Biomedical subjects

K Herrmann

Publications and source records attributed to K Herrmann.

At least 37 records · Page 2Linked to original sources

PubMed1998

Treatment of mice with anti-CD44 after allogeneic bone marrow cell transplantation is lethal.

Because CD44 is known to be of functional importance in hematopoiesis, we were interested in whether anti-CD44 would interfere with syngeneic or allogeneic bone marrow cell engraftment. Syngeneic and allogeneic grafts were accepted by over 80% of mice. In both the syngeneic and the allogeneic host, homing, repopulation, and regain of immunoreactivity was delayed by anti-CD44 treatment. But in the syngeneic host the overall survival rate was unaltered. Instead, less than 25% of anti-CD44-treated, allogeneically reconstituted mice survived by recovery of the host's hematopoietic system, i.e. graft acceptance was close to 0%. The mice died between 4 and 15 days after engraftment and showed severe alterations of the gut. The high death rate of the allogeneically reconstituted mice was specific for anti-CD44 treatment. It did not depend on an ADCC mechanism, could not be abrogated by depletion of T cells, and was only mitigated by depletion of NK cells. According to the histological appearance of the gut, anti-CD44 strengthens a local (gut-associated) graft versus host reaction, which is not mediated by alphabeta T cells and at least not exclusively by NK cells. Because gut death is one of the major reasons for failure in allogeneic bone marrow transplantation, the model of anti-CD44-induced lethality offers itself to clarify the underlying mechanism.

Animals↗

PubMed1998

[Contrast medium studies of the venous system].

PURPOSE: To give an overview of various diagnostic techniques and indications for phlebography in different parts of the body. METHODS: Procedures of conventional phlebography of the lower and upper extremity and cavography are described and their indications in comparison to alternative techniques are discussed. The literature is reviewed with regard to specific advantages and disadvantages of the different methods. RESULTS: Conventional phlebography with iodine contrast media is still considered to be the gold standard in many regards. The diagnosis of acute and chronic thrombotic disease, venous vascular occlusions, hemodynamic malfunctions and anatomic variants of the venous system can readily be established with contrast phlebography. DISCUSSION: Main disadvantages of contrast studies of the venous system are radiation exposure and adverse effects of contrast media. Non-invasive methods such as ultrasound and MR-phlebography are becoming more and more popular and may replace venography. Other techniques such as CT-phlebography and the use of CO2 as contrast medium are under investigation. The latter can be indicated in the case of contraindications against iodine contrast media. CONCLUSION: When choosing diagnostic methods for the venous system, their sensitivity and specificity for specific diagnoses and vascular territories have to be balanced against the risks and disadvantages.

Contrast Media↗

PubMed1998

The monoclonal antibody AS02 recognizes a protein on human fibroblasts being highly homologous to Thy-1.

Recently, we described a novel fibroblast-restricted monoclonal antibody (mAb AS02) that recognizes a membrane-bound antigen. Characterization and isolation of the corresponding antigen showed that mAb AS02 recognized a protein on human fibroblasts that is highly homologous or identical to human Thy-1 antigen (CD90). Partial amino acid sequencing of the corresponding mAb AS02 antigen and comparison with known proteins revealed a 100% homology of the sequenced peptides to the human Thy-1 antigen. Cross-immunodepletion studies with mAb AS02 and an anti-Thy-1 antibody confirmed these results. Utilizing two-dimensional (2D) gel electrophoresis of fibroblast cell extracts and purified antigen, mAb AS02 and the anti-Thy-1-antibody recognized identical protein spots. Furthermore, we demonstrated many identical biochemical properties of the corresponding AS02 antigen and Thy-1 antigen, such as the molecular weight of the core protein and deglycosylation products and the detection of a GPI anchor. In functional assays, the attachment of fibroblasts to collagen I and fibronectin was increased after incubation of fibroblasts with mAb AS02. Therefore, the Thy-1 antigen appears to be involved in the regulation of the adherence of human dermal fibroblasts.

