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Biomedical subjects

M Spycher

Publications and source records attributed to M Spycher.

36 records · Page 2Linked to original sources
PubMed1993

Production and characterization of a mouse/human chimeric antibody directed against human neuroblastoma.

Hybridoma CE7 produces a murine antibody (gamma 1/kappa) which binds to a 190-kDa cell-surface glycoprotein of human neuroblastoma. Because of its tumor specificity, it has been used routinely in clinical pathology to confirm diagnosis of neuroblastoma. We have isolated the gene segments coding for the variable regions of the immunoglobulin H and L chain of this hybridoma. These V genes were used to construct mouse/human chimeric H and L chain genes (gamma 1/kappa) which were then expressed in SP2/0 cells. A cell-binding inhibition assay showed that the specificity of the chimeric CE7 antibody (chCE7) is identical to that of the original CE7. Radioiodinated chCE7 binds to approximately 43,000 sites per neuroblastoma cell with an affinity of 10(10) M-1. In neuroblastoma-bearing nude mice, biodistribution studies with [125I]chCE7 were performed and tumor accumulations of up to 32% of injected dose/g tissue together with low blood and organ uptake were found.

Amino Acid Sequence↗
PubMed1992

Venous leakage--a new therapeutical concept.

According to our opinion, so-called venous leakage is no venous disease but a result of impaired cavernous tissue. Since in over 90% of all patients with venous leakage also arterial disease was discovered and since ultrastructural degenerative processes in the cavernous bodies were detected, we consider traditional corrective venous surgery as unphysiological and illogical. We suggest arterial revascularization combined with a mechanical penis banding as a new therapeutical concept.

Arterial Occlusive Diseases↗
PubMed1992

[Tumor diseases in families of 600 breast cancer patients with special reference to familial adenocarcinomatosis and the Li-Fraumeni-/SBLA syndrome].

In some families breast cancer aggregates as the predominant site-specific neoplasia and in others in association with defined malignancies. In the case of familial adenocarcinomatous (Lynch II-syndrome) it occurs together mainly with colorectal and endometrial carcinoma whereas in the case of the Li-Fraumeni/SBLA-syndrome it belongs to a wider spectrum including sarcoma, brain tumors, lung and laryngeal cancer, leukaemia and adrenocortical carcinoma. The occurrence of these malignancies is reported as they were observed in the families of 600 women suffering from breast cancer.

Adenocarcinoma↗
PubMed1991

Case report 693: Schneckenbecken dysplasia.

Three siblings with SBD from consangineous parents are reported. The prenatal diagnosis of a short-limbed form of dwarfism was made by ultrasonography and the final diagnosis in the index case by radiography, demonstrating a short-limbed, platyspondylic dwarf with a snail-like configuration of the ilium and vertebral bodies, flat on AP and round on lateral view. The histological examination showed a generalized, severe disturbance of cartilage formation with marked hypercellularity of proliferating and resting zones, reduction of intercellular matrix, and shortening of the irregular columns of proliferating cartilage. The ultramicroscopic findings were nonspecific. This is the first report of SBD after the original description, bringing the total to 14 cases in 5 families. The correct radiological diagnosis and the differential diagnosis, in particular thanatophoric dysplasia, are essential for genetic counselling and obstetrical guidance of families affected with this autosomal recessive dysplasia.

Dwarfism↗
PubMed1991

Low number of complement C3b/C4b receptors (CR1) on erythrocytes from patients with essential mixed cryoglobulinemia, systemic lupus erythematosus and rheumatoid arthritis: relationship with disease activity, anticardiolipin antibodies, complement activation and therapy.

