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Biomedical subjects

T Gordon

Publications and source records attributed to T Gordon.

304 records · Page 17Linked to original sources

The cellular and molecular basis of peripheral nerve regeneration.

Functional recovery from peripheral nerve injury and repair depends on a multitude of factors, both intrinsic and extrinsic to neurons. Neuronal survival after axotomy is a prerequisite for regeneration and is facilitated by an array of trophic factors from multiple sources, including neurotrophins, neuropoietic cytokines, insulin-like growth factors (IGFs), and glial-cell-line-derived neurotrophic factors (GDNFs). Axotomized neurons must switch from a transmitting mode to a growth mode and express growth-associated proteins, such as GAP-43, tubulin, and actin, as well as an array of novel neuropeptides and cytokines, all of which have the potential to promote axonal regeneration. Axonal sprouts must reach the distal nerve stump at a time when its growth support is optimal. Schwann cells in the distal stump undergo proliferation and phenotypical changes to prepare the local environment to be favorable for axonal regeneration. Schwann cells play an indispensable role in promoting regeneration by increasing their synthesis of surface cell adhesion molecules (CAMs), such as N-CAM, Ng-CAM/L1, N-cadherin, and L2/HNK-1, by elaborating basement membrane that contains many extracellular matrix proteins, such as laminin, fibronectin, and tenascin, and by producing many neurotrophic factors and their receptors. However, the growth support provided by the distal nerve stump and the capacity of the axotomized neurons to regenerate axons may not be sustained indefinitely. Axonal regenerations may be facilitated by new strategies that enhance the growth potential of neurons and optimize the growth support of the distal nerve stump in combination with prompt nerve repair.

Animals↗

Seasonal mood change and neuroticism: the same construct?

The personality trait of neuroticism has been found to be associated with a polymorphism in the regulatory region of the serotonin (5-HT) transporter gene (5-HTTLPR). This same genetic polymorphism has also been associated with seasonal changes in mood and behavior, or seasonality. The purpose of the current study was to determine whether seasonality and neuroticism are actually the same construct given that they are both associated with the same genetic polymorphism. We administered the Seasonal Pattern Assessment Questionnaire (SPAQ), which measures the severity of seasonality, and the Revised NEO Personality Inventory (NEO-PI-R), which measures the severity of neuroticism, to 45 subjects diagnosed with seasonal affective disorder (SAD). SAD is a clinical expression of seasonality in which patients develop a major depressive disorder in the winter that remits in the summer and can be treated with light therapy. No significant correlation was found between neuroticism and seasonality. We conclude that seasonality and neuroticism are not the same construct, even though the 5-HTTLPR polymorphism is a genetic risk factor for each.

Adult↗

Protein-protein interaction of the Ro-ribonucleoprotein particle using multiple antigenic peptides.

Protein protein interactions play a significant role in maintaining the structural and functional integrity of the cell. We used multiple antigen peptides (MAPs) to analyze such interactions within the Ro (or SSA) ribonucleoprotein complex. Our data showed that 60 kD Ro and La colocalize in the nucleus of the cell. Previous data have indicated that 60 kD Ro and La co-exist via interactions with the hYRNAs. We were interested to see whether 60 kD Ro and La interact with each other through protein protein interactions. MAPs were produced with sequences derived from the autoepitopes of 60 kD Ro. When used in agarose immunodiffusion certain MAPs formed precipitin lines specifically with Ro and La antigens. Used in affinity chromatography the Ro MAPs purified the Ro ribonucleoprotein particle from lymphocyte extract. Solid phase immunoassay and surface plasmon resonance (SPR) confirmed the observations obtained with agarose diffusion. Using SPR, kinetic analyses gave an apparent affinity constant of about 1 x 10(7) M(-1) for Ro-MAP-60 kD Ro interactions. The autoantigens Ro and La are specific targets in autoimmune diseases, particularly systemic lupus erythematosus (SLE) and Sjögren's syndrome, and are known to exist together as a complex with hYRNAs. The present data indicate that there are protein-protein interactions between Ro and La.

