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Biomedical subjects

K Masuda

Publications and source records attributed to K Masuda.

At least 559 records · Page 31Linked to original sources

[Prospective prediction of radiotherapy induced normal tissue injuries].

Variation of the normal tissue response to radiotherapy in animals of a given age, sex and species, and predictive analysis of the post radiotherapy normal tissue injuries for each case were reviewed. The degree of response of mouse hind legs to 25 Gy in a single dose varies from less than 20 Gy equivalent to more than 30 Gy equivalent injuries, implying that there still remains an unknown dose modifying factor whose modification factor is at large. It has been proposed to predict prospectively the post irradiation response of several normal tissues including the lung. Although, it is possible to predict the average degree of normal tissue injuries to a given dose, to predict the response of each case appears to be impossible.

Animals↗

[Yersinia enterocolitis--report of two cases].

We reported two cases of terminal ileitis caused by Yersinia enterocolitica (Y.e.). Y.e. was proven by stool culture in each case. They were admitted to the hospital complaining abdominal pain. They are examined by X-ray and endoscopy in the different time, and their examination revealed edema, coarse mucosa and varioliform elevated lesions with the passage of time.

Adult↗

Aqueous flare intensity and age.

The influence of aging on the blood-aqueous barrier function was assessed by measuring aqueous flare intensity in 203 normal eyes of healthy human subjects aged 20 to 79 years, using the recently developed laser flare-cell meter. The flare intensity correlated well with age (r = 0.502, Spearman r = 0.503, P = 0.00), and the intensity values in the subjects with their ages in the 6th, 7th and 8th decade were significantly higher than the values in the subjects in their 3rd decade (P less than 0.01).

Adult↗

[Effect of acetazolamide on aqueous flare in normal human eyes].

A newly developed instrument for the quantitative measurement of aqueous flare, the laser flare-cell meter, is now being introduced clinically. The present experiment was designed to assess the effect of a commonly administered drug, acetazolamide, on measurements obtained in normal, healthy subjects. Control measurements were taken over a 24 hr period, from 0900 hrs to 0900 hrs of the next day in 12 drug-free, normal, healthy subjects. A second, similar time-course measurement was conducted in the same subjects on another day after oral administration of 500 mg acetazolamide. Results revealed that acetazolamide increased aqueous flare from 2 hrs to 10 hrs post-administration. The peak effect was observed approximately 6 hrs after acetazolamide administration, reaching a level 41% greater than that on the control day. Anterior chamber volume and serum protein concentration were not affected by the drug treatment. The use of the laser flare-cell meter in the clinic and possible mechanisms contributing to the effect of the drug are discussed.

Acetazolamide↗

The role of cytokines in chondrocyte mediated cartilage degradation.

Articular chondrocytes cultured in the presence of recombinant human interleukin 1 alpha (rhIL-1 alpha) or recombinant human tumor necrosis factor alpha (rhTNF alpha) caused increased production of the latent metalloproteinase (collagenase and caseinase) and the proteoglycan release from cartilage. The existences of IL-1 and TNF alpha in the chondrocytes of human articular cartilage were also shown by immunohistochemical staining using polyclonal antibodies. Furthermore, chondrocyte was found to be a producer of interleukin 6 (IL-6), known as a pleiotropic cytokine and thought to be an important mediator of the cell interactions in arthritis. In addition, the production of IL-6 was also shown to be stimulated by rhIL-1 alpha or rhTNF alpha. From our findings, we suggest there exists a very complicated autocrine control system of chondrolysis by the chondrocyte itself.

Animals↗

Antiestrogenic and antitumor effects of droloxifene in experimental breast carcinoma.

The pharmacological effects of droloxifene [E)-a [p-[2-(dimethylamino)ethoxy]phenyl]-a'-ethyl-3-stilbenol, FK435), a new antiestrogen drug, were studied and compared with those of tamoxifen in animals and in vitro cultured cells. Droloxifene showed about 20-fold and 3-fold higher affinity to estrogen receptors (ER) in the rat uterus and human ER positive MCF-7 breast carcinoma cells, respectively, than tamoxifen, and was more active in decreasing uterine weight of mature rats and 17 beta-estradiol-treated immature rats. Tamoxifen increased uterus growth in immature rats, but droloxifene did not, suggesting that droloxifene has no estrogenic effects. Both drugs inhibited the growth of in vitro cultured MCF-7 cells, with droloxifene being the more active agent, but this effect of both drugs was countered by 17 beta-estradiol. Neither drug, however, had effects on the in vitro growth of human ER negative MDA-MB-231 breast carcinoma cells. In vivo, both drugs inhibited the growth of MCF-7 carcinoma implanted subcutaneously in BALB/c nu/nu mice, but not the growth of human ER negative MX-1 breast carcinoma. The results suggest that droloxifene has antitumor effects on human ER positive breast cancers, and would be useful for the treatment of estrogen-dependent breast cancers.

Animals↗

Interstrand DNA-DNA and DNA-protein cross-links by a new antitumor antibiotic, FK973, in L1210 cells.

