Biomedical subjects

A Kraus

Publications and source records attributed to A Kraus.

At least 19 recordsLinked to original sources

PubMed2006

Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: in vivo and in vitro analyses.

Six patients with renal failure due to multiple myeloma (MM) received simultaneous kidney and bone marrow transplantation (BMT) from HLA-identical sibling donors following nonmyeloablative conditioning, including cyclophosphamide (CP), peritransplant antithymocyte globulin and thymic irradiation. Cyclosporine (CyA) was given for approximately 2 months posttransplant, followed by donor leukocyte infusions. All six patients accepted their kidney grafts long-term. Three patients lost detectable chimerism but accepted their kidney grafts off immunosuppression for 1.3 to >7 years. One such patient had strong antidonor cytotoxic T lymphocyte (CTL) responses in association with marrow rejection. Two patients achieved full donor chimerism, but resumed immunosuppression to treat graft-versus-host disease. Only one patient experienced rejection following CyA withdrawal. He responded to immunosuppression, which was later successfully withdrawn. The rejection episode was associated with antidonor Th reactivity. Patients showed CTL unresponsiveness to cultured donor renal tubular epithelial cells. Initially recovering T cells were memory cells and were enriched for CD4+CD25+ cells. Three patients are in sustained complete remissions of MM, despite loss of chimerism in two. Combined kidney/BMT with nonmyeloablative conditioning can achieve renal allograft tolerance and excellent myeloma responses, even in the presence of donor marrow rejection and antidonor alloresponses in vitro.

Adult↗

PubMed2005

Gas chromatographic determination of benzene, toluene, ethylbenzene and xylenes using flame ionization detector in water samples with direct aqueous injection up to 250 microl.

A simple method of solventless extraction of volatile organic compounds (benzene, toluene, ethylbenzene and xylenes) from aqueous samples was developed. This method allows direct injection of large volume of water sample into a gas chromatograph using the sorption capacity of the sorbent Chromosorb P NAW applied directly in the injection port of gas chromatograph. The system prevent water penetration into a column, keep it adsorbed on its surface until the analytes are stripped into a column, and the residual water is purging using split flow. The limit of detection ranging from 0.6 for benzene to 1.1 microg l(-1) for o-xylene and limit of quantification ranging 2.0-3.6 microg l(-1) are lower that those reached by gas chromatography with flame ionization detection and direct aqueous injection before.

Adsorption↗

PubMed2002

Study by scanning tunneling microscopy of hydrogen adsorption and desorption on Si111 7 x 7 at room temperature and at high temperature.

An overview is given on the use of scanning tunneling microscopy (STM) for investigation of the adsorption of hydrogen on Si(111)7 x 7 both at room temperature and at elevated temperature to finally obtain a hydrogen-saturated surface of Si(111). The initial stages are characterized by high reactivity of Si adatoms of the 7 x 7 structure. After adsorption of hydrogen on the more reactive sites in the beginning of the adsorption experiments a regular pattern, which is different for room and elevated temperature, is observed for the less reactive sites. In agreement with previous work, local 1 x 1 periodicity of the rest atom layer and the presence of di- and trihydride clusters is observed for hydrogen-saturated surface. STM has also been used to characterize surfaces from which the hydrogen atoms have been removed by thermal desorption. Finally, tip-induced desorption by large positive sample-bias voltages and by increasing the tunneling current will be described.

Journal Article↗

PubMed2002

[Effect of personality factors and structure on the course of major depression].

The extent to which personality characteristics predict the course of severe depression has been controversially discussed. In a sample of 50 depressed inpatients, the significance of personality characteristics for the prediction of relapse was studied prospectively over 2 years. More than half of the patients studied suffered relapses within this period. Well-known predictors such as the number of previous episodes were confirmed. The personality characteristics studied showed different predictive effects at 1- and 2-year follow-up. Neurosis proved predictive of the 1-year course and outcome but not the 2-year course. In the 2nd year of follow-up, a melancholic personality structure was associated with favourable outcome. This personality type therefore seems to be more appropriate as a predictor of long-term outcome. Comparison with predictive factors described earlier showed that in this study, personality traits influence outcome independently and were not confused by other predictors. Implications for relapse prevention and psychotherapeutic management are discussed.

