Biomedical subjects

C Schwarz

Publications and source records attributed to C Schwarz.

At least 37 records · Page 2Linked to original sources

PubMed2001

[Coronary artery bypass graft dysfunction--clinical presentation, laboratory and electrocardiographic parameters].

The recurrence of symptoms after coronary artery bypass surgery is often caused by bypass-dysfunction. In this study we tried to determine factors related to the long-term patency of arterial and venous bypass grafts. We evaluated all patients with bypass grafts undergoing coronary angiography in the year 1998 at our hospital (163 patients, mean age 67 years, mean interval since the operation 79 months, a total of 341 venous bypasses (VBP), 386 peripheral venous anastomoses and 85 arterial (LIMA = left internal mammarial artery) bypasses. The data were collected by a retrospective analysis of the hospital records. Statistics were performed using the Wilcoxon-Mann-Whitney-U test. After an interval of 53 months LIMA-bypasses were patent without stenosis in 92%. Symptoms were caused in only 2% by a dysfunction of the LIMA-graft. The patency of venous bypass grafts decreased with time (5 years after the operation 74% were patent without stenosis, 5-10 years 56%, more than 10 years 35%, p < 0.01). We found clear relations between the function of the venous grafts and the clinical presentation (patent grafts without stenosis in 43% with acute coronary syndromes, in 57% with stable angina [p = 0.08] and in 86% with atypical angina [p < 0.0001 for the difference between each of the first two and the last syndrome]), the resting-ECG (65% patent VBP without stenosis with normal ST-segments and 49% with abnormal ST-segments, p < 0.01), the body-mass-index (70% patent VBP without stenosis with a BMI < 25 and 56% with a BMI > 30, p = 0.05) and the erythrocyte sedimentation rate after 2 hours (79% patent VBP with an ESR < or = 20 mm vs. 64% with an ESR > 49 mm, p = 0.02). The function of VBP after coronary artery bypass graft (CABG)-procedure depends primarily upon the interval since the operation. In addition, we found correlations with clinical presentation, resting-ECG, body-mass-index and erythrocyte-sedimentation rate as a possible marker of inflammation in bypass-atherosclerosis. Therefore, inflammatory processes seem to play an important role in the development of venous graft dysfunction.

Aged↗

PubMed2001

[Tracheostomy valve with integrated cough flap for improving hands-free speech in laryngectomized patients--development and clinical applications].

BACKGROUND: Following successful voice restoration after laryngectomy either by a voice prosthesis, a surgical shunt or microvascular laryngoplasty, a further goal in rehabilitation is the insertion of a tracheostoma valve, which enables the patient to speak without using his fingers for closure of the tracheostoma. One important disadvantage of the tracheostoma valves, which are available today, is the necessity of removal of the valve in case of coughing, because the valve could be thrown from the stoma by the strong air flow during coughing. As many laryngectomies suffer from chronic bronchitis, this coughing problem is one of the reasons why only few patients could be provided with this useful aid. METHOD: At the department of biomedical engineering of the faculty of medicine at the university of Groningen, the Netherlands, 1994 two prototypes of a tracheostoma valve with an integrated cough lid were developed. These devices contain two separate valve systems: the normal speaking valve and a special coughing valve, which opens at a certain air flow and closes automatically after the coughing attack. Thus no manipulations are necessary during coughing, the patient can speak undisturbed. The ADEVA company (Lübeck, Germany) undertook the industrial production of this new type of tracheostoma valve creating different modifications of the prototype #2. PATIENTS: In four series with 6-8 patients per group the modified tracheostoma valves were tested clinically and the occurring faults or lack of correct function eliminated by small changes in the production. RESULTS: Meanwhile a suitable model for routine use is available, which was tested in 30 patients so far. This suitability was achieved by improvements in the valve mechanism, the valve seal and the adjustment mechanisms for the individual pressure level of the speaking and the coughing valve. CONCLUSION: The newly developed tracheostoma valve with integrated coughing lid (Window, ADEVA-medical Company, Lübeck, Germany) provides further improvement in speech rehabilitation of laryngectomies. The low acceptance of tracheostoma valves, which enable the patient to speak without using his fingers for closure of the tracheostoma, possibly may be raised by this new aid.

