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Biomedical subjects

B L Smith

Publications and source records attributed to B L Smith.

At least 73 records · Page 4Linked to original sources
PubMed1999

Economic impact of automated primary screening for cervical cancer.

OBJECTIVE: To construct a markovian model to project the marginal cost of the AutoPap System as compared to manual cervical cytologic screening. STUDY DESIGN: Data from a clinical trial and published literature were entered into a seven-state markovian decision-analytic model to estimate the marginal cost per year of life saved that could be attributed to changes in primary screening technology. RESULTS: Annual screening with AutoPap produced a meaningful increase in life expectancy of 32.1 days relative to manual screening at a marginal savings of $628 per person (or a marginal savings of $7,144 per life-year saved). Less frequent screening yielded lower positive savings. CONCLUSION: Automated screening for cervical cancer has the potential to significantly improve health care outcomes and reduce cost.

Adolescent↗
PubMed1999

Effect of bracken (Pteridium a quilinum) and dryopteris (Dryopteris juxtaposita) fern toxicity in laboratory rabbits.

Experimental studies with Bracken and Dryopteris ferns @ 25% concentrate ration mixture were conducted in rabbits. Fern fed rabbits showed progressive anaemia, leukopaenia, lymphopaenia and relative heterophilia. Significant elevations in serum enzymes like serum glutamate oxaloactate transminase (SGOT), serum glutamate pyruvate transminase (SGPT), alkaline phosphatase (ALP), urea and creatinine levels were seen. Histopathologically, rabbits showed mild to moderate vascular changes in most of visceral organs, vacuolar degenerative changes in hepatocytes, hypersecretory activity in intestine, presence of casts in renal tubules and degenerative changes in renal tubular lining epithelial cells. Dryopteris fed rabbits showed somewhat more severe degenerative and vascular changes in different intervals. A low level of toxic principle ptaquiloside was detected in Bracken and Dryopteris ferns by thin layer chromatography (TLC) and high-pressure liquid chromatography (HPLC) methods.

Animals↗
PubMed1998

Births and deaths: preliminary data for 1997.

OBJECTIVES: This report presents preliminary data on births and deaths in the United States from the National Center for Health Statistics (NCHS) for 1997. U.S. data on births are shown by age, race, and Hispanic origin of mother. National and State data on marital status, prenatal care, cesarean delivery, and low birthweight are also presented. Mortality data presented include life expectancy, leading causes of death, and infant mortality. METHODS: Data in this report are based on a 99 percent sample of births and more than an 85 percent sample of deaths in the United States in 1997. The records are weighted to independent control counts of births, infant deaths, and deaths 1 year and over received in State vital statistics offices in 1997. RESULTS: According to preliminary data for 1997, the birth rate for teenagers dropped to 52.9 births per 1,000 women aged 15-19 years, 3 percent lower compared with 1996. Birth rates for teenagers have been declining since 1991. Declines for younger teenagers (15-17 years) were greater than for older teenagers. Birth rates for women aged 25-44 years increased 1 to 2 percent; the rate for women aged 20-24 years rose very slightly. The number of births to unmarried women was essentially unchanged and the percent of all births to unmarried women remained at 32.4 percent; the birth rate for unmarried women declined 2 percent. The rate of prenatal care utilization continued to improve. The cesarean delivery rate increased slightly. The overall low birthweight rate increased to 7.5 percent. The largest declines in estimated age-adjusted death rates among the leading causes of death were for Human immunodeficiency virus (HIV) infection (47 percent) and homicide (12 percent). Mortality also decreased for firearm injuries, drug-induced deaths, and alcohol-induced deaths. The age-adjusted death rate increased for Pneumonia and influenza, Chronic obstructive pulmonary diseases, kidney disease, and Septicemia. The preliminary infant mortality rate for 1997 was 7.1 infant deaths per 1,000 live births, down from a rate of 7.3 for 1996. The infant mortality rate for black infants declined 7 percent to 13.7; the white rate was 6.0. Life expectancy reached a record high of 76.5 years in 1997.

