Biomedical subjects
Publications and source records attributed to H Fuse.
A 40-year-old male was referred to the Chiba University Hospital for hypogonadism. He showed many of the phenotypic features of Klinefelter's syndrome. Cytogenetic studies revealed a 48,XXYY karyotype. The significance of the association of this karyotype with incurable skin ulcer is discussed.
RU 27987 is a new ligand for progesterone receptor and binds in high affinity to nuclei of target tissues of progesterone. Using this compound, progestin-binding components in the benign hypertrophic human prostate were studied, and compared with those examined with R 5020, a conventional ligand, in the study of progesterone receptor. In cytosols, the binding affinity of RU 27987 was higher than that of R 5020, and the number of maximum binding sites for RU 27987 seemed to be large but correlated well with those of R 5020. The binder for RU 27987 sedimented at 8.6 S, and the binding was specific to progestational steroids, indicating that binding properties of this binder in the cytosols are identical to those for R 5020. Although there was no binding with R 5020 in the nuclear extract, a small amount of specific binding with RU 27987 was detected. However, the cytosol bound with RU 27987 was not retained in DNA Sepharose and no specific binder for RU 27987 in the nuclear extract was observed in a sucrose density gradient centrifugation. From these observations, it was assumed that the nuclear binding observed was attributable to contamination of the cytosolic binder. The results obtained in the present study suggest that the progestin-binding component in the benign prostatic hypertrophy is not the progesterone receptor but a high affinity binder for progestins whose physiological role is not clear at present.
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Prostatic acid phosphatase (PAP) and prostatic specific antigen (PA) were determined with a Cetus test kit (California, USA) for prostatic cancer and others. Abnormal values of PAP in untreated prostatic cancer were found in 0, 0, 50, 50, 0, 73% of stage A1, A2, CpN0, CNX, D1 and D2 cases, respectively, and those of PA were found in 25, 0, 50, 100, 100, 100% of the same stages, respectively. Grade was not related to the level of PAP or PA. Prostatic hypertrophy showed increased values of PAP and PA in 11.1% and 7.4%, respectively. The levels of PAP were not correlated to those of PA. Endocrine treatment decreased the elevated values of PAP and PA in 60% of the cases. Most of the PAP and PA levels in the cases controlled under endocrine therapy were within normal values, but after relapse most showed elevated levels.
LH-RH analog (Buserelin) was administered in 10 cases of untreated prostatic cancer in our hospitals. All 10 cases had stage D2 disease. Five cases were of moderately differentiated carcinoma and 5 cases were of poorly differentiated carcinoma. The levels of luteinizing hormone and follicle stimulating hormone in blood plasma tended in decrease four weeks after treatment except for one case. The levels of testosterone in blood plasma reached the castrated level four weeks after administration except for the above one case. In adjacent effect by National Prostatic Cancer Project Criteria, the LH-RH proved to be effective in 6 of the 10 cases. The flush of face appeared in two cases, but it disappeared spontaneously. One case had a slight temporal macrohematuria one week after treatment.
Staging pelvic lymphadenectomy was performed on 21 patients with the prostatic cancer of stage A, B and C from January in 1981 to April in 1985. Twelve cases (57%) showed lymph node metastasis. Gleason's scores of the cases with lymph node metastasis proved lower than those of the cases without lymph node metastasis (p less than 0.05). There were no differences in grade between primary tumors and lymph node metastases. The percentage of metastasis to the external iliac, internal iliac and obturator lymph nodes was 55%, 83% and 82%, respectively. Two patients suffered from the delayed healing of the wound and the edema of the lower extremities, respectively, but the other patients had no complication.
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A case of spontaneous rupture of the ureter with Cushing's syndrome is presented. The fragility of the tissue in Cushing's syndrome is thought to render the ureter more susceptible to rupture.
The binding nature of mibolerone in cytosols and nuclear extracts from hypertrophic human prostate was examined in comparison with that of R 1881. The binding of mibolerone in the cytosol and nuclear extract was single and of high affinity when evaluated by the method of Scatchard (1949). Binding of mibolerone with testosterone-binding globulin was not detected. The sedimentation coefficients of the binder for mibolerone in the cytosol and nuclear extract were 10.6 S and 3.6 S, respectively. When triamcinolone acetonide was induced in the binding medium, inhibition of mibolerone binding in the cytosol by testosterone and dihydrotestosterone was potentiated and this may imply that the binding observed in the presence of triamcinolone acetonide was responsible for the binding of the androgen receptor. In the nuclear extract, the binding was attributable mainly to the androgen receptor irrespective of the presence or absence of triamcinolone acetonide. These properties of the binding observed in the hypertrophic human prostate were almost same as those of the binding with R 1881. Although maximum binding sites measured using mibolerone were correlated with those using R 1881 in the cytosols as well as in the nuclear extracts, the values obtained with mibolerone were slightly greater than those with R 1881. Thus, mibolerone seems to be a suitable ligand for measuring the androgen receptor, but when compared with R 1881 no special merits in using mibolerone were detected.
