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Biomedical subjects

J McLaughlin

Publications and source records attributed to J McLaughlin.

At least 19 recordsLinked to original sources
PubMed1992

Serology and anthrax in humans, livestock and Etosha National Park wildlife.

Results are presented from a number of epidemiological studies using enzyme immunoassays (EIA) based on the purified anthrax toxin antigens, protective antigen, lethal factor and oedema factor. Studies on sera from a group of 62 human anthrax patients in Turkey and from cattle in Britain following two unrelated outbreaks of anthrax show that EIA using protective antigen can be a useful diagnostic aid and will detect subclinical infections in appropriate circumstances. A serological survey on wildlife in the Etosha National Park, Namibia, where anthrax is endemic, showed that naturally acquired anthrax-specific antibodies are rare in herbivores but common in carnivores; in carnivores, titres appear to reflect the prevalence of anthrax in their ranges. Problems, as yet unresolved, were encountered in studies on sera from pigs following an outbreak of anthrax on a farm in Wales. Clinical details, including treatment, of the human and one of the bovine outbreaks are summarized and discussed in relation to the serological findings.

Adolescent↗
PubMed1992

1992 Canadian Cancer Statistics.

In Canada, it is estimated that in 1992 115,000 new cases of cancer will be diagnosed. This total excludes 47,200 estimated new cases of non-melanoma skin cancer. The number of new cases is increasing by about 3,000 per year due partly to the aging population, improved registration, earlier detection of cancer and real increases in the incidence of some types of cancer. It is estimated that there will be 58,300 cancer deaths in 1992. By 1992, prostate cancer will have overtaken lung cancer as the leading cancer among men in the four western provinces while lung cancer is expected to exceed breast cancer as the leading cause of cancer deaths among women in some provinces, notably British Columbia. In British Columbia, the relative survival rates for most cancers improved between the periods 1970 to 1974 and 1980 to 1984. However, stomach, lung and pancreatic cancers, which have low survival rates, showed little improvement. This article is based on 1992 estimates of cancer incidence and mortality, cancer trends in Canada and relative cancer survival rates in British Columbia, found in Canadian Cancer Statistics 1992. This publication was prepared at Statistics Canada through a collaborative effort involving the Canadian Cancer Society, Health and Welfare Canada and the provincial/territorial cancer registries.

British Columbia↗
PubMed1991

PCR-detected genital papillomavirus infection: prevalence and association with risk factors for cervical cancer.

In an investigation conducted in student health clinic patients, the polymerase chain reaction was used to detect human papillomavirus (HPV) DNA, thereby allowing measurement of the prevalence of HPV infection and study of the association between HPV infection and risk factors for cervical cancer. Of 159 women eligible to participate, 105 (66%) provided a specimen of cervical cells for HPV typing, and also answered an interviewer-administered questionnaire which sought information on risk factors for cervical cancer. Nucleic acid extracted from cervical cells was screened with primers for HPV types 6, 11, 16, 18, 33 and with an HPV Consensus primer. Overall, the prevalence of HPV infection was 18.1%, while for HPV-6/11 it was 2.9% and for HPV-16/18 it was 10.5%. There were statistically significant increases in risk of HPV infection with a history of ever having smoked cigarettes (overall, and for HPV-16 alone) and with a history of usually having sexual intercourse during menstrual periods (overall, but not for HPV-16), and these associations were independent of the effects of age at first sexual intercourse and number of sexual partners. The latter 2 variables, as well as the total number of occasions of sexual intercourse, a history of anal intercourse, and a history of ever having used oral contraceptives, were not associated with statistically significant alterations in risk of HPV infection.

Adult↗
PubMed1991

Kidney biopsy in systemic lupus erythematosus. II. Survival analyses according to biopsy results.

Renal biopsy specimens from 123 patients with systemic lupus erythematosus (SLE) seen between 1970 and 1984 were assessed according to the World Health Organization classification and according to the presence of proliferative, active, or chronic renal lesions. Survival analysis was used to study the determinants of mortality. Survival rates were higher for patients with minimal lesions, intermediate for patients with focal or diffuse proliferative nephritis, and low for patients with glomerular sclerosis. The presence of proliferative and chronic lesions was associated with a higher risk of dying. Renal biopsy results are helpful in predicting prognosis for all-cause mortality in patients with SLE.

