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Biomedical subjects

A Ravina

Publications and source records attributed to A Ravina.

At least 19 recordsLinked to original sources

In vitro infection with HIV enables human CD4+ T cell clones to induce noncognate contact-dependent polyclonal B cell activation.

Eleven (nine CD4+ and two CD8+) protein purified derivative-specific and eight tetanus toxoid-specific T cell clones (TCC), established from the peripheral blood of healthy persons, were cocultured in vitro with irradiated mononuclear cells from patients infected by HIV in the presence of PHA and polybrene. Two weeks post-HIV exposure, all 17 CD4+, but neither of the two CD8+, TCC exhibited integration of HIV in their genoma, as detected by polymerase chain reaction analysis, and released HIV into their supernatants, as detected by measuring both reverse transcriptase activity and p24 Ag. When co-cultured with either autologous or allogeneic B cells, all CD4+ HIV-infected TCC induced the synthesis of extraordinarily high amounts of IgM, IgG, and IgA. In contrast, their noninfected counterparts could provide helper function for Ig synthesis by autologous B cells only in the presence of the specific Ag (or anti-CD3 antibody), and induced allogeneic B cells to synthesize Ig only upon stimulation with anti-CD3 antibody. The supernatants of HIV-infected TCC failed to stimulate Ig synthesis in B cells. More importantly, when HIV-infected clonal T blasts and B cells were cultured in different chambers separated by a millipore membrane, permeable to molecules but not to cells, Ig synthesis did not occur. The Ig synthesis induced by HIV-infected TCC was also markedly inhibited by the addition in culture of either anti-CD4 or anti-LFA-1 antibody. In contrast, HIV-infected TCC maintained their ability to provide helper function for Ig synthesis in the absence of any stimulus, even after fixation with p-formaldehyde. These data demonstrate that in vitro infection with HIV enables human T cells to stimulate Ig synthesis by B cells by an Ag-nonspecific, MHC-unrestricted, contact-dependent mechanism. This may explain, at least in part, the hypergammaglobulinemia and other phenomena related to polyclonal B cell activation frequently seen in HIV-infected persons.

B-Lymphocytes

[Determination of pancreatic size by ultrasound in diabetics].

Determination of pancreatic size by ultrasound in diabetics showed that the pancreas is smallest in Type 1 (IDDM) diabetes (7.15 +/- 0.55 cm), larger in Type 2 (9.71 +/- 0.81 cm), but significantly greater in nondiabetics (15.17 +/- 0.79 cm). In 10/12 patients referred because of reactive hypoglycemia there was insulin-resistance and the pancreas was smaller than 8 cm. There was no correlation between pancreatic size and duration of diabetes, body size, or body mass index. More normal controls of various ages are needed for definitive assessment.

Body Constitution

Recurrent oral condylomata acuminata and hairy leukoplakia: an early sign of myelodysplastic syndrome in an HIV-seronegative patient.

Oral hairy leukoplakia (OHL) has been observed in all risk groups seropositive for HIV infection. Recently, this lesion has also been described in HIV-seronegative patients with immunosuppression of iatrogenic origin. We report on a HIV-1 and HIV-2 seronegative, heterosexual man affected by refractory anemia with ringed sideroblasts (myelodysplastic syndrome), who developed recurrent oral condylomata acuminata and OHL as an early clinical manifestation. The diagnosis of OHL was confirmed by identifying Epstein-Barr viral particles by electron microscopy and by in situ DNA hybridization. HIV infection was ruled out using polymerase chain reaction and testing for HIV-1 and HIV-2 antibodies.

Anemia, Refractory

[Bedtime administration of metformin may reduce insulin requirements].

