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Biomedical subjects

G Henry

Publications and source records attributed to G Henry.

At least 19 recordsLinked to original sources
PubMed2001

The p38-MAPK/SAPK pathway is required for human keratinocyte migration on dermal collagen.

Human keratinocyte motility plays an important role in the re-epithelialization of human skin wounds. The wound bed over which human keratinocytes migrate is rich in extracellular matrices, such as fibrin, fibronectin, and collagen, and serum factors, such as platelet-derived growth factor and transforming growth factor beta 1. Extracellular matrices and the serum factors bind to cell surface receptors and initiate a cascade of intracellular signaling events that regulate cell migration. In this study, we identified an intracellular signaling pathway that mediates collagen- driven motility of human keratinocytes. Pharmaco logic inhibition of the activation of p38-alpha and p38-beta mitogen-activated protein kinase activation potently blocked collagen-driven human keratinocyte migration. Transfection of the same keratinocytes with the kinase-negative mutants of p38-alpha or p38-beta mitogen-activated protein kinase markedly inhibited keratinocyte migration on collagen. Attachment of keratinocytes to collagen activated p38 mitogen- activated protein kinase, as well as p44/p42 ERKs. Interestingly, activation of the p38 mitogen-activated protein kinase cascade by overexpressing the constitutively active MKK3 and MKK6, MKK3b(E) and MKK6b(E), could neither initiate migration in the absence of collagen nor enhance collagen-driven migration. This study provides evidence that the p38-MAPK/SAPK pathway is necessary, but insufficient, for mediating human keratinocyte migration on collagen.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed2001

Rate of abnormal osteoarticular radiographic findings in pediatric patients.

OBJECTIVE: The objective of our study was to assess the rate of abnormal radiographic findings in the most frequent osteoarticular locations of traumatic injury in a pediatric population. SUBJECTS AND METHODS: During two periods of 12 weeks each, all patients admitted to the pediatric emergency department for osteoarticular trauma who underwent radiography were prospectively included in this study. A connection was drawn between the rate of abnormal radiographic findings for the seven most frequently radiographed locations and the clinical findings. RESULTS: Of 3128 locations of trauma in 2470 children, only 22% of the radiographic examinations were considered to reveal abnormal findings. In decreasing order, the hand and fingers, the ankle, the wrist, the knee, the elbow, the foot and toes, and the forearm were the most frequently examined locations. The rate of abnormal findings was 25.7% for the hand and fingers, 9.0% for the ankle, 42.5% for the wrist, 9.5% for the knee, 33.3% for the elbow, 18.3% for the foot, and 43.2% for the forearm. When only the direct sign of fracture was taken into account, these rates decreased for the ankle and knee to 2.6% and 1.9%, respectively. There was always a significant link between the degree of clinical suspicion and the rate of abnormal radiographic findings. However, fewer than 50% of the cases with high clinical suspicion of fracture were radiographically confirmed. CONCLUSION: It appears necessary, especially in cases of lower limb trauma, to evaluate clinical tests, including the implementation of the Ottawa ankle rules, to reduce the number of unnecessary radiographic examinations. This reduction will improve some parameters of children's quality of life and will significantly decrease the cost of emergency care.

Adolescent↗
PubMed2001

Laparoscopic ultrasound with radiofrequency ablation in cirrhotic patients with hepatocellular carcinoma: technique and technical considerations.

The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. CT-guided percutaneous radiofrequency ablation (RFA) has been shown to be efficacious in treatment of unresectable HCC. CT-guided RFA, however, may fail to detect small intrahepatic metastases and tumor thrombi, which thus minimizes possible gains from the procedure. Recent advances in laparoscopic ultrasound have greatly improved the accuracy in detecting intrahepatic HCC metastases many of which were missed by CT. Combining intraoperative laparoscopic ultrasound with laparoscopic RFA greatly utilizes advances in both fields and is technically feasible. Our objective is to introduce a novel operative combination of laparoscopic ultrasound with laparoscopic RFA in treatment of HCC. Childs class B patients with unresectable HCC were considered for this study. Twelve patients underwent laparoscopic ultrasound and RFA of 17 lesions. Tumors ranged from 0.27 to 7 cm in diameter. Laparoscopic ultrasound identified tumor not detected preoperatively in one patient (8.3%). A single pneumothorax was the only complication. A single patient (8.3%) had recurrent disease and accounted for the only mortality in the study. We conclude that the use of both laparoscopic ultrasound and RFA is an excellent use of existing technology. The procedure combines improved tumor localization with the means to treat patients with unresectable disease. Because RFA is a relatively recent development long-term results are not yet available. Randomized prospective studies comparing RFA with other modalities will determine the ultimate utility of this procedure.

