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Biomedical subjects

J Kraus

Publications and source records attributed to J Kraus.

At least 37 records · Page 2Linked to original sources
PubMed2003

Selective posterior rhizotomy in the treatment of cerebral palsy, first experience in Czech Republic.

BACKGROUND: Selective posterior rhizotomy (SPR) is a surgical treatment of spasticity in patients with cerebral palsy (CP). STARTING POINT: We present the first experience with SPR in Czech Republic. MATERIAL AND METHODS: 14 patients with severe spasticity were indicated for SPR during the period of 2 years (2001-2002). The indication criteria were severe spasticity with clonus, more or less symmetric impairment of lower extremities and increased H/M ratio in preoperative electromyography. SPR was performed in 13 cases, in one patient only the revision and intradural neurolysis of caudal roots was done. In all patients we used osteoplastic laminotomy L2-S1. The intraoperative EMG monitoring with selection of rootlets with abnormal response was performed. Preoperative and postoperative number of spasms, passive range of joint movements, Ashworth scale, Peacock grade and level of functional independence were assessed. The comparison of H/M ratio on EMG before and after surgery was performed. RESULTS: An evident improvement in all tested parameters was noted. The per-operative course in all cases was uneventful. Till now, no persistent complications have been observed. CONCLUSION: SPR improves functional ability in a selected group of CP patients. Our findings regarding clinical outcomes are in agreement with those of other authors. In our experience the extrapyramidal symptoms may not be an absolute contraindication of SPR. (Tab. 5, Fig. 3, Ref. 10.).

Adolescent↗
PubMed2002

Cell surface bound and soluble adhesion molecules in CSF and blood in multiple sclerosis: correlation with MRI-measures of subclinical disease severity and activity.

BACKGROUND: The expression of soluble cell adhesion molecules (AM) in cerebrospinal fluid (CSF) and blood and their significance as measures of disease activity has been extensively studied in patients with multiple sclerosis (MS). In previous studies, we found that cell surface bound AM on mononuclear cells (MNC) in CSF and blood might be useful markers of clinical disease activity in MS patients. OBJECTIVE: To analyze the correlation of cell surface bound and soluble AM in CSF and blood with magnetic resonance imaging (MRI) markers of subclinical disease severity and activity in patients with MS. METHODS: Expression levels of cell surface bound AM on peripheral blood and CSF MNC were determined by flow cytometry analysis in 77 (CSF: 33) MS patients. Concentration levels of the soluble forms of AM were measured by enzyme-linked immunosorbent assay (ELISA). In corresponding cerebral gadolinium (Gd)-enhanced MRI scans, we determined both measures of subclinical disease severity and subclinical disease activity. RESULTS: The expression levels of cell surface bound AM in peripheral blood correlated inversely with parameters for subclinical disease severity and activity on cerebral MRI scans as well as with the disease duration. Furthermore, we found significant correlations between serum levels of soluble AM and patient age but not with disease duration. CONCLUSIONS: Our results suggest that subclinical disease progression may be associated with a decrease of the expression of cell surface bound AM on peripheral blood MNC. This might be a result of activated MNC migration into the CNS.

Adult↗
PubMed2002

Serum cytokine levels do not correlate with disease activity and severity assessed by brain MRI in multiple sclerosis.

