Role of brainstem and spinal noradrenergic and adrenergic neurons in the development and maintenance of hypertension in spontaneously hypertensive rats

Summary In young and adult spontaneously hypertensive rats (SHR), dopamine -hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) activities in discrete areas of the brainstem and spinal cord were measured as indices of noradrenergic and adrenergic neuronal activities. In young SHR, the DBH activities were elevated in the locus coeruleus (LC), A2 cell area and thoracic intermediolateral cell area (IML). The elevation disappeared at adult SHR. In young SHR, no significant change of PNMT activity was observed in the A1, A2, nucleus tractus solitarii (NTS), LC and IML areas, while, in adult SHR, the PNMT activity in the A1 cell area and DBH activity in the NTS were elevated. Lowering of blood pressure by hydralazine decreased the PNMT activity elevated in the A1 cell area and elevated it in the NTS.Plasma levels of norepinephrine and epinephrine, as measured in blood samples collected via aortic cannula at resting state, were much lower than many reported values in blood collected from the decapitated trunk. In young SHR, a significant elevation of plasma norepinephrine and DBH levels was confirmed as signs of peripheral sympathetic nervous activation. The elevation disappeared at adult SHR. Plasma epinephrine levels raised under restraint stress were much higher in SHR at all ages than in normotensive controls.In young SHR, the selective activation of noradrenergic neurons of the IML, A2 and LC areas, accompanied by activation of the peripheral sympathetic nervous system, initiates the hypertension. In adult SHR, the activation of adrenergic neurons in the A1 cell area including the nucleus reticularis lateralis may not be involved in the maintenance of hypertension but may be the results of hypertension.     

Temporal deterioration of wavelength discrimination with successive comparison method

The wavelength discrimination threshold (Δλ) was measured with a successive comparison method, in which two stimuli of different wavelengths were presented in the left and right half of 2.2° or 2.7° bipartite field, respectively, with a certain stimulus onset asynchrony (SOA). The stimulus duration was kept constant at 110 msec. The Δλ value for five different wavelengths, 430, 470, 520, 570 and 610 nm, was found to be constant up to SOA= 60 msec and increased gradually till SOA= 190 msec. The wavelength discrimination functions with SOA of 0 and 550 msec were also obtained for 430 through 650 nm in 10 nm steps. At all wavelengths the values with SOA of 550 msec were about twice as large as those with SOA of 0 msec. The present results indicate that the wavelength discrimination deterioration is complete within a relatively short period of time.     

Purity discrimination: Successive vs simultaneous comparison method

Purity discrimination thresholds (Δp) were measured with successive (SOA = 3 sec) and simultaneous (SOA = 0 sec) comparison methods for seven dominant wavelengths: 410, 480, 500, 530, 570, 600 and 650 nm. The stimulus duration was 1 sec. The Δp values with the successive comparison method were found to he about 1.5–2.0 times larger than those obtained in the simultaneous case. The degree of purity discrimination deterioration shown in this study is similar to that of wavelength discrimination deterioration previously reported (Uchikawa and Ikeda, 1981, Vision Res.21, 591–595). Saturation shifts of stimuli with the successive comparison method were also observed: these were toward increased saturation direction for most dominant wavelengths.     

The valvo-pump, an axial blood pump implanted at the heart valve position: concept and initial results

The valvo-pump, an axial nonpulsatile blood pump implanted at the heart valve position, has been developed. The valvo-pump consists of an impeller and a motor, which are encased in a housing. An impeller with 5 vanes (22.0 mm in diameter) is used. The impeller is connected to a samarium-cobalt-rare earth magnet direct current (DC) brushless motor measuring 21.3 mm in diameter and 18.5 mm in length. Sealing is achieved by means of a ferrofluidic seal. A pump flow of 10.5 L/min was obtained at a pump differential pressure of 3.3 kPa (25 mm Hg), and a flow of 4.9 L/min was obtained at 7.0 kPa (53 mm Hg). Sealing was kept perfect against a pressure of 29.3 kPa (220 mm Hg) at 9,000 rpm.     

Stimulatory effect of ipriflavone on formation of bone-like tissue in rat bone marrow stromal cell culture

The effects of ipriflavone (IP) (10^–5 M) on bone formation were studied in stromal cells from the femoral bone marrow of young adult rats cultured for 21 days in the presence of -glycerophosphate and dexamethasone. Stereoscopic microscopy showed nodule formation after 14 days of culturing, and both the number and the size of the nodules increased with time. The alizarin-red-stained calcified area in the nodules in the IP group was nearly 4 times as large as that in the control after 21 days. Light and electron microscopy revealed the presence of many osteoblast-like cells with developed rough endoplasmic reticulum and Golgi apparatus in the nodules in the control group after 14 days, and a collagenous fibril network was seen among the cells. After 21 days, calcification of the dense collagenous fibril network and bone matrix-like tissue were observed in many nodules, resulting in the formation of bone-like tissue containing osteocyte-like cells. In the IP group, the collagenous fibril network area in the nodules was greater than that in the control after 14 days, and a further increase in both the dense collagenous fibril network area and calcified bone-like tissue area was observed after 21 days. These findings indicate that IP stimulates bone-like tissue formation in the rat bone marrow stromal cell culture, suggesting that the promotion of collagen production by osteoblasts is involved in the stimulation of bone-like tissue formation by IP.     

