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Biomedical subjects

C Johnson

Publications and source records attributed to C Johnson.

At least 37 records · Page 2Linked to original sources
PubMed2002

Does weight loss improve incontinence in moderately obese women?

The aim of this study was to evaluate the effect of weight reduction on urinary incontinence in moderately obese women. This prospective cohort study enrolled moderately obese women experiencing four or more incontinence episodes per week. BMI and a 7-day urinary diary were collected at baseline and on the completion of weight reduction. The study included 10 women with a mean (+/-SD) baseline BMI of 38.3 (+/-10.1) kg/m2 and 13 (+/-10) incontinent episodes per week. Participants had a mean BMI reduction of 5.3 (+/-6.2) kg/ m2 (P < 0.03). Among women achieving a weight loss of > or = 5%, 6/6 had > or = 50% reduction in incontinence frequency compared to 1 in 4 women with < 5% weight loss (P < 0.03). Incontinence episodes decreased to 8 (+/-10) per week following weight reduction (P < 0.07). The study demonstrated an association between weight reduction and improved urinary incontinence. Weight reduction should be considered for moderately obese women as part of non-surgical therapy for incontinence.

Adult↗
PubMed2002

Ultrasound monitoring of temperature change during radiofrequency ablation: preliminary in-vivo results.

Radiofrequency (RF) ablation is an interstitial focal ablative therapy that can be used in a percutaneous fashion and permits in situ destruction of hepatic tumors. However, local tumor recurrence rates after RF ablative therapy are as high as 34% to 55%, which may be due in part to the inability to monitor accurately temperature profiles in the tissue being ablated, and to visualize the subsequent zone of necrosis (thermal lesion) formed. The goal of the work described in this paper was to investigate methods for the real-time and in vivo monitoring of the spatial distribution of heating and temperature elevation to achieve better control of the degree of tissue damage during RF ablation therapy. Temperature estimates are obtained using a cross-correlation algorithm applied to RF ultrasound (US) echo signal data acquired at discrete intervals during heating. These temperature maps were used to display the initial temperature rise and to continuously update a thermal map of the treated region. Temperature monitoring is currently performed using thermosensors on the prongs (tines) of the RF ablation probe. However, monitoring the spatial distribution of heating is necessary to control the degree of tissue damage produced.

Animals↗
PubMed2002

Risk factors for post-stem cell transplant sinusitis.

An understanding of the factors that place the post-transplant patient at increased risk for sinusitis would help identify patients likely to develop disease and possibly allow for interventions that would decrease the incidence or severity of sinus disease. This retrospective study investigates the ability of screening paranasal sinus computed tomographic scans (CTs), clinical history, and potential risk factors for sinusitis, including history of tobacco use, history of allergies or asthma, IgG level, history of sinusitis, remission status and acute graft-versus-host disease (GVHD) to predict post-transplant sinusitis. Medical records and sinus CTs of 100 allogeneic bone marrow recipients were reviewed. There was no increased risk of developing sinusitis post SCT for patients with significant disease on screening CT, symptoms at time of transplant, a history of tobacco use, asthma or allergies, low IgG level, history of sinusitis or for patients at high risk of relapse. Patients with GVHD were 4.3 times more likely than patients without GVHD to develop sinusitis post transplant (95% CI: 1.7-11.0, P = 0.002). Acute GVHD places patients at greater risk of developing sinus infections.

Adult↗
PubMed2002

Radiation therapy following nodal surgery for melanoma: an analysis of late toxicity.

BACKGROUND: The role of adjuvant radiation therapy following resection of malignant melanoma involving regional lymph nodes remains controversial. There is no published randomized trial comparing surgery alone to surgery with postoperative radiation therapy that shows a benefit in terms of local control. Some retrospective studies, however, suggest that radiation given postoperatively reduces local recurrence. One of the obstacles to patients routinely being offered radiation therapy is the concern over the added late toxicity that may occur. The present article is a report of the first 130 patients of a prospective phase II multicentre study in Australia and New Zealand. METHODS: The study was aimed at patients who had had a resection of melanoma in regional nodes or in a regional node basin. The patients were given adjuvant radiation therapy to a recommended dose of 48 Gy in 20 fractions over 4 weeks using accepted radiation techniques for each of the major node sites. This report describes the late toxicity of the treatment received by these patients. RESULTS: The results of late toxicity experienced in the study were acceptable. CONCLUSION: The regimen of radiation therapy used could form the basis for the treatment arm of a randomized trial.

Adult↗
PubMed2001

The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity.

