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P J Durant

Publications and source records attributed to P J Durant.

At least 19 recordsLinked to original sources
PubMed1999

Intranasal immunization confers protection against murine Pneumocystis carinii lung infection.

To evaluate the feasibility of mucosal immunization against Pneumocystis carinii (Pc) experimental infection, female BALB/c mice were intranasally immunized three times with soluble Pc antigens plus cholera toxin fraction B (Pc-CTB); control groups received either Pc antigen, CTB, or phosphate-buffered saline (PBS) alone. Two weeks after the last immunization, five animals from each group were sacrificed, and cellular and humoral immune responses were evaluated. The remaining five mice were CD4 depleted using a monoclonal antibody against mouse CD4 and inoculated with viable Pc. Significantly higher specific lymphoproliferative responses from tracheobronchial lymph node cells, immunoglobulin M (IgM) and IgG antibody levels in serum, and bronchoalveolar lavage (BAL)-derived IgA antibody concentrations were observed in the Pc-CTB group of mice relative to control groups (P < 0.01). Five weeks after challenge, no Pc organisms were observed in the lung smears of the Pc-CTB group, while the animals receiving antigen, adjuvant, or PBS had progressively higher numbers of Pc microorganisms. By Western blot analysis, a strongly reactive 55- to 60-kDa antigen was recognized by BAL IgA and by serum IgG. In summary, mucosal immunization elicited specific cellular and humoral immune responses and protected against Pc lung infection after immunosuppression.

Administration, Intranasal↗
PubMed1998

Antibody to Pneumocystis carinii protects rats and mice from developing pneumonia.

Well-proven mouse and rat models were used to show that polyclonal antisera to Pneumocystis carinii protect against P. carinii pneumonia. Antibodies were obtained from animals that were allowed to recover from severe P. carinii pneumonia after immunosuppression had been stopped and which then were given a booster injection of P. carinii from the same animal species. Mice immunosuppressed with corticosteroids or antibodies to L3T4+ lymphocytes (which are comparable to CD4 cells of humans) and transtracheally inoculated with mouse P. carinii did not develop P. carinii pneumonia if they were passively immunized with antiserum, while mice immunosuppressed and inoculated by identical procedures but not given antibodies developed severe infections. Rats immunosuppressed with corticosteroids and inoculated with rat P. carinii had less severe infections if they were given rat anti-P. carinii antisera. The polyclonal antisera developed in mice provided greater protection for the mice than the polyclonal rat antisera did for the rats; however, the potencies and compositions of the antisera were not quantitated and probably differed. Since both rats and mice can be protected from P. carinii infections with polyclonal antisera, it may be possible to develop vaccines that will elicit protective antibodies in humans.

Animals↗
PubMed1997

Detection of Pneumocystis carinii DNA in air samples: likely environmental risk to susceptible persons.

The means by which humans acquire Pneumocystis carinii is not well understood. Whether it can be acquired from specific environmental sources or transmitted from person to person has not been determined. This study was designed to detect nucleic acids of P. carinii in air samples from various locations, including P. carinii-infected patients' homes and hospital rooms, non-P. carinii-infected patients' hospital rooms, empty hospital rooms, offices at Indiana University, and other homes in different locations. DNA was extracted from cellulose-ester filters through which air samples had been filtered, and the P. carinii DNA was amplified by PCR with primers specific for the internal transcribed spacer regions of rRNA. P. carinii DNA was found in 17 of 30 air samples (57%) from the rooms of P. carinii-infected patients. It was also found in 6 of the 21 other hospital rooms sampled (29%) but was not found in any of the offices, storage areas, or control homes. Environmental sampling suggests that the airborne presence of P. carinii genetic material and infectious organisms is plausible. The organism was also detected in locations where P. carinii patients were not immediately proximate, such as the hospital rooms of non-P. carinii-infected patients.

Air Microbiology↗
PubMed1996

An H(+)-ATPase regulates cytoplasmic pH in Pneumocystis carinii trophozoites.

