Membranous glomerulopathy induced by myeloperoxidase-anti-neutrophil cytoplasmic antibody-related crescentic glomerulonephritis

A 68-year-old woman was referred for evaluation of nephrotic-range proteinuria and a course suggesting rapidly progressive glomerulonephritis. Serum anti-neutrophil cytoplasmic antibody against myeloperoxidase (MPO) was 204 U/ml. A renal biopsy specimen revealed necrotizing glomerulonephritis with crescent formation. However, immunofluorescence showed staining with IgG and C3 along capillary walls. IgG positivity included both IgG1 and IgG4. Electron microscopic examination disclosed both paramesangial and subepithelial deposits. This case suggests that rarely, MPO-ANCA-related crescentic glomerulonephritis may present nephrotic-range proteinuria and show immune deposits along capillary walls.     

Unexpected functional consequences of xenogeneic transgene expression in beta-cells of NOD mice

We describe unexpected alterations in the non-obese diabetic (NOD/Lt) mouse model of type 1 diabetes (T1D) following forced beta-cell expression of non-mammalian genes ligated to an insulin promoter sequence. These include the jellyfish green fluorescent protein (GFP), useful for beta-cell identification, and the bacteriophage P1 Cre recombinase, necessary for beta cell-specific ablation of a gene using a Cre-loxP system. Homozygous expression of GFP, driven by the mouse insulin 1 gene promoter (MIP-GFP) in a single transgenic line of NOD mice, produced T1D in postnatal mice that was not associated with insulitis, but rather beta cell-depleted islets. Hemizygous transgene expression suppressed spontaneous autoimmune T1D in females, and produced a male glucose intolerance syndrome associated with age-dependent declines in plasma insulin content. Among lines of transgenic NOD/Lt mice expressing Cre recombinase driven by the rat insulin 2 promoter (RIP-Cre), high, non-mosaic expression correlated with suppressed T1D development. These findings emphasize the need for careful characterization of genetically manipulated NOD mouse stocks to insure that model characteristics have not been compromised.     

A prospective study of the utility of abdominal radiographs after capsule endoscopy for the diagnosis of capsule retention

BACKGROUND: Capsule retention is a rare but serious complication of capsule endoscopy (CE). The utility of routine abdominal radiographs after CE for the diagnosis of capsule retention is not established. OBJECTIVE: To establish the utility of abdominal radiographs in the diagnosis of capsule retention in patients undergoing CE. DESIGN: Prospective cohort study. PATIENTS: Consecutive patients undergoing CE. SETTING: Mayo Clinic Scottsdale, Arizona, a multispecialty academic medical center. INTERVENTION: Abdominal radiographs were performed on days 3, 7, and 14 after CE. If the patient visualized passage of the capsule, the subsequent abdominal radiograph was cancelled. MAIN OUTCOME AND MEASUREMENTS: Capsule retention, defined as the capsule endoscope seen on the day-14 abdominal radiograph. RESULTS: A total of 115 patients (46% men; mean age 65 years, range 20-88 years) underwent CE, which was performed for obscure GI bleeding in 86%, for suspected Crohn's disease in 5%, and for other indications in 9%. Thirty-four patients (30%) reported spontaneous passage of the capsule by day 3 and an additional 2 patients by day 7. Of the 81 reporting nonpassage by day 3, 66 (82%) underwent abdominal radiographs. Abdominal radiographs in 14 of 66 patients (21%), 3 of 12 (25%), and 2 of 3 (66%) showed a retained capsule on day 3, 7, and 14, respectively. Three patients (2.6%) were diagnosed with capsule retention. Two had serial abdominal radiographs: capsule retention was detected on the day-14 radiographs, and both underwent surgery. Histopathology revealed diaphragm disease of the small intestine in both patients. One patient who did not have serial abdominal radiographs had a small-bowel tumor as the cause of his capsule retention. In all 3 patients, the colon was not visualized on CE. CONCLUSIONS: Capsule retention is a rare but serious complication of CE. Most patients do not visualize capsule passage. For patients who do not visualize capsule passage and, in whom the colon is not visualized on the video imaging, an abdominal radiograph on day 14 will help identify those with capsule retention.     

