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.     

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.     

Effect of 3 mg melatonin on jet lag syndrome in an 8-h eastward flight

In order to assess the effect of melatonin on jet lag a field study was undertaken. The process of re-entrainment of circadian melatonin rhythm was investigated in six subjects. Except during 24-h blood sampling, the subjects were exposed to natural zeitgeber (time giver) outdoors and given 3 mg melatonin at 23:00 h. The subjects were exposed to bright sunlight from 3000 to 12000 lx. All of them showed orthodromic re-entrainment with taking melatonin, while two out of the six did not show orthodromic re-entrainment without taking melatonin. Melatonin accelerated the rate of the re-entrainment of the circadian melatonin rhythm. Melatonin was useful to jet travel from Tokyo to Los Angeles.     

Manometric Evidence of Improved Early Gastric Stasis by Erythromycin after Pylorus-preserving Pancreatoduodenectomy

Gastric stasis is a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD). We demonstrated that it might be attributable to delayed recovery of phase III activity of the gastric migrating motor complex due to low concentrations of plasma motilin caused by resection of the duodenum. Leucine 13-motilin is effective for treating gastric stasis, but it is not yet available for clinical use. Whether erythromycin would improve early gastric stasis after PPPD was tested clinically and by manometry. A manometric tube assembly and a gastrostomy tube were inserted in the stomach of 10 patients at PPPD for pressure recording from the gastric antrum and jejunum and for gastric juice drainage, respectively. After baseline recording, erythromycin 5 mg/kg was given intravenously on day 14 and saline as a placebo on day 17 every 4 hours four times a day. The daily volume of gastric juice output and the gastric motility index were measured. The mean period until the return of gastric phase III was 31 +/- 1 days. Erythromycin significantly increased the gastric motility index from 7.9 +/- 1.3 mmHg to 15.7 +/- 1.8 mmHg (p = 0.0005), whereas saline did not (7.2 +/- 1.6 mmHg to 6.5 +/- 1.2 mmHg; p = 0.21). Erythromycin significantly decreased the gastric juice output from 1,080 +/- 190 ml to 738 +/- 199 ml (p < 0.0001), but the saline injections did not (1,064 +/- 174 ml to 1,115 +/- 189 ml; p = 0.35). Erythromycin, a universally available motilin agonist, is a safe, effective, potent drug for the treatment of early gastric stasis after PPPD.     

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.     

A preliminary study of discrimination among the components of small pulmonary nodules by MR imaging: correlation between MR images and histologic appearance

PURPOSE: To investigate whether magnetic resonance (MR) imaging depicts the internal characteristics of small pulmonary nodules. METHODS: We reviewed MR images of 39 surgically resected pulmonary nodules 3 cm or less and compared the components within the nodules. In 22 malignant nodules, eight histologic components were characterized by signal and enhancement patterns on MR images. RESULTS: MR images obtained from any single sequence discriminated all components in 26 (67%) nodules, whereas the combination of images from various sequences allowed discrimination in 35 (90%). Fourteen of 16 components of aggregated tumor cells showed marked early enhancement. Although fibrotic and necrotic components showed no or slight early enhancement, nine of 10 fibrotic components showed hypointensity and six of seven necrotic components showed hyperintensity on T2-weighted images. Component characterization in eight histologies by MR imaging was possible in 71-100%. CONCLUSION: Our study demonstrated that MR imaging offers the possibility of high tissue-contrast resolution in small pulmonary nodules.