Biomedical subjects

B J Smith

Publications and source records attributed to B J Smith.

At least 109 records · Page 6Linked to original sources

PubMed1999

Flumazenil discrimination by humans under a two-response and a novel-response procedure.

In this study we assessed the discriminative stimulus, self-reported, and performance effects of flumazenil in humans. The first group (n = 6) was trained to discriminate flumazenil (0.56 mg/70 kg i.v.) from saline and tested with flumazenil (0.10, 0.32, 0.56, and 1.0 mg/70 kg) under a two-response drug discrimination procedure. The second group (n = 8) was trained to discriminate flumazenil (0.56 mg/70 kg i.v.) from saline and tested with flumazenil (0.32, 0.56, and 1.0 mg/70 kg), midazolam (0.10, 0.56, and 1.0 mg/70 kg), and caffeine (75 mg/70 kg) under a novel-response drug discrimination procedure. In both groups, flumazenil was acquired and maintained as a discriminative stimulus. Flumazenil dose-dependently increased flumazenil-appropriate responding and ratings of strength of drug effect and sedation, and decreased ratings of stimulant effects and psychomotor performance. Under the novel-response procedure, midazolam produced dose-dependent increases in flumazenil-appropriate responding. However, midazolam produced 43 and 25% novel responding at the intermediate and highest test doses, respectively. Midazolam dose-dependently increased ratings of strength of drug effect and sedation, and decreased ratings of stimulant effects and psychomotor performance. The magnitude of effects on ratings of strength of drug effect and sedation were comparable after flumazenil and midazolam, but psychomotor performance effects were greater after midazolam than after flumazenil. Caffeine produced mostly saline-appropriate responding. The results indicate that flumazenil has agonist effects similar to those of midazolam; however, novel responding after midazolam, and the greater performance decrement after midazolam, suggest that flumazenil does not act as a traditional benzodiazepine agonist.

Adolescent↗

PubMed1998

TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3.

TNF-alpha converting enzyme (TACE; ADAM-17) is a membrane-bound disintegrin metalloproteinase that processes the membrane-associated cytokine proTNF-alpha to a soluble form. Because of its putative involvement in inflammatory diseases, TACE represents a significant target for the design of specific synthetic inhibitors as therapeutic agents. In order to study its inhibition by tissue inhibitors of metalloproteinases (TIMPs) and synthetic inhibitors of metalloproteinases, the catalytic domain of mouse TACE (rTACE) was overexpressed as a soluble Ig fusion protein from NS0 cells. rTACE was found to be well inhibited by peptide hydroxamate inhibitors as well as by TIMP-3 but not by TIMP-1, -2 and -4. These results suggest that TIMP-3, unlike the other TIMPs, may be important in the modulation of pathological events in which TNF-alpha secretion is involved.

ADAM Proteins↗

PubMed1998

F(ab')2 molecules made from Escherichia coli produced Fab' with hinge sequences conferring increased serum survival in an animal model.

Fab's with hinges based on the human gamma1 sequence containing 1, 2, or 4 cysteines have been produced by high level Escherichia coli periplasmic secretion, and coupled in vitro by reduction/oxidation to form F(ab')2. We find that the F(ab')2 made with hinges containing 2 or 4 cysteines have a high level (approximately 70%) of multiple disulphide bonds. These F(ab')2 molecules have an increased pharmacokinetic stability as measured by area under the curve compared to those made by direct coupling through a single disulphide bond. One particular molecule containing 4 hinge cysteines has a greater pharmacokinetic stability than a F(ab')2 formed by chemical cross-linking. F(ab')2 made from the Fab' with 4 hinge cysteines is also relatively resistant to chemical reduction in vitro allowing partial reduction to expose reactive hinge thiols. These hinge sequences provide a simple method for producing robust F(ab')2 in vitro, obviating the need to use chemical cross-linkers, and provide a route to hinge specific chemical modification with thiol-reactive conjugates.

Amino Acid Sequence↗

PubMed1998

Fine structure of the retinal pigment epithelium of Oreochromis niloticus L. (Cichlidae; Teleostei) in light- and-dark adaptation.

The fine structure of the retinal pigment epithelium (RPE) of the cichlid Oreochromis niloticus was investigated in both light- and dark-adaptation. The eyes of four light-adapted and from four dark-adapted O. niloticus were fixed routinely for light and transmission electron microscopy. The RPE consisted of a single layer of columnar cells showing minimal basal infolding but plentiful apical processes that in light-adaptation interdigitated with the photoreceptor outer segments. The epithelial cells were joined by a series of basally-located tight junctions. These cells showed a large vesicular nucleus, plentiful smooth endoplasmic reticulum and polysomes, but only small amounts of rough endoplasmic reticulum. Phagosomes, lysosome-like bodies, lipid droplets, and myeloid bodies were observed. The choriocapillaris was a single layer of large-caliber capillaries, and Bruch's membrane (complexus basalis) was a trilaminate structure typical of teleosts. The RPE melanosomes moved basally (sclerally) in dark-adaptation and apically (vitreally) during light-adaptation. Other morphological features which changed at least to some degree during retinomotor responses were: the location of the RPE nucleus; the location and electron density of the mitochondria; and the location, number, and size of the myeloid bodies. A number of unique morphological changes take place within the RPE cells of this species during the circadian cycle in addition to the movement of melanosomes characterized in other vertebrates.