Adult↗
PubMed1991

Cancer risk in patients with diabetes mellitus.

Cancer incidence was ascertained in a population-based cohort of 51,008 patients in Uppsala, Sweden, who were given a discharge diagnosis of diabetes mellitus during 1965-83. Complete follow-up through 1984 with exclusion of the first year of observation showed that the observed number of cancers in females (1,294) was eight percent higher than expected (relative risk [RR] = 1.1, 95 percent confidence interval = 1.0-1.1), whereas in males the observed number (1,123) was close to the expected (RR = 1.0, 0.9-1.1). Significantly increased risks of pancreatic (RR = 1.4, 1.2-1.7), primary liver (RR = 1.5, 1.2-1.7), and endometrial (RR = 1.5, 1.2-1.8) cancers and a lower than expected number of prostatic cancers (RR = 0.7, 0.7-0.9) were found in this cohort of diabetic patients. The excess risk of pancreatic cancer was similar in females and males and evident both during one through four years (RR = 1.7, 1.4-2.1) and five through nine years (RR = 1.3, 0.9-1.7) of follow-up, but not thereafter. A similar pattern was found for primary liver cancer, but the RRs were generally higher in males than in females.

Adult↗
PubMed1991

Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene.

Two forms of activated BCR/ABL proteins, P210 and P185, that differ in BCR-derived sequences, are associated with Philadelphia chromosome-positive leukemias. One of these diseases is chronic myelogenous leukemia, an indolent disease arising in hematopoietic stem cells that is almost always associated with the P210 form of BCR/ABL. Acute lymphocytic leukemia, a more aggressive malignancy, can be associated with both forms of BCR/ABL. While it is virtually certain that BCR/ABL plays a central role in both of these diseases, the features that determine the association of a particular form with a given disease have not been elucidated. We have used the bone marrow reconstitution leukemogenesis model to test the hypothesis that BCR sequences influence the ability of activated ABL to transform different types of hematopoietic cells. Our studies reveal that both P185 and P210 induce a similar spectrum of hematological diseases, including granulocytic, myelomonocytic, and lymphocytic leukemias. Despite the similarity of the disease patterns, animals given P185-infected marrow developed a more aggressive disease after a shorter latent period than those given P210-infected marrow. These data demonstrate that the structure of the BCR/ABL oncoprotein does not affect the type of disease induced by each form of the oncogene but does control the potency of the oncogenic signal.

Animals↗
PubMed1991

The 5' non-coding region of the BCR/ABL oncogene augments its ability to stimulate the growth of immature lymphoid cells.

The Philadelphia chromosome (Ph1, t9:22;34:q11) is a reciprocal translocation between chromosome 22 and chromosome 9 which results in the formation of the chimeric BCR/ABL oncogene. Alternative forms of BCR/ABL are produced by splicing different sets of exons of the BCR gene to a common set of c-ABL sequences. This results in the formation of an 8.7 kilobase mRNA that encodes the P210 BCR/ABL gene product or a 7.0 kilobase mRNA that encodes the P185 BCR/ABL gene product. Both BCR/ABL transcripts derive their 5' non-coding sequences from the BCR gene locus. This 5' region is over 500 nucleotides in length, has a GC content greater than 75% and has a short open reading frame. To determine if this unusual 5' non-coding region plays a role in BCR/ABL transformation, we prepared retroviral vectors containing identical BCR/ABL coding regions but differing in the length of the BCR 5' non-coding region. Matched viral stocks were evaluated for their ability to transform bone marrow in vitro and for their ability to cause tumors when inoculated into 3- to 4-week-old mice. In this report we present the unexpected finding that the BCR/ABL 5' non-coding region augments the transforming activity of both P210 and P185 BCR/ABL in vitro. In vivo, BCR/ABL is a weak tumorigenic agent and its potency is enhanced by the presence of the 5' non-coding region.

Animals↗
PubMed1990

Base changes at position 792 of Escherichia coli 16S rRNA affect assembly of 70S ribosomes.