Adolescent↗
PubMed1998

H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: comparison of acute and chronic toxicity in rats.

Bracken fern (Pteridium spp.) produces cancer of the urinary bladder and oesophagus in grazing animals and is a suspected human carcinogen. The carcinogenic principle ptaquiloside (PT), when activated to a dienone (APT), forms DNA adducts which eventually leads to tumor. Two groups of female Sprague-Dawley rats were given a chronic dose of 3 mg APT weekly for 10 weeks either by intravenous (i.v.) tail vein or by intragastric (i.g.) route. A third group was given a weekly dose of 6 mg of APT for 3 weeks by the i.g. route corresponding to acute dosing. Both chronic i.v. and i.g. dosed animals showed ischemic tubular necrosis in the kidney but only i.v. dosed animals developed adenocarcinomas of the mammary glands. Acutely dosed i.g. animals produced apoptotic bodies in the liver, necrosis of blood cell precursors in the bone marrow and ischemic tubular necrosis in the kidney but they did not develop tumors. No mutations were found in the H-ras and p53 genes in the mammary glands of either the i.g. rats or the tumor-bearing i.v. rats. However, the mammary glands of a fourth group of rats, which received APT by i.v. and killed before tumor development, carried Pu to Pu and Pu to Py double mutations in codons 58 and 59 of H-ras. This study indicates that the route of administration plays a role in the nature of the disease expression from ptaquiloside exposure. In addition to confirming the role of APT in the PT-induced carcinogenesis our finding suggests that activation of H-ras is an early event in the PT-carcinogenesis model.

Animals↗
PubMed1998

Bracken fern carcinogenesis: multiple intravenous doses of activated ptaquiloside induce DNA adducts, monocytosis, increased TNF alpha levels, and mammary gland carcinoma in rats.

AIMS: (1) establish a rat model for investigating ptaquiloside (PT) carcinogenesis via intravenous dosing; (2) determine the role of activated PT (APT) in this model; and (3) monitor changes at molecular (DNA adducts, TNF alpha levels) and cellular (histopathology) levels. METHODS: Sprague-Dawley rats were dosed with PT or APT intravenously for 10 consecutive weeks. One group of animals was sacrificed immediately for TNF alpha and DNA adduct analyses. A second group of animals was kept alive for 30 more weeks to allow for tumour formation. Tissues were collected at the end of the experiment for histopathological studies. RESULTS: Rats dosed with PT or APT showed marked increase in monocyte and TNF alpha levels. These levels remained high even 30 weeks after the last dosing. Analysis of DNA showed the presence of DNA adducts in APT-treated animals in target organs. In addition, 40% of APT-treated rats developed mammary gland carcinomas. CONCLUSION: This is the first study to demonstrate the potential of activated PT as a carcinogen in vivo. In addition, our findings suggest that PT exposure can be monitored using monocyte and TNF alpha levels.

Adenocarcinoma↗
PubMed1998

Effects of butylated hydroxyanisole and dicoumarol on the toxicity of menadione to rats.

The enzyme DT-diaphorase catalyses the 2-electron reduction of quinones. This reaction may facilitate the detoxification of such compounds, since the hydroquinone so formed can be converted into non-toxic conjugates. There is evidence for the involvement of DT-diaphorase in the detoxification of menadione (2-methyl-1,4-naphthoquinone) in a wide range of cells and tissues in vitro, but no information is available on the possible influence of this enzyme on the harmful effects of menadione in vivo. In animals, menadione is selectively toxic to erythrocytes, causing haemolytic anaemia. In the present study, rats were treated with dicoumarol, an inhibitor of DT-diaphorase, or butylated hydroxyanisole (BHA), a substance that increases the activity of this enzyme in vivo. They were then challenged with a toxic dose of menadione. Dicoumarol increased the severity of menadione-induced haemolytic anaemia while BHA decreased it, consistent with a role for DT-diaphorase in the detoxification of menadione in vivo, as previously described in vitro.

