Twins with Neonatal Pemphigus Vulgaris Born to a Mother with Pemphigus Vulgaris: A Case Report

Abstract: Dichorionic diamniotic twins were born at 37 weeks of gestation by cesarean section to a 34‐year‐old primigravid Japanese woman because the first twin was in breech presentation. The mother had been diagnosed with pemphigus vulgaris prior to her pregnancy. In addition to a high antidesmoglein 3 autoantibody titer, flaccid bullae and erosions on both of the twins’ lips and in their oral cavities at 13 days of age led to the diagnosis of neonatal pemphigus vulgaris. This case highlights the need for awareness that pemphigus vulgaris may not occur immediately after birth.     

EARLY GASTRIC CANCER WITH WIDESPREAD DUODENAL INVASION WITHIN THE MUCOSA

We report a rare case of early gastric cancer confined to the mucosal layer with extensive duodenal invasion, curatively removed with distal gastrectomy. An 84‐year‐old Japanese woman was referred to our hospital with gastric cancer. A barium meal examination and esophagogastroduodenoscopy revealed an irregular nodulated lesion measuring 6.5 x 5.5 cm in the gastric antrum and an aggregation of small nodules in the duodenal bulb. A biopsy specimen showed well‐differentiated adenocarcinoma. The patient underwent distal gastrectomy with partial resection of the duodenal region containing the tumor and regional lymph node dissection, with no complication. Histological examination of the resected tissue confirmed well‐differentiated adenocarcinoma limited to the mucosal layer and without lymph node metastasis. The cancer extended into the duodenum as far as 38 mm distant from the pyloric ring, and the resected margins were free of cancer cells. Gastric cancer located adjacent to the pyloric ring thus has the potential for duodenal invasion, even when tumor invasion is confined to the mucosal layer. In such cases, care should be taken during examinations to detect duodenal invasion, and the distal surgical margin must be negative given sufficient duodenal resection.     

Serum H‐ficolin levels: Clinical association with interstitial lung disease in patients with systemic sclerosis

Ficolins, a group of oligomeric lectins consisting of three isoforms (H‐, L‐ and M‐ficolin), contribute to innate immunity via activating the complement pathway and/or acting directly as opsonins against pathogens and apoptotic cells. Because apoptotic cells likely drive the development of systemic sclerosis (SSc) partly through innate immunity, we assessed the clinical association of serum H‐ficolin levels in SSc patients. Despite no difference in serum H‐ficolin levels between SSc and control subjects, SSc patients with decreased serum H‐ficolin levels tended to have a higher prevalence of interstitial lung disease (ILD). More importantly, serum H‐ficolin levels inversely correlated with ground‐glass opacity score on chest computed tomography in SSc‐ILD patients. Therefore, H‐ficolin‐related innate immunity may be involved in SSc‐ILD development.     

Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain

The sodium-potassium pump (Na⁺,K⁺-ATPase) is responsible for establishing Na⁺ and K⁺ concentration gradients across the plasma membrane and therefore plays an essential role in, for instance, generating action potentials. Cardiac glycosides, prescribed for congestive heart failure for more than 2 centuries, are efficient inhibitors of this ATPase. Here we describe a crystal structure of Na⁺,K⁺-ATPase with bound ouabain, a representative cardiac glycoside, at 2.8 Å resolution in a state analogous to E2·2K⁺·Pi. Ouabain is deeply inserted into the transmembrane domain with the lactone ring very close to the bound K⁺, in marked contrast to previous models. Due to antagonism between ouabain and K⁺, the structure represents a low-affinity ouabain-bound state. Yet, most of the mutagenesis data obtained with the high-affinity state are readily explained by the present crystal structure, indicating that the binding site for ouabain is essentially the same. According to a homology model for the high affinity state, it is a closure of the binding cavity that confers a high affinity.     