Bronchitis↗

PubMed2001

Regulation of renal tubular cell apoptosis and proliferation after ischemic injury to a solitary kidney.

The time course and regulation of apoptosis and cellular regeneration after 30 minutes of acute ischemic injury to a single kidney was elucidated in rats at five time points over 20 weeks. The fraction of apoptotic cells was most prominent at 1 day after the insult in the distal tubule (8% +/- 4% vs 0% +/- 0%, acute renal failure [ARF] vs sham, respectively) and was still elevated at 7 days (2% +/- 2% vs 0% +/- 0%). At that time, the whole kidney mRNA expression of the apoptosis inhibitory genes bcl-xL and bcl-2, as well as that of the apoptosis promotor bax, was significantly reduced. Immunohistochemistry of kidney specimen showed suppression of bcl-2 in the distal tubule but up-regulation in the proximal tubule, whereas bax protein was more strongly expressed in the distal tubule. Cellular proliferation started at day 1 and continued over the following 20 weeks, leading to severe tubular dilation and kidney failure. These data indicate that differential regulation of bcl-2 family members contributes to the early apoptotic clearance of lethally injured tubular epithelial cells after ischemic injury to a solitary kidney.

Animals↗

PubMed2001

Virulence-associated genes in avian pathogenic Escherichia coli (APEC) isolated from internal organs of poultry having died from colibacillosis.

Escherichia coli infections are responsible for significant losses in the poultry industry in many parts of the world. The pathogenesis and the role of virulence factors are not yet totally elucidated. We, therefore, examined 150 E. coli strains isolated from visceral organs of poultry having died from colibacillosis for the presence of virulence-associated genes by PCR. The E. coli strains were investigated for the presence of a total of 17 virulence-associated genes described for diarrheagenic (stx1/2, eae, hlyEHEC, estl, eltI, astA, cdtb), septicemic (hlyA, papC, cnf1/2, fyuA, irp2) and avian pathogenic E. coli (APEC; iucD, tsh, fimC, and hlyE as well as stx2f). Seven genes were significantly distributed among APEC strains, while most of the other investigated genes could be demonstrated only sporadically or not at all. FimC (Type I fimbriae) was detected with the highest prevalence in 92.7% of the isolates. Most of the strains harboring iucD (88.7%) also gave positive results for tsh (85.3%). Genes fyuA (ferric yersiniabactin uptake) (66.0%) and irp2 (iron-repressible protein) (68.0%), necessary for Yersinia to acquire iron in the mouse infection model, were regularly detected in combination. Moreover, we found papC (pyelonephritis-associated pili) in 30.0% and astA (enteroaggregative heat stable toxin) in 17.3% of the field strains. A significant amount of strains (57.3%) harbored a combination of iucD, tsh, fimC, fyuA and irp2 virulence-associated genes, presumably rendering these strains particularly virulent. These findings provide novel insights into the presence and distribution of virulence-associated genes in avian pathogenic E. coli field strains, which will help to more comprehensively characterize APEC in future epidemiological studies. It is assumed that the existence of two iron acquisition systems points towards their important role in virulence. Furthermore, we suggest that characterization of the respective phenotypes in infection models will provide substantial information to better understand the pathogenesis of colibacillosis in poultry.

Animals↗

PubMed2001

Impaired phosphate handling of renal allografts is aggravated under rapamycin-based immunosuppression.

