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Biomedical subjects

S Schwarz

Publications and source records attributed to S Schwarz.

At least 91 records · Page 5Linked to original sources
PubMed2000

Identification of a truncated, but functionally active tet(H) tetracycline resistance gene in Pasteurella aerogenes and Pasteurella multocida.

Molecular analysis of Pasteurella isolates of animal origin for plasmid-encoded tetracycline resistance genes identified a common tet(H)-carrying plasmid of 5.5 kbp in a single isolate of Pasteurella aerogenes and six isolates of Pasteurella multocida. This plasmid carried a truncated Tn5706 element in which one of the IS elements, IS1596, was lost completely and of the other, IS1597, only a relic of 84 bp was left. Sequencing of the resistance gene region and the flanking areas revealed the presence of a deletion in the 3' end of the tet(H) gene which shortened the tet(H) reading frame by 24 bp. The amino acid sequence of the respective TetH protein comprised only 392 amino acids. Despite this deletion, the tet(H) gene conferred high level tetracycline resistance not only to the original Pasteurella isolates but also to the respective Escherichia coli JM107 and C600 transformants as confirmed by MIC determination. The deletion was probably the result from recombinational events. Two possible recombination sites involved in the deletion of tet(H) and that of IS1597 were identified. Macrorestriction analysis of the Pasteurella isolates carrying plasmid pPAT1 confirmed horizontal and vertical transfer of this plasmid.

Animals↗
PubMed2000

5-methylcytosine-DNA glycosylase activity is present in a cloned G/T mismatch DNA glycosylase associated with the chicken embryo DNA demethylation complex.

We previously have shown that DNA demethylation by chicken embryo 5-methylcytosine DNA glycosylase (5-MCDG) needs both RNA and proteins. One of these proteins is a RNA helicase. Further peptides were sequenced, and three of them are identical to the mammalian G/T mismatch DNA glycosylase. A 3,233-bp cDNA coding for the chicken homologue of human G/T mismatch DNA glycosylase was isolated and sequenced. The derived amino acid sequence (408 aa) shows 80% identity with the human G/T mismatch DNA glycosylase, and both the C and N-terminal parts have about 50% identity. As for the highly purified chicken embryo DNA demethylation complex the recombinant protein expressed in Escherichia coli has both G/T mismatch and 5-MCDG activities. The recombinant protein has the same substrate specificity as the chicken embryo 5-MCDG where hemimethylated DNA is a better substrate than symmetrically methylated CpGs. The activity ratio of G/T mismatch and 5-MCDG is about 30:1 for the recombinant protein expressed in E. coli and 3:1 for the purified enzyme from chicken embryos. The incubation of a recombinant CpG-rich RNA isolated from the purified DNA demethylation complex with the recombinant enzyme strongly inhibits G/T mismatch glycosylase while slightly stimulating the activity of 5-MCDG. Deletion mutations indicate that G/T mismatch and 5-MCDG activities share the same areas of the N- and C-terminal parts of the protein. In reconstitution experiments RNA helicase in the presence of recombinant RNA and ATP potentiates the activity of 5-MCDG.

Amino Acid Sequence↗
PubMed2000

Incidence and prognostic significance of fever following intracerebral hemorrhage.

