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Biomedical subjects

J Mayer

Publications and source records attributed to J Mayer.

At least 145 records · Page 8Linked to original sources

Chromosomal assignment of human endogenous retrovirus K (HERV-K) env open reading frames.

The haploid human genome contains at least one human endogenous retrovirus K (HERV-K) env gene displaying an open reading frame, as evidenced by the high antibody titers against HERV-K Env in germ cell tumor patients at the time of tumor detection. However, the chromosomal assignment of an intact HERV-K env sequence is complicated by the existence of 25-30 HERV-K copies per haploid human genome. Recently, we reported the application of the protein truncation test (PTT) to chromosomally assign HERV-K gag open reading frames. Here, we set out to determine the chromosomal distribution of full-length HERV-K env genes. As demonstrated by somatic hybrid mapping and the PTT, HERV-K env open reading frames were found on human chromosomes 7, 19, and Y. By sequencing chromosome-specific HERV-K env subregions, we assigned two recently reported intact HERV-K sequences on human chromosomes 7 and 19, respectively. Chromosomes 7 and 19 and the Y are furthermore candidates for harboring a putative completely intact HERV-K locus.

Chromosome Mapping↗

A clinical algorithm for the management of abnormal mammograms. A community hospital's experience.

Mammography is an important tool in the early detection of breast cancer, but its use has been criticized for stimulating the performance of unnecessary breast biopsies. We retrospectively reviewed the results of breast biopsies preceded by abnormal mammograms at a community hospital for three 5-month periods--baseline, postintervention, and follow-up--to determine the effectiveness of algorithm-based care for patients with an abnormal mammogram. Cases in which there was a definite or implied recommendation for biopsy by a radiologist revealed a baseline positive predictive value of 4% (2/45), a postintervention positive predictive value of 21% (9/42), and a follow-up phase positive predictive value of 18% (5/28). A Fisher's exact test of the preintervention and postintervention positive predictive values after an abnormal mammogram with a "recommendation for biopsy" was significant (n = 87, P = .023). A Kruskal-Wallis analysis of variance to determine if there had been an increase in the mean lesion size of breast cancers detected over the 3 study periods was not significant. The results of this study suggest that developing a clinical algorithm under the leadership of an opinion leader combined with continuing medical education efforts may be efficacious in reducing the incidence of unnecessary surgical procedures.

Algorithms↗

[A new purine analog in the treatment of hematologic malignancy. I. Fludarabine].

New purine analogues, fludarabine, 2-chlorodeoxyadenosine and 2-deoxycoformycin are remarkably active in generally incurable malignant lymphoproliferative disorders. The first part of the review summarises pharmacological properties, the mechanism of action, toxicity and clinical use of fludarabine. Major clinical experience with fludarabine has been obtained in patients with chronic lymphocytic leukaemia (CLL). In the studies in pretreated patients with CLL, the overall response rate was over 50%. In previously untreated patients with CLL response rate of 75-80% was recorded with a high ratio of complete responses. Fludarabine was found to be active agent in indolent lymphoma in phase I/II. Approximately 60% of patients with follicular lymphoma respond to fludarabine monotherapy. Combination of fludarabine with cytosine arabinoside (ara-C) is now successfully used in the treatment of acute myelogenous leukaemia (AML) and myelodysplastic syndrome (MDS). Other potential areas of use for fludarabine include hairy-cell leukaemia, Waldenström's macroglobulinaemia and mycosis fungoides. Myelosupression, especially leuko and lymphopenia is the major dose-limiting adverse effect of fludarabine. A long term reduction in CD4+ T cell count may be associated with an increased incidence of opportunistic infections. Other adverse effects such as nausea and vomiting or neurotoxicity are of mild to moderate severity when the recommended dosage is used.

Antineoplastic Agents↗

[Diagnosis of mycotic infections in oncology patients using the polymerase chain reaction].

Diagnosis of mycotic infections is despite the immense effort devoted to this problem still very inaccurate. A new and promising method is the polymerase chain reaction, PCR, which theoretically can detect a single cell. In their original study the authors decided to develop a new method for the detection of fungi by PCR and to compare this examination with post-mortem findings. Thus it was possible to determine sufficiently reliably the sensitivity and specificity of the method. For the detection of fungi the authors selected the sequence coding for a small subunit of ribosomal RNA (18S rDNA). The method is able to detect the amount of DNA from some 10-100 cells. The sensitivity was 90% and the specificity 92%. The method is so far too laborious for common practice, its simplification would be however very useful.

Adult↗

[High-dose chemotherapy--a new hope for some patients with malignant tumors?].

