Tubulin stimulates adenylyl cyclase activity in rat striatal membranes via transfer of guanine nucleotide to Gs protein

Previous studies of rat cerebral cortex and rat C6 glioma cells have demonstrated that dimeric tubulin is capable of activating the G proteins Gs and Gil via transfer of guanine nucleotide from tubulin to Gs α and Gil α. To provide further information regarding cytoskeletal modulation of adenylyl cyclase, the present study examined effects of tubulin on the activation of the enzyme in rat striatal membranes. Tubulin, prepared from rat brain by polymerization with the hydrolysis-resistant GTP analog 5′-guanylylimidodiphosphate (GppNHp) caused significant activation of adenylyl cyclase by 130%. Furthermore, tubulin-GppNHp activated SKF 38393-sensitive adenylyl cyclase and potentiated forskolin-stimulated activity of the enzyme. When tubulin, polymerized with the hydrolysis-resistant photoaffinity GTP analog[³²p]p³ (4-azidoanilido)-p¹-5′-GTP ([³²P]AAGTP), was incubated with striatal membranes, AAGTP was transferred from tubulin to Gs α as well as Gi α with the extents of nucleotide transfers being 7.6 ± 0.8% and 17.8 ± 1.4% of AAGTP originally bound to tubulin, respectively. These results indicate that, in rat striatum, the tubulin dimer participates in the stimulatory regulation of adenylyl cyclase by transferring guanine nucleotide to Gs α, supporting the hypothesis that tubulin contributes to the regulation of neuronal signal transduction.     

Clinicopathological Significance of Nuclear Accumulation of Tumor Suppressor Gene p53 Product in Primary Lung Cancer

Since the nuclear accumulation of p53 protein is known to correspond well with mutation of the p53 tumor suppressor gene, the authors examined 88 primary lung cancer specimens immunohistochemically using anti-p53 mouse monoclonal antibody, pAb1801, and analyzed the relationship between the immunohistochemical results and clinicopathological features. Nuclear localization of p53 protein was found in 43/88 (49%) tumor specimens, but not in the corresponding normal lung tissues. The percentage of cases showing nuclear p53 localization varied according to the histological type. In squamous cell carcinoma, nuclear p53 localization was found in 15/26 (57%), appearing more frequently than in other histologic types. However, no obvious correlation was observed between nuclear p53 localization and patients' age, sex, history of smoking, TNM factor, degree of differentiation, or any other clinicopathological features analyzed. In adenocarcinoma, nuclear p53 localization was found in 20/46 (43%). Incidence of positive cases was significantly correlated with regional lymph node metastasis, distant metastasis, and pathological stage ( P < 0.05). These results indicate that mutation of the p53 tumor suppressor gene plays an important role in the development of primary lung cancer, and that nuclear accumulation of p53 protein is a potential prognostic factor in adenocarcinoma of the lung.     

One-stage resected case of dumbbell type tumor of the posterior mediastinum

We reported a dumbbell type tumor of the posterior mediastinum. The patient was an asymptomatic 40-year-old male. An abnormal shadow in the right lower lung field was pointed out in a mass survey. We recognized a dumbbell type tumor in the posterior mediastinum by chest CT and MRI. The tumor invaded the intervertebral canal through the spinal foramen. It was most clearly seen by MRI myelography. Operation was performed with the patient in a prone position and with an L-shaped skin incision of the back and 11th intracostal thoracotomy and Th11 laminectomy. The dumbbell type tumor was completely removed by this operation. The pathological diagnosis was Schwannoma. The post operative course was good. The one-stage operation is useful for dumbbell type tumors of the posterior mediastinum.     

Lassa fever associated with effusive constrictive pericarditis and bilateral atrioventricular annular constriction: a case report

A case of Lassa fever associated with effusive constrictive pericarditis and bilateral atrioventricular annular constriction was reported. A 49-year-old man, who had been diagnosed by indirect fluorescent antibody test as the first case of Lassa fever in Japan, was referred to the Hiroo Hospital because of syncope, progressive hepatomegaly, ascites and pericardial effusion in spite of pericardiocentesis and corticosteroid therapy. On admission, his blood pressure was 92/60 mmHg and he had a paradoxical pulse. Two-dimensional echocardiography revealed a localized pericardial effusion adjacent to the right ventricular wall and behind the left ventricular posterior wall. Bilateral atrioventricular annular constriction was also present. On pulsed Doppler echocardiography, the peak inflow velocities of the right and left ventricles increased during atrial systole. Right heart catheterization revealed a mean diastolic pressure gradient of 8 mmHg across the tricuspid valve. After pericardiectomy, a diastolic dip and plateau pattern became evident in the right ventricular pressure tracing, suggesting the presence of residual constriction. However, the atrioventricular annular constriction was no longer evident on two-dimensional echocardiography. This is considered the first reported case of subacute effusive constrictive pericarditis caused by Lassa fever.     

Sweet's syndrome associated with myelodysplastic syndrome

A 49-year-old man was hospitalized because of cutaneous plaques and pancytopenia. Hematological findings, and the skin eruption suggested Sweet's syndrome associated with myelodysplastic syndrome (refractory anemia with excess of blasts; RAEB). Treatment for pancytopenia was attempted without effect. Also we tried treatment with antibiotics. The skin lesions healed and the body temperature returned to normal. This case was unusual in the association of myelodysplastic syndrome with Sweet's syndrome.     

A novel translocation, t(9;17)(q34;q23), in aggressive childhood lymphoblastic lymphoma

In a chromosome study of childhood lymphoblastic lymphoma, we found a novel translocation, t(9;17)(q34;q23), in three patients. They presented with mediastinal mass and no bone marrow involvement. Despite intensive chemotherapy, one patient had no response, the other two relapsed after a brief remission, and all progressed to death. The 9;17 translocation may have a clinical implication for lymphoblastic lymphoma patients in predicting a poor prognosis. Since, in addition to our cases, involvement of the 9q34 breakpoint, together with 2q33, 14q11, or 7q34, has been reported in the literature in four lymphoblastic lymphoma patients, a gene located in 9q34 and referred to as tcl-3 may participate in the genesis of the T cell malignancies carrying these translocations. Furthermore, as is the case in other lymphomas, the reciprocal breakpoint, 17q23, might be the site of a yet unidentified T cell function gene.