Biomedical subjects

A Romito

Publications and source records attributed to A Romito.

12 recordsLinked to original sources

PubMed1998

Delayed hypersensitivity to aminopenicillins is related to major histocompatibility complex genes.

BACKGROUND: Although in some cases delayed hypersensitivity may be observed, beta-lactam antibiotics frequently induce immediate allergic IgE-mediated reactions with the specificity localized in the acyl-side chain structure. Generally, delayed immunologic reactions are related to sensitized T lymphocytes and major histocompatibility complex restricted. OBJECTIVE: To investigate the prevalence of HLA class I and II antigens in patients with delayed hypersensitivity to aminopenicillins in order to evaluate a relationship between major histocompatibility complex immune response genes and aminopenicillins hypersensitivity. METHODS: We assessed 24 patients with history of delayed hypersensitivity to aminopenicillins using (1) skin test with penicilloyl polylysine, minor determinant mixture, benzylpenicillin, amoxicillin, and ampicillin; (2) patch tests with benzylpenicillin, amoxicillin, and ampicillin; (3) RAST for penicilloyls G and V; and (4) oral challenges with amoxicillin, ampicillin, and penicillin V in 18/24 patients. All patients were typed by microlymphotoxicity standard test for HLA class I and II antigens. Statistical analysis by chi2 test 2 x 2 contingency tables, according to Svejgaard, were used for comparison between patients and random Italian population (522 subjects). RESULTS: In the patients group we found higher prevalence of HLA A2 (12/24 = 50%, RR = 6.76 P < .001, EF = 0.425), DRw52 (20/24 = 83.3%, RR = 9.28, P < .001, EF = 0.74), and lower frequency of DR4 (3/24 = 12% ns). CONCLUSIONS: These data suggest that the immune mechanisms involved in adverse reactions to aminopenicillins in vivo are related to genetic markers of immune response and confirms that the presentation of penicillin-hapten determinants to lymphocyte is major histocompatibility complex restricted.

Adolescent↗

PubMed1998

Sudden hearing loss in a patient hepatitis C virus (HCV) positive on therapy with alpha-interferon: a possible autoimmune-microvascular pathogenesis.

Alpha interferon (alpha-IFN) is used for the treatment of various systemic disorders. Side-effects of alpha-IFN therapy can involve numerous organ systems, but sudden hearing loss has only once been recorded. We report a case of sudden hearing loss occurring in a patient with chronic hepatitis C treated with alpha-IFN and recovered five days after the discontinuation of this agent. This is the first record of anti-endothelial cell antibodies detection in a patient with sudden hearing loss. The finding of anti-endothelial cell antibodies suggests an association between sudden hearing loss and microvascular damage during interferon therapy.

Antiviral Agents↗

PubMed1997

Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet.

A 33-year-old patient, with pre-existing diagnosis of 'schizophrenic' disorder, came to our observation for severe diarrhoea and weight loss. Use of single photon emission computed tomography, (99mTc)HMPAO SPECT, demonstrated hypoperfusion of the left frontal brain area, without evidence of structural cerebral abnormalities. Jejunal biopsy showed villous atrophy. Antiendomysial antibodies were present. A gluten-free diet was started, resulting in a disappearence of psychiatric symptoms, and normalization of histological duodenal findings and of (99mTc)HMPAO SPECT pattern. This is the first case in which, in an undiagnosed and untreated coeliac patient with psychiatric manifestations, the (99mTc)HMPAO SPECT demonstrated a dysfunction of frontal cortex disappearing after a gluten-free diet.

Adult↗

PubMed1997

Leucocytoclastic vasculitis associated with hepatitis C virus antibodies.

The actiopathogenesis of leucocytoclastic vasculitis is still unknown, but recently hepatitis C virus (HCV) has been suggested as trigger of autoimmunity. We report a case of a 26-yr-old patient with purpura due to leucocytoclastic vasculitis associated with hepatitis C virus infection. Laboratory findings showed AST, ALT, gamma GT within normal limits, positive antibodies to HCV (IIF and Riba II) and polymerase chain reaction for HCV RNA. Anti-nuclear antibodies, IgG and IgM anti-cardiolipin antibodies, anti-platelet antibodies and anti-neutrophil cytoplasmic antibodies with perinuclear pattern were also present. A skin biopsy specimen of a purpuric lesion showed leucocytoclastic vasculitis with small vessel thrombosis and perivascular deposition of IgM and fibrinogen on immunofluorescence study. This case shows a role of HCV in leucocytoclastic vasculitis; it is possible that this HCV can induce autoimmunity independently of cryoglobulins and liver involvement.