In our previous study FK973, a novel, substituted dihydrobenzoxazine (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11-diazatetracyclo+ ++ [7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-6,9-diyl diacetate), had potent cytotoxic and antitumor effects on murine tumors and human tumors in in vitro and in vivo experiments. In the present study the mechanism(s) of the in vitro cytotoxic effects of the drug on tumor cells were studied. After 1-h exposure of L1210 murine leukemia cells to the drug, the concentration of FK973 required to inhibit cell growth by 50% was approximately 1 microM, which was threefold more potent than the concentration of mitomycin C required. DNA synthesis was selectively inhibited in the cells treated with FK973. Alkaline elution analyses showed that FK973 formed concentration- and time-dependent interstrand DNA-DNA and DNA-protein cross-links in the cells. On the other hand, no DNA single-strand breaks were observed in the cells treated with FK973. When isolated nuclei of L1210 were exposed to FK973 for 1 h, FK973 did not form detectable interstrand DNA-DNA cross-links. We propose that FK973 is activated in the cytoplasm of cells, and forms interstrand DNA-DNA and DNA-protein cross-links which may be important for the induction of its cytotoxicity.

Animals↗

Antitumor activity and hematotoxicity of a new, substituted dihydrobenzoxazine, FK973, in mice.

FK973, a new, substituted dihydrobenzoxazine (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11- diazatetracyclo[7.4.1.0.0]tetra-deca-2,4,6-trien-6,9-diyl diacetate), was obtained by chemical modification of a novel antibiotic which was isolated from the fermentation products of Streptomyces sandaensis No. 6897. FK973 had cytotoxic effects against in vitro cultured human and murine tumor cells. FK973 in doses of 0.032-5.6 mg/kg (i.p.) had stronger antitumor activities and higher chemotherapeutic ratio than mitomycin C against such murine ascitic tumors as P388 and L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma of ovarian origin, Colon 26 carcinoma, Ehrlich carcinoma, and MH134 hepatoma. In tests against murine and human solid tumors implanted s.c. in normal mice and nude mice, respectively, FK973 (i.v.) inhibited growth of murine tumors (M5076 sarcoma, Colon 38 carcinoma, B16 melanoma, and Lewis lung carcinoma) by 66-100% and human tumors (LX-1 lung, MX-1 mammary, and SC-6 stomach carcinoma) by 84-99%. In studies with drug-resistant P388 leukemia, FK973 was also effective against vincristine-resistant P388, moderately effective against mitomycin C (MMC)- and adriamycin-resistant P388, and partially effective against cyclophosphamide-resistant P388 cells in mice. Leukopenic effects of FK973 and MMC in mice were comparable at doses which gave antitumor activity almost equally. FK973 had no effect on the numbers of platelets and red blood cells, whereas MMC markedly decreased both. FK973 decreased the numbers of colony forming units in spleen and in culture and the effect was less than that of MMC. Therefore, FK973 may give weaker myelosuppression than MMC. The results suggest that FK973 will be a beneficial drug for the treatment of cancer.

Animals↗

Coexistence of a nonfunctioning thyroid nodule in Plummer's disease demonstrated by thallium-201 imaging.

A patient with Plummer's disease in whom a coexisting nonfunctioning thyroid nodule was detected by TI-201 imaging is presented. I-123 imaging revealed a hot nodule corresponding to the functioning nodule and little uptake in the rest of the thyroid. In contrast, two areas of abnormalities were noted on a TI-201 image: one corresponded to the hot nodule in I-123 imaging and the other was visualized in the suppressed part of the thyroid in the same lobe. This case revealed that TI-201 imaging is clinically useful in detecting coexisting nodules in the suppressed part of the thyroid.

Adenoma↗

Effects of interleukin-1 and anti-inflammatory drugs on the degradation of human articular cartilage.

It has been suggested that metalloproteases produced by chondrocytes play an important role in cartilage breakdown in joint diseases. The aim of this study was to investigate changes in enzyme activities in human rheumatoid and osteoarthritic articular cartilage. Cartilage fragments were incubated with various drugs for 48 hours. The concentrated culture media were used as enzyme solutions. Collagenase was assayed using FITC-collagen as the substrate. Proteoglycanase (PGase) was measured either by the release of 35S-labelled proteoglycans from cartilage into the medium, or by enzyme assay using proteoglycan monomer bound to fluorescein-conjugated hyaluronic acid as the substrate. Collagenase and proteoglycanase were found only in trace amounts in the concentrated media of healthy cartilage. Interleukin-1 (IL-1) enhanced the enzyme activities significantly. Marked increases of enzyme activities were observed in the concentrated media of rheumatoid (RA) and osteoarthritic (OA) cartilage. The sensitivity to interleukin-1 was also higher in OA and RA cartilage compared with healthy cartilage. Dexamethasone (10(-6) mol/L) markedly depressed enzyme activity. Tiaprofenic acid (4 x 10(-5) mol/L) also decreased enzyme activity, whereas indomethacin (4 x 10(-6) mol/L) and naproxen (3 x 10(-4) mol/L) had no effect.

Anti-Inflammatory Agents, Non-Steroidal↗

[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↗

Diurnal variation of aqueous flare in normal human eyes measured with laser flare-cell meter.

An attempt was made to detect the diurnal variation of aqueous protein concentration (aqueous flare) in normal human eyes. The laser flare-cell meter, which was recently developed to determine aqueous protein concentration quantitatively in vivo, was employed in the study. A preliminary study was performed to evaluate the reproducibility of aqueous flare measurements with the laser flare-cell meter in normal subjects, giving a reproducibility coefficient of 12.5%. The aqueous flare intensity was found to be high in the morning and low in the evening. The quotient between the highest and the lowest value was 1.32. The findings were considered to represent changes in actual aqueous protein concentration and the possible sources of this fluctuation were discussed.

Adult↗