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Biomedical subjects

P Gupta

Publications and source records attributed to P Gupta.

At least 307 records · Page 17Linked to original sources

Infection with human immunodeficiency virus in the Pittsburgh transplant population. A study of 583 donors and 1043 recipients, 1981-1986.

We performed a retrospective serologic survey of 583 organ donors and 1043 transplant recipients for antibodies to human immunodeficiency virus type 1 (HIV-1). Two (0.34%) of the 583 donors and 18 (1.7%) of the 1043 recipients had HIV-1 antibodies by enzyme immunoassay and by Western blot. Two of 5 seropositive recipients tested also had blood cultures positive for HIV-1. Seven (0.7%) of the 1043 transplant recipients had antibodies to HIV-1 before transplantation; 2 of these had hemophilia A, and 5 had previous transfusions. Eleven (1.3%) of 860 recipients followed for 45 days or more seroconverted to HIV-1 a mean of 96 days after transplantation. Likely sources of HIV-1 infection for 3 of these 11 recipients included a seropositive organ donor in 1 patient and high-risk blood donors in 2 patients. A definite source of HIV-1 infection was not found for the other 8 recipients, 3 of whom seroconverted to HIV-1 after institution of blood donor screening for HIV-1 antibodies. Seroconversion to HIV-1 was less common in kidney recipients than in liver, heart, or multiple-organ recipients (P less than 0.02). Nine (50%) of the 18 HIV-1 seropositive transplant recipients died a mean of 6 months after transplant surgery, and 9 (50%) are still alive a mean of 43 months after transplantation. AIDS-like illnesses occurred in 3 of the dead and 1 of the living patients and included pneumocystis pneumonia (3 cases), miliary tuberculosis (1 case), and recurrent cytomegalovirus infection (1 case). These data suggest that the course of HIV-1 infection is not more severe in transplant recipients receiving cyclosporine than in other hosts and that, despite screening of blood and organ donors, a small number of transplant recipients will become infected with HIV-1.

Blotting, Western↗

Association of alpha interferon production with natural killer cell lysis of U937 cells infected with human immunodeficiency virus.

Mononuclear leukocytes from human immunodeficiency virus (HIV)-seronegative and -seropositive homosexual men lysed HIV-infected U937 cells to a significantly greater degree than uninfected U937 cells. Depletion of cell subsets with monoclonal antibodies and complement indicated that the effector cells were primarily of the CD16+ phenotype. Acid-stable alpha interferon (IFN-alpha) production induced by the HIV-infected cells correlated with, although was not an absolute requisite for, preferential lysis of the infected targets. The activity of these CD16+, natural killer (NK) cells decreased in relation to the duration of HIV infection and the presence of acquired immunodeficiency syndrome. Pretreatment of peripheral blood mononuclear cells from HIV-seronegative subjects, but not HIV-seropositive men, with IFN-alpha or recombinant interleukin-2 enhanced lysis of both uninfected and HIV-infected U937 cells. These results suggest that IFN-alpha-associated, NK-like mechanisms are active in the cytotoxic response against HIV-infected cells and that HIV infection results in an early and progressive depression of such responses. Prospective investigations may be useful in determining the role of this NK cell response in the natural history and pathogenesis of HIV infection and the efficacy of therapeutic modalities.

Acquired Immunodeficiency Syndrome↗

Association of human immunodeficiency virus (HIV) p24 antigenemia with decrease in CD4+ lymphocytes and onset of acquired immunodeficiency syndrome during the early phase of HIV infection.

Human immunodeficiency virus (HIV) p24 antigenemia was assessed in a longitudinal study of 52 homosexual men who developed serum antibody to HIV. Antibody seroconversion to HIV as defined by a positive HIV enzyme immunoassay (EIA) confirmed by Western (immuno-) blot was associated with three major patterns of HIV antigenemia. In the first pattern, a transient antigenemia was noted 6 (six subjects) and 12 (one subject) months prior to detection of antibody by HIV EIA and Western blot in 7 (13.5%) of the 52 men. Use of an EIA employing a recombinant envelope protein (ENV9) was able to detect antibody in four of these seven men at the time of this early antigenemia. In the second pattern, HIV p24 antigenemia occurred in 8 (15.4%) of the 52 subjects within the first 12 months after HIV antibody seroconversion. No p24 antigen was detected in the 37 (71.1%) remaining subjects. CD4+ cell numbers were lower in antigen-positive men before and after antibody seroconversion. Development of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was strongly associated with evidence of persistent p24 antigenemia during the early, postseroconversion period. HIV p24 antigenemia may be of value in determining appropriate cohorts for drug therapy trials for subjects with early-phase HIV infection.

AIDS-Related Complex↗

Cell-to-cell transmission of human immunodeficiency virus type 1 in the presence of azidothymidine and neutralizing antibody.