OBJECTIVE: To investigate the incidence and prognostic significance of fever on presentation and during the subsequent 72 hours in patients with spontaneous supratentorial intracerebral hemorrhage (ICH). METHODS: We analyzed 251 patients. On admission, body temperature, Glasgow Coma Scale (GCS) score, age, sex, blood pressure, blood glucose level, and presumed origin of hemorrhage were analyzed. From the initial CT scan, hematoma volume, location, and presence of intraventricular hemorrhage were determined. From the first 72 hours, hematoma enlargement, duration of increased temperatures, blood pressure, and blood glucose level were determined. Outcome was classified on discharge with the Glasgow Outcome Scale (GOS) score. RESULTS: Outcomes included no symptoms in 23 (9%), moderate disability in 64 (26%), severe disability in 104 (41%), vegetative state in 5 (2%), and death in 55 (22%) patients. Prognostic factors retained from a logistic regression model with a dichotomized GOS scale (GOS score of 1 or 2 versus GOS score of 3 to 5) as response variables were GCS score of 7 or less, age older than 75 years, hematoma volume of more than 60 cm3, ventricular hemorrhage, and presence of a coagulation disorder (p < 0.05). Fever was associated with intraventricular hemorrhage. From 196 patients, data from the first 72 hours were analyzed. A total of 18 patients (9%) had normal temperatures throughout the study. The duration of fever (> or =37.5 degrees C) was less than 24 hours in 66 (34%), 24 to 48 hours in 70 (36%), and more than 48 hours in 42 patients (21%). Independent prognostic factors during the first 72 hours were duration of fever, secondary hemorrhage, GCS score of 7 or less, ventricular hemorrhage, hematoma volume of more than 60 cm3, duration of increased blood pressure of more than 48 hours, and duration of increased blood glucose of more than 48 hours. CONCLUSIONS: The incidence of fever after supratentorial ICH is high, especially in patients with ventricular hemorrhage. In patients surviving the first 72 hours after hospital admission, the duration of fever is associated with poor outcome and seems to be an independent prognostic factor in these patients.

Adult↗
PubMed2000

Magnetic evoked potentials in neurocritical care patients with acute brainstem lesions.

OBJECTIVES: Motor evoked potentials (MEPs) are widely used in various neurological diseases, but have not been systematically employed in neurocritical care patients. We evaluated the clinical and predictive value of MEPs by magnetic transcranial stimulation in intensive care patients with acute brainstem lesions of predominantly vascular origin. METHODS: In a prospective trial, a total of 30 patients with acute brainstem lesions were studied. Diagnoses were brainstem infarction (n=15), brainstem hemorrhage (n=3), encephalitis (n=1), basilar artery aneurysm (n=1), and space-occupying cerebellar infarct (n=5), cerebellar hemorrhage (n=3), and brainstem contusion (n=2). We performed MEP tests by transcranial stimulation to the abductor pollicis brevis bilaterally, bilateral somatosensory (SEPs) and auditory evoked (BAEPs) potentials. We determined motor function at the time of electrophysiological testing and after 3 months, the presence of radiologically confirmed lesions, and clinical outcome after 3 months. At the time of MEP recordings, ten patients were comatose, twelve stuporous, seven somnolent and one awake. RESULTS: MEPs were present bilaterally in seventeen, absent unilaterally in eight and bilateral absent in five patients. Absent MEP highly correlated with the presence of persisting motor deficit 3 months later (P<0.0001). Absent MEPs predicted motor deficit after 3 months with a high specificity and more precisely than the clinical examination at the time of MEP testing. MEP findings correlated with the presence of radiologically confirmed lesions within the brainstem (P<0.0001). Combined with SEP and BAEP data, MEPs predicted the presence of unilateral brainstem lesions with high accuracy. CONCLUSIONS: MEP recordings can be safely performed in neurointensive care patients and yield utilizable results. In patients with brainstem lesions, MEPs correlate with radiological findings and predict final motor function more accurately than clinical findings. MEPs are a reliable diagnostic tool for assessing motor function in otherwise unresponsive patients.

Adolescent↗
PubMed2000

Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice.

The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the immune system during immune reactions, causing an elevation of systemic glucocorticoid levels that contribute to preservation of the immune reactions specificities. Previous results from our laboratory had already shown an altered immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone chicken and mouse strains. In the present study, we further investigated the altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in murine lupus. We established the circadian rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as well as the time response curves after injection of interleukin-1 of the first three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormone were normal compared to healthy controls. These data indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our findings may have implications for intrathymic T cell development and the emergence of autoimmune disease.

Adrenal Glands↗
PubMed2000

[Dystonia following peripheral trauma: clinical findings and diagnostic criteria].

