Transforming growth factor-beta 1 cooperates with anti-immunoglobulin for the induction of apoptosis in group I (biopsy-like) Burkitt lymphoma cell lines

Group I Burkitt lymphoma (BL) cell lines, which retain the original biopsy phenotype, have been shown to enter apoptosis in response to a number of external stimuli including serum deprivation, thermal shock, addition of calcium ionophore, and ligation of surface immunoglobulin (Ig) by antibody. Transforming growth factor-beta 1 (TGF beta 1) is known to cause growth arrest in BL lines. Here we show that while it is by itself capable of promoting some degree of apoptosis in group IBL cells, TGF beta 1 cooperates with anti-immunoglobulin to this end. Trimeric soluble recombinant human CD40 ligand (sCD40L) was able to inhibit apoptosis induced by the combination of agonists to some degree, but such rescue proved to be short-lived. Both TGF beta 1 and anti-Ig individually caused BL cells to undergo growth arrest at the G1 phase of cell cycle before their entry into apoptosis: the consequence of sCD40L addition was to maintain the cells in cycle for longer. No induction of the apoptosis-protecting gene, bcl-2, occurred in the presence of sCD40L. These findings are discussed, particularly highlighting the relationship existing between survival and the cell cycle. The strong cooperative effects observed between anti-Ig and TGF beta 1 in promoting apoptosis and the inability of CD40 to signal for long-term rescue raise the potential for a novel therapeutic attack on B-cell lymphoma.     

Moderation of hemophilia A phenotype by the factor V R506Q mutation

Although many examples of unrelated hemophilia A patients carrying identical point mutations in the factor VIII (FVIII) gene have been reported, the clinical phenotype is not always the same among patients sharing the same molecular defect. Possible explanations for this discrepancy include undetected additional mutations in the FVIII gene or coinheritance of mutations at other genetic loci that modulate FVIII function. We report molecular genetic analysis of potential modifying genes in two sets of unrelated patients carrying common FVIII missense mutations but exhibiting different levels of clinical severity. Both mutations (FVIII R1689C and R2209Q) are associated with severe hemophilia A in some patients and mild/moderate disease in others. The common von Willebrand disease type 2N mutation (R91Q) was excluded as a modifying factor in these groups of patients. However, analysis of the recently described factor V (FV) R506Q mutation (leading to activated protein C resistance) identified a correlation of inheritance of this defect with reduced hemophilia A severity. Two moderately affected hemophilia A patients, each with either of two FVIII gene mutations, were heterozygous for FV R506Q, whereas two severely affected patients and two moderately affected patients were homozygous normal at the FV locus. Our results suggest that coinheritance of the FV R506Q mutation may be an important determinant of clinical phenotype in hemophilia A and that modification of the protein C pathway may offer a new strategy for the treatment of FVIII deficiency.     

Fabrication of TiO2 on porous g-C3N4 by ALD for improved solar-driven hydrogen evolution

Porous graphitic carbon nitride (P-g-C₃N₄) thin sheets were fabricated by a one-step calcination of a mixture of urea, melamine, and ammonia chloride at 550 °C. P-g-C₃N₄ showed 48% higher photocatalytic H₂ production from methanol aqueous solution than conventional urea-derived graphitic carbon nitride (g-C₃N₄) because the existence of numerous pores reduces the recombination rate of charge carriers. In order to further enhance the photocatalytic activity, TiO₂ was uniformly deposited on P-g-C₃N₄ by 60–300 cycles of atomic layer deposition (ALD) to form the TiO₂@P-g-C₃N₄ composite. They exhibited much higher photocatalytic hydrogen production rates than both TiO₂ and P-g-C₃N₄. Among all composites, the sample deposited with 180 ALD cycles of TiO₂ showed the highest H₂ production because of optimal diffusion length for electrons and holes. It also performed better than the sample of g-C₃N₄ deposited with 180 cycles of TiO₂.

Schematic of Pt-loaded TiO₂@P-g-C₃N₄ 2D/2D heterojunction structure and the proposed mechanism of charge transfer for photocatalytic H₂ evolution.     

Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients.     

Poor responders to intravenous omeprazole in patients with peptic ulcer bleeding

BACKGROUND/AIMS: Although proton pump inhibitors are highly effective in raising intragastric pH, there still remains a small group of patients who resist acid suppression. A high dose of omeprazole has been shown to reduce rebleeding rate in patients with bleeding peptic ulcers after endoscopic therapy. The primary objective of this study was to assess the incidence of peptic ulcer bleeding patients who were resistant to intravenous omeprazole. The secondary objective was to evaluate the relationship between intragastric pH and rebleeding rate in studied patients after successful endoscopic therapy. METHODOLOGY: Between Oct. 1996 and Aug. 1999, 88 bleeding peptic ulcer patients who had obtained initial hemostasis with endoscopic therapy were enrolled in this study. In these patients, 40 mg of omeprazole was given as intravenous bolus followed by 40 mg intravenously every 6 h for 3 days. Thereafter, omeprazole was given 20 mg orally once daily for 2 months. The intragastric pH was recorded for 24 hours after the first dose of omeprazole. The occurrence of rebleeding was observed for 14 days. RESULTS: The mean intragastric pH value of these 88 patients was 6.07, (95% CI: 5.91-6.23). Four patients (5%) were found to have omeprazole resistance (pH < 4.0, 50% of the time). By the 3rd days after entering the study, more patients with a mean pH < 6 rebled (5/25 vs. 3/63, p<0.05). CONCLUSIONS: About five percent of patients with peptic ulcer bleeding respond poorly to intravenous omeprazole. Rebleeding rate is higher in patients with a mean intragastric pH of less than 6.     

Management of COPD in Asia: A position statement of the Asian Pacific Society of Respirology

Chronic obstructive pulmonary disease (COPD) is a major disease in Asia. However, how to manage specifically Asian COPD patients has not been proposed. Awareness of COPD is very low and underdiagnosis/undertreatment is common in Asian countries. Low utilization of pulmonary function test and inhalers is also a problem. Moreover, high smoking prevalence and air pollution are barriers to managing Asian patients with COPD. The relatively low body mass index of Asian patients with COPD can increase their risk for experiencing adverse effects from COPD drugs. Physicians should consider the unique features of Asian populations with COPD such as the high prevalence rates of bronchiectasis and tuberculosis‐destroyed lungs, biomass smoke exposure and parasitic infection.     

经肛门内镜显微手术切除直肠肿瘤

目的评价经肛门内镜显微手术(TEM)切除直肠绒毛状腺瘤和早期直肠癌的应用效果。方法分析我院总结1995年11月至2001年12月27例TEM手术的临床资料。结果本组患者肿瘤直径中位值2.5cm,肿瘤下缘与齿状线距离(8.9±3.4)cm,肿瘤侵犯直肠周径范围(35.7±17.5)%。平均手术时间(109±46)min。平均住院日4.5d。无围手术期死亡。手术并发症有尿潴留、暂时性大便失禁和慢性阻塞性肺病(COPD)复发。术中2例切穿至腹腔,即刻内镜下修补成功。切缘100%瘤细胞阴性。病理示直肠绒毛状腺瘤14例、直肠腺癌13例,后者包括pTis2例,pT16例和pT25例。直肠癌腔内超声肿瘤T分期符合率为84.6%。5例pT2中2例中转前切除术,1例接受术后放疗,2例无附加任何治疗。平均随访18个月,所有病例无局部复发。死亡2例,但无复发迹象。结论TEM易行且安全,是直肠绒毛状腺瘤和部分T1直肠癌的治愈性手术,也可作为T2直肠癌的姑息性治疗手段。