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Biomedical subjects

F Wada

Publications and source records attributed to F Wada.

At least 55 records · Page 3Linked to original sources

Damaging effect of peripheral mononuclear cells of dermatomyositis on cultured human skin fibroblasts.

When human skin fibroblasts were incubated with mononuclear cells (MNC) from 6 patients with dermatomyositis (DM), striking attachment of MNC around fibroblasts was observed. Simultaneously, cell number and 3H-thymidine incorporation of fibroblasts after 4 days of incubation were significantly decreased. MNC of normal subjects, of patients with systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis, and other miscellaneous diseases with skin manifestations did not show this effect. MNC of patients with DM did not adhere to KYM-1 cells (human rhabdomyosarcoma cell-line) and did not inhibit cell proliferation of these cells. Our study strongly suggests that cell mediated injury of fibroblasts might play an important role in the pathogenesis of DM.

Adult↗

Lobe-specific distribution of a 20,000-dalton nonhistone protein in the dorsolateral prostate of rats.

Distribution of an androgen-dependent, 20,000-dalton nonhistone protein with a pI of about 11.5 (20K-NHP) was examined by electrophoretic techniques. Nuclei of the brain, liver, spleen, skeletal muscle, lung, and thymus of rats contained a negligible amount of 20K-NHP, whereas 20K-NHP was distinctly detectable, in different relative amounts, in the nuclei of the male accessory sex organs, with the dorsolateral prostate having the highest relative content (100%), followed by the coagulating gland (approximately equal to 16%), the ventral prostate (approximately equal to 6%), and the seminal vesicle (approximately equal to 2%). There were heterogeneous distributions of cytosol components, acid phosphatase isozymes, and nonhistone proteins in the dorsolateral prostate. Zinc was localized in the lateral lobe, and fructose and glucose were in the dorsal lobe. Cytosol proteins with pI 7.5, 8.2, and 8.5 were abundant in the dorsal lobe, and proteins with pI 7.4 and 8.0 in the lateral lobe. Acid phosphatase isozymes with pI 7.1, 7.4, 7.7, and 8.0 were abundantly distributed in the lateral lobe. Of the nonhistone proteins, 20K-NHP showed the highest content both in the lateral lobe and in the dorsal lobe. It was found that 20K-NHP was more abundantly distributed in the lateral lobe (maximally four times higher) than in the dorsal lobe. The heterogeneous distribution of 20K-NHP in the dorsolateral prostate was strikingly similar to that of zinc. It appears, therefore, that 20K-NHP is closely related to dorsolateral prostate zinc content.

Acid Phosphatase↗

The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets.

In an animal model of human rickets developed by giving a short-term administration of large doses of EHDP to young rats, concomitant administration of [Asu1,7]eel calcitonin (CT) with EHDP resulted in the promotion of calcification in growth cartilage. In an attempt to clarify the mechanisms related to the accelerated calcification due to CT, the effects of diltiazem, a calcium antagonist, were studied. Diltiazem suppressed, in a dose-dependent manner, the accelerated calcification due to CT in the growth cartilage, as determined by findings on the soft X-ray photos, contact microradiograph and light microscopic histology of the proximal region of the tibia. This suppression was only evident when diltiazem and CT were given concomitantly. If it is assumed that diltiazem inhibits the entry of calcium ion into the cells of growth cartilage, in the same manner as seen in case of smooth muscle and myocardial cells, then our results indicate that intracellular concentrations of calcium might play an important role in the occurrence of accelerated calcification due to CT.

Animals↗

[A case of pulmonary metastasis from renal cell carcinoma in which complete remission was achieved by interferon therapy (r-IFN-alpha A, Ro 22-8181)].

A case of pulmonary metastasis from renal cell carcinoma in which complete remission was achieved using interferon therapy is herein reported. A 54-year-old male underwent left nephrectomy following diagnosis of left renal cancer. Radiotherapy and hormonal therapy were performed postoperatively. Solitary pulmonary metastasis was found in the right lobe 4 months after surgery. The interferon (recombinant human leukocyte A interferon, rIFN-alpha A, Ro 22-8181) was initially administered i.m. at a dose of 3 X 10(6) units per injection every day. Marked response was observed one month after starting the interferon therapy (total: 183 X 10(6) U) and complete disappearance of the tumor was obtained 2 months after commencement of therapy (total: 345 X 10(6) U). The interferon was later injected at a dose of 6 X 10(6) U., 3 times a week because of general fatigue. The duration of complete response has lasted 8 months.

