Clinicopathological study of invasive extramammary Paget's disease: subgroup comparison according to invasion depth.

BACKGROUND: Extramammary Paget's disease (EMPD) is a distinct form of malignant skin neoplasm. Invasive EMPD is relatively rare and its detailed histopathological features have not been investigated to date. METHODS: Surgical specimens were obtained from 51 patients with primary invasive EMPD. Clinical data including lymph node status were retrieved from the patients' medical records. Cases were divided into subgroups according to invasion depth: dermal invasion ≤ 1 mm (minimal invasion) and dermal invasion > 1 mm in depth. Histological patterns (nodular/glandular pattern or micronodular pattern), lymphatic/venous invasion, mitosis and lymph node status were compared between the two groups. RESULTS: The invasive EMPDs included 26 cases (51.0%) with dermal invasion ≤ 1 mm (minimal invasion) and 25 cases (49.0%) with dermal invasion > 1 mm in depth. Lymph node metastasis was detected in 2/26 (7.7%) patients with minimally invasive EMPD. Nodular/glandular pattern (72.0%), lymphatic/venous invasion (52.0%), mitosis (88.0%) and nodal metastasis (88.0%) were all significantly more frequent in cases with dermal invasion > 1 mm, compared to EMPDs with dermal invasion ≤ 1 mm (minimal invasion) (P < 0.001). CONCLUSION: These results suggest that invasive EMPD can be divided according to invasion depth, with a cut-off depth of 1 mm. This might represent the basis for a useful, EMPD-specific staging system.

A morphological study of granulomas induced by subcutaneous injection of leuprorelin acetate.

Leuprorelin acetate-induced granulomas in subcutaneous injection sites have been occasionally reported, but there have been no detailed morphological examinations. Histopathology of leuprorelin acetate-induced granulomas in six patients was studied, and one of them was evaluated by electron microscopy. Study using haematoxylin and eosin staining revealed that there were many intracytoplasmic vacuoles in the granulomas and degeneration of fat tissue. Ultrastructurally, electron-lucent spherical bodies (microcapsules of leuprorelin acetate products) were observed in the granuloma cells. Needle-shaped crystalloid structures in lipid droplets (degenerated lipid droplets) were observed in the granuloma cells and fat tissue. Degeneration of fat tissues caused by leuprorelin acetate is one of main factors responsible for granuloma formation.

Detection of Pb-LIII edge XANES spectra of urban atmospheric particles combined with simple acid extraction.

Pb-LIII edge XANES spectra of atmospheric particles are directly obtained by fluorescent XAFS spectroscopy using a 19-element solid state detector (SSD). Particulate sample was collected on a quartz fiber filter using a high-volume air sampler, and the filter was cut into small pieces (25x25 mm). Then, surface layer of the filter piece was scaled and accumulated in order to enhance the particle density per filter unit. Use of 10 pieces of the surface layer enables the measurement of Pb-LIII edge XANES spectra on beamline BL01B1 at SPring-8, Hyogo, Japan. The shape of the Pb-LIII edge XANES spectra of the particulate sample is similar to the shapes of the spectra for PbS, PbCO(3), PbSO(4) and/or PbCl(2). Additionally, the filter sample is also divided into water-soluble, 0.1 M HCl-extractable, and residual fractions of Pb compounds by a simple acid extraction procedure. We discuss the possibility of Pb speciation in the particulate samples with combination of highly sensitive XANES spectroscopy and simple acid extraction.

Primary effusion lymphoma with skin involvement.

Primary effusion lymphoma (PEL) was once defined as a body cavity-based lymphoma without identifiable contiguous tumour mass, but is now recognised as an independent clinicopathological entity. The case of a 67-year-old Japanese woman with PEL is reported, in which the clinical findings showed a pericardial effusion and multiple erythema on the hypogastrium and inguinal region. The histopathological findings showed a diffuse infiltration of large neoplastic B cells from the dermis to the subcutis. After the disappearance of pericardial effusion without any treatment, she received several rounds of chemotherapy to resolve the skin eruption, but she finally died from multiple organ failure. No tumour mass was observed during the course of her disease.

Significance of AgNOR counts for distinguishing carcinoma from adenoma and hyperplasia in parathyroid gland.

Nucleolar organizer region proteins, which can be stained and visualized by an argyrophil technique (AgNORs), are markers of cell activities, such as DNA transcription and proliferation, and they are useful for differential diagnosis between benign and malignant tumors. We counted both AgNOR numbers in 25 parathyroid lesions (three carcinomas, 11 adenomas, 10 hyperplasias, and one hyperplasia with carcinoma) to determine if the AgNOR number could be useful as a diagnostic aid in parathyroid neoplasms and hyperplasias, because it is often difficult to histopathologically distinguish among these lesions. The AgNOR numbers were significantly higher in carcinomas (3.18 +/- 0.05) than in adenomas (1.67 +/- 0.30, P < .001) or hyperplasias (1.85 +/- 0.16, P < .001), but there was no significant difference between adenomas and hyperplasias. These results suggest that AgNORs may be useful as an adjunct to discriminating carcinomas from adenomas or hyperplasias in the parathyroid gland.

Radiation-induced crosslinks between carboxylic acids and compounds of biological interest.

Various carboxylic acids having short carbon chains (10(-4) or 5 X 10(-4) M) mixed with serum albumin or DNA (1 mg/ml) were irradiated in phosphate buffer solution (10(-3) M, pH 7.0) with 60Co gamma rays. Maleic acid and nicotinic acid showed high binding activity resulting from having an unsaturated double bond and an aromatic ring, respectively. Sodium salts of C18 fatty acids (0.5 mg/ml) such as stearate, oleate, linoleate, and linolenate were also irradiated in the presence of amino acids or nucleobases (10(-4) or 5 X 10(-4) M) in the same buffer solution. The binding yield increased with the increase in the number of double bonds indicating participation of double bonds in the binding.