OBJECTIVE: Chronic and acute dysregulation of the cytokine network has been described in multiple sclerosis (MS). Inflammatory lesions in the central nervous system of MS patients can be assessed by brain magnetic resonance imaging (MRI). This study has been performed to investigate whether changes of cytokines correlate with morphological changes as determined by MRI. MATERIALS AND METHODS: We included 46 patients with relapsing-remitting MS in the study. The serum concentrations of tumor necrosis factor-beta (TNF-beta), TNF receptor-1 (TNFR-1; 55 kDa) and TNFR-2 (75 kDa), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were measured by enzyme linked immunosorbent assay in all patients. Each parameter was correlated with clinical findings and brain MRI parameters. We measured both the number (lesion load) and cumulated area (disease burden) of all lesions on brain MRI. In addition, the number and cumulated area of those lesions showing signs of activity [Gadolinium (Gd)-enhancement, perifocal edema] were determined. RESULTS: A non-significant trend (P < 0.05) was found only for the correlation of serum IFN-gamma levels and the number of active MRI lesions showing both Gd-enhancement and perifocal edema in the subgroup of patients (n=21) with active lesions. When corrected for multiple comparisons, this correlation was not significant anymore, as it was above the corrected P-value of 0.001. We could not observe any further correlation of cytokine levels and MRI parameters. However, TNF-beta serum levels were significantly (P < 0.05) elevated in the patient subgroups with higher number of lesions and disease burden, respectively. CONCLUSION: Our data show that the determination of serum levels of the investigated cytokines and cytokine receptors is not useful as a tool to determine subclinical disease activity and severity as assessed by brain MRI.

Adult↗
PubMed2002

Disturbance in the serum IgG subclass distribution in patients with anti-Hu positive paraneoplastic neurological syndromes.

Autoantibodies in patients with paraneoplastic neurological syndromes (PNS) have been reported to be predominantly IgG1 and IgG3 isotypes. However, no data are available about the IgG subclass distribution of the total serum IgG in these patients. Therefore, we investigated the IgG subclass distribution (given as percentage of total IgG) in 15 anti-Hu positive PNS patients, 15 patients with small cell lung cancer (SCLC) without PNS and 23 healthy controls using a commercial enzyme-linked immunosorbant assay test. Although IgG1 (and to a lower extent IgG3) are the predominant subclasses of the anti-Hu antibodies, PNS and SCLC showed a significant decrease in IgG1 and a concomitant increase in IgG2 compared with healthy controls (P < 0.05, respectively). In contrast, only SCLC patients, but not PNS patients, had higher IgG3 and IgG4 values compared with controls (P < 0.05, respectively). There was no correlation between IgG subclass levels and the titre or the predominant isotype of the antineuronal antibodies. PNS patients with autonomic disturbances had lower IgG4 levels than PNS patients without autonomic disturbances (P < 0.05). Our study demonstrates a disturbance in the IgG subclass distribution in PNS patients which is partly different from SCLC patients. The isotype regulation of the anti-Hu antibody seems to be independent from this phenomenon.

Autoantibodies↗
PubMed2002

Contrasting effects of long-term treatment with IFN-gamma in endothelial cells: increase in IL-6 secretion versus decrease in IL-8 secretion, NF-kappa B, and AP-1 activation.

The benefit of neutrophil exclusion from type 1 T helper cell (TH1) inflammatory processes was demonstrated in clinical studies. Increased recruitment of lymphocytes and monocytes to endothelium and impaired recruitment of polymorphonuclear neutrophils (PMNs) following interferon-gamma (IFN-gamma) treatment were described. The present study demonstrates that a 24 h treatment with IFN-gamma increases interleukin (IL)-6 release but reduces IL-8 secretion of both untreated and of tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells (ECs), favoring the attraction of lymphocytes but not of neutrophils. Alteration of cytokine release was accompanied by reduced basal and TNF-alpha-stimulated nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) activity. However, IFN-gamma application neither altered gene expression of both TNF-alpha receptors (p55 and p75) nor cellular density of TNF-alpha receptor-2 (p75). Therefore, immune-modulatory action of IFN-gamma seems to be mediated by signal transduction molecules.

Antigens, CD↗
PubMed2002

Monosomy 1p36--a recently delineated, clinically recognizable syndrome.

Monosomy 1p36 is a recently delineated contiguous gene syndrome, which is now considered to be one of the most common subtelomeric microdeletion syndromes. We report four unrelated patients with subtle deletions within 1p36 confirmed by high resolution karyotyping and FISH. All exhibited severe psychomotor retardation. Microcephaly, seizures, and visual impairment occurred in three subjects. Results of a first routine karyotyping were unrevealing in three probands. The diagnosis was primarily suggested on the basis of a distinct pattern of facial anomalies in all except the first case. This report illustrates that monosomy 1p36 may be recognized clinically, at least in some patients, whereas the diagnosis is easily missed on routine karyotype.

