Pulmonary non-caseating granuloma in Waldenström macroglobulinemia

Lung involvement is rare in Waldenstr?m macroglobulinemia (WM). We encountered a male patient with WM who complained of breathlessness. Chest X-ray revealed diffuse infiltrative shadow throughout the both lungs. Transbronchial biopsy showed infiltration of atypical plasmacytoid lymphocytes and non-caseating granuloma. We treated the patients with fludarabine phosphate, and both his symptom and X-ray findings were then improved. To our knowledge, this is the first case showing non-caseating granuloma with lung involvement of WM. We discuss a mechanism of non-caseating granuloma formation in this case.     

Unusual developing sites of dengue vectors and potential epidemiological implications

Objective

To identify the unusual breeding sites of two dengue vectors, i.e. Aedes albopictus (Ae. albopictus) and Aedes aegypti (Ae. aegypti).

Methods

During the second half of 2010, we performed an occasional survey in rural (Teluk Tempoyak) and urban (Gelugor) areas of Penang Island, Malaysia, to identify cryptic breeding sites.

Results

In the rural area, we found heterogeneous immature stages of Ae. albopictus in the water bowl of an encaged bird. We also observed Ae. aegypti eggs deposited in the flush tank of a toilet in the urban area.

Conclusions

It can be concluded that both breeding patterns can increase contact with hosts (humans and birds) and presumably population densities of Ae. albopictus and Ae. aegypti, thereby potentially boosting the risks for spread and transmission of arboviral diseases.     

Promising efficacy of the sirolimus-eluting stent in patients with acute myocardial infarction

OBJECTIVES: This study investigated the safety and efficacy of sirolimus-eluting stents (SESs) on early and late outcomes in patients with acute myocardial infarction. METHODS: A series of 100 consecutive patients (September 2004 to November 2005)with acute myocardial infarction undergoing primary stenting using SES ptember 24 hr) was compared with 100 consecutive patients (September 2003 to August 2004) treated with bare metal stent (BMS). The frequency of major adverse cardiac events (MACE) and stent thrombosis, and status of ticlopidine administration were assessed at 270 days. RESULTS: The rates of premature discontinuation of ticlopidine (SES group <3 months: 11%, BMS group <1 month: 11%, p = NS) and stent thrombosis (SES group: 1%, BMS group: 0%, p = NS) were similar in the two groups. At follow-up, restenosis rate and target vessel revascularization rate were lower in the SES group(4% vs 19%, p < 0.001 and 4% vs 10%, p = 0.149, respectively). Furthermore, the occurrence of MACE at 270 days was significantly less frequent in the SES group compared with the BMS group (6% vs. 17%, p = 0.038). Multivariate analysis showed SES use tended to predict 270-day MACE (hazard ratio 0.37, 95% confidence interval 0.14-1.02, p = 0.055). Culprit lesion located in the left main trunk was identified as an independent predictor of 270-day MACE (hazard ratio 5.43, 95% confidence interval 1.07-27.59, p = 0.041). CONCLUSIONS: The use of a SES was not associated with increased risk of stent thrombosis compared with a BMS. With lower rates of restenosis and subsequent target vessel revascularization, SES placement could provide superior outcomes in patients with acute myocardial infarction.     

Mesenchymal Hamartoma of the Liver Accompanied by a Daughter Nodule: Report of a Case

Mesenchymal hamartoma of the liver (MHL) is an uncommon benign tumor found primarily in children younger than 2 years of age. We report a rare case of MHL with a daughter nodule and atypical histological findings in a 14-month-old girl. On admission, computed tomography, magnetic resonance imaging, and angiography showed a solid hypovascular mass with a central cystic area in the liver. Laparotomy revealed a tumor, 8 cm in size, occupying segment 5 and parts of segments 4 and 6 of the liver, and a small nodule, 10 mm in size, in segment 7. Thus, we performed a partial hepatic resection (S4–6) and tumor extirpation (S7). The histological findings of both tumors were the same, but atypical of MHL. Recent studies on the pathogenesis of this tumor have found neoplastic features such as genetic anomalies and malignant transformation. These findings suggest that the conventional approach of completely resecting the tumor whenever possible is the best treatment.     

Protective Role of Genetic Polymorphism of Heat Shock Protein 70-2 for Gastric Cancer Risk

Background Heat shock protein 70-2 (HSP70-2) has a cytoprotective role in various conditions and also protects the gastric mucosa. Recently, polymorphism of HSP70-2 at position 1267 was suggested to be associated with carcinogenesis. We investigated the association of this polymorphism with the risk of gastric cancer in the present study. Methods We examined 223 patients (159 men and 64 women, mean age 64.8 years) with gastric cancer who underwent gastrointestinal endoscopy at our department. The controls were 200 age-matched patients (140 men and 60 women) without gastric cancer diagnosed by gastrointestinal endoscopy. Genotyping was done by PCR-based restriction fragment length polymorphism analysis, and the PCR products were digested with PstI. The two allelic forms, corresponding to the presence or absence of the PstI site, were designated as the P1 allele and P2 allele, respectively. Logistic regression analysis was performed to calculate an odds ratios (ORs) for differences of HSP70-2 polymorphism between the two groups. Results Among the 223 patients with gastric cancer, 46 (20.6%) had P1/P1, 177 (79.4%) were P1 carriers, and 6 (2.7%) were P2/P2. In the control group, 33 (16.5%) patients had P1/P1 polymorphism, 167 (83.5%) were P1 carriers, and 12 (6.0%) were P2/P2. The OR for gastric cancer of subjects with P2/P2 polymorphism relative to P1 carriers was 0.43 (95% CI = 0.16–1.17) (P = 0.097). Among females, the OR for gastric cancer of subjects with P2/P2 polymorphism relative to P1 carriers was 0.10 (95% CI = 0.012–0.838) (P = 0.014). This polymorphism was also associated with a lower risk of middle third cancer (OR = 0.13; 95% CI = 0.02–1.00). Conclusions P2/P2 polymorphism of HSP70-2 at position 1267 was associated with a lower risk of gastric cancer in females.     