NO EVIDENCE FOR PATIENT‐TO‐PATIENT TRANSMISSION OF HEPATITIS C VIRUS DURING UPPER GASTROINTESTINAL ENDOSCOPY: MOLECULAR STUDIES ON THREE ACUTE HEPATITIS C PATIENTS

Background: The risk of patient‐to‐patient transmission of hepatitis C virus (HCV) during endoscopy remains controversial. Using molecular approaches, we examined the possibility of patient‐to‐patient transmission of HCV in three patients who developed acute hepatitis C 1–6 months after examination by upper gastrointestinal endoscopy (UGIE) in a hospital endoscopy unit in Japan. Methods: For the source of HCV infection, we used frozen sera obtained from potential candidates who underwent UGIE earlier than three index patients on the same days in the same unit. HCV genotype was determined by multiplex polymerase chain reaction (PCR) with genotype‐specific primers. The 1087‐nucleotide (nt) sequence of the NS5B region of the HCV genome was compared between index patients and their HCV‐viremic candidates. Results: The three index patients were exclusively infected with HCV of genotype 1b. Among a total of 60 candidate patients who underwent UGIE earlier than the index patients, 14 were positive for anti‐HCV, of whom 12 had detectable HCV‐RNA (1b, n = 9; 2a, n = 1; 2b, n = 2) on sera collected during each UGIE. Shared identity within the 1087‐nt NS5B sequence was less than 95.0% between index patients and HCV/1b‐infected candidates (n = 3, 1 and 5, respectively). None of the remaining 46 candidates who were negative for anti‐HCV at UGIE examination tested positive for HCV‐RNA, nor seroconverted to anti‐HCV on their sera, which most likely excludes the possibility of HCV viremia despite the anti‐HCV‐negative serology at UGIE examination. Conclusion: The present study suggests that patient‐to‐patient transmission of HCV during UGIE is infrequent.     

Aberrant crypt foci as precursors of the dysplasia-carcinoma sequence in patients with ulcerative colitis

PURPOSE: Long-standing ulcerative colitis (UC) predisposes patients to the development of colorectal cancer, but surveillance of colitis-associated cancer by detecting the precancerous lesion dysplasia is often difficult because of its rare occurrence and normal-looking appearance. In sporadic colorectal cancer, aberrant crypt foci (ACF) have been reported by many investigators to be precursor lesions of the adenoma-carcinoma sequence. In the present study, we analyzed the genetic background of ACF to determine whether they could be precursors for dysplasia, and we examined the usefulness of endoscopic examination of ACF as a surrogate marker for surveillance of colitis-associated cancer. EXPERIMENTAL DESIGN: ACF were examined in 28 UC patients (19 patients with UC alone and 9 patients with UC and dysplasia; 2 of those patients with dysplasia also had cancer) using magnifying endoscopy. K-ras, APC, and p53 mutations were analyzed by two-step PCR RFLP, in vitro--synthesized protein assay, and single-strand conformation polymorphism, respectively. Methylation of p16 was analyzed by methylation-specific PCR. RESULTS: ACF that appeared distinct endoscopically and histologically were identified in 27 out of 28 UC patients. They were negative for K-ras, APC, and p53 mutations but were frequently positive for p16 methylation (8 of 11; 73%). In dysplasia, K-ras and APC mutations were negative but p53 mutation (3 of 5; 60%) and p16 methylation (3 of 5; 60%) were positive. There was a significant stepwise increase in the number of ACF from patients with UC alone to patients with dysplasia and to patients with cancer. Univariate and multivariate analyses showed significant correlations between ACF and dysplasia. CONCLUSIONS: We have disclosed an ACF-dysplasia-cancer sequence in colitis-associated carcinogenesis similar to the ACF-adenoma-carcinoma sequence in sporadic colon carcinogenesis. This study suggests the use of ACF instead of dysplasia for the surveillance of colitis cancer and warrants further evaluation of ACF as a surveillance marker in large-scale studies.     

Recurrence of gastric cancer in the jejunal pouch after completion gastrectomy

We herein present a case of recurrence of gastric cancer in the jejunal pouch after total gastrectomy in a 74-year-old man. He had a history of two operations for gastric cancer. The second operation was a completion gastrectomy with jejunal pouch reconstruction and regional lymphadenectomy, for gastric cancer in the cardia of the remnant stomach, performed 2 years and 9 months before the present admission. A follow-up endoscopy showed three elevated tumors along the suture lines in the jejunal pouch in the upper digestive tract. Resection of the jejunal pouch was performed. Gross pathological examination revealed elevated lesions along the staple suture lines in the jejunal pouch. Histopathologically, moderately differentiated tubular adenocarcinoma involving the muscular layer, without lymphatic metastases, was recognized. Recurrence of gastric cancer in the jejunal pouch after resection is rare. We suggest that implantation of exfoliated cancer cells gave rise to the recurrence of tumors on the suture line in this patient. We also review two cases of gastric cancer in the jejunal pouch after resection previously described in the literature.     

Arsenite-induced thymus atrophy is mediated by cell cycle arrest: a characteristic downregulation of E2F-related genes revealed by a microarray approach.

