Rapid reorganization of adult rat motor cortex somatic representation patterns after motor nerve injury.

The potential for peripheral nerve injury to reorganize motor cortical representations was investigated in adult rats. Maps reflecting functional connections between the motor cortex and somatic musculature were generated with intracortical electrical stimulation techniques. Comparison of cortical somatotopic maps obtained in normal rats with maps generated from rats with a facial nerve lesion indicated that the forelimb and eye/eyelid representations expanded into the normal vibrissa area. Repeated testing from an electrode placed chronically in the motor cortex showed a shift from vibrissa to forelimb within hours after facial nerve transection. These comparatively quick changes in motor cortex representation pattern suggest that synaptic relations between motor cortex and somatic musculature are continually reshaped in adult mammals.     

Oral and subcutaneous sumatriptan in the acute treatment of migraine: an open randomized cress-over study

In an open, randomized cross-over study in 124 patients, we compared the efficacy, safety and patient preference of oral and subcutaneous sum triptan in the acute treatment of migraine. Patients were treated for 3 attacks or 3 months and then crossed over. Primary clinical efficacy was defined as a reduction in headache severity on a four-point self-rating scale from severe (3) or moderate (2) to mild (1) or none (0), or mild (1) to none (0). Efficacy was evaluated 2 h after the administration of subcutaneous and 4h after the administration of oral sumatriptan. Subcutaneous sumatriptan was significantly more effective than oral sumatriptan in relieving headache (over all three attacks 78% vs 61% improvement), improving clinical disability (55% vs 41 % improvement) and relieving nausea (69% vs 53%), vomiting (72% vs 32%) and phono- or photophobia (67% vs 49%). Median time to recurrence was shorter after subcutaneous (12.5 h) than after oral sumatriptan (18 h); the number of patients experiencing a recurrence was similar Patients reported more adverse events after subcutaneous sumatriptan (1.32 per attack) than after the oral form (0.85 per attack), but all adverse events were mild to moderate in intensity and of short duration. Patient opinion was more often positive after subcutaneous sumatriptan. These results may be useful in counselling patients to choose between the available marketed formulations of sumatriptan.     

超细β-磷酸三钙/聚-L-乳酸复合材料的制备与骨折内固定器的加工

目的：制备分散性良好的超细β-磷酸三钙(β-TCP)／聚-L-乳酸(PLLA)复合材料及新型可吸收骨折内固定器。方法：通过研磨方法制备β-TCP超细粒子，用一缩二乙二醇作分散剂研磨β-TCP后，再将β-TCP与PLLA超声混合，制得复合材料，经注塑加工制成可吸收骨钉，并采用扫描电镜等方法进行表征。结果与结论：用一缩二乙二醇作分散剂研磨β-TCP后再经超声混合，可以使β-TCP超细粒子在复合材料中分散均匀，粒子大小仅为300nm左右，β-TCP与PLlA基体之间结合良好。超细β-TCP／PLLA复合材料可加工成可吸收骨钉，弯曲强度达到100MPa左右，完全满足松质骨内固定的要求。     

Accelerating effects of epidermal growth factor on skin lesions of pemphigus vulgaris: a double-blind, randomized, controlled trial

BACKGROUND: Pemphigus vulgaris (PV) is a severe blistering disease involving the skin and mucous membranes. The most common causes of death in these patients are adverse effects of drugs, and infection. Skin lesions are one of the important sources of infection. Thus, any local treatment that could reduce healing time of lesions and consequently reduce the total dosage of drugs needed to treat is favourable. OBJECTIVE: To evaluate the efficacy of epidermal growth factor (EGF) in reducing healing time of lesions in patients with pemphigus vulgaris. METHODS: In this randomized, double-blind, within-patient, left/right, controlled trial, 20 hospitalized patients with pathologial and immunohistologial (direct and indirect immunoflourecence) proven pemphigus vulgaris (PV) were chosen. In addition, all patients had at least one appropriate pemphigus lesion on each side of the body that had not healed after 2-week systemic therapy and sterile saline washing. EGF (10 microg/g) in 0.1% silver sulfadiazine cream vs. 0.1% silver sulfadiazine cream alone was applied randomly on one side of the body. RESULTS: Kaplan-Meier survival analysis suggested that median time to heal with application of EGF plus silver sulfadiazine cream was 9 days, in comparison with 15 days for silver sulfadiazine cream alone (log-rank test, P=0.0003). No intervention-related adverse effect was observed during the study. CONCLUSIONS: EGF can significantly reduce healing time of skin lesions in patients with pemphigus vulgaris, at least when this cream base is applied (Cochrane skin group identifier: CSG20).     

Differences in preconceptional and prenatal behaviors in women with intended and unintended pregnancies.

