxidoreductase, EC 1.14.18.1) in the presence of reductants. The efficiency of the tyrosine-to-dopa conversion was examined under varied conditions, such as the substrate-to-tyrosine ratio, concentrations of reductant and oxygen in the reaction solution, pH, temperature and reaction time. The highest dopa yields were achieved with the following optimal conditions for hydroxylation: 0.1 M phosphate buffer at pH 7, 25 mM ascorbic acid, 1 mM tyrosine, 50 micrograms/ml tyrosinase and 20 degrees C. Using these conditions, up to 70% of free tyrosine was converted into dopa, and tyrosine residues in several synthetic peptides were also hydroxylated to dopa residues at ratios as high as free tyrosine. The preparation of hydroxylated analogues of the decapeptide (Ala-Lys-Pro-Ser-Tyr-Pro-Pro-Thr-Tyr-Lys), in particular, may contribute to a better understanding of adhesion in the dopa-containing mussel glue protein.

Ascorbic Acid↗
PubMed1986

C-peptide immunoreactivity and insulin content in the diabetic human pancreas and the relation to the stability of diabetic serum glucose level.

The content of insulin and C-peptide-like immunoreactivity (CPR) were determined in the tail of pancreas from 35 autopsied diabetic and 21 non-diabetic subjects. In the 28 diabetics who had been followed for more than 6 months, the relation between the amount of insulin or CPR in the pancreas and the stability of fasting serum glucose during diabetic life before death was analyzed together with the relation between the serum CPR response to the breakfast tolerance test before death and insulin content at autopsy. As an index of the instability of the blood sugar level, the standard deviation of the mean of 15 successive determinations of fasting serum glucose was used. Both insulin and CPR content in the pancreas were significantly decreased in diabetics as compared with non-diabetics. SD of the mean fasting serum glucose and insulin or CPR content in the tail of pancreas showed a significant inverse correlation on a logarithmic scale (P less than 0.01, r = -0.704 and P less than 0.01, gamma = -0.757, respectively). Serum CPR value during the breakfast tolerance test correlated significantly with the insulin content in the pancreas of diabetic subjects. These findings suggest that one of the causes of the instability of fasting serum glucose levels is the devastation of pancreatic beta-cells and that the pancreatic insulin content is logarithmically and inversely related to fluctuations in fasting serum glucose.

Aged↗
PubMed1986

[Sequential combination therapy with alpha interferon and OK-432 (streptococcal preparation) against advanced renal cell carcinoma].

Renal cell carcinoma (RCC) is one of the most insensitive urologic tumors to either radiotherapy or anticancer chemotherapy. Recently, effectiveness of interferon (IFN) against RCC has been reported. However, because this effect is somewhat limited, a new modality of treatment is needed. We herein report our experience with IFN and OK-432, a streptococcal preparation for patients with advanced RCC. Twenty patients aged from 26 years to 75 years, with an average age of 52.3 years, were entered into this study. Intramuscular injection of human lymphoblastoid interferon (HLBI) at a dose of 3 X 10(6) units was given daily for between 4 and 76 weeks. Treatment with OK-432 then followed HLBI, unless the patient achieved CR or the status of the patient seriously deteriorated during the initial treatment with HLBI. OK-432 was given to 12 patients at a dose of 5KE (Klinische Einheit) 2 days a week for between 10 and 64 weeks. Effectiveness of HLBI therapy was 20% (CR 1 case, MR 3 cases, NC 11 cases, PD 5 cases). With adjuvant OK-432 therapy for patients whose disease proved to be resistant to HLBI, effectiveness was 25% (CR 1 case, MR 2 cases, NC 6 cases, PD 3 cases). The results obtained indicated that OK-432 following IFN is a potentially active antitumor regimen in patients with advanced RCC.

Adult↗
PubMed1985

Insulin, glucagon and somatostatin content of the non-obese diabetic (NOD) mouse pancreas and plasma virus antibodies to Coxsackie B- and reoviruses.

The amounts of insulin, glucagon and somatostatin in the pancreas of NOD mice were determined and the results were compared with those of normal ICR-strain mice, and plasma antibodies to Coxsackie B-3 and reovirus types 1, 2 and 3 were measured. In the pancreas of NOD mice with fasting plasma glucose (FPG) less than 140 mg/100 ml, the insulin content of the male mice was similar to that of the normal controls, ranging to 3.55 +/- 0.31 U/g wet weight of pancreas, but it was already significantly decreased to 0.85 +/- 0.52 U/g in the female mice. In the NOD mice with FPG more than 201 mg/100 ml, it was 0.002 +/- 0.001 U/g. The glucagon content of the pancreas was 7.76 +/- 0.89 micrograms/g in the normal controls and it was decreased slightly in the NOD mice, but the values among the NOD mice were not significantly different. Pancreas somatostatin showed a tendency to be higher in the NOD mice with FPG more than 201 mg/100 ml. Histologically cell infiltration into the pancreatic islets was conspicuous in the hyperglycemic NOD mice, but it was found even in the normoglycemic NOD. Plasma antibodies to Coxsackie B-3 Virus and reovirus types 1, 2 and 3 were not detected at any stage of FPG.

Animals↗