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Biomedical subjects

D Davidson

Publications and source records attributed to D Davidson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Clnk, a novel SLP-76-related adaptor molecule expressed in cytokine-stimulated hemopoietic cells.

We have identified a novel Src homology 2 domain-containing leukocyte protein of 76 kD (SLP-76)-related molecule which we have termed Clnk (for cytokine-dependent hemopoietic cell linker). Unlike its relatives SLP-76 and B cell linker protein (Blnk), Clnk is not expressed uniformly within a given hemopoietic cell lineage. Even though it can be detected in several cell types, including T cells, natural killer cells, and mast cells, its expression seems to be strictly dependent on sustained exposure to cytokines such as interleukin (IL)-2 and IL-3. Strong support for the notion that Clnk is involved in immunoreceptor signaling was provided by the observation that it inducibly associated with at least one tyrosine-phosphorylated polypeptide (p92) in response to immunoreceptor stimulation. Moreover, transient expression of Clnk caused an increase in immunoreceptor-mediated signaling events in a T cell line. Taken together, these results show that Clnk is a novel member of the SLP-76 family selectively expressed in cytokine-stimulated hemopoietic cells. Furthermore, they suggest that Clnk may be involved in a cross-talk mechanism between cytokine receptor and immunoreceptor signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Hospital discharge. Smooth passage.

The introduction of care co-ordinators into a medical directorate two years ago has reduced bed blocking and cut length of stay from 8.5 to 5.9 days. All those appointed were already working in the hospital. There have been some tensions over boundaries with nursing and social work.

Case Management↗
PubMed1999

The spinal manifestations of Stickler's syndrome.

STUDY DESIGN: A review of current knowledge, clinical publications, and recent concepts of the causes of Stickler's syndrome was correlated with a clinical review of the condition at the Children's Hospital of Eastern Ontario, Canada. OBJECTIVES: To acquaint orthopedic spine surgeons with the natural history, associated anomalies, and high incidence of spinal deformity and scoliosis in children with Stickler's syndrome. SUMMARY OF BACKGROUND DATA: Stickler's syndrome is a hereditary, progressive arthro-ophthalmopathy with an autosomal dominant inheritance pattern. The estimated incidence is 1 in 10,000 people, which is slightly more common than Marfan syndrome. METHODS: The experience with Stickler's syndrome was reviewed in seven children, 2-15 years of age, with particular attention to the spinal abnormalities secondary to the connective tissue dysplasia. RESULTS: Six of the children had kyphosis or scoliosis, and four had wedging or flattening of the vertebrae or platyspondylia. In general, the spinal changes became more prominent in the older children with Stickler's syndrome, with the spinal vertebrae affected by the generalized epiphyseal dysplasia. The treatment of scoliosis and kyphosis is no different in children with Stickler's syndrome. The most difficult aspect is in diagnosing the condition. CONCLUSIONS: The importance of recognizing the syndrome is to allow for the investigation and treatment of the many other associated connective tissue disorders associated with Stickler's syndrome, such as the high incidence of retinal detachment, mitral valve prolapse, and mandibular hypoplasia that may result in problems with anesthesia should the spine require surgical stabilization.

Adolescent↗
PubMed1999

Seat belt fracture with late development of an enterocolic fistula in a child. A case report.

STUDY DESIGN: A case report of a 9-year-old boy treated at a pediatric trauma center for a flexion-extension spiral fracture with late development of an enterocolic fistula subsequent to a high-velocity motor vehicle accident. OBJECTIVES: To increase the awareness of possible delayed bowel complications associated with flexion-distraction injuries of the spine in children. SUMMARY OF BACKGROUND DATA: Flexion-distraction fractures of the spine in children wearing lap seat belts, so-called "Chance" fractures, are an increasingly common result of high-velocity collisions. This type of fracture, referred to as a seat-belt fracture, is often associated with duodenal or jejunal tears. Although such intra-abdominal injuries are common in such fractures secondary to this type of trauma, the occurrence of an enterocolic fistula has never been reported. METHODS: A review of all pediatric Chance fractures managed at the Children's Hospital of Eastern Ontario, as well as a literature review of all reported series of flexion-distraction injuries to the spine in children, were performed. RESULTS: The subtle and prolonged symptomatology of this lesion and its similarity to a cast syndrome is emphasized. CONCLUSION: Because the orthopedic surgeon is usually the primary care-giver for children with this type of seat-belt trauma, an appreciation of the possibility of a delayed onset enterocolic fistula with its symptomatology is essential to avoid prolonged morbidity.

