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Biomedical subjects

R Cattaneo

Publications and source records attributed to R Cattaneo.

At least 109 records · Page 6Linked to original sources

Role of N-linked oligosaccharide chains in the processing and antigenicity of measles virus haemagglutinin protein.

The effects of N-linked oligosaccharides on the haemagglutinin (H) protein of measles virus (MV) were assessed with respect to the processing and antigenicity of the molecule. The functional glycosylation sites on the H protein were determined by eliminating each of the five potential positions, Asn-168, Asn-187, Asn-200, Asn-215 and Asn-238, for N-linked glycosylation by oligonucleotide-directed mutagenesis on a cDNA clone. Expression of the mutant H proteins in BHK-21 cells by a recombinant vaccinia virus encoding T7 polymerase indicated that the first four sites were used in the H glycoprotein for the addition of N-linked oligosaccharide chains. Heterogeneity of oligosaccharide processing was demonstrated. One of the four glycosylation sites had a different carbohydrate structure from those of the other three glycosylation sites and this varied glycosylation was responsible for the appearance of two forms of the H protein. The functional glycosylation sites were systematically removed in various combinations from the H protein to form a panel of mutants in which the role of carbohydrate chains, singly or in different combinations, could be evaluated. Investigations of these glycosylation mutants indicated that (i) two of the four individual carbohydrate side-chains have a large influence on the antigenicity of the molecule; (ii) individual carbohydrate side-chains have little effect on the folding and oligomerization of the molecule, and are not sufficient or necessary alone to facilitate the transport of the molecule to the plasma membrane; (iii) at least two carbohydrate side-chains are required for the H protein to move along the exocytic pathway to the plasma membrane and various combinations of oligosaccharide side-chains, irrespective of the carbohydrate localizations, influence equally the processing of the molecule.

Amino Acid Sequence↗

Deforming arthropathy of the hands in systemic lupus erythematosus is associated with antibodies to SSA/Ro and to SSB/La.

Thirteen patients with systemic lupus erythematosus and deforming arthropathy (DA) of the hands were compared with 111 patients with SLE without deforming arthropathy. Clinical features were comparable in the two groups. Patients fulfilling criteria for mixed connective tissue disease (MCTD) were not included in the present study. A higher prevalence of antibodies to SSA/Ro (P < 0.0125) and SSB/La (P < 0.004) were found in the SLE-DA group. The detection of antibodies to SSA/Ro and SSB/La was even more strictly associated with DA in SLE antibodies to SSA/Ro alone (P < 0.002). Regarding the fine specificity of anti-SSA/Ro, a prevalent response to the 52 kD protein of the Ro antigen was found. We conclude that patients with SLE developing deformities of the hands belong to a subset of patients with circulating antibodies to SSA/Ro, particularly to the 52 kD component, and to SSB/La.

Adolescent↗

Distraction osteogenesis in the treatment of stiff hypertrophic nonunions using the Ilizarov apparatus.

The principle of treating stiff hypertrophic nonunions of long bones with distraction using the Ilizarov method permits simultaneous correction of axial deformity, angular deformity, translational deformity, shortening, and, in most instances, infection. Twenty-one hypertrophic nonunions in 19 patients were treated using the Ilizarov apparatus in distraction. Six of these patients had associated chronic osteomyelitis. Ilizarov treatment ranged from four to 12 months (mean, 6.5 months). Follow-up time ranged from three to 11 years. Stable union was achieved in all patients. Angular, axial, and translational deformities were corrected in all patients; length discrepancies were corrected in 18 of 21 patients (86%). Infection resolved in five of the six cases (83%) with chronic osteomyelitis. The sole complication was axial collapse of regenerate bone (in one patient with subsequent loss of 2 cm of lengthening) after premature removal of the Ilizarov fixator. Distraction osteogenesis in the treatment of stiff hypertrophic nonunions offers the most complete method of providing optimal limb function. The process allows the patient to maintain extremity mobility and weight bearing while undergoing treatment.

Adolescent↗

Preliminary experience with Ilizarov method in late reconstruction of radial hemimelia.

We report the outcome of ulnar lengthening with the Ilizarov technique in five adults with radial hemimelia and previous wrist centralization. The indications for ulnar lengthening in these patients were either a functional deficit due to the short ulna or poor appearance that caused the patient significant unhappiness. All patients had a successful lengthening of the ulna, with a gain in length from 4 to 13 cm; however, the procedures were prolonged (7 to 25 months), and all patients experienced complications. At the time of follow-up examination no patient had residual pain or paresthesias. In four of five patients, although ulnar lengthening resulted in somewhat stiffer digits, it improved function of the extremity as a whole. When asked if they would repeat the lengthening, knowing what they know now, all five replied that they would. The technical difficulties encountered in these cases suggest a cautious approach to ulnar lengthening. This is a long, arduous, painful process that requires a psychologically robust patient. If the ulna is very short preoperatively, lengthening can enhance the volume of space accessible to the hand and in that way improve function.

Adult↗

Cell fusion by the envelope glycoproteins of persistent measles viruses which caused lethal human brain disease.

