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Biomedical subjects

S Huber

Publications and source records attributed to S Huber.

At least 109 records · Page 6Linked to original sources
PubMed1990

Effects of acylcarnitine transferase blockade on metabolism and function in the normally and underperfused canine myocardium.

The acylcarnitine transferase blocking agent, sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate (Clomoxir, INN), effectively inhibits free fatty acid oxidation, thereby decreasing myocardial oxygen consumption in the normally perfused myocardium without influencing cardiodynamic parameters. As a consequence, however, arterial free fatty acid levels increase significantly. In an acute dog model, we investigated the hypothesis that the sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate-induced decrease in myocardial oxygen consumption may also improve the energetic situation in the underperfused myocardium. Regional myocardial function was assessed by means of subendocardially inserted ultrasonic crystals, and changes in metabolism were measured regionally by means of a catheter inserted into a local myocardial vein in the underperfused area. The flow in the circumflex coronary artery was reduced on average by 53.5% followed 30 min later by an infusion of sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate (dosage: 20 mg/kg over 20 min). Arterial free fatty acid levels continuously increased, whereas arterial glucose levels decreased. In accordance with the situation in the normally perfused myocardium, free fatty acid uptake and oxygen uptake were also reduced in the underperfused area. However, sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate induced a further, transient increase in end-diastolic segment length and a sustained decrease in systolic shortening in the underperfused area, indicating a further deterioration in regional myocardial function. Control experiments with infusion of 9 g/l sodium chloride showed no change in the degree of regional myocardial dysfunction throughout the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyltransferases↗
PubMed1989

Calcium-binding protein from mouse Ehrlich ascites-tumour cells is homologous to human calcyclin.

A Ca2+-binding protein was purified from mouse Ehrlich ascites-tumour cells. The protein forms monomers and disulphide-linked dimers, which can be separated by reverse-phase h.p.l.c. A partial amino acid sequence analysis demonstrated that the protein has an EF-hand structure. A striking homology was found to rat and human calcyclin (a member of the S-100 protein family), which is possibly involved in cell-cycle regulation.

Amino Acid Sequence↗
PubMed1989

Clinical and experimental aspects of viral myocarditis.

Picornaviruses are frequently implicated as the etiological agents of acute myocarditis. This association is based historically on serological evidence of rising antibody titers to specific pathogens and more recently on identification of viral genomic material in endocardial biopsy specimens through in situ hybridization. Only rarely is infectious virus isolated from either the patient or the heart during periods of maximum myocardial inflammation and injury. Thus, despite a probable viral etiology, much interest centers on the role of the immune system in cardiac damage and the likelihood that the infection triggers an autoimmune response to heart-specific antigens. Heart-reactive antibodies and T cells are found in most myocarditis patients, and immunosuppressive therapy has proven beneficial in many, though not all, cases. Furthermore, murine models of coxsackievirus group B type 3-induced myocarditis also demonstrate that virus infection initiates autoimmunity and that these autoimmune effectors are predominately responsible for tissue injury. How virus-host interactions overcome presumed self-tolerance to heart antigens is discussed, and evidence supporting various theories of virus-initiated autoimmunity and disease pathogenesis are delineated.

Animals↗
PubMed1989

[Congenital ependymoma. Case report and immunohistochemical studies].

Reported in this paper is a congenital ependymoma in an 23-week old foetus. The neoplasm was well vascularised and contained typical ependymal rosettes. The tumour cells did not react with GFAP-antiserum. They reacted weakly with neuron-specific enolase and vimentin and exhibited strong antigenicity with S-100-protein-antiserum. Cytokeratin antigen was recordable from some tumour cells. The tumour was sufficiently mature for classification as ependymoma. Immunohistochemical findings suggested possible ectodermal origin of the tumour cells.

Brain Neoplasms↗
PubMed1989

Coxsackievirus-induced disease. CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice.

