Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (alpha 2 beta 1-integrin)

Platelet adhesion to fibrillar collagens (types I, II, III, and V) and nonfibrillar collagens (types IV, VI, VII, and VIII) was investigated in the presence of physiologic concentrations of divalent cations under conditions of stasis and flow. Under static conditions, platelet adhesion was observed to collagen types I through VII but not to type VIII. Under flow conditions, platelet adhesion to collagen types I, II, III, and IV was almost independent of shear rates above 300/s. Collagen type V was nonadhesive. Platelet adhesion to collagen type VI was shear rate-dependent and optimal at a rate of 300/s. Collagen types VII and VIII showed minor reactivity and supported platelet adhesion only between shear rates 100 to 1,000/s. Monoclonal antibody (MoAb) 176D7, directed against platelet membrane glycoprotein Ia (GPIa; very late antigen [VLA]-alpha 2 subunit), completely inhibited platelet adhesion to all collagens tested, under conditions of both stasis and flow. Platelet adhesion to collagen type III at shear rate 1,600/s was only inhibited for 85%. The concentration of antibody required for complete inhibition of platelet adhesion was dependent on the shear rate and the reactivity of the collagen. An MoAb directed against GPIIa (VLA-beta subunit) partially inhibited platelet adhesion to collagen. These results show that GPIa-IIa is a major and universal platelet receptor for eight unique types of collagen.     

Deficiency of platelet membrane glycoprotein Ia associated with a decreased platelet adhesion to subendothelium: a defect in platelet spreading

A bleeding disorder with absent collagen-induced platelet aggregation and adhesion has been described in a patient whose platelets failed to express surface glycoprotein Ia. We studied the interaction of her platelets with subendothelium in an annular perfusion chamber and the interaction with purified human collagen type III in a rectangular perfusion system under flow conditions. Platelet adherence was almost completely absent both at low and high shear rates. The few platelets which adhered remained in the contact stage without subsequent spreading and aggregate formation. Addition of a monoclonal antibody, which was directed against the von Willebrand moiety of FVIII-VWF, to the blood, completely abolished platelet adherence at high shear rates and had a partial effect at low shear rates. These data indicate that von Willebrand factor plays a role in the initial attachment (contact stage) of platelets to subendothelium. We conclude that the bleeding disorder and excessively prolonged bleeding time in our patient are caused by a new specific defect of the platelet-vessel wall interaction.     

Humoral immune function in pediatric patients treated with autologous bone marrow transplantation for B cell non-Hodgkin's lymphoma. The influence of ex vivo marrow decontamination with anti-Y 29/55 monoclonal antibody and complement

Elimination of neoplastic B cell populations from autologous bone marrow grafts also removes normal B lymphocytes. This is potentially hazardous for the reconstitution of the immune system in patients undergoing high-dose chemotherapy and total body irradiation followed by autologous marrow rescue. Five pediatric patients with B cell non- Hodgkin's lymphoma in first remission undergoing such a regimen were studied. They received bone marrow pretreated with anti-Y 29/55 monoclonal antibody and complement. B and T lymphocyte subpopulations reached normal levels within 6 months after autologous bone marrow transplantation (ABMT), and serum immunoglobulin levels became normal within 4 to 9 months. Vaccination with diphtheria and tetanus toxoid, trivalent poliomyelitis vaccine of the Salk type, and pneumococcal capsular antigens (38 to 54 months after transplantation) gave rise to specific antibody production. ABO isoagglutinins could be demonstrated in all patients. The response pattern was similar to that of patients who received unmanipulated autologous bone marrow. It is concluded that ex vivo anti-Y 29/55 depletion of the marrow graft does not induce relevant disturbances of humoral immune functions.     

The blood-brain barrier models to study apolipoprotein E genotypes in Alzheimer’s disease

Alzheimer’s disease(AD)is a neurodegenerative disease that is characterized by an age-dependent progressive decline of memory,impairment of cognitive functions and changes in personality and behavior.Despite the improvement in understanding of the mechanisms underlying the disease,AD remains an incurable complex disorder with multifaceted pathophysiology to date.Apolipoprotein E(ApoE)is the main cholesterol carrier in the brain that supports lipid transport between brain cells.The individuals carrying the APOE4 allele are known to be at increased risk of developing AD compared with those carrying the more common APOE3 allele.     

EARLY CARCINOMA TONGUE – SURGICAL OPTIONS

A retrospective analysis of 127 surgically treated cases of T-1, T-2 carcinoma of oral tongue during the period 1987-1990 was undertaken. 68.5 per cent (87) underwent hemiglossectomy and 31.5 per cent (40) underwent wide excision. There were loco-regional recurrences in 22 per cent (27). In the hemiglossectomy group 9 per cent (8 of 87) had local recurrences compared to 25 per cent (10 of 40) of wide excision group, (P = 0.01). Mean disease free survival was 40 months and 33 months for hemiglossectomy group and wide excision group respectively, (P = 0.006). It is seen that local recurrences are significantly less for the hemiglossectomy group compared to the wide excision group.KEY WORDS: Disease free survival, Early cancer, Recurrence, Surgery, Tongue     

空气喷磨和酸蚀与树脂突超微结构的关系

目的 体外评价５种处理方法对树脂突超微结构的影响。方法 对照组：对１颗离体磨牙常规预防性树脂充填。其余４颗磨牙用空气喷磨处理,分别用５０μ和２７μ氧化铝微粒,酸处理其中２颗磨牙。窝洞用复合树脂充填后,用１０％盐酸溶解牙釉质,扫描电镜观测树脂突超微结构。结果 对照组呈典型窝状结构。空气喷磨的树脂突呈不规则结构,结合酸蚀的树脂突表面更加粗糙。结论 空气喷磨具有一定的蚀刻作用但不如酸蚀作用强。     

New UNOS rules: historical background and implications for transplantation management. United Network for Organ Sharing.

