p53 serum antibodies as prognostic indicator in head and neck cancer

p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The post-therapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer. Received: 5 December 1996 / Accepted: 4 January 1997     

Fluctuating asymmetry inMacaca fascicularis: A study of the etiology of developmental noise

Fluctuating asymmetry was determined for six cranial measurements in an age-diverse sample of 138 individuals ofMacaca fascicularis. These data were used to choose among four hypotheses concerning the etiology of developmental noise. The hypotheses considered are (1) that developmental noise represents asymmetry in the causal history of a developing organism's interaction with the environment, (2) that it represents stochasticity in the mechanics of growth and induction, (3) that it reflects variation in the initial conditions of a developmental process, and (4) that it represents the random accumulation of noise at a level below that of morphogenetic mechanism. These hypotheses were tested against predictions concerning the intraspecific patterning of fluctuating asymmetry against age and size and the covariation of asymmetry values. Only the predictions of the fourth hypothesis were confirmed by results of this study. These results provide evidence for the view that developmental noise, as reflected by fluctuating asymmetry, is an intrinsic property of developmental systems, and not merely produced by the complexity of the organism's interaction with the environment.     

Book Review: The Development of Animal Form: Ontogeny,Morphology, and Evolution. By Alessandro Minelli,Cambridge University Press,Cambridge, U.K. 2003, (Paperback, 2000). 339 pp, $75.00 (hardback)

International Journal of Primatology -     

Dynamic adoption of anergy by antigen-exhausted CD4+ T cells

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Deciphering the Palimpsest: Studying the Relationship Between Morphological Integration and Phenotypic Covariation

Organisms represent a complex arrangement of anatomical structures and individuated parts that must maintain functional associations through development. This integration of variation between functionally related body parts and the modular organization of development are fundamental determinants of their evolvability. This is because integration results in the expression of coordinated variation that can create preferred directions for evolutionary change, while modularity enables variation in a group of traits or regions to accumulate without deleterious effects on other aspects of the organism. Using our own work on both model systems (e.g., lab mice, avians) and natural populations of rodents and primates, we explore in this paper the relationship between patterns of phenotypic covariation and the developmental determinants of integration that those patterns are assumed to reflect. We show that integration cannot be reliably studied through phenotypic covariance patterns alone and argue that the relationship between phenotypic covariation and integration is obscured in two ways. One is the superimposition of multiple determinants of covariance in complex systems and the other is the dependence of covariation structure on variances in covariance-generating processes. As a consequence, we argue that the direct study of the developmental determinants of integration in model systems is necessary to fully interpret patterns of covariation in natural populations, to link covariation patterns to the processes that generate them, and to understand their significance for evolutionary explanation.     

A COMPARISON OF COVARIANCE STRUCTURE IN WILD AND LABORATORY MUROID CRANIA

Mutations have the ability to produce dramatic changes to covariance structure by altering the variance of covariance-generating developmental processes. Several evolutionary mechanisms exist that may be acting interdependently to stabilize covariance structure, despite this developmental potential for variation within species. We explore covariance structure in the crania of laboratory mouse mutants exhibiting mild-to-significant developmental perturbations of the cranium, and contrast it with covariance structure in related wild muroid taxa. Phenotypic covariance structure is conserved among wild muroidea, but highly variable and mutation-dependent within the laboratory group. We show that covariance structures in natural populations of related species occupy a more restricted portion of covariance structure space than do the covariance structures resulting from single mutations of significant effect or the almost nonexistent genetic differences that separate inbred mouse strains. Our results suggest that developmental constraint is not the primary mechanism acting to stabilize covariance structure, and imply a more important role for other mechanisms.     

Biomechanical adaptation of ulnar cross-sectional morphology in brachiating primates

The forelimbs of hylobatids (gibbons and siamang) are distinctive among tetrapods in that they are loaded in overall tension during normal locomotion. While hylobatid ulnae must also encounter bending stresses in the course of their full range of locomotor behavior, their loading regime differs from that of quadrupedal anthropoids in that these bending stresses are distributed evenly along the bone, are not exerted in a preferred plane, and are probably of generally lower magnitude. This study examines the degree to which hylobatid ulnae are adapted to this suspensory loading regime. We obtained cross-sections of ulnae at various increments along the length of the bone using CAT scans. The sample comprises 476 cross-sections representing the ulnae of 25 individuals from five species of comparable body size. We show that in gibbons and siamang, the patterning of ulnar cross-sectional area and resistance to bending in the dorsoventral plane along the ulnar diaphysis differ from that of similarly sized quadrupedal anthropoids in the manner predicted by a suspensory loading regime. We also find the same pattern for the ulnae of Ateles, whose loading regime may be fairly similar to that of hylobatids. However, we find that the cross-sectional shape of the ulnar diaphysis in hylobatids and Ateles does not differ from that of quadrupedal monkeys in the manner predicted by a suspensory loading regime. © 1995 Wiley-Liss, Inc.     

Primidone blocks RIPK1-driven cell death and inflammation

The receptor-interacting serine/threonine protein kinase 1 (RIPK1) is a key mediator of regulated cell death and inflammation. Recent studies suggest that RIPK1 inhibition would fundamentally improve the therapy of RIPK1-dependent organ damage in stroke, myocardial infarction, kidney failure, and systemic inflammatory response syndrome. Additionally, it could ameliorate or prevent multi-organ failure induced by cytokine release in the context of hyperinflammation, as seen in COVID-19 patients. Therefore, we searched for a RIPK1 inhibitor and present the aromatic antiepileptic and FDA-approved drug primidone (Liskantin®) as a potent inhibitor of RIPK1 activation in vitro and in a murine model of TNFα-induced shock, which mimics the hyperinflammatory state of cytokine release syndrome. Furthermore, we detected for the first time RIPK1 activation in the respiratory tract epithelium of hospitalized patients who tested positive for SARS-CoV-2 infection. Our data provide a strong rationale for evaluating the drug primidone in conditions of hyperinflammation in humans.Subject terms: Cell death and immune response, Translational research