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Biomedical subjects

M C Taylor

Publications and source records attributed to M C Taylor.

At least 37 records · Page 2Linked to original sources

Antigenic variation in trypanosomes.

We review here antigenic variation in African trypanosomes with emphasis on genetic mechanisms and on the expression sites in which the genes for Variant Surface Glycoproteins (VSGs) are expressed. There are multiple expression sites in a trypanosome, but only one of these is active at a time. We discuss recent experiments that provide new information on expression site regulation, i.e., how inactive sites are kept inactive and how the trypanosome switches from expression of one site to expression of another one. Trypanosomes can also change the gene expressed by replacing the gene in an active expression site by another VSG gene. This replacement involves the duplicative transposition of a silent VSG gene into the expression site. We present a model for the mechanism of this transposition that incorporates new features and that explains several unusual characteristics of the transposition process. We also discuss how new knowledge of nutrient uptake, notably uptake of host transferrin by trypanosomes, might be used for vaccine development.

Animals↗

The accuracy and patient preference for self-collected group B Streptococcus cultures.

OBJECTIVE: Our purpose was to determine the accuracy of and patient attitudes regarding self-collected group B Streptococcus cultures. STUDY DESIGN: Women seen for prenatal care at 24 to 42 weeks' gestation were asked to collect distal vaginal and anal samples for group B Streptococcus. Subsequently, distal vaginal and anal samples were obtained by the nurse. The patients were then asked their preference toward self-sampling. RESULTS: A total of 251 women participated in the study. The incidence of positive group B Streptococcus cultures was 12.7%, 9.6%, 10.0%, and 7.6% for the patient-collected vaginal and anal and nurse-collected vaginal and anal specimens, respectively. The incidence of group B Streptococcus carriage was 17.5% and 13.5% for any positive patient- or provider-collected specimens, respectively, and 19.1% for any positive culture. Single patient-collected vaginal and anal and nurse-collected vaginal and anal samples were insensitive for group B Streptococcus carriage (67%, 50%, 52%, 40%, respectively). The combination of patient-collected samples was more sensitive than nurse-collected samples (sensitivity 91.7% vs 70.8%, p < 0.05). Repeat sampling of the vagina or anal canal did not offer significant additional benefit to a single culture. Overall, patient-collected samples were 98.4% accurate in predicting group B Streptococcus carriage versus 94.4% for nurses. A total of 58% of women preferred obtaining their own specimens, whereas 9.6% found the technique difficult. Ninety percent desired the option of self-sampling in the future. CONCLUSIONS: Single vaginal or anal cultures were insensitive in detecting group B Streptococcus carriage. Combined patient-collected cultures were more sensitive than provider-collected specimens. On the basis of accuracy and patient preference, women should be given the opportunity of combined vaginal-anal self-sampling for group B Streptococcus when indicated.

Adolescent↗

VSG gene expression site control in insect form Trypanosoma brucei.

When the African trypanosome Trypanosoma brucei is taken up from mammals by a tse-tse fly, it replaces its variant surface glycoprotein (VSG) coat by a procyclin coat. Transcription of VSG genes stops in the fly, but transcription of sequences derived from the promoter area of the VSG expression site(s) remains high. Whether this is due to continuing high activity of one promoter or to low activity of many promoters was unclear. We have used the small differences between the sequences of different expression sites to show that multiple expression site promoters are active in insect form trypanosomes. This is confirmed by the low expression of single copy marker genes introduced into the transcribed area. However, if the expression site promoter is removed from the genomic location of the expression site and inserted in the non-transcribed spacer of the ribosomal DNA (rDNA), it is derepressed. Derepression of transcription can also be accomplished by replacing the promoter of an expression site by an rDNA promoter. We conclude that the down-regulation of VSG gene expression site promoters in insect form trypanosomes is affected by both the DNA sequence of the promoter and the genomic context in which it resides.

Animals↗

The structure, organization, and expression of the Leishmania donovani gene encoding trypanothione reductase.

