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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 109 records · Page 6Linked to original sources
PubMed2000

[Food as a potential vector for antibiotic resistances. 2: Relevance of lactic acid bacteria].

Transfer of antibiotic resistances via the food chain is possible through the ingestion of resistant parts of the original food microflora. Lactic acid bacteria (especially glycopeptide resistant enterococci) are considered as important vectors because of their ability to transfer resistances by genetic mechanisms. Therefore a literature review and own investigations concerning the incidence and the resistance profile of enterococci from fresh meat were performed. The isolates harboured in part resistances relevant for human medicine. However, they could be isolated only sporadically and could not be demonstrated quantitatively in most cases. The resistance profile differed from those of human clinical origin. These results were confirmed by other authors. Additionally other investigators could prove molecular differences compared to clinical strains. Therefore food can only be considered as a vector if resistance transfer from food isolates to pathogenic microorganisms is possible. Such a transfer could be shown only in very low frequencies. In conclusion so far lactic acid bacteria cannot be considered as the main source for the incidence of antibiotic resistances in man.

Animals↗
PubMed2000

BRCA1 and BRCA2 mutation carriers as potential candidates for chemoprevention trials.

The identification of cancer susceptibility genes offers new avenues for selecting high-risk individuals as subjects for chemoprevention trials. Because carriers of predisposing mutations are at high risk, they are more likely to enroll and comply with chemoprevention trials, and meaningful results can be achieved with smaller numbers of participants and shorter periods of follow-up. Such studies have immediate benefits for carriers themselves, but they are also likely to result in effective chemopreventive strategies for the general population. In this review, we discuss BRCA1 and BRCA2 carriers as potential candidates for breast and ovarian cancer chemoprevention trials. The existence of a large population with a high frequency of easily identifiable BRCA1/2 mutations can provide ample opportunity for such studies. However, the possibility that tumor characteristics and hormonal profile of BRCA1/BRCA2 related cancers are not completely equivalent to cancers in the general population should be borne in mind.

Anticarcinogenic Agents↗
PubMed2000

Cell phenotype-dependent splicing reflecting differential promoter usage for EBNA transcripts in EBV-carrying cells.

Three types of virus-host cell interactions have been described in cells latently infected with EBV: EBNA 1 expression in type I Burkitt's lymphoma cell lines (BL), EBNA 1, LMP1 and 2 expression in most nasopharyngeal carcinomas (NPC) and EBNA 1-6 with LMP 1 and 2 expression in group III BL-lines as well as lymphoblastoid cell lines (LCL). Two group I BL lines that express only EBNA 1 were found to initiate their EBNA 1 mRNA transcription from a promoter in the Bam HI Q-fragment. They use a sequence at +210 bp relative to the Fp transcription initiation site in group I BL cell lines. The Fp promoter-region seems to be activated in the lytic cycle. LCLs initiate their transcription from one of several upstream sites, usually the Cp promoter or, less frequently, one of several Wp-promoters. Using RNA-reverse transcription polymerase chain reaction (RT-PCR), we have now shown that EBV carrying cells that do not express EBNA 2-6 always splice their EBNA mRNA at the Q-exon, while EBNA 2-6 positive cells use either the Cp or one of the Wp promotors. When EBNA 2-6 are downregulated by somatic cell hybridisation between EBNA 1-6 positive B-cell lines and non B-cells of hematopoetic, epithelial or fibroblastic origin that express the phenotype of the non-B cell parent, the parental usage of Cp/Wp is switched off, and the Q-exon is activated. NPC cells show the same pattern of promoter usage as the hybrids with non-B phenotype. Group III BL cells use both promoter regions. Thus, the virus can use two alternative programs, depending on the cell phenotype. The "EBNA-1 only" program is activated from the Q-promoter. In cells with an immunoblastic (LCL or BL group III) phenotype, the upstream Cp/Wp promoters generate a 100 kb. long pre-mRNA, from which all the EBNAs are spliced. As a rule, only one of the two programs is used for each phenotype, except for the BL group III cells that began as group I but subsequently developed into a more LCL-like cell. Such cells used both promoter regions, with or without activation of the lytic cycle.

Animals↗
PubMed1999

A 1-Mb PAC contig spanning the common eliminated region 1 (CER1) in microcell hybrid-derived SCID tumors.

