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S T Martin

Publications and source records attributed to S T Martin.

15 recordsLinked to original sources
PubMed2005

Ozonolysis of mixed oleic-acid/stearic-acid particles: reaction kinetics and chemical morphology.

The ozonolysis of mixed oleic-acid/stearic-acid (OL/SA) aerosol particles from 0/100 to 100/0 wt % composition is studied. The magnitude of the divergence of the particle beam inside an aerosol mass spectrometer shows that, in the concentration range 100/0 to 60/40, the mixed OL/SA particles are liquid prior to reaction. Upon ozonolysis, particles having compositions of 75/25 and 60/40 change shape, indicating that they have solidified during reaction. Transmission electron micrographs show that SA(s) forms needles. For particles having compositions of 75/25, 60/40, and greater SA content, the reaction kinetics exhibit an initial fast decay of OL for low O(3) exposure with no further loss of OL at higher O(3) exposures. For compositions from 50/50 to 10/90, the residual OL concentration remains at 28 +/- 2% of its initial value. The initial reactive uptake coefficient for O(3), as determined by OL loss, decreases linearly from 1.25 (+/-0.2) x 10(-3) to 0.60 (+/-0.15) x 10(-3) for composition changes of 100/0 to 60/40. At 50/50 composition, the uptake coefficient drops abruptly to 0.15 (+/-0.1) x 10(-3), and there are no further changes with increased SA content. These observations can be explained with a combination of three postulates: (1) Unreacted mixed particles remain as supersaturated liquids up to 60/40 composition, and the OL in this form rapidly reacts with O(3). (2) SA, as it solidifies, locks into its crystal structure a significant amount of OL, and this OL is completely inaccessible to O(3). (3) Accompanying crystallization, some stearic acid molecules connect as a filamentous network to form a semipermeable gel containing liquid OL but with a reduced uptake coefficient because of the decrease in molecular diffusivity in the gel. An individual particle of 50/50 to 90/10 is hypothesized as a combination of SA crystals having OL impurities (postulate 2) that are partially enveloped by an SA/OL gel (postulate 3) to explain (a) the abrupt drop in the uptake coefficient from 60/40 to 50/50 and (b) the residual OL content even after high ozone exposure. The results of this study, pointing out the important effects of particle phase, composition, and morphology on chemical reactivity, contribute to an improved understanding of the aging processes of atmospheric aerosol particles.

Journal Article↗
PubMed2005

Aberrant methylation of the Human Hedgehog interacting protein (HHIP) gene in pancreatic neoplasms.

Hedgehog pathway overactivity has been implicated in the development of a variety of human cancers. The Human Hedgehog interacting protein (HHIP), a negative regulator of hedgehog signaling, has been shown to be underexpressed in pancreatic cancers. In this study we determined if the HHIP gene is a target for genetic and epigenetic alterations. While no mutations of HHIP were identified, we found complete methylation of the HHIP promoter CpG island in three pancreatic cancer cell lines, and partial hypermethylation in 13/17 (80%) pancreatic cancer cell lines, 35/75 (46%) primary pancreatic cancers and 14/18 (78%) pancreatic cancer xenografts, but no methylation in 13 normal pancreata. In pancreatic cancer cell lines, complete methylation was associated with absent or reduced HHIP expression by real-time RT-PCR. HHIP expression could be restored in methylated cell lines using epigenetic modifier drugs. Restoring the expression of HHIP in pancreatic cancer cells by 5-aza-2'-deoxycytidine led to a decrease in Gli reporter activity, consistent with downregulation of Hedgehog signaling. These results indicate in some pancreatic adenocarcinomas that HHIP is epigenetically inactivated by promoter methylation, and its silencing could contribute to the increased Hedgehog signaling observed in pancreatic neoplasms.

Adenocarcinoma↗
PubMed2005

Paraesophageal lymph node metastasis from prostatic adenocarcinoma in a patient with esophageal squamous carcinoma.