Adult↗

PubMed1996

Overexpression of Fas antigen on T cells in advanced HIV-1 infection: differential ligation constantly induces apoptosis.

OBJECTIVES: To investigate Fas in peripheral lymphocytes from HIV-1-positive patients at different disease stages with respect to the extent of apoptosis. DESIGN: The study included analysis of Fas involvement in T-cell apoptosis observed during HIV-1 infection. Because ligation of Fas can result in costimulation of proliferation or the induction of apoptosis in uninfected cells, we evaluated the effect on T cells of Fas activation by monoclonal antibodies (MAb) of different specificity from both UB2 and CH11 clones and activation by the Fas ligand (Fas-L). METHODS: Fas was measured by FACS in peripheral blood and in phytohaemagglutinin (PHA)-driven cultures derived from 59 HIV-1-positive individuals with different Centers for Disease Control and Prevention stages. The percentage of apoptotic cells was detected by propidium iodide cell staining. The effect of Fas ligation was assessed in peripheral T cells from patients and healthy controls by a proliferative test measuring the 3H-thymidine uptake. RESULTS: FACS analysis revealed that Fas was predominantly expressed in advanced disease, although it was promptly exposed in PHA cultures from asymptomatic individuals. In several instances, Fas overexpression was associated with substantial subdiploid DNA content in cells from severely lymphopenic patients. The proliferative assay showed a significant inhibition of 3H-thymidine uptake in T cells from all patients following Fas ligation by the immunoglobulin (Ig) G1 MAb from the UB2 clone. This was in contrast to the apparent cell activation detected in controls and the weak suppression observed in Fas-positive cell lines. In addition, the IgM anti-Fas and recombinant Fas-L concentrations inducing a moderate inhibition of fresh T cells from controls strongly depressed the proliferative rate of cells from patients. CONCLUSIONS: Our data suggest that Fas overexpression parallels the progression of the disease and that the increased susceptibility of T cells from HIV-1-infected individuals to undergo apoptosis may include a Fas pathway. Functionally exhausted T cells in advanced HIV-1 infection are primed to apoptosis because of their high sensitivity to Fas stimulation even using the IgG1 MAb, which is unreactive to the death domain of Fas. This suggests that the increased sensitivity of Fas is apparently unrelated to its trimeric ligation and supports the hypothesis that Fas pathway plays a role in increasing the lymphocyte apoptosis during the disease.

Adult↗

PubMed1996

Recurrent perimyocarditis following a non penetrating chest trauma. A case report.

A young man, after a non penetrating chest trauma, developed recurrent episodes of fever, chest pain, pleural and pericardial effusion, without laboratory evidence of viral infections, or positivity for conventional autoimmunity markers. A clearcut positivity for more specific cardiac autoantibodies, against Beta 1 adrenoceptors (AB1AA), was found (at all dilutions from 1:20 to 1:160). A full dosage of Prednisone rapidly relieved all symptoms, whereas antibiotic therapy had been previously uneffective. At a follow-up control after three months, the patient was healed and AB1AA were positive only at dilutions 1:20 and 1:40. As silent viral myocarditis was apparently ruled out by serological negativity for viral infections, it is possible that autoimmunity could have played a primary pathogenetic role for the development of pericarditis in this patient. Further work is needed to ascertain whether or not AB1AA detection could be a specific marker of cardiac autoimmunity phenomena.

Adult↗

PubMed1995

Long-term therapy with recombinant human erythropoietin (rHu-EPO) in progressing multiple myeloma.