To investigate the function of base 792 of 16S rRNA in 30S ribosomes of Escherichia coli, the wild-type (adenine) residue was changed to guanine, cytosine, or uracil by oligonucleotide-directed mutagenesis. Each base change conferred a unique phenotype on the cells. Cells containing plasmid pKK3535 with G792 or T792 showed no difference in generation time in LB broth containing ampicillin, whereas cells with C792 exhibited a 20% increase in generation time in this medium. To study the effect on cell growth of a homogeneous population of mutant ribosomes, the mutations were cloned into the 16S rRNA gene on pKK3535 carrying a spectinomycin-resistance marker (thymine at position 1192), and the cells were grown with spectinomycin. Cells containing G792 or C792 showed 16% and 56% increases in generation time, respectively, and a concomitant decrease in 35S assimilation into proteins. Cells with T792 did not grow in spectinomycin-containing medium. Maxicell analyses indicated decreasing ability to form 70S ribosomes from 30S subunits containing guanine, cytosine, or uracil at position 792 in 16S rRNA. It appeared that C792-containing 30S ribosomes had lost the ability to bind initiation factor 3.

Base Sequence↗
PubMed1990

Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL.

The v-abl gene in Abelson virus induces pre-B-cell lymphoma in mice while the BCR/ABL oncogene is associated with chronic myelogenous leukemia and some cases of acute lymphocytic leukemia in humans. Understanding the mechanisms by which these oncogenes affect various cell types has been hampered by a paucity of experimental systems that reproduce the range of biological effects associated with them. We have developed an experimental system in which murine hematopoietic stem cell populations are infected with either v-abl or BCR/ABL retroviruses and are used to reconstitute lethally irradiated mice. Irrespective of the form of activated abl, greater than 90% of the animals reconstituted with such cells develop tumors. About 50% of them develop a myeloproliferative syndrome that shares several features with the chronic phase of chronic myelogenous leukemia; the remaining animals succumb to pre-B-cell lymphomas. The myeloproliferative syndrome is characterized by large numbers of clonally derived, infected myeloid cells. This model will allow study of the mechanism by which activated abl genes affect hematopoietic precursors in chronic myelogenous leukemia. Furthermore, our results demonstrate that introduction of an activated abl gene into the appropriate target cell, not the structure of the gene, is the major determinant in myeloid cell specificity.

Abelson murine leukemia virus↗
PubMed1989

Alternative forms of the BCR-ABL oncogene have quantitatively different potencies for stimulation of immature lymphoid cells.

The Philadelphia chromosome (t9:22;q34:q11) is found in more than 90% of patients with chronic myelogenous leukemia, in 10 to 20% of patients with acute lymphocytic leukemia, and in 1 to 2% of patients with acute myelogenous leukemia. Alternative chimeric oncogenes are formed by splicing different sets of BCR gene exons on chromosome 22 across the translocation breakpoint to a common set of ABL oncogene sequences on chromosome 9. This results in an 8.7-kilobase mRNA that encodes the P210 BCR-ABL gene product commonly found in patients with chronic myelogenous leukemia or a 7.0-kilobase mRNA that produces the P185 BCR-ABL gene product found in most Philadelphia chromosome-positive patients with acute lymphocytic leukemia. To compare the efficiency of growth stimulation by these two proteins, we derived cDNA clones for each with identical 5' and 3' untranslated regions and expressed them from retrovirus vectors. Matched stocks were compared for potency to transform immature B-lymphoid lineage precursors. The growth-stimulating effects of P185 for this cell type were found to be significantly greater than those of P210. Structural changes in BCR may regulate the effectiveness of the ABL tyrosine kinase function, as monitored by lymphocyte growth response. Changes in mitogenic potency may help to explain the more acute leukemic presentation usually associated with expression of the P185 BCR-ABL oncogene.

Cell Division↗
PubMed1989

Mapping of the creatine kinase M gene to 19q11----q12 in the rabbit genome.

The chromosomal localization of the gene for creatine kinase M has been determined to be on rabbit chromosome 19 at q11----q12 by in situ molecular hybridization. The results show significant cross-hybridization of the creatine kinase, muscle (CKMM) probe to the previously mapped creatine kinase, brain (CKBB) locus at 20q13----qter, and therefore provide independent support for the localization of CKBB at that site.

Animals↗
PubMed1989

Evaluation of a diffusion strategy for school-based hypertension education.

