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Biomedical subjects

J Hammer

Publications and source records attributed to J Hammer.

At least 37 records · Page 2Linked to original sources
PubMed2004

Mapping of the immunodominant T cell epitopes of the protein topoisomerase I.

OBJECTIVES: To identify the immunodominant T cell epitopes of the topoisomerase I protein in patients with systemic sclerosis (SSc) and control subjects, using computational analysis software (TEPITOPE) and T cell proliferation assays. METHODS: Six oligopeptides, predicted by TEPITOPE software as potential topoisomerase protein epitopes, were used to perform T cell proliferation assays in 21 patients with SSc and 15 healthy controls. RESULTS: A positive response to at least one of the peptides was seen in 10/21 patients and 7/15 healthy controls. Among responders, the proliferative response was limited to a single peptide in 6/7 healthy controls, whereas 5/10 patients responded to more than one peptide. In responding patients a significant correlation was found between disease duration and number of peptides inducing a response (p = 0.007). CONCLUSIONS: Several T cell epitopes of the topoisomerase I protein have been identified and evidence has been found to suggest epitope spreading in patients with SSc.

Adult↗
PubMed2004

Diagnostic yield of alarm features in irritable bowel syndrome and functional dyspepsia.

OBJECTIVE: The diagnostic value of the addition of alarm symptoms in distinguishing functional from organic gastrointestinal disease remains uncertain. We aimed to establish the value of alarm features in differentiating between organic disease and irritable bowel syndrome (IBS) and functional dyspepsia (FD). METHODS: A total of 568 consecutive patients (63% female; mean age 44.7 years) completed a detailed symptom questionnaire and then received a complete diagnostic workup, as required. Questionnaire data were collected prospectively and audited retrospectively; the treating physician was blinded to the results of the questionnaires. Patients were coded and allocated to the following diagnostic groups: IBS, FD, organic diseases of the upper gastrointestinal tract, or organic diseases of the lower gastrointestinal tract. Logistic regression was used to identify the best subset of symptoms that discriminated organic disease from functional illness. Separate models compared IBS (n = 214) with diseases of the lower gastrointestinal tract (n = 66), and FD (n = 70) with diseases of the upper gastrointestinal tract (n = 250). RESULTS: Age (50 years at symptom onset: odds ratio (OR) 2.65 (95% confidence interval 1.4-5.0); p = 0.002) and blood on the toilet paper (OR 2.7 (1.4-5.1);p = 0.002) emerged as alarm features that discriminated IBS from lower gastrointestinal illness. A diagnosis of IBS was typically associated with female sex (OR2.5 (1.3-4.6); p = 0.004), pain on six or more occasions in the previous year (OR 5.0 (2.2-11.1); p<0.001), pain that radiated outside of the abdomen (OR 2.9 (1.4-6.3); p = 0.006), and pain associated with looser bowel motions (OR 2.1 (1.1-4.2); p = 0.03). A model incorporating three Manning criteria and alarm features yielded a correct diagnosis of IBS in 96% and a correct diagnosis of organic disease in 52% of cases. Alarm features did not discriminate FD from upper gastrointestinal disease. Patients with FD were significantly more likely to report upper abdominal pain (OR 3.7 (1.7-8.3); p = 0.002) and significantly less likely to report aspirin use (OR 0.26 (0.1-0.6); p = 0.001). The predictive value of symptoms in diagnosing FD was only 17%. CONCLUSIONS: Symptoms plus alarm features have a high predictive value for diagnosing IBS but the predictive value for a diagnosis of FD remains poor. Current criteria for the diagnosis of IBS should incorporate relevant alarm features to improve the diagnostic yield.

Abdominal Pain↗
PubMed2004

Chemical nociception in the jejunum induced by capsaicin.

