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Biomedical subjects

J Price

Publications and source records attributed to J Price.

At least 109 records · Page 6Linked to original sources
PubMed1997

Blepharospasm and hemifacial spasm. Randomized trial to determine the most appropriate location for botulinum toxin injections.

PURPOSE: The purpose of the study is to analyze the effectiveness and side effects of botulinum toxin using four different treatment site applications to determine the most successful treatment regime with the least side effects. METHODS: In a prospective trial, 92 patients (50 blepharospasm and 42 hemifacial spasm) were assigned randomly to 1 of 4 different treatment groups (standard [S], brow [B], inner orbital [IO], or outer orbital [OO]). Each treatment group had a different pattern of injection sites in the orbicularis. A total of 285 treatments were given, and the mean follow-up time was 16.4 months. RESULTS: In the blepharospasm group, patients assigned to the standard group had a significantly longer duration of effect than for those in the brow, inner orbital, and outer orbital groups (8.1 weeks compared with 4.5, 4.2, and 3.1 weeks, respectively; P < 0.001). In the hemifacial spasm group, patients in the outer orbital group had significantly shorter duration of effect than those in standard, brow, or inner orbital group (7.2 weeks compared with 12.6, 12.8 and 10.4 weeks, respectively; P < 0.001). The four major complications of botulinum toxin treatment were epiphora, ocular irritation, ptosis, and diplopia. The inner orbital treatment produced significantly more episodes of ptosis (13% of treatments). However, the standard treatment produced the most epiphora and ocular irritation (18% of treatments). CONCLUSIONS: The position of the injection sites around the orbicularis influences the effectiveness and side effects of botulinum toxin treatment for patients with blepharospasm and hemifacial spasm. The further the treatment is away from the eyelid margin, the lower the risk of ocular side effects. The standard treatment produces the longest duration of effect in the blepharospasm group but with the most transient ocular irritation and epiphora. In the hemifacial spasm group, the brow treatment has an equally long duration of effect as that of the standard treatment with fewer side effects.

Aged↗
PubMed1997

Mast cell ultrastructure in the inferior turbinate and stroma of nasal polyps.

Fourteen unselected adult patients with nasal polyps had ultrastructural examination of mast cells from matching biopsies of the polyp and inferior turbinate. Between three and 10 blocks were examined for each patient in both tissues and every mast cell that had a nucleus was photographed for study. Fifty-three mast cells were found within the stroma of nasal polyps and 54 in the submucosa of the inferior turbinate biopsies. The number of granules ranged between 13 and 167 (mean 60) for polyps and 18 and 148 (mean 61) in the inferior turbinate. The mast cells appeared essentially normal in the inferior turbinate of four patients. The degree of degranulation of the mast cells was calculated as in previous studies and then averaged for both the polyp and the inferior turbinate of each patient. There was greater degranulation in the nasal polyp compared to inferior turbinate (p = 0.03). These results were compared with mast cell degranulation found in the normal nose and in the inferior turbinate of patients with perennial allergic rhinitis which we previously published. The inferior turbinates in these patients were more degranulated than the normal nose (p = 0.0001) but were similar to that found in patients with perennial allergic rhinitis. This suggested that some degree of degranulation may occur throughout the nose in two thirds of the patients with nasal polyps which supports the theory that mast cell reactions are not limited to the polyps in a proportion of patients.

Adult↗
PubMed1997

Gentamicin and tobramycin pharmacokinetics in pediatric bone marrow transplant patients.

