A new prospective against HIV infection: induction of murin CCR5-downregulating antibodies.

Natural resistance to HIV is widely growing in humans. An example of an extremely efficacious resistance is represented by exposed seronegative (ESN) subjects, i.e. individuals who, despite repeated sexual and/or parenteral exposure to HIV, remain seronegative and apparently uninfected. A small group within ESN produces anti-CCR5 antibodies which cause antigen down-modulation and a CCR5 minus phenotype. It has been previously demonstrated that a single conformed extracellular domain (corresponding to first cystein loop) of CCR5 is recognized by ESN antibodies. In order to verify the possibility to induce and reproduce infection-protecting anti-CCR5 antibodies in individuals at high risk of HIV infection, we generated immunogens containing the relevant CCR5 peptide. Since the first cysteine loop of human CCR5 is identical in sequence to its mouse homologue, mice were immunized according to an intra-peritoneal procedure with CCR5 peptide loop, #90-103. Anti-CCR5-responses elicited in mice did share the same specificity and functions as human anti-CCR5 immunoglobulins previously identified in ESN cohorts. In particular, murine IgG and IgA: 1. Specifically recognize both mouse and human CCR5. 2. Down-modulate CCR5 expression on CD4+ cells of both untreated mice and human. 3. Downregulate "in vivo" peripheral CCR5 expression on mice CD4+CCR5+ cells. 4. Inhibit CD4+ CCR5+ lymphocytes chemotaxis. These findings show that CCR5-mediated effects on CD4+ cells can be achieved in mice both "in vitro" and "in vivo". Therefore, novel immune strategies aimed at generating partial or complete immune protection through anti-CCR5 downregulation at genital mucosa could be elicited successfully also in monkey and eventually in humans.

[Three cases of congenital cutaneous candidosis]. / Tre casi di Candidosi Cutanea Congenita.

We report three cases of term newborns with Congenital Cutaneous Candidosis (CCC) occured in a ten months period. Two of these showed respiratory distress that require mechanical ventilation and the administration of exogenous surfactant in one case. All the three cases recovered after therapy with fluconazole. Early onset of severe respiratory distress may require intubation and mechanical ventilation, and systemic involvement requires systemic antimichotic therapy. We did not find any predisposing factors of such a rare disease, in spite of the occurrence of three cases in a short period of time.

[The Silver-Russel syndrome]. / La sindrome di Silver-Russel.

The authors report a case of Silver-Russel syndrome with severe deficit growth observed since intrauterine life. They describe the major features, that are constant and the minor features, that are variable and numerous. The features not always are present at birth. The A. exclude in this case a genetic cause and suggest a possible motherly cause.

Induction of murine mucosal CCR5-reactive antibodies as an anti-human immunodeficiency virus strategy.

The genital mucosa is the main site of initial human immunodeficiency virus type 1 (HIV-1) contact with its host. In spite of repeated sexual exposure, some individuals remain seronegative, and a small fraction of them produce immunoglobulin G (IgG) and IgA autoantibodies directed against CCR5, which is probably the cause of the CCR5-minus phenotype observed in the peripheral blood mononuclear cells of these subjects. These antibodies recognize the 89-to-102 extracellular loop of CCR5 in its native conformation. The aim of this study was to induce infection-preventing mucosal anti-CCR5 autoantibodies in individuals at high risk of HIV infection. Thus, we generated chimeric immunogens containing the relevant CCR5 peptide in the context of the capsid protein of Flock House virus, a presentation system in which it is possible to engineer conformationally constrained peptide in a highly immunogenic form. Administered in mice via the systemic or mucosal route, the immunogens elicited anti-CCR5 IgG and IgA (in sera and vaginal fluids). Analogous to exposed seronegative individuals, mice producing anti-CCR5 autoantibodies express significantly reduced levels of CCR5 on the surfaces of CD4+ cells from peripheral blood and vaginal washes. In vitro studies have shown that murine IgG and IgA (i) specifically bind human and mouse CD4+ lymphocytes and the CCR5-transfected U87 cell line, (ii) down-regulate CCR5 expression of CD4+ cells from both humans and untreated mice, (iii) inhibit Mip-1beta chemotaxis of CD4+ CCR5+ lymphocytes, and (iv) neutralize HIV R5 strains. These data suggest that immune strategies aimed at generating anti-CCR5 antibodies at the level of the genital mucosa might be feasible and represent a strategy to induce mucosal HIV-protective immunity.

[Potentials of echography in the diagnosis of gallbladder carcinoma]. / Possibilità dell'ecografia nella diagnosi del carcinoma colecistico.