Dystonia is a rare neurological complication after peripheral trauma. Incidence and pathophysiology of post-traumatic dystonia are not known. Predisposing factors are sympathetic reflex dystrophia, pre-existing movement disorders or a family history of movement disorders. The main diagnostic goal is to exclude other causes of secondary dystonia. Objective criteria for posttraumatic dystonia are not established, and therefore differentiation from psychogenic dystonia frequently remains difficult. Careful psychiatric examination is obligatory. Clinical criteria are consistency of the symptoms over time and the presence of symptoms compatible with organic dystonia. Polygraphic EMG examinations provide objective correlates of the movement disorder, but exact EMG criteria for the diagnosis of dystonia have yet to be established.

Adult↗
PubMed2000

Characterization of steroid hormone sensitivity in human breast cancers maintained ex vivo under organotypical culture conditions.

PURPOSE: The methodology we propose combines the immunohistochemical determination of the oestrogen and progesterone receptors (ER and PgR) with the characterization of the oestradiol- and progesterone-induced influence on cell proliferation in breast cancers in order to characterize their steroid hormone sensitivity at both the "static" and "dynamic" level. METHODS: ER and PgR have been immunohistochemically quantified by means of computer-assisted microscopy. Cell proliferation has been determined by means of tritiated thymidine autoradiography in tumour samples maintained in vitro as organotypic cultures. A series of 14 patients was investigated. RESULTS: Of the 14 breast cancers under study, one with an unequivocally "very ER-rich"/"very PgR-rich" immunohistochemical phenotype totally failed to exhibit any modification in its cell proliferation level after both oestradiol and progesterone stimulation. Two cases definitively associated with an "ER-poor"/"PgR-poor" immunohistochemical phenotype nevertheless responded noticeably to the dynamic stimulation of their cell proliferation by oestradiol and progesterone. While our series of cases covers 14 patients only, it suffices to demonstrate the limits of ER and PgR determination in characterizing steroid hormone sensitivity in breast cancer. DISCUSSION: The present work therefore presents an in vitro approach to test growth regulation of human breast cancer by steroid hormones. The clinical value of the present approach should be further determined by showing that steroid hormone-induced modifications in cell proliferation level are actually associated with clinical response.

Aged↗
PubMed2000

The role of microsatellite instability in gastric low- and high-grade lymphoma development.

DNA mismatch repair genes and their dysfunction as evidenced by microsatellite instability (MSI) play an important role in the pathogenesis of a variety of tumors, most prominently hereditary nonpolyposis colorectal cancer (HNPCC). However, their role in development of extranodal lymphomas has not been established yet. We therefore evaluated for MSI 25 gastric low-grade marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue type and 31 gastric high-grade diffuse large B-cell lymphomas (DLBCLs) with 29 and 118 microsatellites, respectively. Compared with HNPCC, the overall level of MSI was much lower with a mean of 2.6% MSI-positive repeats in the DLBCLs; the frequency of MSI showed a tendency to increase with age (P = 0.01), as did MSI variability (P = 0.02). Low-grade mucosa-associated lymphoid tissue lymphomas displayed even less MSI (sevenfold) than DLBCLs (P = 0.009). MSI frequency thus increases with the transition from low- to high-grade disease and with age; it does not seem to initiate lymphomagenesis. Other microsatellites than those typically mutated in HNPCC frequently revealed MSI in these lymphomas, especially dinucleotide repeats on chromosomes 3, 5, and 18. To facilitate rapid screening of lymphomas for MSI and to establish a tool for future MSI frequency comparisons, we recommend to use repeats D3S1261, D3S1530, D5S346, D17S250, D18S474, and DCC.

Adult↗
PubMed2000

Effects of estradiol and estradiol sulfamate on the uterus of ovariectomized or ovariectomized and hypophysectomized rats.

