K-Ras gene status and expression of Ras/mitogen-activated protein kinase (MAPK) signaling molecules in ameloblastomas

BACKGROUND: To clarify the roles of rat sarcoma (Ras)/mitogen-activated protein kinase (MAPK) signaling pathway in oncogenesis and cytodifferentiation of odontogenic tumors, K-Ras gene status and expression of Ras, Raf1, MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK)1, and ERK1/2 proteins were analyzed in ameloblastomas as well as in tooth germs. METHODS: Paraffin sections of 10 tooth germs and 46 benign and 6 malignant ameloblastomas were examined immunohistochemically for the expression of K-Ras, Raf1, MEK1, and ERK1/2. Frozen tissue samples of 22 benign ameloblastomas and 1 malignant (metastasizing) ameloblastoma were analyzed by direct DNA sequencing to detect K-Ras gene alteration. RESULTS: Immunohistochemical reactivity for K-Ras, Raf1, MEK1, and ERK1/2 was detected in both normal and neoplastic odontogenic epithelium, and these molecules were reactive chiefly with odontogenic epithelial cells neighboring the basement membrane. Plexiform ameloblastomas showed slightly stronger expression of these Ras/MAPK signaling molecules than follicular ameloblastomas. Keratinizing cells and granular cells showed decreased reactivity for the signaling molecules. Basal cell ameloblastomas showed slightly stronger reactivity for the signaling molecules than did the other subtypes. K-Ras immunoreactivity in malignant ameloblastomas was lower than that in dental lamina of tooth germs. Direct DNA sequencing showed a GGT to GCT point mutation at codon 12 of K-Ras gene in one ameloblastoma. Conclusion: Expression of K-Ras, Raf1, MEK1, and ERK1/2 in tooth germs and ameloblastomas suggests that Ras/MAPK signaling pathway functions to regulate cell proliferation and differentiation in both normal and neoplastic odontogenic epithelium. K-Ras gene status implied that K-Ras mutations might play a minor role in oncogenesis of odontogenic epithelium.     

Preoperative diagnosis of internal mammary node metastases in patients with breast cancer by using ultrasonography]

US findings of 81 patients with breast cancer were analyzed respectively to evaluate the usefulness of US in the preoperative diagnosis of internal mammary mode metastases. The internal mammary area (I.M.A.) in which internal mammary nodes lie was shown as a hypoechoic stripe in a sagittal scan along the sternum and as a triangular or spindle-shaped hypoechoic area in a transverse scan in the intercostal space. The US features of each I.M.A. in the first three intercostal spaces were divided into three patterns: Pattern-A wad defined as widening of the ipsilateral side of the I.M.A. compared with the contralateral side; Pattern-C was defined as normal at both sides of the I.M.A. Pathological examination confirmed the node metastases in 85.7% of intercostal scans showing Pattern-A and in 35% of intercostal scans showing Pattern-B. Only one of 189 intercostal scans showing Pattern-C had nodal metastases. The overall accuracy was 88.1% in 243 intercostal scans and 90.1% in 81 patients. We conclude that US is useful in the detection of internal mammary node metastases in patients with breast cancer.     

Germinoma with granulomatous reaction arising from the corona radiata; case report and review of articles]

We report a rare case of germinoma with granulomatous reaction arising from the corona radiata. This 20-year-old man was admitted to our hospital complaining of progressive motor weakness on the right side. CT demonstrated a poorly demarcated high density area in the left corona radiata, which was heterogeneously enhanced after administration of contrast medium. Moreover, the continuity of the mass to the ventricular wall was confirmed on MRI. At the first operation, subtotal removal of the tumor was performed through a fronto-parietal craniotomy. The diagnosis for the specific neoplasm was not established histologically, but granuloma caused by fungal infection was the most likely cause of the lesion. We tried amphotericin B (AmB), and remission of the tumor was obtained. However, during the following 3 months, the size of the tumor gradually enlarged again. AmB was repeatedly administered, but this time the treatment was ineffective. Six months later, on May 21, 1990, the second operation was performed and histological examination revealed typical germinoma consisting of two-cell pattern. Subsequently, the patient underwent focal irradiation of 33 Gy to the tumor site, and the tumor completely disappeared. As intracranial germinomas are observed to be successfully cured by radiotherapy and/or chemotherapy, choice of the therapeutic management must be carefully determined according to the histological diagnosis, especially in young people. A variety of locations of germinomas and the accompanying granulomatous reactions could create some diagnostic confusion, so great care must be taken in the treatment of much intracranial germinomas.     

