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Biomedical subjects

D Chalmers

Publications and source records attributed to D Chalmers.

At least 37 records · Page 2Linked to original sources
PubMed1997

Amelioration of relapsing experimental autoimmune encephalomyelitis with altered myelin basic protein peptides involves different cellular mechanisms.

T-cells specific for a region of human myelin basic protein, amino acids 87-99 (hMBP87-99), have been implicated in the development of multiple sclerosis (MS) a demyelinating disease of the central nervous system. Administration of soluble altered peptide ligand (APL), made by substituting native residues with alanine at either positions 91(91K > A or A91) or 97 (97R > A or A97) in the hMBP87-99 peptide, blocked the development of chronic relapsing experimental autoimmune encephalomyelitis (R-EAE), in the SJL mouse. The non-encephalitogenic APL A91, appears to induce cytokine shifts from Th1 to Th2 in the target T-cells, whereas the encephalitogenic superagonist APL A97 causes deletion of the MBP87-99 responsive cells. Thus, single amino acid changes at different positions in the same peptide epitope can lead to APL capable of controlling auto-immune disease by different mechanisms.

Animals↗
PubMed1996

Rat homolog of mouse interleukin-1 receptor accessory protein: cloning, localization and modulation studies.

A protein which facilitates the binding between interleukin-1 (IL-1) and the type I IL-1 receptor (designated as interleukin-1 receptor accessory protein, IL-1RAcP) has recently been cloned in mouse cells. In the present study, a rat homolog of the mouse IL-1RAcP was isolated from a rat superior cervical ganglion library. The deduced 570 amino acid sequences between rat and mouse IL-1RAcP have > 95% sequence identity to each other with similar predicted signal peptide sequence (20 amino acids), extracellular domain (339 amino acids), a single transmembrane domain (24 amino acids) and a long intracellular domain (187 amino acids). The rat IL-1RAcP has approximately 25% sequence identity to the rat type I IL-1 receptor and a predicted extracellular domain with three immunoglobulin-like loops. RNase protection assays demonstrated that rat IL-1RAcP is expressed in both brain and peripheral tissues with the highest densities present in liver and brain areas such as hypothalamus, cerebral cortex, hippocampus and cerebellum; significantly lower densities were present in lung and in immune tissues such as thymus and spleen. The presence of IL-1RAcP in brain was confirmed by in situ hybridization histochemical studies with a discrete localization present in the dentate gyrus of the hippocampus. The IL-1RAcp was down-regulated in parallel with the type I IL-1 receptor in the liver following endotoxin treatment in rats. These data demonstrating the presence and modulation of a rat homolog of a mouse IL-1RAcP, which is highly expressed in brain and peripheral tissues containing type I rat IL-1 receptor, further suggest the importance of the interaction between the two proteins in rat in modulating the actions of IL-1. On the other hand, the presence of the IL-1RAcP in brain areas which show an absence of type I IL-1 receptors suggests additional functions for this protein in the rat.

Amino Acid Sequence↗
PubMed1996

Incidence of death and hospitalization from assault occurring in and around licensed premises: a comparative analysis.

The aim of the research was to: determine the incidence of serious assault in and around licensed premises in New Zealand, and to compare the circumstances of assault with those that occurred in other locations. For the period 1978-87, inclusive, 49 assault fatalities occurred in or around licensed premises representing 9.4% of all homicides and 12.9% where a place was specified. The comparable figures for assaults resulting in hospitalization in 1988 were: 251, 10.2% and 18.4%, respectively. Further analyses suggests that our estimate of the incidence rate is likely to be an underestimate due to changes over time in the large number of assault cases which have no specific place of occurrence identified. In comparison with homes homicides in licensed premises were more likely to involve: males; Maori, unarmed fights and brawls; unknown assailants; alcohol; occur during the evening and toward the end of the week; and result in head injury. For non-fatal events similar differences were found. In comparison with homes non-fatal assaults were more likely to involve: males; young adults, Maori, the unemployed, unarmed fights and brawls, and head injury. There have been a number of significant policy changes in New Zealand since 1988 which may have resulted in a change to the situation reported here.

Adolescent↗
PubMed1996

Neurobiology of corticotropin releasing factor (CRF) receptors and CRF-binding protein: implications for the treatment of CNS disorders.

