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H C Jones

Publications and source records attributed to H C Jones.

At least 19 recordsLinked to original sources
PubMed2004

Reduced subcommissural organ glycoprotein immunoreactivity precedes aqueduct closure and ventricular dilatation in H-Tx rat hydrocephalus.

The H-Tx rat has fetal-onset hydrocephalus associated with closure of the cerebral aqueduct and a reduction in the secretory cells of the subcommissural organ (SCO), a circumventricular organ situated in the dorsal wall of the cerebral aqueduct. The objective of this study was to determine the role of the SCO in hydrocephalus pathogenesis. Serial brain sections through aqueduct regions containing the SCO from H-Tx rats, together with non-hydrocephalic Fischer F344 rats, were studied at E16, before hydrocephalus onset, at E17, the beginning of onset, and at P0 when the hydrocephalus was overt. Tissues were immunostained by AFRU, an antibody against the SCO glycoprotein, and for the intermediate filament nestin. The area of SCO cells with AFRU immunostaining and the severity of lateral ventricle dilatation were quantified by image analysis. At E16 all fetuses had distinct SCO ependymal cells, open aqueducts and normal lateral ventricles. The H-Tx fetuses fell into two groups with large areas and small areas of AFRU immunoreactivity, all with a full complement of SCO cells. By E17, fetuses with small areas of immunoreactivity had reduced numbers of tall SCO secretory cells, and most had aqueducts closed posteriorly and dilated ventricles. Three additional fetuses with small areas of immunoreactivity had narrow but patent aqueducts and normal ventricles, and another had an open aqueduct and dilated ventricles. At P0, pups previously identified as hydrocephalic had small areas of AFRU immunoreactivity, an aqueduct that was closed anteriorly but open posteriorly, ventricular dilatation, and an absence of SCO secretory cells. The aqueduct even when closed was lined by typical ependymal cells throughout. Decreased nestin immunostaining accompanied the SCO changes. It is concluded that reduced SCO glycoprotein immunoreactivity precedes both aqueduct closure and expansion of the lateral ventricles in the H-Tx rat.

Animals↗
PubMed2001

Genome-wide linkage analysis of inherited hydrocephalus in the H-Tx rat.

Inherited hydrocephalus in humans has received very little attention, most probably because known occurrences are sporadic and systematic investigation is difficult. The H-Tx rat, one of a number of rodent strains with inherited hydrocephalus, has a complex inheritance with more than one postulated susceptibility gene and 40% penetrance. The aim of this study was to perform a genome-wide scan on backcross progeny derived from H-Tx and Fisher F344 rats, to identify genomic regions associated with hydrocephalus. Penetrance of hydrocephalus in (H-Tx x F344) F1 x H-Tx was 12.3%. All severely hydrocephalic progeny (n = 185) and a subset of normal progeny (n = 128) were screened with 110 simple sequence length polymorphisms (SSLPs) with 83% coverage of the genome. A significant susceptibility locus was found on chromosome (Chr) 11 (LOD = 3.1). Three loci with suggestive linkage were found on Chr 17 (LOD = 2.4), on Chr 9 (LOD = 1.94), and on Chr 19 (LOD = 1.91). For the loci on Chr 11 and 19, hydrocephalus was associated with the heterozygous genotype, while the other two were recessive. Although none of the four loci was essential for the hydrocephalic phenotype, the additive effects of two, three, or four loci increased the penetrance in a linear fashion. Altogether these four loci accounted for 13.5% of the total variance. It is concluded that hydrocephalus in the H-Tx rat is associated with two, possibly four genetic loci, but that there may be additional undefined genetic and environmental influences.

Animals↗
PubMed2001

Chromosomal linkage associated with disease severity in the hydrocephalic H-Tx rat.

