Myxoid leiomyoma of the vulva: a case report

A case of myxoid leiomyoma of the vulva in a 29-year-old pregnant woman was encountered. The leiomyoma was a well-circumscribed solitary mass measuring 4 x 4 x 4.5 cm and, microscopically, composed of spindle-shaped cells and an abundant matrix characterized by a myxoid change. These spindle-shaped cells were arranged in a plexiform pattern. The cytological findings on the aspiration biopsy and the histological features were well correlated. Review of the reported smooth muscle tumors of vulval origin indicates that the myxoid change occurs invariably in younger women and, in some cases, association with pregnancy is suggested.     

Alterations of myoepithelial cells in the rat mammary gland during pregnancy, lactation and involution, and after estradiol treatment

Hormone-induced alterations of myoepithelial cells in the mammary gland have not been fully investigated. The aim of the present study was to examine whether myoepithelial cells are altered in response to hormonal conditions. The immunohistochemical findings of smooth muscle actin for myoepithelial cells were studied during pregnancy, lactation and involution, and after estradiol dipropionate (ED) treatment (50, 500, 1000 microg/kg per week for 1-4 weeks) using a total of 71 Wistar female rats. Myoepithelial cells showed a stratified appearance around ducts during pregnancy, extended cytoplasmic processes with wider distance during lactation, and vacuolated cytoplasm after weaning. ED treatment (50-1000 microg/kg per week) for 1 week increased myoepithelial cells to a variable degree, achieving a level similar to that in pregnancy, but ED treatment for 4 weeks reduced them as the dose elevated. The present study showed that the myoepithelial cells became hyperplastic or hypertrophic by low-dose ED treatment within the physiological range, while weaning pups, and excess high-dose ED treatment beyond the physiological range or prolonged ED treatment induced reduction of the myoepithelial cells. Results indicate that myoepithelial cells themselves are also altered by hormonal conditions coordinating the mammary gland development.     

A Histopathological Study of Multi-hormone Producing Proliferative Lesions in Estrogen-induced Rat Pituitary Prolactinoma

Rats with estrogen-induced prolactin-producing pituitary adenoma (E2-PRLoma) have been employed as an animal model of human PRL-producing pituitary adenoma in a large number of studies. Presently, we found that long-term administration of estrogen to SD rats resulted in the development of E2-PRLomas, some of which included multi-hormone producing nodules. We herein report results of histopathological analyses of these lesions. PRLoma models were created in female SD rats by 22 weeks or longer administration of a controlled-release preparation of estradiol at a dose of 10 mg/kg/2 weeks. Ten of the 11 PRLoma model rats had proliferative nodular lesions composed of large eosinophilic cells like gonadotrophs inside the PRLoma. These lesions were positive for PRL, TSHβ, and α subunits and were negative for GH, LHβ, ACTH, and S-100. Double immunostaining revealed that these large eosinophilic cells showed coexpression of PRL and TSHβ, PRL and α subunits, and TSHβ and α subunits. Those results clarified that long-term estrogen administration to female SD rats induced multi-hormone producing neoplastic pituitary nodules that expressed PRL, TSHβ, and α subunits. We studied these neoplastic nodules obtained by laser microdissection to acquire findings similar to those of the immuno­histochemical analysis. We consider that this animal model is useful for pathogenesis analyses and therapeutic agent development concerning human multi-hormone producing pituitary adenomas.     

Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat

BACKGROUND AND PURPOSE

The P2X7 receptor is implicated in inflammation and pain and is therefore a potential target for therapeutic intervention. Here, the development of a native tissue radioligand binding, localization and ex vivo occupancy assay for centrally penetrant P2X7 receptor antagonists is described.

EXPERIMENTAL APPROACH

Autoradiography studies using the P2X7 antagonist radioligand [³H]-A-804598 were carried out in rat brain and spinal cord. Subsequent in vitro binding and ex vivo occupancy assays were performed using rat cortex homogenate.

