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Biomedical subjects

A J Davidson

Publications and source records attributed to A J Davidson.

At least 19 recordsLinked to original sources
PubMed2003

The dystrophin associated protein complex in zebrafish.

Many cases of muscular dystrophy in humans are caused by mutations in members of the dystrophin associated protein complex (DAPC). Zebrafish are small vertebrates whose bodies are composed predominantly of skeletal muscle, making them attractive models for studying mammalian muscle disorders. Potential orthologs to most of the human DAPC proteins have been found in zebrafish by database screening. Expression of the sarcoglycans, dystroglycan and dystrophin has been confirmed by western blotting. Immunohistochemical and biochemical techniques localize these proteins to the muscle cell membrane in adult zebrafish. Morpholino (MO) experiments designed to inhibit the translation of dystrophin mRNA produce juvenile zebrafish that are less active than zebrafish injected with control morpholinos. Western blot analysis of the dystrophin morpholino-injected zebrafish shows concurrent reduction of dystrophin and the sarcoglycans, suggesting that these proteins, like those in mammals, are part of a complex whose integrity is dependent on dystrophin expression. These results indicate that the zebrafish is an excellent animal model in which to approach the study of dystrophin and its associated proteins.

Amino Acid Sequence↗
PubMed2003

Is the food-entrainable circadian oscillator in the digestive system?

Food-anticipatory activity (FAA) is the increase in locomotion and core body temperature that precedes a daily scheduled meal. It is driven by a circadian oscillator but is independent of the suprachiasmatic nuclei. Recent results that reveal meal-entrained clock gene expression in rat and mouse peripheral organs raise the intriguing possibility that the digestive system is the site of the feeding-entrained oscillator (FEO) that underlies FAA. We tested this possibility by comparing FAA and Per1 rhythmicity in the digestive system of the Per1-luciferase transgenic rat. First, rats were entrained to daytime restricted feeding (RF, 10 days), then fed ad libitum (AL, 10 days), then food deprived (FD, 2 days). As expected FAA was evident during RF and disappeared during subsequent AL feeding, but returned at the correct phase during deprivation. The phase of Per1 in liver, stomach and colon shifted from a nocturnal to a diurnal peak during RF, but shifted back to nocturnal phase during the subsequent AL and remained nocturnal during food deprivation periods. Second, rats were entrained to two daily meals at zeitgeber time (ZT) 0400 and ZT 1600. FAA to both meals emerged after about 10days of dual RF. However, all tissues studied (all five liver lobes, esophagus, antral stomach, body of stomach, colon) showed entrainment consistent with only the night-time meal. These two results are inconsistent with the hypothesis that FAA arises as an output of rhythms in the gastrointestinal (GI) system. The results also highlight an interesting diversity among peripheral oscillators in their ability to entrain to meals and the direction of the phase shift after RF ends.

Animals↗
PubMed2002

Flexoelectric switching in a bistable nematic device.

We present a continuum theory model of switching in a bistable nematic liquid crystal device. The bistability of the device investigated relies on the fact that one of the cell surfaces exhibits two stable anchoring states, that is, two surface director orientations are locally stable. Since the other surface exhibits monostable, homeotropic anchoring there are two possible ground state director orientations within the cell, depending on the director orientation at the bistable surface. We first investigate the stability of these base states and find a critical surface anchoring strength below which only one of the states is stable. We also investigate the process of switching between the two stable states through the application of an electric field and the presence of a flexoelectric polarization. At high field strengths the dielectric interaction with the applied field will dominate the flexoelectric effect and may hinder switching. We find, therefore, that a window of possible field strengths exists within which switching occurs.

Journal Article↗
PubMed2002

Cytokine mRNA expression pattern in horses with large intestinal disease.

The aim of this study was to investigate cytokine expression patterns in the large intestinal mucosa of horses, particularly in diseases associated with inflammation. Many cases of equine colitis remain without a definitive diagnosis and survival rates are poor. In humans, colitis is associated with increased expression of pro-inflammatory cytokines. To examine if similar responses occur in horses, we investigated il -2, il -4, il -5, il -10, tnfalpha, ifngamma and tgfbeta messenger rna expression in large intestinal mucosa. Samples were obtained from animals with large intestinal disease (n=15) or from horses which had different levels of cyathostomin infection (n=9) and analysed by reverse transcription-polymerase chain reaction. il -2 was detected at all sites, whilst il -4 was detected at all but one site. The presence of il -10, il -5, ifngamma and tgfbeta varied with no significant differences amongst groups (P>0.4). Detection of tnfalpha was significantly different between the group of horses that had infiltrative inflammatory bowel disease and those with larval cyathostominosis (P=0.028) and those that were helminth negative (P=0.014). These results indicate a possible role for tnfalpha in the pathogenesis of equine infiltrative inflammatory bowel disease.