Infantile hydrocephalus results in neurological deficits despite surgical treatment. Fetal-onset hydrocephalus in humans can be caused by developmental abnormalities that are genetic in origin. The H-Tx rat has hydrocephalus with 40% penetrance and a polygenic inheritance. A backcross with Fisher F344 inbred strain produced a total of 1500 progeny with 17.5% hydrocephalus. Of these, only 12.3% had overt disease and the remaining 5.2% had mild disease seen only after fixation of the brain. Disease severity was measured for all affected rats using the ratio of ventricle to brain width. The severity measure confirmed that there are two populations, mild hydrocephalus (M; ratio, <0.4) and severe hydrocephalus (S; ratio, >0.4), with a small overlap. For genotyping, the two populations were each subdivided based on the ratio measure to give a total of four groups of increasing severity. After an initial genome scan with microsatellite markers, all hydrocephalic rats and a subset of 128 normal progeny were genotyped on chromosomes 4, 9, 10, 11, 17 and 19. Rats in the mildest group had association with a locus on chromosome 4 (LOD 2.4), whereas those in the severest group were associated with a locus on chromosome 17 (LOD 3.2). All except the least affected group were associated with a heterozygous genotype on chromosomes 10 and 11 (LOD 4.5 and 3.5, respectively). Chromosomes 9 and 19 had weak linkage to hydrocephalus. The number of hydrocephalus-associated loci carried by each rat correlated with the severity of disease. It is concluded that the severity of hydrocephalus in H-Tx is influenced by different genetic loci.

Animals↗
PubMed2000

The expression of inherited hydrocephalus in H-Tx rats.

OBJECTIVES: H-Tx rats develop severe hydrocephalus in late gestation. The breeding colony maintained at the University of Florida stems from one pair obtained in 1992. The aims of this study were to characterize the expression of hydrocephalus in the H-Tx rat colony, to perform within-strain and between-strain DNA analysis and to examine hydrocephalus expression in specific breeding experiments. METHODS AND OBSERVATIONS: Matings between normal rats produce hydrocephalic offspring almost without exception, and the overall frequency is stable between generations at 40%. However, frequency varies with parity, being only 27% in the first litters, and it also varies with sex, there being an excess of male hydrocephalics. Mating between shunt-treated hydrocephalic rats did not increase the frequency. DNA typing with microsatellite markers showed that there was some residual heterogeneity in the colony despite inbreeding for 22 generations, although it did not segregate with hydrocephalus. Test mating with two other inbred strains, F344 and LEW produced some affected pups in the LEW cross only. A backcross experiment between H-Tx and F344 produced 12.3% severely-affected pups and 5.4% pups with a mild form, indicating the presence of several susceptibility genes. CONCLUSIONS: All animals in our H-Tx colony are homozygous for the hydrocephalus loci, but there is incomplete penetrance.

Animals↗
PubMed2000

Progressive tissue injury in infantile hydrocephalus and prevention/reversal with shunt treatment.

Infantile hydrocephalus, despite shunt treatment, can leave children with a variety of persistent neurological deficits. A rat strain (H-Tx) with inherited fetal-onset hydrocephalus, is a natural model for the study of progressive tissue changes resulting from hydrocephalus and the effects of shunt placement. The cerebral cortex of rat pups has been studied at post-natal day 4 (P4), early stage hydrocephalus and equivalent to a third trimester human fetus, at P11, intermediate stage hydrocephalus and equivalent to a newborn human infant, and at P21 at advanced stage hydrocephalus. At P4, there is interstitial edema (increased water, sodium and chloride) and a non-reversible change in membrane lipids, particularly the phosphomonoesters. By P11, there are additional, non-reversible, changes in intracellular potassium and energy metabolites (ATP and phosphocreatine). At P21, the cells are severely damaged and further intracellular changes include a decrease in N-acetylaspartate (NAA) and loss of amino acids and many organic osmolytes. The interstitial edema is approximately 75% reversed after shunt treatment. The loss of energy metabolites, NAA and osmolytes can be prevented by early shunt treatment at P4, but the subsequent potassium loss is not prevented. Shunt at P11 does not prevent loss of NAA or aspartate, but osmolytes are normalized. It is concluded that persistent tissue damage is initiated by changes in cell membrane components leading to a decrease in energy metabolism and loss of cell homeostasis. A more complete understanding of the mechanisms involved could lead to new approaches for therapy.