Anemia, Hemolytic↗
PubMed1998

Evaluating human breast ductal carcinomas with high-resolution magic-angle spinning proton magnetic resonance spectroscopy.

We report the results of a study of human breast ductal carcinomas, conducted by using high resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1HMRS). This recently developed spectroscopic technique can measure tissue metabolism from intact pathological specimens and identify tissue biochemical changes, which closely correspond to tumor in vivo state. This procedure objectively indicates diagnostic parameters, independent of the skill and experience of the investigator, and has the potential to reduce the sampling errors inherently associated with procedures of conventional histopathology. In this study, we measured 19 cases of female ductal carcinomas. Our results demonstrate that: (1) highly resolved spectra of intact specimens of human breast ductal carcinomas can be obtained; (2) carcinoma-free tissues and carcinomas are distinguishable by alterations in the intensities and the spin-spin relaxation time T2 of cellular metabolites; and (3) tumor metabolic markers, such as phosphocholine, lactate, and lipids, may correlate with the histopathological grade determined from evaluation of the adjacent specimen. Our results suggest that biochemical markers thus measured may function as a valuable adjunct to histopathology to improve the accuracy of and reduce the time frame required for the diagnosis of human breast cancer.

Adult↗
PubMed1998

An audit of therapeutic drug monitoring service provision by laboratories participating in an external quality assessment scheme.

Therapeutic drug monitoring services were investigated in a questionnaire sent to all subscribers to the United Kingdom National External Quality Assessment Scheme for Therapeutic Drug Assays. Questions were posed on assay availability and use, target ranges, and reporting procedures for digoxin, lithium, phenytoin, phenobarbitone, carbamazepine, theophylline, and valproic acid. One hundred fifty-seven laboratories replied and, except for lithium, 45% reported in mass units, 34% in molar units, and 22% a mixture of mass and molar units. Target ranges for lithium, digoxin, carbamazepine, and phenobarbitone were highly variable but ranges for phenytoin, theophylline, and valproic acid were more consistent. Immunoassay was the most popular methodology although high-performance liquid chromatography was commonly used for anticonvulsants. Paper copies of results were provided by 93% of laboratories, 40% reported by telephone, 12% by fax, and 28% by computer. Additional data, mainly dose, time of last dose, and duration of therapy were requested by 55% to 67% of laboratories. Grades of staff authorizing results ranged from nurses to senior consultants, and collaboration with pharmacists occurred in 26% of laboratories. Most laboratories provided a daily analytical service and 73% offered a 24-hour emergency service. This audit unexpectedly identified use of a wide range of target concentrations, particularly for digoxin and lithium.

Drug Monitoring↗
PubMed1998

Aquaporin-1 and endothelial nitric oxide synthase expression in capillary endothelia of human peritoneum.

Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endothelium of the peritoneum and is impaired in the case of peritoneal inflammation. The water channel aquaporin (AQP)-1 has been proposed to be the ultrasmall pore in animal models. To substantiate the role of AQP-1 in the human peritoneum, we investigated the expression of AQP-1, AQP-2, and endothelial nitric oxide synthase (eNOS) in 19 peritoneal samples from normal subjects (n = 5), uremic patients treated by hemodialysis (n = 7) or PD (n = 4), and nonuremic patients (n = 3), using Western blotting and immunostaining. AQP-1 is very specifically located in capillary and venule endothelium but not in small-size arteries. In contrast, eNOS is located in all types of endothelia. Immunoblot for AQP-1 in human peritoneum reveals a 28-kDa band (unglycosylated AQP-1) and diffuse bands of 35-50 kDa (glycosylated AQP-1). Although AQP-1 expression is remarkably stable in all samples whatever their origin, eNOS (135 kDa) is upregulated in the three patients with ascites and/or peritonitis (1 PD and 2 nonuremic patients). AQP-2, regulated by vasopressin, is not expressed at the protein level in human peritoneum. This study 1) supports AQP-1 as the molecular counterpart of the ultrasmall pore in the human peritoneum and 2) demonstrates that AQP-1 and eNOS are regulated independently of each other in clinical conditions characterized by peritoneal inflammation.

