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Biomedical subjects

J Alexander

Publications and source records attributed to J Alexander.

At least 595 records · Page 33Linked to original sources

Growth of Mycobacterium lepraemurium in nonstimulated and stimulated mouse peritoneal-derived and bone marrrow-derived macrophages in vitro.

Mycobacterium lepraemurium cells were found to multiply in normal mouse peritoneal-derived and bone marrow-derived macrophages in vitro. Whereas activated peritoneal-derived macrophages demonstrated marked bacteriostasis for M. lepraemurium, significant bactericidal activity was exhibited by activated bone marrow-derived macrophages. However, only a small proportion of the bacterial were killed by activated bone marrow-derived macrophages with subsequent and enhanced bacteria growth. It is suggested that a rapid turnover of monocytes in active lesions is required to control mycobacterial infections in vivo. These results would suggest that careful consideration be given to the choice of the host cell in studies involving obligate intracellular parasites.

Antigens, Bacterial↗

Effect of cyclophosphamide treatment on the course of Mycobacterium lepraemurium infection and development of delayed-type hypersensitivity reactions in C57B1 and BALB/c mice.

Pre-treatment of Mycobacterium lepraemurium susceptible, BALB/c, and resistant, C57Bl, mice with cyclophosphamide markedly altered the development of delayed hypersensitivity during footpad infections with this organism. A tuberculin-type response demonstrated by untreated C57Bl mice was significantly intensified after week 3 in cyclophosphamide-pre-treated mice although this response had returned to normal levels by week 8. A Jones-Mote-type response demonstrated throughout experiments by untreated BALB/c mice was considerably increased in magnitude by week 3 in cyclophosphamide-pre-treated mice. By week 6 this response had become considerably protracted and was of the tuberculin-type. By week 8 however this response had started to diminish and by week 12 cyclophosphamide-treated and untreated BALB/c mice produced similar Jones-Mote-type responses when skin-tested. Cyclophosphamide pre-treatment had no effect on the growth of M. lepraemurium in C57Bl mice over 12 weeks. In BALB/c mice however cyclophosphamide-pre-treated mice demonstrated considerable resistance to infection at weeks 8 and 10 after infection but not thereafter. Whereas the magnitude of the delayed hypersensitivity response in C57Bl mice could not be correlated with resistance such a relationship could be demonstrated in BALB/c mice.

Animals↗

Videotape immediate playback: a tool in rehabilitation of persons with amputations.

This study attempted to measure whether immediate videotape feedback would improve the degree of motor learning and ambulation performances of amputee patients. Twelve amputee patients were randomly assigned either to a control or to an experimental group. Subjects in the experimental group were videotaped during four sessions at weekly intervals and were permitted to view tapes to discuss their performances with the experimenter, to attempt to correct mistakes and to view the second effort again. Members of the control group were also videotaped at weekly intervals but they did not view the tapes or discuss their performances. Initial and final tapes of both groups were rated by a group of physicians and physical therapists on an Amputee Gait Rating Scale which consisted of objective behavioral measures of ambulation. Reliability of ratings was determined and difference scores between the groups were calculated. Results indicate that immediate television feedback is a valuable adjunct in the teaching process for the amputee patient.

Adult↗

Reducing the risk of cardiovascular disease: effects of a community-based campaign on knowledge and behavior.

In 1972 the Stanford Heart Disease Prevention Program launched a three-community field study. A multimedia campaign was conducted for two years in two California communities (Watsonville and Gilroy), in one of which (Watsonville) it was supplemented by an intensive-instruction program with high-risk subjects. A third community (Tracy) was used as a control. The campaigns were designed to increase participants' knowledge of the risk factors for cardiovascular disease, to change such risk-producing behavior as cigarette smoking, and to decrease the participants' dietary intake of calories, salt, sugar, saturated fat, and cholesterol. Results of a sample survey indicate that substantial gains in knowledge, in behavioral modification, and in the estimated risk of cardiovascular disease can be produced by both methods of intervention. The intensive-instruction program, when combined with the mass-medica campaign, emerged as the most effective for those participants who were initially evaluated to be at high risk. The results after two years of intervention are reported for effects on knowledge and behavioral change for the total participant samples and for the high-risk subsamples in each of the three communities.

