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Biomedical subjects

C Hart

Publications and source records attributed to C Hart.

At least 37 records · Page 2Linked to original sources
PubMed1995

Catecholaminergic inhibition by hypercortisolemia in the paraventricular nucleus of conscious rats.

Administration of glucocorticoids decreases the release of corticotropin-releasing hormone and in vitro turnover of norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, and immobilization (IMMO) markedly increases NE release and stimulates corticotropin-releasing hormone neurons in the PVN. This study assessed whether hypercortisolemia affects in vivo indexes of catecholaminergic activation in the PVN. Microdialysis was used to simultaneously measure PVN microdialysate concentrations of NE, the neuronal NE metabolite dihydroxyphenylglycol, the extraneuronal NE metabolite methoxyhydroxyphenylglycol, and the dopamine metabolite dihydroxyphenylacetic acid before, during, and after 2 h of IMMO. Catecholamine synthesis was examined based on elevations of 3,4-dihydroxyphenylalanine levels after local perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. Cortisol (CORT; 25 mg/kg.day) or vehicle (VEH; saline) was infused sc for 7 days via an osmotic minipump. CORT-treated rats had lower basal NE, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid levels and significantly smaller levels of all these compounds during IMMO than VEH-treated rats. CORT-treated rats also had less NSD-1015-induced accumulation of microdialysate 3,4-dihydroxyphenylalanine at baseline and during IMMO than VEH-treated rats. Basal and IMMO-induced plasma ACTH and corticosterone responses were reduced in CORT-treated rats. The results indicate that chronic hypercortisolemia decreases basal levels and stress-induced increments in indexes of release, metabolism, turnover, and synthesis of catecholamines in the PVN and suggest that glucocorticoids restrain the limit of hypothalamo-pituitary-adrenocortical axis activation during stress by attenuating catecholamine synthesis and release in the PVN.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Epidemiology of spinal cord injuries: a reflection of changes in South African society.

The records of all patients (492 males and 124 females) admitted into a spinal rehabilitation programme over a period of 6 years were reviewed. Most of the patients were in the age group 20-29 years and trauma accounted for 89% of all spinal cord lesions. Gunshot injuries were the commonest (36%), followed by injuries related to motor vehicle accidents (MVA) (25%), stab wounds (20%) and falls from heights (2.4%). Aetiological patterns changed over the 6 year period covered: gunshot injuries increased markedly and stab wounds decreased in number. The records of a medico-legal laboratory in the same geographic region revealed the same trend. Neurological recovery rates were better in patients with stab wounds and nontraumatic lesions than in those with MVA-related injuries and gunshot wounds. When compared to similar studies from other countries, our results show a disproportionately high incidence of violent injuries, particularly gunshot wounds, in South African plegic patients. We concluded that the recent sociopolitical changes and especially the general escalation of violence in the country, is reflected in the observed changes in the epidemiology of spinal cord injuries.

Accidents, Traffic↗
PubMed1993

Specific neurophysiological effects of systemic nicotine on neurons in the nucleus accumbens.

Extracellular recordings of single neurons within the nucleus accumbens (NAS) of halothane-anesthetized rats have revealed that systemic nicotine injections (0.5 and 1.0 mg/kg, s.c.) inhibit the action potentials of normally inactive NAS neurons, evoked by fimbria stimulation (fimbria-driven responses, n = 18). These nicotine inhibitions of fimbria-driven NAS action potentials appear to be centrally mediated because they were reversed by subsequent systemic injections of the centrally acting nicotinic acetylcholine (nAch) antagonist, mecamylamine (1.0 mg/kg, s.c., n = 6) but not by the peripherally acting nAch antagonist, hexamethonium (2.0 mg/kg, s.c., n = 6). Fimbria-driven NAS neurons were also tested with morphine (2.5 mg/kg, s.c.) in some experiments. Consistent with many past observations (Hakan et al., 1989), morphine did not affect these driven neurons. In other experiments, nicotine-induced inhibition of NAS fimbria-driven units was followed by haloperidol (0.5 mg/kg, s.c.), in attempts to reveal the possible role of dopamine in these effects. Haloperidol was successful at reversing nicotine inhibitions in only some cases (n = 2/6). Thus, the role of dopamine in these NAS responses to nicotine remains unclear. In contrast to the fimbria-driven NAS responses, spontaneously active NAS neurons were not affected by nicotine injections yet were subsequently inhibited with systemic morphine. These results suggest a specific neuropharmacological organization in the region of the nucleus accumbens that may relate to the qualitative and subjective differences in the experimental effects of different psychoactive drugs. Iontophoretic studies designed to localize further the site of these nicotine effects on NAS neurons are in progress.

