Although hyponatremia (HN) has been reported among endurance athletes, its etiology often remains uncertain and of great interest to clinicians and physiologists. This case report presents physiologic evidence regarding the etiology and development of HN during exercise in the heat. A 21-yr-old male volunteer (K.G.) unexpectedly experienced symptomatic HN during a research investigation that involved controlled sodium (Na+) intake (137 mEq Na+.d-1 for 7d) and exercise-heat acclimation (41 degrees C; 30 min.h-1, 8 h.d-1 for 10 d). Fluid balance, physiologic variables, and hematologic/hormone data were measured before and after the HN episode, with similar measurements recorded for nine unaffected volunteers. The results indicated: 1) HN was verified in K.G. (plasma Na+ < 130 mEq.l-1) after only 4 h of mild, intermittent exercise in heat; 2) K.G.'s heart rate, rectal temperature, blood pressure, and Na+ losses in sweat and urine were < or = control subjects at all times; 3) between hours 4-7, an inappropriately large release of vasopressin coincided with a decrease of urine volume to 0 ml.h-1. It was concluded that a large intake (10.3 l.7h-1) and retention (2.77 l.7h-1) of water and a "low normal" initial plasma Na+ (134 mEq.l-1) were primary factors in the development of HN in K.G., whereas Na+ losses in sweat and urine were normal and served only to exacerbate HN.

Adult↗

PubMed1992

Identification of the proximate peroxisome proliferator(s) derived from di (2-ethylhexyl) adipate and species differences in response.

Identification of the proximate peroxisome proliferator(s) derived from di (2-ethylhexyl) adipate (DEHA) has been achieved using primary hepatocyte cultures derived from different species and cyanide-insensitive fatty acyl CoA oxidase (PCO) as a marker enzyme for peroxisome proliferation. In rat and mouse hepatocytes, the parent compound (DEHA) had no effect on peroxisomal beta-oxidation, but primary metabolites of DEHA, mono (2-ethylhexyl) adipate (MEHA) and 2-ethylhexanol (EH), were approximately equipotent in PCO induction (5-fold at 0.5 mM final concentration). The secondary metabolite of DEHA, 2-ethylhexanoic acid (EHA), was in both species the most potent peroxisome proliferator (25- and 9-fold induction in mice and rats, respectively, at 1 mM final concentration). At 2 mM final concentration a tertiary metabolite of DEHA, 2-ethyl-5-hydroxyhexan-1-oic acid, was less effective in mouse and rat hepatocytes at inducing PCO (15- and 5-fold, respectively). 2-Ethyl-5-oxohexan-1-oic acid and 2-ethylhexan-1,6-dioic acid had little effect (2-3-fold in both rat and mouse hepatocytes). Thus, EHA was identified as the proximate peroxisome proliferator of DEHA and mouse hepatocytes were approximately twice as sensitive as rat hepatocytes to peroxisome proliferation due to MEHA, EH and EHA. We investigated further species differences in response to peroxisome proliferators by using guinea pig and marmoset primary hepatocyte culture. None of the chemicals studied stimulated peroxisomal beta-oxidation in these species up to a final concentration of 2 mM. Higher concentrations lead to cytotoxicity. This lack of sensitivity of guinea pig and marmoset hepatocytes is in agreement with previous studies with di (2-ethylhexyl) phthalate metabolites, suggesting the absence of a threat of hepatocarcinogenic damage to these species and confirming that primary hepatocytes cultures are useful models for investigating the phenomenon of peroxisome proliferation.

Adipates↗

PubMed1992

Pulmonary-renal syndrome in association with anti-GBM and IgM ANCA.

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Adult↗

PubMed1992

Choice between inactivated and oral poliovirus vaccines in India.

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Cost-Benefit Analysis↗

PubMed1992

Expression of NCAM isoforms during skeletal myogenesis in the mouse embryo.

We have examined the developmental patterns of neural cell adhesion molecule (NCAM) gene expression in embryonic mouse skeletal muscle cells by in situ hybridization. Moreover, by utilising exon-specific cRNA probes, we have examined tissue specific splicing of the NCAM gene. We show that there is a distinct sequence of NCAM isoform expression during skeletal muscle development. Since NCAMs are also expressed in other cell types, particularly neurons, NCAM mRNAs have been colocalised with acetylcholine receptor alpha (AChR alpha) gene transcripts to identify muscle-specific expression. NCAM is first detected in somites as they first form, prior to their differentiation into muscle and nonmuscle compartments. Myotomes, the first skeletal muscle masses to form in the embryo, express mRNAs for the transmembrane 180 and 140 kDa isoforms of NCAM. Both of these transcripts are also detected in the neural tube, and their spatial pattern of expression changes with development. Transcripts containing the muscle-specific domain (MSD) of the NCAM gene are not detected prior to 11 days postcoitum (p.c.), at a time when rostral somites already contain well-developed myotomes. As the level of MSD mRNAs increases at 12 days p.c., the 140 and 180 kDa transcript levels decrease in skeletal muscle masses. The level of all NCAM isoform transcripts declines between 13 and 15 days p.c. in muscle. However, the 180 and 140 kDa NCAM isoforms are expressed at a high level in neural tissue and in other locations in the developing embryo such as in smooth muscle, around vibrissae follicles, and in the perichondrial zone of digits.

Animals↗

PubMed1992

The distribution of clones of neurons in the rat somatosensory cortex.

We have labelled clones of neurons in the cerebral cortex of rats by introducing a retroviral vector, called BAG, into the cerebral vesicles of embryos in utero. BAG encodes the enzyme beta-galactosidase, which acts as a histochemical marker for the subsequent identification of clones derived from infected precursor cells. We have studied the distribution of neuronal clones in the rat somatosensory cortex, and have asked whether clonally-related neurons were dispersed randomly. We have discovered that they are not. Rather, clones disperse predominantly such that the earliest progeny of ventricular zone cell are found posterolateral to later generated cells. This distribution fits with what would be expected were neurons dispersed passively in accordance with the lateral to medial cortical neurogenic gradient.

