Regulation of T-cell receptor signalling by membrane microdomains

There is now considerable evidence suggesting that the plasma membrane of mammalian cells is compartmentalized by functional lipid raft microdomains. These structures are assemblies of specialized lipids and proteins and have been implicated in diverse biological functions. Analysis of their protein content using proteomics and other methods revealed enrichment of signalling proteins, suggesting a role for these domains in intracellular signalling. In T lymphocytes, structure/function experiments and complementary pharmacological studies have shown that raft microdomains control the localization and function of proteins which are components of signalling pathways regulated by the T-cell antigen receptor (TCR). Based on these studies, a model for TCR phosphorylation in lipid rafts is presented. However, despite substantial progress in the field, critical questions remain. For example, it is unclear if membrane rafts represent a homogeneous population and if their structure is modified upon TCR stimulation. In the future, proteomics and the parallel development of complementary analytical methods will undoubtedly contribute in further delineating the role of lipid rafts in signal transduction mechanisms.     

Malignant effusions are sources of fibronectin and other promigratory and proinvasive components

Metastatic dissemination is the primary cause of death in ovarian cancer (OvCa) patients, and dissemination to pleural and peritoneal effusions is a common clinical event. Effusion samples were collected from 15 OvCa patients. Twenty-six samples were collected prospectively, two were archival, and eight were taken from patients with other malignancies. Twenty-nine samples were from malignant ascites, and seven specimens were pleural fluids. In addition, six ascites and two pleural fluids from noncancer patients were studied as effusion controls. Effusion supernatants were tested for migration-stimulation activity, using A2058 human melanoma cells as the index responder cell. Malignant samples induced a 400-1200% increase in migration. Sixty percent of the migration was inhibited by incubation of the malignant fluid with antifibronectin (FN) antibody, in contrast to 75% inhibition of control fluid-stimulated migration (P = 0.017). Gelatin zymography and Western blot analyses showed that latent and activated MMP-2 and MMP-9 collagenases, and tissue inhibitor of metalloproteinase-2 (TIMP-2) were present in all malignant fluids. Serial samples were taken from several patients, and a trend for correlation between MMPs and clinical behavior of the tumors was shown. Free TIMP-2 correlated with CA-125 levels in two patients for whom serial samples were available. The demonstration of promigratory and proinvasive activity in malignant effusions is consistent with their association with other metastatic disease in OvCa patients and their function as a haven for metastatic cells.     

Standardization of flap design for oropharyngeal reconstruction after cancer ablation surgery

A variety of residual defects containing many sulci and fossae in the oropharyngeal cavity make it extremely difficult to achieve an adequate flap design as well as the functional reconstruction of the complex defects after ablation surgery for oropharyngeal tumors. This study attempted to standardize flap design for the different types of defects in order to produce a better functional reconstruction of intra-oral defects. The oropharyngeal defects were classified into 6 Zones. When the defect involves only the mouth floor, it was classified as Zone 1. A hemi tongue was classified as Zone 2. A defect involving the mouth floor and a part of the tongue was classified as Zone 3. A defect involving the mouth floor, a part of the tongue and the tonsil was classified as Zone 4. A defect involving the mouth floor, a part of the tongue, tonsil and soft palate was classified as Zone 5. A defect involving the pharyngeal wall was classified as Zone 6. The following four types of forearm free flap designs were applied to each defective Zone accordingly: Type I flap design - an unilobed design for reconstructing Zone 1, 2 and 6 defects, Type II design - bilobed design for reconstructing Zone 3 defects, Type III design - trilobed design for reconstructing Zone 4 defects and Type IV design for reconstructing Zone 5 defects. During 1999 to 2002, 91 patients with oropharyngeal defects underwent a reconstruction using these standardized forearm free flap designs. The Type I design was used in 41 cases, the Type II design in 18 cases, the Type III design in 10 cases and the Type IV design in 22 cases. In all patients, the decannulation was successful, and the swallowing and deglutination functions were within the normal parameters. There was less nasal escape of the voice and the regurgitation of food than that observed using the conventional flap design method. Effective and functional reconstructions with minimal morbidities are possible with the application of the standardized forearm free flap design in oropharyngeal defects.     

Medial septal and median raphe innervation of vasoactive intestinal polypeptide-containing interneurons in the hippocampus

Vasoactive intestinal polypeptide-immunoreactive interneurons are known to form three anatomically and neurochemically well-characterized neuron populations in the hippocampus. Two of these establish synaptic contacts selectively with other GABAergic cells (interneuron-selective cells), whereas the third type innervates pyramidal cell bodies and proximal dendrites like a conventional basket cell. Our aim was to examine which of the vasoactive intestinal polypeptide-containing interneuron populations are among the targets of GABAergic septohippocampal and serotonergic raphe-hippocampal pathways. Anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with double immunocytochemistry for vasoactive intestinal polypeptide was used at the light and electron microscopic levels. Our results show that both interneuron-selective cells and vasoactive intestinal polypeptide-containing basket cells receive synaptic input from the medial septum and median raphe nucleus. The GABAergic component of the septohippocampal pathway establishes multiple contacts on both cell types. In the case of the raphe-hippocampal projection, single or double contacts were more frequent on vasoactive intestinal polypeptide-positive interneuron selective cells (76%), whereas multiple contacts predominated on basket cells (83%). The extrinsic GABAergic innervation of interneuron-selective cells in the hippocampus indicates a complex interaction among GABAergic systems, which might ensure the timing and rhythmic synchronization of inhibitory processes in the hippocampus. On the other hand, our results suggest that the serotonergic effect on perisomatic inhibition is exerted via vasoactive intestinal polypeptide-containing basket cells that are functionally distinct from their parvalbumin-positive relatives, which appear to escape control of serotonergic as well as local interneuron-selective cells.     

