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Biomedical subjects

M Susani

Publications and source records attributed to M Susani.

At least 109 records · Page 6Linked to original sources

Infrared laser stapedotomy.

A pulsed holmium: YAG laser (lambda = 1980 nm) was used to perform 0.4 mm stapedotomy fenestrations in human stapes footplates from freshly dissected cadavers under simulated surgical conditions. The energy was coupled into a 400 microns core diameter nylon fiber. Thermal gradients were then measured following laser applications and tissue responses examined by light microscopy. The results of this study suggest the feasibility of using a surgical holmium: YAG laser in middle ear surgery.

Humans↗

Value of bladder wash cytology in the follow-up of patients with bladder carcinoma receiving intravesical chemoprophylaxis with mitomycin C.

511 bladder wash cytologic findings in 121 patients receiving intravesical chemoprophylaxis with mitomycin C after transurethral resection of stage pTa to stage pT2 bladder carcinoma were retrospectively analyzed. In 42 recurrent tumors, sensitivity of detection by cytology amounted to 67% in GIII tumors, 56% in GII tumors, and 20% in GI tumors. 16% of G0 tumors were cytologically positive. 33% of a total of 30 endoscopically detected recurrent GI-GIII tumors yielded negative results at bladder wash cytology, the findings were suspicious in 27%, while only 40% of all recurrences had a positive bladder wash cytology. Positive cytologic findings combined with normal endoscopic results were obtained in 24 patients. 15 of these (62%) developed recurrences after a mean interval of 15 months (3-60 months) during or after metaphylaxis. When suspicious findings were included, 20 of 30 carcinomas were detected, while 7 of 12 G0 tumors were overgraded. Bladder wash cytology has its merits for early detection of recurrences, since almost two thirds of the patients with positive cytologic findings and negative endoscopy developed a recurrent tumor at a later date. Whether or not positive cytology combined with negative endoscopic results should lead to therapeutic consequences remains to be discussed.

Administration, Intravesical↗

Capillary leak syndrome during low dose granulocyte-macrophage colony-stimulating factor (rh GM-CSF) treatment of a patient in a continuous febrile state.

A 20 years old man with peripheral primitive neuroectodermal tumor involving the bone marrow received 12 Gy fractionated total body irradiation, 140 mg/m2 melphalan, 1800 mg/m2 etoposide, and 1500 mg/m2 carboplatin for consolidation of first remission. Thereafter, 250 micrograms/m2/day recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) (Behring Werke) were administered as continuous infusion 4 days after infusion of autologous bone marrow and peripheral stem cells to accelerate granulocyte reconstitution for control of a continued febrile state. The clinical picture of capillary leak syndrome developed with weight gain, pleural effusions and peripheral edema. The patient's condition stabilized after discontinuation of rh GM-CSF. Eight days later he died of invasive aspergillosis. The clinical course of our patient suggests a potentially fatal toxic effect of rh GM-CSF, even in low dose, in the setting of septicemia or fungemia.

Adult↗

Transcellular transport and membrane insertion of the C5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy.

Deposition of the C5b-9 complex of C in glomeruli of rats with experimental membranous nephropathy (MN) is essential for the development of proteinuria. In this investigation C5b-9 was localized in the passive Heymann nephritis (PHN) by immunoelectron microscopy with a mAb specific for C5b-9(m) neoantigen. Its distribution was compared with that in another model of MN induced by successive injections of cationic human IgG and rabbit anti-human IgG into rats. In PHN C5b-9 was found: 1) in the immune deposits (ID), and on the cell membranes of foot processes close to the ID; 2) in clathrin-coated pits of the glomerular epithelial cells (GEC) close to the ID and in membrane vesicles in the cytoplasm, separated from sheep IgG and the gp330 Ag; 3) in high concentration in multivesicular bodies of GEC; and 4) in association with membrane vesicles in the urinary space which presumably are the exocytosed content of membrane vesicular bodies. By contrast, in the cationic IgG-MN model C5b-9 was found mostly in ID, but rarely within the GEC. By freeze-fracture electron microscopy we have further identified 200- to 250-A intramembrane particles in PHN in the cell membranes of the "soles" of the foot processes which resemble membrane inserted human C5b-9(m). Degradation products of C5b-9 were further detected by immunoblotting of a 100,000 x g pellet of PHN rat urine. These results indicate that, in PHN, C5b-9 is inserted into the cell membranes of GEC, and that it is selectively endocytosed and transported across GEC by a cellular mechanism which apparently protects the cell from accumulation of membrane-inserted C5b-9.

Animals↗

A beta 1-integrin receptor for fibronectin in human kidney glomeruli.