Very few peripheral blood lymphocytes of seropositive individuals are presumably actively infected with human immunodeficiency virus type 1 (HIV-1). During coculture of lymphocytes of a seropositive individual with mitogen-stimulated normal peripheral blood lymphocytes, the number of infected cells becomes amplified such that detectable HIV-1 is produced. We report here that in addition to transmission by extracellular virus, cell-to-cell transmission is responsible for spreading HIV-1 infection from infected to uninfected cells. Azidothymidine and virus-neutralizing antibody had no effect on cell-to-cell transmission of HIV-1. Monoclonal antibodies to the CD4 receptor, but not to the CD3 receptor, prevented cell-to-cell transmission, which suggests that CD4 receptor-mediated cell fusion is involved in cell-to-cell transmission. Spread of infection in a cell-to-cell manner may be important in development of drug therapies for HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Expression and posttranslational processing of preprodynorphin complementary DNA in the mouse anterior pituitary cell line AtT-20.

A recombinant plasmid containing the rat prodynorphin cDNA was introduced into the mouse anterior pituitary corticotroph cell line AtT-20. These cells normally express and posttranslationally process proopiomelanocortin, but not prodynorphin. Stable transformants were isolated and analyzed for the expression and processing of prodynorphin. The stably transformed AtT-20 cells that expressed a 1.3-kilobase prodynorphin mRNA also expressed prodynorphin protein and processed it to dynorphin peptides. The peptides included leucine-enkephalin, beta-neoendorphin, dynorphin-A8, and dynorphin-B, as identified by gel filtration and reverse phase HPLC followed by RIA using peptide-specific antisera. These results demonstrate that AtT-20 cells efficiently and accurately process prodynorphin at both dibasic sites and monobasic cleavage sites, indicating that the AtT-20 cells contain enzymes capable of cleaving the precursor not only at dibasic residues but also at monobasic residues. The release of prodynorphin-derived peptides paralleled secretion of endogenous proopiomelanocortin-derived peptides when stimulated by CRF, a natural secretagogue for ACTH.

Amino Acid Sequence↗

Krukenberg's tumor in the young population.

Krukenberg's tumor secondary to gastric adenocarcinoma was identified in a 20-year-old woman. The patient died ten weeks after surgery, which included total hysterectomy, bilateral salpingo-oophorectomy, tumor debulking, and subtotal gastrectomy. Her unexpected advanced disease and fulminant course led the authors to review the literature for other reports of Krukenberg's tumor in the young person. However, the age category was not studied specifically in most series, and only a few cases involving patients of very young age were detailed. The present case appears to be only the fifth involving a patient aged 20 years.

Adenocarcinoma↗

Binding of phytohemagglutinin to bovine B lymphocytes and its role in stimulation of expression of bovine leukemia virus genome.

Phytohemagglutinin (PHA) is known to increase the synthesis of bovine leukemia virus (BLV) particles and viral antigens in short-term culture of BLV-infected neoplastic and non-neoplastic lymphocytes. This stimulation of BLV expression has been shown to be due to enhanced transcription of the viral genome by a PHA-induced protein. We have investigated the binding of 125I-labelled PHA to BLV-infected bovine B lymphocytes and subsequent events that may lead to the stimulation of BLV-p25 synthesis. We found that PHA binding to the infected cells were rapid, but only a small fraction of the bound PHA is translocated to nucleus. However, bound PHA dissociated rapidly from the cell membrane, but not from the nucleus when PHA is removed from the culture medium. Furthermore, continuous presence of PHA was not essential for optimal stimulatory activity, instead a minimum incubation with PHA for 6 hr. followed by culturing the infected cells in its absence, was sufficient to exhibit maximal stimulatory activity. Our results raise the possibility that interaction of PHA with the plasma membrane probably triggers synthesis of a protein which in turn enhances the transcription of BLV genome in vitro.

Animals↗

HIV heterosexual transmission in hemophilia couples: lack of relation to T4 number, clinical diagnosis, or duration of HIV exposure.

Six (13%) of 45 female partners of 45 HIV antibody positive [Ab(+)] hemophiliacs in Western Pennsylvania have become HIV Ab(+), a mean of 10.4 months from the time of first exposure. By comparison, the mean time from first exposure to the last/recent exposure in the HIV Ab(-) female partners was 54.2 months. All six hemophiliacs who transmitted HIV to their female partners were asymptomatic, with mean T4 of 403 +/- 51/mm3 at the time of estimated seroconversion in the female; currently, their mean T4 is 203 +/- 75/mm3, which is not different from that in hemophiliac men whose partner remains HIV Ab(-) (170 +/- 22/mm3). Thus, in this population, heterosexual transmission occurs early and is unrelated to clinical or immunologic status in the hemophiliac. The risk of HIV transmission in persistently HIV Ab(-) female partners is unknown but appears low.

Adult↗

Ultrastructural reappraisal of endometrial glandular changes in women wearing Cu-T200 device for longer duration.

The present communication deals with the effects of Copper-T200 Sq mm intrauterine device on the endometrial glands in the women using it for a longer duration i.e. up 8 years. The ultrastructural changes in the lining endometrial glands were studied during both non-ovulatory and ovulatory phases of the menstrual cycle. The ultrastructural studies demonstrated significant progressive changes in the lining endothelial cells of endometrial glands. The findings showed marked accumulation of glycogen in the cells in secretory phase of the endometrial cycle. Ultrastructural changes in glandular lining cells were more pronounced in women using Cu-IUCD for 4-8 years having distorted morphology with disrupted cell organelles, swollen mitochondria, irregular pattern of microvilli, deposition of electron dense material on cell surface and narrowing of glandular lumen.

