Microscopic polyangiitis associated with diffuse panbronchiolitis

There are several case reports of systemic vasculitis associated with chronic suppurative lung diseases. We describe a 46-year-old female, previously diagnosed as having diffuse panbronchiolitis (DPB), presenting with hemosputum and dyspnea. Her serum titer of MPO-ANCA was positive together with a high titer of BPI-ANCA. Chest X-ray and chest CT scan showed pulmonary hemorrhage, and the renal biopsy specimen revealed necrotizing, crescentic glomerulonephritis. She was diagnosed as having ANCA-associated vasculitis, and more specifically, microscopic polyangiitis accompanied by DPB. She was treated with methylprednisolone pulse therapy, followed by intravenous cyclophosphamide. This case suggested a possible association with chronic bacterial infection, which may play a role in the pathogenesis of ANCA-associated vasculitis.     

Vanadyl‐TrBR4‐Catalyzed Oxidative Polymerization of Diphenyl Disulfide

A newly established catalyst system for oxygen‐oxidative polymerization of diphenyl disulfide is reported. Combination of vanadyl compounds (e.g., VO(acac)₂) and triphenylmethylium tetrakis(pentafluorophenyl)borate (TrB(C₆F₅)₄) proceeds the polymerization to give poly(1,4‐phenylene sulfide) (PPS) at 100 °C. When triphenylmethylium tetrafluoroborate (TrBF₄) is applied with vanadyl tetraphenylporphyrin (VO(TPP)) or N,N′‐(ethylenebis(salicylideneaminato))oxovanadium (VO(salen)), PPS is also given via polymerization under conditions near 160 °C. Combination of the vanadyl complex and the borate affords the first protic‐acid‐free catalytic system for the polymerization of the disulfide, suggesting the overall reaction to produce PPS and H₂O from O₂ and protons that are eliminated from the monomer.

     

A Gain‐of‐Function Mutation in NALCN in a Child with Intellectual Disability,Ataxia, and Arthrogryposis

NALCN and its homologues code for the ion channel responsible for half of background Na⁺‐leak conductance in vertebrate and invertebrate neurons. Recessive mutations in human NALCN cause intellectual disability (ID) with hypotonia. Here, we report a de novo heterozygous mutation in NALCN affecting a conserved residue (p.R1181Q) in a girl with ID, episodic and persistent ataxia, and arthrogryposis. Interestingly, her episodes of ataxia were abolished by the administration of acetazolamide, similar to the response observed in episodic ataxia associated with other ion channels. Introducing the analogous mutation in the Caenorhabditis elegans homologue nca‐1 induced a coiling locomotion phenotype, identical to that obtained with previously characterized C. elegans gain‐of‐function nca alleles, suggesting that p.R1181Q confers the same property to NALCN. This observation thus suggests that dominant mutations in NALCN can cause a neurodevelopmental phenotype that overlaps with, while being mostly distinct from that associated with recessive mutations in the same gene.     

Randomized controlled trial: PPI-based triple therapy containing metronidazole versus clarithromycin as first-line treatment for Helicobacter pylori in adolescents and young adults in Japan

Background/Aims

Treating Helicobacter pylori infection in young people is effective for preventing gastric cancer. This study compares the efficacy of triple therapies in adolescents and young adults in Japan.

Risk stratification for the development of chronic pulmonary aspergillosis in patients with Mycobacterium avium complex lung disease

Background

The number of patients with pulmonary nontuberculous mycobacterial disease complicated by chronic pulmonary aspergillosis (CPA) has been increasing. Additionally, CPA is reportedly associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). In the present study, we aimed to identify risk factors for developing CPA and stratify the risk for CPA development in patients with MAC-LD.

Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1beta production in Helicobacter pylori infection

BACKGROUND & AIMS: Although epidemiological studies suggest that interleukin (IL)-1 genetic polymorphisms are involved in Helicobacter pylori-related gastric carcinogenesis, the data are conflicting regarding the effects of these polymorphisms on IL-1beta production. METHODS: IL-1B-511 polymorphism was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and IL-1RN variable number of tandem repeats was determined by PCR. Mucosal IL-1beta levels were measured by enzyme-linked immunosorbent assay. To determine which factors influence mucosal IL-1beta levels, gastric inflammation, and atrophy, multiple regression analyses were performed. RESULTS: We studied 117 H. pylori-infected Japanese patients. Carriers of the IL-1B-511T/T genotype or IL-1RN*2 allele had higher mucosal IL-1beta levels than noncarriers (partial regression coefficient [PRC] +/- SE), TT versus CC: 37.6 +/- 6 [antrum] and 32.1 +/- 6 [corpus] pg/mg protein (P < 0.001 for each), *1/*2 versus *1/*1: 24 +/- 8 [antrum] (P <0.01) and 36.5 +/- 7 [corpus] (P <0.001). Simultaneous carriers of IL-1B-511T/T genotype and IL-1RN*2 allele had the highest IL-1beta levels (82.9 +/- 12 [antrum] and 87.2 +/- 11 [corpus]) and showed a synergistic effect between 2 loci. The *1/*2 carriers were closely related to atrophy (PRC +/- SE; 0.87 +/- 0.4 [antrum] and 0.93 +/- 0.4 [corpus], P < 0.05), whereas being a carrier of the -511T/T genotype was related to severe gastric inflammation. CONCLUSIONS: IL-1 genetic polymorphisms influenced H. pylori-related gastric mucosal IL-1beta levels and were related to gastric inflammation and atrophy, factors thought to be important in gastric carcinogenesis.     

Chronic necrotizing pulmonary aspergillosis in pneumoconiosis: clinical and radiologic findings in 10 patients.

STUDY OBJECTIVE: To characterize clinical, radiographic, and CT findings of chronic necrotizing pulmonary aspergillosis (CNPA) in patients with pneumoconiosis. METHODS: We studied 10 patients with pneumoconiosis who were seen at Asahi Rosai Hospital and received a clinical diagnosis of CNPA during a 15-year period, and detailed the long-term clinical and radiologic courses of four cases. RESULTS: All patients were men, ranging in age from 48 to 77 years (mean, 60.1 years). Their occupational histories included pottery making (n = 9) and coal mining (n = 1). Chest radiographic findings by the International Labor Organization profusion grading system were greater than category 2. All patients were symptomatic, with a productive cough, hemoptysis, and dyspnea. Serum findings were positive for the Aspergillus antibody in seven patients. The radiologic findings consisted of parenchymal infiltrates and cavities mostly containing mycetoma, which generally involved the upper lobes. The disease progressed slowly; in one patient, broad destruction of the lung was observed after > 10 years without antifungal administration. Most of the patients experienced clinical and radiologic improvement after receiving antifungal therapy, by oral, inhaled, or intracavitary administration. CONCLUSIONS: Chronic persistent or progressive upper-lobe infiltrates and cavities in patients with pneumoconiosis should raise the possibility of CNPA. Early diagnosis and initiation of effective therapy are recommended to achieve a better outcome.     

Serum total homocysteine concentrations and risk of mortality from stroke and coronary heart disease in Japanese: The JACC study

Evidence for association between serum total homocysteine (tHcy) level and cardiovascular disease is limited in Asian populations. We conducted a nested case-control study under JACC Study. A total of 39,242 subjects aged 40-79 years provided serum samples at baseline surveys between 1988 and 1990. Control subjects were selected by matching for sex, age, community and year of serum storage. Serum tHcy levels were measured by high-performance liquid chromatography. During the 10-year follow-up, there were 444 deaths due to total cardiovascular disease, including 310 total stroke (131 hemorrhage and 101 ischemic strokes) and 134 coronary heart diseases. The risks of mortality from ischemic stroke, coronary heart disease, and total cardiovascular disease were significantly higher in individuals with the highest serum tHcy quartile (>or=15.3micromol/L) than in those with the lowest quartile (<10.5micromol/L); the respective multivariable odds ratios (95% CI) were 4.35 (1.12-16.9), 3.40 (1.17-9.86), and 1.68 (1.02-2.77). The multivariable odds ratios associated with a 5-micromol/L increase in tHcy were 1.49 (1.01-2.18), 2.01 (1.21-3.35), and 1.15 (1.00-1.32), respectively. High serum tHcy levels were associated with increased mortality from ischemic stroke, coronary heart disease and total cardiovascular disease among Japanese.