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Biomedical subjects

A De Maria

Publications and source records attributed to A De Maria.

At least 37 records · Page 2Linked to original sources
PubMed1994

CD8+ cytolytic T lymphocytes become infected in vitro in the process of killing HIV-1-infected target cells.

In the present study the requirements for in vitro infection of antigen-specific CD8+ cytotoxic T lymphocytes (CTL) with human immunodeficiency virus -1(HIV-1) were investigated. CD3+CD8+CD4- HIV-1 nef-specific CTL become infected with HIV-1 after short-term co-culture with HLA-matched HIV-1-infected CD20+ B lymphoblastoid cells (B-LCL) which are specifically killed. Similar results were observed with an allospecific CD8+ CTL population. In addition, co-culture experiments showed that once infected with HIV-1, these CD8+ CTL could spread the infection further to uninfected CD4+ lymphocytes. In contrast, CD8+ CTL did not become infected with HIV-1 when co-cultured with HLA-mismatched HIV-1-infected B-LCL which are not killed. These observations in vitro could have relevance in peripheral lymphoid organs contributing to the progressive decrease of HIV-specific CD8+ CTL activity that is associated with the progression to AIDS.

CD4-Positive T-Lymphocytes↗
PubMed1994

Transfer of HIV-1 to human tonsillar stromal cells following cocultivation with infected lymphocytes.

The susceptibility of normal human tonsillar stromal cells (HTSCs) to infection by HIV-1 was assessed using transmission electron microscopy (TEM), immunocytochemistry, and HIV-1-specific PCR analyses. Our results demonstrate that HTSCs are efficiently infected following cocultivation with the HIV-1-infected lymphoblastoid cell line GY1. Infected stromal cells contain intracellular viral particles present as free virus or associated with phagocytic vesicles. These particles express the HIV-1-specific p24 antigen as assessed by immunocytochemical analyses using an HIV-specific anti-p24 monoclonal antibody. Moreover, PCR analysis of genomic DNA isolated from particle-bearing tonsillar stromal cells identified HIV-1-specific sequences not present in either uninfected stromal cells or parental GY1 uninfected cells. The mechanism by which HIV-1 infects HTSCs does not appear to be CD4 mediated, as none of the human tonsillar stromal cell lines express CD4 as assessed by flow cytometry, immunohistochemistry, and PCR analysis. Taken together, these results demonstrate that human tonsillar stromal cells can be infected by HIV-1, and that subsequent to infection the viral genome is reverse transcribed, and integrated into the stromal cell DNA. The infection of HTSCs may contribute to HIV-1-mediated pathogenesis indirectly as a viral reservoir or directly by structural and functional modification of the lymphoid microenvironment.

Antibodies, Monoclonal↗
PubMed1994

Occurrence of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic T cell activity in apparently uninfected children born to HIV-1-infected mothers.

Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) activity against different viral antigens, including env, gag/pol, and nef, was detected in peripheral blood lymphocytes of as many as 25% of uninfected children born to HIV-1-infected mothers. The relatively high frequency of this finding in uninfected, exposed children suggests that CTL-mediated immunity may play a key role in the control or even elimination of the virus. Further characterization of this natural model of potentially protective immunity could provide new insight and suggest further strategies for the development of HIV-1 vaccines.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Survival with AIDS in Massachusetts, 1979 to 1989.

OBJECTIVES: The goal of the study was to determine survival time after diagnosis of acquired immunodeficiency syndrome (AIDS) and to identify predictors of survival. METHODS: We conducted a population-based prospective survival analysis of all Massachusetts-resident adult AIDS patients diagnosed from January 1, 1979, through December 31, 1988. RESULTS: Median survival was 406 days, with a 5-year survival rate of 3%. Age older than 40 years (P = .001), a diagnosis other than Kaposi's sarcoma (P = .001), and a history of intravenous drug use (P < or = .01) were associated with shorter survival after confounding was controlled. Survival increased as year of diagnosis became more recent (P < .0001). This temporal effect was strongest for patients with Pneumocystis carinii pneumonia. Individuals with Kaposi's sarcoma, Hispanics, homosexual men who were concurrent intravenous drug users, and residents of the greater Boston standard metropolitan statistical area, excluding the city of Boston, did not experience increases in survival over time. CONCLUSIONS: With the exception of cases initially defined by Kaposi's sarcoma, recently diagnosed AIDS case subjects survive longer than those diagnosed earlier in the epidemic. Further work is needed to determine whether this effect is due to lead-time bias or better treatment after diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[Anaplastic carcinoma of the thyroid: long-term survival].