Carcinoma, Renal Cell↗

A human prostatic growth factor (hPGF): partial purification and characterization.

A growth factor capable of stimulating DNA synthesis of BALB/3T3 cells was purified about 1,000-fold from the cytosol of human benign hypertrophic prostates by heparin-Sepharose chromatography; the growth factor bound to the column in the presence of 0.5 M NaCl was eluted with 1.5-1.7 M NaCl. Its molecular weight and isoelectric point were estimated to be 11,000-13,000 and 10.5, respectively. It was sensitive to heat- and acid-treatments but resistant to disulfide-reducing agent. The final preparation was able to stimulate DNA synthesis at 10 ng/ml. The degree of stimulation was dependent on serum concentration in the assay system; the degree of maximum stimulation increased about 5 times as serum concentration increased from 0.2 to 2%.

Cytosol↗

Quantitative solubilization of nonhistone chromosomal proteins without denaturation using zwitterionic detergents.

Of three kinds of commercial zwitterionic detergents [SB 12, SB 14, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps)], SB 12 and Chaps were more useful than SB 14 because of high solubility and less interference with protein assay. Efficiency for protein solubilization at pH 6-9 was higher for SB 12 than for Chaps with either calf thymus chromatin or rat liver nuclei. At pH 9 and ionic strength (I) = 0.35, 1% SB 12 and 1% Chaps were capable of solubilizing about 70% and about 47% of total proteins in rat liver nuclei, respectively. Core histones in rat liver nuclei were extracted to a lesser extent with Chaps than with SB 12. DNA-dependent RNA polymerase and isopeptidase activities were barely inactivated by 1% Chaps at pH 8-9, but isopeptidase activity was inhibited by 0.3% SB 12. These facts indicate that whereas SB 12 is effective for solubilization of whole nuclear proteins, Chaps is suitable for the selective extraction of nonhistone chromosomal proteins without denaturation.

Animals↗

Localization of prostatic basic protein ("probasin") in the rat prostates by use of monoclonal antibody.

Isolated nuclei of the rat prostates contain a unique androgen-dependent basic protein, "probasin". Despite that it was hardly detectable in the cytosol centrifugally prepared from the prostates, immunofluorescent histological analysis of whole tissues using monoclonal antibody, which was raised against probasin purified from the nuclei, revealed that probasin was abundantly localized in the lumen and acinal regions of the epithelium, but hardly in the nuclei. Previous extraction of secretory fluid from the prostates caused about 60% decrease in the probasin content of isolated nuclei. These suggest that probasin was originally a secretory component in the prostates, being redistributed from the secretory fluid and granule into nuclei during fractionation of subcellular components.

Androgen-Binding Protein↗

Differences in nonhistone protein changes in rat ventral and dorsolateral prostate during sexual maturation.

Age-related changes of chromosomal proteins in the dorsolateral and ventral prostates of rats from 6 to 31 weeks of age were studied by SDS-polyacrylamide gel electrophoresis. A nonhistone protein having a molecular weight of about 20,000 (20K-NHP), abundantly localized in the dorsolateral prostate, increased rapidly in content during the early stage of sexual maturation (6-11 weeks of age) in association with increases of serum testosterone concentration and prostatic tissue weight. Serum testosterone concentration decreased after week 11 and then remained constant until week 31. In contrast, the 20K-NHP content continued to increase after 11 weeks of age in the dorsolateral prostate, but not in the ventral prostate. The rapid increase of 20K-NHP in the dorsolateral prostate during the early stage of sexual maturation could not be attained in immature rats (5 weeks of age) by injection of excess amounts of androgens and/or prolactin for a week. But the 20K-NHP content in the ventral prostate of rats treated with testosterone propionate was almost the same as that of mature rats.

Androgens↗

Comparison of subcellular proteins of normal prostate, benign prostatic hypertrophy, and prostatic cancer: presence of BPH-associated nonhistone proteins.

