Hippocampal volume asymmetry and age at illness onset in males with schizophrenia

To determine whether there are disturbances of hippocampal volume asymmetry in schizophrenic patients, we obtained contiguous, I-mm-thick magnetic resonance images in 28 males with chronic schizophrenia and in 28 age-matched healthy males. The schizophrenic patients showed a bilateral reduction in volume of the hippocampal formation (HF; left 7.0%; right 8.7%). This reduction was significantly associated with the severity of disorganization syndrome (P < 0.0005). A significant asymmetry in the HF volume was found in the control subjects (P = 0.006), but not in the patients (P = 0.40). There was a significant positive correlation between the asymmetry index and the patient’s age at the onset of schizophrenia (r = 0.46,P = 0.01). Results indicate that a disturbance in the normal asymmetry of the HF may be a characteristic in schizophrenia, particularly in patients with an early onset of the illness.     

Transarterial internal radiation therapy with I-131 lipiodol for multifoca hepatocellular carcinoma: Immediate and long-term results

Transarterial internal radiation with I-131 Lipiodol (TAIR) was performed in 21 patients with multifocal hepatic carcinoma. Eight patients were treated by TAIR alone and 13 by combination of TAIR and intraarterial infusion ofcis-diamminedichloroplatinum (CDDP) and/or adriamycin mitomycin C oil suspension (ADMOS). TAIR was found effective immediately and long-term. Serum α-fetoprotein (AFP) levels dropped to 50% or less in 7 of 14 patients. Eleven of 21 patients (52%) showed 50% or greater decrease in tumor size. The overall 1-year survival rate was 43% and 67% in patients who received 50 Gy or greater tumor dose. Lipiodol distribution pattern of the tumor indicated some difference in the prognosis between the scattered pattern and solid pattern. The solid pattern showed a statistically significant better survival rate. Patients treated with TAIR alone versus those treated with TAIR and chemotherapy showed no difference in their survival rate.     

Alpha9beta1: a novel osteoclast integrin that regulates osteoclast formation and function.

We identified a previously unknown integrin, alpha(9)beta(1), on OCLs and their precursors. Antibody to alpha(9) inhibited OCL formation in human marrow cultures, and OCLs from alpha(9) knockout mice had a defect in actin ring reorganization and an impaired bone resorption capacity. INTRODUCTION: Integrins play important roles in osteoclast (OCL) formation and function. Mature OCLs mainly express alpha(v)beta(3) integrin, a heterodimer adhesion receptor that has been implicated in osteoclastic bone resorption. We identified ADAM8, a disintegrin and metalloproteinase, as a novel stimulator of OCL differentiation and showed that the disintegrin domain of ADAM8 mediated its effects on OCL formation. Because the disintegrin domain of ADAM8 does not bind Arg-Gly-Asp (RGD) sequences, we determined which integrin bound ADAM8 and characterized its role in OCL formation and activity. MATERIALS AND METHODS: Chinese hamster ovary cells (CHO) expressing different integrin subunits were tested for their capacity to bind the disintegrin domain of ADAM8. Mouse or human bone marrow cells and purified OCL precursors were tested for alpha(9)beta(1) integrin expression by Western blot, immunocytochemistry, and real-time RT-PCR. A monoclonal antibody to human alpha(9) was used to block alpha(9)beta(1) on OCL precursors stimulated by 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] or RANKL. Vertebrae of 7-day-old alpha(9)(-/-) mice and wildtype (WT) littermates were compared using bone histomorphometry and 3D microCT analysis. RESULTS: Alpha(9) integrin was expressed by mouse and human bone marrow-derived OCLs and their precursors. Importantly, the anti-alpha(9) antibody inhibited human OCL formation stimulated by 1alpha,25(OH)(2)D(3) or RANKL dose-dependently. Furthermore, analysis of OCLs formed in marrow cultures from alpha(9)(-/-) mice showed that the OCLs formed were more contracted and formed significantly less bone resorption pits on dentin slices. Histologic analysis of alpha(9)(-/-) vertebrae showed thickened trabecular regions and retained cartilage within vertebral bodies of alpha(9)(-/-) mice. 3D microCT analysis of alpha(9)(-/-) vertebrae also showed a significant increase in trabecular bone volume/total tissue volume and a tendency for decreased trabecular separation compared with WT mice. CONCLUSIONS: These results support a previously unknown role for alpha(9)beta(1) integrin in OCL formation and function.     

