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Biomedical subjects

C A Hardy

Publications and source records attributed to C A Hardy.

12 recordsLinked to original sources

A clinical, cytogenetic and molecular study of ten probands with supernumerary inv dup (15) marker chromosomes.

Ten probands with moderate to severe developmental delay were found to have a supernumerary inv dup (15) chromosome. These patients and their families were studied by both cytogenetic and molecular methods. Cytogenetic polymorphisms associated with the 15p short arm suggested a maternal derivation for the marker chromosome in all informative cases. One marker was directly maternally inherited. Molecular analysis employing Southern blotting and polymerase chain reaction (PCR) of microsatellite repeats demonstrated the presence of extra alleles in the 15q11q13 region. All ten of the probands demonstrated an extra band at one or more locus without recourse to densitometry. All of the inv dup (15) markers were comparable in size to a G group chromosome but there were differences in the positions of the breakpoints in 15q. There was an inconsistent relationship between marker size, gene dosage and severity of phenotype.

Adolescent

A clinical, cytogenetic, and molecular study of 40 adults with the Prader-Willi syndrome.

A clinical, cytogenetic, and molecular study has been carried out on 40 adults with a firm diagnosis of Prader-Willi syndrome. A cytogenetically detectable deletion was observed in 58% while further subjects had a deletion which was detectable by molecular methods only, giving a total of 76%. Four cases of maternal uniparental disomy (UPD) were all female. Three of them were heterodisomic while the fourth was isodisomic. Two male probands were heterozygous at all loci tested yet did not have UPD. Although methylation studies showed that one of them had a single band using probe PW71, the other one had two bands. Psychiatric studies suggest that females with maternal UPD are indistinguishable psychologically from those with a paternal deletion in 15q11q13.

Adolescent

Sympathetic nervous system modulation of the immune system. II. Induction of lymphocyte proliferation and migration in vivo by chemical sympathectomy.

We have used chemical sympathectomy with 6-hydroxydopamine (6-OHDA) in adult mice to study the role of the sympathetic nervous system (SNS) in regulating cellular proliferation and migration in lymphoid organs. Following sympathectomy, an increase in inguinal and axillary lymph node (LN) weight and cellularity was observed. This increase paralleled increased cellular proliferation in vivo, as measured by uptake of [125I]deoxyuridine (125IUdR). Transient increases in cellular proliferation also were observed in spleen and bone marrow following sympathectomy. Administration of desipramine prior to 6-OHDA to prevent sympathectomy resulted in control levels of proliferation. beta-Adrenoceptor blockade just prior to or following 6-OHDA treatment did not alter the enhanced proliferation. Migration of normal 51Cr-labelled lymphocytes into inguinal and axillary LN was enhanced in sympathectomized recipients. Conversely, cells from sympathectomized animals showed diminished migration to these LN upon transfer into intact recipients. These results demonstrate that depletion of NA innervation alters cellular proliferation and lymphocyte migration in primary and secondary lymphoid organs.

Animals

Family studies in Prader-Willi syndrome.

Clinical, cytogenetic and molecular studies have been undertaken in the families of 52 probands with Prader-Willi syndrome. The maternal age at the birth of a proband with a deletion in 15p11q13 was on average 8 years less than that of the mothers of probands with uniparental disomy (UPD), the paternal age was on average 7 years less. Seven probands with UPD were all female, as were 7 patients who had neither a detectable chromosomal abnormality nor UPD. Cytogenetic and molecular polymorphisms in proximal chromosome 15 indicated that for probands with a 15q11q13 deletion, inheritance of both the maternal and the intact paternal homologue is random in their unaffected sublings. Pigmentation studies suggest that probands who have a deletion in 15q11q13 have lighter colouring than other family members implying that D15S12 may not be imprinted.

Adult

Altered T-lymphocyte response following aggressive encounters in mice.