Accidents, Traffic↗
PubMed1999

Interactions of CD45-associated protein with the antigen receptor signaling machinery in T-lymphocytes.

CD45 is a transmembrane protein tyrosine phosphatase playing an essential role during T-cell activation. This function relates to the ability of CD45 to regulate p56(lck), a cytoplasmic protein tyrosine kinase necessary for T-cell antigen receptor (TCR) signaling. Previous studies have demonstrated that CD45 is constitutively associated in T-lymphocytes with a transmembrane molecule termed CD45-AP (or lymphocyte phosphatase-associated phosphoprotein). Even though the exact role of this polypeptide is unclear, recent analyses of mice lacking CD45-AP have indicated that its expression is also required for optimal T-cell activation. Herein, we wished to understand better the function of CD45-AP. The results of our studies showed that in T-cells, CD45-AP is part of a multimolecular complex that includes not only CD45, but also TCR, the CD4 and CD8 coreceptors, and p56(lck). The association of CD45-AP with TCR, CD4, and CD8 seemed to occur via the shared ability of these molecules to bind CD45. However, binding of CD45-AP to p56(lck) could take place in the absence of other lymphoid-specific components, suggesting that it can be direct. Structure-function analyses demonstrated that such an interaction was mediated by an acidic segment in the cytoplasmic region of CD45-AP and by the kinase domain of p56(lck). Interestingly, the ability of CD45-AP to interact with Lck in the absence of other lymphoid-specific molecules was proportional to the degree of catalytic activation of p56(lck). Together, these findings suggest that CD45-AP is an adaptor molecule involved in orchestrating interactions among components of the antigen receptor signaling machinery. Moreover, they raise the possibility that one of the functions of CD45-AP is to recognize activated Lck molecules and bring them into the vicinity of CD45.

Animals↗
PubMed1999

Lymph node tumor volumes in patients undergoing sentinel lymph node biopsy for cutaneous melanoma.

BACKGROUND: Regional lymph node tumor volumes in patients undergoing sentinel lymph node (SN) biopsy (SNB) for treatment of cutaneous melanoma have not been described. The objectives of this study were to describe the lymph node tumor volumes typically seen in this population and to correlate tumor volumes with tumor thickness and positive SN characteristics. METHODS: Review of a consecutive series of patients with clinically localized cutaneous melanoma who underwent SNB of nonpalpable regional lymph node basins followed by complete lymphadenectomy (LND) was performed. Multiple lymph node sections from positive SNs and nonsentinel nodes (NSNs) in LND specimens were examined microscopically. Individual tumor deposit diameters were measured using an ocular micrometer. Aggregate tumor volumes were calculated for SN and LND specimens. Tumor volumes and SN and LND positivity rates were correlated with tumor thickness, the number of positive SNs, and the presence of multiple SN tumor deposits. RESULTS: SNB procedures were performed for 149 melanomas in 189 regional nodal basins. The mean tumor depth was 2.48 mm. The mean number of SNs/basin was 2.1. Thirty-two of 149 SNB procedures (21.5%) revealed a total of 34 nodal basins with at least one positive SN. The median tumor volume in positive SNs was 4.7 mm3 (range, 0.1-3618 mm3; mean, 209 mm3). The median aggregate tumor volume in positive LND specimens was 4.9 mm3 (range, 0.1-3618 mm3; mean, 224 mm3). Six basins (17.6%) contained at least one positive NSN. The regional node aggregate tumor volume correlated weakly with tumor thickness (Pearson's correlation coefficient = .302, P = .0934). NSN positivity was not predicted by tumor thickness, American Joint Committee on Cancer tumor stage, number of positive SNs, or number of metastatic deposits within SNs. CONCLUSIONS: Most melanoma-positive SNs contain minute tumor volumes. Tumor thickness and patterns of SN metastases may not be predictive of tumor burden or the presence of positive NSNs.

