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Biomedical subjects

S F Queener

Publications and source records attributed to S F Queener.

At least 19 recordsLinked to original sources
PubMed1992

Inoculated mouse model of Pneumocystis carinii infection.

A transtracheally inoculated mouse model of Pneumocystis carinii has been developed using BALB/c mice. The advantage of this strain of mice include that they are widely available, inexpensive, and were not infected with Pneumocystis before inoculation. Inoculated mice that were not treated had a mean infectivity score of 4.1 compared with inoculated mice treated with the effective anti-Pneumocystis drug combination of trimethoprim plus sulfamethoxazole, which had a mean infectivity score of 0.1, an approximately 4 log difference. The inoculated BALB/c mouse provides a model to serve as a valuable addition to rat models currently used, providing a source of organisms from a different host for cross-species comparisons and for studies of drug efficacy for therapy and prophylaxis. The inoculated mouse is especially cost effective and allows testing of compounds in short supply.

Aminoquinolines↗
PubMed1992

Efficacy of intermittent dosage of 8-aminoquinolines for therapy or prophylaxis of Pneumocystis pneumonia in rats.

Experimental 8-aminoquinolines from Walter Reed Army Institute for Research are effective for prophylaxis or therapy of Pneumocystis carinii pneumonia in rat models. In the present study, primaquine, WR6026, and WR238605 were tested in prophylaxis and treatment models of P. carinii pneumonia to compare the effectiveness of continuous versus intermittent dosing. For treatment of P. carinii pneumonia, the drugs showed detectable effects when given once every 4 days (primaquine and WR6026 at doses greater than 8 mg/kg; WR238605 at doses greater than 2 mg/kg). For prophylaxis, WR6026 and WR238605 were effective given alone daily (WR6026 at doses greater than 0.25 mg/kg; WR238605 at doses greater than 0.57 mg/kg). WR6026 and WR238605 at 4 mg/kg given once every 4 days for prophylaxis were as effective as daily trimethoprim-sulfamethoxazole. These studies suggest that higher doses of 8-aminoquinolines administered at appropriate intervals may be as effective as continuous dosing for prophylaxis of P. carinii pneumonia.

Aminoquinolines↗
PubMed1992

Antimicrotubule benzimidazoles inhibit in vitro growth of Pneumocystis carinii.

Nine antimicrotubule benzimidazole derivatives tested in a Pneumocystis carinii culture system with human embryonic lung fibroblast monolayers inhibited organism proliferation. The concentrations of drugs inhibitory in culture ranged from 10 to 0.1 micrograms/ml, with thiabendazole being the least effective (10 micrograms/ml) and parbendazole being the most effective (0.1 microgram/ml). The parent compound, benzimidazole, was inactive at 10 micrograms/ml. Demonstration that this group of compounds has activity against P. carinii provides a new potential target that can be exploited, the microtubules. Also, the variability in the effectiveness of the compounds provides the basis for studies of structure-activity relationships, which were initiated in this study.

Antiprotozoal Agents↗
PubMed1992

An enzyme-linked immunosorbent assay for enumeration of Pneumocystis carinii in vitro and in vivo.

An enzyme-linked immunosorbent assay (ELISA) to quantitate Pneumocystis carinii organisms from culture supernatant and rat lung has been developed. A polyclonal antibody specific to P. carinii was produced in Sprague-Dawley rats by allowing P. carinii-infected animals to recover from infection. This antibody reacted strongly to P. carinii proteins of 50 to 55 kDa and weakly to those of 33 and 116 kDa. The ELISA used this convalescent-phase antibody to quantitate the number of P. carinii organisms in lung homogenates of infected rats and supernatants from infected tissue cultures which were used to screen drugs for P. carinii. The results of the ELISA were compared with those of direct microscopic counting of organisms, and the two methods were highly correlated (r > 0.9). Thus, the ELISA can be used as an alternative method for the quantitation of P. carinii organisms, and it is superior to the conventional microscopic method because it is easier to perform and less labor-intensive.

Animals↗
PubMed1978

Vitamin-D-dependent rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D.

Studies were done to determine the cause for hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in a 22-year-old black woman. The patient had normal serum 25-hydroxyvitamin D (14 ng per milliliter) and markedly elevated serum 1,25-dihydroxyvitamin D (137 pg per milliliter). Vitamin D3, 4000 units per day for four weeks, increased the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to as high as 29 and 297 pg per milliliter, respectively, and corrected the hypocalcemia and secondary hyperparathyroidism. The results suggest that the disorder results from impaired end-organ response to 1,25-dihydroxyvitamin D. We propose that the entity be called vitamin-D-dependent rickets Type II.