Coronary flow velocity waveforms in aortic stenosis and the effects of valve replacement

In 6 patients with pure aortic stenosis, the flow velocity waveforms in the left anterior descending coronary artery were studied using an 80-channel 20-MHz pulsed Doppler velocimeter before and immediately after aortic valve replacement. All patients showed normal coronary arteriograms. The left anterior descending coronary artery flow velocity waveform in aortic stenosis was characterized by a reverse flow in the first half of systole and a slowly increasing diastolic inflow. After aortic valve replacement, the reverse flow in the first half of systole disappeared in all patients, but an end-systolic reverse flow was discerned in 5 of 6 patients. The increasing rate of the diastolic inflow was augmented in all patients. After aortic valve replacement, the time from onset of diastole to the diastolic peak velocity was shortened from 176.8 +/- 28.8 to 90.5 +/- 18.8 ms (p less than 0.01), and the diastolic peak velocity increased from 90.5 +/- 28.0 to 122.5 +/- 17.2 cm/s (p less than 0.05). Blood pressure and heart rate, however, did not change significantly before and after valve replacement. These changes in the left coronary artery velocity waveforms after valve replacement suggest the beneficial effects of removal of aortic stenosis on human coronary artery inflow.     

Anti-inflammatory effect of spironolactone on human peripheral blood mononuclear cells

We evaluated the effect of alacepril, CV-11974, and spironolactone on the production of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in cultured human peripheral blood mononuclear cells stimulated with angiotensin (Ang) II. Alacepril, CV-11974, and spironolactone significantly reduced the enhanced production of MCP-1 and TNF-alpha induced by exogenous Ang II. Specifically, 10 muM of spironolactone significantly reduced cytokine production, compared to the same dose of alacepril or CV-11974. These findings indicate that spironolactone may contribute to ameliorate the prognosis of patients with cardiovascular diseases by reducing Ang II-induced inflammation, although further exploration including determining the mechanisms would be required.     

Surgical Management of Small Gastrointestinal Stromal Tumors of the Stomach

Small gastrointestinal stromal tumors (GISTs) (<3 cm) occasionally are found in the stomach during endoscopy. There is no consensus about the surgical management of these small tumors, although this clinical issue is crucial because some of the tumors show unexpected malignant behavior. In this study, we evaluated the clinical management of patients with gastric GISTs who underwent surgical resection. Altogether, 31 patients with gastric GISTs were examined retrospectively. Surgical resection was fundamentally indicated for the patients with gastric GISTs suspected to be malignant by endoscopy or endoscopic ultrasonography (EUS). The malignant grade of the GISTs was evaluated by the mitotic rate, tumor size, and MIB-1 index. EUS was useful for differentiating benign from malignant GISTs; but by limiting the study to patients with small tumors (<3 cm), the diagnostic value of EUS was not satisfactory for defining the surgical indication. Tumors that were <50 mm were successfully treated by laparoscopic surgery. Of the 31 patients, 4 had a relapse of the disease, and 1 of those 4 patients had a small tumor (30 mm). All of the recurrences were classified in the high risk category. Surgery is indicated for gastric GISTs that are ≥20 mm or are suspected to be malignant based on EUS findings. Laparoscopic resection is feasible and is recommended as the treatment of choice for patients with tumors < 50 mm. Risk assessment can be most useful for predicting recurrence.     

Impaired insulin-regulated membrane aminopeptidase translocation to the plasma membrane in adipocytes of Otsuka Long Evans Tokushima Fatty rats

Insulin-regulated membrane aminopeptidase (IRAP) translocates to the plasma membrane with glucose transporter-4 (GLUT4) on insulin stimulation. However, this may be impaired in patients at risk of diabetes. Recently a novel technique has been developed to assess cell surface IRAP activity dynamically using a fluorogenic membrane impermeable substrate. In this study we measured the cell surface IRAP activity and 3-O-[methyl-14C]-D-Glucose uptake in adipocytes isolated from Otsuka Long Evans Tokushima Fatty rats (OLETF), developed as a model of type 2 diabetes mellitus, to evaluate whether the translocation of GLUT4/IRAP vesicles is affected. On the addition of insulin, the cell surface IRAP activity promptly increased to reach equilibrium in a hormone dose-dependent manner. OLETF rats showed significantly lower equilibrium activity than control rats (P<0.01). Time to reach the equilibrium was also significantly longer in the OLETF case, and adipocytes isolated from OLETF rats demonstrated both a delay and a reduction in 3-O-[methyl-14C]-D-Glucose uptake. This impairment in all parameters was alleviated by treatment with pioglitazone. Continuous measurement of cell surface IRAP activity allowed accurate evaluations of GLUT4/IRAP vesicle translocation and of the establishment of defects in OLETF rats.