Possible association of oestrogen and Cryba4 with masticatory muscle tendon-aponeurosis hyperplasia.

OBJECTIVE: Masticatory muscle tendon-aponeurosis hyperplasia, which is associated with limited mouth opening, progresses very slowly from adolescence. The prevalence rates of this disease are higher among women than among men, suggesting oestrogen involvement. As parafunctional habits are frequently observed, mechanical stress is likely involved in the pathogenesis and advancement of this disease. To elucidate the pathological condition, we examined the effect of oestrogen on tenocyte function and the relationship between mechanical stress and crystallin beta A4 (Cryba4), using murine TT-D6 tenocytes. MATERIALS AND METHODS: Cell proliferation assays, RT-PCR, real-time RT-PCR, Western blot analysis and mechanical loading experiments were performed. RESULTS: The physiological dose of oestrogen increased the levels of scleraxis and tenomodulin in TT-D6 tenocytes. In contrast, forced expression of Cryba4 inhibited scleraxis expression in these cells. Surprisingly, oestrogen significantly promoted cell differentiation in the Cryba4-overexpressing TT-D6 tenocytes. Moreover, tensile force induced Cryba4 expression in these tendon cells. CONCLUSION: Oestrogen and Cryba4 may be associated with the progression of masticatory muscle tendon-aponeurosis hyperplasia.

Osteopontin Deficiency Suppresses Tumor Necrosis Factor-α-Induced Apoptosis in Chondrocytes.

OBJECTIVE: Apoptosis of chondrocytes in articular cartilage has been observed in rheumatoid arthritis patients. However, molecules involved in such chondrocyte apoptosis in arthritic joints have not been fully understood. We previously observed that apoptosis of chondrocytes is enhanced in a murine arthritis model induced by injection with anti-type II collagen antibodies and lipopolysaccharide (mAbs/LPS), and osteopontin (OPN) deficiency suppresses chondrocyte apoptosis in this arthritis model in vivo. To understand how OPN deficiency renders resistance against chondrocyte apoptosis, we examined the cellular basis for this protection. DESIGN: Chondrocytes were prepared from wild-type and OPN-deficient mouse ribs, and tumor necrosis factor (TNF)-α-induced cell death was examined based on lactate dehydrogenase (LDH) release assay and TUNEL assay. RESULTS: TNF-α treatment induced LDH release in wild-type chondrocytes, while OPN deficiency suppressed such LDH release in the cultures of these cells. TNF-α-induced increase in the number of TUNEL-positive cells was observed in wild-type chondrocytes, while OPN deficiency in chondrocytes suppressed the TNF-α induction of TUNEL-positive cells. OPN deficiency suppressed TNF-α-induced increase in caspase-3 activity in chondrocytes in culture. Furthermore, OPN overexpression in chondrocytes enhanced TNF-α-induced apoptosis. CONCLUSION: These results indicated that the presence of OPN in chondrocytes is involved in the susceptibility of these cells to TNF-α-induced apoptosis.

Treatment of metastatic uterine leiomyosarcoma with cisplatin, pirarubicin, and ifosfamide.

We present the unusual case of a 27-year-old Japanese woman who exhibited recurrences of metastatic tumors from uterine leiomyosarcoma after five operations. Chemotherapy with cisplatin, pirarubicin, and cyclophosphamide was ineffective. Substituting ifosfamide for cyclophosphamide, we obtained a complete response. The Gynecologic Oncology Group (GOG) in the United States has recognized the efficacy of ifosfamide and mesna in the treatment of patients with advanced or recurrent uterine sarcomas. Here we report on the efficacy of ifosfamide in addition to cisplatin and pirarubicin.

Immunohistochemical study of c-erb B-2 expression in malignant mixed müllerian tumors of the female genital tract.