The actions of CRF in the brain and in the periphery are mediated through multiple binding sites. There are three receptors, CRF1, CRF2 alpha and CRF2 beta, which encode 411, 415 and 431 amino acid proteins and transduce signals via the stimulation of intracellular cAMP production. The recent identification of high-affinity non-peptide CRF receptor antagonists should allow for rapid progress in drug development of CRF receptor antagonists. In addition to the receptors, the actions of CRF in brain and in the periphery can also be modulated by a binding protein of 322 amino acids. Ligands of CRF-BP, such as CRF (6-33) can elevate brain levels of 'free' CRF and improve learning and memory without stress-like side effects of CRF receptor agonists. Urocortin, a mammalian CRF-related peptide with close sequence homology to fish urotensin, interacts with CRF1, CRF2 receptors and with CRF-BP. These data indicate that CRF receptor antagonists may be useful for the treatment of the disease states where CRF is elevated such as anxiety and depression, anorexia nervosa and stroke and that ligand inhibitors of CRF-BP may be used to elevate brain levels of 'free' urocortin and other CRF-related peptides.

Animals↗
PubMed1995

Corticotropin releasing factor binding protein (CRF-BP) is expressed in neuronal and astrocytic cells.

Corticotropin releasing factor (CRF) binding protein (CRF-BP) was measured in media and cell lysates of primary rat astrocytes, microglia and neurons with the use of a ligand immunoradiometric assay (LIRMA). A low basal level of CRF-BP was detected in the media and cell lysates from primary neuronal and astrocyte cells after 48 h in culture. No basal expression of CRF-BP was detected in cell lysates or media from primary microglial cultures. The CRF-BP expressed in cultured astrocytes and neurons had the same pharmacological characteristics as the human recombinant molecule. After forskolin, IBMX or forskolin/IBMX treatment, a robust increase in secreted CRF-BP levels in the media from astrocytes and neurons, but not microglia, was observed. An increase in CRF-BP-like immunoreactivity in cell lysates was also observed after IBMX/forskolin treatment. In situ hybridization analysis revealed that CRF-BP mRNA was increased in primary cultured astrocytes after IBMX/forskolin stimulation suggesting that regulation was at the level of gene transcription. 'Axon sparing' lesions produced with 0.12 M quinolinic acid in PBS injected intracerebrally (unilaterally into dorsal hippocampus) resulted in loss of CRF-BP expression in neurons. These data provide evidence for the differential localization and regulation of CRF-BP in different cell types in brain and suggest that CRF-BP expression may be locally increased in disease states associated with astrocytosis and gliosis.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Cloning and expression of the A2a adenosine receptor from guinea pig brain.

A full-length complementary DNA (cDNA) clone encoding the guinea pig brain A2 adenosine receptor has been isolated by polymerase chain reaction (PCR) and low-stringency-hybridization screening of a guinea pig brain cDNA library. This cDNA contains a long open reading frame encoding a 409-amino acid-residue protein which is highly homologous to the A2 adenosine receptors previously cloned from other species. Hydrophobicity analysis of the deduced protein sequence reveals seven hydrophobic regions, characteristic of a member of the G-protein-coupled receptor superfamily. Radioligand binding assay and functional (GTPase and cAMP) assays of the receptor, transiently expressed in mammalian cells, demonstrate typical characteristics of the A2 type adenosine receptor. The messenger RNA (mRNA) of this A2 receptor is found in the brain, heart, kidney and spleen. Receptor autoradiography with [3H]CGS21680, a specific A2 agonist, and in situ hybridization with A2 cRNA probe in guinea pig brain indicate that the receptor is expressed exclusively in the caudate nucleus. The pharmacological profile and anatomical distribution of this receptor indicate that it is of the A2a subtype. This work represents the first cloning of an A2a receptor in a rodent species, offers a complete pharmacological characterization of the receptor and provides an anatomical comparison between binding profile and gene expression of the receptor.

Amino Acid Sequence↗
PubMed1994

Steroid-growth factor interaction in human prostate cancer. 1. Short-term effects of transforming growth factors on growth of human prostate cancer cells.

