Role of von Willebrand factor in mediating platelet-vessel wall interaction at low shear rate; the importance of perfusion conditions

We have previously observed that von Willebrand factor (vWF) plays an important role in platelet deposition on subendothelium at low values of wall shear rate (200 to 400 seconds-1). In the present study, we have investigated the mechanism responsible for such a defect in platelet deposition at low shear rates in the absence of vWF. Blood from both normal and von Willebrand's disease (vWD) animals was exposed to de-endothelialized aorta from normal pigs for a range of shear rates (200 to 3,000 seconds-1) and exposure times (three to 30 minutes) in a tubular perfusion chamber. Variations in the method of inhibiting coagulation (none, heparin, citrate, hirudin, and EDTA) and of perfusing blood (in vitro v ex vivo) were compared by determining the influence of wall shear rate and vWF on the deposition of 111In-labeled platelets on subendothelium. Whereas platelet deposition was reduced in the absence of vWF for all experimental variations at high shear rates (greater than 850 seconds-1), a defect was observed at low shear rates only when heparinized blood was exposed by means of an ex vivo perfusion system. Maximum sensitivity of the measurement occurs under ex vivo perfusion conditions due to the reduced ability of platelets to deposit in normal blood when recirculated in vitro. Our results indicate that vWF mediates platelet-vessel wall interaction even at low shear rates and that such effect can only be observed in systems where platelet function is minimally affected by the experimental conditions.     

经鼻KTP激光泪囊鼻腔造瘘术的临床治疗效果

背景 　　评估经鼻KTP激光泪囊鼻腔造瘘术(ENL-DCR)的临床治疗效果.……     

Abnormal spectrin in hereditary elliptocytosis

An abnormal alpha subunit of erythrocyte spectrin has been described in hereditary pyropoikilocytosis (HPP), a rare hemolytic anemia characterized by erythrocyte budding and fragmentation. In HPP spectrin, the N terminal domain of the alpha subunit (alpha I T80) shows increased susceptibility to tryptic digestion, resulting in cleavage to a 50,000-d peptide, presumably due to a change in primary structure of the alpha I domain which alters conformation and generates the new cleavage site. The functional result of this conformational alteration is marked impairment of spectrin oligomer formation in vitro, consistent with the established role of alpha I T80 in spectrin self-association. In the present study, we demonstrate an abnormal spectrin alpha subunit in two kindreds with hereditary elliptocytosis (HE) that is qualitatively identical to HPP spectrin. Clinical expression of HE in these families ranges from mild elliptocytosis without hemolysis to severe poikilocytic hemolytic anemia clinically resembling HPP. In all affected individuals, a fraction of alpha I T80 is abnormal, as shown by its cleavage during mild tryptic digestion to the 50 kd peptide described in HPP; the fraction of alpha I T80 affected is directly proportional to the severity of clinical expression of HE. Spectrin oligomer formation is likewise impaired to a degree which correlates with hematologic disease. One of the HE kindreds studied demonstrated polymorphism in the spectrin alpha II domain, previously described as a frequent occurrence in blacks. This family also demonstrates a variant alpha III domain in spectrin that has not previously been described. We conclude that the abnormality in the alpha I domain originally described in HPP spectrin is shared by a subset of patients with HE; the severity of clinical expression, ranging from mild nonhemolytic HE to poikilocytic hemolytic anemia, is related to the fractional quantity of the alpha subunit that is affected.     

Recurrence of hepatitis C virus infection after orthotopic liver transplantation

Identification of the hepatitis C virus--the main cause of posttransfusion and sporadic non-A, non-B hepatitis--and the development of a diagnostic serological test have allowed us to study possible recurrence of this type of hepatitis after liver transplantation. Six of 34 consecutive transplant recipients were found to have had antibodies to hepatitis C before transplantation. All six patients had possible exposure to hepatitis C through blood transfusion or intravenous drug use. Five of the six patients were positive for antibodies to hepatitis C after 1 yr of follow-up. Two of these patients had clinical and histological evidence of acute viral hepatitis in their allografts. In one patient this led to hepatic injury and dysfunction of two successive grafts. In contrast, none of the twenty-eight patients who were seronegative for hepatitis C virus antibodies before transplantation has converted to seropositivity after transplantation despite perioperative blood transfusions. These results suggest that hepatitis C diagnosed serologically recurs in a minority of transplant recipients and that de novo seroconversion must be uncommon.     

