A critical role of sterols in embryonic patterning and meristem programming revealed by the fackel mutants of Arabidopsis thaliana

Here we report a novel Arabidopsis dwarf mutant, fackel-J79, whose adult morphology resembles that of brassinosteroid-deficient mutants but also displays distorted embryos, supernumerary cotyledons, multiple shoot meristems, and stunted roots. We cloned the FACKEL gene and found that it encodes a protein with sequence similarity to both the human sterol reductase family and yeast C-14 sterol reductase and is preferentially expressed in actively growing cells. Biochemical analysis indicates that the fk-J79 mutation results in deficient C-14 sterol reductase activity, abnormal sterol composition, and reduction of brassinosteroids (BRs). Unlike other BR-deficient mutants, the defect of hypocotyl elongation in fk-J79 cannot be corrected by exogenous BRs. The unique phenotypes and sterol composition in fk-J79 indicate crucial roles of sterol regulation and signaling in cell division and cell expansion in embryonic and post-embryonic development in plants.     

Sinonasal teratocarcinosarcoma: ultrastructural and immunohistochemical evidence of neuroectodermal origin

The authors report a case of sinonasal teratocarcinosarcoma in a 37-year-old man, which was located in the anterior skull base and extended to the right nasal cavity and paranasal sinuses. The tumor was surgically resected twice, but it could not be removed completely. Microscopically, it was mainly composed of primitive cell nests within a moderately cellular stroma. The components of squamous cell epithelia with focal teratoid appearance and adenocarcinomatous differentiation were observed. There were many rhabdomyoblasts scattered in the nests and stroma. Ultrastructurally, the primitive cells had many neural processes with parallel microtubules, resembling olfactory neuroblastoma. Rhabdomyoblasts showed various degrees of skeletal muscle differentiation. Some of the stromal spindle cells had actin filaments with dense patches and dense core granules. Immunohistochemically, the primitive cells were positive for epithelial markers, neuron-specific enolase, synaptophysin, and myogenic regulatory proteins. The rhabdomyoblasts showed immunoreactivity for myoid markers, cytokeratin, epithelial membrane antigen, and synaptophysin. Most of the stromal spindle cells were positive for smooth muscle actin, neuron-specific enolase and synaptophysin. The immunohistochemical and ultrastructural findings suggest that primitive cells had the most primitive phenotype of placodes, and support the possibility that sinonasal teratocarcinosarcoma is essentially a neuroectodermal tumor with divergent differentiation.     

Chondrosarcomatous differentiation in metastatic deposit of serous papillary cystadenocarcinoma

A rare case of serous papillary cystadenocarcinoma of the ovary showing chondrosarcomatous differentiation in a metastatic deposit late in the clinical course is reported. A 49-year-old female underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for bilateral ovarian tumors. Histological diagnosis was serous papillary cystadenocarcinoma of both ovaries with lymph node metastasis. After six courses of chemotherapy, she was confirmed to be in complete remission following a second laparotomy. Following additional chemotherapy, a third laparotomy disclosed swollen left inguinal lymph nodes. In one of these nodes, approximately 5.0 cm in greatest diameter, the predominant histological features were: chondrosarcoma of the bone and soft tissue, with small foci of serous papillary adenocarcinoma and squamous epithelium. A histological transition between mesenchymal and epithelial areas was identified. Immunohistochemical positivity for broad-spectrum cytokeratin (AE1/AE3), vimentin, epithelial membrane antigen, and S-100 protein was observed in both chondrosarcomatous and epithelial areas. The current evidence may suggest that the chondrosarcomatous differentiation was derived from the metastatic epithelial component.     

Short-term and long-term stimulation of Na+−H+ exchange in cortical brush-border membranes during compensatory growth of the rat kidney