Adult↗
PubMed1977

Pentobarbital sleeping time and waking blood levels in spontaneously hypertensive rats.

Pentobarbital sleeping times and blood levels on arousal were determined in spontaneously hypertensive rats (SHR) and normotensive controls (WKR). Sleeping time for SHR was significantly less than for WKR, but blood levels of [14C]pentobarbital at awakening were not significantly different. The shorter sleeping time in SHR appears not to result from decreased brain sensitivity to pentobarbital. Instead, SHR appear to differ from WKR in the rate of metabolic clearance of the drug or in the distribution of the drug between blood and brain.

Animals↗
PubMed1976

On the lipolytic action of parathyroid hormone in man.

An investigation was carried out to determine whether bovine PTH stimulates lipolysis in human fat tissue, whether this action is mediated by cyclic adenosine 3', 5'-monophosphate and whether the N-terminal 1-34 peptide of bovine PTH is responsible for the lipolytic effect. Studies were also performed to determine if parathyroid extract (PTE) produces lipolysis in normal subjects and in patients with pseudohypoparathyroidism in whom there is a defect in the adenylate system in response to PTH in the renal cortex and presumably in the skeletal system as well. It was found that highly purified bovine PTH in the concentration range between 10(-9) M and 10(-5) M stimulated lipolysis in vitro by human fat in a dose-dependent manner. Significant increases in glycerol production were observed at concentrations of PTH as low as 10(-9) M and maximal increases were seen at 10(-6) M. The hormone significantly increased the concentration of cyclic adenosine 3' ,5'-monophosphate in fat tissue. The synthetic N-terminal 1-34 peptide of bovine PTH was as effective as the native hormone in stimulating glycerol production at a concentration of 10(-9) M-10(-6) M. PTE, 100 mU per kg per min for 30 min given intravenously, produced transient increases in the concentration of plasma free fatty acid in each of eight normal subjects, three patients with hypoparathyroidism and eight patients with pseudohypoparathyroidism. Purified bovine PTH also increased plasma free fatty acid in each of two normal subjects. It is concluded that PTH stimulates lipolysis in human subcutaneous fat, that this action of the hormone is mediated through cyclic adenosine 3', 5'-monophosphate and that the N-terminal 1-34 peptide portion of the hormone is responsible for this lipolytic action. Further, PTE stimulates lipolysis in vivo in man. There appears to be no defect in the adenylate cyclase system in the fat cell in response to PTH in patients with pseudohypoparathyroidism.

Adipose Tissue↗
PubMed1976

Demonstration that cyclic adenosine 3',5'-monophosphate mediates the lipolytic action of parathyroid hormone.

Studies were carried out with rat epididymal fat pads first to compare the effects of the synthetic N-terminal 1-34 peptide of bovine parathyroid hormone and of the native hormone to determine whether this portion of the molecule is responsible for the lipolytic action of the hormone and second to determine whether this biologic action of parathyroid hormone is mediated by cyclic adenosine 3',5'-monophosphate. The N-terminal polypeptide was as effective as the native hormone in stimulating lipolysis in the concentration range between 10(-8) M and 10(-6) M. Parathyroid hormone stimulated lipolysis by isolated fat cells. The concentration of cyclic adenosine 3',5'-monophosphate in the fat pads was significantly increased by the hormone (10(-6)M). Lipolytic stimulation by parathyroid hormone (10(-6)M) was diminished by insulin (100 muU/ml) and prostaglandin E1 (1 mug/ml), both of which are known inhibitors of lipolysis. The findings indicate that the amino-terminal 1-34 peptide portion of parathyroid hormone is responsible for the lipolytic action and that this effect is mediated through cyclic adenosine 3',5'-monophosphate.

Adipose Tissue↗
PubMed1976

Acquired resistance to parathyroid hormone.

Studies are presented in a patient with pseudohypoparathyroidism who showed a partial response to parathyroid extract. Resistance to the extract was observed after its short-term administration for the gourth time. Serum from the patient contained antibodies of the gamma G globulin class which bound 125I-labelled bovine parathyroid hormone. Prior incubation of parathyroid hormone with the serum prevented the activation in vitro of adenylate cyclase from pork renal cortex. The antibodies were directed primarily toward the C-terminal portion of the molecule. Thus, clinical resistance to parathyroid hormone is attributed to specific antibodies.

