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Biomedical subjects

E Bender

Publications and source records attributed to E Bender.

At least 19 recordsLinked to original sources
PubMed1998

Association between corticosteroid use and vertebral fractures in older men with chronic obstructive pulmonary disease.

Osteoporosis is a major complication of long-term corticosteroid administration, but the magnitude of the effect in patients with chronic obstructive pulmonary disease (COPD) is not well defined. In a cross-sectional study, we evaluated the association between steroid use and vertebral fractures in 312 men, 50 yr of age or older, with COPD. Subjects were evaluated according to their corticosteroid use: Never Steroid Users (NSU) (n = 117), Inhaled Steroid Users (ISU) (n = 70), and Systemic Steroid Users (SSU) (n = 125). The prevalence of one or more vertebral fractures was 48.7% in the NSU group, 57.1% in the ISU group, and 63.3% in the SSU group. Compared with NSU, SSU were two times as likely to have one or more vertebral fractures: age-adjusted odds ratio (OR) = 1.80; 95% CI, 1.08 to 3.07. This relationship was primarily due to a strong association between continuous systemic steroid use and vertebral fractures: age-adjusted OR = 2.36; 95% CI, 1.26 to 4.38. In addition, fractures in SSU were more likely to be multiple and more severe. A weaker relationship existed between inhaled steroid use and vertebral fractures: age-adjusted OR = 1.35; 95% CI, 0.77 to 2.56 compared with NSU. These data indicate that vertebral fractures are common in older men with COPD; the likelihood of these fractures is greatest in those men using continuous systemic steroids.

Administration, Inhalation↗
PubMed1997

Strong indication for a breast cancer susceptibility gene on chromosome 8p12-p22: linkage analysis in German breast cancer families.

Chromosomal losses involving the short arm of chromosome 8 are frequent in a variety of tumor types, including breast cancer, suggesting the presence of one or more tumor suppressor genes in this region. Previous linkage analysis and studies of loss of heterozygosity (LOH) have suggested the presence of a putative third breast cancer susceptibility gene around D8S505 at 8p12-p22. We have performed linkage analysis in two German breast cancer families, showing negative lod scores with 17q and 13q markers, using seven adjacent microsatellite markers from 8p12-p22. Incorporating LOH data from tumors of the affected family members a maximum cumulative three-point lod score of 3.30 at theta = 0.00 was obtained with D8S137 and D8S131. Our findings considerably strengthen the evidence for a third breast cancer susceptibility locus (BRCA3) mapping to the short arm of human chromosome 8.

Adult↗
PubMed1997

BRCA1 mutations and phenotype.

More than 100 mutations have been described for the breast-cancer-susceptibility gene BRCA1. The paper describes phenotypical aspects of three selected mutations located at the beginning, in the middle, and at the end of the gene. A remarkable decrease of the age of diagnosis of the mammary carcinoma is observed with increasing length of the putative gene product, combined with greater severity of the disease.

Adult↗
PubMed1997

[Functional voice quality assessment in curative microsurgery of laryngeal malignancies. Postoperative voice rehabilitation based on the "laryngeal double valve function"].

According to Negus and Pressman the sphincter systems of the vocal folds and the ventricular folds form a respiratory "laryngeal double valve function". Correspondingly, we found a physiological phonation system of the glottis and a pathological-compensatory one of the supraglottis. They appear to be regulated through an automatic phonatory control system with the glottal phonatory function evidently acting as sensor level. In order to confirm this hypothesis, objective voice analyses with glottal-relevant parameters of 26 voice-rehabilitated patients after minimally invasive laser surgery of glottal carcinomas are presented and integrated into a "hoarseness diagram" with the coordinates roughness and breathiness. Using statistically deliminated acoustic dusters, our data show a qualitative hierarchy of different postoperative phonation mechanisms. They demonstrate the influence of the vibratory capacity of glottal and supraglottal structures on the quality of the vibratory closure. Both functional parameters evidently determine the resulting voice quality in the sense of our hypothesis.

Female↗
PubMed1997

Deletion mapping and linkage analysis provide strong indication for the involvement of the human chromosome region 8p12-p22 in breast carcinogenesis.

We have identified a high frequency of loss of heterozygosity (LOH) on the human chromosome region 8p12-p22 in a panel of microdissected familial (86% LOH) and sporadic (74% LOH) breast tumours. The two most frequently deleted regions were defined around marker D8S133 and in a broader centromeric region bounded by markers D8S137 and D8S339. We cannot unequivocally characterize the 8p12-p22 loss as an early or a late event in breast carcinogenesis. In parallel, we have performed linkage analysis in four German breast cancer families. A location score greater than 13.67 corresponding to a LOD score of 2.97 at the marker D8S137 has been obtained. Our results considerably strengthen the evidence for a breast cancer susceptibility gene(s) located on the short arm of the chromosome region at 8p12-p22.

