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Biomedical subjects

B L Smith

Publications and source records attributed to B L Smith.

At least 91 records · Page 5Linked to original sources
PubMed1997

Modification of calcite crystal growth by abalone shell proteins: an atomic force microscope study.

A family of soluble proteins from the shell of Haliotis rufescens was introduced over a growing calcite crystal being scanned in situ by an atomic force microscope (AFM). Atomic step edges on the crystal surface were altered in shape and speed of growth by the proteins. Proteins attached nonuniformly to the surface, indicating different interactions with crystallographically different step edges. The observed changes were consistent with the habit modification induced by this family of proteins, as previously observed by optical microscopy. To facilitate further studies in this area, AFM techniques and certain AFM imaging artifacts are discussed in detail.

Animals↗
PubMed1997

Carotid endarterectomy in patients less than 50 years old.

PURPOSE: The purpose of this study was to compare the results of carotid endarterectomy (CEA) in a young population with premature atherosclerosis with the results of an older control group, examining perioperative morbidity and mortality data, recurrent stenosis and symptoms, late stroke, and survival data. METHODS: We retrospectively studied 26 patients less than 50 years old (mean, 43.2 +/- 3.8 years) and 30 patients greater than 55 years old (mean, 69.1 +/- 7.4 years) who underwent CEA during the same time period. Data were obtained regarding demographics, atherosclerotic risk factors, indication for CEA, perioperative complications, recurrent stenosis and symptoms, late stroke, and survival. RESULTS: Smoking was more prevalent among young patients who underwent CEA (92% vs 70%; p = 0.036). Young patients were also more likely to be symptomatic at presentation (92% vs 57%; p = 0.003). The perioperative mortality rate (0% vs 0%) and neurologic morbidity rate (0% vs 3%; p = 1.000) were low for the study patients. During a mean follow-up of 67 +/- 42.7 months, there was no significant difference in survival rate (5-year survival rate, 93% vs 81%; p = 0.373), rate of late ipsilateral (4% vs 3%) and contralateral (4% vs 3%) stroke, restenosis and occlusion (26.9% vs 14.3%), recurrent symptoms (22% vs 17%), reoperation (11.5% vs 5.7%), or contralateral disease (17% vs 23%) development that required surgery for the study or the control cohorts. CONCLUSIONS: Our data show that there is a high incidence of smoking and symptomatic presentation among young patients in whom carotid occlusive disease develops. CEA may be performed in young patients with low perioperative morbidity and mortality rates. Recurrent disease, late stroke, and survival rates are not significantly different than for older patients. Follow-up with serial duplex ultrasound and reoperation for symptomatic and high-grade asymptomatic restenosis may decrease the risk of late stroke.

Adult↗
PubMed1997

Hepatogenous photosensitisation in fallow deer (Dama dama) in New Zealand.

An outbreak of hepatogenous photosensitisation occurred in fallow deer and was diagnosed as facial eczema on the basis of liver lesions and plasma enzyme changes over 56 weeks. Clinical signs of photosensitisation were not as obvious as they are in sheep and cattle. The condition occurred over autumn and in the following spring. Six of 23 deer died or were destroyed. Concentrations of plasma total bilirubin, total bile acids and cholesterol increased, as well as the activities of aspartate transaminase, glutamic dehydrogenase, lactic dehydrogenase, alkaline phosphatase and gamma glutamyltransferase. Albumin:globulin ratios declined due to moderate increases in globulin and minor reductions in albumin. Many of the plasma enzyme activities did not return to normal after autumn and increased to even higher values during the spring outbreak of photosensitisation. Minor plasma biochemical changes were also detected in non-photosensitive deer in the same herd.

Journal Article↗
PubMed1997

A zinc-containing intraruminal device for facial eczema control in lambs.

A zinc-containing intraruminal device has been developed for protecting lambs against facial eczema. The rate of release of zinc from the device has been optimised, and its safety in use established. Under both experimental and farm conditions, the device gave excellent protection against the liver injury associated with facial eczema. The device relies upon erosion for release of zinc, and disappears completely when its charge of zinc has been released, leaving no metal or plastic residue in the rumen. This device has the potential to greatly ameliorate the problem of facial eczema in New Zealand.

Journal Article↗
PubMed1997

Does information from axillary dissection change treatment in clinically node-negative patients with breast cancer? An algorithm for assessment of impact of axillary dissection.