Adult↗
PubMed2000

Cellular basis for age-related differences in cardiac excitation-contraction coupling.

Clinical experience indicates that infants and young children respond to a variety of cardiovascular pharmacological and physiological interventions differently than adults. What is less clear, however, are the cellular and molecular mechanisms that contribute to these age-related differences. Based largely upon results from animal models, it is apparent that developmental changes occur in numerous pathways and proteins involved in the regulation of contractile function and in the determinants of inotropic responsiveness. The purposes of this review are to provide a brief overview of cardiac excitation-contraction and to illustrate some of the important age-related differences in the mechanisms involved in calcium regulation in the heart. This scientific foundation may help to explain certain clinical observations in the very young. Furthermore, it is hoped that a better understanding of the fundamental processes involved in controlling cardiac contractile function will stimulate additional research in the search for more specific, rational and age-appropriate cardiovascular therapeutics.

Journal Article↗
PubMed2000

Phase I/II trial of recombinant methionyl human tumor necrosis factor binding protein PEGylated dimer in patients with active refractory rheumatoid arthritis.

OBJECTIVE: To evaluate the safety, immunogenicity, pharmacokinetics, and efficacy of intravenous administration of tumor necrosis factor binding protein (TNFbp) dimer in patients with rheumatoid arthritis (RA). METHODS: This phase I/II study was a multicenter, randomized, double blind, placebo controlled, ascending dose study evaluating TNFbp dimer administered by i.v. infusion. Thirty-three patients with RA divided into 3 cohorts received TNFbp dimer (30, 100, 300 microg/kg) or placebo during a 5 min infusion at baseline and at 3 and 6 weeks; patients were followed at routine intervals after each infusion through 77 days postinfusion. Pharmacokinetics were analyzed using a log-linear regimen and comparisons were made between half-life after first, 2nd, and 3rd doses. Plasma TNFbp dimer concentrations and serum antibody levels were used in the measurement of pharmacokinetics. RESULTS: Administration of 30 microg/kg of TNFbp dimer was generally well tolerated; the maximum tolerated dose was 100 microg/kg. No serious adverse events were reported. A significant antibody response affected the half-life and clearance of TNFbp dimer at each dose group. Anti-TNFbp antibodies were noncytotoxic and nonagonistic. Clinical evaluations provided evidence of in vivo activity of TNFbp dimer in these patients. CONCLUSION: TNFbp dimer administered to patients with long standing RA resulted in significant antibody production to the study drug. This effect reduced the half-life and clearance of the TNFbp. This TNFbp will not be a viable option for treating patients with RA secondary to immunogenicity.

Adult↗
PubMed2000

Thyroid function in cord blood.

OBJECTIVE: To determine the biochemical parameters of thyroid function in the cord blood of Saudi infants. METHODS: Cord blood samples sent to the Pathology Department for screening for congenital hypothyroidism were used to determine the reference ranges for thyrotropin, free thyroxine, free triiodothyronine, thyroxine-binding globulin and thyroglobulin. All the measurements were carried out by immunoassay (Elisa, microparticle enzyme immunoassay or chemiluminescence immunoassay). Reference ranges were calculated after exclusion of outliers. RESULTS: Reference ranges for thyrotropin, free thyroxine and thyroxine-binding globulin were similar to published values, whereas those for free triiodothyronine and thyroglobulin were different. CONCLUSION: For correct interpretation of the parameters of thyroid function in cord blood it is essential to have reference ranges based on the laboratory's current methods and derived from the local population.

