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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 73 records · Page 4Linked to original sources
PubMed2001

Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families.

Autistic disorder is a neurodevelopmental disorder with a complex genetic etiology. Observations of maternal duplications affecting chromosome 15q11-q13 in patients with autism and evidence for linkage and linkage disequilibrium to markers in this region in chromosomally normal autism families indicate the existence of a susceptibility locus. We have screened the families of the Collaborative Linkage Study of Autism for several markers spanning a candidate region covering approximately 2 Mb and including the Angelman syndrome gene (UBE3A) and a cluster of gamma-aminobutyric acid (GABA(A)) receptor subunit genes (GABRB3, GABRA5, and GABRG3). We found significant evidence for linkage disequilibrium at marker D15S122, located at the 5' end of UBE3A. This is the first report, to our knowledge, of linkage disequilibrium at UBE3A in autism families. Characterization of null alleles detected at D15S822 in the course of genetic studies of this region showed a small (approximately 5-kb) genomic deletion, which was present at somewhat higher frequencies in autism families than in controls.

Alleles↗
PubMed2001

Environmental causes of human cancers.

Epidemiological studies have clearly shown a causal association between tobacco exposure and various human cancers, hepatitis B and C infection and hepatocellular carcinoma, human papilloma viruses and cervical cancer, and the occupational origin of certain human cancers is well established. The identification of the environmental causes of human cancers has been a long and difficult process. Much remains to be understood about the role of specific components of the diet and the interaction of different risk factors in the aetiology of human cancers. Withstanding the progress made on the understanding of the cancer process and their potential impact in the therapy of cancer, primary prevention remains, in developed and developing countries, the most effective measure to reduce cancer mortality.

Diet↗
PubMed2001

Fear memory retrieval induces CREB phosphorylation and Fos expression within the amygdala.

Fear memory retrieval has been shown to induce a protein-synthesis dependent re-consolidation of memories within the amygdala. Here, using immunocytochemistry, we investigated the molecular basis of this process in the rat and show that retrieval of a cued fear memory induces the activation, by phosphorylation, of the transcription factor CREB within the basal and lateral nuclei of the amygdala, as well as expression of the CREB-regulated immediate-early gene, c-fos, in the basal amygdala. We also show an increase in CREB phosphorylation within the central nucleus of the amygdala following behavioural testing, with an accompanying increase in Fos-immunoreactive nuclei in animals retrieving the cued association. There were no changes in either phosphorylated CREB or Fos in the hippocampus following exposure to discrete fear stimuli. These results show that activation of CREB, which has been shown to be involved in the formation of long-term fear memories, also accompanies memory retrieval, and also suggest a role for CREB phosphorylation in memory re-consolidation following retrieval.

Amygdala↗
PubMed2001

Involvement of the central nucleus of the amygdala and nucleus accumbens core in mediating Pavlovian influences on instrumental behaviour.

Pavlovian conditioned cues exert a powerful influence on instrumental actions directed towards a common reward, this is known as Pavlovian-to-instrumental transfer (PIT). The nucleus accumbens (NAcc) has been hypothesized to function as an interface between limbic cortical structures required for associative conditioning, like the amygdala, and response mechanisms through which instrumental behaviour can be selected and performed. Here we have used selective excitotoxic lesions to investigate the involvement of subnuclei of the amygdala as well as the core and shell regions of the nucleus accumbens on PIT in rats. Within the amygdala, selective lesions of the central nucleus (CeN), but not of the basolateral nucleus (BLA), abolished the PIT effect. In addition, selective lesions of the NAcc core, but not the NAcc shell, also abolished PIT. None of the lesions impaired the acquisition of Pavlovian food cup approaches or instrumental responding itself. These data demonstrate that the CeN and NAcc core are central components of the neural system mediating the impact of Pavlovian cues on instrumental responding. We suggest that this effect may depend upon the regulation of the dopaminergic innervation of the NAcc core by projections from the CeN to the ventral tegmental area.

Amygdala↗
PubMed2001

Bacterial translocation in a non-lethal rat model of peritonitis.