Estradiol sulfamate (J995), estradiol-17beta with a substituted sulfamate group in position 3, has much higher systemic estrogenic activity after oral administration than 17beta-estradiol (E2) due to reduced hepatic metabolism of the drug. The lower dose necessary for achievement of adequate systemic estrogenic effects results in a substantial reduction of otherwise commonly observed hepatic side-effects. This makes J995 a strong candidate as an estrogen suitable for oral administration. The present study was performed to examine and compare the effects of J995 and E2 on the uterus after oral or subcutaneous administration to ovariectomized or ovariectomized+hypophysectomized female rats, in particular on the levels of the estrogen receptor (ER) (alpha+beta), ERalpha mRNA and insulin-like growth factor-I (IGF-I) mRNA. The ER levels were determined using a ligand binding assay and the mRNA levels using solution hybridization. The doses of J995 or E2 were chosen to achieve comparable uterotrophic activity. The rats were treated with hormones for 7 days and the treatment was initiated 14 days after surgery. We conclude that there are no major differences in the uterine response to treatment with J995 or E2 with respect to the effects on ER and ERalpha mRNA levels. The IGF-I mRNA level though, is more affected by J995 than by E2 after 7 days of treatment, indicating a prolonged effect of J995.

Administration, Oral↗
PubMed2000

Molecular analysis of tetracycline resistance in Salmonella enterica subsp. enterica serovars Typhimurium, enteritidis, Dublin, Choleraesuis, Hadar and Saintpaul: construction and application of specific gene probes.

A total of 65 epidemiologically unrelated tetracycline-resistant isolates of the six Salmonella enterica subsp. enterica (Salm.) serovars Dublin, Choleraesuis, Typhimurium, Enteritidis, Hadar and Saintpaul were investigated for the presence of tetracycline resistance genes. For this, specific gene probes of the tetracycline resistance genes (tet) of the hybridization classes A, B, C, D, E and G were constructed by cloning PCR-amplified internal segments of the respective tet structural genes. These gene probes were sequenced and used in hybridization experiments with plasmid DNA or endonuclease digested whole cell DNA as targets. Only tet(A) genes were detected on plasmids in all Salm. Dublin isolates as well as in single isolates of Salm. Choleraesuis and Salm. Typhimurium. Genes of the hybridization classes B, C, D and G, but also in some cases those of class A, were located in the chromosomal DNA of the corresponding Salmonella isolates. Restriction fragment length polymorphisms (RFLPs) of tet gene carrying fragments were detected in chromosomally tetracycline-resistant isolates. These RFLPs might represent valuable additional tools for the identification and characterization of tetracycline-resistant Salmonella isolates.

Antiporters↗
PubMed2000

A CpG-rich RNA and an RNA helicase tightly associated with the DNA demethylation complex are present mainly in dividing chick embryo cells.

In the developing chicken embryo, active DNA demethylation requires both RNA and proteins (Nucleic Acids Res. 25, 2375-2380, 1997; ibid. 25, 4545-4550, 1997, FEBS Lett. 449, 251-254, 1999a). In vitro assays indicate that in the 5- and 12-day-old embryos the highest specific activity of 5-methylcytosine DNA glycosylase is found in the brain, the eyes and the skin. In situ hybridization with antisense CpG-rich RNA tightly associated to the DNA demethylation complex shows a restricted expression pattern only in proliferating tissues such as the neuroepithelia of the brain in 5-day-old embryos. The RNA is absent in differentiated tissues like the skeletal and heart muscle, liver and the crystallin-producing cells in the lens. The CpG-rich RNA is transcribed in a developmental stage-specific rather than in a cell-specific manner. In contrast transcripts of DNA methyltransferase are found in dividing and quiescent cells. In situ hybridization with a probe of a RNA helicase which is also associated with the DNA demethylation complex shows a very similar localization in mitotically active tissues as the CpG-rich RNA. The content of 5-methylcytosine in individual cells was determined with a specific monoclonal antibody and cytometric analysis on tissue sections. The results indicate that proliferating cells have on the average 15% more methylated cytosines than non-dividing cells. This represents roughly 3x10(6) more methylation sites per haploid genome.

Animals↗
PubMed2000

Molecular analysis of the translational attenuator of a constitutively expressed erm(A) gene from Staphylococcus intermedius.