Amino Acid Sequence↗

Ozone inhibition of tissue cholinesterase in guinea pigs.

This study sought to determine if ozone at levels known to induce bronchial hyperreactivity in guinea pigs would inhibit tissue cholinesterase activity. Male, Hartley guinea pigs were exposed to filtered air, 0.1 ppm ozone, or 0.8 ppm ozone for 1 hr. Two hours after exposure, brain, lung, and diaphragm tissue samples were frozen for assay of cholinesterase activity. Brain cholinesterase activity was only minimally inhibited in either ozone exposure group. Both levels of ozone significantly inhibited lung cholinesterase activity compared to control animals' activity: a 17% decrease in activity in the 0.1 ppm ozone group (P less than .05) and a 16% decrease in the 0.8 ppm ozone group (P less than .05). Ozone at 0.8 ppm also inhibited activity in the diaphragm by 14% (P less than .02). To determine the degree of involvement of cholinesterase inhibition in bronchial hyperreactivity, parathion pretreated animals were challenged with histamine and the pulmonary function changes monitored. Parathion-treated animals had a peak resistance increase of 330 +/- 104% (mean +/- SE), while the control vehicle animals' increase was 165 +/- 48%. The differences were not statistically significant, but show that cholinesterase inhibition may contribute to ozone-induced bronchial hyperreactivity.

Animals↗

Relation of diet to LDL cholesterol, VLDL cholesterol, and plasma total cholesterol and triglycerides in white adults. The Lipid Research Clinics Prevalence Study.

The association of diet with low density lipoprotein cholesterol (LDL-C) and total triglycerides, as well as with total and very low density lipoprotein cholesterol (VLDL-C), was investigated in a random sample of 4374 white participants aged 20 to 59 years seen by the Lipid Research Clinic Prevalence Study. Carbohydrate and total calories were negatively associated with LDL-C. There was also a statistically significant positive association of LDL-C with the percentage of total calories from fat. These three findings are generally consistent with what other cross-sectional studies have reported for the relation of diet with total cholesterol levels. The only diet variables significantly related to triglyceride levels in both men and women were the percentage of calories from fats, particularly polyunsaturated fatty acids (PFA), the P/S ratio, and the number of grams of PFA per day, all of which were inversely associated with the level of this lipid.

Adult↗

One-month exposure to inhaled endotoxin produces a dose-dependent increase in stored mucosubstances in rat intrapulmonary airways.

This study examined the production of stored mucosubtances in rats after repeated exposure to aerosolized endotoxin, a common contaminant of bioaerosols. Male Fischer 344 rats were exposed to aerosolized saline (sham control) or endotoxin (target concentrations of 0.05, 0.5, and 5.0 micrograms/m3) for 3 h/day, 5 days/week for 4 weeks. Following the final exposure, the left lung of each animal was lavaged and the right lung and nasal cavity were fixed with buffered formalin. Morphometric examination of Alcian blue/Periodic acid Schiffs-stained (AB/PAS) lung sections demonstrated dose-dependent increases in stored intraepithelial mucosubstances in the intrapulmonary airways of endotoxin-exposed rats. Threefold and eightfold increases in stored mucosubstances were observed in generation 5 airways of animals exposed to 0.5 or 5.0 microgram/m3 endotoxin, respectively (p < .05). This mucous cell metaplasia in the intrapulmonary airways was not accompanied by evidence of lung inflammation or increased AB/PAS-staining high molecular weight material in lavage fluid. Furthermore, despite significant deposition of endotoxin aerosols (mass median aerodynamic diameter of 1.9 microns) in the nasal cavity, no significant changes in stored mucosubstances were observed in the nasal septum. In animals repeatedly exposed to 5.0 micrograms/m3 endotoxin and allowed to recover for 1 month, stored mucosubstances in the intrapulmonary airway were still more than fivefold greater than control values. Thus, in rats, repeated exposure to inhaled endotoxin produced a persistent mucous cell metaplasia only in the intrapulmonary airways.