Our aim was to assess whether the amount of complement C3b/C4b receptors (CR1) on erythrocytes shows a correlation to disease activity in various connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and essential mixed cryoglobulinemia (EMC). Using an anti-CR1 monoclonal antibody, 26 patients with SLE, 34 with RA and 22 patients with EMC were investigated for erythrocyte CR1 expression. The control group consisted of 30 healthy individuals. The mean number of CR1/erythrocyte in the control group was 568 +/- 197 (range 174-1060), significantly higher than studied (EMC:379 +/- 248; p = 0.0005;SLE 147 +/- 56, p less than 0.0001; RA 298 +/- 177, p less than 0.0001). In patients with RA and in SLE, but not in patients with EMC, the number of CR1 numbers and anticardiolipin antibody (aCl) titers (r2 = 0.493; p = 0.034). A statistically significant correlation between CR1 numbers and CH50 values was found in patients with SLE, while in 3 patients with RA 4 months of therapy with cyclosporine A led to a further 30% reduction in CR1 number. Our conclusions are that (a) the decreased expression of erythrocyte CR1 is apparently a common feature of patients with various connective tissue diseases; (b) several acquired factors such as disease activity, complement activation, aCl and drugs may contribute to the loss of CR1 from erythrocytes; (c) in patients with RA and SLE, but not in patients with EMC, CR1 enumeration on erythrocytes may serve as a variable for clinical monitoring.

Adult↗
PubMed1991

[Electron microscopy of the exocrine pancreas in experimental acute hypercalcemia].

Hypercalcemia has been associated with acute pancreatitis clinically and in the experimental animal. We studied the pancreatic ultrastructure in acute experimental hypercalcemia. Anesthetized cats (Pentobarbital, 0.55 mg/kg) received Ca++ (Calcium-Gluconate: 0.6 mmol/kgh; n = 4), K+ (KCl: 1.1 mmol/kgh; n = 4) or NaCl (0.9%; n = 4) locally through retrograde infusion into the splenic artery. Biopsies for electron microscopy (EM) were taken at three hours. Eight cats received intravenous Ca++ (0.6 mmol/kgh, 0.3 mmol/kgh after three hours) or NaCl (0.9%) for 12 hours. Biopsies were collected in two animals in three-hour intervals, and in all animals at twelve hours. After local calcium infusion necrotizing pancreatitis was seen macroscopically in the body of the pancreas. Biopsies for EM showed acinar cell necrosis, hydrops of nuclei and mitochondria and needle-like precipitates in the cytoplasma in the center of calcium perfusion. Biopsies taken from the peripheral region of the macroscopically altered tissue revealed desorganisation of the acinar polarisation and the endoplasmic reticulum, with zymogen granules appearing in the basolateral cell-portion. After intravenous calcium administration no macroscopical changes were seen. In EM acinar cells showed dilatation and proliferation of the golgi apparatus and increased number of condensing vacuoles indicating stimulation. Again, disorganisation of acinar cell polarisation was present. Control animals treated with K+ or NaCl showed normal pancreatic ultrastructure. The morphological changes after calcium infusion indicate direct damage to the acinar cell. Our results suggest that hypercalcemia induced pancreatitis could originate in the acinar cell.

Acute Disease↗
PubMed1991

[Venous leakage--a new therapeutic concept].

According to our opinion, so-called venous leakage is not a venous disease but a result of impaired cavernous tissue. Since in over 90% of all patients with venous leakage arterial disease has also been discovered, and since in addition ultrastructural degenerative processes have also been detected in the cavernous bodies, we consider the traditional treatment in the form of venous surgery unphysiological and illogical. We suggests arterial revascularization combined with mechanical penis banding as a new therapeutic concept.

Erectile Dysfunction↗
PubMed1987

[Mucopolysaccharidosis 6-A (Maroteaux-Lamy disease): comparison of clinical and pathologico-anatomic findings in a 27-year-old patient].

The autopsy of the 27-year-old patient suffering from a severe form of mucopolysaccharidosis type VI-A (Maroteaux-Lamy) described in the article by Rampini et al. revealed the compressive cervical myelopathy (C1) to be due to a severe, slit-like deformity of the vertebral canal which was due to a massive thickening of the ligaments, dislocation of the posterior arch of the atlas and broadening of the dura. The massive, generalized disorder of the enchondral ossification involving mainly tubular bones and spine, led to short stature, arthrosis of large joints, and to an angular thoraco-lumbar kyphoscoliosis. Our patient had a massive V-shaped stenosis of the upper third of the trachea. The atrio-ventricular valves of the heart were thickened, and there was fibrosis of the endocardium. The cardiac conduction system displayed fibrosis and foam cell transformation of the fibroblasts in the bundle of His, a lesion not previously reported. Light and electron microscopic investigation showed a massive increase of mucopolysaccharides mainly in the matrix of the fibrous tissue and of the cartilage. Furthermore, the fibroblasts and chondrocytes as well as the hepatocytes and the ganglion cells of the central nervous system contained increased amounts of glycosaminoglycans.