Direct evidence for ex vivo expansion of human hematopoietic stem cells

To characterize human hematopoietic stem cells (HSCs), xenotransplantation techniques such as the severe combined immunodeficiency (SCID) mouse repopulating cell (SRC) assay have proven the most reliable methods thus far. While SRC quantification by limiting dilution analysis (LDA) is the gold standard for measuring in vitro expansion of human HSCs, LDA is a statistical method and does not directly establish that a single HSC has self-renewed in vitro. This would require a direct clonal method and has not been done. By using lentiviral gene marking and direct intra-bone marrow injection of cultured CD34+ CB cells, we demonstrate here the first direct evidence for self-renewal of individual SRC clones in vitro. Of 74 clones analyzed, 20 clones (27%) divided and repopulated in more than 2 mice after serum-free and stroma-dependent culture. Some of the clones were secondary transplantable. This indicates symmetric self-renewal divisions in vitro. On the other hand, 54 clones (73%) present in only 1 mouse may result from asymmetric divisions in vitro. Our data demonstrate that current ex vivo expansion conditions result in reliable stem cell expansion and the clonal tracking we have employed is the only reliable method that can be used in the development of clinically appropriate expansion methods.     

Is omeprazole or misoprostol superior for improving indomethacin-induced delayed maturation of granulation tissue in rat gastric ulcers?

BACKGROUND AND AIMS: Proton pump inhibitors (PPI) and prostaglandin (PG) preparations are believed to both prevent NSAID-induced gastric ulcers and promote the delayed healing of gastric ulcers by NSAIDs, but it remains unclear which of these drugs is superior. The aim of this study was to clarify which achieved better healing of NSAID-induced gastric ulcers, not only with respect to epithelialization but also repair of the submucosal tissues. METHODS: We used acetic acid to induce gastric ulcers in rats, and compared the changes between a control group, NSAID group, NSAID + PPI group and NSAID + PG group. After removing the stomach of each animal, an ulcer index was calculated and the collagen content and type III collagen content of granulation tissue were measured. We also studied fibroblast dynamics, including proliferation, collagen synthesis, differentiation into myofibroblasts, and apoptosis. RESULTS: Indomethacin prevented re-epithelialization of the ulcers, interfered with fibroblast function, and also delayed the replacement of type III collagen. Omeprazole promoted epithelialization, but could not fully reverse the influence of indomethacin on granulation tissue maturation. A concomitant dose with misoprostolreversed it completely. CONCLUSIONS: From our point of view in this study in the use of experimental ulcers, it was thought that compensation of PG should have priority to gastric acid inhibition in terms of healing of NSAID-induced gastric ulcer.     

Myeloablative allogeneic hematopoietic stem cell transplantation for non-Hodgkin lymphoma: a nationwide survey in Japan

We retrospectively surveyed the data of 233 patients who underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) for non-Hodgkin lymphoma (NHL). Donors were HLA-matched relatives in 154 patients (66%) or unrelated volunteers in 60 (26%). Ninety patients (39%) were in complete remission. One hundred ninety-three (83%) received a total body irradiation (TBI)-based regimen, and 40 (17%) received a non-TBI-based regimen. Acute graft-versus-host disease (GVHD) occurred in 155 (67%) of the 233 evaluable patients; grade II to IV in 90 (39%), and grade III to IV in 37 (16%). Treatment-related mortality (TRM) was observed in 98 patients (42%), and 68% of them were related to GVHD. In a multivariate analysis, chemoresistance, prior autograft, and chronic GVHD were identified as adverse prognostic factors for TRM. Relapse or progression of lymphoma was observed in 21%. The 2-year overall survival rates of the patients with indolent (n = 38), aggressive (n = 111), and lymphoblastic lymphoma (n = 84) were 57%, 42%, and 41%, respectively. In a multivariate analysis, chemoresistance, prior autograft, and prior radiotherapy were identified as adverse prognostic factors for overall survival. Although myeloablative allo-HSCT represents an effective therapeutic option for patients with NHL, more work is still needed to decrease TRM and relapse.     

An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway

Although associations between endotoxin exposure or respiratory infection and asthma have been recognized, the genetic effects in these conditions are unclear. Toll-like receptors (TLRs) play an essential role in innate host defense and in the control of adaptive immune responses. IL-1R-associated kinase-M (IRAK-M) and single immunoglobulin IL-1R-related molecule (SIGIRR) negatively regulate TLR-signaling pathways. To investigate whether polymorphisms in these genes were associated with asthma or asthma-related phenotypes, we screened these genes for polymorphisms by direct sequencing of 24 asthmatics and identified 19 variants in IRAK-M and 12 variants in SIGIRR. We next conducted linkage disequilibrium mapping of the genes, and examined the association of polymorphisms and haplotypes using 391 child patients with asthma, 462 adult patients with asthma, and 639 controls. None of the alleles or haplotypes of IRAK-M and SIGIRR were associated with asthma susceptibility or asthma-related phenotype. Our results indicate that polymorphisms in IRAK-M and SIGIRR are not likely to be associated with the development of asthma in the Japanese population.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.