Congenital Hypothyroidism↗
PubMed1999

The effects of parathyroidectomy on nutritional and biochemical status of hemodialysis patients with severe secondary hyperparathyroidism.

The nutritional and biochemical parameters of 15 chronic hemodialysis (HD) patients with severe secondary hyperparathyroidism who had undergone total parathyroidectomy (PTX), with a forearm implant, were retrospectively studied at 1, 3, 6, and 12 months pre- and post-PTX. The concentrations of serum calcium and phosphorous significantly decreased in the first 6 months post-PTX. The concentration of blood urea nitrogen significantly increased at 6 and 12 months post-PTX. In contrast with control chronic HD patients who had no weight gain after nonparathyroid surgery, there was a progressive weight gain leading to a significantly higher dry weight at 12 months post-PTX. There was no significant change in serum potassium, albumin, cholesterol, transferrin, bicarbonate, hematocrit, normalized protein catabolic rate (nPCR), or erythropoietin dose at any time point post-PTX. The biochemical parameters of the 8 patients who had more than 5% weight gain, during 12 months post-PTX, were not statistically different from the remaining 7 cases who had weight gain less than 5% (or had lost weight) in the same time period. The same was true for 4 patients with weight gain of more than 10% versus the latter group. In conclusion, HD patients with severe secondary hyperparathyroidism are prone to progressive weight gain post-PTX, which reaches significance by the twelfth month. In 53% of the patients, the weight gain is more than 5% above the baseline. The nutritional and biochemical parameters pre-PTX were not helpful in distinguishing those who developed significant weight gain post-PTX.

Adult↗
PubMed1999

Formation of stable covalent dimer explains the high solubility at pH 4.6 of lactose-beta-lactoglobulin conjugates heated near neutral pH.

The solubility of lactose-beta-lactoglobulin conjugates at pH 4.6, after heating near neutral pH in phosphate buffer/0.116 M NaCI, was investigated by size exclusion chromatography and compared with unmodified protein. Heated conjugates in the temperature range 65-90 degrees C showed greater solubility at pH 4.6. The proportion of soluble protein increased with the number of bound lactose molecules. Total solubility was obtained for conjugates with nine lactose residues attached per monomer of beta-lactoglobulin. The protective effect of bound sugar toward precipitation was associated with the formation of soluble disulfide cross-linked dimers, highly accessible to trypsin digestion. These results suggested that bound lactose, through steric hindrance and high surface hydrophilicity, prevents the thiol-disulfide exchange reactions of the polymerization-aggregation process of lactose-beta-lactoglobulin conjugates.

Chromatography, Gel↗
PubMed1999

Maternal age- and gestation-specific risk for trisomy 21.

OBJECTIVE: To provide estimates of maternal age- and gestational age-related risks for trisomy 21. METHODS: The prevalence of trisomy 21 was examined in 57,614 women who had fetal karyotyping at 9-16 weeks of gestation for the sole indication of maternal age of 35 years or more. On the basis of the maternal age distribution and the reported maternal age-related risk for trisomy 21 at birth, the expected number of trisomy 21 cases was calculated for each gestational age subgroup (9-10 weeks, 11-14 weeks and 15-16 weeks). The ratio of the observed to expected number of cases of trisomy 21 was then calculated and regression analysis was applied to derive a smoothened curve. The formula for maternal age- and gestational age-related risk was then applied to a population of 96,127 pregnancies that were examined at 10-14 weeks to calculate the expected number of trisomy 21 pregnancies, and this number was compared to the observed number of 326. RESULTS: In the 57,614 pregnancies there were 538 cases of trisomy 21. The relative prevalences of trisomy 21, compared to a prevalence of 1.0 at 40 weeks, was 10 exp(0.2718 x log(10)(gestation)2 - 1.023 x log10(gestation) + 0.9425). On the basis of the estimated maternal age- and gestational age-related risks, the expected number of trisomy 21 cases at 10-14 weeks of gestation in the 96,127 pregnancies was 329 (95% confidence interval 291-361), which was not significantly different from the observed number of 326 cases (chi2 = 0.02). CONCLUSION: The risk for trisomy 21 increases with maternal age and decreases with gestation. The prevalence of trisomy 21 at 12 and 16 weeks of gestation is higher than the prevalence at 40 weeks by 30% and 21%, respectively.

