Juxtaposition of the T-cell receptor alpha-chain locus (14q11) and a region (14q32) of potential importance in leukemogenesis by a 14;14 translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia.

We describe a t(14;14)(q11;q32) translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia (AT). By using a battery of joining (J)-segment probes from the T-cell receptor (TCR) alpha-chain locus TCRA, three distinct J alpha rearrangements were observed. One rearrangement reflected a normal TCRA variable (V) region V alpha-to-J alpha recombination. The second rearrangement was caused by the translocation even itself, which joined a DNA segment from 14q32 centromeric to the immunoglobulin heavy chain locus (IGH) and a J alpha gene located approximately 75 kilobases (kb) 5' of the TCRA constant region gene (C alpha). A third rearrangement involved a 17-kb internal deletion 3' to the translocation, a rearrangement within the J alpha locus that has been observed once before in a patient with AT. Analysis of these three rearrangements underscores the increase in aberrant locus-specific recombination in lymphocytes from patients with AT. Furthermore, these studies support the view that a growth-effecting gene is present in the 14q32 region that participates in the leukemogenic process.     

Insulin-like growth factor binding protein-1 as a predictor of glucose-stimulated hyperinsulinemia in prepubertal obese children

OBJECTIVE: The present study was undertaken to examine the association of a glucose-stimulated insulin response with the fasting insulin-like growth factor-binding protein (IGFBP)-1 concentration in prepubertal obese children. SUBJECTS AND METHODS: The fasting levels of serum insulin and IGFBP-1 were measured in 17 obese and 16 control children. Furthermore, we performed an oral glucose tolerance test in obese children and examined the association of the area under the curve (AUC) for insulin with the fasting IGFBP-1 level. RESULTS: The mean serum level of IGFBP-1 was significantly lower in obese children (41.0 +/- 4.8 micrograms/l. P < 0.005) than in controls (91.2 +/- 9.9 micrograms/l). Although there was an inverse relationship between the fasting levels of serum insulin and IGFBP-1 in all subjects (r = -0.42, P < 0.05), no significant correlation between these two parameters was observed in the obese group alone. In obese children, the fasting IGFBP-1 level correlated inversely with AUC-insulin (r = -0.70, P < 0.005), whereas there was no significant relationship between the fasting insulin level and AUC-insulin. CONCLUSION: The present study suggests that the serum level of IGFBP-1 may be an early predictor of insulin resistance in prepubertal obesity.     

Coronary reperfusion using an extracorporeal circulating system performed in cases with abruptly obliterated coronary arteries: a new method]

For the cases with the abruptly obliterated coronary artery during angioplasty or angiography, emergency bypass surgery is mandatory. However, a "bail-out" perfusion catheter with multiple side-holes, which maintains antegrade coronary flow, is not efficient in preventing the myocardium from developing ischemia, because blood flow is interfered due to pressure-dependent perfusion mechanism in the shock state. We developed a new perfusion catheter coupled with an extracorporeal circulating system and a perfusion pump. Its effectiveness and safety were tested experimentally in canine hearts. The system is composed of a perfusion catheter (125 cm in length) with 4 side-holes within 1.5 cm of the catheter tip, and a rolar pump. Maximum flow volumes were 123 ml/min, 84 ml/min, and 52 ml/min for 4.5F, 4.3F, and 4F perfusion catheters, respectively. The left anterior descending coronary artery (LAD) was ligated after the perfusion catheter was advanced into the proximal LAD under fluoroscopic control. To avoid formation of pericatheter intracoronary thrombi, 50 U/kg/hr heparin was continuously injected during a 5-hour ligation. In the nonperfusion group (n = 4), the ST segments elevated in all dogs; 2 died of ventricular fibrillation within 30 min, and one was confirmed to have myocardial necrosis by NBT staining. In the perfusion group (n = 4), neither ECG changes nor hemodynamic deterioration was observed. Intracoronary thrombi were not observed in any surviving dogs. Coronary perfusion using our new device was performed in 2 patients: one patient, a 73-year-old man with 99% stenosis in the very proximal portion of his LAD, had massive intimal dissection after PTCA, and angiography revealed total occlusion of his proximal LAD and LCX. Coronary perfusion was immediately initiated by advancing the perfusion catheter into his LAD. After that the patient recovered from shock. Emergency bypass surgery was successfully performed after 120 min coronary perfusion with the support of IABP and inotropics. The other patient, a 58-year-old man with effort angina, had intimal dissection in the proximal portion of his right coronary artery, which was supplying collaterals to the mid LAD and LCX. Successful bypass surgery was performed 320 min after the coronary perfusion without IABP and inotropics. In conclusion, coronary reperfusion with an extracorporeal circulating system proved to have a greater effect than did passive perfusion in such cases with cardiogenic shock.     