Amino Acid Sequence↗

PubMed1998

The computerized patient record.

Interest in electronic medical records and computerized patient records began with a desire to efficiently retrieve data for outcomes research. One of the best ways to improve medical care is through good clinical outcomes research, which requires accurate, detailed clinical information. In investigating different systems for recording and codifying the information, the authors found that no real systems existed. The detailed information collected for outcomes research could be used for a variety of other processes in the business of health care and is thus worthy of being efficiently recorded.

Computer Systems↗

PubMed1998

[Comparison of a high-end ultrasound system with a spiral CT scanner in screening for liver metastases].

AIM: To assess prospectively the sensitivity of a high-end ultrasound system in comparison to a spiral computed tomographic scanner in screening for liver metastases. METHOD: 88 consecutive patients with malignant diseases were examined using gray-scale sonography and contrast enhanced two-phase spiral computed tomography during arterial dominant and portal venous phase. For both methods all focal lesions of the liver were reported. RESULTS: 99 focal lesions of the liver were detected by gray-scale sonography and/or two-phase spiral computed tomography. The sensitivity for gray-scale sonography was 93.9% (93 of 99 lesions) and for two-phase spiral computed tomography (71.7% (71 of 99 lesions), respectively. CONCLUSION: Screening for liver metastases should be performed by using a diagnostic method with a high sensitivity. Gray-scale sonography with a high-end ultrasound system fulfill' these requirements.

Adult↗

PubMed1998

[A comparison of the monitor and alternator findings of digital thoracic images with the aid of a computer-supported procedure].

PURPOSE: To compare softcopy and hardcopy reading of chest radiographs a software tool was designed for creating lesions with clearly defined size, location and contrast. METHOD: An ROC study was performed using a set of chest radiographs with 300 simulated small nodules and linear details displayed on film and on a 1 K monitor. Six observers participated in the study. ROC curves were generated on the basis of 7200 decisions. RESULTS: There was no significant difference in observer performance overall (AUC = Area under curve). Monitor: 0.84 +/- 0.08 vs. AUC, Film: 0.84 +/- 0.08). Slight, but not statistical significant differences were found in the detection of low-contrast lung nodules and of linear lung details. CONCLUSION: Soft-copy reading using a high quality 1 K CRT display provides the same accuracy for the detection of subtle computer-simulated lesions as hardcopy reading. A software tool could be used for assigning optimal characteristics of CRT- and hardcopy displays using clearly defined lesions as a gold standard.

Computer Simulation↗

PubMed1998

CTLA4Ig inhibits airway eosinophilia and hyperresponsiveness by regulating the development of Th1/Th2 subsets in a murine model of asthma.

Complete T-cell activation requires two distinct signals, one delivered via the T-cell receptor, and the second "co-stimulatory" signal through CD28/B7 ligation. Previous studies showed that the blockade of CD28/B7 ligation alters differentiation of Th1/Th2 lymphocyte subsets in vitro and in vivo. The present study was designed to determine the effect of a CD28/B7 antagonist (CTLA4Ig) on Th1/Th2 development in Schistosoma mansoni-sensitized and airway-challenged mice. Treatment of mice with CTLA4Ig beginning 1 wk after sensitization abolished airway responsiveness to intravenous methacholine determined 96 h following antigen challenge. We also found a significant reduction in bronchoalveolar lavage (BAL) eosinophilia, and reduced peribronchial eosinophilic infiltration and mucoid-cell hyperplasia. Furthermore, CTLA4Ig treatment significantly decreased interleukin (IL)-4 and IL-5 content in BAL fluid in vivo, and the production of IL-5 by lung lymphocytes stimulated with soluble egg antigen (SEA) in vitro. In contrast, the content of interferon-gamma in BAL fluid and supernatant from SEA-stimulated lung lymphocytes from CTLA4Ig-treated mice was increased significantly compared with untreated animals. Thus, CTLA4Ig inhibits eosinophilic airway inflammation and airway hyperresponsiveness in S. mansoni-sensitized and airway-challenged mice, most likely due to attenuated secretion of Th2-type cytokines and increased secretion of Th1-type cytokines.

