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Biomedical subjects

S Davidson

Publications and source records attributed to S Davidson.

At least 19 recordsLinked to original sources
PubMed2006

A remote and highly conserved enhancer supports amygdala specific expression of the gene encoding the anxiogenic neuropeptide substance-P.

The neuropeptide substance P (SP), encoded by the preprotachykinin-A (PPTA) gene, is expressed in the central and medial amygdaloid nucleus, where it plays a critical role in modulating fear and anxiety related behaviour. Determining the regulatory systems that support PPTA expression in the amygdala may provide important insights into the causes of depression and anxiety related disorders and will provide avenues for the development of novel therapies. In order to identify the tissue specific regulatory element responsible for supporting expression of the PPTA gene in the amygdala, we used long-range comparative genomics in combination with transgenic analysis and immunohistochemistry. By comparing human and chicken genomes, it was possible to detect and characterise a highly conserved long-range enhancer that supported tissue specific expression in SP expressing cells of the medial and central amygdaloid bodies (ECR1; 158.5 kb 5' of human PPTA ORF). Further bioinformatic analysis using the TRANSFAC database indicated that the ECR1 element contained multiple and highly conserved consensus binding sequences of transcription factors (TFs) such as MEIS1. The results of immunohistochemical analysis of transgenic lines were consistent with the hypothesis that the MEIS1 TF interacts with and maintains ECR1 activity in the central amygdala in vivo. The discovery of ECR1 and the in vivo functional relationship with MEIS1 inferred by our studies suggests a mechanism to the regulatory systems that control PPTA expression in the amygdala. Uncovering these mechanisms may play an important role in the future development of tissue specific therapies for the treatment of anxiety and depression.

Amygdala↗
PubMed2006

Leptin, insulin, insulin-like growth factors and their binding proteins in cord serum: insight into fetal growth and discordancy.

OBJECTIVE: Singleton infants with intrauterine growth restriction have an adaptive hormonal profile characterized by decreased levels of IGF-1, IGF-2, IGFBP-3 and insulin and elevated levels of IGFBP-1 and IGFBP-2. This study examined the association between cord serum levels of six growth factors and anthropometric features at birth in twins in order to determine the intrauterine growth factor interactions and to characterize the specific hormonal profile of small discordant twins. DESIGN: Prevalent case-control study. PATIENTS: Twenty pairs of discordant twins (5 monozygotic, 15 dizygotic) and 20 pairs of concordant twins (6 monozygotic, 14 dizygotic) matched for gestational age. MEASUREMENTS: Cord blood levels of IGF-1, IGF-2, IGFBP-1, IGFBP-3, insulin, leptin and anthropometric measurements at birth. Intra- and inter-pair differences and correlation coefficients were calculated, and the data were fitted to multivariate regression models. RESULTS: In both discordant and concordant groups, the smaller twins had a significantly lower level of IGF-1 (P < 0.03) and significantly higher level of IGFBP-1 (P < 0.02) than their larger cotwins. IGFBP-1 was inversely correlated with IGF-1 (P < 0.05). Insulin levels were significantly higher in the smaller discordant than the smaller concordant twins (P < 0.001) and in the larger discordant than the larger concordant twins (P < 0.004). Among the monozygotic twins, the leptin level was significantly higher in the larger discordant than the larger concordant twins (P < 0.025). Percentage birth weight discordancy was statistically correlated with twin-pair differences in IGF-1 and IGFBP-1. CONCLUSIONS: Of the six factors studied, IGF-1 appears to be the main indicator of intrauterine growth. Twin discordancy may involve compensatory rather than adaptive mechanisms or a multihormone relative resistance syndrome.

Birth Weight↗
PubMed2005

Cardioprotection mediated by urocortin is dependent on PKCepsilon activation.

Urocortin (Ucn) is an endogenous cardioprotective agent that protects against the damaging effects of ischemia and reperfusion injury in vitro and in vivo. We have found that the mechanism of action of Ucn involves both acute activation of specific target molecules, and using Affymetrix (Santa Clara, CA) gene chip technology, altered gene expression of different end effector molecules. Here, from our gene chip data, we show that after a 24 h exposure to Ucn, there was a specific increase in mRNA and protein levels of the protein kinase C epsilon (PKCepsilon) isozyme in primary rat cardiomyocytes compared with untreated cells and in the Langendorff perfused ex vivo heart. Furthermore, a short 10 min exposure of these cells to Ucn caused a specific translocation/activation of PKCepsilon in vitro and in the Langendorff perfused ex vivo heart. The importance of the PKCepsilon isozyme in cardioprotection and its relationship to cardioprotection produced by Ucn was assessed using PKCepsilon-specific inhibitor peptides. The inhibitor peptide, when introduced into cardiomyocytes, caused an increase in apoptotic cell death compared with control peptide after ischemia and reperfusion. When the inhibitor peptide was present with Ucn, the cardioprotective effect of Ucn was lost. This loss of cardioprotection by Ucn was also seen in whole hearts from PKCepsilon knockout mice. These findings indicate that the cardioprotective effect of Ucn is dependent upon PKCepsilon.