During the course of a study on macrolide, lincosamide and streptogramin B resistance among staphylococci from animal sources, a Staphylococcus intermedius isolate was found to carry a constitutively expressed erm(A) gene on the 70 kb plasmid pSES29. The molecular basis of constitutive erm(A) expression was investigated by cloning and sequence analysis of the erm(A)-associated translational attenuator. Two point mutations in this regulatory region were detected. These mutations cause constitutive erm(A) gene expression by destabilization of mRNA secondary structures required for the inducible type of erm(A) gene expression.

Animals↗
PubMed2000

Bedside monitoring of cerebral blood flow in patients with acute hemispheric stroke.

OBJECTIVE: To test the practicability of a new double indicator dilution method for bedside monitoring of cerebral blood flow (CBF) and to assess the clinical value of CBF monitoring as a prognostic tool for outcome and in therapy of elevated intracranial pressure (ICP) in patients with acute hemispheric stroke. DESIGN: Prospective study. Clinical evaluation of a new method. SETTING: Neurological intensive care unit of a university hospital. PATIENTS: Ten patients with acute complete middle cerebral artery territory- or hemispheric infarctions. INTERVENTIONS: Two combined fiberoptic thermistor catheters were placed in the right jugular bulb and in the thoracic aorta. Central venous injections of ice-cold indocyanine green dye were performed. CBF was estimated by calculating the mean transit times of the cold bolus and dye. MEASUREMENTS AND MAIN RESULTS: A total of 104 reproducible CBF measurements were obtained. No complications associated with the method were observed. Twelve pairs of measurements were performed within 30 mins with unchanged clinical conditions. The standard deviation of repeated measurements was 2.7 mL/100 g/min; the interrater reliability was between 0.95 and 0.99. The median CBF in patients who died (n = 4) was lower (27 mL/100g/min) than in those who survived (n = 6) (45 mL/100g/ min). Patients who died more frequently had low CBF values of <30 mL/100g/min (22 of 38; 58%) than patients who survived (10 of 54; 19%). A total of 37 CBF measurements were done during ICP elevation of >20 mm Hg. In patients who survived, ICP elevations were only associated with low CBF values in 5 of 26 events; whereas in patients who died, ICP elevations were associated with low CBF values in 8 of 11 events. CONCLUSIONS: The new double indicator dilution technique may be suitable for serial bedside CBF measurement. It is easy to perform and can be rapidly repeated in the ICU environment. Validation of the method by comparison with standard methods is needed. The preliminary data indicate that bedside monitoring of CBF may give prognostic information for outcome and may guide therapy of elevated ICP in patients with malignant hemispheric infarction.

Acute Disease↗
PubMed2000

Right atrial pressure predicts hemodynamic response to apneic positive airway pressure.

OBJECTIVE: To evaluate if the preexistant filling state, assessed by right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), and right ventricular end-diastolic volume index (EDVI), would define the subsequent hemodynamic effects of increases in airway pressure (Paw). DESIGN: Prospective open clinical study. SETTING: Postoperative intensive care unit, university hospital. PATIENTS: Twenty-two consecutive ventilator-dependent patients with mild to severe acute lung injury with Murray scores (scoring infiltrates on chest radiograph, oxygenation index, lung compliance, and the level of positive end-expiratory pressure) ranging from 0.5 to 3.0 without history of preexisting cardiopulmonary disease. INTERVENTIONS: Paw varied during apnea from 0 to 10, 20, and 30 cm H2O using inspiratory hold maneuvers of 15 secs. MEASUREMENTS AND MAIN RESULTS: Cardiac index and right ventricular ejection fraction were measured by the thermodilution technique. We made measurements in triplicate using manual injection of iced saline. Right ventricular volumes were calculated. Increasing Paw induced variable changes in cardiac index among subjects (+6% to -43% change from baseline 0 cm H2O Paw values), which correlated with percentage changes in both stroke index (r2 = .89) and right ventricular EDVI (r2 = .75), whereas heart rate and right ventricular ejection fraction did not change. The change in cardiac index from 0 to 30 cm H2O Paw correlated with baseline values for RAP, PAOP, and right ventricular EDVI (r2 = .68, .43, and .34, respectively, p < 0.01). Increases in RAP correlated with lung compliance if baseline RAP was >10 mm Hg but did not if it was < or =10 mm Hg. Similarly, patients with baseline RAP < or =10 mm Hg had a greater decrease in cardiac index than patients with a RAP >10 mm Hg (for 30 cm H2O Paw: -30% +/- 9% vs. -8% +/- 7%, p < .01). CONCLUSIONS: Apneic positive Paw decreased cardiac output mainly by reducing venous return. From the investigated filling variables, RAP was most sensitive in predicting the hemodynamic response, followed by PAOP and right ventricular EDVI. Patients with RAP < or =10 mm Hg, if subjected to aggressive positive pressure ventilation, are at risk of hemodynamic deterioration and organ hypoperfusion.