Adult↗

PubMed2002

Biochemical deficiency of pyridoxine does not affect interleukin-2 production of lymphocytes from patients with Sjögren's syndrome.

BACKGROUND: There is evidence that pyridoxine deficiency may alter the immune response. It is not known whether a deficiency of this vitamin is evident in subjects with primary Sjögren's syndrome (SS). OBJECTIVE: We studied whether subjects with primary SS showed a biochemical deficiency of pyridoxine, and if it is associated with abnormal production of interleukin-2 from lymphocytes stimulated in vitro with phytohemagglutinin (PHA). DESIGN: Two studies were conducted, (i) biochemical and nutritional assessments were performed in a cross-over study in subjects with primary SS, who were supplemented with 25 mg/day of pyridoxine or placebo for 3 months. After 1 month washout, they were supplemented for 3 months with placebo, (ii) patients with SS and matched controls received pyridoxine or placebo for 45 days, and a blood sample was obtained to study IL-2 production and expression in T-lymphocytes stimulated with PHA. RESULTS: Subjects with primary SS showed limited dietary intake of pyridoxine and biochemical deficiency of this vitamin assessed through the activation coefficient of the erythrocyte aspartate aminotransferase. The biochemical deficiency did not affect production nor mRNA expression of IL-2 from T-lymphocytes stimulated in vitro with PHA compared with the control group. Supplementation of subjects with primary SS with 25 mg/day with pyridoxine for 45 days did not produce any significant change as compared to those patients supplemented with placebo. CONCLUSIONS: Subjects with primary SS showed biochemical deficiency of pyridoxine, possibly due to limited intake of this vitamin which was corrected by supplementation with pyridoxine. However, IL-2 production and mRNA expression from stimulated lymphocytes were unaffected by supplementation, probably because the deficiency was not severe enough to affect the immune system. SPONSORSHIP: This work was supported by the National Council of Science and Technology (CONACYT), Mexico, grant no. 212226-5-0902PM.

Adult↗

PubMed2002

The wafer test: a semi-quantitative test to screen for xerostomia.

OBJECTIVE: To develop a screening test for xerostomia. METHODS: A cross-sectional study was conducted among 152 healthy subjects aged <20-60 yr, 30 patients with primary Sjögren's syndrome and 60 patients with other connective tissue diseases, sampled randomly. A validated screening questionnaire for sicca syndrome and the Schirmer-1 and wafer tests were carried out in all subjects. In addition, non-stimulated whole salivary flow was measured in a random sample of 113 participants. The main outcome was the time of dissolution of the wafer. RESULTS: Time of dissolution of the wafer was 2.8+/-2.1 min in the healthy group, 3.3+/-1.5 min in the connective tissue diseases group, and 9.2+/-3.9 min in the primary Sjögren's syndrome group (P<0.001). The correlation coefficient between the wafer test and non-stimulated whole salivary flow was -0.60 [95% confidence interval (CI) -0.47, -0.71]. A cut-off value of 4 min ('wafer 4') showed sensitivity of 92.9%, specificity of 71.7%, a positive predictive value of 31.7%, a negative predictive value of 98.6%, accuracy of 74.3%, an ROC (receiver operating curve) value of 82.3 and a likelihood ratio of 3.3 (95% CI 2.3, 4.6) for xerostomia. The proportion of patients with wafer 4 was 8% in the healthy group, 23% in the connective tissue diseases group and 93% in the primary Sjögren's syndrome group (P<0.001). Wafer 4 was a significant predictor of xerostomia after controlling for age, gender, temperature and relative humidity. CONCLUSION: The wafer test is valid and reliable for identifying subjects with xerostomia.

Adult↗

PubMed2001

Immunonutrition--supplementary amino acids and fatty acids ameliorate immune deficiency in critically ill patients.

