Primary pulmonary valve papillary fibroelastoma

Papillary fibroelastoma (PFE) is a rare and benign cardiac tumor typically found on the valvular endocardium. In most cases, PFE is identified incidentally on echocardiography or during cardiac surgery. The patient was a 73-year-old man who had been treated for hepatocellular carcinoma for 5 years. On echocardiography, a 2.5-cm diameter mass was detected in the pulmonary trunk just above the pulmonary valve. Through a transpulmonary arterial approach with cardiopulmonary bypass, the mass identified on the commissure of the right and posterior pulmonary cusp was surgically excised together with the attached endocardium. Despite the benign histology of PFE, lethal embolic events such as stroke, myocardial infarction, and pulmonary embolism are reported in some cases. To prevent such complications, tumor identification and surgical excision are essential.     

Fatal necrotic enteritis associated with Clostridium perfringens in wild crows (Corvus macrorhynchos)

Sporadic outbreaks of fatal enteritis occurred among free-living wild crows (‘large billed’ or ‘wok’ crow; Corvus macrorhynchos) in an open-air park in Japan in 2002. Eight crows were found dead during February, followed by two more in September, and five of the eight were examined histopathologically. At necropsy, all cases showed a markedly dilated small intestine, especially the jejunum and ileum, with large amounts of gas, and dark red to greenish–brown soft content. The necrotic intestinal wall was markedly thickened with multifocal haemorrhages. All cases had multifocal white foci in the liver, and four cases showed marked splenomegaly. Histologically, there was severe necrotic enteritis characterized by extensive mucosal necrosis and multifocal haemorrhages, as well as inflammatory cell infiltrations. A prominent pseudo-membrane formation was noted in the affected intestine. Severe adhesive peritonitis was also observed in three cases. Gram-positive bacilli were present in large numbers in the lumen, and in and around necrotic lesions in the affected intestine. The bacilli were positive for Clostridium perfringens enterotoxin type A by immunohistochemistry, and were also positive for C. perfringens type A using the immunofluorescence method. C. perfringens was isolated by anaerobic culture from the intestinal contents. The present enteritis was thought to be induced by proliferated C. perfringens in the intestine, and to be the cause of death.     

Clostridium perfringens foodborne outbreak due to braised chop suey supplied by chafing dish

On February 13, 2002, a public health center in Hiroshima Prefecture, Japan, was notified that many individuals living at the Japan Maritime Self-Defence Force base had symptoms resembling those of food poisoning. Self-administered questionnaires requesting information regarding meal consumption and symptoms were distributed to all 281 members at the base. A case of the illness was defined as a member who had had watery or mucousy stool, or loose stool with abdominal cramps, more than twice a day after consuming dinner on February 12. Control of the illness was defined as a member with no symptoms. The dinner on February 12 was significantly associated with the illness (Mantel-Haenszel odds ratio: 3.59, 95% confidence interval: 1.06-12.20). A case-control study showed that, among the food supplied at dinner on February 12, the braised chop suey was significantly associated with the illness (odds ratio: 12.30, 95% confidence interval: 1.90-521.00). The braised chop suey had been stored in a chafing dish. An environmental investigation indicated that Clostridium perfringens (C. perfringens) in the chafing dish proliferated under an inappropriate heat-retention temperature, and the contaminated braised chop suey could have caused the food poisoning. This study demonstrated that the recommended heat-retention temperature (over 65 degrees C) should be confirmed thoroughly.     

Localization and expression of chondromodulin-I in the rat cornea

The localization and expression in the rat cornea of chondromodulin-I (ChM-I), an inhibitory angiogenesis factor, were examined by immunohistochemistry, Western blot analysis, ribonuclease protection assay, and real-time PCR assay. We found immunoreactivity for ChM-I in the epithelial layer but not the stromal layer or endothelial layer in the cornea, in addition to the positive ChM-I immunoreactivity in other sites in the eye such as the sclera, retina, and ciliary body. The ChM-I immunoreactivity was most intense at the outside of the basal cells and in their cytoplasm while the intensity of the immunoreactivity decreased gradually from the wing cells to the superficial cells in the corneal epithelial layer. No reactivity however, was detected in the Bowman's membrane or conjunctival epithelial cells which had continuity with the corneal epithelial cells. The expression of ChM-I mRNA was demonstrated in the cornea at one-third less intensity than that in the sclera with choroids and retinal pigment epithelium by ribonuclease protection assay and real-time PCR. ChM-I in the corneal epithelial layer may prevent neovascularization and maintain avascularity in the cornea.     

