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Biomedical subjects

A Burkhardt

Publications and source records attributed to A Burkhardt.

At least 19 recordsLinked to original sources

Complementary therapy and cardiac surgery.

Mind-body techniques and complementary care may assist people who are undergoing surgery and those recovering from cardiac surgery to cope with the event, the process of recovery, and accompanying lifestyle changes. These approaches can provide cardiac patients with nonpharmacologic tools that may prevent further coronary artery disease and the development of dysrhythmias. The Complementary Care Center at Columbia-Presbyterian Medical Center was developed to clinically apply and research the use of nonallopathic, complementary modalities with patients receiving care at the medical center, including those undergoing cardiac surgery.

Adaptation, Psychological↗

Expression of exogenous p59fyn modulates signaling in an immature B cell line, WEHI-231.

The WEHI-231 B lymphoma line is representative of immature B cells, which undergo growth arrest/apoptosis following cross-linking of surface immunoglobulin M (sIgM). In B cells, sIgM engagement has been shown to induce immediate (within seconds) activation of src family protein tyrosine kinases (PTKs) such as p53lyn/56lyn, p55blk, p56lck and p59fyn which are associated with B cell antigen receptor (BCR) complex. However, p59fyn expression is very low in both normal immature B cells and apoptosis-prone B cell lines, including WEHI-231. Such a finding prompted us to investigate the effects of ectopic expression of p59fyn in growth regulation of WEHI-231 cells. We have obtained WEHI-231 transfectants expressing the exogenous p59fyn by retroviral mediated gene transfer method. The transfectants demonstrated increased [Ca2+]i level in both the non-stimulated condition and sIgM cross-linking. The expression of ectopic p59fyn also increased the sensitivity of the transfectants to growth arrest signal by sIgM cross-linking. The results suggest that p59fyn can modulate signal transduction and growth regulation when expressed in the immature B cell line.

Animals↗

Biotherapy of B-cell precursor leukemia by targeting genistein to CD19-associated tyrosine kinases.

B-cell precursor (BCP) leukemia is the most common form of childhood cancer and the second most common form of acute leukemia in adults. Human BCP leukemia was treated in a severe combined immunodeficient mouse model by targeting of the tyrosine kinase inhibitor Genistein (Gen) to the B cell-specific receptor CD19 with the monoclonal antibody B43. The B43-Gen immunoconjugate bound with high affinity to BCP leukemia cells, selectively inhibited CD19-associated tyrosine kinases, and triggered rapid apoptotic cell death. At less than one-tenth the maximum tolerated dose more than 99.999 percent of human BCP leukemia cells were killed, which led to 100 percent long-term event-free survival from an otherwise invariably fatal leukemia. The B43-Gen immuno-conjugate might be useful in eliminating leukemia cells in patients who have failed conventional therapy.

Animals↗

[Schwannoma of the gastric wall].

Clinical and ultrasound examination showed a tumor adjacent to the posterior gastric wall in two patients with noncharacteristic upper abdominal pain. The structure of the at least fist-size masses was partly solid, partly cystic and on palpation appeared soft and spongy with a smooth surface. Colour ultrasound showed a high vascularity. All these factors were confirmed by computerized tomography. History as well as clinical and ultrasound examination suggested the diagnosis of schwannoma and this was confirmed by histopathology following laparotomy.

Aged↗

Odontogenic myxoma--characterisation of the extracellular matrix (ECM) of the tumour stroma.

In order to elucidate the origin of the odontogenic myxoma, the composition and the structural organisation of the extracellular matrix (ECM) of this tumour were characterised. Collagen type I, VI, procollagen type III, undulin, tenascin and fibronectin were demonstrated in biopsy material of 4 cases by polyclonal antibodies. The tumour stroma showed a pronounced reaction for collagen type I. Fibroblasts displayed an intense intracytoplasmatic reaction for procollagen type III, and collagen type I was not found in the fibroblasts of the adjacent normal oral mucosa. In contrast to the surrounding connective tissue, label for collagen type VI was weak, as was the reaction for fibronectin and tenascin. Undulin was almost undetectable. The immunohistochemical results suggest that the odontogenic myxoma is characterised by an as yet unobserved structural organisation of ECM proteins, a secretion defect of fibrillar collagens type I and III with no resemblance to physiological tooth development.

