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Biomedical subjects

J G Wheeler

Publications and source records attributed to J G Wheeler.

At least 73 records · Page 4Linked to original sources
PubMed1991

The ability of polymorphonuclear leukocyte priming agents to overcome influenza A virus-induced cell dysfunction.

The major mortality and morbidity resulting from influenza virus infections are due to secondary bacterial infections which occur in association with virus-induced inhibition of polymorphonuclear leukocyte (PMNL) function. The present study was undertaken to determine if compounds which prime PMNL function to subsequent stimulation with N-formylmethionyl-leucylphenylalanine (FMLP) or phorbol 12-myristate 13-acetate (PMA) can overcome influenza A virus (IAV)-induced inhibition of the PMNL chemiluminescence response to these stimuli. Granulocyte-macrophage colony stimulating factor (GM-CSF), guanosine triphosphate (GTP), and 1-oleoyl-2-acetylglycerol (OAG) were able to prime the PMNL response to FMLP and/or PMA and totally or partially overcome IAV-induced PMNL dysfunction in cells stimulated with FMLP or PMA. A direct correlation was found between the extent of PMNL priming due to GM-CSF, GTP, and OAG and the capacity of these compounds to overcome virus-induced PMNL dysfunction. The implications of these findings in regard to the mechanism by which priming agents overcome IAV-induced cell dysfunction and the potential of these compounds as therapeutic agents to treat secondary bacterial infections are discussed.

Diglycerides↗
PubMed1991

Investigation of sites of pseudorabies virus latency, using polymerase chain reaction.

Pseudorabies virus (PRV) latency was investigated, using polymerase chain reaction (PCR). A PCR protocol was developed that specifically amplified a 217-base pair sequence within the gene encoding the essential glycoprotein gp50 of PRV. Using this PCR procedure, the gp50 sequence was amplified from tissues of pigs infected with various doses of PRV (Becker strain). At postinoculation day 64, viral isolation was performed on nasal swab specimens and homogenates of tonsils and trigeminal nerve ganglia obtained from 11 PRV-convalescent, seropositive pigs. Results were negative in all cases. By use of PCR, 11 of 11 pigs had PRV-positive trigeminal nerve ganglia and brain stem, 10 of 11 pigs had PRV-positive tonsils, and 9 of 11 pigs had PRV-positive olfactory bulbs.

Animals↗
PubMed1990

Influenza A virus alters structural and biochemical functions of the neutrophil cytoskeleton.

Influenza A virus (IAV) has previously been shown to alter chemotactic, oxidative, and secretory functions of polymorphonuclear leukocytes (PMNL). Because of the role of cytoskeletal proteins in these processes, studies were carried out to determine if IAV altered the PMNL cytoskeleton. PMNL were incubated with buffer of IAV, stimulated with f-met-leu-phe (FMLP), fixed and stained with NBD-phallacidin (NBD-Ph) and studied by flow cytometry. Mean F-actin fluorescence was increased 18% in virus treated cells pre-FMLP stimulation and 13% 5 and 10 min post-FMLP (P less than .03); no significant difference in F-actin fluorescence was noted in virus treated PMNL 15-30 s post-FMLP compared to control cells. PMNL exposed to the same conditions were solubilized and actin content was determined following SDS-PAGE of triton insoluble precipitates. Increased actin was recovered from virus treated compared to buffer treated cells before and after FMLP stimulation in the 8,000g precipitates (P less than .001). Immunofluorescent microscopy studies of F-actin distribution were done in PMNL stained with NBD-Ph following FMLP stimulation for 10 min. These studies showed an increased lamellipod F-actin/uropod F-actin ratio in PMNL pre-incubated with IAV compared to controls (4.6 vs. 1.0; P less than .025). Phosphorylation of specific cytoskeletal proteins was examined after immunoprecipitation. IAV alone altered phosphorylation of both vimentin and vinculin, and in stimulated PMNL virus led to decreased phosphorylation of vimentin and vinculin. These data show distributional and biochemical effects of IAV on PMNL cytoskeletal proteins, indicating additional targets for IAV interference in the PMNL signal-transduction-function process.

Actin Cytoskeleton↗
PubMed1990

99Tcm-nanocolloid imaging in inflammatory bowel disease.

We have used 99Tcm-labelled nanocolloid in an attempt to locate areas of inflamed bowel wall or abscesses in five patients with ulcerative colitis and nine with Crohn's disease. The scintigraphic findings were evaluated by comparison with those of recent barium studies and, in three patients, with surgical findings at laparotomy. It proved difficult to localize segments of inflamed bowel accurately with 99Tcm-nanocolloid because of the accumulation of radioactivity in the gut lumen, especially 2 or more hours after injection. However, there was little uptake of the labelled nanocolloid by areas of inflamed gut wall in the period before 2 h. When 99Tcm-nanocolloid scans were compared with 111In-WBC scans in eight patients who had both investigations, 99Tcm-nanocolloid scintigraphy was considerably less sensitive than 111In-WBC scintigraphy. One abscess was located correctly; the other was obscured by nearby bladder and bone marrow radioactivity. We conclude that 99Tcm-nanocolloid scanning is neither sensitive nor reliable enough for assessing the location of inflamed bowel wall or the presence of abscess in patients with inflammatory bowel disease.