DBA/2 male mice inoculated intraperitoneally with 1.8 X 10(5) plaque-forming units (PFU) coxsackievirus B-3 (CVB3) showed extensive inflammatory cell infiltration of the myocardium and acinar tissue of the pancreas in 7 days. Selective depletion of T lymphocyte subpopulations indicated that CD4 cells were either completely or partially responsible for cell damage in both organs. Other organs such as the liver were infected and contained virus titers equivalent to those seen in the heart and pancreas but showed no apparent tissue injury. The role of the CD4 cell was confirmed by positive selection of either T cell subpopulation from CVB3-immune lymphocytes in vitro and adoptive transfer of these cells into T cell-deficient (thymectomized, irradiated, bone marrow reconstituted, TXBM) DBA/2 recipients. Lymphocytes from CVB3-infected donor mice were adsorbed to myocyte, skin fibroblast, or liver vascular endothelial cell (VEC) monolayers. The adherent population was retrieved and adoptively transferred into uninfected syngeneic recipients. When killed 7 days later, the animals receiving unfractionated immune lymphocytes or cells eluted from heart monolayers developed both myocarditis and pancreatitis. Anti-Thy 1.2 and C' treatment of the unfractionated cells completely abrogated transfer of disease. Cells eluted from either fibroblast or liver VEC monolayers showed no pathogenicity. Adsorption of immune cells to heart monolayers in the presence of anti-IAd (class II major histocompatibility complex antigen, MHC) inhibited attachment of the pathogenic T cell, whereas anti KdDd (a class I MHC antigen) had no effect.

Animals↗
PubMed1989

[Systemic salmonella infections in chemotherapy in 2 children with acute lymphoblastic leukemia].

A 15 year old patient with acute lymphoblastic leukemia, previously diagnosed as being a salmonella carrier, developed S. typhimurium sepsis after allogeneic bone marrow transplantation, in spite of pretreatment with chloramphenicol. Clinical improvement and termination of salmonella excretion were achieved by treatment with multiple antibiotics. Another patient with acute lymphoblastic leukemia, a 3 year old boy not previously identified as a salmonella carrier, also developed sepsis and osteomyelitis, together with pathological fractures during chemotherapy. Chloramphenicol, administered after isolation of S. typhimurium from blood cultures, led to resolution of the bony defects, complete recovery, and cessation of salmonella excretion. Selective cultures for salmonellae seem indicated in patients with malignant diseases, prior to chemotherapy.

Adolescent↗
PubMed1988

The structure of human collagen type IX and its organization in fetal and infant cartilage fibrils.

Human collagen type IX was isolated from the media of organ cultures of fetal or infant hyaline cartilage. It consisted of three distinct, disulfide-bonded polypeptides of 115, 84, and 72 kDa, respectively. Digestion with chondroitinase ABC reduced the apparent molecular mass of the 115-kDa chain to about 65 kDa demonstrating that also human collagen type IX is a proteoglycan. In the electron microscope, the molecule had a rigid rod-like structure with characteristic kinks and with a globular domain at one end. Digestion of human collagen type IX with pepsin leads to somewhat heterogeneous fragments. Affinity-purified antibodies to the mixture of fragments specifically reacted with the fragment HMW without cross-reaction with chicken HMW. LMW of both species were recognized to the same low extent. Mechanically generated fibril fragments from human fetal cartilage were heterogeneous in diameter. Significantly, they could be immunostained for collagen type IX in a D-periodic pattern and regardless of the fibril diameter. Some fibrils were poorly labeled, again independently of the diameter. Therefore, the role of collagen type IX in cartilage probably is not to control directly the lateral growth during fibrillogenesis but rather to stabilize the fibril network.

Animals↗
PubMed1988

Isolation and sequence analysis of the glycosaminoglycan attachment site of type IX collagen.

