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Biomedical subjects

T Reichert

Publications and source records attributed to T Reichert.

At least 19 recordsLinked to original sources

[Antiangiogenic and anti-immunosuppressive therapeutic strategies in human head and neck squamous cell carcinoma (HNSCC)].

BACKGROUND: Angiogenesis and tumor-associated immunosuppression are two of the hallmarks of carcinogenesis. In previous studies we demonstrated in vitro that HNSCC tumor cells attract monocytes via monocyte chemotactic protein-1 (MCP-1) and activate them via transforming growth factor-beta 1(TGF-beta1) to secrete interleukin (IL)-1alpha, which in turn stimulates tumor cells to secrete increased levels of the angiogenic and immunosuppressive vascular endothelial growth factor (VEGF). These findings suggest that interaction between the immune system and VEGF-mediated angiogenesis is important for progression of HNSCC. Recent studies in vitro show that retinoic acid (RA) downregulates the release of MCP-1 and TGF-beta1 by tumor cells. Therefore, we investigated the ability of RA to modulate the ability of tumor cells to recruit and activate monocytes for participation in VEGF-mediated angiogenesis and immunosuppression in vivo. MATERIAL AND METHODS: Mice (ten/group) were injected daily with RA (160 microg/kg) for 3 weeks. After that time mice were sacrificed, and paraffin sections of tumors were obtained and stained for VEGF-A, CD68, and PECAM (CD31) by immunohistochemistry. The lungs, liver, and myocardium were analyzed for macro- and micrometastases. The plasma protein levels of VEGF-A and MCP-1 were determined by ELISA. RESULTS: In RA-treated mice tumors regressed completely and RA prevented metastases (p=0.00) and macrophage infiltration (p=0.007). Treated mice downregulated VEGF-A (0 pg/ml) and MCP-1 (12 pg/ml) in peripheral blood (p=0.001). CONCLUSION: Our findings suggest a new therapeutic possibility: the development of treatment protocols that can block each of the ways in which tumors induce new blood vessel growth and immunosuppression of the host.

Angiogenesis Inhibitors↗

Downregulation of the constitutive tapasin expression in human tumor cells of distinct origin and its transcriptional upregulation by cytokines.

Human tumor cells frequently exhibit abnormalities in the major histocompatibility complex (MHC) class I surface expression which can be due to structural alterations and/or dysregulation of various components of the MHC class I antigen processing machinery, such as HLA class I heavy and light chains, the peptide transporter and the proteasome subunits. Although several cofactors critical for proper MHC class I assembly have been identified, their contribution to the immune escape phenotype of tumor cells has not been analyzed. In order to determine whether tapasin deficits are an integral part of immune escape mechanisms of human tumors, we studied the constitutive and cytokine-regulated expression pattern of tapasin in malignant cells of distinct histology. Heterogeneous and reduced expression levels of tapasin were found in small-cell lung carcinoma, pancreatic carcinoma, colon carcinoma, head an neck squamous cell carcinoma and renal cell carcinoma cell lines. Tapasin downregulation was also prominent in surgically removed tumor lesions when compared to normal controls. The impaired tapasin expression is often associated with low MHC class I cell surface expression. In addition, various cytokines, including interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-4, but not granulocyte-macrophage colony stimulating factor (GM-CSF), transcriptionally upregulate to a distinct extent and in a time-dependent manner tapasin expression in tumor cells. Thus, deficient tapasin expression appears to be a frequent event in human tumor cells. Its restoration by cytokines further suggests that impaired tapasin expression in tumors is rather due to dysregulation than to structural alterations.

Antiporters↗

[Tissue damage and regeneration after laser surgery using different scanning systems].

INTRODUCTION: Laser systems are frequently used in dentistry. New laser scanner technologies are promising more homogeneous ablation of pathological ablations of the skin and mucosa. The theoretical advantages of these systems have not yet been sufficiently evaluated by histological findings. For this reason, we compared two laser scanners with different scanning patterns in this study (Silktouch and Swiftlase, by Sharplan, Germany). MATERIALS AND METHODS: In this animal study (79 male Osborn-Mendel rats), skin defects of 3-mm diameter were lasered on to the backs of the animals, one for each method mentioned above (defocused laser, Swiftlase, and Silktouch). The histological investigations were conducted, depending on the time after surgery (9 h, 1, 2, 3, 4, 5, 6, 7, 9, 11, or 13 days). On the clinical site, we evaluated the visible ablation rate, homogeneity and morphology of the wound surface and the degree of carbonization. In the histomorphological investigations, we determined the degree of thermal damage as well as the morphology of the necrotic area and reepithelization pattern of the surface. RESULTS: The Silktouch scanner clinically showed a homogeneous ablation rate with less carbonization than the Swiftlase scanner. In the histological specimen, this correlated with an increase in the tissue ablation rate and decreasing thermal damage to the surrounding tissue. Especially in the early wound-healing period, there was a more rapid reepithelization after the use of the Silktouch scanner. These differences could not be evaluated in the later wound-healing period. Compared to the defocused laser ablation, both scanning systems seem to have benefits within these parameters. CONCLUSIONS: The results of this study seem to show a diminished perifocal damage and reduced clinical postoperative morbidity achieved by using laser scanning systems. Compared to the Swiftlase laser, the Silktouch seems to deliver better results.

