I'm not a doctor. I just play one on the Internet.
Explore the source record for details and available documents.
American Medical Association↗
Biomedical subjects
M Scott
Publications and source records attributed to M Scott.
Paraganglioma of the nasal cavity.
Explore the source record for details and available documents.
Adult↗
Theory of Frequency-Dependent Polarization of General Planar Electrodes with Zeta Potentials of Arbitrary Magnitude in Ionic Media.
Electrode polarization effects have long aggravated the efforts of low frequency analysis, particularly those investigations carried out on biological material or in highly conductive media. Beginning from elementary equations of electrostatics and hydrodynamics, a comprehensive model is devised to account for the screening of a general planar electrode by an ionic double layer. The surface geometry of the planar electrode is left unspecified to include any type of micromachined array. Building on the previous work by DeLacey and White (1982, J. Chem. Soc. Faraday Trans. 2 78, 457) using a variational theorem, we extend their numerical results with compact analytic solutions, analogous to the Debye-Hückel potential for dc systems, but applicable now to dynamic ac experiments. The variational approach generates functions that are not restricted by perturbation expansions or numerical convergence, representing optimal approximations to the exact solutions. Copyright 2000 Academic Press.
Journal Article↗
Theory of Frequency-Dependent Polarization of General Planar Electrodes with Zeta Potentials of Arbitrary Magnitude in Ionic Media.
The expressions obtained in the previous paper for electrode polarization are applied to a homogeneous planar electrode and a planar array of electrodes used in the generation of nonuniform fields. The effective far field experienced outside the double layer is computed for both electrodes, and sample spectra are provided. The effective far field expression contains the electrode impedance and the effects of concentration polarization due to the static double layer on the electrode generated by the zeta potential. The effective far field results are compact and contain simple integrals that can be evaluated numerically. Copyright 2000 Academic Press.
Journal Article↗
Development of a pharmacy residency program in home care.
A residency training program developed by a college of pharmacy in conjunction with a home care company is described. The 12-month program is based on the ASHP Residency Learning System and the goal statements and educational objectives of ASHP's accreditation standard for pharmacy practice residency training with emphasis in home care. Establishing the program involved identifying goals, objectives, and learning experiences consistent with the expected outcomes. Specific objectives for meeting goals in four categories--practice foundation skills, direct patient care, drug information and drug policy development, and practice management--were linked to expected program outcomes. Learning experiences that would lead to achievement of the program objectives and outcomes were selected and organized into one- to eight-week rotations (e.g., in acute care, care of pediatric patients, pain management, nutrition, patient education and counseling, and administration and practice management). Throughout the program, residents gain experience in pharmaceutical services and research. Skills in care planning and monitoring are emphasized, as is practicing pharmaceutical care in an interdisciplinary environment. Residents who have completed the program have found employment immediately as pharmacy managers of home infusion centers. Pharmacy residency training in home care provides the experience needed to function as a competent clinician and manager who can identify and solve problems to improve patient care.
Education, Pharmacy↗
Persistence of human papillomavirus type 16 infection is associated with lack of cytotoxic T lymphocyte response to the E6 antigens.
Our cross-sectional study suggested that cytotoxic T lymphocyte (CTL) responses have a protective effect in squamous intraepithelial lesion (SIL) development. More CTL responses in women with human papillomavirus type 16 (HPV 16) infection without SILs than with SILs were detected. In the current longitudinal study, the role of CTL in clearing HPV 16 infection in women without SILs was investigated. Women with HPV 16 infection (n=51) were enrolled, along with HPV 16-negative control women (n=3). Twenty-two (55%) of 40 women who cleared HPV 16 infection had an E6 CTL response at least once, compared with none of 9 women who had HPV 16 persistence (P=.003). Such a difference was not demonstrated for E7; 25 (63%) of 40 women who cleared HPV 16 infection responded, versus 5 (56%) of 9 women with persistence (P=.720). It appears that lack of response to E6 is important in the persistence of HPV 16 infection.
Adolescent↗
The p53-independent tumoricidal activity of an adenoviral vector encoding a p27-p16 fusion tumor suppressor gene.
