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Biomedical subjects

M K Smith

Publications and source records attributed to M K Smith.

At least 19 recordsLinked to original sources
PubMed2003

Human coronavirus 229E: receptor binding domain and neutralization by soluble receptor at 37 degrees C.

Truncated human coronavirus HCoV-229E spike glycoproteins containing amino acids 407 to 547 bound to purified, soluble virus receptor, human aminopeptidase N (hAPN). Soluble hAPN neutralized the infectivity of HCoV-229E virions at 37 degrees C, but not 4 degrees C. Binding of hAPN may therefore trigger conformational changes in the viral spike protein at 37 degrees C that facilitate virus entry.

Amino Acid Sequence↗
PubMed2002

In vitro and in vivo efficacy of photofrin and pheophorbide a, a bacteriochlorin, in photodynamic therapy of colonic cancer cells.

This study was designed to investigate the efficacy of photodynamic therapy (PDT) in treating colonic cancer in a preclinical study. Photofrin, a porphyrin mixture, and pheophorbide a (Ph a), a bacteriochlorin, were tested on HT29 human colonic tumor cells in culture and xenografted into athymic mice. Their pharmacokinetics were investigated in vitro, and the PDT efficacy at increasing concentrations was determined with proliferative, cytotoxic and apoptotic assessments. The in vivo distribution and pharmacokinetics of these dyes (30 mg/kg, intraperitoneal) were investigated on HT29 tumor-bearing nude mice. The inhibition of tumor growth after a single 100 J/cm2 PDT session was measured by the changes in tumor volume and by histological analysis of tumor necrosis. PDT inhibited HT29 cell growth in culture. The cell photodamage occurred since the time the concentrations of Ph a and Photofrin reached 5.10(-7) M (or 0.3 microg/mL) and 10 microg/mL, respectively. A photosensitizer dose-dependent DNA fragmentation was observed linked to a cleavage of poly(ADP-ribose) polymerase and associated with an increased expression of mutant-type p53 protein. PDT induced a 3-week delay in tumor growth in vivo. The tumor injury was corroborated by histological observation of necrosis 48 h after treatment, with a correlated loss of specific enzyme expression in most of the tumor cells. In conclusion, PDT has the ability to destroy human colonic tumor cells in vitro and in vivo. This tumoricidal effect is likely associated with a p53-independent apoptosis, as HT29 cells express only mutated p53. The current study suggests a preferential use of Photofrin in PDT of colonic cancer because it should be more effective in vivo than Ph a as a consequence of better tumor uptake.

Animals↗
PubMed2001

[15]crown-5: an unsymmetrical bifacial hydrogen-bond acceptor in crystal engineering.

Reaction of [15]crown-5 with erbium nitrate and a range of nickel salts results in the formation of the hydrogen-bonded chain species [Er(NO3)3(H2O)3]. [15]crown-5 H2O (3), [Ni(H2O)6]Br2 [15]crown-5 2H2O (4), [Ni(H2O)6](ClO4)2 x [15]crown-5 2H2O (5), [Ni(H2O)6](NO3)2 [15]crown-5 2H2O (6) and [[Ni(H2O)4]2(muCl)2]Cl2 [15]crown-5 (7). Complexes 3-5 exhibit low symmetry structures with 2-4 unique crown ether molecules, whereas 6 and 7 are more symmetrical. The factors contributing to this behaviour are discussed within the wider context of [15]crown-5 structures in the Cambridge Structural Database.

Journal Article↗
PubMed2001

Telerobotic laparoscopic cholecystectomy: initial clinical experience with 25 patients.