Biopsy↗
PubMed1999

Expression of tandem invertase genes associated with sexual and vegetative growth cycles in potato.

The organisation of two invertase genes (invGE and invGF) linked in direct tandem repeat within the potato genome is detailed. The genes exhibit a similar intron/exon structure which differs from previously described plant invertase genes; while intron locations are conserved between the genes, minor differences in exon length are seen. Both genes encode enzymes with putative extracellular location. Biochemical analysis of gene expression showed expression in floral tissues for both genes, with expression of the upstream gene (invGE) also detected in leaf tissue. Promoter sequences from both genes have been fused to the beta-glucuronidase (GUS) reporter gene (uidA) and transformed into potato. One promoter-GUS reporter construct was also transformed into tobacco. Histochemical analysis of transgenic lines defined specific expression from the downstream (invGF) promoter in potato and tobacco pollen, with expression first detected in the late uninucleate stage of tobacco microspore development. The invGE promoter determined expression in pollen and other floral tissues, but also at lateral nodes in stem, root and tuber. An association of invertase expression with generative tissue, both in vegetative and sexual modes of growth, is indicated.

Base Sequence↗
PubMed1999

Influence of naltrexone on cue-elicited craving among hazardous drinkers: the moderational role of positive outcome expectancies.

This study was designed to elucidate mechanisms by which naltrexone (NTX) influences drinking among hazardous drinkers. Thirty-six hazardous drinkers received 50 mg NTX or placebo on 2 separate occasions before participation in a taste test procedure with low-alcohol beer. Urges to drink before consumption, beer volume consumed, and perceived stimulation and sedation after consumption were assessed. Although NTX did not influence beer consumption, hazardous drinkers who reported high positive reinforcement expectancies rated their urges to drink as significantly lower when they were on NTX compared with placebo. Positive outcome expectancies also moderated the effects of NTX on subjective reports of stimulation following drinking. These findings suggest that naltrexone may be particularly effective at reducing alcohol cue-elicited positive reinforcement for those with high positive alcohol outcome expectancies.

Adult↗
PubMed1999

An Epstein-Barr virus that expresses only the first 231 LMP1 amino acids efficiently initiates primary B-lymphocyte growth transformation.

An Epstein-Barr virus (EBV) recombinant (MS231) that expresses the first 231 amino acids (aa) of LMP1 and is truncated 155 aa before the carboxyl terminus transformed resting B lymphocytes into lymphoblastoid cell lines (LCLs) only when the infected cells were grown on fibroblast feeder cells (K. M. Kaye et al., J. Virol. 69:675-683, 1995). Higher-titer MS231 virus has now been compared to wild-type (WT) EBV recombinants for the ability to cause resting primary B-lymphocyte transformation. Unexpectedly, MS231 is as potent as WT EBV recombinants in causing infected B lymphocytes to proliferate in culture for up to 5 weeks. When more than one transforming event is initiated in a microwell, the MS231 recombinant supports efficient long-term LCL outgrowth and fibroblast feeder cells are not required. However, with limited virus input, MS231-infected cells differed in their growth from WT virus-infected cells as early as 6 weeks after infection. In contrast to WT virus-infected cells, most MS231-infected cells could not be grown into long-term LCLs. Thus, the LMP1 amino-terminal 231 aa are sufficient for initial growth transformation but the carboxyl-terminal 155 aa are necessary for efficient long-term outgrowth. Despite the absence of the carboxyl-terminal 155 aa, MS231- and WT-transformed LCLs are similar in latent EBV gene expression, in ICAM-1 and CD23 expression, and in NF-kappaB and c-jun N-terminal kinase activation. MS231 recombinant-infected LCLs, however, require 16- to 64-fold higher cell density than WT-infected LCLs for regrowth after limiting dilution. These data indicate that the LMP1 carboxyl-terminal 155 aa are important for growth at lower cell density and appear to reduce dependence on paracrine growth factors.