Measles virus (MV) rarely induces lethal diseases of the human central nervous system characterized by reduced expression of the viral envelope proteins and by lack of viral budding. The MV envelope contains two integral membrane proteins, termed fusion (F) protein and hemagglutinin (H) protein, and a membrane-associated matrix (M) protein. Previously, analysis of MV genes from autopsy material indicated that the M protein and the F protein intracellular domain are often drastically altered by mutations. Here, we present evidence that truncation of the F protein intracellular domain does not impair fusion function, and we suggest that this alteration interferes with viral budding. Unexpectedly, certain combinations of functional F and H proteins were unable to induce syncytium formation, an observation suggesting that specific F-H protein interactions are required for cell fusion. We also found that three of four H proteins of persistent MVs are defective in intracellular transport, oligosaccharide modification, dimerization, and fusion helper function. Thus, MVs replicating in the brain at the terminal stage of infection are typically defective in M protein and in the two integral membrane proteins. Whereas the M protein appears dispensable altogether, partial preservation of F-protein function and H-protein function seems to be required, presumably to allow local cell fusion. Certain subtle alterations of the F and H proteins may be instrumental for disease development.

Autopsy↗

Applications of the Ilizarov method in the humerus. Lengthenings and nonunions.

Between 1982 and 1992, Ilizarov's method was used in 68 lengthenings and 29 nonunions of the humerus. Special rings along with the arches similar to those used for femoral lengthening were used to allow unrestricted motion at the elbow and shoulder. These patients were followed for an average of 5.1 years. In cases of lengthening, average length achieved was 9 cm, with duration of treatment being 5 to 14 months. Overall results in most cases were excellent. In cases of nonunion, the duration of treatment averaged 226 days. Of the 29 nonunions, 25 healed. Our results, including no major complications, support the continued use of Ilizarov's technique in humeral lengthening and nonunions of the humerus.

Adolescent↗

Evaluation of serum levels of soluble interleukin-2 receptor as an indicator of disease activity in systemic lupus erythematosus.

Serum levels of the soluble form of the interleukin-2 receptor (sIL-2R) were measured in the sera of 32 patients with systemic lupus erythematosus. A significant correlation was observed between the levels of sIL-2R and the SLAM score of disease activity (R:0.40; p: less than 0.05). The correlation was slightly lower than those between the SLAM score and the levels of anti-dsDNA or of the complement activity. The levels of sIL-2R were not significantly correlated with those of serum anti-ds-DNA and complement, nor with a sign of peripheral blood B cell hyperactivity, such as the spontaneous in vitro production of anti-DNA antibodies.

Adult↗

Subacute sclerosing panencephalitis is typically characterized by alterations in the fusion protein cytoplasmic domain of the persisting measles virus.

Our recent extensive analysis of three cases of subacute sclerosing panencephalitis (SSPE) revealed intriguing genetic defects in the persisting measles virus (MV): the fusion (F) genes encoded truncated cytoplasmic F protein domains (Cattaneo et al., Virology 173, 415-425, 1989). Now this MV genomic region has been investigated in eight additional SSPE cases by PCR amplification, replacement cloning into a vector containing the F gene of a lytic MV, in vitro expression, and sequencing. In all cases at least part of the clones showed mutations leading to F protein truncations, elongation, or nonconservative amino acid replacements. It is proposed that alteration of the F protein cytoplasmic domain may play a critical role in the development of SSPE.

Amino Acid Sequence↗

Immunological and gadolinium-DTPA MRI evaluation of relapsing remitting multiple sclerosis.

The levels of lymphocytes, blood lymphocytes subsets (CD3+, CD4+, CD8+, DR+, CD25+, CD4+, CD45RA+, CD4+, CD29+ cells) and sIL-2r of 10 patients affected by relapsing-remitting multiple sclerosis were serially studied. The identification of the activity of the disease was made by gadolinium-DTPA (Gd-DTPA) MRI. The immunological determinations and the MRI of the brain and spinal cord were performed every 14th day for a period of three months. No significant difference of the immunological values were found between the presence and the absence of Gd-DTPA enhancing areas, except lymphocytes (p < 0.05). These immunological parameters, evaluated in the peripheral blood, are not a marker of disease activity in relapsing-remitting MS patients.

Adult↗

Efficacy and tolerability of medium-term treatment with simvastatin in primary hypercholesterolaemia.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, a new class of hypolipidaemic agents, have been recently shown to be effective in lowering both total and low-density lipoprotein (LDL)-cholesterol. In the present study 20 patients were treated with simvastatin for six months. Various dosing regimens of 10, 20, and 40 mg/day were employed. Administration of simvastatin 10 to 40 mg/day resulted in a 24.7 to 35.8% reduction in LDL-cholesterol levels and in a 19.5 to 26.9% decrease of total cholesterol levels. Moreover, simvastatin increased high-density lipoprotein-cholesterol and induced a decrease in plasma triglycerides. The side-effect profile was similar to other observations and included reversible transaminase elevations, myalgia and gastrointestinal complaints. From the present study simvastatin seems to be well tolerated in the short- to medium-term and to be effective; however, its long-term tolerability needs to be confirmed.

Adult↗