BACKGROUND: Immunonutrition with omega-3 fatty acids and the "conditionally essential" amino acids arginine, glutamine, cysteine, and taurine can enhance the immune response in critically ill patients. This is due to the immunomodulating properties of these nutrients. Immunonutrition is especially important when a patient's immune response is compromised, as is the case post-operatively or after trauma. Immune deficiency is severely aggravated in sepsis and the systemic inflammatory response syndrome (SIRS). The resulting metabolic stress is characterized by glycolysis, lipolysis, and proteolysis, which may escalate to an hypercatabolic response or "autocannabilism." Catabolic metabolism results in insufficiency of both specific and unspecific immunocompetent cells. CONCLUSIONS: Immunonutrition should be started early in such patients for an optimal beneficial effect, preferably via the enteral route. It should include medium chain and long chain triglycerides, polyunsaturated omega-3 and omega-6 fatty acids (in the ratio 1:2), olive oil, and conventional amino acid preparations supplemented with the conditionally essential amino acids arginine, glutamine, cysteine, and taurine.

Adjuvants, Immunologic↗

PubMed2001

Axl receptor tyrosine kinase expression in human lung cancer cell lines correlates with cellular adhesion.

Axl is a receptor tyrosine kinase (RTK) with oncogenic potential and transforming activity. Since Axl bears structural similarities to cell adhesion molecules such as neural cell adhesion molecule (NCAM) (FNIII domains), it is thought that Axl might play a role in adhesion. In this study, we have analysed the expression of the Axl protein and its ligand, Gas6, in human lung cancer cell lines of different histological origin. Axl expression occurred in approximately 60% of non-small cell lung cancer (NSCLC) cell lines, which grow adherently, and in normal bronchial epithelial cells (NHBE), but not in cell lines of small cell lung cancer origin (SCLC), which grow in suspension. A number of SCLC sublines, which could be selected spontaneously or after oncogene transfection for adherent growth, all expressed Axl protein. Overexpression of Axl per se, however, did not induce any change in the adhesion phenotype. All Axl-expressing cell lines demonstrated a membrane-bound 140 kD form, as well as a soluble 85 kD form, detectable in supernatant, of Axl-RTK. Expression of the Axl ligand Gas6 was detected in approximately 80% of all cell lines investigated. We conclude from these data that loss of Axl expression is a feature of SCLC tumour cells. Axl expression appears to be a consequence of cellular adhesion and possibly influences differentiation in human lung cancers.

Blotting, Western↗

PubMed2000

The Akt/protein kinase B-dependent anti-apoptotic pathway and the mitogen-activated protein kinase cascade are alternatively activated in human glioblastoma multiforme.

We investigated the activation of two important signal transduction pathways in human glioblastoma cells and found a constitutive phosphorylation of either Akt or mitogen-activated protein kinase (MAPK) under serum free conditions. In all but one cell line Wortmannin-sensitive activation of Akt could be attributed to the loss of functional PTEN protein. All cell lines with Akt activation exhibited only weak phosphorylation of the MAPK signal pathway, whereas those without constitutive Akt activation demonstrated high levels of phosphorylated MAPK under serum free conditions. Our data might indicate the presence of two functional subtypes of glioblastoma multiforme, since Akt and MAPK are involved in cellular survival and proliferation signalling, respectively.

Apoptosis↗

PubMed2000

Differential frequencies of p16(INK4a) promoter hypermethylation, p53 mutation, and K-ras mutation in exfoliative material mark the development of lung cancer in symptomatic chronic smokers.

PURPOSE: The aim of this study was to investigate the frequency of three (epi)genetic alterations (p53 and K-ras mutations and p16(INK4a) promoter hypermethylation) in symptomatic chronic smokers compared with patients with lung cancer and to evaluate the use of exfoliative material for such analyses. PATIENTS AND METHODS: Fifty-one patients with histologically confirmed lung cancer and 25 chronic smokers (> 20 pack-years) were investigated for mutations in the K-ras (codon 12) and p53 (codons 248, 249, and 273) genes and for allelic hypermethylation of the p16(INK4a) gene. DNA was isolated from sputum and bilateral bronchial lavage, and brushings were taken at bronchoscopy. RESULTS: Forty-one genetic lesions were detected within exfoliative material from the group of 51 patients with lung cancer and 10 lesions in the chronic smoker group. K-ras mutations occurred exclusively in the lung cancer group, whereas p53 mutations and p16(INK4a) promoter hypermethylation were also found in chronic smokers. Three of eight chronic smokers who harbored an (epi)genetic alteration were subsequently diagnosed with lung cancer. Analysis of sputum yielded information equivalent to that of samples obtained during bronchoscopy. CONCLUSION: p16(INK4a) promoter hypermethylation and p53 mutations can occur in chronic smokers before any clinical evidence of neoplasia and may be indicative of an increased risk of developing lung cancer or of early disease. K-ras mutations occur exclusively in the presence of clinically detectable neoplastic transformation. Molecular analysis of sputum for such markers may provide an effective means of screening chronic smokers to enable earlier detection and therapeutic intervention of lung cancer.