B-Lymphocytes↗
PubMed1999

Prospective study of fluorodeoxyglucose-positron emission tomography imaging of lymph node basins in melanoma patients undergoing sentinel node biopsy.

PURPOSE: To prospectively compare positron emission tomography (PET) imaging of regional lymph node basins to sentinel node biopsy (SNB) in patients with American Joint Committee on Cancer (AJCC) stage I, II, and III melanoma localized to the skin. METHODS: Patients with cutaneous melanoma with Breslow's depth greater than 1 mm (AJCC T2-4N0M0) or localized regional cutaneous recurrence (TxN2bM0) underwent whole-body imaging of glucose metabolism with fluorodeoxyglucose (FDG) PET followed by SNB. PET scans were interpreted in a blinded fashion and compared with histologic analyses of SNB specimens and clinical follow-up examination. Nodal tumor volumes were estimated. RESULTS: Eighty-nine lymph node basins were evaluated by FDG-PET and SNB in 70 assessable patients. Eighteen patients (25.7%) had lymph node metastases at the time of FDG-PET imaging: 17 proved by SNB (24.3%) and one by follow-up examination (1.4%). Median tumor volume in positive sentinel node basins was 4.3 mm3 (range, 0.07 to 523 mm3). Sensitivity of SNB for detection of occult regional lymph node metastases was 94.4%, specificity was 100%, positive predictive value (PPV) was 100%, and negative predictive value (NPV) was 98.6%. Sensitivity of FDG-PET was 16.7%, specificity was 95.8%, PPV was 50%, and NPV was 81.9%. At a median follow-up duration of 16.6 months, seven patients (10%) developed recurrent disease. PET predicted one recurrence (14.3%) in a node basin missed by SNB. CONCLUSION: FDG-PET is an insensitive indicator of occult regional lymph node metastases in patients with melanoma because of the minute tumor volumes in this population. FDG-PET does not have a primary role for staging regional nodes in patients with clinically localized melanoma.

Adult↗
PubMed1999

Mechanism for dexamethasone inhibition of neutrophil migration upon exposure to lipopolysaccharide in vitro: role of neutrophil interleukin-8 release.

The mechanism by which dexamethasone (DEX) inhibits neutrophil (PMN) recruitment to a site of inflammation, such as the newborn lung with bronchopulmonary dysplasia, is not completely understood. The aim of our study was to determine whether DEX inhibits neutrophil-induced neutrophil recruitment by inhibition of interleukin- (IL) 8 release from PMNs, and if there are developmental differences. PMNs isolated from cord blood (CB) and adults (A) were studied. We first measured the effect of DEX (10(-10) to 10(-4) M) on PMN migration to an exogenous IL-8 standard (10(-8) M) using PMNs of CB (n = 3) and A (n = 3), over 1 h in a chemotaxis chamber. Second, we determined the effect of DEX (0 and 10(-10) to 10(-6) M) on IL-8 release (immunoassay) from PMNs of CB (n = 7) or A (n = 7) after incubation with lipopolysaccharide (LPS, 1 ng/mL) for 6 and 18 h. Third, the chemoattractant activity of culture media from the second experiment was studied with and without IL-8 antibody. DEX at concentrations of 10(-10) to 10(-4) M had no direct effect on PMN migration in vitro to an exogenous IL-8 standard. After LPS exposure, IL-8 release was greatly increased for PMNs from CB compared with A. DEX (10(-10) to 10(-4) M) resulted in a dose-dependent inhibition of IL-8 release from PMNs exposed to LPS for 6 and 18 h incubation. Increased PMN migration activity was only found with media of PMNs of CB with no DEX. At 18 h, media-induced migration activity was decreased if DEX (10(-7) M), IL-8 antibody, or DEX (10(-7) M) with IL-8 antibody were present during the incubation with LPS: there was an 88, 86, and 101% reduction in migration activity, respectively. We conclude that DEX inhibits PMN-induced PMN migration, predominantly via inhibition of IL-8 release for PMNs of the newborn. We suggest that a 10-fold lowering of the standard DEX dose may effectively reduce lung inflammation in bronchopulmonary dysplasia.

