Vibrio vulnificus wound infections after contact with the Baltic Sea, Germany.
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Bathing Beaches↗
Biomedical subjects
C Frank
Publications and source records attributed to C Frank.
Potentiation of irinotecan sensitivity by Se-methylselenocysteine in an in vivo tumor model is associated with downregulation of cyclooxygenase-2, inducible nitric oxide synthase, and hypoxia-inducible factor 1alpha expression, resulting in reduced angiogenesis.
Until recently, the use of Se-methylselenocysteine (MSC) as selective modulator of the antitumor activity and selectivity of anticancer drugs including irinotecan, a topoisomerase I poison, had not been evaluated. Therapeutic synergy between MSC and irinotecan was demonstrated by our laboratory in mice bearing human squamous cell carcinoma of the head and neck tumors. In FaDu xenografts, a poorly differentiated tumor-expressing mutant p53, the cure rate was increased from 30% with irinotecan alone to 100% with the combination of irinotecan and MSC. Cellular exposure to cytotoxic concentration of SN-38, the active metabolite of irinotecan (0.1 microM) alone and in combination with noncytotoxic concentration of MSC (10 microM) did not result in additional enhancement of chk2 phosphorylation and downregulation of specific DNA replication-associated proteins, cdc6, MCM2, cdc25A, nor increase in PARP cleavage, caspase activation and the 30-300 kb DNA fragmentation induced by SN-38 treatment. MSC did not alter significantly markers associated with apoptosis, nor potentiate irinotecan-induced apoptosis. These results indicate that apoptosis is unlikely to be one of the main mechanism associated with the observed in vivo therapeutic synergy. In contrast, significant downregulation of cyclooxygenase-2 (COX-2) expression and activity was observed in the cells exposed to SN-38 in combination with MSC compared to SN-38 alone. Moreover, the inhibition of PGE(2) production was also observed in the cells treated with the combination as compared with SN-38 alone. Analysis of tumor tissues at 24 h after treatment with synergistic modality of irinotecan and MSC revealed significant downregulation of COX-2, inducible nitric oxide synthase (iNOS) and hypoxia-induced factor-1alpha expression (HIF 1alpha). Moreover, decreased microvessel density was observed after irinotecan treatment with the addition of MSC. These results suggest that observed therapeutic synergy correlates with the inhibition of neoangiogenesis through the downregulation of COX-2, iNOS and HIF-1alpha expression.
Animals↗
Curcumin treatment protects rat retinal neurons against excitotoxicity: effect on N-methyl-D: -aspartate-induced intracellular Ca(2+) increase.
Curcumin, an extract from the plant Curcuma longa with well-known antioxidant and anti-inflammatory activities, was tested as protective agent against excitotoxicity in rat retinal cultures. A 24 h-treatment with curcumin reduced N-methyl-D: -aspartate (NMDA)-mediated excitotoxic cell damage, estimated as decrease of cell viability and increase in apoptosis. The protection was associated with decrease of NMDA receptor-mediated Ca(2+) rise and reduction in the level of phosphorylated NR1 subunit of the NMDA receptor. These results enlighten a new pharmacological action of the plant extract, possibly mediated by a modulation of NMDA receptor activity.
Animals↗
[Nation-wide outbreak of Salmonella Give in Germany, 2004].
