Biomedical subjects

N King

Publications and source records attributed to N King.

At least 55 records · Page 3Linked to original sources

PubMed1999

Recognition of work-related diseases: an original collaborative project in Québec.

Establishing the causal link between disease and working conditions is no easy task. In Québec, an original collaborative project combining epidemiology, community organization, and medical care has evolved over the years in order to promote the recognition of work-related diseases, particularly among non-unionized workers. This article will describe this innovative project as well as its achievements, strengths, and weaknesses.

Journal Article↗

PubMed1998

Genetic linkage to the serotonin transporter protein and 5HT2A receptor genes excluded in generalized social phobia.

Social phobia, particularly the generalized form, is strongly familial and frequently comorbid with major depression, panic disorder, and obsessive-compulsive disorder. It has also recently been shown to be responsive to selective serotonin reuptake inhibitors. We conducted a study to determine if generalized social phobia is genetically linked to either of two candidate genes: the serotonin transporter protein (5HTT) gene, or the 5HT2A receptor (5HT2AR) gene. Rates of social phobia (using several phenotype definitions) were ascertained and blood samples obtained from consenting first-degree family members of generalized social phobic probands. 5HT2AR and 5HTT genotyping was performed using the polymerase chain reaction (PCR). Linkage was tested using LINKAGE and GENEHUNTER software. No evidence of linkage was found; power analysis indicated that failure to find linkage was unlikely due to inadequate statistical power. These findings reasonably exclude linkage between generalized social phobia and the 5HTT or 5HT2AR genes in these samples, although modifier effects cannot be ruled out. Other 5HT receptor subtypes or indirect modulatory effects of 5HT on other neurotransmitter systems may be involved.

Adolescent↗

PubMed1998

Effect of regular training on the myocardial and plasma concentrations of taurine and alpha-amino acids in thoroughbred horses.

Exercise induces significant changes in the free intracellular amino acid pool in skeletal muscle but little is known of whether such changes also occur in cardiac muscle. In this study the effect of regular exercise on the size and the constituents of the free amino acid pool in the hearts and in the plasma of thoroughbred horses was investigated. The total free intracellular amino acid pool in the hearts of control horses was 30.9 +/- 1.2 mumol/g wet weight (n = 6). Glutamine but not taurine was present at the highest concentration (13.5 +/- 0.9 and 7.7 +/- 0.69 mumol/g wet weight for glutamine and taurine respectively). As for the rest of the amino acids in the pool, only glutamate and alanine were present at levels greater than 1 mumol/g wet weight (4.6 +/- 0.25 and 1.7 +/- 0.14 for glutamate and alanine respectively). The tissue to plasma ratio was highest for taurine at 155, followed by glutamate at 111, aspartate and glutamine at 37, alanine at 5.8 and ratios of less than 3 for the rest of the amino acids. The total free intracellular amino acid pool in the hearts of exercised horses was slightly but not significantly lower than control (28.1 +/- 1.1 mumol/g wet weight, n = 6). Regular exercise increased the intracellular concentration of threonine, valine, isoleucine, leucine and phenylalanine but was only significant (p < 0.05) for threonine. This work has documented the profile of taurine and protein amino acids in the heart and in the plasma of thoroughbred horses and showed that in contrast to skeletal muscle, heart muscle does not show major changes in amino acids during regular exercise.

Amino Acids↗

PubMed1998

Characteristics of L-alanine transport in cardiac sarcolemmal vesicles and into isolated cardiac myocytes.