OBJECTIVE: The authors assessed the impact of axillary dissection on adjuvant systemic therapy recommendations in patients with breast cancer. SUMMARY BACKGROUND DATA: With increasing use of systemic therapy in node-negative women and the desire to reduce treatment morbidity and cost, the need for axillary dissection in clinically node-negative patients with breast cancer has been challenged. METHODS: Two hundred eighty-two women with clinically negative axillae were analyzed using a model treatment algorithm. Systemic therapy was assigned with and without data from axillary dissection. Treatment shifts based on axillary dissection data were scored. RESULTS: Twenty-seven percent of clinically node-negative women had pathologically positive nodes. Eight percent of T1a and 10% of T1b tumors had positive nodes and would have been undertreated without axillary dissection. Seven percent of premenopausal women with tumors < 1 cm and 13% with tumors > or = 1 cm had treatment changed by axillary dissection. For women 50 to 60 years of age, 10% with tumors < 1 cm, 17% with tumors 1 to 2 cm with positive prognostic features, and 4% with poor prognostic features had significant treatment shifts after axillary dissection. For clinically node-negative women older than 60 years of age not eligible for chemotherapy, only 3% of those with tumors < 1 cm and none of those with tumors > or = 1 cm had their treatment changed by findings at axillary dissection. Treatment shifts based on axillary dissection were larger if the treatment algorithm allowed for more varied or more aggressive treatment options. CONCLUSIONS: Data obtained from axillary dissection will alter adjuvant systemic therapy regimen in a significant number of clinically node-negative women younger than 60 years of age and for older women eligible to receive chemotherapy.

Adult↗
PubMed1997

Dynamic echo-planar imaging of the breast: experience in diagnosing breast carcinoma and correlation with tumor angiogenesis.

PURPOSE: To correlate quantitative echo-planar magnetic resonance (MR) imaging measures of gadopentetate dimeglumine tumor uptake with histologic diagnoses and microvessel density (MVD) and to compare dynamic echo-planar imaging of breast lesions with conventional dynamic MR imaging techniques. MATERIALS AND METHODS: The study group comprised 63 patients (aged 13-70 years) with 71 breast lesions who underwent conventional and echo-planar MR imaging. The T1 values, change in gadopentetate dimeglumine concentration, and extraction-flow products were calculated with the echo-planar imaging data and were correlated with histologic findings and MVD estimates. Extraction-flow product data normalized to pectoral muscle gadopentetate dimeglumine concentration in invasive cancers was also correlated with MVD. RESULTS: On average, cancer T1 values were shorter than benign values, but there was substantial overlap between the two groups. Cancers had higher extraction-flow products than benign lesions (P < .001). Sensitivity, specificity, positive predictive value, and negative predictive value were 83%, 79%, 67%, and 90%, respectively. Receiver operating characteristic analysis showed improved performance with extraction-flow products than with percentages of signal intensity change. Among the invasive cancers, there was no significant correlation between extraction-flow product and MVD. CONCLUSION: The T1 value remains important in more precise quantitative estimation of gadopentetate dimeglumine uptake in breast tumors, which helps improve the specificity of dynamic imaging. Tumor MVD affects the contrast medium enhancement of breast lesions, but other factors contribute.

Breast↗
PubMed1997

Amebicidal activity of wild animal serum.

The sera of 16 species of wild animals representing 5 classes of vertebrates were assayed for amebicidal activity against species of Naegleria. The greatest activity was observed for sera of bullfrogs, muskrats, and raccoons, all of which are animals associated with water. In contrast, the sera from animals such as toads, box turtles, sparrows, and squirrels exhibited minimal or no amebicidal activity. In general, pathogenic Naegleria tended to be less susceptible than nonpathogenic Naegleria to the lytic effect of raccoon serum. Heat-inactivated serum was not amebicidal, suggesting that perhaps complement may be involved in the serum-mediated lysis of amebas.

Amebiasis↗
PubMed1996

Surface topographies at subnanometer-resolution reveal asymmetry and sidedness of aquaporin-1.

Aquaporin-1 (AQP1) is an abundant protein in human erythrocyte membranes which functions as a specific and constitutively active water conducting pore. Solubilized and isolated as tetramer, it forms well-ordered two-dimensional (2D) crystals when reconstituted in the presence of lipids. Several high resolution projection maps of AQP1 have been determined, but information on its three-dimensional (3D) mass distribution is sparse. Here, we present surface reliefs at 0.9 nm resolution that were calculated from freeze-dried unidirectionally metal-shadowed AQP1 crystals as well as surface topographs recorded with the atomic force microscope of native crystals in buffer solution. Our results confirm the 3D map of negatively stained AQP1 crystals, which exhibited tetramers with four major protrusions on one side and a large central cavity on the other side of the membrane. Digestion of AQP1 crystals with carboxypeptidase Y, which cleaves off a 5 kDa intracellular C-terminal fragment, led to a reduction of the major protrusions, suggesting that the central cavity of the tetramer faces the outside of the cell. To interpret the results, sequence based structure predictions served as a guide.

