Surgical repair of a common atrium in an adult.

We report a rare successful surgical repair of a common atrium (CA) with mild tricuspid valve (TV) regurgitation due to valvular annulus enlargement in a 39-year-old man, who had a complete atrial septum defect (ASD) without the characteristic of an endocardial cushion defect. The left-to-right shunt ratio was 85 percent and the Qp/Qs was 6.7 due to the CA. Left ventriculogram revealed no evidence of typical goose-neck deformity and no mitral valve regurgitation. The operation consisted of making a new atrial septum with an autologous pericardial patch and tricuspid annuloplasty (DeVega) using extracorporeal circulation. There was no evidence of a cleft on the anterior leaflet of the mitral valve or the septal leaflet of the TV. The postoperative echocardiogram showed no residual shunt flow through a new atrial septum and no TV regurgitation, and atrioventricular (AV) dissociation did not occur. We consider this procedure to be widely applicable in consideration of the favorable results obtained after surgical treatment.     

Drug Binding to α1-Acid Glycoprotein Studied by Circular Dichroism

The interactions of acidic and basic drugs with ₁-acid glycoprotein (₁-AGP) were investigated using circular dichroism (CD) measurements. Extrinsic Cotton effects were generated by the binding of drugs to ₁-AGP. The CD data suggested the presence of a single binding site on the ₁-AGP molecule. The induced ellipticities of the acidic drug–₁-AGP system decreased with increasing pH, while the ellipticities for the basic drugs increased with pH. The ellipticities for all drugs were reduced by the addition of fatty acids. Furthermore, the induced ellipticities decreased in the presence of cesium chloride for basic drugs bound to ₁-AGP. The extrinsic Cotton effects therefore appear to result from hydrophobic interaction with ₁-AGP for the acidic drugs and from hydrophobic and electrostatic interactions for the basic drugs.     

Characterization of htAKR, a novel gene product in the aldo-keto reductase family specifically expressed in human testis

In human testis, expression of a novel member of the aldo-keto reductase family was identified. Based on its testis-specific expression, we termed this protein human testis aldo-keto reductase (htAKR). In addition to four major isoforms, the existence of multiple alternatively spliced products of htAKR was detected using RT-PCR followed by nested PCR. htAKR was a homologue of mouse liver keto-reductase, AKR1E1, with close similarity in their genomic organizations. htAKR4, the longest isoform, was expressed as a non-fused native form. It exhibited a limited activity toward 9,10-phenanthrenequinone, while no activity toward the steroids or prostaglandins was demonstrated. Using the laser capture microdissection technique and RT-PCR, expression of htAKR was detected in testicular germ cells as well as in interstitial cells. The levels of htAKR mRNA in the tissues obtained from seminoma were much lower than those in normal testes. A significant decline in the htAKR expression was observed when NEC8, a cell line originated from a human testicular germ cell tumour, was exposed to phorbol 12-myristate 13-acetate or 5alpha-dihydrotestosterone. These results indicate that the expression of htAKR, down-regulated in the testicular tumour, is possibly controlled by mitogenic and hormonal signals.     

A novel t(2;6)(p12;q23) appearing during transformation of follicular lymphoma with t(18;22)(q21;q11) to diffuse large cell lymphoma

Follicular lymphoma is characterized genetically by t(14;18)(q32;q21), whereas t(18;22)(q21;q11), a rare variant form of t(14;18), has been preferentially observed in chronic lymphocytic leukemia (CLL). We describe here an unusual case of follicular lymphoma with a t(18;22)(q21;q11), that progressed to diffuse large cell lymphoma with a novel t(2;6)(p12;q23). Spectral karyotyping revealed that add(2)(p12) and add(6)(q23) were derived from a t(2;6)(p12;q23). Fluorescence in situ hybridization analysis confirmed rearrangements of the BCL2 gene at 18q21 and the BCL6 gene at 3q27. Our results indicate that a reciprocal translocation involving 6q23 could be implicated in the progression of follicular lymphoma and that t(18;22) may have a specific role in the pathogenesis of follicular lymphoma as well as CLL.     