Aged↗

PubMed2000

Fibre-type specific modification of the activity and regulation of skeletal muscle pyruvate dehydrogenase kinase (PDK) by prolonged starvation and refeeding is associated with targeted regulation of PDK isoenzyme 4 expression.

Using immunoblot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoenzymes PDK2 and PDK4, we demonstrate selective changes in PDK isoenzyme expression in slow-twitch versus fast-twitch skeletal muscle types in response to prolonged (48 h) starvation and refeeding after starvation. Starvation increased PDK activity in both slow-twitch (soleus) and fast-twitch (anterior tibialis) skeletal muscle and was associated with loss of sensitivity of PDK to inhibition by pyruvate, with a greater effect in anterior tibialis. Starvation significantly increased PDK4 protein expression in both soleus and anterior tibialis, with a greater response in anterior tibialis. Starvation did not effect PDK2 protein expression in soleus, but modestly increased PDK2 expression in anterior tibialis. Refeeding for 4 h partially reversed the effect of 48-h starvation on PDK activity and PDK4 expression in both soleus and anterior tibialis, but the response was more marked in soleus than in anterior tibialis. Pyruvate sensitivity of PDK activity was also partially restored by refeeding, again with the greater response in soleus. It is concluded that targeted regulation of PDK4 isoenzyme expression in skeletal muscle in response to starvation and refeeding underlies the modulation of the regulatory characteristics of PDK in vivo. We propose that switching from a pyruvate-sensitive to a pyruvate-insensitive PDK isoenzyme in starvation (a) maintains a sufficiently high pyruvate concentration to ensure that the glucose-->alanine-->glucose cycle is not impaired, and (b) may 'spare' pyruvate for anaplerotic entry into the tricarboxylic acid cycle to support the entry of acetyl-CoA derived from fatty acid (FA) oxidation into the tricarboxylic acid cycle. We further speculate that FA oxidation by skeletal muscle is both forced and facilitated by upregulation of PDK4, which is perceived as an essential component of the operation of the glucose-FA cycle in starvation.

Animals↗

PubMed2000

Targeted upregulation of pyruvate dehydrogenase kinase (PDK)-4 in slow-twitch skeletal muscle underlies the stable modification of the regulatory characteristics of PDK induced by high-fat feeding.

In using Western blot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoforms PDK2 and PDK4, this study demonstrates selective PDK isoform switching in specific skeletal muscle types in response to high-fat feeding that is associated with altered regulation of PDK activity by pyruvate. The administration of a diet high in saturated fats led to stable (approximately 2-fold) increases in PDK activities in both a typical slow-twitch (soleus [SOL]) muscle and a typical fast-twitch (anterior tibialis [AT]) muscle. Western blot analysis revealed that high-fat feeding significantly increased (approximately 2-fold; P < 0.001) PDK4 protein expression in SOL, with a modest (1.3-fold) increase in PDK2 protein expression. The relative increase in PDK4 protein expression in SOL was associated with a 7.6-fold increase in the pyruvate concentration that was required to elicit a 50% active pyruvate dehydrogenase complex, which indicates a marked decrease in the sensitivity of PDK to inhibition by pyruvate. In AT muscle, high-fat feeding elicited comparable (1.5- to 1.7-fold) increases (P < 0.05) in PDK4 and PDK2 protein expression. Loss of sensitivity of PDK to inhibition by pyruvate was less marked. The data suggest that a positive correlation exists between increases in PDK4 expression and the propensity with which muscles use lipid-derived fuels as respiratory substrates rather than with the degree of insulin resistance induced in skeletal muscles by high-fat feeding. In conclusion, high-fat feeding leads to selective upregulation of PDK4 expression in slow-twitch muscle in response to high-fat feeding in vivo, which is associated with a pronounced loss of sensitivity of PDK activity to acute inhibition by pyruvate. Thus, increased PDK4 expression may underlie the stable modification of the regulatory characteristics of PDK observed in slow-twitch muscle in response to high-fat feeding.

