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Biomedical subjects

Fabrizio Guarneri

Publications and source records attributed to Fabrizio Guarneri.

At least 19 recordsLinked to original sources

Human thyroid autoantigens and proteins of Yersinia and Borrelia share amino acid sequence homology that includes binding motifs to HLA-DR molecules and T-cell receptor.

We previously reported that the spirochete Borrelia burgdorferi could trigger autoimmune thyroid diseases (AITD). Subsequently, we showed local amino acid sequence homology between all human thyroid autoantigens (human thyrotropin receptor [hTSH-R], human thyroglobulin [hTg], human thyroperoxidase [hTPO], human sodium iodide symporter [hNIS]) and Borrelia proteins (n = 6,606), and between hTSH-R and Yersinia enterocolitica (n = 1,153). We have now updated our search of homology with Borrelia (n = 11,198 proteins) and extended our search on Yersinia to the entire species (n = 40,964 proteins). We also searched the homologous human and microbial sequences for peptide-binding motifs of HLA-DR molecules, because a number of these class II major histocompatibility complex (MHC) molecules (DR3, DR4, DR5, DR8, and DR9) are associated with AITD. Significant homologies were found for only 16 Borrelia proteins (5 with hTSH-R, 2 with hTg, 3 with hTPO, and 6 with hNIS) and only 19 Yersinia proteins (4 with hTSH-R, 2 with hTg, 2 with hTPO, and 11 with hNIS). Noteworthy, segments of thyroid autoantigens homologous to these microbial proteins are known to be autoantigenic. Also, the hTSH-R homologous region of one Borrelia protein (OspA) contains an immunodominant epitope that others have found to be homologous to hLFA-1. This is of interest, as the hLFA-1/ICAM-1 ligand/receptor pair is aberrantly expressed in the follicular cells of thyroids affected by Hashimoto's thyroiditis. A computer-assisted search detected antigenic peptide binding motifs to the DR molecules implicated in AITD. In conclusion, our in silico data do not directly demonstrate that Borrelia and Yersinia proteins trigger AITD but suggest that a restricted number of them might have the potential to, at least in persons with certain HLA-DR alleles.

Amino Acid Motifs↗

Pseudo-delusory syndrome caused by Limothrips cerealium.

BACKGROUND: Limothrips cerealium (or "grain thrips") is an insect of the phylum Arthropoda, known as parasite of plants of the family Gramineae; human infestation is not frequently described in literature. MATERIALS AND METHODS: We report the case of a 59-year-old female farmer, come to observation because of intense itching and sensation of "walking insects" on her head, with no objective cutaneous signs except lesions due to scratching. After repeated visits, in which negative results of clinical and laboratory tests suggested the diagnosis of "delusory syndrome" (Ekbom's syndrome), we finally isolated on her head some insects, identified by stereomicroscopy as L. cerealium. Careful inspection of the house of our patient allowed us to identify, as possible source of parasites, a wheat field and a deposit of grains used for animal feeding. Temporarily removing the patient from her usual environment resulted in complete clinical resolution. RESULTS: Peculiarity of symptoms caused by this parasite and consequent problems for a correct diagnosis are discussed, as well as possible solutions.

Agricultural Workers' Diseases↗

Identification of potentially cross-reactive peanut-lupine proteins by computer-assisted search for amino acid sequence homology.

