CRI-EM is a human idiotype highly specific for scleroderma.
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Antibodies, Anti-Idiotypic↗
Biomedical subjects
M Zanetti
Publications and source records attributed to M Zanetti.
[Magnetic resonance tomography in osteoid osteoma: more confusion than benefit?].
The purpose of this evaluation was the description of potentially misleading MR appearances of osteoid osteoma. The MR images of 10 patients with osteoid osteoma were retrospectively evaluated and compared to radiographic, intraoperative and histologic findings. 4 of the 10 abnormalities were located in the proximal femur, two in the lumbar spine, and one each in the tibial plateau, in the cervical spine, in the sacrum and in the first metacarpal. 8 of the 9 nidi visible on standard radiographs and/or CT scans were demonstrated on MR images. Edema was visible within the bone marrow in 3, within soft tissue in 2 and in both locations in 4 MR examinations. The soft tissue abnormalities were circumscribed in 3 patients and could be misdiagnosed as soft tissue tumors or an abscess in these patients. One of 5 osteoid osteomas located in the proximity of a joint mimicked septic arthritis. The MR appearance of osteoid osteoma may be misleading. However, false diagnoses usually can be avoided with a careful search of a nidus. MR imaging in osteoid osteoma is important for differential diagnosis.
Adolescent↗
Selective interaction of a conformationally-constrained Arg-Gly-Asp (RGD) motif with the integrin receptor alphavbeta3 expressed on human tumor cells.
Two antigenized antibodies (AgAbs) were engineered to express peptidic Arg-Gly-Asp (RGD) motifs present in extracellular matrix molecules. The RGD tripeptide sequence was inserted in the third hypervariable loop of an immunoglobulin human/mouse chimeric heavy chain gene as a single or three repeat yielding two antibodies termed gamma1RGD and gamma1(RGD)3, respectively. The antibodies were used to target specific cell-surface receptors of the integrin type expressed by three human tumor cell lines, a melanoma (M21), and osteosarcoma (KRIB) and a fibroblastoma (WI-38). Based on in vitro adhesion assays and flow cytometric analysis, we found that all three cell lines interacted with gamma1(RGD)3 but not with gamma1RGD. Binding of tumor cells to surface-immobilized gamma1(RGD)3 was inhibited in a dose-dependent manner by the RGD-containing synthetic peptides GdRGDSP and RGDS. These synthetic peptides, but no a GDR-containing control peptide, interfered with the binding of tumor cells to surface-immobilized human fibronectin. In their soluble form, neither fibronectin nor gamma1(RGD)3 inhibited tumor cell adhesion to surface-immobilized fibronectin. Gamma1(RGD)3 specifically recognized integrin alphavbeta3 based on two criteria: reactivity with purified integrin receptors and binding to variants of M21 melanoma cells expressing alphavbeta3, alphaIIbbeta3 or no beta3 integrins, respectively. Collectively, our results indicate that the (RGD)3 loop in the antigenized antibody mimics the ligand function of natural extracellular matrix proteins and has a restricted receptor specificity for the alphavbeta3 integrin which is not inherent to short RGD containing peptides.
Amino Acid Sequence↗
Magnetic resonance imaging of injuries to the ankle joint: can it predict clinical outcome?
OBJECTIVE: To predict clinical outcome after ankle sprains on the basis of magnetic resonance (MR) findings. DESIGN AND PATIENTS: Twenty-nine consecutive patients (mean age 32.9 years, range 13-60 years) were examined clinically and with MR imaging both after trauma and following standardized conservative therapy. Various MR abnormalities were related to a clinical outcome score. RESULTS: There was a tendency for a better clinical outcome in partial, rather than complete, tears of the anterior talofibular ligament and when there was no fluid within the peroneal tendon sheath at the initial MR examination (P = 0.092 for either abnormality). A number of other MR features did not significantly influence clinical outcome, including the presence of a calcaneofibular ligament lesion and a bone bruise of the talar dome. CONCLUSION: Clinical outcome after ankle sprain cannot consistently be predicted by MR imaging, although MR imaging may be more accurate when the anterior talofibular ligament is only partially torn and there are no signs of injury to the peroneal tendon sheath.
Adolescent↗
Rapid prototyping (stereolithography) in the management of intra-articular calcaneal fractures.