Adaptation, Ocular↗

PubMed1998

Photoreceptor fine structure in Oreochromis niloticus L. (Cichlidae; Teleostei) in light- and dark-adaptation.

The structure and arrangement of both light- and dark-adapted retinal photoreceptors of Oreochromis niloticus L. were studied. Eyes of four light-adapted and four dark-adapted O. niloticus were fixed routinely for light and transmission electron microscopy. Rods, single cones, and double (twin) cones were present in a ratio of 30:1:2, respectively. Light-adapted rods were tall, extending into the retinal epithelial layer. Rod inner segments showed a distal ellipsoid of mitochondria that narrowed dramatically in the myoid region. Dark-adapted rod inner segments were much shorter with a thicker myoid region, indicating photomechanical movement. Rod synaptic spherules were small, with both superficial synapses and invaginated sites. Single cones were similar to individual members of a double cone. Cone outer segments consisted of uniform discs with a single incisure. All cones displayed a short, tapering outer segment, a large ellipsoid of mitochondria, and a myoid region rich in organelles. Both members of double cones had extensive subsurface cisternae along their contiguous surfaces. Cone inner segments changed little throughout the circadian cycle, suggesting an absence of significant retinomotor movements. Large, vesicular cone nuclei were located adjacent to or through the external limiting membrane. The cones' synaptic pedicles had larger synapses than rod spherules, with more of both invaginated (ribbon) and conventional (superficial) synaptic sites. Cone photoreceptors were arranged in a repeating square mosaic pattern with a single cone surrounded by four double (twin) cones. The photoreceptors of the Nile tilapia presented basic piscine characteristics, and also some more species-specific features.

Adaptation, Ocular↗

PubMed1998

Retrospective temporal and spatial mobility of adult Iowa women.

Human exposure assessments require a linkage between toxicant concentrations in occupied spaces and the receptor's mobility pattern. Databases reporting distinct populations' mobility in various parts of the home, time outside the home, and time in another building are scarce. Temporal longitudinal trends in these mobility patterns for specific age and gender groups are nonexistent. This paper describes subgroup trends in the spatial and temporal mobility patterns within the home, outside the home, and in another building for 619 Iowa females that occupied the same home for at least 20 years. The study found that the mean time spent at home for the participants ranged from a low of 69.4% for the 50-59 year age group to a high of 81.6% for the over 80-year-old age group. Participants who lived in either one- or two- story homes with basements spent the majority of their residential occupancy on the first story. Trends across age varied for other subgroups by number of children, education, and urban/rural status. Since all of these trends were nonlinear, they indicate that error exists when assuming a constant, such as a 75% home occupancy factor, which has been advocated by some researchers and agencies. In addition, while aggregate data, such as presented in this report, are more helpful in deriving risk estimates for population subgroups, they cannot supplant good individual-level data for determining risks.

Adult↗

PubMed1998

Effect of loading on bone regenerated at implant dehiscence sites in humans.

Few investigations have studied the long-term fate of bone formed following the technique of guided tissue regeneration. The aim of the present study was to evaluate bone fill around implant fixtures with dehiscence defects and to study its response to loading. Ten patients were treated with overdentures supported by 2 fixtures ad modum Brånemark. A third 7 mm x 3.75 mm diameter fixture was placed for the purposes of the study in the most anterior part of the mandible with a dehiscence defect of 4 to 5 mm on the buccal aspect (and 3 to 4 threads exposed) which was covered with a Gore-Tex membrane and buried beneath the mucosa. Fixtures were exposed after 5 months (stage 2), ball abutments connected and loaded through an overdenture for 1 year. Nine fixtures were functioning well after 1 year of loading, 6 of which were retrieved with a trephine for histological examination and compared with 6 unloaded fixtures retrieved in our previously reported study. The bone area filling the thread profiles (BA%) and the bone to metal contact (BMC%) were measured in the 3 most apical and 3 most coronal thread profiles on the buccal and lingual surfaces. Statistically significant higher BMC% (P < 0.01) were observed in loaded fixtures in the apical regions (buccal: loaded 51%, unloaded 25%; lingual: loaded 49%, unloaded 24%). Differences approached significance for the regeneration site (loaded 22%, unloaded 6%) but were no different for the coronal lingual region (loaded 28%, unloaded 20%). There were no differences for BA%. This study confirms that there is an increase in bone to metal contact with time and following fixture loading and that this may also occur with bone regenerated under Gore-Tex membranes.