OBJECTIVES: This study examined whether pregnancy intention was associated with cigarette smoking, alcohol drinking, use of vitamins, and consumption of caffeinated drinks prior to pregnancy and in early pregnancy. METHODS: Data from a telephone survey of 7174 pregnant women were analyzed. RESULTS: In comparison with women whose pregnancies were intended, women with unintended pregnancies were more likely to report cigarette smoking and less likely to report daily vitamin use. Women with unintended pregnancies were also less likely to decrease consumption of caffeinated beverages or increase daily vitamin use. CONCLUSIONS: Pregnancy intention was associated with health behaviors, prior to pregnancy and in early pregnancy, that may influence pregnancy course and birth outcomes.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Secretion of vascular endothelial growth factor/vascular permeability factor from human luteinized granulosa cells is human chorionic gonadotrophin dependent

Vascularization is a prominent event during corpus luteum formation, providing low density lipoproteins for steroid biosynthesis and enabling transport of secreted steroids. The process of vascularization is controlled by specific regulators. Vascular endothelial growth factor (VEGF), otherwise named vascular permeability factor (VPF), induces endothelial cell proliferation as well as angiogenesis in vivo and increases capillary permeability. Here we report the expression of VEGF/VPF mRNA by cultured human luteinized granulosa cells (GC) for at least 10 days. Without HCG VEGF/VPF expression declined after day 4 and by day 10 was reduced to approximately 30% of the value at day 4. However, after culture in the presence of 1 U/ml human chorionic gonadotrophin (HCG), expression of VEGF/VPF mRNA by GC was four times greater than control experiments by day 10, and increased 100% from day 4 to day 10. Simultaneously, HCG supplementation increased VEGF/VPF secretion by GC. Medium VEGF/VPF on day 3 was 13 pM without and 11 pM with HCG. Medium VEGF/VPF on day 10 was 6 pM without HCG and 29 pM with HCG. These results suggest that vascularization of the corpus luteum is induced by HCG-mediated effects of VEGF/VPF.      

Targeting of human cytotoxic T lymphocytes to MHC class II-expressing cells by staphylococcal enterotoxins.

The staphylococcal enterotoxins (SE) comprise a family of structurally related phage-encoded bacterial proteins, which are the most potent mitogens known for murine and human T lymphocytes. In this report we describe a novel cytotoxic mechanism, where SE directs human CD3+ T lymphocytes to mediate strong cytotoxicity against target cells of irrelevant nominal specificity. The SE-dependent cellular cytotoxicity (SDCC) occurred at picomolar concentrations of SE and involved the initial binding of the SE to the target cells and subsequent triggering of the cytotoxic T cells. SDCC was induced by SEA, SEB, SEC1 and SED, which indicates that this is a common property conserved among all SE. Certain antibodies to the HLA-DR molecule efficiently blocked SDCC. Major histocompatibility complex (MHC) class II+ RAJI cells and HLA-DR-transfected murine L cells were sensitive to SDCC, whereas the MHC class II- RJ.2.2.5 RAJI cell mutant and untransfected L cells were completely resistant to SDCC. These results demonstrate that the MHC class II antigen is the target molecule in SDCC. HLA-DR molecules acted as receptors for SE and the complex was recognized by T lymphocytes in a polyclonal fashion. SDCC was mediated by allospecific cytotoxic CD8+ T cells, by cloned CD8+ T cells and by fresh human peripheral blood mononuclear cells. The SDCC phenomenon provides a rapid, potent and specific mechanism for elimination of HLA-DR+ target cells. We suggest that SDCC is an important combat strategy, employed by the bacteria to avoid specific MHC class II antigen-dependent immune recognition, by inducing T-cell dependent autologous lysis of MHC class II-expressing cells.     

Amidolytic assay for procoagulant activity of lymphoid and tumor cells

Among the effector molecules induced in monocytes by the cellular immune response is tissue factor (TF), the initiating receptor/cofactor of the extrinsic coagulation protease cascade that is also frequently observed on human tumor cells. Other cellular activators have also been described on monocytes and tumor cells. Analyses of the cellular immune procoagulant response would be aided by a simple and efficient form of quantitation. An assay for cellular procoagulant activity (PCA) induction and expression was developed utilizing the chromogenic thrombin substrate tosyl-Gly-Pro-Arg-p-nitroanilide acetate. The constitutive or induced PCA of a variety of cells was analyzed. Peripheral blood mononuclear cells, peritoneal exudate cells, 13762 Mat B (III) mammary carcinoma cells, 1591-RE fibrosarcoma cells, the macrophage cell line WEHI-265, a detector of PCA inducing lymphokines, or mixtures of these cells were incubated with or without stimuli, e.g., endotoxin, in 96-well microplates. After incubation the cells were assayed for PCA by addition of the chromogenic substrate for thrombin using fibrinogen depleted plasma as a source of the coagulation proteins factors VII, X, V and prothrombin. The absorbance at 405 nm was determined. Spontaneous cleavage of the chromogenic substrate restricted the assay to total analysis times of less than 14 min. The 13762 Mat B (III) rat tumor which constitutively expressed tissue factor-like procoagulant activity induced measurable substrate hydrolysis with as few as 100 cells/well. It was observed that the chromogenic substrate assay was approximately twice as sensitive as conventional clotting assays for procoagulant activity. Endotoxin stimulated human peripheral blood mononuclear cells and mouse peritoneal exudate cells were readily analyzed. The procoagulant activity of approximately 280 LPS-stimulated human monocytes generated sufficient thrombin to provide a significant measurable signal within 10 min. Also supernatants from mixed lymphocyte cultures as well as from immune lymphocyte responses to syngeneic tumor cell cultures induced procoagulant activity in the macrophage like cell line WEHI-265 as determined with the assay for thrombin generation. The hydrolysis of the substrate was attributed to thrombin formation since the induced cleavage was abolished by hirudin, the highly specific active site inhibitor of thrombin. This chromogenic thrombin assay can be used for measuring induction of viable cell expression or total cellular procoagulant activity rapidly and efficiently in large replicate numbers suitable for a variety of analyses of cellular immune responses including clonal analyses of gene induction.