Animals↗
PubMed2005

Technical note: technique for dissection and analysis of the rumen in young calves.

This paper discusses a technique used to evaluate rumen development in young calves, including removal, dissection, and analysis of tissue. The method allowed for examination of the different sacs of the rumen (dorsal, ventral, cranial, and caudal) using scanning electron microscopy to measure papillae denseness and histology slides to measure papillae length and width. Computer software was used to produce accurate measurements of papillae. The rumens of young calves were dissected, and samples were taken from the cranial, caudal, ventral, and dorsal sections. Calves were part of a nutrition research study, and dietary treatments did have an effect on development measurements such as length, width, and papillae denseness.

Animal Nutritional Physiological Phenomena↗
PubMed2004

Clinical characteristics of 110 miliary tuberculosis patients from a low HIV prevalence country.

SETTING: A university teaching hospital in Karachi, Pakistan. OBJECTIVE: To define the clinical characteristics and outcome of miliary tuberculosis (TB) patients from a low human immunodeficiency virus (HIV) prevalence country. DESIGN: Review of adult miliary TB patients admitted between 1994 and 2001. Clinical characteristics of those dying from miliary TB were compared with those of the survivors. RESULTS: Most of the 110 cases reviewed were middle aged or elderly, with a female preponderance. An underlying medical condition was present in 47%. Presenting symptoms were of several weeks' duration, and mostly constitutional (fever and weight loss). Common laboratory findings included anaemia (62%), lymphopaenia (71%), hyponatraemia (74%), elevated serum alkaline phosphatase (57%) and hypoalbuminaemia (92%). Typical miliary pattern was observed in 77% of radiographs. Sputum smear and culture were positive in respectively 36% and 52% of those tested. Biopsy was performed in selected patients. Mean hospital stay was 8.8 days, and mortality was 30%. Those who died were significantly older than survivors and had a more fulminant course. Presence of altered mental status, lung crackles, leucocytosis, thrombocytopaenia and the need for ventilation were associated with increased mortality. CONCLUSION: Miliary TB carries a high mortality. It should be considered in patients who present with prolonged systemic symptoms. A positive TB culture or biopsy is needed to establish a diagnosis.

Adolescent↗
PubMed2003

Neurobehavioral and autonomic effects of hammock positioning in infants with very low birth weight.

PURPOSE: This study was designed to determine whether supine positioning of infants born preterm in a hammock instead of the prone position affects their neuromuscular maturity, growth, and autonomic stability. METHODS: Twenty healthy infants who were born premature with very low birth weight (VLBW) (<1500 g) were randomized into two groups. Subjects were pair-matched for weight (difference less than 100 g), gestational age (difference less than eight days), and postnatal age (difference less than eight days). Ten infants were placed supine in a hammock for three hours daily for ten consecutive days, and ten infants were maintained nested in the prone position. Neuromuscular maturity (based on three neurological parameters adopted from the Ballard examination), heart rate, respiratory rate, and weight gain (g/cal) were compared between the groups. RESULTS: Compared with nested prone positioning, supine positioning in a hammock was associated with a higher neuromuscular maturity score (p < 0.003) and a more relaxed condition, as expressed by lower heart rate and respiratory rate (p < 0.05 and p < 0.01, respectively). CONCLUSIONS: Maintaining infants who were born preterm with VLBW in the supine position in a hammock may positively affect their autonomic stability and neuromuscular maturity.

Journal Article↗
PubMed2003

Effects of amounts and degradability of dietary protein on lactation, nitrogen utilization, and excretion in early lactation Holstein cows.

Five treatment diets varying in crude protein (CP) and rumen undegradable protein (RUP) were calculated to supply a postruminal lysine to methionine ratio of about 3:1. Diets were fed as a total mixed ration to 65 Holstein cows that were either primiparous (n = 28) or multiparous (n = 37) from 21 to 120 d in milk to determine effects on lactation and nitrogen utilization. Crude protein % and calculated RUP (% of CP) of diets [on a dry matter (DM) basis] were: 1) 19.4, 40 (HPMU), 2) 16.5, 34 (LPLU), 3) 16.8, 40 (LPMU), 4) 16.8, 46 (LPHU), 5) 17.2, 43 (LPHU + UREA), which is the result of adding 0.4% of the diet DM as urea to LPHU. The corn silage-based treatment diets contained an average of 24% acid detergent fiber and 1.6 Mcal/kg net energy of lactation. Milk urea nitrogen (MUN) concentrations and body weights (BW) were used to calculate predicted amounts of urinary nitrogen (N) using the relationship: urinary N (g/d) = 0.0259 x BW (kg) x MUN (mg/dl). Cows fed HPMU had greater CP and RUP intakes, which resulted in higher concentrations of plasma urea nitrogen, rumen ammonia, MUN, and predicted urinary N. Milk yield, fat yield, fat percent, protein yield, and protein percent were not significantly different among treatments. Parity primarily affected parameters that were related to body size and not measurements of N utilization. The interaction of treatment and parity was not significant for any measurements taken. In this study, cows fed LPHU had significantly lower MUN and predicted urinary N without limiting production. These results demonstrate the potential to optimize milk production while minimizing N excretion in lactating dairy cattle.