High-dosage chemotherapy is at present a very intensively investigated therapeutic procedure which rises great expectations. Administration of large doses of cytostatics is made possible by subsequent transplantation of autologous or allogenic haematopoietic progenitor cells (transplantation of peripheral stem cells or bone marrow). This reduces markedly the haematological toxicity of chemotherapy and it is possible to administer cytostatics in amounts at the non-haematological toxicity borderline. In the first part of the paper theoretical principles of high-dosage chemotherapy are analyzed, the relationship between the dosage of the drug and its effect. The author describes also cytostatics used in regimens of high dosage chemotherapy and discusses general toxic effects of this treatment.

Antineoplastic Agents↗

[Autologous transplantation of peripheral hematopoietic cells in a patient with multiple myeloma and renal insufficiency].

High dosage melfalan chemotherapy with subsequent autologous blood stem cell transplantation in suitably selected patients with multiple myeloma greatly increases the probability that complete remission will be achieved and it prolongs the mean survival period as compared with classical chemotherapy. Till recently patients with multiple myeloma and renal insufficiency were not included in transplantation programmes. Only recently several papers were published abroad which indicate the possibility to implement transplantations also in these patients. The authors describe the treatment, incl. the first autologous transplantation of blood stem cells in a patient with multiple myeloma and renal insufficiency.

Adult↗

Integrated optical NIR-evanescent wave absorbance sensorfor chemical analysis.

A new, long-path integrated optical (IO) sensor for the detection of non-polar organic substances is described. The sensing layer deposited on a planar multimode IO structure is built by a suitable silicone polymer with lower refractive index (RI). It acts as a hydrophobic matrix for the reversible enrichment of non-polar organic contaminants from water or air. Light from the near-infrared (NIR) range is coupled into the planar structure and the evanescent wave part of the light field penetrating into the silicone layer interacts with the enriched organic species. As a result, light is absorbed at the characteristic frequencies of the corresponding C-H, N-H or O-H overtone and combination band vibrations of the analytes. To perform evanescent field absorbance (EFA) measurements, the arc-shaped strip waveguide structure of 172 mm interaction length was adapted to a tungsten-halogen lamp and an InGaAs diode array spectrograph over gradient index fibers. Dimethyl-co-methly(phenyl)polysiloxanes with varying degrees of phenylation were prepared and used as sensitive coating materials for the IO structure. Light attenuation in the arc-shaped waveguides is high and typical insertion losses in the range of 14-18 dB were obtained. When the coated sensors were brought in contact with aqueous samples, the light transmission decreases, which is due to the formation of H(2)O micro-emulsions in the silicone superstrates. Nevertheless, after reaching constant light transmissions, absorbance spectra of aqueous trichloroethene samples were successfully collected. For gas measurements, where water cross sensitivity problems are absent, the sensitivity of the IO device for trichloroethene was tested as a function of the RI of the silicone superstrate. The slope of the TCE calibration function increases by a factor of 10 by using a poly(methylphenylsiloxane) layer with a RI of 1.449 instead of poly(dimethylsiloxane) (RI: 1.41). A comparison of the IO-EFA and an earlier developed fiber-optic EFA sensor for trichloroethene measurements in the gas phase showed an increase in sensitivity per unit length of the waveguide by a factor of up to 120.

Journal Article↗

Optimisation of an integrated optical evanescent wave absorbance sensor for the determination of chlorinated hydrocarbons in water.

The suitability of an integrated optical chemical sensor for the determination of highly volatile chlorinated hydrocarbons in aqueous solutions has been proven. The analytes are detected by NIR absorption spectrometry in the evanescent field of an integrated optical strip waveguide generated in a BGG31 (Schott, Germany) glass substrate, which is coated with a hydrophobic polymer superstrate as sensing layer. It has been shown that the sensitivity increases when the refractive index of the superstrate is increased from 1.333 up to 1.46. Different UV-cured polysiloxanes with low cross sensitivity to water have been prepared. Due to the good light transmission properties of the IO-sensors prepared by this method, quantitative measurements have been performed with the model system trichloroethene (TCE) in water. A detection limit of 22 ppm has been found and the sensor response times (t(90)-value) are between five and fourteen minutes for a coating thickness of around 30 microm. The sensor response is totally reversible. The analyte desorbes in air within 2 min. The enrichment of trichloroethene in the polysiloxane coating can be described by film diffusion through the aqueous boundary layer as rate determining step.

Journal Article↗

Tissue engineering scaffolds using superstructures.

Here, scaffolds as cell and tissue carriers are approached from an engineering point of view, emphasizing material superstructuring in the design of supports. Superstructure engineering provides optimal spatial and nutritional conditions for cell maintenance by the arrangement of structural elements (e.g. pores or fibres) so as to vary the order of cell to cell contact. This approach is illustrated in the design of several scaffolds: knitted fabrics as three-dimensional superstructures for optimized osteosynthesis implants, a new injectable open porous implant system, an angiopolar non-degradable ceramic cell carrier, and an injectable or microsurgically implantable entangled carrier system. The implications for tissue engineering are discussed.

