PubMed Health⌕ Search

Biomedical subjects

J Mester

Publications and source records attributed to J Mester.

At least 19 recordsLinked to original sources

Molecular characterization of rifampin-resistant isolates of Mycobacterium tuberculosis from Hungary by DNA sequencing and the line probe assay.

Two regions of rpoB associated with rifampin resistance were sequenced in 29 rifampin-resistant (determined by the proportion method) isolates of Mycobacterium tuberculosis obtained from patients from three counties in Hungary. Of the 29 resistant strains, 27 had a mutation in either the 81-bp region (26 strains) or the N-terminal region (1 strain), while the other 2 strains had no mutations in either region. The locations and frequencies of the mutations differed from those previously reported. The most common mutation in this study, D516V, was found in 38% of the Hungarian strains, a frequency 2 to 10 times higher than that found in studies from other countries. These same 29 isolates were also evaluated with the Inno-LiPA Rif. TB test (LiPA), a reverse hybridization assay for the rapid detection of rifampin resistance. Although LiPA detected the presence of an rpoB mutation in 26 of the resistant isolates, the type of mutation could not be determined in 4 isolates because the mutations present were not among those included on the LiPA strip. In addition, a silent mutation in one of the rifampin-susceptible control strains was interpreted as rifampin resistant by LiPA. These findings demonstrate the importance of validating this rapid molecular test by comparison with DNA sequence results in each geographic location before incorporating the test into routine diagnostic work.

Antitubercular Agents↗

Insulin-like growth factor binding proteins and mitogenic activity of partially fractionated sheep amniotic fluid.

Amniotic fluid collected from ewes on various days of gestation was examined for the presence of insulin-like growth factor (IGF) binding proteins. IGF-binding proteins with a molecular mass of 40-45 kDa appeared at day 41 of gestation. The level of these major IGF-binding proteins increased during pregnancy and reached a maximum at day 106. Smaller IGF-binding molecules with an approximate molecular mass of 35 kDa and 25 kDa appeared at day 90, also reaching a concentration peak at day 106. The mitogenic activity of sheep amniotic fluid after chromatography on Sephadex G-50 was separated into two peaks. The peak having lower molecular mass corresponded to an elution profile of 125I-IGF-I. The first peak, having higher molecular mass, was eluted immediately after the void volume of column. Electrophoresis and ligand blotting showed that proteins in the first peak had similar properties as IGF-binding proteins.

3T3 Cells↗

Mitogenic activity of high molecular weight forms of insulin-like growth factor-II in amniotic fluid.

Amniotic fluid (AF) collected from ewes and goats at mid gestation displayed mitogenic activity in mouse fibroblasts. Upon fractionation of this material by size exclusion chromatography, the mitogenic activity was resolved into two peaks, whose activity was inhibited by an anti-IGF type 1 receptor blocking antibody. One of the peaks contained IGF-I and IGF-II (mature form), whereas the other contained high M(r) precursor forms of IGF-II. The presence in this latter fraction of IGF-binding proteins (IGFBP) suggests that the AF IGFBPs do not efficiently inhibit the mitogenic activity of the high M(r) forms of IGF-II. In agreement with this conclusion, exogenous IGFBP-1 failed to affect this activity. Analysis of IGF-II in sheep AF showed that the AF concentrations of both forms of IGF-II increased dramatically from mid pregnancy until 106-120 days of gestation, and fell thereafter. The amniotic IGFBPs followed a similar evolution. High M(r) forms of IGF-II were also found in human AF, with a pattern of electrophoretic migration different from that of sheep. We suggest that the precursor forms of IGF-II may play an important role in foetal development.

Amniotic Fluid↗

B-ind1, a novel mediator of Rac1 signaling cloned from sodium butyrate-treated fibroblasts.

