Polyol pathway activity in streptozotocin-diabetic rat lens

We have examined polyol pathway kinetics in the lenses of rats made diabetic with streptozotocin. At up to 11 days after diabetes induction, the lenses were isolated and subjected to 'pulse-chase' studies: the lenses were incubated with [13C]glucose and lens metabolism followed by [13C]nuclear magnetic resonance (NMR) spectroscopy. Proton NMR spectroscopy was also performed to measure the hexose monophosphate shunt (HMPS) activity. The results showed that (1) the activity of aldose reductase increased initially and decreased after 11 days of diabetes; (2) the fructose pool increased initially but started to decline after 3 days; (3) the HMPS activity increased nearly 40% immediately after diabetes induction; and (4) the turnover rates of glucose, alpha-glycerophosphate (GP), lactate, sorbitol, and fructose were 80.8 +/- 2.6, 10.1 +/- 1.4, 47.7 +/- 3.7, 7.9 +/- 0.9 and 5.2 +/- 2.2 nmol hr-1 lens-1 (34 mg wet weight lens-1), respectively. Up to 35% of lactate appeared to derive from the polyol pathway. Further, GP was rapidly metabolized, although its fate is currently unknown. These results reveal a far more complex pattern of glucose metabolism in the diabetic lens than that in lenses incubated in high glucose.     

Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma

We report a case of a 15-year-old girl with new onset seizures, who had a mixed dysembryoplastic neuroepithelial tumor (DNT) and ganglioglioma of the right parieto-occipital lobe. The tumor appeared well demarcated and exhibited a low T1 and a high T2 signal on magnetic resonance imaging. Architecturally it was in large part intracortical and multinodular, but also featured a leptomeningeal component. The former corresponded to DNT, a proliferation of oligodendroglia-like cells (OLCs) arranged in nodules, as well as comprising a diffuse internodular element featuring “floating neurons” in a mucoid matrix. The leptomeningeal portion of the lesion was a ganglioglioma consisting of large neurons and astrocytes in association with marked desmoplasia. Spacially, the two components abutted one another but appeared distinct. Immunohistochemistry showed the neurons of the ganglioglioma to be positive for class III β-tubulin, synaptophysin, and chromogranin A, whereas the astrocytic cells stained only for glial fibrillary acidic protein. Most OLCs in the DNT were positive for S-100 protein. This apparently mixed lesion suggests that a close histogenetic relationship exists between DNT and ganglioglioma. We postulate that the pluripotential progenitor cells residing in the subpial granular layer may have given rise to the cortical DNT and to the leptomeningeal ganglioglioma. To our knowledge, this is the first detailed histological, immunochemical and ultrastructural report of a mixed DNT and ganglioglioma. Received: 11 August 1997 / Revised, accepted: 24 November 1997     

A case of renal angiomyolipoma with bone formation

A case of renal angiomyolipoma with bone formation is reported. A 61-year-old woman was admitted to our hospital with one month history of fever. About 15 cm in diameter mass was palpated in her right lower abdomen. Plain abdominal roentgenography, ultrasonography and computed tomography showed marked calcification in the cephalic portion of the right kidney, tumors surrounding right kidney and another tumor in the right lower abdomen. All these tumors and the kidney constituted a big mass continuously, and no fatty component was demonstrated. Total excision of the mass including the kidney was performed. The mass was 30 X 24 X 10 cm in size and 3,240 g in weight. Histologically, the tumor was compatible to renal angiomyolipoma. But, radiopaque shadows which looked like calcification were disclosed to be bones, and fatty tissues were not seen so much. Therefore, the name "benign mesenchymoma" was thought to be more acceptable than angiomyolipoma in this case. Preoperative diagnosis of renal angiomyolipoma is the demonstration of fatty densities in the tumor, and the characteristic extrarenal development should also be taken into consideration. Furthermore, the bone formation of angiomyolipoma, which is very rare might be an important finding to angiomyolipoma.     

