Impact of systemic or mucosal immunity to adenovirus on Ad-based Ebola virus vaccine efficacy in guinea pigs.

Background: Approximately 35% of the North American population and an estimated 90% of the sub-Saharan African population have antibodies against adenovirus serotype 5 (AdHu5) that are capable of neutralizing AdHu5-based vaccines. In mice, intranasal delivery of AdHu5 expressing the Zaire ebolavirus glycoprotein human adenovirus serotype 5 (Ad) containing the genes for the Zaire ebolavirus glycoprotein (ZGP) under the expressional control of a cytomegalovirus immediate early promoter (CMV)) can bypass systemic preexisting immunity, resulting in protection against mouse-adapted Zaire ebolavirus (Mayinga 1976).

Methods: Guinea pigs administered an adenovirus-based Ebola virus vaccine either intramuscularly or intranasally in the presence of systemically or mucosally induced adenovirus immunity were challenged with a lethal dose of guinea pig-adapted Zaire ebolavirus (Mayinga 1976) (GA-ZEBOV).

Modelling strategies for controlling SARS outbreaks.

Severe acute respiratory syndrome (SARS), a new, highly contagious, viral disease, emerged in China late in 2002 and quickly spread to 32 countries and regions causing in excess of 774 deaths and 8098 infections worldwide. In the absence of a rapid diagnostic test, therapy or vaccine, isolation of individuals diagnosed with SARS and quarantine of individuals feared exposed to SARS virus were used to control the spread of infection. We examine mathematically the impact of isolation and quarantine on the control of SARS during the outbreaks in Toronto, Hong Kong, Singapore and Beijing using a deterministic model that closely mimics the data for cumulative infected cases and SARS-related deaths in the first three regions but not in Beijing until mid-April, when China started to report data more accurately.

HIV-1 infection is facilitated in T cells by decreasing p56lck protein tyrosine kinase activity.

Several studies have suggested an important role for the protein tyrosine kinase p56lck (Lck) in HIV infection; however, the exact nature of this role remains unclear. Using a series of well characterized Jurkat-derived cell lines having a wide range of Lck kinase activity, our results showed that, while the entry of HIV-1 into these cell lines was similar, the kinetics of virus production by these cells were very different. Cells expressing a kinase-inactive Lck showed accelerated viral replication, whereas, cells expressing Lck with normal or elevated enzymatic activity showed a delay in virus replication that was proportional to the initial level of endogenous Lck activity.

VPAC1 is a cellular neuroendocrine receptor expressed on T cells that actively facilitates productive HIV-1 infection.

Objective: A lack of productive HIV-1 infection of Kit225 compared to Jurkat T cells, despite similar levels of CD4 and HIV-1 chemokine co-receptors, was found to correlate with the expression of vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide receptor-1 (VPAC1). We therefore examined a role for this seven-transmembrane G protein-coupled neuroendocrine receptor in modulating HIV-1 infection.

Methods: Reverse transcription-PCR was used to show the level of VPAC1 expression in different T-cell lines.

Numerical modelling of the perturbation of HIV-1 during combination anti-retroviral therapy.

A competitive, chaos-free, implicit, finite-difference method is developed and used for a novel deterministic model for the perturbation of HIV by combination antiretroviral therapy. The compartmental model monitors the interaction between HIV and CD4(+) T cells, its principal target and site of replication in vivo, in the presence of reverse transcription inhibitors and protease inhibitors. The model exhibits two steady states, an uninfected (trivial) steady state (with no virus present) and an endemically infected state (with virus and infected T cells present).

Infrequent detection of human herpesvirus 6 DNA in peripheral blood mononuclear cells from multiple sclerosis patients.

Several studies have suggested an association between human herpesvirus 6 (HHV-6) infection and multiple sclerosis. As HHV-6 is predominantly a T-cell tropic virus, we examined the frequency of detection of HHV-6 genome in peripheral blood mononuclear cells from relapsing-remitting (n = 32) and chronic progressive (n = 14) patients and from healthy (n = 17) and neurological (n = 7) controls. Two sensitive polymerase chain reaction assays were used to target different regions within the HHV-6 genome.

Studies on the development and survival periods of the non-parasitic stages of Boophilus microplus (Canestrini), in the climatic conditions of Ranchi (India).

Engorged female ticks of Boophilus microplus were exposed in wire-gauze cylinders and glass tubes in an experimental grass plot at monthly intervals during 1989, and egg laying, egg development and larval survival periods observed and recorded. Rainfall and atmospheric relative humidity had an important influence on tick activity. Egg production was maximum, hatching percentage was high, incubation and prehatch periods were short, and larval survival and total longevity periods were long for ticks exposed during the warm and humid rainy season from June to September.