OBJECTIVE: To study the expression of c-erb B-2 in gynecologic malignancies, especially in malignant mixed müllerian tumors (MMTs). METHODS: Using immunohistochemical techniques, we examined 6 cases of primary MMT, 6 cases of leiomyosarcoma (LMS), 7 cases of endometrial adenocarcinomas, and 10 cases of normal endometria. RESULTS: The expression of c-erb B-2 was observed in the carcinomatous area of all 6 cases of MMT (100%), the sarcomatous area of 5 of 6 cases of MMT (83.3%), in 1 of the 6 cases of LMS (16.7%), in all 7 cases of adenocarcinoma (100%), and in all cases of normal epithelial cells (100%), but was not observed in any of the cases of normal stromal cells (0%). CONCLUSION: The results suggest that the carcinomatous and sarcomatous elements of MMT are similar in their expression of c-erb B-2. MMT differed immunohistochemically from pure sarcoma cells and normal stromal cells, but resembled pure carcinoma cells and normal epithelial cells of the female genital tract.

Adenocarcinoma arising from a mature cystic teratoma of the ovary: a case report of successful treatment with cisplatin-based chemotherapy.

A case of mucin-producing adenocarcinoma arising from a mature cystic teratoma of the right ovary is reported in a 67-year-old multiparous Japanese woman. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and adjuvant chemotherapy containing cisplatin, Adriamycin, and cyclophosphamide with the diagnosis of ovarian cancer, probable stage Ic. Treatment was successful even though the tumor extended through the cyst wall.

[Characterization of intraoperative rupture of epithelial ovarian cancer at early stage].

OBJECTIVE: To investigate whether intraoperative rupture of epithelial ovarian cancer. influences the prognosis. METHODS: Between 1984 and 1994, 46 patients with stage Ia and Ic epithelial ovarian cancer were treated at Oita Medical University Hospital. Of 46 patients, 20 had stage Ia tumors, 16 stage Ic secondary to capsular invasion-serosal disease or positive ascites or washings (stage Ic-ascites), and 10 stage Ic secondary to intraoperative rupture (Ic-rupture). Survival analysis was performed to compare the three groups of patients. RESULTS: The ages (mean +/- SD) of patients with stage Ia, Ic-ascites and Ic-rupture at the first diagnosis were 40.1 +/- 17.0, 47.6 +/- 13.4 and 52.8 +/- 15.7, respectively. The age of the stage Ia group tended to be lower than those of the Ic-ascites and Ic-rupture groups. At operation, ovarian tumors of all patients in the Ic-rupture group were firmly adhered to surrounding organs, had markedly thin weak cyst walls and were easily ruptured during operation. Fourteen of 20 patients in the Ia group (70%), 5 of 16 patients in the Ic-ascites group (31.3%) and 3 of 10 patients in the Ic-rupture group (30%) showed signs of mucinous cystadenocarcinoma. The incidence of mucinous cystadenocarcinoma in Ia group was significantly lower than in the Ic-ascites (p < 0.025, chi 2-test) and Ic-rupture (p < 0.05, chi 2-test) groups. The Kaplan-Meier survival plot for stage Ia, Ic-ascites and Ic-rupture patients revealed a probability of 5-year survival of 100%, 87.5% and 63.5%, respectively. The probability of 5-year survival in the Ic-rupture group tended to be lower than that in other groups. CONCLUSIONS: The results of our study suggest that intraoperative rupture of a malignant ovarian cystic tumor may worsen the prognosis of patients with the FIGO stage I epithelial ovarian cancer.

[Clinical features of epithelial ovarian cancer in young reproductive women].

A 10-year retrospective review of epithelial carcinoma of the ovary was performed about 95 patients which were diagnosed and treated at the Oita Medical University Hospital. The patients' ages at the first diagnosis ranged from 15 to 85 years with a mean of 51.6 years. Twenty-two of 95 patients (23.2%) were below the age of 40. Most patients analysed in this study complained of lower abdominal pain, lower abdominal mass, and/or lower abdominal fullness. Sixteen of 22 patients under the age of 40 (72.7%) and 27 of 73 patients over the age of 40 (37.0%) were diagnosed as having mucinous cystadenocarcinoma. The incidence of mucinous cystadenocarcinoma below the age of 40 was significantly higher than that over the age of 40 (p < 0.005, chi 2-test). Eleven patients below the age of 40 had FIGO stage Ia grade 1 disease and 2 of these patients were pregnant. The incidence of stage Ia disease under the age of 40 was significantly higher than that over the age of 40 (p < 0.005, chi 2-test). Both pregnant patients and 5 other patients with stage Ia disease were treated with only unilateral salpingo-oophorectomy. All patient with stage Ia disease had no evidence of recurrence within 5 years. This suggests that conservative surgery may be considered as the treatment for the FIGO stage Ia grade 1 ovarian cancer.

