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Biomedical subjects

K Marumo

Publications and source records attributed to K Marumo.

At least 55 records · Page 3Linked to original sources

Antitumor effects of interleukin 2 against renal cell carcinoma: basic study and clinical application.

In order to determine an optimum mode for systemic administration of recombinant interleukin 2 (rIL2), the effects of rIL2 on lymphocyte-mediated cytotoxicity against renal carcinoma cells were studied in vitro. Augmentation of the cytotoxicity by rIL2 was dose- and time-dependent. The optimum dose of rIL2 was 100-500 units (Jurkat units)/ml, and 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 untolerable adverse effects, the daily dose was set at 1 X 10(6) units, and rIL2 was given to 12 patients with metastatic renal cell carcinoma. Two-hour intravenous drip infusions containing 5 X 10(5) units of rIL2 was given daily 2 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. Three patients showed complete response, 7 patients no change, and 2 patients progressive disease. Serious adverse effects due to capillary leak syndrome were not observed. We conclude that low-dose rIL2 is safe and has potential antitumor effects.

Aged↗

[Effects of recombinant interleukin 1 beta on peripheral blood cells and induction of lymphokine-activated killer activity in patients with urological malignancies].

Subcutaneous injection of human recombinant interleukin 1 (IL-1) beta was given to 9 patients with urological malignancies (5 renal cell carcinoma, 2 bladder carcinoma, 1 renal pelvic tumor, and 1 testicular tumor), at an initial dose of 1 x 10(4) units on days 1 and 2, and there after weekly for 4 weeks. The dose was increased by 1 x 10(4) units weekly up to final dose of 4 x 10(4) units. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in week 2 and week 4, and lymphokine-activated killer (LAK) activity against Daudi cells was measured using 4 hr 51Cr-release assay, after incubation with human recombinant interleukin 2 (IL-2) of 50 units/ml for 72 hours. Proliferation of lymphocytes was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 hours. IL-1 beta increased the number of peripheral blood granulocytes and lymphocytes, but did not increase the numbers of monocytes and platelets. IL-1 beta significantly augmented IL-2-induced LAK activity in vitro, but this augmentation was neither accompanied by the increase of IL-2 receptor-positive cell ratio in peripheral blood lymphocytes nor enhancement of IL-2-induced proliferation of lymphocytes. Administration of IL-1 beta increased LAK activity of the patients, despite the fact that IL-1 beta did not increase LAK activity in vitro. The result suggests that IL-1 beta-stimulated LAK activity may be mediated by the induction of some cytokines in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Immunotherapy and urological malignancy].

Immunotherapy gained popularity as a treatment modality for malignant diseases in the 1960s. A number of trials, using tumor vaccines, immunopotentiators, interferons, cytokines and others, demonstrated antitumor effects in several urological malignancies, and, to date, immunotherapy plays a major role in treatment of advanced renal cell carcinoma and superficial bladder carcinoma. Interferon or interleukin-2, which became available for large scale clinical trial with the development of bioengineering, however, were shown to be not effective as initially expected, by single agent. Rational design of new strategies with multiple agents in combination based on basic and clinical research, should provide progress in treatment of urological malignancies.

BCG Vaccine↗

[A clinical evaluation of AMS Hydroflex in the treatment of impotence].

The AMS Hydroflex penile prosthesis was implanted in 34 organic impotence patients between June 20, 1986 and Aug. 6, 1990. Patients ages ranged between 26 and 71 with an average of 50.5. The causes of impotences were; 17 cases of post-radical pelvic surgery, 7 cases of injury, 6 cases of diabetes and 4 of others. First evaluation was made after 12 weeks of implantation in terms of patient satisfaction with sexual intercourse and post operative complication. Sixteen patients (47.1%) were highly satisfied with intercourse, 13 (38.2%) satisfied with intercourse, 2 (5.9%) slightly dissatisfied even with successful intercourse, 1 (2.9%) with no improvement and 2 (5.9%) could not follow. Utility of the prosthesis, e.g. effectiveness and safety was; high utility in 20 (58.8%), good utility in 11 (32.4%), slight utility in 1 (2.9%), no favorable in 1 (2.9%) and no judgement in 1 (2.9%). The overall effectiveness and safety of the Hydroflex was demonstrated based on the above findings. Long term evaluation was made from the initial implantation of the device up to the termination of the trial with average of 19.2 months and was mentioned altogether.