Animals↗

Monoclonal TCR mRNA transcripts are preferentially detected in the TCR variable alpha chain in CD8(+) T-lymphocytes: implications for immunomonitoring.

Clinical trials have started to implement tumor-associated antigens in the form of antigenic peptides in order to augment CD8(+) T-cell responses directed against autologous cancer cells. One of the surrogate markers for successful immunization is the characterization of T-lymphocytes reacting to the immunizing peptide as determined by CDR3-length and DNA-sequence analysis. Most of the recent studies examining ex vivo T-cell responses in patients with cancer have focussed on expression and prevalence of the TCR Beta variable region, predominantly in non-sorted T-cell populations. Here, we show that clonal T-cell receptors (TCRs), as defined by DNA-fragment analysis and DNA-sequencing, appear to be predominantly present in the CD8(+) T-cell population and that these clonal TCRs are preferentially TCR-VA chains. This has been found to be true for PBL obtained from normal healthy subjects or from patients suffering from cancer, as well is in tumor specimens obtained from patients with cervical cancer. We suggest that a detailed analysis of the TCR-repertoire in patients undergoing immunotherapy, should include: i) examination of both TCR VA and VB families. ii) The absence of TCR VA or VB families should be noted and iii) these studies should be performed on CD4(+) or CD8(+) sorted T-cells or, if tissue specimens are analyzed, should be accompanied by a CD4 and CD8 staining.

Antigens, Neoplasm↗

The integrated operating room system - a pathway to the or 2000 and beyond.

The need to create a new kind of operating room (OR) is obvious from the situation today. Although a number of innovative and even futuristic OR concepts have been proposed, the challenge to implement the OR of the future has never been met. In the Integrated OR System project we came to the conclusion that we have to proceed to new values and new approaches to make the OR of the next millennium happen. By following those new roads we will not only overcome the deficiencies of the OR today but also create a platform that allows easy inclusion of upcoming technology.

Journal Article↗

[Basaloid squamous epithelial carcinoma of the mouth mucosa].

The basaloid-squamous carcinoma (BSC) that was first described in 1986 by Wain et al. for the head and neck region is a rare distinct variant of squamous cell carcinoma (SCC). The cardinal histopathologic feature is a biphasic cellular pattern of basaloid and squamous components. BSC has been confused with solid adenoid cystic carcinoma (ACC). Although the number of reported cases is small, BSC appears biologically virulent, with a propensity to aggressive local behavior, early regional and distant metastasis, and subsequent poor survival. We report the clinicopathological characteristics of 4 new cases and compare their immunohistochemical features with those of solid ACC and conventional SCC. Our results show that BSC, ACC and SCC react to CK 5/6. SCC is CK 10- and CK 13-positive, while BSC and ACC are negative for these markers. BSC and ACC react to CK 8, but in ACC only the luminal cells are CK 8 positive: therefore ACC has a glandular pattern. Our findings indicate that the immunohistochemical differences between BSC and ACC can facilitate their differential diagnosis. Because the biologic behavior of BSC differs from ACC and SCC, distinction among these tumor types is warranted.

Adult↗

The immune profile of multiple sclerosis: T-lymphocyte effects predominate over all other factors in cyclophosphamide-treated patients.

It is widely believed that multiple sclerosis is a T-cell mediated autoimmune disease associated with abnormalities in immunoregulation. This large, prospective study evaluated the lymphocyte immunophenotypic profile of 246 MS patients, divided clinically into a remitting/relapsing group (n = 176) and a progressive group (n = 70), and compared their results to those of 117 healthy controls. All patients were found to have significantly elevated percentage and absolute numbers of IL2R+CD3+ cells as well as depressed percentages of CD45RA+CD4+ cells. However, when the factor of treatment with cyclophosphamide (CY) versus no treatment or treatment with other agents was used to group patients, dramatic declines in both percentages and absolute numbers of CD45RA+CD4+ cells were discovered. These declines were associated specifically with CY and and could be explained by this factor independent of the clinical state of the patient. The effects were seen in patients undergoing current treatment or in those exposed to CY in the near or remote past. These findings highlight the confounding effect of specific treatments on the immune profile of MS patients groups and suggest that there may be important implications for cellular function and clinical outcome in these and other patient groups.