OBJECTIVE: To describe the pharmacokinetic parameters of gentamicin and tobramycin in pediatric bone marrow transplant patients. DESIGN: Retrospective medical record review. SETTING: Pediatric bone marrow transplant unit in a university teaching hospital. MAIN OUTCOME MEASURES: Pharmacokinetic parameters (apparent volume of distribution [Vd] in L/kg, half-life [t1/2] in h, elimination rate constant [ke] in h-1, clearance [Cl] in mL/min/1.73 m2 and mL/min/kg) calculated from serum concentrations. PATIENTS: Thirty-three patients aged 15 years or less who underwent bone marrow transplant and received gentamicin or tobramycin. RESULTS: Mean pharmacokinetic parameters were Vd 0.32 +/- 0.07 L/kg, t1/2 2.32 +/- 0.65 h, Cl 1.71 +/- 0.53 mL/min/kg, and Cl 86.2 +/- 24.5 mL/min/1.73 m2. Factors such as disease state, type of marrow graft, gender, or exposure to cyclosporine had no significant effect on pharmacokinetic parameters. Linear regression indicated a weak relationship between serum creatinine (SCr) and Cl in mL/min/kg (r = 0.59), but no relationship was found between SCr and Cl in mL/min/1.73 m2, between age and apparent Vd, or between SCr and apparent Vd. Models for estimating Cl and Ke developed by multiple regression were somewhat predictive (r = 0.7). Required calculated maintenance dosages to obtain therapeutic concentrations were 8, 7, and 6 mg/kg/d in children 6 or younger, 7-12, and 13-15 years, respectively. CONCLUSIONS: The mean Cl and apparent Vd for all ages are similar to those reported in pediatric oncology patients who had not undergone marrow transplantation. Children 6 years or younger had lower than expected Cls and larger apparent Vds than did the older children. Dosages estimated to be necessary to achieve therapeutic concentrations were 6-8 mg/kg/d.

Adolescent↗
PubMed1997

Pax6-dependent regulation of adhesive patterning, R-cadherin expression and boundary formation in developing forebrain.

Mutations in the gene for the transcription factor, Pax6, induce marked developmental abnormalities in the CNS and the eye, but the cellular mechanisms that underlie the phenotype are unknown. We have examined the adhesive properties of cells from the developing forebrain in Small eye, the Pax6 mutant mouse. We have found that the segregation normally observed in aggregates of cortical and striatal cells in an in vitro assay is lost in Small eye. This correlates with an alteration of in vivo expression of the homophilic adhesion molecule, R-cadherin. Moreover, the boundary between cortical and striatal regions of the telencephalon is dramatically altered in Small eye: radial glial fascicles do not form at the border, and the normal expression of R-cadherin and tenascin-C at the border is lost. These data suggest a link between the transcription factor, Pax6, R-cadherin expression, cellular adhesion and boundary formation between developing forebrain regions.

Animals↗
PubMed1997

Prevention and treatment of lymphedema after breast cancer.

Through personal experience, these two health care professionals discovered that the threat of lymphedema and its risk factors is often underestimated by clinicians. What they learned may help you provide better care for your patients with breast cancer.

Breast Neoplasms↗
PubMed1997

Simple epithelium keratins are required for maintenance of hepatocyte integrity.

Keratin 8 (K8)-deficient adult mice develop a severe disease of the gastrointestinal tract characterized mainly by colorectal hyperplasia and inflammation. Given that hepatocytes contain K8/K18 heteropolymers only, this animal model was used to assess the contribution of these simple epithelium keratins to hepatocyte structural and functional integrity. Homozygous mutant (HMZ), heterozygous, and wild-type (WT) mice were examined for hepatocyte structural and metabolic features and their survival to partial hepatectomy. Except for the presence of few necrotic foci, no other tissular or cellular alterations were observed in nonhepatectomized HMZ mouse livers; glycogen and lipid peroxidation levels were essentially normal, but a small reduction in bile flow was observed. In response to a single pentobarbital injection, HMZ mice had longer sleeping times than heterozygous and WT mice. After a two-thirds partial hepatectomy under pentobarbital anesthesia, all HMZ mice died within a few hours, whereas those anesthetized with ether survived for 1 to 2 days. One hour after hepatectomy after pentobarbital anesthesia, many hepatocytes contained erythrocytes and large vacuoles in the cytoplasm, which suggests damage at the plasma membrane level in response to a sudden increase in portal blood flow. In line with these findings, an uptake of trypan blue by HMZ but not WT mouse hepatocytes was observed during a 10 ml/minute perfusion via the portal vein with a dye-supplemented buffer. Subsequent cellular dispersion led to viable WT mouse hepatocytes but largely nonviable HMZ mouse hepatocytes. Better viability was obtained at lower perfusion rates. Partially hepatectomized heterozygous mice developed liver steatosis, a condition that was not associated with a change in K8 content but perhaps linked to the presence of the neo gene. Transgenic HMZ mouse rescue experiments with a full-length K8 gene confirmed that the phenotypic alterations observed in partially hepatectomized HMZ mice were caused by the disruption of the K8 gene. Taken together, these findings demonstrate that simple epithelium keratins are essential for the maintenance of hepatocyte structural and functional integrity.