Animals↗

PubMed2000

Aberrant p21 regulation in radioresistant primary glioblastoma multiforme cells bearing wild-type p53.

OBJECT: A clearer understanding of the cellular mechanisms involved in the response to ionizing radiation is pivotal to the development of new therapeutic strategies for glioblastoma multiforme (GBM). To gain insight into dynamic functional aspects of cell cycle regulation and the control of apoptosis in GBMs, the authors investigated the molecular changes induced by ionizing radiation in genetically characterized primary GBMs in vitro compared with secondary GBMs, Grades II and III gliomas, and three GBM cell lines. METHODS: Irradiation of primary GBMs bearing wild-type (wt) p53 invariably fails to invoke the G, checkpoint and apoptosis in vitro. In approximately half of these primary GBMs a defect lies at or above the level of p53 because transcriptional activation of p21 and bax after irradiation does not occur. The failure of a p21 response to irradiation is invariably accompanied by overexpression of p21 mRNA under nonirradiated conditions. In all remaining primary GBMs transcriptional activation of p21 after irradiation does occur, suggesting that a defect downstream from p21 prevents G, arrest. CONCLUSIONS: These results show that the G, checkpoint and the p53 pathway are dysfunctional in primary GBMs in vitro, despite the presence of an intact p53 gene. The data also suggest that primary GBMs may be divided into two categories on the basis of their p21 response to irradiation.

Adult↗

PubMed2000

[Cross cultural psychometric comparison of major depression in Chile and Germany].

BACKGROUND: Depressive symptoms and personality features of patients with mood disorders are supposed to have a strong variability in cross cultural studies. The clinical profile, the outcome and the treatment response seem to be different across the world. AIM: To investigate the differences and similarities of major depressive disorders in Chile and Germany. MATERIAL AND METHODS: Sixty seven Chilean and German depressive inpatients, without comorbidity on axis I or II were studied. Diagnosis of depression was based on DSM IV and ICD 10 criteria for major depression. Symptomatology was assessed using the self reporting questionnaire (SRQ-20), the Symptom checklist-90-revisited (SCL 90-R), the Beck inventory for Depression (BDI), and the Hamilton scale for depression (HAM-D). Personality was assessed with the Munich Personality Scale. RESULTS: Only the SRQ-20 shows significantly higher tendency towards depression among Chilean patients. At the personality level, Chileans exhibited higher scores in extroversion, neuroticism, esoteric and isolating tendencies. CONCLUSIONS: These results help to understand differences and similarities between depressive syndromes across cultures. They suggest that the relation between symptomatology, some personality traits and severe major depression has little variability across cultures.

Adult↗

PubMed1999

Expression of alternatively spliced mdm2 transcripts correlates with stabilized wild-type p53 protein in human glioblastoma cells.

A puzzling finding in various human tumors, including glioblastoma multiforme (GBM), is the stabilization of wild-type (wt) p53 protein. The biological significance of this phenomenon and the mechanism by which it occurs are unexplained. Recent reports have revealed that mdm2 exerts its negative regulation on the p53 signal by directly binding p53 protein and thereby instigating its proteasomal degradation. mdm2 has been shown to exist in alternatively spliced forms in human ovarian and bladder carcinomas, and recently in GBM, with loss or disruption of its p53 binding domain. Here we report that alternatively spliced transcripts of mdm2 are present in 7 of 16 human GBM primary cell cultures and in the established GBM cell lines LN 229 and LN 18. Sequencing demonstrated loss of the amino terminal p53 binding domain in these alternatively spliced mdm2 transcripts, and an out-of-frame splicing in the majority of cases. A significant correlation between the presence of mdm2 splice variants and increased expression of wt p53 protein was observed. Furthermore, in the presence of an mdm2 splice variant, wt p53 stabilization occurred despite coincident MDM2 amplification. Our findings suggest that wt p53 protein stabilization may arise as a consequence of alternative splicing of mdm2. Such a mechanism might account for wt p53 protein accumulation in GBM cells, even in the presence of MDM2 gene amplification.

Binding Sites↗

PubMed1999

Molecular genetic characterisation of intracerebrally transplanted brain tumours.