Adult↗
PubMed1986

Pathogenesis of osteochondrosis juvenilis Scheuermann.

In osteochondrosis juvenilis Scheuermann, foci of various sizes in the cartilaginous end plates of the vertebral bodies display a loosening or complete interruption of the collagen fibers. These findings, together with an alteration and occasional absence of the growth zone, may result in the typical deformation of the vertebral bodies. Electron micrographs of the areas with optically absent collagen fibers reveal collagen fibrils. They are arranged in an irregular pattern. We conclude that a disturbance of collagen or ground substance biosynthesis is of importance in the pathogenesis of juvenile osteochondrosis.

Adolescent↗
PubMed1983

The alternative complement pathway control protein H binds to immune complexes and serves their detection.

During solubilization of immune complexes C3b becomes fixed to the immunoglobulin part and serves as a receptor for the alternative complement pathway control protein H. The H-C3b immune complex interaction can be made detectable using 4% polyethyleneglycol to separate free from bound 125I-H. Tetanus toxoid (Te)/anti-Te complexes kept soluble with fresh serum and containing 125 IU of specific antibody bound 18% of 125I-H; when fresh serum was chelated with 10 mM EDTA, 125I-H binding was only 5%. On sucrose density gradients, the H-binding material sedimented in the range of 12 to 30 S. In 36 serum samples from rheumatoid arthritis (RA) patients and in 12 serum samples from patients with systemic lupus erythematosus (SLE), 125I-H binding was significantly elevated to 9.5 +/- 4.7% (mean +/- 1 SD) and 13.3 +/- 5.6%, respectively, while 125I-H binding by 36 normal human sera was 4 +/- 2%. RA samples (17/36, 47%) and SLE samples (9/12, 75%) had H-binding values increased by more than 2 SD above the normal mean. The serum samples were also assessed for conglutinin- and C1q-binding activities; a significant correlation between H and C1q binding was observed (P less than 0.001); there was no correlation between H and conglutinin binding. Although binding to immune complexes through its interaction with C3b, H clearly detects a population of complexes other than conglutinin, thus expanding the possibilities of further characterizing pathological complexes.

Antigen-Antibody Complex↗
PubMed1983

Erection and priapism: a new physiopathological concept.

For normal erection two mechanisms are essential: the first provides increased arterial inflow, most probably this is obtained due to the activity of the intimal cushions within the arteriae helicinae and within the shunt vessels. The second mechanism uses increased arterial blood flow; this could be obtained due to the activity of the trabecular muscle fibers of the corpora cavernosa. In consequence, we would deal with two different types of priapism: one type--high-flow priapism--occurs at the level of the arteriae helicinae and the intimal cushions and provokes a high-flow situation, and the second type, with blood stasis in the corpora cavernosa, occurs at the level of the trabeculae due to persistent contraction of the smooth muscle fibers. The prognosis of the second type is much less favorable and should be cured by surgery within the first 48 h.

Humans↗
PubMed1978

[Revitalization of bovine xenograft used for repair of experimental tracheal defects (author's transl)].

In 12 mongrel dogs tracheal defects of different size were covered by bovine xenografts. The grafts were subjected to electronmicroscopic examination 2 to 19 months after implantation. Following the ingrowht of fibroblasts and capillaries a basal membrane is formed on the side of the previous graft lumen. After 4 to 5 months this membrane is covered from the tracheal margins by microvillous cells. After 8 months ciliated epithelia and goblet cells are developed by cell metaplasia. Although the graft becomes revitalized and integrated into the tracheal wall, the layer of ciliated epithelia is interrupted by less differentiated cells. The possible causes for this phenomenon are discussed. Thus bovine xenograft used for the repair of tracheal defects has the following advantages: total revitalization, no shrinkage, less prone to infection and formations of ciliated epithelia.

Animals↗
PubMed1978

[Revitalization of bovine xenografts used for experimental arterial replacement in dogs (author's transl)].

