Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.     

Left atrial thrombus causing pulmonary embolism by passing through an atrial septal defect.

A 66-year-old woman admitted with dyspnea on exertion had atrial fibrillation and left ventricular dysfunction. Echocardiography revealed an atrial septal defect (ASD) and a soft, easily deformable thrombus in the dilated left atrium. The atrial mass suddenly disappeared on the 10th day after admission, and contrast-enhanced chest computed tomography and pulmonary blood flow scintigraphy showed that the thrombus had detached from the left atrium, floated into the right atrium through the ASD and caused pulmonary embolism. This is the first documented case of a left atrial thrombus causing pulmonary embolism by passing through an ASD. When an ASD is present, it is important to consider not only paradoxical thromboembolism (from the right to the left atrium), but also pulmonary embolism caused by thromboembolism from the left to the right atrium.     

MgH2–CoO: a conversion-type composite electrode for LiBH4-based all-solid-state lithium ion batteries

Several studies have demonstrated that MgH₂ is a promising conversion-type anode toward Li. A major obstacle is the reversible capacity during cycling. Electrochemical co-existence of a mixed metal hydride-oxide conversion type anode is demonstrated for lithium ion batteries using a solid-state electrolyte. 75MgH₂·25CoO anodes are obtained from optimized mixing conditions avoiding reactions occurring during high-energy ball-milling. Electrochemical tests are carried out to investigate the cycling capability and reversibility of the on-going conversion reactions. The cycling led to formation of a single-plateau nanocomposite electrode with higher reversibility yield, lowered discharge–charge hysteresis and mitigated kinetic effect at high C-rate compared to MgH₂ anodes. It is believed that reduced diffusion pathways and less polarized electrodes are the origin of the improved properties. The designed composite-electrode shows good preservation and suitability with LiBH₄ solid electrolyte as revealed from electron microscopy analyses and X-ray photoelectron spectroscopy.

The findings point to a means of guided formation of MgH₂–CoO conversion-type nanocomposite electrode for all-solid-state Li-ion batteries.     

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

BackgroundRadial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding.MethodsPatients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days.ResultsIn the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; P_interaction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; P_interaction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant.ConclusionsOur findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.     

A Rare Case of Ectopic Adrenocorticotropic Hormone Syndrome with Recurrent Olfactory Neuroblastoma

A 40-year-old woman who had a history of recurrent olfactory neuroblastoma presented with full moon face, central obesity, buffalo hump, impaired glucose tolerance and bilateral cervical lymph node swelling. Laboratory tests showed morbidly elevated levels of adrenocorticotropic hormone (ACTH) and cortisol, which were not suppressed by high-dose (8 mg) dexamethasone. Biopsies of the enlarged cervical lymph nodes revealed ACTH-positive metastatic olfactory neuroblastoma, and ectopic ACTH syndrome was diagnosed. Metyrapone was used to suppress cortisol production and resulted in decreased levels of ACTH and cortisol. Bilateral cervical tumor resection further reduced the ACTH and cortisol levels, accompanied by a reduction in the metyrapone dosage. Cushing''s syndrome was alleviated through ACTH-producing tumor removal.     

Development of Epstein-Barr virus-associated gastric cancer: Infection,inflammation, and oncogenesis

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells originate from a single-cell clone infected with EBV. However, more than 95% of patients with gastric cancer have a history of Helicobacter pylori (H. pylori) infection, and H. pylori is a major causative agent of gastric cancer. Therefore, it has long been argued that H. pylori infection may affect the development of EBVaGC, a subtype of gastric cancer. Atrophic gastrointestinal inflammation, a symptom of H. pylori infection, is observed in the gastric mucosa of EBVaGC. Therefore, it remains unclear whether H. pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H. pylori and EBV infections act independently on gastric cancer formation. It has been reported that EBV infection assists in the onco-genesis of gastric cancer caused by H. pylori infection. In contrast, several studies have reported that H. pylori infection accelerates tumorigenesis initiated by EBV infection. By reviewing both clinical epidemiological and experimental data, we reorganized the role of H. pylori and EBV infections in gastric cancer formation.     