Adult↗
PubMed1987

Pre-operative radionuclide localization of intracerebral lesions: a five-year experience.

Intracerebral lesions demonstrated by computerized tomography usually require histological confirmation to determine subsequent management. Tissue samples are generally obtained by craniotomy or burr hole biopsy; either procedure can prove negative if a lesion is small, deep, or very superficial. Pre-operative imaging and localization reduce biopsy failures. Before the introduction of this straight forward radionuclide technique, our biopsy success rate using conventional localization methods was 88%. In a 5-year period, 200 patients underwent pre-operative radionuclide localization, with an improvement in the overall biopsy success rate to 92.7% (95.5% for lesions which took up radionuclide). Patients have benefitted from reduced operating time and improved post-operative recovery rates. About 85% of all intracerebral lesions may be expected to accumulate radionuclide. However in our series, 93.2% were sufficiently well visualized for a siting marker to be placed with confidence. Within this group, low grade astrocytomas (Kernohan Grades I and II) showed a predictably low incidence of imaging (30.8%). For the majority of lesions which present difficulties in biopsy due to size or site, the radionuclide method is a simple procedure which increases the chance of obtaining positive tissue with the minimum of surgical intervention.

Biopsy↗
PubMed1987

Pathogenesis of the impaired gall bladder contraction of coeliac disease.

We have investigated the possibility that the abnormally decreased gall bladder contraction after meals in patients with coeliac disease might result in part from an abnormality in the gall bladder response to endogenous cholecystokinetic hormones--for example, cholecystokinin and motilin--rather than solely from decreased secretion of such hormones. Eight patients with untreated coeliac disease and nine controls received intravenous infusions of the pure synthetic cholecystokinin analogue caerulein, 2-16 ng/kg/hour. Gall bladder emptying was measured on a minute-by-minute basis using 99mTc-HIDA scans. In the patients with coeliac disease, gall bladder emptying was greatly decreased (34.6 +/- 9.9 v 61.5 +/- 7.5% at 60 minutes, p less than 0.02), and a much greater dose of caerulein was needed to initiate gall bladder contraction (3.80 +/- 1.08 v 1.49 +/- 0.56 ng/kg, p less than 0.02). These results suggest that the abnormal gall bladder contraction in coeliac disease is not simply because of impaired release of cholecystokinin. Although mechanical factors secondary to the increased gall bladder size in patients with coeliac disease might to some extent account for the findings, the alternative explanation is that the gall bladder muscle is for some reason resistant to the action of cholecystokinetic agents. A similar phenomenon affecting the pancreas might contribute to the abnormally decreased pancreatic secretion found in coeliac disease.

Adult↗
PubMed1987

Buffy coat transfusions in neonates with sepsis and neutrophil storage pool depletion.

A randomized study was initiated in neonates with neutropenia (absolute peripheral neutrophil count less than 1,500/microL) and suspected bacterial infection. Twenty infants with proven infection were enrolled, nine of whom had depletion of bone marrow stores of maturing neutrophils (less than or equal to 7% metamyelocyte, band and mature forms per 100 nucleated cells). These nine were randomized to receive 15 mL/kg of either buffy coat transfusions (group 2) or plasma and blood products (group 3). The remaining 11 (group 1) were observed. Peripheral neutrophil counts were monitored to determine the neutrophil response to transfusions. There were ten of 11 patients in group 1, two of four in group 2, and two of five in group 3 who lived at least seven days. No complications of transfusion were noted. No difference in the rate of peripheral neutrophil increase was found among the three groups. The study was stopped when it became clear that sufficient numbers of patients could not be entered into the study, in a reasonable period of time, to prove or disprove a clinically significant improvement in outcome. Although in vitro testing of the buffy coat preparations showed normal function in three of four cases, the clinical quality of the buffy coats may have been inadequate because of poor availability of whole fresh blood less than 24 hours old. The role of neutrophil transfusions in these patients remains unclear.

Agranulocytosis↗
PubMed1986

Suppression of endocytosis in neutrophils by influenza A virus in vitro.

The effect of influenza A virus on the endocytic pathway in polymorphonuclear leukocytes (PMNLs) and the relationship of altered endocytic activity to virus-induced inhibition of other PMNL functions were examined with virus that caused decreased phagosomelysosome fusion and bacterial killing (depressing virus [DV]) and virus that did not (non-DV). Binding of both viruses to PMNL surface receptors was similar, but uptake of DV into PMNLs was decreased compared with that of non-DV. Both viruses were associated with the PMNL plasma membrane and were in endosomes. DV caused less stimulation of pinocytosis than did non-DV. The rate of exocytosis of fluoresceinated-dextran (FL-dextran) from cells stimulated with DV was significantly less than for non-DV. When PMNLs were pretreated with buffer, DV, or non-DV and then exposed to FL-dextran and N-formylmethionylleucylphenylalanine, the pinocytosis of FL-dextran was significantly less in cells pretreated with DV as compared with non-DV or buffer.