Child↗
PubMed2001

[Lysosomal sphingomyelinase deficiency: spectrum of phenotypes in Czech and Slovak patients].

BACKGROUND: We present a series of 25 patients (from 21 families) with deficiency of lysosomal sphingomyelinase (acid sphingomyelinase, ASM), diagnosed during the last 30 years. METHODS AND RESULTS: Diagnosis was established by finding specific sphingomyelin storage pattern in bone marrow histiocytes and in some bioptical and postmortem tissues (presence of sphingomyelin liquid crystals) and finally by proving ASM deficiency in white blood cells and in cultured fibroblasts. Range of clinical manifestations of our patients notably exceeded the the known main (A,B) phenotypes described so far. In the group of type A patients (clinically overt neurovisceral symptomatology) there was significant tendency to prolonged course. Classical fulminant course with death between 5 to 45 months of age was seen only in a subgroup of 5 patients. In other type A patients (n = 8) the course was prolonged attaining 5 years of age, the end of the first (8, and 9 years), second (14, 17 years), third (22 years), fourth (32 years) and fifth decades (41 years). Three of these patients (aged 5, 22 and 41 years) are living. The series of patients with dominant visceral involvement (n = 12) consisted of three phenotypically different subgroups. One with chronic purely visceral affection and prolonged course (n = 4) corresponding to the classical type B, the second with chronic course and largely subclinical neurological affection (n = 4) and the third with accelerated fatal visceral affection (death in age range 31 months-9 years) without (n = 1) or with clinically minor signs of brain damage (n = 3). CONCLUSIONS: Study of the presented series of ASM deficient patients disclosed remarkable phenotypical variability. Two main factors seem to be responsible. Variability in the storage intensity in the two main tissue compartments (neuronal and visceral), and the absence of proportionality in their affection in some instances. The described phenotype variability enlarges significantly the known spectrum of phenotypes in ASM deficiency.

Child↗
PubMed2001

Regulation of mu-opioid receptor gene transcription by interleukin-4 and influence of an allelic variation within a STAT6 transcription factor binding site.

Morphine and the endogenous opioid peptide beta-endorphin exert neuromodulatory as well as immunomodulatory effects, which are transduced by mu-opioid receptors. In this report we show that stimulation with interleukin-4 induces mu-opioid receptor transcripts in human primary blood cells (T cells and polymorphonuclear leukocytes), immune cell lines (Raji, U-937, and HMEC-1), and dendritic cells. In nonstimulated immune cells this gene is silent. In addition, mu receptor transcription is up-regulated by interleukin-4 in cultures of primary rat neurons. Transient transfection experiments in Raji and SH SY5Y neuronal cells with human and rat reporter gene constructs linked the interleukin-4 effect directly to cis-active mu receptor promoter elements located at nucleotide -997 on the human gene and nucleotide -727 on the rat gene. The interleukin-4 response elements function orientation independently. They bind STAT6 transcription factors as shown by electrophoretic mobility shift assays. In the human gene, a single nucleotide polymorphism within the interleukin-4 response element reduces the trans-activating potential of this element by 50%, which may affect the phenotype of persons carrying this variation. These findings provide a molecular basis for understanding bidirectional interactions between the opioid system and the immune system.

Alleles↗
PubMed2001

Murrastifoline-F: first total synthesis, atropo-enantiomer resolution, and stereoanalysis of an axially chiral N,C-coupled biaryl alkaloid.