We have developed an elimination test to identify chromosomal regions that contain tumor inhibitory genes. Monochromosomal human/mouse microcell hybrids are generated and passaged through SCID mice. Derived tumors are then analyzed for deletions on the transgenomic chromosome. Using this strategy, we have previously identified a 1.6-cM common eliminated region 1 (CER1) on human 3p21. 3. We now report that CER1 contains 14 markers that are deleted in 19 SCID-derived tumors. A 1-Mb PAC contig that spans CER1 was assembled. Five chemokine receptor genes (CCR1, CCR3, CCR2, CCR5, and CCR6) were localized in CER1 in a 225-kb cluster. The lactotransferrin gene (LTF, or lactoferrin, LF), which reportedly has tumor inhibitory activity, also maps to CER1. Our results create a basis for characterization and further functional testing of genes within CER1.

Animals↗
PubMed1999

A long-term memory obtained by genetic immunization results in full protection from a mammary adenocarcinoma expressing an EBV gene.

We have tested the capability of a plasmid DNA (pDNA) expressing the EBV nuclear Ag-4 (EBNA-4) to evoke a T cell response-associated protective immune response against a tumor expressing this gene. We have found that ACA mice immunized with EBNA-4-expressing plasmid were partially protected against syngeneic mammary carcinoma line (S6C) expressing EBNA-4 (S6C-E4). This protection was enhanced by coimmunizing mice with EBNA-4- and GM-CSF-expressing plasmids, and a full protection was achieved by coimmunizing mice with EBNA-4- and IFN-gamma-expressing plasmids. Furthermore, mice that have rejected the EBNA-4-positive tumor were also resistant against a subsequent challenge with the original nontransfected tumor line. We then checked for the ability of pDNA immunization to provide a protective long-term memory response. We indeed found that even after 3 mo from the last immunization, full protection was obtained by this method, as compared with full tumor outgrowth in the control-immunized group. These findings support the concept that a nonviral, pDNA-based vaccination strategy is useful to fully protect from the outgrowth of tumors expressing this EBV gene.

Adenocarcinoma↗
PubMed1999

Loss of heterozygosity in tumor cells requires re-evaluation: the data are biased by the size-dependent differential sensitivity of allele detection.

Normal tissue contamination of tumors may eclipse the detection of loss of heterozygosity (LOH) by microsatellite analysis and may also hamper isolation of tumor suppressor genes. To test the potential impact of this problem, we prepared artificial mixtures of mouse-human microcell hybrid lines that carried different alleles of the same chromosome 3 marker. After performing an allele titration assay, we found a consistent difference between the LOH of a high molecular weight (H) allele and the LOH of a low molecular weight (L) allele of the same CA repeat marker. It follows that normal tissue admixtures will be less of a problem when LOH affects a H allele than with a L allele. Random screening of 100 papers published between 1994 and 1999 revealed that the loss of a L allele was recorded at about half the frequency (52%) of loss of a H allele. To avoid this bias, we have developed rules for the evaluation of LOH data. We suggest that the loss of a L allele should be given more weight than the loss of a H allele in LOH studies using microsatellite markers.

Alleles↗
PubMed1999

Analysis of NotI linking clones isolated from human chromosome 3 specific libraries.

We have partially sequenced more than 1000 NotI linking clones isolated from human chromosome 3-specific libraries. Of these clones, 152 were unique chromosome 3-specific clones. The clones were precisely mapped using a combination of fluorescence in situ hybridization (FISH) and hybridization to somatic cell or radiation hybrids. Two- and three-color FISH was used to order the clones that mapped to the same chromosomal region, and in some cases, chromosome jumping was used to resolve ambiguous mapping. When this NotI restriction map was compared with the yeast artificial chromosome (YAC) based chromosome 3 map, significant differences in several chromosome 3 regions were observed. A search of the EMBL nucleotide database with these sequences revealed homologies (90-100%) to more than 100 different genes or expressed sequence tags (ESTs). Many of these homologies were used to map new genes to chromosome 3. These results suggest that sequencing NotI linking clones, and sequencing CpG islands in general, may complement the EST project and aid in the discovery of all human genes by sequencing random cDNAs. This method may also yield information that cannot be obtained by the EST project alone; namely, the identification of the 5' ends of genes, including potential promoter/enhancer regions and other regulatory sequences

Animals↗
PubMed1999

Epstein-Barr virus genomes are found predominantly in IgA-positive B cells in the blood of healthy carriers.

B lymphocytes have been identified as the main reservoir of latent Epstein-Barr virus (EBV) in healthy virus carriers. We have established a semi-quantitative PCR method to estimate the EBV genome load in the blood B-cell subpopulation in healthy individuals. EBV DNA was detected in subfractionated IgM-, IgG- and IgA-positive B cells. Between 80% and 90% of the viral DNA was found in the IgA-positive compared with the IgA-negative fraction.

B-Lymphocytes↗
PubMed1999

Living anatomy of the atrioventricular junctions. A guide to electrophysiologic mapping. A Consensus Statement from the Cardiac Nomenclature Study Group, Working Group of Arrhythmias, European Society of Cardiology, and the Task Force on Cardiac Nomenclature from NASPE.