Abatacept↗

PubMed1997

Transforming growth factor-beta reverses deficient expression of type (I) collagen in cultured fibroblasts of a patient with metageria.

Metageria is a generalized form of acrogeria belonging to the group of premature aging syndromes and is characterized by loss of subcutaneous fat, thinning of the dermis, multiple teleangiectasias and mottled hyperpigmentation. The skin changes present suggest that an altered formation of extracellular matrix might be involved in the pathogenesis of this disease. Fibroblasts obtained from the skin of a patient with this disease revealed a marked reduction of type I collagen expression to about 20% of control levels both at the mRNA and protein level. In addition decreased decorin but unchanged type IV collagen and fibronectin mRNA levels were found. Similar although less pronounced changes were observed in fibroblasts obtained from the sister of this patient showing skin changes compatible with acrogeria. To further analyze the deficient expression of type I collagen run on analysis was performed revealing a decrease of transcription of type I collagen. Incubation of the cells with transforming growth factor-beta, a strong inducer of type I collagen and extracellular matrix formation, restored type I collagen expression both at the mRNA and protein level to amounts comparable with normal skin fibroblasts. These results are consistent with a defect in type I collagen transcription that is readily reversed after incubation with transforming growth factor beta. The deficient synthesis of type I collagen and decorin by dermal fibroblasts might thus contribute to an altered formation of the extracellular matrix resulting in the poikilodermic skin changes observed in this patient.

Adult↗

PubMed1997

Systemic scleroderma. Multicenter trial of 1 year of treatment with recombinant interferon gamma.

OBJECTIVE: To confirm significant improvement of the skin score in systemic sclerosis by treatment with interferon gamma in a larger group of patients and to investigate on a molecular level the influence of interferon gamma on collagen type I messenger RNA expression. DESIGN: Open, noncontrolled multicenter study. SETTING: Five outpatient clinics specializing in the care of systemic scleroderma. PATIENTS: Thirty-two patients suffering from the diffuse or limited form of systemic sclerosis and progressive disease were recruited; 20 patients finished the study. INTERVENTION: Each patient received interferon gamma, 50 micrograms subcutaneously 3 times a week for 1 year. MAIN OUTCOME MEASURE: Skin score, collagen type I messenger RNA in skin biopsy specimens. RESULTS: The patients who completed the study showed an unchanged median skin score after 1 year of therapy. In addition, similar collagen type I messenger RNA levels were detected in skin biopsy specimens taken from involved skin before and after therapy in these patients. CONCLUSIONS: Treatment of systemic scleroderma with interferon gamma is associated with stabilization of the skin score and lack of worsening of visceral involvement.

Female↗

PubMed1997

[Computer-assisted evaluation of mammography images. Initial clinical experiences].

UNLABELLED: Preceding studies have shown that a second independent reviewer of conventional mammographies increases the detection rate of features typical for malignancy by up to 15%. METHODS: In order to test a computer-aided diagnostic (CAD) system (ImageChecker, R2 Technology, USA) for the detection of pathologic criteria in conventional mammography, 96 mammographies were retrospectively evaluated using ImageChecker. Thirty-five of these mammographies had been diagnosed as not showing pathologies, and 61 had depicted histologically confirmed malignancy. RESULTS: Detecting 41 of 61 breast malignancies, ImageChecker showed a diagnostic sensitivity of 70.5%. All malignancies accompanied by microcalcifications were identified by ImageChecker, whereas 18 cases characterized by parenchymal opacity without microcalcifications were not marked. On the average, 1.95 markers per image were set, giving a total of 187 markers in this study. 63% of all markers showed normal tissue and were thus false positive. CONCLUSIONS: Pathologic parenchymal opacities in mammography are a well-known problem for all CAD systems in use. Despite this major drawback, even now ImageChecker can provide tremendous support in routine interpretation of conventional mammographies.