Animals↗
PubMed2001

Glycemic control in English- vs Spanish-speaking Hispanic patients with type 2 diabetes mellitus.

BACKGROUND: Hispanic individuals compose the fastest growing minority group in the United States, yet little is known about how language impacts their health care. The primary objective of this study was to determine whether the inability to speak English adversely affected glycemic control in Hispanic patients with type 2 diabetes mellitus. METHODS: This retrospective cohort study selected 183 Hispanic patients with type 2 diabetes mellitus aged 35 to 70 years from a public health care system; patients were Spanish-speaking (SS) only, and control patients were English-speaking (ES) or bilingual. Clinical information was collected via telephone survey, and data on health care use, diagnosis, and glycosylated hemoglobin A(1c) (HbA(1c)) values were obtained from administrative and laboratory information systems. RESULTS: Values of HbA(1c) for SS (mean, 9.1%; range, 5.0%-15.3%) and ES (mean, 9.0%; range, 4.9%-16.2%) patients with diabetes mellitus and the total number of hospitalizations related and unrelated to diabetes mellitus did not differ (P =.86). Spanish-speaking patients had a diagnosis of diabetes mellitus for fewer years than ES patients (8.2 and 11.2 years, respectively; P =. 01). Spanish-speaking patients were less likely to understand their prescriptions; 22% of SS patients reported no comprehension vs 3% of ES patients (P =.001). There was a trend toward decreased prevalence of insulin use among SS patients compared with ES patients (30% vs 42%, respectively; P =.07). CONCLUSIONS: Glycemic control in Hispanic patients was not related to their ability to speak English. This finding may be explained by a high degree of language concordance between patients and providers.

Adult↗
PubMed2001

Molecular cloning of a human Vent-like homeobox gene.

We have isolated a previously unknown human homeobox-containing cDNA, VENT-like homeobox-2 (VENTX2), using PCR with a bone marrow cDNA library and primers designed from the VENTX1 (alias HPX42) homeobox sequence. Here we describe the molecular cloning, chromosomal localization to 10q26.3, and functional analysis of this gene. The 2.4-kb human VENTX2 cDNA encoded a protein with a predicted molecular weight of 28 kDa containing a homeodomain with 65% identity to the Xenopus laevis ventralizing gene Xvent2B. VENTX2 antisera detected a 28-kDa protein in cells transfected with a VENTX2 expression construct, in a human erythroleukemic cell line and in bone marrow samples obtained from patients in recovery phase after chemotherapy. The similarity of the homeodomains from VENTX2 and the X. laevis Vent gene family places them in the same homeodomain class. Consistent with this structural classification, overexpression of VENTX2 in zebrafish embryos led to anterior truncations and failure to form a notochord, which are characteristics of ventralization.

Amino Acid Sequence↗
PubMed2001

Immunisation of cattle with recombinant acetylcholinesterase from Dictyocaulus viviparus and with adult worm ES products.

Dictyocaulus viviparus causes a serious lung disease of cattle. For over 30 years, a radiation-attenuated larval vaccine has been used with success; however, this vaccine has several disadvantages. A more stable vaccine against D. viviparus, capable of stimulating prolonged protective immunity, would be beneficial. Recent research has been directed at adult worm ES components that may be involved in parasite survival in the host. One component is the secreted enzyme, acetylcholinesterase (AChE), a target for circulating antibody in infected calves. Here, we describe a study where protection was investigated in calves immunised with either native adult ES products or a recombinant parasite AChE. These antigens were administered twice with Freund's incomplete adjuvant. Subsequently, all calves were challenged with 700 L3 and their worm burdens and immune responses compared with those in calves that received an anthelmintic-abbreviated infection and challenge control calves. Significant levels of protection were not obtained in the immunised groups but significant immunity was achieved in the calves that received the anthelmintic abbreviated infection. Antibody responses amongst the groups were different, with significantly higher IgG1 responses in the immune, infected group and in adult ES recipients. Significantly higher IgG2 responses were found in the latter group. Following challenge, the groups that received the abbreviated infection and the fusion protein produced specific antibody that bound the native enzyme. No differences were observed between groups in peripheral blood mononuclear cell responsiveness to either antigen. However, adult ES products appeared to have a mitogenic effect on these cells, whilst the fusion protein exhibited an inhibitory effect. These results suggest that in this form, AChE is not a potential vaccine candidate and that adult ES products, in contrast to previous experiments in guinea pigs, do not contain protective components.