During cardiac insults, heart cells synthesise and accumulate alanine as a part of the anaerobic energy production pathway. The transport of alanine presumably influences this pathway, making it important to characterise the L-alanine transporter in the heart. In this study, we have investigated the transport of L-alanine across the sarcolemma using a novel approach, namely utilisation of two preparations: cardiac sarcolemmal vesicles and cardiac myocytes. Both preparations were isolated from the heart of the same mammalian species. L-Alanine uptake in both preparations was sodium dependent. In the sarcolemmal vesicles, the sodium dependent component was electrogenic and saturated with an estimated Michaelis-Menten constant (Km) and maximal reaction velocity (Vmax) of 0.48+/-0.18 mM and 279.97+/-64.17 pmol/mg per min respectively at room temperature. In the isolated myocytes, L-alanine uptake was linear in sodium-containing media, with an estimated Km and Vmax of 9.65+/-0. 76 mM and 169.81+/-13.22 pmol/ microl per min respectively at 10 degreesC for the sodium-dependent component. Inhibition of cotransport by a variety of substrates indicated that L-alanine uptake in the heart is mediated by an A- or ASC-like system. These characteristics of L-alanine transport suggest that under ischaemic conditions, L-alanine efflux will be activated, thus allowing for the continuous utilisation of other amino acids for energy production.

Alanine↗

PubMed1998

Assessment of long-term psychological well-being following intensive care.

The aim of this research, which remains in progress, has been the examination of long-term psychological consequences for survivors of intensive care. Seventy-two patients were followed up for 1 year, after discharge from the Intensive Care Unit (ICU) at St James's University Hospital in Leeds. Major objectives of the study included assessment of patients' sense of well-being at specified intervals post-discharge, and identification of ICU-related variables which might influence psychological recovery. Psychometric assessments used were the General Health Questionnaire 28-item version, the Rosenberg Self-esteem Scale, and the Impact of Event scale. This paper describes findings from the research so far. An exploratory analysis of the data suggests that distinctions can be drawn among surviving patients with regard to psychological recovery, by way of variables such as type of illness, mode of admission and amount of recall. The work expands previous research into post-ICU psychology and quality of life, and should allow increased understanding of this patient group.

Adult↗

PubMed1998

Comparison of the traditional paper visual analogue scale questionnaire with an Apple Newton electronic appetite rating system (EARS) in free living subjects feeding ad libitum.

OBJECTIVE: Assessing the value of a newly developed electronic visual analogue scale questionnaire (Apple Newton Message Pad) with the traditional paper method for appetite rating. DESIGN: In a random, crossover design, subjects completed both electronic and paper questionnaires to compare results obtained by the two methods; individual methods were completed consecutively to assess test-retest reliability; preference was established using a questionnaire. SETTING/SUBJECTS: Healthy, free-living adults were studied for comparison of methods (n = 12), test-retest reliability (n = 8) and preference (n = 13). INTERVENTION: Visual analogue scales were completed each waking hour to assess appetite. Preference was assessed after both methods were completed. RESULTS: There was no significant difference in the hourly results obtained by the paper and electronic methods for 'desire to eat', 'how much can you eat now', 'urge to eat' and 'preoccupation with thoughts of food'. Small differences in 'hunger' and 'fullness' ratings were noted (approximately 5% mean difference between methods, P < 0.05), but patterns of change and sensitivity for these and all other parameters remained similar for both methods across the visual analogue scale. Test-retest reliability demonstrated was similar for both methods. Seven (54%) subjects preferred to use the paper questionnaire, five (38%) the electronic method and one (8%) had no preference. CONCLUSIONS: The electronic Apple Newton questionnaire is as sensitive and reliable as the paper method, has the advantage that it automatically records the time of data acquisition and data collection and processing are more efficient for the researcher. The two methods should not be used interchangeably.

Adult↗

PubMed1998

Investigation of dopamine system genes in obsessive-compulsive disorder.

Evidence from anatomical, pharmacological, and animal studies on the involvement of the dopamine system in obsessive-compulsive disorder (OCD) is mounting. This, along with evidence for a genetic diathesis provided by family and twin studies, prompted us to conduct genetic association studies of dopamine system genes in OCD. We genotyped OCD patients (n > 100) and matched controls for four loci: (1) a 40-base-pair repeat in the dopamine transporter gene; (2) the TaqIA polymorphism and the serine/cysteine variation in the D2 dopamine receptor gene; (3) an MscI polymorphism in the D3 dopamine receptor gene; and (4) a 48-base-pair repeat in the D4 dopamine receptor gene. Significant differences in allele frequencies were found between patients and controls for the D4 receptor gene, although replication is required with family-based controls before any conclusions can be entertained. This study represents the first comprehensive assessment of the roles of dopamine system genes in OCD.