PURPOSE: In spring and summer 2004, a multistate outbreak of infections caused by Salmonella enterica serovar Give (S. Give), a relatively rare serovar in Germany, was detected. In order to identify a common exposure and to describe the characteristics of infections caused by S. Give, an outbreak investigation was performed. MATERIALS AND METHODS: In addition to passive surveillance through mandatory case-reporting, active case-finding was conducted. A case-control study was undertaken in order to identify the probable vehicle of infection. S. Give strains were isolated and molecular subtyping was performed by pulsed-field gel electrophoresis (PFGE). Rates of hospitalization were assessed in patients with S. Give infection, and compared to the rates found in patients infected by the most common serovar in Germany, S. enteritidis. RESULTS: From March to July 2004, 115 cases of gastroenteritis caused by S. Give were identified, with highest incidences being observed in the states of Lower Saxony and Saxony-Anhalt. Consumption of raw minced pork was strongly associated with S. Give infections (OR: 8.0; 95% CI 2.3-27.7; P = 0.001). This result was confirmed by the detection of common outbreak strains in isolates from both patients and pork, using PFGE. Infections caused by S. Give lead to hospitalization in 55% of patients > or = 60 years, but only in 17 % of younger patients (OR: 6.0; 95% CI 2.1-16.3; P < 0.001) and 33% in patients > or = 60 years with infections caused by S. enteritidis (OR: 2.5; 95% CI 1.1-5.4; P = 0.02). CONCLUSION: This is, to our knowledge, the first documented multistate outbreak of salmonellosis associated with the consumption of raw minced pork in Germany. Since contamination of pork meat with Salmonella cannot be avoided, people with risk factors for severe infection should generally avoid the consumption of raw minced pork. The high hospitalization rates in patients > or = 60 years infected with S. Give possibly indicate a higher virulence of this specific serovar. Even in non-typhoidal salmonellosis, early antibiotic therapy should be considered depending on infecting serovar, age and medical history of the patient.
Age Factors↗
Dysphagia following chemoradiation for locally advanced head and neck cancer.
BACKGROUND: To assess the prevalence, severity and morbidity of dysphagia following concurrent chemoradiation for head and neck cancer. PATIENTS AND METHODS: Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. Modified barium swallow (MBS) studies were performed if the patients complained of dysphagia or if there was clinical suspicion of aspiration. The severity of dysphagia was graded on a scale of 1-7. If significant abnormalities were found, swallowing studies were repeated until resolution of dysphagia. RESULTS: Between March 1999 and May 2002, 55 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. Aspiration pneumonia was observed in eight patients, three during treatment and five following treatment. Five patients died from pneumonia. Two patients developed respiratory failure requiring intubation as a complication of pneumonia. At a median follow-up of 17 months (range 6-48 months), 25 patients (45%) developed severe dysphagia requiring prolonged tube feedings for more than 3 months (22 patients) or repeated dilatations (three patients). Among 33 patients who underwent MBS following treatment, 12 patients (36%) had silent aspiration (grade 6-7 dysphagia). Thirteen patients (39%) developed grade 4-5 dysphagia which required prolonged enteral nutritional support to supplement their oral intake. Most patients had severe weight loss (0-21 kg) during treatment, likely due in part to mucositis in the orodigestive tube. CONCLUSIONS: Dysphagia is a common, debilitating and potentially life-threatening sequela of concurrent chemoradiation for head and neck malignancy. Physicians should be aware that the clinical manifestations of aspiration may be unreliable and insidious, because of the depressed cough reflex. Modified and traditional barium swallows should be performed following treatment to assess the safety of oral feeding and the structural integrity of the pharynx and esophagus. Patients with severe dysphagia may benefit from rehabilitation. Tube feeding should be continued for those with aspiration.
Adult↗
Initial study of arthropod succession on pig carrion in a central European urban habitat.