KEY RESULTS

P2X7 expression was shown to be widespread throughout the rat brain, and in the grey matter of the spinal cord. In binding assays in rat cortex homogenate, ∼60% specific binding was achieved at equilibrium. In kinetic binding assays, k_on and k_off values of 0.0021·min⁻¹·nM⁻¹ and 0.0070·min⁻¹ were determined, and the K_d derived from kinetic measurements was consistent with that derived from saturation analysis. Novel P2X7 antagonists inhibited the binding of [³H]-A-804598 to rat cortex P2X7 receptors with K_i values of <40 nM. In an ex vivo occupancy assay, a P2X7 antagonist dosed orally to rats caused a concentration-dependent inhibition of the specific binding of [³H]-A-804598 to rat cortex.

CONCLUSIONS AND IMPLICATIONS

The present study describes the development of an assay that allows localization of P2X7 receptors, the measurement of the binding affinity of P2X7 receptor antagonists in native tissue, and provides a means of determining central P2X7 receptor occupancy. These assays could form an important part of a P2X7 drug discovery programme.     

Acceleration of the proliferative activity of esophageal carcinoma with invasion beyond the muscularis mucosae; immunohistochemical analysis using MIB-1 for the Ki-67 antigen

Squamous cell carcinoma of the esophagus with cancer invasion beyond the muscularis mucosae is known to have lymph node metastasis and lymphatic or blood vessel invasion compared with intramucosal carcinoma. In submucosal and T2-3 carcinoma, lymph node and lymphatic/vascular involvement are shown more frequently, leading to a poor prognosis. Therefore, we examined proliferative activity of esophageal squamous cell carcinoma including early carcinoma in relation to clinicopathological findings. 77 cases of esophageal squamous cell carcinoma, including 23 cases of mucosal carcinoma (Tis+T1a), 35 cases of submucosal carcinoma (T1b) and 19 cases of advanced invasive carcinoma (T2+T3) undergoing surgical resection without preoperative treatment were studied using monoclonal antibody MIB-1 for Ki-67 antigen immunohistochemically, and the labeling index (LI) was calculated. The LI of MIB-1 positive nuclei correlated with the depth of cancer invasion was significantly increased in the cancer invading beyond the musculais mucosae. The LI at the invasive tip was significantly higher than that at the core of differentiated carcinoma. The LI values at both invasive tip and core of poorly differentiated carcinoma were higher than those of differentiated carcinoma with significant difference. The LI at the invasive tip of the carcinoma with lymph node metastasis or lymphatic invasion was significantly higher than that without them. Proliferative activities of esophageal cancer cell, immunostaining with MIB-1, had correlations to depth of tumor invasion, differentiation, lymph node metastasis and lymphatic invasion with significant difference. But if invading deeper than m3, the proliferative activity did not increase anymore.     

A huge fecalith associated with dialysis-related gastrointestinal amyloidosis

A 60-year-old man who had been receiving dialysis for more than 30 years was admitted for treatment of cellulitis in his right thigh on November 7, 2003. He suffered from an ileus on December 14 and was found to have a huge, 7-cm-diameter, well-circumscribed fecalith, incarcerated at the splenic flexure of the colon. It was proving difficult to pass this naturally and surgical removal was thought to be too risky. Using a colonoscope and a water-jet probe, the fecalith was broken up; the ileus then improved and the patient was able to take oral fluids. Unfortunately, he died of cardiac failure on February 13, 2004. We conducted an autopsy, with his family's consent, and found generalized amyloidosis. Deposits of amyloid were seen in all layers of the colon. Because of this, we hypothesized that peristalsis had been poor and this had led to paralytic ileus due to stasis, which, in turn, had led to the formation of the huge fecalith. In Japan it is not rare for a patient to be on dialysis for more than 25 years and it may be that this is a cause of generalized amyloidosis. There have been no such cases of fecalith associated with gastrointestinal amyloidosis described previously, which is why we decided to report this case here.