Adult↗
PubMed1999

Safety of withdrawing inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn.

OBJECTIVE: Because of case reports describing hypoxemia on withdrawal of inhaled nitric oxide (I-NO), we prospectively examined this safety issue in newborns with persistent pulmonary hypertension who were classified as treatment successes or failures during a course of I-NO therapy. METHODS: Randomized, placebo-controlled, double-masked, dose-response clinical trial at 25 tertiary centers from April 1994 to June 1996. Change in oxygenation and outcome (death and/or extracorporeal membrane oxygenation) during or immediately after withdrawing I-NO were the principal endpoints. Patients (n = 155) were term infants, <3 days old at study entry with echocardiographic evidence of persistent pulmonary hypertension of the newborn. Exclusion criteria included previous surfactant treatment, high-frequency ventilation, or lung hypoplasia. Withdrawal from treatment gas (0, 5, 20, or 80 ppm) started once treatment success or failure criteria were met. Withdrawal of treatment gas occurred at 20% decrements at <4 hours between steps. RESULTS: The patient profile was similar for placebo and I-NO groups. Treatment started at an oxygenation index (OI) of 25 +/- 10 (mean +/- SD) at 26 +/- 18 hours after birth. For infants classified as treatment successes (mean duration of therapy = 88 hours, OI <10), decreases in the arterial partial pressure of oxygen (PaO(2)) were observed only at the final step of withdrawal. On cessation from 1, 4, and 16 ppm, patients receiving I-NO demonstrated a dose-related reduction in PaO(2) (-11 +/- 23, -28 +/- 24, and -50 +/- 48 mm Hg, respectively). For infants classified as treatment failures (mean duration of therapy = 10 hours), no change in OI occurred for the placebo group (-13 +/- 36%, OI of 31 +/- 11 after the withdrawal process); however a 42 +/- 101% increase in OI to 46 +/- 21 occurred for the pooled nitric oxide doses. One death was possibly related to withdrawal of I-NO. CONCLUSION: For infants classified as treatment successes, a dose response between the I-NO dose and decrease in PaO(2) after discontinuing I-NO was found. A reduction in I-NO to 1 ppm before discontinuation of the drug seems to minimize the decrease in PaO(2) seen. For infants failing treatment, discontinuation of I-NO could pose a life-threatening reduction in oxygenation should extracorporeal membrane oxygenation not be readily available or I-NO cannot be continued on transport.

Administration, Inhalation↗
PubMed1999

The role of bilateral talectomy in the management of bilateral rigid clubfeet.

Severe clubfoot is a common sequela of arthrogryposis multiplex congenita and myelomeningocele. Talectomy is a practical surgical procedure to assist in the correction of severe, rigid equinovarus foot deformity. However, the results of talectomy may be less predictable in rigid bilateral equinovarus foot deformity than in the treatment of unilateral clubfoot. To determine the outcome of talectomy in the treatment of bilateral rigid clubfoot, we reviewed the cases of all patients at our center who underwent bilateral talectomy. Seven children were treated for bilateral talipes equinovarus with talectomy. The patient group consisted of 3 children with arthrogryposis, 3 with myelomeningocele, and 1 with Duchenne muscular dystrophy. The age at surgery averaged 6 years and ranged from 1 year and 10 months to 15 years and 7 months. The length of follow-up averaged 5 years and 6 months and ranged from 3 years to 12 years and 6 months. Three feet had a good and 7 feet a satisfactory correction of the deformity. Four feet had poor results. Bilateral talectomy was found overall to be a successful and predictable procedure, with low morbidity for the attainment of functional feet.