Adult↗
PubMed1997

Cloning and expression of a human serotonin 5-HT4 receptor cDNA.

Using a combination of library screening and nested PCR based on a partial human serotonin 5-HT4 receptor sequence, we have cloned the complete coding region for a human 5-HT4 receptor. The sequence shows extensive similarity to the published porcine 5-HT4A and rat 5-HT4L receptor cDNA; however, in comparison with the latter, we find an open reading frame corresponding to only 388 amino acids instead of 406 amino acids. This difference is due to a frame shift caused by an additional cytosine found in the human sequence after position 1,154. Moreover, we also found the same additional cytosine in the rat 5-HT4 sequence. We confirmed the occurrence of the sequence by examining this part of the sequence in genomic DNA of 10 human volunteers and in rat genomic DNA. Based on a part of the genomic 5-HT4 receptor sequence that was identified in the cloning process, there seem to be at least two possible splice sites in the coding region of the gene. The human 5-HT4 receptor, transiently expressed in COS-7 cells, showed radioligand binding properties similar to 5-HT4 receptors in guinea pig striatal tissue. [3H]GR 113808 revealed K(D) values of 0.15 +/- 0.01 nM for the human receptor and 0.3 +/- 0.1 nM in the guinea pig tissue. Binding constants were determined for four investigated 5-HT4 antagonists and three agonists, and appropriate binding inhibition constants were found in each case. Stimulation of transfected COS-7 cells with 5-HT4-specific agonists caused an increase in cyclic AMP levels.

Amino Acid Sequence↗
PubMed1996

BRCA1 mutations in German breast-cancer families.

We analyzed germline mutations of the BRCA1 gene in 20 German breast/ovarian-cancer families. BRCA1 mutations co-segregating with breast-cancer susceptibility were identified in 3 of these families. All mutations were found to generate a premature stop codon leading to the synthesis of truncated BRCA1 proteins of different length. Nine polymorphisms were detected in BRCA1, 4 of which have not been described previously. Analysis of familial tumors for LOH revealed that only the disease-related allele of BRCA1 was present.

Adult↗
PubMed1996

Inhibition of experimental liver metastasis by combined treatment with tamoxifen and interferon.

The demonstration of estrogen receptors (ERs) in the liver has established it as a hormonally responsive organ. Estrogens have been imputed to have a role in the development of benign and malignant liver tumors. The detection of ERs in samples of normal liver tissue and in hepatocellular carcinomas suggested a treatment strategy with anti-hormonal drugs, i.e. tamoxifen, as used clinically for the treatment of breast cancer. The objective of this study was to test the effect of tamoxifen and tamoxifen in combination with other agents [5-fluorouracil (5-FU) and interferon (IFN)] against experimental liver metastases of human colorectal tumor cells xenografted into nude mice. A human colorectal tumor cell line, LoVo, was injected into the spleens of nude mice. This produces liver metastases in virtually 100% of the mice in 6-8 weeks. One week before tumor cell implantation, all mice were ovariectomized. Treatment was started 3 days after the intrasplenic injections. This consisted of 5 mg tamoxifen pellets (60-day release) implanted s.c., 5-FU given i.p. once a week for 4 weeks on a 46 mg/kg basis and IFN given s.c., daily for 4 weeks, 3 x 10(5) units/injection. The effect of tamoxifen alone on liver metastases was not significantly different from untreated controls. Tamoxifen in combination with IFN and 5-FU, however, resulted in 50-67% inhibition of liver metastases, as compared with the controls. The effectiveness of the treatment was in the order: tamoxifen + IFN > tamoxifen + 5-FU + IFN > tamoxifen + 5-FU. Thus, IFN may be useful as a potentiating agent in combination with tamoxifen for the treatment of estrogen-dependent tumors.

Adenocarcinoma↗
PubMed1994

Human monoclonal Fab fragments from a combinatorial library prepared from an individual with a low serum titer to a virus.

An IgG1k lambda Fab library was generated on the surface of phage beginning with bone marrow RNA from a healthy 22-year-old human donor. The donor had been immunized to measles in his early childhood but had only a low serum titer to a measles antigen preparation. The resulting library of approximately 10(7) clones was panned against the measles antigen preparation and three positive Fab-producing clones identified by ELISA. One of the Fabs was found to be specific to measles and to bind with high apparent affinity (10(8) M-1). The other two bind with lower affinity and show marked cross-reactivity with a number of other antigens. They possess heavy chains derived, with extensive somatic modification, from the single member gene family VH6. The study indicates that both high-affinity specific antibodies and lower affinity polyreactive antibodies can be derived from the library approach under appropriate conditions.

Adult↗
PubMed1994

[Limits of osseous reconstruction of the mandible with autologous spongiosa, hydroxyapatite granules and titanium mesh, especially after radiotherapy].

