Adhesion polypeptides are useful for the prevention of peritoneal dissemination of gastric cancer

We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. We previously reported the establishment of an extensively peritoneal-seeding cell line, OCUM-2MD3, from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both 21 and 31 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the ability of OCUM-2MD3 cells to bind to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD, and two RGD derivatives significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination given YIGSR sequenc e intraperitoneally was obviously longer than that of untreated mice. The survival of mice treated with RGD was also improved, and this effect was increased using the RGD derivatives, poly(CEMA-RGDS) and CM-chitin RGDS. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM, and consequently inhibit peritoneal implantation. The peritoneal injection of adhe-sion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients. © Rapid Science Ltd.     

Detection of lung nodules on digital chest radiographs: potential usefulness of a new contralateral subtraction technique

PURPOSE: To evaluate the potential usefulness of a contralateral subtraction technique developed for radiologists' performance in the detection of subtle lung nodules on chest radiographs. MATERIALS AND METHODS: Fifty chest radiographs (25 normal and 25 abnormal with a subtle lung nodule) that were digitized with a 0.175-mm pixel size and 4,096 gray levels were used. Twelve radiologists (10 attending and two residents) participated in observer tests and read both original and contralateral subtraction images with a sequential testing method. Radiologists' performance was evaluated by means of receiver operating characteristic analysis with use of a continuous rating scale. The beneficial and detrimental effects of the contralateral subtraction technique on the radiologists' performance were also evaluated. RESULTS: The area under the receiver operating characteristic curve values obtained without and with contralateral subtraction images were 0.926 and 0.962, respectively. Results indicated that the contralateral subtraction images significantly (P <.05) improved diagnostic accuracy, particularly for radiologists with limited experience. CONCLUSION: The contralateral subtraction technique can assist radiologists in the correct identification of subtle lung nodules on chest radiographs.     

Carotid-cardiac baroreflex function does not influence blood pressure regulation during head-up tilt in humans

The influence of the carotid-cardiac baroreflex on blood pressure regulation was evaluated during supine rest and 40 degrees head-up tilt (HUT) in 9 healthy young subjects with and without full cardiac vagal blockade. The carotid baroreflex responsiveness, or maximal gain (G(MAX)), was assessed from the beat-to-beat changes in heart rate (HR) and mean arterial pressure (MAP) by the variable neck pressure and suction technique ranging in pressure from +40 to -80 Torr, with and without glycopyrrolate (12.0 +/- 1.0 microg/kg body weight; mean +/- SE). In the supine position, glycopyrrolate increased the HR to 91 +/- 3 bpm, from 54 +/- 3; MAP to 89 +/- 2 mmHg, from 76 +/- 2; and cardiac output to 6.8 +/- 0.3 l.min(-1), from 4.9 +/- 0.3 (P < 0.05). The G(MAX) of the carotid baroreflex control of HR was reduced to -0.06 +/- 0.01 bpm.mmHg(-1), from -0.30 +/- 0.02 (P < 0.05) with no significant effect on the G(MAX) of the carotid baroreflex control of MAP. During HUT the carotid baroreflex control of MAP was unchanged, though the G(MAX) of the carotid baroreflex control of HR was increased (P < 0.05). During HUT, central blood volume, assessed by electrical thoracic admittance, and total vascular conductance were decreased with and without glycopyrrolate. Furthermore, glycopyrrolate reduced G(MAX) of the carotid baroreflex control of HR during HUT (P < 0.05) with no significant effect on G(MAX) of the carotid baroreflex control of MAP. These data suggest that during supine rest and HUT-induced decreases in central blood volume, the carotid baroreflex control of HR is mediated primarily via parasympathetic activity. Furthermore, the maintenance of arterial blood pressure during postural stress is primarily mediated by arterial and cardiopulmonary reflex regulation of sympathetic activity and its effects on the systemic vasculature.     

Japanese family with Greig cephalopolysyndactyly syndrome, including bilateral seven toes, and esotropia, over three generations.

We report a Japanese family with Greig cephalopolysyndactyly syndrome (GCPS), in which the grandmother, mother, and daughter were affected. They each had the same characteristics including bilateral seven toes, hypertelorism, and esotropia. Bilateral seven toes and esotropia had followed over three generations and have not previously been reported in this syndrome. The present case with bilateral seven toes and esotropia may be a new type.     