Laparoscopy-assisted spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein

Herein, we report the successful performance of a laparoscopy-assisted spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein for a patient with pancreatic cystadenoma, as a minimally invasive procedure with the preservation of function. The laparoscopy-assisted distal pancreatectomy procedure involved detaching the spleen and the distal pancreas from the retroperitoneum by a hand-assisted procedure, removing them from the peritoneal cavity through a small incision, and detaching the distal pancreas by ligating and transecting the short gastric artery and vein and the branches of the splenic artery and vein, while the spleen and main splenic artery and vein were preserved under direct view. The pancreatic parenchyma was transected with a stapling device (TL-30), and continuous suturing was added to the resected margin. The patient’s postoperative course was uneventful; the patient started to eat and walk on postoperative day 2 and was discharged on day 8. It is considered that the combination of hand-assisted and laparoscopy-assisted distal pancreatectomy, with conservation of the splenic artery and vein, is a minimally invasive and clinically useful technique for treating tumors of cystic disease of the pancreas with low-grade malignant potential, or benign solitary neuroendocrine tumors.     

Follow-up studies of Hokkaido residents with Kawasaki disease

OBJECTIVES: Sixteen national surveys of Kawasaki disease in Japan from 1970 to 2000 have identified a total of 169,117 patients with Kawasaki disease. Based on that figure, 8,460 residents of Hokkaido probably have a history of Kawasaki disease. It is also estimated that almost 270 Hokkaido residents would have Kawasaki disease-related coronary artery disease. We underwent follow-up studies of Hokkaido residents > or = 15 years with Kawasaki disease. METHODS: We mailed a questionnaire to the departments of internal medicine, cardiology or cardiovascular surgery inquiring about the health status of patients with Kawasaki disease at 451 hospitals with 20 or more beds in Hokkaido. RESULTS: We obtained replies from 185 hospitals (41.0%). Only 11 hospitals(5.9%) reported experience of patients with Kawasaki disease(with or without coronary artery disease) at hospital follow-up. Detailed patient histories for 60 patients from 7 hospitals were obtained: Twenty patients had Kawasaki disease complicated with coronary artery disease, whereas 40 patients had a history of Kawasaki disease and no present coronary artery disease. Thirty-seven patients without coronary artery disease were followed up at one hospital. The 60 patients were aged from 15 to 36 years. Thirty-nine patients(65%) were in the 15 to 20 year age bracket. Coronary aneurysms were recognized in 25 patients(24 males and 1 female) with Kawasaki disease(41.7%) at the onset of the disease. Twenty patients had an aneurysm(s) in the left main trunk and/or the left anterior descending artery, and 13 patients in the right coronary artery. There was a history of myocardial infarction in four patients (6.7%) and nine patients(15.0%) still suffered from angina pectoris. Aortocoronary bypass surgery was performed in one patient, whereas two patients required percutaneous coronary intervention. CONCLUSIONS: Our study suggests that the majority of Hokkaido residents with Kawasaki disease(with or without coronary artery disease) are not being followed up at area hospitals. The characteristics of patients who were followed up included age < or = 20 years, male sex and the presence of severe coronary artery disease other than circumflex involvement.     

Lysophosphatidic acid transactivates both c-Met and epidermal growth factor receptor, and induces cyclooxygenase-2 expression in human colon cancer LoVo cells

AIM: To examine whether lysophosphatidic acid (LPA) induces phosphorylation of c-Met and epidermal growth factor receptor (EGFR), both of which have been proposed as prognostic markers of colorectal cancer, and whether LPA induces cyclooxygenase-2 (COX-2) expression in human colon cancer cells. METHODS: Using a human colon cancer cell line, LoVo cells, we performed immunoprecipitation analysis, followed by Western blot analysis. We also examined whether LPA induced COX-2 expression, by Western blot analysis. RESULTS: Immunoprecipitation analysis revealed that 10 umol/L LPA induced tyrosine phosphorylation of c-Met and EGFR in LoVo cells within a few minutes. We found that c-Met tyrosine phosphorylation induced by LPA was not attenuated by pertussis toxin or a matrix metalloproteinase inhibitor, in marked contrast to the results for EGFR. In addition, 0.2-40 umol/L LPA induced COX-2 expression in a dose-dependent manner. CONCLUSION: Our results suggest that LPA acts upstream of various receptor tyrosine kinases (RTKs) and COX-2, and thus may act as a potent stimulator of colorectal cancer.