Action Potentials↗
PubMed1993

Host range selection of vaccinia recombinants containing insertions of foreign genes into non-coding sequences.

A simple yet powerful selection system was developed for the insertion of foreign genes in vaccinia virus. The selection system utilizes the vaccinia virus K1L (29K) host range gene which is located in HindIII M. This gene is necessary for growth in RK-13 cells but not in BSC40 or CV-1 cells. A vaccinia mutant (vAbT33) unable to grow on RK-13 cells was constructed having sequences at the 3' end of the K1L gene and the adjacent M2L gene deleted and replaced with the beta-galactosidase gene regulated by the BamHI F (F7L) promoter. A recombination plasmid containing the hepatitis B surface (HBs) antigen gene regulated by the M2L promoter and the complete sequence of the K1L gene was used to insert the HBs gene into vAbT33. The M2L negative K1L positive recombinant was easily isolated in two rounds of plaque purification by plating the virus on RK-13 cell monolayers. The K1L gene selection system allows the isolation of recombinants arising at frequencies as low as 1/100,000. It was noted that recombinants containing vaccinia sequence duplications (promoters) resulted in intragenomic recombinations that eliminated all sequences between the duplications. A second recombination plasmid was constructed that allowed insertion into the vaccinia genome without the loss of vaccinia coding sequences. This was achieved by insertion of the pseudorabies virus GIII gene regulated by the vaccinia H5R (40K) promoter between the translation and transcription stop signals at the 3' end of the K1L gene. The K1L gene transcription stop signal thus became the stop signal for the inserted GIII gene and an upstream transcription stop signal present in the H5R promoter fragment provided the stop signal for the K1L gene. This manipulation of the vaccinia genome had no effect on the accumulation or 5' end of the M2L gene transcripts. Although the insertion lengthened the 3' end and lowered the accumulation of K1L transcripts it altered neither the virulence nor the immunogenicity of the recombinant.

Base Sequence↗
PubMed1992

Streptokinase resistance: when might streptokinase administration be ineffective?

OBJECTIVE: (a) To develop an assay for streptokinase resistance. (b) To determine the prevalence of streptokinase resistance in patients presenting with acute myocardial infarction for the first time. (c) To determine the prevalence of streptokinase resistance in patients after exposure to streptokinase or streptococcal infection. DESIGN: Open, prospective. PATIENTS: 30 healthy volunteers. 40 patients admitted to the coronary care unit at Addenbrooke's Hospital with suspected acute myocardial infarction, 12 patients 12 months after streptokinase treatment, eight patients 24 months after streptokinase treatment, and sera from 12 patients with raised anti-streptolysin O (ASO) titres. METHODS: Three assays were used; a dilution neutralisation assay, an enzyme linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) anti-streptokinase antibodies, and an in vitro fibrin plate lysis assay. All measurements were performed on venous blood samples. RESULTS: Neutralisation and IgG antibody titres were positively correlated. Mean (SEM) antistreptokinase concentrations in the 30 controls were 87 (10) U/ml (neutralisation assay) and 28 (6.3) U/ml (ELISA). Corresponding concentrations in patients before streptokinase were 68 (6.1) U/ml and 18 (4.5) U/ml with a mean fibrin plate assay 117 (7.1)% that of controls. Resistance to streptokinase was detectable in one patient after 72 hours and in all patients by day 10. By day 10 concentrations were 4388 (919) U/ml, 773 (109) U/ml, and 17 (5.4)%. At both 12 and 24 months resistance was present in 75% of patients. Similarly 66% of high ASO titre sera showed resistance. The fibrin plate lysis assay detected significantly reduced streptokinase dependent fibrinolysis in vitro in the absence of raised total concentrations of antistreptokinase antibodies. CONCLUSIONS: The prevalence of streptokinase resistance in patients presenting with their first myocardial infarction is low. Resistance develops early after treatment and is still present in 75% of patients after 24 months. Retreatment with streptokinase is likely to be suboptimal even after 24 months. The fibrin plate lysis assay detects resistance in patients with normal concentrations of streptokinase antibodies. Streptococcal infection is associated with a high incidence of streptokinase resistance.