Animals↗
PubMed1996

Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine.

Clozapine is an atypical antipsychotic with affinity for a broad range of receptors, including serotonin (5-HT) and dopamine receptors. It is successful in treating about 60% of patients refractory to other antipsychotic drugs. Since genetic variation in clozapine's neurotransmitter receptor targets may affect clinical response through altering drug binding or receptor expression, we have studied a His452Tyr polymorphism in the 5-HT2A receptor (HTR2A) in a sample of 153 schizophrenic patients undergoing clozapine treatment and 178 normal controls. An association was found between the allele Tyr452 and poor clinical response.

Alleles↗
PubMed1996

Identification of active site residues essential to 4-chlorobenzoyl-coenzyme A dehalogenase catalysis by chemical modification and site directed mutagenesis.

4-Chlorobenzoyl-coenzyme A (4-CBA-CoA) dehalogenase catalyzes the hydrolysis of 4-CBA-CoA to 4-hydroxybenzoyl-coenzyme A (4-HBA-CoA) via a nucleophilic aromatic substitution pathway involving the participation of an active site carboxylate side chain in covalent catalysis. In this paper we report on the identification of conserved aspartate, histidine, and tryptophan residues essential to 4-CBA-CoA catalysis using chemical modification and site-directed mutagenesis techniques. Treatment of the dehalogenase with diethyl pyrocarbonate resulted in complete loss of catalytic activity (Kinact = 0.17 mM-1 min-1 at pH 6.5, 25 degrees C) that was fully regained by subsequent treatment with hydroxylamine. The protection from inactivation afforded by enzyme bound 4-HBA-CoA indicated that the essential histidine residues are located at the active site. Replacement of conserved histidine residues 81, 90, 94, and 208 with glutamine residues resulted in a significant loss of catalytic activity only in the cases of the histidine 81 and 90 mutants. Substrate and product ligand binding studies showed that binding is not significantly inhibited in these mutants. Site directed mutagenesis of a selection of conserved aspartate and glutamate residues, identified aspartate 145 as being essential to dehalogenase catalysis. Ligand binding studies showed that this residue is not required for tight substrate/product binding. Chemical modification of the dehalogenase with N-bromosuccinimide resulted in full loss of catalytic activity that was prevented by saturation of the active site with product ligand, providing evidence favoring an essential active site tryptophan. Phenylalanine replacement of conserved tryptophan residues 179 and 137 reduced catalytic activity only in the latter (Kcat = 0.03% of wild-type dehalogenase). On the basis of these results and the recently determined X-ray crystal structure of the complex of 4-CBA-CoA dehalogenase and 4-HBA-CoA [Benning, M. M., Taylor, K.L., Liu, R.-Q., Yang, G., Xiang, H., Wesenberg, G., Dunaway-Mariano, D., Holden, H.M. (1996) Biochemistry 35,8103-8109] we propose that aspartate 145 functions as the active site nucleophile, that tryptophan 137 serves as a hydrogen bond donor to the aspartate 145 C = O, and that histidine 90 serves to deprotonate the bound H2O molecule.

Amino Acids↗
PubMed1996

The regulation of the expression, phosphorylation, and protein associations of pp125FAK during rat brain development.

