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Biomedical subjects

G Schaefer

Publications and source records attributed to G Schaefer.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence of erectile dysfunction among middle-aged men in a metropolitan area in Germany.

The comparison of results of previous studies on the prevalence of erectile dysfunction is hampered due to differences in study design and research instruments including definitions used. The aim of the study was to determine the prevalence of erectile dysfunction/erectile disorder (ED) using different definitions. An epidemiological cross-sectional study was conducted between May and November 2002 in Berlin, Germany. A total of 6000 men between 40 and 79 years of age were randomly selected by the Berlin Office of Vital Statistics and were sent a questionnaire by mail. The prevalence of ED was determined using five different methods. A total of 1915 questionnaires were eligible for analysis. The five different definitions yielded age-adjusted ED prevalence rates between 18 and 48%. Age was strongly correlated with all five definitions (P<0.001). These results indicate the need for standardized criteria when conducting future studies on ED and may aid in designing public health and clinical management strategies.

Adult↗
PubMed2001

Cutting edge: FISP (IL-4-induced secreted protein), a novel cytokine-like molecule secreted by Th2 cells.

Th cell subsets, namely Th1 and Th2 cells, play an important role in mounting an immune response against invading pathogens. Several genes are selectively up-regulated during differentiation and effector phases of Th subsets. In this study, we report the identification of a novel cytokine-like molecule designated FISP (IL-4-induced secreted protein), which is selectively expressed and secreted by Th2 cells. Detectable levels of FISP are observed only 3 days after initiation of Th2 differentiation. Expression of FISP in developing Th cells requires at least two signals: TCR signaling involving protein kinase C activation and STAT6-dependent IL-4R signaling.

Amino Acid Sequence↗
PubMed2001

Angiogenesis in prostate cancer: biology and therapeutic opportunities.

Tumor growth is limited in size without the incorporation of new blood vessels. Tumor cells release soluble factors (angiogenic factors) that induce neovascularization and allow subsequent growth beyond 2-3 mm in diameter meeting the need for cellular uptake of oxygen and nutrients. This process is referred to as the 'angiogenic switch' and indicates the acquisition of an angiogenic phenotype. Tumor angiogenesis requires an imbalance between proangiogenic and antiangiogenic factors with formation of new vessels being a highly regulated process. In this review we discuss the mediators of angiogenesis, the strategies for manipulating angiogenic factors, and possible therapeutic applications with a special emphasis on prostate cancer.

Angiogenesis Inducing Agents↗
PubMed2001

Interactions between 2-fluoroadenine 9-beta-D-arabinofuranoside and the kinase inhibitor UCN-01 in human leukemia and lymphoma cells.

Interactions between the purine analogue 2-fluoroadenine 9-beta-D-arabinofuranoside (F-ara-A) and the kinase inhibitor UCN-01 have been examined in human leukemia cells (U937 and HL-60) with respect to induction of mitochondrial damage, caspase activation, apoptosis, and loss of clonogenic survival. Simultaneous or subsequent exposure of F-ara-A-treated cells (2 microM) to UCN-01 (100 nM) resulted in a marked potentiation of apoptosis, manifested by loss of mitochondrial membrane potential (delta psi(m)), cleavage/activation of procaspase-9 and procaspase-3, DNA fragmentation, and degradation of poly-ADP(ribosyl) polymerase. Coadministration of UCN-01 with F-ara-A was also associated with diminished phosphorylation of the cdc25 phosphatase. In contrast, exposure of cells to the sequence UCN-01, followed by F-ara-A, resulted in only a modest increase in apoptotic cells. The ability of UCN-01 to potentiate F-ara-A-mediated lethality was not mimicked by the selective PKC inhibitor bisindolylmaleimide, nor did treatment of cells with UCN-01 enhance formation of F-ara-ATP or increase incorporation of [3H]F-ara-A into DNA. Enhanced apoptosis in cells exposed sequentially or simultaneously to F-ara-A and UCN-01 was accompanied by a substantial reduction in colony formation (e.g., to 0.01% of control values). Cotreatment with UCN-01 also increased F-ara-A-mediated apoptosis and loss of delta psi(m) in U937 cells ectopically expressing Bcl-2, although not to the same extent as that observed in empty-vector controls. Finally, simultaneous exposure (24 h) of malignant B lymphocytes from the pleural effusion of a patient with indolent non-Hodgkin's lymphoma to F-ara-A and UCN-01 ex vivo resulted in a striking increase in apoptosis, as determined by terminal deoxynucleotidyltransferase-mediated nick end labeling assay. These findings indicate that UCN-01 increases F-ara-A-induced mitochondrial damage and apoptosis in human leukemia cells in a sequence-dependent manner, and that these events occur in at least some primary human lymphoma cells.