SUMMARY. Esophageal squamous carcinomas induce regional immune suppression in the domain of the tumor while the global immune system remains intact. We report a patient with a squamous esophageal carcinoma, who was discovered at esophagectomy to have paraesophageal lymph node metastases from a prostatic adenocarcinoma. No other sites of metastatic disease were identified. This supports the concept that regional immune suppression by esophageal squamous cancers facilitates growth of metastases in the local lymph nodes.

Adenocarcinoma↗
PubMed2001

Structure-activity relationships of mineral dusts as heterogeneous nuclei for ammonium sulfate crystallization from supersaturated aqueous solutions.

Mineral inclusions, present in aqueous atmospheric salt droplets, regulate crystallization when relative humidity decreases by providing a surface for heterogeneous nucleation and thus reducing the critical supersaturation. Although laboratory studies have quantified these processes to some extent, the diverse atmospheric mineralogy presents more chemical systems than practically feasible for direct study. Structure--activity relationships are necessary. To that end, in the present work the interactions of ammonium sulfate with corundum, hematite, mullite, rutile, anatase, and baddeleyite were studied by diffuse reflectance fourier transform infrared spectroscopy (DRIFTS) and by epitaxial modeling. The spectroscopic results show that shifts in sulfate peak positions due to chemisorption are not a correlative indicator of the efficacy of heterogeneous nucleation. In contrast, epitaxial modeling results of unreconstructed surfaces explain the sequence of critical supersaturations for constant particle size. If validated by further work, this computer modeling method would provide an important structure--activity tool for the estimation of heterogeneous nucleation properties of the atmospheric mineralogy.

Aluminum Oxide↗
PubMed1994

Evidence for conformational dynamics and molecular aggregation in cytochrome P450 102 (BM-3).

The native molecular weight of affinity-purified cytochrome P450 102 from barbiturate-induced Bacillus megaterium has been studied by sedimentation methods and HPLC size-exclusion chromatography. Sedimentation velocity experiments yielded an s020,w = 9.244 S for the holocytochrome, but the diffusion coefficient was unexpectedly large and varied widely with centrifugal field, ionic strength, and protein concentration. Addition of 50 mM DL-dithiothreitol (DTT) caused a small decrease in the value of s020,w, but D20 still did not behave as expected. The sedimentation coefficients were consistent with a molecular weight of about 200,000, and the diffusion coefficients indicated molecular aggregation. Sedimentation equilibrium analyses suggested that the native enzyme was a mixture of monomer, dimer, trimer, and tetramer. However, after incubation of P450 102 with DTT, sedimentation equilibrium demonstrated that the enzyme was dimeric (molecular weight 236,000). HPLC size-exclusion chromatography of the cytochrome showed the presence of four peaks, which corresponded to 1.45-mer, 2.06-mer, 3.02-mer, and a higher molecular weight fraction; aggregated forms accounted for about 52% of the P450 102. Incubation of the enzyme with DTT caused a shift toward the 1.45-mer, but dimer, trimer, and the high molecular weight peak still persisted; the shift was not attributable to disulfide bond reduction. The 1.45-mer was determined to be a monomeric species of significantly asymmetric geometry. Together, the results indicated that cytochrome P450 exists with monomer, dimer, trimer, etc. in equilibrium, contrary to the expectation that this soluble P450 would be monomeric.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacillus megaterium↗
PubMed1994

Membrane topology of liver microsomal cytochrome P450 2B4 determined via monoclonal antibodies directed to the halt-transfer signal.

The membrane topology of cytochrome P450 2B4 from the endoplasmic reticulum has been studied with highly-purified liver microsomes in a site-directed immunochemical approach. Microsomes were prepared from phenobarbital-induced rabbits, and the resulting microsomal fraction was washed 6 additional times with 0.1 M pyrophosphate buffer to effect removal of significant quantities of adventitiously-bound protein. Monoclonal antibodies were prepared against residues 18-29 of P450 2B4 (Leu18-Leu-Phe-Arg-Gly-His-Pro-Lys-Ala-His-Gly-Arg29), essentially corresponding to the halt-transfer signal. This region was chosen due to its mutually-exclusive location in the two alternative membrane topology models currently tenable [Black, S.D. (1992) FASEB J.6, 680-685]. Model "A" contains a single transmembrane anchor peptide with the amino terminus projecting into the lumen of the endoplasmic reticulum, while model "B" exhibits a hairpin loop of the first approximately 46 residues inserted into the membrane with the amino terminus located on the cytosolic side of the lipid bilayer; the halt-transfer signal peptide would be located at the cytosolic surface of the membrane in model "A" or as a loop on the lumenal side of the membrane in model "B". Nine antibodies, denoted as MmAbA, MmAbC, MmAbD, MmAbF, MmAbH, MmAbI, MmAbK, MmAbL, and MmAbP, were produced, and all were identified as IgM/kappa subtypes. Western blotting demonstrated that the antibodies could readily recognize P450 2B4 in microsomes. ELISA assays showed that all of the antibodies exhibited strong binding to intact microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Detergent effects in rabbit liver microsomal UDP-glucuronosyltransferase studied by means of a continuous spectrophotometric assay with p-nitrophenol.