Alteration of p53 Clonality Accompanying Colorectal Cancer Progression

The aim of this study was to clarify whether or not the status of gene alteration is heterogeneous in intramucosal carcinoma and homogeneous within invasive carcinoma. We selected 10 colorectal carcinoma cases (1 mucosal, 5 submucosal and 4 advanced carcinomas including 2 cases with lymph node metastasis) and analyzed the p53 gene sequence. Six colorectal cancers in this study showed heterogeneity in p53 mutations in cells from the intramucosal part. In the invasive part of a carcinoma, p53 mutation status was homogeneous intratumorally in all cases. These data indicate that, in regard to p53 gene alterations, colorectal cancers can be composed of various subclones when limited to the mucosa, but clonal selection occurs when one of these subclones commences invasion to the submucosa, generating a monoclonal invasive carcinoma.     

Genetic Alterations of Mixed Hyperplastic Adenomatous Polyps in the Colon and Rectum

Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or even carcinomas. These polyps are considered to be different from ordinary hyperplastic polyps and may have a preneoplastic potential. We investigated APC and K- ras mutations in MHAPs of the colon and rectum, and also in colorectal adenomas and hyperplastic polyps to identify molecular differences between MHAPs, adenomas and hyperplastic polyps, using direct sequencing of mutation cluster regions (MCR) in APC and K- ras . No APC mutations were identified in 12 MHAPs and 8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic mutations. K- ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8 (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was found in a carcinoma arising in an MHAP. Mutations other than APC mutations may play a role in the development of MHAPs.     

根据日本乡村绝经后妇女腰椎骨密度的随访研究制定骨质疏松的护理卫生方针

为了检测妇女绝经后发生骨量减少的相关指标进而倡导依据生活方式的特点对绝经后妇女骨质疏松的发生采取相应的预防和护理方针，我们对日本乡村的绝经后妇女（末次月经后六个月或更长时间算起）进行了为期4a的随访。我们运用双能X线骨密度仪（DXA）对腰椎骨密度（BMD）进行检测并对各种变量，包括年龄、绝经时的年龄、骨折史、日常摄奶量以及吸烟习惯进行多元分析，结果表明这些因素对于腰椎骨密度（BMD）的恢复是不相关联的。 在这些变量中，骨折史被证明对于相关人群是最具危险性的，这些对象有高比例的骨量减少（6．6％），其次是不规律的摄奶（13．6％）和吸烟（9．3％）。在护理中使用的作用于足跟骨的检测骨密度的设备被证实与作用于腰椎的DXA设备可以相互替代。依据这些结果，针对居住在日本乡村的绝经后妇女制订了相应的预防骨质疏松的方针。这些卫生指导方针依据特定区域的生活方式而制定并可适用于其他的人群和区域。在本文中，作者列出了不同的有助于预防绝经后妇女出现骨质疏松的方法并进行了调查。     

Malignant B-lymphoid cells with bone lesions express receptor activator of nuclear factor-kappaB ligand and vascular endothelial growth factor to enhance osteoclastogenesis.

PURPOSE: Receptor activator of nuclear factor-kappaB ligand (RANKL) is a key mediator of osteoclastogenesis. Because certain types of tumor cells aberrantly express RANKL, and because bone destruction also develops in B-cell lymphomas of bone origin, we investigated RANKL expression and the mechanisms of osteoclastogenesis in B-lymphoid neoplasms. EXPERIMENTAL DESIGN AND RESULTS: Immunohistochemistry of bone specimens resected from patients with primary B-cell lymphoma of bone with bone destruction revealed that lymphoma cells express RANKL as well as vascular endothelial cell growth factor (VEGF). The tumor cells isolated from the bone specimens enhanced osteoclastogenesis in vitro. In contrast, B-cell lymphoma infiltrating to the bone marrow without bone destruction did not express RANKL. Both RANKL and VEGF were expressed by a portion of B-lymphoid cell lines, including Daudi and IM-9. These RANKL-expressing tumor cells enhanced osteoclastogenesis from RAW264.7 cells and human monocyte-derived preosteoclasts in the absence of stromal cells/osteoblasts in a RANKL-dependent manner. Furthermore, conditioned media from Daudi cells enhanced transmigration of preosteoclasts that was inhibited by anti-VEGF antibody, suggesting that tumor cell-derived VEGF mediates recruitment of osteoclast precursors. Moreover, cocultures of B-lymphoid cell lines with osteoclasts enhanced the growth of B-lymphoid cells. CONCLUSIONS: Some malignant B cells aberrantly express functional RANKL as well as VEGF to enhance osteoclastogenesis. The coexpression of RANKL and VEGF may also contribute to the close cellular interactions with osteoclastic cells, thereby forming a vicious cycle between osteoclastic bone destruction and tumor expansion in bone.