Breast Neoplasms↗

PubMed1997

[MR mammography. Preoperative marking of non-palpable breast lesions with the Magnetom open at 0.2 T].

PURPOSE: To answer the following questions: whether reliable detection of lesions is possible in low-field-MRI-system (Magnetom Open 0.2 T) equipped with currently available hard- and software components in comparison to high field system (Magnetom Impact 1.0 T). Furthermore, whether localization of lesions suspect in MR-mammography can be realized in MR system of low field (Magnetom Open 0.2 T). PATIENTS AND METHODS: In 11 patients, suspect lesions were diagnosed in diagnostic MR-mammography acquired with high field system (Magnetom Impact 1.0 T) and were compared to low field MR-mammographies of 0.2 T (Magnetom Open 0.2 T). In six of the 11 patients a suspect lesion was localized using wire marking. RESULTS: All lesions considered suspect in diagnostic MR-mammography (Magnetom Impact 1.0 T) were also clearly identified in the 0.2 T system (Magnetom Open). In six cases wire marking was performed without any complications and with an accuracy of < or = 0.5 cm distance to the lesion. CONCLUSION: Although studies in the 0.2 T system clearly showed inferior SNR (34.6 vs. 83.1) and CNR (14.6 vs. 43.5) compared to studies with the high field system, all lesions considered suspect in diagnostic MR-mammography were reliably identified also in 0.2 T studies. Due to its open construction permitting permanent access to the breast and due to sufficient image quality, the Magnetom Open is suitable for interventions on the breast.

Biopsy↗

PubMed1997

The fibroblast-specific MAb AS02: a novel tool for detection and elimination of human fibroblasts.

The unwelcome presence of fibroblasts in many cell cultures prevents the long term cultivation of various cell types and work with pure populations. Recently, we described a novel fibroblast-specific monoclonal antibody (MAb AS02) that recognises a membrane-bound antigen. We have now developed a method using the fibroblast-specific MAb AS02 immobilised on goat-anti-mouse-magnetic beads to separate contaminating fibroblasts. An endothelial cell line experimentally contaminated with 5%-50% fibroblasts was successfully purified. Additionally, an endothelial cell line with an initial fibroblast contamination of 1.5% was prepared. A proportion of each preparation was cultured with no separation step being performed, whereas the remainder was cultured after purification with MAb AS02 to exclude the presence of a minor number of fibroblasts (<0.1%). The proportion of fibroblasts increased up to 38% in the fifth passage of culture without elimination of the low initial fibroblast contamination, whereas in the fraction with the separation step, no fibroblasts were detectable by flow cytometry, even after the fifth passage. We also used the antibody to detect the presence of naturally contaminating fibroblasts in thyrocyte cultures. After cultivation of thyrocyte cultures over five passages, the number of fibroblasts increased dramatically up to 50%-80% of the whole population. Subsequently, we successfully applied the method for complete elimination of naturally contaminating fibroblasts from freshly isolated thyrocyte cultures from enzymatically digested thyroid glands. Thus, MAb AS02 is a fibroblast-specific marker that is a useful tool for the detection and elimination of contaminating fibroblasts. The specificity of MAb AS02 permits the universal application of this antibody for human cell cultures of interest.

Animals↗

PubMed1997

Double-blind, placebo-controlled study of intralesional interferon gamma for the treatment of localized scleroderma.