We describe here that DE1-adenovirus vectors (AV) expressing a p27-p16 fusion molecule, termed W9, induce tumor cell apoptosis when overexpressed in a wide range of tumor cell types. However, in primary human cells derived from a variety of normal tissues, AV-W9 induced minimal apoptosis. In tumor cells AV-W9 demonstrated 5- to 50-fold greater tumoricidal activity than either of the parental molecules p16 and p27. In these studies, AV-W9 elicited apoptosis independent of the p53 and Rb status of the tumor cells. In several murine tumor models AV-W9 demonstrated p53-independent antitumor activity. It completely prevented tumor formation in two ex vivo models, whereas the parental molecules resulted in partial protection. Furthermore, AV-W9 induced tumor regression or suppressed tumor growth when introduced intratumorally into preestablished tumors in mice. This effect may be mediated through tumor cell apoptosis or antiangiogenic activity of AV-W9. Thus, this novel chimeric molecule is more potent and capable of killing a broader spectrum of tumors than the parental p16 and p27 molecules independent of the tumor cell p53 and phenotype and represents a powerful new therapeutic agent for cancer gene therapy.
Adenoviridae↗
Idiopathic slow-transit constipation is not associated with mutations of the RET proto-oncogene or GDNF.
PURPOSE: Idiopathic slow-transit constipation is a severe disorder of unknown cause. The onset in early childhood and history of constipation or Hirschsprung's disease in close family relatives suggest that slow-transit constipation could have a genetic basis. Several germline mutations have been described in Hirschsprung's disease, including mutations of RET and the gene encoding its ligand glial cell-derived neurotrophic factor. The aim of this study was to screen a panel of 16 cases of familial idiopathic slow-transit constipation, including 4 families in which there were relatives with Hirschsprung's disease, for RET and glial cell-derived neurotrophic factor mutations previously identified in Hirschsprung's disease. METHODS: Genomic DNA from 16 patients with slow-transit constipation and four relatives with Hirschsprung's disease was analyzed using single strand and heteroduplex conformation polymorphism analysis at two conditions and by direct DNA sequencing using the fluorescent dideoxy terminator method. RESULTS: Although common sequence polymorphisms were demonstrated with a frequency comparable with published data, no published or new mutation was seen in any of the exons of RET or glial cell-derived neurotrophic factor. CONCLUSIONS: Mutation of RET or glial cell-derived neurotrophic factor is not a frequent cause of idiopathic slow-transit constipation.
Adult↗
Activation of apoptosis-linked caspase(s) in NMDA-injured brains in neonatal rats.
Unilateral injection of 50 nmol of N-methyl-D-aspartate (NMDA) into the left posterior striatum of 7 day-old rat pups induces massive neuronal loss in the ipsilateral hemisphere in 5 days. In this model of excitotoxicity, the form of neuronal death (necrosis vs apoptosis) has not been clearly addressed. Here we report evidence of DNA laddering in the ipsilateral hemisphere 24 h after the NMDA injection. Activation of apoptosis-linked caspase(s) was also identified, as evidenced by (i) the formation of caspase-produced 120 kDa alpha-spectrin breakdown product (SBDP120) and (ii) increase in hydrolysis of caspase-3 substrate acetyl-DEVD-7-amido-4-methylcoumarin in the homogenate from the ipsilateral hemisphere. Lastly, we note that i.p. injection (100 mg/kg) of a pan caspase inhibitor Z-D-DCB attenuates the levels of SBDP120. Our results suggest the presence of caspase-activation in this rat pup model of NMDA toxicity.
Animals↗
The effect of maternal exposure to flaxseed on spermatogenesis in F(1) generation rats.
