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Biomedical subjects

M M Shaw

Publications and source records attributed to M M Shaw.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1989

Prevalence and treatment of asthma in the Michigan Medicaid patient population younger than 45 years, 1980-1986.

The prevalence and outpatient treatment of asthma were studied in the Michigan Medicaid patient population by use of computerized physician, hospital, and pharmacy reimbursement data to mark and track asthma-related medical transactions. Asthma cases were defined as patients with evidence of at least two diagnoses and prescription drug transactions consistent with asthma. More than 52,000 cases were thus identified. The period prevalence of asthma was estimated on a year-by-year basis. The prevalence of asthma in the population increased from 2.0 per 100 Medicaid patients in 1980 to 2.8 per 100 Medicaid patients in 1986. Prevalence decreased with age until the age of 20 years and increased thereafter, and was higher in male children than in female children. In contrast, asthma was more prevalent in female adults than in male adults. Prevalence was higher in black subjects than in other races and higher in urban residents than in rural residents. The total number of reimbursements for antiasthma medications increased from 60,000 per year to 120,000 per year, and the average number of antiasthma prescriptions per Michigan Medicaid asthma case increased at the rate of 6.6% per year during the study interval. Changes in the preferred types of asthma treatment consistent with changes that have occurred in the general population were observed. These data suggest that the relative and absolute occurrence of asthma and asthma treatment in the Michigan Medicaid population is increasing.

Adolescent↗
PubMed1975

Effect of intracranial pressure of meglumine iothalamate ventriculography.

Intraventricular pressure was studied in 12 patients undergoing ventriculography with a water soluble positive contrast medium. Isovolumetric instillation of meglumine iothalamate into the lateral ventricles and the anterior part of the third ventricle caused only a small increase in ventricular fluid pressure (1.3 +/- 0.3 mmHg), but the pressure increased markedly (46.3 +/- 3.7 mmHg; P less than 0.001) when the contrast medium entered the posterior end of the third ventricle, aqueduct of Sylvius,, and fourth ventricle. This sharp increase in intracranial pressure could not be attributed solely to the postural changes or to alterations in arterial blood pressure. Possible mechanisms are discussed.

Adolescent↗
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↗
PubMedDate not supplied

An ELISA method for quantitation of Pneumocystis carinii in culture and lung.

Numbers of Pneumocystis carinii in cultures or tissues traditionally have been determined by counting organisms on Giemsa-stained slides. For cultures, 10 microliters of culture supernatants have been sampled and counted on days 1, 3, 5 and 7. Infectivity scores of P. carinii-infected animal lung have been determined by three examiners scoring lung impression smears stained with Giemsa using a roughly logarithmic scale. Both counting procedures are tedious and time consuming. We have developed an enzyme-linked immunosorbent assay (ELISA) system which uses culture supernatants (in vitro) or homogenized animal lung (in vivo) as antigen, convalescent rat sera as primary antibody, and goat anti-rat alkaline phosphatase-conjugated immunoglobulin G as secondary antibody. The ELISA method shows good correlation with manual counts of Giemsa stains and allows a more rapid, more efficient method for quantitating P. carinii in both culture and infected lung.

Animals↗
PubMedDate not supplied

Culture and filtration methods for obtaining Pneumocystis carinii trophozoites and cysts.

Two methods for acquisition of Pneumocystis carinii (Pc) trophozoites and cysts are reported. One method, the isolation of Pc from infected rat lung, provides large numbers of trophozoites and cysts but retains rat proteins. Ground lung is filtered through a series of Nucleopore filters from 10 to 3 microns; 1 g of rat lung yields an average of 1.1 x 10(9) Pc trophozoites and 1 x 10(7) cysts. The second method, propagation of Pc in culture with human embryonic lung cells on microcarrier beads, provides Pc trophozoites which are relatively free of host lung material. Cultured organisms may be filtered to remove rare culture monolayer cells. Organisms harvested from filtered lung are free from intact host cells and cell nuclei, however, host cell proteins and host DNA remain. Organisms from culture have minimal host contamination.

Animals↗
PubMedDate not supplied

Suppressive effect of deferoxamine on the growth of Pneumocystis carinii in vitro.

The effects of the iron chelator deferoxamine on the growth of rat-derived Pneumocystis carinii in culture with human embryonic lung fibroblasts were studied. Growth inhibition was calculated by comparison of trophozoite numbers in replicate samples of supernatant of treated and untreated samples. Deferoxamine, in concentrations safely achievable in humans (5-15 micrograms/ml, corresponding to 7.6-22.8 microM), reproducibly suppressed P. carinii growth in a dose-dependent manner. The suppressive effect was reversed by prior iron saturation of the deferoxamine. Since the utility of current therapeutic agents for P. carinii disease is limited by toxicity and incomplete efficacy, the role of iron chelation as an adjunct to anti-Pneumocystis chemotherapy merits further investigation.

Antifungal Agents↗