BACKGROUND: Impaired phosphate handling of the renal allograft is a common problem and of multifactorial origin. The aim of the study was to elucidate whether a rapamycin- or a mycophenolate-based immunosuppressive therapy aggravates the renal phosphate leak in kidney transplant recipients. METHODS: Renal phosphate handling was determined in thirty-eight cadaveric allograft recipients, with good renal function at 8, 12, 20 and 28 weeks after transplantation. Nineteen patients (group 1) received triple immunosuppression with rapamycin, cyclosporine and prednisolone, nineteen other transplant recipients received mycophenolate mofetil, cyclosporine and prednisolone immunosuppression (group 2), and six healthy subjects (group 3) served as controls. After 12 weeks of stable graft function, group 1 patients were divided further into two subgroups. Ten patients were kept on their immunosuppressive regimen (group 1A), whereas the remaining nine randomly chosen subjects had their cyclosporine withdrawn; they were thus maintained on a dual immunosuppression regimen with prednisolone and a higher dosage of rapamycin (group 1B). RESULTS: Renal phosphate reabsorption was significantly lower in group 1 at 8 and 12 weeks after transplantation as compared with groups 2 and 3. At 20 weeks after transplantation, patients with rapamycin-based immunosuppression (groups 1A and 1B) continued to exhibit hypophosphataemia and impaired renal phosphate handling. Group 1B had the lowest TmP/ GFR compared with all groups. At 28 weeks, renal phosphate reabsorption and plasma phosphate levels were no longer different between patient groups and controls. CONCLUSION: These data suggest that rapamycin-based immunosuppression prolongs the phosphate leak of the allografted kidney, leading to low serum phosphate levels during the first weeks after transplantation.

Adult↗

PubMed2001

Characterization of antiapoptotic activities of Chlamydia pneumoniae in human cells.

Chlamydia pneumoniae is an obligate intracellular bacterium which frequently causes airway infection in humans and has been implicated in atherosclerosis. Here we show that infection with C. pneumoniae protects HeLa human epithelioid cells against apoptosis induced by external stimuli. In infected HeLa cells, apoptosis induced by staurosporine and CD95-death-receptor signaling was strongly reduced. Upon treatment with staurosporine, generation of effector caspase activity, processing of caspase-3 and caspase-9 and cytochrome c redistribution were all profoundly inhibited in cells infected with C. pneumoniae. Bacterial protein synthesis during early infection was required for this inhibition. Furthermore, cytochrome c-induced processing and activation of caspases were inhibited in cytosolic extracts from infected cells, suggesting that a C. pneumoniae-dependent antiapoptotic factor was generated in the cytosol upon infection. Infection with C. pneumoniae failed to induce significant NF-kappaB activation in HeLa cells, indicating that no NF-kappaB-dependent cellular factors were involved in the protection against apoptosis. These results show that C. pneumoniae is capable of interfering with the host cell's apoptotic apparatus at probably at least two steps in signal transduction and might explain the propensity of these bacteria to cause chronic infections in humans.

2,4-Dinitrophenol↗

PubMed2001

Effects of CYP7A1 overexpression on cholesterol and bile acid homeostasis.

The initial and rate-limiting step in the classic pathway of bile acid biosynthesis is 7alpha-hydroxylation of cholesterol, a reaction catalyzed by cholesterol 7alpha-hydroxylase (CYP7A1). The effect of CYP7A1 overexpression on cholesterol homeostasis in human liver cells has not been examined. The specific aim of this study was to determine the effects of overexpression of CYP7A1 on key regulatory steps involved in hepatocellular cholesterol homeostasis, using primary human hepatocytes (PHH) and HepG2 cells. Overexpression of CYP7A1 in HepG2 cells and PHH was accomplished by using a recombinant adenovirus encoding a CYP7A1 cDNA (AdCMV-CYP7A1). CYP7A1 overexpression resulted in a marked activation of the classic pathway of bile acid biosynthesis in both PHH and HepG2 cells. In response, there was decreased HMG-CoA-reductase (HMGR) activity, decreased acyl CoA:cholesterol acyltransferase (ACAT) activity, increased cholesteryl ester hydrolase (CEH) activity, and increased low-density lipoprotein receptor (LDLR) mRNA expression. Changes observed in HMGR, ACAT, and CEH mRNA levels paralleled changes in enzyme specific activities. More specifically, LDLR expression, ACAT activity, and CEH activity appeared responsive to an increase in cholesterol degradation after increased CYP7A1 expression. Conversely, accumulation of the oxysterol 7alpha-hydroxycholesterol in the microsomes after CYP7A1 overexpression was correlated with a decrease in HMGR activity.

Adenoviridae↗

PubMed2001

Two types of neurons in the rat cerebellar nuclei as distinguished by membrane potentials and intracellular fillings.