The fibronectin receptor (FNR) is a transmembrane heterodimeric glycoprotein which shares a common beta 1-chain with several other members of the integrin family of adhesion receptors. The authors have prepared a membrane fraction of isolated human glomeruli, from which two proteins (apparent molecular weights 120 kd and 140 kd) bound to a fibronectin-column, and were selectively released by the synthetic peptide Arg-Gly-Asp-Ser. These molecules were labeled in immune overlays by an antibody raised against the FNR from human placenta that recognizes both the FNR-specific a-chain and the group-specific beta 1-integrin chain. In sections of normal human kidneys this antibody labeled predominately the mesangia and the peripheral capillary walls of glomeruli by an immunoperoxidase procedure. Quantitative immunoelectron microscopy, using an indirect immunogold procedure, revealed a preferential localization along the cell membranes of mesangial, epithelial, and endothelial cells that face the mesangial matrix or the glomerular basement membrane (GBM). In kidney biopsies from patients with various glomerular diseases (membranous and other forms of glomerulonephritis, minimal change disease) the distribution was similar to that in normal glomeruli. These findings indicate that a beta 1-integrin-related FNR is present in normal and diseased human glomeruli.

Adult↗

Differentiation of mononuclear blood cells into macrophages, fibroblasts and endothelial cells in thrombus organization.

The organization of thrombi and emboli may be performed exclusively by mononuclear blood cells which represent precursors of various mesenchymal cell types. Between the 10th and 20th day after the onset of blood clotting, mononuclear cells within the fibrinous matrix differentiate into (1) macrophages responsible for hematoclasia and hematophagocytosis, (2) endothelial cells lining autolytic slits in the fibrinous matrix and forming new capillaries, and (3) fibroblasts and even smooth muscle cells building up a young mesenchymal connective tissue.

Cell Differentiation↗

Angiogenesis from mononuclear cells in thrombi.

In organizing thrombi angiogenesis is not dependent on invasion of vasa vasora from the vascular wall. Mononuclear cells of the monohistiocytic system are always present within the clotted blood and are capable of differentiation into various types of mesenchymal cells, including endothelial cells. At first autolytic slits and clefts appear in the fibrinous superficial areas of the thrombus. They are gradually lined by spindle-shaped "pre-endothelial" cells that already possess immunohistological properties of endothelial cells but still resemble primitive mesenchymal cells ultrastructurally. Later these cells gain connection with each other by pseudopodia, overlapping and interdigitation until the channels in the fibrinous matrix are covered by an uninterrupted layer of cells. These cells are now characterized ultrastructurally by the appearance of specific endothelial organelles (Weibel-Palade bodies). Circulation within these channels begins from the blood stream. In addition, angiogenesis by sprouting of vasa vasora from the vascular wall occurs in those areas of the thrombus in contact with the vessel wall. In blood vessels with on unimpaired intimal layer, angiogenesis by invasion of capillaries occurs at an earlier date than capillary formation by mononuclear cells.

Adolescent↗

Identification of a 400-kd protein in the brush borders of human kidney tubules that is similar to gp330, the nephritogenic antigen of rat Heymann nephritis.

The nephritogenic antigen of Heymann nephritis (HN)--a well-studied experimental rat model disease of human membranous glomerulonephritis (MGN)--was recently shown to be a 330-kd glycoprotein (gp330) which is present in the membranes of both the rat tubular brush borders and of podocytes. Because the pathogenic antigen(s) of MGN are unknown, the authors have searched for a gp330-like molecule in human kidney and for its role in MGN. The authors here report that a membrane protein (apparent molecular weight 400 kd) is present in human kidney which is immunologically cross-reactive with rat gp330. By immunoelectron microscopy (using rabbit anti-rat gp330 IgG or a monoclonal anti-400-kd IgG) this molecule is similarly localized in human proximal tubules, but it is absent from the podocytes of human glomeruli. The 400-kd molecule is not detected in the glomerular immune deposits of 30 biopsies of MGN. It is proposed that this is due to the lack of the 400-kd protein in human glomeruli which prevents the formation of initial 400-kd anti-400-kd IgG immune complexes in situ.

Animals↗

Organisation of experimental thrombosis by blood cells. Evidence of the transformation of mononuclear cells into myofibroblasts and endothelial cells.

To clarify whether thrombus organisation was carried out by local cell activity or by elements of the circulating blood we developed an artificial prosthesis, made of an impermeable polyurethane material with an athrombogenic surface but with a central part consisting of a DACRON velour ring which was thrombogenic. We implanted these devices into the aorta of 10 sheep. In these animals, organisation of the central thrombus by local aortic cells could be excluded. After varying periods of time (2-84 days), the device was removed and the organized thrombus investigated by light and electron microscopy. From our investigations the organisation process with the development of mesenchymal cellular elements proceeded in 3 steps: The activation of the mononuclear macrophage system, the appearance of myofibroblastic cells and endothelial formation. The activation of the mononuclear macrophage system is probably induced by chemospecific products of metabolism arising from aging thrombotic material. Apart from mononuclear elements such as monocytes, macrophages, and giant cells we observed fibroblast-like and myofibroblast-like cells. The matrix contained collagen. Endothelium developed on the surface of the organizing thrombus. The final stage was characterized by the formation of a pseudovessel wall, which followed the pattern of the vascular model. Our findings support the hypothesis that a thrombus may be organized by cells derived from the circulating blood.

