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Biomedical subjects

M C Mazzilli

Publications and source records attributed to M C Mazzilli.

At least 37 records · Page 2Linked to original sources

Oligotyping of celiac multiplex families with the 11th International Histocompatibility Workshop reagents.

Using PCR and SSO probes from the 11th International Histocompatibility Workshop, we oligotyped for HLA-DRB1 gene and DQA1*0501, DQB1*0201 alleles 10 celiac families each with 2 affected children. All families belong to the Italian population except for one, whose mother is originally from Cape Verde island. 8/10 sibling pairs share the DQA1*0501/B1*0201 heterodimer, inherited in cis or in trans arrangement. All the dimer-negative patients were DR4-positive.

Adult↗

An anti-HLA class I monoclonal antibody alters the progression in the cell cycle of phytohemagglutinin-activated human T lymphocytes.

The monomorphic anti-HLA Class I monoclonal antibody 01.65 inhibits the incorporation of tritiated thymidine ([3H]TdR) in Phytohemagglutinin (PHA)-activated human T lymphocytes. Our data indicate that 01.65 affects the average duration of the cell cycle by increasing the length of the early S subphase. As a consequence of the increase in the doubling time of the cell population, the absolute number of cells at harvesting time was reduced in 01.65-treated cultures compared to that of untreated cultures. The lengthening of the S-phase and the decrease in the cell number can together quantitatively account for the reduction of [3H]TdR incorporation observed in 01.65-treated cultures.

Antibodies, Monoclonal↗

Expression of class II MHC antigens in the intestinal epithelium of pediatric celiac disease.

Class II MHC antigen expression in the intestinal epithelium of 28 small bowel biopsies from 23 celiac patients were studied by means of indirect immunofluorescence and immunoperoxidase using monoclonal antibodies. Patients were divided on the basis of diet into two subgroups: 15 subjects on a gluten-containing diet (GCD) and 13 on a gluten-free diet (GFD). The control group included 10 pediatric subjects with normal intestinal mucosa who underwent intestinal biopsy for chronic diarrhea or short stature. DR antigens and invariant chain were expressed in all patients, regardless of the diet, as well as in the control subjects. DQ was found in one patient only on GCD. DP antigens were present in 12/15 patients on GCD, and in 2/13 on GFD (Fisher's exact test, p = 8.8 x 10(-4), as well as in 3/10 control subjects. In 4/5 celiac patients, DP antigens, which were undetectable on GFD, could be demonstrated after gluten challenge. The results of the study show that DR antigens are expressed by intestinal mucosa of celiac patients independently of their gluten exposure and that DQ antigens are consistently undetectable. Statistically significant differences in expression of DP antigens on enterocytes of celiac patients on GCD and their neoexpression after gluten challenge may represent a basis for further investigation.

Adolescent↗

mAb KUL/05 identifies a denaturation-resistant determinant shared by class II MHC products DR, DQ and DP.

mAb KUL/05, a novel murine monoclonal antibody, reacts with molecules displaying the typical tissue distribution and molecular profile of class II MHC antigens. An extensive scrutiny employing serological and immunochemical assays on DR homozygous and DR alpha- mutant cell lines has shown that this reagent displays some additional, interesting features, namely mAb KUL/05 (a) binds in a broadly monomorphic fashion to cells of DR1 through seven specificities, (b) recognizes a determinant shared by a large proportion of DR, DQ and DP beta chains from most haplotypes, in both their monomeric and alpha chain-associated forms, and (c) reacts with frozen, acetone-fixed, as well as conventional, formalin-fixed, paraffin embedded tissues. Thus, mAb KUL/05 is likely to represent a useful adjunct for the study of the expression of class II MHC products in normal and pathological tissue specimens.

Animals↗

A study of HLA class II antigens in an Italian paediatric population with coeliac disease.

One hundred and twenty-one Italian children with coeliac disease (CD) have been compared with a control population from the same geographical area for the distribution of HLA-DR and DQ antigens. The pattern of an increase in DR3, DR7, and of heterozygotes DR5/7 was associated with an excess of heterozygotes DQw2/DQw3 in the CD population. These findings suggest that epitopes determined by specific combinations of DQ alpha and beta chains (combinatorial determinants) predispose to the disease.

Adolescent↗

A mouse monoclonal antibody against a polymorphic determinant in a defined subset of DR molecules.

The hybridoma technique was used to produce a mouse monoclonal antibody, designated as XI 21.4, which belongs to the IgG2a class. It is active in complement-dependent cytotoxicity and detects a B-cell antigenic determinant associated with DR1, DR4, DRw10, and, possibly, DRw9. Microfingerprinting of the immunoprecipitate from a homozygous DR4 cell line shows a typical alpha DR pattern and a beta pattern coinciding with that of DR4 molecules.

