Characterization of the Asian myopathy patients with VCP mutations.

BACKGROUND AND PURPOSE: Mutations in the valosin-containing protein (VCP) gene are known to cause inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and familial amyotrophic lateral sclerosis (ALS). Despite an increasing number of clinical reports, only one Asian family with IBMPFD has been described. METHODS: To characterize patients with VCP mutations, we screened a total of 152 unrelated Asian families who were suspected to have rimmed vacuolar myopathy. RESULTS: We identified VCP mutations in seven patients from six unrelated Asian families. Five different missense mutations were found, including a novel p.Ala439Pro substitution. All patients had adult-onset progressive muscle wasting with variable involvement of axial, proximal, and distal muscles. Two of seven patients were suggested to have mild brain involvement including cerebellar ataxia, and only one showed radiological findings indicating a change in bone. Findings from skeletal muscle indicated mixed neurogenic and myogenic changes, fibers with rimmed vacuoles, and the presence of cytoplasmic and nuclear inclusions. These inclusions were immunopositive for VCP, ubiquitin, transactivation response DNA-binding protein 43, and also histone deacetylase 6 (HDAC6), of which function is regulated by VCP. Evidence of early nuclear and mitochondrial damage was also characteristic. CONCLUSIONS: Valosin-containing protein mutations are not rare in Asian patients, and gene analysis should be considered for patients with adult-onset rimmed vacuolar myopathy with neurogenic changes. A wide variety of central and peripheral nervous system symptoms coupled with rare bone abnormalities may complicate diagnosis.

Clinical usefulness of sialyl SSEA-1 antigen as tumor marker for ovarian cancer as compared with CA125, CA19-9, TPA, IAP, CEA and ferritin.

In order to determine the clinical significance of sialyl SSEA-1 antigen, we compared its usefulness as a tumor marker for ovarian cancer with simultaneously measured CA125, CA19-9, TPA, IAP, CEA and ferritin. The sialyl SSEA-1 antigen in serum was measured by radioimmunoassay with an "FH-6" Otsuka Kit. The immunohistochemical localization of sialyl SSEA-1 antigen in ovarian carcinoma tissues was determined by an immunoperoxidase method using FH-6 monoclonal antibody. Among fifty-one patients with ovarian cancer, the incidence of elevated serum levels was 54.9% with sialyl SSEA-1 antigen, 90.2% with CA125, 48.8% with CA19-9, 78.0% with TPA, 73.1% with IAP, 17.1% with CEA and 63.4% with ferritin. On the other hand, among the patients with uterine malignancies and gynecologic benign tumors, the incidence of elevated sialyl SSEA-1 antigen levels in serum was lower than that of other tumour markers. In the patients with ovarian cancer, the serum levels of sialyl SSEA-1 antigen increased in accordance with the advance of the clinical stage and were also correlated with the effect of therapy. In the examination of immunohistochemical localization of sialyl SSEA-1 antigen, a positive reaction occurred in 10 out of 30 ovarian carcinoma specimens. Intense staining appeared in the secretory materials, in the luminal surface of the glands, and in the cytoplasm of cells. Thus, sialyl SSEA-1 antigen appears to be a useful tumor marker for the diagnosis of ovarian cancer, especially when measured simultaneously with CA125, CA19-9, TPA, ferritin and IAP.

[Experimental study on the effect of UFT with concomitant radiotherapy of uterine cervical cancer].

In order to examine effectiveness of the chemotherapy with concomitant radiotherapy, an experimental study was designed using AMCC-1 cell line established from a human uterine cervical carcinoma in our laboratory. The growth of AMCC-1 cells cultured in plastic flask was inhibited significantly in the group treated with a half of minimal effective doses of 60Co and 5-FU in comparison with the control group. The 5-FU treatment after radiation inhibited the AMCC-1 cell growth more effectively than that before radiation. The growth of AMCC-1 tumor transplanted into nude mice was inhibited significantly in the group given a combination chemoradiotherapy, consisted of oral administration of three quarters of minimal effective dose of UFT for fourteen consecutive days and radiation of a half of minimal effective dose of 60Co. The oral administration of UFT after radiation inhibited the AMCC-1 tumor growth more effectively than that before radiation. These results suggest that the radiotherapy with administration of UFT was more effective against uterine cervical cancer than radiation alone and it is important to administer UFT orally after radiation as well as before radiation.

[Chlamydia trachomatis infection in the female patients].