We conducted a carrion succession study within a restricted urban backyard in the city of Vienna, Austria (16 degrees 22'E, 48 degrees 12'N) from May to November 2001 to analyze sequence and composition of the local carrion visiting fauna. Two medium sized clothed domestic pig carcasses (Sus scrofa Linnaeus), were used as surrogate human models. In total, 42 arthropod species from the families Calliphoridae, Sarcophagidae, Sepsidae, Piophilidae, Muscidae, Fanniidae, Sphaeroceridae, Phoridae, Drosophilidae, Anthomyiidae, and Lauxaniidae (Diptera), Formicidae, Braconidae, Pteromalidae, and Vespidae (Hymenoptera), Silphidae, Staphylinidae, Histeridae, Cleridae, and Dermestidae (Coleoptera), as well as species from the orders Isopoda and Acari were collected during the decomposition of these carcasses. A significant feature in this study was the high abundance of Calliphora vomitoria (L.) and Chrysomya albiceps (Wiedemann). In the experiment conducted May to June, larvae and adults of C. vomitoria outnumbered all other blow fly species, followed by Protophormia terraenovae (Robineau-Desvoidy), C. vicina Robineau-Desvoidy, and Lucilia sericata (Meigen). C. vomitoria is generally considered to be rural in distribution, where it prefers shaded locations. The presence of this species in rural as well as in urban habitats in Austria precludes this species as biogeographic indicator. In the study beginning in August large numbers of female adults of the nonindigeous blow fly C. albiceps began oviposition at day 3 after placement of the cadaver. The predatory second and third instars of C. albiceps larvae subsequently almost monopolized the cadaver. C. albiceps is generally described as tropical and subtropical species. The observed northward expansion of its range beyond southern Europe obviously decreases the value of C. albiceps in estimating place of death, in that it is no longer exclusive to southern regions. Our results clearly show, that caution must be used when drawing conclusions from succession data generated in different geographic areas. Moreover, this study demonstrates, that arthropod mediated decomposition of a 44 kg exposed pig carcass in a central European urban habitat can be completed within 3 wk.
Animals↗
Modulation of glutamate release and excitotoxicity by adenosine A2A receptors.
Because an increased glutamate outflow is thought to play a crucial role in triggering excitotoxic neuronal death, drugs able to regulate glutamate release could be effective for the management of neurodegenerative diseases. In this article, the authors discuss the hypothesis that adenosine A2A receptor antagonists (A2A antagonists) may belong to the aforementioned category. In rats bilaterally lesioned with the excitotoxin quinolinic acid (QA) in the striatum, the A2A antagonist SCH 58261 significantly reduced the motor, EEG, and neuropathologic changes induced by the lesion. Such effects of SCH 58261 occurred only at low doses and were paralleled by an inhibition of QA-stimulated glutamate release. The role played by A2A antagonists in the regulation of glutamate outflow was also confirmed by preliminary results obtained in the model of paired-pulse stimulation in corticostriatal slices. Conversely, based on data obtained in cultured striatal neurons, A2A antagonists appear unable to directly inhibit NMDA effects. In conclusion, A2A antagonists show clear neuroprotective effects in models of brain injury, although their actual therapeutic potential needs to be confirmed in a wider range of doses and in models of neurodegenerative diseases in which presynaptic and postsynaptic effects play different relative roles.
Adenosine A2 Receptor Antagonists↗
Relative quantification of HLA-DRA1 and -DQA1 expression by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).
Polymorphism in the upstream regulatory region (URR) of the MHC class II DQA1 gene defines 10 different alleles named QAP (DQA1 promoter). In vitro studies have suggested that allelic polymorphism in the HLA-DQA promoter region may result in differences in HLA-DQA1 gene expression. In the present study, we used real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify differences in HLA-DQA1 gene expression. After the isolation of total mRNA, reverse transcription into cDNA was carried out using random hexamer priming and moloney murine leukaemia virus (MMLV) reverse transcriptase. Quantification of DQA1 mRNA species using a set of six group-specific primer pairs for the detection of HLA-DQA1*01, *02, *03, *04, *05 and *06 was carried out on an ABI PRISM GeneAmp 7700 Sequence Detection System (Perkin Elmer, Foster City, CA) with real-time detection and quantification taking advantage of the fluorescence TaqMan technology (Perkin Elmer, Foster City, CA). Normalization of cDNA templates was achieved by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) quantification. In addition, the total amount of mRNA produced by HLA-DQA1 and HLA-DRA1 expression was quantified for comparison. Subsequently, this approach was validated using Raji and HUT-78 cell lines and tested with peripheral mononuclear cells (PBMC) of 45 samples taken from healthy volunteers. The sensitivity was determined with > or = 10(2) copies. Comparison of the allele-specific DQA1 expression with the total expression of DQA1 and DRA1 mRNA indicated that DQA1*04 expression was increased compared with the expression of other alleles of the DQA1 gene. Thus, allele-specific quantification of DQA1 gene products could be achieved by real-time RT-PCR suitable for the analysis of differential expression of DQA1 mRNAs in homozygote and heterozygote combinations.