Adult↗
PubMed2000

Serum procalcitonin levels in bacterial and abacterial meningitis.

OBJECTIVES: To test the hypothesis that serum procalcitonin (PCT) levels are elevated in patients with bacterial meningitis and remain within normal limits in patients with abacterial meningitis. DESIGN: Prospective case series. SETTING: Tertiary care center. PATIENTS: A total of 30 patients (13 men and 17 women) with a mean age of 52 yrs, having acute bacterial (n = 16) or abacterial (n = 14) meningitis. INTERVENTIONS: Blood and cerebrospinal fluid samples. MEASUREMENTS AND MAIN RESULTS: Patients with abacterial meningitis were younger and had a shorter hospital stay. Of 16 patients with bacterial meningitis, 14 were in a septic condition at admission, but only 5 of 14 patients with abacterial meningitis were in a septic condition at admission. At discharge, 12 patients were without symptoms, 9 patients were moderately disabled, and 9 were severely disabled. No patient died. At admission, PCT, C-reactive protein, white blood cell and cerebrospinal fluid leukocyte counts, and cerebrospinal fluid protein and lactate levels were higher and the serum/cerebrospinal fluid glucose quotient was lower in patients with bacterial meningitis as compared with those with abacterial meningitis (p < .001). PCT was the variable with the highest specificity for bacterial infections (100%), but there were false-negative findings in five patients with bacterial meningitis (a sensitivity of 69%). Persistently elevated or increasing PCT levels after 2 days were associated with an unfavorable clinical course. CONCLUSIONS: Our results indicate that PCT is a useful additional variable for distinguishing bacterial from abacterial meningitis. In patients with abacterial meningitis, PCT levels do not increase even in cases of viral sepsis. Elevated PCT levels indicate a bacterial origin with high specificity, but false-negative results can occur.

Adolescent↗
PubMed2000

Effects of nonsteroidal antiinflammatory drugs on inflammatory bowel disease: a case-control study.

OBJECTIVE: The aim of this study was to determine whether a relationship exists between the use of nonsteroidal antiinflammatory drugs (NSAIDs) and exacerbation or onset of inflammatory bowel disease (IBD). METHODS: Sixty consecutive IBD patients admitted to the hospital were carefully interviewed to ascertain whether they used NSAIDs and the relationship in time and duration to the exacerbation (or onset) of the IBD; 62 patients with irritable bowel syndrome were similarly interviewed and served as controls. RESULTS: In 31% of our IBD population there was a correlation between use of NSAIDs and IBD activity, whereas in only 2% of the irritable bowel syndrome population who used NSAIDs did this relationship exist. CONCLUSIONS: NSAIDs provoke disease activity in both ulcerative colitis and Crohn's disease and should be avoided in patients with a history of IBD whenever possible.

Adolescent↗
PubMed2000

Identification of a plasmid-borne chloramphenicol-florfenicol resistance gene in Staphylococcus sciuri.

The 16.5-kbp plasmid pSCFS1 from Staphylococcus sciuri mediated combined resistance to chloramphenicol and florfenicol. The gene responsible for this resistance property, cfr, was cloned and sequenced. The amino acid sequence of the Cfr protein revealed no homology to known acetyltransferases or efflux proteins involved in chloramphenicol and/or florfenicol resistance or to other proteins whose functions are known.

Amino Acid Sequence↗