Adult↗

Age-related changes in human blood lymphocyte subpopulations. II. Varying kinetics of percentage and absolute count measurements.

A reference range for lymphocyte populations, with particular emphasis on T lymphocyte subsets, was obtained for normal individuals covering age cohorts from birth through adulthood. This report confirms and extends findings from a developmental reference range published earlier (1). Absolute numbers of WBC, lymphocytes, and T, B, and NK subsets decline significantly during childhood. However, differences in the rate of decline of certain lymphocyte subsets leads to discordance between absolute numbers and percentages. Those lymphocyte subsets which decline less rapidly with age than the total lymphocyte count will show an increase in percentage, whereas those which decline more rapidly will show further declines in percentage values. T cell percentages were seen to increase over time whereas B cell percentages decline. Markers of immaturity such as CD45RA on CD4 cells and CD38 on CD8 cells declined in both percentages and absolute numbers. Activation markers, such as HLA-DR on CD8 cells and IL2-R on CD3 cells, increased in percentages with time but changed inconsistently in cell number from infancy to adulthood. These findings extend the lymphocyte references range to markers thought to be informative in various disease states, including HIV infection.

Adolescent↗

EGFR and PCNA expression in oral squamous cell carcinomas--a valuable tool in estimating the patient's prognosis.

We investigated 100 cases of oral squamous cell carcinomas immunohistologically with respect to the expression of the epidermal growth factor receptor (EGFR) and the proliferating cell nuclear antigen (PCNA). The results were correlated with a new malignancy grading of the invasive tumour areas and the clinical outcome of the patients to estimate the individual prognosis. In conclusion, the amount of antigen expression of both antigens increases with the increasing grade of malignancy of the oral squamous cell carcinoma. Furthermore, there is a statistically significant correlation between the amount of antigen expression and the patient's prognosis. An overexpression of EGFR and PCNA is associated with a short survival of the patient. Both antigens detect relevant tumour biological parameters and are worthy factors in estimating the individual prognosis in patients suffering from oral squamous cell carcinomas.

Adult↗

The role of osteonectin in human tooth development: an immunohistological study.

We investigated immunohistologically 160 teeth and dental germs in various stages of tooth development taken from human individuals (13th week of pregnancy to the 24th year of life) to study the osteonectin expression in dental hard tissue. In the course of dentinogenesis, the predentin, the odontoblasts, and their cell processes show a positive osteonectin staining reaction. During cementogenesis, osteonectin is synthesized by cement-producing fibroblasts, cementoblasts, and cementocytes. The expression of osteonectin during dentinogenesis and cementogenesis is closely related to the development of the respective calcified tissue. All cells of the inner and outer enamel epithelium, the cells of the stratum reticulare and stratum intermedium, the ameloblasts, and the enamel substance are osteonectin negative, just as dentin and cement are. The results of this study indicate one important physiological role of osteonectin as a protein associated with the formation of collagen containing mineralizing tissues like human bone, as well as human dentin and cement.

Adolescent↗

Intravascular ultrasound imaging of arterial wall architecture.

Intravascular ultrasound (IVUS) is a promising new technique for assessing vascular morphology and structure. Controversy exists whether the three-layer appearance of the arterial wall correctly reflects the histologic structures of the intima, media, and adventitia. We performed an experimental study to clarify the three-layer appearance. The vessel wall architecture was analyzed by IVUS on eight different kinds of plastic cylinders, 24 normal blood vessels from pigs, and 59 human arterial segments. A distinct three-layer appearance was observed on all the plastic cylinders when the ultrasound beam was perpendicular to the wall. A three-layer appearance was also seen in the arterial wall, in the muscular (iliac, femoral artery) and elastic types (aorta), when the echo beam was perpendicular to the vessel wall. The three-layer pattern was even observed on the arterial wall when the intima was removed. Furthermore, the removed intima itself provided a three-layer image. Histologic examination showed that there was no correspondence between the IVUS three-layer appearance and the intima, media, and adventitia. Moreover, we also performed IVUS on nine patients who suffered from aortic dissection. Intravascular ultrasonic visualization of the dissected intima showed a distinct three-layer pattern. The pattern disappeared when: (1) the echo beam was not perpendicular to the vessel wall; (2) there was connective tissue around the vessel wall; (3) there was arterial wall calcification; or (4) the vessel wall was too thick or the distance between the ultrasound transducer and the vessel wall was too large.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of osteonectin mRNA and protein during human embryonic and fetal development.

