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Biomedical subjects

R Davis

Publications and source records attributed to R Davis.

At least 109 records · Page 6Linked to original sources
PubMed1998

Stable expression of manganese superoxide dismutase (MnSOD) in insulinoma cells prevents IL-1beta- induced cytotoxicity and reduces nitric oxide production.

The fact that insulin-producing islet beta-cells are susceptible to the cytotoxic effects of inflammatory cytokines represents a potential hinderance to the use of such cells for transplantation therapy of insulin-dependent diabetes mellitus (IDDM). In the current study, we show that IL-1beta induces destruction of INS-1 insulinoma cells, while having no effect on a second insulinoma cell line RIN1046-38 and its engineered derivatives, and that this difference is correlated with a higher level of expression of manganese superoxide dismutase (MnSOD) in the latter cells. Stable overexpression of MnSOD in INS-1 cells provides complete protection against IL-1beta-mediated cytotoxicity, and also results in markedly reduced killing when such cells are exposed to conditioned media from activated human or rat PBMC. Further, overexpression of MnSOD in either RIN- or INS-1-derived lines results in a sharp reduction in IL-1beta-induced nitric oxide (NO) production, a finding that correlates with reduced levels of the inducible form of nitric oxide synthase (iNOS). Treatment of INS-1 cells with L-NMMA, an inhibitor of iNOS, provides the same degree of protection against IL-1beta or supernatants from LPS-activated rat PBMC as MnSOD overexpression, supporting the idea that MnSOD protects INS-1 cells by interfering with the normal IL-1beta-mediated increase in iNOS. Because NO and its derivatives have been implicated as critical mediators of beta-cell destruction in IDDM, we conclude that well regulated insulinoma cell lines engineered for MnSOD overexpression may be an attractive alternative to isolated islets as vehicles for insulin replacement in autoimmune diabetes.

Animals↗
PubMed1998

Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme.

Tumor necrosis factor-alpha (TNFalpha) is a cytokine that induces protective inflammatory reactions and kills tumor cells but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Soluble TNFalpha is released from its membrane-bound precursor by a membrane-anchored proteinase, recently identified as a multidomain metalloproteinase called TNFalpha-converting enzyme or TACE. We have cocrystallized the catalytic domain of TACE with a hydroxamic acid inhibitor and have solved its 2.0 A crystal structure. This structure reveals a polypeptide fold and a catalytic zinc environment resembling that of the snake venom metalloproteinases, identifying TACE as a member of the adamalysin/ADAM family. However, a number of large insertion loops generate unique surface features. The pro-TNFalpha cleavage site fits to the active site of TACE but seems also to be determined by its position relative to the base of the compact trimeric TNFalpha cone. The active-site cleft of TACE shares properties with the matrix metalloproteinases but exhibits unique features such as a deep S3' pocket merging with the S1' specificity pocket below the surface. The structure thus opens a different approach toward the design of specific synthetic TACE inhibitors, which could act as effective therapeutic agents in vivo to modulate TNFalpha-induced pathophysiological effects, and might also help to control related shedding processes.

ADAM Proteins↗
PubMed1998

Diffraction-based cell detection using a microcontact printed antibody grating.

An optical detector has been fabricated that is specific for targeted bacterial cells, by stamping an antibody grating pattern on a silicon surface. The antibody grating alone produces insignificant optical diffraction, but upon immunocapture of cells, the optical phase change produces a diffraction pattern. This technique eliminates much of the surface modifications and the secondary immunochemical or enzyme-linked steps that are common in immunoassays. Microcontact printing provides an alternative to previously reported photolithographic-mediated antibody patterning processes and uses a photolithographic process simply to produce the elastomeric stamp. We have stamped antibodies directly onto clean native oxide silicon substrates with no other chemical surface treatments. Direct binding of the antibodies to the silicon occurs in a way that still allows them to function and selectively bind antigen. The performance of the sensor was evaluated by capturing Escherichia coli O157:H7 cells on the antibody-stamped lines and measuring the intensity of the first-order diffraction beam resulting from the attachment of cells. The diffraction intensity increases in proportion to the cell density bound on the surface.