Sodium butyrate is a multifunctional agent known to inhibit cell proliferation and to induce differentiation by modulating transcription. We have performed differential display analysis to identify transcriptional targets of sodium butyrate in Balb/c BP-A31 mouse fibroblasts. A novel butyrate-induced transcript B-ind1 has been cloned by this approach. The human homologue of this transcript contains an open reading frame that codes for a protein of 370 amino acids without known functional motifs. In transfected cells, the B-ind1 protein has been found to potentiate different effects of the small GTPase Rac1, such as c-Jun N-terminal kinase activation and transcriptional activity of nuclear factor kappaB (NF-kappaB). In addition, we have demonstrated that B-ind1 forms complexes with the constitutively activated Rac1 protein. To investigate the role of B-ind1 in Rac1 signaling, we have constructed several deletion mutants of B-ind1 and tested their ability to affect the activation of NF-kappaB by Rac1. Interestingly, the fragment encoding the median region of human B-ind1 acted as a dominant-negative variant to block Rac1-mediated NF-kappaB activity. These data define B-ind1 as a novel component of Rac1-signaling pathways leading to the modulation of gene expression.

Animals↗

Performance evaluation of PET scanners: testing of geometric arc correction by off-centre uniformity measurement.

The aim of this study was to demonstrate the necessity of an off-centre uniformity measurement during performance evaluation and acceptance testing of a positron emission tomography (PET) system. To this end, the effect of different methods of geometric arc correction on image uniformity was considered. The arc correction routine of the system software of a particular PET scanner family was tested in computer simulations, phantom measurements and a patient study. Various methods of geometric arc correction--nearest neighbour interpolation, linear interpolation and cubic smoothing spline interpolation--were applied to the same data. Uniformity was evaluated both visually and quantitatively using intensity profiles and regions of interest. The arc correction routine of the PET scanner family produced significant ring artefacts and led to overestimation of tracer uptake by up to 15%. Since uniformity measurements are usually performed using a cylindrical phantom at the centre of the transverse field of view, these artefacts are not detected. In conclusion, the standards for performance evaluation of a PET scanner should be extended by inclusion of an off-centre uniformity measurement at the edge of the transverse field of view. On the basis of our comparison of different methods for geometric arc correction, we suppose that cubic smoothing spline interpolation might improve the relation between statistical noise reduction and spatial resolution as compared with conventional linear interpolation.

Artifacts↗

Training and overtraining markers in selected sport events.

PURPOSE: Varieties of symptoms are supposed to detect overtraining (OT). Besides the problems of diagnosis and analysis in elite athletes, a daily monitoring of training status takes place with measurement of the parameters serum urea (SU) and serum creatine kinase (CK); therefore, their meaningfulness will be examined, with special respect inter- and intra-individually. METHODS: Data were obtained from determinations during training from athletes in rowing and athletes of international level. RESULTS: For 6981 SU determinations (male, N = 717; female, N = 285), a slightly asymmetric normal distribution was found (male, 80%, 5-7 mmol x L(-1); female, 75%, 4-6 mmol x L(-1)). Values for women were approximately 1.5 mmol x L(-1) lower. Individual variability was enormous; there seems little point in setting fixed value as 8.3 mmol x L(-1) for men and 7.0 mmol x L(-1) for women as a critical limit for OT. CK has also been measured and evaluated in sports as an essential parameter for determination of muscular stress. Frequency distributions of CK in 2790 samples (male, N = 497; female, N = 350) presented an asymmetric normal distribution with distinct trend toward higher values being evident for the range between 100 and 250 U x L(-1). Conspicuously elevated values occurred in the ranges 250-350 U x L(-1) and 1000-2000 U x L(-1). Men's maximal values were 3000 U x L(-1) and 1150 U x L(-1) for women. Individual variability was enormous. Athletes with chronically low CK exhibited mainly low variability; those with chronically higher values exhibited considerable variability. CONCLUSIONS: Establishment of both parameters should be useful to determine individual baselines from a large number of samples. Determinations should be made at least every 3 d in standardized conditions. If a large increase is observed in combination with reduced exercise tolerance after a phase of exertion (2-4 d), then the possibility of a catabolic/metabolic activity or insufficient exercise tolerance becomes much more likely.