Animals↗

Monoclonal antibodies to HLA-DP-transfected mouse L cells.

Mouse L cells transfected with human HLA-DP (DPw4) alpha and beta genes were used to make monoclonal antibodies in C3H mice. A polymorphic antibody, DP11.1, was obtained, as well as several monomorphic antibodies. In ELISAs, DP11.1 bound to DPw4 cells and, more weakly, to DPw2, but not DPw1, -3, -5, or -6, using HLA homozygous cells. It also bound to L-cell transfectants expressing either DPw2 or DPw4 products. From B lymphoblastoid cell lysates labeled with [35S]methionine, the antibody immunoprecipitated alpha and beta chains of a similar size to those precipitated by a well-characterized DP monoclonal antibody, B7/21.2. Immunoblotting indicated that the DP11.1 antibody was directed against the alpha chain. This result confirms partial sequence data that showed that the DP alpha chain, as well as DP beta, is polymorphic, and that DPw2 and -4 alpha chains are very similar, if not identical.

Animals↗

A mouse monoclonal antibody detecting the allospecificity HLA-A3.

Balb/c mice were immunized with a human B-lymphoblastoid cell line typed HLA-A3, B7. The splenocytes of the immunized mice were fused with a murine myeloma. Supernatants of the cultures were screened against the immunizing cell line in fluorochromasia. Positive cultures were expanded and cloned. One of the clones, X 15.4, was expanded and brought to ascites in Balb/c mice. Monoclonality of the antibody X 15.4, which belongs to the class IgM and immunoprecipitates a molecule of 44000 daltons, was demonstrated by isoelectric focusing. By complement dependent cytotoxicity the ascites only reacted with the lymphocytes of all HLA-A3 individuals from a panel of 146 donors, showing no crossreactions. X 15.4 appears to be one of the very rare xenomonoclonal antibodies suitable for HLA typing.

Animals↗

HLA-ABC and DR antigens in celiac disease. A study in a pediatric Italian population.

HLA phenotypes of 64 Italian pediatric patients with celiac disease (CD) were compared with those of a group of healthy controls. DR3 and DR7 are significantly increased as reported in other populations. In addition an increase of heterozygotes DR5/DR7 was observed in our patients. The Hardy-Weinberg distribution in the patients group shows a disequilibrium due to the genotype DR5/DR7. Our data confirm that more than one HLA gene product is associated with CD: one with DR3 and the other with DR7.

Adolescent↗

Delineation of syndromes due to partial 6q imbalances. Trisomy 6q21 leads to qter and monosomy 6q221 leads to qter in two unrelated patients.

Two unrelated patients carrying imbalances involving the long arm of chromosome 6 are described. In the first trisomy 6q21 leads to qter had segregated from a maternal translocation t(6;16)(q15;q24). The clinical data of the proposita are compared with those of three other published cases. A partial 6q trisomy syndrome is postulated characterized by: growth deficiency of prenatal onset, psychomotor retardation, craniofacial abnormalities (microcephalia, hypertelorism, downward slanting palpebral fissures, flattened nasal bridge, long philtrum, hypoplastic perioral features, large jaw resulting in a round appearance of the face, receding chin, malformed ears) and dysmorphic extremities (contractures of limbs due to short flexor tendons, hypoplastic fingers, toes and nails). In the second case, monosomy 6q221 leads to qter resulted from a de novo rearrangement and was responsible for mental retardation and facial dysmorphism (reduced biparietal diameter, hypotelorism, absent eyebrows, prominent nose, ptosis, receding chin, dysmorphic ears). Studies of HLA and PGM3 segregation showed normal inheritance patterns and ruled out the location of these genes in bands 6q221 leads to qter.

Abnormalities, Multiple↗

HLA and chronic active hepatitis.

42 patients (33 males and 9 females) with chromic active hepatitis (CAH) mostly HBsAg+, were typed for 24 alleles of the A and B loci. Diagnosis was performed according to the criteria outlined by the European Association for the Study of the Liver. The increased frequency of HLA-A3 (47.6% instead of 19.1% in 266 healthy controls) is significant after correction. The relative risk is 3.83. The phenotypic association A3/Bw35 is also increased (28.5% instead of 6.0 in the control group). The risk of the A3/Bw35 association is 6.25. The risk of A3 calculated in patients lacking Bw35 is 1.6. A family study in 5 patients over 5 showed an haplotype A3/Bw35.

Chronic Disease↗