Search PubMed⌕ Search

Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 253 records · Page 14Linked to original sources
PubMed1996

Targeted expression of human O(6)-methylguanine-DNA methyltransferase (MGMT) in transgenic mice protects against tumor initiation in two-stage skin carcinogenesis.

Carcinogenesis proceeds in discrete steps involving initiation and promotion. There is ample evidence that the underlying cause of initiation is mutation, whereas for tumor promotion different hypotheses exist postulating the involvement of both epigenetic and genetic changes. DNA repair protects against tumor formation, but it has not been proven whether protection occurs at the level of tumor initiation or promotion. Since the most advanced experimental system for studying multistep carcinogenesis is the mouse skin, we generated transgenic mice that overexpress the human DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in their epidermal cells by virtue of cytokeratin (Ck) promoters. Total cellular methyltransferase activity was found to be significantly higher in skin protein extracts of transgenic as compared to nontransgenic mice. CkMGMT transgenic mice along with nontransgenic controls were treated according to the multistage skin carcinogenesis protocol. For initiation, a single subthreshold dose of N-nitroso-N-methylurea (MNU) or 7,12-dimethylbenz(a)anthracene (DMBA) was topically applied to the dorsal skin of the mice. Tumor promotion was carried out by repeated 12-O-tetradecanoylphorbol-13-acetate application. Our results clearly show that CkMGMT transgenic mice are strongly protected against MNU- but not DMBA-initiated skin tumor formation. As compared to nontransgenic controls, transgenic mice exhibited an approximately 6-fold reduction of skin tumor incidence after treatment with 20 micromol or 50 micromol MNU followed by 12-O-tetradecanoylphorbol-13-acetate. These results provide direct and the most compelling evidence to date that the DNA lesion O6-methylguanine is of decisive importance in tumor initiation, and that the protective effect of the repair protein MGMT in carcinogenesis is due to prevention of initiation without affecting tumor promotion.

Animals↗
PubMed1996

An unknown spondylo-meta-epiphyseal dysplasia in sibs with extreme short stature.

In three sibs of Jordanian descent a unique type of severe spondylo-meta-epiphyseal dysplasia results in extreme disproportionate dwarfism. They have a distinct facial appearance with hypotelorism, prognathia, and hypodontia. The limbs are short and the hands and feet stubby. Radiologically, the irregular end plates of the vertebral bodies, the very small and late appearing epiphyseal ossification centres, and the hypoplastic acetabular roofs are most impressive. Histopathologic studies of the growth plate demonstrate characteristic findings with fingerprint-like inclusion bodies in the hypertrophic chondrocytes. This seems to be a distinct, autosomal recessive skeletal dysplasia.

Adolescent↗
PubMed1996

Photoinactivation of trypanothione reductase and glutathione reductase by Al-phthalocyanine tetrasulfonate and hematoporphyrin.

The irradiation of Trypanosoma congolense trypanothione reductase (TR), human erythrocyte (HGR) and yeast glutathione reductase (YGR) with visible light in the presence of Al-phthalocyanine tetrasulfonate (A1PcS4) or hematoporphyrine (Hp) caused a time-dependent inactivation of these enzymes. TR was inactivated more rapidly than either HGR or YGR. Half-maximal rates of inactivation were determined in the presence of 100 microM Hp and 1.4-17 microM AlPcS4. The photosensitized irradiation modified the disulfide substrate-binding sites of these enzymes, most likely the conserved catalytic histidine residue. In the dark, AlPcS4 acted as a reversible inhibitor competitive with the disulfide substrate of TR and HGR. These findings suggest the possible use of photosensitized irradiation for preventing the transmission of trypanosomiasis by blood transfusion.