BACKGROUND: Bacterial translocation from the gut may occur under a variety of different clinical circumstances and has been implicated in the development of multiple organ failure. The aim of this study was to determine the distribution of bacterial translocation occurring in a model of chemically induced peritonitis. We also sought to document the degree of the associated immune and inflammatory response. METHODS: Though a midline laparotomy, rats were injected with 5 mg of zymosan (in 0.2 ml of saline) into the subomental space. After 4, 18, 24, 48 and 96 h, a number of endpoints evaluated: intraperitoneal cellular influx, TNF-alpha and interleukin-6 concentrations and myeloperoxidase activity. Bacterial cultures were initiated from the free peritoneal fluid, mesenteric lymph nodes, liver, lung, and kidney. Imprints were also made of the peritoneal mesothelial surface to determine its integrity. RESULTS: When comparing rats injected with zymosan with the controls, there was evidence of a peritoneal inflammatory response within 4 hours. Facultative gram negative bacteria were found to be growing in the mesenteric lymph nodes and in the peritoneal fluid at 48 h. Anaerobic organisms were also cultured from the peritoneal fluid at 48 h. No organisms were cultured from the liver, lung or kidneys. In addition there was a significant increase in intraperitoneal cell numbers (predominantly neutrophils, P < 0.05), myeloperoxidase activity (P < 0.05) and TNF-alpha and IL-6 concentrations (P < 0.05). There was extensive loss of the peritoneal mesothelial cells. The peritoneal inflammatory changes and bacterial translocation had resolved by 96 h. CONCLUSION: Bacterial translocation can be induced by the presence of an acute inflammatory focus in the peritoneal cavity. The translocation and inflammatory changes were associated with extensive loss of mesothelial cells. Nonetheless, these changes all resolved, indicating that the peritoneal cavity has a significant capacity to deal with such insults. A clearer understanding of the cellular and molecular events involved in the resolution phase could lead to improvements in the treatment of peritonitis.

Journal Article↗
PubMed2001

Vital capacity inhalation induction with sevoflurane: an alternative to standard intravenous induction for patients undergoing cardiac surgery.

OBJECTIVE: To determine the respiratory and cardiovascular effects of a high concentration vital capacity induction with sevoflurane compared with an intravenous induction with etomidate in patients scheduled for elective coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized, double-blind, controlled clinical trial. SETTING: Cardiothoracic unit at a university hospital referral center. PARTICIPANTS: Twenty-two patients undergoing elective CABG surgery. INTERVENTIONS: The study group (group S) received a vital capacity gaseous induction with sevoflurane 8% (n = 12) and the control group (group E) were given etomidate, 0.2 to 0.3 mg/kg (n = 10). Anesthesia was supplemented with fentanyl, 8 microg/kg, and vecuronium, 0.1 mg/kg, in both groups. MEASUREMENTS AND MAIN RESULTS: The speed of induction of anesthesia was comparable between the groups. There was a significant increase in minute ventilation after induction of anesthesia in both groups. This increase was associated with a small reduction in PaCO2. There were no clinically significant changes in pH and PaO(2). The incidence of breath-holding and the need for an oropharyngeal airway were similar between the groups. Both groups had similar reductions in mean arterial pressure and cardiac output during the study period; however, a downward trend in mean pulmonary artery pressure was noted in group S, whereas in group E it remained unchanged. Absolute plasma epinephrine and norepinephrine values were low during the precardiopulmonary bypass period in both groups. CONCLUSIONS: The technique of vital capacity inhalation induction with 8% sevoflurane offers a rapid onset of anesthesia, satisfactory airway control, and a good hemodynamic profile. Consideration should be given to the benefits of single-agent anesthesia and lowered pulmonary artery pressure during the precardiopulmonary bypass period. In addition to CABG surgery, this technique could be considered in patients with coronary artery disease undergoing noncardiac surgery, particularly for procedures in which spontaneous ventilation is preferred.

Aged↗
PubMed2001

Specific inhibition of the rat ligand-gated ion channel P2X3 function via methoxyethoxy-modified phosphorothioated antisense oligonucleotides.

P2X3 is one receptor of a family of seven ligand-gated ion channels responding to purines. Increasing evidence indicates its involvement in neuronal signaling and in pain. However, there is currently no selective inhibitor known for this subtype. In order to obtain such a specific inhibitor, a variety of antisense oligonucleotides (ASO) against rat P2X3 was tested, and dose-dependent, sequence-specific downregulation of the rat P2X3 receptor (expressed in a Chinese hamster ovary cell line [CHO-K1]) on the mRNA, protein, and functional levels was observed. Using real-time quantitative PCR, a dose-dependent downregulation of P2X3 mRNA by ASO, as compared with untreated and mismatch controls, was demonstrated. Subsequently, downregulation by the two most potent ASO was confirmed at the protein level by Western blot. Sequence specificity was shown by titration of mismatches to the original selected oligonucleotide, and this correlated with progressive loss of P2X3 inhibition. The functional response of the P2X3 receptor was examined using whole-cell voltage clamping. Upon application of 10 microM of a nonspecific agonist, alpha,beta-methylene-ATP (alphabeta meATP), pretreatment with increasing amounts of the most active ASO 5037 correlated with a decrease in depolarization. The ability to specifically downregulate the P2X3 receptor by ASO treatment will allow investigation of the biologic role of this receptor in neuronal tissues and eventually in in vivo models of chronic pain.

