Combined pure red cell aplasia and autoimmune hemolytic anemia in systemic lupus erythematosus with anti-erythropoietin autoantibodies

A 42-year-old woman with systemic lupus erythematosus was admitted to our hospital because of severe anemia. Her bone marrow was almost normocellular and erythroblasts were nearly absent. Laboratory data showed elevated levels of lactate dehydrogenase and positive findings on Coombs' tests. On the basis of these findings, her anemia was diagnosed as the overlap of pure red cell aplasia with autoimmune hemolytic anemia. Radioimmunoprecipitation assay revealed that her serum was positive for anti-erythropoietin antibodies before therapy. Furthermore, the autoantibodies inhibited proliferation of an erythropoietin-dependent cell line in a dose-dependent manner. Immunosuppressive treatment improved the anemia accompanied with disappearance of the autoantibodies.     

Gastrobiliary motility is not coordinated in patients with non-ulcer dyspepsia of normal gastric emptying time: simultaneous sonographic study

BACKGROUND: Disorders of the motor function of the upper gastrointestinal tract have been implicated in the pathogenesis of non-ulcer dyspepsia. Approximately 50% of patients with abdominal symptoms (without ulcer) have normal gastric emptying. Apart from gastric emptying, other mechanisms are very important in the etiology of non-ulcer dyspepsia. METHODS: Gastric emptying and gallbladder motility were simultaneously investigated in 16 patients with non-ulcer dyspepsia and in 15 healthy controls. Fasting blood samples were taken, and pepsinogen levels were assayed. RESULTS: Gastric emptying time, fasting antral diameter, and post-prandial antral diameter were not significantly different between the patients with non-ulcer dyspepsia and the controls. Fasting gallbladder volume, the time required to reach minimal gallbladder residual volume, minimal gallbladder residual volume, and the serum levels of pepsinogen were not significantly different. Simple linear regression was used to summarize the relationship between gastric emptying time and time required to reach minimal gallbladder residual volume. In the controls, the gastric emptying time and time required to reach minimal gallbladder residual volume were linearly related. However, in the patients with non-ulcer dyspepsia, they were not related. CONCLUSIONS: These observations suggest that disturbance of coordination between gastric emptying and gallbladder emptying is a cause of the symptoms of non-ulcer dyspepsia.     

Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints

OBJECTIVE: We have reported that articular cartilage showed early stage degeneration at 7 and 14 days after immobilization, moderate degeneration at 28 days, and severe degeneration at 42 days in rabbits. To test whether apoptosis occurs in association with p53 expression in chondrocytes during the process of articular cartilage degeneration, we investigated the degree of cartilage degeneration, the frequency of apoptotic cells, and the levels of p53 mRNA in rabbits and mice after knee immobilization. METHODS: Right knees of male Japanese white rabbits were immobilized in full extension with fiberglass casts for up to 42 days. Similarly, right knees of male p53 wild-type [p53 (+/+)] and p53 null [p53 (-/-)] mice were immobilized in full extension with bandage tape for up to 84 days. Apoptotic cells were confirmed by TUNEL staining on the sections of knee joints. Total RNA of articular chondrocytes obtained from Day 0 or immobilized knees was analyzed semiquantitatively by RT-PCR using specific primers for p53. RESULTS: Articular cartilage degenerated after immobilization of p53 (+/+) mouse knees, but not after immobilization of p53 (-/-) knees. Apoptotic cells were observed in articular cartilage in the femur and tibia of rabbits and p53 (+/+) mice after immobilization. However, only a few apoptotic cells were observed at the same sites in p53 (-/-) mice. In RT-PCR analysis, the levels of p53 mRNA obtained from immobilized groups were significantly higher than those of Day 0 groups in rabbit and p53 (+/+) mouse knees. CONCLUSION: Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints.     

Increased plasma thioredoxin in patients with acute myocardial infarction

BACKGROUND AND HYPOTHESIS: Thioredoxin is an important biomarker for oxidative stress. We investigated whether thioredoxin levels were elevated in patients with acute myocardial infarction (AMI) and were associated with the results of coronary reperfusion. METHODS: The present study determined plasma thioredoxin levels in 51 patients with AMI, 30 patients with stable exertional angina (SEA), and 30 patients with chest pain syndrome (CPS). Plasma sampling was performed on admission, at 12 h, 1 week, 2 weeks, and 4 weeks in patients with AMI, and after admission in patients with SEA and CPS. RESULTS: Plasma thioredoxin levels on admission were higher in patients with AMI than in those with SEA and CPS. Plasma thioredoxin levels in patients with AMI were decreased in 12 h without further change thereafter. However, thioredoxin levels in patients with AMI remained higher than in those with SEA. In multivariate analysis, higher levels of thioredoxin on admission were a risk factor for failure in emergent reperfusion therapy in patients with AMI independent of other factors. CONCLUSION: Plasma thioredoxin levels are elevated in patients with AMI, and higher thioredoxin levels may predict subsequent failed coronary reperfusion therapy in patients with AMI.     

Primary malignant peripheral nerve-sheath tumor of the common bile duct

Primary malignant peripheral nerve-sheath tumors of the common bile duct are extremely rare. To our knowledge, the published literature contains no previous case report of this disease. Here we report on a 58-year-old Japanese woman with a primary malignant peripheral nerve-sheath tumor of the common bile duct, which was completely resected. A hypoechoic mass was identified in the hepatic hilus, using ultrasonography and computed tomography. Endoscopic retrograde cholangiography revealed a smooth stricture and deviation of the common bile duct. Laparotomy exposed a firm mass around the common bile duct that had not invaded the surrounding tissues. Partial resection of the common bile duct and cholecystectomy were performed as the treatment of choice. The final histopathological diagnosis was malignant peripheral nerve-sheath tumor arising from the wall of the common bile duct.     