Animals↗
PubMed1996

Exopolysaccharide Production and Attachment Strength of Bacteria and Diatoms on Substrates with Different Surface Tensions

Attachment strength and exopolysaccharide (EPS) production of Pseudomonas sp. (bacteria) and the diatom Amphora coffaeformis were studied on six different substrata with surface tensions between 19 and 64.5 mN m-1. Test panels of the materials were exposed to bacterial cultures between 3 and 120 hours, and to diatom cultures between 48 and 72 hours. Exopolysaccharide production by surface-associated cells was measured using the phenol sulfuric acid method. Attachment studies were run by exposing test panels to laminar flow pressure using a radial flow chamber. Highest EPS production by bacteria and diatoms was recorded on substrata with surface tensions above 30 mN m-1. Lowest EPS production occurred on substrata between 20 and 25 mN m-1. Highest EPS production and strongest adhesion was found on polycarbonate (33.5 mN m-1). Both test organisms improved their attachment strength with exposure time on most materials. However, amounts of produced EPS and improvement of attachment indicated that mechanisms other than polysaccharide production are more important on substrata with low surface tensions (<25 mN m-1). Simply producing more polysaccharides is not sufficient to overcome weak attachment on materials with low surface tensions. For example, adhesion of Pseudomonas sp. and A. coffaeformis on polytetrafluorethylene/perfluor-copolymer (PFA; 22 mN m-1) and glass (64.5 mN m-1) was equally strong although EPS production was much higher on glass than on PFA. This is somewhat surprising for A. coffaeformis because polysaccharide production has been considered the most important attachment mechanism of A. coffaeformis.

Journal Article↗
PubMed1996

Endothelin-induced inositol phosphate formation in rat kidney. Studies on receptor subtypes, G-proteins and regulation during ontogenesis.

The aim of this study was to characterize the properties of endothelin (ET)-receptor subtypes mediating inositol phosphate (IP)-formation in rat kidney and their regulation during ontogenesis. In renal cortical slices of adult rats (12-16 weeks old) ET's concentration-dependently increased IP-formation with an order of potency ET-1 >> ET-3. While the non-selective ET-receptor antagonist bosentan (10 microM) completely suppressed ET-induced IP-formation, the ETA-receptor antagonist BQ-123 (10 microM) inhibited it only by 70%, the ETB-receptor antagonist IRL 1038 (1 microM) by 25%; combined application of BQ-123 + IRL 1038 caused complete inhibition of ET-1-induced IP-formation. Pretreatment of isolated renal cells with pertussis toxin (PTX, 500 ng/ml) overnight did not attenuate but significantly increased ET-1-induced IP-formation. Ontogenetic studies in renal sites from neonatal, 1, 2, 3, 6, 12 and 24 weeks old rats revealed that ET-1-induced IP-formation maturation-dependently declined being highest in neonatal rats (increase: 169% over basal) and lowest in 24 weeks old rats (increase: 47% over basal). This decline in ET-induced IP-formation was accompanied by a decrease in renal ET-receptor number and the amount of immunodetectable Gq/11 (assessed by Western-blotting using the QL-antiserum). Moreover, ET-receptor subtypes changed during the maturation process: from neonates to 12 weeks old rats number and functional responsiveness of ETA-receptors declined, while that of ETB-receptors increased. We conclude that in adult rat renal cortex ET-induced IP-formation is mediated by activation of both ETA- and ETB-receptors and does not involve a PTX-sensitive G-protein. ET-induced IP-formation declines during the maturation process; this is associated with a decrease in ET-receptor number and the immunodetectable amount of Gq/11.

Age Factors↗
PubMed1996

Mutations of p53 in Barrett's esophagus and Barrett's cancer: a prospective study of ninety-eight cases.