Enhanced expression of endothelin-1 and endothelin-converting enzyme-1 in acute hypoxic rat aorta.

Deeply anesthetized male Wistar rats were perfused by Hanks' balanced salt solution bubbled with either 95%air and 5%CO2 (normoxic group) or 95%N2 and 5%CO2 (hypoxic group) from the thoracic aorta for 30 min, and the isolated abdominal aortae from both groups were used for electron microscopy, immunocytochemistry of endothelin (ET)-1 and ET-converting enzyme (ECE)-1, and in situ hybridization of preproET-1 mRNA. A remarkable increase in the number of Weibel-Palade (WP) bodies, storage sites of ET-1 and ECE-1, occurred in the hypoxic group when compared to the normoxic group. Immunoreactivities for ET-1 and ECE-1, and signals for preproET-1 mRNA were seen along the endothelia of both groups, but the intensities were significantly elevated in the hypoxic group. The increase in the number of ECE-1 immunoreactive gold particles was noticed especially in WP bodies in the hypoxic group. These findings indicate the enhancement of preproET-1 synthesis in the aortic endothelial cells as well as the acceleration of ET-1 processing in increased WP bodies in such cells in an experimentally hypoxic condition of the rat aortae.

Inhibition of phase III activity by acid in canine stomach.

Very few phase III activity of the interdigestive migrating contractions (phase III) occurs in the stomach of fasted duodenal ulcer patients. But the mechanism is not well understood. In this study, we studied the effect of gastric and duodenal acidification on the spontaneous phase III activity in the upper gastrointestinal tract of conscious dogs. Gastric and duodenal motor activity in 5 conscious dogs was monitored by means of chronically implanted force transducers. Intragastric pH changes were measured by placing a pH glass electrode in the gastric antrum. Intragastric and intraduodenal acidification was achieved by i.v. infusion of histamine, and by intragastric and intraduodenal instillation of acidic solutions of different pHs. The plasma motilin concentrations were measured by radioimmunoassay. Histamine (40 micrograms/kg/h) inhibited spontaneous phase III activity, but the histamine-induced inhibition was completely prevented by pretreatment with famotidine, a potent histamine H2 receptor antagonist (0.3 mg/kg, i.v.). Intragastric acidification at pH 1.0 strongly inhibited spontaneous phase III activity, but an acidic solution at pH 2.0 had no effect in inhibiting phase III activity. Intraduodenal acidification at pH 1.0 also inhibited spontaneous phase III activity. Histamine injection and gastric and duodenal acidification at pH 1.0 strongly suppressed motilin release. It is concluded that gastric and duodenal acidification at pH 1.0 inhibits the occurrence of the spontaneous phase III activity, and the suppression of endogenous release of motilin due to gastric and duodenal acidification at pH 1.0 is involved in this inhibitory mechanism.

Inhibition of stress-stimulated colonic propulsion by alpha 2-adrenoceptor antagonists in rats.

Alpha2-adrenoceptor antagonists have been reported to stimulate colonic motor activity, but the effect on colonic motor dysfunction is unclear. We have investigated the effect of alpha 2-adrenoceptor antagonists on wrap-restraint stress-stimulated and normal colonic propulsion in rats. Colonic propulsion was evaluated by the transit of a charcoal marker along the colon. Faecal pellets output was also measured. A 30-min exposure to wrap-restraint stress starting 120 min after infusion of the charcoal marker significantly stimulated colonic transit with a concomitant increase in faecal pellets. Yohimbine and idazoxan, alpha 2-adrenoceptor antagonists, clonidine, an alpha 2-adrenoceptor agonist, and atropine suppressed wrap-restraint stress-stimulated colonic transit and faecal excretion in a dose-dependent manner. Ondansetron and YM060, 5-hydroxytryptamine3 (5-HT3) receptor antagonists, potently inhibited wrap-restraint stress-stimulated colonic transit, but only weakly inhibited faecal excretion. Neither alpha 2-adrenoceptor antagonists nor atropine had any significant effect on normal colonic transit, whereas clonidine and the 5-HT3 receptor antagonists inhibited it. alpha 2-Adrenoceptor antagonists as well as clonidine, atropine and 5-HT3 receptor antagonists inhibit the stress-induced colonic motor dysfunction in rats.

Effect of alpha-2 adrenoceptor antagonists on colonic function in rats.

We studied the effect of alpha-2 adrenoceptor antagonists on colonic function stimulated by water-avoidance stress, 5-hydroxytryptamine (5-HT), bethanechol and castor oil by comparison with the effects of atropine and a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, ondansetron. Yohimbine, idazoxan and atropine, but not ondansetron, significantly inhibited water-avoidance stress-stimulated faecal excretion. Yohimbine and idazoxan inhibited neither 5-HT- nor bethanechol-stimulated faecal excretion. In contrast, atropine inhibited both 5-HT- and bethanechol-stimulated faecal excretion and ondansetron inhibited 5-HT-stimulated faecal excretion. Yohimbine did not inhibit the incidence of diarrhoea induced by castor oil, but idazoxan significantly inhibited diarrhoea observed during a 1-h period after the administration of castor oil. Both atropine and ondansetron inhibited diarrhoea during a 2-h period after the administration of castor oil. These findings suggest that alpha-2 adrenoceptor antagonists specifically inhibit colonic motor function stimulated by stress in rats.