Aging↗
PubMed1999

Decreased c-fos expression in experimental neonatal hydrocephalus: evidence for reduced neuronal activation.

Although neonatal hydrocephalus often results in residual neurological impairments, little is known about the cellular mechanisms responsible for these deficits. The immediate early gene, fos (c-fos), functions as a "third messenger" to regulate protein synthesis and is a good marker for neuronal activation. To identify functional changes in neurons at the cellular level, the authors quantified fos RNA expression and localized fos protein in the H-Tx rat model of congenital hydrocephalus. Tissue samples from sensorimotor and auditory regions were obtained from hydrocephalic rats and age-matched, normal litter mates at 1, 6, 12, and 21 days of age (four-six animals in each group) and processed for immunohistochemical analysis of fos and Northern blot analysis of RNA. At 12 days of age, hydrocephalic animals exhibited significant decreases in the ratio of fos immunoreactive cells to Nissl-stained neurons from both cortical regions, but no statistical differences were noted in fos expression. At 21 days of age, both the ratio of fos immunoreactive cells to Nissl-stained neurons and fos expression decreased significantly. The number of fos-positive neurons decreased in all cortical layers but was most prominent in layers V through VI. This decrease did not appear to be caused by neuronal death because examination of Nissl-stained sections revealed many viable neurons within the areas where fos immunoreactivity was absent. These results suggest that progressive neonatal hydrocephalus reduces the capacity for neuronal activation in the cerebral cortex, primarily in those neurons that provide corticofugal projections, and that this impairment may begin during relatively early stages of ventriculomegaly.

Journal Article↗
PubMed1999

Evidence that oxidative stress is associated with the pathophysiology of inherited hydrocephalus in the H-Tx rat model.

Oxidative stress can contribute to many neurological disease processes. Because many events known to involve oxidative stress (infection, hemorrhage, brain trauma) are accompanied by hydrocephalus, the present study sought to evaluate the relationship between oxidative stress and the progression of hydrocephalus. Assays for reactive oxygen species (ROS), using dichlorofluorescein (DCF) fluorescence, and lipid peroxidation, using malondialdehyde (MDA), were performed on brain tissue from the cerebral cortex, cerebellum, basal ganglia, and hippocampus of 4-, 10-, and 25-day-old normal and hydrocephalic H-Tx rats. These rats inherit hydrocephalus at a rate of 30-50% and represent a unique model for studying the progression of hydrocephalus. When hydrocephalic and normal H-Tx rats were compared, ROS levels were significantly higher in the cerebral cortex of 4-day-old and in the cerebellum and hippocampus of 4- and 10-day-old hydrocephalic rats. ROS levels also were significantly higher in the basal ganglia of 25-day-old hydrocephalic rats. MDA levels were significantly higher in the hippocampus and basal ganglia of 25-day-old hydrocephalic rats. There were no significant differences in MDA levels at younger ages. These results indicate that, in H-Tx rats, oxidative stress is associated with the progression and molecular pathophysiology of hydrocephalus. This association suggests that oxidative brain damage may represent an important factor resulting from or contributing to the pathogenesis of hydrocephalus.

Animals↗
PubMed1999

Shorter dosing interval of opiate solution shortens hospital stay for methadone babies.

BACKGROUND AND OBJECTIVES: Methadone maintenance is the standard of care for pregnant opiate addicts. However, withdrawal of an infant from methadone after birth often results in a lengthy hospital stay. This study identified potentially modifiable factors that are associated with the length of hospital stay of infants of mothers on methadone. METHODS: This study used a retrospective case series of patients from a university hospital in Texas. Eligible participants included 41 neonates born between January 1991 and December 1996 to mothers taking methadone at time of delivery. Charts were reviewed for factors relating to administration of opiates to the newborn, and the length of the hospital stay was recorded for each infant. Bivariate and multiple regression analyses were performed using length of hospital stay as the outcome measure. RESULTS: Higher peak dose of tincture of opiate solution (TOS) and longer dosing interval were found to be related to longer length of hospital stay. These variables explained 23% of the variation in length of stay. CONCLUSIONS: Lower peak doses of TOS and shorter dosing intervals may be associated with shorter hospital stays for infants with neonatal abstinence syndrome secondary to maternal methadone treatment.