Aquaporin 1↗
PubMed1996

The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.

The aquaporin family of membrane water transport proteins are expressed in diverse tissues, and in brain the predominant water channel protein is AQP4. Here we report the isolation and characterization of the human AQP4 cDNAs and genomic DNA. Two cDNAs were isolated corresponding to the two initiating methionines (M1 in a 323-aa polypeptide and M23 in a 301-aa polypeptide) previously identified in rat [Jung, J.S., Bhat, R.V., Preston, G.M., Guggino, W.B. & Agre, P. (1994) Proc. Natl. Acad. Sci. USA 91, 13052-13056]. Similar to other aquaporins, the AQP4 gene is composed of four exons encoding 127, 55, 27, and 92 amino acids separated by introns of 0.8, 0.3, and 5.2 kb. Unlike other aquaporins, an alternative coding initiation sequence (designated exon 0) was located 2.7 kb upstream of exon 1. When spliced together, M1 and the subsequent 10 amino acids are encoded by exon 0; the next 11 amino acids and M23 are encoded by exon 1. Transcription initiation sites have been mapped in the proximal promoters of exons 0 and 1. RNase protection revealed distinct transcripts corresponding to M1 and M23 mRNAs, and AQP4 immunoblots of cerebellum demonstrated reactive polypeptides of 31 and 34 kDa. Using a P1 and a lambda EMBL subclone, the chromosomal site of the human AQP4 gene was mapped to chromosome 18 at the junction of q11.2 and q12.1 by fluorescence in situ hybridization. These studies may now permit molecular characterization of AQP4 during human development and in clinical disorders.

Alternative Splicing↗
PubMed1996

The HIV nef protein associates with protein kinase C theta.

Expression of the human immunodeficiency virus (HIV) Nef protein has been linked to both decreased cell surface expression of CD4 and an impairment of signal transduction. The recently reported association of Nef with an unidentified serine kinase provides a clue as to how Nef might exert its effects. Considering the key role of protein kinase C (PKC) in T cell activation, we investigated the possibility that Nef interacts with PKC. Our results, using two approaches for detecting interactions between Nef and PKC isozymes in Jurkat cells, show that Nef interacts preferentially with thetaPKC. The interaction of Nef and thetaPKC is independent of calcium, enhanced by phospholipid activators of PKC and not affected by a PKC pseudosubstrate peptide. Phorbol 12-myristate 13-acetate and phytohemagglutinin stimulation of Jurkat cells expressing Nef fails to produce the usual translocation of thetaPKC from the cytosol to the particulate fraction; translocation of betaPKC and epsilonPKC was unaffected. Indeed, there appears to be a net loss of thetaPKC in Nef-expressing cells following stimulation. The loss of thetaPKC, which may be a result of inhibition of its binding to RACKs due to Nef binding, could contribute to the various impairments of T cell function associated with HIV infection and Nef expression.

Biological Transport↗
PubMed1996

Functional analysis of aquaporin-1 deficient red cells. The Colton-null phenotype.

The aquaporin-1 (AQP1) water transport protein contains a polymorphism corresponding to the Colton red blood cell antigens. To define the fraction of membrane water permeability mediated by AQP1, red cells were obtained from human kindreds with the rare Colton-null phenotype. Homozygosity or heterozygosity for deletion of exon I in AQP1 correlated with total or partial deficiency of AQP1 protein. Homozygote red cell morphology appeared normal, but clinical laboratory studies revealed slightly reduced red cell life span in vivo; deformability studies revealed a slight reduction in membrane surface area. Diffusional water permeability (Pd) was measured under isotonic conditions by pulsed field gradient NMR. Osmotic water permeability (Pf) was measured by change in light scattering after rapid exposure of red cells to increased extracellular osmolality. AQP1 contributes approximately 64% (Pd = 1.5 x 10(-3) cm/s) of the total diffusional water permeability pathway, and lipid permeation apparently comprises approximately 23%. In contrast, AQP1 contributes > 85% (Pf = 19 x 10(-3) cm/s) of the total osmotic water permeability pathway, and lipid permeation apparently comprises only approximately 10%. The ratio of AQP1-mediated Pf to Pd predicts the length of the aqueous pore to be 36 A.

Aquaporin 1↗
PubMed1996

Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer.