Anisotropy↗

A comparative analysis of embryo implantation potential in patients with severe teratozoospermia undergoing in-vitro fertilization with a high insemination concentration or intracytoplasmic sperm injection.

The objective of this study was to assess fertilization, implantation and pregnancy rates in infertile patients with severe teratozoospermia [P (poor prognosis) pattern sperm morphology assessed by strict criteria] treated by in-vitro fertilization (IVF) using a high insemination concentration (HIC), or by intracytoplasmic sperm injection (ICSI). This was a retrospective cohort study performed in an academic tertiary institution. The outcome of 115 consecutive ICSI cycles was compared to that of a similar number of cycles of IVF with HIC performed during a similar time frame and matched by woman's age and basal serum (cycle day 3) follicle stimulating hormone concentrations. The inclusion criteria were sperm morphology </=4% normal forms (P pattern) and >/=1x10(6) total motile spermatozoa per ejaculate. The diploid fertilization rate in the HIC-IVF group was 86% and in the ICSI group 68% (P < 0.05). Importantly, an equal number of embryos was transferred to both groups of patients. The morphological quality of the embryos (proportion of transfers having superior morphology embryo scores) was significantly better in the ICSI group than in the patients receiving HIC-IVF. Although there was a clear trend for better implantation and pregnancy rates in the ICSI group, these differences were not statistically significant. We conclude that, although HIC-IVF resulted in a higher fertilization rate than ICSI in patients with severe teratozoospermia, ICSI produced a significantly higher proportion of morphologically superior embryos with a tendency towards a higher implantation potential. Therefore, teratozoospermic patients having adequate numbers of motile spermatozoa should be offered ICSI as an alternative to modified (HIC) IVF treatment.

Cohort Studies↗

A novel subepidermal blistering disease with autoantibodies to a 200-kDa antigen of the basement membrane zone.

Several components of the basement membrane zone (BMZ) have been identified as antigenic targets in autoimmune bullous diseases. We report a novel disease with autoantibodies to a BMZ antigen that is different from the targets described so far. The patient suffering from this disorder showed tense bullae and severe mucous membrane involvement rapidly responding to oral tetracyclines and colchicine. Histopathologic findings resembled those of dermatitis herpetiformis. Direct immunofluorescence microscopy showed linear deposits of IgG and C3 at the BMZ. By indirect immunofluorescence studies on split human skin, using both 1 M NaCl and suction blistering for dermal-epidermal separation, IgG antibodies localized exclusively to the dermal side of the split. The antibodies were mainly of the IgG4 sub-class. By Western blot analysis of epidermal and dermal extracts, the patient's serum unequivocally reacted with a dermal antigen of 200 kDa. It did not recognize bullous pemphigoid antigens (the autoantigen of epidermolysis bullosa acquisita), purified preparations of laminin-1 and laminin-5, or the recently described 105-kDa BMZ antigen. By immunoblotting of concentrated conditioned SCC-25 medium, the patient's antibodies reacted with a band of 200 kDa and several bands of lower molecular weight. No reactivity was seen with extracts of cultured human fibroblasts. By indirect immunogold electron microscopy, immunoreactants localized to the lower lamina lucida. After clearance of skin lesions, both indirect immunofluorescence and Western blot analysis became negative. This patient suffers from a novel autoimmune bullous disease with autoantibodies to a 200-kDa antigen of the BMZ.

Animals↗

A novel subepidermal blistering disease with autoantibodies to a 200-kDa antigen of the basement membrane zone.

Several components of the basement membrane zone (BMZ) have been identified as antigenic targets in autoimmune bullous diseases. We report a novel disease with autoantibodies to a BMZ antigen that is different from the targets described so far. The patient suffering from this disorder showed tense bullae and severe mucous membrane involvement rapidly responding to oral tetracyclines and colchicine. Histopathologic findings resembled those of dermatitis herpetiformis. Direct immunofluorescence microscopy showed linear deposits of IgG and C3 at the BMZ. By indirect immunofluorescence studies on split human skin, using both 1 M NaCl and suction blistering for dermal-epidermal separation, IgG antibodies localized exclusively to the dermal side of the split. The antibodies were mainly of the IgG4 subclass. By Western blot analysis of epidermal and dermal extracts, the patient's serum unequivocally reacted with a dermal antigen of 200 kDa. It did not recognize bullous pemphigoid antigens, the autoantigen of epidermolysis bullosa acquisita, purified preparations of laminin-1 and laminin-5, or the recently described 105-kDa BMZ antigen. By immunoblotting of concentrated conditioned SCC-25 medium, the patient's antibodies reacted with a band of 200 kDa and several hands of lower molecular weight. No reactivity was seen with extracts of cultured human fibroblasts. By indirect immunogold electron microscopy, immunoreactants localized to the lower lamina lucida. After clearance of skin lesions, both indirect immunofluorescence and Western blot analysis became negative. This patient suffers from a novel autoimmune bullous disease with autoantibodies to a 200-kDa antigen of the BMZ.