Attitude to Health↗

Application of glass capillary-column gas chromatography-mass spectrometry to the studies of human diseases.

Open-tubular glass capillary columns have been used in gas chromatography in combination with mass spectrometry (GC-MS) and computer methods to study human diseases. Patients with maple syrup urine disease excrete not only alpha-keto and alpha-hydroxy acids but also six other metabolites which hitherto have been overlooked. The GC-MS methods demonstrated that a group of patients suffering from hereditary progressive loss of hearing have an impaired metabolism of leucine, leading to the accumulation of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. GC using the capillary columns proved suitable for mapping of the carbohydrate profile of human seminal fluid and for the analyses of organic compounds accumulating in human adipose tissue. The high resolving power and long life of the glass capillary columns suggest that they will be valuable in the diagnosis and study of human disorders.

Adipose Tissue↗

Carcinoma of the esophagus in Africans: establishment of a continuously growing cell line from a tumor specimen.

Biopsy material, from a patient with an esophageal carcinoma of a type occurring relatively frequently in Africans in some regions of Southern Africa, has been adapted to cell culture conditions and has developed into a continuously growing tumor cell line. The cells have a squamous pattern of growth which they maintain, without piling up, even in heavily confluent cultures.

Adenoviruses, Simian↗

Microscopy of stained urine smears to determine the need for quantitative culture.

Consecutive specimens (2,564) of urine were cultured quantitatively, and Gram-stained smears were prepared from centrifugates as well as from the uncentrifuged specimens. About half of the specimens harbored organisms, and the quantity seen in smears of the centrifugates correlated reasonably well with the numbers of viable organisms cultured from the specimens. For example, smears of 900 centrifugates had one or more organisms per oil immersion field; 712 of their respective specimens proved to have colony counts of 10(5) or greater, and 120 had 10(4) to less than 10(5). For 188 specimens, however, the smears falsely predicted greater than or equal to 10(5) colony-forming units (many of these fell into the group that had 10(4) to less than 10(5)) but failed to predict clinically significant concentration of 10(5) or greater in only 31. Predictive values are presented also for lesser quantities of organisms seen in such smears. With rare exception, smears of centrifugates were superior to those of whole specimens as predictors of the concentration of viable organisms. Evaluation of smears proved not to be biased by the operator; values did not deviate significantly depending upon whether one or several microbiologists performed the evaluations.

Bacteria↗

Should fiberoptic bronchoscopy aspirates be cultured?

The reliability of fiberoptic bronchoscopy as a method to study the bacteriology of the lower respiratory tract was tested. The procedure used was suction aspiration through the inner channel after topical anesthesia with lidocaine. To detect contamination by oropharyngeal bacteria, the aspirates were cultured in patients with no evidence of active infection, comparison was made with results of transtracheal aspiration cultures, and the aspirate was tested for the presence of an oral dye marker. Results with all 3 methods of analysis indicated contamination with oropharyngeal bacteria that were presumably introduced during instrumentation through the upper airways. An additional factor studied was the effect of topical anesthetics. Analysis of aspirates showed that as much as 96 per cent of the specimen was anesthetic solution. Lidocaine also proved toxic to lower respiratory tract pathogens, although there were significant differences between bacterial species. It was concluded that fiberoptic bronchoscopy as performed in this study does not reliably reflect the bacteriology of the lower respiratory tract.

Anti-Bacterial Agents↗

Adaptation of cells derived from human malignant tumours to growth in vitro.

Forty-five human malignant tumour specimens were cultivated in vitro in an attempt to determine the necessary conditions for tumour cell maintenance and to establish permanently-growing cell lines. Continuously-growing cultures were derived from five tumours, including carcinomas of the oesophagus and colon, a hepatoma, a mesothelioma and a retroperitoneal sarcoma. The carcinoma of the oesophagus and the hepatoma, which have adapted fully to in vitro conditions, can be regarded as established cell lines.