Anaplastic carcinoma of the thyroid is a highly aggressive neoplasm with quickly total course. It is characterized by an average survival of 4-12 months. It infiltrates precociously into the windpipe, oesophagus, vessels of the neck and gives distant metastases in 10-48% of cases. In 30.8 to 80% of cases, this carcinoma originates in an old multinodular goiter. The hypothesis has been also advanced that this neoplasm could derive from a pre-existent well-differentiated carcinoma. The improvement in diagnostic techniques (especially immunohistochemistry) allows a more correct definition of this neoplasm, permitting a differential diagnosis with other tumours (lymphoma, medullary carcinoma, hemangioblastoma) with which in the past it has been erroneously identified. The results reported in the literature are controversial as regards long-term survival, but usually it is less than one year. Longer survival must lead to the suspicion of wrong diagnosis. A relatively better prognosis is observable in intraglandular forms, "minimi" neoplastic focus and young patients. The presence of regional metastatic lymph nodes doesn't seem to modify the prognosis. Instead, a factor which can condition the prognosis is the type of therapy. Now a days the most efficacious curative treatment is the multinodal one (surgery, radio- and chemotherapy). The best results about survival and quality of life have been obtained using chemo-radiotherapy before operation and chemotherapy after it.

Carcinoma↗
PubMed1993

[Short-stay in patients surgically treated for thyroid disease].

The improvement in anesthesiology and greater experience of medical staff have permitted short-stay surgery. The authors in this pages report their knowledge of thyroid short-stay surgery. Their series numbers twenty-two lobectomies for uninodular the thyroid disease and one enucleoresection for a nodule of pyramidal lobe. Short-stay surgery has been proposed to euthyroid patients, selected according to age, residence and health (lack of associated pathologies such as cardiopathy, bronchopathy, hepatopathy, nephropathy, allergy, calcemic disorders and dysphony) and confirmed in the presence of histological extemporary diagnosis of "adenoma" (21 cases). The histological extemporary diagnosis of "carcinoma" has lengthened hospital stay. Among the lobectomies, 21 were executed in general anaesthesia and 1 in acupuncture. The enucleoresection was executed in local anaesthesia. Only in eighteen cases was a "Penrose" deainage used, removed after 24 hours. The choice of thyroid short-stay surgery, particularly in day-hospital, must arise from a careful selection of patients. Besides, this surgery requires an administrative and sanitary structure which permits a constant patient's check at hare too.

Adult↗
PubMed1993

Zidovudine therapy of HIV-1 infection during pregnancy: assessment of the effect on the newborns.

Zidovudine (ZDV) administration during pregnancy has been suggested for the prevention of mother-to-child HIV-1 transmission. Reliable levels of the drug have been observed in the fetus and in the newborn. Seven HIV-1-infected pregnant women who declined to have abortions and whose immunological status required antiretroviral treatment were administered oral ZDV 18 mg/kg in four daily doses, the initial dose being administered anytime from the 16th to the 30th week of gestation up until the time of delivery. Follow-up of the seven infants from birth with a mean duration of 22 months (range 16-32 months) revealed mild drug-related toxicity: anemia in two infants and macrocytosis in all seven, both conditions resolved by the second month of life. All infants remained HIV-1 seronegative, according to the 1987 CDC classification, and all stayed clinically well. Other virological parameters including virus culture, in vitro antibody production, and polymerase chain reaction, repeatedly performed in the infants, remained negative. Although none of the mothers transmitted HIV-1 infection to the offspring, the size of this study and the relatively low transmission rate (13%) in Europe do not permit us to draw a definite conclusion about treatment efficacy in preventing maternal-fetal transmission. However, the drug caused only limited toxicity among the infants, and its administration to large numbers of mothers in treatment trials should be considered relatively safe for both mother and child.

Female↗
PubMed1992

Selective increase of a subset of T cell receptor gamma delta T lymphocytes in the peripheral blood of patients with human immunodeficiency virus type 1 infection.

Increased proportions of the small lymphoid subset expressing T cell receptor (TCR) gamma delta occur in different infectious diseases, particularly in mycobacterial infections. In this study the two main subsets of TCR gamma delta+ cells in peripheral blood mononuclear cells (PBMC) of 54 patients with human immunodeficiency virus type 1 infection were analyzed. These subsets were defined by indirect immunofluorescence techniques and FACS analysis using BB3 and A13 monoclonal antibodies, which specifically react with V delta 2- and V delta 1-encoded forms of TCR gamma delta. The proportion of BB3+(V delta 2+) and A13+(V delta 1+) cells was analyzed in purified PBMC populations. Patients were stratified according to Walter Reed (WR) clinical stage. A sharp increase in percentage of A13+(V delta 1+) cells was observed in all stages of the disease. In addition, a strict correlation was found with stage of the disease and percentage of CD8+ PBMC. An inverse correlation was found with the proportion of CD4+ PBMC. An early (WR2) inversion of the V delta 2-to-V delta 1 ratio was consistently detected even before the inversion of the CD4-to-CD8 ratio.