Administration, Inhalation↗

Clinical optimization and multicenter validation of antigen-specific cut-off values on the INNO-LIA ANA update for the detection of autoantibodies in connective tissue disorders.

OBJECTIVES: The INNO-LIA ANA Update is a qualitative multiparameter line immunoassay for detection of autoantibodies to several different antigens associated with connective tissue disorders. We sought to optimize and validate the cut-off values for its antigen-specific components: SmB, SmD, RNP-70k, RNP-A, RNP-C, SSA/Ro52, SSA/Ro60, SSB/La, Cenp-B, Topo-I, Jo-1, ribosomal P, and histones. Our aim was to achieve 98% specificity for each of the markers, with respect to differential disease controls, while maintaining sensitivity. METHODS: For optimization, the cut-off value of the different antigen lines was fixed to achieve this specificity using an in-house set of 955 patient samples. Specificity was validated at multiple sites using a different set of 330 samples obtained from 158 apparently healthy blood donors, 100 patients with a variety of infections, 20 each with Wegener's granulomatosis, inflammatory bowel disease, and primary antiphospholipid syndrome, and 12 with psoriatic arthritis. Sensitivity was evaluated, using this optimized cut-off control, in 147 patients with scleroderma, 93 with Sjögren's disease, 40 with systemic lupus erythematosus, 40 with rheumatoid arthritis, 39 with mixed connective tissue disease, and 19 with polymyositis. Sensitivity and specificity of the INNO-LIA ANA Update were determined using the clinical diagnosis as reference. RESULTS: The optimized cut-off values resulted in a specificity 98% or more for all LIA markers except one (histones 97.8%) in the validation set of 330 samples. The sensitivity for each marker tested in 378 samples from the target patient groups was comparable to that reported in the literature. CONCLUSION: The INNO-LIA ANA Update shows uniformly high specificities combined with sensitivities very similar to those of reference assays, in a single test format.

Antigens↗

[The crisis in psychiatry and the protection of the civil rights of mentally ill patients].

In Poland a basic opinion of the mental health care system is that it considers that mental disorders are illnesses and that an ill person is weaker (worse) and less useful in the social distribution of roles and tasks. Consequently, the ill are excluded from the main-stream of social life: they are deprived of jobs by an easy and early recognition of disability, and the granting of disability pensions, by civil law prohibition of marriage, criminal law ban on sexual contacts etc. A person has little chance for a just life if he/she is deprived of the possibility of working, founding a family, if he/she receives an inadequate pension, remains sexually isolated and on the margin of public life. This medical model of care includes a lot of discriminatory features in the area of human and civil rights of the mentally ill. The discussion concentrated on selected features of the crisis in world psychiatry as well as the practical, ideological, clinical, institutional and organizational difficulties of Polish psychiatry. The main goal of this paper is the raising of psychiatry's awareness of its faults, in order to induce the creation of a new system of mental health care, free of the discriminatory stigmas of the ill and more adequately adapted the ideas of a contemporary democratic state.

Civil Rights↗

Metal fume fever.

Metal fume fever is an acute self-limited illness induced most commonly by inhalation of zinc oxide fumes. The affected individual characteristically experiences the rapid onset of intense shaking chills, fever, and body aches a few hours after exposure, and symptoms dissipate spontaneously. While the occurrence of metal fume fever appears to be widespread and the current TLV/PEL of 5 mg/m3 and STEL of 10 mg/m3 may not be fully protective, no chronic health sequelae have been documented to date. Nonetheless, as any worker who has experienced a full-blown case will likely testify, metal fume fever remains one of the more noxious short-term illnesses contracted in the workplace, and its prevention deserves serious attention.

Fever↗