Age of Onset↗

PubMed1998

Effect of two delivery systems for recombinant human bone morphogenetic protein-2 on periodontal regeneration in vivo.

Resorbable collagen membranes for guided tissue regeneration in periodontal therapy have shown promise but are not osteoinductive. As recombinant human bone morphogenetic protein-2 (rhBMP-2) is known to have an affinity for collagen, the use of this osteoinductive agent incorporated into a collagen vehicle may act as a suitable carrier to promote periodontal regeneration. The aim of this study was to investigate the effects of two different collagen delivery systems for rhBMP-2 in rat periodontal fenestration defects. Using the collagen membrane delivery system, 3 groups of adult Wistar rats which had surgical defects created on the right side of the mandible involving the removal of bone and exposure of the molar roots were treated with either rhBMP-2 in colagen membrane (BMPm) (n = 12 animals), or collagen membrane only (COLm) (n = 12), or were left untreated (UN) (n = 14). Using the collagen gel delivery system, surgical defects were treated with either rhBMP-2 incorporated in a collagen gel carrier (BMPg) (n = 5) or had collagen gel only (COLg) (n = 6). Animals were killed 10 d postoperatively and tissues processed for histology. New bone formation was significantly greater in BMPg compared with both BMPm and controls (p < 0.05). However, new cementum formation was significantly greater in BMPm (721 +/- 166 micron2, mean +/- SE) compared with COLm, COLg and UN (p < 0.02) (190 +/- 44 micron2, 327 +/- 114 micron2 and 172 +/- 33 micron2, respectively) and more than 1.5 times BMPg (451 +/- 158 micron2). In conclusion, both carrier systems for rhBMP-2 significantly increased new bone formation compared with controls during the early stages of periodontal wound healing. However, the more slowly dissolving collagen membrane carrier system for rhBMP-2 produced significantly greater new cementum compared with the collagen gel carrier, suggesting that a more prolonged exposure of rhBMP-2 is required to increased cementogenesis.

Alveolar Bone Loss↗

PubMed1998

The effect of root surface demineralization on bone morphogenetic protein-2-induced healing of rat periodontal fenestration defects.

The purpose of this study was to investigate the effect of acid conditioning of root surfaces during recombinant human bone morphogenetic protein-2 (rhBMP-2) induced periodontal regeneration in vivo. The buccal aspect of molar roots were denuded of their periodontal ligament through a bony window created in the mandible of 34 Wistar rats under general anesthesia. Three groups of 11 or 12 animals received either 10 microL of 50 g/mL rhBMP-2 in a collagen gel over the surgical defect (BMP) or 10 microL of collagen gel only (COL) or were left untreated (UN). Each of the 3 groups were further subdivided into those that received prior root acid conditioning with 35% phosphoric acid gel and those without acid conditioning. Animals were sacrificed 10 days after surgery and the tissues processed for histological examination. The BMP groups with and without acid conditioning developed significantly more bone over the second molar (3.89+/-0.86% and 7.62+/-0.93%, respectively; mean+/-SE), compared with the respective COL (1.24+/-0.26% and 2.77+/-0.52%) and UN groups (1.34+/-0.35% and 3.69+/-0.37%) (P <0.05). Furthermore, significantly more bone was found in the BMP non-acid conditioned group compared with all other groups (P <0.05). Acid conditioning promoted significantly more ankylosis (50%) compared with non-acid conditioning (6.3%) (P=0.007). New cementum formation was greatest in the BMP acid conditioned group (628.4+/-253.8 microm2) and lowest in the non-acid conditioned UN group (207.6+/-36.4 microm2) (P <0.05). This is the first known report evaluating the effects of root acid conditioning after a single application of rhBMP-2 in vivo. Results suggest that root conditioning agents operating at low pH administered into the periodontal wound impairs early BMP-induced osteogenesis while simultaneously promoting BMP-induced cementogenesis.