From January, 1960 to March, 1984, we studied 65 cases of prostatic cancer resistant to endocrine therapy. Treatment with ifosfamide or combination chemotherapy with vincristine, ifosfamide and peplomycin was performed in some of the 65 cases above mentioned. More cases were systemic reactivation than local reactivation. Poorly differentiated cancer accounted for the majority of the reactivated cancer. Concerning adjacent effects, treatment with ifosfamide was superior to combination chemotherapy. There was no difference between the distant effects of both chemotherapies. The patients with no effects showed predominance of pathologically low differentiated cell type. The 6-month survival rate of patients with chemotherapy was significantly higher than that of patients with other therapies. Toxicities of chemotherapies were leucopenia, digestive disturbances and falling out of hair. Hematuria and pulmonary fibrosis occurred in some cases.
Prostatic acid phosphatase was determined with Merck-Kanto's test kit on the cases of prostatic cancer experienced at our University Hospital from August in 1983 to February in 1985. Untreated cases were 4 stage A cases, 1 stage B case, 3 stage C cases, 3 stage D1 cases and 12 stage D2 cases. Nine cases were determined before and after hormonal treatment. From 67 controlled cases and 19 recurrent cases, 144 and 56 samples were selected, respectively. This method showed good reproducibility and even the serum stored at -80 degrees C after separation could be used for determination by addition of tartrate just before the measurement. The occurrence of abnormal values in untreated prostatic cancer cases, was 0% for stage A, 1 case for stage B, 33% for stage C and D1 and 75% for stage D2. Hormonal treatment decreased the high values of 5 cases and 1 case returned to normal. Compared to the recurrent cases, controlled cases showed a significantly larger ratio of negative, and it suggests that the test is useful for follow-up. Prostatic hypertrophy showed the increase of the value in 6% of the cases. Both prostatitis and urinary tract stone cases remained in the normal range.
The serum sialic acid concentration in 17 male healthy adults, 11 patients with acute prostatitis and 12 patients with acute epididymitis was measured with a specific enzymatic assaykit. The concentration was studied in relation to erythrocyte sedimentation rate, total serum protein and its fraction, C-reactive protein, and white blood cell count. Blood samples were obtained from the patients immediately before antimicrobial chemotherapy and the subsequent 3, 5, 7, 14, and 28 days. The pretreatment sialic acid concentration in the patients was significantly greater than that in the control subjects (P greater than 0.001). The mean serum sialic acid concentration in the patients reached a maximum level 3 days after the beginning of the treatment, and then gradually decreased. There was a significant correlation between the daily change of the serum sialic acid level and those of the erythocyte sedimentation rate, alpha2-globulin, and alpha1-globulin. Serum sialic acid proved to be a useful biochemical marker in acute prostatitis and acute epididymitis.
A 52-year-old woman was admitted, complaining of an abdominal mass and jaundice. The abdominal mass was revealed to be myoma uteri. We explored her hormonal data for her virilizing signs. Urinary 17KS and pregnanetriol levels were elevated and decreased by cortisol administration. She was diagnosed to have 21-hydroxylase deficiency and has been well controlled at our out-patient clinic.
From August, 1981 to May, 1984, we measured gamma-seminoprotein in the serum of 51 untreated patients with prostatic cancer in the Chiba University Hospital. Prostatic acid phosphatase (radioimmunoassay) in serum was also measured in these patients. We also measured gamma-seminoprotein and prostatic acid phosphatase in serum of patients under control by hormonal treatment and of reactivated patients. In untreated stage B and stage C cases, positive rate of gamma-seminoprotein in serum was larger than that of prostatic acid phosphatase. Therefore the measurement of gamma-seminoprotein in serum is considered to be useful in the diagnosis of early prostatic cancer. Four weeks after hormonal treatment, gamma-seminoprotein in the serum of 74% of the patients returned to the normal level. The positive rate of gamma-seminoprotein in the serum of reactivated patients is significantly larger than that of the patients under control by hormonal therapy.
Response rate of prostatic cancer to endocrine therapy is approximately 80%, but more than half of responders show relapse by five years. Factors influencing prognosis are histological grade, stage, effect of elevated acid phosphatase, and androphilic protein observed histochemically. Relapse may be attributable to progression and clonal selection.
A transplantable tumor CUB-II, a subline derived from the Dunning R 3327 rat prostatic adenocarcinoma, contains a unique sex steroid-binding protein. The protein possesses binding sites for androgens as well as for estrogens, and the binding affinity to androgen is higher than that to estrogen. The sedimentation coefficient of the protein is 10S. Sodium thiocyanate inhibits the binding to both sex steroids. This type of binding is not present in the 0.4M KC1 extract of nuclei. These results suggest that the binding protein is not the receptor for steroid hormones in spite of its high affinity binding to androgens and estrogens. Since the original tumor does not contain such protein, production of this binding protein seems to take place during culture in vitro and/or serial transplantations of the tumor.