Studies on motile-Aeromonas infection: incidence of motile-Aeromonas in river mud, river water and fresh-water fish

During the period from October 1982 to July 1984, a total of 1,157 specimens that consisted of 132 river and lake water, 514 river and lake muds, and 511 fresh-water fish caught in both Tama River and Sagami River were examined the presence of the organisms. Of them, 132 (100%) river and lake waters, 304 (59.1%) river and lake muds, and 462 (90.4%) intestinal contents of fresh-water fish were found to have harbor a mean concentration of 1.3 x 10(3)/l, 1.6 x 10(6)/g, and 1.1 x 10(6)/g of motile-Aeromonas respectively. However, nonseasonal variation was observed in the incidence of the organisms throughout the period of investigation. When attempts were made to classify the isolates by the method described Popoff et al., 17 (14.2%) of 120 water-isolates were typed as A. hydrophila, 33 (27.5%) as A. sobria and 35 (29.2%) as A. caviae respectively. And the rest of the 35 (29.2%) remained untypable. As for the 176 mud-isolates, 38 (21.6%) were typed as A. hydrophila 23 (13.1%) as A. sobria and 41 (23.3%) as A. caviae respectively. And the rest of 74 (42.0%) remained untypable. Some efforts were made on the 1,056 strains obtained from fresh-water fish, and 182 (17.2%) were typed as A. hydrophila, 332 (31.4%) as A. sobria and 206 (19.5%) as A. caviae respectively. And the rest of the 336 (31.8%) remained untypable.     

IFN-inducible protein 10 (CXCL10) regulates tubular cell proliferation in renal ischemia-reperfusion injury

Although renal tubular cell proliferation after acute tubular necrosis is an important and essential response in the recovery of renal dysfunction in acute renal failure, the precise factors and mechanisms of tubular cell regeneration remain unclear. Here, we describe our studies using a neutralizing antibody (Ab) against interferon-inducible protein of 10 kDa (IP-10; CXCL10) that indicate a role for CXCL10 in tubular cell proliferation after renal ischemia-reperfusion injury. Tissue necrosis and interstitial infiltrating numbers were comparable between anti-CXCL10 Ab-treated and control mice treated with IgG at the 24 and 48 h time points after reperfusion. In contrast, the numbers of Ki67-positive proliferating tubular cells were significantly increased in anti-CXCL10 Ab-treated mice 48 h after reperfusion. In accordance with the in vivo findings,in vitro studies using murine tubular epithelial cells indicated an antiproliferative effect of CXCL10 upon the intensity of cell proliferation and the number of Ki67-positive cells. These data suggest that CXCL10 plays a role in the regulation of tubular cell proliferation following renal ischemia-reperfusion injury.     

Evaluation of Oncotype DX Recurrence Score as a prognostic factor in Japanese women with estrogen receptor-positive, node-negative primary Stage I or IIA breast cancer

Purpose

We sought to evaluate the use of the Onco type DX Breast Cancer Assay for identifying candidates for adjuvant therapy in patients with estrogen receptor (ER)-positive, node-negative primary Stage I or IIA breast cancer.

Methods

A retrospective case–control study was conducted on 40 patients who underwent surgery between 2000 and 2008. Cases (n = 10) were patients who had metastases after surgery. Controls (n = 30) were patients who did not develop metastases and were individually matched to their case with respect to age. All patients were analyzed with regard to age, tumor size, histological grade, HER2 status, and the values of Recurrence Score (RS), ER score and PgR score generated by Onco type DX. We also divided the patients into low, intermediate or high-risk groups according to individual RS values.

Results

RS, risk category and histological grade were associated with metastases in patients with ER-positive, node-negative Stage I or IIA breast cancer. However, ER status, tumor size and PgR status were not associated with metastases. Histological grade was associated with RS value and the distribution pattern of risk category (P < 0.001 for each).

Conclusions

Both histological grade and risk-category classification were effective in identifying women at risk of developing distant metastases after initial therapy for ER-positive, node-negative Stage I or IIA breast cancer. These patients may benefit from the addition of adjuvant therapy at diagnosis.     

Attenuation of biventricular pressure gradients by cibenzo-line in an 18-year-old patient with hypertrophic obstructive cardiomyopathy.

