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Biomedical subjects

C Sander

Publications and source records attributed to C Sander.

At least 19 recordsLinked to original sources

[Dermato-oncological rehabilitation].

National insurance companies in Germany support health cures for patients with malignant tumors (malignant melanoma, squamous cell carcinoma, Merkel cell tumor, malignant cutaneous lymphoma). The clinical requirements are an invasively growing tumor, problems of self-assurance, and dis-integration of the patient regarding his social and/or professional environment. The decision for a health cure is made by the treating dermatologist in the hospital. In this context, the following sociomedical criteria should be applied: impairment, disability, and handicap. Usually, rehabilitation starts after the patient is discharged from the hospital. The inpatient rehabilitation program should be performed at an institution capable of providing dermatological and psychological treatment. The dermatologist acts as a manager for the members of the rehabilitation team (psychologists, physiotherapists, social workers, and ergo-therapists). In conclusion, dermato-oncologic rehabilitation plays an important role in re-integrating the patient into his professional life to avoid retirement.

Combined Modality Therapy↗

Reversal of established delayed type hypersensitivity reactions following therapy with IL-4 or antigen-specific Th2 cells.

Delayed-type hypersensitivity reactions (DTHR) are mediated by IFN-gamma-producing CD4+ (Th1) or CD8+ T cells (Tc1) and can be prevented by steering T cells toward an IL-4-producing Th2 or Tc2 phenotype. It is currently accepted that T cells can be directed toward a Th2 or Tc2 phenotype only during the initiation of an immune response. Once established, the cytokine pattern of immune reactions is believed to be stable. Therefore, inhibition of DTHR by the induction of Th2/Tc2 responses, termed immune deviation, is considered only as a prevention but not as a therapy of harmful DTHR. Here we demonstrate that therapeutic immune deviation can reverse established contact hypersensitivity (CHS), a Th1/Tc1-mediated DTHR. One or two weeks after induction of CHS, mice received either a single cycle of IL-4 therapy or adoptive transfer of antigen-specific Th2 cells. This treatment generated a novel state of immunity that provided long-lasting protection against tissue destruction and neutrophil recruitment during subsequent antigen exposures. Therapeutic immune deviation of established CHS was dependent on CD4+ T cells and the induction of endogenous IL-4 synthesis. Thus, a population of immunoregulatory Th2 cells persists during advanced inflammatory responses that can be used for therapeutic deviation of established DTHR.

Adoptive Transfer↗

Quantitation of human herpes virus 8 DNA in paraffin-embedded biopsies of HIV-associated and classical Kaposi's sarcoma by PCR.

BACKGROUND: Kaposi's sarcoma occurs in patients seropositive and seronegative for the human immunodeficiency virus (HIV) and has been associated with human herpes virus 8 (HHV8). The purpose of this study was to determine and to compare the amount of HHV8 DNA in formalin-fixed tissue sections of Kaposi's sarcoma. METHODS: From 27 biopsies of Kaposi's sarcoma patients, tissue sections were taken and deparaffinized. Four patients were HIV seronegative and 13 were HIV seropositive. After extraction of DNA copy numbers of HHV8 and beta-globin were determined in every sample by quantitative PCR ELISA using an internal quantitation standard. Results were expressed as HHV8 per beta-globin. RESULTS: No significant differences were found between biopsies from HIV-positive and HIV-negative patients (14.8+/-19.6 HHV8 per 1000 beta-globin in HIV-positive versus 18.0+/-23.5 in HIV-negative patients). CONCLUSIONS: These data suggest that HHV8 viral load in Kaposi's sarcoma is relatively low and does not differ in HIV-positive and HIV-negative samples. The importance of viral load determination for prognosis or treatment monitoring remains to be elucidated.

AIDS-Related Opportunistic Infections↗

Completeness in structural genomics.