Pneumocystis carinii is an opportunistic fungus which causes interstitial pneumonia in patients with acquired immunodeficiency syndrome (AIDS). Cytoplasmic pH (pHi) regulation in short-term-cultured P. carinii trophozoites was studied using the fluorescent dye 2',7'-bis-(2-carboxyethyl)-5-(-6)-carboxyfluorescein. With an extracellular pH of 7.4, the mean baseline pHi of P. carinii trophozoites was 7.40 +/- 0.10 (n = 8). This steady-state pHi was not significantly affected in the absence of extracellular Na+ or K+. Moreover, steady-state pHi was maintained in the nominal absence of HCO3- and was not affected by the Cl-/HCO(3-)-exchanger inhibitor 4, 4'-di-isothiocyanato-dihydrostilbene-2, 2'-disulphonic acid (100 microM), or the Na+/H(+)-exchanger inhibitor N-ethyl-N-isopropylamiloride (100 microM). In contrast, the general inhibitors of ATPases, N-ethylmaleimide (1 mM), and dicyclohexylcarbodi-imide (100 microM), and the inhibitor of yeast H(+)-ATPase, diethylstilbestrol (12.5-100 microM), decreased pHi, while the K+/H(+)-ATPase inhibitor omeprazole (50-400 microM), and the vacuolar-type H(+)-ATPase inhibitor bafilomycin A1 (1-5 microM) only produced a dose-dependent acidification of the cells when used at high concentrations. In addition, steady-state pHi depended on the availability of cellular ATP, since it was decreased by the ATP synthase inhibitors oligomycin (1 microgram/ml) and sodium azide (1 mM), and by the uncoupler of oxidative phosphorylation carbonyl cyanide p-trifluorophenylhydrazone (1 microM), agents that were able to deplete significantly the intracellular ATP levels. Taken together, these results are consistent with an important role of an H(+)-ATPase similar to those found in other fungi in the regulation of pHi homoeostasis in P. carinii trophozoites.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1984

Age-related decrease in sensitivity to glucagon and dibutyryl cyclic AMP inhibition of fatty acid synthesis in hepatocytes isolated from obese female Zucker rats.

Hepatocytes were isolated from 3 and 5 month old female genetically obese Zucker rats and their lean littermate controls. An age-dependent loss in sensitivity of fatty acid synthesis to inhibition by both glucagon and dibutyryl cyclic AMP was observed with hepatocytes from the obese rats. Hepatocytes from lean animals were much more sensitive to these agents, regardless of age. Low concentrations of glucagon and dibutyryl cyclic AMP actually produced some stimulation of fatty acid synthesis with hepatocytes prepared from the older obese rats. 5-Tetradecyloxy-2-furoic acid, a compound which inhibits fatty acid synthesis, was a very effective inhibitor of fatty acid synthesis by hepatocytes isolated from all rats used in the study. An inhibition of lactate plus pyruvate accumulation and a strong stimulation of glycogenolysis occurred in response to both glucagon and dibutyryl cyclic AMP with hepatocytes from both age groups of lean and obese rats. The results suggest that with aging of the obese female Zucker rat some step of hepatic fatty acid synthesis becomes progressively less sensitive to inhibition by glucagon and dibutyryl cyclic AMP. This may play an important role in maintenance of obesity in these animals.

Aging↗
PubMed1983

Lupus erythematosus-like disease due to hydrazine.

A case of systemic lupus erythematosus-like disease due to occupational exposure to hydrazine is described. The patient had four of the 1982 revised criteria for SLE (malar rash, photosensitivity, antinuclear antibody, and antibody to nDNA) and genetically is a slow acetylator with the HLA DR2,3 phenotype. Many of her healthy family members had antibodies to nuclear constituents. Lymphocytes from the patient and an identical twin sister, but not from three normal control subjects, showed inhibition of pokeweed mitogen-stimulated IgG synthesis after five daily exposures of each subject to hydrazine. Chemicals such as hydrazine in the environment can induce cases of SLE-like disease in predisposed persons.

Adult↗
PubMed1981

Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats.