Antibodies↗
PubMed1992

Empowering employees to take charge of their performances.

To retain staff and operate effectively, an agency must reward and develop its personnel. One Wisconsin agency worked with its staff to develop a review tool that enabled the staff to take part in their own evaluation and thus perform to their best abilities.

Employee Incentive Plans↗
PubMed1991

Two cases of interstitial deletion 1p.

We report two cases of interstitial deletion of the short arm of chromosome 1. The first was a 10 year old boy whose karyotype was 46,XY,del(1) (p22.1p31.2); the second was a 6 month old boy with a chromosome complement of 46,XY,del(1) (p22.3p31.3). A number of the malformations observed were common to both cases. There has been one previously reported case with the same breakpoints as our case 1 and a phenotype that was strikingly similar.

Abnormalities, Multiple↗
PubMed1991

Ruptured petrous carotid aneurysm presenting with otorrhagia and epistaxis.

Aneurysm formation and rupture within the petrous internal carotid artery (ICA) is an extremely rare occurrence with approximately 10 such cases in the literature. Etiologies of petrous ICA aneurysms include atherosclerosis, closed head trauma, iatrogenic injury during mastoid surgery, chronic middle ear infections, and congenital causes. Therapeutic options include carotid artery ligation, aneurysm resection with or without reconstruction, and radiographically controlled vessel occlusion. The case of a patient who presented with otorrhagia, epistaxis, and transient focal neurologic signs due to a ruptured petrous ICA aneurysm is presented. The incidence, etiology, and anatomy of these aneurysms is reviewed, and the various tests for determining adequacy of collateral cerebral blood flow are described. Factors that affect the selection of surgical versus radiologic control of these lesions are also discussed.

Adult↗
PubMed1990

Cytokine modulation of keratinocyte cytokines.

There is increasing evidence that epidermal cytokines may have an important role in mediating inflammatory and immune responses in the skin. A number of cell types in the epidermis are capable of secreting cytokines including keratinocytes, Langerhans cells, melanocytic cells, and even Merkle cells. Keratinocytes are the major source of cytokines in the epidermis and have been reported to secrete IL-1, IL-3, IL-6, IL-8, CSF, TNF alpha, TGF alpha, TGF beta, and PDGF. Normally these cytokines are not actively secreted by keratinocytes; however, a number of agents are capable of mediating keratinocyte cytokine production, including cytokines themselves. We examined the effect of a number of cytokines on keratinocyte IL-1, IL-6, GM-CSF, and PDGF production. It was found that these keratinocyte cytokines are all modulated by one or more cytokines, including several that keratinocytes themselves secrete. These effects appear to be mediated by high-affinity cytokine receptors on keratinocytes. We are only beginning to understand the molecular mechanisms underlying the production, regulation, and precise role of keratinocyte cytokines in normal and diseased skin; however, recent studies suggest that cytokines secreted by epidermal cells and lymphoid cells may be important modulators of keratinocyte cytokine production.

Animals↗
PubMed1989

Chromosome 1 studies in Wilms' tumor.