Drug Administration Schedule↗
PubMed1998

Progressive changes in cortical water and electrolyte content at three stages of rat infantile hydrocephalus and the effect of shunt treatment.

Infantile hydrocephalus causes injury to the developing brain and despite surgical treatment, neurological deficits persist. The H-Tx rat develops inherited hydrocephalus in late gestation. Rapid postnatal ventricular enlargement, results in severe hydrocephalus by 21 days after birth. This is accompanied by changes in cortical morphology and metabolite content that indicate possible changes in intracellular composition. This study has tested the hypothesis that tissue water and electrolyte content is altered in hydrocephalus. The objective was to gain further insight into the mechanisms leading to neuronal damage. Water and electrolyte content (Na+, Cl-, and K+) were measured in the cerebral cortex of control and hydrocephalic rats at 4, 11, and 21 days after birth, and at 21 days in rats that received alleviating shunt surgery at 4 or 11 days. At all ages, hydrocephalic tissue was significantly increased over control for cortical water, Na+, and Cl- content. Additionally, at the intermediate (11-day) and advanced (21-day) stages there were significant decreases in K+ content, consistent with previous observations of decreases in organic osmolytes and energy metabolites. This suggests that by 11 days there are intracellular changes, probably through impaired membrane homeostatic mechanisms. In shunt-treated rats, the extracellular constituents were almost normal, although a small increase over control values persisted. The decrease in intracellular K+ was not corrected in either group of shunt-treated rats. It is concluded that early hydrocephalus is characterized by extracellular edema that largely reverses with shunt treatment. Subsequently, as the hydrocephalus progresses, there is a breakdown of cell homeostasis and an irreversible loss of intracellular constituents.

Animals↗
PubMed1998

The relation between CSF pressure and ventricular dilatation in hydrocephalic HTx rats.

The relation between increased cerebrospinal fluid (CSF) pressure and ventricular enlargement in infantile hydrocephalus is uncertain, variable, and probably dependent on the etiology of the condition. The HTx rat has early-onset hydrocephalus due to aqueduct stenosis in late gestation with ventricular dilatation present in fetuses. Increased CSF pressure, however, is first detected at postnatal day 10 or later. How the transition from low pressure to raised pressure hydrocephalus takes place, is not clear. In order to study this, we investigated how CSF pressure is related to the magnitude of ventricular dilatation using hydrocephalic and control HTx rats at postnatal days 15 and 21. At 15 days, the CSF pressure for hydrocephalics was 31.1 +/- 3.6 mm H2O (mean +/- SEM) which was not significantly higher than the controls at 19.9 +/- 2.8 mm H2O. At 21 days, the pressure was significantly higher in hydrocephalics at 50.9 +/- 7.5 mm H2O compared to 24.3 +/- 3.6 mm H2O for controls, p < 0.05. The mean volume of the lateral ventricles was 409.3 mm3 at day 15 and 478.8 mm3 at day 21, whereas age-matched control rats in a previous study had ventricles of 14 and 25 mm3. At each age there was a significant linear relationship between CSF pressure and ventricle volume, p < 0.05 at day 15 and p < 0.01 at day 21. Closer examination of the data, however, showed that 5/10 hydrocephalics at day 15 and 4/10 at day 21 had CSF pressures that were within the 95% confidence limits of the mean pressures for the control groups. The ventricle volumes of these low pressure hydrocephalics were between 100 and 280 mm3 which was several times larger than the ventricles in control rats. CSF pressure in the remaining 15 day rats ranged from 30 to 53 mm H2O and in the 21 day rats from 46 to 90 mm H2O and the ventricles were between 280 and 1050 mm3. The results suggest that up to a critical volume the infant rat brain can accommodate additional CSF without an increase in pressure. At this volume there is a "break point" beyond which additional fluid results in further expansion along with an increase in CSF pressure.

Animals↗