BACKGROUND AND AIMS: Chemonociception in the human small intestine has not been studied extensively. Although capsaicin can cause intestinal sensations, it is not known if this is due to stimulation of chemoreceptors or to motor changes. Our aims were to evaluate motor activity during capsaicin induced nociception and to compare qualities of jejunal nociception induced by capsaicin and mechanical distension. METHODS: Twenty nine healthy subjects swallowed a tube with a perfusion site at the ligament of Treitz and, 7 cm distally, a barostat balloon. Phasic motor activity was measured around the perfusion site and the balloon. Capsaicin solutions (40, 200, and 400 microg/ml) 2.5 ml/min were perfused for 60 minutes or until severe discomfort occurred. A graded questionnaire for seven different sensations was completed every 10 minutes and after capsaicin perfusion was replaced by saline perfusion because of severe discomfort. Sensations arising from pressure controlled distensions were assessed before and after capsaicin perfusion when sensations had stopped (n = 19), or during capsaicin administration when no discomfort was reported (n = 5). RESULTS: Capsaicin perfusion induced feelings of pressure, cramps, pain, and warmth. The quality and abdominal location of these sensations were similar to those induced by distension, except for warmth (p<0.01) and pressure (p<0.05). Seven of 12 subjects receiving 40 microg/ml capsaicin and all subjects receiving higher capsaicin concentrations developed discomfort. Perfusion had to be stopped after 55 (3.3), 15 (5.7), and 10 (2.2) minutes with 40, 200, and 400 microg/ml capsaicin, respectively, whereafter the sensations disappeared within 10 minutes. Repeated capsaicin (200 microg/ml) applications significantly reduced the time until discomfort occurred (p = 0.01). Jejunal tone was not altered by capsaicin but phasic activity proximal to the perfusion site was reduced during capsaicin induced discomfort (p<0.001). Pain thresholds during distensions were not different before and after capsaicin perfusion. CONCLUSION: Despite the similarities in abdominal localisation and perceptional quality of capsaicin and distension induced sensations, our results rule out the fact that abdominal discomfort evoked by capsaicin involves sensitisation of mechanoreceptors or an increase in phasic and tonic motor activity. Capsaicin evokes abdominal sensations by stimulation of chemoreceptors which proves the existence of chemonociception in the human small intestine.

Abdomen↗
PubMed2004

Expression analysis of MAC30 in human pancreatic cancer and tumors of the gastrointestinal tract.

Meningioma-associated protein, MAC30, is a protein with unknown function and cellular localization that is differentially expressed in certain malignancies. In the present study, the expression of MAC30 in a variety of normal and cancerous human gastrointestinal tissues, with special emphasis on pancreatic tissues was analyzed. Quantitative RT-PCR was utilized to compare MAC30 expression levels. In situ hybridization and immunohistochemistry were carried out to localize MAC30 mRNA and protein expression in normal and cancerous tissue samples of the esophagus, stomach, colon and pancreas. Furthermore, the effects of TGF-beta on the transcription of MAC30 mRNA were examined in pancreatic cancer cells. MAC30 mRNA was expressed in a wide variety of normal human tissues, being most abundant in testicular and gastric tissue samples. MAC30 mRNA levels were significantly increased in breast and colon cancer, but significantly decreased in pancreatic and renal cancer. TGF-beta down-regulated MAC30 mRNA levels in certain pancreatic cancer cells. MAC30 protein was localized in normal pancreatic tissues, mainly in acinar and islet cells, and in normal colon, gastric and esophageal tissues especially in the mucosal cells. MAC30 was strongly present in tubular complexes in pancreatic cancer tissues but weak to absent in pancreatic cancer cells of primary tumors and metastases. In contrast, esophageal, gastric and colon tumors displayed strong MAC30 immunoreactivity in the cancer cells. In conclusion, MAC30 is expressed in various normal and diseased human tissues. MAC30 up-regulation in certain tumors and down-regulation in others suggests that this protein plays a distinct role in human malignancies.

Adult↗
PubMed2003

Development and validation of the Diabetes Bowel Symptom Questionnaire.

BACKGROUND: Although gastrointestinal symptoms occur frequently, there is no validated measure of gastrointestinal symptoms in patients with diabetes mellitus. AIM: To develop the Diabetes Bowel Symptom Questionnaire. METHODS: A questionnaire derived from previously validated symptom measures was compiled to assess all relevant gastrointestinal and diabetes items. Face and content validity were ascertained by expert review. One hundred and sixty-eight patients with diabetes mellitus completed the instrument, and reliability was evaluated by a test-re-test procedure 1 week later. Concurrent validity was evaluated by an independent physician interview (n = 33). Measures of glycaemic control (glycated haemoglobin and plasma glucose) were compared with self-reported glycaemic control on a five-point Likert scale in diabetic out-patients (n = 166). RESULTS: The questionnaire had adequate face and content validity. There was good to excellent test-re-test reliability for the gastrointestinal and diabetes items (median kappa: 0.63 and 0.79, respectively); concurrent validity was good to excellent (median kappa: 0.47 and 0.65, respectively), except for the items assessing the severity of gastrointestinal symptoms. Both glycated haemoglobin (P < 0.0001) and plasma glucose (P = 0.005) correlated significantly with self-reported glycaemic control. CONCLUSION: The Diabetes Bowel Symptom Questionnaire appears to be a useful measure of gastrointestinal symptoms and glycaemic control in diabetes mellitus, and should have applicability in epidemiological and clinical studies.