Trypanothione reductase (TR) is an NADPH-dependent flavoprotein oxidoreductase central to thiol metabolism in the trypanosomatids. We report here the cloning by expression of the Leishmania donovani gene. It is single copy, expresses a 2.6-kb transcript and a 52-kDa protein and is located on a 1.1-Mbp chromosome. The 491 amino acid sequence has 76% similarity to Crithidia fasciculata and 67% similarity to Trypanosoma cruzi, Trypanosoma congolense and Trypanosoma brucei TR. Residues recognising the adenosine pyrophosphate moiety of NADPH and FAD, and residues in the catalytic site segment (A47-A67) involving electron transfer from TR to trypanothione disulphide (T(S)2) were completely conserved. Thus inhibitors of TR are likely to be active against the enzyme from all the parasitic trypanosomatids. Two peptide inserts (39-47, 131-140) seen in other TR genes and a C-terminal extension of 19 residues were also present. When the gene was introduced back into L. donovani at high copy number using the pTEX expression vector, we detected elevated expression of TR RNA and a 14-fold increase in TR activity. Transfection and overexpression of the TR gene will facilitate studies of gene function and of the dependence of trypanosomatids on TR for protection against oxidative stress.

Amino Acid Sequence↗

Phenotype of recombinant Leishmania donovani and Trypanosoma cruzi which over-express trypanothione reductase. Sensitivity towards agents that are thought to induce oxidative stress.

Trypanothione reductase is thought to be important in maintaining an intracellular reducing environment in trypanosomatids. To investigate the role of trypanothione reductase we transfected Leishmania donovani and Trypanosoma cruzi with an expression vector containing the L. donovani trypanothione reductase gene and achieved over-expression of enzyme activity (10-14-fold) in transformed cells. Following treatment of L. donovani cells with the thiol-oxidizing agent diamide, the ability to regenerate dihydrotrypanothione from trypanothione disulphide was considerably enhanced in cells which over-expressed trypanothione reductase. However, the growth of transformed and control cells was equally sensitive to inhibition by nifurtimox, nitrofurazone and gentian violet, drugs that are thought to act by inducing oxidative damage. Likewise, growth of transformed and control cells were equally susceptible to inhibition by hydrogen peroxide, and control and transformed L. donovani promastigotes metabolized hydrogen peroxide at comparable rates. Thus, these experiments suggest that the ability to regenerate dihydrotrypanothione from trypanothione disulphide is not a rate-limiting step in the metabolism of hydrogen peroxide.

Animals↗

Coping, defending, and the relations between moral judgment and moral behavior in prostitutes and other female juvenile delinquents.

Twenty female juvenile delinquents who acknowledged engaging in prostitution, 20 juvenile delinquents who denied doing so, and 20 same-age control subjects responded to Colby and Kohlberg's (1987) Moral Judgment Interview (MJI), a moral dilemma about prostitution, and Joffe and Naditch's (1977) test of coping and defending. Delinquents scored lower on moral maturity and coping and higher on defensiveness than nondelinquents. Post hoc analyses revealed that low-coping delinquents (but not high-coping delinquents or control subjects) made significantly lower level moral judgments on the prostitution dilemma than on the less personally relevant MJI dilemmas. Groups did not differ in their prescriptive judgments on the MJI, but prostitutes made weaker judgments against prostitution than the other delinquents. Prescriptive judgments were not related to moral maturity. The results elucidate the relation between moral judgment and moral behavior.

Adaptation, Psychological↗

Catch them young.

Explore the source record for details and available documents.

Adolescent↗

Factors influencing the effectiveness of extracorporeal shock-wave lithotripsy of biliary duct calculi.

