Association of Carotid Intraplaque Hemorrhage and Territorial Acute Infarction in Patients with Acute Neurological Symptoms Using Carotid Magnetization-Prepared Rapid Acquisition with Gradient-Echo

Objective

The purpose of our study was to assess prevalence of carotid intraplaque hemorrhage (IPH) and associations between territorial acute infarction and IPH on magnetization-prepared rapid acquisition with gradient-echo (MPRAGE) in patients with acute neurologic symptoms.

Methods

83 patients with suspected acute neurologic symptoms were evaluated with both brain diffusion weighted imaging (DWI) and carotid MPRAGE sequences. Carotid plaque with high signal intensity on MPRAGE of >200% that of adjacent muscle was categorized as IPH. We analyzed the prevalence of IPH and its correlation with territorial acute infarction.

Results

Of 166 arteries, 39 had a carotid artery plaque. Of these arteries, 26 had carotid artery stenosis less than 50%. In all carotid arteries, MR-depicted IPH was found in 7.2% (12/166). High-signal intensity on DWI was found in 17.5% (29/166). Combined lesion with ipsilateral high-signal intensity on DWI and IPH on carotid MPRAGE sequence was found in 6 lesions (6/166, 3.6%). Of patients with carotid artery plaque, MR-predicted IPH was found in 30.8% (12/39) and match lesions with high-signal intensity on DWI and MPRAGE was found in 15.4% (6/39). MR-predicted IPH was significantly higher prevalence in high-grade stenosis group (p=0.010). Relative risk between carotid MPRAGE-positive signal and ipsilateral high-signal intensity on DWI in arteries with carotid artery plaques was 6.8 (p=0.010).

Conclusion

Carotid MPRAGE-positive signal in patients was associated with an increased risk of territorial acute infarction as detected objectively by brain DWI. The relative risk of stroke was increased in high-grade stenosis categories.     

An alternative extrinsic pathway of human blood coagulation

To study the interrelationships of the major human coagulation pathways, factor X activation in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin were added to plasma samples containing 3H-labeled factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin the rate of factor X activation in factor VIII or factor IX deficient plasma was only 10% of the activation rate seen for normal or factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, restored normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these experiments, it is inferred that normal activation of factor X in plasma due to dilute thromboplastin requires factors VII, IX and VIII. An alternative extrinsic pathway that involves factors VII, IX, and VIII may be a major physiologic extrinsic pathway, and this pathway may help to explain the clinical observations of bleeding diatheses in patients deficient in factors IX or VIII.     

Minor histocompatibility antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T-cell clones inhibit human hematopoietic progenitor cell growth by a mechanism that is dependent on direct cell-cell contact

HLA-identical bone marrow transplantation (BMT) may be complicated by graft-versus-host disease or graft rejection. Both complications are thought to be initiated by recognition of minor histocompatibility (mH) antigens by HLA-restricted mH-antigen-specific T lymphocytes. Using HLA- A2-restricted mH antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T lymphocyte (CTL) clones, we studied the recognition by these CTL clones of interleukin-2 (IL-2)-stimulated T cells (IL-2 blasts), BM mononuclear cells (BMMNCs), and hematopoietic progenitor cells (HPCs). We showed that, when IL-2 blasts from the BM donors who were investigated were recognized by the HA-1-, -2-, and -4-, and HY- specific CTL clones, their BMMNCs and HPCs were recognized as well by these CTL clones, resulting in antigen-specific growth inhibition of erythrocyte burst-forming units (BFU-E), colony-forming units- granulocyte (CFU-G), and CFU-macrophage (CFU-M). the HA-2-specific CTL clone, however, inhibited BFU-E and CFU-G growth from four donors to a lesser extent than from two other donors. We further investigated whether inhibitory cytokines released into the culture medium by the antigen-specific stimulated CTLs or by stimulated BMMNCs were responsible for suppression of HPC growth or whether this effect was caused by direct cell-cell contact between CTLs and HPCs. HPC growth inhibition was only observed after preincubation of BMMNCs and CTLs together for 4 hours before plating the cells in semisolid HPC culture medium. When no cell-cell contact was permitted before plating, neither antigen-stimulated CTL nor antigen-nonstimulated CTLs provoked HPC growth inhibition. Culturing BMMNCs in the presence of supernatants harvested after incubation of BMMNCs and CTL clones together for 4 or 72 hours did also not result in HPC growth inhibition. Both suppression of HPC growth and lysis of IL-2 blasts and BMMNCs in the 51Cr-release assay appeared to be dependent on direct cell-cell contact between target cells and CTLs and were not caused by the release of inhibitory cytokines into the culture medium by antigen-specific stimulated CTLs or by stimulated BMMNCs. Our results show that mH-antigen-specific CTLs can inhibit HPC growth by a direct cytolytic effect and may therefore be responsible for BM graft rejection after HLA-identical BMT.     