Resting CD4(+) T cells with CD38(+)CD62L(+) produce interleukin-4 which contributes to enhanced replication of T-tropic human immunodeficiency virus type 1

A significant increase in the CD38(+) population among T lymphocytes has been observed in human immunodeficiency virus type 1 (HIV-1)-infected carriers. We previously reported a higher replication rate of T-tropic HIV-1 in the CD4(+)CD38(+)CD62L(+) than CD38(-) subset under conditions of mitogen stimulation after infection. Here, we revealed a similarly high susceptibility in the CD38(+) subset on culture with conditioned medium containing Th2 cytokine, interleukin (IL)-4 that was produced endogenously from this subset on stimulation with mitogen or anti-CD3 antibody for 3 days. The contribution of IL-4 to the upregulated production of virus in the CD38(+) subset was confirmed by culture of this subset with recombinant human IL-4. In contrast, the rate of replication in the CD38(-) subset was not augmented in the conditioned medium from either subset or with IL-4. However, there were no differences in the surface expression of IL-4 receptor or HIV-1 receptors CD4 and CXCR4 between the two subsets. Thus, the CD4(+)CD38(+)CD62L(+) subset comprises a specific cell population secreting endogenous Th2 cytokine that contributes to the efficient production of T-tropic HIV-1 through upregulation at a certain stage of the viral life cycle, probably after the adsorption step.     

Two cases of limited cutaneous nodular amyloidosis with primary Sj?gren's syndrome]

We described two female patients with primary Sj?gren's syndrome associated with localized cutaneous nodular amyloidosis (LCNA), in which amyloid protein was derived from immunoglobulin light chain. Case 1; a 70-year-old female had complained with polyarthralgia, low-grade fever and parotid gland swelling. She was diagnosed as primary Sj?gren's syndrome. Three years later she noticed brown color small tumor on the thigh and yellow to brown nodules on the bilateral calves of legs. Skin biopsy from the left thigh revealed amyloid L protein deposition, which was positive for anti-lambda light chain staining, in almost entire dermis. Infiltration of lymphocytes and plasma cells around the amyloid deposit were prominent. Case 2; a 51-year-old female had noticed increasing eruption on the hip. Skin biopsy revealed amyloid L protein deposition in the dermis, which was negative for anti-lambda nor kappa light chain staining. When she was refereed to our hospital, she complained of xerostomia and xerophthalmia. She was diagnosed as primary Sj?gren's syndrome. In both cases, histological examination of a minor salivary gland biopsy revealed infiltration of lymphocytes and plasma cells but not amyloid deposit. Serum M protein and urine Bence-Jones protein were not detected. These cases represent localized amyloidosis without systemic involvement. It is widely recognized that Sj?gren's syndrome is frequently accompanied by B cell lymphoproliferative disorders. In LCNA, infiltration of plasma cells around the amyloid deposits was frequently prominent. The relation between these two disorders is discussed.     

Theory-based analysis of anti-inflammatory effect of infliximab on Crohn’s disease and rheumatoid arthritis

In Japan, the recommended dosage regimens of infliximab (IFX) for treatment of rheumatoid arthritis (RA) and Crohn’s disease (CD) are different. However, the differences have not been analyzed theoretically. In a previous study, we constructed a pharmacokinetic–pharmacodynamic model to investigate the effects of IFX for CD and found it useful to establish a rational dosage regimen of IFX for individual patients with CD. In the present study, we investigated whether the theory-based model could be used for cases of RA and also used it to evaluate the validity of the dosage regimen. The results obtained with our model were in good agreement with observed tender joint count (TJC) ratio data, which was considered to show the validity of our analysis. Thus, we concluded that the model could be used for patients with RA. Furthermore, a second administration of IFX given 2 weeks after the first infusion was important to achieve remission in the early stage of RA. We also compared the estimated pharmacodynamic parameters of RA with those of CD. The elimination rate constant of inflammation in RA was greater than that in CD, suggesting that the recovery from inflammation in RA is faster than that in CD, and indicating a reason for the difference in dosage between RA and CD. In conclusion, use of our model in light of the individual quantitative factor of tumor necrosis factor (TNF)-α allows establishment of IFX dosage regimens for individual patients.     