We had previously identified p53 mutations in Barrett's esophagus and therefore began a multiinstitutional study to determine their significance as a marker for malignancy. Ninety-eight patients from four institutions were studied. Forty-eight patients (37 men and 11 women, mean age 56.2 years) had Barrett's esophagus with metaplasia or dysplasia but no evidence of malignancy at a mean follow-up of 2.2 years. Barrett's esophagus was classified as metaplasia with no evidence of dysplasia in 32 patients, as low-grade dysplasia in 13, and as high-grade dysplasia in three. The other 50 patients (46 men and four women, mean age 60.2 years) had adenocarcinoma arising in Barrett's esophagus. Tissues from normal stomach or esophagus, tumor, and Barrett's esophagus were obtained for deoxyribonucleic acid analysis by endoscopic biopsy from patients with Barrett's esophagus or cancer or during operations on some patients with Barrett's cancer. Exons 5 through 9 of the p53 gene were studied for mutations by single-strand conformational polymorphism analysis after polymerase chain reaction amplification. Mutations detected by single-strand conformational polymorphism analysis were confirmed by deoxyribonucleic acid sequencing. None of the tissue samples from patients with Barrett's esophagus alone and no dysplasia or low-grade dysplasia had any p53 mutations, but one of the three patients with high-grade dysplasia and no evidence of invasive malignancy did have a p53 mutation. Of the 50 patients with Barrett's cancer, however, 23 (46%) had p53 mutations in Barrett's epithelium, tumors, or both. Twenty of these patients had p53 mutations in the tumor only (n = 16) or in both tumor and Barrett's epithelium (n = 4), suggesting that the mutation plays a direct role in carcinogenesis. Mutations in Barrett's epithelium were found in one patient in the group without malignancy and in seven patients with cancer (one with no dysplasia, two with low-grade dysplasia, and five with high-grade dysplasia). In three patients with cancer, mutations occurred only in Barrett's epithelium, suggesting that such mutations may also be a marker for genomic instability. Mutations were predominantly found in exons 5, 7, and 8, and transitions from guanine to adenine were the most frequent changes. Mutations of p53 are clearly involved in the pathogenesis of Barrett's cancer for a subset of patients (46%), and the fact that we could detect mutations in premalignant Barrett's epithelium supports the hypothesis that p53 mutations may be a useful marker for patients at increased risk for development of invasive cancer.

Adenocarcinoma↗
PubMed1996

Linkage and cytogenetic mapping of a CAG repeat containing human cDNA to 3p24.2-p22.

A trinucleotide (CAG)n repeat containing cDNA was isolated from a human cDNA library and sequenced. The locus was mapped by linkage analysis in the CEPH families and by cytogenetic analysis to 3p24.2-p22. We have additionally excluded this gene as a candidate for small cell lung carcinoma by the analysis of cell lines carrying homozygous deletions for the 3p chromosomal region.

Chromosome Mapping↗
PubMed1996

Synergistic stimulatory effects of tumour necrosis factor alpha and interferon gamma on replication of human immunodeficiency virus type 1 and on apoptosis of HIV-1-infected host cells.

Differential and sometimes contradictory effects have been described for tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) on replication of human immunodeficiency virus type 1 (HIV-1). The authors examined individual and coordinate action of these cytokines on HIV-1 expression, and on apoptosis of HIV-1-infected host cells by determination of reverse transcriptase activity in cell culture supernatant, expression of HIV-1-RNA and production of p24 antigen in the promonocytic cell line U937 and its persistently HIV-1-infected clone U1. Apoptosis was demonstrated by typical cleavage of cellular DNA at internucleosomal regions in promonocytic and T-lymphocytic cell lines. TNF-alpha alone markedly stimulated HIV-1 replication in U1 cells at the transcriptional and on the translational level. Exclusive application of IFN-gamma only slightly enhanced HIV-1 expression, whereas it synergistically potentiated stimulatory effects of TNF-alpha. Both cytokines also synergistically induced apoptosis in HIV-1-infected host cells. Co-ordinate action of TNF-alpha and IFN-gamma is suggested to represent an important mechanism for disease progression in HIV infection. These findings demonstrate that cytokine effects on viral expression may vary depending on their single or combined application.

Apoptosis↗
PubMed1996

Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover.