Antibodies↗
PubMed1998

South American camelids in the United Kingdom: reproductive failure, pregnancy diagnosis and neonatal care.

The results of a postal questionnaire survey conducted between December 1992 and March 1993 indicated that a third of mated female South American camelids in the United Kingdom failed to produce offspring. This failure did not include abortions or stillbirths, which accounted for up to 4 per cent and up to 3 per cent of further reproductive losses respectively. The most common method of pregnancy diagnosis was observation (40 to 70 per cent). Plasma progesterone estimations and ultrasonography were used by a small proportion of respondents. A combination of methods was seldom used. Between 25 and 46 per cent of camelid owners housed their animals at parturition and 50 to 82 per cent routinely dipped the navel of the newborn calf. Neonatal mortality was an important cause of loss.

Animal Husbandry↗
PubMed1998

Outward currents in Drosophila larval neurons: dunce lacks a maintained outward current component downregulated by cAMP.

Outward current modulation by cAMP was investigated in wild type (wt) and dunce (dnc) Drosophila larval neurons. dnc is deficient in a cAMP phosphodiesterase and has altered memory. Outward current modulation by cAMP was investigated by acute or chronic exposure to cAMP analogs. The analysis included a scrutiny of outward current modulation by cAMP in neurons from the mushroom bodies (mrb). In Drosophila, the mrb are the centers of olfactory acquisition and retention. Based on outward current patterns, neurons were classified into four types. Downmodulation of outward currents induced by acute application of cAMP analogs was reversible and found only in type I and type IV neurons. In the general wt neuron population, approximately half of neurons exhibited cAMP-modulated, 4-aminopyridine (4-AP)-sensitive currents. On the other hand, a significantly larger fraction of mrb neurons in wt (70%) was endowed with cAMP-modulated, 4-AP-sensitive currents. Only 30% of the dnc neurons displayed outward currents modulated by cAMP. The deficit of cAMP-modulated outward currents was most severe in neurons derived from the mrb of dnc individuals. Only 4% of the mrb neurons of dnc were cAMP-modulated. The dnc defect can be induced by chronic exposure of wt neurons to cAMP analogs. These results document for the first time a well defined electrophysiological neuron phenotype in correlation with the dnc defect. Moreover, this study demonstrates that in dnc mutants such a deficiency affects most severely neurons in brain centers of acquisition and retention.

Animals↗
PubMed1998

South American camelids in the United Kingdom: population statistics, mortality rates and causes of death.

A survey of the health of South American camelids in the United Kingdom was carried out between December 1992 and June 1993; 123 members of the British Camelid Owners and Breeders Association and 19 non-members were sent questionnaires and usable responses were received from 84 (59 per cent). In total 689 camelids were included, and in 1992, 66 per cent were Ilama, 21 per cent alpaca and 13 per cent guanaco. Their ages ranged from less than six months to over 10 years, with animals aged two to five years constituting the largest proportion. The mortality rates between 1990 and 1992 were 2.7 to 3.3 per cent for Ilama, 3.5 to 6.9 per cent for alpaca and 0 to 11.4 per cent for guanaco. The highest mortality was in animals less than six months and more than 10 years old; 4 to 11 per cent of Ilama deaths and 17 to 33 per cent of alpaca deaths were in animals aged less than six months and a high proportion of these occurred during the first week of life. In the cases for which a cause was reported, accidents and injury accounted for 20 per cent of Ilama deaths, and perinatal deaths accounted for 22 per cent of alpaca deaths. A third of the deaths were reported as being of unknown cause, and a veterinary diagnosis was reported in less than half of the cases. These data suggest that attention to the environment and housing conditions of Ilama, the neonatal care of alpaca and improvements in diagnosis are priorities for reducing the mortality and improving the health of South American camelids in the UK.