Ammonia↗
PubMed2001

Detection of Leishmania infantum by PCR, serology and cellular immune response in a cohort study of Brazilian dogs.

The sensitivity and specificity of PCR, serology (ELISA) and lymphoproliferative response to Leishmania antigen for the detection of Leishmania infantum infection were evaluated in a cohort of 126 dogs exposed to natural infection in Brazil. For PCR, Leishmania DNA from bone-marrow was amplified with both minicircle and ribosomal primers. The infection status and time of infection of each dog were estimated from longitudinal data. The sensitivity of PCR in parasite-positive samples was 98%. However, the overall sensitivity of PCR in post-infection samples, from dogs with confirmed infection, was only 68%. The sensitivity of PCR varied during the course of infection, being highest (78-88%) 0-135 days post-infection and declining to around 50% after 300 days. The sensitivity of PCR also varied between dogs, and was highest in sick dogs. The sensitivity of serology was similar in parasite-positive (84%), PCR-positive (86%) and post-infection (88%) samples. The sensitivity of serology varied during the course of infection, being lowest at the time of infection and high (93-100%) thereafter. Problems in determining the specificity of serology are discussed. The sensitivity and specificity of cellular responsiveness were low. These data suggest that PCR is most useful in detecting active or symptomatic infection, and that serology can be a more sensitive technique for the detection of all infected dogs.

Animals↗
PubMed2001

Risk factors for HIV/AIDS and hepatitis C among the chronic mentally ill.

OBJECTIVE: The objective of this study was to document the prevalence of risk factors for HIV/AIDS and hepatitis C among people with chronic mental illness treated in a community setting. METHOD: 234 patients attending four community mental health clinics in the North-western Health Care Network in Melbourne, Australia, completed an interviewer-administered questionnaire which covered demographics, risk behaviour and psychiatric diagnosis. RESULTS: The sample was 58% male, and 79% of the sample had a primary diagnosis of schizophrenia. Forty-three per cent of mentally ill men and 51% of mentally ill women in the survey had been sexually active in the 12 months preceding the survey. One-fifth of mentally ill men and 57% of mentally ill women who had sex with casual partners never used condoms. People with mental illness were eight times more likely than the general population to have ever injected illicit drugs and the mentally ill had a lifetime prevalence of sharing needles of 7.4%. CONCLUSIONS: The prevalence of risk behaviours among the study group indicate that people with chronic mental illness should be regarded as a high-risk group for HIV/AIDS and hepatitis C. It is essential that adequate resources and strategies are targeted to the mentally ill as they are for other high-risk groups.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Cardiovascular risk factors for people with mental illness.

OBJECTIVE: The objective of this study was to document the prevalence of risk factors for cardiovascular disease among people with chronic mental illness. METHOD: A cross-sectional survey was conducted of 234 outpatients attending a community mental health clinic in the North-western Health Care Network in Melbourne, Australia. Prevalence of smoking, alcohol consumption, body mass index, hypertension, salt intake, exercise and history of hypercholesterolemia was assessed. RESULTS: Compared with a community sample, the mentally ill had a higher prevalence of smoking, overweight and obesity, lack of moderate exercise, harmful levels of alcohol consumption and salt intake. No differences were found on hypertension. Men, but not women, with mental illness were less likely to undertake cholesterol screening. CONCLUSIONS: Psychiatric outpatients have a high prevalence of cardiovascular risk factors which may account for the higher rate of cardiovascular mortality among the mentally ill. Further research is needed to trial and evaluate interventions to effectively modify risk factors in this vulnerable population.

Adolescent↗
PubMed2001

Suicidal children and adolescents with first emergency room presentations: predictors of six-month outcome.