The first total synthesis of the Murraya alkaloid murrastifoline-F (3), an unsymmetric, N,C-bonded heterobiarylic biscarbazole, is described. Starting from the likewise naturally occurring-but here synthetically prepared-"monomer" murrayafoline-A (6), lead tetraacetate-mediated oxidative non-phenolic biaryl coupling gives 3 as the main regioisomer. The existence of this natural product as a pair of stable atropo-enantiomers was demonstrated analytically through LC-CD investigations. Preparatively, the racemate resolution succeeded by O-demethylation, derivatization with Mosher's reagent, and chromatographic separation of the resulting diastereomers. The absolute configurations of the atropisomers were assigned by CD spectroscopy in combination with quantum chemical CD calculations at the stage of the alkaloid 3 and by ROESY experiments of the diastereomeric Mosher derivatives. In the root extract of the curry leaf plant Murraya koenigii (Rutaceae), murrastifoline-F (3) was found to exist as a 56:44 mixture in favor of the M-enantiomer, by LC-CD coupling.

Alkaloids↗
PubMed2001

Loss of locomotor sensitisation in response to morphine in D1 receptor deficient mice.

Mice lacking D1 receptors were used to study the role of these receptors in morphine-induced antinociception and locomotor sensitisation. In the hot-plate test D1 receptor deficient (-/-) and wild-type (+/+) mice showed similar reaction times under basal conditions. A single injection of 1.25 mg/kg and 2.5 mg/kg morphine resulted in a stronger antinociceptive response in D1 receptor deficient mice than in wild-type animals. Tolerance to the analgesic effect did not develop in both groups of animals when 12.5 mg/kg morphine was chronically applied twice daily for 13 days. There was no change in basal locomotor activity between saline-injected wild-type and D1 receptor deficient mice. After chronic treatment wild-type mice showed a continuous increase in locomotor activity, indicating the development of sensitisation. In contrast, a subchronic administration of morphine did not change locomotor activity in mutant mice. The lack of the development of locomotor sensitisation in D1 deficient mice was associated with reduced levels of immunoreactive mu opioid receptors in dorsal striatal patches as compared to wild-type mice. In contrast, no change in the distribution of immunoreactive mu receptors could be detected in areas related to pain pathways such as the spinal cord. Taken together, these results suggest an involvement of D1 receptors in morphine-induced locomotor activity and analgesia.

Analgesics, Opioid↗
PubMed2001

Uterine tumor resembling ovarian sex-cord tumor--a case report and review of the literature.

A uterine tumor resembling an ovarian sex-cord tumor (UTROSCT) is a very rare lesion with only 38 cases reported in the literature so far. Here, we show an additional case of a pure UTROSCT with a DNA stemline at 1c in a 49-year-old woman presenting with abnormal vaginal bleeding. Problems in differential diagnosis arise mainly due to the variable histological picture of UTROSCT. Immunohistochemically, these tumors express cytokeratin, epithelial membrane antigen, vimentin, and smooth muscle actin. Moreover, in some cases, CD99 and alpha-inhibin are detectable. Although 36% of UTROSCT have infiltrative margins, almost all of them behave benignly. It is thus questionable whether the same prognostic criteria apply for these tumors as for endometrial stromal sarcomas. However, in the so-called mixed UTROSCT, the endometrial stromal sarcoma component determines the outcome.

Antigens, Neoplasm↗
PubMed2001

Induction of sTNF-R1 and sTNF-R2 by interferon beta-1b in correlation with clinical and MRI activity.

OBJECTIVES: To investigate the influence of interferon (IFN) beta-1b on the serum levels of sTNF-R1, sTNF-R2 and TNF-beta in patients with multiple sclerosis (MS) in correlation with clinical and MRI activity. MATERIALS AND METHODS: Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-lb every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine levels were measured by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease of every patient. RESULTS: In the treatment group we found an obvious increase of sTNFR1 and sTNF-R2 (P < 0.001) and relatively stable serum levels of TNFbeta with no statistical significance (P = 0.56). In the control group, sTNF-R1 showed a significant decrease (P < 0.001) during the same observation period of 15 months. During the 15-month observation period, the MRI-responders group had significant larger mean AUC (area under the concentration-time curve) values of sTNF-R1 (P = 0.04) and sTNF-R2 (P = 0.01) when compared to the group of MRInonresponders. CONCLUSION: The present data suggest that IFN beta-1b induces the expression and shedding of TNF-R1 and TNF-R2. The magnitude of an increase of sTNF-Rs may be a marker for the effectiveness of treatment with IFN beta-1b.