Animals↗
PubMed2001

Sex differences in brain maturation during childhood and adolescence.

Brain development during childhood and adolescence is characterized by both progressive myelination and regressive pruning processes. However, sex differences in brain maturation remain poorly understood. Magnetic resonance imaging was used to examine the relationships between age and sex with cerebral gray and white matter volumes and corpus callosal areas in 118 healthy children and adolescents (61 males and 57 females), aged 6-17 years. Gender groups were similar on measures of age, handedness, socioeconomic status and Full Scale IQ. Significant age-related reductions in cerebral gray and increases in white matter volumes and corpus callosal areas were evident, while intracranial and cerebral volumes did not change significantly. Significant sex by age interactions were seen for cerebral gray and white matter volumes and corpus callosal areas. Specifically, males had more prominent age-related gray matter decreases and white matter volume and corpus callosal area increases compared with females. While these data are from a cross-sectional sample and need to be replicated in a longitudinal study, the findings suggest that there are age-related sex differences in brain maturational processes. The study of age-related sex differences in cerebral pruning and myelination may aid in understanding the mechanism of several developmental neuropsychiatric disorders.

Adolescent↗
PubMed2001

Comparison of resource utilization and outcome between pediatric and adult intensive care unit patients.

OBJECTIVE: To compare resource utilization and outcomes between cohorts of pediatric and adult intensive care unit (ICU) patients from a single institution. DESIGN: Prospective, observational cohort study. SETTING: A large, urban, tertiary care medical center. PATIENTS: A total of 780 patients consecutively admitted to the pediatric ICU, adult medical ICU, and adult surgical ICU. MEASUREMENTS AND MAIN RESULTS: ICU, hospital and 6-month survivals and hospital costs from index ICU admission. Predicted mortality by Pediatric Risk of Mortality III and Acute Physiology and Chronic Health Evaluation II. Health status at 6 months from index ICU admission. Pediatric patients had lower ICU (7.8% vs. 13.7%; p =.01), hospital (10.1% vs. 16.9%; p =.009), and 6-month (16.2% vs. 29.2%; p <.001) mortalities compared with adult patients. Adult patients had significantly lower probability of survival for 6 months from initial ICU admission compared with pediatric patients. The difference in survival was primarily accounted for by adult and pediatric medical patients. No differences could be observed between pediatric and adult ICU patients for mean hospital costs ($33,316 +/- $48,467 vs. $32,877 +/- $46,411; p =.92). Pediatric and adult patients incurred increasing costs with increasing risks of mortality. More than 50% of pediatric patients had a risk of mortality <0.5% compared with 1.2% of adult patients, but there was no difference in the mean use of ICU-specific interventions. CONCLUSIONS: Pediatric critical care patients have better short-term and longer-term survival compared with adult patients. The difference in survival is accounted for by the lower survival of adult medical patients. Despite the survival differences, pediatric and adult ICU patients incur similar hospital costs, and the proportions of patients who receive active ICU interventions are similar.

Journal Article↗
PubMed2001

Variables associated with disparities in treatment of patients with schizophrenia and comorbid mood and anxiety disorders.

OBJECTIVE: The study compared self-reported comorbid affective and anxiety disorder diagnoses and treatments of African-American and Caucasian subjects in a large sample of patients who had a diagnosis of schizophrenia. METHODS: A total of 685 patients receiving treatment for schizophrenia were interviewed as part of the Schizophrenia Patient Outcomes Research Team study. The associations of race with past and current diagnoses and with current treatment for depression, mania, and anxiety disorders were assessed with multivariate analyses. RESULTS: African Americans were significantly less likely than Caucasians to report having a past or current diagnosis of depression, manic-depression, or anxiety disorder and to be receiving current treatment for these disorders. Gender, education, and marital status were also associated with presence of a comorbid diagnosis and receipt of treatment. CONCLUSIONS: The study suggests the possibility of racial and other disparities in the diagnosis and treatment of patients with schizophrenia and comorbid affective and anxiety disorders. Although various causal explanations are plausible, all point toward the need for enhanced cross-cultural competence at all levels of mental health care, especially in the diagnosis and treatment of comorbid psychiatric illnesses.