Adolescent↗
PubMed1998

Expression of the Rh-related glycoprotein (Rh50).

The Rh50 glycoprotein is suspected of being involved in Rh antigen expression. We prepared Rh50 cDNA from a human bone marrow library by polymerase chain reaction and then subcloned this cDNA into various vectors. The vector containing Rh50 cDNA produced a 30-kDa nonglycosylated form of Rh50 in a rabbit reticulocyte lysate system and produced partially glycosylated Rh50 (32 kDa) when microsomes were added to the system. COS-1 cells transiently transfected with the vector containing Rh50 cDNA produced partially glycosylated Rh50 (32 kDa) recognized by a Rh50-specific antibody. Surface expression of Rh50 in K562 cells was also detected by flow cytometry using mouse monoclonal antibody (2D10) specific to Rh50. Partially glycosylated Rh50 (32 kDa) was again isolated from the lysates of K562 cells metabolically labeled with [35S]-methionine or [3H]-mannose using anti-Rh50 antisera. These systems (K562 and COS-1 cells) should prove useful for studying the transport of Rh proteins within the cell and the necessary components needed for Rh antigenicity at the cell surface.

Animals↗
PubMed1998

Sex differences in exercise motivation and body-image satisfaction among college students.

The current study was an expansion of one by Cash, Novy, and Grant in 1994, in which responses of 101 female nursing students were examined for associations between reasons for exercise, frequency of exercise, and body-image satisfaction. In the current study, 78 male and 100 female undergraduates between the ages of 18 and 25 years (M = 21.2, SD = 1.9) from various majors completed a demographics/frequency of exercise survey, two body-assessment inventories, and the Reasons for Exercise Inventory of Silberstein, Striegel-Moore, Timko, and Rodin. Contrary to Cash, et al.'s findings, only health and fitness reasons were predictive of women's frequency of exercise, and women's dissatisfaction with specific bodily attributes was not significantly related to any reasons for exercising; however, like women in their sample, the current students who experienced more situational body dissatisfaction exercised for appearance and weight control. Sex comparisons indicated similar dissatisfaction with specific bodily attributes among men and women, but values were not significantly associated with any reasons for exercising. Women reported higher situational body dissatisfaction and exercising for appearance-related reasons more than men. Current participants may represent a more diverse group than previously tested, and the inventory's factor structure may not be generalizable to men and women.

Adolescent↗
PubMed1998

Relationship between the Wide Range Achievement Test 3 and the Wechsler Individual Achievement Test.

The present study examined the relationship between the Wide Range Achievement Test 3 and the Wechsler Individual Achievement Test for a sample of children with learning disabilities in two rural school districts. Data were collected for 87 school children who had been classified as learning disabled and placed in special education resource services. Pearson product-moment correlations between scores on the two measures were significant and moderate to high; however, mean scores were not significantly different on Reading, Spelling, and Arithmetic subtests of the Wide Range Achievement Test 3 compared to those for the basic Reading, Spelling, and Mathematics Reasoning subtests of the Wechsler Individual Achievement Test. Although there were significant mean differences between scores on Reading and Reading Comprehension and on Arithmetic and Numerical Operations, magnitudes were small. It appears that the two tests provide similar results when screening for reading, spelling, and arithmetic.

Achievement↗
PubMed1997

The three-dimensional structure of aquaporin-1.

