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.
A new descriptive framework for voice quality perception (Kreiman, Gerratt, Kempster, Erman, & Berke, 1993) states that when listeners rate a voice on some quality dimension (e.g., roughness), they ...compare the stimulus presented to an internal standard or scale. Hypothetically, substituting explicit, external standards for these unstable internal standards should improve listener reliability. Further, the framework suggests that internal standards for vocal qualities are inherently unstable, and may be influenced by factors other than the physical signal being judged. Among these factors, context effects may cause drift in listeners' voice ratings by influencing the internal standard against which judgments are made. To test these hypotheses, we asked 12 clinicians to judge the roughness of 22 synthetic stimuli using two scales: a traditional 5-point equal appearing interval (EAI) scale and a scale with explicit anchor stimuli for each scale point. The stimulus set included a relatively large number of normal and mildly rough voices. We predicted that this would produce an increase in the perceived roughness of moderately rough stimuli over time for the EAI ratings, but not for the explicitly anchored ratings. Ratings made using the anchored scale were significantly more reliable than those gathered using the unanchored paradigm. Further, as predicted, ratings on the unanchored EAI scale drifted significantly within a listening session in the direction expected, but ratings on the anchored scale did not. These results are consistent with our framework and suggest that explicitly anchored paradigms for voice quality evaluation might improve both research and clinical practice.
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