In 16 mongrel dogs bovine xenografts of 4 to 12 cm of length were used for arterial replacement. The grafts were removed after 30 minutes and up to 13 months for electronmicroscopic examination. The graft was shown to be significantly thrombogenic during the first six weeks after implantation. After 8 to 10 weeks an increasing revitalization of the graft is found starting from the ends of the canine artery. A cover of endothelial cells is formed in the graft lumen. The graft wall is enforced by formation of collagen and elastic fibers originating from capillaries and fibroblasts. Revitalization of the graft is limited to a rim of 2 to 3,5 cm next to the anastomoses with the canine artery. The remaining graft segment shows revitalization only on the outside wall. Degenerative changes take place in the inner layer of the graft with time passing.

Animals↗
PubMed1977

[Dihydralazine-induced acute hepatitis with IgM deficiency].

Two patients with IgM-deficiency developed acute, recurrent HB3-Ag negative hepatitis with bridging necrosis following ingestion of low daily doses of dihydralazine. The association between the drug and the liver disease appears probable, as recurrence of hepatitis followed each exposure. One patient developed high titers of antimitochondrial antibodies and the other low titers of antibodies against smooth muscles. The relationship between IgM-deficiency and dihydralazine hepatitis is not clear. Investigation of patients with IgM-deficiency for drug hypersensitivity and liver disease may provide additional information.

Acetylation↗
PubMed1976

Generalized gangliosidosis: acid beta-galactosidase deficiency with early onset, rapid mental deterioration and minimal bone dysplasia.

This report concerns a 3-month-old girl with rapidly progressive psychomotor retardation, hepatomegaly, vacuolated lymphocytes, minimal bone dysplasia and normal excretion of acid mucopolysaccharides. A deficiency of acid beta-galactosidase was demonstrated in isolated leucocytes and in a liver biopsy. The diagnosis of generalized gangliosidosis due to deficiency of beta-galactosidase was also based on the absence of the enzyme activity from cultured fibroblasts. The diagnosis was confirmed on autopsy at 16 months by typical histology, electron microscopy and biochemistry of the organs. beta-galactosidase deficiency has been demonstrated in various clinical conditions ranging from generalized gangliosidosis with severe mental retardation to clinical pictures resembling Morquio's disease and normal intelligence. The heterogeneity of the clinical manifestations in beta-galactosidase deficiency could be explained by different residual activities of a structurally mutated enzyme towards its various substrates.

Bone Diseases, Developmental↗
PubMed1975

Niemann-Pick's disease. Clinical, biochemical and ultrastructural findings in a case of the infantile form.

A diagnosis of Niemann-Pick disease type A was made in a 6-month-old boy on the grounds of progressive psychomotor retardation, hepatosplenomegaly, typical foam cells in the bone marrow and a deficiency of sphingomyelinase in a liver biopsy. Typical ultrastructural changes in lysosomes were found in hepatocytes and in Schwann cells. In spite of the absence of gross morphological changes in the axons and in the myelin sheath of the peripheral nerve biopsy, the nerve conduction velocity in the patient was greatly reduced. The ultrastructural aspect of the lysosomal inclusion suggested the storage of a phospholipid. Biochemical analysis of the liver biopsy demonstrated an increased content of total phospholipid of which sphingomyelin made up for more than 60%. The significance of these data are discussed.

Cholesterol↗
PubMedDate not supplied

Breast cancer in first degree relatives of 180 female breast cancer patients.

The risk of breast cancer and of all malignancies was assessed in first degree relatives of 180 women with breast cancer using a historical cohort study approach. The standardized incidence ratio (SIR) was significantly (p < 0.05) increased for breast cancer in mothers: 1.97 (95% Confidence Interval (CI): 1.27 to 2.91) and in all female first degree relatives: 1.55 (95% CI: 1.08 to 2.15). For breast cancer in sisters it was 1.12 (95% CI: 0.56 to 2.01). For all malignancies the SIR for mothers was 1.12 (95% CI: 0.85 to 1.44), for sisters 1.09 (95% CI: 0.77 to 1.49) and for all female first degree relatives 1.08 (95% CI: 0.89 to 1.32). This study confirms previous investigations showing that breast cancer occurs more frequently in female first degree relatives of women with breast cancer than in the general population.

Adult↗