Biomarkers↗

Comparison of rate of development and rate of change for benign and malignant breast calcifications at the lumpectomy bed.

OBJECTIVE: The study purpose was to evaluate the rate of development and the rate of change for benign and malignant breast calcifications at the lumpectomy bed. MATERIALS AND METHODS: Retrospective review identified 53 new calcifications at the lumpectomy bed in patients with available mammograms and medical records. Breast Imaging Reporting and Data System (BI-RADS) categories were retrospectively assigned on the basis of initial prospective recommendation for yearly follow-up (category 2), 6-month follow-up (category 3), or biopsy (category 4 or 5). Outcomes were defined as benign for no recurrence at the lumpectomy bed on biopsy or follow-up and malignant if biopsy-proven at the lumpectomy bed. RESULTS: The median rate of development after lumpectomy was 23 months (range, 2-174 months) for benign and 39 months (range, 15-112 months) for malignant calcifications. Fifteen (28%) of 53 calcifications were classified as BI-RADS category 3. Twelve (80%) of 15 were downgraded to BI-RADS category 2 at a median follow-up of 6.5 months (range, 6-16 months); none represented recurrent disease. Three (20%) of 15 were upgraded to BI-RADS category 4 at the 6-month follow-up, one despite stability (benign) and two for increasing pleomorphism (malignant). Nine (17%) of 53 calcifications were classified as BI-RADS category 4 or 5; six (67%) of the nine were malignant and three (33%) were benign at biopsy. Twenty-nine (55%) of 53 calcifications were classified as BI-RADS category 2, none representing recurrent disease. CONCLUSION: Benign calcifications at the lumpectomy bed usually develop earlier than malignant calcifications, but the rate of development overlaps. Most calcifications initially placed in the probably benign category evolve quickly to more benign or more malignant morphology. Most calcifications heralding recurrence appear suspicious on first presentation.

Adult↗

FDG PET detection of unknown primary tumors.

UNLABELLED: The management of patients presenting with metastases of unknown primary origin remains a clinical challenge despite a large variety of imaging modalities. The aim of this study was to evaluate FDG PET in detecting the sites of primary cancer in these patients. METHODS: Fifty-three patients with metastatic cervical adenopathy (n = 44) or extracervical metastases (n = 9) of unknown primary origin were included after extensive but inconclusive conventional diagnostic work-up. Patients received 370 MBq FDG (10 mCi) intravenously, and whole-body images were acquired at 60 min after injection. Clinical, surgical, and histopathologic findings and complete correlative imaging were used to assess the results. RESULTS: In 27 of 53 patients FDG PET showed focal tracer accumulations corresponding to potential primary tumor sites located in the lungs (n = 12), the palatine tonsil (n = 5), the salivary glands (n = 2), the nasopharynx (n = 1), the oropharynx (n = 3), the maxillary sinus (n = 1), and the larynx (n = 1). Moreover, in 2 patients FDG PET revealed lesions suspected to be tumors in the breast and the ileocolonic area. In 20 (37.8%) of these 53 patients FDG PET was true-positive, identifying the primary tumor in the lungs (n = 10), the head and neck region (n = 8), the breast (n = 1), and the ileocolonic area (n = 1). In 6 of 27 patients FDG PET was false-positive, predominantly identifying suspicious areas in the palatine tonsil (n = 3). One patient denied further diagnostic work-up after PET; thus, positive PET could not be evaluated. In 26 of 53 patients PET did not reveal lesions suspected to be the primary. However, primary tumors were not found in these patients at clinical follow-up. CONCLUSION: FDG PET is a valuable diagnostic tool in patients with cancer of unknown primary because it imaged unknown primary tumors in about one third of all patients investigated. In addition, FDG PET assists in both guiding biopsies for histologic evaluation and selecting the appropriate treatment protocols for these patients.

Adult↗

Low-cost, small-animal shelf for simultaneously assessing several small animals with a whole-body PET scanner.