Ten newly diagnosed patients with Wilms' tumor had blood and tumor samples taken for cytogenetic analysis. DNA was also extracted from these samples, along with blood obtained from both parents and an age- and sex-matched control. Molecular biological techniques were employed to study changes present in these samples with respect to chromosome 1. Two DNA probes, PIB 174 and PFBl, mapping to 1q12-qter and 1p12-pter, respectively, were examined for the presence of restriction fragment length polymorphisms (RFLPs) and to detect copy numbers of sequences homologous to the probes. These were normalized with respect to themselves and with regard to a control probe P30. No RFLPs were found with the restriction enzymes used. However, seven patients showed a marked alteration in hybridization signal in tumor and/or blood samples compared to control samples and the control probe. This was apparent using probe PFBl, but just failed to reach statistical significance using nonparametric testing. This would suggest that submicroscopic chromosome 1 changes are present more often in Wilms' tumor than previously recognized, and they may play a leading role in the genesis of this tumor.

Blotting, Southern↗
PubMed1989

A family of type I keratin genes and the homeobox-2 gene complex are closely linked to the rex locus on mouse chromosome 11.

Type I and type II keratins are major constituents of intermediate filaments that play a fundamental role in the cytoskeletal network. By using both somatic cell hybrids and conventional and interspecific linkage crosses, several genes encoding type I keratins, including the epidermal keratin K10, were shown to be closely linked to the homeobox-2 complex and the rex locus on mouse chromosome 11. The absence of crossovers between type I keratin-encoding genes and rex (N = 239), a locus affecting hair development, raises the possibility that mutations at rex and neighboring loci affecting skin and hair development involve type I keratin genes.

Alleles↗
PubMed1988

Direct detection of HIV RNA expression in seropositive subjects.

The polymerase chain reaction (PCR) and reverse transcription were used to assess human immunodeficiency virus type 1 (HIV1) RNA expression in peripheral blood mononuclear cell samples from seropositive subjects. HIV RNA was detected from seropositive subjects who had no symptoms, lymphadenopathy syndrome, and acquired immunodeficiency syndrome. DNA PCR of the samples used for RNA extraction showed that seventeen of eighteen (94%) contained HIV proviral DNA. Eleven (65%) of the seventeen DNA-positive samples were also positive for HIV RNA, including samples from four patients undergoing antiviral drug treatment. Serum HIV antigen assays detected only six (32%) of the nineteen PCR-positive samples. Owing to the speed and high sensitivity of PCR for HIV detection, this technique will be suitable for monitoring antiviral therapy and the virus load of people with HIV infections.

Cells, Cultured↗
PubMed1988

Insulin-related materials in the nervous system of vertebrates and non-vertebrates: possible extrapancreatic production.

Studies from multiple laboratories with a range of methods raised the possibility that insulin production occurs naturally at extrapancreatic sites. Part A covers the presence of insulin-related materials in organisms that do not have an endocrine pancreas, including unicellular prokaryotes and eukaryotes as well as multicellular non-vertebrate animals (insects et al.) and plants. Part B covers possible production of insulin by extrapancreatic tissues of vertebrates that are remote from a source of pancreatic insulin e.g. early chick embryos and mammalian cells in culture. Part C covers possible extrapancreatic insulin production in mammals in vivo. Each section ends with an outline summary with evidence in favor of and against the hypothesis.

Amino Acid Sequence↗
PubMed1987

Frog brain and liver show evolutionary conservation of tissue-specific differences among insulin receptors.

The insulin receptors of frog brain and liver show features typical of other insulin receptors with regard to affinity and specificity of binding to insulins and proinsulin, solubility in Triton X-100, binding to and elution from wheat germ agglutinin, and insulin-sensitive tyrosine kinase activity. Likewise, the brain and liver receptors differ from one another in electrophoretic mobility and susceptibility to treatment with neuraminidase, analogous to brain and liver receptors of reptiles, birds, and mammals; while the functional implications of these differences are unknown, their evolutionary conservation for 400-500 million years suggests the possibility that they might have importance.

Animals↗