The pancreas is a complex organ that consists of separate endocrine and exocrine cell compartments. Although great strides have been made in identifying regulatory factors responsible for endocrine pancreas formation, the molecular regulatory circuits that control exocrine pancreas properties are just beginning to be elucidated. In an effort to identify genes involved in exocrine pancreas function, we have examined Mist1, a basic helix-loop-helix transcription factor expressed in pancreatic acinar cells. Mist1-null (Mist1(KO)) mice exhibit extensive disorganization of exocrine tissue and intracellular enzyme activation. The exocrine disorganization is accompanied by increases in p8, RegI/PSP, and PAP1/RegIII gene expression, mimicking the molecular changes observed in pancreatic injury. By 12 m, Mist1(KO) mice develop lesions that contain cells coexpressing acinar and duct cell markers. Analysis of the factors involved in cholecystokinin (CCK) signaling reveal inappropriate levels of the CCK receptor A and the inositol-1,4,5-trisphosphate receptor 3, suggesting that a functional defect exists in the regulated exocytosis pathway of Mist1(KO) mice. Based on these observations, we propose that Mist1(KO) mice represent a new genetic model for chronic pancreas injury and that the Mist1 protein serves as a key regulator of acinar cell function, stability, and identity.

Animals↗
PubMed2001

Adenocarcinoma arising in a transplanted pancreas.

Tumor transmission or de novo tumor development in the transplanted organ is a rare event. Appreciation of the organ-specific risk factors for tumor development and careful inspection of the organ at procurement may reduce but not eliminate this complication. We report the first known combined kidney-pancreas recipient who developed adenocarcinoma in the transplanted pancreas. Molecular typing of the tumor by DNA sequencing supports donor derivation of the tumor. Despite cessation of immunosuppression and reconstitution of the recipient's immune response, the patient died from metastatic pancreatic adenocarcinoma. Comparison is made to the reported outcomes after diagnosis of renal cell carcinoma that appeared early after transplantation

Adenocarcinoma↗
PubMed2001

Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3.

Usher syndrome type 3 (USH3) is an autosomal recessive disorder characterized by progressive hearing loss, severe retinal degeneration, and variably present vestibular dysfunction, assigned to 3q21-q25. Here, we report on the positional cloning of the USH3 gene. By haplotype and linkage-disequilibrium analyses in Finnish carriers of a putative founder mutation, the critical region was narrowed to 250 kb, of which we sequenced, assembled, and annotated 207 kb. Two novel genes-NOPAR and UCRP-and one previously identified gene-H963-were excluded as USH3, on the basis of mutational analysis. USH3, the candidate gene that we identified, encodes a 120-amino-acid protein. Fifty-two Finnish patients were homozygous for a termination mutation, Y100X; patients in two Finnish families were compound heterozygous for Y100X and for a missense mutation, M44K, whereas patients in an Italian family were homozygous for a 3-bp deletion leading to an amino acid deletion and substitution. USH3 has two predicted transmembrane domains, and it shows no homology to known genes. As revealed by northern blotting and reverse-transcriptase PCR, it is expressed in many tissues, including the retina.

Abnormalities, Multiple↗
PubMed2001

Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.

BACKGROUND: A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years. METHODS: Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. RESULTS: The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. CONCLUSIONS: All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Administration, Oral↗
PubMed2001

Characterization of the allosteric anion-binding site of O-acetylserine sulfhydrylase.

A new crystal structure of the A-isozyme of O-acetylserine sulfhydrylase-A (OASS) with chloride bound to an allosteric site located at the dimer interface has recently been determined [Burkhard, P., Tai, C.-H., Jansonius, J. N., and Cook, P. F. (2000) J. Mol. Biol. 303, 279-286]. Data have been obtained from steady state and presteady-state kinetic studies and from UV-visible spectral studies to characterize the allosteric anion-binding site. Data obtained with chloride and sulfate as inhibitors indicate the following: (i) chloride and sulfate prevent the formation of the external aldimines with L-cysteine or L-serine; (ii) chloride and sulfate increase the external aldimine dissociation constants for O-acetyl-L-serine, L-methionine, and 5-oxo-L-norleucine; (iii) chloride and sulfate bind to the allosteric site in the internal aldimine and alpha-aminoacrylate external aldimine forms of OASS; (iv) sulfate also binds to the active site. Sulfide behaves in a manner identical to chloride and sulfate in preventing the formation of the L-serine external aldimine. The binding of chloride to the allosteric site is pH independent over the pH range 7-9, suggesting no ionizable enzyme side chains ionize over this pH range. Inhibition by sulfide is potent (K(d) is 25 microM at pH 8) suggesting that SH(-) is the physiologic inhibitory species.

Allosteric Site↗
PubMed2001

Detecting colorectal cancer in stool with the use of multiple genetic targets.