OBJECTIVE: To determine the safety and feasibility of performing telerobotic laparoscopic cholecystectomies. This will serve as a preliminary step toward the integration of computer-rendered three-dimensional preoperative imaging studies of anatomy and pathology onto the patient's own anatomy during surgery. SUMMARY BACKGROUND DATA: Computer-assisted surgery (CAS) increases the surgeon's dexterity and precision during minimally invasive surgery, especially when using microinstruments. Clinical trials have shown the improved microsurgical precision afforded by CAS in the minimally invasive setting in cardiac and gynecologic surgery. Future applications would allow integration of preoperative data and augmented-reality simulation onto the actual procedure. METHODS: Beginning in September 1999, CAS was used to perform cholecystectomies on 25 patients at a single medical center in this nonrandomized, prospective study. The operations were performed by one of two surgeons who had previous laboratory experience using the computer interface. The entire dissection was performed by the surgeon, who remained at a distance from the patient but in the same operating room. The operation was evaluated according to time of dissection, time of assembly/disassembly of robot, complications, immediate postoperative course, and short-term follow-up. RESULTS: Twenty of the 25 patients had symptomatic cholelithiasis, 1 had a gallbladder polyp, and 4 had acute cholecystitis. Twenty-four of the 25 laparoscopic cholecystectomies were successfully completed by CAS. There was one conversion to conventional laparoscopic cholecystectomy. Set-up and takedown of the robotic arms took a median of 18 minutes. The median operative time for dissection and the overall operative time were 25 and 108 minutes, respectively. There were no intraoperative complications. There was one postoperative complication of a suspected pulmonary embolus, which was treated with anticoagulation. All patients were tolerating diet at discharge. CONCLUSIONS: Laparoscopic cholecystectomy performed by CAS is safe and feasible, with operative times and patient recovery similar to those of conventional laparoscopy. At present, CAS cholecystectomy offers no obvious advantages to patients, but the potential advantages of CAS lie in its ability to convert the surgical act into digitized data. This digitized format can then interface with other forms of digitized data, such as pre- or intraoperative imaging studies, or be transmitted over a distance. This has the potential to revolutionize the way surgery is performed.

Acute Disease↗
PubMed2001

Use of molecular markers to study the effects of environmental impacts on genetic diversity in brown bullhead (Ameirus nebulosus) populations.

Conservation biology needs sound biological information in order to maintain biological diversity in the face of the current rate of loss. An important component of the information needed is the level of genetic diversity within and between populations, especially for those species faced with exposure to environmental stressors. We applied multilocus DNA profile analysis (highly variable number tandem repeats [HVNTR] and randomly amplified polymorphic DNA [RAPD] techniques) and allozyme analysis to test whether individuals from historically degraded sites display levels of genetic diversity different from individuals taken from reference sites. Four Lake Erie tributaries, two impacted and two reference sites, were the sources of brown bullhead (Ameiurus nebulosus) samples. Pairwise comparison of the sampled populations demonstrated an association of decreased genetic diversity with exposure of brown bullhead to stressors using both RAPD and HVNTR analysis.

Animals↗
PubMed2000

Quantities and associations of lead, zinc, cadmium, manganese, chromium, nickel, vanadium, and copper in fresh Mississippi delta alluvium and New Orleans alluvial soils.

The topic of this study is the effect of anthropogenic metals on the geochemical quality of urban soils. This is accomplished by comparing the metal contents and associations between two alluvial soils of the lower Mississippi River Delta, freshly deposited alluvial parent materials and alluvial soils collected from a nearby urban environment. Fresh alluvium samples (n = 97) were collected from the Bonnet Carré Spillway. The urban alluvial soil samples (n = 4026) were collected from New Orleans and stratified by census tracts (n = 286). The Spillway samples tend to have less Pb and Zn than generally noted for the baseline of natural soils. Except for Mn and V, Spillway alluvium contains significantly less metal than urban soils. For Spillway samples, the median metal content (in microg g(-1)) is 4.7 Pb, 11.1 Zn, 0.7 Cd, 164 Mn, 0.8 Cr, 3.9 Ni, 3.2 V, and 3.9 Cu. For urban soils, the median metal content (in microg g(-1)) is 120 Pb, 130 Zn, 3.2 Cd, 138 Mn, 2.1 Cr, 9.8 Ni, 3.8 V, and 12.7 Cu. Metal associations also differ between Spillway alluvium and urban alluvial soils. Fresh alluvium correlation coefficients between individual metals vary from 0.87 to 0.99 (P < 10(-13)) except for Cr which ranges from 0.57 to 0.68 (P < 10(-7)). The urban soil correlation coefficients for metals and the index value are 0.40-0.98. In urban soils, Pb, Zn, Cr, and Cu are dominant metals and highly associated, with a correlation coefficient ranging from 0.83 to 0.98 (P < 10(-25)). Their strong association justifies the use of GIS to map the integrated soil metal index (sum of the medians of metals by census tract) of New Orleans. Although also positively correlated (0.40-0.68, P < 10(-10)), Cd, Mn, Ni and V differ in their distribution in the city compared to Pb, Zn, Cr and Cu. Overall, significantly higher metal values occur in the inner city and lower values occur in outlying areas. The human health impact of the mixture of metals is not well understood. This study provides empirical data about the mixture and distribution of metals in New Orleans alluvial soils. Given common technical development, especially of traffic flows in cities, similar patterns of soil metals are expected for all US cities and probably international cities as well. Primary prevention of urban metal accumulations is necessary to enhance and sustain the development of urban culture.