Autoantibodies↗

Detection of Borna disease virus (BDV) antibodies and BDV RNA in psychiatric patients: evidence for high sequence conservation of human blood-derived BDV RNA.

In several vertebrate species, Borna disease virus (BDV), the prototype of a new group of animal viruses, causes central nervous system disease accompanied by diverse behavioral abnormalities. Seroepidemiological data indicate that BDV may contribute to the pathophysiology of certain human mental disorders. This hypothesis is further supported by the detection of both BDV antigens and BDV RNA in peripheral blood mononuclear cells (PBMCs) of patients with psychiatric disorders and the isolation of BDV from such PBMCs. Here we describe serological and molecular epidemiological studies on psychiatric patients and healthy individuals from the area of Homburg, Germany. Using a novel Western blot (immunoblot) assay, we found a BDV seroprevalence of 9.6% among 416 neuropsychiatric patients, which is significantly higher than the 1.4% found among 203 healthy control individuals. Human sera displayed a prominent immunoreactivity against the virus nucleoprotein, the p40 antigen. Reverse transcriptase-mediated PCR analysis of RNA extracted from PBMCs of a subset of 26 of the neuropsychiatric patients revealed that 50% were BDV RNA positive. Three of the 13 BDV RNA-positive patients also had BDV-positive serology, whereas one patient with serum antibodies to BDV p40 antigen did not harbor detectable BDV RNA in PBMCs. BDV p40 and p24 sequences derived from human PBMCs exhibited both a high degree of inter- and intrapatient conservation and a close genetic relationship to animal-derived BDV sequences.

Adolescent↗

Analytical performance of an immunologic-based periodontal bacterial test for simultaneous detection and differentiation of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia.

The analytical performance of a membrane-based immunoassay for the simultaneous detection and differentiation of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia (including Prevotella nigrescens) was investigated. Positive reactions were observed for 71 of 71 reference strains and recent oral isolates of A. actinomycetemcomitans, P. gingivalis, and P. intermedia. No cross-reactivity was observed with 39 other common oral and environmental species. The specificity of the test was unaffected by the presence of potential oral interferents including whole blood, white blood cells, mucin, saliva, toothpastes, and oral rinses. A proficiency test by dental professionals using a standardized set of unknown simulated samples yielded a sensitivity of 97% (116/120) and a 100% specificity (240/ 240). An additional group including dental professionals and high school students was shown to be 99% proficient (1385/1397) in distinguishing proper from improper test function when processing control samples with normal test devices and devices with simulated error conditions. Comparisons to a culture standard for 104 subgingival plaque samples collected from 26 adult periodontitis patients yielded > 98% specificity for each of the test bacteria. In addition, the detection threshold for the test was determined to be equivalent to 10(4) cultivable test bacteria when compared to the culture standard. The data indicate that this membrane immunoassay is a valid and easy-to-use method for the detection of A. actinomycetemcomitans, P. gingivalis, and P. intermedia in subgingival plaque, at levels above the detection threshold of the test.

Adult↗

[Treatment of multiple myeloma].

A new era of multiple myeloma management includes new approaches such as genetic marking and gene therapy, immunotherapy, stimulation of graft versus myeloma effect, etc. Intensive clinical research is also focused on the detection of minimal residual disease and bone marrow purging. Clinical trials have begun and the first results are promising, though preliminary. The combinations of new types of therapeutical approaches with the most efficient regimens used until now could form a new type of MM management strategy that better involves minimal residual disease.

Humans↗

New approaches to management of multiple myeloma.

A new era of multiple myeloma (MM) management includes new approaches such as genetic marking and gene therapy, immunotherapy, stimulation of graft versus myeloma effect, etc. Intensive clinical research is also focused on the detection of minimal residual disease and bone marrow purging. Autoregulatory loop of myeloma cells and detection of genes responsible for pathological transformation of B-line cells is of great research interest. Clinical trials have begun and the first results are promising, though preliminary. The safety of the patients and the public must be major concern of all investigators. The combinations of new types of therapeutical approaches with the most efficient regimens used until now could form a new type of MM management strategy that better involves minimal residual disease.

Bone Marrow Purging↗