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Biomedical subjects

J Graf

Publications and source records attributed to J Graf.

At least 37 records · Page 2Linked to original sources
PubMed2001

CD30-mediated cell cycle arrest associated with induced expression of p21(CIP1/WAF1) in the anaplastic large cell lymphoma cell line Karpas 299.

One of the major characteristics of anaplastic large cell lymphomas (ALCL) is the expression of the Ki-1/CD30 antigen. While the receptor mediates NF-kappaB-activation in Hodgkin's lymphomas, some data suggest the CD30-mediated apoptosis of other CD30-expressing cells. We were able to demonstrate that activation of CD30 leads to different effects regarding cell proliferation of the ALCL-derived cell lines Karpas 299 and JB6. Western and Northern blotting analysis revealed that CD30-induced growth inhibition of Karpas 299 cells correlated with a strong upregulation of the cell cycle inhibitor p21(CIP1/WAF1). We found a non activating point mutation at codon 273 in exon 8 of the p53 gene in Karpas 299 cells which indicates an p53-independent mechanism for induced p21 expression. Abundant p21 protein expression resulted in hypophosphorylation of the retinoblastoma protein (Rb) and inhibition of the proliferating cell nuclear antigen (PCNA). CD30-stimulated cells showed no indications of apoptotic cell death, like genomic DNA fragmentation or cleavage of the caspase-3 target protein poly (ADP-ribose) polymerase (PARP). Our results indicate that CD30 is able to mediate an p21-associated cell cycle arrest in ALCL with possible implications for prognosis and clinical treatment.

Antibodies↗
PubMed2001

Thrombosis in Behcet's disease: report of a case followed by a systematic review using the methodology of evidence-based medicine.

BACKGROUND: Behcet's disease (BD) is a rare systemic inflammatory disease of unknown aetiology with a variety of organ manifestations. METHODS: A case of Behcet's disease complicated by deep vein thrombosis (DVT) and inferior vena cava thrombosis referred to our institution is reported. In addition, a structured literature search using the methodology of evidence-based medicine for the localization of venous lesions, treatment modalities, and outcome of patients with Behcet's disease and concurrent thrombosis was performed. A modified validity score was assigned by established methods. RESULTS: In total, 214 citations were identified using our search strategy. Among these citations, 10 papers including a total of 32 patients (25 male, 7 female) met the inclusion criteria and were incorporated into this overview together with our patient. All studies consisted of serial case reports without control subjects. Neither localization of venous lesions, nor treatment modalities were homogeneous not allowing general recommendations. CONCLUSIONS: No data are available from controlled studies regarding treatment modalities of patients presenting with Behcet's disease complicated by concurrent thrombosis. This lack of evidence implicates the need for large scale and co-ordinated registries including data on the acute treatment as well as the prevention of future thrombotic events in this clinical setting. The diagnostic criteria of the "International Study Group for Behcet's Disease" may well serve as a basis for this approach.

Adult↗
PubMed2001

Intracellular calcium in the isolated rat liver: correlation to glucose release, K(+) balance and bile flow.

This study correlates whole organ measurements of intracellular calcium concentration ([Ca(2+)](i)) with hormone-induced (epinephrine, vasopressin) changes of liver functions (glucose release, K(+) balance and bile flow). [Ca(2+)](i) was measured in the isolated perfused rat liver using the sensor Fura-2 and applying liver surface fluorescence spectroscopy. The technique was improved by (i) minimizing biliary elimination of the sensor by employing a rat strain deficient in canalicular organic anion transport (TR(-) mutation) and (ii) by correcting for changes of interfering intrinsic organ fluorescence that was shown to depend on the oxidation-reduction state (NAD(P)H content) of the organ. Epinephrine (50 nM) elicits an instantaneous peak rise of [Ca(2+)](i) to approx. 400 nM, followed by a sustained elevation that depends on the presence of extracellular Ca(2+). The rise of [Ca(2+)](i) coincides with initiation of glucose release, transient K(+) uptake, and transient stimulation of bile flow. Vasopressin (2 nM) exerts qualitatively similar effects. The transient rise of bile flow is attributed to Ca(2+)-mediated contraction of the pericanalicular actin-myosin web of hepatocytes.

Animals↗
PubMed2001

Helicobacter sp. flexispira bacteremia in an immunocompetent young adult.

A young immunocompetent patient was admitted for a febrile illness with malaise, arthralgias, painful leg swelling, and polyserositis. Shortly prior to becoming ill, the patient had traveled to the Northern African desert. The symptoms disappeared during treatment with antibiotics (doxycycline and ceftriaxone) but recurred twice after stopping therapy. A motile gram-negative fusiform rod was isolated from a blood culture taken on the first admission. Analysis of the 16S rRNA gene of the blood culture isolate revealed close similarity with Helicobacter sp. flexispira taxon 8 (99.9% identity), a species that was previously reported as "Flexispira rappini." This is the first reported case of a recurrent Helicobacter sp. flexispira bacteremia in an adult, immunocompetent patient.