BACKGROUND: Colorectal cancer cells are shed into the stool, providing a potential means for the early detection of the disease using noninvasive approaches. Our goal was to develop reliable, specific molecular genetic tests for the detection of colorectal cancer in stool samples. METHODS: Stool DNA was isolated from paired stools and primary tumor samples from 51 colorectal cancer patients. Three genetic targets-TP53, BAT26, and K-RAS-were used to detect tumor-associated mutations in the stool prior to or without regard to the molecular analyses of the paired tumors. TP53 gene mutations were detected with a mismatch-ligation assay that detects nine common p53 gene mutations. Deletions within the BAT26 locus were detected by a modified solid-phase minisequencing method. Mutations in codons 12 and 13 of K-RAS were detected with a digital polymerase chain reaction-based method. RESULTS: TP53 gene mutations were detected in the tumor DNA of 30 patients, all of whom had the identical TP53 mutation in their stools. Tumors from three patients contained a noninherited deletion at the BAT26 locus, and the same alterations were identified in these patients' stool specimens. Nineteen of 50 tumors tested had a K-RAS mutation; identical mutations were detected in the paired stool DNA samples from eight patients. In no case was a mutation found in stool that was not also present in the primary tumor. Thus, the three genetic markers together detected 36 (71%) of 51 patients (95% confidence interval [CI] = 56% to 83%) with colorectal cancer and 36 (92%) of 39 patients (95% CI = 79% to 98%) whose tumors had an alteration. CONCLUSION: We were able to detect the majority of colorectal cancers by analyzing stool DNA for just three genetic markers. Additional work is needed to determine the specificity of these genetic tests for detecting colorectal neoplasia in asymptomatic patients and to more precisely estimate the prevalence of the mutations and sensitivity of the assay.

Aged↗
PubMed2001

Peroxisome proliferator-activated receptor gamma-mediated transcriptional up-regulation of the hepatocyte growth factor gene promoter via a novel composite cis-acting element.

Hepatocyte growth factor (HGF) is a pleotropic polypeptide that can function as a morphogen, motogen, mitogen, angiogen, carcinogen, and tumor suppressor, depending on the target cell and tissue. Previous studies from our laboratory using transgenic mice have shown that HGF gene expression is tightly regulated at the transcriptional level and that the upstream regulatory elements are crucial for the control of HGF gene transcription. In the present study, we have identified and characterized one of these elements as a peroxisome proliferator-activated receptor gamma (PPARgamma)-responsive element. This regulatory element was localized at -246 to -233 base pairs upstream from the transcription start site of the HGF gene promoter having the sequence GGGCCAGGTGACCT. Gel mobility shift and supershift assays demonstrated that this cis-acting element strongly binds to the PPARgamma isoforms as well as to chicken ovalbumin upstream promoter-transcription factor, a member of the orphan nuclear receptor subfamily. Mutational analysis and gel mobility band shift assays indicated that the binding site is an inverted repeat of the AGGTCA motif with two spacers (inverted repeat 2 configuration) and that the two spacers are important for PPARgamma binding. This binding site overlaps with functional binding sites for activating protein-2, nuclear factor 1, and upstream stimulatory factor, and together, they constitute a multifunctional composite binding site through which these different transcription factors exert their regulatory effects on HGF promoter activity. Functional assays revealed that PPARgamma, with its ligand, 15-deoxy-prostaglandin J2, strongly stimulates HGF promoter activity. On the other hand, nuclear factor 1, activating protein-2, and chicken ovalbumin upstream promoter-transcription factor transcription factors repress the stimulatory action of PPARgamma by competing with PPARgamma for their overlapping binding sites. Furthermore, for the first time, our studies demonstrate that the PPARgamma ligand, 15-deoxy-prostaglandin J2, induces endogenous HGF mRNA and protein expression in fibroblasts in culture.

3T3 Cells↗
PubMed2001

Why do juvenile fish utilise mangrove habitats?

Three hypotheses to discern the strong positive association between juvenile fish and mangrove habitat were tested with field and laboratory experiments. Artificial mangrove structure in the field attracted slightly more juvenile fish than areas without structure. Artificial structure left to accumulate fouling algae attracted four-times the total number of juvenile fish than areas without structure or areas with clean structure. Community composition of fish attracted to structure with fouling algae was different when compared with areas with no structure or clean structure; five species were attracted by structure with fouling algae whilst two species were associated with structure regardless of fouling algae. Algae were linked to increased food availability and it is suggested that this is an important selection criteria for some species. Other species were apparently attracted to structure for different reasons, and provision of shelter appears to be important. Predation pressure influenced habitat choice in small juvenile fish in laboratory experiments. In the absence of predators, small juveniles of four out of five species avoided shelter but when predators were introduced all species actively sought shelter. Large fish were apparently less vulnerable to predators and did not seek shelter when predators were added to their tank. Feeding rate was increased in the mangrove habitat for small and medium-sized fish compared with seagrass beds and mudflats indicating increased food availability or foraging efficiency within this habitat. Larger fish fed more effectively on the mudflats with an increased feeding rate in this habitat compared with adjacent habitats. The most important aspect of the mangrove habitat for small juvenile fish is the complex structure that provides maximum food availability and minimises the incidence of predation. As fish grow a shift in habitat from mangroves to mudflat is a response to changes in diet, foraging efficiency and vulnerability to predators.