The cell surface receptor Fas (FasR, Apo-1, CD95) and its ligand (FasL) are mediators of apoptosis that have been shown to be implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and one of the two major cytolytic pathways mediated by CD8+ cytolytic T cells. To gain further understanding of the Fas system., we have analyzed Fas and FasL expression during mouse development and in adult tissues. In developing mouse embryos, from 16.5 d onwards, Fas mRNA is detectable in distinct cell types of the developing sinus, thymus, lung, and liver, whereas FasL expression is restricted to submaxillary gland epithelial cells and the developing nervous system. Significant Fas and FasL expression were observed in several nonlymphoid cell types during embryogenesis, and generally Fas and FasL expression were not localized to characteristic sites of programmed cell death. In the adult mouse, RNase protection analysis revealed very wide expression of both Fas and FasL. Several tissues, including the thymus, lung, spleen, small intestine, large intestine, seminal vesicle, prostate, and uterus, clearly coexpress the two genes. Most tissues constitutively coexpressing Fas and FasL in the adult mouse are characterized by apoptotic cell turnover, and many of those expressing FasL are known to be immune privileged. It may be, therefore, that the Fas system is implicated in both the regulation of physiological cell turnover and the protection of particular tissues against potential lymphocyte-mediated damage.

Animals↗
PubMed1996

Sulfadiazine-associated nephrotoxicity in patients with the acquired immunodeficiency syndrome.

We performed a computerized search on sulfadiazine-associated nephrotoxicity reported in human immunodefiency virus (HIV)-infected patients in the international literature. Including an original case report, we summarized 35 acquired immunodefiency syndrome (AIDS) patients from 1987 to 1995 in an analysis comparing their features to historical HIV-negative controls from the 1940s and 1950s. Likely due to a high prevalence of potential risk factors, incidence of sulfadiazine-associated renal impairment was 1.9%-7.5% in AIDS patients and 1%-4% in HIV-negative controls. Its occurrence appeared to be delayed in HIV-infected patients with a median of about 3 weeks of medication compared with about 10 days in HIV-negative subjects. Correspondingly, the cumulative sulfadiazine dose at manifestation doubled in AIDS patients with a median of 84 g versus 40 g in controls. Patients usually presented with flank or lumbar pain, oliguria, and (macro) hematuria. Urinalysis showed typical "sheaves of wheat" crystalluria, erythrozyturia, and, less commonly, leukozyturia and proteinuria. Echogenic (mostly peripelvic) densities, renal stones, and hydronephrosis are frequent findings on ultrasound examination, whereas X-ray examination possesses a low diagnostic sensitivity. The principle aim of therapy in these patients is to (re)institute the physicochemical urinary solubility of sulfadiazine and its metabolites. For this purpose, forced rehydration and, most importantly, urine alkalinization proved to be effective measures without an absolute need to withhold the drug. Provided prophylactic and therapeutic recommendations are complied with, outcome of this drug-related side effect is usually excellent, and rare relapses will similarly respond well.

AIDS-Related Opportunistic Infections↗
PubMed1996

Biological degradation of tannins in sericea lespedeza (Lespedeza cuneata) by the white rot fungi Ceriporiopsis subvermispora and Cyathus stercoreus analyzed by solid-state 13C nuclear magnetic resonance spectroscopy.

Leaves of sericea lespedeza exhibit a high proportion of condensed tannin, resulting in poor forage quality. The white rot fungi Ceriporiopsis subvermispora and Cyathus sterocoreus are known to preferentially degrade lignin in a variety of plants and were evaluated for their ability to degrade condensed tannin from sericea leaves with the aim of improving digestibility. Relative levels of condensed tannin, cutin, pectin, and cellulose were monitored as a function of fungal treatment by solid-state cross-polarization and magic angle spinning 13C nuclear magnetic resonance spectroscopy. Total soluble phenolics, soluble tannins, and soluble and insoluble proanthocyanidin levels in fungus-treated and control samples were measured by established chemical techniques. Results indicate that both species of fungus preferentially degrade condensed tannin and that C. subvermispora is markedly superior to C. stercoreus in this capacity.

Anthocyanins↗
PubMed1996

[Early squamous epithelial carcinoma of the esophagus--multicentricity, metastatic pattern and prognosis].