Adult↗
PubMed2003

Current management of acute bronchiolitis in Switzerland.

INTRODUCTION: Acute bronchiolitis is the most common lower respiratory tract infection in the first year of life. Current expert opinion and scientific data suggest that pharmaceutical agents have little impact on the natural course of the disease. METHODS: Postal questionnaires were sent to all Swiss paediatricians to assess their current practice for treating acute bronchiolitis in children. RESULTS: Of a total of 937 questionnaires, 541 (58%) were returned. Of the respondents, 422 (78%) treat children with acute bronchiolitis. Up to 99% of paediatricians used bronchodilators in the outpatient and inpatient management, either routinely (up to 62%) or occasionally (37%). Steroids were used by 41% of the respondents in outpatient management and by 57% in inpatient management. The paediatric respiratory physicians tended to use bronchodilators and corticosteroids less frequently than the general paediatricians. CONCLUSIONS: A wide variation in the treatment of bronchiolitis was noted. Despite lack of evidence of benefit most Swiss paediatricians use pharmaceutical agents in the management of acute bronchiolitis. In particular, bronchodilators and corticosteroids were used in inpatient management in Switzerland much more frequently than recently reported for Australian paediatricians. National guidelines could be helpful in reducing the variations in the management of acute bronchiolitis in our country.

Acute Disease↗
PubMed2003

Microarray-based identification of differentially expressed growth- and metastasis-associated genes in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. To improve diagnosis and treatment, key mechanisms of deregulated molecular functions have to be identified. Using microarray analysis, the expression patterns of 5600 human genes were assessed in PDAC by comparison with the normal pancreas and chronic pancreatitis (CP). The expression of 467 of 5600 genes was increased in PDAC in comparison to the normal pancreas, and the expression of 120 of these genes was not increased in CP. In addition, 341 of 5600 genes were expressed at decreased levels in PDAC tissues, of which 96 were decreased in comparison to both normal and CP tissues. Thus, a total of 808 of 5600 human genes were differentially expressed in pancreatic cancer. The identification of a large panel of altered genes in PDAC will stimulate additional studies that will lead to improved understanding of the molecular mechanisms underlying pancreatic malignant growth.

Adenocarcinoma↗
PubMed2002

Techniques for measurement of thoracoabdominal asynchrony.

Respiratory motion measured by respiratory inductance plethysmography often deviates from the sinusoidal pattern assumed in the traditional Lissajous figure (loop) analysis used to determine thoraco-abdominal asynchrony, or phase angle phi. We investigated six different time-domain methods of measuring phi, using simulated data with sinusoidal and triangular waveforms, phase shifts of 0-135 degrees, and 10% noise. The techniques were then used on data from 11 lightly anesthetized rhesus monkeys (Macaca mulatta; 7.6 +/- 0.8 kg; 5.7 +/- 0.5 years old), instrumented with a respiratory inductive plethysmograph, and subjected to increasing levels of inspiratory resistive loading ranging from 5-1,000 cmH(2)O. L(-1). sec(-1). The best results were obtained from cross-correlation and maximum linear correlation, with errors less than approximately 5 degrees from the actual phase angle in the simulated data. The worst performance was produced by the loop analysis, which in some cases was in error by more than 30 degrees. Compared to correlation, other analysis techniques performed at an intermediate level. Maximum linear correlation and cross-correlation produced similar results on the data collected from monkeys (SD of the difference, 4.1 degrees ) but all other techniques had a high SD of the difference compared to the correlation techniques. We conclude that phase angles are best measured using cross-correlation or maximum linear correlation, techniques that are independent of waveform shape, and robust in the presence of noise.

Airway Obstruction↗
PubMed2002

[18F-fluorodeoxyglucose positron emission tomography in colorectal cancer: value in primary staging and follow-up].

Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) is a encouraging imaging technique allowing a highly sensitive whole-body search for malignant foci detected by their increased glucose metabolism compared with benign tissues. Several studies are now available that indicate its added value for diagnosis and staging of colorectal cancer. In all, patient management seems to be changed in 20-30% of patients who undergo Fluorodeoxyglucose positron emission tomography in addition to standard staging procedures. Fluorodeoxyglucose positron emission tomography is also useful in monitoring radiation therapy and chemotherapy. Regarding preoperative staging of primary colorectal cancer the literature is very limited.

Colorectal Neoplasms↗
PubMed2001

Survey of children supported by long-term mechanical ventilation in Switzerland.

OBJECTIVE: The aim of the present study was to identify the number of children, from birth to 16 years of age, on long-term mechanical ventilation in Switzerland, and to establish their current location, underlying diagnoses and ventilatory needs. METHODS: Postal questionnaires were sent to all chest physicians (pulmonologists), intensive care specialists, neurologists, national health care organisations, rehabilitation services and ventilator suppliers known or thought to be involved in paediatric long-term ventilation in Switzerland. RESULTS: Detailed information was obtained on 32 children from 7 centers. Underlying disorders included congenital central hypoventilation syndrome (CCHS, 41%), neuromuscular disorders (41%), spinal cord injury (6%), craniofacial anomalies (6%) and others (6%). 10 children received positive pressure ventilation by tracheostomy and 19 children by nasal mask. Two children were ventilated by phrenic nerve pacing and one child with the help of a pneumatic belt. Children with CCHS were almost equally divided into nasal mask and tracheostomy users. Ventilation for 16-24 hours a day was necessary in 5 children, exclusively during sleep in 24 children and only episodically in 3 children. All but 2 children were cared for at home. The majority of families received home care support. The most common reasons for readmission into hospital were regular follow-up examinations and respiratory tract infections. The children were mainly admitted to paediatric intensive care units. CONCLUSIONS: There are few ventilator-supported children in Switzerland and most of them are cared for at home. Nevertheless, there is a need to establish a system for continuing data collection in this particular patient population to assess outcome and quality of home care support and to follow incidence trends.

Adolescent↗
PubMed2001

A novel linear amphipathic beta-sheet cationic antimicrobial peptide with enhanced selectivity for bacterial lipids.

All known naturally occurring linear cationic peptides adopt an amphipathic alpha-helical conformation upon binding to lipids as an initial step in the induction of cell leakage. We designed an 18-residue peptide, (KIGAKI)3-NH2, that has no amphipathic character as an alpha-helix but can form a highly amphipathic beta-sheet. When bound to lipids, (KIGAKI)3-NH2 did indeed form a beta-sheet structure as evidenced by Fourier transform infrared and circular dichroism spectroscopy. The antimicrobial activity of this peptide was compared with that of (KIAGKIA)3-NH2, and it was better than that of GMASKAGAIAGKIAKVALKAL-NH2 (PGLa) and (KLAGLAK)3-NH2, all of which form amphipathic alpha-helices when bound to membranes. (KIGAKI)3-NH2 was much less effective at inducing leakage in lipid vesicles composed of mixtures of the acidic lipid, phosphatidylglycerol, and the neutral lipid, phosphatidylcholine, as compared with the other peptides. However, when phosphatidylethanolamine replaced phosphatidylcholine, the lytic potency of PGLa and the alpha-helical model peptides was reduced, whereas that of (KIGAKI)3-NH2 was improved. Fluorescence experiments using analogs containing a single tryptophan residue showed significant differences between (KIGAKI)3-NH2 and the alpha-helical peptides in their interactions with lipid vesicles. Because the data suggest enhanced selectivity between bacterial and mammalian lipids, linear amphipathic beta-sheet peptides such as (KIGAKI)3-NH2 warrant further investigation as potential antimicrobial agents.

Amino Acid Sequence↗
PubMed2001

Genomics approaches to drug discovery.

New approaches to drug discovery have come about in recent years as a result of important advances in genomics and bioinformatics. The availability of genome-scale sequence data, the development of new tools for high-throughput gene expression monitoring, and improvements in the ability to analyze large data sets have revolutionized the field. In this article, we discuss three applications of genomics data in the drug discovery process: target discovery, prodrug strategies, and vaccine development.