Animals↗
PubMed1998

Minor head injury in children: current management practices of pediatricians, emergency physicians, and family physicians.

OBJECTIVE: To describe variation in the clinical management of minor head trauma in children among primary care and emergency physicians. DESIGN: A survey of pediatricians, family physicians, and emergency physicians drawn from a random sample of members of the American Academy of Pediatrics, the American Academy of Family Physicians, and the appropriate American Medical Association specialty listings, respectively. Physicians were given clinical vignettes describing children presenting with normal physical examination results after minor head trauma. Different clinical scenarios (brief loss of consciousness or seizures) were also presented. Information was gathered on initial and subsequent management steps most commonly used by the physician. RESULTS: Surveys were returned by 765 (51%) of 1500 physicians. Of these, 303 (40%) were pediatricians, 269 (35%) family practitioners, and 193 (25%) emergency physicians. For minor head trauma without complications, observation at home was the most common initial physician management choice (n = 547, 72%). Observation in office or hospital was chosen by 81 physicians (11%). Head computed tomographic (CT) scan was chosen by 7 physicians (1%) and skull x-ray by 24 physicians (3%) as the first management option. Most physicians (n = 445, 80%) who initially chose observation at home would obtain a CT scan if the patient showed clinical deterioration. In the original scenario, if the patient had also sustained a loss of consciousness, 383 physicians (58%) altered management. Of these, 120 (18%) chose CT, 13 (2%) chose skull x-ray, 1 (1%) chose magnetic resonance imaging, 141 (21%) chose inpatient observation, and 125 (19%) chose a combination of CT scanning and observation. With seizures, 595 (90%) altered management, with 176 physicians (27%) choosing CT scan, 5 (1%) skull x-ray, 60 (9%) inpatient observation, and 299 (45%) a combination of radiological evaluation and observation. CONCLUSIONS: Most physicians surveyed chose clinic or home observation for initial management of minor pediatric head trauma. Clinical management was more varied when patients had sustained either loss of consciousness or seizures. Further study of the appropriate management of minor head trauma in children is needed to guide physicians in their care.

Adolescent↗
PubMed1998

Event-related brain potentials during an extended visual recognition memory task depict delayed development of cerebral inhibitory processes among 6-month-old infants with Down syndrome.

Development of cerebral inhibitory processes among individuals with Down syndrome (DS) may be delayed at an early age. In support of this hypothesis, sensory-evoked potentials (EPs) and event-related brain potentials (ERPs) have previously delineated altered habituation to stimuli among infants with DS. The purpose of the current study was to provide extended experience with visual stimuli among 6-month-old infants with and without DS (nDS) to determine if altered ERP and behavioral response decrements would be evident even after repeated presentations of stimuli. An 80/20% oddball paradigm was employed. Infants with DS and nDS were matched according to age and gender. Infants with DS demonstrated significantly larger Nc areas, Nc peak amplitudes, Nc2 areas and, inversely, significantly smaller peak Pb amplitudes when compared to infants nDS. Contrasts of the two study groups were most robust within ERP measures from frontal (Fz) and parietal (Pz) recording sites. Infants with DS also demonstrated a significantly slower decrement of most ERP components with repetitive stimulus experience. Most noteworthy was the observation of little or no decrement of ERP components at Fz among infants with DS. Both infants with DS and nDS demonstrated significantly larger Nc peak amplitudes, Nc areas, Nc2 areas, Pb peak amplitudes and NSW areas to rare stimuli. While significant probability and experiential trends were observed in visual fixation measures across both study groups, there were no significant differences of visual attention between infants with DS or nDS. These data demonstrate the value of ERPs within the study of atypical cognitive development during infancy and support the concept of altered inhibitory processes in the brain of infants with DS.

Brain↗
PubMed1998

Total enteral nutrition versus total parenteral nutrition during pediatric extracorporeal membrane oxygenation.

