scholarly journals Less MDM2 Improves Tumor Suppression by p53 Without Shortening Life Span in Animal Model

2006 ◽  
Vol 5 (2) ◽  
pp. 136-136
2021 ◽  
Author(s):  
Alexander Wolf

Understanding the molecular mechanisms of normal aging is a prerequisite to significantly increase human health span. Caloric restriction (CR), which delays aging in most animal models, serves as a yardstick to evaluate interventions extending life span. However, mice given unlimited access to food suffer severe obesity and benefits from CR might be through reducing obesity-associated mortality. Health gains from CR depend on the control mice being gluttonous enough and less obese mouse strains benefit far less from CR. Most pharmacologic interventions reported to mimic CR and increase life span in mice, including resveratrol, rapamycin, nicotinamide mononucleotide and metformin, also reduce mouse body weight. In primates, CR does not delay aging unless the control group is eating enough to suffer from obesity-related disease. Human survival peaks at a BMI achievable without CR. CR mimetics are just diet aids and CR should not be regarded as increasing longevity in healthy weight individuals. Instead, I propose the tumor suppression theory of aging: most phenotypes of aging are the consequence of tumor-suppressive cell senescence that has evolved to limit the tumorigenic potential of clonally expanding cells. A variant of the somatic mutation theory of aging, oncogenic mutations and clonal expansion (opposed to functional impairment) are postulated as the most relevant consequence of somatic mutations. Irreversible cell cycle arrest, accumulating senescent cells, the senescence-associated secretory phenotype and subsequent stem cell depletion eventually cause tissue dysfunction, loss of regeneration and the majority, if not most, phenotypes of aging.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.


Author(s):  
G. C. Smith ◽  
R. L. Heberling ◽  
S. S. Kalter

A number of viral agents are recognized as and suspected of causing the clinical condition “gastroenteritis.” In our attempts to establish an animal model for studies of this entity, we have been examining the nonhuman primate to ascertain what viruses may be found in the intestinal tract of “normal” animals as well as animals with diarrhea. Several virus types including coronavirus, adenovirus, herpesvirus, and picornavirus (Table I) were detected in our colony; however, rotavirus, astrovirus, and calicivirus have not yet been observed. Fecal specimens were prepared for electron microscopy by procedures reported previously.


Author(s):  
J. Metuzals

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.


Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.


Author(s):  
V.J.A. Montpetit ◽  
S. Dancea ◽  
S.W. French ◽  
D.F. Clapin

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.


2020 ◽  
Vol 29 (3) ◽  
pp. 1389-1403
Author(s):  
Jessica Brown ◽  
Kelly Knollman-Porter

Purpose Although guidelines have changed regarding federally mandated concussion practices since their inception, little is known regarding the implementation of such guidelines and the resultant continuum of care for youth athletes participating in recreational or organized sports who incur concussions. Furthermore, data regarding the role of speech-language pathologists in the historic postconcussion care are lacking. Therefore, the purpose of this retrospective study was to investigate the experiences of young adults with history of sports-related concussion as it related to injury reporting and received follow-up care. Method Participants included 13 young adults with history of at least one sports-related concussion across their life span. We implemented a mixed-methods design to collect both quantitative and qualitative information through structured interviews. Participants reported experiencing 42 concussions across the life span—26 subsequent to sports injuries. Results Twenty-three concussions were reported to a parent or medical professional, 14 resulted in a formal diagnosis, and participants received initial medical care for only 10 of the incidents and treatment or services on only two occasions. Participants reported concussions to an athletic trainer least frequently and to parents most frequently. Participants commented that previous experience with concussion reduced the need for seeking treatment or that they were unaware treatments or supports existed postconcussion. Only one concussion incident resulted in the care from a speech-language pathologist. Conclusion The results of the study reported herein shed light on the fidelity of sports-related concussion care management across time. Subsequently, we suggest guidelines related to continuum of care from injury to individualized therapy.


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