We investigated the temporal and spatial distribution of osteonectin during human embryonic and fetal development, using in situ hybridization and immunohistochemistry. Osteonectin gene expression was generally found in cells exhibiting high rates of matrix production/proliferation. In mineralized tissue, a strong signal was obtained in osteoblasts, odontoblasts, and chondrocytes of the upper hypertrophic and proliferative zones. Chondrocytes of the mineralized zone showed no expression throughout the different stages of development. Strong osteonectin expression was found in odontoblasts of developing teeth. In addition, osteonectin mRNA and protein were detected in several non-mineralized tissues: steroid-producing cells of the adrenal gland and the gonads, kidney (glomeruli), lung (bronchi), skin, megacaryocytes, and large vessels. Histochemistry confirmed the results and detected extracellular osteonectin in bone and in the zone of mineralized cartilage only. The localization of osteonectin in bone, cartilage, and teeth is consistent with a role in the initiation of mineralization. However, the organ-specific distribution in non-mineralized tissues suggests an important multifunction role of this protein during human development.

Abortion, Spontaneous↗

[Skin symptoms of chronic inflammation of a tooth root apex].

Cutaneous manifestations of a periradicular inflammation are now uncommon. In most cases the periradicular infection results in the development of an apical granuloma. If there is proliferation of resting epithelial cells in this granuloma a cyst will develop, the so-called radicular cyst. A rare form of periradicular inflammation is the so-called chronisch granulierende Entzündung nach Partsch [Partsch's chronic granulomatous inflammation]. In this case the granulation tissue spreads through the bone and results in a cutaneous odontogenic sinus. We report on a female patient in whom complete healing was obtained by removal of the periradicular process and excision of the sinus tract.

Adult↗

Lymphocyte subset reference ranges in adult Caucasians.

We report here the distributions of lymphocyte populations bearing the following antigens: CD3 (T cells), CD19 (B cells), CD4 (T helper/inducer cells), CD8 (T suppressor/cytotoxic and some NK cells), and CD3-, CD16+, and/or CD56+ (NK cells). At four sites, analyses were performed on healthy, normal subjects between the ages of 18 and 70, using identical flow cytometry systems and techniques. Reference ranges (unadjusted for sex differences and age variation) are CD3 (61 to 85%), CD19 (7 to 23%), NK (6 to 29%), CD4 (28 to 58%), and CD8 (19 to 48%). The lymphocyte subpopulation distributions for all antigens were found to be similar at all sites. By combining data from all sites, it has been possible to estimate age variation and sex differences for each of these subpopulations. Age and sex associated differences are substantial for some lymphocyte subsets (CD3, CD4, NK cells), and proper accounting of these effects is essential in evaluating the individual patient, if further disease-related variation is to be accurately and consistently assessed. It appears possible to recommend reference ranges for lymphocyte population parameters applicable across national and laboratory boundaries. These ranges provide a basis for comparing results from different institutions and for combining such results on subjects and patients from several institutions, provided the methodology and equipment are identical at all sites.

Adolescent↗

[Experimental evaluation of the accuracy and safety of intraluminal ultrasound].

In this in vitro investigation, we studied the feasibility and accuracy as well as the safety of intravascular ultrasound imaging. Plastic cylinders were used in order to validate measurements of luminal area, perimeter, diameter, and wall thickness. Fifty-nine segments of human arteries were also examined by intravascular ultrasound; then the results regarding the luminal area, perimeter, and wall thickness were compared with the corresponding histopathologic section. Close correlations were found in plastic cylinder studies (r = 0.999, 0.999, 0.998, and 0.994 for area, perimeter, diameter, and wall thickness, respectively). There was also an excellent correlation between intravascular ultrasound imaging and pathologic measurements (r = 0.993, 0.994, and 0.915 for luminal area, perimeter, and wall thickness). Five different cylinders, with a volume of 2, 5, 10, 20, and 50 mls, were employed to evaluate the effect of ultrasound on temperature. Ten blood samples anticoagulated with EDTA were used to detect the effects of ultrasound on blood elements. In the course of time, the ultrasound caused a slight increase of solution temperature (from 23.9 degrees C to 24.6 degrees C after 1-h examination in a 2-ml cylinder) and the temperature change became less obvious as the solution volume increased (the temperature raised 0.3 degrees C in the 2-ml cylinder, 0.1 degrees C in the 20-ml cylinder, but no change was detectable in the 50-ml cylinder after 10 min). No significant differences about WBC, RBC, and platelet counts were found between test and control group (p greater than 0.1) before and 5, 10, 15, 30, and 60 min after ultrasound examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