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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 19 recordsLinked to original sources
PubMed1992

Rate of death from cervical cancer among native Indian women in British Columbia.

OBJECTIVE: To compare the rates of death from cervical cancer among native Indian women and non-native women in British Columbia from 1953 to 1984. DESIGN: Retrospective analysis of data retrieved from the British Columbia Division of Vital Statistics. MAIN OUTCOME MEASURES: Age-standardized death rate and relative rate. RESULTS: The rate of death from cervical cancer was significantly higher among the native women than among the non-native women throughout the study period. No deaths from cervical cancer were recorded in women under 20 years of age. Among those 20 to 64 the relative rate increased from 3.83 in 1953-62 to 6.53 in 1973-84; among those 65 or more it decreased slightly. For the entire study period the relative rate for women 20 to 64 years old was 5.95 and for those 65 or older 2.98. CONCLUSION: The rate of death from cervical cancer among native women in British Columbia is unacceptably high, probably because the provincial screening program does not reach as many native women as it does non-native women.

Adult↗
PubMed1992

Screening for neuroblastoma in the north of England.

OBJECTIVE: To determine the feasibility of establishing a system of screening for neuroblastoma. DESIGN: Prospective study of mass screening in four clearly defined geographical areas. SETTING: Four health districts of the Northern region of England. SUBJECTS: 20,829 babies aged 6 months, 92% of target population. INTERVENTIONS: Collection of urine on filter paper for analysis of content of homovanillic and vanillylmandelic acid in relation to urinary creatinine concentrations. MAIN OUTCOME MEASURES: Derivation of reference range. Identification of babies with homovanillic or vanillylmandelic acid > 3 SD above the mean (positive cases). Investigation of positive cases for evidence of neuroblastoma. RESULTS: The upper limit of normal (3 SD above the mean) for vanillylmandelic acid was 15 mumol/mmol creatinine and for homovanillic acid 24 mumol/mmol creatinine. Of the 20,829 babies screened, 2537 (12.2%) required a second sample to be taken because the first sample was inadequate. Of these, 527 (2.5%) provided a liquid urine specimen and 10 (0.04%) had positive results for neuroblastoma. Two of them had neuroblastoma (true positives) and eight did not (false positives). A further three children from the cohort were subsequently found to have neuroblastoma; they had raised homovanillic acid or vanillylmandelic acid values, or both, but screened negative at 6 months. CONCLUSIONS: Screening for neuroblastoma is possible in the health care system of the United Kingdom. Evaluation of the efficacy of screening in reducing the mortality from neuroblastoma requires a controlled trial.

Creatinine↗
PubMed1992

Community prevalence survey of children's blood lead levels and environmental lead contamination in inner Sydney.

OBJECTIVE: To determine the distribution of blood lead levels in preschool children in inner Sydney and identify possible sources of environmental lead. DESIGN: Cross sectional community based prevalence survey of children and the houses in which they live, and a survey of volunteer children. SETTING: Mort Bay and Summer Hill, residential localities in inner Sydney. PARTICIPANTS: Ninety-five children aged 9-48 months able to be identified in a defined geographic area and 63 children aged 9-48 months volunteered by their parents. OUTCOME MEASURES: Concentrations of lead in venous blood of all children and in samples from the home environment of Mort Bay children. RESULTS: Four of the children (2.5%) had blood lead levels > or = 1.21 mumol/L (25 micrograms/dL, the current Australian threshold of concern), 27 (17.1%) had levels > or = 0.72 mumol/L (15 micrograms/dL, the new US threshold for individual intervention) and 80 (50.6%) had levels > or = 0.48 mumol/L (10 micrograms/dL, the new US threshold for community intervention). Blood lead concentrations were significantly correlated with concentrations of lead in "sink" soil (r = 0.555, P = 0.026), play area soil (r = 0.492, P = 0.016) and dust from vacuum cleaners (r = 0.428, P = 0.05), and with age of child (r = -0.182, P = 0.023). The presence of the child during house renovation was a strong predictor of having a blood lead level above 0.72 mumol/L (15 micrograms/dL) (odds ratio, 4.6; 95% confidence interval, 1.8-11.7, P = 0.001). CONCLUSIONS: Lead in soil and in household dust in older areas of Sydney is likely to represent a significant health hazard to young children. Many thousands of children may be affected in Sydney and other Australian cities. There is an urgent need for expanded prevalence surveys, public education and the development of strategies for the abatement of lead in urban environments.