Adult↗
PubMed2001

The news on health care funding: a study of reporting in the Australian print media for 1996.

OBJECTIVES: To review the coverage of health care funding and resourcing issues in the quality printed media in Australia. METHODS: Content analysis of all articles in six major print publications with detailed commentary on four major issues. RESULTS: One thousand one hundred and fifty articles were published over 12 months, most in the front three pages. Coverage of many issues was prompted by an event, such as an election, government budget or policy announcement. Although issues were rarely personalized, the use of an individual authoritative spokesperson was, with some individuals becoming well recognised as experts. In general, these experts represented vested interest or lobby groups. The media discussion rarely dealt with the system as a whole, and generally approached a topic or issue in isolation from its inter-relationships with other issues. CONCLUSION: Health care funding stories are newsworthy but more for their political interest than as reflection of a social debate about values. Media reports rarely deal with the complexity of health policy issues, or challenge the assumptions and positions put forward.

Australia↗
PubMed2001

In vitro models to study cellular differentiation and function in human prostate cancers.

In Vitro Models to Study Cellular Differentiation and Function in Human Prostate Cancers. To augment the currently available models of human prostate cancer in vitro, we have established extended life-span epithelial cultures from biopsies of well-differentiated prostate cancers. The genetic identity of the target cells was assessed by allelotyping, using microsatellites located on chromosome 8p, and microdissection of tissues and primary cell cultures. Cells with an extended life span (PxE6) were derived by recombinant retrovirus infection to introduce the human papilloma virus E6 gene (epithelial cells). Immunophenotyping of the resultant cell strains confirmed retention of differentiated cell functions, and the genotype of the E6-expressing epithelial cells was stable, while SV40-immortalized cultures were more unstable, leading to tetraploidy. All PxE6 cells eventually senesced, but an immortalized epithelial culture, P4E6, was derived from one of the epithelial cultures. The properties of this cell line, which remains close to diploid, are similar to those of early prostate cancer cells, and it retains expression of many prostate-associated antigens, such as prostate-specific antigen (PSA).

Allelic Imbalance↗
PubMed2001

A simple, rapid method for measuring the percentage of water in alcohols used for dehydrating tissues.

A method is described for determining the concentration of water in alcohols that have been used for dehydrating specimens. The alcohol to be tested is added dropwise to 5.0 ml of xylene, counting the number of drops that causes turbidity, then the number of additional drops required to make the liquid transparent again. The amount of alcohol required to clear the turbidity increases steeply with water content, providing an easy and reliable assay method for water content of 90% to 97% alcohol baths. Alcohol containing 2% or less water does not become turbid when xylene is added.

Alcohols↗
PubMed2001

[What do we know about ATM protein expression in breast tissue?].

The great majority of breast cancer cases are not associated with a mutated gene of high penetrance such as BRCA1, BRCA2 and TP53. Genes of low penetrance, frequently mutated in the general population, might play an important role in breast cancer development. The ATM gene, which encodes the ATM protein, mutated in the disorder ataxia telangiectasia (AT) could be such a susceptibility gene. Indeed, 1% of the general population is estimated to be AT heterozygote and females have an increased risk of developing breast cancer. The ATM protein is involved in the signalling pathway of DNA double-strand breaks. Studies on its expression in normal breast tissues have shown that ATM is expressed in the epithelial cells of breast ducts, but not in the myoepithelial cells. In sclerosing adenosis, a benign lesion of the breast, the ATM protein is expressed in both cell types whereas its expression is absent or reduced in tumour epithelial cells in about 30-50% of invasive carcinomas. Moreover, the study of the p53 status in some of these tumours has revealed that the ATM/p53 signalling pathway is frequently altered either by a very low ATM expression or by the presence of a mutated p53. It remains to be determined whether alterations in the expression of other proteins also involved in this DNA damage signalling cascade are specifically associated with breast cancer development and/or a radiosensitive phenotype seen in some breast cancer patients after radiotherapy.

Ataxia Telangiectasia Mutated Proteins↗