Activation-induced cell death in T cell hybridomas is due to apoptosis. Morphologic aspects and DNA fragmentation.

Some T cell hybridomas, upon activation via the TCR, rapidly undergo cell death. In this paper, we demonstrate that this activation-induced cell death (AICD) is accompanied by morphologic changes seen at the electron and light microscopy levels. The most striking changes are an extensive condensation of the chromatin and formation of membrane blebs.

Clinico-biochemical use of serum acetylcholine esterase following treatment with synthetic pyrethroids, cypermethrin and fenvalerate, in cattle and buffalo experimentally infested with Boophilus microplus.

Following treatment, cypermethrin and fenvalerate, were found to have inhibitory effect on serum acetylcholine esterase (AchE) activity of cattle and buffalo experimentally infested with B. microplus. The pattern of AchE activity in infested-pyrethroid-treated group was found to be significantly different from either healthy or tick-infested control.

Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes.

One mechanism by which the immune system develops the ability to discriminate self from nonself is the deletion of autoreactive T-cell clones during thymic maturation. The drug cyclosporin A (CsA) has been shown to interfere with this process, allowing the escape of normally 'forbidden' T-cell clones and the appearance of autoimmune disease. Recently, it has been demonstrated that immature thymocytes undergo programmed cell death (apoptosis) upon activation via the T-cell receptor.

Specific inhibition of cell-surface T-cell receptor expression by antisense oligodeoxynucleotides and its effect on the production of an antigen-specific regulatory T-cell factor.

We have used antisense oligodeoxynucleotides corresponding to genes encoding the variable (V) region of the T-cell receptor (TCR) alpha and beta chains (V alpha and V beta) to control TCR expression in T-cell hybridomas. Two hybridomas, A1.1 and B1.

Structural and evolutionary implications of the packaging of DNA for differentiation and proliferation in the lymphocyte.

During the differentiation of the clonally distributed lymphocytes of mouse and man into mature resting B and T cells, their DNA becomes tightly packed into dense heterochromatin masses and exhibits very little transcriptional activity; it also becomes extensively nicked, containing some 3000-4000 single-strand breaks per diploid genome. The nuclear matrix is sparse and poorly organized and there are but trace amounts of the matrix-linked enzyme DNA topoisomerase II; the nucleus of these small cells is surrounded by a thin rim of cytoplasm. The resting cell can thus be considered (by analogy to a sperm cell) as a vector for transporting tightly packed and relatively inert genetic information to all parts of the body.

A quantitative decatenation assay for type II topoisomerases.

Type II topoisomerases catalyze decatenation of the catenated network of kinetoplast DNA [J. C. Marini, K.

DNA topoisomerase I and II activities during cell proliferation and the cell cycle in cultured mouse embryo fibroblast (C3H 10T1/2) cells.

We have used C3H 10T1/2 cells to examine the regulation of topoisomerase activities during cell proliferation and the cell cycle. The specific activity of topoisomerase I was about 4-fold greater in proliferating (log phase) cells than in non-proliferating (confluent) cells. In synchronized cells, the bulk of the increased activity occurred during or just prior to S phase, depending upon the method of synchronization.

Histochemical alterations in the duodenum of goats experimentally infected with Paramphistomum cervi.

Certain histochemical alterations in the different tunics of duodenum in kids were studied 20, 40, 60 and 80 days post-infection (DPI) with Paramphistomum cervi and the results compared with those of uninfected kids. There was a general reduction of polysaccharide complex substances and glycogen at 20 DPI. A marked decrease in polysaccharide complex substances and glycogen at 20 DPI.

Histopathology of the duodenum and rumen of goats during experimental infections with Paramphistomum cervi.

On microscopic examination after experimental infection with Paramphistomum cervi, tissue reactions in the duodenum were more pronounced during early stages of the infection (20th day post-infection (DPI)). Immature parasites were seen migrating to the muscularis layer, and focal infiltration of macrophages and lymphocytes was observed in the lamina propria and in the interstitial tissue of Brunner's gland. At places, there was cystic dilatation of Brunner's gland.

Heavy sarcocystosis in the ocular musculature of cattle and buffaloes.

A high prevalence of 71.5 per cent and 69.7 per cent of sarcocystosis was observed in the ocular musculature of cattle and buffaloes respectively, in Bihar, India.