Case of ruptured gastroduodenal arterial pseudoaneurysm with penetration to the duodenum, successfully treated with transcatheter arterial embolization]

A 77-year-old man, who underwent segmental pancreatectomy for intraductal papillary mucinous adenoma in 2001, was referred to our hospital with complaints of hematemesis and melena on January, 2004. Emergency upper gastrointestinal endoscopy showed a pulsating submucosal protrusion in the duodenal bulb, which was identified as a gastroduodenal arterial aneurysm measuring 1.5cm on abdominal CT imaging. Transcatheter arterial embolization of the aneurysm with metallic coils was successfully performed. Periodically repeated endoscopic examination has revealed the coils protruding into the duodenal lumen without any serious complication.     

Amelioration by topical bunazosin hydrochloride of the impairment in ocular blood flow caused by nitric oxide synthase inhibition in rabbits.

We investigated whether topical instillation of an alpha(1)-adrenergic blocker would improve an insufficient blood supply in the optic nerve head (ONH) and visual function, in rabbits. The effect of systemic NOS inhibition on visual-evoked potentials (VEPs) and hemodynamics in ONH were determined. VEPs were recorded before and every 15 min during a 120-min observation period after an intravenous injection of 50 mg/kg N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. Capillary blood flow in ONH was evaluated by the laser speckle method throughout the same period. Then, we investigated the effect of topical instillation of a recently developed alpha(1) adrenergic blocker, bunazosin hydrochloride (0.01%), 60 min prior to the intravenous L-NAME (50 mg/kg) on the changes by NOS inhibition. The VEP amplitudes were reduced by L-NAME (10, 20, and 50 mg/kg) in a dose-dependent manner, while the VEP implicit time was unchanged, and no significant changes were detected in the electroretinogram. The reductions in ONH capillary blood flow and VEP amplitudes caused by L-NAME (50 mg/kg) were significantly suppressed by an instillation of bunazosin hydrochloride. These results indicate that blocking alpha(1)-adrenergic receptors may ameliorate the impairments in blood flow and retinal function caused by NOS inhibition. The enhancement of basal vascular tone due to deprivation of continuous NO production may be diminished by this alpha(1)-adrenergic blocker.     

IgG Anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in guillain-barré syndrome

To investigate the pathophysiological role of anti-GM1 antibody in Gullain-Barre syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patientsrpar;, or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathopsiological mechanisms in IgG anti-GM1)positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers.     

Human leukocyte antigens in Fisher's syundrome

We performed human leukocyte antigens(HLA)typing for class I antigens on 19 Japanese patients with Fisher's syndrome. We demonstrated a statistically significant association between the disease and the HLA-B39 antigen.     

Ipsilateral atrophy in children with hemispheric cerebral tumors: CT findings

The CT findings of 19 children under 16 years of age with primary brain tumors in the cerebral hemisphere were investigated with special reference to the existence of cerebral hemiatrophy ipsilateral to the side of the tumor. "Ipsilateral cerebral hemiatrophy" was observed in four of 19 cases (21%). These included two cases with germinoma in the basal ganglia and two with low-grade astrocytoma in the frontal and occipital cortex. This peculiar CT finding was not specific to the location or histology of the tumor. The four cases were characterized by slow progression, which contrasted with the rapid progression of tumors shown in seven cases with a mass effect on CT.