Child, Preschool↗
PubMed1992

Steady-state messenger RNA and activity correlates with sensitivity to N1,N12-bis(ethyl)spermine in human cell lines representing the major forms of lung cancer.

Our previous results from a limited number of cell lines have suggested that the bis(ethyl)polyamine analogues exert a phenotype-specific response in human lung cancer cells. In the present study, we have extended this work to analyze the response of the 4 major forms of human lung cancer to the polyamine analogue N1,N12-bis(ethyl)spermine (BESpm). The results suggest that non-small cell phenotypes are much more sensitive to the cytotoxic effects of BESpm than the small cell lung carcinoma phenotype. Further, there appears to be a positive association between the level of induction of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) in response to the analogue and the kinetic response of cells. Specifically, cells in which SSAT activity is highly induced by BESpm are killed by the compound. Although induction of SSAT appears to occur at both the level of increased steady-state mRNA and enzyme activity, SSAT activity appears to be a better indicator of cell sensitivity to BESpm than SSAT mRNA levels. These results have significance both for the potential use of polyamine analogues in treating specific forms of human lung cancer and for understanding the regulation of SSAT at the molecular level.

Acetyltransferases↗
PubMed1992

Expression of the gene encoding tyrosine hydroxylase in a subpopulation of quail dorsal root ganglion cells cultured in the presence of insulin or chick embryo extract.

Avian sensory ganglia contain a population of normally latent autonomic precursors with catecholaminergic potentialities. The present study examines the expression of the tyrosine hydroxylase (TH) gene in quail dorsal root ganglia (DRG) by both in situ hybridization and polymerase chain reaction (PCR) techniques. In situ hybridization using quail TH cDNA as a probe demonstrated the presence in DRG cell cultures of TH mRNA in a subpopulation of cells that never express the adrenergic phenotype in vivo. Expression of the TH gene in autonomic precursor cells of DRG in culture is totally dependent on the presence either of insulin or chick embryo extract. The numbers of catecholaminergic cells expressing TH mRNA and TH immunoreactivity evolve in a closely similar manner during the culture period. Using two primers, specific for highly conserved 5' regions of TH cDNA, it was possible to detect the same band of DNA amplified by PCR in total RNA from DRG cultures grown in the presence of insulin, sympathetic ganglia and adrenal gland. No amplified DNA was detected in uncultured DRG cells. These data further indicate that, under the influence either of insulin or a still unknown factor contained in the CEE, the TH gene is induced in a subpopulation of DRG cells.

Animals↗
PubMed1992

A strategy for generating monoclonal antibodies against recombinant baculovirus-produced proteins: application to the Bcl-2 oncoprotein.

A strategy is described for production of monoclonal antibodies against recombinant proteins that are produced using the baculovirus expression system and that requires no prior purification of the protein of interest. Crude lysates prepared from cultured Sf9 insect cells infected with recombinant or control baculoviruses are absorbed to nitrocellulose filters and used in a dot-immunobinding assay for screening hybridomas. The monoclonal antibody-producing hybridomas are derived by immunization of mice with a synthetic peptide corresponding to a hydrophilic region in the recombinant protein of interest. By using the baculovirus-produced recombinant protein as the screening antigen and by comparing antibody binding to filters containing control Sf9 lysates, hybridomas are identified that produce monoclonal antibodies with specific reactivity for the recombinant protein of interest and that can then subsequently be used to assist in the large-scale purification of the recombinant protein from baculovirus-infected cells. We applied this method to recombinant 26-kDa human Bcl-2 (B-cell lymphoma/leukemia-2), an integral membrane oncoprotein that regulates programmed cell death ("apoptosis") in hematolymphoid cells through unknown mechanisms. Two mouse monoclonal antibodies were produced that specifically bound the recombinant Bcl-2 baculoprotein in both solution and solid-phase assays.

Amino Acid Sequence↗
PubMed1992

Locoregional disease.

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Combined Modality Therapy↗
PubMed1992

Duplicate publication.

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Duplicate Publications as Topic↗
PubMed1992

3-amino-1,2,4-triazole inhibits macrophage NO synthase.