The purpose of this research was to evaluate the effectiveness of hypertension (HBP) education within a population of sixth grade students (n = 1204) and their parents (n = 1446). The "3Rs and HBP" curriculum attempts to diffuse the HBP information from teachers, to pupils and then to parents using the sixth grade son/daughter as a "health messenger." This curriculum was tested with and without a home blood pressure measurement component versus controls in 21 schools randomly assigned to the three conditions. Postintervention data were collected from students at school and from their parents at home interviews. Students were compared for knowledge, blood pressure measurement skill, and home diffusion activities. Parents were compared for knowledge, risk factor reduction, blood pressure, care-seeking, and compliance behaviors. Student self-esteem and family interactions were investigated as possible intervening variables in the diffusion process. Student knowledge, BP measurement skills, and diffusion to parents was increased by the 3Rs and HBP curriculum with the home component. Parental effects beyond the diffusion process were limited to knowledge improvement in certain groups. Family interaction (level and style) was found to be a significant intervening variable in the diffusion process.

Child↗
PubMed1988

Expression of a distinctive BCR-ABL oncogene in Ph1-positive acute lymphocytic leukemia (ALL).

The Philadelphia chromosome (Ph1) is a translocation between chromosomes 9 and 22 that is found in chronic myelogenous leukemia (CML) and a subset of acute lymphocytic leukemia patients (ALL). In CML, this results in the expression of a chimeric 8.5-kilobase BCR-ABL transcript that encodes the P210BCR-ABL tyrosine kinase. The Ph1 chromosome in ALL expresses a distinct ABL-derived 7-kilobase messenger RNA that encodes the P185ALL-ABL protein. Since the expression of different oncogene products may play a role in the distinctive presentation of Ph1-positive ALL versus CML, it is necessary to understand the molecular basis for the expression of P185ALL-ABL. Both P210BCR-ABL and P185ALL-ABL are recognized by an antiserum directed to BCR determinants in the amino-terminal region of both proteins. Antisera to BCR determinants proximal to the BCR-ABL junction in CML immunoprecipitated P210BCR-ABL but not P185ALL-ABL. Nucleotide sequence analysis of complementary DNA clones made from RNA from the Ph1-positive ALL SUP-B15 cell line, and S1 nuclease protection analysis confirmed the presence of BCR-ABL chimeric transcripts in Ph1-positive ALL cells. In Ph1-positive ALL, ABL sequences were joined to BCR sequences approximately 1.5 kilobases 5' of the CML junction. P185ALL-ABL represents the product of a BCR-ABL fusion gene in Ph1-positive ALL that is distinct from the BCR-ABL fusion gene of CML.

Amino Acid Sequence↗
PubMed1988

A flagellar pocket membrane fraction from Trypanosoma brucei rhodesiense: immunogold localization and nonvariant immunoprotection.

In contrast to the abundance of detailed information on variant-specific surface coat antigens of African trypanosomes, data on possible common or nonvariant antigens within these protozoa are surprisingly limited. In this study, the cellular localization and protective potential of a previously characterized flagellar pocket membrane (FPM) fraction were determined. Immunogold staining of live trypanosome suspensions at 0 to 4 degrees C by using anti-FPM hyperimmune serum raised in rabbits as the primary antibody revealed specific staining of the parasite surface at the emergence of the flagellum from the flagellar pocket. The same specificity of immunogold localization was obtained for each of three distinct variable antigenic types (VATs) of a serodeme of Trypanosoma brucei rhodesiense Wellcome strain. Products of translated mRNA preparations from each of the VATs were precipitated by the FPM antiserum and revealed identical banding patterns when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. Immunization of mice with FPM fraction protected them against infection by two of the VATs; the third VAT was afforded poor protection. This is the first demonstration of the combined cellular localization, nonvariant nature, and protective potential of a membrane fraction from African trypanosomes.

Animals↗
PubMed1988

The effects of chronic otitis media on motor performance in 5- and 6-year-old children.

Two 16-member groups of 5- and 6-year-old children, one group with a history of chronic otitis media and one without such a history, were tested on three measures of motor performance. These were the Motor Accuracy Test-Revised, the Stott Test of Motor Impairment, and measures of duration of standing balance. These instruments assess, respectively, fine motor coordination, overall motor skills, and balance. On each of these measures, children with a history of chronic otitis media scored lower than children without such a history. However, when these scores were compared statistically, no significant differences were found between the two groups. Because the results of this study were inconclusive, routine motor performance evaluation of children with a history of chronic otitis media is not advocated at this time.

Child↗