Adult↗
PubMed2001

Identification of novel polymorphisms in intron 7 of the human p53 gene in acute myeloid leukemia and healthy donors.

Screening for mutations by PCR-SSCP in exons 5 to 9 of the p53 gene in 38 bone marrow or peripheral blood specimens of patients with acute myeloid leukemia (AML) showed abnormal shifts in 9 cases. One reflected a mutation in exon 8, whereas in the other cases there were no exonic mutations identified by sequencing. As PCR primers were chosen annealing in the introns flanking the exon region, following sequencing of the encompassing introns identified 5 base substitutions at various sites in intron 7. Two of them have been described previously [1] and 3 novel polymorphisms could be identified. To determine whether these polymorphisms are linked to the pathogenesis of AML, we screened peripheral blood specimens of 26 healthy controls. We found identical base substitutions in 6 out of 26 controls. Our data suggest that these polymorphisms are not related to the pathogenesis of AML.

Acute Disease↗
PubMed2000

Effects of insulin-like growth factor I on basal and stimulated glucose fluxes in rat liver.

Effects of insulin-like growth factor I (IGF-I) and insulin on glucose and potassium fluxes were examined by measuring transhepatic glucose and potassium balance in isolated perfused rat livers. At 1 nM, both IGF-I and insulin decreased basal glucose release by approximately 64% (P < 0.05). Adrenaline (epinephrine)-stimulated glucose release (42.6 +/- 4.5 micromol/g of liver within 30 min) was inhibited (P < 0.05) by approximately 32 and approximately 52% during IGF-I and insulin exposure, which was accompanied by reduced cAMP release (-71 and -80%, P < 0.05). IGF-I- and insulin-induced reduction of glucose release only decreased during calcium-free perfusion, but not during inhibition of phosphoinositide 3-kinase by wortmannin. Both IGF-I and insulin induced net potassium uptake, while insulin also attenuated the response to adrenaline. In conclusion, IGF-I causes (i) insulin-like inhibition of hepatic glycogenolysis, even at low, nanomolar concentrations, which is associated with decreased cAMP release, reduced in the absence of Ca(2+), but not mediated by phosphoinositide 3-kinase, (ii) reduction of adrenaline-induced glycogenolysis and (iii) net potassium uptake under basal conditions.

Androstadienes↗
PubMed2000

Ultrastructural findings after intraarticular application of hyaluronan in a canine model of arthropathy.

We investigated the effect of intraarticularly applied hyaluronic acid (hyaluronan) on the cartilaginous structure of experimentally induced chondromalacia patellae in dogs. For the induction of chondromalacia, we used the Pond-Nuki technique, which involved severance and resection of the anterior cruciate ligament, as a canine model of arthropathy in 27 foxhounds (three groups of nine animals each). In a pilot study, we evaluated the effect of resection of the anterior cruciate ligament with no therapy. Patellar specimens were retrieved at 3, 6, and 12 weeks postoperatively. Subsequently, we compared a treatment group that received intraarticular injections of hyaluronan with a placebo group that received saline solution. The groups were compared at 3, 6, and 12 weeks postoperatively. Three animals from the treatment and placebo groups received five injections of hyaluronan during one of the 4-week intervals (weeks 3-6, 6-9, or 12-15). Specimens were retrieved 5 weeks after the last injection. In both groups, the uninvolved contralateral knee served as a control. The specimens were taken from the medial and lateral patellar poles. Histological analysis included light microscopy and transmission electron microscopy. The structural and ultrastructural changes were assessed qualitatively and were quantified with use of a modified Mankin score. Our results indicate that chondromalacia patellae may be induced with the Pond-Nuki technique. We found a significant reduction (p < 0.01) of cartilaginous lesions in the hyaluronan group compared with the placebo group. Our results suggest that intraarticularly applied hyaluronan is effective in delaying the degenerative process of cartilage degradation. Therefore, we conclude that the use of hyaluronan may be indicated during the early stages of chondromalacia.

Adjuvants, Immunologic↗
PubMed2000

Evaluation of the SOFA score: a single-center experience of a medical intensive care unit in 303 consecutive patients with predominantly cardiovascular disorders. Sequential Organ Failure Assessment.