Adult↗

Evaluation of the new rapid rabies immunodiagnosis technique.

The rapid rabies enzyme immuno-diagnosis (RREID) kit was evaluated for its sensitivity and specificity in comparison to fluorescent antibody technique (FAT) and biological test (BT) for the diagnosis of rabies. While 93 per cent correlation was observed in case of fresh brain samples, 71 per cent correlation was noted with glycerol preserved samples, where RREID was more sensitive than FAT. RREID test can be employed for rapid diagnosis of rabies, when facilities for FAT are not available. However, to test, at one time, small number of specimens, the RREID kit needs to be modified.

Animals↗

HIV-1-specific production of IFN-gamma and modulation by recombinant IL-2 during early HIV-1 infection.

Specific cellular immune responses to human immunodeficiency virus type 1 (HIV-1) were assessed in mononuclear leukocyte cultures from homosexual men with documented, early phase HIV-1 infection. Cell cultures from men with a mean duration of 1.3 yr (range, 0.3 to 2.2 yr) of HIV-1 infection were treated with UV-inactivated, whole, purified HIV-1 Ag together with various concentrations of rIL-2. Cell supernatants were harvested after 5-day incubation and assayed for IFN activity against encephalomyocarditis virus in human WISH cells. IFN subtypes were characterized by neutralization of antiviral activity with antiserum specific for human IFN-gamma and IFN-alpha. Results showed that cultures from 68% (17 of 25) of the HIV-1-seropositive subjects produced "immune" IFN-gamma in response to whole HIV-1 Ag plus rIL-2. IFN-gamma was induced in only 20% (5 of 25) of cultures treated with HIV-1 Ag alone. Enhancement of HIV-1-specific IFN-gamma production by rIL-2 was synergistic rather than additive in that titers induced by the mixture were consistently higher than the sum of IFN titers induced by HIV-1 or rIL-2 alone. This effect was not demonstrable in cultures from 18 HIV-1-seronegative men. Similarly, HIV-1-immune specific augmentation of IFN-gamma production by rIL-2 was noted for PENV9, a recombinant HIV-1 envelope glycoprotein gp41 and gp120 fragment. Production of IFN-gamma may be an important, HIV-1-immune specific parameter in the host response to this retrovirus.

Acquired Immunodeficiency Syndrome↗

Use of cryopreserved normal peripheral blood lymphocytes for isolation of human immunodeficiency virus from seropositive men.

The possibility was investigated of using frozen stocks of phytohemagglutinin (PHA)-stimulated normal human peripheral blood lymphocytes (PBL) in cocultivation with human immunodeficiency virus (HIV)-infected lymphocytes for the isolation of HIV. Fresh and cryopreserved PBL from eight healthy volunteers were compared for their susceptibility to HIV infection in vitro. Fresh lymphocytes, as well as lymphocytes that were stimulated with PHA before or after cryopreservation, displayed comparable susceptibilities to HIV infection in vitro. In addition, HIV was recovered in all cases when lymphocytes stimulated with PHA before or after cryopreservation were cocultured in parallel with PBL from 15 patients with acquired immune deficiency syndrome. However, the cryopreserved PBL were less efficient in isolating HIV from asymptomatic men.

Acquired Immunodeficiency Syndrome↗

Caffeine: a new look at an age-old drug.

Caffeine is ubiquitous in our environment and is the most widely used psychoactive drug in the world. Caffeine works on every system in the body mediated by the central nervous system. Caffeine has the opposite effect of adenosine and is the antagonist at the inhibitory A1-receptor. Caffeine elevates the free fatty acid mobilization and could enhance weight loss through pre-exercise caffeine ingestion. However, this hypothesis remains to be proven until an increase in fat oxidation is found. Caffeine is metabolized to more than 25 metabolites in man. Less than 5% of the caffeine is found in the urine as unchanged drug. The half-life of caffeine ranges from 1.5 to 9.5 hours. Smoking decreases the half-life of caffeine. Caffeine is used for the treatment of apnea of prematurity and as an additive in several analgesics and migraine remedies, and as a panacea for hyperkinetic children. Although much work has been done to establish the relationship between caffeine and cancer and mutagenicity, none of these have established a cause-effect relationship. The consumption of caffeine products in moderation appears to be safe at this point.

Apnea↗

Study on pinocytosis and antigen presentation by murine peritoneal macrophages to T cells in vitro after cisplatin treatment.

Macrophage monolayers showed significantly increased rate of pinocytosis on incubation with cisplatin (10 micrograms/ml). Further, the rate of pinocytosis was compared with macrophages treated with LPS (10 micrograms/ml). Cisplatin treated macrophages also showed enhanced capacity of antigen presentation to T cells in vitro. The antigen presenting capacity of cisplatin treated macrophages was compared with the antigen presenting capacity to LPS treated macrophages.

Animals↗