UDP-glucuronosyltransferase (UDPGT) has been studied with a continuous spectrophotometric assay employing UDP-glucuronic acid and p-nitrophenol as substrates. Activity is linearly dependent on the microsomal protein concentration. Male rabbit liver phenobarbital-induced microsomes exhibited a rate of 7.10 microM p-nitrophenol conjugated per minute at 37 degrees C. Addition of small amounts of Tergitol NP-10 caused an approximately 4-fold increase in conjugation activity; maximal activation was observed at 0.01% (v/v) detergent. However, inclusion of additional detergent caused significant inhibition of activity, such that 0.5% Tergitol caused the rate to fall 2.5-fold below the activity observed in the absence of detergent. Membrane solubilization was studied by light scattering. At maximal stimulation of p-nitrophenol UDPGT activity, the membrane was solubilized only approximately 17%. At the point of 50% solubilization, activity was still 91% of maximum. Complete membrane solubilization was achieved at approximately 0.2% Tergitol, and transferase activity had fallen slightly below the rate observed in the absence of detergent. Possible explanations for the unusual detergent-dependence of microsomal p-nitrophenol UDPGT activity are discussed.

Animals↗
PubMed1989

Idiom interpretation in isolation versus context: a developmental study with adolescents.

Idiom interpretation under two different presentation modes, Isolation and Context, was examined developmentally in 475 adolescents ages 14 through 17. Results demonstrated that accuracy was greater for idioms in Context than idioms in Isolation, and that accuracy for both presentation modes slowly improved during the target age range. However, even the oldest subjects had not yet mastered the task in either mode. Qualitative analysis indicated that No Response, Literal, and Unrelated error types were produced most often by the youngest subjects but tended to decrease as subject age increased. In general, more No Response, Literal, Related, and Unrelated error types were produced for idioms in Isolation than in Context, but more Restatement errors were produced for idioms in Context. It was also found that idiom interpretation was significantly correlated to specific measures of literacy in 16-year-olds.

Adolescent↗
PubMed1986

Comparison of resuscitation of sheep and dogs after bupivacaine-induced cardiovascular collapse.

This study evaluated interspecies sensitivity and ability to resuscitate pentobarbital anesthetized sheep and dogs after cardiovascular toxic doses of bupivacaine. Every minute, 3 mg/kg of bupivacaine was injected into the right atrium over the course of 10 sec until cardiovascular collapse occurred. While the bupivacaine was given, the animals were made apneic for 90 sec and then ventilated with 100% oxygen. After the bupivacaine administration, cardiovascular collapse occurred in the form of electromechanical dissociation progressing to asystole in dogs, whereas in sheep the predominant rhythm was ventricular fibrillation leading to asystole. Resuscitation was performed using open chest heart massage, bretylium for treatment of ventricular tachycardia and fibrillation, and epinephrine with atropine for treatment of electromechanical dissociation or asystole. The initial dose of bupivacaine used to cause cardiovascular collapse was 3.5 +/- 1.2 mg/kg in sheep and 24.6 +/- 8.5 mg/kg in dogs (P less than 0.01). All sheep and dogs were resuscitated from the first cardiovascular collapse. The resuscitation time was 2.1 +/- 1.0 min in dogs and 36.9 +/- 15.4 min in sheep (P less than 0.01). All dogs could be resuscitated after two additional cardiovascular collapses induced by bupivacaine, but no sheep could be resuscitated after a second cardiovascular collapse. Concentrations of bupivacaine in cardiac tissue and serum levels of bupivacaine after the last resuscitation attempt were significantly greater in the dogs than in the sheep. We conclude that sheep are more sensitive to bupivacaine than dogs, but that even sheep can be resuscitated after cardiovascular collapse produced by bupivacaine.

