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Biomedical subjects

M Drews

Publications and source records attributed to M Drews.

At least 55 records · Page 3Linked to original sources
PubMed1996

Activation of human umbilical vein endothelial cell progelatinase A by phorbol myristate acetate: a protein kinase C-dependent mechanism involving a membrane-type matrix metalloproteinase.

Matrix metalloproteinases play an important role in tumor invasion, angiogenesis and inflammatory tissue destruction. The 72-kd gelatinase A is the most widely distributed. Along with the 92-kd gelatinase B, it plays an important role in basement membrane turnover. Gelatinase A is secreted as progelatinase A and, when activated, can cause extracellular matrix destruction. The physiologic mechanism of this activation is not well understood. Based on the importance of endothelial cells in inflammation and cancer, we sought in this study to systematically study the PMA-induced activation of endothelial cell progelatinase A. Using HUVEC, we demonstrated that PMA-induced activation of progelatinase A in these vascular endothelial cells (a) was protein kinase C-dependent as it was blocked by H-7; (b) occurred through cell-mediated events as PMA was unable to activate progelatinase A in a cell-free system and that low dose tissue inhibitor of metalloproteinases-2, but not tissue inhibitor of metalloproteinases-1, totally inhibited PMA-induced activation; (c) was accompanied by an increase in the membrane-type matrix metalloproteinase (MT-MMP). We also found that the combination of PMA and the cytokine tumor necrosis factor-alpha increased HUVEC secretion and activation of gelatinase B. In conclusion, our data show that PMA activation of vascular endothelial cell progelatinase A is a cell membrane event that is at least partially mediated through a PKC-dependent mechanism and is accompanied by an increase synthesis of MT-MMP. These data suggest a role for MT-MMP in the activation of progelatinase A in vascular endothelial cells.

Cell Membrane↗
PubMed1996

Ultrastructural changes in the small intestinal epithelium after total resection of the colon.

UNLABELLED: The aim of the study was to analyze ultrastructural changes in the mucosa of the small intestine after total resection of the colon in 29 patients (familial polyposis in 21, ulcerative colitis in 8). We studied specimens of the small intestinal mucosa obtained from ano- and rectoscopy. The specimens were routinely processed for transmission electron microscopy. Early after the operation (up to 4-5 months) we observed marked structural disorders of the mucosal epithelium and regenerative cell atypia (dysplasia-like changes). At 6 months after the operation we found rapidly progressing normalization of the epithelial mucosa and its mimicking the epithelium of the colon: increased amount of mucous cells, formation of vacuolized cells, almost complete atrophy of microvilli on the surface of enterocytes, increase of the intercellular space (retention space). Foci with dysplasia features were quite numerous in group I, in contrast to group II where they were sporadic. CONCLUSION: the epithelium of small intestinal mucosa has the ability of convergence towards the epithelium of colon.

Adenomatous Polyposis Coli↗
PubMed1996

[Primary hyperparathyroidism--diagnostic problems].

Parathyroid imaging with 99m Tc-MIBI, introduced at the beginning of the 90's seems to be a promising method for parathyroid adenomas localization. The aim of the study was to assess the efficacy of parathyroid imaging with 99m Tc-MIBI for preoperative localization of parathyroid adenomas and to compare that method with the high-resolution ultrasonography. Thirteen patients with primary hyperparathyroidism of duration from 2 to 25 years were included in the study. The presence of parathyroid adenomas was confirmed by histopathology in all patients. The sensitivity for scintigraphy and ultrasonography was 92.8% and 78.5%, the number of false positive results was 0 and 2 and false negative-0 and 1, respectively. Parathyroid imaging with 99m Tc-MIBI is a useful method for parathyroid adenomas localization, and in contrast to ultrasonography its sensitivity does not decrease if a parathyroid adenoma is located ectopically. Nevertheless, because of the greater accessibility, lower costs and its simplicity ultrasonography should be used as a screening modality for parathyroid adenoma localization.

Adolescent↗
PubMed1995

Thrombin induces the activation of progelatinase A in vascular endothelial cells. Physiologic regulation of angiogenesis.