Proteins in the cytosol, postnuclear particulate, and nuclear fractions from seven specimens of normal prostate from bladder cancer patients, 14 specimens of benign hypertrophic prostate (BPH), and three specimens of cancerous prostate were analyzed and compared by SDS-polyacrylamide slab gel electrophoresis. Abundant protein species in the cytosol fractions were 60K (species having a molecular weight of about 60,000) and 42K; their relative contents were about 35% for 60K and about 12% for 42K. In the postnuclear particulate fraction, 42K was the most abundant (about 10% of the total). The contents of these major protein species were similar in specimens of normal and diseased prostates. In addition, there are marked similarities in the electrophoretic patterns for all the protein (24-29 species) in the cytosol and postnuclear particulate fractions of the human prostate, except for four minor species in the cytosol fraction. Of the nuclear proteins, the content of core histones (H2A, H2B, H3, and H4) was fundamentally similar among all the specimens, whereas the content of H1 histone was different from one specimen to another. The most remarkable and significant difference was that the 42K-NHP (nonhistone protein having a molecular weight of about 42,000), 55K-NHP, and 190K-NHP concentrations were significantly higher in BPH than in normal and cancerous prostates.

Chromosomal Proteins, Non-Histone↗

Changes of an androgen-dependent nuclear protein during functional differentiation and by dedifferentiation of the dorsolateral prostate of rats.

Nuclei of the dorsolateral prostate of rats contain a large amount of androgen-dependent non-histone protein (20K-NHP) (mol. wt. not equal to 20,000; pI not equal to 11.5) (Matuo et al. (1]. Its content in the nuclei increased most markedly during 4-8 weeks of age, when functional differentiation of the prostate was most active on the basis of the changes of major cytosol proteins and zinc. Nuclei of the Dunning tumors originating in the dorsolateral prostate were found to lack 20K-NHP regardless of androgen dependency, indicating the disappearance of the 20K-NHP from the nuclei by dedifferentiation. These suggest that the 20K-NHP is an important nuclear protein for differentiation of the dorsolateral prostate cells.

Aging↗

Biochemical difference between ventral and dorsolateral prostates: effects of castration and administration of the antiandrogen 16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one on SDS-electrophoretic patterns of subcellular proteins from rat prostates.

Protein species in the cytosol, postnuclear particulate, and nuclear fractions from the ventral and dorsolateral prostates of rats castrated or injected with antiandrogen, 16 beta-ethyl-17 beta-hydroxy-4- oestren -3-one ( EHOO ), were analyzed by SDS-polyacrylamide gel electrophoresis. The effects of EHOO injection on the contents of the most abundant species in all three fractions of ventral prostate were similar to the effects of castration, but the effects of EHOO and castration were only similar on the nuclear fraction in the dorsolateral prostate. The most sensitive species to castration in the three subcellular fractions of dorsolateral prostate were the same as those to EHOO injections; this was not the case for the cytosol and nuclear fractions in the ventral prostate.

Androgen Antagonists↗

[Effect of drug-administration on physiological function of hemoglobin (author's transl)].

Hemoglobin and cytochrome P-450 have in common heme structure (i.e. protoporphyrin (IX), binding ability to molecular oxygen or carbon monoxide and enzyme-like activity (i.e. aniline hydroxylation; J.B.C. 251 3442, 1976). We have already reported the interactions between hemoglobin and several drugs, aminopyrine, aniline and steroid hormones, as determined from the spectral changes of hemoglobin. Similar results were obtained with many other drugs. Difference spectra of methemoglobin induced by most chemicals tested had a trough at 402 approximately 403 nm and a peak at 420 approximately 430 nm. Methanol and ethanol formed a peak at 403 nm and a trough at 420 nm. Difference spectra of oxyhemoglobin induced by most chemicals tested had a peak at 400 approximately 403 nm and a trough at 420 nm. Each of steroid hormones and amino acids tested induced a characteristic spectral change of methemoglobin or oxyhemoglobin. The effect of drug-administration on oxygen affinity of hemoglobin was then examined. We measured oxygen half saturation pressure (P50) using whole blood or purified hemoglobin. Addition of meclofenoxate HCl, PAS-Na and IHMS to purified hemoglobin solution increased P50. Whole blood samples, before and one hour after drug-administration, from 33 inpatients, 13 outpatients and 20 normal subjects (not on drug-administration) were used to determine delta P50 of 12 outpatients were within normal range (-0.5 approximately +0.5 mmHg). Those of 14 inpatients, however, were distributed out of range. The determination of delta P50 may be useful as a screening test for inappropriate drug-administration.

Adult↗