The administration of metformin, as glucophage retard, at bedtime instead of supper time may improve diabetes control by reducing morning hyperglycemia. This modification of glucophage treatment was tried in 3 groups of diabetic patients: I. those with secondary failure of routine treatment with sulfonylurea (SU) and glucophage; II. those with combined SU and bedtime insulin; III. Type 1 patients with early morning hypoglycemia. The first 3 months of observation in 258 patients showed that 136 (52.7%) reacted very well to the change. In Group I the addition of insulin to SU could be postponed. In Group II, night insulin could be reduced or eliminated. In Group III, evening or night insulin could be reduced by up to 70%. There was no early morning hypoglycemia nor morning hyperglycemia. The success rate in the 2 Type 2 groups was better (72% and 60%) than in the Type 1 group (34%). 30 patients (11.6%) had to stop the treatment because of side effects of the glucophage (mainly diarrhea or nausea). So far, we have found no clinical signs that might indicate which patients might benefit from this modification of treatment. A fasting blood sugar done within 2-3 days after the change in treatment may immediately indicate whether the new treatment is effective.

Blood Glucose

Reduced production of interleukin 2 and interferon-gamma and enhanced helper activity for IgG synthesis by cloned CD4+ T cells from patients with AIDS.

Purified T lymphocytes (E rosetting cells) isolated from peripheral blood (PB) of four patients with acquired immune deficiency syndrome (AIDS) were cloned under culture conditions (phytohemagglutinin plus interleukin 2) which allow clonal expansion of most T lymphocytes. A total number of 101 T cell clones (37 CD4+ and 64 CD8+) from PB of AIDS patients and of 188 T cell clones (115 CD4+ and 73 CD8+) from PB of four normal controls were obtained and tested for their helper function as well as for their capacity to release lymphokines. Unstimulated CD4+ TCC from patients with AIDS showed enhanced helper function for IgG synthesis in vitro in both autologous and normal allogeneic B cells in comparison to clonable CD4+ T cells of normal donors. Such activity was further potentiated by addition to the cell cultures of anti-CD3 monoclonal antibody. The majority of CD4+ T cell clones from AIDS patients showed a reduced ability to produce interleukin 2 and interferon-gamma in response to activation with phytohemagglutinin. However, most of them released greater amounts of soluble factor(s) able to promote B cell proliferation of anti-IgM-activated normal B cells and to induce the differentiation of normal B lymphocytes into IgG-secreting cells. These data demonstrate that most surviving CD4+ T cells in PB of patients with AIDS belong to a T cell subset producing B cell growth and differentiation factors, which may contribute to the B cell hyperactivation seen in AIDS patients.

Acquired Immunodeficiency Syndrome

Continuous subcutaneous insulin infusion. Improved blood glucose in pregnant diabetics.

The effect of continuous subcutaneous insulin infusion (c.s.i.i.) on the control of blood-glucose concentration and outcome of pregnancy was assessed in two pregnant diabetics (class B and class C White classification) who were poorly controlled with conventional insulin therapy. The insulin pump was carried in a holster and enabled the patients to ambulate freely. The patients were able to refill the syringe, to augment the infusion rate at mealtime and to change the implantation site of the needle weekly, and thus, were able to leave the hospital. Daily glucose profiles were assessed 1-3 times a week, and the infusion rate was readjusted accordingly. Twenty-four hours glucose profiles were obtained from both patients during inpatient conventional insulin regimens, and then, during c.s.i.i. which was maintained for 41 and 145 days, respectively. Mean 24 hours glucose concentrations were reduced from 156 to 113 mg/100 ml, mean fasting glucose from 152 to 106 mg/100 ml, and mean diurnal variation (maximal excursion) from 75 to 65 mg/100 ml. The favourable results achieved with the c.s.i.i. enabled both patients to reach the 18th week of gestation and to deliver healthy non-macrosomic infants, who had uneventful and morbid-free neonatal periods. Since the c.s.i.i. supplies insulin in a more physiological manner than twice daily regimens, better control of blood sugar and body fuel metabolism may be achieved. By extending the therapy to the early stages of pregnancy, or if possible to pre-conceptional period, reduced perinatal mortality and morbidity may be anticipated.

Adult