Amino Acid Sequence↗
PubMed2001

T-helper cell-response to MHC class II-binding peptides of the renal cell carcinoma-associated antigen RAGE-1.

Recently, epitope prediction software for HLA-DR binding sequences has become available. In view of the importance of T helper (Th) cell activation in immunotherapy of cancer and evidences supporting immunogenicity of renal cell carcinoma (RCC), we have tested 4 peptides of RAGE-1 binding promiscuously to HLA-DR molecules for induction of an immune response. The peptides predicted by the TEPITOPE program using a stringent threshold were derived from the open reading frame 2 and 5 of RAGE-1. Induction of response was evaluated by culturing peripheral blood mononuclear cells (PBMC) in the presence of peptide-loaded dendritic cells (DC) to determine proliferative activity and cytokine expression. Two out of 5 donors did not respond to any of the 4 peptides, 2 donors responded to one peptide and one donor responded to two other peptides. Notably, as revealed by blocking studies and T cell subtype definition, peptides bound to MHC class II molecules and peptide pulsed DC exclusively activated CD4+ T cells, which were of the Th1 subtype. With respect to clinical application it is important that (un)responsiveness of individual donors' PBMC was a very consistent feature. Though we have not tested explicitly whether these peptides correspond to naturally processed peptides, the possibility to define those patients whose Th might respond to in silico predicted peptides of RAGE-1, by an in vitro assay, could well be a helpful step towards setting up a RAGE-1 based immunotherapeutic protocol.

Adult↗
PubMed2001

In vivo effects of adenosine A(2) receptor agonist and antagonist on neuronal and astrocytic intermediary metabolism studied with ex vivo (13)C MR spectroscopy.

The effect of adenosine A(2) receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-ethylcarboxamidoadenosine (CGS 21680) and antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) on [1-(13)C]glucose and [1,2-(13)C]acetate metabolism was studied in rats by (13)C magnetic resonance (MR) spectroscopy and HPLC. In the cortex a significant reduction was observed in the amounts of [2-(13)C]GABA and [3-(13)C]aspartate from [1-(13)C]glucose in CGS 21680. In the subcortex the concentration of labelled [4-(13)C]glutamate was increased in both treatment groups. The amounts of [2 + 3-(13)C]succinate and [3-(13)C]lactate were increased in the CGS 21680 group compared to control, and the DMPX group showed an increase in the total amount of [6-(13)C]N-acetyl aspartate compared to control in the subcortex. Astrocyte metabolism was only affected in the cortex as shown by a decrease in the pyruvate carboxylase/pyruvate dehydrogenase ratio in glutamate and glutamine in the treatment groups. Labelling from [1,2-(13)C]acetate was not much affected by CGS 21680 or DMPX. However, the amount of [1,2-(13)C]acetate in cortex and subcortex was reduced in the DMPX group. In the cortex a reduction in the labelling of [3-(13)C]GABA in the DMPX group compared to control and an increase in the total amount of taurine in both treatment groups was detected. The present study shows that A(2) receptor agonist and antagonist have similar effects; however, in cortex GABAergic neurones and astrocytes were affected in contrast to subcortex, where glutamatergic neurones showed the greatest changes.

Acetates↗
PubMed2001

Acute lung injury: pathophysiology, assessment and current therapy.

Acute respiratory distress syndrome (ARDS) is a clinically defined entity describing the severity of diffuse alveolar injury caused by direct or indirect injury to the lung. Pathophysiology, clinical course and outcome of ARDS depend on the underlying cause, the severity of the disease and co-morbidities. Pulmonary function tests show restrictive lung disease, which is characterised by a reduction in lung compliance and functional residual capacity, resulting in marked ventilation-perfusion inequality. Current ventilator strategies aim to minimise ventilator-induced lung injury by targeting mechanical ventilation between the lower and upper inflection point of the pressure volume curve. This includes recruitment manoeuvres and the use of high PEEP to open the atelectatic lung and the use of permissive hypercapnia and the limitation of peak inspiratory pressure below 35 cm H2O to avoid overinflation. The clinical benefit of newer modes of ventilatory support such as inverse ratio ventilation, high frequency oscillatory ventilation, surfactant replacement, prone positioning and inhaled nitric oxide has yet to be determined in children.

Child↗