Adult↗
PubMed1997

Chemotherapy-induced myocardial necrosis in a patient with chronic lymphocytic leukemia.

Cardiac toxicity following the administration of chemotherapeutic agents is well documented. Vinca alkaloids, as well as high-dose cyclophosphamide, have been associated with myocardial ischemia. The present report describes a case of acute myocardial infarction occurring in a patient with no antecedent cardiac history who received both vincristine and conventional chemotherapeutic doses of cyclophosphamide for the treatment of chronic lymphocytic leukemia. Physicians should possess a heightened awareness of this potentially serious complication.

Aged↗
PubMed1997

Inhibition of bovine trypsin by the phosphorylated N-terminal part beta(1-105) of beta-casein.

The sensitivities of the R25-I26 bond on bovine beta-casein and on its N-terminal fragment beta(1-105) to trypsin digestion were compared by monitoring the liberation of the beta(1-25) product. It was shown that this peptide bond was poorly and slowly hydrolysed on beta(1-105), while it is highly susceptible to trypsin attack when whole protein is used as substrate. The marked resistance of beta(1-105) is linked to its inhibitory effect on trypsin activity (apparent K'i = 1.2 x 10(-6) M), as demonstrated by using a related chromogenic substrate. Indeed, a preincubation step of trypsin with beta(1-105) leads to a more pronounced inhibitory effect. The progress curves obtained with and without preincubation show that beta(1-105) acts as a slow binding inhibitor on trypsin activity. These findings promise further insight into the action and the regulation of proteolytic enzymes.

Amino Acid Sequence↗
PubMed1997

Biochemical and ultrastructural indices of muscle damage after a twenty-one kilometre run.

Increased serum concentrations of intracellular proteins are generally accepted as good indicators of muscle damage. The mechanism of this damage is, however, poorly understood. Twenty male runners completed a 21 km run in as fast a time as possible. Blood samples were obtained from each subject just prior to, immediately after, and 24 hr after the run. Samples were analysed for haemoglobin, haematocrit, creatine kinase (CK), myoglobin (Mb) and malondialdehyde (MDA) concentrations and corrected for percentage change in plasma volume (PV). Percutaneous muscle biopsies were taken from the lateral gastrocnemius muscle of 6 of the subjects 24 hr before and 24 hr after the run and examined by electron microscopy. Mb levels in the serum increased significantly (p < 0.001) immediately post-exercise, while CK levels increased significantly (p < 0.001) at 24 hours post-exercise. The PV corrected serum MDA levels were very close (p = 0.06) to a significant increase immediately post-exercise. Ultrastructural examination of pre-exercise samples revealed evidence of muscle changes consistent with endurance exercise training, but no further damage was evident at 24 hr post-exercise. It is thus suggested that the increased serum levels of CK and Mb after the 21 km run may be a result of free radical induced cell membrane damage and increased permeability, as evidenced by elevated serum MDA levels, and not due to mechanical muscle damage.

Adult↗
PubMed1996

Local cerebral glucose metabolism in patients with long-term behavioral and cognitive deficits following mild traumatic brain injury.

A retrospective study of 20 patients with mild traumatic brain injury (MTBI) examined brain regions of interest by comparing [18F]-2-deoxyglucose PET, neuropsychological test results, and continuing behavioral dysfunction. Abnormal local cerebral metabolic rates (rLCMs) were most prominent in midtemporal, anterior cingulate, precuneus, anterior temporal, frontal white, and corpus callosum brain regions. Abnormal rLCMs were significantly correlated statistically with 1) overall clinical complaints, most specifically with inconsistent attention/concentration and 2) overall neuropsychological test results. The authors conclude that 1) even mild TBI may result in continuing brain behavioral deficits; 2) PET can help elucidate dysfunctional brain circuitry in neurobehavioral disorders; and 3) specific brain areas may correlate with deficits in daily neurobehavioral functioning and neuropsychological test findings.

Adolescent↗