Classically, three classes of neurons in the cerebellar nuclei (CN), defined by different projection targets and content of transmitters, have been distinguished. However, evidence for different types of neurons based on different intrinsic properties is lacking. The present study reports two types of neurons defined mainly by their intrinsic properties, as determined by whole-cell patch recordings. The majority of cells (type I, n = 63) showed cyclic burst firing whereas a small subset (type II, n = 7) did not. Burst firing was used to distinguish the two types of neurons because, as it turned out, pharmacological interference could not be used to convert the non-bursting cells to bursting ones. Some of the membrane potentials exclusively present in type I neurons, such as sodium and calcium plateau potentials, low-threshold calcium spikes, and a slow calcium-dependent afterhyperpolarization, were found to contribute to the generation of burst firing. Other membrane potentials of type I neurons were not obviously related to the generation of bursts. These were 1) the lower amplitude and width of the action potential during spontaneous activity, 2) a sequence of afterhyperpolarization-afterdepolarization-afterhyperpolarization following each spike, and 3) the high spontaneous firing rate. In contrast, type II neurons lacked slow plateau potentials and low threshold spikes. Their action potentials showed higher amplitude and width and were followed by a single deep afterhyperpolarization. Furthermore, they showed a lower firing rate at rest. In both types of neurons, a delayed inward rectification was present. Neurons filled with neurobiotin revealed that the sizes of the somata and dendritic fields of type I neurons comprised the whole range known from Golgi studies, whereas those of the few type II neurons recovered were found to be in the lowest range. In view of their size and scarcity, we propose that type II neurons may correspond to CN interneurons.

Action Potentials↗

PubMed2001

Dynamic modulation of mossy fiber system throughput by inferior olive synchrony: a multielectrode study of cerebellar cortex activated by motor cortex.

We investigated the effects of climbing fiber synchrony on the temporal dynamics of mossy fiber system throughput in populations of cerebellar Purkinje cells (PCs). A multielectrode technique was used in ketamine-anesthetized rats that allowed both complex and simple spikes (CSs and SSs) to be recorded from multiple PCs simultaneously in lobule crus IIa. Stimulation of the tongue area of the primary motor cortex (TM1) was used to evoke cerebro-cerebellar interaction. At the single PC level, robust short-term interactions of CSs and SSs were observed after TM1 stimulation that typically consisted of an immediate depression and subsequent enhancement of SS firing after the occurrence of a CS. Such modulations of SS rate in a given PC were as robustly correlated to the CSs of simultaneously recorded PCs as they were to the CS on its own membrane-and did not require a CS on its own membrane-indicating a network basis for the interaction. Analyses of simultaneously recorded PCs using the normalized joint perievent time histogram demonstrated that CS and SS firing were dynamically correlated after TM1 stimulation in a manner that indicated strong control of mossy fiber system throughput by CS synchrony. For < or =300 ms after TM1 stimulation, most PCs showed episodic modulations in SS rate that appeared to be entrained by the population rhythm of climbing fiber synchrony. SS rhythmicity also was modulated dynamically by CSs, such that it was depressed by CSs and facilitated by their absence. Like the modulations in SS rate, a given PC's modulation in SS rhythmicity did not require it to fire a CS but was, on those instances, equally correlated to the synchronous CSs of other PCs. The data indicate that the climbing fiber system controls the temporal dynamics of SS firing in populations of PCs by using synchrony to engage intracerebellar circuitry and modulate mossy fiber system throughput.

Action Potentials↗

PubMed2001

Early investigation of silver-coated Silzone heart valves prosthesis in 126 patients.