Cadmium↗
PubMed2000

A simplified pneumotachometer for the quantitative assessment of velopharyngeal incompetence.

By applying pipe flow rate mechanics, the authors have developed a simple and inexpensive device that can measure oral and nasal airflow and pressure quantitatively. It allows clinicians to document objectively the degree of velopharyngeal incompetence and nasal airway obstruction. This device is a modified U-manometer with a Y-connector to a collection bag. This prototype is being used in the authors' cleft palate clinic and they have found it useful in documenting quantitatively the amount of nasal air escape from either nostril with the corresponding pressure and flow. The primary measurement, which is reproducible and reliable, is the product of a cross-sectional area of oronasal communication and the pressure differential between the oral and nasal cavity. With some modifications, this device can be adapted to estimate the size of the oronasal communication.

Airway Obstruction↗
PubMed1999

The urban environment and children's health: soils as an integrator of lead, zinc, and cadmium in New Orleans, louisiana, U.S.A.

Soils are evaluated as a diagnostic tool of environmental conditions that influence health. The samples for this study are urban topsoil (0-2.5 cm depth) samples (n=4026) analyzed for Pb, Zn, and Cd by inductively coupled plasma-atomic emission spectrometry (ICP-AES). The parent materials for New Orleans soils are derived from the Mississippi River, and alluvium from the Bonnet Carré Spillway (n=31) serve as control samples for this study. The urban samples were stratified by census tract (n=286). Blood Pb (BL) levels of children </=6 years were also stratified by census tract and paired with soil Pb (SL) (n=175). A significant association (P=1.2x10(-23)) was found between median BL and median SL. The association was modeled by BL=3.06+0.33 (SL)(0.5) (correlation coefficient=0.69 between the modeled BL and the observed BL and P=3.5x10(-22)). A median SL threshold (>/=310 microgram g(-1) and <310 microgram g(-1)) for higher metal census tracts (HMCTs) and lower metal census tracts (LMCTs), respectively, represents median BL exposures above and below 9 microgram dL(-1). HMCTs and LMCTs were characterized by demographic and socioeconomic data. HMCTs are more likely (P=4. 5x10(-6)) inhabited by Blacks than by Whites. Of 13,803 children </=6 years in HMCTs, 75% are Black and 22% are White, with other making up the remaining 3%. In LMCTs, the Black to White children ratio is 50:50. In HMCTs, socioeconomic indicators for Blacks are depressed compared to Whites. Zn and Cd are potentially phytotoxic in HMCTs. Children exhibit a steep rise in BL at SL <100 microgram g(-1), and empirically, a safe SL for most children is around 80 microgram++ g(-1). SL is a useful diagnostic tool, and curtailing SL may complement primary Pb prevention for children.

Cadmium↗
PubMed1999

Hypothesis testing with the similarity index.

Multilocus DNA fingerprinting methods have been used extensively to address genetic issues in wildlife populations. Hypotheses concerning population subdivision and differing levels of diversity can be addressed through the use of the similarity index (S), a band-sharing coefficient, and many researchers construct hypothesis tests with S based on the work of Lynch. It is shown in the present study, through mathematical analysis and through simulations, that estimates of the variance of a mean S based on Lynch's work are downwardly biased. An unbiased alternative is presented and mathematically justified. It is shown further, however, that even when the bias in Lynch's estimator is corrected, the estimator is highly imprecise compared with estimates based on an alternative approach such as 'parametric bootstrapping' of allele frequencies. Also discussed are permutation tests and their construction given the interdependence of Ss which share individuals. A simulation illustrates how some published misuses of these tests can lead to incorrect conclusions in hypothesis testing.

DNA Fingerprinting↗
PubMed1999

Genetic diversity of Typha latifolia (Typhaceae) and the impact of pollutants examined with tandem-repetitive DNA probes.

