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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 163 records · Page 9Linked to original sources
PubMed2001

Plasma cortisol, cortisone and urinary glucocorticoid metabolites in preterm infants.

OBJECTIVE AND METHODS: In the fetal circulation, there is a low cortisol:cortisone (F:E) ratio ( approximately 0.3) suggesting high activity of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2). The circulating F:E ratio rises after birth in term infants, but little is known about infants born prematurely. Our hypothesis was that the low fetal plasma F:E ratio would persist in infants born prematurely, due to persistently high tissue 11betaHSD2 activity. To test this hypothesis, a longitudinal observational study of plasma F, E levels and urinary F and E metabolites was performed in 22 preterm infants of 24-31 weeks gestation. RESULTS: Median plasma F was 234-380 nmol l(-1), median 124-177 nmol l(-1) from 1 to 14 days age. Plasma F fell with increasing postnatal and postconceptional age. The F:E ratio was 3 in the first week of life, and thereafter was 1-2, falling with postnatal age. Urinary glucocorticoid metabolites were low in quantity ( approximately 48-120 microg kg(-1) day(-1)), consisted of E metabolites until term, and did not reflect the plasma F:E ratio. CONCLUSIONS: The fetal plasma F:E ratio did not persist in these preterm infants, due to tenfold higher levels of F. The F:E ratios were similar to those reported in term infants. These data suggest that the low F:E ratio in utero is due to low fetal production of cortisol, and effective placental inactivation of maternal F by 11betaHSD2.

Aging↗
PubMed2001

Behavioral/environmental intervention improves learning after cerebral hypoxia-ischemia in rats.

BACKGROUND AND PURPOSE: In premature infants, many of whom experience ischemic brain insults, the environment of rearing influences cognitive outcome. We developed a model to evaluate the effect of rearing conditions on learning after unilateral cerebral hypoxia-ischemia (HI) in 7-day-old (P7) rats. We hypothesized that neonatal handling would benefit rats recovering from an episode of HI. METHODS: Seventeen litters of P7 Long-Evans rats underwent either HI (right carotid ligation followed by 1.5 hours in 8% O(2)) or control procedures. From P8 to P14, randomized litters were either handled (15 minutes of separation from dam per day) or nonhandled. After P55, learning was tested in the Morris water maze. To evaluate injury severity, hippocampal, cortical, and striatal volumes were measured. RESULTS: In water-maze performance, ANCOVA revealed an interaction between handling and severity of hippocampal damage. Among HI rats, handled rats learned faster when hippocampal damage was moderate (P<0.01, repeated-measures ANOVA), with no benefit when damage was mild or severe. CONCLUSIONS: These observations suggest the beneficial cognitive effect of neonatal handling was limited to animals with moderate damage. Neonatal handling in post-HI rats may be a useful model in which to study mechanisms underlying the benefits of post-HI developmental intervention.

Animals↗
PubMed2001

Fidelity of supported employment programs and employment outcomes.

This study attempted to identify critical components of a supported employment program that were strongly correlated with competitive employment outcomes in a state mental health system. Researchers used a supported employment fidelity scale to rate programs at ten community mental health centers in Vermont. The staff at the centers concurrently assessed competitive employment outcomes for 2,639 clients who had been diagnosed as having severe and persistent mental illness. Higher competitive employment rates were strongly correlated with overall program fidelity and with two program components, namely, providing services in the community as opposed to providing them in the clinic and using full-time employment specialists as opposed to staff with mixed roles.

Adolescent↗
PubMed2001

Patterns of hemiparesis recovery in lacunar and partial anterior circulation infarct stroke syndromes.

OBJECTIVE: To investigate patterns of hemiparesis recovery in lacunar (LACI) and partial anterior circulation infarct (PACI) stroke syndromes. DESIGN: Prospective observational study. SETTING: District general hospital and stroke rehabilitation ward. SUBJECTS: Forty-seven patients (25 LACI and 22 PACI) with a first-ever stroke causing a hemiplegia. Average age 76.4 years (range 59-88). MEASURES: Outcome measures assessed disability (Barthel Index), limb power (Motricity Index) and mobility (Rivermead Mobility Index) at baseline and 3, 6, 9, 12, 16 and 24 weeks post stroke onset. RESULTS: The time to maximum recovery, time to 50% recovery and area under the recovery curve was determined for each of the outcome measures. There were no statistical differences between these recovery parameters between the PACI and LACI stroke syndromes. CONCLUSION: Classification of hemiplegic stroke into PACI or LACI syndromes does not distinguish distinctive recovery patterns.

Aged↗
PubMed2001

Switching on and off transgene expression within lactotrophic cells in the anterior pituitary gland in vivo.

To further develop our understanding of anterior pituitary (AP) function and to aid the development of gene therapy strategies for the treatment of pituitary diseases, adenovirus (Ad)-mediated gene transfer to the AP gland will be a useful tool. Although successful widespread gene transfer within the AP has been achieved using first generation Ads the ability to control transgene expression would be very beneficial when studying AP regulatory functions and delivering a potentially therapeutic gene into the AP gland. A dual adenoviral vector system encoding for cell type-specific and regulatable transcription units was developed to achieve transcriptionally targeted transgenesis within specific cell populations in the adult AP gland. To achieve regulatable transgene expression within predetermined AP cells, the tetracycline-responsive transcriptional elements have been engineered to be under the control of human, lactotroph-specific PRL (hPRL) promoter elements within a dual adenoviral vector system. The inducibility, cell type specificity, and levels of transgene expression were characterized in vitro and in vivo and compared with the strong ubiquitous beta-actin/human cytomegalovirus (CAG) promoter. Inducible expression of the marker gene beta-galactosidase under the control of the hPRL promoter was restricted to lactotrophic tumor cell lines and lactotrophic cells within primary AP cultures. Lactotroph cell type specificity and inducible transgene expression were also observed within the AP gland in vivo, and this could be switched on or off. Administration of doxycycline abrogated transgene expression both in vitro and in vivo. Our results also provide evidence that an excess of trans-activator is needed to achieve maximal transgene expression. Our data indicate that combined transcriptional and inducible transgenesis can be achieved using adenoviral vectors that allow spatial and temporal restriction of transgene expression within the adult AP gland in vivo.