Alkaloids↗
PubMed2001

Structural requirements for ErbB2 transactivation.

ErbB2 is a unique member of the ErbB family of receptor tyrosine kinases that is distinguished by the fact that no ligand has yet been identified. Due to the absence of an ErbB2 ligand, alternative mechanisms are used for ErbB2 activation. As such, when ErbB2 is overexpressed, kinase activation occurs in the absence of ligand because of constitutive homodimerization. However, at normal expression levels ErbB2 acts as the shared coreceptor for the ErbB family, and these heterodimeric complexes are activated in response to the partner ligand. While the extracellular domain and transmembrane domains are necessary for ErbB2 transactivation, the carboxy terminus is also required. Specifically, ligand-dependent ErbB2 transactivation requires a discrete three-amino-acid segment, located at the C-terminus of ErbB family members ErbB3, ErbB4, and the epidermal growth factor receptor. Transactivation of ErbB2 via the three-amino-acid segment likely represents a conserved mechanism for regulated signaling by the ErbB family of receptors.

Amino Acid Sequence↗
PubMed2000

Cutting edge: Chandra, a novel four-transmembrane domain protein differentially expressed in helper type 1 lymphocytes.

Development of naive Th cells into Th1 and Th2 effector populations requires coordinated expression of a complex set of genes. In this study, we have identified a novel four-transmembrane domain protein, Chandra, that is differentially expressed in Th1 cells. Chandra expression is observed in STAT4- and IFN-gamma-deficient mice, indicating that Chandra is not an IL-12- or IFN-gamma-responsive gene. Interestingly, Chandra mRNA is detected in anti-CD3-activated T cells from STAT6-deficient mice in the absence of any differentiation conditions. Furthermore, neutralization of IL-4 signaling is sufficient to induce transcription of Chandra in anti-CD3-activated T cells from wild-type mice, demonstrating that STAT6 signaling is required to repress Chandra expression in activated T cells and Th2 subsets. This is the first demonstration of a differentially expressed four-transmembrane domain protein in Th1 cells.

Amino Acid Sequence↗
PubMed1999

A discrete three-amino acid segment (LVI) at the C-terminal end of kinase-impaired ErbB3 is required for transactivation of ErbB2.

ErbB3 is unique among other members of the receptor tyrosine kinase family of growth factor receptors in that its kinase domain is enzymatically impaired. This renders it incapable of transducing a signal in response to ligand binding. However, in conjunction with ErbB2, ErbB3 is a potent mediator of signaling by the growth factor heregulin. Heregulin binding to ErbB3 induces formation of a heterodimeric complex with ErbB2, and this results in transactivation of the ErbB2 kinase. Although interaction between the extracellular domains of these receptors is an essential part of this process, it was not clear whether interaction between the cytoplasmic domains is also necessary for transactivation. By examining the abilities of a series of cytoplasmic domain mutants of ErbB3 to activate ErbB2, we have found a discrete sequence of three amino acid residues (LVI), located at the carboxyl-terminal end of the impaired ErbB3 kinase region, that is obligatory for transactivation. We conclude that formation of a functional ErbB2-ErbB3 signaling complex requires the presence of a specific structural feature within the ErbB3 cytoplasmic domain and suggest that ErbB2 transactivation results from a physical interaction between the cytoplasmic domains of these receptors.

Amino Acid Sequence↗
PubMed1997

Serial in vivo passage of HIV-1 infection in Macaca nemestrina.

In an earlier study we found that pigtailed macaques (Macaca nemestrina) that were experimentally infected with human immunodeficiency virus type 1 (HIV-1) initially became viremic and seroconverted, but HIV-1 replication diminished markedly over time. In an attempt to develop a longer term pathogenic model, blood from HIV-1-infected macaques was serially transfused into three groups of naive macaques. Transfer was successful through two transfusions as shown by repeated virus isolations and confirmed by the development of cell-free plasma viremia and by seroconversion. Three to five weeks after transfusion, plasma levels of HIV-1 RNA from several macaques in the first two groups exceeded those of the initially inoculated macaques. However, animals in the third group had diminished RNA levels, were virus culture negative, and did not seroconvert. Sequence analyses of env-region clones from infected animals revealed only minimal changes over the course of the passages. These results confirm HIV-1 replication in M. nemestrina during the acute phase of infection. However, adaptation of HIV-1 to a macaque-pathogenic variant did not occur during serial passage, possibly because the animals were able to restrict HIV-1 replication below a level required for a pathogenic variant to emerge. Whether such containment is a function of the host's immune response or a virus cell incompatibility remains to be determined.

Adaptation, Physiological↗
PubMed1997

Gamma-heregulin: a novel heregulin isoform that is an autocrine growth factor for the human breast cancer cell line, MDA-MB-175.

