Total blood lymphocyte counts in hemochromatosis probands with <Emphasis Type="Italic">HFE</Emphasis>C282Y homozygosity: relationship to severity of iron overload and HLA-A and -B alleles and haplotypes

Background  

It has been reported that some persons with hemochromatosis have low total blood lymphocyte counts, but the reason for this is unknown.     

Specificity of autoantibodies in autoimmune thrombocytopenia

In 42 patients with autoimmune thrombocytopenia (AITP) and a positive direct platelet suspension immunofluorescence test (PSIFT), the antigenic specificity of the autoantibodies was studied. Because the autoantibodies were often not detectable in the serum and additional HLA antibodies may disturb the reaction pattern with the platelet panel, we used eluates prepared from the patients' platelets for this study. Thirty-five patients had antibodies equally reactive with normal platelets, irrespective of their antigenic make-up, but not with the platelets from two Glanzmann's disease patients. Absorption and elution experiments in two patients showed that his was probably not due to the presence of a combination of anti-Zwa and anti-Zwb antibodies. Thus, the majority of autoantibodies against platelets seems to be directed against antigenic determinants not present on Glanzmann's disease platelets, but perhaps located on the platelet-membrane glycoproteins IIb and/or IIIa. In ten patients, antibodies of no, or still unknown, specificity were detected. Three of these had additional antibodies not reactive with the platelets of the two Glanzmann patients.     

A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon

BACKGROUND & AIMS: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans. Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. METHODS: Fluid secretion, [3H]-mannitol permeability, and release of rat mast cell protease II and prostaglandin E2 were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer. RESULTS: Toxin A (5 micrograms) and antigalactose (250 micrograms) but not control immunoglobulin (250 micrograms) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release. Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E2, but only toxin A produced acute inflammation of rat colonic mucosa. Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 10(-8) mol/L, respectively. CONCLUSIONS: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc. (Gastroenterology 1996 Jun;110(6):1704-12)     

Watery Diarrhea in a Patient with Myasthenia Gravis, Thymoma, and Immunodeficiency

An elderly man with thymoma, myasthenia gravis, and hypogammaglobulinemia developed profuse watery diarrhea. Infusions of gamma-globulin caused the diarrhea to resolve. The patient succumbed to fulminant bronchopneumonia. At necropsy he was found to have widespread cytomegalovirus infection with duodenal and ileal ulceration, subtotal villous atrophy, marked nonspecific inflammation of the small intestine and bronchopneumonia. In addition Herpes simplex infection and invasive candidiasis were present. Patients with immunodeficiency are susceptible to a variety of gastrointestinal pathogens, particularly viral.     

一氧化氮和一氧化氮合酶与肿瘤放疗敏感性的关系

一氧化氮(nitricoxide,NO)的生物学作用具有复杂性和多样性,在基础条件下诱导型一氧化氮合酶(induciblenitricoxidesynthase,iNOS)活性很低,当机体遭受微生物内外毒素、炎症介质等刺激时iNOS可诱导合成大量的NO.肿瘤生物学上一般认为高水平的NO对肿瘤细胞具有直接的细胞毒作用,而较低水平的NO具有生长刺激作用.多种试验显示NO的供体能增加肿瘤的放疗敏感性.研究认为,NO的生物学作用可能是通过p53依赖途径介导的.调节NO杀灭肿瘤或促进肿瘤生长,p53起到关键性的作用.已有多种药品作为放射敏化剂,NO供体药物在体内给药可能导致系统低血压,增加肿瘤血液灌注和氧合作用,具有潜在的促进肿瘤生长的作用,限制了其临床使用.直接将iNOS基因转染入肿瘤细胞内,肿瘤内的乏氧环境,可降低iNOS的活性而影响NO的产量.携带iNOS基因的腺病毒(adenoviralvectorcarryingtheiNOScDNA,AdiNOS)转染靶细胞导致iNOS过表达,产生大量NO,有望成为一种增加肿瘤放疗敏感性有效可行的方法.     

Tumor necrosis factor alpha-induced endothelial tissue factor is located on the cell surface rather than in the subendothelial matrix

Because there is no consensus regarding the precise distribution of induced endothelial tissue factor (TF), we studied TF activity in and on tumor necrosis factor alpha-stimulated cultured human umbilical vein endothelial cells (ECs) and their underlying matrix. TF was mainly expressed on the cell surface. Only small traces were found on the apical surface suggesting that TF is predominantly located on the basolateral side of the cell membrane. The presence of TF on the cell surface was confirmed by flow cytometry. Subendothelial TF activity appeared to be dependent upon the procedure used to remove the stimulated EC monolayer. Whereas ammonium hydroxide or hypotonic lysis resulted in relatively high levels of matrix-associated TF, virtually no TF was found on the matrix after mild enzymatic detachment of stimulated ECs. Cell removal with EDTA resulted in intermediate levels of matrix-associated TF. Neither the enzymatic treatment nor EDTA degraded or removed this TF activity. Similar patterns were observed for matrix-associated TF antigen and EC surface markers. Electron microscopic analysis showed cell fragments on the matrix after monolayer lysis. The findings strongly suggest that induced endothelial TF associated with the subendothelial matrix actually represents TF on EC remnants.     

Serum uric acid level in newly diagnosed essential hypertension in a Nepalese population: A hospital based cross sectional study

Objective

To develop the missing link between hyperuricemia and hypertension.

Methods

The study was conducted in Department of Biochemistry in collaboration with Nephrology Unit of Internal Medicine Department. Hypertension was defined according to blood pressure readings by definitions of the Seventh Report of the Joint National Committee. Totally 205 newly diagnosed and untreated essential hypertensive cases and age-sex matched normotensive controls were enrolled in the study. The potential confounding factors of hyperuricemia and hypertension in both cases and controls were controlled. Uric acid levels in all participants were analyzed.

Results

Renal function between newly diagnosed hypertensive cases and normotensive healthy controls were adjusted. The mean serum uric acid observed in newly diagnosed hypertensive cases and in normotensive healthy controls were (290.05±87.05) µmol/L and (245.24±99.38) µmol/L respectively. A total of 59 (28.8%) participants of cases and 28 (13.7%) participants of controls had hyperuricemia (odds ratio 2.555 (95% CI: 1.549-4.213), P<0.001).

Conclusions

The mean serum uric acid levels and number of hyperuricemic subjects were found to be significantly higher in cases when compared to controls.