Pregnant Sprague-Dawley rats were exposed to a flaxseed (20 or 40%), flaxmeal (13 or 26%) or standard NIH AIN-93 (0% flaxseed control) diet throughout gestation and until their offspring were weaned. After weaning, F(1) generation males were placed in the same diet treatment groups as their mothers for 70 days. Statistically significant differences were not observed between either low-dose or high-dose flaxseed and flaxmeal-treated animals and the 0% flaxseed control animals for testis weights, homogenization resistant spermatid counts, daily sperm production rates, epididymal weights, seminal vesicle weights, seminiferous tubule fluid testosterone concentrations and the percentage of sperm abnormalities. The following statistically significant differences were observed when treated groups and the 0% flaxseed control groups were compared: (1) increases in serum LH in the 20% and 40% flaxseed treatment groups and in serum LH and testosterone in the 26% flaxmeal treatment group; (2) increases in the cauda epididymal weight from the 20% and 40% flaxseed groups; (3) increases in cauda epididymal sperm numbers/g epididymis from the 20% and 40% flaxseed and the 13% and 26% flaxmeal treatment groups; (4) a decrease in prostatic weight from the 20% flaxseed and 13% and 26% flaxmeal treatment groups. Prostate weight in the 40% flaxseed treatment group was lower but not statistically significantly different than the 0% flaxseed control group. Histological effects on spermatogenesis were not observed in either the control group, flaxmeal or the flaxseed treated groups.
Analysis of Variance↗
Preliminary evaluation of an in vitro test for assessment of excitotoxicity by measurement of early gene (c-fos mRNA) levels.
Using primary cultures of mouse cerebellar granule cells as an in vitro model system, it has been demonstrated that different profiles of temporal expression of the c-fos proto-oncogene are observed under non-excitotoxic and excitotoxic conditions. A ratio has been derived previously for the steady-state level of c-fos mRNA after 30 min and 240 min which suggests that a 240 min/30 min ratio of greater than 1 correlates with excitotoxicity, whereas a ratio of less than 1 correlates with a non-excitotoxic outcome. Moreover, a positive correlation is seen with abrogation of excitotoxicity in response to selective excitatory amino acid receptor antagonists. This test, proposed as a specific biomarker for excitotoxicity is undergoing prevalidation. Excitotoxicity is defined as neuronal cell death mediated by hyperactivation of glutamate receptor subtypes and therefore might be expected to be prevented by selective glutamate receptor antagonists. In preliminary evaluation studies, we have conducted work under the direction of the European Center for Validation of Alternate Methods (ECVAM) using compounds specified by ECVAM that have been subdivided into four groups based on known or presumed actions. These groups comprise: Group 1-endogenous/synthetic excitotoxins; Group 2-environmental, putative excitotoxins; Group 3-neurotoxic but non-excitotoxic compounds, and Group 4-non-toxic compounds. The results of this study support the proposal that the c-fos mRNA time-ratio test is a specific biomarker of excitotoxicity. Just as importantly, this test has the potential for application in screening newly-designed EAA receptor antagonists in the search for clinically relevant drugs to treat a variety of neuropathologies.
Animals↗
Dieldrin resistance in Lucilia cuprina (the australian sheep blowfly): chance, selection and response.
Discrete-generation population cages of Lucilia cuprina were initiated with dieldrin-resistant allele (Rdl ) frequencies of 1 or 5% and maintained for 17 generations on media with concentrations of dieldrin in the range 0-0.006% (w/v). The probability of the initial establishment of the Rdl allele in a population was consistently greater at the 5% frequency and dependent on the concentration of dieldrin in the medium for both starting frequencies. Once the resistant allele was established responses to selection were concentration-dependent. It was concluded that in the absence of dieldrin the susceptible allele was selectively favoured, at 0. 00005% (w/v) concentration selection and random genetic drift influenced changes in allele frequency and at concentrations above this the Rdl allele was at a selective advantage. Fixation of Rdl occurred at the higher concentrations. The influence of random genetic drift and selection on the genetic response during the evolution of insecticide resistance is discussed.
Alleles↗
Evidence for a unique expression of CD4 on murine vaginal CD4+ cells.