BACKGROUND AND AIM OF THE STUDY: Permanent silver (Silzone) coating of the sewing cuff of St. Jude Medical prosthetic heart valves may reduce the rate of prosthetic valve endocarditis (PVE). However, the incidence of paravalvular leaks and stroke in patients after implantation of Silzone-coated heart valve prostheses is largely unknown. METHODS: Complications were analyzed among 126 consecutive patients (78 males, 48 females; mean age 64.7 years; range: 40-80 years) who received Silzone-coated prostheses at our institution between February 1998 and December 1999. Among patients, 94 had aortic valve replacement, 29 mitral valve replacement, and three had aortic and mitral valve replacement. Concomitant cardiac procedures (mainly coronary bypass) were performed in 47 patients (37.3%). RESULTS: Hospital mortality was 1.6% (2/126) and freedom from valve-related mortality 99.2+/-0.9%. Total follow up was 137.4 patient-years, and 98.4% complete. Strokes or transitory ischemic attacks (TIAs) occurred in four cases (two strokes, two TIAs; stroke rate 1.5%/year; 95% CI 0.4-2.6%/year; stroke+TIA rate 3%/year; 95% CI 0.4-5.25%/year). There was no case of prosthetic valve dysfunction or PVE. Freedom from reoperation due to procedure-associated complications was 97.6% (one aortic dissection, two major bleeds). Paravalvular leak was detected in 19 cases, and graded trivial or mild in 17 cases (11 grade 0-I, six grade I), and moderate in two cases (grade I-II in one, grade II in one). No patient needed reoperation due to paravalvular leak. Left ventricular (LV) function was normal in 80 cases, but was impaired mildly in 20 cases, moderately in 16, and severely in eight. Bicycle exercise testing in 92 patients (73%) showed median exercise performance (81.4+/-23.9% of normal) after correction for age and weight. Cerebral magnetic resonance imaging was performed in 64 patients (50.8%); median MRI score was 2.0+/-1.8 according to a 12-scaled score system. CONCLUSION: The overall incidence of echocardiographic paravalvular leak graded more than trivial or mild was low (1.6%) in patients followed for a mean of 1.1+/-0.5 years (range: 1-27 months) after valve replacement with Silzone-coated heart valve prostheses. No patient required reoperation due to paravalvular leak; moreover, the stroke rate (1.5%/year) was low in these patients. The present data indicated no significant disadvantages or higher rate of complications related to silver coating compared with other, non-silver-coated prostheses. Future investigation is needed to determine long-term outcome.

Adult↗

PubMed2000

[Effect of blood glucose and blood pressure control on progression of diabetic nephropathy].

Although diabetic nephropathy is a slowly progressing, well studied disease, it is the most common cause of end stage renal disease in industrialized countries. Recently the first randomized controlled long term trials about microvascular complications in patients with type 2 diabetes have been published. Only seven years ago the first hallmark papers about metabolic control and ACE inhibition emerged. This review highlights the current status of prevention and therapy of diabetic nephropathy by metabolic and blood pressure control in type 1 and type 2 diabetic patients, depending on their stage of nephropathy (normo-, micro-, or macroalbuminuria). In patients with type 1 diabetes and normo- or microalbuminuria, strict metabolic control has been shown to slow the progression of nephropathy. In macroalbuminuric patients an aggressive antihypertensive treatment, preferably with an ACE inhibitor, is more important than the metabolic control. ACE inhibitor therapy has also been proven beneficial in microalbuminuric patients, but not yet in normotensive, non-albuminuric type 1 patients. Because of the high prevalence of hypertension in patients with type 2 diabetes, a strict antihypertensive treatment is more important than metabolic control for the prevention of progression of microvascular disease. Since most patients need a combination of antihypertensive medications a recommendation for a single substance class can not be given.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Serotonin suppresses subthreshold and suprathreshold oscillatory activity of rat inferior olivary neurones in vitro.