The Effect of Electrical Stimulation and lsokinetic Exercise on Muscular Power of the Quadriceps Femoris

The purpose of this study was to compare the power and strength changes, of the quadriceps femoris muscle group, following 6 weeks of training. Twenty-seven moderately trained, female subjects were placed into three equated groups: electrical stimulation plus isokinetic exercise (ES + IE), isokinetic exercise (IE), and electrical stimulation (ES). A CybexQ I1 isokinetic dynamometer was used for testing the quadriceps ' power and strength output at the velocities of 0, 30, 100, and 180 O/ sec. The ES + IE and ES groups received faradic stimulation (progressive from 10- 20 mA) from a Multitone Multifaradic Unit (model F283, Multitone Electric Co., London, England). In addition, the ES + IE group performed isokinetic contractions concurrently with the faradic stimulation. Thigh circumference (TC) and time to peak tension (TPT) were also calculated during the pre-, mid-, and post-tests. Results indicated that a significant power increment was evident between the pre- and posttests and the pre- and mid-tests for the combined groups (p < 0.05). However, there were no significant power increases between the three separate groups at the four velocities. Significant power differences (P c 0.05) for the combined groups between the pre- and post-tests and the pre- and mid-tests at the isokinetic velocities of 30 and OO/sec were also identified. TPT and TC did not change significantly for any group over the 6-week training period. This study indicated that the combined effects of ES + IE, IE, and ES are potentially effective means of improving power and strength; however, data did not reveal one method of training as being significantly superior to another. J Orthop Sports Phys Ther 1986;8(5):260-268.     

食品中可能存在的致癌剂和致突变剂

在近20年中,流行病学研究结果提供了有力的证据表明,与人类饮食有关的某些因子,对人为肿瘤发生的可能性具有主要的决定性影响。可引起特殊肿瘤发病率和死亡率增减的饮食状况已被分析。尽管有几种途径在饮食调节肿瘤发病率中是重要的,但一种     

No evidence for paternal mtDNA transmission to offspring or extra-embryonic tissues after ICSI

There is a risk that ICSI may increase the transmission of mtDNA diseases to children born after this technique. Knowledge of the fate and transmission of paternal mitochondrial DNA is important since mutations in mitochondrial DNA have been described in oligozoospermic males. We have used an adaptation of solid phase mini-sequencing to exclude the presence of levels of paternal mtDNA >0.001% in ICSI families. This method is more sensitive than those used in previous studies and is sufficient to detect the likely paternal contribution (approximately 0.1-0.5% from simple calculations of expected dilution during fertilization). Using this method, we were able to detect concentrations as low as 0.001% paternal mtDNA in a maternal mtDNA background. No paternal mtDNA was detected in the embryonic (blood or buccal swabs) tissue of children born after ICSI nor in extra-embryonic tissue (placenta or umbilical cord). In conclusion, we did not detect paternal mtDNA in blood, buccal swabs, placenta or umbilical cord of children born after ICSI. We have found no evidence that ICSI increases the risk of paternal transmission of mtDNA and hence of mtDNA disorders.     

Errorless learning and the cognitive rehabilitation of memory-impaired schizophrenic patients

BACKGROUND: In recent years, evidence has accumulated that a significant proportion of schizophrenic patients have severe memory impairment, which cannot be attributed to the effects of medication, chronicity or institutionalization. Our group has demonstrated that memory impairment is associated with poor psychosocial outcome and treatment resistance. Work on the classical amnesic syndrome has suggested that memory training is facilitated by adopting an 'errorless learning' approach, where subjects do not experience failure during learning. This is based on the theory that the preserved implicit memory of amnesic patients results in implicitly remembered incorrect responses interfering with target items, in the absence of a functioning explicit memory system to allow differentiation. METHOD: We compared three groups of subjects, memory-impaired schizophrenic patients, memory unimpaired schizophrenic patients and healthy controls. RESULTS: An errorless learning approach conferred a significant advantage on the memory-impaired schizophrenic group, bringing their performance up to the level of both control groups. In contrast, adopting a traditional trial and error, or errorful approach resulted in markedly impaired performance in the memory-impaired schizophrenic group only. CONCLUSIONS: We conclude that errorless learning approaches may be worthy of further evaluation in the cognitive rehabilitation of memory-impaired schizophrenic patients.     

Dendritic cell-mediated T cell polarization

Effective defense against diverse types of micro-organisms that invade our body requires specialized classes of antigen-specific immune responses initiated and maintained by distinct subsets of effector CD4⁺ T helper (Th) cells. Excessive or detrimental (e.g., autoimmune) responses by effector T cells are controlled by regulatory T cells. The optimal balance in the development of the different types of effector and regulatory Th cells is orchestrated by dendritic cells (DC). This review discusses the way DC adapt the T cell response to the type of pathogen, focusing on the tools that DC use in this management of the T cell response.