The entry and exit of water from cells is a fundamental process of life. Recognition of the high water permeability of red blood cells led to the proposal that specialized water pores exist in the plasma membrane. Expression in Xenopus oocytes and functional studies of an erythrocyte integral membrane protein of relative molecular mass 28,000, identified it as the mercury-sensitive water channel, aquaporin-1 (AQP1). Many related proteins, all belonging to the major intrinsic protein (MIP) family, are found throughout nature. AQP1 is a homotetramer containing four independent aqueous channels. When reconstituted into lipid bilayers, the protein forms two-dimensional lattices with a unit cell containing two tetramers in opposite orientation. Here we present the three-dimensional structure of AQP1 determined at 6A resolution by cryo-electron microscopy. Each AQP1 monomer has six tilted, bilayer-spanning alpha-helices which form a right-handed bundle surrounding a central density. These results, together with functional studies, provide a model that identifies the aqueous pore in the AQP1 molecule and indicates the organization of the tetrameric complex in the membrane.

Animals↗
PubMed1997

Cloning and chromosomal localization of mouse aquaporin 4: exclusion of a candidate mutant phenotype, ataxia.

Aquaporin-4 is a mammalian water channel protein that is predominately expressed in brain, where it is believed to mediate water homeostasis. Here we report the isolation and characterization of the cDNA for mouse Aqp4 and map the gene to the proximal region of mouse chromosome 18. This region contains the neurological mutation ataxia, but further analysis reveals that Aqp4 is not responsible for the ataxia phenotype.

Amino Acid Sequence↗
PubMed1997

Escherichia coli RNA polymerase activity observed using atomic force microscopy.

Fluid tapping-mode atomic force microscopy (AFM) was used to observe Escherichia coli RNA polymerase (RNAP) transcribing two different linear double-stranded (ds) DNA templates. The transcription process was detected by observing the translocation of the DNA template by RNAP on addition of ribonucleoside 5'-triphosphates (NTPs) in sequential AFM images. Stalled ternary complexes of RNAP, dsDNA and nascent RNA were adsorbed onto a mica surface and imaged under continuously flowing buffer. On introduction of all four NTPs, we observed some DNA molecules being pulled through the RNAP, some dissociating from the RNAP and others which did not move relative to the RNAP. The transcription rates were observed to be approximately 0.5-2 bases/s at our NTP concentrations, approximately 5 microM. The RNA transcripts were not unambiguously imaged in fluid. However, in experiments using a small single-stranded (ss) circular DNA template, known as a rolling circle, transcripts up to 1 or 2 microns long could be observed with tapping mode AFM once the samples were dried and imaged in air. This confirmed our observations of the transcriptional activity of RNAP adsorbed onto mica. This work illustrates that the development of tapping-mode in fluid has made it possible to use AFM to follow biological processes at the molecular level and get new insights about the variability of activity of individual molecules bound to a surface.

Aluminum Silicates↗
PubMed1997

Visualization of poly(A)-binding protein complex formation with poly(A) RNA using atomic force microscopy.

Poly(A)-binding protein (PABP) is an RNA-binding protein that binds specifically to the poly(A) tail of messenger RNAs in eukaryotes. The PABP/poly(A) tail complex has been implicated as being important in promoting the efficient initiation of translation as well as in maintaining the integrity of the mRNA. PABP binds poly(A) cooperatively with a packing density of one PABP molecule per 25 adenosine residues. We have investigated the complexes formed between purified PABP and poly(A) RNA using atomic force microscopy (AFM). PABP alone was observed to be primarily in a monomer form with a height of 1.0 +/- 0.2 nm. Following binding to poly(A), PABP appeared to be present in variable size complexes that bound lengthwise along the RNA. This size of the PABP/poly(A) complex appeared to be maximal, suggesting that PABP binding to poly(A) may be self-limiting. Poly(A) RNA alone appeared to contain a knob-like structure that largely disappeared once PABP was bound. The use of AFM has therefore provided potential new insights into the complexes formed by this RNA-binding protein.

Aluminum Silicates↗