Mucosal cell-mediated immunity (CMI) by CD4+ T cells is postulated to be important for host defence against several vaginal pathogens. In addition to the recognized phenotypic distinctions of resident vaginal T lymphocytes, we recently provided evidence by fluorescence-activated cell sorter (FACS) that murine vaginal CD4+ T lymphocytes, are differentially recognized by two epitope-distinct anti-CD4 antibodies, suggesting that the CD4 protein on vaginal CD4+ cells is atypically expressed. In the present study, we confirm this by FACS and immunohistochemistry under non-denaturing conditions using two additional anti-CD4 antibodies. However, positive immunohistochemical staining of vaginal CD4+ cells under denaturing conditions revealed that the CD4 epitope in question is indeed present within the CD4 protein. Using reverse transcription polymerase chain reaction, amplification of CD3, T-cell receptor-beta (TCR-beta), and TCR-delta mRNA from lymph node and vaginal tissue, and CD4 mRNA from lymph node tissue was demonstrable. In contrast, amplification of CD4 mRNA from vaginal tissue, vaginal enriched lymphoid cells, or a purified (FACS-sorted) population of vaginal-specific CD4+ cells using two distinct primer sets was not demonstrable. Altogether, our results provide evidence that the CD4 protein on vaginal CD4+ T cells is conformationally distinct compared with its systemic counterpart, either as a result of a unique CD4 mRNA sequence or from a stable interaction of soluble CD4 with the surface of vaginal T cells.
Animals↗
Comparison of orbital colour Doppler findings with computed tomography angiography.
Colour Doppler imaging (CDI) of orbital vessels is noninvasive but may be fallacious, while computed tomography (CT) angiography displays a visual outline of orbital vessels. We compared clinical findings of the two methods in 33 patients with a wide variety of clinical conditions. It was not possible to visualize the central retinal arteries with CT angiography, but it was possible to show the intracranial carotid, which CDI could not. Changes in the ophthalmic arteries on CDI usually showed changes in calibre on CT angiography. Patients with unexplained or gross visual loss often showed marked abnormalities on CT scanning, not entirely consistent with the clinical picture. Several patients showed marked ectasia of the intracranial carotid along with variable clinical findings. Findings on CT angiography complement and augment those on CDI, and are likely to be more clinically valuable in the future.
Adult↗
Development of a molecular probe to baboon interleukin-10 mRNA for in situ hybridization during experimental schistosomiasis.
A nucleic acid probe complementary to baboon interleukin 10 (IL-10) mRNA was developed for in situ hybridization. Highly conserved IL-10 protein sequences from several mammals were aligned to design oligonucleotide primers flanking a 270-bp sequence of the target cDNA. RNA was isolated from stimulated peripheral blood mononuclear cells (PBMC). IL-10 cDNA was reverse-transcribed from the total PBMC RNA and amplified with the polymerase chain reaction (PCR). Cloning and sequencing of the PCR product confirmed it to be of baboon IL-10 origin, with 97.8% identity to human and 100% identity to macaque mRNA sequences. The baboon IL-10 DNA probe hybridized in Southern blots to a 7.9-Kbp or 8.6-Kbp band after digestion of genomic baboon DNA with Bam H1 or Eco R1, respectively. Preliminary results with an antisense riboprobe derived from this sequence showed the presence of IL-10 mRNA in sections of granulomatous tissues.
Animals↗
Affinity-tagged miniprion derivatives spontaneously adopt protease-resistant conformations.
An abridged PrP molecule of 106 amino acids designated PrP106 can form infectious miniprions in transgenic (Tg) mice (29). Addition of six-histidine (His(6)) affinity tags to selective sites within PrP106 resulted unexpectedly in new PrP proteins that spontaneously adopted protease-resistant conformations when expressed in neuroblastoma cells and Tg mice. Acquisition of protease resistance depended on the length, charge, and placement of the affinity tag. Introduction of the disease-linked mutation E200K into the sequence of PrP106(140/6His) increased the recovery of protease-resistant PrP fivefold, whereas introduction of the mutations C213A and Delta214-220 did not affect the recovery of protease-resistant PrP. Treatment of cultured cells expressing affinity-tagged PrP106 mutants with polypropyleneimine dendrimer rendered these proteins sensitive to protease digestion in a manner similar to wild-type PrP(Sc). We conclude that certain affinity-tagged PrP106 proteins spontaneously fold into conformations partially resembling, yet distinct from, wild-type PrP(Sc). These proteins might be useful tools in the identification of new disease-causing mutations as well as for screening compounds for therapeutic efficacy.