Type IX collagen from chick embryonic cartilage is unique among the collagens in that it contains chondroitin sulfate covalently linked to the alpha 2(IX) polypeptide chain. We have isolated and sequenced the glycosaminoglycan-containing peptide released by collagenase digestion from type IX collagen, labeled biosynthetically with [35SO4] and 3H-aminoacids. This peptide was purified by gel filtration and, following chondroitinase ABC digestion, by reverse-phase high performance liquid chromatography. The amino acid sequence obtained for this peptide has 23 residues, beginning and ending with a collagenous sequence, indicating that it spans an internal noncollagenous domain. Comparison of this sequence with the one predicted from cDNA clone pYN 1738 for the alpha 1(IX)chain and pYN 1731 and pDM 222 for the alpha 2(IX)chain revealed the peptide to be the noncollagenous NC3 domain of alpha 2(IX). The glycosylated sequence Val-Glu-Gly-Ser*-Ala-Asp- of type IX collagen does not have the Ser-Gly normally functioning as the attachment sequence but does have an acidic residue preceding the serine which should improve the acceptability of this sequence for the xylosyltransferase. That it is an adequate acceptor can be inferred from the observation that type IX collagen carries a glycosaminoglycan chain on over 70% of the molecules isolated.

Amino Acid Sequence↗
PubMed1988

D-periodic distribution of collagen type IX along cartilage fibrils.

It has recently become apparent that collagen fibrils may be composed of more than one kind of macromolecule. To explore this possibility, we developed a procedure to purify fibril fragments from 17-d embryonic chicken sternal cartilage. The fibril population obtained shows, after negative staining, a uniformity in the banding pattern and diameter similar to the fibrils in situ. Pepsin digestion of this fibril preparation releases collagen types II, IX, and XI in the proportion of 8:1:1. Rotary shadowing of the fibrils reveals a d-periodic distribution of 35-40-nm long projections, each capped with a globular domain, which resemble in form and dimensions the aminoterminal globular and collagenous domains, NC4 and COL3, of type IX collagen. The monoclonal antibody (4D6) specific for an epitope close to the amino terminal of the COL3 domain of type IX collagen bound to these projections, thus confirming their identity. Type IX collagen is therefore distributed in a regular d-periodic arrangement along cartilage fibrils, with the chondroitin sulfate chain of type IX collagen in intimate contact with the fibril.

Animals↗
PubMed1987

Variation in susceptibility of Balb/c mice to coxsackievirus group B type 3-induced myocarditis with age.

The severity of cardiac lesions in coxsackievirus group B, type 3 (CVB3)-infected Balb/c mice depends upon both the age and the sex of the animal at the time of viral inoculation. Suckling animals (1-3 weeks old) of either sex develop few cardiac lesions. Thereafter, males rapidly demonstrate increasing disease susceptibility peaking at 16-18 weeks old and then decreasing susceptibility from 20 to 40 weeks of age. Female susceptibility increases much more gradually and myocarditis in this sex never reaches maximal levels as seen in males. Increased susceptibility correlates with virus concentrations in the heart and anti-CVB3 titers in the serum. Cardiac injury is dependent on functional T lymphocytes since treatment of the animals with rabbit anti-mouse thymocyte serum abrogates inflammation and myocyte necrosis. Sex-associated steroid hormones influence both virus concentrations and immune responses in mice and are probably responsible for variations in disease susceptibility throughout the animal's life.

Aging↗
PubMed1987

A major, six-armed glycoprotein from embryonic cartilage.

Here we describe the isolation and identification of a major cartilage glycoprotein which is co-extracted along with typical hyaline cartilage components such as collagen types II and IX from chicken embryo sternum. In polyacrylamide gel electrophoresis it migrates as a high molecular mass protein (greater than 10(6) daltons) which on reduction gives rise to a prominent doublet at 205/195 kd and minor bands at 220 and 170 kd. The intact molecule sediments as a 13S component in rate zonal centrifugation, indicative of a highly extended conformation in solution. In these properties it closely resembles myotendinous antigen, a glycoprotein recently detected in a number of embryonic tissues, including cartilage. This identity was confirmed by immunoblotting using a monoclonal antibody (M1) specific for myotendinous antigen. Electron micrographs of the rotary shadowed molecule revealed an unusual six-armed structure, indistinguishable in form and dimensions from hexabrachion, a recently discovered contaminant of cellular fibronectin preparations. These structures could be decorated with the M1-antibody, demonstrating that hexabrachion is myotendinous antigen. This extended, potentially multivalent molecule could provide an ideal substrate to connect widely spaced components in a highly hydrated tissue such as cartilage.