BACKGROUND: Localized scleroderma is characterized by circumscribed fibrotic plaques and may progress to widespread skin involvement and fibrosis. Interferon gamma (IFN-gamma) has been shown to be a potent inhibitor of collagen synthesis and of the migration and proliferation of dermal fibroblasts. OBJECTIVE: Our purpose was to determine whether IFN-gamma is effective in the treatment of localized scleroderma. METHODS: A double-blind, randomized, placebo-controlled, multicenter study was conducted. Twenty-four patients with progressive lesions received 100 micrograms of IFN-gamma or placebo subcutaneously on 5 consecutive days for 2 weeks followed by 100 micrograms of IFN-gamma or placebo once weekly for 4 weeks. Thereafter patients were observed for 18 weeks. To determine whether improvement could be related to an altered level of collagen messenger RNA (mRNA), biopsy specimens were taken from uninvolved and involved skin before and after therapy. RESULTS: The patients treated with IFN-gamma or placebo showed no significant difference in size or fibrosis of lesions or collagen type I mRNA synthesis. However, a reduction in the number of new lesions was observed in the IFN-gamma-treated group. The biopsy specimens obtained from involved skin showed a moderate increase of type I collagen and a significant decrease in the small proteoglycan decorin mRNA levels. CONCLUSIONS: The results indicate that IFN-gamma is ineffective in the treatment of localized scleroderma, but may inhibit the development of new lesions.

Collagen↗

PubMed1997

Molecular analysis of different phases in human wound healing.

Cultured granulation fibroblasts grown from punch biopsies of the same lower arm area, obtained 3, 6, 9 and 14 days after wounding, were used as a human wound healing model in comparison to quiescent fibroblasts. We investigated the expression of key extracellular matrix components at the protein level by flow cytometry and mRNA steady state levels by Northern blotting of the different fibroblasts and compared these data to the ability to migrate towards a chemotactic signal. Procollagen alpha 1 (I), fibronectin and matrix metalloprotease-1 synthesis was strongly up-regulated at the mRNA steady state level on days 3 and 14. Tissue inhibitor of metalloprotease-1 mRNA is only 20% down-regulated between day 3 and 14. Chemotaxis towards conditioned medium reflects a net effect of several factors and is distinctly different from chemotaxis towards platelet-derived growth factor, which peaks at day 3. Compared to the protein level, the enhanced expression of the corresponding PDGF receptor beta chain mRNA is delayed by 3 to 6 days. PDGF receptor alpha shows no regulatory changes during the observation period. This data further supports the idea that functionally divergent subpopulations of fibroblasts exist during wound healing.

Adult↗

PubMed1997

Transient absence of CD44 expression and delay in development by anti-CD44 treatment during ontogeny: a surrogate of an inducible knockout?

Because the lack of some adhesion molecules induced by site-directed mutagenesis has been described to be lethal, whereas the lack of others apparently has no effect, we were interested in seeing whether the developing organism might gradually adapt to the absence of adhesion molecules. Therefore, we chose a form of transient interference by i.v. injection of antibody into pregnant rats. As a model, we selected CD44, which has been reported to play a key role during embryogenesis. Rats received either an antibody recognizing an epitope on the CD44 standard isoform (CD44s) or on exon v6 (CD44v6). In the presence of anti-CD44s, delivery was frequently delayed, and intrauterine abortions were often observed. The fetuses were smaller, particularly the anlage of the hair follicle of the whisker, and the formation of alveoli in the lung, of the tubular system of the kidney, and of villi in the gut was delayed. The development of fetuses receiving anti-CD44v6 was hampered until days 16-18 of gestation. Immunodetection revealed a weaker expression of the target molecules at the implantation site and the complete absence of CD44s and CD44v6 expression in fetal tissue until day 12. During the late stages of gestation, the expression pattern of CD44 resembled that of 2-3-day-younger fetuses of untreated rats. Interestingly, degradation of hyaluronate was also delayed, particularly in the kidney. Thus, the diaplacental antibody passage was very efficient and should make it possible to obtain a clearly defined and differentiated concept of the requirements for the CD44 molecule during ontogeny and also for fail-safe mechanisms. Both experiences may be missed in the knockout proper.

Animals↗

PubMed1997

Conversion of an infrared densitometer for radiochromic film analysis.