Adult↗

Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients.

The frequency of spontaneous 6-thioguanine (TG)-resistant peripheral blood lymphocytes in five unrelated Werner syndrome (WS) patients was determined using an autoradiographic labeling assay. The average frequency of TG-resistant lymphocytes was eightfold higher in WS patients than in sex- and age-matched normal control donors. This finding and previous identification of increased spontaneous chromosomal rearrangements and deletions in WS cells or cell lines suggest that WS is a human genomic instability or mutator syndrome.

Adult↗

Discriminant analysis of cellular fatty acids of Candida species, Torulopsis glabrata, and Cryptococcus neoformans determined by gas-liquid chromatography.

We used discriminant analysis of cellular fatty acid compositions determined by gas-liquid chromatography to differentiate yeastlike fungi (a total of 190 strains; including 37 Candida albicans strains, 21 Candida krusei strains, 13 Candida guilliermondii strains, 37 Candida tropicalis strains, 10 Candida pseudotropicalis strains, 24 Candida parapsilosis strains, 32 Torulopsis glabrata strains, and 16 Cryptococcus neoformans strains). Previous results with a standard strain of C. albicans indicated that reproducible fatty acid chromatograms can be obtained with cells grown in a medium of 2% Sabouraud glucose agar at 35 degrees C for between 48 and 72 h. These conditions were also maintained in cultures of the other organisms that we studied. The cellular fatty acid compositions of the organisms were determined quantitatively by gas-liquid chromatography and analyzed by discriminant analysis. The total correct identification expressed as relative peak percent was 95.8% (89.2% for C. albicans to 100% for C. krusei, C. guilliermondii, C. pseudotropicalis, T. glabrata, and C. neoformans). The total correct identification expressed as the common peak (palmitic acid) ratio was 94.7% (87.5% for C. parapsilosis to 100% for C. pseudotropicalis, T. glabrata, and C. neoformans). Both results suggest that cellular fatty acid compositions can be differentiated by this method.

Candida↗

Immunologic effects of recombinant interferon-gamma in patients with renal cell carcinoma.

Immunologic and antitumor effects of human recombinant interferon-gamma were studied in patients with renal cell carcinoma. A daily dose of 6 to 12 x 10(6) units/m2 of interferon-gamma was given by intravenous drip infusion or intramuscular injection to nine patients over a period varying from two to 16 weeks. Antibody-dependent cell-mediated cytotoxicity and OKIa1-positive monocytes count increased significantly after the therapy was started. Interferon-gamma transiently increased OKT3- and OKT4- positive lymphocyte count. Tumor regression was not observed when clinical response was evaluated in seven patients. Two others, who had no measurable metastases, were not evaluated, because interferon-gamma were given to them as post-operative adjuvant therapy. Our results indicate that interferon-gamma stimulated monocytes and enhanced cell-mediated cytotoxicity; they also suggest the necessity of combining monoclonal antibodies and other biological response modifiers that effect tumor-associated antigens.

Adult↗

[O-serotypes, biochemical properties and antimicrobial susceptibilities of Serratia marcescens isolated from clinical specimens (2nd report)].

O-serotypes, biochemical properties and drug resistances of Serratia marcescens (129 strains) isolated from clinical specimens in Showa University Fujigaoka Hospital from April 1985 to March 1987, were compared with those of the previous results (Jpn J Clin Pathol 35:555-560, 1987). The isolation frequencies of serotype O 3 and O 23 strains were 35.7% and 8.5%, respectively. These strains with serotype O 3 or O 23 were wide-spread in the hospital. The urea-positive strains which occupied 61.2% of all isolates tended to increase more than those of the previous report. The isolation frequency of gelatin-positive and melibiose-negative strains was 85.5%. The resistance rate of all isolates to latamoxef and aminoglycosides significantly increased, comparing with the previous report (p less than 0.01, chi 2-test). The susceptibility of serotype O 3 strains to gentamicin and minocycline significantly increased (p less than 0.005). All of serotype O 23 strains were urea-negative. The resistance rate to kanamycin, tobramycin, gentamicin and nalidixic acid was higher than that of the other serotype strains. Furthermore, the resistance rate to ofloxacin showed the lowest (8.6%) among pyridonecarboxylic acids.