Use of a Paracorporeal Pneumatic Ventricular Assist Device for Postoperative Cardiogenic Shock in Two Children with Complex Cardiac Lesions

Pneumatic ventricular assist device (VAD) was utilized for cardiogenic shock after intracardiac operation in two children with complex cardiac anomalies based with single ventricle. In the first case (a 10-year-old), after a modified Fontan operation, VAD was placed between the functional left atrium and ascending aorta, serving as a "artificial single ventricle" with neither pumping chamber nor artificial support in the right side of the heart. The systemic circulation was maintained by keeping relatively high central venous pressure. In another child (a 3-year-old) who underwent repair of incompetent atrioventricular valve leaving intracardiac lesions, VAD was placed between the common atrium and ascending aorta, serving as a pump for both pulmonary and systemic circulation with regulation of pulmonary blood flow through an aortopulmonary Gore-Tex shunt. The circulatory assist with VAD was utilized for 5 and 6 days, respectively. Although weaning from the device was not feasible in both patients because of the pulmonary dysfunction, these experience showed the possible use of VAD for cardiogenic shock after surgery in patients with complex cardiac anomalies.     

Stromal cells in hemangioblastoma: neuroectodermal differentiation and morphological similarities to ependymoma

The histogenesis of stromal cells in hemangioblastoma is inconclusive despite a long-term controversy. An immunohistochemical and ultrastructural study was conducted for 17 cases of cerebellar hemangioblastoma. A wide range of immunohistological markers, targeting epithelial, mesenchymal, endothelial and neuroectodermal tissues, was used. In all cases, the microscopic hallmark characterizing hemangioblastomas, that is, lipid-containing stromal cells and a fine capillary network, known as a reticular variant, was noted. Stromal cells showed a variable immunoreactivity for neuroectodermal markers, such as S-100 protein, CD56, CD57, CD99, and neuron-specific enolase. This result, in conjunction with the absence of immunoreactivity for epithelial, mesenchymal, and endothelial markers, likely suggests neuroectodermal differentiation of stromal cells. In three cases, another component, known as a cellular variant, where epithelioid tumor cells were arranged in nests encircled by capillaries and/or in pseudorosette-like structures, was noted. Glial fibrillary acidic protein-immunoreactivity, which was totally absent in cases only showing the reticular pattern, was noted in two of them, suggesting a distinctive sign of glial differentiation in a proportion of hemangioblastomas. Ultrastructurally, microvilli-like projections in intracytoplasmic vacuoles were demonstrated in stromal cells. This result, taken together with the neuroectodermal hypothesis of stromal cells, suggests that hemangioblastomas may occasionally exhibit morphological similarities to ependymomas.     

Toxic effects of benzyl and allyl isothiocyanates and benzyl-isoform specific metabolites in the urinary bladder after a single intravesical application to rats.

Allyl isothiocyanate (AITC) is known to be weakly carcinogenic, whereas benzyl isothiocyanate (BITC) has been suggested to exert carcinogenicity toward the rat urinary bladder. To elucidate direct toxic effects of isothiocyanates (ITCs), BITC, AITC, or BITC-metabolites conjugated either with glutathione, cysteinylglycine, cysteine, or mercapturic acid were intravesically instilled into female F344 rats. Exposure to AITC and BITC at 2.8 mg/kg body weight, and the same mol quantity (37 micromol/kg) of BITC-metabolites was for 2 h. Nineteen hours thereafter, the animals were intravenously administered 5-bromo-2'-deoxyuridine (BrdU) and killed 1 h later. BITC caused more profound toxic damage than AITC. Among the BITC-metabolites, cytotoxicity was evident with intermediate glutathione or cysteinylglycine conjugates, whereas the mercapturic acid, considered to be the major final urinary metabolite, exerted little effects. BrdU labeling was essentially dependent on the degree of cytotoxic potential of each compound. Considering the previous study results demonstrating the generation of free BITC from metabolites in urine, the present results support the idea that cytotoxic activity of orally administered ITCs is derived from free forms cleaved from conjugated metabolite(s) in urine.     