Analysis of Variance↗

PubMed1998

In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients.

The effect of exemestane (6-methylenandrosta-1,4-diene-3,17-dione) 25 mg p.o. once daily on in vivo aromatization was studied in 10 postmenopausal women with advanced breast cancer. Aromatization was determined before treatment and after 6-8 weeks on therapy by administering a bolus injection of [3H]androstenedione (500 microCi) and [14C]estrone (5 microCi) followed by measurement of the isotope ratio of urinary estrogens after high-performance liquid chromatography purification. In addition, plasma endogenous estrogens were measured with highly sensitive radioimmunoassays after separation with high-performance liquid chromatography. Treatment with exemestane suppressed whole body aromatization from a mean pretreatment value of 2.059% to 0.042% (mean suppression of 97.9%). Plasma levels of estrone, estradiol, and estrone sulfate were found to be suppressed by 94.5%, 92.2%, and 93.2%, respectively. This is the first study revealing near total aromatase inhibition in vivo with the use of a steroidal aromatase inhibitor. The observation that exemestane is a highly potent aromatase inhibitor, together with the fact that the drug is administered p.o. and causes limited side effects, suggests that exemestane is a promising new drug for the treatment of hormone sensitive breast cancer.

Administration, Oral↗

PubMed1997

Absence of linkage for schizophrenia on the short arm of chromosome 5 in multiplex Canadian families.

A VNTR for the human dopamine transporter gene (DAT-1) has been localized to chromosome 5p15.3. Silverman et al. [1996] found evidence for genetic linkage of the D5S111 locus, located just centromeric to DAT-1, to schizophrenia and related disorders in a large Hispanic family. We evaluated five markers on 5p, including D5S111 and the DAT-1 VNTR, in five multiplex schizophrenic families, assuming autosomal dominant transmission (subjects assessed n = 122, DNAs available n = 96, individuals with schizophrenia and schizoaffective disorder n = 36, broader spectrum disorders n = 14). LOD scores were negative across all families for all markers tested, and overall LOD scores were strongly negative (<-2.0, theta = 0) across all five families for each of the markers typed. Thus, there is no evidence to support the linkage of markers in this region of chromosome 5 to schizophrenia in this sample of families.

Canada↗

PubMed1997

Increased prevalence of the seven-repeat variant of the dopamine D4 receptor gene in patients with obsessive-compulsive disorder with tics.

The polymorphism characterized by a varying number of 48 bp repeats (VNTR) in the dopamine D4 receptor (DRD4) gene was examined in 61 obsessive-compulsive disorder (OCD) probands with and without tics. Most of the OCD patients with tics showed at least one copy of the 7-fold variant compared to those affected subjects without tics (91 vs. 48%, respectively, Yates corrected chi2 = 5.54, P = 0.018). Similarly, a higher number of copies of this common variant were detected in the group of probands displaying tics compared to those OCD's without tics (Yates corrected chi2 = 4.66, P = 0.03). Our study suggests that the seven-repeat allele of the DRD4 gene could be a factor in the phenotypic variance of tics among OCD individuals.

Alleles↗

PubMed1997

Identification and mutational analysis of the immunodominant IgE binding epitopes of the major peanut allergen Ara h 2.