Aminoglycosides↗

Mussel glue protein has an open conformation.

Both native glue protein from marine mussels and a synthetic nonhydroxylated analog were analyzed by far-uv CD under a variety of conditions. Analysis of the CD spectra using various models strongly suggest a primarily random coil structure for both forms of the protein, a fact also supported by the absence of spectral change for the glue protein upon dilution into 6 M guanidine hydrochloride. The nonhydroxylated analog, which consists of 20 repeats of the peptide sequence Ala-Lys-Pro-Ser-Tyr-Pro-Pro-Thr-Tyr-Lys, was further characterized by enzyme modification using mushroom tyrosinase. Enzymatic hydroxylation of tyrosines was found to be best fit by a model containing two rate constants, 5.6 (+/- 0.6) X 10(-3) and 7.2 (+/- 0.3) X 10(-2) min-1. At equilibrium, HPLC analysis of digests showed nearly 100% conversion of Tyr-9 and only 15 to 35% conversion of Tyr-5. The Chou and Fasman rules for predicting structure were applied to the repeat sequence listed above. The rules predict the absence of alpha helix and beta pleated sheets in the structure of this peptide. On the other hand, beta turns are predicted to be present with Tyr-5 being in the region of highest probability. These data suggest that the protein in solution has only a small amount of secondary structure.

Amino Acid Sequence↗

Immunologic study of human recombinant interleukin-2 (low-dose) in patients with advanced renal cell carcinoma.

Immunologic and antitumor effects of human recombinant interleukin-2 was studied in patients with advanced renal cell carcinoma. Intravenous drip infusion for inpatients or subsequent subcutaneous injection for outpatients at a daily dose of 1 x 10(6) units of interleukin-2 was given over a period varying from twenty-one to two hundred forty days to 13 patients. Natural killer cell activity increased 20 percent or more in 11 of the 13 patients, and lymphokine-activated killer cell activity increased 40 percent or more in 9 of the patients tested. Interleukin-2-receptor positive cells and HLA-DR positive cells in peripheral blood lymphocytes increased in 12 and 11 patients, respectively. Two patients achieved complete response; 1 had a partial response; 6 had no change; and 2 had progressive disease. Two patients were not evaluated because the therapy had been discontinued in less than four weeks. We conclude that low-dose interleukin-2 enhances patients' immunity and has a potential antitumor activity against renal cell carcinoma.

Adult↗

Degradation of 125I-glucagon, -pancreatic polypeptide and -insulin by acid saline extract of rat submaxillary gland and their protection by proteinase inhibitors.

The acid saline extract (ASE) of rat submaxillary gland exerts a powerful degrading effect on 125I-glucagon. In order to study the degradation of other 125I-peptides by ASE and the effects of their inhibitors, 125I-pancreatic polypeptide (PP) and 125I-insulin were used together with 125I-glucagon. The degradation studies were done by the trichloroacetic acid (TCA) method or gel filtration. Besides 125I-glucagon, 125I-PP was found to be destroyed by ASE in the ordinary immunoassay system using the TCA method, but 125I-insulin was intact in the presence of ASE. Leupeptin, and to a lesser extent p-chloromercuriphenyl-sulfonic acid (PCMS) and N-ethylmaleimide, inhibited the destruction of 125I-glucagon or -PP under the TCA method. PCMS was especially protective at high concentrations, for example 16 mM. These findings were confirmed by gel filtration of the assay mixture. In the presence of leupeptin (0.4 mM) and PCMS (16 mM), no shift in the peak of labelled glucagon or PP occurred. Thus ASE degrades not only 125I-glucagon but -PP, and thiol proteinase inhibitors have a strong inhibitory action on them.