Adult↗

PubMed1998

SPECT electronic collimation resolution enhancement using chi-square minimization.

An electronic collimation technique is developed which utilizes the chi-square goodness-of-fit measure to filter scattered gammas incident upon a medical imaging detector. In this data mining technique, Compton kinematic expressions are used as the chi-square fitting templates for measured energy-deposition data involving multiple-interaction scatter sequences. Fit optimization is conducted using the Davidon variable metric minimization algorithm to simultaneously determine the best-fit gamma scatter angles and their associated uncertainties, with the uncertainty associated with the first scatter angle corresponding to the angular resolution precision for the source. The methodology requires no knowledge of materials and geometry. This pattern recognition application enhances the ability to select those gammas that will provide the best resolution for input to reconstruction software. Illustrative computational results are presented for a conceptual truncated-ellipsoid polystyrene position-sensitive fibre head-detector Monte Carlo model using a triple Compton scatter gamma sequence assessment for a 99mTc point source. A filtration rate of 94.3% is obtained, resulting in an estimated sensitivity approximately three orders of magnitude greater than a high-resolution mechanically collimated device. The technique improves the nominal single-scatter angular resolution by up to approximately 24 per cent as compared with the conventional analytic electronic collimation measure.

Algorithms↗

PubMed1998

Analytic treatment of resolution precision in electronically collimated SPECT imaging involving multiple-interaction gamma rays.

The widely applied single-interaction analytic expression characterizing the energy resolution component of the angular resolution precision for an electronically collimated point source is extended to include multiple-interaction Compton scatter sequences as well as sequences terminated by photoelectric absorption. The analytic formulation is developed using the statistical variance of the mean for components comprising composite, multivariate resolution precision estimators. It is demonstrated that enhanced resolution precision in the incident interaction scatter angle is attained when use is made of information from multiple interactions. An improvement in the resolution precision of up to approximately 40% is observed for triple Compton scatter. Comparison of the analytic estimates with Monte Carlo/chi-square results shows good agreement.

Chi-Square Distribution↗

PubMed1998

Residential 222Rn exposure and lung cancer: testing the linear no-threshold theory with ecologic data.

In most rigorous epidemiologic studies, such as case-control and cohort studies, the basic unit of analysis is the individual. Each individual is classified in terms of exposure and disease status. However, in ecologic epidemiologic studies, the unit of analysis is some aggregate group of individuals. Summary measures of exposure and disease frequency are obtained for each aggregate, and the analyses focus on determining whether or not the aggregates with high levels of exposure also display high disease rates. The ecologic study design has major limitations, including ecologic confounding and cross level bias. Cohen has attempted to circumvent these limitations by invoking the linear no-threshold theory of radiation carcinogenesis to derive aggregate "exposures" from individual-level associations. He asserts that, "while an ecologic study cannot determine whether radon causes lung cancer, it can test the validity of a linear-no threshold relationship between them." Cohen compares his testing of the linear no-threshold relationship between radon exposure and lung cancer to the practice of estimating the number of deaths from the person-rem collective dose, dividing the person-rem by the number of individuals in the population to derive the individual average dose, and then determining individual average risk by dividing the number of deaths by the number of individuals in the population. We show that Cohen's erroneous assumptions concerning occupancy rates and smoking effects result in the use of the wrong model to test the linear no-threshold theory. Because of these assumptions, the ecologic confounding and cross level bias associated with Cohen's model invalidate his findings. Furthermore, when more recent Iowa county lung cancer incidence rates are regressed on Cohen's mean radon levels, the reported large negative associations between radon exposure and lung cancer are no longer obtained.

Air Pollutants, Radioactive↗

PubMed1998

Spatial variation of residential radon concentrations: the Iowa Radon Lung Cancer Study.

Homeowners and researchers frequently estimate the radon concentrations in various areas of the home from a single radon measurement often performed in the home's basement. This study describes the spatial variation of radon concentrations both between floors and between rooms on the same floor. The geometric mean basement and first floor radon concentrations for one-story homes were 13.8% and 9.0% higher, respectively, as compared to their counterparts in two-story homes. The median first floor/basement ratio of radon concentrations for one-story homes was 0.60. The median ratios between first floor/basement and second floor/basement for two-story homes were 0.51 and 0.62, respectively. The mean coefficient of variation for detectors placed on the same floor was 9.5%, which was only 2.6% higher than the mean coefficient of variation found for collocated (duplicate) quality control detectors. The wide individual variations noted in radon concentrations serve as a reminder of the importance of performing multiple radon measurements in various parts of the home when estimating home radon concentrations.