BACKGROUND: Allergic cross-reactions are an issue of major concern because of implications for public health. The molecular basis of cross-allergy is the similarity of epitopes belonging to proteins of different organisms. Lupine is an emerging cause of food allergy, which has become a 'hot topic' because of recent large-scale introduction into processed foods and frequent cross-reactions with other members of the legume family. However, no lupine allergen has been characterized thus far. Prompted by a recently reported case of peanut-lupine cross-allergy, we wished to identify the possible cross-reactive allergen(s) between the two vegetal species. METHODS: We used computer-aided amino acid sequence comparison, a well-established technique for the study of protein homology, and followed the FAO/WHO guidelines for the identification of potential allergens. We also performed a three-dimensional modeling of the suspected cross-reactive proteins to compare their molecular surfaces. RESULTS: We found a highly significant sequence homology and molecular similarity between allergen Ara h 8 of peanut and pathogenesis-related protein PR-10 of white lupine. Another protein of lupine, the beta-conglutin precursor, was found to be significantly homologous to the Ara h 1 allergen of peanut. The molecular surfaces of Ara h 8 and PR-10 were remarkably similar. CONCLUSIONS: Our in silico data allow to predict the allergenicity of PR-10 and beta-conglutin precursor of white lupine according to FAO/WHO guidelines. Amino acid sequence homology also suggests that these proteins could be responsible, at least in part, for some of the allergic cross-reactions between peanut and lupine reported in the literature.

Allergens↗

Cutis laxa in Kabuki make-up syndrome.

Kabuki make-up syndrome (KMS; OMIM#147920) is a multiple congenital anomalies/mental retardation syndrome of unknown cause, first described independently by Niikawa and Kuroki. It is characterized by a peculiar facial appearance, mild to moderate mental retardation, skeletal abnormality, joint laxity, short stature, and unusual dermatoglyphic patterns. Several additional malformations (eg, cleft palate), cardiovascular defects, genitourinary and gastrointestinal tract anomalies, otologic and ophthalmologic abnormalities, and recurrent infections are also frequently present. It is mostly sporadic, although some familial cases have been reported. Inheritance is thought to be autosomal dominant or X-linked recessive; several chromosomal abnormalities have been found, but none of them seems to be specific to KMS. The fact that the majority of patients are sporadic and show a wide spectrum of clinical features rules out the hypothesis that KMS is a condition with a microdeletion involving several contiguous genes. We recently observed an Italian boy with typical KMS associated with cutis laxa, which, to our knowledge, is an uncommon finding in KMS, never reported in more than 350 KMS cases previously described in the literature.

Abnormalities, Multiple↗

Solitary asymptomatic nodule of the great toe.

Subungual exostosis is a benign osteocartilaginous tumor of the ungual apparatus, particularly of the toes. It affects both sexes equally, more frequently in the second and third decades of life. We describe a 6-year-old girl who came to our attention because of the enlargement of a pinkish nodule in the distal part of the nail bed of the first toe, progressively elevating the nail plate. History, X-ray imaging and histopathologic examination led us to confirm our clinical suspicion, excluding any other possible cause of the subungual mass. The peculiar features of this clinical entity, and the possibility of effective treatment by practical surgical techniques, are discussed.

Bone Neoplasms↗

Isomorphic response after saphenectomy in a patient with granuloma annulare.

Physical trauma has been reported as an etiologic factor of granuloma annulare, resembling a Koebner phenomenon. Moreover, granuloma annulare frequently arises at the same location of a previously healed, unrelated skin disease, mainly herpetic infection. These data seem to suggest that granuloma annulare might be a peculiar pattern of skin reaction to different stimuli, either physical or biologic, in predisposed subjects. In the case reported herein, the onset of a typical lesion of granuloma annulare at the site of saphenectomy might be explained as the result of an aberrant wound healing process, with release, by keratinocytes and/or Langerhans cells, of lymphocyte-derived chemotactic cytokines, capable of promoting the development of the granulomatous lesion.

Diabetes Mellitus, Type 2↗

Correlation between endocrinological parameters and acne severity in adult women.