Animals↗
PubMed1986

Identification of the type IX collagen polypeptide chains. The alpha 2(IX) polypeptide carries the chondroitin sulfate chain(s).

Type IX collagen has recently been shown to contain glycosaminoglycan chain(s) and furthermore to be immunologically identical with proteoglycan Lt (Vaughan, L., Winterhalter, K. H., and Bruckner, P. (1985) J. Biol. Chem. 260, 4758-4763). Here we demonstrate that the chondroitin sulfate carrying 115-kDa polypeptide of type IX collagen corresponds to the alpha 2(IX) chain. In addition the 84- and 68-kDa polypeptides were identified as the alpha 1(IX) and the alpha 3(IX) chains, respectively. This conclusion is based on a comparison of the tryptic fingerprints of the 84-, 115-, and 68-kDa chains of type IX collagen on high performance liquid chromatography with the similarly treated C2, C3, and C5 chains of the peptic fragment HMW. In addition, we provide evidence that both the C3 and C4 components of HMW are derived from the alpha 2(IX) chain.

Amino Acids↗
PubMed1986

Antigen-specific suppressor T cells prevent cardiac injury in Balb/c mice infected with a nonmyocarditic variant of coxsackievirus group B, type 3.

Two variants of coxsackievirus group B, Type 3 (CVB3o and CVB3M) infect Balb/c cardiac tissue equally, but only one variant (CVB3M) induces myocarditis. Various studies indicate that disease resistance in CVB3o-infected mice results from generation of suppressor cells. Low-dose cyclophosphamide (50 mg/kg body weight) treatment enhances inflammation in both CVB3M and CVB3o-infected animals, which clearly demonstrates that CVB3o has the capacity to induce disease, but inhibitory factors must exist preventing myocarditis. Spleen cells obtained from mice 10 days after CVB3o inoculation inhibited myocarditis induction in CVB3M-infected recipients, which confirms the presence of suppressor cells in these animals. The suppressor cell belongs to the Lyt 2+ subclass of T lymphocytes and specifically interferes with CVB3-induced myocarditis but fails to inhibit T-cell-mediated cardiac injury triggered by an unrelated virus, encephalomyocarditis virus.

Animals↗
PubMed1986

Coxsackievirus B-3 myocarditis. T-cell autoimmunity to heart antigens is resistant to cyclosporin-A treatment.

A cardiotropic variant of coxsackievirus group B, Type 3 (CVB3) induces myocarditis in inbred Balb/c mice. Myocardial injury is predominantly mediated by T lymphocytes recognizing normal myocyte antigens, making this an autoimmune disease. Nonetheless, the autoimmune response cannot be inhibited by cyclosporin A (CSA) treatment of the infected animals. Mortality in treated mice was increased 2-4 times, but neither virus-specific antibody or cytolytic T-lymphocyte responses were affected, and maximal virus concentrations in the hearts of CSA-treated and control animals were similar. Cardiac damage remains T-cell-mediated, because mice given both CSA and rabbit anti-thymocyte serum (ATS) failed to develop significant myocardial inflammation. CSA did suppress immunity in Balb/c mice to an allogeneic C57B1 lymphoma, EL4. Subcutaneous inoculation of mice with 2.5 X 10(6) ascites tumor cells resulted in 100% of the CSA-treated animals having tumors averaging 340 mg 10 days later, compared with less than 10% of control animals having tumors averaging only 30 mg. Humoral immunity to the tumor was absent in CSA-treated mice. Therefore, whether CSA induces immunosuppression depends upon the antigenic stimulus used.

Animals↗