Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p<0.01). The incidence of the D/D genotype in MwA (25.9%) was significantly higher than that in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34, adjusted for age and gender). No differences in the remaining groups were found. Our results support the conclusion that the D allele and the D/D genotype in the ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible relationship between ACE activity and the pathogenesis of migraine.     

Chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC, which has rarely been reported in Japan. In this communication, the authors report two Japanese cases of chromophobe RCC together with the immunohistochemical findings. The tumors were composed of sheets and cribriform glands formed by tumor cells with cloudy and reticular cytoplasm. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm-Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more frequent than that to Lotus tetragonolobus agglutinin. The results of this study suggest that the tumor cellq possessed phenotypes similar to the distal nephron rather than to the proximal tubular cells.     

Modulation of endotoxin-induced histamine synthesis by cytokines in mouse bone marrow-derived macrophages

Inflammation Research -     

Evaluation of a Membrane Filter Assay System, Ortho HCV Ab Quik Pack, for Detection of Anti-Hepatitis C Virus Antibody

A simple membrane immunoassay assay system, Quik Pack, for the detection of hepatitis C virus antibody was compared with two enzyme-linked immunosorbent assays (ELISAs) in a study of 600 serum samples. Quik Pack exhibited excellent sensitivity and specificity: 96.0 and 99.7%, respectively, versus the ELISA-2 and 99.7 and 99.4%, respectively, versus the ELISA-3.     

Amplification of cell-associated immunological memory by secondary antigenic stimulus. Secondary type increase in memory.

In mice primed with a mixture of bovine serum albumin (BSA) and adjuvant (capsular polysaccharide of Klebsiella pneumoniae (CPS-K)) cell-associated immunological memory was increased secondarily after a second injection of BSA alone, whereas a primary injection of BSA alone into normal unprimed mice did not result in detectable memory. The optimum antigen doses for expression of the primary and secondary memories of adoptively transferred cells from unboosted primed donors or boosted donors in in vivo culture systems were very similar, although those observed in intact mice were very different, as reported previously. The size of the secondary memory of adoptively transferred cells from boosted donors was more than ten times greater than that of the primary memory of adoptively transferred cells from unboosted primed donors. The lag period for increase of the secondary memory was shorter than that for the primary memory. Both primary and secondary memories increased during a long period (up to 3 months) after the antigenic stimulus. From the results of this study it was concluded that cell-associated immunological memory could be amplified in a secondary fashion upon contact with a second stimulus.     

Expression and function of X chromosome-linked inhibitor of apoptosis protein in Sjögren's syndrome

Apoptotic cell death in acinar and ductal epithelial cells is thought to play an important role in the development of salivary gland dysfunction in patients with Sjogren's syndrome (SS). We examined the expression of anti-apoptotic molecules in salivary glands from patients with SS. The labial salivary glands from six human T-cell leukemia virus (HTLV)-I-seronegative and eleven HTLV-I-seropositive SS patients were analyzed by immunohistochemistry. In vitro experiments were performed with a human salivary gland cell line (HSG cells). Immunohistologic analyses revealed that Bcl-2 and Bcl-x were preferentially expressed in salivary infiltrating mononuclear cells more than acinar and ductal epithelial cells. In contrast, strong X chromosome-linked inhibitor of apoptosis protein (XIAP) expression was evident in both acinar and ductal epithelial cells. The pattern of expression of these anti-apoptotic molecules was similar in both HTLV-I-seropositive and HTLV-I -seronegative SS patients. Western blot analysis confirmed expression of XIAP in cultured HSG cells. The expression of XIAP in HSG cells was increased by IL-1beta, TGF-beta1, or IL-10. However, XIAP expression was down-regulated by TNF-alpha, which induced apoptotic cell death of HSG cells with an increase in caspase-3 activity. These effects of TNF-alpha in HSG cells were antagonized by IL-1beta, TGF-beta1, or IL-10. Our results suggest that XIAP is important in regulating apoptotic cell death of acinar and ductal epithelial cells in patients with SS.     