Adult↗

The effect of cancer diagnosis and treatment on hand function.

Cancer diagnosis and treatment can have a profound effect upon hand function, presenting a challenge to the occupational therapist. The therapist who specializes in oncology or hand therapy must have knowledge of the medical treatment model in regard to cancer conditions and must be able to set realistic goals that consider the patient's medical prognosis as well as the effect the disease or medical treatment has on the patient's physical and emotional functioning. The challenge to therapists in this area of practice will be to conduct research to verify or validate the effectiveness of the occupational therapy interventions currently provided. As cancer is diagnosed at earlier stages of the disease and survival improves after cancer treatment, hand therapy may improve the functional outcomes of persons with cancer. This judgment of rehabilitation oncology practice will need to be confirmed by research.

Antineoplastic Agents↗

Tissue markers of potentially malignant human oral epithelial lesions.

Tissue markers of potential malignancy have been sought for many years. Cell surface markers, particularly blood group and histocompatibility antigens, have shown great promise and several squamous carcinoma antigens have been identified--but not fully studied in potentially malignant lesions. Growth factors and receptors also need further study. Cytoplasmic markers of potential malignancy have been examined and, of these, keratins, filaggrin, and some carcinoma antigens show most promise. Nuclear analyses have promise but are time-consuming and expensive. Image cytometric analyses appear to be sensitive and predictive: oncogene and tumour suppressor analyses remain to be fully evaluated. New investigative techniques at the cellular and molecular level show increasing promise at defining potentially malignant oral epithelial lesions but more prospective studies are required.

Biomarkers↗

Comparison of tyrosine kinase activation by mitogenic and nonmitogenic anti-IgD antibodies.

Low concentrations of anti-Ig dextran conjugates that stimulate very high levels of B cell proliferation and Ig secretion stimulate no detectable increases in tyrosine phosphorylation. To study this point further, we compared tyrosine phosphorylation patterns induced by mitogenic and nonmitogenic anti-Ig antibodies. Whereas the mitogenic, strongly cross-linking, antibody H delta a/1 induced greater levels of tyrosine phosphorylation than did the nonmitogenic antibody FF1-4D5, the pattern of substrate phosphorylation was equivalent. At lower concentrations of H delta a/1, which were still mitogenic, the degree of phosphorylation that was induced was similar to that induced by high concentrations of FF1-4D5. Both antibodies stimulated comparable increases in the kinase activity of the three src-related kinases present in normal B cells and linked to the IgR, i.e., Blk, Fyn, and Lyn. These results suggest that the extent of tyrosine kinase activation is proportional to mIg cross-linking, that induction of B cell DNA synthesis may require little tyrosine kinase activation, and that activation of tyrosine kinase per se does not necessarily lead to B cell DNA synthesis.

Animals↗

Apoptotic cell death and tissue remodelling during mouse mammary gland involution.

During post-lactational mammary gland involution, the bulk of mammary epithelium dies and is reabsorbed. This massive cell death and tissue restructuring was found to be accompanied by a specific pattern of gene expression. Northern blot analysis showed that weaning resulted in a dramatic drop in ODC, a gene involved in synthesis of a component of milk, and the nearly simultaneous induction of SGP-2, a gene associated with apoptotic cell death. These changes were followed by decreases in expression of milk protein genes to basal levels and expression of genes associated with regulation of cell proliferation and differentiation, p53, c-myc and TGF-beta 1. Subsequently, additional genes implicated in stress response, tissue remodelling, and apoptotic cell death were transiently expressed, expression peaking at about 6 days post-weaning. A non-random degradation of DNA yielding the oligonucleosomal length fragmentation pattern typical of apoptotic cell death (Wyllie, 1980; Wyllie et al., 1980) was detected in association with morphological changes and gene expression. The correlations between: (a) changes in morphology, (b) pattern of gene expression and (c) changes in DNA integrity suggest that complementary programs for cell death and tissue remodelling direct post-lactational mammary gland involution.