OBJECTIVE: To evaluate the adequacy, tolerance, and complications of enteral nutrition, compared with parenteral nutrition, in pediatric patients requiring extracorporeal membrane oxygenation (ECMO). DESIGN: A retrospective chart review of all patients placed on extracorporeal life support from January 1991 through December 1995. SETTING: Medical/surgical pediatric intensive care unit at Egleston Children's Hospital, a tertiary care pediatric center. PATIENTS: Twenty-nine consecutive pediatric patients who required ECMO and were provided nutritional support, either enterally or parenterally. Group A consisted of 14 patients who were provided nutritional support using total parenteral nutrition. Group B consisted of 15 patients. Two patients were excluded from group B because their ECMO run was <36 hrs, leaving insufficient data for analysis. The remaining 13 patients were provided total enteral nutrition during ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Both groups were similar in age, weight, pre-ECMO oxygenation index, alveolar-arterial oxygen difference, type, and duration of ECMO (p = NS). Comparison of percent ideal body weight on admission did not show a statistical difference between groups A and B (p = .883). There was no difference between the two groups in the time needed to achieve caloric goal (p = .536) from the initiation of ECMO. No complications were associated with the utilization of enteral feedings. Savings for the nutritional supplement was estimated to be $170 per day for the enterally fed group. The percentage of patients surviving was higher in the enterally fed patients compared with the parenterally fed group (79% vs. 100%), although this difference was not statistically significant (p = .47). CONCLUSIONS: Enteral nutrition in patients receiving either venoarterial or venovenous ECMO is well tolerated, provides adequate nutrition, is cost effective, and is without complications, as compared with parenteral nutrition. These data suggest that total enteral nutrition can be safely administered for nutritional support in pediatric patients undergoing either venoarterial or venovenous ECMO.

Adolescent↗
PubMed1998

Binge/purge symptoms and comorbidity in adolescents with eating disorders.

OBJECTIVE: To identify the diagnostic subtypes of eating disorders (EDs), the psychiatric comorbid diagnoses, and associated specific and nonspecific psychopathology in a series of 120 adolescents undergoing standardized assessment for an ED. METHOD: Consecutive patients referred to our large pediatric hospital for ED assessment completed a semistructured diagnostic interview for children and adolescents. The following self-report scales were administered to assess specific and nonspecific psychopathology: the Children's Depression Inventory (CDI), the Brief Symptom Inventory (BSI), the Eating Disorder Inventory 2 (EDI-2), and the Family Assessment Measure (FAM-III) of family functioning. RESULTS: Female subjects with a mean age of 14.5 years and a mean body mass index (BMI) of 18.1 comprised 93% of the sample. The restrictive subtypes of anorexia nervosa (AN) (43%) and eating disorder not otherwise specified (EDNOS) (16%) were the most common diagnoses. Patients with restricting symptoms (R) could be grouped together because they were more similar to each other with respect to self-report symptoms of psychopathology than they were to patients with binge/purge (B/P) symptoms and vice versa. Patients with R endorsed significantly fewer subjective symptoms, both ED-specific and nonspecific, and rated their families functioning better than did B/P patients. Comorbid, current major depressive disorders and dysthymic disorders occurred in 66% of subjects, but depressive, dysthymic, and oppositional disorders occurred in 96% of those with B/P symptoms. Severity of the CDI was the best single discriminator between R and B/P subjects. CONCLUSIONS: Adolescents with EDs in the early stage of their illness are similar to adults with EDs in the following ways: they meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for subtypes of EDs (excluding amenorrhea) and commonly have comorbid psychiatric disorders, especially depressive disorders. Patients with B/P symptoms can be distinguished from restricting subjects because they endorse significantly more ED-specific and nonspecific psychopathology and have a higher frequency of comorbid Axis I diagnoses (especially depressive disorders) than restricting patients. Oppositional defiant disorder (ODD) occurs more commonly in adolescents with EDs associated with B/P symptoms.