Journal Article↗
PubMed2001

Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia.

The recessively inherited developmental disorder, cartilage-hair hypoplasia (CHH) is highly pleiotropic with manifestations including short stature, defective cellular immunity, and predisposition to several cancers. The endoribonuclease RNase MRP consists of an RNA molecule bound to several proteins. It has at least two functions, namely, cleavage of RNA in mitochondrial DNA synthesis and nucleolar cleaving of pre-rRNA. We describe numerous mutations in the untranslated RMRP gene that cosegregate with the CHH phenotype. Insertion mutations immediately upstream of the coding sequence silence transcription while mutations in the transcribed region do not. The association of protein subunits with RNA appears unaltered. We conclude that mutations in RMRP cause CHH by disrupting a function of RNase MRP RNA that affects multiple organ systems.

Alleles↗
PubMed2001

Regulation of DNA binding and trans-activation by a xenobiotic stress-activated plant transcription factor.

As-1-type cis-elements augment transcription of both nuclear and pathogen genes in response to stress and defense cues in plants. Basic/leucine zipper proteins termed "TGA factors" that specifically bind as-1 elements are likely candidates for mediating these transcription activities. Our earlier work has shown that 2, 4-dichlorophenoxyacetic acid-induced xenobiotic stress enhances trans-activation by a chimeric fusion protein of the yeast Gal4 binding domain and TGA1a, a TGA factor of tobacco. Here we demonstrate that xenobiotic stress also enhances the ability of native TGA1a to bind as-1 and activate transcription of a known target gene. In addition, the previously identified xenobiotic stress-responsive domain of TGA1a was found to inhibit this factor's trans-activation potential by a mechanism that appears to involve stimulus-reversible interactions with a nuclear repressor protein. Results from these and other studies can now be placed in the context of a working model to explain basal and xenobiotic stress-induced activities of TGA1a through its cognate cis-acting element.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2001

Thought Field Therapy-soothing the bad moments of Kosovo.

Trauma in Kosovo was treated with Thought Field Therapy (TFT) during five separate trips by members of the Global Institute of Thought Field Therapy, in the year 2000. Clinicians from Sweden, the United Kingdom, and the United States were joined in Kosovo by four physicians who transported them to remote war-torn villages where patients with severe trauma were treated. Treatment was given to 105 patients with 249 separate traumas. Total relief was reported by 103 of the patients, and for 247 of the separate traumas. Follow-up data averaging five months revealed no instance of relapse.

Adolescent↗
PubMed2001

Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: results of a phase I multi-center study.

Cystic fibrosis (CF) is characterized by defective cystic fibrosis transmembrane regulator (CFTR) expression and function, associated with abnormal ion transport and mucociliary clearance, and clinical lung disease. Triphosphate nucleotides such as uridine-5'-triphosphate (UTP) and INS 365, may be useful for CF through actions, mediated via P2Y(2) extracellular receptors, on chloride and liquid secretion, and ciliary beat frequency. INS 365 may offer chemical stability advantages over UTP. In a randomized, double-blind, multicenter phase I study, we studied the safety and maximally tolerated dose of escalating, single doses of aerosolized INS 365, in adult and pediatric patients with mild to moderate CF lung disease (FEV(1) > or = 45% predicted). In four successive dose cohorts of adult patients (n = 12 per cohort, age > or = 18 years) and four successive pediatric dose cohorts (n = 12 per cohort, age 5-12 years), patients were randomized 3:1 active/placebo (0.9% saline) to evaluate doses of 20, 40, 80, and 100 mg INS 365 delivered by nebulizer (Pari Star ). Sputum was collected pre- and post-dosing to obtain preliminary results on clinical efficacy. After each dose cohort, a Data Safety Monitoring Committee (DSMC) reviewed the data. Forty-eight adult and 36 pediatric patients completed the protocol (up to 100 mg for adults, 80 mg for pediatric patients). The predominant adverse events were cough, wheezing, chest tightness, and a decrease in FEV(1) (occurring in 8/48 adults, and 5/36 pediatric patients), which occurred predominantly in the 80-mg and 100-mg dose cohorts. Though a few adult patients had a tendency to increase sputum production, there was little consistent effect noted on sputum production in this acute, single-dose study. The data suggest that aerosolized INS 365 is safe when delivered at single doses of up to 40 mg in adults and children with CF, but that higher doses are unlikely to be tolerated.

Adolescent↗