Acetylcholinesterase↗
PubMed2001

Food-anticipatory activity persists after olfactory bulb ablation in the rat.

Restricted daily food access acts as an entraining stimulus (zeitgeber) for a circadian clock, the feeding-entrainable oscillator (FEO). There are many properties of a daily meal that could potentially convey timing information to the FEO. Olfactory cues associated with feeding are one such property. In order to rule out olfaction as a necessary entraining stimulus, olfactory bulbectomized and sham-operated male Sprague--Dawley rats had access to food for 2 h each day. Food bin approach behavior was monitored as an index of food-anticipatory activity (FAA). Both groups entrained to the daily meal with an increase in feeder approach time several hours before meal onset. There were no significant differences in the timing or the amount of FAA between groups. Furthermore, FAA was maintained during 3 days of food deprivation in both groups. In accordance with previous studies, the results show that olfactory cues are not necessary for the entrainment of FAA.

Animals↗
PubMed2001

Persistence of meal-entrained circadian rhythms following area postrema lesions in the rat.

Rats anticipate daily meals with increased approaches to a feeder and an increase in core body temperature. Food-anticipatory activity (FAA) is thought to be under the control of a feeding-entrained circadian oscillator (FEO). Ibotenic acid and electrolytic lesions in the region of the parabrachial nuclei (PBN) in the rat severely disrupt FAA (feeder approaches) and temperature rhythms. The PBN receive dense input from the area postrema (AP), which lacks a blood-brain barrier and thus has access to humoral factors in the systemic circulation. The present study assesses development and maintenance of FAA in rats with cautery lesions of the AP. The results demonstrate that AP lesions do not alter FAA. This experiment does not support the hypothesis that the AP in the caudal brainstem detects and relays circulating signals from the periphery that trigger FAA.

Animals↗
PubMed2001

Use of the Bispectral Index monitor to aid titration of propofol during a drug-assisted interview.

We report two drug-assisted interviews with propofol in an 18-year-old with the diagnosis of Complex Regional Pain Syndrome type 1. We describe difficulty in titration of propofol in the first interview. Consequently, in the second interview, the Bispectral Index (BIS) monitor was applied to assist adjustment of the propofol infusion. This facilitated the achievement of a prolonged sedative-hypnotic state for a successful neuropsychological evaluation. Pertinent information was obtained from this patient. However, the role of drug-assisted interviews as a technique needs to be further elucidated.

Adolescent↗
PubMed2001

The differences in the bispectral index between infants and children during emergence from anesthesia after circumcision surgery.

UNLABELLED: The bispectral index (BIS) correlates with consciousness during adult anesthesia. In this prospective, blinded study of children (n = 24) and infants (n = 25) undergoing elective circumcision, we evaluated BIS and consciousness level during emergence from anesthesia. Anesthesia was maintained with sevoflurane, and a penile nerve block was performed in each patient before surgical stimulation. At the completion of surgery, the sevoflurane was decreased stepwise from 0.9% in increments of 0.2%, and arousal was tested with a uniform auditory stimulus given after a steady state of end-tidal sevoflurane concentration was achieved at each step. The BIS increased significantly as the sevoflurane concentrations decreased in children (0.9%, 62.5 +/- 8.1; 0.7%, 70.8 +/- 7.4; and 0.5%, 74.1 +/- 7.1; P < 0.001 for 0.7% and 0.5% compared with 0.9%), but a similar relationship was not demonstrated in infants. The BIS values at 0.7% and 0.5% sevoflurane were significantly higher in children than infants (P < 0.02 and P < 0.002, respectively). In both children and infants, the BIS increased significantly from pre- to postarousal (children, 73.5 +/- 7 to 83.1 +/- 12, P = 0.01; infants, 67.8 +/- 10 to 85.6 +/- 13.6, P < 0.001). The BIS at which arousal was possible with the stimulus tended to be higher in children than in infants (P = 0.06). IMPLICATIONS: In this study comparing the Bispectral index (BIS) in infants and children undergoing circumcision surgery by use of a standardized surgical and anesthetic technique, a significant decrease in BIS was detected in children during a stepwise decrease in end-tidal sevoflurane concentration. A similar relationship was not demonstrated in infants less than 1 yr old. In both children and infants, BIS increased significantly from pre- to postarousal. Additional studies are necessary to determine changes in BIS with maturational changes in the electroencephalogram.