The effect of serotonin on membrane potential oscillations of inferior olivary neurones was studied in brainstem slices from 10- to 19-day-old rats. Serotonin at 50 and 5 microM induced a mean depolarization of 9.4 and 7.7 mV, respectively, that was preceded by a reversible suppression of subthreshold membrane potential oscillations. These effects were not changed by 1 microM tetrodotoxin and the suppression of subthreshold oscillations persisted after current-mediated restoration of resting potential. In spontaneously active neurones, serotonin abolished the rhythmicity of action potential firing without affecting spike frequency. Serotonin reduced the slope of the calcium-mediated rebound spike and both the duration and amplitude of the subsequent afterhyperpolarization. Serotonin also shifted the voltage dependence of the rebound spike to more negative values. Hyperpolarizing current pulses (200 ms) revealed that serotonin increased the pre-rectification and steady-state components of membrane resistance by 37 and 38 %, respectively, in 66 % of neurones, but decreased these parameters by 14 and 20% in the remaining cells. The serotonin effects were antagonized by 5 microM methysergide or 1-5 microM ketanserin and were mimicked by 10-20 microM dimethoxy-4-iodoamphetamine but not 10 microM 8-hydroxy-2-(di-N-propylamino)-tetralin. The data indicate that serotonin suppresses the rhythmic activity of olivary neurones via 5-HT2 receptors by inhibition of the T-type calcium current in combination with membrane depolarization due to activation of a cation current (Ih) and block of a resting K+ current (fast IK(ir)). This modulatory action of serotonin may account for the differential propensity of olivary neurones to fire rhythmically during different behavioural states in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2000

Receptor recognition by a hepatitis B virus reveals a novel mode of high affinity virus-receptor interaction.

The duck hepatitis B virus model system was used to elucidate the characteristics of receptor (carboxypeptidase D, gp180) interaction with polypeptides representing the receptor binding site in the preS part of the large viral surface protein. We demonstrate the pivotal role of carboxypeptidase D for virus entry and show its C-domain represents the virus attachment site, which binds preS with extraordinary affinity. Combining results from surface plasmon resonance spectroscopy and two-dimensional NMR analysis we resolved the contribution of preS sequence elements to complex stability and show that receptor binding potentially occurs in two steps. Initially, a short alpha-helix in the C-terminus of the receptor binding domain facilitates formation of a primary complex. This complex is stabilized sequentially, involving approximately 60 most randomly structured amino acids preceding the helix. Thus, hepadnaviruses exhibit a novel mechanism of high affinity receptor interaction by conserving the potential to adapt structure during binding rather than to preserve it per se. We propose that this process represents an alternative strategy to escape immune surveillance and the evolutionary pressure inherent in the compact hepadnaviral genome organization.

Amino Acid Sequence↗

PubMed2000

[Pathophysiology of acute renal failure at the cellular level].

The influence of inflammation on post-ischemic acute renal failure (ARF) has only recently be appreciated. In this review we therefore discuss the cellular events occurring in ARF with special emphasis on the impact of inflammatory processes on the pathogenesis of ARF. Furthermore, the spectrum of injury leading to sublethal or lethal cell damage and the time course, occurrence and regulation of the two distinct forms of cell death, necrosis and apoptosis will be described extensively. Especially apoptosis and its regulation has been studied only marginally in the setting of ischemic ARF. This overview is mainly focused on tubular cell injury since tubular epithelial cells are the major victims of ischemia whereas cells inside the glomerular tuft show only little pathology. The models of tubular injury described in this paper are ranging from primary cultures of isolated human tubular epithelial cells to experimental ischemic renal failure in rats, and to clinical settings of human ischemic ARF. The cellular events highlighted in this review are the influence of the expression of cellular adhesion molecules on the pathophysiology of ARF, and the regulation and time course of apoptosis. Examples of these processes are being illustrated by figures exhibiting morphology and immunohistochemistry of cell proliferation and cell death regulatory proteins.

Acute Kidney Injury↗

PubMed2000

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Journal Article↗

PubMed2000

Diabetes mellitus and islet cell specific autoimmunity as adverse effects of immunsuppressive therapy by FK506/tacrolimus.