Adjuvants, Immunologic↗
PubMed2001

Early predictors of mortality in penetrating compared with closed brain injury.

INTRODUCTION: Although brain injury incidence rates have been decreasing, the proportion of these injuries which are penetrating has been increasing. This study compares mortality amongst persons with penetrating and closed brain injuries and explores the relationship of early predictors of mortality. METHODS: The study included 795 moderately or severely brain injured individuals identified through the UCLA Brain Injury Research Centre. Logistic regression was used to predict mortality by GCS level and brain injury type, controlling for age, gender, and presence of multiple trauma. RESULTS: Of the 795 individuals, 110 had penetrating and 685 had closed brain injury. Case fatality rates were higher for penetrating than closed injuries for all GCS, gender, age, and cause of injury categories. When controlling for GCS level at admission, age, gender, and multiple trauma, those with penetrating injuries were 6.6 (95% CI = 3.9-11.1) times more likely to die. CONCLUSIONS: As the pool of information about survival and recovery from penetrating injuries grows, decisions regarding clinical care and prevention activities can be more appropriately focused.

Adolescent↗
PubMed2001

Cloning of genomic DNA of Lactococcus lactis that restores phage sensitivity to an unusual bacteriophage sk1-resistant mutant.

An unusual, spontaneous, phage sk1-resistant mutant (RMSK1/1) of Lactococcus lactis C2 apparently blocks phage DNA entry into the host. Although no visible plaques formed on RMSK1/1, this host propagated phage at a reduced efficiency. This was evident from center-of-infection experiments, which showed that 21% of infected RMSK1/1 formed plaques when plated on its phage-sensitive parental strain, C2. Moreover, viable cell counts 0 and 4 h after infection were not significantly different from those of an uninfected culture. Further characterization showed that phage adsorption was normal, but burst size was reduced fivefold and the latent period was increased from 28.5 to 36 min. RMSK1/1 was resistant to other, but not all, similar phages. Phage sensitivity was restored to RMSK1/1 by transformation with a cloned DNA fragment from a genomic library of a phage-sensitive strain. Characterization of the DNA that restored phage sensitivity revealed an open reading frame with similarity to sequences encoding lysozymes (beta-1,4-N-acetylmuramidase) and lysins from various bacteria, a fungus, and phages of Lactobacillus and Streptococcus and also revealed DNA homologous to noncoding sequences of temperate phage of L. lactis, DNA similar to a region of phage sk1, a gene with similarity to tRNA genes, a prophage attachment site, and open reading frames with similarities to sun and to sequences encoding phosphoprotein phosphatases and protein kinases. Mutational analyses of the cloned DNA showed that the region of homology with lactococcal temperate phage was responsible for restoring the phage-sensitive phenotype. The region of homology with DNA of lactococcal temperate phage was similar to DNA from a previously characterized lactococcal phage that suppresses an abortive infection mechanism of phage resistance. The region of homology with lactococcal temperate phage was deleted from a phage-sensitive strain, but the strain was not phage resistant. The results suggest that the cloned DNA with homology to lactococcal temperate phage was not mutated in the phage-resistant strain. The cloned DNA apparently suppressed the mechanism of resistance, and it may do so by mimicking a region of phage DNA that interacts with components of the resistance mechanism.

Amino Acid Sequence↗
PubMed2001

Prognostic value of soluble tumor necrosis factor receptors 1 and 2 in multiple sclerosis patients treated with interferon beta-1b.