HLA-DQ Antigens↗
Temperature-related development of the parasitoid wasp Nasonia vitripennis as forensic indicator.
Development times of the forensically significant parasitic wasp Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae) from oviposition to pupation, and from oviposition to adult emergence, were studied in the laboratory at temperatures of 15-35 degrees C using host pupae of the blowfly Protophormia terraenovae (Robineau-Desvoidy) (Diptera: Calliphoridae). Total developmental time of N. vitripennis from oviposition to adult emergence (mean+/-SD) was 43.5+/-2.4, 22.5+/-1.1, 14.8+/-1.7 and 11.3+/-0.9 days when reared at 15, 20, 25 and 30 degrees C, respectively. At 35 degrees C, N. vitripennis did not develop successfully. The rate of total immature development (1/days) increased with temperature. From linear regression of development rates, it was determined that the minimum threshold (tL) for total immature development was 9.8 degrees C (approximately 10 degrees C). Above this threshold, the overall thermal constant (K) for N. vitripennis was found to be 224.3+/-1.7 degree-days.
Animals↗
The Chk1-Cdc25C regulation is involved in sensitizing A253 cells to a novel topoisomerase I inhibitor BNP1350 by bax gene transfer.
Promotion of apoptosis may potentiate the sensitivity of tumor cells to chemotherapeutic agents, thus improving the efficacy of cancer treatment. The transfection of the proapoptotic bax gene, which results in the overexpression of bax protein, augments the growth inhibition of A253 cells by BNP1350. Increased drug response was associated with the induction of DNA fragmentation in the size of 30-200 Kb, generating a cleaved fragment of 18 kDa from full-length 21 kDa bax and the cleavage of PARP. A253/vec cells treated with 0.07 microM(IC50) of BNP1350 accumulated in G2 phase at 24 h after drug removal. In contrast, A253/Bax cells treated with an equimolar concentration of BNP1350 primarily displayed a G1 phase accumulation with a concurrent decrease in G2 phase. Certain cell cycle regulatory protein expression and activities were altered following drug exposure in both cell lines under similar conditions. Cdk2- and cdc2-associated H1 kinase activities were markedly increased in the A253/Bax cell line with marginal increased activity in the A253/vec cell line. A chk1 activity assay was performed with GST-cdc25C (200-256) or GST-cdc25C(S216A) (200-256) fusion proteins as the substrate. Increased chk1 activity was observed in the A253/vec cell line, with little change in the A253/Bax cell line, when exposed to equimolar concentrations of BNP1350 (0.07 microM). A Western blot of immunoprecipitated chk1 indicated that increased chk1 phosphorylation following DNA damage induced by BNP1350 was accompanied by the observed G2 accumulation in the A253/vec cell line, while only a slight increase in chk1 phosphorylation was seen in the A253/Bax cell line. A decreased expression of cdc25C was observed in the BNP1350-treated A253/Bax cells, but not in the A253/vec cell line. Following exposure to BNP1350, increased binding of 14-3-3 proteins to chk1 occurred in both cell lines, with more being observed in the A253/vec cell line. The data have shown that inhibition of the chk1 pathway accompanied by the abrogation of G2 arrest is involved in sensitizing A253 cells to BNP1350 by bax gene transfer. These findings suggest that bax gene transfer sensitizes A253 cells to BNP1350 through apoptosis promoting and G2/M DNA damage checkpoint regulatory pathways.
Apoptosis↗
Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1.
