Clinical features and molecular genetic analysis in a Turkish family with oral white sponge nevus.

BACKGROUND: Oral white sponge nevus (WSN) is a rare autosomal dominant benign condition, characterized by asymptomatic spongy white plaques. Mutations in Keratin 4 (KRT4) and 13 (KRT13) have been shown to cause WSN. Familial cases are uncommon due to irregular penetrance. Thus, the aim of the study was: a) to demonstrate the clinical and histopathological features of a three-generation Turkish family with oral WSN b) to determine whether KRT4 or KRT13 gene mutation was the molecular basis of WSN. MATERIAL AND METHODS: Out of twenty members of the family ten were available for assessment. Venous blood samples from six affected and five unaffected members and 48 healthy controls were obtained for genetic mutational analysis. Polymerase chain reaction was used to amplify all exons within KRT4 and KRT13 genes. These products were sequenced and the data was examined for mutations and polymorphisms. RESULTS: Varying presentation and severity of clinical features were observed. Analysis of the KRT13 gene revealed the sequence variant Y118D as the disease-causing mutation. One patient revealed several previously unreported polymorphisms including a novel mutation in exon 1 of the KRT13 gene and a heterozygous deletion in exon 1 of KRT4. This deletion in the KRT4 gene was found to be a common polymorphism reflecting a high allele frequency of 31.25% in the Turkish population. CONCLUSIONS: Oral WSN may manifest variable clinical features. The novel mutation found in the KRT13 gene is believed to add evidence for a mutational hotspot in the mucosal keratins. Molecular genetic analysis is required to establish correct diagnosis and appropriate genetic consultation.

The values of intratumoral mast cell count and Ki-67 immunoreactivity index in differential diagnosis of uterine smooth muscle neoplasms.

In this study, the role of the count of intratumoral mast cells was examined and compared with the proliferative activity exhibited by Ki-67 indices in the differential diagnosis of uterine smooth muscle tumors. Sixteen cases of leiomyosarcoma, nine cases of atypical leiomyoma and 16 cases of ordinary leiomyoma were included. The pathological features of the cases were determined by reviewing the archive materials including the patient records and hematoxylin-eosin-stained sections. Toluidine blue stain was used to highlight the intratumoral mast cells and they were counted in at least 40 high power fields. A standard streptavidin-biotin method was applied to the sections to highlight the Ki-67 immunoreactive tumor cell nuclei. These proliferative cells were counted in at least 10 high-power fields. Atypical leiomyomas tended to have a higher quantity of intratumoral mast cells than leiomyosarcomas and ordinary leiomyomas (P = 0.027 and P = 0.021, respectively). Leiomyosarcomas tended to have higher Ki-67 immunoreactivity rates than atypical leiomyomas, although the difference was not statistically significant (P = 0.82). We concluded that the quantity of intratumoral mast cells is useful in the differential diagnosis between leiomyosarcomas and atypical leiomyomas, while the cell proliferation rate expressed by Ki-67 immunoreactivity has a limited value.

Intraglomerular microlesions in renal angiomyolipoma.

A unique case of bilateral multiple intrarenal angiomyolipomas in a 21-year-old woman with tuberous sclerosis is reported. The microscopic examination showed peculiar intraglomerular microlesions, epithelioid areas, microscopic foci of renal cell carcinoma and renal cysts, and the classical features of angiomyolipoma lesion. HMB-45 positivity was detected within some nodules and epithelioid areas. Intraglomerular microlesions were composed of adipose and smooth-muscle cells within the glomerular capillary tuft. These lesions, which were continuous with the capillary tuft, did not show any attachment to the Bowman's capsule. These findings suggest that these are not a consequence of an infiltration from the outside but were originated from inside the glomerulus. The simultaneous presence of multiple angiomyolipoma nodules either inside or outside the glomeruli, multifocality and bilaterality of these lesions, together with the HMB-45 positivity and the finding of scattered epithelioid areas supports the theory that there is a progenitor cell giving origin to all these lesions, the cell which has been named as perivascular epithelioid cell by most authors.

Role of endothelins in trinitrobenzene sulfonic acid-induced colitis in rats.

To determine the role of endothelins (ET) on experimental colitis, following intracolonic trinitrobenzene sulfonic acid administration, rats were given orally either bosentan (BS), a nonselective ET receptor antagonist (100 mg/kg in 5% arabic gum), or arabic gum by gavage for 2 or 14 days. Macroscopic damage scores obtained in the vehicle (1.4+/-0.4), acute (4.8+/-0.6) and chronic (3.8+/-0.3) colitis groups were significantly higher than in the control group (0). BS treatment reduced the scores in both acute (3+/- 0.5) and chronic (2.3+/-0.5) colitis groups. Myeloperoxidase (MPO) activities of colonic tissues were elevated in acute and chronic colitis groups (325.1+/-44.9 and 431.8+/-54.6 U/g wet weight) as compared with the control group (73.6+/-11 U/g wet weight). Plasma protein oxidation levels were found to be significantly increased in the chronic colitis group (1,158.1+/-63.4 nmol/ml) compared with the control, ethanol and acute colitis groups (274.3+/-23.1, 490+/-52.2 and 422.2+/-50.5 nmol/ml). BS treatment significantly reduced both the protein oxidation level (375.5+/-46.9 nmol/ml) and MPO activity (167.5+/-35.8 U/g wet weight). The results of the present study suggest the involvement of ETs in the pathogenesis of colonic injury in this animal model of colitis.

Bombesin ameliorates colonic damage in experimental colitis.

In the present study we investigated the possible therapeutic effects of bombesin on an experimentally induced colitis model in rats. Inflammation of the colon was induced by a single intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS) at 8 cm from the anus. Immediately after the induction of colitis, some rats were given bombesin (10 microg/kg; subcutaneously) three times a day for 14 days, while another group received vehicle treatment. On day 14, the rats were decapitated and plasma carbonyl content and tissue myeloperoxidase level, as an index of granulocyte infiltration into intestinal tissue, were determined in order to obtain an objective evaluation of colonic injury. In the colitis group, increased macroscopic damage score, elevated MPO level and high plasma carbonyl content, together with the microscopic appearance revealed severe inflammatory changes resembling IBD. Bombesin treatment attenuated the TNBS-induced colonic damage and stimulated histopathologically apparent mucosal proliferation, suggesting that bombesin may play a role in protecting gut integrity.