The results of surgical treatment of 65 patients with pT1 squamous cell carcinoma of the esophagus and the histologic workup of the specimens were analyzed. The treatment of choice was transthoracic enbloc esophagectomy (n = 45); in 16 patients with very distal carcinoma and restrained lung function transhiatal esophagectomy was performed. Two patients with concomitant early gastric carcinoma or lymphoma had total esophagogastrectomy, and in 2 other patients cervical esophagectomy was performed. The postoperative 30-day mortality was 6.1%. 74% of the cases had an infiltration of the submucosa, whereas in 26% the carcinoma was limited to the mucosa. No patients with mucosal carcinoma had lymph node metastases, whereas 23% of the patients with submucosal infiltration showed lymph node involvement. Tumors of other organs, especially stomach and hypopharynx, were found in 15.4% of the patients. The 5-year survival rate of the total group of 65 patients was 61.3%. As 3 patients with mucosal carcinoma died during long-term follow-up due to recurrence or second cancer, no significant prognostic difference was found between patients with mucosal or submucosal infiltration. The survival curves of patients with pN0 and those with pN1 tumors were not significantly different.

Adult↗
PubMed1996

Systemic uptake of 5-aminosalicylic acid from olsalazine and eudragit L coated mesalazine in patients with ulcerative colitis in remission.

UNLABELLED: Aminosalicylates are used to maintain remission in patients with ulcerative colitis. Since there are potential systemic side effects of 5-aminosalicylic acid (5-ASA) and long term treatment is necessary for maintenance therapy preparations with low rates of absorption in the small intestine would be optimal for this indication. In this trial olsalazine (Dipentum), a 5-ASA dimer, and an eudragit L coated mesalazine preparation (Salofalk) were compared. PATIENTS AND METHODS: Fifteen patients with ulcerative colitis in clinical and endoscopical remission were randomized in a cross over design. They either received a 2 x 2 capsules of olsalazine 250 mg or 3 x 2 tablets mesalazine 250 mg, these being the doses recommended for maintenance therapy. After a five days equilibration period morning pre-dose serum samples and 24 hour urine were collected on two consecutive days and analyzed for 5-ASA and acetylated 5-ASA. Subsequently, patients were crossed over to receive the alternative preparation and were evaluated after five days correspondingly. RESULTS: Uptake of 5-ASA from mesalazine was significantly higher than from olsalazine (p < 0.0001). Plasma concentrations of 5-ASA were 3.4 times and of acetyl-5-ASA 3.2 times higher after mesalazine administration than after olsalazine. The same applies to the 24 hour 5-ASA and acetyl-5-ASA urinary excretion (median: 3.2 versus 1.0 mmol/24 hr) as well as to the percentage of administered dose (32.4 versus 17.7%). All patients finished the trial and no major systemic side effects occured with either preparation. CONCLUSION: Systemic uptake of 5-ASA from olsalazine was significantly lower than from eudragit L coated mesalazine. Therefore, olsalazine is less likely to produce side effects and seems to be especially suited for maintenance therapy in ulcerative colitis.

Adult↗
PubMed1996

[Inflammatory esophageal diseases caused by herpes simplex virus infections--overview and report of 15 personal cases].

Frequency of herpes simplex virus(HSV)-induced esophagitis was reported to range from 0.5% to 6% in non-selected patients according to autopsy and clinical studies. In case of gastrointestinal involvement, affinity of herpes simplex virus to squamous epithelia predisposes the esophagus to be affected. Typically, patients complain about acute onset of odynophagia, retrosternal pain, or symptoms of gastrointestinal blood loss, while systemic signs of inflammation are often absent. Endoscopic examination usually reveals disseminated, roundish mucosal defects with distinct borders preferably in the distal part of the esophagus. If suspected clinically and by endoscopy, a histological and/or cytological diagnosis should be achieved by carefully taking multiple biopsies from the edge of the suspicious lesions. Antiviral therapy is not obligatory, since HSV esophagitis often resolves spontaneously. In the presence of preexisting immunodeficiency, marked clinical symptoms, or complicated course, however, the guanosine analogue aciclovir is the treatment of choice. In view of a comparably low sensitivity of macroscopic assessment and an expected increase in incidence of this viral infection, a high index of suspicion for this disorder appears to be necessary for all clinicians working in the field of endoscopy. Based on 15 personal observations recorded from 1983 to 1995, epidemiological, pathogenetic, morphological, and clinical features of HSV esophagitis will be summarized and discussed in the light of the pending literature on this subject.

Adolescent↗