Male "viable motheaten" (me(v)) mice, with a naturally occurring mutation in the gene of the SH2 domain protein tyrosine phosphatase SHP-1, are sterile. Known defects in sperm maturation in these mice correlate with an impaired differentiation of the epididymis, which has similarities to the phenotype of mice with a targeted inactivation of the Ros receptor tyrosine kinase. Ros and SHP-1 are coexpressed in epididymal epithelium, and elevated phosphorylation of Ros in the epididymis of me(v) mice suggests that Ros signaling is under control of SHP-1 in vivo. Phosphorylated Ros strongly and directly associates with SHP-1 in yeast two-hybrid, glutathione S-transferase pull-down, and coimmunoprecipitation experiments. Strong binding of SHP-1 to Ros is selective compared to six other receptor tyrosine kinases. The interaction is mediated by the SHP-1 NH(2)-terminal SH2 domain and Ros phosphotyrosine 2267. Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling.
3T3 Cells↗
Pulley anatomy for the radial side of the wrist.
This is the first presentation in the literature of a radial tendon flexor pulley in the distal forearm adjacent to the flexor carpi radialis. The clinical significance is that in performing wrist tendon arthroplasty, this structure and, in close proximity, the sensory branch of the median nerve may be encountered. Whether cutting the pulley of the flexor carpi radialis is clinically significant in changing wrist biomechanics is unknown.
Cadaver↗
Centroblastic-centrocytic non-Hodgkin's lymphoma stage I-III: patterns of failure following radiotherapy.
AIM: To investigate the patterns of failure and survival after involved-field or more extensive radiotherapy for centroblastic-centrocytic non-Hodgkin's lymphoma (NHL) as well as the impact of radiotherapy dose on local control. PATIENTS AND METHODS: 47 patients with Stage I-III centroblastic-centrocytic NHL were treated with involved-field (IF) extended-field radiotherapy (EF-RT) or total lymphatic irradiation (TLI). The involved regions received 25.5-50 Gy, non-involved regions were treated with a dose of 26 Gy in most cases. RESULTS: In Stage I/II, the majority of relapses (64%) were nodal and were located adjacent or distant to the former radiation portals. 79% of relapses occurred after IF-RT, 21% after EF-RT or TLI. 5-year overall survival (OAS) after EF-RT/TLI and IF-RT for Stages I/II was 85% and 83%, respectively (n.s.); relapse free survival (RFS) was 73% and 61%, respectively (n.s.). A tendency for better overall survival was found for patients who relapsed at one or two sites (5-year overall survival 100%) compared to patients with three or more relapse sites (5-year overall survival 0%). For Stage III overall survival was 72%, freedom from progression (FFP) was 27% at 5 years. We found a dose-effect correlation for local control with a relapse rate of 31% after 26-34 Gy and 4% after application of 36 Gy; no relapses occurred after doses of 40 Gy or more. CONCLUSION: In involved lymph node regions a relatively small number of relapses was observed after application of a minimal dose of 36 Gy. In Stages I/II most relapses were located outside the radiation portals, yet EF-RT was not superior to IF-RT in terms of overall survival and relapse free survival. Prospective randomized trials are necessary to prove a potentially favorable effect of more extended radiotherapy portals (TLI or TNI [total nodal irradiation]) and to evaluate the optimal radiotherapy dose.
Adult↗
Optimistic explanatory style and dispositional optimism in HIV-infected men.
OBJECTIVE: This study examined associations of two types of optimism (Peterson and Seligman's optimistic explanatory style and Scheier and Carver's dispositional optimism) with each other as well as with symptoms and immune status among human immunodeficiency virus (HIV)-infected men. METHOD: We related both types of optimism to HIV symptoms and to CD4 counts in a cross-sectional study of 78 men, and to change in CD4 counts in a 2-year prospective study of a subsample of these men. RESULTS: Analyses controlled for age, education, employment status, duration since diagnosis, and azidothymidine (AZT) use. The two types of optimism were only minimally related to each other (r=.25). Cross-sectionally, higher levels of both types of optimism were associated with having fewer HIV symptoms, but a more optimistic explanatory style was related to having poorer immune status (lower CD4). Prospectively, an optimistic explanatory style was a substantial predictor of greater decline in CD4 counts after 2 years, after controlling for baseline CD4. Dispositional optimism was unrelated to CD4 counts. Neither health behaviors nor coping strategies mediated these relationships, and the relationships of optimistic explanatory style (and to a lesser extent, dispositional optimism) were independent of negative affectivity. CONCLUSIONS: These optimism measures tap different types of optimism, and although both are related to better subjective health in HIV-infected men, an optimistic explanatory style predicts greater decline in immune status over time. This latter relationship may be related to the unique stress and life experiences associated with having HIV.