Adolescent↗
PubMed1998

Double pathology in Rasmussen's syndrome: a window on the etiology?

The syndrome of chronic encephalitis with epilepsy (Rasmussen's syndrome) typically occurs in children and is characterized by the development of intractable focal seizures, progressive hemiparesis and intellectual deterioration. The etiology is unknown, and the pathological abnormalities vary from those of active disease, with numerous microglial nodules, with or without neuronophagia, perivascular round cells and glial scarring, to those of remote disease, demonstrated by neuronal loss, gliosis and perivascular round cells but few microglial nodules. We describe five patients presenting with clinical features typical of Rasmussen's syndrome, in whom pathological examination showed a second, previously unsuspected pathology in addition to the changes of chronic encephalitis. Two of the patients had vascular abnormalities bearing some resemblance to cavernous angiomata, one had a tumor, one had tuberous sclerosis, and one the forme fruste of tuberous sclerosis. The coexistence of a second pathology in these patients may provide information about the underlying mechanism of this rare condition.

Adolescent↗
PubMed1998

The influence of dental unit design on percutaneous injury.

The handpiece receptacle of a European, buggy-whip-style dental unit is in a different location than that of a conventional dental unit. This study investigated whether this difference affects the incidence of percutaneous injuries among dental professionals. The researchers asked dental professionals to record descriptions of percutaneous injuries they sustained during a period of 30 workdays. Findings indicated that most injuries were bur-related and that there was no statistically significant difference between the European and the conventional dental units with respect to the incidence of percutaneous injury.

Accidents, Occupational↗
PubMed1998

The effects of immersiveness on physiology.

The effects of varying levels of immersion in virtual reality environments on participant's heart rate, respiration rate, peripheral skin temperature, and skin resistance levels were examined. Subjective reports of presence were also noted. Participants were presented with a virtual environment of an airplane flight both as seen from a two-dimensional computer screen and as seen from within a head-mounted display. Subjects were randomly assigned to different order of conditions presented, but all subjects received both conditions. Differences between the non-phobics' physiological responses and the phobic's response when placed in a virtual environment related to the phobia were noted. Also noted were changes in physiology based on degree of immersion.

Adult↗
PubMed1998

p53 mutations in malignant gliomas.

A population-based series of incident cases of malignant glioma were analyzed for mutations in the tumor suppressor gene p53. Exons 4-8 were screened using PCR-single-strand conformation analysis and confirmed through direct sequencing. Of 62 tumors analyzed, 12 (19%) contained mutations in p53: one 18-bp duplication in exon 5, five point mutations in exon 4, three point mutations in exon 7, two point mutations in exon 8, and a splice-site mutation at the exon 6/intron 7 boundary. In contrast to previous studies of malignant glioma, the prevalence of transversion mutations (56%) was higher than transition mutations (33%). A large proportion of transversion mutations occurred in exon 4, a region that is not routinely screened in gliomas. We present here an improved method for screening exon 4 (and other GC-rich regions) of p53 using PCR-single-strand conformation analysis. The high frequency of transversion mutations suggests a role for exogenous carcinogens in the etiology of malignant glioma.

Adolescent↗
PubMed1998

Physical fitness: how to help older patients live stronger and longer. (1).

Most older Americans are not physically fit and do not exercise regularly. This is especially true of older women, who are weaker than men and become disabled and dependent in the later years at a much greater rate. Exercise can increase the body's metabolism and make it more efficient in burning calories. Physical fitness also makes respiration more efficient. Evidence suggests strongly that the physically fit live 2 to 3 years longer and have a better quality of life than sedentary individuals. Any time is the best time for a person of any age to start exercising. Exercise is movement--dancing, walking, lifting a weight, using the body. Older individuals tend to be willing to exercise if they are given appropriate recommendations and follow-up.

Aged↗