Genetic diversity at variable-number-tandem-repeat (VNTR) loci was examined in the common cattail, Typha latifolia (Typhaceae), using three synthetic DNA probes composed of tandemly repeated "core" sequences (GACA, GATA, and GCAC). The principal objectives of this investigation were to determine whether: (1) the previously reported almost complete lack of polymorphism at allozyme loci in this species was indicative of a reduced amount of genetic diversity at VNTR loci as well; (2) VNTR markers were informative about possible clonal propagation; and (3) significant differences in genetic structure of sampling sites were associated with differences in environmental levels of pollutants at those sites. Previously, widespread sampling across the eastern United States, surveying across ten allozyme loci, has detected only two genotypes, involving a difference at a single locus, among 104 populations. In this study, the amount of genetic diversity detected at VNTR loci: (1) among ramets (N = 40; 40 genotypes detected) collected at ∼8-km intervals along a 320-km transect; (2) among ramets (N = 220; 117 genotypes detected) from five study sites separated by 50-3000 m; and (3) even among ramets within each study site [N = 44 per site; from 13 to 34 genotypes detected per site (270 m(2))] exceeds that previously found in those more geographically widespread allozyme surveys. Among the 260 ramets analyzed here, the mean number of bands scored per individual was 48.61 (SD = 2.80). Mean genetic similarity among ramets collected along the 320-km transect was 0.91, which was within the range of mean genetic similarity within the five study sites (range: 0.89-0.95). Among the five study sites, 61% of the samples analyzed appeared to be clonal ramets, with up to 12 clones detected for 44 ramets sampled within a site. Clones grew intermingled and ranged up to 39 m in extent. Permutation tests of genetic similarity revealed significant genetic differentiation between each of the five study sites. Consistent with the previous allozyme studies, T. latifolia was characterized by extremely low genetic variation relative to levels of polymorphism detected at VNTR loci in other plant species. Estimated heterozygosity among ramets along the 320-km transect ranged from 0.11 to 0.13, while that within the five study sites ranged from 0.05 to 0.12. Estimates of F(st) (0.32-0.41) also indicated considerable genetic subdivision among these stands. Significantly higher genetic diversity was detected at the two study sites that chemistry and toxicity data indicate to be the most severely impacted by pollutants. Although this correlation does not establish cause and effect, the results of this study indicate that the analysis of genetic diversity at VNTR loci may be a useful tool for monitoring anthropogenic-induced changes in the genetic structure of natural populations of plants.

Journal Article↗
PubMed1999

Effect of elevated levels of ornithine decarboxylase on cell cycle progression in skin.

By crossing TG.AC v-Ha-ras and K6/ODC transgenic mice, we found previously that an activated ras and follicular ornithine decarboxylase (ODC) overexpression cooperate to generate spontaneous tumors in the skin. Cellular proliferation was dramatically increased in the K6/ODC transgenic skin, as evidenced by elevated proliferating cell nuclear antigen and Ki67 expression compared with nontransgenic littermates. Keratinocytes isolated from transgenic skin also displayed increased clonal growth. Paradoxically, expression of the growth inhibition-associated proteins p53, p21Waf1, p27Klp1, and Bax was increased with ODC overexpression in the skin. ODC overexpression did not affect cyclin D/cyclin-dependent kinase 4 (Cdk4)-dependent phosphorylation of retinoblastoma protein but stimulated cyclin E/Cdk2 and cyclin A/Cdk2-associated kinase activity, with minimal effect on the levels of these proteins. Thus, ODC/polyamine-induced activation of cyclin E/Cdk2 and cyclin A/Cdk2-associated kinase activity may cooperate with the ras induction of cyclin D/Cdk4/6-associated retinoblastoma protein phosphorylation to not only stimulate proliferation but ultimately contribute to tumor development.

Animals↗
PubMed1998

Induction by alkaloids and phenobarbital of Family 4 Cytochrome P450s in Drosophila: evidence for involvement in host plant utilization.

In vertebrates, cytochrome P450s of the CYP2 and CYP3 families play a dominant role in drug metabolism, while in insects members of the CYP6 and CYP28 families have been implicated in metabolism of insecticides and toxic natural plant compounds. A degenerate 3' RACE strategy resulted in the identification of fifteen novel P450s from an alkaloid-resistant species of Drosophila. The strong (17.4-fold) and highly specific induction of a single gene (CYP4D10) by the toxic isoquinoline alkaloids of a commonly utilized host-plant (saguaro cactus) provides the first indication that members of the CYP4 family in insects may play an important role in the maintenance of specific insect-host plant relationships. Strong barbiturate inducibility of CYP4D10 and two other D. mettleri P450 sequences of the CYP4 family was also observed, suggesting a pattern of xenobiotic responsiveness more similar to those of several vertebrate drug-metabolizing enzymes than to putative vertebrate CYP4 homologs.