OBJECTIVE: The purpose of this work was to establish a low-cost device for simple positioning of several small animals within a whole-body PET scanner. METHODS: The device was designed as a stackable shelf for 3 x 3 animals, similar to a stackable shelf for wine bottles. It was constructed from ordinary PVC drain pipe and acrylic panes. RESULTS: The shelf simplified accurate and reproducible positioning of the animals and, therefore, supported automatic data processing. Deterioration of image quality by attenuation of photons within the shelf itself was rather small. CONCLUSION: The small-animal shelf is a useful, low-cost device for simultaneously assessing up to 9 small animals with a whole-body PET scanner.

Acrylic Resins↗

Estrogen induction of the cyclin D1 promoter: involvement of a cAMP response-like element.

Estrogens induce cell proliferation in target tissues by stimulating progression through the G(1) phase of the cell cycle. Induction of cyclin D1 expression is a critical feature of the mitogenic action of estrogen. We have determined a region between -96 and -29 in the cyclin D1 promoter that confers regulation by estrogens in the human mammary carcinoma cells MCF-7. This region encompasses a unique known transcription factor binding site with a sequence of a potential cAMP response element (CRE-D1). The induction is strictly hormone dependent and requires the DNA binding domain as well as both AF-1 and AF-2 domains of the estrogen receptor (ER) alpha. Destruction of the CRE-D1 motif caused complete loss of estrogen responsiveness. Both c-Jun and ATF-2 transactivated the cyclin D1 promoter in transient transfection experiments, and a clear additional increase was detected when ER was cotransfected with either c-Jun or with c-Jun and ATF-2 but not with ATF-2 alone. Furthermore, the expression of a dominant negative variant of c-Jun, TAM67, completely abolished the induction of the cyclin D1 promoter both in the absence and presence of ER. We show that ATF-2 homodimers and ATF-2/c-Jun heterodimers, but not c-Jun homodimers, were able to bind the CRE of the cyclin D1 promoter. To interpret these results, we propose a mechanism in which ATF-2/c-Jun heterodimers bind to the CRE-D1 element and mediate the activation of cyclin D1 promoter by the ER. This mechanism represents a pathway by which estrogens control the proliferation of target cells.

Activating Transcription Factor 2↗

Sodium butyrate induces G2 arrest in the human breast cancer cells MDA-MB-231 and renders them competent for DNA rereplication.

When exposed to sodium butyrate (NaBut), exponentially growing cells accumulate in G1 and G2 phases of the cell cycle. In the human breast cancer cell line MDA-MB-231, an arrest in G2 phase was observed when the cells were released from hydroxyurea block (G1/S interface) in the presence of NaBut. The inhibition of G2 progression was correlated with increased contents both of total p21(Waf1) and of p21(Waf1) associated with cyclin A and with an inhibition of cyclin A- and B1-associated histone H1 kinase activities measured in cell lysates, as well as with dephosphorylation of the RB protein. A decrease in the cell contents of cyclins A and B1 was also observed but this decrease was preceded by p21(Waf1) accumulation. When NaBut was removed from the culture medium of cells blocked in G2 phase, p21(Waf1) level decreased and, instead of proceeding to mitosis, these cells resumed a progression toward DNA rereplication. These results suggest that the induction of p21(Waf1) by NaBut leads to the inhibition of the sequential activation of cyclin A- and B1-dependent kinases in this cell line, resulting in the inhibition of G2 progression and rendering the cells competent for a new cell division cycle.

Breast Neoplasms↗

Salivary gland protection by amifostine in high-dose radioiodine therapy of differentiated thyroid cancer.