Many studies demonstrate increased androgen levels and high prevalence of polycystic ovaries in women affected by acne. We evaluated the relationship between clinical features, ultrasonographic data on polycystic ovaries and hormonal parameters in 129 women >17 years of age with acne. Serum levels of androgens of ovarian and adrenal origin were measured. Menstrual cycle regularity, hirsutism, body mass index and ultrasonographic evaluation of ovaries were recorded. Raised levels of at least one androgen were evident in a majority of our patients. Only 19% of them had polycystic ovary syndrome. Hirsutism and acne severity correlated negatively with serum sex hormone-binding globulin (SHBG) levels (p<0.05). No correlation between acne severity and hirsutism was found. In post-pubertal women, severity of acne seems to depend on peripheral hyperandrogenism, with a negative relationship between the acne severity and serum SHBG levels. We strongly recommend the evaluation of serum SHBG levels in women with acne in order to select patients who can have a better response to appropriate hormonal regimes.

Acne Vulgaris↗

Homologies between proteins of Borrelia burgdorferi and thyroid autoantigens.

Subclinical exposure to microbic antigens that share amino acid sequence homology with self antigens might trigger autoimmune diseases in genetically predisposed individuals via molecular mimicry. Genetic predisposition to Graves' disease (GD) or Hashimoto's thyroiditis (HT) is conferred by HLA loci DR3 or DR5, respectively. Yersinia enterocolitica (YE) outer proteins (YOPs) are candidate triggers based on the high prevalence of serum antibodies (Ab) against YOPs in autoimmune thyroid diseases (AITD) and reactivity of these Ab with hTSH-R, suggesting homology between YOPs and hTSH-R. We have reported previously that the spirochete Borrelia burgdorferi (Bb) could be another trigger. We have explored further the homology of hTSH-R with YE and Bb. Using the Basic Local Alignment Search Tool (BLAST), we found four matches with YE and five matches with Bb . Residues 22-272, 186-330, 319-363 and 684-749 of hTSH-R matched YopM, Ysp, exopolygalacturonase and SpyA of YE (identity 23-31%, similarity 40-48%). Residues 112-205, 127-150, 141-260, 299-383 and 620-697 of hTSH-R matched outer surface protein A, flagellar motor rotation protein A, two hypothetical proteins (BBG02 and BBJ08) and DNA recombinase/ATP dependent helicase of Borrelia (identity 27-50%, similarity 40-75%). Interestingly, the above hTSH-R regions coincide with (or include) known human T-cell epitopes: aa 52-71, 140-176, 240-270, 340-380 and 441-661. Our data strengthen the hypothesis of Bb and YE as environmental triggers of AITD in genetically predisposed persons through molecular mimicry mechanisms.

Autoantigens↗

Recombinant human erythropoietin influences revascularization and healing in a rat model of random ischaemic flaps.

In order to ascertain whether erythropoietin plays a role in early and late repair processes following ischaemic skin flap injury, a dorsal, caudally based skin flap was created in rats. The rats were successively divided into four groups. Group 1 was not treated. The other groups were treated with a subcutaneous administration of 0.9% NaCl saline solution (group 2), a subcutaneous administration of vehicle (group 3) or a subcutaneous administration of 300 IU/kg/day of recombinant human erythropoietin (group 4). We evaluated the possible relationships between neutrophil accumulation, myeloperoxidase activity and content in flap tissue, flap survival, flap temperature (using telethermography) and flap revascularization (using videocapillaroscopy). Necrosis in the flap was significantly less extensive in group 4 than in groups 1, 2 and 3. A significant increase in neutrophil infiltration occurred between the 1st and 24th hour in these groups, but this was not observed in group 4. These findings were confirmed by biochemical data of myeloperoxidase activity and malonyldialdehyde content. Between the 1st and 7th days, we recorded an increase of about 20% in flap temperature in groups 1, 2 and 3, whereas no significant variation was observed in group 4. On the 7th day, videocapillaroscopic findings showed an increase in the mean vascularization index in group 4. Our findings suggest that recombinant human erythropoietin administration can improve the wound healing process, in both early and late stages of injury, by reducing inflammatory response, increasing the density of capillaries in ischaemic flaps and allowing earlier repair of a damaged area.

Animals↗