Endocytosis↗
PubMed1986

Investigation of possible vaccine-induced epizootics of infectious bovine rhinotracheitis, using restriction endonuclease analysis of viral DNA.

Viral DNA was extracted from each of 14 modified-live (ML) bovine herpesvirus 1 vaccines, representing all of the ML infectious bovine rhinotracheitis virus (IBRV) vaccines licensed by the US Department of Agriculture for use in cattle. Restriction endonucleases Pst I and Bgl II were used to establish restriction enzyme patterns for the vaccinal viruses. Viral DNA from isolates obtained from 6 field samples of IBRV (1 from Colorado, 1 from West Virginia, 3 from Wisconsin, 1 from South Dakota) were digested with restriction endonucleases, and patterns were compared to evaluate the role of vaccinal virus in these field epizootics of infectious bovine rhinotracheitis. Animals from which field samples were obtained had been vaccinated with ML IBRV vaccine before the epizootic of infectious bovine rhinotracheitis occurred in the herds. In 2 of the 6 field samples, DNA restriction endonuclease analyses patterns from the isolates were indistinguishable from the pattern for the vaccinal viruses used. In the remaining 4 field samples, DNA restriction endonuclease analyses patterns of the IBRV from isolates were different from those of the vaccinal viruses.

Animals↗
PubMed1985

Intralipid infusion in neonates: effects on polymorphonuclear leukocyte function.

In vivo and in vitro studies were done to assess the effects of Intralipid (IL) on neonatal polymorphonuclear leukocyte (PMNL) function. No significant abnormalities of chemotactic (CT) or chemiluminescent (CL) activities were noted in cord or adult PMNLs incubated with IL (10 mg/ml) when compared with paired controls incubated with buffer. In 14 premature and term neonates, IL was infused at 1 g/kg/24 h. Postinfusion CL activity of PMNLs was not significantly different from preinfusion CL activity. Although previous animal and human studies have shown abnormalities of PMNL function using higher infusion rates, slow infusion of IL at 1 g/kg/24 h produced no detectable alteration in PMNL oxidative function. The safety of long-term therapy with higher doses of IL remains to be proven.

Adult↗
PubMed1978

Isolation of bovine adenovirus type 7 from calves with pneumonia and enteritis.

Bovine adenovirus type 7 was isolated from a 10-month-old calf with fibrinopurulent pneumonia and from 2 newborn calves with pneumoenteritis. The viruses were isolated on calf lung and adrenal gland cell cultures and were identified as serotype 7 by immunoelectron microscopy and serum-neutralization tests.

Adenoviridae↗
PubMedDate not supplied

Aflatoxin exposure, malaria and hepatitis B infection in rural Gambian children.

Aflatoxin-albumin adduct levels were measured in serum samples obtained from a group of Gambian children. The relationships between exposure to aflatoxin and the prevalence of malaria, between exposure and humoral and cellular responses in vitro to defined malaria antigens and, amongst children with evidence of exposure to hepatitis B infection, between aflatoxin and carriage of the hepatitis B surface antigen (HBsAg), were assessed. Aflatoxin-albumin adduct was found in nearly all serum samples collected during a survey performed at the end of the dry season and levels of adduct were generally high (up to 720 pg aflatoxin-lysine equivalent/mg albumin). Higher levels of aflatoxin-albumin adduct were detected in Wollof children than in children of other ethnic groups and marked variation in mean adduct levels between villages was observed. Aflatoxin-albumin adduct levels were higher in children who were HbsAg positive and in children with Plasmodium falciparum parasitaemia than in controls. However, levels of adduct had no consistent effect on either malaria-specific antibody responses, lymphoproliferative responses in vitro, or morbidity from malaria during the subsequent rainy season. Much lower levels of aflatoxin-albumin adduct were detected in repeat samples obtained at the end of the rainy season. There was poor correlation between dry and rainy season levels of adduct in individual children. We have shown that Gambian children are exposed to high levels of aflatoxin. The seasonal variation of aflatoxin-albumin adduct and marked fluctuation of adduct with time in individual children need to be considered in the future planning of epidemiological studies using this marker of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗
PubMedDate not supplied

Human leucocyte antigen (HLA) and malaria morbidity in a Gambian community.

Human leucocyte antigen (HLA) class I and class II typing was performed on 177 children in a rural area of The Gambia who were followed for 2 years in a longitudinal study of malaria morbidity. A comparison was made between those who experienced an episode of clinical malaria in one or both years and those who showed no evidence of infection in either year. No convincing association was found between morbidity and class I phenotype. An overall association of morbidity with the distribution of class II haplotypes was seen, but association with individual DR-DQ haplotypes were not conclusive.

Animals↗