Nucleolus-associated J chains in myeloma cells: clinical significance

Bone marrow aspirates from 20 patients with multiple myeloma (MM), 4 with smoldering multiple myeloma (S-MM), 1 with idiopathic Bence Jones proteinuria (I-BJP), and 6 with primary macroglobulinemia (PMG) were examined for nucleolus-associated J chain. The incidence of nucleolar J chain-positive (J+) cells among nucleolated cells producing M-component was measured. This incidence (94.0-100%) in terminal MM was significantly higher than that (0-58.0%) in non-terminal MM. Judging from a low incidence in the remission phase, chemotherapy might cause a selective elimination of less differentiated myeloma cells with J+ nucleoli and might have some effect on J chain synthesis. The incidence of nucleolar J+ cells was very low in S-MM. The IgM cells in PMG, where J chain is present in a disulfide-linked form, had no or few J+ nucleoli. No correlation between the incidence of nucleolar J+ cells among nucleolated plasma cells and the percentage of nucleolated cells or that of J+ cells was found. Large J+ nucleoli seemed to be another morphological feature indicating anaplastic myeloma cells. A high incidence of nucleolar J+ cells may be one of the indicators for progressive disease.     

Genetic alteration in carcinoid tumors of the lung.

Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis.     

VALUE OF COMPUTED TOMOGRAPHY FOR EVALUATING THE INJECTION SITE IN ENDOSONOGRAPHY‐GUIDED CELIAC PLEXUS NEUROLYSIS

Endosonography‐guided celiac plexus neurolysis (EUS‐CPN) safely and effectively relieves pain associated with intra‐abdominal malignancies when the neurolytic is accurately injected. We applied contrast medium to evaluate the ethanol injection sites in patients who received EUS‐CPN due to abdominal pain caused by malignancies. We injected, under the guidance of endoscopic ultrasonography (EUS), ethanol containing 10% contrast medium into the celiac plexus of patients with intra‐abdominal pain due to malignancies. Immediately after the endoscopic therapy, patients underwent computed tomography (CT) to confirm the injection site. Images of distribution of injected solutions were classified into three groups. Injected solution dispersed in unilateral and bilateral anterocrural space was defined as ‘unilateral injection’ or ‘bilateral injection’, respectively. Injected solution located out of the anterocrural space was defined as ‘inappropriate injection’. Pre‐ and postprocedure pain was assessed using a standard analog scale. Before and 2, 4, 8, 12, and 16 weeks after the procedure, pain scores were evaluated. From April 2003 to May 2005, 13 patients were enrolled in this study. Improvement of pain score in the ‘bilateral injection’ and ‘unilateral injection’ groups was significantly superior to the change in the ‘inappropriate injection’ group. Although EUS‐CPN was effective in eight of 13 patients (61.5%), additional EUS‐CPN to the ‘inappropriate injection group’ increased the response rate to 84.6%. Injection of ethanol to the anterocrural space by EUS‐CPN produced adequate pain relief. Immediate examination by CT for confirmation of injection sites after EUS‐CPN would increase the likelihood of induction of pain relief.     

Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome.

The purpose of the present study was to elucidate the cardiac structure and function in patients who have metabolic syndrome but no history of cardiovascular disease by analyzing echocardiographic findings. Echocardiographic examination was performed to screen for cardiovascular disease in 135 patients who were in their sixties. Patients were divided into metabolic syndrome (n=65, age: 65+/-2.7 years) and non-metabolic syndrome (n=70, age: 66+/-2.5 years) groups based on the criteria for metabolic syndrome proposed by the Japanese Society of Hypertension and seven other societies in 2005. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial filling (A velocity), and the ratio of E to A (E/A) was assessed by the transmitral flow. The Tei index, which reflects both LV diastolic and systolic function, was also calculated. There were no differences in relative wall thickness, LV mass index, or LVEF between the two groups. However, both the EIA and Tei index were significantly different between the metabolic syndrome (0.66+/-0.14 and 0.36+/-0.07, respectively) and non-metabolic syndrome (0.88+/-0.25 and 0.29+/-0.09) groups (p<0.001). These results indicate that patients with metabolic syndrome can have cardiac diastolic dysfunction even if they have neither LV hypertrophy nor systolic dysfunction.     

Difference in sensitivity to alkaline phosphatase treatment between rat reticulocyte membranes in which beta-adrenoceptor desensitization was induced by isoproterenol, dibutyryl cAMP and phorbol ester

The effect of alkaline phosphatase (3.1.3.1) on desensitization of beta-adrenoceptor-responsive adenylate cyclase and the role of phosphorylation in desensitization were examined. Treatment of rat reticulocytes with isoproterenol, dibutyryl cAMP and tetradecanoyl phorbol acetate (TPA) caused the desensitization of beta-adrenoceptor-coupled adenylate cyclase. When the membranes from dibutyryl cAMP- and TPA-desensitized cells were incubated with alkaline phosphatase for 60 min at 30 degrees C, pH 8.0, the desensitization of isoproterenol-stimulated adenylate cyclase was markedly attenuated in both preparations. When the membranes from isoproterenol-desensitized cells were treated with alkaline phosphatase under the same conditions, the attenuation of the desensitization of alkaline phosphatase was less than in the case of treatment with dibutyryl cAMP or TPA. In other words, isoproterenol-induced desensitization was more resistant to alkaline phosphatase treatment. Isoproterenol- and dibutyryl cAMP-induced desensitization of NaF-stimulated adenylate cyclase were also attenuated by alkaline phosphatase treatment. Although the stability of the Gs-catalytic unit complex of adenylate cyclase was reduced by isoproterenol treatment, the reduction of stability was also decreased by alkaline phosphatase treatment.     

Evaluation of renal first pass blood flow with a functional image technique in hypertensive patients

The renal circulation of patients with essential hypertension and renovascular hypertension was evaluated using ^99mTc-DTPA. The first renal peak count (the first C_max; FC_max), time phase distribution (the first T_max; FT_max), and blood velocity (the FC_max/FT_max) were calculated by digital imaging. This yields a visual image of the renal circulation. We consider that the increase in the renal first pass blood flow in patients with essential hypertension is best observed pixel by pixel. The FC_max and FC_max/FT_max images before and after treatment by percutaneous transluminal renal angioplasty in patients with renovascular hypertension clearly show its therapeutic effect. The FI technique, therefore, has the advantage that it can be performed at the same time as the conventional routine examinations of renal function. This makes it very useful clinically.