A study was carried out on 27 patients (22 women and 5 men) suffering from gallbladder carcinoma confirmed through surgery or autopsy. The examinations were performed with a real-time scanner and 3.5 MHz transducer. Lately, higher resolution transducers (5 MHz and 7.5 MHz) have been employed which have proven more effective due to their improved resolution. The importance is stressed of scanning patients in different positions in order to allow stones and echogenic material to redistribute inside the gallbladder. A correct diagnosis was obtained in 20/27 cases. Bile duct metastases were correctly evaluated by US in 13/13 cases; liver metastases in 25/27 patients. US proved unreliable in those cases where lymph nodes were involved (0/4). Six patients underwent scanning few months, or even years, before the onset of the symptoms. Three patients presented with fundic tumors, whose wall thickening and shadowing of the external wall had been incorrectly evaluated. In the other 3 cases the gallbladder was filled with stones and had thick and constricted walls. There was only a case of invisible carcinoma. Gallbladder carcinoma has often an unfavorable prognosis due to its being diagnosed in an advanced stage. The prognosis of such patients can be improved through an earlier US diagnosis only. The first step in this direction seems to be the identification of the precursor lesions.

[Ileal carcinoid observed in a very advanced phase in presence of metastasis to the left thigh soft tissues, both kidneys, liver, and left lung]. / Carcinoide dell'ileo giunto alla osservazione in fase molto avanzata in presenza di metastasi delle parti molli della coscia sinistra e di entrambi i reni oltre che del fegato e del polmone sinistro.

Reference is made to the APUD system and the APUDoma concept, and stress is laid on certain correlations noted between the histochemical features, endocrine activity, and topographical distribution of digestive tract carcinoids. Lastly, a description is given of a advanced stage, when metastases were already present on the soft parts of the left thigh, and in both kidneys, the liver, and the left lung. The occasion is taken to put forward some observations of a clinical, prognostic, and diagnostic order.

[Risk factors for cystic kidney disease in hemodialysis patients]. / Fattori di rischio nella malattia cistica renale dell'emodializzato.

Acquired bilateral cystic transformation of kidneys in patients on chronic dialysis has been increasingly noted by morphological and clinical studies. Our study aims to identify a group of high-risk patients for incidence and extent of such disease. We studied with ultrasonography 87 patients on maintenance hemodialysis (60 men and 27 women), median age 58 years (range 18 to 81), mean duration of hemodialysis 75 months (range 2-256). The presence of cysts was divided into five grades from 0 no cysts to 4 more than 15 cysts detected for each kidney. 74 patients 85% of our dialytic population had acquired cystic disease; cysts varied in size from 0.5 to 4.5 cm in diameter. The cysts were found in 97% of patients dialyzed for more than 8 years and in 73% of patients on hemodialysis for less than 3 years. The incidence of cystic disease was highly and significantly correlated with the duration of dialysis, the grade correlated with duration of chronic renal failure and hemodialysis. The extent of disease appears to be increased in males. Because of high incidence of disease in long term dialysis patients ultrasonography monitoring is recommended for patients on dialysis for more than 3 years with more attention for males.

[AIDS-related neoplasms: a clinico-radiological study]. / Neoplasie correlate con AIDS: studio clinico-radiologico.

Although high-grade non-Hodgkin's lymphoma (NHL) and an unusually aggressive form of Kaposi's sarcoma (KS) remain the most common malignancies seen in AIDS patients, other tumors such as cervical cancer, Hodgkin's disease and others, have been increasingly observed, probably because these patients now live longer. We report the imaging findings of 80 AIDS patients with pathologically confirmed neoplasms from a series of 340 AIDS patients examined 1986-1994. Twenty-four of 80 patients had NHL, 4 Hodgkin's disease, 31 KS, 4 cervical cancer, 2 leukemia, 2 testicular, 1 larynx, 2 lung, 2 breast, 1 esophagus, 1 stomach, 1 liver, 2 kidney and 3 adrenal carcinomas. Twenty of 24 NHLs exhibited extranodal involvement--to the liver (13/24), brain (9/24), lung (7/24) and gastrointestinal tract (6/24). Visceral KS involved the gastrointestinal tract (6/32), lung (4/32) and liver (2/32). The most accredited pathogenetic theories concerning the role of HIV infection in oncogenesis advocate the effect of multiple growth factors produced by HIV-infected lymphocytes (KS) or the disregulation of B-cells caused by T-cell destruction (NHL). The atypical morphostructural features of AIDS-related tumors are discussed--e.g., atypical presentation, occurrence in younger individuals, aggressive clinical course and poor response to conventional therapy--together with the differential diagnostic problems, especially vs. opportunistic infections.