We have studied both the expression and the interactions of focal adhesion kinase (FAK) during brain development. We have discovered that during different periods of development, FAK apparently has different properties. During the early stage of neurogenesis, FAK is phosphorylated, shows multiple isoforms, and interacts with the proto-oncogenes, src, fyn, and lyn. At this stage, FAK also interacts with both the N- and C-terminal SH2 domains of GAP, a negative regulator of the ras pathway. During later embryonic development, none of these protein interactions are apparent even though FAK is still predominantly phosphorylated. By adulthood FAK is largely unphosphorylated and migrates as a single protein species on SDS--PAGE. We discuss these results in terms of the dynamic cell movements that occur during embryonic brain development.

Age Factors↗
PubMed1996

Selective adhesion of cells from different telencephalic regions.

We asked whether specifications of different regions of the rodent and avian telencephalon during development involved the acquisition of differential adhesive properties. Cells from different regions were aggregated in a short-term aggregation assay, and their segregation was analyzed. Both neurons and precursor cells from cortex segregate from striatal cells at early, but not later, stages, whereas cells from rodent neocortex and hippocampus segregated only during later stages. Segregation was abolished when Ca2+-dependent but not Ca2+-independent adhesion molecules were selectively removed. Thus, selective adhesion appears to be a conserved mechanism that restricts cellular mixing and might serve to maintain positional information during forebrain development. A candidate for mediating the Ca2+-dependent segregation is the CD15 (Lewis(x)) carbohydrate epitope, which is selectively expressed by mammalian cortex but not striatum.

Animals↗
PubMed1996

Synthesis, biodistribution, and estrogen receptor scintigraphy of indium-111-diethylenetriaminepentaacetic acid-tamoxifen analogue.

This study was aimed at developing a hydrophilic diethylenetriaminepentaacetic acid-tamoxifen (DTPA-Tam) analogue for use in imaging estrogen receptor positive (ER+) lesions. In rat uterine cytosol, the IC50 of DTPA-Tam conjugate was 1 microM and of tamoxifen, 2 microM. Biodistribution, autoradiography, and radionuclide imaging of 111In-DTPA-Tam in breast-tumor-bearing rats showed that tumor-to-tissue ratios increased steadily between 30 min and 48 h. The in vivo response of MCF-7 breast cancer xenografts to tamoxifen and DTPA-Tam in nude mice demonstrated that DTPA-Tam could reduce tumor growth rate. These results indicate that DTPA-Tam, a new hydrophilic ER+ ligand, might be useful in diagnosing ER+ lesions.

Animals↗
PubMed1996

Hepatitis C genotypes in Australian haemophilia patients.

BACKGROUND: Differences in the hepatitis C virus (HCV) genotype influence the severity of HCV related liver disease and response to interferon therapy. HCV infection is frequent in Australian haemophilia patients who have been exposed repeatedly to multiple HCV genotypes through non HCV virally inactivated clotting factor concentrates. The distribution of the various HCV genotypes in Australian haemophilia patients is unknown. AIM: To examine the HCV genotype distribution and clinical features of HCV associated liver disease in Australian haemophilia patients. METHODS: Forty patients with bleeding disorders who were known to be both HCV antibody and polymerase chain reaction (PCR) positive were evaluated by direct sequencing of the PCR products for the HCV genotype. RESULTS: Genotype 1 was found in 65% of patients (26/40), type 2 in 5% (2/40) and type 3 in 30% (12/40). No genotypes 4 to 6 were found. There was no association between the HCV genotype and the severity of haemophilia, alanine transaminase levels, or the presence of portal hypertension. Unlike European, Asian and American studies where the majority of type 1 infection is subclass 1b, in Australian haemophilia patients it is subclass 1a (73%-19/26) which may have a better prognosis and response to interferon. CONCLUSIONS: Despite patients with haemophilia being exposed to multiple HCV genotypes, it appears that there is no selection advantage of one genotype over another. Australian haemophilia patients with HCV have a different genotype distribution to that reported in other countries and care should be observed in interpreting non Australian studies concerning HCV.

Adolescent↗
PubMed1996

Preventing the Wernicke-Korsakoff syndrome in Australia: cost-effectiveness of thiamin-supplementation alternatives.