A novel neuregulin isoform, termed gamma-HRG, was cloned and characterized from the human breast cancer cell line, MDA-MB-175. As observed with other neuregulins, gamma-HRG, is a product of alternative mRNA splicing of the neuregulin gene. Gamma-HRG contains the EGF-like and immunoglobulin-like domains that are commonly found in other family members, but lacks a transmembrane and cytoplasmic region. The new isoform possesses a unique N-terminal region that includes a hydrophobic domain that may function as a secretion signal. A purified recombinant version of gamma-HRG competes for binding to soluble ErbB3- and ErbB4-IgG fusion proteins with affinities similar to those observed for rHRGbeta1(177-244). Gamma-HRG has a wide distribution in mesenchymal or neuronal tissues but in contrast to other neuregulins, it is not present in breast, lung, liver and small intestine. Expression of gamma-HRG with its cognate receptors, ErbB3 and ErbB2 suggested that the growth of the MDA-MB-175 cell line might be a result of the autocrine stimulation of a growth factor signaling pathway. Treatment of MDA-MB-175 cells with an anti-ErbB2 monoclonal antibody that interferes with the ligand-dependent formation of ErbB2-ErbB3 heterodimer complexes shows a strong growth inhibitory effect on this cell line. Moreover, incubation with a receptor-IgG fusion protein that neutralizes secreted gamma-HRG, also inhibits cell growth. These data suggest that the secretion of gamma-HRG by MDA-MB-175 cells leads to the formation of a constitutively active receptor complex and stimulates the growth of these cells in an autocrine manner.

Alternative Splicing↗
PubMed1997

Identification of two homologs of the Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species.

Simian retroperitoneal fibromatosis (RF) is a vascular fibroproliferative neoplasm which has many morphological and histological similarities to human Kaposi's sarcoma (KS). Like epidemic KS in AIDS patients, RF is highly associated with an immunodeficiency syndrome (simian acquired immunodeficiency syndrome [SAIDS]) caused by a retrovirus infection. Recently, a new gammaherpesvirus, called Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), has been identified in KS tumors, suggesting that KS has a viral etiology. Our previous experimental transmission studies and epidemiological data suggest that RF also has an infectious etiology. In order to determine whether a similar virus is also associated with RF, we have assayed for the presence of an unknown herpesvirus using degenerate PCR primers targeting the highly conserved DNA polymerase genes of the herpesvirus family. Here we provide DNA sequence evidence for two new herpesviruses closely related to KSHV from RF tissues of two macaque species, Macaca nemestrina and Macaca mulatta. Our data suggest that KSHV and the putative macaque herpesviruses define a new group within the subfamily Gammaherpesvirinae whose members are implicated in the pathogenesis of KS and KS-like neoplasms in different primate species.

Amino Acid Sequence↗
PubMed1996

A putative signal recognition particle receptor alpha subunit (SR alpha) homologue is expressed in the hyperthermophilic crenarchaeon Sulfolobus acidocaldarius.

A 1.64 kb genomic DNA sequence from the hyperthermophilic crenarchaeon Sulfolobus acidocaldarius is composed of two adjacent genes. The first functionally unassigned open reading frame (orf-1) comprises 450 base pairs. The second 1.1 kb large open reading frame encodes the putative signal recognition particle receptor alpha subunit (SR alpha). Both genes are expressed under the heterotrophic growth conditions of the organism. The main transcript of orf-1 appears as a monocistronic RNA in Northern hybridization. With regard to SR alpha the transcription pattern was investigated by reverse transcription polymerase chain reaction and primer extension analysis. A polyclonal antiserum directed against E. coli lacZ'/Sulfolobus SR alpha fusion protein detects a 40.5 kDa protein (p41) in agreement with the 41.4 kDa as deduced from the nucleotide sequence.

Base Sequence↗
PubMed1994

Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin.

The heregulin/neu differentiation factor gene products were purified and cloned based on their ability to stimulate the phosphorylation of a 185-kDa protein in human breast carcinoma cell lines known to express erbB2. However, not all cells that express erbB2 respond to heregulin, indicating that other components besides erbB2 may be required for heregulin binding. Cells that are transfected with the closely related receptor, erbB3, display a single class of lower affinity heregulin binding sites than has been previously observed on breast carcinoma cell lines. Little or no stimulation of tyrosine phosphorylation in response to heregulin occurs in cells that are transfected with erbB3 alone. Transfection of cells with erbB3 and erbB2 reconstitutes a higher affinity binding receptor, which is also capable of generating a tyrosine phosphorylation signal in response to heregulin. A monoclonal antibody to erbB2 will inhibit heregulin activation of tyrosine phosphorylation and binding in cells transfected with both receptors but not with erbB3 alone. In cells expressing erbB2 and erbB3, both proteins become tyrosine-phosphorylated upon interaction with heregulin. Direct interaction between heregulin and the two proteins was demonstrated by chemical cross-linking experiments using 125I-heregulin followed by immunoprecipitation with antibodies specific for erbB2 or erbB3.