Murine macrophages activated by interferon-gamma and lipopolysaccharide become leishmanicidal through a process involving L-arginine-derived nitrogen oxidation products. Both nitrite secretion and parasite killing by activated macrophages were inhibited by 3-amino-1,2,4-triazole as well as the related compound, 3-amino-1,2,4-triazine. Moreover, NO synthase activity in cytosolic extracts of activated cells was inhibited by both compounds. 4-amino-1,2,4-triazole, an isomer of 3-amino-1,2,4-triazole, was without effect. Our results suggest that besides its known inhibitory effect on catalases and peroxidases, 3-amino-1,2,4-triazole is an inhibitor of NO synthase. The resemblance between the tautomeric form of 3-amino-1,2,4-triazole and the guanidino group of L-arginine, the natural substrate for NO synthase, might be responsible for the observed inhibition.

Amino Acid Oxidoreductases↗
PubMed1992

Polymerase chain reaction-aided analysis of gene expression in frozen tissue sections.

A simple method for the detection and localization of mRNA in single frozen breast biopsy tissue sections is described. Several extraction procedures were compared. Resuspending sections, which could be left at 0 or -70 degrees C for up to 20 min in H2O containing RNAse inhibitor, optimally released RNA with minimal DNA contamination. Reverse transcription followed by polymerase chain reaction amplification using specific primers yielded products visible by ethidium bromide staining (abundant sequences) or after Southern blotting (low copy message). We found that it was possible, by microdissection, to separate stromal and tumor cells and demonstrated differential expression of several genes in the two populations. With 40 cycles of amplification, dissected stromal and tumor tissue both yielded products encoding glyceraldehyde 3'-phosphate dehydrogenase but only the tumor cells gave products with primers specific for either keratin 19, heat shock protein 89 alpha or the fig oncogene, which encodes one of the fibroblast growth factor receptors that we have recently found to be expressed in breast cancers. With refinement of the dissection technique this offers a very sensitive analytical tool for measuring and defining the cellular sites of synthesis of low-abundance message, requiring only single histological sections.

Base Sequence↗
PubMed1992

The purified yeast pre-mRNA splicing factor PRP2 is an RNA-dependent NTPase.

Unlike autocatalyzed self-splicing reactions, nuclear pre-mRNA splicing requires transacting macromolecules and ATP. A protein encoded by the PRP2 gene of Saccharomyces cerevisiae is required, in conjunction with ATP, for the first cleavage-ligation reaction of pre-mRNA splicing. In this study, we have purified two forms of the PRP2 gene product with apparent molecular weights of 100 kDa and 92 kDa, from a yeast strain overproducing the protein. Both proteins were indistinguishable in their ability to complement extracts derived from a heat-sensitive prp2 mutant. Furthermore, we show that the PRP2 protein is capable of hydrolyzing nucleoside triphosphates in the presence of single-stranded RNAs such as poly(U). However, purified PRP2 by itself did not unwind double-stranded RNA substrates. The fact that an RNA-dependent NTPase activity is intrinsic to PRP2 may account for the ATP requirement in the first catalytic reaction of pre-mRNA splicing.

Adenosine Triphosphatases↗
PubMed1992

Phenotypic plasticity of avian embryonic sympathetic neurons grown in a chemically defined medium: direct evidence for noradrenergic and cholinergic properties in the same neurons.

Avian embryonic sympathetic ganglia possess both catecholaminergic and cholinergic features and can synthesize noradrenaline (NAd) and acetylcholine (ACh) simultaneously. In the present study we sought to determine (1) whether or not this coproduction of NAd and ACh corresponds to the existence of two non-overlapping populations, and (2) to what extent the levels of synthesis are influenced by non-neuronal ganglion cells. We have focused on the correlation between the immunocytochemically demonstrable presence of the noradrenergic and cholinergic enzymes tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT), respectively, and the synthesis of the corresponding neurotransmitters in embryonic quail sympathetic neuronal and non-neuronal cells purified by fluorescence-activated cell sorting. We show that (1) freshly sorted neurons synthesize both NAd and ACh, whereas non-neuronal cells produce neither; (2) the overwhelming majority of the sympathetic neurons display TH immunoreactivity; (3) about half of the TH-positive neurons are recognized by an anti-ChAT antibody in an artificial medium that selectively enhances synthesis and/or accumulation of ACh; (4) the non-neuronal cells are important for survival of the neurons and potentiate their synthesis of ACh in this medium, and (5) finally, we present evidence that expression of TH in noradrenergic neurons and in small intensely fluorescent cells of sympathetic ganglia is differentially regulated.

Animals↗