Current nomenclature for the atrioventricular (AV) junctions derives from a surgically distorted view, placing the valvar rings and the triangle of Koch in a single plane with antero-posterior and right-left lateral coordinates. Within this convention, the aorta is considered to occupy an anterior position, although the mouth of the coronary sinus is shown as being posterior. Although this nomenclature has served its purpose for the description and treatment of arrhythmias dependent on accessory pathways and atrioventricular nodal reentry, it is less than satisfactory for the description of atrial and ventricular mapping. To correct these deficiencies, a consensus document has been prepared by experts from the Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. It proposes a new anatomically sound nomenclature that will be applicable to all chambers of the heart. In this report, we discuss its value for description of the AV junctions, establishing the principles of this new nomenclature.

Atrioventricular Node↗
PubMed1999

[Effects of inpatient rehabilitation on cardiovascular risk factors in patients with coronary heart disease. PIN-Study Group].

BACKGROUND AND OBJECTIVE: The prognostically favourable effect of secondary prevention in patients with proven coronary heart disease (CHD: documented myocardial infarction, angiographically proven coronary artery stenosis > 60% and/[or] status after coronary artery surgery) has been demonstrated. But it has not been adequately shown to what extent the guidelines laid down by specialist societies is being followed in routine clinical practice. Nor have there been any large-size standardized investigations of whether in-hospital rehabilitation decreases cardiovascular risk factors. It was the aim of this study to investigate the acute effects on cardiovascular risk factors of in-hospital post-infarction rehabilitation. PATIENTS AND METHODS: From January to May 1997, at 18 rehabilitation clinics, 2441 consecutive patients (22% women, aged 65 +/- 10 years, 78% men, aged 60 +/- 10 years) with proven CHD were included in this post-infarction after-care (PIN) study. During their hospital stay (26 +/- 5 days) they undertook physical training appropriate for cardiological follow-up treatment, as well as various other modes of treatment to affect risk factors. Diagnosis, treatment and standardized data were prospectively recorded on admission and discharge. RESULTS: At discharge the proportions of patients with conventionally defined risk factors were significantly lower than on admission (P < 0.001). The proportion was 8% in patients with arterial blood pressure > 140/90 mm Hg (vs. 24% on admission), 5% in smokers (vs. 39% on admission), 30% vs. 60% in patients with cholesterol levels > 200 mg/dl, 67% vs. 87% in those with low density lipids > 100 mg/dl, 15% vs. 22%, in those with serum triglyceride levels > 200 mg/dl, 11% vs. 14% in those with glucose levels > 140 mg/dl, and 15% vs. 18% in patient with a body/mass index > 30 kg/m2. There was an increase in the proportion of patients who during their hospital stay were prescribed additional drugs: from 85% to 86% for acetylsalicylic acid (P < 0.05), 61% to 77% for beta-adrenergic receptor blockers, 33% to 67% for cholesterol synthesis enzyme (CSE) inhibitors, and 51% to 57% for angiotensin converting enzyme (ACE) inhibitors. CONCLUSION: Modifiable cardiovascular risk factors can be reduced by various methods of rehabilitation and more intensive drug treatment during hospitalization. By taking account of evidence-based medicine favourable conditions can be created for longterm ambulant after-care.

Aftercare↗
PubMed1999

Safety of low-density lipoprotein cholestrol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial).

Reduction in plasma lipids has been recognized as one of the primary cardiovascular risk reduction strategies in the secondary prevention of coronary heart disease (CHD). The primary end points of TARGET TANGIBLE were the safety (adverse events and laboratory measurements) and efficacy (responder rates) of therapy with atorvastatin versus simvastatin with the aim of achieving low-density lipoprotein (LDL) cholesterol lowering to < or =100 mg/dl (2.6 mmol/L). A total of 3,748 CHD patients with LDL cholesterol levels > or =130 mg/dl (3.4 mmol/L) entered a run-in diet phase of 6 weeks without any lipid-lowering drug therapy. At the end of the diet phase, 2,856 patients met the lipid criteria and were randomized to active treatment for 14 weeks. Patients received 10 to 40 mg of either drug in an optional titration design at 2:1 randomization for atorvastatin versus simvastatin. Adverse event rates were statistically equivalent (p<0.01) for simvastatin (35.7%) and for atorvastatin patients (36.3%). Both drugs were well tolerated; <5% of patients in both groups were withdrawn due to adverse events. In all, 37 atorvastatin patients (2%) and 27 simvastatin patients (3%) had serious adverse events. Drug-related side effects (elevations in creatine kinase, liver enzymes) occurred in both groups at similar rates with 10 atorvastatin patients (0.5%) and 5 simvastatin patients (0.5%) presenting confirmed transaminase elevations >3 x the upper limit of the normal range. Significantly fewer patients in the atorvastatin group (n = 724) required titration to 40 mg compared with the simvastatin group (n = 514) (38% vs. 54%, respectively; p<0.001). Atorvastatin resulted in a significantly greater number of patients reaching the LDL cholesterol goal than those treated with simvastatin, with 67% of atorvastatin patients and 53% of simvastatin patients reaching the target LDL cholesterol level of < or =100 mg/dl (2.6 mmol/L) (p<0.001). Both atorvastatin and simvastatin are safe for use by patients in the secondary prevention of CHD, with patients in both drug groups having similar adverse event rates. Despite the use of concomitant medications there was no drug-induced rhabdomyolysis with either atorvastatin or simvastatin.