Adolescent↗
PubMed2001

The association of foster care or kinship care with adolescent sexual behavior and first pregnancy.

OBJECTIVE: Each year more than 500 000 children enter out-of-home placement. Few outcome studies of these children specifically address high-risk sexual behavior and adolescent pregnancy. Our study investigated the relationship between living in kinship or foster care and high-risk reproductive behaviors in a nationally representative sample of women. METHODS: Data from 9620 women ages 15 to 44 years in the 1995 National Survey of Family Growth were analyzed in a cross-sectional study. Three groups-foster (n = 89), kinship (n = 513), and comparison (n = 9018)-were identified on the basis of self-reported childhood living situations. Bivariate and multiple linear regression analyses were performed. The outcome variables were age at first sexual intercourse and at first conception and the number of sexual partners. RESULTS: After adjustment for multiple predictor variables, foster care was associated with younger age at first conception (difference: 11.3 months) and having greater than the median number of sexual partners (odds ratio: 1.7, 1.0-2.8). Kinship care was associated with younger age both at first intercourse (difference = 6 months) and at first conception (difference: 8.6 months) and having greater than the median number of sexual partners (odds ratio: 1.4, 1.1-1.8). There were no differences between the kinship and foster groups. CONCLUSIONS: A history of living in either foster or kinship care is a marker for high-risk sexual behaviors, and the risk is comparable in both out-of-home living arrangements. Recognition of these risks may enable health care providers to intervene with high-risk youth to prevent early initiation of sexual intercourse and early pregnancy.

Adolescent↗
PubMed2000

Epidemiology of Pneumocystis carinii pneumonia in an era of effective prophylaxis: the relative contribution of non-adherence and drug failure.

OBJECTIVE: To determine the relative contribution of patient non-adherence, provider failure to prescribe prophylaxis, and drug failure to the continued occurrence of Pneumocystis carinii pneumonia (PCP), and to determine correlates of non-adherence. DESIGN: Retrospective case-control study. METHODS: Patients with confirmed or presumptive PCP from May 1995 to September 1997 who had at least 6 months of prior HIV care (cases) were compared to controls matched for initial CD4 cell count and date of initial HIV care. RESULTS: The incidence of PCP declined by 85% in the 28 months of the study. Of the 118 cases of PCP identified, 59 (50%) were in HIV care for > 6 months prior to PCP diagnosis. In a multivariate logistic regression model, risk factors for PCP among patients in HIV care were patient non-adherence [odds ratio (OR), 12.4; 95% confidence interval (CI), 6.4-23.5], use of prophylaxis other than trimethoprim-sulfamethoxazole (OR, 27.0; 95% CI, 13.8-52.9), and absence of antiretroviral use (OR, 7.5; 95% CI, 4.5-12.5). Provider non-adherence occurred in one out of 59 cases (2%), and five out of 106 controls (5%). Of the patients who developed PCP on prophylaxis, 18 cases (30%) appeared due to drug failure; there were no cases of apparent drug failure among patients on trimethoprim-sulfamethoxazole. In multivariate analysis, non-adherence was more common among patients of non-white race, those with a history of injecting drug use, and those with active substance abuse or psychiatric illness. CONCLUSIONS: Patient non-adherence was the most common reason for the occurrence of PCP among patients in HIV care; provider non-adherence was uncommon. Drug failure occurred only among patients on prophylaxis other than trimethoprim-sulfamethoxazole.

AIDS-Related Opportunistic Infections↗
PubMed2000

Turning mesoderm into blood: the formation of hematopoietic stem cells during embryogenesis.

The formation of hematopoietic stem cells during development occurs by a multistep process that begins with the induction of ventral mesoderm. This mesoderm is patterned during gastrulation by a bone morphogenetic protein (BMP) signaling pathway that is mediated, at least in part, by members of the Mix and Vent families of homeobox transcription factors. Following gastrulation, a subset of ventral mesoderm is specified to become hematopoietic stem cells. Key determinants of hematopoietic fate include the product of the zebrafish cloche gene and the basic helix-loop-helix transcription factor SCL. Future studies in Xenopus and zebrafish should reveal other critical factors in this developmental pathway.