Animals↗
PubMed1986

Resuscitation from bupivacaine-induced cardiovascular toxicity during partial inferior vena cava occlusion.

The hemodynamic effects and ability to resuscitate animals experiencing bupivacaine cardiovascular toxicity after partial inferior vena cava occlusion were investigated in anesthetized dogs (n = 12). Partial occlusion of the inferior vena cava resulted in a 12% decrease in mean arterial pressure, a 62% decrease in cardiac output, a 66% decrease in stroke volume, and a 135% increase in systemic vascular resistance. Bupivacaine, 20 mg/kg intravenously, resulted in cardiovascular collapse in all animals. The resuscitation time for animals without partial caval occlusion was 2.1 +/- 0.5 min, whereas that for animals with partial caval occlusion was 22.2 +/- 6.9 min (P less than 0.05). Significantly increased amounts of epinephrine and NaHCO3 were required to resuscitate the animals with caval occlusion. We conclude that partial inferior vena cava occlusion can significantly alter the ability to resuscitate animals experiencing bupivacaine cardiovascular toxicity.

Animals↗
PubMed1985

Successful cardiovascular resuscitation after massive intravenous bupivacaine overdosage in anesthetized dogs.

We investigated whether anesthetized dogs (n = 6) could be resuscitated from massive cardiovascular toxic intravenous bupivacaine overdoses. Five mg/kg of bupivacaine was given into the right atrium over 10 sec every minute until cardiac collapse occurred. At the same time the bupivacaine was given, the animals were made apneic for 90 sec (to mimic the clinical situation in which seizures often render patients apneic) and then ventilated with 100% oxygen. After bupivacaine administration, cardiovascular collapse occurred in the form of ventricular tachycardia, or more commonly, electromechanical dissociation. Resuscitation was performed using open-chest heart massage, bretylium for ventricular tachycardia, and epinephrine with atropine for electromechanical dissociation and bradycardia. After successful resuscitation, each animal was again given bupivacaine as above until cardiovascular collapse occurred and resuscitation was performed again. Each dog underwent three arrests and resuscitations. The total cumulative bupivacaine dose was 64.1 +/- 26.8 mg/kg. We conclude that anesthetized dogs receiving massive cardiovascular toxic doses of bupivacaine can be resuscitated easily and consistently with appropriate therapy.

Animals↗
PubMed1985

Bupivacaine cardiovascular toxicity: comparison of treatment with bretylium and lidocaine.

Using anesthetized dogs, this study compared treatment with lidocaine or bretylium for bupivacaine-induced cardiovascular toxicity. Pentobarbital-anesthetized and -ventilated dogs (n = 10) were given a bolus dose of bupivacaine, 4 mg/kg, and a constant infusion of 0.2 mg X kg-1 X min-1 to produce steady-state serum levels of 7.1 +/- 1.8 microgram/ml of bupivacaine. Using burst ventricular pacing, the ventricular tachycardia threshold was determined, along with hemodynamic and electrophysiologic parameters. The animals were then treated with bretylium, 20 mg/kg (n = 5), or lidocaine, 2 mg/kg, followed by a continuous infusion of lidocaine, 0.1 mg X kg-1 X min-1 (n = 5). Bupivacaine-induced alterations in cardiac output, stroke volume, heart rate, and systemic vascular resistance were corrected by bretylium but not lidocaine. Bupivacaine caused a significant lowering of the ventricular tachycardia threshold, which was consistently raised by bretylium, while lidocaine was either ineffective or caused a further lowering of the threshold. Bupivacaine caused a significant increase in the Q-TU interval and resulted in an undulating polymorphic ventricular tachycardia, similar to that seen in Torsades de Pointes.

Animals↗