An Exploratory Study of Dapagliflozin for the Attenuation of Albuminuria in Patients with Heart Failure and Type 2 Diabetes Mellitus (DAPPER)

Background and Aims

Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly.

Methods

DAPPER (UMIN000025102) is a multicenter, randomized, open-labeled, parallel-group, standard treatment-controlled study, which is designed to evaluate whether dapagliflozin, one of the SGLT-2 inhibitors, decreases albuminuria in T2D patients with CHF and exerts cardioprotective effects on the failing heart. The patients are randomized to either of the dapagliflozin (5 or 10 mg, once daily orally) or control group (administration of anti-diabetic drugs administered other than SGLT 2 inhibitors). The estimated number of patients that need to be enrolled is 446 in total (223 in each group). The primary objective is the changes in the urinary albumin-to-creatinine ratio from the baseline after 2-year treatment. The key secondary objectives are (1) the safety of dapagliflozin and (2) the cardiovascular and renal efficacies of dapagliflozin.

Conclusion and Perspectives

DAPPER study investigates whether dapagliflozin decreases albuminuria and exerts beneficial effects on the failing heart in T2D patients. (UMIN000025102).

     

Different effects of pravastatin and cerivastatin on the media of the carotid arteries as assessed by integrated backscatter ultrasound.

BACKGROUND: Currently, there are various types of statins used in the treatment of hyperlipidemia and coronary artery disease. The purpose of this study was to compare the effects of a lipophilic statin (cerivastatin) with those of a hydrophilic statin (pravastatin) on the carotid arterial media using integrated backscatter (IB) ultrasound. Cerivastatin (C) has a strong anti-proliferative effect (APE) on smooth muscle cells (SMCs), whereas pravastatin (P) has a weak effect. METHODS AND RESULTS: The IB values in the media of 72 segments of carotid arteries were measured in 36 patients with hyperlipidemia before and after statin therapy or diet for 6 months (C, n=13: P, n=12: diet, n=11). In addition, IB values of 34 segments of carotid arteries were measured in 34 patients without coronary risk factors. Intima - media thickness (IMT) and arterial stiffness (stiffness beta) were measured by conventional echo at the same time. IB values did not significantly change in the P group (12.8+/-3.5 vs 12.7+/-2.7 dB), but decreased in the C group (12.1 +/-2.9 vs 10.0+/-2.7 dB, p<0.01). Also, stiffness beta did not significantly change in the P group (8.3+/-3.1 vs 7.6+/-2.5), but decreased in the C group (10.1+/-4.3 vs 7.9+/-3.3, p<0.05). IB values correlated with age (r=0.70, p<0.01) and stiffness beta (r=0.67, p<0.01) in the 34 patients without coronary risk factors. CONCLUSIONS: Statin therapy with cerivastatin, but not pravastatin, decreased the IB values of the carotid media and arterial stiffness. The difference between these 2 statins may be related to their effective dose range.     

Genetic Recombination in Escherichia coli: The Role of Exonuclease I

The indirect suppression of recB(-) and recB(-)recC(-) mutations by the sbcB(-) allele is caused by the loss of a nuclease active on denatured DNA. Results from enzyme purifications and studies with a specific antiserum demonstrate that the activity present in sbcB(+) strains, and lost in sbcB(-) strains, is exonuclease I. It is likely that sbcB is the structural gene for exonuclease I. The loss of exonuclease I activity restores the recombination proficiency of Escherichia coli cells that has been lost by mutations in the recB and/or recC genes. This indicates that in the absence of the recB-recC-determined enzyme, exonuclease I prevents recombination. Hypothetical pathways illustrating this conclusion are presented.