By the simple incorporation of a high intensity red LED into a typical infrared film densitometer, radiochromic film can be analysed using existing detectors and scanning software. Results show an accurate dose measurement using radiochromic film and this system compared to conventional detectors for percentage depth dose and penumbral measurements in high and low energy x-ray beams. A small circuit including a red Light Emitting Diode (LED) was positioned inside the film densitometer which does not obscure the infrared source. The red and infrared diodes work independently. For 6 MV x-rays, the 80%/20% penumbral width at 15 mm depth for a 10 x 10 cm field at 100 cm SSD was measured to be 3.5 mm with radiochromic film as compared to 3.3 with corrected diode measurements. Percentage depth doses were measured to within +/- 3% of ionisation chamber data at 6MV and within +/- 2% for 250 kVp x-ray with the film placed parallel to the beam direction in both cases.

Absorptiometry, Photon↗

PubMed1996

Differential distribution of AMPA receptors and glutamate during pre- and postnatal development in the visual cortex of ferrets.

Immunohistochemical methods were used to study the distribution and time-course of appearance of cells expressing glutamate and alpha-amino-3-hydroxy-5-methyl-4-isoaxazole propionic acid (AMPA)-type glutamate receptors (GluR1 and GluR2/3) during development of the ferret visual cortex. Glutamate is present in many neurons in the ventricular zone, intermediate zone, developing cortical plate, and marginal zone as early as embryonic day (E) 34 (birth is at E41 in ferrets). Glutamate attains its adult distribution coincident with the completion of cellular migration. By contrast, GluR1 immunoreactivity emerges more slowly. By birth, GluR1 immunoreactivity is present only in a few neurons in the marginal zone and ventricular zone but is abundant in the marginal zone and subplate, where synaptogenesis commences. The number and staining intensity of GluR1-positive cells increases dramatically during the first two postnatal weeks and is maximal between the second and third week, before slowly declining to adult levels. Cortical cells immunopositive for GluR2/3 follow a similar pattern, although their distribution differs: GluR2/3-positive cells are mainly pyramidal cells. During the first postnatal week, GluR2/3 is also transiently present in fibers in the intermediate zone, which at this stage contains many thalamocortical and callosal and corticofugal axons. The abundance of glutamate at fetal stages, especially in the ventricular zone, is consistent with the previously proposed role of glutamate in mediating trophic effects in vivo, as previously demonstrated in vitro. The expression of AMPA receptors, as well as their transient overexpression, confirms the results of in situ hybridization studies and may imply a developmental role in neuronal differentiation for these receptors, in addition to their mature role in mediating cortical transmission.

Animals↗

PubMed1996

Expression of CD44 splice variants in human skin and epidermal tumours.

Splice variants of the adhesion molecule CD44 (CD44v) are important in the lymphatic spread of rat carcinoma cells. In several human tumours expression of CD44v correlates with tumour progression. However, little is known about the physiological functions of distinct variant exons. Here we report on the immunohistological evaluation of CD44 expression in normal human skin and epidermal tumours which do not metastasise, or do so vary rarely. Frozen tissues were stained with a panel of monoclonal antibodies, recognizing epitopes of the CD44 standard isoform, as well as of variant exons v5, v6, v7, v7-v8 and v10. Stratum basale and spinosum as well as the root shaft of hairs reacted strongly with the whole panel of anti-CD44 antibodies. Stratum corneum, acinar cells of sebaceous and eccrine sweat glands stained with anti-CD44v5, anti-CD44v6 and anti-CD44v7, but not with anti-CD44v10, the latter recognizing the "epithelial isoform" (CD44v8-v10) of CD44. Ductal cells of glands and apocrine glands did not express CD44v. Compared with its expression in normal human skin, CD44v expression was reduced in basal cell carcinoma and squamous cell carcinoma of the skin. This was particularly true of CD44v10. The expression of CD44v in normal skin and dermal appendages indicates that not all combinations of variant exons are involved in tumour progression. Since the epithelial isoform is particularly downregulated in basal cell carcinoma and squamous cell carcinoma of the skin, it is unlikely that exons v8-v10 play a role in tumour progression. Rather, they may be of functional importance in maintenance of the epidermal structure.

Animals↗