In order to better define potential mechanisms of growth regulation in human prostate cancer cells, we have compared biological responses (such as short-term response to both transforming growth factor alpha and beta; TFG alpha and TFG beta) in relation to hormone sensitivity of LNCaP, DU145, and PC3 cells. Androgen receptor (AR) and epidermal growth factor receptor (EGF-R) content of each cell line was also investigated. In addition, expression of EGF, TGF alpha, and TGF beta was evaluated through immunofluorescent staining. Growth of androgen non-responsive PC3 cells was stimulated by TGF alpha (about 35%) and inhibited by TGF beta (more than 50%), with respect to controls, after 48 h exposure. Conversely, AR-positive, hormone-responsive LNCaP cells proved to be poorly sensitive, at least short-term, to either growth factor. Furthermore, high levels of both EGF-R and TGF alpha, and a fairly high amount of EGF, were found in DU145 cells and, to a lesser extent, in LNCaP cells; in contrast, PC3 cells exhibited low expression levels of both receptors (EGF-R) and ligands (EGF, TGF alpha), but displayed remarkable TGF beta binding and relatively high levels of endogenous TGF beta. Overall, these results suggest a differential sensitivity to TGF alpha and TGF beta by prostate cancer cells; TGF alpha response seems not to be proportional to the EGF-R content of individual cell lines.

Androgens↗
PubMed1994

Cloning and characterization of a pharmacologically distinct A1 adenosine receptor from guinea pig brain.

Three full-length cDNA clones encoding the guinea pig A1 adenosine receptor have been isolated by polymerase chain reaction (PCR) and low-stringency hybridization screening of a guinea pig brain cDNA library. These three cDNAs, though differing in their 5' untranslated regions, contain the same open reading frame encoding a 326 amino acid residue protein with seven hydrophobic alpha-helices long enough to form the transmembrane domains, suggesting that it belongs to the G protein-coupled receptor superfamily. This protein is highly homologous to the A1 adenosine receptors previously cloned from other species. Pharmacological characterization of this receptor transiently expressed in mammalian cells demonstrates that, despite its high homology to A1 adenosine receptors of other species, the guinea pig A1 adenosine receptor displays a unique pharmacological profile: high affinity for the A1-selective antagonist CPX, yet very low affinity for some A1-selective agonists such as CCPA, CHA and R-PIA. Northern blotting for different guinea pig tissues and in situ hybridization for guinea pig brain sections reveal an abundant and broad distribution of mRNA of this A1 subtype receptor in the brain.

Adenosine↗
PubMed1994

Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera.

The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non-Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.

Amino Acid Sequence↗
PubMed1993

Dispositional traits as risk in problem drinking.

A trait-dispositional paradigm for conceptualizing personality provided the framework for investigating the relationship between personality dispositions and drinking problems. This approach was compared directly with personality research based on the Minnesota Multiphasic Personality Inventory (MMPI). A total of 241 subjects (192 men and 49 women) were tested at a mandatory Driving While Intoxicated (DWI) first-offender education program. Information was gathered from the Michigan Alcoholism Screening Test (MAST), Blood Alcohol Concentration (BAC) at time of arrest, and two personality tests--the MacAndrew Alcoholism Scale (MAC) and the Problem Drinker Trait List (PDTL). The psychometric properties of the PDTL were analyzed and compared with those of the MAC. In comparing the two personality tests in terms of their capacity to predict drinking problems over a wide range of drinking severity, the PDTL performed as well or better than the MAC, particularly for drinkers with low arrest BAC. Comparative analysis between the best predictor items of the MAC and of the PDTL revealed little relationship between the item domains. The predictive trait clusters of the PDTL for men were Emotionality/Depressiveness, Impulsivity, and Low Self-Confidence, whereas predictive clusters for women included Depressiveness, Overcontrol, and Alienation.

Adult↗
PubMed1992

Motor vehicle road crashes during the fourteenth and fifteenth years of life.

From a sample of 848 teenagers, 50 individuals reported a total of 52 motor vehicle road crash events: 42 involved a car, six a motorcycle, and four a bus, over a two year period. Males and females were equally represented in each type of crash. Twenty-one of the car crashes, four of the motorcycle crashes and three of the bus crashes involved injury. The injuries sustained in the motorcycle crashes were predominantly to the extremities and in the other crashes they were mainly to the head or face. On average drivers less than 25 years of age had more passengers in their cars and were involved in more nighttime crashes. A seat belt was worn in only 18 (44%) of the car crashes. A motorcycle helmet was worn in four of the six motorcycle crashes. Six (15%) crashes were reported to have involved alcohol. The main areas of risk associated with motor vehicle road crashes involving teenagers and young adults have been addressed by legislation or the graduated drivers' licensing system. An evaluation of these measures is required to establish whether they are effective.

Accidents, Traffic↗
PubMed1992

Postmarketing surveillance of captopril for hypertension.