The algorithm for the allocation of donor hearts used by the United Network for Organ Sharing (UNOS) was changed in January 1999. The new scheme alters the medical urgency criteria from a 2-tiered to a 3-tiered system. Blood type O and blood type B candidates are less disadvantaged and pediatric candidates are somewhat advantaged with regard to adolescent donors. The new allocation algorithm allows an individual with life-threatening ventricular arrhythmias to be listed in the highest urgency status. Increased regulation will occur with the establishment of a review for the highest urgency status and the establishment of regional review boards.     

Ciprofloxacin inhibits advanced glycation end products-induced adhesion molecule expression on human monocytes

BACKGROUND AND PURPOSE

Advanced glycation end products (AGEs) subtypes, proteins or lipids that become glycated after exposure to sugars, can induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde-derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) are involved in inflammation in diabetic patients; monocytes are activated by these AGEs. Ciprofloxacin (CIP), a fluorinated 4-quinolone, is often used clinically to treat infections associated with diabetis due to its antibacterial properties. It also modulates immune responses in human peripheral blood mononuclear cells (PBMC) therefore we investigated the involvement of AGEs in these effects.

EXPERIMENTAL APPROACH

Expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 was examined by flow cytometry. The production of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, prostaglandin E₂ (PGE₂) and cAMP were determined by enzyme-linked immunosorbent assay. Cyclooxygenase (COX)-2 expression was determined by Western blot analysis. Lymphocyte proliferation was determined by [³H]-thymidine uptake.

KEY RESULTS

CIP induced PGE₂ production in monocytes, irrespective of the presence of AGE-2 and AGE-3, by enhancing COX-2 expression; this led to an elevation of intracellular cAMP in monocytes. Non-selective and selective COX-2 inhibitors, indomethacin and NS398, inhibited CIP-induced PGE₂ and cAMP production. In addition, CIP inhibited AGE-2- and AGE-3-induced expressions of ICAM-1, B7.1, B7.2 and CD40 in monocytes, the production of TNF-α and IFN-γ and lymphocyte proliferation in PBMC. Indomethacin, NS398 and a protein kinase A inhibitor, H89, inhibited the actions of CIP.

CONCLUSIONS AND IMPLICATIONS

CIP exerts immunomodulatory activity via PGE₂, implying therapeutic potential of CIP for the treatment of AGE-2- and AGE-3-induced inflammatory responses.     

Deterioration of gas exchange in patients with severe thrombotic thrombocytopenic purpura with respiratory failure during therapeutic plasma exchange

Therapeutic plasma exchange (TPE) is a procedure performed on patients suffering from various disorders, including thrombotic thrombocytopenic purpura (TTP). As we noted a frequent transient deterioration in respiratory function when the procedure was performed on intensive care unit (ICU) patients, we studied retrospectively the incidence of respiratory deterioration during and shortly after TPE and looked for a probable correlation with a change in the white blood cell (WBC) counts. Over a period of 10 months six patients with TTP, five of whom had parenchymal lung disease due to different medical reasons, underwent TPE. The oxygen saturation was measured continuously before, during, and after TPE; additionally, the WBC and differential counts were measured pre‐ and post‐TPE. The ratio of the oxygen saturation by pulse oxymetry (SpO₂) to the fraction of inspired oxygen (FiO₂) was calculated before, during and after TPE. In these five patients with lung disorders, there was a consistent trend of a decreasing SpO₂/FiO₂ quotient during and within 2 h post TPE compared to the pre‐TPE value. The decrease in SpO₂/FiO₂ range was 0.20–0.89 with an average of 0.56. In the same 5 patients there was an increase in the WBC count in the range of 2.3–19.7 × 10⁹/L with an average increase of 9.3 × 10⁹/L. The percent neutrophils of the total WBC counts also increased following most of the sessions, this increase was in the range of 1–15 % with an average of 7%. The effect of TPE on the SpO₂/FiO₂ ratio and the correlation to the WBC count and to a possible neutrophil activation has not been previously reported. We postulate that TPE can accentuate respiratory deterioration in patients with TTP who already have acute lung injury. This may be due to the priming and activation of the leukocytes that could lead to the release of cytokines and inflammatory mediators during the procedure. Thus, it is important to be aware of the possible deterioration in respiratory function and gas exchange while administering TPE to patients with pre‐existing parenchymal lung injury. J. Clin. Apheresis. 16:143‐147, 2000. © 2001 Wiley‐Liss, Inc.