BACKGROUND: Mutations in a germ-line allele of the BRCA1 gene contribute to the familial breast cancer syndrome. However, the prevalence of these mutations is unknown in women with breast cancer who do not have the features of this familial syndrome. We sought BRCA1 mutations in women who were given a diagnosis of breast cancer at an early age, because early onset is characteristic of a genetic predisposition to cancer. METHODS: Clinical information and peripheral-blood mononuclear cells were obtained from 418 women from the Boston metropolitan area in whom breast cancer was diagnosed at or before the age of 40. A comprehensive BRCA1 mutational analysis, involving automated nucleotide sequencing and a protein-truncation assay, was undertaken in 30 of these women, who had breast cancer before the age of 30. In addition, the BRCA1 mutation 185delAG, which is prevalent in the Ashkenazi Jewish population, was sought with an allele-specific polymerase-chain-reaction assay in 39 Jewish women among the 418 women who had breast cancer at or before the age of 40. RESULTS: Among 30 women with breast cancer before the age of 30, 4 (13 percent) had definite, chain-terminating mutations and 1 had a missense mutation. Two of the four Jewish women in this cohort had the 185delAG mutation. Among the 39 Jewish women with breast cancer at or before the age of 40, 8 (21 percent) carried the 185delAG mutation (95 percent confidence interval, 9 to 36 percent). CONCLUSIONS: Germ-line BRCA1 mutations can be present in young women with breast cancer who do not belong to families with multiple affected members. The specific BRCA1 mutation known as 185delAG is strongly associated with the onset of breast cancer in Jewish women before the age of 40.

Adult↗
PubMed1996

Mechanism of bracken fern carcinogenesis: evidence for H-ras activation via initial adenine alkylation by ptaquiloside.

Bracken fern (Pteridium spp.) causes cancer of the oesophagus and the urinary bladder in cattle and sheep. Ptaquiloside (PT) is believed to be the carcinogenic principle which alkylates DNA when activated to its unstable dienone form (APT) under alkaline conditions. In this report we present evidence for the presence of PT-DNA adducts in the ileum of bracken fem-fed calves using the 32P-postlabelling assay. H-ras mutations were also observed in the ileum using single strand conformation polymorphism (SSCP) technique. Mutations corresponding to adenine to pyrimidine transversions in the codon 61 of H-ras were identified by the cycle sequencing method. In vitro DNA alkylation studies showed that APT alkylated H-ras primarily at the adenines. In addition, the rate of depurination of alkylated adenine was sequence dependent. Investigation of DNA template activity using a plasmid DNA showed that DNA synthesis by T7 DNA polymerase was terminated by the presence of all alkylated bases but certain apurinic sites allowed the DNA synthesis to continue. These results suggest that initial alkylation of adenine by PT in codon 61 followed by depurination and error in DNA synthesis lead to activation of H-ras proto-oncogene.

Adenine↗
PubMed1996

Toxic and antibiotic properties of red thread, Laetisaria fuciformis.

An isolate of Laetisaria fuciformis in axenic culture did not produce toxic metabolites in concentrations sufficient to affect rats or sheep or mammalian cells in tissue culture, nor did it produce ergot alkaloids, paxilline or zearalenone in amounts detectable by ELISA. It did produce diffusable compound(s) inhibitory to a range of Gram-positive and -negative bacteria but not to the mould species tested.

Animal Feed↗
PubMed1996

Perception of breast cancer risk among women in breast center and primary care settings: correlation with age and family history of breast cancer.

BACKGROUND: A great deal of information about breast cancer risk is available to the public. The accuracy of impressions formed from this information is unknown. METHODS: A total of 750 women attending a breast center and 112 women attending a primary care office completed written surveys of their perceptions of average population risk, personal lifetime risk, and personal 10-year risk of getting breast cancer. Data sufficient to apply the Gail model were obtained, and a calculated estimate of risk was generated. Ratios of perceived to calculated risk were correlated with the respondent's age, family history of breast cancer, and location in a breast center or primary care office. RESULTS: Women in both practice settings overestimated population risk by more than twofold. Eighty percent overestimated personal lifetime risk by more than 50% and 35% by more than fivefold. Only 7% significantly underestimated risk. Ten-year risk estimates were even more inaccurate, with 69% overestimating risk by more than fivefold, 46% by more than 10-fold, and 17% by more than 20-fold. Results from a primary care population were nearly identical. Women at the extremes of age were most inaccurate in estimating risk. It was surprising that family history had little impact on perception of personal risk. CONCLUSIONS: Women in both breast center and primary care settings have a fals:ly high perception of both short-term and long-term breast cancer risk. Health care providers should recognize these misconceptions and be aware that many women may benefit from risk counseling.

Adult↗