Over the past twenty years the titanium mesh combined with autologous iliac crest spongiosa and hydroxylapatite has performed well in the restoration of mandibular discontinuity defects in 79 patients. In 14 irradiated patients with a transplant bed of inferior quality, however, complications and failures occurred more often than in the 65 not irradiated patients. The results of our investigation clearly show, that the success of mandibular reconstruction mainly depends on a well vascularized transplant bed.

Adult↗
PubMed1993

Linkage analysis in German breast cancer families with early onset of the disease, using highly polymorphic markers from the chromosome 17q11-q24 region.

Linkage analysis in German breast cancer families with early onset of the disease by using six markers on chromosome 17q11-q24 has been carried out. In the region between markers D17S250 and GH, three markers showed positive LOD scores at an estimated distance of zero. Evidence for linkage is greatest for D17S250, with a LOD score of 2.42.

Adult↗
PubMed1993

Recombinant human antibodies: linkage of an Fab fragment from a combinatorial library to an Fc fragment for expression in mammalian cell culture.

The combinatorial phage library approach to immunoglobulin repertoire cloning recently made it possible to isolate gene fragments encoding human immunoglobulin G1 Fabs binding with high affinity to specific antigens. Here we describe the construction of genes encoding whole human anti-tetanus toxoid antibodies based on one of these gene fragments and the efficient expression of these constructs by co-transfection of separate heavy and light chain vectors into a Chinese hamster ovary cell line constitutively expressing a viral transactivator protein. This system will be generally useful for the rapid analysis of recombinant antibodies derived from combinatorial libraries.

Amino Acid Sequence↗
PubMed1990

Secretory synthesis of human interleukin-2 by Streptomyces lividans.

To study the ability of Streptomyces lividans to produce heterologous proteins by secretion, we directly fused DNA encoding the leader peptide of the alpha-amylase inhibitor, tendamistat, produced by Streptomyces tendae, with DNA encoding the mature part of interleukin-2 (IL-2). Such cloned fusion constructs are translated in S. lividans, in spite of the quite different codon usage. The active Il-2 is secreted into the culture broth, though the amounts are much less than that of the alpha-amylase inhibitor. The presence of IL-2 in the supernatants could be demonstrated both by an activity assay and by immunoblotting. In addition to the secreted form, three different species of Il-2 antibody immunoreactive proteins, with different Mrs, are either present in the cells or attached to the cells. This indicates that inefficient processing and translocation of the precursor is a major reason for the low activities found in the supernatant.

Base Sequence↗
PubMed1990

Synthesis and secretion of hirudin by Streptomyces lividans.

To examine the secretory production of heterologous proteins by Streptomyces lividans, we fused the DNA encoding the signal peptide of the alpha-amylase inhibitor tendamistat, derived from S. tendae with a synthetic gene encoding the thrombin inhibitor hirudin. The analysis of secretion by immunoblots revealed an efficient translocation of hirudin through the membrane, with no detectable immunoreaction among the cellular proteins. The secreted hirudin was stable in the shaking culture for about 6 days. A comparison of the hirudin secreted by S. lividans and recombinant reference hirudin from yeast by immunoblots and thrombin inhibition assays shows that hirudin from Streptomyces has a lower specific activity, which may be due to a different aminoterminal sequence or to inexact processing of the precursor.

Amino Acid Sequence↗
PubMed1990

[The use of 60Co-gamma ray-sterilized calf serum in cell culture].

The use of 60Co-gamma-radiation-sterilised calf sera in cell culturing is reported in this paper. Evidence was produced to the effect that 60Co-gamma-irradiation, using a dosage of 3 kGy and a dose rate of 8 kGy/h, of fetal calf serum, neonatal calf serum, and calf serum did not substantially alter the growth-stimulating properties of those sera during 42-day tests. With almost all cell lines and sera used, for all practical purposes, they were identical with the properties of control sera. The following cell lines were used in the experimental programme: one human mammary tumor, MaTu, one human embryonic cell line--E VI, one bat lung cell line--Tb1-Lu, and one human rhabdomyosarcoma--A 204. Growth stimulation was twelve percent below the control value only with Tb1-Lu on Eagle-MEM culturing medium with 3-kGy-irradiation of neonatal calf serum. On the other hand, cell growth was stimulated by 28 percent in A 204 on RPMI 1640 culturing medium, again with 3-kGy-irradiation of neonatal calf serum. Loss of activity by up to 30 percent, depending on the serum used, must be expected from irradiation doses of 10 kGy and 20 kGy which are capable of causing drastic reduction or even complete elimination of serum-borne microorganisms (Bender et al., 1989). Sera irradiated that way would be only conditionally applicable, when it comes to highly vulnerable cell strains.

Animals↗