Identification of glycoprotein Ib as a target for autoantibody in idiopathic (autoimmune) thrombocytopenic purpura

An antibody (DIL) from a patient with idiopathic thrombocytopenic purpura (ITP) was shown to have autospecificity on the basis of reactions with autologous platelets that were identical to those obtained with platelets from normal subjects. DIL antibody also reacted strongly in an immunofluorescence test with platelets from a patient with Glanzmann's thrombasthenia, but failed to react with platelets from a patient with the Bernard-Soulier syndrome who was known to be deficient in glycoprotein Ib (GPIb). Purified GPIb and control platelets, but not Bernard-Soulier platelets, inhibited the lytic activity of DIL. Using the GPIb-specific monoclonal antibody AP1 and one-dimensional rocket electrophoresis into gels containing rabbit antihuman platelet membrane antibody, it was shown that staphylococcal protein A-Sepharose beads coated with DIL antibody selectively remove GPIb from solubilized platelet preparations. By crossed immunoelectrophoresis it was found that DIL recognizes a determinant on GPIb on the membrane side of the cleavage site of the platelet calcium- activated protease (calpain). These studies provide direct evidence for binding of a platelet autoantibody to a determinant on GPIb relatively close to the site of insertion of this protein into the platelet membrane.     

Imatinib therapy prior to myeloablative allogeneic stem cell transplantation

It is unknown whether imatinib prior to myeloablative haematopoietic stem cell transplantation (HSCT) increases transplant-related toxicity. Among the side effects induced by imatinib, myelosuppression and liver injury might worsen HSCT outcomes. We retrospectively analysed engraftment, liver toxicity, acute graft-versus-host disease (aGVHD) incidence and 100-day mortality in 30 patients with BCR/ABL-positive leukaemias who received imatinib before HSCT and compared results of 48 age-matched controls who did not receive preceding imatinib. Both neutrophil and platelet engraftment occurred more rapidly among imatinib patients but the differences adjusted for Gratwohl scale were not statistically significant (P = 0.18 and 0.22, respectively). The adjusted hazards of having liver function tests (LFTs) >1.5 normal increased and the adjusted durations of elevated LFTs were not significantly different. The estimated adjusted difference in mean peak bilirubin values was also not significantly different (P = 0.48). However, the adjusted hazard of increased creatinine >1.5 normal was significantly higher in the imatinib group (HR = 4.09, P = 0.02). The adjusted odds of grades II-IV aGVHD were similar in both groups (OR = 0.86, P = 0.78), and while the adjusted odds of 100-day mortality were lower among imatinib patients, the difference was not significant (OR = 0.65, P = 0.60). These data do not provide any evidence that imatinib preceding HSCT increases acute transplant-related toxicities.     

Electrophysiological recordings from the rat prostate gland in vitro: identified single-cell and transepithelial (lumen) potentials

OBJECTIVE: To develop a preparation for the in vitro maintenance of the rat prostate gland and thus allow intracellular and transepithelial voltage measurements. MATERIALS AND METHODS: Ventral prostate glands from male rats were dissected free of connective tissue, separated into smaller lobes and maintained in vitro at 30 degrees C. Voltages were recorded with sharp micropipettes in identified cellular and luminal compartments, differentiated by several electrophysiological and histological parameters, including intracellular staining. RESULTS: Intracellular epithelial membrane potentials (median -40 mV) and transepithelial or luminal potentials (mean -4.2 mV) were recorded successfully. Luminal epithelial cells were dye-coupled. Prostate tissue could be maintained in vitro with no apparent electrophysiological or structural deterioration for up to approximately 7 h. CONCLUSION: Rat prostate tissue can be successfully maintained in vitro and electrophysiological recordings made from identified cellular compartments.     

Ionic and pharmacologic characteristics of epithelial cells in a semi-intact preparation of the rat ventral prostate gland

BACKGROUND: The essential ionic and pharmacologic characteristics of epithelial cells within the ducts of the prostate gland are not well known. METHODS: Experiments were carried out on segments of ventral prostate glands from adult male rats. By using sharp microelectrodes, intracellular epithelial cell and transepithelial (lumen) potentials were recorded in response to ionic substitution and application of ion channel blockers, hormones, and other pharmacologic agents related to prostatic function. RESULTS: Membrane permeabilities to K(+), Na(+), and Cl(-) were found to account for approximately 43% of the resting membrane potential, whereas some 39% was likely to be metabolic in origin. The membrane potential also responded to adrenaline, acetylcholine, insulin, prolactin, testosterone, nerve growth factor, and nitric oxide. The lumen potential was found to be particularly sensitive to citrate, prolactin, and testosterone. CONCLUSION: It was concluded that the basal membrane potential of prostatic epithelial cells is associated with a relatively high Na(+):K(+) permeability ratio and metabolic dependence. The hormonal and pharmacologic sensitivity observed is consistent with the functional characteristics of the prostate gland.     

HLA-DMA allele polymorphism: no impact on kidney allograft outcome

The purpose of this study was to analyze the association of HLA-DMA alleles with rejection episodes and early graft loss (EGL) in renal transplant recipients. One hundred and eighty four HLA-DMA alleles were retrospectively analyzed by DNA sequence analysis in 92 kidney transplant recipients. The gene frequencies of HLA-DMA *0101, *0102, *0103 and *0104 were found to be similar in all recipients, regardless of rejection vs non rejection episodes and EGL incidence. In conclusion, HLA-DMA allele polymorphism did not impact renal allograft outcome.     

Crystalline lenses of newborn infants in scanning electron microscope.Preliminary report

Results of examination of 6 transparent infant lenses in a scanning microscope are presented. Discussed is the structure of the termination of the zonula on the lens capsule and the appearance of lenticular fibres in the cortical and nuclear layers.     

Smoking cessation in England: Intentionality,anticipated ease of quitting and advice provision

Smoking prevalence in England continues to reduce but further reduction is increasingly difficult. Cessation policy has successfully targeted those who want to quit but further reduction will need to shift attention to more difficult ‘core smoker’ populations. Following the established ‘stages of change’ perspective, this paper considers the characteristics of people who do not intend to quit smoking, anticipate difficulties in quitting and have not received advice about quitting. We deploy multilevel models of data drawn from the Health Survey for England years 2002–2004, and the NHS Primary Care Trust Patient Surveys for 2004 and 2005. It was found that variations in intentionality and anticipated ease of quitting are associated with individual factors such as smoking intensity, parental smoking, age/length of time as a smoker and the nature of the advice-giving consultation. Household composition and household income are also implicated in the intention to quit and anticipated difficulties in quitting. Once individual and household factors are taken into account the only identifiable area-level variation is reduced intentionality towards quitting in rural areas. We conclude by arguing that further gains in smoking cessation must focus on understanding the characteristics of ‘hard-to-engage’ populations.