Adenylyl Cyclases↗
PubMed1976

A radioimmunoassay for serum calcitonin in the rat.

A radioimmunoassay for serum calcitonin in the rat is described. Materials for assay of human calcitonin are employed. The sensitivity of the assay is 3 pg and corresponds to a lower limit of detection of 60 pg/ml for peripheral serum. The normal range is up to 650 pg/ml in rats weighing between 125 and 200 g. Serum calcitonin is not detectable in thyroparathyroidectomized animals. It increases and varies directly with the serum calcium after intraperitoneal administration of the ion. Values for serum calcitonin in male and female rats are comparable under basal conditions and after calcium. The radioimmunoassay should allow the further characterization of calcitonin secretion in response to physiologic and pathophysiologic stimuli in this species.

Animals↗
PubMed1975

Solubilization of calcitonin-responsive renal cortical adenylate cyclase.

Purification of pork renal cortex membranes yielded a particulate adenylate cyclase retaining good sensitivity to stimulation by parathyroid hormone and glucagon and a modest but significant response to porcine calcitonin. Treatment of this partially purified membrane fraction with 0.5% Lubrol PX and 5 mM NaF released adenylate cyclase activity into a fraction which was not sedimented by centrifugation for 20 min at 37,000 X g or for 2 hours at 100,000 X g and passed through a Millipore filter (0.22 mum pore). This solubilized adenylate cyclase was stimulated by porcine calcitonin and NaF but not by parathyroid hormone or glucagon. On gel filtration (Sephadex G-200) in the presence of 1mM dithiothreitol and 5mM NaF, the major portion of the adenylate cyclase activity eluted with the void volume of the column and showed 2.0-fold stimulation with 10 muM calcitonin. Binding of 125I-labeled porcine calcitonin was demonstrated in the 37,000 X g and the 100,000 X g supernatants. From 74 to 86% of the observed binding could be blocked by the addition of unlabeled porcine calcitonin to the reaction mixture. Addition of salmon calcitonin, parathyroid hormone, or glucagon blocked only 12 to 18% of the binding. The dose-response curves for inhibition of binding of iodinated calcitonin by unlabeled calcitonin and the activation of adenylate cyclase by the hormone each showed 50% maximal effect at a concentration between 4.5 and 8 muM porcine calcitonin and maximal effect at a concentration between 33 and 66 muM porcine calcitonin.

Adenylyl Cyclases↗
PubMed1975

Calcitonin: a general survey.

Since the initial discovery of calcitonin, a considerable amount of information has been obtained concerning structure, function, secretion, and effects of the hormone from a number of species. The purpose of the present report is to review the studies of structure and function, the factors that influence secretion and synthesis, and the effects and mechanism of action of calcitonin. The clinical uses of the hormone and syndromes of calcitonin excess are discu,sed.

Amino Acid Sequence↗
PubMedDate not supplied

Isolation and characterization of rat lung Pneumocystis carinii gp120.

The principal glycoprotein (gp120) of Pneumocystis carinii obtained from infected rat lung was isolated by differential extraction and size-exclusion chromatography. The purified glycoprotein was cleaved with CNBr to two peptides of approximately 27 and 33 kDa. Amino acid sequences were obtained from both peptides. Proteolytic digestion with V8 protease yielded several peptides and sequences were obtained from peptides of 10 and 19 kDa. The cyanogen bromide cleavage results led to the conclusion that gp120 exists as a homodimer.

Amino Acid Sequence↗
PubMedDate not supplied

Inoculated mouse model of Pneumocystis carinii pneumonia.

A transtracheally inoculated mouse model of Pneumocystis carinii has been developed using BALB/c mice, a widely available strain free of latent P. carinii infection. The mean infectivity score of untreated inoculated mice was 4.1 compared to the mean infectivity score of 0.1 for trimethoprim/sulfamethoxazole (50/250 mg/kg) treated inoculated mice, approximately a four-log difference. An inoculated mouse model of P. carinii infection provides both a source of organisms from a different host and an animal model for study of drugs for therapy and prophylaxis which is less costly than rats and which requires less drug than required for rats.

Animals↗