The purpose of this study was to evaluate and compare the diagnostic performance of stereolithography vs workstation-based three-dimensional (3D) reformations in intra-articular calcaneal fractures. A total of 30 intra-articular calcaneal fractures were examined using standard radiographs, coronal CT scans, and 2D and 3D reformations. The CT data were transferred to an outside institution, and stereolithograms were produced from photopolymer resin employing a laser beam system. 3D reformations and stereolithograms were analyzed in a blinded fashion by two staff radiologists. Receiver-operating-characteristic (ROC) curves were obtained for six clinically significant fracture components. Standard radiographs, coronal CT scans, and 2D reformations served as the standard of reference. The area under the ROC curves for 3D reformations and stereolithograms were 1.0 and 0.98 for abnormal tuber angles, 0.91 and 0.91 for anterior and middle talo-calcaneal joint involvement, 0. 90 and 0.95 for involvement of the posterior talo-calcaneal joint, 0. 65 and 0.78 for the presence of a lateral bulge, 0.80 and 0.81 for the involvement of the calcaneocuboidal joint, and 0.62 and 0.67 for the presence of a "tongue-type" fracture. No statistically significant difference was demonstrated for the two methods (Wilcoxon signed-rank test, p = 0.138). Based on our results stereolithograms did not prove to be statistically superior to workstation-based 3D reformations. Stereolithograms may still be useful for teaching purposes and for surgical planning at a thinking-efficacy level.
Adult↗
Contrast media in MR arthrography of the glenohumeral joint: intra-articular gadopentetate vs saline: preliminary results.
The purpose of this investigation was to compare gadopentetate and saline as contrast media in MR arthrograms of the glenohumeral joint. In 60 consecutive patients MR arthrograms with either gadopentetate (n = 26) or saline (n = 34) were performed. After injection of gadopentate, 3D gradient-echo (GE) images were obtained (TR 32 ms, TE 10 ms, flip angle 40 degrees). With saline, double-echo steady-state images (heavily T2-weighted 3D GE images) were obtained (TR 40 ms, TE 9/45 ms, flip angle 40 degrees). In the last 14 of these patients T2-weighted turbo spin-echo (SE) images were added (TR 2900 ms, TE 96 ms). Contrast-to-noise ratios standardized for imaging times proved to be superior for the gadolinium arthrograms compared with GE and SE saline arthrograms (intra-articular fluid vs subacromial fat: p = 0.0001 and 0.0008; intra-articular fluid vs supraspinatus tendon: p = 0.0001 and 0.046). Using a qualitative scoring system gadolinium arthrograms were superior to saline arthrograms (p < 0.0001 and p < 0.0001). Saline arthrograms in combination with GE and SE sequences are inferior to gadopentetate arthrograms with GE sequences.
Adolescent↗
Immunity to Plasmodium falciparum malaria sporozoites by somatic transgene immunization.
Immunity against the human malaria parasite Plasmodium falciparum was induced using somatic transgene immunization, a method to effectively target B lymphocytes in vivo. A single inoculation of plasmid DNA containing an immunoglobulin heavy-chain gene coding in the complementarity-determining region 3 for three repeats of the sequence Asn-Ala-Asn-Pro (NANP), a B-cell epitope of P.falciparum sporozoites, induced antibodies against NANP in all mice. A booster with an antibody antigenized with the NANP peptide, or challenge with P. falciparum sporozoites, demonstrated the establishment of immunologic memory. Immunity to a parasite antigen can be induced by exploiting mechanisms in which B lymphocytes are both the source of the immunogen as well as the effector mechanism of immunity. The results indicate that somatic transgene immunization is a potential approach for vaccination against foreign pathogens.
Animals↗
Engineering vaccines with heterologous B and T cell epitopes using immunoglobulin genes.
Antibodies engineered in their variable domain to express epitopes of heterologous antigens-antigenized antibodies-function as immunogens. Only the third complementarity-determining region (CDR3) of the H chain has been used as the site of epitope expression, as this loop has the highest natural variability in length and amino acid composition. We demonstrate that the CDR2 can be engineered to express a 12-amino acid peptide, which is a T-cell determinant that enhances the response to a B-cell epitope peptide of Plasmodium falciparum expressed in the CDR3 of the same variable domain. Mice with this gene inoculated into the spleen mounted an antibody response against the B-cell epitope higher than mice receiving the gene coding for the B-cell epitope only. In vitro studies established that the two epitopes were independently immunogenic in vivo.
Animals↗
A cross-reactive idiotype in scleroderma.