Animals↗
PubMed1984

Acquired von Willebrand's disease in the myeloproliferative syndrome.

An acquired hemorrhagic disorder developed in two patients in association with postsplenectomy thrombocytosis and leukocytosis during the course of the myeloproliferative syndrome. The presence of acquired von Willebrand's disease in these individuals was demonstrated by a decrease or absence of the larger von Willebrand factor (vWF) multimers, alteration of the repeating vWF multimeric "triplet," decreased ristocetin cofactor activity (vWF:RCo), and prolonged bleeding time. The bleeding stopped in both patients after treatment with either 1-deamino-[8-D-arginine]-vasopressin (DDAVP) or Cohn fraction I. Treatment with thrombocytapheresis and azathioprine or busulfan resulted in reduction of the elevated platelet and white cell counts and was associated with partial correction of the vWF abnormalities and remission of the hemostatic abnormalities. In five additional patients with the myeloproliferative syndrome, but without bleeding symptoms, large multimers of plasma vWF were diminished also. These findings suggest that acquired von Willebrand's disease should be considered when a bleeding diathesis develops during the course of the myeloproliferative syndrome.

Adult↗
PubMed1984

Breast carcinoma in elderly women: pathology, prognosis, and survival.

There is a widely held belief that breast carcinoma occurring in elderly women is characterized by a relatively favorable prognosis and unusual histologic types of tumors. To assess these topics in a single patient group, 169 women (greater than or equal to 75 years) treated by mastectomy for primary operable breast carcinoma at Memorial Hospital (1964 to 1970) were identified. Followup revealed that 117 patients (70 percent) died. Thirty-eight women (22 percent) developed recurrent breast carcinoma and 35 (21 percent) were known to have died of the disease. Death was attributable to a cause other than breast carcinoma in 82 cases (49 percent). Remaining alive were 48 patients (28 percent) including 3 with recurrent carcinoma. Four patients (2 percent) were lost to followup. The age-adjusted survival experience of our elderly breast cancer patients was significantly poorer than that of a standard population when compared by the life table method. This difference appeared largely to reflect the mortality effect of breast cancer. Median times to recurrence (25 mo) and to death from breast carcinoma (27 mo) were not prolonged. Pathologic analysis revealed that some tumor types with a relatively favorable prognosis (mucinous, papillary, infiltrating lobular) occur more often in elderly women. However, this probably has little bearing on overall prognosis in the group since infiltrating duct carcinoma which constitutes nearly three-quarters of the tumors was responsible for 86 percent of deaths due to breast carcinoma.

Axilla↗
PubMed1977

Retropsoas and subgluteal abscesses following paracervical and pudendal anesthesia.

Retroperitoneal abscesses are uncommon in obstetrics and gynecology. Recently, seven reported cases of retropsoas-subgluteal abscesses following paracervical-pudendal anesthesia have been reported, and we have seen two additional cases. The infrequent occurrence and diagnostic difficulties make these abscesses especially dangerous. They can result in substantial patient morbidity and mortality. They must be suspected in patients receiving paracervical-pudendal anesthesia prior to vaginal delivery in whom hip pain subsequently develops. Therapy consists of prompt surgical exploration and drainage and appropriate antibiotic therapy.

Abscess↗
PubMed1975

Pregnancy and pulmonary tuberculosis.

There are 1565 premature and full-term deliveries in patients with tuberculosis at The New York Hospital included in this report. About 10% of the patients had active pulmonary tuberculosis immediately before or during gestation. The obstetric management of the patient with inactive tuberculosis is similar to that of the nontuberculous woman. In patients with active or recently active tuberculosis, delivery under regional anesthesia, with forceps when necessary to avoid excessive straining during the second stage of labor, is advised. Tuberculosis is not an indication for cesarean section. Chemotherapy is now the cornerstone of all therapy for tuberculosis; the various regimens and modifications depend on the type and extent of the disease. The best combination of drugs is isoniazid and ethambutol. Therapy in all cases must be multiple drug, continuous, and long-term. Prophylactic isoniazid is used infrequently during pregnancy and only in special circumstances. Results of treatment with the newer antituberculosis drugs show that the disease progressed in less than 1% of patients between 1957 and 1972 compared to 3 to 4% of patients from 1933 to 1956. Infants born to the 1565 tuberculous mothers reported here were of average weight, and none of the 1588 infants (23 sets of twins) had congenital tuberculosis. Patients should be carefully followed postpartum with sputum tests and x-rays. They should also be given medical and socioeconomic counseling.

Antitubercular Agents↗