Antiproliferative effects of 5-fluorouracil and interferon-alpha in combination on a hepatocellular carcinoma cell line in vitro and in vivo

Background and Aim: We investigated the antiproliferative effects of interferon‐alpha (IFN‐α) and 5‐fluorouracil (5‐FU) in combination on a hepatocellular carcinoma (HCC) cell line. Method: In the in vitro study, IFN‐α and/or 5‐FU was added to the culture of the poorly differentiated‐type HCC cell line, HAK‐1B, and their antiproliferative effects and additional or synergic effects in combination treatment were examined. In the in vivo study, HAK‐1B cells were transplanted into nude mice and the changes in tumor volume and weight, apoptosis, BrdU and cyclin A positive cells, and artery‐like blood vessels were investigated. Expressions of angiogenesis factors and IFN‐α receptor (IFNAR‐2) were examined in the developed tumors. Results: In vitro growth of HAK‐1B cells was suppressed dose‐dependently to 5‐FU, but the addition of IFN‐α did not induce additional or synergic effects. In vivo growth in terms of tumor diameter and weight was suppressed at most in the IFN‐α + 5‐FU (combination) group, that is, the tumor volume became 29.3% and the tumor weight became 54.7% of the control. In the combination group, numbers of BrdU‐positive S‐phase cells and cyclin A positive cells increased together with the increase in apoptotic cells, but there was no significant relation between the tumor shrinkage effects and angiogenesis factors or artery‐like blood vessels. In the combination group, INFAR‐2 decreased significantly in comparison to the other groups. Conclusion: The synergic growth‐suppression effects in the current in vivo study using the combination treatment are attributable to the enhanced induction of S‐phase arrest and of apoptosis.     

Delayed Treatment with YM90K,an AMPA Receptor Antagonist,Protects against Ischaemic Damage after Middle Cerebral Artery Occlusion in Rats

The neuroprotective effect of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist YM90K [6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione monohydrochloride] has been examined in a rat middle cerebral artery occlusion model. Intravenous infusion of YM90K (2·5–20mgkg^?1h^?1 for 4 h) starting immediately after occlusion of the middle cerebral artery significantly reduced the cortical infarct volume 24 h after occlusion compared with the control group. The protection at the highest dose was 39% (P<0·05). Similar protective effects were observed when YM90K (20mgkg^?1h^?1 for 4 h) was delayed up to 2 h after middle cerebral artery occlusion (45% reduction, P<0·05). CNS1102 [N-(1-naphthyl)-N′-(3-ethylphenyl)-N′-methylguanidine hydrochloride], a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, also reduced the cortical infarct volume when 1·3mgkg^?1 was administered by intravenous bolus injection immediately after middle cerebral artery occlusion, followed by intravenous infusion at 0·785 mgkg^?1h^?1 for 4 h (35% reduction, P<0·05). This neuroprotective effect was not observed when administration was delayed 1 h after middle cerebral artery occlusion. These results suggest that AMPA receptors might play a more important role than NMDA receptors in the late development of neuronal cell damage after focal cerebral ischaemia and that AMPA receptor blockade would be one beneficial strategy in treating acute stroke.     

Increased Mast Cell Density in Peritoneal Endometriosis Compared with Eutopic Endometrium with Endometriosis

PROBLEM: Factors regulating fibrosis in peritoneal endometriosis are poorly understood. We hypothesized that mast cell proteases may play a role in the process of fibrosis in peritoneal endometriosis. As the first step in examining the possible contribution of mast cells to fibrosis, we investigated their distribution in peritoneal endometriosis lesions according to their macroscopic appearance. METHOD OF STUDY: Mast cells were identified by immunohistochemistry using monoclonal antibody against mast cell tryptase on formalin-fixed, paraffin-embedded sections. Mast cell density (mean mast cell count per 0.13 mm² of stroma) was measured using a computerized image analysis system. RESULTS: Mast cell density was significantly increased in black peritoneal lesions compared with red peritoneal lesions in endometriosis. CONCLUSIONS: Mast cells may be involved in the pathogenesis of peritoneal endometriosis.     

Relationship between odor perception and depression in the Japanese elderly

Abstract Odor perception has been studied in patients with various mental disorders; however, no consensus has been reached as to its detection, identification, or pleasantness/unpleasantness of odors especially in patients with depression. One hundred and nineteen normal elderly individuals living at home were exposed to odors of rose, perfume, white ginger, Indian ink, cigarette smoke, milk, feces and orange scent using the scratch and sniff method. They were asked to rate the strength of each odor, its pleasantness or unpleasantness, their liking for it, and their familiarity with it. They were also asked to complete a self-rating depression scale (SDS). The relationship of the score of each psychological olfactory scale with the SDS score and the difference in the score of each psychological scale between high-SDS and low-SDS groups are discussed.     