CD4 Antigens↗
PubMed1991

Productive infection of CD4+ and CD8+ mature human T cell populations and clones by human herpesvirus 6. Transcriptional down-regulation of CD3.

The susceptibility to infection by human herpes-virus 6 (HHV-6) of mature human T lymphocytes belonging to the two major subpopulations (i.e., CD3+ CD4+ CD8- and CD3+ CD4- CD8+) was investigated by using CD4+ or CD8+ T cell populations and clones derived from normal adult peripheral blood. Productive HHV-6 infection was observed in both CD4+ and CD8+ T cells. By days 2 to 6 after infection, increasing numbers of cells exhibited characteristic morphologic alterations, becoming enlarged, uniformly rounded and refractile as a consequence of the virus-induced cytopathic effect. During the course of HHV-6 infection, analysis of the surface membrane phenotype of the T cell populations and clones revealed a progressive decline in the expression of the CD3/TCR complex, whereas other T cell-associated markers (e.g., CD2) were unaffected. Northern blot analysis of mRNA extracted from HHV-6-infected T cells demonstrated a dramatic loss of the specific messages for the gamma-, delta-, and epsilon-chains of CD3. Infection by HHV-6, but not by HSV-1 or human CMV, elicited CD3/TCR down-regulation also in the neoplastic T cell line Jurkat. The down-regulation of CD3/TCR was dependent upon live virus infection, because previous inactivation of HHV-6 by heat (56 degrees C for 1 h) or UV light (16 J/m2) totally abrogated the effect. Expression of the immediate early or early genes of HHV-6 was not sufficient to induce CD3/TCR modulation, as indicated by studies with the viral DNA polymerase inhibitor phosphonoformic acid. The observation that both major subsets of mature TCR-alpha beta+ T lymphocytes are susceptible to HHV-6 infection indicates that this virus may have a broad spectrum of activity on the immune system. The transcriptional down-regulation of the CD3/TCR complex, by affecting a critical T cell recognition function, could be relevant to HHV-6 pathogenesis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Infection of CD8+ T lymphocytes with HIV. Requirement for interaction with infected CD4+ cells and induction of infectious virus from chronically infected CD8+ cells.

In this study, we have investigated the basic requirements for HIV-1 infection of CD8+ lymphocytes in vitro. Unfractionated PBL obtained from healthy HIV-1 seronegative donors were activated with PHA and infected in vitro with HIV-1LAV. Based on immunofluorescent labeling, the vast majority of cells (85 to 97%) surviving peak virus replication belonged to the CD8+ subset and only a small percentage (0.5 to 1.5%) were CD4+. Amplification of HIV-1 proviral sequences by polymerase chain reaction performed on the sorted surviving CD8+ cells demonstrated that CD8+ cells harbored HIV-1 proviral DNA. In addition, stimulation of these HIV-1-infected, CD8(+)-sorted cells either with PHA or anti-CD2 mAb resulted in induction of virus replication, as measured by reverse transcriptase activity. Electron microscopic analysis of CD8+ cells chronically infected with HIV-1 and stimulated with PHA showed typical virions budding from, and associated with, the surface of cells immunolabeled with gold beads directed toward the CD8 molecule. Infection of CD8+ cells with HIV-1 occurred only when CD4+ cells were present in the PHA-activated lymphocyte population exposed to HIV-1 at the beginning of the culture or when sorted CD8+CD4- lymphocytes were cocultured with autologous sorted CD8-CD4+ cells that had been previously infected with HIV-1. Coculture of these cells with PHA-blasts and incubation of their supernatants with a CD4+ cell line showed that these chronically infected CD8+ cells could spread HIV-1 infection to uninfected CD4+ cells after stimulation with PHA or anti-CD2 mAb. Therefore, these results suggest that the minimal requirement for in vitro infection of CD3+CD8+CD4- lymphocytes is the presence of infected CD4+ cells and that infected CD8+ T lymphocytes can further spread the infection to CD4+ cells.

Antigens, CD↗
PubMed1991

Induction of CD4 and susceptibility to HIV-1 infection in human CD8+ T lymphocytes by human herpesvirus 6.