Adaptation, Physiological↗

Rapid modulation of lipogenesis by clofibrate in rat and monkey hepatocytes.

Previous studies have proposed various possible mechanisms for the hypolipidemic actions of clofibrate. In the present study, isolated liver cells freshly prepared from rats and squirrel monkeys were used to investigate the acute effects of sodium clofibrate (sodium chlorophenoxyisobutyrate) on hepatic lipogenesis. Incubation of liver cells with levels of the drug (1 mM) known to lower plasma lipid level in vivo produced a rapid inhibition of [14C]acetate incorporation into cellular lipids. The degree of inhibition caused by the drug was not diminished by preincubation with an excess of unlabeled acetate. Conversion of [14C]acetate to 14CO2 was not significantly altered by sodium clofibrate at 1--3 mM levels, but was decreased at 5--10 mM levels. Incorporation of [14C]acetate into all lipid classes was suppressed by this agent, but inhibition of sterol synthesis was more pronounced than that of fatty acids. Sodium clofibrate (1 mM) reduced the synthesis of sterols from either labeled acetate or labeled mevalonate to a similar degree, but the decline was augmented in each case by a 30-min preincubation of the cells with sodium clofibrate. Addition of fatty acids to cell incubations stimulated sterol generation from [14C] acetate or from [3H] mevalonate, but did not reverse the inhibitory effects of the drug. These results suggest (a) the sodium clofibrate rapidly interferes with hepatic fatty acid and sterol synthesis by direct or indirect actions at diverse loci; (b) that these effects probably occur after acetyl-CoA formation and do not stem from precursor pool dilution; (c) that sodium clofibrate diminishes sterol production at post-mevalonic and perhaps also at pre-mevalonic sites; (d) that a similar pattern of inhibition occurs with sodium clofibrate in the presence of added fatty acids; and (e) that rat and primate livers demonstrate similar metabolic responses to the drug.

Acetates↗

Fusion of host cell secondary lysosomes with the parasitophorous vacuoles of Leishmania mexicana-infected macrophages.

Secondary lysosomes of cultured mouse peritoneal macrophages were labeled with the electron-dense colloid saccharated iron oxide; the identity of the labeled structures was checked by the Gomori reaction for acid phosphatase. Amastigotes of Leishmania mexicana mexicana derived from mouse lesions were used to infect these macrophages in vitro. In electron micrographs of thin sections of infected macrophages the labeled secondary lysosomes were seen fused with the parasitophorous vacuoles without preventing subsequent multiplication of the parasites. A similar fusion probably occurs in vivo, and may provide a pathway through which not only nutrients but also drugs and host antibodies could reach the intracellular parasite.

Acid Phosphatase↗

Effect of the antiphagocytic agent cytochalasin B on macrophage invasion by Leishmania mexicana promastigotes and Trypanosoma cruzi epimastigotes.

Unstimulated mouse peritoneal exudate cells were cultured on coverslips in Medium 199 containing 10 per cent (v/v) calf serum. Cytochalasin B dissolved in dimethyl sulphoxide (DMSO) and diluted in Medium 199 was added to cultures to give final concentrations of 1, 5 and 10 mug/ml. Equal numbers of Leishmania mexicana promastigotes, Trypanosoma cruzi epimastigotes and sheep red cells were added to 24 hr cultures incubated at 37 C. The macrophage monolayers were fixed and stained at various time intervals. L. mexicana promastigotes sheep red blood cells were found to attach to macrophages in the presence of the drug but did not enter the cells. When the medium containing the cytochalasin was replaced with normal medium phagocytosis of the adherent parasites and red cells followed rapidly. T. cruzi epimastigotes were found inside macrophages in both drug-treated and drug-free cultures although the number found to be intracellular in the latter was significantly greater. This study suggest that L. mexicana promastigotes enter macrophages by being phagocytosed, whereas T. cruzi epimastigotes can actively penetrate these cells.

Animals↗