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The morphology, integration, and functional efficacy of striatal grafts differ between cell suspensions and tissue pieces.

In order to develop a surgical protocol for use in clinical trials of striatal transplantation in Huntington's disease (HD), the issues involved in the preparation and implantation of the embryonic striatal tissue must be addressed. Rodent models of HD offer the best experimental paradigm with which to study various aspects of striatal transplantation. In this article we present the results of an investigation of the role of trypsin and the process of trituration in the preparation of cell suspensions compared to the use of solid pieces of tissue. The embryonic material was derived from the lateral ganglionic eminence (LGE) and implanted into the excitotoxically lesioned striatum of the host rats. Twelve weeks following implantation, retrograde tracing of projections from the graft to the globus pallidus was performed. Grafts derived from cell suspensions triturated in the presence of trypsin contained larger quantities of striatal tissue within the graft and more DARPP-32-positive medium spiny neurons than grafts implanted as fragments of tissue. Afferent and efferent connectivity was also better in the trypsinized suspension graft group. Modest recovery in paw reaching was observed contralateral to the grafted side in animals implanted with solid fragments of embryonic striatal tissue. No relationship was observed between functional effect and the graft anatomy. These results suggest that local graft host interaction may also be involved in graft-mediated functional recovery.

Acetylcholinesterase↗

Temperature dependence of certain integrated membrane functions in macrophages.

We have studied the effect of temperature on uptake and degradation of molecules entering mouse peritoneal macrophages by fluid-phase, adsorptive and receptor-mediated pinocytosis, and on degradation of their intracellular proteins. Uptake of [3H]sucrose and uptake and degradation of formaldehyde-treated 125I-labelled human serum albumin and 125I-labelled mannose-bovine serum albumin continued, but were progressively slowed as the temperature decreased from 37 degrees C to 20 degrees C. The uptake and degradation were completely abolished at approximately 15 degrees C. Arrhenius plots for adsorptive and fluid uptake were unilinear, whereas that for receptor-mediated endocytosis showed an inflection point at approximately 20 degrees C. The results did not indicate any distinction between adsorptive and fluid pinocytosis. An 'intracellular turnover time' calculated for mannose-bovine serum albumin taken up by the specific route is 19-24 min and this time calculated for human serum albumin is, in contrast, 99 min. Studies of the kinetics of degradation of both endocytosed and endogenous proteins showed similarity in the temperature cut-off of degradation of endocytosed and endogenous long-half-life proteins (congruent to 15 degrees C) and continuance of endogenous short-half-life degradation at much lower temperatures.

Animals↗

Human histologic evidence of integration of functionally loaded hydroxyapatite-coated implants placed simultaneously with sinus augmentation: a case report 2 1/2 years postplacement.

This article histologically and clinically presents a case report showing two retrieved implants that were placed simultaneously at the time of the antral augmentation. These implants were retrieved 2.5 years after placement and 2 years after loading. To our knowledge, this is the first human histological case report of implants that were simultaneously placed with a sinus lift and loaded.

Adult↗

Lexical processing and text integration of function and content words: evidence from priming and eye fixations.

The results of two experiments comparing processing of function words and content words are reported. In Experiment 1, priming was present for both related function and related content word pairs, as measured in lexical decision response times. In Experiment 2, participants' eye movements were monitored as they read sentences containing either a high- or a low-frequency function or content target word. Average word length and word frequency were matched across the function and content word conditions. Function words showed frequency effects in first-fixation and gaze duration that were similar to those seen for content words. Clear differences in on-line processing of function and content words emerged in later processing measures. These differences were reflected in reading patterns and reading time measures. There was inflated processing time in the phrase immediately following a low-frequency function word, and participants made more regressions to the target word in this condition than in the other three conditions. The priming effects in lexical decision and the word frequency effects in initial processing measures in silent reading for both word types were taken as evidence of common lexical processing for function and content words. The observed differences in later processing measures in the eye-movement data were taken as evidence of differences in the role that the two word types have in sentence processing beyond the lexical level.

Attention↗

Cutting edge: extracellular signal-regulated kinases 1/2 function as integrators of TCR signal strength.

Altered signaling through the TCR is currently showing promise for immunotherapy. However, the molecular mechanisms are not completely understood. Therefore, we investigated whether varying the strength of TCR engagement in various human T cells would yield different second messenger responses. The kinetics and duration of extracellular signal-regulated kinase (ERK) activation, central to multiple cellular responses, are distinctly dependent on the T cell activation state (naive vs effector), strength of TCR cross-linking, and input from the phosphatidylinositol-3 kinase pathway, which is regulated by cytokines and growth factors. Moreover, the duration of ERK activation affects c-Fos expression, a component of the AP-1 transcription complex. Thus, the character of ERK activation, transient or sustained, acts as a signal integrator to quantify the strength of TCR engagement and direct the cellular response.