Autoantibodies to centromere proteins (anti-CENPs) and to topoisomerase-I are highly specific for scleroderma. Unlike most autoantibodies in other diseases, these autoantibodies are mutually exclusive. We have analysed the idiotypes (Ids) expressed by anti-CENP-B, antitopoisomerase-I, and IgGs from 20 scleroderma patients. Rabbit anti-Ids were prepared to antitopoisomerase-I from two scleroderma patients, and to anti-CENP-B from four patients. These six anti-Ids were used to study the purified autoantibodies from 20 scleroderma patients: four antitopoisomerase-I, 10 anti-CENP-B, and six purified IgG from scleroderma patients who were negative for both autoantibodies. In addition, we studied sera from 40 normal autoantibody-negative controls, and sera and purified immunoglobulins from 17 systemic lupus erythematosus (SLE) patients containing high titres of anti-double-stranded DNA, and/or autoantibodies to extractable nuclear antigens (ENA). Using direct binding, and competitive inhibition ELISAs and immunoblots, we identified an Id present in the heavy chains of all the affinity-purified antitopoisomerase-I, and anti-CENP-B. Interestingly, this Id was also present in the immunoglobulins of the scleroderma patients who had neither of the two autoantibodies. By contrast, cross-reactive Id-EM was not found in the sera or immunoglobulins from 17 SLE patients, or in the sera from 40 normal subjects. Several samples from two patients showed that this cross-reactive Id-EM was stable over time. The scleroderma disease-specific autoantibodies may be identified through a common structural feature at the variable region of the heavy chain: cross-reactive Id-EM.
Animals↗
Somatic transgene immunization with DNA encoding an immunoglobulin heavy chain.
A plasmid DNA containing a chimeric immunoglobulin heavy-chain gene with tissue-specific promoter and enhancer elements was used as a model system to study the events triggered by a single intraspleen DNA inoculation in adult C57Bl/6 mice. A single intraspleen inoculation was followed in a week by secretion of transgene immunoglobulins and production of immunoglobulin M (IgM) anti-immunoglobulins. Their kinetics of serum appearance were almost superimposable. While anti-immunoglobulin antibodies remained detectable for over 6 months, transgene immunoglobulins disappeared after 3-4 weeks. However, transgene mRNA was detected in the spleen for 4 months. A multiplex polymerase chain reaction (PCR) analysis on splenic genomic DNA 17 days after inoculation demonstrated that the transgene was integrated in the host chromosomal DNA. The nucleotide sequence of the rearranged VDJ region from splenic genomic DNA was identical to that of the parental plasmid DNA, hence ruling out that hypermutation had occurred. A booster injection of immunoglobulin encoded by the transgene on day 200 elicited a typical secondary immune response with IgG1 and IgG2b antibodies. These results demonstrate that a single inoculation of an immunoglobulin heavy-chain DNA targeted to spleen lymphocytes leads to spontaneous integration of the transgene into the host DNA, and that this is sufficient to initiate immunity and establish immunologic memory. Our data also show that minute amounts (<100 ng/ml) of an endogenously produced protein secreted in the microenvironment of a lymphoid tissue generate immunity and establish immunologic memory rather than tolerance.
Animals↗
Morton neuroma and fluid in the intermetatarsal bursae on MR images of 70 asymptomatic volunteers.
PURPOSE: To determine the prevalence and size of presumed Morton neuromas and fluid in the intermetatarsal bursae on magnetic resonance (MR) images. MATERIALS AND METHODS: In 70 asymptomatic subjects, transaxial T1-weighted spin-echo and T2-weighted turbo spin-echo images were obtained of the right forefoot. The prevalence and size of presumed Morton neuromas (diagnosed with MR imaging criteria) were evaluated, and the sizes were compared with those of 16 symptomatic, surgically proved Morton neuromas. The prevalence and diameter of fluid collections in the intermetatarsal bursae were evaluated on the T2-weighted images. RESULTS: Twenty-four Morton neuromas were diagnosed in 21 subjects (prevalence, 30%). The transverse diameter of the neuromas was 3-7 mm (mean, 4.5 mm) versus 4-8 mm (mean, 5.6 mm) in symptomatic subjects; this difference was significant (P = .0075). The prevalence of fluid in the intermetatarsal bursa was 20%, 47%, 49%, and 0% for the first through fourth intermetatarsal spaces. The transverse diameter of the fluid collection was 1-4 mm. CONCLUSION: The diagnosis of Morton neuroma at MR imaging may be relevant only when the transverse diameter is 5 mm or more and can be correlated to clinical findings. Fluid collections in the first three intermetatarsal bursae with a transverse diameter of 3 mm or less can be considered physiologic.
Adult↗
Leucine metabolism and protein dynamics in the human kidney.
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Adult↗
An approach combining rapid cDNA amplification and chemical synthesis for the identification of novel, cathelicidin-derived, antimicrobial peptides.
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Amino Acid Sequence↗
Efficacy of MR imaging in patients suspected of having Morton's neuroma.