Structural genomics has the goal of obtaining useful, three-dimensional models of all proteins by a combination of experimental structure determination and comparative model building. We evaluate different strategies for optimizing information return on effort. The strategy that maximizes structural coverage requires about seven times fewer structure determinations compared with the strategy in which targets are selected at random. With a choice of reasonable model quality and the goal of 90% coverage, we extrapolate the estimate of the total effort of structural genomics. It would take approximately 16,000 carefully selected structure determinations to construct useful atomic models for the vast majority of all proteins. In practice, unless there is global coordination of target selection, the total effort will likely increase by a factor of three. The task can be accomplished within a decade provided that selection of targets is highly coordinated and significant funding is available.

Algorithms↗

Genome sequences and great expectations.

To assess how automatic function assignment will contribute to genome annotation in the next five years, we have performed an analysis of 31 available genome sequences. An emerging pattern is that function can be predicted for almost two-thirds of the 73,500 genes that were analyzed. Despite progress in computational biology, there will always be a great need for large-scale experimental determination of protein function.

Animals↗

Genomic medicine and the future of health care.

Genomic technologies and computational advances are leading to an information revolution in biology and medicine. Simulations of molecular processes in cells and predictions of drug effects in humans will advance pharmaceutical research and speed up clinical trials. Computational prognostics and diagnostics that combine with genotyping and molecular profiling may soon cause fundamental changes in the practice of health care.

Clinical Trials as Topic↗

Analysis of the TCRBV repertoire of T cells in normal, human skin: evidence for a restricted diversity.

Alpha beta T cells constitute an important component in the first line of immunologic defense in human skin. In order to determine the local selection forces driving T cell diversity, we studied the T cell receptor repertoire in normal human skin and compared it with that of matched blood samples. Using semiquantitative reverse transcription-polymerase chain reaction the expression of T cell receptor beta-chain V genes was determined. The majority of skin, but not blood T cells, revealed a bias towards usage of T cell receptor beta-chain V2 and V6. Whereas sequencing of T cell receptor beta-chain V2 and V6 polymerase chain reaction products showed a heterogeneous clonal distribution within these beta-chain V gene families, the analysis of other selected either over- or underrepresented beta-chain V gene families (BV3, BV12, BV13S1, BV17) revealed numerous identical T cell receptor beta-chain V transcript sequences that were not detected in blood. Restricted T cell receptor diversity in terms of beta-chain V gene preferences or clonal expansion was observed in skin samples of donors from all ages (0.5-87 y). Hence, the repertoire of T cells in normal human skin is apparently subjected to skin-specific selection throughout life. According to our data, this process could involve superantigens, which favor polyclonal accumulation of T cells using certain beta-chain V genes, as well as antigens, which induce clonal T cell expansion. Our results furthermore indicate, that T cell receptor beta-chain V repertoire restrictions do not necessarily result from disease-associated activation of the skin immune system, but could reflect regular mechanisms of immunologic homeostasis within the epithelial surface of the body.

Adolescent↗

CAST: an iterative algorithm for the complexity analysis of sequence tracts. Complexity analysis of sequence tracts.

MOTIVATION: Sensitive detection and masking of low-complexity regions in protein sequences. Filtered sequences can be used in sequence comparison without the risk of matching compositionally biased regions. The main advantage of the method over similar approaches is the selective masking of single residue types without affecting other, possibly important, regions. RESULTS: A novel algorithm for low-complexity region detection and selective masking. The algorithm is based on multiple-pass Smith-Waterman comparison of the query sequence against twenty homopolymers with infinite gap penalties. The output of the algorithm is both the masked query sequence for further analysis, e.g. database searches, as well as the regions of low complexity. The detection of low-complexity regions is highly specific for single residue types. It is shown that this approach is sufficient for masking database query sequences without generating false positives. The algorithm is benchmarked against widely available algorithms using the 210 genes of Plasmodium falciparum chromosome 2, a dataset known to contain a large number of low-complexity regions. AVAILABILITY: CAST (version 1.0) executable binaries are available to academic users free of charge under license. Web site entry point, server and additional material: http://www.ebi.ac.uk/research/cgg/services/cast/

Algorithms↗

Early detection of lymph node metastases by 7.5 MHz-ultrasound examination in a patient with primary malignant melanoma of the lung.