Animals↗
PubMed2000

The extent of undiagnosed HIV infection among emergency department patients: results of a blinded seroprevalence survey and a pilot HIV testing program.

This study was performed to determine the rate of previously undiagnosed HIV infection among patients presenting to an urban emergency department (ED) and to assess the feasibility of routinely offering voluntary HIV testing in this setting. HIV serostatus was determined anonymously among consecutive acute medicine and trauma ED patients (aged 18-55) who had blood drawn as part of their medical care. Excess serum was aliquoted and coded with an anonymous study code. Before performing HIV testing, the number of persons with previously reported HIV infection was determined by linkage with the state HIV/AIDS reporting registry. Concurrent with the blinded HIV serosurvey, ED patients were offered voluntary HIV testing in a pilot program. Overall, 76 of 2,155 (3.5%) adult ED patients in the blinded survey were HIV-seropositive, 15 of whom (0. 7% of those tested, 20% of those HIV-seropositive) had no infection previously reported to the state HIV/AIDS registry. In the pilot program, six of the 156 (3.8%) individuals who underwent voluntary HIV testing were HIV-seropositive, including three of 53 (5.6%) individuals without prior HIV testing. Of the six HIV-seropositive subjects, one was previously diagnosed, while five of the remaining 155 (3.2%) represented previously undiagnosed infections. Overall, 3. 5% of ED patients from whom blood was obtained for other reasons tested positive for HIV antibody, 20% of whom were previously undiagnosed. Implementation of the voluntary testing program uncovered newly diagnosed infection among 3.2% of those tested. An ED may be an important setting for routinely offering HIV testing, especially for patients who have not been previously tested for HIV.

Adolescent↗
PubMed2000

Feeding-entrained circadian rhythms are attenuated by lesions of the parabrachial region in rats.

Rats anticipate daily restricted meals with increased approaches to a feeder and an increase in core body temperature. Food anticipatory activity (FAA) is thought to be under the control of a feeding-entrained circadian oscillator. Although numerous forebrain lesions have failed to permanently abolish FAA, the hindbrain has not been investigated. The parabrachial nuclei (PBN) integrate information from visceral and gustatory afferents. This region is also innervated by neurons in the area postrema that have access to the peripheral circulation. Therefore, it is possible that this region plays a role in triggering FAA. In two experiments, a total of 19 rats were given ibotenic acid or electrolytic lesions targeted at the PBN. The PBN-lesioned animals showed a marked attenuation in anticipatory approaches to the food bin relative to sham-operated controls. Some animals did not anticipate the meal at all. In addition, the expected increase in core body temperature was severely attenuated in the PBN-lesioned animals compared with controls. The most likely interpretation of these data is that the PBN serve as a relay for information about the zeitgeber (food in the gut) or as a clock output pathway, but not as the site of the feeding-entrained circadian oscillator.

Adaptation, Physiological↗
PubMed1999

Plasma glucagon, glucose, insulin, and motilin in rats anticipating daily meals.

The circadian food entrainable oscillator (FEO) mediates an increase in activity preceding access to periodic meals. The FEO is anatomically independent of the suprachiasmatic nucleus (SCN), but its locus remains to be established. Whether the FEO is located in the central nervous system (CNS) or in the periphery, it seems reasonable to assume that there is a link of communication between the digestive system and the CNS because only nutritive meals entrain the FEO. Subdiaphragmatic vagotomy and visceral deafferentation with capsaicin do not eliminate food-anticipatory activity (FAA), indicating that a neural signal is not necessary. The present study investigates the hypothesis that humoral signals from the digestive system act upon the CNS to trigger or entrain FAA. Intact rats and rats with SCN lesions were entrained to daily meals and then sacrificed prior to FAA or during FAA, but before meal access. Average plasma concentrations of glucose and insulin were nearly identical in both groups. Plasma and duodenal mucosal motilin concentrations also were not different between the two times. Corticosterone was elevated during anticipation, but the difference was not statistically reliable. Glucagon concentration was decreased during FAA compared to concentration prior to FAA in both intact and SCN-lesioned subjects. This difference was not observed in control rats fasted for the same number of hours, but not previously entrained to a daily meal. Although the decrease in glucagon could be a signal that initiates FAA, a causal role remains to be established.

Animals↗