Animals↗

Intraepithelial lymphocytes and Langerhans cells in the oral mucosa--dynamic aspects.

In the oral epithelium a constant population of non-epithelial immunocompetent cells--lymphocytes and Langerhans cells exists. 3025 such cells of the murine and 542 of the normal human oral mucosa were documented photographically at the ultrastructural level. Location within the epithelium, morphological signs of locomotion, membrane configuration and labeling of the intercellular substance by ruthenium red were registered. About 40 per cent of the lymphocytes and 70 per cent of the Langerhans cells show signs of locomotion, predominantly in a lateral and basal direction. Occasional cells crossing the basal lamina are seen. Close apposition, or rarely a denticulated surface and lysis of desmosomes were present, both probably indications of cellular interactions. Ruthenium red labeling of the glycocalix is continuous forming a homogeneous layer between epithelial and non-epithelial cells and between intraepithelial cells, suggesting an even distribution of antigens and the lack of preformed spaces for intraepithelial cells. Murine and human intraepithelial cells exhibited no major differences.

Animals↗

[The color and structure of the human iris. 2. Studies of 200 twins].

Subject of the present report is an investigation of the heredity of 30 iris characteristics. The material basis of this sample of twins (100 monozygotic and 100 dizygotic pairs), the largest ever taken as a basis for the purpose of iris research, consists of standardized colour photographs of the examined persons' irises and iris-microscopic observations. The pairs of twins are compared to 100 non-related casual pairs in order to render a better estimation of the degree of heredity of the features possible. On every occasion several classes were constituted for the concordance verification. These classes result from the number of the classes of the forms of markedness and present different levels of similarity. The different distribution of the twin pairs and the control pairs on the concordance classes are always examined for their statistical significance, and for each group of pairs a concordance value is computed. The intervals between the concordance values of the monozygotic and dizygotic pairs and the control pairs indicate the degree of heredity of the investigated feature. Taking all the compiled factors and conditions into consideration, an evaluation of the features as heredity features is made. Though a hereditary component can be observed for all iris characteristics, only about a third could be called heredity features. Quantity of pigment and the hitherto undescribed limiting layer folds were evaluated as "very good", whereas pigment colour in the fine analysis, quality of the anterior stroma leaf, frequency of iris crypts and iris frill position were judged as "good". Tone of blue, markedness of Woelfflin nodules, quantity and markedness of contractional rings could be evaluated as "moderately good" as to their heredity. On the basis of the prior concordance investigations for each of the 300 pairs, a "similarity index" and a "concordance index" were computed in order to arrive at evidence as to the degree of similarity of the single pairs; i.e. in order to detect the limits of the similarity between non-identical twins and the dissimilarity between identical twins. This concluding investigations lead to the question of the possibility of a diagnosis of genetic identicalness solely on the basis of the comparison of irises.

Adolescent↗

[The color and structure of the human iris. 1. Morphological studies].