Angiogenesis requires degradation of vascular basement membrane prior to migration and proliferation of endothelial cells; proteinases are essential ingredients in this process. Because of thrombin's multiple effects on endothelium, we have examined its role in matrix metalloproteinase activation using human umbilical vein endothelial cells. Gelatin zymography of endothelial conditioned media revealed a prominent 72-kDa progelatinase A band. Addition of alpha-thrombin to endothelial cells resulted in the generation of 64 and 62 kDa gelatinolytic bands which is consistent with the activation of progelatinase A; thrombin had no effect in the absence of cells. This effect requires the proteolytic site of thrombin since progelatinase A activation was abolished by specific inhibitors of thrombin. Matrix metaloproteinase inhibitors diminished thrombin-induced activation of progelatinase A. Pretreatment of endothelial cells with excess tissue inhibitor of metalloproteinase-2 or a COOH-terminal fragment of progelatinase A abrogated thrombin-mediated activation of progelatinase A presumably by competing with the COOH terminus of native progelatinase A for interaction with an activator site on endothelial plasma membranes. Although membrane-type matrix metalloproteinase was demonstrated in endothelial cells by Northern and Western blotting, the receptor function of this molecule in thrombin-induced activation of progelatinase A needs to be clarified. Progelatinase A activation did not require intracellular signal transduction events mediated by the thrombin receptor. These data demonstrate that 1) endothelial cells express a novel activation mechanism for progelatinase A, 2) proteolytically active thrombin regulates this activation mechanism, and 3) activation occurs independently of the functional thrombin receptor.

Amino Acid Chloromethyl Ketones↗
PubMed1994

Different pattern of T cell receptor delta gene rearrangement in tumour-infiltrating lymphocytes and peripheral blood in patients with solid tumours.

Tumour-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) from four patients with renal-cell carcinoma (three paired with blood), two colon carcinomas (both paired with blood) and two melanomas (blood was not available) were analysed for the T cell receptor (TCR) delta gene repertoire. Polymerase chain reaction analysis, employing a panel of specific primers for TCR delta gene segments, showed different gene rearrangement patterns in TIL and PBL in all patients. Simultaneous analysis of TIL and PBL revealed the presence of lymphoid cells in the tumour tissue that were not present in the periphery. These results demonstrate that, although tumour-infiltrating lymphocytes contain gamma/delta T cells within the range observed in peripheral blood, these cells differ from those in peripheral blood in their gene repertoire and this may account for selective accumulation or/and in situ amplification of gamma/delta lymphocytes at the tumour site, indicating a unique type of host reaction against tumour.

Base Sequence↗
PubMed1991

Total thyroidectomy in the treatment of Basedow's ophthalmopathy.

Four patients in the age 42-63 (3 females and 1 male) with Basedow's disease and hyperthyroidism were investigated. Visual changes were classified to the IV group of American Thyreologic Society's classification. A total thyroidectomy was performed when status of euthyreosis has been obtained. Check examinations were carried out 6, 12 and 18 months after surgery. It has been confirmed that total thyroidectomy performed in patients with thyroid ophthalmopathy leads to reduction of infiltrative changes in the orbit. However, this can be stated not earlier than 12 months after surgery.

Adult↗
PubMed1988

Host reactions to Mycoplasma pneumoniae infections in guinea-pigs preimmunized systemically with the adhesin of this pathogen.

Guinea-pigs developed systemic and local humoral responses after intraperitoneal immunization with the isolated adhesin (168 kDa protein) of Mycoplasma pneumoniae cells. Hilar lymphocytes of these animals showed proliferation after in vitro stimulation with the 168 kDa protein or sonicated M. pneumoniae whole cell antigen. Animals preimmunized and subsequently infected with M. pneumoniae showed increased M. pneumoniae-specific IgG, IgA and adherence inhibiting antibody activities. Nevertheless these animals developed severe lung lesions of lympho-histiocyte infiltrations. Furthermore hilar lymph nodes were depleted of immunocompetent lymphocytes, suggesting a cell transfer of specific stimulable lymphocytes to the inflammation sites.

Adhesins, Bacterial↗
PubMed1988

Immunological reaction of guinea-pigs following intranasal Mycoplasma pneumoniae infection and immunization with the 168 kDa adherence protein.

Humoral responses to Mycoplasma pneumoniae proteins, especially the 168 kDa protein, were demonstrated by Western blotting in sera and bronchial washings of all groups of infected or immunized guinea-pigs. However, infection was not prevented by these local and systemic antibodies. Hilar lymphocytes of infected and immunized guinea-pigs were stimulated in vitro by sonicated M. pneumoniae antigen and by the 168 kDa protein. Stimulation was significantly lower in animals which had been infected twice or had been preimmunized and challenged by infection. Histologically the most severe lesions were seen in the twice-infected group followed by the preimmunized group which was subsequently infected.

Animals↗