Hepatocytes isolated from genetically obese female Zucker rats and lean female Zucker rats were compared. Hepatocytes from fed obese rats exhibited greater rates of fatty acid synthesis, more extensive accumulation of lactate and pyruvate from their glycogen stores, increased rates of net glucose utilization but produced less ketone bodies from exogenous fatty acids and had lower citrate levels than hepatocytes from lean rats. Lipogenesis was not as sensitive to dibutyryl cyclic AMP (DBcAMP) inhibition in hepatocytes from obese rats but glycogenolysis was stimulated to the same extent by this nucleotide in both preparations. Ketogenesis was less sensitive to stimulation by DBcAMP in hepatocytes from obese rats. A difference in sensitivity of lipogenesis to DBcAMP was not found when lactate plus pyruvate was added to the incubation medium, suggesting that a greater rate of glycolysis by hepatocytes from obese rats accounts for their relative insensitivity to DBcAMP. Citrate levels were elevated by DBcAMP to a greater extent in hepatocytes from obese rats. Hepatocytes prepared from lean rats starved for 48 hr were glycogen depleted and lacked significant capacity for lipogenesis and glycogen synthesis. In contrast, hepatocytes isolated from starved obese rats retained considerable amounts of liver glycogen and exhibited detectable rates of lipogenesis and glycogen synthesis. Hepatocytes prepared from starved lean rats gave faster apparent rates of lactate gluconeogenesis than hepatocytes prepared from starved obese rats. Thus, hepatocytes prepared from obese Zucker rats are more glycogenic, glycolytic, and lipogenic but less ketogenic and glucogenic than hepatocytes prepared from lean rats.

Animals↗
PubMed1980

Hydrazine and lupus.

Explore the source record for details and available documents.

Clinical Laboratory Techniques↗
PubMedDate not supplied

Regulation of the formation of stable adducts between acetaldehyde and blood proteins.

Recent reports have described increased levels of a fast-moving hemoglobin (Hb) fraction in alcoholic patients and formation in vitro of stable adducts between acetaldehyde and Hb as well as between acetaldehyde and albumin. In the present study, we have found that factors other than acetaldehyde concentration can influence the rate of stable adduct formation. HbAo was purified and its 2,3-diPglycerate removed by dialysis. Under anaerobic condition and at 37 degrees, acetaldehyde (5 microM) reacted with deoxyHbAo to form 0.26 +/- 0.02 (+/- SEM) nmol of stable adduct/149 nmol Hb in 2 hr. By comparison, acetaldehyde reacted more slowly with oxyHbAo and carbonylHbAo; the rates were 0.21 +/- 0.01 (p less than 0.001) and 0.18 +/- nmol/149 nmol Hb/2 hr (p less than 0.001), respectively. Pyridoxal 5'-phosphate (50-500 microM), under anaerobic condition, inhibited by 36-56 percent the irreversible binding of acetaldehyde to deoxyHbAo. Ascorbic acid (2.5-10 mM) increased by 31-46 percent (p less than 0.001) the irreversible binding of acetaldehyde to human serum albumin and by 8-10 percent (p less than 0.05) the irreversible reaction of acetaldehyde with serum proteins. We conclude that the nonenzymatic binding of acetaldehyde to Hb, human serum albumin and serum proteins is influenced by factors other than acetaldehyde concentration. These factors include oxygen tension, pyridoxal 5'-phosphate and ascorbic acid. Among these factors, oxygen tension may be the most important in vivo.

Acetaldehyde↗
PubMedDate not supplied

Genetic diversity of Pneumocystis carinii derived from infected rats, mice, ferrets, and cell cultures.

The degree of strain and/or species diversity among Pneumocystis carinii isolates is unknown. As a first approach to the study of P. carinii genetic relatedness, we compared the pulsed field gel electrophoretic karyotypes of P. carinii derived from lung homogenates of three immunosuppressed host animals: rats transtracheally inoculated with P. carinii-infected mouse lung; and ferrets which developed reactivated latent P. carinii pneumonia. Rat P. carinii propagated on HEL299 cells was also examined. Karyotypes of P. carinii DNA from both rat lung homogenate and cell culture were identical (14 bands, 315-680 kb). In contrast, mouse and ferret P. carinii DNA karyotypes were each distinctly different from the rat P. carinii samples (mouse P. carinii 15 bands, 315-610 kb; ferret P. carinii nine bands, 410-760 kb). Three distinct rat P. carinii gene probes reacted with both Southern-transferred rat and mouse P. carinii DNA but not with ferret P. carinii DNA. Thus, P. carinii from rat, mouse, and ferret are genetically diverse. The results are consistent with recently reported antigenic and nucleic acid sequence differences among P. carinii isolates recovered from different hosts.

Animals↗