Recombinant human erythropoietin (rHu-EPO) is an effective growth factor for erythroid progenitor cells in anemia provoked by several conditions, including bone marrow tumors such as multiple myeloma (MM). We studied a group of 54 patients with MM undergoing second-induction chemotherapy. Thirty of them were randomly assigned to receive rHu-EPO at an initial dosage of 150 units/kg body weight three times a week, increased to 300 units/kg from the sixth week to the end of the 24-week study. Hemoglobin (Hb) levels increased in 77.7% of these patients by the eighth week. In addition, five transfusion-dependent patients in treatment with the VMCP protocol completed the trial without requiring blood supplement after the third month, whereas seven control patients required frequent supplements. Monthly assessment of hematologic parameters demonstrated the ability of rHu-EPO to increase reticulocyte counts, whereas five patients became resistant to the second-induction chemotherapy in apparent concurrence with their rHu-EPO therapy. The response to rHu-EPO in four of the five MM patients receiving cytotoxic protocols combined with alpha-interferon (alpha-IFN) included an increase of serum IgM after the third month. This effect was not demonstrable in any other group, including three rHu-EPO-untreated patients undergoing alpha-IFN + VMCP combined therapy, as well as rHu-EPO-treated patients not receiving alpha-IFN. Our data suggest that alpha-IFN plus rHu-EPO treatment in MM patients is effective in restoring normal B cell function. These results may reflect in vivo the modulation of normal human B cells and lymphoblasts by rHu-EPO observed in vitro.

Anemia↗

PubMed1994

Molecular specificities of CD4+ T cell-reactive IgM in human immunodeficiency virus (HIV-1) infection.

The molecular targets and biological properties of lymphocytotoxic sera in 11 human immunodeficiency virus (HIV)+ subjects in CDC stages II to IVC were investigated. A purified soluble CEM membrane used as the CD4+ T cell clonotypic model in immunoblotting techniques revealed a homogeneous pattern of IgM-mediated reactivity to a 43.5-kDa membrane component in 10 sera. Conversely, CEM membrane-reactive IgG from these sera were weakly reactive to various antigens with no prevalent specificity. ELISA assay against purified 25.5-, 43.5-, and 60.8-kDa CEM membrane antigens revealed a significant affinity of IgM from sera 3, 8, 9, and 10 for the 43.5-kDa receptor, thus confirming the high specificity of these cytotoxic antibodies for their substrate. Additional experiments included the idiotypic saturation of purified IgM molecules with increasing amounts of the 43.5-kDa antigen. Functional inhibition of CEM-reactive IgM by their antigen was dose-dependent. The maximum inhibition of the ELISA reactivity was detected at 1/7 antigen/antibody concentration. By contrast, a significant decline of cytotoxic properties of sera 8, 9, and 10 to CEM lymphoblasts was noted only when equivalent concentrations of the 43.5-kDa receptor and purified IgM were incubated. In addition, the 43.5-kDa antigen appeared to be the preferential target of cytotoxic IgM in HIV-1 infection, since purified cytotoxic IgM from two SLE patients were not inhibited by this molecule. Our data provide specific molecular support for earlier evidence of exacerbation by T cell-reactive antibodies of the lymphopenia associated with HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Distribution and antigenic analysis of circulating F(ab')2-reactive IgG in patients with HIV-1 infection.

Serum titers and molecular specificity of anti-F(ab')2 antibodies were investigated in human immunodeficiency virus type 1 (HIV-1) infection with respect to their supposed cytopenic role on CD4+ cells. The levels of antibodies to F(ab')2 fragment and to HIV-1 glycoprotein epitopes were measured by immunoenzymatic methods in an HIV-1+ population, including 86 drug addicts, 12 sexually infected patients, and 1 hemophiliac, grouped into Walter Reed (WR) clinical stages 2 to 6 of HIV-1 infection. Monoclonal F(ab')2-reactive IgM and IgG from cloned Epstein-Barr B cell transformants of selected patients were also investigated in regards to their HIV-1 glycoprotein specificities and cytotoxicity to the CD4+ cell membrane antigens (CEM) lymphoblasts by a Terasaki assay. Group A (51 sera from WR2 patients) showed the highest titers of IgG anti-F(ab')2 with no correlation to positivities to gp120, whereas sera with undetectable anti-F(ab')2 levels from group B (37 WR5 and WR6 patients) and from group C (11 WR3-WR6 patients with lymphocytotoxin-associated lymphopenia) were reactive to the virus envelope. Both anti-F(ab')2 monoclonal IgM and IgG failed to cross-react with the HIV-1 glycoproteins and the CD4+ CEM. Based on our data, anti-F(ab')2 antibodies are apparently unrelated to the CD4+ lymphopenia occurring in HIV-1-infection. In addition, their inability to bind the HIV-1 gp120 as sequence homologue of the CH1 domain of IgG suggests that their molecular target could include a few epitopes located within the VH and VL regions, thus supporting their potential role of antiidiotype molecules as described in autoimmunity.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