Adenoviridae↗
PubMed2001

Activation of MAPK by TRH requires clathrin-dependent endocytosis and PKC but not receptor interaction with beta-arrestin or receptor endocytosis.

To determine whether the interaction of the TRH receptor with beta-arrestin is necessary for TRH activation of MAPK, cells expressing either intact or truncated, internalization-defective TRH receptors were transfected with a beta-arrestin-green fluorescent protein conjugate. In cells expressing the wild-type pituitary TRH receptor, TRH caused translocation of the beta-arrestin-green fluorescent protein conjugate from the cytosol to the plasma membrane within 30 sec. After 5 min, the beta-arrestin-green fluorescent protein conjugate was visible in vesicles, where it colocalized with rhodamine-labeled TRH. In hypertonic sucrose, the beta-arrestin-green fluorescent protein conjugate translocated to the plasma membrane after TRH addition but did not internalize. In cells expressing the truncated TRH receptor, TRH did not cause translocation of the beta-arrestin-green fluorescent protein conjugate. TRH activated MAPK strongly in cells expressing intact or truncated TRH receptors, indicating that the receptor does not need to bind beta-arrestin or internalize. MAPK activation by TRH, epidermal growth factor, and phorbol ester was strongly inhibited by hypertonic sucrose and concanavalin A, which block movement of proteins into coated pits and coated pit assembly. Hypertonic sucrose did not affect MAPK activation in cells overexpressing MAPK kinase 1. Dominant negative dynamin, which blocks conversion of coated pits to vesicles, also reduced receptor internalization and TRH activation of MAPK. TRH activation of MAPK required PKC but was insensitive to pertussis toxin and did not require ras, epidermal growth factor receptor kinase, or PI3K. These results show that the TRH receptor itself does not need to bind beta-arrestin or undergo sequestration to activate MAPK but that the endocytic pathway must be intact.

Arrestins↗
PubMed2001

Homework in elementary physical education: a pilot study.

As physical education continues to decline in importance in the public school curriculum, it has become increasingly important for physical educators to provide opportunities for activity in nontraditional formats. This pilot study used a research design to examine the effects of homework in physical education. 607 children in Grades 3, 4, and 5 participated. Independent t tests indicated that girls participated at a higher rate than boys and that there were no significant differences among grades. A one-way analysis of variance indicated a significant difference in rate of students' participation by class. A significant difference was also noted by month of the school year.

Attitude↗
PubMed2001

CD8alpha(-) and CD8alpha(+) subclasses of dendritic cells undergo phenotypic and functional maturation in vitro and in vivo.

Dendritic cells (DCs) are essential for the priming of immune responses. This antigen-presenting function of DCs develops in sequence in a process called maturation, during which they become potent sensitizers of naïve T cells but reduce their ability to capture and process antigens. Some heterogeneity exists in mouse-DC populations, and two distinct subsets of DCs expressing high levels of CD11c can be identified on the basis of CD8alpha expression. We have studied the phenotype and maturation state of mouse splenic CD8alpha(-) and CD8alpha(+) DCs. Both subsets were found to reside in the spleen as immature cells and to undergo a phenotypic maturation upon culture in vitro in GM-CSF-containing medium or in vivo in response to lipopolysaccharide. In vitro and in vivo analyses showed that this maturation process is an absolute requisite for DCs to acquire their T-cell priming capacity, transforming CD8alpha(-) and CD8alpha(+) DCs into potent and equally efficient activators of naïve CD4(+) and CD8(+) T cells. Furthermore, these results highlight the importance that environmental factors may have on the ability of DC subsets to influence Th responses qualitatively; i.e., the ability to drive Th1 versus Th2 differentiation may not be fixed immutably for each DC subset.

Adoptive Transfer↗
PubMed2001

The initial attitudes of patients toward longer maintenance hemodialysis.

UNLABELLED: Longer hemodialysis (HD) as practiced in parts of Europe and Japan may improve both blood pressure control and patient survival. Nevertheless, in the USA, the trend has been to shorten dialysis time using larger dialyzers and increased blood flows. Many patients find the notion of shorter dialysis enticing. Most are unaware ofthe potential benefits of longer dialysis. We surveyed stable chronic HD patients in an urban area, the vast majority of whom received conventional 4-hour treatments, regarding their attitude toward extending their dialysis time to 5 hours. They were informed that longer dialysis has been associated with better blood pressure control and improved survival. One hundred and sixteen patients completed questionnaires during a single dialysis session. Forty-six (40%) agreed to extended dialysis while 70 (60%) did not. There was no difference between the groups with respect to the following variables: age, race, etiology of ESRD, time on dialysis, marital status, number of children at home, number residing in the household, education, or employment status. Male gender was associated with a positive response (p = 0.03). Various suggested and spontaneous reasons were given for a negative response. CONCLUSION: With minimally detailed information, 4 in 10 patients were willing to extend their treatment time to 5 hours in the hope of improving morbidity and survival. No sociodemographic variable except gender was associated with a positive response.

Adult↗
PubMed2001

A call for help.

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Black or African American↗