Animals↗
Dominant-negative inhibition of prion formation diminished by deletion mutagenesis of the prion protein.
Polymorphic basic residues near the C terminus of the prion protein (PrP) in humans and sheep appear to protect against prion disease. In heterozygotes, inhibition of prion formation appears to be dominant negative and has been simulated in cultured cells persistently infected with scrapie prions. The results of nuclear magnetic resonance and mutagenesis studies indicate that specific substitutions at the C-terminal residues 167, 171, 214, and 218 of PrP(C) act as dominant-negative, inhibitors of PrP(Sc) formation (K. Kaneko et al., Proc. Natl. Acad. Sci. USA 94:10069-10074, 1997). Trafficking of substituted PrP(C) to caveaola-like domains or rafts by the glycolipid anchor was required for the dominant-negative phenotype; interestingly, amino acid replacements at multiple sites were less effective than single-residue substitutions. To elucidate which domains of PrP(C) are responsible for dominant-negative inhibition of PrP(Sc) formation, we analyzed whether N-terminally truncated PrP(Q218K) molecules exhibited dominant-negative effects in the conversion of full-length PrP(C) to PrP(Sc). We found that the C-terminal domain of PrP is not sufficient to impede the conversion of the full-length PrP(C) molecule and that N-terminally truncated molecules (with residues 23 to 88 and 23 to 120 deleted) have reduced dominant-negative activity. Whether the N-terminal region of PrP acts by stabilizing the C-terminal domain of the molecule or by modulating the binding of PrP(C) to an auxiliary molecule that participates in PrP(Sc) formation remains to be established.
Animals↗
Combined intraportal infusion of acetylcholine and adrenergic blockers augments net hepatic glucose uptake.
Portal glucose delivery in the conscious dog augments net hepatic glucose uptake (NHGU). To investigate the possible role of altered autonomic nervous activity in the effect of portal glucose delivery, the effects of adrenergic blockade and acetylcholine (ACh) on hepatic glucose metabolism were examined in 42-h-fasted conscious dogs. Each study consisted of an equilibration (-120 to -20 min), a control (-20 to 0 min), and a hyperglycemic-hyperinsulinemic period (0 to 300 min). During the last period, somatostatin (0.8 microg. kg(-1). min(-1)) was infused along with intraportal insulin (1.2 mU. kg(-1). min(-1)) and glucagon (0.5 ng. kg(-1). min(-1)). Hepatic sinusoidal insulin was four times basal (73 +/- 7 microU/ml) and glucagon was basal (55 +/- 7 pg/ml). Glucose was infused peripherally (0-300 min) to create hyperglycemia (220 mg/dl). In test protocol, phentolamine and propranolol were infused intraportally at 0.2 microg and 0.1 microg. kg(-1). min(-1) from 120 min on. ACh was infused intraportally at 3 microg. kg(-1). min(-1) from 210 min on. In control protocol, saline was given in place of the blockers and ACh. Hyperglycemia-hyperinsulinemia switched the net hepatic glucose balance (mg. kg(-1). min(-1)) from output (2.1 +/- 0.3 and 1.1 +/- 0.2) to uptake (2.8 +/- 0.9 and 2.6 +/- 0.6) and lactate balance (micromol. kg(-1). min(-1)) from uptake (7.5 +/- 2.2 and 6.7 +/- 1.6) to output (3.7 +/- 2.6 and 3.9 +/- 1.6) by 120 min in the control and test protocols, respectively. Thereafter, in the control protocol, NHGU tended to increase slightly (3.0 +/- 0.6 mg. kg(-1). min(-1) by 300 min). In the test protocol, adrenergic blockade did not alter NHGU, but ACh infusion increased it to 4.4 +/- 0.6 and 4.6 +/- 0.6 mg. kg(-1). min(-1) by 220 and 300 min, respectively. These data are consistent with the hypothesis that alterations in nerve activity contribute to the increase in NHGU seen after portal glucose delivery.
Acetylcholine↗