Cystic parathyroid adenoma with coexistent sarcoid granulomas

Summary A 55-year-old woman with sarcoidosis developed hyperparathyroidism that was associated with fluctuating serum calcium levels. Ultrasonography and a computed tomography (CT) scan of the neck demonstrated a cystic lesion in the lower posterior area of the left thyroid lobe. Histological examination after subsequent surgery revealed sarcoid granulomas within a parathyroid adenoma. The pathogenesis of this rare association is discussed.     

Malignant fibrous histiocytoma of the uterus

A primary, malignant pleomorphic giant cell tumor of the uterus was studied by light and electron microscopy. The tumor was characterized by spindle cells, plump epithelioid cells, pleomorphic giant cells, osteoclast-like giant cells, and foamy xanthomatous cells. Histochemically, tumor cells did not show either myogenic or epithelial characteristics. Immunohistochemically, tumor cells were devoid of evidence of desmin, cytokeratin, myoglobin, and lysozyme (muramidase), but vimentin was weakly positive, and alpha 1-antichymotrypsin was weakly positive in the cytoplasm of pleomorphic giant cells. Ultrastructurally, tumor cells did not show either myogenic or epithelial features, but they resembled a variant of malignant fibrous histiocytoma. The present case was classified as a storiform-pleomorphic and giant cell type of malignant fibrous histiocytoma of the soft tissues. The uterus is considered to be an additional possible site of malignant fibrous histiocytoma.     

Improvement of solubility and oral bioavailability of a poorly water-soluble drug, TAS-301, by its melt-adsorption on a porous calcium silicate

The aim of the present study was to improve the solubility and oral bioavailability of a poorly water-soluble drug, 3-bis(4-methoxyphenyl) methylene-2-indolinone (TAS-301), by its melt-adsorption on a porous calcium silicate, Florite RE (FLR), without any solvents. The melt-adsorbed products were prepared by two methods: the small-scale batch method and the twin screw extruder method. The drug was melted and adsorbed on FLR (i.e., "melt-adsorption"), above its melting point. Crystallinity of the drug in the melt-adsorbed product was estimated by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis. The dissolution test was conducted by the JP XIII paddle method. Oral absorption of the melt-adsorbed product was studied in fasted and fed dogs. The melt-adsorbed products prepared by the two methods were in powder forms. The drug existed in an amorphous state in the product and hardly recrystallized even after storing at a stressed condition (60 degrees C/80% RH for 3 days). The TAS-301 dissolution rate from the melt-adsorbed product was markedly enhanced compared with drug crystals. The area under the plasma concentration-time curve (AUC) and peak concentration (C(max)) values of the drug after dosing the melt-adsorbed product were significantly greater than those after dosing the drug crystals. The solubility and bioavailability of TAS-301 were improved by its melt-adsorption on FLR. The present findings suggest melt-adsorption is a useful technique for improving solubility and bioavailability of poorly water-soluble drugs.     

Eosinophilic myelitis associated with atopic diathesis: a combined neuroimaging and histopathological study

Histologically proven eosinophilic myelitis has rarely been reported except in connection with parasitism. To clarify its clinicopathological features, we conducted a nationwide survey of biopsy-proven eosinophilic myelitis of unknown cause throughout Japan. Six such cases were collected and studied immunologically and pathologically. All were young to middle-aged men. All showed a protracted and fluctuating course with mild disability for 3-25 (mean 12.5) months before biopsy. Magnetic resonance imaging revealed localized lesions of T2-high and T1-iso signal intensity with a partial gadolinium enhancement in all cases. Cerebrospinal fluid (CSF) examinations were completely normal except for modest pleocytosis in two cases. Eosinophilia was present in the peripheral blood in two cases but was absent from the CSF of all cases. In spite of the chronic nature of the disease, spinal cord pathology revealed very active lesions with marked cell infiltration consisting mainly of CD8(+) T cells and varying numbers of eosinophils in the perivascular areas and the parenchyma. Both the myelin and axons were severely disrupted in all cases. Moreover, eosinophil cationic protein (ECP), an activated eosinophil product, was heavily deposited in the tissues. All but one case had hyperIgEemia and mite antigen-specific IgE in the sera, and two had accompanying atopic disorders. The present study thus revealed idiopathic eosinophilic myelitis to be a localized and persistent inflammation of the spinal cord, with distinct clinicopathological features, that has a possible link to atopic diathesis.     