Immunosuppressive effect of restraint stress on the initiation of allergic rhinitis in mice

BACKGROUND: Exposure to acute stressors modulates both innate and acquired immune function. However, little is known about whether stress has the potential to modulate the pathogenesis of allergic rhinitis. OBJECTIVES: To determine the effects of acute restraint stress on the initiation of allergic rhinitis in a murine model. METHODS: CBA/J mice were repeatedly intranasally sensitized with phospholipase A2 (PLA2) from honeybee venom without adjuvant. Restraint stress was applied using uniform cylinders once a week for a continuous 8-hour period, on five occasions in total. Production of PLA2-specific antibodies and degree of nasal and blood eosinophilia were compared between stressed and control mice. RESULTS: Repeated intranasal sensitization with PLA2 induced PLA2-specific IgE and marked eosinophilia in both the nose and blood in CBA/J mice. Exposure to restraint stress significantly inhibited production of PLA2-specific IgE, IgG1 and IgG2a. Conversely, the stress exerted no significant effect on eosinophilia. CONCLUSIONS: Exposure to acute restraint stress inhibits antigen-specific antibody production, but not local or systemic eosinophilia. The results of this study suggest that acute stress has the potential to modulate the initiation of allergic rhinitis.     

Stromal-derived factor-1alpha/CXCL12-CXCR 4 axis is involved in the dissemination of NSCLC cells into pleural space

Malignant pleural effusion (PE) is one of the poor prognostic factors in non-small cell lung cancer (NSCLC), and the detailed mechanism of the malignant PE formation is not fully elucidated. Recently, CXCR4, a receptor for chemokine stromal-derived factor-1alpha (SDF-1alpha) that can induce chemotaxis of cells, was reported to be expressed on NSCLC. In this study, we hypothesized that the SDF-1alpha/CXCR4 axis may be involved in the dissemination of malignant cells into pleural space, and investigated its expression, function, and signaling pathway using NSCLC cell lines and clinical samples from 43 patients with NSCLC with malignant PE. We found functional expression of CXCR4 on NSCLC cell lines, and also found that SDF-1alpha could induce migration via phosphatidylinositol 3 (PI-3) kinase- and p44/42 mitogen-activated protein kinase-dependent manner. The SDF-1alpha levels in malignant PE were significantly higher than those in transudate PE and showed a significant positive correlation with PE volumes. The sensitivity and specificity for prediction of recurrence of malignant PE was 61.5% and 83.3%, respectively (cutoff SDF-1alpha = 2,500 ng/ml), and better than those using pH of PE. Cancer cells in malignant PE expressed CXCR4, and mesothelial cells of the pleura stained positive for SDF-1alpha. The SDF-1alpha/CXCR4 axis is involved in the dissemination of NSCLC cells into pleural space.     

Mucinous cystadenoma of the testis

A 35-year-old man complained of a painless enlargement of the right testis. Imaging diagnostic procedures demonstrated a multiloculated cystic tumor, 9 cm in maximal diameter, in the right testis with hydrocele. Orchidectomy specimen showed that the tumor was confined within the testis and separated from the epididymis. The locules of the tumor were lined by single-layered columnar epithelium, intermingled with MUC2 immunopositive goblet and chromogranin-A immunopositive neuroendocrine cells, exhibiting intestinal differentiation. No ciliated cell, teratomatous element or intratubular germ cell neoplasia were seen. Channels of rete testis were compressed peripherally by the tumor but there was no connection with the tumor locules. The tumor was diagnosed as mucinous cystadenoma of the testis. This seems to be the first published case of benign mucinous cystadenoma occurring within the testis. This intratesticular tumor with intestinal differentiation may represent a benign monodermal teratoma.     

Roles of the Maltese cross form in the development of parasitemia and protection against Babesia microti infection in mice

Babesia microti, a hemoprotozoan parasite of rodents, is also important as a zoonotic agent of human babesiosis. The Maltese cross form, which consists of four masses in an erythrocyte, is characteristic of the developmental stage of B. microti. Monoclonal antibody (MAb) 2-1E, which specifically recognizes the Maltese cross form of B. microti, has been described previously. In the present study, we examined the roles of the Maltese cross form during the infectious course of B. microti in mice. The number of the Maltese cross form increased in the peripheral blood of infected mice prior to the peak of parasitemia. With confocal laser scanning microscopy, MAb 2-1E was found to be reactive with the ring form, with the parasites undergoing transformation to the Maltese cross form and subsequent division, and also with extracellular merozoites. Furthermore, the Maltese cross form-related antigen (MRA) gene was isolated from a B. microti cDNA library by immunoscreening with MAb 2-1E, and the nucleotide sequence was determined. Genomic analyses indicated that the MRA gene exists as a single-copy gene in B. microti. Immunization of mice with recombinant MRA induced significant protective immunity against B. microti infection. These findings indicate that the Maltese cross form plays important roles in both the development of parasitemia and the protective response against the infection.