The objective of this study was to investigate the effect of interferon (IFN) beta-1b on the serum levels of soluble tumor necrosis factor receptor 1 (sTNF-R1) and sTNF-R2 in patients with multiple sclerosis (MS) in correlation with clinical and magnetic resonance image (MRI) activity. Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-1b every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine receptor levels were assessed by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease. In the treatment group, the MRI responders had significantly larger mean values for the area under the concentration-time curve of sTNF-R1 (p = 0.04) and sTNF-R2 (p = 0.01) when compared to the MRI nonresponders during the 15-month observation period. With regard to an increase in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment, we observed a sensitivity of 33 and 58%, respectively, a specificity of 90 and 60%, respectively, and a positive predictive value of 80 and 64%, respectively, for MRI response during the 15-month observation period. A decrease in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment had a sensitivity of 40 and 20%, respectively, a specificity of 100 and 100%, respectively, and a positive predictive value of 100 and 100%, respectively, for further MRI nonresponse (during the 15-month observation period). The present data suggest that assessment of sTNF-Rs may contribute to the identification of subgroups of patients who are likely to respond better than others to treatment with IFN beta-1b. This could help to establish a cost-effective prescription pattern for this expensive treatment, which is of importance for the future management of patients with MS.

Adult↗
PubMed2000

Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer.

Although micrometastatic cancer cells in lymph nodes can be detected by monoclonal antibodies against epithelial or tumor-associated antigens, it remains unclear whether these cells are precursors of overt metastases or shedded tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characteristics of such micrometastases. In lymph nodes classified as tumor free by conventional histopathological staging, tumor cells were identified with monoclonal antibody Ber-EP4 in 89 of 126 patients (71%) with completely resected (R0) esophageal carcinomas. Multivariate survival analysis underlined the strong and independent prognostic significance of Ber-EP4-positive cells in "node-negative" (pN0) patients. To assess the biology of Ber-EP4-positive cells, we established tumor cell lines from an immunohistochemically positive lymph node and the autologous primary tumor. p53 mutational analysis and multiplex-fluorescence in situ hybridization revealed common aberrations shared between both cell lines, whereas an insertion of chromosome 13 material in the short arm of chromosome 1 was only observed in micrometastatic cells. The tumorigenicity and metastatic potential of both cell lines were demonstrated in severe combined immunodeficient mice. In conclusion, our data provide first direct evidence for the malignant potential of micrometastatic cancer cells.

Adenocarcinoma↗
PubMed2000

Nondynamic kinetic resolution of configurationally stable biaryl lactones by reduction with oxazaborolidine-activated borane: AM1 studies and experimental verification

The complete mechanistic course of the atroposelective ring opening of a lactone-bridged biaryl, dinaphth[2,1-c:1',2'-e]oxepin-3-(5H)-one (3), with a chiral oxazaborolidine-BH3 complex was calculated using the semiempirical AM1 method. The first hydride transfer to the activated carbonyl function of the adduct complexes was elaborated to be the selectivity-determining step in the postulated five-step mechanism. The calculated enantioselectivity is in good accordance with the experimental results, so that related calculations were performed on the atroposelective ring opening of a sterically strongly hindered and therefore also configurationally stable six-membered biaryl lactone, 1,3-di-tert-butyl-6H-benzo[b]naphtho[1,2-d]pyran-6-one (6f). These calculations predicted a highly (M)-selective reduction of 6f (kM/kP = 358 at -78 degrees C), which, after the smooth preparation of 6f by intramolecular biaryl coupling in high yields, was fully confirmed experimentally (kM/kP > 200 at -78 degrees C). Isolation of the intermediate hydroxy aldehyde (M)-14 at the beginning of the reaction with the same enantiomeric excess as found for the corresponding alcohol (M)-7f conclusively showed the first hydride transfer step to determine the selectivity of this process. The good agreement of computationally predicted and experimentally confirmed values proves the suitability of the AM1 method for mechanistic studies on even such complex reactions and opens a most efficient overall synthesis of sterically highly hindered biaryls, in excellent chemical (for the ring closure) and optical (for the ring cleavage) yields and for any desired axial configuration.

Journal Article↗