1. A scheme for augmented spontaneous reporting of adverse drug events using advanced view data systems was developed and applied to study 67,698 consecutive patients prescribed captopril in general practice for the treatment of hypertension. 2. Captopril was an effective hypotensive agent in this population, as only 1.9% of patients were withdrawn because of apparent inefficacy. 3. Adverse effects of captopril resulted in withdrawal of treatment in 8.9% of recipients, and such effects were more frequent in elderly and female recipients. 4. Skin reactions--usually maculopapular rashes--tended to occur early during therapy whereas cough occurred much later and was reported more frequently in non-smokers. 5. Some 1.1% of recipients died during follow-up. There was no evidence of any unusual or unexpected causes of death which might be partially or totally captopril-related in the study cohort. 6. The study confirms the feasibility of large scale postmarketing surveillance studied in general practice and allowed risk benefit assessments to be made on the use of captopril for treating hypertension.

Aged↗
PubMed1992

Local hyperthermia for prostatic disease: in vitro studies on human prostatic cancer cell lines.

Local hyperthermia for benign and malignant prostatic disease remains largely empirical. In an attempt to understand the biological action of hyperthermia, and its potentiation by antiandrogen seen in clinical practice, the interaction of the two has been studied in prostatic cancer cell lines. Human prostatic cancer cell lines LNCaP and DU 145 were studied to examine the effects of heat shock treatment (HST), androgen (5 alpha-dihydrotestosterone: 5 alpha DHT) and antiandrogen (hydroxyflutamide: OH-Flut) on cell growth and survival. Response (measured as increased DNA content) to 5 alpha DHT demonstrated that LNCaP was androgen sensitive, whereas DU 145 was androgen insensitive; OH-Flut stimulated LNCaP growth but had no effect on DU 145 growth. Thermotolerance was exhibited by DU 145 cells but not by LNCaP cells. The combination of HST followed by OH-Flut markedly reduced survival of LNCaP cells compared with HST alone. This effect was not observed in DU 145 cells. The enhanced cytotoxic effect of antiandrogen and hyperthermia could minimise the effect of thermotolerance in malignant cells surviving initial hyperthermia treatment and might suggest real clinical value for the combination or sequence.

Cell Division↗
PubMed1991

Co-victimization of African-American children who witness violence: effects on cognitive, emotional, and behavioral development.

This article reports the prevalence of violence and co-victimization among African-American youth in Chicago. Results of a violence screening survey were compiled on 1035 school children, aged 10 to 19 years. Police crime statistics are compared to illustrate the magnitude of the problem of youth and violence. Results indicate that 75% of the participating boys and 10% of participating girls had witnessed the shooting, stabbing, robbing, or killing of another person in their own lives. The survey itself did not identify the effects of co-victimization on the participants. Previous research is incorporated in the development of tentative hypotheses for intervention in public schools.

Adolescent↗
PubMed1990

Unintentional injuries to students at school.

Unintentional injuries at school have been identified as a significant public health problem. A major barrier to the development of injury prevention policy has been the absence of national data on the circumstances of injuries to students which occur at school. This study sought to determine the incidence, nature, and circumstances of injuries which resulted in death or hospitalization. Fatalities were identified from national mortality data for 1977-86 inclusive. Coroners' files were then examined to obtain details of the circumstances of injury. Hospitalization cases were identified from the national hospital discharge summary for 1986. Fifteen fatalities were identified. The circumstances of the deaths were diverse with the most frequent event being a fall (n = 4). A total of 1013 first admissions to hospital were identified, giving an overall incidence rate of 152/100,000 students/year. Injury rates declined with increasing age, and males had higher rates than females for all ages. Fractures of the upper and lower limbs and intracranial injury represented more than three-quarters of all injury. The two leading causes of injury, falls, and incidents involving striking against or being struck by a person or object, represented 89% of all incidents. The use of playground equipment and involvement in sporting activity were two of the more common aspects of many injury events. The results suggest that prevention policy should place emphasis on those in their first 2 years of schooling, falls from playground equipment, provision of protective equipment for sporting activities, sporting activities designed to minimize physical contact, establishment of standardized injury referral procedures, first-aid training, and a standardized injury reporting system.

Adolescent↗
PubMed1988

Need for victimization screening in a black psychiatric population.

Recent reports indicate that violence toward others is a major public health problem in the black community; however, there are very few empirical studies that delineate the severity of the problem. In an effort to add to the meager data on violence in the black community, the authors compiled the results of a victimization screening form obtained from a black outpatient psychiatric population. Recommendations are made that black psychiatric populations be screened for histories of victimization, as victimization is common in this population group and will have a significant impact on treatment.

Adolescent↗