Alcoholic Wernicke's encephalopathy has been commonplace in Australia for many years and, as this syndrome is attributed to a deficiency in the diet, it should be preventable. This study employs conventional cost-effectiveness methodology to compare the economic efficiency of several thiamin-supplementation alternatives that have been proposed for the prevention of Wernicke's encephalopathy. A series of rankings of these measures is derived from an estimated cost per case averted for each of the alternatives studied. These rankings identify the least cost-effective thiamin-supplementation alternative as that of enriching bread-making flour with thiamin.

Alcohol Amnestic Disorder↗
PubMed1996

Improved yield of peripheral blood progenitor cells on the Cobe Spectra.

The efficiency of leucapheresis using the Cobe Spectra depends on the observation of the operator to monitor the haematocrit (Hct) in the collection line at the recommended Hct of 1%. Cells were harvested by processing 3 x total blood volume (TBV) over 3-4 h. During the harvest the manual Hct and the colony-forming units granulocyte-macrophage (CFU-GM) concentrations were analysed in the collection line in the observed Hct range of 1-7.5%. There was a correlation between the manual and observed Hct (r = 0.97). The CFU-GM concentration was normalised to allow comparison between patients. The increase was statistically significant between 1-2% (P = 0.04) and 1-3% Hct (P = 0.05). The increase in CFU-GM concentration remained at the termination of harvest, indicating that not all available CFU-GM were harvested. The optimum concentration of progenitor cells was found to be at 3% Hct. We postulate that this may permit the collection of sufficient cells on one occasion to allow PBPC autografting in the majority of patients who respond to mobilisation.

Adult↗
PubMed1995

Association between clozapine response and allelic variation in the 5-HT2C receptor gene.

A cysteine to serine substitution at amino acid 23 in the 5-HT2C receptor gene alters the pharmacological properties of the protein. We investigated this polymorphism in subjects with schizophrenia resistant to conventional neuroleptic drugs, and analysed our data for allelic association between the disease state or clinical response to the atypical antipsychotic drug, clozapine. Ninety percent of subjects who had one or more 5-HT2Cser alleles (19/21) were classified as clozapine responders compared with 59% (84/141) without this allele (chi 2 = 7.7, p = 0.005), suggesting that this mutation is a predictor of good response to clozapine. There was no association between schizophrenia and the 5-HT2Cser allele, but our results indicate that the 5-HT2C receptor may contain the major site of action through which clozapine mediates its antipsychotic effects.

Alleles↗
PubMed1995

Lysine residues at positions 234 and 236 in yeast porin are involved in its assembly into the mitochondrial outer membrane.

Various point mutations of lysyl residues in yeast mitochondrial porin (283 residues) were tested for their ability to assemble in vitro into the outer membranes of intact yeast mitochondria. Assembly was evaluated by protection from proteinases. The extent of assembly of two of the mutants, K234E and K236E porins, was much less than for wild-type in either post-translational or co-translational assembly assays. Lysine to glutamate mutants at other positions and K234R porin assembled as well as wild-type, but K234Q porin was poorly inserted. When both Lys-234 and Lys-236 were mutated, K234R/K236R porin was inserted better than K234Q/K236Q porin, which was inserted better than K234E/K236E; however, none of these mutants assembled as well as wild-type porin. It was concluded that optimal assembly of yeast porin depended on the presence of positively charged residues at both positions 234 and 236 and a lysine at one of these positions. After undergoing the assembly reaction, mutants that were vulnerable to proteinase K (i.e. K234E, K234Q, and K236E porins) seemed to be incompletely digested and were, to varying degrees, resistant to extraction by Na2CO3 (pH 11.5). These experiments suggested that these mutants were incompletely inserted into the outer membrane. Both Lys-234 and Lys-236 are included in an internal pentapeptide, VKAKV, that is conserved in porins from protists, plants, and animals, and it is possible that, at least, the lysines in this tract are one of the signals for the membrane assembly of these proteins.

Amino Acid Sequence↗