OBJECTIVE: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score, the total maximum SOFA (TMS) score, and a derived variable, the deltaSOFA (TMS score minus total SOFA score on day 1) in medical, cardiovascular patients as a means for describing the incidence and severity of organ dysfunction and the prognostic value regarding outcome. DESIGN: Prospective, clinical study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: A total of 303 consecutive patients were included (216 men, 87 women; mean age 62 +/- 12.6 years; SAPS II 26.2 +/- 12.7). They were evaluated 24 h after admission and thereafter every 24 h until ICU discharge or death between November 1997 and March 1998. Readmissions and patients with an ICU stay shorter than 12 h were excluded. MAIN OUTCOME MEASURE: Survival status at hospital discharge, incidence of organ dysfunction/failure. INTERVENTIONS: Collection of clinical and demographic data and raw data for the computation of the SOFA score every 24 h until ICU discharge. MEASUREMENTS AND MAIN RESULTS: Length of ICU stay was 3.7 +/- 4.7 days. ICU mortality was 8.3% and hospital mortality 14.5%. Nonsurvivors had a higher total SOFA score on day 1 (5.9 +/- 3.7 vs. 1.9 +/- 2.3, p < 0.001) and thereafter until day 8. High SOFA scores for any organ system and increasing number of organ failures (SOFA score > or = 3) were associated with increased mortality. Cardiovascular and neurological systems (day 1) were related to outcome and cardiovascular and respiratory systems, and admission from another ICU to length of ICU stay. TMS score was higher in nonsurvivors (1.76 +/- 2.55 vs. 0.58 +/- 1.39, p < 0.01), and deltaSOFA/total SOFA on day 1 was independently related to outcome. The area under the receiver-operating characteristic curve was 0.86 for TMS, 0.82 for SOFA on day 1, and 0.77 for SAPS II. CONCLUSIONS: The SOFA, TMS, and deltaSOFA scores provide the clinician with important information on degree and progression of organ dysfunction in medical, cardiovascular patients. On day 1 both SOFA score and TMS score had a better prognostic value than SAPS II score. The model is closely related to outcome and identifies patients who are at increased risk for prolonged ICU stay.

Cardiovascular Diseases↗
PubMed2000

Computed tomographic angiography findings in 103 patients following vascular events in the posterior circulation: potential and clinical relevance.

We studied the diagnostic value of computed tomographic angiography (CTA) in the posterior circulation as a noninvasive substitute for intra-arterial digital subtraction angiography (DSA). We prospectively investigated 103 patients with acute stroke in the posterior circulation. All patients underwent CTA and Doppler ultrasound, and DSA was performed in 22 patients. Vascular findings were classified in categories according to the type of lesion and the location in the vertebral, basilar, or posterior cerebral artery. In the first part of the analysis we examined the correlation between CTA and intra-arterial DSA (n=22), and in the second part that between CTA and Doppler ultrasound (n=103). Intra-arterial DSA identified 11 stenoses, 13 occlusions, and 3 hypoplasias. The correlation between DSA and CTA was best for the basilar artery (all lesions were identified with CTA). Of the 14 lesions detected in the vertebral artery by DSA 13 were also detected by CTA, but the specific type of lesion was identified in only 7 cases. The correlation between CTA and Doppler ultrasound was lower. In conclusion, CTA is thus a reliable method for detecting lesions in the posterior circulation and may replace DSA in many cases. However, particularly in the vertebral artery DSA remains the superior technique.

Adult↗
PubMed2000

Novel effects of a transposon insertion in the Vibrio fischeri glnD gene: defects in iron uptake and symbiotic persistence in addition to nitrogen utilization.

Vibrio fischeri is the sole species colonizing the light-emitting organ of the Hawaiian squid, Euprymna scolopes. Upon entering the nascent light organ of a newly hatched juvenile squid, the bacteria undergo morphological and physiological changes that include the loss of flagellation and the induction of bioluminescence. These and other events reveal a pattern of genetic regulation that is a response to the colonization of host tissue. In this study, we isolated and characterized a glnD:mTn5Cm mutant of V. fischeri. In addition to the predicted defects in the efficiency of nitrogen utilization, this glnD mutant had an unexpected reduction in the ability to produce siderophore and grow under iron-limiting conditions. Although the glnD mutant could colonize juvenile squid normally over the first 24 h, it was subsequently unable to persist in the light organ to the usual extent. This persistence phenotype was more severe if the mutant was pregrown under iron-limiting conditions before inoculation, but could be ameliorated by the presence of excess iron. These results indicate that the ability to respond to iron limitation may be an important requirement in the developing symbiosis. Supplying the glnD gene in trans restored normal efficiency of nitrogen use, iron sequestration and colonization phenotypes to the glnD:mTn5Cm mutant; thus, there appears to be a genetic and/or metabolic linkage between nitrogen sensing, siderophore synthesis and symbiosis competence in V. fischeri that involves the glnD gene.