Cell type-selective expression of green fluorescent protein and the calcium indicating protein,yellow cameleon,in rat cortical primary cultures

A cell type-specific green fluorescent protein (GFP) expression system in rat cortical primary cultures has been developed for the fluorescence labeling of brain cells. Lipid-mediated transfection (lipofection) was employed, allowing the establishment of a convenient efficient system for the analysis of individual cells. To achieve cell type-specific labeling, GFP expression vectors containing the rat neuron-specific enolase (NSE) gene promoter, human glial fibril acidic protein (GFAP) gene promoter, human elongation factor (EF-1alpha) gene promoter, or human cytomegalovirus (CMV) immediate early promoter were constructed, and their specificities examined. Vectors containing the CMV or GFAP promoter resulted primarily in GFP expression in astrocytes, while those containing the EF1-alpha or NSE promoter resulted primarily in GFP expression in neurons. This labeling system was applied to the morphological analysis of living neurons and to cell type-selective calcium imaging. Confocal microscopy revealed that individual GFP-expressing neurons had processes, which were longer than 500 microm and bore spine-like protrusions. A calcium-indicating GFP variant, yellow cameleon (YC2.1), was expressed in the same system, and cell type-selective calcium imaging performed. On pharmacological stimulation, YC2.1-expressing neurons responded to depolarizing stimuli, but not to the metabotropic glutamate receptor agonist, trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (tACPD), while astrocytes responded only to tACPD.     

Primary neck management among patients with cancer of the oral cavity without clinical nodal metastases: A decision and sensitivity analysis

BACKGROUND: A standardized neck management strategy for oral cancer patients without clinical nodal metastases remains to be established. Consequently, a decision and sensitivity analysis of two neck management protocols, involving either prophylactic neck dissection or careful observation, was conducted using the Oral Cancer Registry of Kyushu, Japan. METHODS: We calculated probabilities of subclinical nodal metastases and 5-year survival using the registry data. A two-way sensitive analysis was conducted using the probabilities and parameters of the complete nodal metastasis resection rate (x) and a utility rating that describes the health state induced by dissection (y) compared with the neck condition in a careful-observation group. RESULTS: We solved the threshold curve for y and x for the expected utility between the two groups. The results showed that prophylactic neck dissection must guarantee a complete resection of subclinical nodal metastases with no disadvantage to health state to be evaluated as equally satisfactory as careful observation. CONCLUSIONS: Careful observation involving standardized systematic preoperative and postoperative screening of the neck seems preferable to prophylactic neck dissection for oral cancer patients without subclinical nodal metastases.     

Platelet-derived growth factor, basic fibroblast growth factor, and interferon gamma increase type IV collagen production in human fetal mesangial cells via a transforming growth factor-beta-dependent mechanism.

BACKGROUND: Glomerulosclerosis is characterized by glomerular accumulation of extracellular matrix following mesangial cell proliferation. The precise pathomechanism of glomerulosclerosis is still undetermined. Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (b-FGF) are known to be mitogenic for mesangial cells, and interferon gamma (IFN-gamma) is known to have an inhibitory effect on mesangial cell proliferation. We attempted to clarify the role of these cytokines on mesangial matrix production using cultured human fetal mesangial cells (HMC). METHODS: HMC were incubated with these cytokines for 24-72 h and the levels of type IV collagen and TGF-beta in the cell supernatants were measured by enzyme immunoassay. RESULTS: PDGF, b-FGF, and IFN-gamma stimulated type IV collagen production by HMC in a dose- and time-dependent manner. The anti-TGF-beta neutralizing antibody clearly inhibited their stimulatory effect on type IV collagen production. PDGF and b-FGF also stimulated TGF-beta production by HMC in a dose-dependent manner, although IFN-gamma did not. CONCLUSION: PDGF, b-FGF, and IFN-gamma stimulate type IV collagen production in cultured HMC via a TGF-beta-dependent mechanism.     

Head-and-neck stages I and II extranodal non-Hodgkin's lymphomas: real classification and selection for treatment modality

PURPOSE: We re-evaluated histopathological specimens of head and neck early-stage extranodal non-Hodgkin's lymphoma (NHL) using the revised European and American lymphoma (REAL) classification, and also investigated the relationship between the clinical characteristics and histopathological classification in an attempt to evaluate the usefulness of this new classification system in selecting treatment modalities. MATERIALS AND METHODS: Between 1979 and 1995, 117 patients with histologically confirmed stages I and II NHL of head-and-neck extranodal regions were treated. Of these patients, 110 specimens were available for re-evaluation. Sixty-four patients had Stage I, and 46 had Stage II diseases. All but 3 had received radiation therapy, and 59 patients were also treated with intensive combination chemotherapy. RESULTS: There were 32 extranodal marginal-zone B-cell lymphomas, 57 diffuse large B-cell lymphomas, 11 peripheral T/NK-cell lymphomas, and 10 others. The 5- and 10-year cause-specific survival rates for all patients were 72% and 62%, respectively. Patients with extranodal marginal-zone B-cell lymphoma or other low-grade B-cell lymphomas demonstrated higher survival rates than patients with other lymphomas. Patients with peripheral T/NK lymphomas showed the lowest survival rate. CONCLUSION: The REAL classification accurately indicated the prognosis of patients with NHL. These results suggest that appropriate treatment modalities can be selected using this classification.