The aim of the present study was the characterisation of genetic alterations in two different experimental gliomas, induced in rats from the inbred strain BDIX by transplacental ethylnitrosourea with subsequent serial transplantation. The genes investigated have been shown previously to be altered during human glial tumour progression and include the gene for the epidermal growth factor receptor (EGFR), the genes for the cell cycle regulators cyclin dependent kinase 4 (CDK4), cyclinD1 (cycD1), the p16 gene (MTS1/INK4) and the retinoblastoma gene (RB). Using a semi-quantitative PCR-based screening method no gross alterations could be detected in these genes, demonstrating that nitrosourea-induced glial tumours of rats do not harbour those genetic changes which typically arise in human malignant gliomas. Thus, the use of this tumour model for gene therapy trials is questionable.

Animals↗

PubMed1999

Detection of epithelial cells in dried blood stains by reverse transcriptase-polymerase chain reaction.

The identification of menstrual blood stains can be improved by detection of messenger ribonucleic acid (mRNA) specific for epithelial (endometrial) cells. RNA molecules, however, are believed to be unstable and require careful sample processing. In this study, we have investigated the extraction of RNA suitable for reverse transcriptase-polymerase chain reaction (RT-PCR) from dried blood stains stored for up to six months. With a modified RNA isolation protocol, it was possible to obtain RNA from dried blood stains with at least 5 x 10(2) leukocytes. In an additional experiment, we evaluated the RNA isolation from mixed stains composed of leukocytes and T47D cells, a breast cancer-derived cell line with epithelial origin. Detection of 10(2) T47D cells in a total number of 10(5) leukocytes was possible by amplification of cytokeratin 19 mRNA and progesterone receptor-mRNA specific for hormonally regulated epithelial cells. In both experiments amplification results were not dependent on storage time with similar data from one day to six months. Furthermore, it was possible to identify dried menstrual blood samples by showing the presence of mRNA specific for epithelial cells. These results demonstrate for the first time, that RNA suitable for RT-PCR, can be isolated from forensic specimens stored up to at least six months, and that a small number of epithelial (endometrial) cells can be identified in dried blood specimens. Using this method, it will be possible to identify the origin of small and partially degraded blood samples which can be especially useful in forensic evaluation of cases with sexual offense.

Base Sequence↗

PubMed1998

Treatment of malnutrition with 1.1% amino acid peritoneal dialysis solution: results of a multicenter outpatient study.

A peritoneal dialysis (PD) solution containing 1.1% amino acids as the osmotic agent was evaluated in a 3-month randomized, prospective, open-label study in malnourished PD patients. Patients in the treatment group (DAA) received one or two exchanges daily with the amino acid solution, depending on tolerance, in place of glucose solutions. Controls (DD) received their usual therapy with glucose dialysate. Fifty-four DAA and 51 DD patients completed the study. In DAA, but not in DD patients, there was a significant increase at month 3 in serum insulin-like growth factor-1 (IGF-1) levels and significant decreases in serum potassium (all 3 months) and inorganic phosphorus levels (months 1 and 3), indicating a general anabolic response. Prealbumin and transferrin levels were significantly increased in DAA but not in DD patients at month 1, but the groups did not differ at months 2 and 3. In patients with baseline albumin levels less than 3.5 g/dL (bromcresol green [BCG] method), DAA patients showed increases in albumin, transferrin (months 1 and 2), and prealbumin levels (all 3 months) relative to baseline values, whereas these serum protein levels were unchanged in DD patients, although the changes from baseline did not differ between groups. In this subgroup, midarm muscle circumference (MAMC) did not change in DD or DAA patients. In patients with baseline albumin levels of 3.5 g/dL or greater, DD patients had decreases in albumin and total protein levels at all 3 months and in prealbumin levels at months 1 and 2, relative to baseline. In DAA patients, there were fewer changes in serum proteins. MAMC increased significantly from baseline in DAA but not in DD patients, although changes from baseline did not differ between DAA and DD groups. DAA patients showed no changes in peritoneal membrane transport characteristics. The results indicate that treatment with one or two exchanges daily of this amino acid-based PD solution is safe and provides nutritional benefit for malnourished PD patients.

Amino Acids↗