Animals↗

[Clinical, endocrinological and pathohistologic aspects of beta-HCG positive seminoma].

The most important aspects of the clinical findings, endocrinology and course of the disease in 14 patients with the histological diagnosis of pure seminoma of the testis and positive serum beta-HCG levels are presented. In addition to routine investigations, immunohistochemical examination of the formalin-fixed specimen by the immunoperoxidase technique was also carried out. Serum alpha-feto-protein levels remained normal in all 14 patients. There was no correlation between serum beta-HCG level and tumour stage. The longest period of observation was 76 months and the shortest 8 months. Patients with no evidence of metastatic disease (5 patients, N0M0) or patients with low-stage disease (5 patients, N1 or N2M0) respond very well to radiotherapy. 4 patients (N3-N4M0) with large retroperitoneal metastases or distant lymph node metastases underwent different combinations of treatment.

Adult↗

[Importance of the intracellular detection of alpha-fetoprotein and beta-human chorionic gonadotropin in a testicular tumor using immunoperoxidase].

30 patients with testicular cancer (20 seminoma, 10 non-seminomatous tumours) were investigated with respect to the determination of alpha-fetoprotein and beta-human chorionic gonadotropin in formalin-fixed slices by means of the indirect immunoperoxidase technique. The immunohistochemical method detected HCG-producing cells in 8 seminoma, whereas routine histology revealed syncytiotrophoblastic giant cells in 4 cases only. The immunohistochemical results and the serum AFT, and/or HCG values obtained by radioimmunoassay corresponded well in all patients with non-seminomatous tumours. Direct evidence of HCG production in the primary tumour can be important in therapeutic decisions, especially in patients with seminoma. The direct proof of AFP in the primary tumour might answer in the future the question of the incidence and the prognostic impact of yolk sac tumour parts in malignant teratomas.

Chorionic Gonadotropin↗

Experimental synovitis induced by intraarticular administration of alpha 2-macroglobulin-proteinase complexes.

Rheumatoid synovial collagenase was prepared from tissue cultures from rheumatoid arthritis patients, obtained after synovectomy. Alpha 2-macroglobulin was isolated from human plasma and complexed with collagenase or trypsin. Formation of both types of complexes was proven by sodium dodecyl sulfate and rate electrophoresis. Normal rabbits were injected intraarticularly into the right knee, on days 0, 3, and 6, with either alpha 2-macroglobulin-collagenase or alpha 2-macroglobulin-trypsin complexes. Control injections of alpha 2-macroglobulin, trypsin, or rheumatoid synovial collagenase were applied to the left knee joint cavity. Groups of rabbits were killed 18 hours, 1 week, or 3 weeks after the last injection, and cellular exudation into synovial fluid and morphologic alterations of synovium were investigated. Joints injected with alpha 2-macroglobulin showed no synovitis, while joints injected with collagenase showed an experimental synovitis. Alpha 2-macroglobulin-proteinase complexes, however, induced a synovitis, which was more severe than that occurring after injection of proteinases only. In the early stages, synovium showed perivascular accumulation of inflammatory cells, infiltration with neutrophils, proliferation of synovial cells, and exudation of inflammatory cells into synovial fluid. Later stages were characterized by infiltration with mononuclear cells and fibroplasia.

Animals↗

Transcription of a zein gene introduced into sunflower using a Ti plasmid vector.

A maize genomic clone containing a zein gene (Z4) was inserted into the T-region of the T37 Ti plasmid. Agrobacterium tumefaciens cells carrying this modified Ti plasmid were used to inoculate sunflower stemlets. Callus tissue active in nopaline synthesis was grown from a single transformed cell. DNA analysis of this tissue showed that the zein gene plus T-DNA was present in approximately 12 copies per diploid sunflower genome. A 1000 +/- 100 base RNA homologous to a zein probe could be isolated from the engineered sunflower tissue and the 5' end of this RNA was determined by S1 nuclease mapping. Two transcription start sites were detected. The positions of these transcription start sites and the ratio of the amounts of the two transcripts are identical for the Z4 gene in sunflower and in maize endosperm. Although the zein RNA isolated from the engineered sunflower tissue could be translated in a wheat germ system to yield an immuno-precipitable protein of the expected mol. wt., the presence of the zein protein in the sunflower tissue could not be demonstrated.

DNA, Recombinant↗