During intrathymic T-cell ontogenesis, functionally competent CD3+CD4+CD8- and CD3+CD4-CD8+ T lymphocytes develop from immature CD4-CD8- thymocytes after transiently acquiring a double-positive CD4+CD8+ phenotype. The partition between CD4+CD8- and CD4-CD8+ T cells is generally considered to be irreversible, although a small percentage of circulating CD3+ T lymphocytes coexpressing CD4 and CD8 molecules has been identified. It has been suggested that in CD8+ T cells the CD4 genes may be methylated and thus highly repressed, whereas in CD4+ T cells the CD8 genes are unmethylated and their transcription can be induced by physiological stimuli such as interleukin-4. Here, we demonstrate that infection with human herpesvirus 6 (HHV-6), a virus proposed as a potential cofactor in AIDS, dramatically upregulates the expression of CD4--the receptor for human immunodeficiency virus type-1 (HIV-1)--in a human neoplastic T-cell line. More importantly, HHV-6 induces de novo expression of CD4 messenger RNA and protein in normal mature CD8+ T lymphocytes, rendering them susceptible to infection with HIV-1. These findings demonstrate that human CD3+CD4-CD8+ T lymphocytes can reacquire CD4 in the post-thymic life and elucidate a novel mechanism--receptor regulation--through which HHV-6 may positively interact with HIV-1 in coinfected patients.

Antibodies, Monoclonal↗
PubMed1990

[Hypocalcemia after total thyroidectomy. Therapeutic considerations].

One of the post-operative complications of total thyroidectomy is the onset of a transitory or permanent hypocalcemic syndrome. Hypocalcemia is caused by different physiopathological mechanisms that operate either individually or in association (parathyroidal deficit, deficiency of bone calcium subsequent to parathyroid osteodystrophy, acute emission of calcitonin into the circulation). Calcemia levels were studied p.o. in a selected group of 25 patients who had undergone total extracapsular thyroidectomy with the apparent preservation of the parathyroid glands. Totals thyroidectomy has been performed in 15 patients with euthyroid goitre, in 4 with papillary carcinoma, in 3 with diffuse toxic goitre and in 3 with multinodular toxic goitre. Eight patients received drug and diet therapy since calcemia levels were lower than 7.5 mg/ml. Fifteen days after the operation, calcemia levels in 21 patients were subliminal and dihydrotachysterol therapy was commenced. Hypocalcemia was permanent in only one case.

Calcium↗
PubMed1990

CD8+ T lymphocytes of patients with AIDS maintain normal broad cytolytic function despite the loss of human immunodeficiency virus-specific cytotoxicity.

In this study, we have investigated the potential mechanisms responsible for the loss of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic activity in the advanced stages of HIV-1 infection. We have demonstrated that HIV-1-specific cytotoxic T lymphocytes are predominantly contained within the CD8+DR+ subset. Furthermore, we have shown by a redirected killing assay that there is a dichotomy between HIV-1-specific cytolytic activity and broad cytolytic potential since the cytolytic machinery of CD8+DR+ cells is still functioning even in patients with AIDS who have lost their HIV-1-specific cytolytic activity. In addition, by comparative analysis of these two types of cytolytic activity over time we have demonstrated a progressive loss of HIV-1-specific cytolytic activity in the advanced stages of the disease, whereas the cytolytic potential remained unchanged regardless of the clinical stage. As previously shown in patients with AIDS, even in asymptomatic HIV-1-seropositive patients, CD8+DR+ cells from the same patient, compared to CD8+DR- lymphocytes, showed a substantial reduction in their ability to proliferate in vitro in response to different stimuli, such as mitogens (phytohemagglutinin and phorbol 12-myristate 13-acetate) and monoclonal antibodies directed against CD3, CD2, and CD28 molecules, and displayed a defective clonogenic potential. Thus, on the basis of these results we propose that the loss of HIV-1-specific cytolytic activity in HIV-1-infected individuals may result at least in part from a progressive decrease in the pool of HIV-1-specific cytotoxic T lymphocytes belonging to the CD8+DR+ subset whose ability to expand has been impaired.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Diagnosis of human immunodeficiency virus 1 infection in infants: in vitro production of virus-specific antibody in lymphocytes.

In children born to mothers infected with human immunodeficiency virus 1 (HIV-1), a diagnosis of HIV infection cannot be based on a positive antibody result until at least 18 months of age. There is therefore an urgent need for simple and reliable methods of diagnosing HIV infection in these infants. The sensitivity and specificity of a test using the in vitro antibody production of HIV-specific IgG was assessed in children whose infection status was known and compared with virus and antigen detection. In vitro antibody production sensitivity was 90 to 95%, at least as sensitive as virus culture in antibody-positive infected children. In the first 2 months there is a relatively high proportion of false positive results, possibly a result of contamination by maternal cells. However, after this period in vitro antibody production is a simple, inexpensive and reliable tool for early diagnosis.

AIDS-Related Complex↗