Hippocampal input to preoptic thermosensitive neurons in the rat

The effects of electrical stimulation of ventral subiculum (VSB) of the hippocampus of the thermosensitive neurons in the preoptic area were studied in urethane-anesthetized rats. VSB stimulation affected thermosensitive neurons more frequently (92.1%, 58 of 63) than thermally insensitive neurons (71.4%, 55 of 77). The majority of the VSB-responsive thermosensitive neurons (33 of 44 warm-units and 11 of 14 cold-units) were initially inhibited following stimulation. The result provides further support for the involvement of hippocampus in the central control of thermoregulation.     

JC virus genotyping using formalin-fixed, paraffin-embedded renal tissues

Recently genotyping of JC virus (JCV) DNA in renal tissue was reported to be useful to identify the geographic origin of unidentified cadavers. In the above study, autopsied tissue samples without storage or stored in a frozen state were used. This study examined JCV DNA sequence modifications caused by formalin-fixation, in an attempt to elucidate whether formalin-fixed, paraffin-embedded tissue samples can also be used to determine the genotypes of JCV DNA in the kidney. In four cases, a 610 bp typing region of the JCV genome was PCR-amplified from renal tissues stored for 1 year in three different states: frozen at -80 degrees C [Amaker, B.H., Chandler, F.W., Huey, L.O., Colwell, R.M., 1997. Molecular detection of JC virus in embalmed, formalin-fixed, paraffin-embedded brain tissue. J. Forensic Sci., 1157-1159], formalin-fixed, paraffin-embedded [Ault, G.S., Stoner, G.L., 1992. Two major types of JC virus defined in progressive multifocal leukoencephalopathy brain by early and late coding region DNA sequences. J. Gen. Virol. 73, 2669-2678], and soaked in 5% formalin [Baksh, F.K., Finkelstein, S.D., Swalskey, P.A., Stoner, G.L., Ryschkewitsch, C.F., Randhawa, P.R., 2001. Molecular genotyping of BK and JC virus in human polyomavirus-associated interstitial nephritis after renal transplantation. Am. J. Kidney Dis. 38 (2), 354-365]. The amplified fragments were cloned, and the resultant clones were sequenced. In frozen samples, single sequences ('original' sequences) were detected in all cases. In formalin-fixed, paraffin-embedded samples, not only the original sequences but also those with 1-6 base substitutions were detected. From formalin-soaked samples, the original sequences and those with 1-5 and 10-13 substitutions were detected. The genotyping of JCV DNA was not hampered by the presence of 1-6 substitutions, but a shift in JCV genotypes was observed in sequences with 10-13 substitutions. Thus, it was concluded that the genotypes of JCV DNA in the kidney can be determined only with specimens stored in a frozen state or formalin-fixed for a short time.     

Evidence for a link between mechanical and electrical alternans in acutely ischaemic myocardium of anaesthetized dogs.

In order to examine the relation between mechanical alternans and associated electrical alternans during acute myocardial ischaemia, we determined the effect of a ventricular premature beat and calcium antagonists on mechanical and electrical alternans during acute coronary occlusion in anaesthetized dogs. Isometric contractions and unipolar electrocardiograms were recorded from ischaemic myocardium. During coronary occlusion, mechanical alternans was accompanied by electrical alternans, which was an alternate change in the ST segment elevation, i.e. the higher ST and the lower ST. Electrical alternans was frequently discordant and in some cases accompanied by discordant mechanical alternans. Both discordant electrical and mechanical alternans became concordant and were potentiated after the ventricular premature beat. In all cases, concordant mechanical alternans was accompanied by concordant electrical alternans and vice versa. In this situation, the higher and the lower ST corresponded to the larger and the smaller contractions respectively. Thus, a fixed correspondence was observed between mechanical and electrical alternans. A fixed correspondence was also observed between mechanical alternans and the variation in the time taken for repolarization of the monophasic action potential. Verapamil and diltiazem inhibited both electrical and mechanical alternans. The present results support the idea that a common mechanism, such as a beat-to-beat cycle of the transmembrane and intracellular movement of calcium ions, may play a role in the mechanisms of electrical and mechanical alternans.