Primary malignant melanoma of the lung (PMML) is a rare neoplasm that may be misdiagnosed as one of the more common types of lung cancer. Most cases are characterized by a very poor prognosis, ultimately leading to the patient's death. Since an optimal systemic treatment schedule is not established so far, early detection of lymph node metastases may be important for surgical interventions. We report on a 55-year-old male patient with a primary bronchial malignant melanoma of his left lower lobe that was treated by pneumonectomy. 11 and 17 months after removal of the PMML, suspicious lymph nodes in the patient's left axilla were identified by 7.5 MHz-ultrasound examinations. Again surgical treatment was performed and histopathology showed lymph node metastases of malignant melanoma. During adjuvant therapy with interferon alpha (3 x 6 Mio IE per week) no further relapse has been observed with a follow-up of 8 months after the last operation. An overview of primary melanoma of the lung is given and diagnostic options are discussed. The 7.5 MHz-ultrasound examination appears to be especially helpful in the early detection of lymph node metastases leading to early initiation of surgical treatment possibly associated with a prolonged survival in our patient.

Antineoplastic Agents↗

Mast cells in an angiosarcoma complicating xeroderma pigmentosum in a 13-year-old girl.

A cutaneous angiosarcoma, a rare tumor that occurs almost exclusively in sun-exposed skin of individuals older than 50 years, developed in an adolescent with Xeroderma pigmentosum (XP). As this is the second report of a child with angiosarcoma and XP, ultraviolet-induced DNA damage may be involved in the pathogenesis of this tumor. Strongly increased numbers of mast cells were found, particularly in the peripheral tumor area, which may reflect with the requirement of mast cells for the growth of vascular structures or a role for mast cells in the antitumor immune response.

Adolescent↗

[Metastases in malignant melanoma despite histologically negative sentinel lymph node: should the concept be changed?].

AIM: The Sentinel Lymph Node (SLN) is of considerable prognostic relevance, because extended lymph node dissection may not be performed in patients presenting with histologically negative SLN. The aim of the present study was to prove the prognostic value of the SLN-concept in these patients. METHODS: So far the clinical follow-up of 162 patients with histologically proven malignant melanoma and metastatically uninvolved (negative) SLN was investigated. Histological examination included standard methods (HE-Test) and special histochemical techniques (S-100, HMB-45). All patients underwent clinical examination, ultrasonic diagnosis of the regional lymph nodes, and x-ray of the chest every 3 months. RESULTS: Despite of negative SLN-findings in 8/162 patients metastases of the malignant melanoma were found after a time period of 5-27 months. Three patients presented with recurrence in the previously mapped (negative) SLN-basin. In another case the scintigraphically visualized SLN could not be identified intraoperatively by means of the hand-held gamma probe. One patient showed intransit-metastases or skin-metastases, respectively; another patient recurred in the scar area. One patient showed hematogenic dissemination (liver) which is not detectable by lymphoscintigraphy; in another patient metastases were found outside the primary lymphatic basin (cervical). CONCLUSION: In our patient group 4.9% presented with metastases despite negative SLN while published data report up to 11% (observation period 35 months), among them only 3 patients (1.9%) being real concept failures. Our results underline that there is no evidence to change this concept in patients with clinically early stage.

Adult↗

Protein folds and families: sequence and structure alignments.

Dali and HSSP are derived databases organizing protein space in the structurally known regions. We use an automatic structure alignment program (Dali) for the classification of all known 3D structures based on all-against-all comparison of 3D structures in the Protein Data Bank. The HSSP database associates 1D sequences with known 3D structures using a position-weighted dynamic programming method for sequence profile alignment (MaxHom). As a result, the HSSP database not only provides aligned sequence families, but also implies secondary and tertiary structures covering 36% of all sequences in Swiss-Prot. The structure classification by Dali and the sequence families in HSSP can be browsed jointly from a web interface providing a rich network of links between neighbours in fold space, between domains and proteins, and between structures and sequences. In particular, this results in a database of explicit multiple alignments of protein families in the twilight zone of sequence similarity. The organization of protein structures and families provides a map of the currently known regions of the protein universe that is useful for the analysis of folding principles, for the evolutionary unification of protein families and for maximizing the information return from experimental structure determination. The databases are available from http://www.embl-ebi.ac.uk/dali/

Databases, Factual↗