Animals↗
PubMed2000

In vitro validation of gastric air tonometry using perfluorocarbon FC 43 and 0.9% sodium chloride.

Monitoring splanchnic perfusion by means of gastric intramucosal tonometry is carried out using saline, or more recently, air tonometry using the Tonocap. The objective of this study was the validation of the Tonocap in saline and perfluorocarbon FC 43. The two methods underestimated the predefined PCO2 value by an average of 10%, with clinically acceptable precision. Accuracy of the Tonocap improved at high PCO2 values (9.33 and 9.94 kPa), whereas saline tonometry was superior at low PCO2 values (3.99 and 3.75 kPa). The Tonocap provides a fast and reliable estimation of the PCO2, and with the revised software requiring only 10 min of equilibration, will increase the comparability of future studies.

Fluorocarbons↗
PubMed2000

Ca2+-activated Cl- channels can substitute for CFTR in stimulation of pancreatic duct bicarbonate secretion.

This study addresses the mechanisms by which a defect in CFTR impairs pancreatic duct bicarbonate secretion in cystic fibrosis. We used control (PANC-1) and CFTR-deficient (CFPAC-1; DeltaF508 mutation) cell lines and measured HCO3- extrusion by the rate of recovery of intracellular pH after an alkaline load and recorded whole cell membrane currents using patch clamp techniques. 1) In PANC-1 cells, cAMP causes parallel activation of Cl- channels and of HCO3- extrusion by DIDS-sensitive and Na+-independent Cl-/HCO3- exchange, both effects being inhibited by Cl- channel blockers NPPB and glibenclamide. 2) In CFPAC-1 cells, cAMP fails to stimulate Cl-/HCO3- exchange and Cl- channels, except after promoting surface expression of DeltaF508-CFTR by glycerol treatment. Instead, raising intracellular Ca2+ concentration to 1 micromol/l or stimulating purinergic receptors with ATP (10 and 100 micromol/l) leads to parallel activation of Cl- channels and HCO3- extrusion. 3) K+ channel function is required for coupling cAMP- and Ca2+-dependent Cl- channel activation to effective stimulation of Cl-/HCO3- exchange in control and CF cells, respectively. It is concluded that stimulation of pancreatic duct bicarbonate secretion via Cl-/HCO3- exchange is directly correlated to activation of apical membrane Cl- channels. Reduced bicarbonate secretion in cystic fibrosis results from defective cAMP-activated Cl- channels. This defect is partially compensated for by an increased sensitivity of CF cells to purinergic stimulation and by alternative activation of Ca2+-dependent Cl- channels, mechanisms of interest with respect to possible treatment of cystic fibrosis and of related chronic pancreatic diseases.

Adenosine Triphosphate↗
PubMed2000

Severe transmyocardial ischemia in a patient with tension pneumothorax.

OBJECTIVE: To report tension pneumothorax (TP) as a cause of severe myocardial ischemia. DESIGN: Clinical case report. SETTING: Medical intensive care unit of a university hospital. PATIENTS: One patient with severe shock attributable to right TP after unsuccessful percutaneous central venous catheterization. INTERVENTIONS: Blood pressure, electrocardiogram (ECG), chest radiograph, and echocardiography during and after shock. MEASUREMENTS AND MAIN RESULTS: On admission the patient was in profound state of shock (heart rate 140 beats/min, blood pressure 65/30 mm Hg). Twelve-lead ECG showed pronounced ST segment elevation in leads II, III, aVF, and V4-V6. Chest radiograph revealed right TP with complete displacement of the mediastinum and the heart to the left side. Immediate right-sided tube thoracostomy resulted in reexpansion of the lung followed by instantaneous hemodynamic and respiratory improvement as well as nearly complete resolution of the ECG changes. Peak value of the creatine phosphokinase was 4140 U/L without significant elevation of the MB isoenzyme at any time. Moreover, the initial hypokinesia of the posterior and lateral left ventricular wall resolved completely, as demonstrated by echocardiography. CONCLUSION: The specific condition of TP may lead to impaired systolic and diastolic coronary artery blood flow affecting ventricular repolarization and T-wave configuration in ECG indicative of transmyocardial ischemia. General symptoms, namely hypotension, tachycardia, and hypoxemia, are likewise typical for cardiogenic shock attributable to myocardial infarction. Yet any therapeutic measure directed toward revascularization, such as thrombolysis or even percutaneous transluminal coronary angioplasty, would have had devastating consequences. Therefore, thorough physical examination of our patient was pivotal in disclosing the true origin of profound shock.

Aged↗