OBJECTIVE: To examine risk of future documented suicide attempts and emergency room (ER) returns among children and adolescents with first suicidal ER presentations. METHOD: A total of 548 consecutive ER presentations of suicidal 5- to 19-year-olds to a Canadian center over a 1-year period (1997-1998) were reviewed. Relative risk analyses were performed on 224 first-time patients (mean age 14.6+/-2.1) to determine the strength of associations between predictors and outcomes (ER return and suicide attempts). RESULTS: At 6-month follow-up, 32.6% (n = 73) had returned to the ER, 24.1% (n = 54) had a documented suicide attempt, and 14.3% (n = 32) required psychiatric hospitalization. Predictors for both ER return and future documented suicide attempts included 15- to 19-year age range, past foster/group home placement, past mental health care, a suicide plan, reported mood symptoms, sobriety at ER visit, and general substance use. Child welfare guardianship and abuse history were also predictors of ER returns. CONCLUSIONS: Clinicians should be aware of these risk factors when assessing and managing suicidal youths with first ER presentations.

Adolescent↗
PubMed2001

Insulin, insulin-like growth factors-I and -II and insulin-like growth factor binding protein-3 in newborn serum: association with normal fetal head growth and head circumference.

The insulin-like growth factors (IGF) and their binding proteins (IGFBP) have been implicated in the regulation of fetal weight and length. The aim of our study was to determine the relationship between head circumference at birth and serum levels of IGF-I, IGF-II, IGFBP-3 and insulin in full-term appropriate-for-gestational age (AGA) infants. Serum samples were obtained from 77 singleton full-term neonates, 69 AGA and 8 small-for-gestational age (SGA). The AGA infants were divided into three groups by head circumference: Group 1: < or = 3rd percentile; Group 2: at 50th percentile; Group 3: > or = 97th percentile. Serum levels of IGF-I, IGF-II, IGFBP-3 and insulin were determined with commercial kits and immunometric methods. There were no statistically significant differences in mean serum levels of IGF-I, IGF-II and IGFBP-3 between the groups. A significantly higher mean serum insulin level was noted in the AGA infants with a head circumference > or = 97th percentile compared to those with a head circumference < or = 3rd percentile (4.6 +/- 0.3 vs 3.3 +/- 0.6 microU/ml; p = 0.04), and in AGA infants with a head circumference above the 50th percentile compared to those with a head circumference below the 50th percentile (4.4 +/- 0.4 vs 3.3 +/- 0.3 microU/ml; p = 0.01). AGA infants with a head circumference above or below the 50th percentile did not differ statistically in their mean IGF-II and IGFBP-3 serum level, while IGF-I differed statistically between the groups (18 +/- 2.7 vs 11.6 +/- 1.6 ng/ml, respectively; p = 0.045). Using univariate analysis, head circumference correlated positively with insulin (r = 0.29; p = 0.016) and with IGF-I (r = 0.26; p = 0.03). A stepwise multivariate linear regression analysis, however, did show statistically significant correlation of head circumference with birth weight (f = 36; p = 0.0001), and only marginally with birth length (f = 4.7; p = 0.06) and insulin (f = 3.4; p = 0.07). No correlations were found between head circumference and IGF-I, IGF-II or IGFBP-3. These data suggest that apart from genetic and nutritional factors, insulin may play a role in promoting intrauterine head growth, as reflected by head circumference at birth.

Cohort Studies↗
PubMed2001

Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix.

Hypoxic tumors are known to be more malignant, to be more likely to metastasize, and to have a poor prognosis. They are also radio- and chemoresistant. For this reason, it is desirable that a clinically useful marker of hypoxia is found, so that treatment with radiotherapy and bioreductive chemotherapy can be rationally applied to individual patients. Glut-1 is a facilitative glucose transporter that is ubiquitously expressed in normal tissue and expressed at higher levels in a number of tumors. Its potential as an intrinsic hypoxia marker arises from its dual control in hypoxic conditions by reduced oxidative phosphorylation and the hypoxia-inducible factor (HIF-1) oxygen-sensing pathway. Eppendorf histography, by virtue of its proven predictive qualities, is a suitable gold standard used in our laboratory to validate new hypoxia markers. Using this technique, pretreatment pO(2) measurements were performed on 54 patients with locally advanced cervical carcinoma. Then, immunohistochemical staining was used to detect Glut-1 protein in individual tumor biopsy sections. Both measurements were made before initiation of treatment. By using a low-tech scoring system, pO(2) was found to correlate weakly with Glut-1 score (r = 0.28; P = 0.04). To extrapolate this correlation to the known adverse effects of tumor hypoxia on outcome, we examined the prognostic significance of Glut-1 staining in a retrospective series of 121 patients. An absence of Glut-1 significantly increased the likelihood of metastasis-free survival (P = 0.022) but did not significantly effect disease-free or recurrence-free survival. These findings suggest that Glut-1 be an intrinsic marker of hypoxia that can easily be applied in a clinical setting.

Biomarkers, Tumor↗