The induction of diabetes has been recognised as adverse effect of the immunsuppressive drug FK506/Tacrolimus. The aim of this study was to clarify whether insulinopenia or insulin resistance dominates and whether islet cell autoantibodies are present in patients treated by FK506. We investigated 58 patients 1-3 years after liver transplantation while under therapy with FK506 or CsA and prednisolone (0-7.5 mg) for basal blood glucose levels and islet-cell specific autoantibodies. A subgroup of 20 patients on FK506, 10 patients on cyclosporin and 15 healthy volunteers were metabolically tested by oGTT. Five patients had diabetes pre-transplantation. After transplantation, 9/28 FK506-treated patients developed newly diagnosed diabetes compared to 0/25 cyclosporin-treated patients (p<0.01). Both patient groups showed significantly higher fasting blood glucose, insulin or C-peptide levels compared to controls. Through the oGTT, FK506-treated patients without diabetes, but not cyclosporin-treated patients, had higher C-peptide levels compared to controls (p<0.05). Five/32 patients on FK506 compared to 0/26 patients on cyclosporin (p<0.05) had islet cell specific autoantibodies, mainly ICA without GAD- or IA2-Ab, a feature described for latent autoimmune diabetes in adults. ICA positivity was correlated to the diabetes associated HLA haplotype DR4/DQ*0302 (p<0.05). Although the interpretation of our metabolic data in patients with concomitant liver disease and prednisolone therapy has limitations, we suggest insulin resistance caused by treatment with FK506. However, manifestation of diabetes was associated with relative insulinopenia rather than insulin resistance in patients on FK506. Immunsuppressive therapy by FK506 was not able to suppress islet cell autoimmunity, and may even induce it in genetically predisposed patients.

Adult↗

PubMed2000

Apolipoprotein E polymorphism: survival and neurological outcome after cardiopulmonary resuscitation.

BACKGROUND AND PURPOSE: The apolipoprotein E 3/3 (apoE 3/3) genotype is associated with a reduced risk of developing Alzheimer's disease and with a favorable neurological outcome after traumatic head injury. In vitro studies suggest that the most common genotype, apoE 3/3, may be involved in neuroprotective and neuroregenerative mechanisms. The aim of this study was to determine whether the apoE 3/3 genotype has an impact on survival and neurological outcome after cardiopulmonary resuscitation. METHODS: Eighty patients with cardiac arrest were investigated prospectively for their apoE genotype. Epidemiological data were assessed according to recommended guidelines. Patients were divided into 2 groups, ie, with the apoE 3/3 genotype present or absent, and tested for differences in survival and neurological outcome. Further statistical analysis with respect to survival and neurological outcome was performed by using a stepwise logistic regression analysis. RESULTS: Patients with the apoE 3/3 genotype had a significantly higher survival rate (64% versus 33%, P:=0.007) and more often a favorable neurological outcome (55% versus 27%, P:=0. 013) compared with patients with other apoE genotypes. The apoE 3/3 genotype was shown to be a substantial predictive factor for a favorable neurological outcome (odds ratio 3.2) and was, apart from other essential factors, predictive for survival (odds ratio 4.4) after cardiopulmonary resuscitation. CONCLUSIONS: These data give evidence that patients with the apoE 3/3 genotype have a better chance of recovery after cardiopulmonary resuscitation than do patients with apoE genotypes other than 3/3.

Alleles↗

PubMed1999

Glutamine deprivation induces the expression of GADD45 and GADD153 primarily by mRNA stabilization.

The expression of the growth arrest- and DNA damage-inducible genes, GADD45 and GADD153/CHOP (C/EBP-homologous protein), as well as GRP78 (glucose-regulated protein of 78 kDa) was examined in several human breast cell lines subjected to acute glutamine (GLN) deprivation. GLN deprivation caused rapid elevation of GADD45 and GADD153/CHOP mRNA levels in cells that were highly dependent upon GLN for growth and viability. Both GADD mRNAs were rapidly elevated up to several hundred-fold. In contrast, GRP78 expression was elevated by no more than 4-fold by GLN deprivation. The magnitude of GADD up-regulation roughly correlated with the extent of GLN dependence of each cell line. The levels of all three mRNAs were responsive to alterations of ambient GLN content in a physiologically relevant concentration range that corresponded to the affinities of cellular GLN transporters. Provision of GLN-derived metabolites partially inhibited the induction of GADD expression in GLN-deprived cells. Nuclear run-on assays and mRNA decay studies suggested that the primary mechanism leading to increased GADD mRNA levels was not transcriptional, but rather that GADD45 and GADD153/CHOP expression were up-regulated in response to GLN deprivation via marked stabilization of these mRNAs. These results suggest that the expression of GADD genes contributes to growth arrest and/or protection from metabolic damage during GLN-poor conditions.

Breast Neoplasms↗