Alkaloids↗
PubMed1998

A matrix-located processing peptidase of plant mitochondria.

Nuclear-encoded mitochondrial precursor proteins are proteolytically processed inside the mitochondrion after import. The general mitochondrial processing activity in plant mitochondria has been shown to be integrated into the cytochrome bc1 complex of the respiratory chain. Here we investigate the occurrence of an additional, matrix-located processing activity by incubation of the precursors of the soybean mitochondrial proteins, alternative oxidase, the FAd subunit of the ATP synthetase and the tobacco F1 beta subunit of the ATP synthase, with the membrane and soluble components of mitochondria isolated from soybean cotyledons and spinach leaves. A matrix-located peptidase specifically processed the precursors to the predicted mature form in a reaction which was sensitive to orthophenanthroline, a characteristic inhibitor of mitochondrial processing peptidase (MPP). The specificity of the matrix peptidase was illustrated by the inhibition of processing of the alternative oxidase precursor in both soybean and spinach matrix extracts upon altering a single amino acid residue in the targeting presequence (-2 Arg to Gly). Additionally, there was no evidence for general proteolysis of precursor proteins incubated with the matrix. The purity of the matrix fractions was ascertained by spectrophotometric and immunological analyses. The results demonstrate that there is a specific processing activity in the matrix of soybean and spinach in addition to the previously well characterized membrane-bound MPP integrated into the cytochrome bcl complex of the respiratory chain.

Cell Nucleus↗
PubMed1998

Co-operation between follicular ornithine decarboxylase and v-Ha-ras induces spontaneous papillomas and malignant conversion in transgenic skin.

Ornithine decarboxylase (ODC) is aberrantly regulated in tumor cells and results in high basal levels of ODC and polyamines in many epithelial tumors. To determine if elevated ODC/polyamine levels can co-operate with a mutant Ha-ras gene in mouse skin tumorigenesis, double transgenic mice were generated by breeding K6/ODC transgenic mice with TG.AC v-Ha-ras transgenic mice. A K6 keratin promoter drives the ODC transgene in K6/ ODC transgenic mice, which results in elevated ODC/ polyamine levels directed to the outer root sheath cells of hair follicles. TG.AC transgenic mice carry a v-Ha-ras transgene while still retaining two normal c-Ha-ras alleles. Transgenic mice that possess only the K6/ODC or the v-Ha-ras transgene did not develop tumors unless treated with either a carcinogen or a tumor promoter, respectively. However, a high percentage of double transgenic mice possessing both the K6/ODC and v-Ha-ras transgenes developed spontaneous tumors. All tumors were well-differentiated keratoacanthomas, some of which progressed to carcinomas within 2 months. The development and the maintenance of these ODC/ras tumors was ODC-dependent since alpha-difluoromethylornithine (DFMO), a specific ODC inhibitor, prevented the formation and caused the regression of these tumors. These findings indicate that ODC overexpression and an activated Ha-ras are sufficient to produce a high rate of malignant transformation in an animal model. The ODC/ras double transgenic mouse provides a simple in vivo model without the use of chemical carcinogens or tumor promoters in which to test downstream effectors that play a key role in mediating the development of epithelial tumors resulting from the cooperation between ODC and v-Ha-ras.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Ornithine decarboxylase overexpression leads to increased epithelial tumor invasiveness.

Ornithine decarboxylase (ODC) overexpression cooperates with genetic lesions such as an activated c-rasHa to enhance epithelial tumorigenesis. To assess the invasiveness of ODC-overexpressing cells, two noninvasive epidermal cell lines, nontumorigenic BK-1 cells, and the papilloma-derived cell line SP-1 were infected with a replication-defective retrovirus that overexpresses ODC, inoculated into deepithelialized rat tracheas, and transplanted into athymic nude mice. After 5 weeks, ODC-overexpressing BK-1 cells remained localized on the luminal surface of the tracheal xenotransplants, whereas the ODC-overexpressing SP-1 cells were extremely invasive, with the whole tracheal wall penetrated. This invasiveness of ODC-overexpressing SP-1 cells was accompanied by elevated proteinase expression, including increased urokinase plasminogen activator activity in ODC-overexpressing cells and elevated stromelysin-1 mRNA expression in the stromal cells of invaded tracheal transplants.

Animals↗