Immunohistochemical study of c-erb B-2 protein expression in endometriosis.

Using immunohistochemical techniques, we studied the expression of c-erb B-2 in normal human endometrial tissue (n = 8), endometriosis interna (adenomyosis) (n = 8) and endometriosis externa (endometriotic cyst of the ovary) (n = 6). The glandular epithelium of normal endometrial tissue specimens in the proliferative phase stained positively. Most of the cases of endometriosis studied showed no expression of c-erb B-2 in glandular epithelium. No expression was detected in either the normal or endometriotic stromal cells. Results suggest that c-erb B-2 is not significantly involved in the pathogenesis of endometriosis.

Ureteral obstruction caused by endometriosis.

The diagnosis of ureteral obstruction caused by endometriosis can be difficult. We present a 51-year-old multiparous Japanese women who had undergone right salpingo-oophorectomy at the age of 19 years. She underwent total hysterectomy, left salpingo-oophorectomy, and adhesiotomy of the right ureter after the diagnosis of myoma uteri and endometriosis was made. Microscopic examination of the surrounding resected tissue confirmed the typical endometriotic origin. In addition to intravenous and retrograde pyelography, computerized tomography was useful to establish the diagnosis of ureteral obstruction caused by an extrinsic mass of endometriotic tissue.

Sudden death due to pulmonary tumor embolism in a patient with endodermal sinus tumor of the ovary.

Only 2 cases of fatal pulmonary tumor embolism have been described in patients having malignant tumors of the ovary. Both were diffuse microtumor emboli in the pulmonary arteries of elderly individuals. We present a teen-aged patient who died suddenly due to a massive tumor embolism of the right main pulmonary artery after a two-year remission of an endodermal sinus tumor of the ovary. Upon her first admission, she was treated with radical operation and insufficient chemotherapy. Two years later, she was readmitted to our hospital because of the sudden onset of dyspnea and shock; and she died 5 hours after readmission. A case of endodermal sinus tumor of the ovary with fatal pulmonary tumor embolism is described.

Scanning electron microscopy of endometriotic lesions in the pelvic peritoneum and the histogenesis of endometriosis.

OBJECTIVE: To determine whether the epithelium of an endometriotic lesion has eutopic endometrial glandular epithelium morphology or not for the histogenesis of endometriosis. METHOD: Scanning electron microscopy (SEM) of the endometrium was done for 25 cases. Histologically proven endometriotic lesions of 10 of these 25 cases were processed for SEM. Peroneum samples of another 15 cases without histological endometriosis were also studied. RESULT: Three of 10 cases with histologically proven endometriotic lesions revealed endometrium-like morphology by SEM, whereas normal appearing peritoneum without histological endometriosis in 15 cases showed no endometrium-like structures by SEM. CONCLUSION: Although abovementioned results did not support retrograde menstruation and implantation, they suggested a possibility of derivation from the endometrium.

Ultrastructural study of glandular epithelium in adenomyosis in comparison with those of proliferative endometrium and well-differentiated endometrial cancer.

Adenomyotic glandular tissue from five patients underwent electron microscopic investigation to observe its ultrastructural characteristics. The adenomyotic epithelium was compared with that of proliferative normal epithelium (two patients) and well-differentiated endometrial adenocarcinoma (two patients). The results revealed that morphologically the adenomyotic glandular epithelium is somewhat less differentiated than proliferative endometrium and that its cytoplasmic organelles have some similarities with those of endometrial cancer. Whether these similarities predispose the adenomyotic glandular tissue to malignant degeneration remains to be elucidated.

Effects of interferon on intrahepatic human leukocyte antigens and lymphocyte subsets in patients with chronic hepatitis B and C.