Intermale aggression is a natural form of psychosocial stress that can alter a variety of physiological functions, including immune function. In Experiment 1, daily fighting between pairs of previously isolated male mice differentially altered immunological measures of T-cell responsiveness in dominant and submissive animals. Submissive mice had lower T-cell proliferation and IL-2 production, when compared to dominant, nonfought, or witness mice. Since the fighting behavior often results in wounding of the submissive animal, Experiment 2 used a relatively nonaggressive test to determine whether the immunological differences between dominant and submissive mice were due to wounding or due to the psychosocial state of dominance. Dominant mice had elevated T-cell proliferation and IL-2 production when compared to the other treatment groups. Therefore, it appears that in dominant/submissive pairs of mice a severe physical stress, such as intense fighting, influences the immune system in a different manner than psychological or mild aggressive encounters.

Aggression

Age- and sex-related induction of excessive grooming and "wet-dog" shakes by the codeinone RX 336-M in the rat.

Peripheral administration of the dihydrocodeinone RX 336-M (6 mg/kg) stimulated vigorous "wet-dog" shakes and excessive grooming in young drug-naive rats. The effects of RX 336-M were greater in younger than in older animals of both sexes, and were greater in 39-day-old male rats than in female rats of the same age. In a second experiment, female rats were pretreated with testosterone benzoate (1 mg/kg/day) for 1 week prior to testing the effects of RX 336-M at 39 days of age. The sex hormone pretreatment enhanced the ability to RX 336-M to induce "wet-dog" shakes and excessive grooming in female rats. The results suggest that both sex- and hormone-dependent developmental status are critical in the display of the so-called "quasi-morphine withdrawal syndrome." The results imply, and are consistent with previous studies which suggest, that different neural mechanisms underlie the behavioral responses induced by ACTH and RX 336-M.

Age Factors

The progression of behavioral and pathological effects of the parasite Toxocara canis in the mouse.

Toxocara canis, the parasitic roundworm of the dog may infect aberrant hosts including mice and humans. The present study examined the behavioral and pathological changes at each of three postintubation periods (Period 1: 8-10 days, 2: 49-51 days, and 3: 84-86 days postintubation, respectively) in independent groups of mice intubated with 1000 eggs of T. canis. Eight-ten days after intubation Toxocara infected animals typically showed depressed levels of activity relative to saline-intubated controls. The scope and severity of behavioral changes were attenuated when different mice were tested 49-51 days after infection, and then became more severe when the third set of animals was tested 84-86 days after intubation. While brain pathology increased over the three periods, visceral organs showed marked pathology 8-10 days after intubation followed by a decrease in severity. These data suggest that Toxocara associated pathological changes in visceral organs and in the brain have behavioral consequences in mice. Given the similarity in migratory pathways of this parasite in rodents and humans, and the findings of T. canis larvae in human brain tissue, the results of this animal study may have implications concerning the possible etiology of behavioral disorders for children who have a known history of pica for dirt.

Animals

The effects of dietary fat and lead ingestion on blood lead levels in mice.

To examine the effects of dietary fat on the levels of lead in the blood, 34-40-d-old male mice were fed normal or high-fat diets along with distilled water for an initial 48-h exposure period. Following this session, subjects from each diet condition were administered either 0, 0.075, or 0.5% lead acetate through the drinking water during the next 48 h along with their respective diets. Atomic absorption was used to analyze blood-lead levels. At each concentration of lead, the high-fat diet increased the blood lead content over subjects fed the control diet. The highest blood lead levels were found in the 0.5% lead acetate, high-fat diet condition. The importance of nutritional considerations in understanding lead toxicity is discussed.

Animals

Performance evaluation: continuous lumbar epidural anesthesia skill test.

The evaluation of skills in anesthesiology residents is usually subjective and lacks demonstrable reliability. Therefore, an objective criterion-referenced skill test for measuring performance of continuous lumbar epidural anesthesia was developed. For such a test to be useful, it is necessary to demonstrate agreement among rater-observers. Eight performances of continuous lumbar epidural anesthesia were recorded on video tape and simultaneously rated by nine anesthesiology faculty observers to determine inter-rater reliability. Inter-rater agreement was analyzed by determining coefficient kappa for each item and the entire test. Coefficient kappa for the entire test was 0.82 indicating a high degree of agreement between raters on the performance or nonperformance of various items. Development and utility of skill tests are discussed.

Anesthesia, Epidural