The effect of unilateral nephrectomy on Na⁺–H⁺ exchange in rat renal cortical brush-border membrane vesicles (BBMV) was studied by the method of acridine orange fluorescence quenching. The exchanger activity in BBMV from remnant kidney increased rapidly by 70–75% within first 30 min following uninephrectomy. Only a slight further increase was found in later stages of renal growth, i.e. 30 min to 7 days following uninephrectomy. The changes in antiporter activity were restricted toV _max, whereas theK _m for Na⁺ was similar in control and compensatory growing kidney. The increase of Na⁺–H⁺ exchange at 15 min was not affected by actinomycin D in vivo, whereas the increase at 48 h was completely abolished indicating that protein synthesis could be involved in the late, but not in the initial stimulation of renal Na⁺–H⁺ exchange. The late, but not the initial stimulations of Na⁺–H⁺ exchange were associated with elevated activities of cortical (Na⁺+K⁺)-ATPase indicating that changes in antiporter activity precede those in the (Na⁺+K⁺)-pump. The early stimulation of Na⁺–H⁺ exchange in BBMV in one kidney was induced also by the occlusion of blood flow through the contralateral kidney for 15 min, without removing it. Thirty min after the occlusion was removed and the reflow established, the Na⁺–H⁺ exchange in BBMV from the intact kidney decreased to the control values. The observed modulations in renal Na⁺–H⁺ exchanger may be regulated by phosphorylation-dephosphorylation events. In support, the concentration of a well known protein kinase C activator, 1,2-diacylglycerol, in the cortical tissue of the remnant kidney increased up to 100% within 5 min following unilateral nephrectomy and preceded the increase in Na⁺–H⁺ exchange. The early stimulation of Na⁺–H⁺ exchange may be a trigger in initiating the kidney growth.     

Expression of matrix metalloproteinase-2 (MMP-2) and of membrane-type-1-matrix metalloproteinase (MT1-MMP) in transitional cell carcinoma of the upper urinary tract

Tumor cell invasion and metastasis are biologically dependent on the proteolytic destruction of surrounding matrix components. Matrix metalloproteinase-2 (MMP-2) is able to cleave type IV collagen, and membrane-type-1-matrix metalloproteinase (MT1-MMP) induces activation of proMMP-2. We investigated the expression of MMP-2 and MT1-MMP using in situ hybridization and immunohistochemistry in 102 cases of transitional cell carcinoma of the upper urinary tract (TCC-UUT). A positive expression of each metalloproteinase was recognized in all samples and was apparent within the cytoplasm of tumor epithelial cells and/or stromal cells situated at the interface between tumor and stroma. Our analysis of clinicopathologic findings showed a relationship between MMP-2 and MT1-MMP expression and stage. The correlation between the MMP-2 protein staining score for tumor epithelial cells and overall survival rate reached significance in the univariate analysis. However, only stage was associated with disease-free and overall survivals in the multivariate analysis. In conclusion, the detection of MMP-2 and MT1-MMP would appear to be of limited value in informing the prognosis of TCC-UUT.     

Clinicopathological study of a hilar nodule in the livers of long-term survivors with biliary atresia

With the application of liver transplantation for patients with biliary atresia (BA), we have had the opportunity to review the clinicopathologic features of the native livers from 10 transplanted BA patients. A single large nodule at porta hepatis (hilar nodule) was noted in three of 10 patients, and an ill-defined nodule-like lesion at porta hepatis was present in two other patients. The three BA patients with hilar nodules were long-term survivors, compared to the patients with nodule-like and those without nodules. The hilar nodules measured between 5.0 cm and 8.0 cm and histologically, they were partly surrounded by fibrous septa with relatively well-preserved liver architectures and fewer inflammatory cells at the portal triads when compared to the surrounding cirrhotic lesions. No nuclear or cellular atypia was observed. Proliferating cell nuclear antigen labeling index was higher in the surrounding cirrhotic lesions than the hilar nodules. The nodule-like lesions at porta hepatis also showed similar light microscopic and immunohistochemical features as the hilar nodules. These hilar nodules did not seem to contain any malignant potential. The benign histology with relatively well-preserved liver architecture and the preferential site of occurrence at porta hepatis where bile seemed to flow more smoothly, suggested possible residues of less-affected hepatic tissues.     

Vacuolated cell mesothelioma of the pericardium resembling liposarcoma: a case report

We report a case of localized pericardial mesothelioma with unusual histological features in a 44-year-old woman. Her radiological imagings showed an 11-cm pericardial tumor, between the heart and aortic arch. Microscopically, the tumor was predominantly composed of vacuolated cells and vaguely reminiscent of well differentiated "lipoma-like" liposarcoma, but only small foci of the tumor showed the papillotubular configuration. Histochemically, the tumor cells contained hyaluronic acid in the vacuoles but no lipids. Immunohistochemically, they showed immunoreactivity for cytokeratin, calretinin, vimentin, and epithelial membrane antigen. Ultrastructural study showed that the vacuoles of the tumor cells were intracytoplasmic lumina. The intracytoplasmic lumina and the surface membranes of the tumor cells had many long and slender microvilli with focal bush-like appearance. Desmosomes between adjacent cells were occasionally observed. To our knowledge, this is the first case report of epithelial type mesothelioma predominantly composed of vacuolated tumor cells, microscopically mimicking liposarcoma.