Anticholesteremic Agents↗
PubMed1999

Horizontal transfer of DNA by the uptake of apoptotic bodies.

In this study we have raised the question of whether DNA can be transferred from one cell to another by phagocytosis of apoptotic bodies. We have used integrated copies of the Epstein-Barr virus (EBV) as a marker to follow the fate and expression pattern of apoptotic DNA in the phagocytotic host. Apoptosis was induced in EBV-carrying cell lines by irradiation before cultivation with either human fibroblasts, macrophages, or bovine aortic endothelial cells. Analysis of the expression pattern of EBV-encoded genes was performed by immunofluorescent staining as well as in situ hybridization. Cocultivation of apoptotic bodies from lymphoid cell lines containing integrated but not episomal copies of EBV resulted in expression of the EBV-encoded genes EBER and EBNA1 in the recipient cells at a high frequency. Fluorescence in situ hybridization analysis showed uptake of human chromatin as well as integrated EBV-DNA into the nuclei of bovine aortic endothelial cells. These data show that DNA may be rescued and reused from apoptotic bodies by somatic cells. In addition, our findings suggest that apoptotic bodies derived from EBV-carrying B lymphocytes may serve as the source of viral transfer to cells that lack receptors for the EBV virus in vivo.

Animals↗
PubMed1999

Identification of new tumor suppressor genes based on in vivo functional inactivation of a candidate gene.

As a step towards developing a new functional test for the identification of tumor suppressor genes, human wild type and mutant RB genes were expressed in the mouse A9 fibrosarcoma cell line under the transcriptional regulation of the tetracycline repressor using two new vectors: pLNCtTA and pETI. Following passage of the transfectants in immunodeficient SCID mice, the wild type RB gene was deleted or functionally inactivated already after the first passage in all 20 tumors tested. In contrast, a non-functional mutant RB gene was maintained in all 10 tumors studied. These results suggest that tests for the identification of tumor suppressor genes may be based on their functional inactivation in vivo, rather than on growth suppression.

Animals↗
PubMed1999

Expression of cyclin D2 and D3 in lymphoid lesions.

The D-type cyclins, involved in the regulation of G1 progression of the cell cycle, are expressed in a lineage-specific manner. Normal hematopoietic cells express cyclin D2 and/or D3. In order to determine whether their expression pattern changes in lymphoid tumors, we examined cyclin D2 and D3 expression in non-neoplastic and neoplastic lymphoid lesions, using a sensitive immunohistochemical amplification method. Centroblasts in lymphoid follicles of reactive lymph nodes expressed exclusively cyclin D3 and no D2. Interfollicular areas contained scattered cyclin D3 and D2 positive cells. By double staining, cyclin D3 was detected in CD79a positive B cells, CD3 positive T cells and CD68 positive macrophages. Cyclin D2 was present only in CD3 positive T cells. Neoplastic lymphoid lesions included 33 B cell lymphomas, 9 T cell lymphomas and 12 Hodgkin's lymphomas. The B cell lymphomas comprised 9 follicular lymphomas (FL), 1 Burkitt lymphoma (BL), 22 diffuse large cell lymphomas (DL) and 1 chronic lymphocytic leukemia (CLL). All 9 FLs and the single BL expressed exclusively cyclin D3, similarly to germinal center B cells, that represent their cells of origin. Six DLs expressed both cyclin D2 and D3, while 6 expressed only D3. Among the 9 pleomorphic T cell lymphomas, medium and large cell type, 5 expressed cyclin D2. Cyclin D3 was also detected in scattered cells in 4 of 9 cases and was highly expressed in 2 of 9 T cell lymphomas. The majority of Hodgkin's lymphomas expressed both cyclin D2 and D3 in Hodgkin/Reed-Sternberg (HRS) cells. The high frequency of positive cells indicates that both cyclins were expressed in the same cells.

Adolescent↗