Aging↗

PubMed1992

The phenylpropionic acid load test: experience with 72 children at-risk for beta-oxidation disorders.

The urinary excretion of metabolites of orally administered phenylpropionic acid (PPA) in 72 children, aged 2 days to 16 years, thought to be at-risk of medium acyl CoA dehydrogenase deficiency has been studied. Forty had presented as Reye Syndrome, 9 as a Reye-like syndrome and 24 were sibs of decreased RS, sibs of RLS cases or sibs of infants who had died suddenly and without explanation where an autopsy revealed the presence of very heavy fatty infiltration of the liver. These studies demonstrated that PPA metabolites are maximally excreted during the 3 hours following the oral load and that this urine collection should be diagnostic. PPA loading is a relatively simple, safe test which is part of the investigation of a patient suspected of having an inborn error of metabolism.

Acyl-CoA Dehydrogenase↗

PubMed1992

Collagens facilitate epithelial migration in restitution of native guinea pig intestinal epithelium.

An in vitro intestinal epithelial wound/repair model in which epithelium is stripped from villus tips and the wound is resealed during the following 60 minutes has previously been described. The process, termed epithelial restitution, results in part from the rapid migration of epithelial cells shouldering the wound over the denuded basement membrane. The present report examines the requirements for epithelial cell-basement membrane interactions during restitution in this model. Addition of heparin, soluble matrix components, or a variety of antibodies to matrix components (laminin; fibronectin; collagen I, III, IV) does not impair restitution. Although inhibition of protein synthesis alone also does not retard restitution, in the simultaneous presence of antibody to type III and IV collagen restitution is impeded as judged functionally and structurally. Preincubation of tissues with 20 mmol/L cis-OH-proline (a condition known to inhibit cellular secretion of newly synthesized collagen) similarly inhibited structurally and functionally defined restitution only if antibodies to type III and IV collagen were simultaneously present. These results suggest that collagen-epithelial cell interactions are important in restitution after injury, and if necessary, collagen can be produced locally and rapidly at the site of injury to allow restitution to normally proceed.

Animals↗

PubMed1992

Molecular biology of African trypanosomes: development of new strategies to combat an old disease.

African trypanosomes are protozoan parasites that cause a number of diseases of man and domesticated animals in large regions of sub-Saharan Africa. The diseases have proven to be particularly difficult to prevent or to effectively treat due to features of both the trypanosome and the insect vector, the tsetse fly. The habitat of the tsetse and its resistance to insecticides have rendered vector control efforts ineffective. Attempts to develop a vaccine against the African trypanosomes has been dwarfed by the parasite's ability to change the composition of its exposed surface antigens. This process of antigenic variation allows the parasite to avoid the host's immune response and presents the host with a seemingly endless antigenic repertoire. Since conventional approaches to the control of African trypanosomiasis have largely met with failure, there has been a renewed interest in identifying novel aspects of the biology, biochemistry, and molecular biology of trypanosomes that might be exploited to develop new targets for vaccines or chemotherapy. Importantly, this research has opened a virtual Pandora's box of exciting biochemical and molecular surprises, which makes the African trypanosomes not only important medical pathogens but also an exciting experimental system for the basic scientist. In this review, the authors will describe some of the most recent and intriguing developments in the field of molecular parasitology.

Animals↗

PubMed1992

A cadaveric study comparing discography, magnetic resonance imaging, histology, and mechanical behavior of the human lumbar disc.

The aims of this study were 1) to compare discography and magnetic resonance imaging scanning on cadaver specimens and to correlate these imaging procedures by examining all the discs histologically; and 2) to study the extent to which the amplitude of rotational movement in the neutral and flexed position at a certain level correlates with the morphologic appearance of that disc. Twenty-four human lumbar spines were harvested from cadavers between the ages of 19 and 75 years. Each specimen underwent standard radiography, magnetic resonance imaging scanning, discography, histologic examination, and measurement of axial rotation in a torsion apparatus. For practical reasons, all specimens did not undergo all of the examinations. Not all peripheral anular lesions were detected by discography. Histology showed rim lesions of the anterior anulus in 18% of discs with normal discography. The overall incidence of anterior and posterior anular tears was greater in discs where larger amplitudes of rotation were observed. To which extent the one is a consequence of the other or vice versa is not clear. Magnetic resonance imaging was found to be less specific than discography. However, it must be emphasized that no axial magnetic resonance imaging scans were taken in this study. Discs with significantly decreased amounts of nuclear material (observed at histology) can still produce normal magnetic resonance imaging images. Infolding of the inner layers of the anulus fibrosus (33% anterior, 4% posterior) was a frequently observed feature.

Adult↗

PubMed1992

Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs.

We studied 135 lumbar discs from 27 spines removed post-mortem from subjects of an average age of 31.5 years. Defects of the annulus fibrosus were classified as peripheral, circumferential or radiating; the nucleus pulposus as normal, moderately or severely degenerate. Peripheral tears were more frequent in the anterior annulus, except in the L5-S1 disc. Circumferential tears were equally distributed between the anterior and the posterior annulus. Almost all the radiating tears were in the posterior annulus, and closely related to the presence of severe nuclear degeneration. Histology suggested that peripheral tears were due to trauma rather than biochemical degradation, and that they developed independently of nuclear degeneration. The association of peripheral annular lesions with low back pain is uncertain but our study suggests that they may have a role in the pathogenesis of discogenic pain.

Adolescent↗