Telomere length changes in patients with aplastic anaemia

To investigate telomere changes in patients with aplastic anaemia (AA) and clinical factors influencing the telomere dynamics, telomere length (TL) was measured in peripheral blood mononuclear cells using Southern blot analysis of 42 patients with AA and 39 healthy normal controls. Nineteen patients received supportive treatment only, while the remaining 23 patients received immunosuppressive therapy with anti-thymocyte globulin or anti-lymphocyte globulin +/- cyclosporin A. In AA patients, TL was on average 1.41 kb shorter than that of age-matched normal controls (P < 0.001). In patients treated with immunosuppression, the mean TL of non-responders was significantly shorter than that of age-matched normal controls (P < 0.001), while no difference in TL was detected in responders compared with controls. Positive correlation was observed between the extent of telomere shortening, the severity of neutropenia (P = 0.05) and the degree of mean corpuscular volume elevation (P = 0.005) at the time of the study. However, there was no correlation with time elapsed since diagnosis (P = 0.214). These findings suggest that haematopoietic stem cells in patients with AA rapidly lose TL at the onset of the disease. The TL shortening may reflect the severity of impairment of haematopoiesis.     

Immunohistochemical localization of membrane and alpha-granule proteins in human megakaryocytes: application to plastic-embedded bone marrow biopsy specimens

Using a new technique for antigen localization, we have demonstrated platelet proteins in megakaryocytes in plastic-embedded biopsy specimens of normal human bone marrow. In a series of 25 specimens, megakaryocytes showed labeling with antibodies to the integral membrane glycoproteins IIIa, IIb, and the IIb-IIIa complex; granule membrane protein 140; and five alpha-granule matrix proteins: thrombospondin, factor VIII-related antigen, beta-thromboglobulin, platelet factor 4, and fibrinogen. The antibodies to the membrane glycoproteins IIIa, IIb, and IIb-IIIa produced diffuse cytoplasmic staining and heavier staining on the plasma membrane, whereas the antibodies to the alpha-granule matrix proteins produced a distinct granular staining within the cytoplasm. Staining for granule membrane protein 140 was also granular in distribution. Rare mononuclear cells consistent with megakaryocyte precursors were labeled with these markers. Other enzyme histochemical and lectin-binding studies showed that the enzyme alpha-naphthyl acetate esterase, the lectin Ulex europaeus I, and the periodic-acid Schiff reaction were consistent, but not specific, markers of megakaryocytes. This immunohistochemical technique should facilitate the examination of qualitative and quantitative changes in megakaryocytes in a variety of physiologic and pathologic processes.     

Effect of a muscle strengthening exercise program for pelvic control on gait function of stroke patients

[Purpose] The purpose of this study was to investigate the effects of strengthening exercises for the hip extensors on the gait performance and stability of patients with hemiplegia. [Subjects and Methods] The subjects were fifteen stroke patients (ten males, five females). The experimental subjects performed a hip extensor strengthening exercise (HESE) program for a total of four weeks. [Results] The experimental subjects showed significant improvements after the HESE program. Especially, walking speed and the affected side stance phase time significantly increased after the HESE program. Furthermore, the affected side stride length and symmetry index in the stance phase significantly increased after HESE program. [Conclusion] These results suggest that the HESE program may, in part, help to improve gait performance ability and stabilize physical disability after stroke.Key words: Stroke patients, Hip extensor strengthening exercise (HESE) program, Gait function     

Effects of conventional overground gait training and a gait trainer with partial body weight support on spatiotemporal gait parameters of patients after stroke

[Purpose] The purpose of this study was to confirm the effects of both conventional overground gait training (CGT) and a gait trainer with partial body weight support (GTBWS) on spatiotemporal gait parameters of patients with hemiparesis following chronic stroke. [Subjects and Methods] Thirty stroke patients were alternately assigned to one of two treatment groups, and both groups underwent CGT and GTBWS. [Results] The functional ambulation classification on the affected side improved significantly in the CGT and GTBWS groups. Walking speed also improved significantly in both groups. [Conclusion] These results suggest that the GTBWS in company with CGT may be, in part, an effective method of gait training for restoring gait ability in patients after a stroke.Key words: Gait training, Spatiotemporal gait parameters, Stroke patients