With recent advances in the development of detection methods, the number of STD (Sex transmitted disease) cases detected is greater than ever. Among many STD, Chlamydia trachomatis (= CT), a microbe that has been given a great deal of attention in the urologic field as a cause of nonspecific urethritis and has a characteristic life cycle, has been gradually proved to exist commonly and to become a cause of various obstetrical and gynecological diseases. However, as it is clinically still unknown which symptoms are actually influenced by CT, we studied infection with CT in 706 cases, consists of a group of patients with some symptoms and an asymptomatic group mainly consisting of pregnant women. As a result, the positive rate was found to be 12.3% (87 cases); 10.8% (21 out of 194) in asymptomatic pregnant women, 11.0% (13 out of 118) in patients with cervicitis, and 14.9% (30 out of 202) in patients with adnexitis including PID. As to age, the positive rate was highest, 23.1%, in patients under 20 years old. In fact, 1) CT positive pregnant women are not rare, and 2) CT was detected in high frequency in the young generation under 20 years old; and in these young women, the possibility of transmission of the disease to the infant in the birth canal should be considered in connection with future pregnancy and delivery. Tubal sterility may also result. We concluded that it was necessary to establish a satisfactory examination system.

Studies on experimentally induced hydrosalpinges in rabbits--experimental approach for tubo-microsurgery.

Hydrosalpinx proved macroscopically and microscopically which was quite similar to that observed in the damage human fallopian tube could be induced by ligation of the rabbit fallopian tube. Where ligatures have been placed on two places of the fallopian tube, hydrosalpinx can be induced in 100 percent of cases if ligation is done securely. About 1-2 weeks after ligation, no change of ciliated cells was observed in the mucosal fold in SEM findings, nor was there much change in the external shape of non-ciliated cells even though hydrosalpinx was induced. With the lapse of time after development of hydrosalpinx, however, both of these cells on the surface of the mucosal fold gradually changed to loose their normal shapes. After 15 weeks, ciliated cells all but disappeared to be replaced by large, filled, irregular non-ciliated cells. Accordingly, hydrosalpinx in the early stage can be cured fully by tubal salpingostomy using microsurgery. In the case of hydrosalpinx many hours after ligation, however, end-to-end anastomosis of the normal regions should be performed since no recovery can be expected.

[Clinical effect of gamma-oryzanol on climacteric disturbance -on serum lipid peroxides (author's transl)].

Though gamma-Oryzanol has been applicated as the autonomic agent in various fields for a few decades, recently its effect on lipid metabolism comes to be much more interested. We studied on the effect of gamma-Oryzanol on climacteric disturbance, and besides on the difference of lipid peroxides level which has an important and indispensable connection with mary syndromes involving aging. We obtained the following results from 40 subjects with climacteric disturbance after administration of gamma-Oryzanol Fine Particule 1.5 g (gamma-Oryzanol 300 mg included) for 4 to 8 weeks. 1. 90% of the cases improved generally; Excellent 16 (40%), Good 14 (35%), Effective 6 (15%), No change 4 (10%). 2. Effect on climacteric disturbance was judged by the Kupperman method and the Ueda method; generally recovered 85%, 80% each. 3. Significantly reduced total cholesterol, triglyceride and increased HDL-cholesterol were noted in cases with hyperlipidemia (TC greater than or equal to 220 mg/dl, TG greater than or equal to 140 mg/dl, HDL-chol. less than or equal to 45 mg/dl). Therefore, atherogenic index was excellently recovered. 4. In cases with climacteric disturbance lipid peroxides level was high, and they were significantly recovered by administration of gamma-Oryzanol. 5. During this study, no side effects have been recognized and no particular change in function test was found. Thus, we confirmed the efficacy and utility of gamma-Oryzanol on many complaints in climacteric disturbance and also on lipid metabolism.

[Clinical experience with gentamicin in urinary tract infections (author's transl)].

1) Gentamicin (GM) was intramuscularly injected to 1 patient with simple acute cystitis and to 21 patients with complicated chronic urinary tract infections in the doses of 40-160 mg per day for 3-12 days (mean: 5-2 days). 2) The clinical effect was excellent in 6, good in 9, poor in 7, which is classified as excellent in 1 with simple acute cystitis, good in 5 and poor in 5 out of 11 with complicated chronic cystitis, and excellent in 4, good in 4 and poor in 2 out of 10 with complicated chronic pyelonephritis. 3) In complicated urinary tract infections, the effective rate was 61.5% (8/13) in GM 80 mg/day dosage group and 75.0% (6/8) in GM 120 mg/day dosage group. 4) No abnormal change was noted in the kidney, liver and auditory function throughout this clinical study. 5) When GM therapy is conducted in the treatment of complicated urinary tract infections, it is considered that more favorable clinical results could be obtained with dosage of GM 120 mg/day or more. However, in this case a caution has to be paid to the kidney and auditory functions.