The authors examined the effectiveness of extracorporeal shock-wave lithotripsy on patients who had bile-duct stones. Thirty-eight patients were treated with an unmodified HM-3 Dornier lithotripter; 35 (92%) patients either passed the stone fragments spontaneously or had them reduced to a size which allowed removal by percutaneous or endoscopic techniques. As stone size increased so did the number of shocks required for satisfactory fragmentation, the number of treatments and the rate of post-treatment manipulation. The number of stones was not as important a variable as the authors expected. Pre-treatment sphincterotomy was not always necessary and was of no benefit in terms of spontaneous passage of fragments. Complications were minor. Extracorporeal shock-wave lithotripsy of stones throughout the biliary tree is a safe, effective and invaluable adjunct in the management of bile-duct stones.

Adult↗

Extracorporeal shock wave lithotripsy (ESWL) in the management of complex biliary tract stone disease.

The use of extracorporeal shock wave lithotripsy (ESWL) in the management of ten patients with complex biliary tract stones is described. General or epidural anesthesia was used in all cases, and stone fragmentation was performed, using an unmodified Dornier HM3 waterbath lithotripter (Dornier Medical Systems Inc., Marietta, GA). In all cases, biliary drainage was established before the procedure to allow contrast visualization during and after the procedure, as well as to ensure free drainage of the common bile duct. Indications for ESWL included failure of basket extraction (4 cases), unfavorable anatomy (duodenal diverticulum, previous Billroth II reconstruction, hepatic duct stone, gallbladder stone, cystic duct remnant stone), and immaturity of the T-tube tract (2 cases). Cholangitis was the presenting diagnosis in four cases. Fragmentation of the stones was successful in all patients; in two cases, two ESWL sessions were needed for stone disruption. Morbidity was minimal (there was a minor elevation of LDH and transaminases and asymptomatic hemobilia and hematuria); pancreatitis did not occur. After ESWL, hospital stays ranged from 1 to 13 days (mean of 5.3 days). ESWL can be a valuable adjunct in the management of patients with complex biliary stones.

Adult↗

Extracorporeal shock-wave lithotripsy in the management of bile duct stones.

Extracorporeal shock-wave lithotripsy (ESWL) was performed in 16 patients with bile duct stones. Dornier HM3 water-bath equipment (Dornier Medical Systems, Marietta, GA) was used in all procedures. All patients had either a T-tube or a nasobiliary, cholecystostomy, or transhepatic biliary drainage tube in place at the time of the lithotripsy. In 12 patients, the indication for ESWL was the failure of or anticipated difficulty with basket extraction of the stones, either via a T-tube tract or by means of endoscopic sphincterotomy. In the other four patients, ESWL was performed immediately after retained stones were found on a postoperative cholangiogram, even though no difficulty was anticipated in removing the stones by means of basket extraction. In 15 (94%) of the 16 patients, the stones were successfully fragmented. The fragments passed spontaneously in nine patients but had to be removed by basket in five patients. In one patient, the fragments could not be extracted by basket. The number of ESWL shocks used in a single session ranged from 525 to 3200. Three patients had two ESWL sessions. No significant complications were observed. ESWL is a successful method for the management of patients with bile duct stones when used in conjunction with other nonsurgical techniques. It was also the only treatment required in 56% of our patients.

Adult↗

Prognostic factors in colorectal carcinoma of young adults.

To determine why the prognosis for colorectal cancer in young adults is poor, survival and prognostic factors in patients under 40 years of age were compared with those in patients between 40 and 50 years of age. In a 10-year period, 122 patients less than 50 years of age (88 between 40 and 50 years) presented at the Victoria General Hospital in Halifax, NS, with colorectal cancer. Their charts were retrospectively reviewed. Follow-up was obtained for all patients. Of the 34 patients younger than 40 years, 71% (24) were men compared with 38% (33) of older patients. Symptoms, their duration and the location of primary tumours were similar in the two groups. Patients younger than 40 years presented with advanced lesions (Dukes' stages C and D) in 67% of cases compared with 52% of the older group. Mucinous tumours were twice as common in patients less than 40 years old (p = 0.036) and actuarial survival rates were lower at all stages for the same group. The authors conclude that the poorer prognosis in patients less than 40 years of age is not due to late symptom reporting or delay in diagnosis, but to more aggressive disease.

Adult↗