Adult↗
CD4 positive peripheral T cells from patients with systemic lupus erythematosus (SLE) are clonally expanded.
T cell activation was analysed in peripheral CD4+ T cells from both systemic lupus erythematosus (SLE) patients with active and inactive disease as well as in normal healthy donors (NHD) to investigate the involvement of CD4+ T cells in the etiopathogenesis of SLE. CD4+ T cell receptor (TCR) beta-chain transcripts, containing the complementarity determining region 3 (CDR3), were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analysed by high-resolution polyacrylamide gel electrophoresis. In addition the CDR3 of both clonally activated as well as heterogeneous Vbeta families from SLE patients were analysed at the molecular level. We observed a restricted CDR3 length polymorphism in peripheral CD4+ T cells from SLE patients compared with NHD, more pronounced in patients with high disease activity. Furthermore, in some Vbeta families single peaks in the histogram indicated nearly monoclonal T cell expansion. Sequencing of selected TCR beta-chains revealed a increased content of acidic amino acids in the CDR3 encoded by either proximal Jbeta elements or N nucleotides. We conclude that CD4+ T cells from peripheral blood of SLE patients display features of a secondary antigen driven immune response. The bias of the CDR3 towards acidic amino acids suggests the involvement of positively charged antigens.
Amino Acid Sequence↗
Case report: successful use of rectally administered levodopa-carbidopa.
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Administration, Oral↗
What drugs are our frail elderly patients taking? Do drugs they take or fail to take put them at increased risk of interactions and inappropriate medication use?
OBJECTIVE: To determine whether there were discrepancies between what medications frail elderly outpatients took and what physicians thought they took and whether discrepancies put patients at risk of taking inappropriate drugs and of increasing the potential for drug interactions. DESIGN: Case series. SETTING: Day Hospital Program at St Mary's of the Lake Hospital in Kingston, Ont. PARTICIPANTS: One hundred twenty community-living elderly patients attending the Day Hospital Program in 1998. Three patients and two family physicians declined to participate. MAIN OUTCOME MEASURES: Lists of medications being taken by patients compared with lists of medications in physicians' charts. Category according to explicit criteria that each drug fell into and risk of drug interactions as determined by the Clinidata Drug Interaction Program. RESULTS: Of the 120 patients, 115 had at least one discrepancy between their lists of medications and their physicians' lists. Of the 1390 medications on the lists, 521 (37%) were being taken by patients without their doctors' knowledge, 82 (6%) were not being taken by patients when doctors thought they were, and 133 (10%) were on both patients' and their doctors' lists but with dosages or frequency of administration that were different. More potential drug interactions were identified on patients' lists than on physicians' lists. No increase in risk of inappropriate drug use was identified. CONCLUSION: Family physicians are often unaware of all the medications their patients are actually taking. Medications used by patients without physicians' knowledge increase the likelihood of drug interactions. Family physicians should look at and inquire about all medications, including over-the-counter drugs, their patients are actually taking.
Aged↗
2-Chloro-adenosine induces a glutamate-dependent calcium response in C2C12 myotubes.
Adenosine and its derivatives may induce acute changes, i.e., injury and death, in muscle cells. In the present work, we evaluated the intracellular calcium concentration in C2C12 myogenic cells differentiated in vitro to form myotubes and exposed to a metabolically stable analogue of adenosine, 2-chloro-adenosine. The compound was able to significantly modify ionic homeostasis by sensitizing muscle cells to the excitatory amino acid glutamate. A single exposure to glutamate led to a marked increase in intracellular calcium level. This is the first demonstration that adenosine analogues can regulate muscle cell integrity and function via an indirect increase of intracellular calcium ions.
2-Chloroadenosine↗