[Apoptosis or programmed cell death: regulatory and pathophysiological mechanisms].

Apoptosis is an active death process genetically encoded to eliminate abnormal or unwanted cells. The phenomenon is induced by a cascade of molecular events leading to nucleolysis by endonucleases and involves a number of membrane receptors and cytoplasmic proteins. These structures (including Fas, müllerian inhibiting substance, p53 and the c-myc oncogene) contribute, by interactive regulatory mechanisms, to the promotion or inhibition of apoptosis, on the basis of both external stimulus and cell activation state. Since apoptosis is a selective process to suppress defective cells, deregulation of genes encoding for such apoptosis-related proteins could be relevant in the growth of several tumors. Remarkably, overexpression of the bcl-2 gene in a few experimental lymphomas has been associated with neoplastic proliferation because of its inhibitory effect on apoptosis. Conversely, early activation of Fas, an apoptosis-inducing gene on HIV-infected CD4+ lymphocytes, is thought to aggravate T cell lymphopenia in HIV infection by increasing the level of normal apoptosis. Genetic deregulation of apoptosis has also been postulated in the pathogenesis of several diseases. Indeed, while preliminary studies suggest that apoptosis plays a role in autoimmune disorders including systemic lupus erythematosus, the pathogenesis of a few degenerative neuropathies, such as Alzheimer's disease, could depend on a similar altered mechanism in apoptosis of neuronal cells. However, no studies are presently available to suggest that exploitation of molecular events of apoptosis would imply therapeutic progress.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

[Methods for assessing programmed cell death].

Apoptosis, namely programmed cell death, is a fundamental mechanism involved in both organogenesis and tissue homeostasis. Since this process is genetically controlled, its defective regulation plays a role in the pathogenesis of several diseases including inflammatory and degenerative disorders, autoimmunity and neoplasia. Several methods have been suggested to identify the cellular events including the modification of cell size, cytoplasmic condensation and nuclear degradation occurring during this phenomenon. The cell morphologic changes can be observed in detail by electronic microscopy, while the chromatin cleavage is well detected by both electrophoretic and flow cytometry techniques, using various fluorochromes able to bind specifically the double-stranded DNA. Here we review the different techniques to evaluate apoptosis with respect to their sensitivity in both qualitative and quantitative analyses.

Apoptosis↗

PubMedDate not supplied

[Malignant neoplasms and AIDS. Review of the literature and critical considerations on a case of epidermoid carcinoma of the anus].

During the past few years the neoplasms defining the diagnosis of AIDS are in apparent evolution and a new distribution of specific tumors is currently reported in the literature. Besides the Kaposi's sarcoma, non-Hodgkin's lymphomas, and uterine cervical carcinoma, other malignancies are frequently diagnosed in HIV+ population, particularly during the advanced stages of the infection. The pathogenesis of such an increase of tumor diffusion is apparently related to the persistence of several herpes viruses including HHV8 and HPV whose molecular interaction with HIV may contribute to the genetic variations suitable for tumor development. The epidermoid anal carcinoma is a tumor whose appearance is increasingly recurrent in HIV+ patients, although it is not considered as an AIDS-defining neoplasia. This tumor is prevalent in HIV+ homosexual men, in particular during the full-blown immunodeficiency disease. Here we report the case of a patient whose diagnosis of AIDS was emphasized by the concurrent presence of the anal tumor.

Acquired Immunodeficiency Syndrome↗