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.

Systemic Inflammation and Multimodal Biomarkers in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (Aß) and Tau) and exacerbates AD pathology. Neuroinflammation can also be induced by systemic influences (factors from outside the central nervous system). However, the role of systemic inflammation in AD pathophysiology is much less understood. Thus, our main objective in this study was to verify whether the presence of serum cytokines (IL-1ß, IL-6, IL-10, IL-12, and TNF-α) affects different AD biomarkers: Aß1-42 and Tau protein levels, hippocampal volumes (HV), and default mode network functional connectivity (DMN FC) in healthy elderly controls, amnestic mild cognitive impairment (aMCI) patients due to AD, and mild AD patients. To accomplish this, we acquired 3-T MRI, blood, and cerebrospinal fluid (CSF) samples from 42 healthy controls, 55 aMCI patients due to AD, and 33 mild AD patients. Comparing the groups, we found that the mild AD patients presented smaller HV, disrupted DMN FC, and proportionally less IL-1ß than the controls. The aMCI patients only differed from the controls in DMN FC. In intra-group comparison, aMCI and mild AD with detectable levels of cytokines (TNF-α, IL-1ß, IL-10, and IL-12) had decreased DMN FC. On the other hand, patients with detectable levels of IL-10 and IL-12 presented a more favorable AD biomarkers profile (larger HV, more CSF Aß1-42, and less p-Tau), indicating a possible protective role of these ILs. Our findings indicate a possible relationship between systemic inflammation with DMN FC disruption, hippocampal atrophy, and CSF protein levels in the subjects with mild AD and aMCI.

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.

Combinatory effects of androgen receptor deficiency and hind limb unloading on bone.

Male sex hormones play a critical role in regulation of bone metabolism. In male mice lacking androgen receptor (AR), osteopenia and high turnover state in bone remodeling have been reported. However, androgen receptor's role in disuse-induced osteopenia is not known. Therefore, we examined the effects of AR deficiency on unloading-induced bone loss. Wild type or androgen receptor deficient mice (ARKO) were subjected to hind limb unloading (HU) or normal housing (Control). The groups of mice were as follows; wild type control mice (Group WT-Cont), ARKO control mice (Group ARKO-Cont), wild type HU mice (Group WT-HU), and ARKO-HU mice (Group ARKO-HU). HU reduced cancellous bone mass in ARKO (ARKO-HU) by about 70% compared to ARKO-Cont and this reduction rate was over two-fold more than that of wild type (WT-HU) (reduction by less than 30% compared to WT-Cont). Combination of ARKO and HU (ARKO-HU) resulted in the least levels of cortical bone mass and bone mineral density among the four groups. ARKO-HU group indicated the highest levels of systemic bone resorption marker, deoxypyridinoline. Osteoclast development levels in the cultures in ARKO-HU derived bone marrow cells were the highest among the four groups. These data suggest that combination of androgen receptor deficiency and hind limb unloading results in exacerbation of disuse-induced osteopenia due to the enhanced levels of bone resorption.

Cloning a novel developmental regulating gene, Xotx5: its potential role in anterior formation in Xenopus laevis.

The vertebrate Otx gene family is related to otd, a gene contributing to head development in Drosophila. In Xenopus, Xotx1, Xotx2, and Xotx4 have already been isolated and analyzed. Here the cloning, developmental expression and functions of the additional Otx Xenopus gene, Xotx5 are reported. This latter gene shows a greater degree of homology to Xotx2 than Xotx1 and Xotx4. Xotx5 was initially expressed in Spemann's organizer and later in the anterior region. Ectopic expression of Xotx5 had similar effects to other Xotx genes in impairing trunk and tail development, and especially similar effects to Xotx2 in causing secondary cement glands. Taken together, these findings suggest that Xotx5 stimulates the formation of the anterior regions and represses the formation of posterior structures similar to Xotx2.

Expression of Xenopus T-box transcription factor, tbx2 in Xenopus embryo.

We report here the cloning and expression of the Xenopus orthologue of the T-box transcription factor gene Tbx2 (optomotor-blind in Drosophila). Tbx2 is first detected in the ventral mesodermal cells just above the yolk plug at late gastrula. At the neurula stage it is strongly expressed in the cement gland, dorsal root ganglia, and otic vesicle region. At the tailbud stage strong Tbx2 expression is observed in the dorsal part of the optic cup and trigeminal ganglia, and it is also expressed in the branchial arches, heart anlage, nasal pit, proctodeum, and the region around the pronephros.

Expression of Brachyury-like T-box transcription factor, Xbra3 in Xenopus embryo.

The Xenopus Brachyury-like Xbra3 gene is a novel T-box gene that is closely associated with Xenopus Brachyury. The expression pattern of Xbra3 during development is similar to that of Xbra. During gastrulation Xbra3 is expressed in the marginal zone, with a gradient of increasing expression from ventral to dorsal. In the early neurula stage Xbra3 is expressed in the notochord and posterior mesoderm, but by the tailbud stage its expression is restricted to the forming tailbud and the posterior portion of the notochord.

Molecular cloning of XNLRR-1, a Xenopus homolog of mouse neuronal leucine-rich repeat protein expressed in the developing Xenopus nervous system.

We report the isolation and characterization of a Xenopus sequence, XNLRR-1, that is closely related to a gene for mouse neuronal leucine-rich repeat protein (NLRR-1). The cDNA clone is 4179 bp long and encodes a putative transmembrane glycoprotein of 718 amino acids, containing 12 leucine-rich repeats followed by one C2-type immunoglobulin-like domain and one fibronectin type-III repeat. XNLRR-1 is transcribed mainly in the developing eye area and the ventricular zone from diencephalon to hindbrain and slightly in spinal cord in Xenopus tadpoles. The similarity of the XNLRR-1 gene to other known cell adhesion molecules, together with the expression pattern, suggests that XNLRR-1 is involved in interactions at the neuronal cell surface.

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.