BACKGROUND: Salivary gland impairment following high-dose radioiodine treatment is a well-recognized side effect, in general caused by free radicals. Therefore, it seemed promising to evaluate the radioprotective effect of the radical scavenger amifostine in patients receiving high-dose radioiodine therapy. PATIENTS AND METHOD: Quantitative salivary gland scintigraphy using 100 to 120 MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid cancer prior to and 3 months after radioiodine treatment with 6 GBq I-131. Eight patients were treated with 500 mg/m2 amifostine prior to high-dose radioiodine treatment and compared retrospectively with 9 control patients. Xerostomia was graded according to WHO criteria. RESULTS: In 9 control patients high-dose radioiodine treatment significantly (p < 0.01) reduced Tc-99m-pertechnetate uptake by 35.4 +/- 22.0% and 31.7 +/- 21.1% in parotid and submandibular glands, respectively. Of these 9 patients, 3 exhibited xerostomia Grade I (WHO). In contrast, in 8 amifostine-treated patients, there was no significant (p = 0.878) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. CONCLUSION: Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be reduced significantly by amifostine. This may help to increase patients' quality of life in differentiated thyroid cancer.

Adult↗

Biological reaction to vibration--implications for sport.

In many situations of everyday life, vibration load occurs. Here whole body vibration in vehicles, such as boats, cars, helicopters and others as well as hand-transmitted vibration (motor saws etc.) can be named. As vibration is assumed liable to cause various threats to human health, a great number of studies in work science focussed on dose-effect relations and concepts for prevention. Although in many sports remarkable vibration load also occurs, there is very little research on the potential dangers and benefits of vibration stimuli, e.g. on whole body vibration and the implications for muscular activity and neuromuscular control in sport. In personal studies the damping behaviour and training effects under whole body vibration were investigated. Various research areas have been studied in order to approach the relevant topics: neuromuscular and posture control, energy metabolism in terms of oxygen uptake under whole body vibration and local concentration of phosphates by means of 31P-MRS. Furthermore the effects of a strength training under whole body vibration were analysed. The results underline that vibration is a neglected research topic in sport science from the preventive point of view as well as from the one focussing on the improvement of sport performance.

Energy Metabolism↗

[F-18 FDG PET for detection of occult primary tumor in patients with lymphatic metastases of the neck region].

BACKGROUND: The occult primary tumor remains an important diagnostic problem in patients with lymph node metastases despite a large variety of imaging modalities. Therefore, the aim of our study was to evaluate the impact of F-18-FDG-positron-emission-tomography (PET) in these patients. METHODS: The study group included a total of 28 patients aged 39 to 84 years with cervical lymph node metastases of a histologically confirmed squamous cell carcinoma (n = 24) or an undifferentiated carcinoma (n = 4). All patients received 370 MBq F-18-FDG intravenously, and whole-body images were acquired at 60 min p.i. with an ECAT EXACT 47 (921) (Siemens, CTI). All lesions were evaluated either by histology or by CT/MRI. RESULTS: In 12 patients PET did not reveal suspected tumorous lesions. In contrast in 16/28 patients PET showed focal tracer accumulations corresponding to potential primary tumor sites located in the lungs (n = 7), in the region of the tonsilla palatina (n = 5), in the submandibular gland (n = 1), in the nasopharynx (n = 1), in the larynx (n = 1), or at the base of the tongue (n = 1). In nine out of these 16 patients, the primary was confirmed in the lungs in 5 patients, in the larynx, at the base of the tongue, in the nasopharynx, and the tonsilla palatina in one patient each, respectively. Moreover, in 6 out of 16 patients, PET was false-positive. One patient refused further evaluation of PET findings. CONCLUSIONS: In approximately one third of all patients, PET detected the primary tumor site, which significantly influenced further therapeutic procedures. Thus, F-18-FDG-PET may be a valuable diagnostic tool in the detection of the primary tumor in patients with cervical lymph node metastases.

Adult↗

Salivary gland protection by S-2-(3-aminopropylamino)-ethylphosphorothioic acid (amifostine) in high-dose radioiodine treatment: results obtained in a rabbit animal model and in a double-blind multi-arm trial.