We investigated the effects of interferon therapy on hepatocyte human leukocyte antigen class I and class II antigen expression and intrahepatic lymphocyte subsets in patients with chronic viral hepatitis B (n = 11) and C (n = 10). Interferon-alpha was administered intramuscularly in doses ranging from 3 to 18 million international units daily for 4 wk. Liver biopsy specimens were obtained just before and immediately after treatment, and the specimens were stained by the indirect immunoperoxidase method for evaluation of human leukocyte antigen expression and lymphocyte subsets. Before therapy, no significant difference was noted between hepatitis B and C in human leukocyte antigen class I antigen expression on hepatocytes or in the lymphocyte subsets in the intralobular and portal areas. After interferon-alpha treatment, hepatocyte expression of human leukocyte antigen class I antigens and serum beta 2-microglobulin levels were virtually unchanged in chronic viral hepatitis C patients, but both were increased in chronic viral hepatitis B patients. Human leukocyte antigen class II antigens were not expressed during treatment. The mean number of intralobular CD3+ and CD8+ cells and the mean serum ALT level decreased significantly in chronic viral hepatitis C patients (p less than 0.05) but not in chronic viral hepatitis B patients. The mean number of intralobular CD4+ cells was unaffected by interferon therapy in both groups. In all 21 patients, the changes in CD8+ cell numbers paralleled the changes in serum ALT levels. Our findings suggest that T-cell cytotoxicity may play an important role in hepatocyte damage in both chronic viral hepatitis C and chronic viral hepatitis B and that the response to interferon-alpha differs in these two types of hepatitis.

Comparison of ultrastructure adenomyotic glandular epithelium with that of attached epithelium of inner wall of chocolate cyst, with particular reference to histogenesis of endometriosis.

Clinically we rather frequently treat infertile women with endometriosis, either external or internal. Nowadays the study of the histogenesis of endometriosis is urgently required by patients who suffer from sterility because of endometriotic foci. To evaluate the histogenesis of endometriosis, we first electron microscopically examined the adenomyotic glandular epithelium as a distinct candidate for endometriosis interna. Furthermore we studied the chocolate cyst of the ovary as representative of endometriosis externa which is very important from the standpoint of the infertility clinic. In this report we carefully compared the ultrastructure of the adenomyosis with the ovarian chocolate cyst, and endeavoured to explore the histogenesis of endometriosis through this ultrastructural comparison. As a result it was found that the nuclear membrane showed tremendous irregularity in the ovarian chocolate cyst compared with the smooth nuclear membrane in the adenomyotic glandular epithelium.

[The study of cyclic maintenance chemotherapy with cisplatin, adriamycin, and cyclophosphamide (cyclic PAC chemotherapy) in patients with advanced ovarian cancer].

The efficacy of two methods of chemotherapy in the treatment of patients with advanced ovarian cancer was compared on the basis of survival curves; one consisted of remission induction therapy alone with a combination of cisplatin (CDDP), adriamycin (ADM) and cyclophosphamide (CPM) (induction PAC therapy), and the other consisted of induction PAC therapy and additional maintenance therapy with cyclic PAC (cyclic PAC therapy). The subjects of the study were patients with advanced ovarian cancer in stages III and IV. Sixty-eight patients received induction PAC therapy alone and seventeen patients received both induction and cyclic PAC therapy. Demographic factors such as age at initial presentation, the stage of cancer (III or IV), surgical procedure, histological classification, number of courses of induction PAC, response rate, site of residual tumor after surgery and induction PAC therapy, and reduction rate of CA125 were compared in the two groups. When analyzed by the chi 2 test, none of these factors was significantly different in the two groups. Patients in the induction PAC therapy group received a median total dosage of CDDP 360 mg, ADM 235mg, and CPM 2.246mg. Patients in the cyclic PAC therapy group received CDDP 592mg, ADM 490mg, and CPM 4.642mg. Thus, the dosage of anticancer agents administered to the latter group was about twice as great as that administered to the former group. According to the Kaplan-Meier method, survival rates for the induction PAC therapy group were 88.2% for one year, 50.0% for two years, 28.0% for three years, and 8.8% for five years. The median survival period was 23 months.(ABSTRACT TRUNCATED AT 250 WORDS)