Thymus atrophy is induced by a variety of chemicals, including environmental contaminants and is used as a sensitive index to detect their adverse effects on lymphocytes. In the present study we adopted a toxicogenomics approach to identify the pathways that mediate the atrophy induced by arsenite. We also analyzed gene expression changes observed in the course of thymus atrophy by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dexamethasone (DEX), and estradiol (E2), to determine whether arsenite induces atrophy by activating an arsenite-specific pathway or the same pathways as other chemicals. These compounds were intraperitoneally administered to C57BL/6 mice at doses that reduce thymus weight by approximately 30% within 3 days, and gene expression changes in the thymus 24 h after the administration were analyzed by using microarrays and real-time PCR. The microarray analysis showed that arsenite specifically downregulates a variety of E2F target genes that are involved in cell cycle progression. The same genes were also downregulated when mouse B-cell lymphoma A20 cells were exposed to arsenite. Arsenite exposure of the A20 cells was confirmed to induce cell cycle arrest, mainly in the G(1) phase, and reduce cell number. Cell cycle arrest in the G(1) phase was also confirmed to occur in the thymocytes of the arsenite-exposed mice. These results indicate that arsenite induces thymus atrophy through E2F-dependent cell cycle arrest. The results of this study also show that analysis of gene expression in thymuses is a useful method of obtaining clues to the pathways that mediate the effects of atrophy-inducing chemicals.     

Prevention by acetylsailcylic acid of liver cirrhosis and carcinogenesis as well as generations of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances caused by a choline-deficient, L-amino acid-defined diet in rats

Effects of acetylsailcylic acid (ASA) (aspirin) on the pathogenesisof fatty liver, cirrhosis and hepatocarcinogenesis caused bya choline-deficient L-amino acid-defined (CDAA) diet were examinedin male Fischer 344 rats fed a CDAA diet supplemented with 0,0.1, 0.2, 0.4 or 0.8% ASA for 30 weeks. ASA at concentrationsof >0.2% prevented the development of both cirrhosis andpreneoplastic and neoplastic nodules, but without any directlyassociated prevention of fatty changes. ASA also prevented hepatocyteproliferation and the generation of thiobarbituric acid-reactivesubstances and 8-hydroxydeoxyguanosine caused by feeding theCDAA diet, analyzed, respectively, after 1, 12 and 12 weeks.The results clearly indicate that the anti-inflammatory drugASA, which is not a lipotropic factor, can prevent the pathogenesisof cirrhosis and hepatocarcinogenesis caused by a CDAA diet,which is possibly partly associated with the prevention of reactiveoxygen species production.     

Different Roles of 8-Hydroxyguanine Formation and 2-Thiobarbituric Acid-reacting Substance Generation in the Early Phase of Liver Carcinogenesis Induced by a Choline-deficient, l-Amino Acid-defined Diet in Rats

The present study was performed to assess the roles of hepatocellular oxidative damage to DNA and constituents other than DNA in rat liver carcinogenesis caused by a choline-deficient, l -amino acid-defined (CDAA) diet by examining the effects of the antioxidant N, N' -diphenyl- p -phenylenediamine (DPPD). The parameters used for cellular oxidative damage were the level of 8-hydroxyguanine (8-OHGua) for DNA and that of 2-thiobarbituric acid-reacting substance (TBARS) for constituents other than DNA. A total of 40 male Fischer 344 rats, 6 weeks old, were fed the CDAA diet for 12 weeks with or without DPPD (0.05, 0.10 or 0.20%) or butylated hydroxytoluene (BHT, 0.25%). In the livers of the rats, the numbers and sizes of glutathione S -transferasc (EC 2.5.1.18) placental form (GSTP)- and/or γ-glutamyltransferase (GGT, EC 2.3.2.2)-positive lesions and levels of 8-OHGua and TBARS were determined. The GSTP-positive lesions of 0.08 mm² or larger were all stained positively for GGT as well in cross-sectional area, whereas the smaller lesions were generally negative for GGT. DPPD and BHT reduced the size of the GSTP-positive lesions without affecting their total numbers. At the same time, they reduced TBARS generation without affecting 8-OHGua formation in DNA. The present results indicate that oxidative DNA damage (represented by 8-OHGua formation) and damage to constituents other than DNA (represented by TBARS generation) may play different roles in rat liver carcinogenesis caused by the CDAA diet; the former appears to be involved in the induction of phenotypically altered hepatocyte populations while the latter may be related to the growth of such populations.