An 18-year-old male patient with biventricular hypertrophic obstructive cardiomyopathy (HOCM) had successful reduction of the pressure gradients by cibenzoline. At 11 months after birth, he was first diagnosed with cardiac murmurs and by the age of 5 years, he was diagnosed with subpulmonic infundibular stenosis with a pressure gradient of 10 mmHg by cardiac catheterization. At the age of 14, re-catherterization revealed hypertrophic cardiomyopathy with isolated obstruction of the right ventricular outflow tract, with a pressure gradient of 70 mmHg, but no obstruction in the left ventricle. He began daily treatment with 30 mg propranolol. At the age of 18, he was admitted for cardiac evaluation. An echocardiogram revealed left mid-ventricular and subpulmonic obstructions associated with pressure gradients of 88 mmHg and 65 mmHg, respectively. A single oral dose of 200 mg of cibenzoline decreased the pressure gradients in the left and right ventricles (38 mmHg and 36 mmHg, respectively). He was then given 300 mg daily of cibenzoline, and both pressure gradients remained low without any complications 8 months later at the time of discharge.     

A case of bronchial gland cell-type adenocarcinoma with relapsed pneumonia and hemoptysis]

We report a case of bronchial gland cell-type adenocarcinoma with recurrent pneumonia and hemoptysis. After persistent hemoptysis since the summer of 1999, a 26-year-old female patient was admitted to our hospital because of bacterial pneumonia of the left lower lobe in March 2000. Treatments with antibiotics resulted in only a transient improvement of the pneumonia, and so she was re-admitted for an investigation of the recurrent pneumonia accompanied with hemoptysis. Bronchofiberscopy revealed a polypoid lesion at the orifice on the left B10 bronchus. Although the microscopic examination of the biopsied specimens showed only non-specific inflammatory changes, a left lower lobectomy was performed. The pathological examination of the resected lung confirmed that the polypoid region was bronchial gland cell type adenocarcinoma at the stage of pT1N0M0.     

Association of the FAM167A–BLK region with systemic sclerosis

Objective

An association of single‐nucleotide polymorphisms (SNPs) in the FAM167A (previously referred to as C8orf13)–BLK region with systemic lupus erythematosus (SLE) has been demonstrated in Caucasians and in Asians. Recent studies have shown that many genes, including IRF5, STAT4, and PTPN22, are shared susceptibility genes in multiple autoimmune diseases. We undertook the current study to examine whether the FAM167A–BLK region is also associated with susceptibility to systemic sclerosis (SSc).

Methods

Japanese patients with SSc (n = 309) and healthy controls (n = 769) were enrolled in a 2‐tiered case–control association study. In tier 1, 124 patients and 412 controls were tested to determine association of 16 tag SNPs encompassing the FAM167A–BLK region with SSc. In tier 2, an additional 185 patients and 357 controls were analyzed for SNP rs13277113.

Results

Two haplotype blocks that correspond approximately to FAM167A and BLK were observed. In tier 1 of the study, the rs13277113A allele in the BLK block exhibited the most significant association with SSc after correction for multiple testing (permutated P = 0.024). Two SNP haplotypes formed by rs13277113 and the most significant SNP in the FAM167A block did not exhibit stronger association. When samples from tier 1 and tier 2 were combined, the rs13277113A allele was significantly associated with SSc (odds ratio 1.45 [95% confidence interval 1.17–1.79], P = 6.1 × 10⁻⁴). Association or a tendency toward association of rs13277113A with SSc was observed regardless of a patient's autoantibody profile or whether a patient had diffuse cutaneous or limited cutaneous SSc.

Conclusion

Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A–BLK region is a common genetic risk factor for both SLE and SSc.

     

Differential detection of nuclear envelope autoantibodies in primary biliary cirrhosis using routine and alternative methods

Background  

Detection of autoantibodies giving nuclear rim pattern by immunofluorescence (anti-nuclear envelope antibodies - ANEA) in sera from patients with primary biliary cirrhosis (PBC) is a useful tool for the diagnosis and prognosis of the disease. Differences in the prevalence of ANEA in PBC sera so far reported have been attributed to the methodology used for the detection as well as to ethnic/geographical variations. Therefore, we evaluated the prevalence of ANEA in sera of Greek patients with PBC by using methods widely used by clinical laboratories and a combination of techniques and materials.