Low grade malignant peripheral nerve sheath tumour: varied cytological and histological patterns

BACKGROUND: A small number of malignant peripheral nerve sheath tumours (MPNSTs) are low grade, and the nature of these low grade tumours has never been systematically assessed. AIMS: To describe the clinicopathological, immunohistochemical, and ultrastructural features of low grade MPNST and to discuss the main differential diagnoses. METHODS: Four cases of low grade MPNST were studied, including one coexistent with neurofibromatosis type 1. The tumours were analysed with respect to nuclear atypia, cellularity, nuclear enlargement, hyperchromasia, mitotic rate, and necrosis. Immunohistochemistry was performed by standard techniques, and an ultrastructural study was performed on one tumour. RESULTS: The ages of the patients ranged from 32 to 72 years (mean, 58). Two were male and two were female. Three tumours occurred in the deep tissue, including one in the retroperitoneum, and one was located in the dermal and subcutaneous tissue. The maximum diameters of the tumours ranged from 3.5 to 8.0 cm. Microscopically, all tumours showed moderate hypercellularity, an increased nuclear to cytoplasmic ratio, and hyperchromasia, but exhibited varied growth patterns, including those that were atypical neurofibroma-like, low grade fibromyxoid sarcoma-like, low grade epithelioid, and haemangiopericytoma-like. All tumours showed immunoreactivity for S-100 protein and vimentin. CONCLUSIONS: These findings suggest that careful clinical and histological evaluation, along with S-100 protein immunostaining, are essential for the accurate diagnosis of low grade MPNST.     

Generation of thyroglobulin-specific T-cell clones derived from F1 Fisher rats.

We established T-cell clones from 'poor-responder' Fisher rats specific for thyroglobulin (Tg) with a view to examining Tg presentation by cloned Fisher rat thyroid (FRTL) cells. From the screening of 60 T-cell clones, three high-responding Tg-specific clones (B21.01, B21.04 and B21.05) were isolated from the lymph nodes of F1 generation (Fisher x 'high-responder' Buffalo) female rats immunized with murine Tg in complete Freund's adjuvant (CFA). Three T-cell clones expressed a W3/25+, OX-8- phenotype and responded specifically to murine and rat Tg in T-cell proliferation assays with Fisher rat antigen-presenting cells and secreted IL-2 as measured using a murine cytotoxic T-lymphocyte line (CTLL-2). Both B21.04 and B21.05 T-cell clones were capable of providing helper T-cell function for rat Tg antibody production in syngeneic reconstitution cultures in vitro. In contrast, clone B21.01 inhibited Tg antibody secretion. These data demonstrate that 'poor-responder' Fisher rats are capable of mounting significant T-cell responses to Tg in an F1 generation. Such Tg-specific T-cell clones will allow us to analyse their interaction with cloned Fisher rat thyroid cells and determine the role, if any, of thyroid cell antigen self-presentation to the immune system.     

Lack of chemopreventive efficacy of DL-selenomethionine in colon carcinogenesis

Epidemiologic observations and laboratory research have suggested that dietary selenium reduces the risk of colon cancer. Selenium-enriched brewer's yeast as a dietary supplement reduces the incidence of and mortality from cancer of the colon in humans. It is not clear whether the observed inhibitory effect is due to selenomethionine, or to other forms of selenium, or to a mixture of the selenium compounds present in selenium-enriched brewer's yeast. Therefore, bioassay described in this study examined the chemopreventive efficacy of 10 and 15 ppm selenomethionine, equivalent to 3.6 and 5.4 ppm as selenium, against azoxymethane (AOM)-induced colon carcinogenesis. At five weeks of age, groups of male F344 rats were fed diets containing 0 (control diet), 10 or 15 ppm selenomethionine. At seven and eight weeks of age, all rats except those in vehicle-treated groups received s.c. injections of AOM at a dose rate of 15 mg/kg body wt. The rats were maintained on their respective diets for 52 weeks and were then sacrificed. Colon tumors were processed and evaluated histopathologically. Colon tumor incidence and multiplicity were analyzed statistically. No obvious toxic effects were observed following dietary administration of 10 or 15 ppm selenomethionine as indicated by body weight gain. Administration of 10 or 15 ppm selenomethionine had no significant effect on colon tumor incidence and multiplicity. This study suggests that i) selenomethionine lacks chemopreventive efficacy against AOM-induced colon carcinogenesis and ii) other forms of selenium or a mixture of selenium compounds present in selenium-enriched brewer's yeast need to be evaluated for their chemopreventive efficacy.