The characteristics of cytotoxic T lymphocyte (CTL) and natural killer (NK) cell recognition of and binding to target cells (conjugate formation), and the precise mechanism(s) by which the target ...cells are triggered to undergo apoptotic cell lysis are now being deciphered at the cellular and molecular levels. Involvement of a multitude of cell surface molecules, in addition to T cell receptor (TCR)-major histocompatibility (MHC)-peptide complexes, in the binding and signalling for lymphocyte-mediated lysis has been demonstrated. Two proposed mechanisms of lymphotoxicity currently appear to be valid: (i) a membranolytic one initiated by the formation of pores in target cell membranes by secreted molecules of lymphocyte origin, such as perforin and granzymes, and (ii) a nonsecretory one initiated by receptor-mediated triggering of apoptosis-inducing target cell surface molecules, but not involving the secretion of pore-forming agents and granzymes. Perforin and granzymes are probably involved in lymphocyte activation and are likely mediators of the membranolytic pathway of lymphotoxicity. Existence of the nonsecretory and receptor-triggered lytic mechanism was indicated by (i) the prelytic fragmentation of the target cell's DNA, which precedes release of intracellular (51Cr-labeled) components, (ii) the demonstration of cytolytic effector cells that are either devoid of or express background levels of lytic granules and perforin, and (iii) the observation that some CTL lyse target cells under conditions at which perforin and granzymes are neither secreted nor lytic, e.g. Ca2+o < 1 micromolar. These two mechanisms are not mutually exclusive and are probably used by different types of effector cells or by the same effector cells at different stages of differentiation. In fact, recent perforin gene knock-out experiments support the existence of both.
Common CASR polymorphisms do not increase chronic pancreatitis risk Takáts, A.; Berke, G.; Szentesi, A. ...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... et al.,
July 2021, 2021-07-00, 20210701, Letnik:
21
Journal Article
Common CASR variants in Hungarian chronic pancreatitis patients Takáts, A.; Berke, G.; Szentesi, A. ...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... et al.,
November 2020, 2020-11-00, 20201101, Letnik:
20
Journal Article
Laryngeal Transplantation in 2005: A Review Birchall, M. A.; Lorenz, R. R.; Berke, G. S. ...
American journal of transplantation,
January 2006, 2006, 2006-Jan, 2006-01-00, 20060101, Letnik:
6, Številka:
1
Journal Article
Recenzirano
Odprti dostop
There is no good surgical, medical or prosthetic solution to the problems faced by those with a larynx whose function is irreversibly damaged by tumor or trauma. Over the past 10 years, the pace of ...research designed to establish laryngeal transplantation as a therapeutic option for these persons has increased steadily. The biggest milestone in this field was the world's first true laryngeal transplant performed in Cleveland, Ohio in 1998. The recipient's graft continues to function well, in many respects, even after 7 years. However, it has also highlighted the remaining barriers to full‐scale clinical trials. Stimulated by these observations, several groups have accumulated data which point to answers to some of the outstanding questions surrounding functional reinnervation and immunomodulation. This review seeks to outline the progress achieved in this field by 2005 and to point the way forward for laryngeal transplantation research in the 21st century.
The reliability of listeners' ratings of voice quality is a central issue in voice research because of the clinical primacy of such ratings and because they are the standard against which other ...measures are evaluated. However, an extensive literature review indicates that both intrarater and interrater reliability fluctuate greatly from study to study. Further, our own data indicate that ratings of vocal roughness vary widely across individual clinicians, with a single voice often receiving nearly the full range of possible ratings. No model or theoretical framework currently exists to explain these variations, although such a model might guide development of efficient, valid, and standardized clinical protocols for voice evaluation. We propose a theoretical framework that attributes variability in ratings to several sources (including listeners' backgrounds and biases, the task used to gather ratings, interactions between listeners and tasks, and random error). This framework may guide development of new clinical voice and speech evaluation protocols, ultimately leading to more reliable perceptual ratings and a better understanding of the perceptual qualities of pathological voices.
The CTL's kiss of death Berke, Gideon
Cell,
04/1995, Letnik:
81, Številka:
1
Book Review, Journal Article
Recenzirano
Odprti dostop
The potent and specific lytic activity of CTLs can occur by at least two distinct pathways. In the secretion and perforin-mediated pathway, the direct effect(s) on the target cell membrane of the ...pore-forming agent perforin, probably in conjunction with granzymes, also secreted from the CTLs, causes the target's demise. Intercytoplasmic transfer of granzymes is believed to be involved in inducing target apoptosis. In the Fas-mediated pathway, engagement of a CTL membrane ligand with an apoptosis-inducing target cell surface receptor, such as the FasL with Fas, triggers programmed disintegration of the CTL-bound target; secretion of granzymes and pore formation by perforin are not involved in this receptor-mediated mechanism. Despite the fundamental differences in their onset for both pathways, the downstream sequence of events that culminate in target cell apoptosis appears to be similar. Further studies will resolve this enigma.
Objectives: It has been estimated that more than 70% of patients with Parkinson disease experience voice and speech disorders characterized by weak and breathy phonation, and dysarthria. This study ...reports on the efficacy of treating Parkinson patients who have glottal insufficiency.
Study Design and Methods: Thirty‐five patients underwent collagen augmentation of the vocal folds for hypophonia associated with Parkinson disease, using a new technique of percutaneous injection with fiberoptic guidance. Patient response to the collagen augmentation was determined by telephone survey.
Results and Conclusions: The procedure required minimal patient participation and was safely performed on all the patients who were studied. Results of the survey indicated that 75% of patient responses demonstrated satisfaction with the technique, compared with 16% of patient ratings reflecting dissatisfaction. These results were moderately correlated with the duration of improvement of the dysphonia. Results of this preliminary evaluation demonstrate that voice deficits in Parkinson disease are amenable to vocal fold augmentation. Because this procedure requires minimal patient participation and can be safely performed in an office setting, it may also be useful in other severely debilitating neuromotor diseases that result in glottal insufficiency and hypophonia.
Dysphonic voices are often analyzed using automated voice analysis software. However, the reliability of acoustic measures obtained from these programs remains unknown, particularly when they are ...applied to pathological voices. This study compared perturbation measures from CSpeech, Computerized Speech Laboratory, SoundScope, and a hand marking voice analysis system. Sustained vowels from 29 male and 21 female speakers with mild to severe dysphonia were digitized, and fundamental frequency (F0), jitter, shimmer, and harmonics- or signal-to-noise ratios were computed. Commercially available acoustical analysis programs agreed well, but not perfectly, in their measures of F0. Measures of perturbation in the various analysis packages use different algorithms, provide results in different units, and often yield values for voices that violate the assumption of quasi-periodicity. As a result, poor rank order correlations between programs using similar measures of perturbation were noted. Because measures of aperiodicity apparently cannot be reliably applied to voices that are even mildly aperiodic, we question their utility in quantifying vocal quality, especially in pathological voices.