OBJECTIVE: The purpose of our study was to evaluate the role of MR imaging in patients with suspected Morton's neuroma and to assess the value of various MR sequences in this diagnosis. MATERIALS AND METHODS: Thirty-two consecutive patients with suspected Morton's neuroma were studied using a 1.0-T MR scanner. Axial T1- and T2-weighted spin-echo, short inversion time inversion recovery, and enhanced T1-weighted fat-suppressed spin-echo images were obtained on each patient. Eighteen intermetatarsal spaces in 16 of the 32 patients were evaluated surgically. Contrast-to-noise ratios for Morton's neuroma versus surrounding fat were calculated and standardized for imaging times. RESULTS: In 15 of 18 intermetatarsal spaces, a Morton's neuroma was surgically proven. Thirteen true-positive, two false-negative, three true-negative, and no false-positive MR diagnoses were given. In six of 15 proven neuromas, the clinical examiner was not able to identify the correct intermetatarsal space. The MR diagnoses in the 16 remaining patients who did not undergo surgery were Morton's neuroma (n = 8), stress fracture (n = 1), foreign body reaction (n = 1), tendon sheath ganglion (n = 1), postoperative changes (n = 2), and no abnormality (n = 3). Standardized contrast-to-noise ratios (+/- SD) were 2.42 +/- 0.72 for T1-weighted images; 1.43 +/- 1.13 for T2-weighted images; 1.26 +/- 1.47 for short inversion time inversion recovery images; and 0.83 +/- 0.59 gadolinium-enhanced fat-suppressed images. The differences were statistically significant for the T1-weighted spin-echo images versus the three other sequences (p = .001-.018), but not among the other sequences (p = .209-.710). CONCLUSION: MR imaging is accurate in diagnosing Morton's neuroma and may be important for correct localization. A limited examination employing axial T1-weighted spin-echo images is adequate; additional sequences should be employed only for differential diagnosis.
Female↗
Evidence for acute stimulation of fibrinogen production by glucagon in humans.
Fibrinogen, an acute-phase protein, and glucagon, a stress hormone, are often elevated in many conditions of physical and metabolic stress, including uncontrolled diabetes. However, the possible mechanisms for this association are poorly known. We have studied the acute effects of selective hyperglucagonemia (raised from -200 to -350 pg/ml for 3 h) on fibrinogen fractional secretion rate (FSR) in eight normal subjects during infusion of somatostatin and replacement doses of insulin, glucagon, and growth hormone. Fibrinogen FSR was evaluated by precursor-product relationships using either Phe (n = 8) or Leu (n = 2) tracers. Hyperglucagonemia did not change either plasma Phe or Tyr specific activity. After hyperglucagonemia, fibrinogen FSR increased by approximately 65% (from 12.9 +/- 3.6 to 21.5 +/- 6.1% per day, P < 0.025) using plasma Phe specific activity as the precursor pool. FSR increased by approximately 80% (from 16.6 +/- 4.8 to 29.4 +/- 8.8% per day, P < 0.025) if plasma Phe specific activity was corrected for the ketoisocaproate/Leu enrichment (or specific activity) ratio to obtain an approximate estimate of intrahepatic Phe specific activity. FSR increased by approximately 60% when using plasma Tyr specific activity as precursor pool (n = 8) (P < 0.05), as well as when using the Leu tracer precursor-product relationship (n = 2). In conclusion, selective hyperglucagonemia for approximately 3 h acutely stimulated fibrinogen FSR using a Phe tracer method. Thus, glucagon may be involved in the increase of fibrinogen concentration and FSR observed under stressed or pathologic conditions.
Adult↗
Ig VH-dependent interaction between immunoglobulins and CD4.
CD4 interacts with the immunoglobulin (Ig)-VH domains by a virtue of its solvent-exposed C and C strands. These two strands also contribute to the full HIV-gp120 binding and participate significantly in binding to class II MHC molecules. In this paper we hypothesize that any high-affinity interaction between serum (or membrane-expressed) Ig and CD4 may have impact on early T cell activation events. The existing data provide evidence for different outcomes of a high affinity Ig/CD4 interaction on T cell proliferation and cytokine secretion: costimulation and inhibition. We will also discuss how a low affinity CD4/Ig interaction could play an important role in B cell stimulation initiated through surface Ig receptors, and how CD4 may be involved in shaping the B cell repertoire.
Animals↗
Ligand function of antigenized antibodies expressing the RGD motif.
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Amino Acid Sequence↗
[Sonography of the musculoskeletal system].
Beside standard radiographs, bone scintigraphy and MR imaging, ultrasonography plays an important role in assessing abnormalities of the musculoskeletal system. Ultrasonography is widely available, inexpensive and provides high-contrast resolution; however, interobserver variability is a major problem. Ultrasonography should only be employed by experienced examiners and for proven indications in order to prevent inadequate results. Most peer-reviewed publications have evaluated the role of ultrasonography for abnormalities of the rotator cuff and the achilles tendon. Ultrasonography also commonly provides useful information in hip, knee, foot, and wrist abnormalities as well as in the initial work-up in suspected infection or neoplasm; moreover, the role of ultrasonography in some less accepted indications is discussed, such as in meniscal and cruciate ligament injuries as well as in Morton's neuroma.
Achilles Tendon↗