4-Chloromercuribenzenesulfonate↗

Natural killer cell activity and recycling capacity of natural killer cells in patients with carcinoma of the prostate.

Natural killer (NK) cell activity and recycling capacity of NK cells in patients with carcinoma of the prostate (CaP) was determined by combining the 51Cr-release cytotoxicity assay and single cell cytotoxicity assay in agarose. The NK cell activity in patients with advanced CaP (stage D) was significantly lower than the NK cell activity of normal controls and that of patients with localized CaP (stage B and C). The number of active NK cells in the peripheral blood lymphocytes was similar in all groups tested including normal controls, patients with localized CaP, and patients with advanced CaP. Maximal killing potential (Vmax) and maximal recycling capacity (MRC) were significantly reduced in patients with advanced CaP as compared to patients with localized CaP or normal controls. Obtained results indicated that the depressed NK cell activity in advanced CaP was not due to a reduced number of active NK cells but due to the decreased recycling capacity of the individual NK cells.

Adult↗

[Cisplatin combination chemotherapy in advanced lung cancer in the aged].

Eleven aged patients over 65 years of age with advanced lung cancer (mean age = 70.8 +/- 1.4, non-small cell:small cell = 9:2, stage III:IV = 5:6) were treated with combination chemotherapy consisting of cisplatin (50 or 80 mg/m2) and vincaloids (vindesine 3 mg/m2 or etoposide 80 mg/m2). To evaluate this cisplatin combination therapy, the aged group was compared with a young group consisting of eleven patients (mean age = 53.3 +/- 1.7, non-small cell:small cell = 9:2, stage III:IV = 5:6) matched for cell type, stage and dose regimen. The mean dose of cisplatin was 58.2 mg/m2 in the aged and 63.6 mg/m2 in the younger group. A notable reduction in tumor size was observed in 9.1% of the aged and 27.3% of the young, while one-year survival rate was 63.6% in the aged and 72.7% in the young. The common side effects were nausea and vomiting, while diarrhea was seen in 18.2% of the aged. Neutropenia, anemia and thrombocytopenia were found in both groups and the time course of myelosuppression in the aged (18.2 +/- 0.8 days) was significantly shorter than that in the younger patients (22.0 +/- 1.4 days, p less than 0.05). With regard to nephrotoxicity, creatinine clearance rate in the aged decreased remarkably from 56.9 to 38.9 ml/min, while there was no significant change in BUN, serum creatinine and urine NAG between the aged and the young. Disorders of electrolytes such as hypokalemia and hyponatremia were seen in 45.5% of the aged. We conclude that advanced lung cancer in the aged was effectively treated with cisplatin combination therapy with tolerable nephrotoxicity and myelosuppression.

Aged↗

[The significance of moment analysis of spirogram].

In order to assess the significance of moment analysis of transit times on spirograms, we investigated the characteristics of this analysis and the distribution of mechanical time constants of the lung derived from this method. Assuming the log-normal distribution of time constants, mu is the mean and sigma is the standard deviation of the natural logarithms of the time constants. The normal value for mu was -0.64 +/- 0.41 and for sigma was 1.54 +/- 0.42 (mean +/- 1 S.D.) in 94 normal males. The smoking habits enhanced the response of sigma on age-effect, but did not enhance the response of V25/HT. Compared with the normal group, excessive sigma was observed in the patients with bronchial asthma, pulmonary emphysema and interstitial lung disease. Mu was especially greater in the patients with the former two diseases. In bronchial asthma, mu decreased and forced expiratory volume in 1 second (FEV 1.0) increased after inhalation of salbutamol, but these did not always correlate. Mu correlated with some clinical conditions. Moment analysis was available on the volume-time profile of quiet breathing with good reproducibility. The first moment (alpha 1) and standardized first moment (alpha 1') showed an increase in bronchial asthma and pulmonary emphysema, and decreased with treatment in bronchial asthma. It was concluded that the moment analysis of transit times on spirogram is useful as an index of time-course aspects of expiration.

Adult↗