Rheologic predictors of the severity of the painful sickle cell crisis

Deformable sickle erythrocytes have been reported by Mohandas and Evans to be more adherent to vascular endothelium than rigid irreversibly sickled cells (ISC). To define the clinical implications of this finding we have determined genetic, hematological, clinical, and rheological characteristics of sickle erythrocytes obtained from 65 patients with sickle cell anemia and fetal hemoglobin (Hb F) levels less than 15%. The alpha-globin gene number had a significant effect on the hematological parameters, the percentage of dense cells, ISC number, and HB A2 levels. The presence or absence of alpha thalassemia, however, had no effect on the frequency and severity of the sickle cell painful crisis (r = 0.06, P greater than .05). RBC deformability, determined by an ektacytometer, showed great heterogeneity among patients with three or four alpha-globin genes. Linear regression analyses of the data showed significant positive correlation of the frequency and severity of the painful crisis with RBC deformability (r = 0.49, P less than .001), and negative correlations with the percentage of dense cells (r = -0.37, P = .002), and the percentage of ISC (r = -0.46, P less than .001). We propose that the more deformable the sickle RBC are, the greater their adherence to vascular endothelium, and the more they cause vaso-occlusive crises, RBC deformability and the percentage of dense cells (or ISC) seem to have a predictive value of the frequency and severity of painful crises in sickle cell anemia.     

Waveform analysis of clotting test optical profiles in the diagnosis and management of disseminated intravascular coagulation (DIC)

Transmittance waveform charts the changes in light transmittance on standard coagulation assays, such as the prothrombin time (PT) and activated partial thromboplastin time (APTT). Analysis and characterization of these data on photo-optical coagulation analysers provides additional qualitative and quantitative information to that obtained using the clotting time alone. The most thoroughly evaluated clinical application is that of the biphasic APTT waveform with disseminated intravascular coagulation (DIC). The degree of waveform abnormality correlates directly with the severity of haemostatic dysfunction and allows for both the prediction and monitoring from non-overt to overt DIC. As its performance is simple and rapid, this provides the means for targeting therapeutic intervention to an earlier stage of DIC. The recent identification that the mechanism underlying the biphasic waveform is a complex that exists in vivo between C reactive protein with very low density lipoprotein, provides potentially important insights into the molecular pathogenesis of DIC. Thus, in addition to the immediate clinical utility in diagnostic practice, it has important applications as a research tool. Preliminary experience in the application of this technology to the diagnosis and management of the haemophilias and the lupus anticoagulant syndrome has also provided evidence of the power and utility of waveform analysis in essentially simple clotting assays.     

Intravenous thrombolysis and endovascular thrombectomy for acute ischaemic stroke in patients with Moyamoya disease - a systematic review and meta-summary of case reports

Journal of Thrombosis and Thrombolysis - Patients with Moyamoya disease (MMD) can present with ischaemic or haemorrhagic stroke. There is no good evidence for treatment strategies in MMD-associated...     

Smooth Muscle-associated Contractile Protein in Human and Experimental Acute Leukaemias*

Summary: Smooth muscle-associated contractile protein in human and experimental acute leukaemias. Cells from ten human myeloblastic leukaemias and from spontaneous rat myeloblastic and lymphoblastic leukaemias were examined by indirect immunofluorescence with human serum containing smooth muscle antibody. Strong positive cell outline staining of blast cells was seen in cryostat sections of rat leukaemic lymph nodes, spleen and liver. In cell smears of human and rat leukaemias, cell outline fluorescence was restricted to cells in close contact with each other. Membrane immunofluorescence tests of suspensions of viable leukaemic cells were negative. Specificity of the immunofluor-escent staining reaction was established by failure to obtain staining with normal serum, or with smooth muscle antibody serum neutralized by homogenates of smooth muscle or extracts containing actin derived from smooth muscle. These observations suggest that smooth muscle-associated microfilaments are present in leukaemic blast cells and that expression of the antigen is dependent on cell- cell contact. The presence of this antigen may facilitate leukaemic infiltration of tissues.     

The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jakob disease, and other neurologic diseases.

Sera from 65 patients with spongiform virus encephalopathies (29 with kuru, 36 with Creutzfeldt-Jakob disease), 79 with other neurologic diseases, and 65 control subjects were examined for reactivity in immunoblots of preparations of myelinated axons and neurofilaments from mouse brain. The sera reacted most frequently with the 200-kDa and 150-kDa neurofilament proteins and less frequently with the 70-kDa neurofilament protein and a 62-kDa neurofilament-associated protein. The sera reacted with the same proteins as those which reacted with rabbit and mouse polyclonal antibodies and mouse monoclonal antibody to neurofilament proteins. Serum reactions were also seen with Trixon X-100 extracts of chimpanzee brain and bovine spinal cord but not with Triton extracts of liver, kidney, and muscle.     

Malignant Transformation of the Mouse Anorectal Epithelium Induced by an Inoculated Human Cancer Cell Line

Four kinds of human cancer cell lines and one mouse cancer cell line were inoculated into the subepithelial area of the anorectum of female nude mice. Among the cell lines, two cell lines (KATO III and Lu 135) showed the potential enforcement of atypical changes in the adjacent mouse anorectal epithelium. Moreover, the submucosal invasion of the malignant transformed cells of the mouse epithelium was demonstrated in specimens obtained from three KATO III-inoculated mice. This exciting and novel phenomenon clearly demonstrates the need to change the present general concept of a single-cell origin of cancer tissue. This valuable and novel discovery may change the basis of oncology research while also providing new ideas for projects to investigate the mechanisms of carcinogenesis from several aspects such as molecular biology, cell biology, and pathology. Moreover, the novel experimental design itself is also extremely useful as a simple model for investigating the mechanisms of oncogenesis.