NUCLEAR MAGNETIC RESONANCE STUDY ON SOLVENT DEPENDENCE OF SIDE CHAIN CONFORMATIONS OF TYROSINE AND TRYPTOPHAN DERIVATIVES

The stereoselectively β-deuterated species of Ac-Ar-NHMe, Ac-Ar-OH and Ac-Ar-OEt (Ar = Tyr and Trp) and H-Trp-NHMe were synthesized. 270-MHz ¹H n.m.r. spectra of the normal and deuterated species of these aromatic amino acid derivatives were analyzed. For most of the tyrosine and tryptophan derivatives in various polar and nonpolar solvents, the lower-field and higher-field β-proton signals were found to be due to the pro-S and pro-R protons, respectively. However, the alternative assignments apply for H-Trp-NHMe in aqueous solution and for Ac-Tyr-NHMe and Ac-Trp-NHMe in nonpolar solvents. Such alternative assignments of β-proton signals were also found for H-Phe-NHMe, Ac-Phe-NMe₂ and Ac-Phe-OtBu. From the analyses of the ¹H n.m.r. spectra of tyrosine and tryptophan derivatives, the vicinal coupling constants and rotamer populations about the C_α-C_β bond were determined in various solvents. The rotamer populations of H-Trp-NHMe, Ac-Ar-NHMe, Ac-Ar-OH and Ac-Ar-OEt depend significantly on solvent polarity. Each of these four types of derivatives exhibits specific solvent-polarity dependences of rotamer populations. The solvent dependences of rotamer populations were substantially reduced on replacement of α-carbonyl group by methylene group, suggesting the effect of this carbonyl group in the solvent dependence of rotamer populations.     

Clinical Structural Anatomy of the Inferior Pyramidal Space Reconstructed Within the Cardiac Contour Using Multidetector‐Row Computed Tomography

Although many studies have described the detailed anatomy of the inferior pyramidal space, it may not be easy for cardiologists who have few chances to study cadaveric hearts to understand the correct morphology of the structure. The inferior pyramidal space is the part of extracardiac fibro‐adipose tissue wedging between the 4 cardiac chambers from the diaphragmatic surface of the heart. Many cardiologists have interests in pericardial adipose tissue, but the inferior pyramidal space seems to have been neglected. A number of important structures, including the coronary sinus, atrioventricular node, atrioventricular nodal artery, membranous septum, muscular atrioventricular sandwich (previously called the “muscular atrioventricular septum”), atrial septum, ventricular septum, aortic valvar complex, mitral valvar attachment, and tricuspid valvar attachment are associated with the inferior pyramidal space. We previously revealed its 3‐dimensional live anatomy using multidetector‐row computed tomography. Moreover, the 3‐dimensional understanding of the anatomy in association with the cardiac contour is important from the viewpoints of clinical cardiac electrophysiology. The purpose of this article is to demonstrate extended findings regarding the clinical structural anatomy of the inferior pyramidal space, which was reconstructed in combination with the cardiac contour using multidetector‐row computed tomography, and discuss the clinical implications of the findings.     

Hepatitis C virus RNA present in saliva but absent in breast-milk of the hepatitis C carrier mother

In order to examine whether saliva and breast-milk are mediators of the vertical transmission of hepatitis C virus (HCV) from an HCV carrier mother, serum, saliva, and breast-milk samples from 11 HCV carrier mothers were collected at the time of delivery, and at approximately 1- to 3-month intervals for as long as 30 months postpartum. Serum was also sampled from their children. All samples were analysed for the presence of HCV RNA, using the nested polymerase chain reaction method. No HCV RNA was detected in any breast-milk samples. In saliva, HCV RNA was detected in four of the 11 mothers (36%). These four mothers also had liver function abnormalities. Hepatitis C virus RNA was not detected in any serum samples of the children, and all children had normal liver function. The children were monitored for periods from 2 to 44 months. During this period, there was no evidence of virus transmission. Breast-milk is not likely to be a source of mother-to-child transmission of HCV. Maternal saliva may harbour HCV, but it may not result in infant infection.     

Immunological features of patients with primary biliary cirrhosis (PBC) overlapping systemic sclerosis: A comparison with patients with PBC alone

To characterize the immunological features of patients with primary biliary cirrhosis (PBC) overlapping systemic sclerosis (SSc), 26 patients with PBC were classified according to the presence of scleroderma-related features (Raynaud's phenomenon, sclerodactyly etc.). The patients were classified into 10 patients with PBC overlapping SSc (PBC-SSc), four patients with some scleroderma-related features although not meeting the criteria of SSc (PBC-SSc spectrum) and 12 patients with PBC alone. Sera from PBC-SSc showed a significantly higher positivity to anti-centromere antibody (P < 0.01) and to E1β of pyruvate dehydrogenase complex (P < 0.005) than those from patients with PBC alone. The same tendency was observed in PBC-SSc spectrum patients. Patients with PBC exhibiting scleroderma-related features, in both the PBC-SSc and PBC-SSc spectrum, may comprise a subset in PBC, not only clinically, but also immunologically.