Contrasting effects of nifedipine and verapamil on myocardium and vascular smooth muscle at two levels of coronary occlusion in the dog

The calcium flux inhibitors nifedipine and verapamill have recently been used in the setting of both classical Heberden's and variant angina. It has also been suggested that these agents may preserve function and viability of threatened myocardium. The effects of these agents on the relationship between myocardial blood flow and contraction in the setting of partial coronary occlusion is unknown. Thus 39 open-chest dogs underwent partial coronary occlusion to diastolic perfusion pressures of 25 or 40 mm Hg. The dogs then received intracoronary infusions of 10 μg nifedipine or 100 μg verapamil. Myocardial blood flow was measured with tracer microspheres and myocardial shortening was assessed with ultrasonic crystals. At 25 mm Hg nifedipine improved myocardial shortening while blood flow did not change. In contrast, verapamil caused shortening to be abolished but also did not change blood flow. At 40 mm Hg nifedipine, while not affecting shortening, caused a “redistribution” of blood flow from endocardium; in contrast, verapamil again caused shortening to be abolished, but only increased epicardial blood flow leaving endocardial flow intact. Thus verapamil and nifedipine have differing effects. Nifedipine is a potent vasodilator at doses having no negative inotropic effects. In addition, nifedipine can cause a transmural “redistribution” of blood flow from endocardium to epicardium. In contrast, verapamil is also a potent vasodilator, but has profound negative inotropic effects.     

Influence of load of hepatitis A virus on disease severity and its relationship with clinical manifestations in patients with hepatitis A

Background and Aim: The purpose of the present study was to investigate the influence of viral load on disease severity and analyze the possible relationship of the load of hepatitis A virus (HAV) with disease severity and laboratory findings. Methods: Fifty‐eight patients diagnosed with acute hepatitis A were used in the current study, of whom 12 patients progressed to severe acute hepatitis (s‐AH) defined on the basis of a prothrombin time (PT) of <40% and 46 patients were diagnosed as having mild acute hepatitis (m‐AH). The load of HAV was measured with real‐time polymerase chain reaction. Results: Peak viral load showed a significant correlation with alanine aminotransferase (ALT) (r = 0.363, P = 0.0048) and PT levels (r = ?0.330, P = 0.0110). In terms of disease severity, there was a significant correlation with ALT (r = 0.462, P = 0.0012) and PT levels (r = 0.400, P = 0.0059) in the m‐AH group, but not in the s‐AH group. A significant positive correlation of peak viral load with the C‐reactive protein level (r = 0.270, P = 0.0400) and a significant negative correlation of peak viral load with the platelet count (r = ?0.313, P = 0.0015) was also found. Conclusions: The load of HAV was closely correlated with liver damage and disease severity in m‐AH, but not in s‐AH. The load of HAV was also closely associated with the increase in C‐reactive protein level and enhancement of thrombocytopenia.     

Clinical characteristics of upper airway resistance syndrome

Polysomnographic findings and clinical symptoms were investigated in 14 cases of upper airway resistance syndrome. The mean scores of the Epworth sleepiness scale and self-rating depression scale in eight cases were 13.5 and 38.6, respectively. The mean sleep latency of the multiple sleep latency test in four cases was 10.2 min. Seven cases were treated with continuous positive airway pressure (CPAP), and one with hormone replacement therapy. The most common symptom was daytime sleepiness. Five cases had hypertension. CPAP reduced increasing negative esophageal pressure (Pes) and frequency of EEG arousals, and improved hypertension in one case. Hormone replacement therapy ameliorated increasing negative Pes and clinical symptoms.     

Antihypertensive constituents in Sanoshashinto

It has been reported that Sanoshashinto (SanHuangXieXinTang, 三黃瀉心湯), which is composed of Rhei Rhizoma, Scutellariae Radix, and Coptidis Rhizoma, exhibits vasorelaxant effects in vitro and lowers blood pressure of patients. Based on this discovery, in this study, a mixture containing those three materials and combinations of them were extracted with methanol, and the extracts were fractionated into different parts. Effects of all extracts and fractions on high concentration of potassium chloride (High K+)- or noradrenaline (NA)-induced contractions of isolated rat aortic rings or helical strips were examined. Qualitative and quantitative HPLC analyses of the extracts and the fractions revealed that the contents of baicalin and berberine in Sanoshashinto methanol extract (SHXXTM) were higher than those of the other constituents. All pharmacological and HPLC data were analyzed by principal component analysis (PCA) software and the results indicated that baicalin, berberine, palmatine, baicalein, and wogonoside contributed significantly to the pharmacological activity. Furthermore, spontaneously hypertensive rats (SHRs) that were orally given SHXXTM or a baicalin–berberine combination showed significantly reduced increase in the rate of systolic blood pressure (SBP) compared to the control group. These findings suggested that Sanoshashinto has significant vasorelaxant effects in vitro and antihypertensive effects in vivo, and baicalin and berberine, which were the principal constituents of Scutellariae Radix and Coptidis Rhizoma, were the main antihypertensive constituents in Sanoshashinto. It was speculated that baicalin and berberine produced vasorelaxant effects by activating the NO/cGMP pathway and that the BKCa channel and the DAG/PKC/CPI-17 pathway were also involved.