Hepatitis B virus markers and antibodies to hepatitis C virus in Japanese patients with hepatocellular carcinoma

Sera from Japanese patients with chronic liver disease were tested for hepatitis B virus (HBV) markers and antibodies to hepatitis C virus (anti-HCV), and the results were correlated to the presence of hepatocellular carcinoma. In chronic non-A, non-B liver disease, anti-HCV prevalence was high both in patients with hepatocellular carcinoma (78/89, 88%) and without it (66/84, 79%), while previous HBV infection was more common in patients with hepatocellular carcinoma (65/89, 73%) than in those without it (46/84, 55%) (P<0.05). Coexistence of anti-HCV and antibodies to HBV was observed frequently in patients with hepatocellular carcinoma (56/89, 63%) compared with patients without it (39/84, 46%) (P<0.05). In chronic HBV carriers, anti-HCV was more common in patients with hepatocellular carcinoma (12/38, 32%) than in those without it (3/62, 5%) (P<0.01). These results suggest that infection with the two viruses may be a risk factor for more serious liver disease.This work was supported by a Grant-in-Aid from the Ministry of Education, Science and Culture, Japan.     

Glycyrrhizin withdrawal followed by human lymphoblastoid interferon in the treatment of chronic hepatitis B

Seventeen patients with chronic hepatitis B were treated with a 4-week administration of glycyrrhizin followed by a 4-week treatment with human lymphoblastoid interferon, then followed for 6 months after the end of treatment. All were positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B virus-associated DNA polymerase (DNA-p) for at least 6 months before entry. All patients were Japanese and none of them were homosexuals. Eleven patients lost DNA-p activity and 10 of them lost HBeAg. Three of these 10 patients had antibody to HBeAg. In 10 patients who became HBeAg-negative, alanine aminotransferase levels after glycyrrhizin administration were higher and initial DNA-p activities relatively lower than the levels found in seven patients who remained HBeAg-positive. The immunomodulater provided by a short course of glycyrrhizin before administration of human lymphoblastoid interferon may be an effective treatment for patients with chronic hepatitis B.     

Healthy HTLV-I carriers in Japan: the haematological and immunological characteristics

The haematological and immunological characteristics of 34 healthy anti-HTLV-I antibody-positive individuals (HTLV-I carriers) in southwestern Japan were examined. No significant difference was noted between carriers and the controls in counts of RBC, WBC and the absolute number of lymphocytes. The serum IgG in the carriers was higher than that of the controls. The percentages of OKT4, OKT8, OKIa1 and B1-positive cells were found to be normal in the peripheral blood of the carriers, whereas the percentages of OKT11 and anti-Tac-positive cells were significantly higher in the carriers than in the controls. A correlation was observed between the percentages of anti-Tac-positive cells and the titres of anti-HTLV-I antibody in the carriers. After a 72 h incubation of peripheral blood lymphocytes with medium alone, the percentage of anti-Tac-positive cells tended to decrease in the controls, but to increase in carriers, with the appearance of large blastoid cells resembling blastic transformed lymphocytes cultured with mitogen. Tac and Ia antigens were markedly expressed on these large blastoid cells.     

The effects of molecular structure on sol-to-gel transition of biodegradable poly(depsipeptide-co-lactide)-g-PEG copolymers

We report on the effects of number and length of PEG chains in poly(depsipeptide-co-dl-lactide)-g-poly(ethylene glycol) (P(DG-dl-LA)-g-PEG) copolymers on their sol-to-gel transition behavior. The graft-type copolymer is suitable for the systematic study of the effects of molecular structure and hydrophilic/hydrophobic balance on its sol-to-gel transition. We prepared various P(DG-dl-LA)-g-PEG copolymers through coupling reactions between the pendant carboxylic acid groups of P(GD-dl-LA) and the end hydroxyl group of MeO-PEG having various molecular weights. Temperature-responsive sol-to-gel transition of the obtained copolymer solution in phosphate-buffered solution (pH 7.4, ionic strength = 0.14) was investigated by the test tube inverting method and rheological measurements. P(GD-dl-LA)-g-PEG copolymer prepared from higher molecular weight PEG showed higher sol-to-gel transition temperatures compared with the copolymers prepared from lower molecular weight PEG, although these copolymers have similar weight content of PEG (23–24?wt.%). Similar trends were observed for groups of copolymers whose PEG contents were 27 or 30?wt.%. These results are informative for providing strategies on rational design of thermo-gelling polymers.     

A novel de novo point mutation of the OCT‐binding site in the IGF2/H19‐imprinting control region in a Beckwith–Wiedemann syndrome patient

The IGF2/H19‐imprinting control region (ICR1) functions as an insulator to methylation‐sensitive binding of CTCF protein, and regulates imprinted expression of IGF2 and H19 in a parental origin‐specific manner. ICR1 methylation defects cause abnormal expression of imprinted genes, leading to Beckwith–Wiedemann syndrome (BWS) or Silver–Russell syndrome (SRS). Not only ICR1 microdeletions involving the CTCF‐binding site, but also point mutations and a small deletion of the OCT‐binding site have been shown to trigger methylation defects in BWS. Here, mutational analysis of ICR1 in 11 BWS and 12 SRS patients with ICR1 methylation defects revealed a novel de novo point mutation of the OCT‐binding site on the maternal allele in one BWS patient. In BWS, all reported mutations and the small deletion of the OCT‐binding site, including our case, have occurred within repeat A2. These findings indicate that the OCT‐binding site is important for maintaining an unmethylated status of maternal ICR1 in early embryogenesis.