Sleep deprivation affects inflammatory marker expression in adipose tissue

Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation.     

Dibromomannitol in the treatment of chronic granulocytic leukemia: a prospective randomized comparison with busulfan

Dibromomannitol (DBM) is a new agent for the treatment of chronic granulocytic leukemia. A propsective evaluation of the drug was undertaken in a randomized comparison with busulfan. Forty previously untreated, Philadelphia chromosome-positive cases were treated, with 20 patients in each treatment group. The protocol provided for continuous maintenance therapy after remission induction, with a crossover to the opposite drug in patients who became refractory to the primary agent but are without evidence of blastic tranformation. There were 14 remissions in the DBM group and 15 in those treated with busulfan. The rate of decrease of the elevated leukocyte count was more rapid with DBM, but prolonged disease control off treatment occurred in only three of 14 cases as opposed to nine of fifteen busulfan-treated patients who required a median delay of 12 mo before maintenance could be initiated. Hypoplasia occurred in one DBM patient and two busulfan cases. Following recovery, crossover to the opposite drug in two cases again resulted in hypopllasia. Increased skin pigmentation, amenorrhea, pulmonary fibrosis, and cytologic dysplasia, commonly associated with busulfan adminstration, were also noted with DBM. The median duration of disease control with busulfan was 34 mo and 26 mo with DBM. There was no signigicant difference in the incidence of blastic transformation, and median survival for both groups was 44 mo. DBM appears to be as effective as busulfan in the treatment of the chronic phase of CGL but with a more predictable myelosuppressive action. The principal advantage of busulfan over DBM is the fact that more than half the busulfan-treated patients experienced prolonged disease control off treatment.     

GENERATION AND PARTIAL CHARACTERIZATION OF MONOCLONAL ANTIBODIES AGAINST SOLUBILIZED MEMBRANE FRACTION OF HUMAN SPERMATOZOA

Human sperm membrane antigens extracted by deoxycholate (DOC) were used to immunizeBALB/c mice.Hybrid cell lines secreting sperm-specific monoclonal antibodies were generatedby cell fusion in a semi-solid medium and screened by indirect immunofluorescent assay usinglive and methanol-fixed sperm.Out of 850 hybrid clones from cell fusion,28 were shownto secrete sperm-specific antibodies which reacted with the acrosome,equatorial segment,whole surface plasma membrane or tail of spermatozoa.Finally,seven hybrid cell lineswere established and shown to secrete monoclonal antibodies which had no cross-reactivitywith arty human tissues other than testis and sperm.The majority were also shown toinhibit fertilization of mouse oocytes in vitro and human sperm penetration of zona-freehamster ova.Western blot analysis revealed that some of these antibodies reacted withsperm membrane antigens of distinct molecular size.     

Reproductive function after liver transplantation

Successful pregnancy outcomes are possible after liver transplantation. Although there are risks to the mother and fetus, there has not been an increased incidence of malformations noted in the newborn of liver recipients. Close, coordinated care involving the hepatologist, surgeon, and high-risk obstetrician is essential to ensure a favorable outcome. Immunosuppression peripartum should be maintained at appropriate levels. Of note, a small subset of recipients may suffer worsened graft function during pregnancy. Recurrent liver disease, especially viral hepatitis, and CMV infection appear to pose significant risks to mother and offspring, respectively, although the magnitude of the risks is unknown. It therefore would seem prudent to consider pregnancy only in female liver recipients who have passed at least 1 year with stable graft function. In addition, new immunosuppressive regimens further add to the lack of information regarding pregnancy safety. The NTPR is an ongoing database to collect information and pregnancy outcomes. That information should be helpful in counseling recipients and in pregnancy management.