Peri-ventricular grey stimulation versus motor cortex stimulation for post stroke neuropathic pain.

Central post stroke pain is often difficult to manage satisfactorily with conventional treatment modalities for pain. In the last decade functional neurosurgery has offered hope with motor cortex stimulation achieving significant alleviation of pain in some patients. Unfortunately this has led to the neglect of chronic stimulation of deep grey matter as another modality of treating this condition. In this article we present our experience with motor cortex stimulation and that with deep grey matter stimulation in patients with post stroke pain. We argue that both modalities have a significant role and that what is required are better methods of identifying particular patients who are more likely to respond to one or the other.     

The Stiff Elbow

Elbow motion is essential for upper extremity function to position the hand in space. Unfortunately, the elbow joint is prone to stiffness following a multitude of traumatic and atraumatic etiologies. Elbow stiffness can be diagnosed with a complete history and physical exam, supplemented with appropriate imaging studies. The stiff elbow is challenging to treat, and thus, its prevention is of paramount importance. When this approach fails, non-operative followed by operative treatment modalities should be pursued. Upon initial presentation in those who have minimal contractures of 6-month duration or less, static and dynamic splinting, serial casting, continuous passive motion, occupational/physical therapy, and manipulation are non-operative treatment modalities that may be attempted. A stiff elbow that is refractory to non-operative management can be treated surgically, either arthroscopically or open, to eliminate soft tissue or bony blocks to motion. In the future, efforts to prevent and treat elbow stiffness may target the basic science mechanisms involved. Our purpose was to review the etiologies, classification, evaluation, prevention, operative, and non-operative treatment of the stiff elbow.     

Polymerization of human prion peptide HuPrP 106–126 to amyloid in nucleic acid solution

Summary.  The human prion peptide PrP106–126 polymerizes in the presence of DNA both in its circular and linearized forms under solution conditions where the peptide alone does not polymerize. The polymerization process has been monitored by the increase in the fluorescence of anilino naphthalene sulfonic dye which detects the availability of the hydrophobic surface(s) in the aggregate as a consequence of polymerization. The polymerization is a nucleation dependent phenomenon as is evidenced from an existence of a lag period before the onset of the polymerization and a strong dependence of the polymerization on the prion peptide concentrations. The reaction is dependent on the pH as seen from rapid polymerization at pH 5 compared to the reaction at neutral pH where no polymerization is observed after a relatively long period of incubation. The polymer has been characterized as amyloid by using new absorbing and emitting species resulting from the interaction of the polymer with the amyloid specific fluorescent dye, Thioflavine S. This is probably the first demonstration that an endogenous macromolecule can influence the polymerization of a prion peptide. We have previously shown that there is a conformational change in the nucleic acid as a consequence of this interaction. This prion peptide is considered as a model to understand prion diseases as is evidenced from its toxicity towards primary brain cells in culture. The peptide encompasses one of the important amyloidogenic regions of the normal cellular prion protein. Demonstration of nucleic acid induced polymerization of the normal and scrapie prion isoforms accompanying a change in the nucleic acid conformation can establish a possible role of nucleic acid in prion disease. Received January 8, 1997 Accepted March 4, 1998     

Depletion of O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine in three-dimensional collagen cultures of normal human breast epithelial cells.

O6-Alkylguanine--DNA alkyltransferase (AGT) is a protein which removes the promutagenic O6-alkylguanine lesion induced in DNA by alkylating agents. Our results demonstrate that freshly isolated organoids from reduction mammoplasty specimens contain significant levels of AGT activity. AGT activity in breast epithelial cells shows interindividual variation. Constitutive levels of AGT activity remain unchanged during short-term serum-free culture of breast epithelial cells inside three-dimensional rat-tail collagen gel matrix. In the present study, we optimized conditions for depleting AGT activity in human breast epithelial cells cultured in three-dimensional collagen gel matrix using O6-methylguanine and O6-benzylguanine which are substrates for AGT. AGT activity was efficiently inactivated by exposure of cells to O6-methylguanine or O6-benzylguanine. Inactivation with O6-benzylguanine was more rapid, of greater magnitude and consistency and occurred at lower concentrations than with O6-methylguanine. Near-complete inactivation (> 99.5%) of AGT activity was reproducibly achieved with 50 microM O6-benzylguanine. In contrast, 500 microM O6-methylguanine was needed to obtain a maximal effect and this reduced AGT activity by only 53-93% of control. Within 30 min of adding the free base, 50 microM O6-benzylguanine depleted 95% of the levels of AGT compared to 30% inhibition with 500 microM O6-methylguanine. The profile for restoration of AGT activity was different following a 24 h incubation and subsequent removal of each of the guanine derivatives. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. In contrast, following removal of 500 microM O6-methylguanine, the activity was restored from its nadir of 16% of control values reaching pretreatment levels after 5 days. These results suggest that treatment with O6-benzylguanine may be used to modulate the incidence of transforming mutations in cultured human breast epithelial cells treated with chemical carcinogens which give rise to O6-alkylguanine adducts.     

荧光原位杂交技术分析人结肠菌群方法研究

建立荧光原位杂交技术分析人体内结肠菌群的方法。取受试者新鲜粪便 ,选用 5种特异性的 16SrRNA寡核苷酸探针 ,检测粪便样本收集后的保存时间、温度 ,离心条件及样本固定液存放时间对杂交计数结果的影响。结果建立最佳实验条件为 :粪便样本收集后应尽快在 4℃下保存 ,放置时间不要超过 12小时即作处理 ;样本的适宜离心条件为 70 0g 2分钟 ;样本用多聚甲醛固定后在 - 80℃下存放时间不要超过 5个月。该方法具有较好的稳定性 ,可以有效地检出个体之间结肠菌群的差异。     

Stimulation of thrombopoiesis in mice bearing experimental tumors

Significant increase (p less than 0.05) in circulating platelet counts was observed in a wide spectrum of experimental tumors in mice. The mechanism of this abnormality was investigated in strain A mice bearing a transplantable ascites tumor, Sarcoma 180 (S 180). Thrombocytosis observed in the tumor hosts was not due to prolonged platelet surviva], as 51Cr platelet half-life was normal. On the other hand, stimulation of thrombopoiesis, expressed in terms of platelet 75Selenomethionine (75SeM) incorporation, appeared to be the primary reason for elevated platelet counts in the tumor-bearers. Evaluation of thrombopoietic activity in the femoral marrow and spleen by measuring organ uptake of 75SeM and megakaryocyte counts indicated that tumor-induced stimulation in thrombopoiesis may be attributed to enhancement in splenic activity. Pretreatment of normal mice with tumor ascites or tumor cell-conditioned medium resulted in enhancement in thrombopoiesis. The findings suggest the production of some factor(s) by the tumor cells which probably mediate the stimulation of platelet production in tumor hosts.