Since differentiated thyroid cancer has an excellent prognosis, reduction of long-term side effects of high-dose radioiodine treatment (HD-RIT), i.e. salivary gland impairment is important. Thus, radioprotective effects of amifostine were studied. Salivary gland function was quantified by scintigraphy both in rabbits and patients. Fifteen rabbits were studied prior to and up to 6 months after HD-RIT applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to HD-RIT, and five served as controls. Animals were examined histopathologically. Fifty patients with differentiated thyroid cancer were evaluated prospectively prior to and 3 months after HD-RIT with either 3 or 6 GBq 131I in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously prior to HD-RIT, and 25 patients receiving physiological saline solution served as controls. Complete ablation of the thyroid was achieved in all rabbits four weeks after HD-RIT. In control rabbits 6 months after HD-RIT parenchymal function was reduced significantly (p < 0.0001) by 75.3 +/- 5.3% and 53.6 +/- 17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits parenchymal function was not significantly reduced. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. In control patients, salivary gland function was significantly (p < 0.001) reduced by 40.2 +/- 14.1% and 39.9 +/- 15.3% in parotid and submandibular glands, respectively, three months after HD-RIT, and 11 patients developed xerostomia. In 25 amifostine-treated patients, salivary gland function was not significantly reduced (p = 0.691), and xerostomia did not occur. Thus, parenchymal damage in salivary glands induced by high-dose radioiodine therapy can be reduced significantly by amifostine. This may improve quality of life of patients with differentiated thyroid cancer.

Adult↗

[Onco-PET: lesion detection by monitor versus standardized film documentation].

AIM: Lesion detection and localization of 2-[18F]fluoro-2-deoxy-D-glucose (F-18-FDG) Onco-PET-Investigations are usually performed on-line at the computer display. The aim of the present study was to evaluate the clinical efficacy of a standardized film documentation as an alternative approach. METHODS: 100 Onco-PET-investigations without attenuation correction were analyzed with regard to number and localization of lesions suspicious of malignancy. A standardized documentation on film was developed including 1. transversal slices of the brain, 2. coronal slices and maximum-intensity-projections (MIPs) of the head/neck region and 3. of the trunk and 4. MIPs of the legs. These transparencies were analyzed at the light box. An additional analysis on the computer display was performed slice by slice in coronal, transversal and sagittal directions for the whole body. RESULTS: A total of 315 lesions were detected in 100 patients. In 96/100 patients the two modalities agreed both in number and localization of tumor-suspicious lesions. 7 lesions in the legs of 3 patients didn't show when interpreting the films (MIPs only). In 2/100 patients additional analysis on the computer display caused a change in the localization of 9/315 lesions. 8 of these were located in the legs. When adding coronal slices for the documentation of the lower extremities all the lesions were shown. Moreover, all lesions were localized correctly except one clinically non-relevant change of localization out of a total of 322 lesions. CONCLUSION: The newly developed standardized documentation supports the concept of film reading and reporting of onco-PET investigations, restricting an additional on-line analysis to rare cases only. Furthermore, the intention of the "Arbeitsgemeinschaft Standardisierung" (work group standardisation) are met, i.e. to ease analysis of follow-up studies acquired at different places.

Documentation↗

Quantitative salivary gland scintigraphy.

OBJECTIVE: Uptake of 99mTc-pertechnetate in salivary glands reflects intact salivary gland parenchyma. However, no standardized protocol for an accurate quantification of parenchymal function has been established so far. METHODS: In this paper we report on a validated acquisition protocol supplying a normal database for standardized quantitative salivary gland scintigraphy. RESULTS: The major advantage of salivary gland scintigraphy, as compared to other imaging modalities, is that both parenchymal function and excretion fraction of all four major salivary glands (i.e., parotid and submandibular glands) can be simultaneously quantified with a single intravenous injection. CONCLUSION: Quantitative salivary gland scintigraphy is demonstrated to be a suitable imaging modality for research applications in evaluating the effects of radioprotective drugs on salivary glands. Salivary gland scintigraphy is easy to perform, reproducible and well-tolerated by the patient.

Adolescent↗