A major peanut allergen, Ara h 2, is recognized by serum IgE from > 90% of patients with peanut hypersensitivity. Biochemical characterization of this allergen indicates that it is a glycoprotein of approximately 17.5 kDa. Using N-terminal amino acid sequence data from purified Ara h 2, oligonucleotide primers were synthesized and used to identify a clone (741 bp) from a peanut cDNA library. This clone was capable of encoding a 17.5-kDa protein with homology to the conglutin family of seed storage proteins. The major linear immunoglobulin E (IgE)-binding epitopes of this allergen were mapped using overlapping peptides synthesized on an activated cellulose membrane and pooled serum IgE from 15 peanut-sensitive patients. Ten IgE-binding epitopes were identified, distributed throughout the length of the Ara h 2 protein. Sixty-three percent of the amino acids represented in the epitopes were either polar uncharged or apolar residues. In an effort to determine which, if any, of the 10 epitopes were recognized by the majority of patients with peanut hypersensitivity, each set of 10 peptides was probed individually with serum IgE from 10 different patients. All of the patient sera tested recognized multiple epitopes. Three epitopes (aa27-36, aa57-66, and aa65-74) were recognized by all patients tested. In addition, these three peptides bound more IgE than all the other epitopes combined, indicating that they are the immunodominant epitopes of the Ara h 2 protein. Mutational analysis of the Ara h 2 epitopes indicate that single amino acid changes result in loss of IgE binding. Two epitopes in region aa57-74 contained the amino acid sequence DPYSP that appears to be necessary for IgE binding. These results may allow for the design of improved diagnostic and therapeutic approaches to peanut hypersensitivity.

2S Albumins, Plant↗

PubMed1997

The intrinsic Cl- conductance of mouse kidney cortex brush-border membrane vesicles is not related to CFTR.

Brush-border membrane vesicles (BBMV) were prepared from whole Balb/c mice kidneys by a Mg2+ precipitation technique. The presence of an intrinsic Cl- conductance co-expressed with Na+/glucose cotransport was inferred by the anion dependence of [14C]glucose uptake and overshoot with inward Na(+)-anion gradients. In Na(+)-equilibrated conditions, an inside-negative membrane potential difference (p.d.) produced by an inward Cl- gradient alone was capable of driving intravesicular [14C]glucose accumulation. The apparent anion conductance had a selectivity of Br- = I- = Cl- > F- > > gluconate, was inhibited by 0.5 mM 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) but was unaffected by 0.5 mM 4,4'-diisothiocyanatostilbene 2,2'-disulphonate (DIDS). BBMV were isolated from mice in which the CFTR gene had been disrupted by a termination mutation (-/-) and compared with normal litter mates (+/+) and heterozygotes (-/+)[18]. [14C]Glucose uptake in NaCl media was significantly greater than glucose uptake in Na gluconate media for all three genotypes measured at 20 s: for homozygous -/- animals [14C]glucose uptake was increased by 2.80 +/- 0.53 fold in Cl- media compared to gluconate media, n = 6; for wild-type +/+, by 2.16 +/- 0.53 fold, n = 8; and for heterozygous +/- animals, by 2.17 +/- 0.45 fold, n = 8. The observation of a Cl-(-)dependent component in BBMV isolated from homozygous -/- mutant animals shows that the chloride conductance in these vesicles cannot be due to CFTR expression.

Animals↗

PubMed1997

Children's nighttime fears.

Some children experience persistent night-time fears that interfere with their daily functioning. Initially, we present developmental considerations necessary to an understanding of severe night-time fears. We postulate that severe night-time fears are probably due to a complex interaction of biological, environmental, and cognitive-mediational processes. Several assessment procedures are outlined: behavioral interviews, diagnostic interviews, fear survey schedules for children, home monitoring on the part of parents, and darkness toleration tests. Traditional behavioral interventions, and more recent cognitive-behavioral interventions, are evaluated in terms of their research foundations. Cognitive-behavioral strategies appear to have the more empirical support, although we draw attention to several methodological limitations.

Child↗

PubMed1997

Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene.