Collagenous gastroduodenitis coexisting repeated Dieulafoy ulcer: A case report and review of collagenous gastritis and gastroduodenitis without colonic involvement

Collagenous gastritis (CG) is a rare disorder characterized by the thick collagenous subepithelial bands associated with mucosal inflammation. There have been approximately fifty reports in the literature since it was first described in 1989. According to previous reports, CG is heterogeneous and classified into two groups—(1) cases limited to the gastric mucosa in children or young adults, and (2) CG associated with collagenous colitis in elderly adults presenting with chronic watery diarrhea. In Japan, only nine previous cases were reported, and all of them were young adults. We report a case of CG with collagenous duodenitis in a 22-year-old female. She had repeated upper gastrointestinal bleeding from a Dieulafoy lesion of the fornix, but had no symptoms of malabsorption or diarrhea. Endoscopic findings revealed striking nodularity with a smooth islet-shaped normal area in the antrum and the body. The pathological findings of nodular mucosa showed the deposition of collagen bands just under the mucoepithelial lesion. In addition, she had collagenous duodenitis in part of the bulbs, and a colonoscopy showed no abnormalities. We provide a literature review of CG and collagenous gastroduodenitis without colonic involvement.     

Establishment of a human nonluteinized granulosa cell line that transitions from the gonadotropin-independent to the gonadotropin-dependent status

The ovary is a complex endocrine organ responsible for steroidogenesis and folliculogenesis. Follicles consist of oocytes and two primary steroidogenic cell types, the granulosa cells, and the theca cells. Immortalized human granulosa cells are essential for researching the mechanism of steroidogenesis and folliculogenesis. We obtained granulosa cells from a 35-yr-old female and immortalized them by lentivirus-mediated transfer of several genes so as to establish a human nonluteinized granulosa cell line (HGrC1). We subsequently characterized HGrC1 and investigated its steroidogenic performance. HGrC1 expressed enzymes related to steroidogenesis, such as steroidogenic acute regulatory protein, CYP11A, aromatase, and gonadotropin receptors. Stimulation with FSH increased the mRNA levels of aromatase, which consequently induced the aromatization of androstenedione to estradiol. Activin A increased the mRNA levels of the FSH receptor, which were synergistically up-regulated with FSH stimulation. HGrC1 also expressed a series of ligands and receptors belonging to the TGF-β superfamily. A Western blot analysis showed that bone morphogenetic protein (BMP)-4, BMP-6, and BMP-7 phosphorylated small mother against decapentaplegic (Smad)1/5/8, whereas growth differentiation factor-9 phosphorylated Smad2/3. BMP-15 and anti-Müllerian hormone phosphorylated Smad1/5/8 while also weakly phosphorylating Smad2/3. These results indicate that HGrC1 may possess the characteristics of granulosa cells belonging to follicles in the early stage. HGrC1 might also be capable of displaying the growth transition from a gonadotropin-independent status to gonadotropin-dependent one.     

Efficacy of rosuvastatin for the treatment of non‐alcoholic steatohepatitis with dyslipidemia: An open‐label,pilot study

Aim: Statins, an inhibitor of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, are reported to be useful for the treatment of non‐alcoholic steatohepatitis (NASH). Currently, there is no proven therapy for NASH. In this study, we assessed the efficacy of rosuvastatin in NASH patients with dyslipidemia. Methods: Nineteen patients with biopsy‐proven NASH with dyslipidemia who agreed to participate in this prospective study were enrolled. The patients were treated for 24 months with 2.5 mg/day rosuvastatin. Clinical and histological alterations were comparatively evaluated before and after treatment. Standard weight‐loss counseling was continued during the treatment period. Follow‐up liver biopsy was performed in nine patients. Results: Twenty‐six percent of patients had hyperlipoproteinemia type IIa and 74% had hyperlipoproteinemia type IIb at baseline. Body mass indices were not significantly changed during the treatment. The levels of transaminases were relatively low at the beginning, and were not significantly changed during the treatment. Lipid profiles were significantly improved by the treatment with rosuvastatin for 24 months. While non‐alcoholic fatty liver disease activity score and fibrotic stage did not change significantly in all patients, they were improved in 33.3% and 33.3% individual patients, and stayed stable in 33.3% and 55.6%, respectively. Conclusion: NASH‐related metabolic parameters improved with therapy including histology in some patients. However, one of nine patients had progression of fibrosis during the treatment. Our pilot study demonstrated the efficacy of rosuvastatin for the treatment of NASH with dyslipidemia, even if transaminases are not so elevated and controlled trials are needed in the future.     

Radiographic remodeling of the shoulder joint in a patient with rheumatoid arthritis after 4 years of treatment with etanercept

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