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Biomedical subjects

M Jennings

Publications and source records attributed to M Jennings.

At least 55 records · Page 3Linked to original sources

Characterization of monoclonal antibodies that distinguish simian immunodeficiency virus isolates from each other and from human immunodeficiency virus types 1 and 2.

Two monoclonal antibodies (MAbs) against p27 and one against p17 of simian immunodeficiency virus (SIV) from rhesus macaques were produced and characterized by reacting with disrupted, viral antigens on immunoblots. Human immunodeficiency virus type 1 (HIV-1), HIV-2 and SIV isolates from sooty mangabey, stump-tailed macaque, rhesus macaque and African green monkey (SIVSM, SIVStM, SIVMAC and SIVAGM) were used for comparative analysis. The p27 monoclonal antibodies HE3 and FA2 reacted with SIVMAC and SIVSM, but not with HIV-1, HIV-2, SIVStM and SIVAGM. The p17 monoclonal antibodies reacted with SIVMAC and SIVStM, but not HIV-1, HIV-2, SIVSM and SIVAGM. The differential reactivity of these monoclonal antibodies indicated that common conserved antigenic epitopes are shared between SIVMAC and SIVSM with respect to p27 MAbs and between SIVMAC and SIVStM with respect to p17. Since these MAbs reacted differently with the SIV isolates, they are useful reagents for comparative pathogenesis studies for differentiating SIV isolates.

Animals↗

Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals.

Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.

Adjuvants, Immunologic↗

Effect of virus dose and nonoxynol-9 on the genital transmission of SIV in rhesus macaques.

One inoculation of cell-free SIVmac (50 TCID50) caused persistent viremia in nine of 13 female rhesus macaques inoculated intravaginally. Persistent viremia was produced in two of four male rhesus macaques by twice placing cell-free SIVMAC (50 TCID50) onto the skin and urethral os of the penis. Placing a spermicide containing nonoxynol-9 into the vaginal canal prior to repeated intravaginal inoculations of SIV prevented transmission of the virus in three of six female rhesus macaques.

Administration, Intravaginal↗

Culicoides: biological vectors of Akabane virus.

Akabane virus replicated in Culicoides nubeculosus and Culicoides variipennis after intrathoracic inoculation and was maintained in both species of midge for at least 9 days post-infection. The virus also replicated to high concentration in C. variipennis after oral infection and was transmitted through a membrane by this species of midge 7-10 days after infection. The experiments described in this paper provided the first definitive evidence that Culicoides spp. are able to act as fully competent vectors of Akabane virus.

Animals↗

Genital mucosal transmission of simian immunodeficiency virus: animal model for heterosexual transmission of human immunodeficiency virus.

An animal model for the heterosexual transmission of human immunodeficiency virus (HIV) was developed by the application of simian immunodeficiency virus (SIV) onto the genital mucosas of both mature and immature, male and female rhesus macaques. Virus preparations were infused into the vaginal vaults or the urethras (males) of the animals through a soft plastic pediatric nasogastric feeding tube. The macaques that were infected by this route (six males and nine females) developed SIV-specific antibodies, and SIV was isolated from peripheral mononuclear cells of all seropositive animals. One male and one female infected by this route developed severe acquired immunodeficiency syndrome-like disease with retroviral giant-cell pneumonia. As few as two inoculations of cell-free SIV containing 50 50% tissue culture infective doses induced persistent viremia. Cell-free virus preparations were capable of producing infection by the genital route. Much higher doses of virus were required to transmit SIV by this route than are required for transmission by intravenous inoculation. Thus, it appears that the mucous membranes of the genital tract act as a barrier to SIV infection. Spermatozoa and seminal plasma were not required for the genital transmission of SIV. Rarely, SIV was recovered from mononuclear cells in semen and vaginal secretions. The SIV-rhesus macaque model is suitable for assessing the role of cofactors in heterosexual transmission of HIV and will be useful for testing the effectiveness of spermicides, pharmacologic agents, and vaccines in preventing the heterosexual transmission of HIV.

Acquired Immunodeficiency Syndrome↗

Postexposure immunotherapy of simian immunodeficiency virus (SIV) infected rhesus with an SIV immunogen.

An inactivated whole simian immunodeficiency virus (SIV) immunogen given to healthy, seropositive rhesus macaques 4 months after infection had no effect on the humoral immune response to SIV, the presence of antigenemia, cell-associated viremia, or disease course. Further immunotherapeutic trials in this highly susceptible animal model should be carried out sooner after exposure, before significant loss of CD4 cells has occurred. The SIV infected macaque model will continue to serve an essential role in development and testing of anti-AIDS drugs and immunogens.

Animals↗

Blue rubber bleb naevus disease: an uncommon cause of gastrointestinal tract bleeding.

A 23 year old woman presented with facial pain, a right parotid tumour and iron deficiency anaemia. She had several cutaneous venous swellings and tumours with a similar appearance were found in the large bowel. Histological examination of the parotid tumour and angiography of the skin and gut lesions confirmed that they were venous in origin. The aetiology, classification, and complications of disorders of the venous system and the importance of using a tourniquet to examine the peripheral veins is discussed.

Adult↗

The entrapment of [14C]ascorbic acid in human erythrocytes.