Adolescent↗
PubMed1999

Effects of naltrexone on alcohol self-administration in heavy drinkers.

The mechanisms underlying the suppressant effects of naltrexone (NTX) on ad libitum alcohol drinking in a bar/restaurant setting were investigated in heavy beer drinkers. Fifty-one male and female heavy drinkers (mean age = 22) received 50 mg of NTX or placebo (PBO), p.o., on two separate occasions in a randomized, double-blind crossover protocol. After 7 days of taking medication, subjects were provided with the opportunity to consume beer ad libitum during two, 90-min test sessions that were held 1 to 2 weeks apart. Blood samples were collected on test days to ensure medication compliance and to measure blood levels of NTX and the active beta-naltrexol. Less beer was consumed during NTX treatment. NTX decreased urges to consume alcohol. NTX-treated subjects also took significantly longer to finish each glass of beer and were more likely to terminate beer drinking early. Self-report stimulation and ratings of positive mood states were lower during NTX treatment. Negative side effects of NTX, such as nausea and headache, were reported more frequently with NTX. Not all of the subjects decreased their beer intake on NTX, and some subjects drank more beer. Nonresponders to NTX were not related to blood levels of the active metabolite beta-naltrexol or to a family history of alcoholism. Overall, the results of this study suggest that NTX affects a number of the components of alcohol drinking sequence, including lowering cravings, decreasing the positive reinforcing effects of alcohol, and increasing headache and nausea, each of which may contribute to reducing alcohol intake.

Adult↗
PubMed1999

The formation of the feather pattern in chick skin after a proportion of cells have been killed by X-irradiation.

The formation of periodic patterns is of fundamental importance in embryonic development. One of the simplest and most frequently observed patterns is the maintenance of a minimum distance between neighbouring elements, for example between teeth, hair, feathers, digits etc. Theoretical models describing these phenomena have been proposed for feather patterning. However, there has been no detailed quantitative analysis of the relationship between cell population density and feather spacing. To define the relation between these quantities and specifically to test the prediction of a mathematical model, we have examined the formation of the feather pattern after varying proportions of the dermal cells have been killed by X-irradiation. It is known that the development of a feather primordium is normally associated with an increase in cell population density in the dermis. Using X-ray irradiation of the skin in vivo and in vitro, we show that the relation between cell population density and spacing of feather primordia indicates the importance of a threshold number of cells for feather patterning. Moreover, there is a prima facie case for supposing that X-rays act on feather spacing system, reducing the ability of dermal cells to prevent spreading of the pattern. Thus, X-irradiation may have a secondary effect on the spacing of primordia rather than, or as well as, affecting the mechanisms that determine their primary positions.

Animals↗
PubMed1999

The real story.

Explore the source record for details and available documents.

Hospital Administration↗
PubMed1999

Symphalangism in children. Case report and review of the literature.

Symphalangism is an uncommon syndrome characterized by fusion of the interphalangeal joints of the hands and feet. The fusion can involve the proximal or the distal joints; however, involvement of the proximal interphalangeal joints is more common. Symphalangism often is associated with several other skeletal and nonskeletal abnormalities. Analysis of the pedigrees of affected families reveals this trait to be autosomal dominant. The authors present the case of a 9-year-old boy with bilateral symphalangism of the proximal interphalangeal joints in the fingers and toes. His father is affected similarly. A comparison of these cases with those published in the literature indicates that although the radiologic appearance of symphalangism appears disabling, the fused phalanges seldom cause disability or loss of function of the hand. Surgical intervention is not required in most patients. The father and son reported also had capitellar hypoplasia and subluxation of the radial head associated with limitation of elbow flexion and extension.

Adult↗