Obsessive compulsive disorder (OCD) is a common illness, characterized by anxiety-provoking thoughts and the need to perform rituals. OCD is most commonly treated with a class of pharmacological agents known as serotonin reuptake inhibitors (SRIs). SRIs block the reuptake of serotonin (5-HT) into the presynaptic neuron, a process mediated by the serotonin transporter (5-HTT). The successful use of SRIs in OCD has led to the hypothesis that 5-HTT may play a pivotal role in the pathogenesis of OCD. We decided to study this hypothesis from a genetic perspective, because family and twin studies suggest that there is a strong genetic component to OCD. In addition, the sequence of the gene for 5-HTT is available, and a 44-bp insertion/deletion polymorphism has been detected in the promoter region of the gene. There is evidence that this polymorphism alters expression of the transporter protein. We typed 72 OCD patients and 72 matched controls, and found no statistically significant difference between the two groups (chi 2 = 4.319, P = 0.115, 2 d.f.). We observed however a trend towards increased homozygosity in the patient group. We also rated (retrospectively) the patients' clinical responses to SRIs. No association was observed between these ratings and the promoter region polymorphism in the serotonin transporter gene. Given the pharmacological evidence favoring a role for 5-HTT in OCD and SRI response, further genetic evaluation of the serotonin transporter in OCD is indicated.

Adult↗

PubMed1997

Mild head injury: neuropathology, sequelae, measurement and recovery.

Head injuries are common in industrialized countries and the majority of them are defined as 'minor' or 'mild' injuries (MHI). These terms, however, can be misleading because the sequelae that often follow such injuries can cause significant detriment to psychosocial and interpersonal functioning Clinical psychologists in most areas of specialism are likely to encounter MHI because of their high frequency and the types of problems they can cause. An overview of the body of knowledge on this subject is therefore of some importance. This paper reviews the literature concerning the neuropathology, measurement, sequelae and recovery of MHI. The following subjects are addressed: (i) the relationship between the neuropathology of severe head injury and the neuropathology of MHI; (ii) the limitations of traditional measures of head injury severity (e.g. post-traumatic amnesia) when applied to MHI; (iii) factors relevant to the recovery of post-concussion symptoms following MHI; and (iv) intervention and treatment following MHI.

Brain↗

PubMed1997

Recombinant human bone morphogenetic protein-2 promotes wound healing in rat periodontal fenestration defects.

Although there is considerable interest in the use of bone morphogenetic protein (BMP) to promote periodontal regeneration, little is known of its effects on the early stages of wound healing. The aim of this study was to investigate the effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) on an early stage of post-operative wound healing and following complete healing (10 and 38 days, respectively) in a rat model of periodontal regeneration. The buccal aspects of molar roots were carefully denuded of their periodontal ligament through a bony window created in the mandibles of Wistar rats under general anesthesia. After the root surfaces were acid-conditioned, a 10-microL quantity of 50 microg/mL rhBMP-2 in a collagen gel solution was placed into the surgically created defect in test animals; in controls, either a 10-microL quantity of only collagen gel was received, or the defect was untreated. Animals were killed 10 days or 38 days after surgery and the tissues processed for histological examination. Transverse 5-microm sections were stained for the identification of new bone, cementum, and collagen fiber formation. In the 10-day study groups, new bone formation over the second molar and beyond the defect was significantly increased in the test group (p < 0.02), although there was no evidence of increased ankylosis. RhBMP-2 stimulated more than twice the area of cementum growth coronally compared with controls (712 +/- 286 microm2 and 258 +/- 57 microm2, respectively). Connective tissue attachment, including the number and width of collagen bundles, was similar in both test and controls. Complete healing without any evidence of ankylosis had occurred in all animals 38 days post-operatively, and no significant differences were observed between test and control groups. In conclusion, a single dose of rhBMP-2 increased the rate of normal intramembranous bone formation and selectively enhanced cementum formation coronally during early wound healing. However, the finding that rhBMP-2 induced bone formation at some distance from the defect suggests the importance of developing a suitable delivery system to maintain the concentration of BMP-2 at the site of implantation for potential therapeutic use.

Alveolar Bone Loss↗