Radioactively labelled ascorbic acid and dehydroascorbic acid, when incubated with human blood, migrate irreversibly into human red blood cells. Isolation and characterization of the moieties trapped within the cells via infrared spectroscopy established both their identities as L-ascorbic acid. Evidence in the form of the degree of in vitro entrapment of ascorbic acid as a function of the times of incubation and the effect of incubation temperature, anion recognition site inhibitor, and active transport inhibitor on the rate of entrapment support the hypothesis that ascorbic acid is oxidized on or near the surface of the red blood cell to dehydroascorbic acid which migrates through the lipid portion of the cell wall and is reduced back to ascorbic acid within the cell. The resulting L-ascorbic acid can not pass through the cell wall and is therefore entrapped.

Ascorbic Acid↗

Unique p24 epitope marker to identify multiple human immunodeficiency virus variants in blood from the same individuals.

The human immunodeficiency virus (HIV) was isolated from the blood of 192 of 410 seropositive individuals. Original isolations were made in peripheral blood mononuclear cell (PBMC) cultures, and only one-fifth of the HIV isolates could be adapted to replicate in continuous T-cell lines. Of the 192 HIV isolates, 42 had the characteristic p24 antigen marker of the acquired immunodeficiency syndrome-associated retrovirus type 2 strain of HIV (HIV ARV-2) and 150 resembled the human T-cell lymphotropic virus type III strain of HIV (HIV HTLV-III). Significantly, primary PBMC cultures from two patients yielded multiple variants. When these variants were exposed to continuous T-cell lines, only one of them continued to replicate. The remaining variants were lost and could not be reisolated following passage back into PBMC cultures. We conclude the following from these studies: PBMC cultures are more efficient at isolating HIV than continuous T-cell lines are; some patients harbor more than one genetic variant of HIV in the blood at the same time; and continuous T-cell lines are likely to yield only a portion of the HIV variants originally present in the blood.

Antigens, Viral↗

Carboplatin and recurrent childhood brain tumors.

Carboplatin, a cisplatin analogue, was administered as an intravenous (IV) one-hour infusion in a 4-consecutive weekly dose schedule to 44 patients with recurrent childhood brain tumors. Twenty-four patients were registered on our phase I, and 20 on our phase II studies. The maximum tolerable dose derived from our phase I study was 210 mg/m2/wk in patients with solid tumors, and the recommended dose for subsequent pediatric phase II studies was 175 mg/m2/wk. This dose was administered to 14 patients in the phase I and all 20 patients in the phase II study. Nine of 36 (25%) evaluable patients in the combined studies experienced objective responses for a median duration of 10+ months. Seven of nine responders had received prior cisplatin. Disease-specific response rates were as follows: medulloblastoma, six of 14 (43%) with three complete (CR) and three partial responses (PR); pineoblastoma, one of one (PR); germinoma, one of two (CR); and brainstem glioma, one of eight (13%) (PR). Carboplatin had mild emetic effects but no significant auditory or renal toxicity. Thrombocytopenia (less than 49,000) was encountered in nine of 28 (32%) evaluable trials at a dose of 175 mg/m2/wk. Because of its low potential for auditory, renal, and emetic toxicity, ease of administration, and high disease-specific activity, carboplatin deserves further study in multiagent phase II and III trials, especially in chemotherapy-sensitive diseases such as medulloblastoma.

Adolescent↗

Further data on the distribution of biting midges in southern Europe and the Mediterranean area, with special reference to Culicoides imicola.

Studies on the Culicoides midges of Spain and Turkey suggest that the range of C. imicola may extend to about 40 degrees N. However, catches of midges from mainland Greece, Sicily and Italy failed to reveal the presence of this species. These findings are discussed in the light of the possibility of the occurrence of bluetongue (BT) disease in these areas, consequent upon windborne spread of infected vectors from countries where the disease is endemic.

Animals↗

Oral infection of Culicoides (Diptera, Ceratopogonidae) with viral agents, using fine glass needles.

Oral infection of haematophagous insects with arboviruses to test their vector competence can be a difficult procedure in the laboratory since "wild caught" insects often prove reluctant to feed, once captured. This paper describes a technique using virus-charged glass needles to infect Culicoides spp. orally with bluetongue virus (BTV). C. variipennis, a known vector of BTV, was found to support virus multiplication with this technique, giving results comparable to those obtained using standard oral infection procedures. Other species of Culicoides that had previously been difficult or impossible to infect orally in the laboratory also engorged upon virus suspensions. The technique provides a means of assessing the vector competence of these and other similar Culicoides species.

Administration, Oral↗

Laboratory infection of the mosquito, Toxorhynchites brevipalpis (Diptera, Culicidae), with bluetongue virus.

The use of Toxorhynchites brevipalpis as a system for the propagation and isolation of bluetongue virus (BTV) was investigated. BTV was found to multiply in T. brevipalpis after infection by intrathoracic inoculation. Virus concentrations of up to 6.9 log 10 TCID50 per mosquito were found within 7 days of infection and were maintained for at least 6 days. Virus could be detected by an indirect fluorescent antibody test applied to head and thorax tissue smears. These results are comparable to those obtained after inoculation of Culicoides variipennis with the same virus. Comparison of T. brevipalpis and baby hamster kidney (BHK) cells as systems for isolation of BTV showed that there was little difference in sensitivity between the two systems for the stock BTV used. Field samples were not available for test. It was concluded that the use of T. brevipalpis as an isolation system for BTV would have no apparent advantage if BHK cells were available.

Animals↗