Cell Separation↗

Linking up with the community: a fertile strategy for a university hospital?

PURPOSE: To systematically identify, describe and characterise the collaborative initiatives, which have been established between the Academic Medical Centre/University of Amsterdam and local health care providers in the adjacent community. BACKGROUND: The viability of university hospitals is jeopardised. Their narrowed orientation on delivering the most advanced services to the sickest patients challenges their missions in patient care, science and education. By linking up with local health care providers, university hospitals create synergistic relationships that should secure these three academic missions for the future. METHODS: We conducted a multiple case study in two stages. Initially, division leaders and the director of integrated care were consulted to identify all existing collaborative initiatives of the Academic Medical Centre. Successively, face-to-face interviews were held with the leaders of these initiatives. During these interviews data were primarily collected through a questionnaire. Notes of the interviewer, and documents (if available) were also collected. The analysis focused on systematically describing and characterising the initiatives using the concept of 'community-based integrated care'. RESULTS: Twenty-seven heterogeneous initiatives were identified. Half of these initiatives are targeted to the adjacent community of the Academic Medical Centre, but only four of them are initiated on the basis of community information and involve the community and/or patients. Furthermore, the extent of integration differed per dimension. Functional integration within the initiatives has been relatively low, clinical integration mixed, and professional integration quite advanced. CONCLUSIONS: The results indicate that a considerable number of collaborative initiatives have emerged. Still, these initiatives are loosely 'community-based' and hardly focus on the full integration of care services. This suggests that the community linkages of the Academic Medical Centre in Amsterdam could be further developed by gaining the full support of all clinical departments for the strategic approach and by adapting an overall hospital perspective to monitor the progress towards community-based integrated care.

Journal Article↗

How best to use echocardiography for definitive assessment. Methods of estimating valvular integrity, LV function, pulmonary pressure.

In patients with myocardial infarction, echocardiography helps predict outcome, as well as guide the selection of interventional strategies. By assessing the extent of valvular dysfunction and abnormalities in LV and RV size and function, echocardiography can help determine whether surgery is needed in patients with valvular heart disease. Both pulmonary artery pressures and LV function can be evaluated and quantified with ultrasonically derived data. Although echocardiography cannot document active infection, vegetations may appear as areas of valvular thickening. The role of echocardiography will continue to evolve as new techniques are developed.

Contrast Media↗

Effect of swim-up sperm washing and subsequent capacitation on acrosome status and functional membrane integrity of normal sperm.

OBJECTIVE: Sperm preparation techniques select sperm population with improved sperm motion characteristics. We sought to determine whether the swim-up technique selects spermatozoa with the ability to undergo hypoosmotic swelling, and how swim-up and subsequent capacitation affect the acrosome reaction rate. METHODS: Semen specimens from 15 normal donors were divided into unprocessed, swim-up, and capacitated groups, and sperm motion characteristics, ability to undergo hypoosmotic swelling, and acrosome reaction rate were measured. RESULTS: Sperm motility, viability, and all motion characteristics (except linearity) were significantly increased in both swim-up and capacitated specimens. The ability to respond to hypoosmotic swelling was significantly higher in the spermatozoa isolated by swim-up. The percentage of acrosome-reacted spermatozoa remained unchanged in both unprocessed and swim-up groups, but was significantly higher in the capacitated group. CONCLUSIONS: Swim-up isolates sperm with greater ability to undergo hypoosmotic swelling, but does not change the acrosome reaction rate. In vitro capacitation of spermatozoa selected by swim-up enhances the acrosome reaction rate.

Acrosome↗

The transporter associated with antigen processing (TAP): structural integrity, expression, function, and its clinical relevance.

BACKGROUND: The transporter associated with antigen processing (TAP), a member of the family of ABC transporters, plays a crucial role in the processing and presentation of the major histocompatibility complex (MHC) class I restricted antigens. TAP transports peptides from the cytosol into the endoplasmic reticulum, thereby selecting peptides matching in length and sequence to respective MHC class I molecules. Upon loading on MHC class I molecules, the trimeric MHC class I/beta2-microglobulin/ peptide complex is then transported to the cell surface and presented to CD8+ cytotoxic T cells. Abnormalities in MHC class I surface expression have been found in a number of different malignancies, including tumors of distinct histology, viral infections, and autoimmune diseases, and therefore represent an important mechanism of malignant or virus-infected cells to escape proper immune response. In many cases, this downregulation has been attributed to impaired TAP expression, which could be due to structural alterations or dysregulation. This review summarizes the physiology and pathophysiology of TAP, thereby focusing on its function in immune responses and its role in human diseases.

ATP-Binding Cassette Transporters↗