The material basis of this investigation consists of empirical findings and colour photographs of the irises of 200 pairs of twins and 100 control pairs. For the morphological investigation first-born twins and control persons are combined to constitute a comparative group of 400 non-related testees. Research by means of the iris microscope and the evaluation of standardized iris photographs led to the development of a catalogue of features which describes 10 iris characteristics for the iris colour and 20 for the iris structure. For each feature different degrees of markedness are defined and their frequency is determined. Similarly, intraindividual right/left and sex differences as well as age-dependencies and the relation between the features are examined. The setting-up of features includes outlining an iris-colour class system in order to render a better and more practicable determination of eye colour possible. As a substitute for Martin/Schulz's table of eye-colour, which describes only eye-colour phenomena, 4 iris-colour classes are set up whose main criterion of classification is the quantity of pigment. When we consider the testees of all age classes, sex differences have no statistical relevance as for iris colour. Only in the case of male testees may an intensive decrease of blue and brown iris colour in favour of combination colours (yellow pigment colours in particular) be observed during the phase of puberty. Therefore, the brightening postulated in the relevant literature can be confirmed. With regard to female testees, in contrast, pigment shifting is of no statistical relevance. After a slight brightening the irises numerically re-darken at the adult-stage to the initial child level, i.e. they become "dark again" rather than just become "darker". Within the iris structure only the characteristics of the anterior stroma leaf show sex differences. They are, however, only weakly marked and can be described merely as a trend. Over the whole range of the age classes, there are no outstanding structural differences. The different iris characteristics concerning iris colour stand in a significant relation to each other. When we consider the statistically relevant relations between structural features, it becomes clear that particularly reduced and particularly intact iris characteristics correlate. Thus, we can distinguish between an intact type of iris and a reduced one. Three quarters of the testees, however, combine reduced and intact properties with medium degrees of markedness.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Pulmonary toxicity of the combination of bleomycin and peplomycin--an experimental study in rats.

Combination of the two drugs bleomycin (BLM) and peplomycin (PEP) may enhance their antineoplastic effects; however, it is not known as to whether this enhancement is accompanied by a concomitant increase in toxicity, especially toxic lung damage. A histologic and stereologic investigation was carried out to compare the pulmonary toxicity of BLM, PEP, and a combination of the two drugs in animals. A total of 180 female Wistar rats were randomly assigned to 4 groups: 45 animals were treated with daily i.p. injections of 4 mg/kg BLM, 45 rats received 2.5 mg/kg i.p. PEP daily, 45 animals were given i.p. injections of a combination of 2.5 mg/kg BLM and 1 mg/kg PEP, and 45 rats received 1 ml 0.9% NaCl solution. Histological examination of the lungs demonstrated varying degrees of exudative and fibrosing alveolitis in animals treated with BLM, PEP, and BLM-PEP. Stereological analysis revealed a significant thickening of the alveolar wall after 20-60 days and a significant decrease in the surface density of alveolar walls after 40-60 days in all treated groups. Both histological examination and stereological parameters indicated more pronounced inflammatory changes in the alveolar walls and a prior loss of alveolar surface after 20 and 30 days in animals receiving PEP and PEP-BLM as compared with those undergoing BLM treatment. After 40-60 days, during which time irreversible fibrotic changes prevailed, significant stereological differences between the three treated groups could not be detected. Thus, our experimental observations did not show any potentiation of the toxic pulmonary effect of BLM and PEP following their combined administration.

Animals↗

Prevention of bleomycin-induced fibrosing alveolitis with indomethacin: stereological studies on rat lungs.

The prevention of the pulmonary toxicity of bleomycin (BLM) has been investigated in experimental models where pulmonary damage was induced with one intra-tracheal dose of BLM. The present investigation was carried out as a pre-clinical study in which BLM was administered systemically. The non-steroid anti-inflammatory drug indomethacin (INDO) was chosen as a possible candidate for pulmonary protection. Twenty female Wistar rats were treated daily with 4 mg/kg (7.3 units) BLM intra-peritoneally for 50 days and 20 rats with BLM and with 1 mg/kg INDO subcutaneously for 62 days. There were 20 animals as controls. Histological examination revealed fibrosing alveolitis in the BLM-treated group which was markedly suppressed in the combination group. Quantitative morphological (stereological) parameters demonstrate that BLM induced alveolar wall thickening (+45%), pulmonary fibrosis (+110%), and an increase of alveolar wall nuclei and of intra-alveolar macrophages (volume densities +43% and +133%, P less than 0.001). In contrast, after combination with INDO significant differences to the control group could not be detected except for a slight increase of intra-alveolar macrophages (+62%). Thus, INDO is a highly efficient agent in the prevention of BLM-induced pulmonary damage.

Animals↗