Adult↗

PubMed1998

Regional peripheral vascular supply based on the superficial temporal artery in dogs and cats.

Cutaneous arterial blood supply to the temporal region was evaluated in 8 dogs and 8 cats. Subtraction radiography and angiography of the carotid and superficial temporal arteries were used in 4 dogs and 4 cats to determine arterial blood supply to the temporal region and frontalis muscle. A myocutaneous axial pattern flap based on the superficial temporal artery and frontalis muscle may be indicated for cosmetic reconstruction in dogs and cats following surgical resection of neoplastic lesions or traumatic wounds in the maxillofacial region. The frontalis muscle was identified as the thin subcutaneous continuation of the platysma muscle extending cranially and rostrally. Dissection of the temporal region in 4 dogs and 4 cats revealed the subcutaneous location of the superficial temporal artery as it continues rostrally from the caudal aspect of the zygomatic arch.

Angiography↗

PubMed1998

Surgical treatment of intractable epilepsy attributable to multiple sclerosis.

Surgically removing a focus of epileptogenicity attributable to a multiple sclerosis (MS) plaque has not previously been considered a treatment option. Medically intractable partial epilepsy due to a chronically situated MS plaque is uncommon because most cases are self-limiting or managed with antiepileptic medication. We report a case of partial epilepsy resulting from such a plaque situated at the gray-white interface in the anterior parahippocampal gyrus. A favorable outcome was achieved by resection of the epileptogenic area.

Adult↗

PubMed1998

Evaluation of the effects of risedronate on hepatic microsomal drug metabolizing enzyme activities following administration to rats for 14 days: lack of an induction response.

Risedronate ([1-hydroxy-2-(3-pyridinyl)-ethylidene[bis]phosphonic acid] monosodium salt) was evaluated for induction of hepatic microsomal drug metabolizing enzymes in male and female Sprague Dawley rats (N = 4/sex/dose group). Main study animals received water (vehicle control), risedronate (0.1, 0.8, 4, or 16 mg/kg/day) or phenobarbital (80 mg/kg/day, positive control) by daily oral gavage for 14 consecutive days. Recovery study animals received water, risedronate (16 mg/kg/day) or phenobarbital (80 mg/kg/day) by daily oral gavage for 14 consecutive days and then were maintained drug-free for 14 days to evaluate the reversibility of any observed effects. At the conclusion of each study the animals were sacrificed, the liver removed, weighed and the microsomal subcellular fraction prepared. The hepatic microsomal fraction was then evaluated for protein content, cytochrome P450, and the activities of aniline hydroxylase, aminopyrine N-demethylase, ethoxycoumarin O-deethylase and p-nitrophenol UDP-glucuronosyltransferase. Risedronate was well tolerated during the dosing phase of the study as evidenced by clinical observations, body weight gain and food consumption which were not significantly different from the vehicle controls. Risedronate did not significantly increase (P > 0.05) liver weight, liver/body weight ratio, protein content, P450, aniline hydroxylase, aminopyrine N-demethylase, ethoxycoumarin O-deethylase or p-nitrophenol UDP-glucuronosyltransferase in rats of either sex when compared to vehicle controls. As expected, the hepatic microsomal enzyme inducer phenobarbital significantly increased (P < 0.05) liver weight, liver/body weight ratio, protein content (males only), P450, aniline hydroxylase (males only), aminopyrine N-demethylase (males only), ethoxycoumarin O-deethylase and p-nitrophenol UDP-glucuronosyltransferase in rats relative to vehicle controls. Following the 14 day drug-free recovery period the induction parameters increased by phenobarbital reversed to vehicle control levels. The results obtained in this well controlled study indicate that risedronate is not an inducer of hepatic microsomal drug metabolizing enzymes in the rat.

Animals↗

PubMed1998

High resolution recording of late cortical surface potentials N1 and gamma band response (GBR).

The present investigation was conducted to help determine whether source activity of the direct recorded N1 response differed from that of the gamma band response (GBR). Auditory evoked cortical potential data from two patients with intractable epilepsy undergoing prolonged video EEG monitoring after implantation of subdural electrodes is reported in this investigation. Evoked responses were recorded to 1000-Hz tone bursts. The data were then filtered digitally to resolve the GBR. The voltage fields were subsequently viewed topographically. Although both responses originated in the supratemporal cortex, the N1 and GBR voltage field patterns differed. These results are consistent with the view that the sources of N1 and the GBR are different, suggesting that these components emanate from functionally distinct neuronal pools.

Adult↗

PubMed1998

Trends in predoctoral education in geriatric dentistry.

Historically, education in geriatric dentistry has been limited in both quantity and quality. More recently, a number of educational initiatives have been developed in response to the growing number of older adults and their changing oral health status and dental treatment needs. A survey of U.S. and Canadian dental schools examined curriculum trends and assessed the effectiveness of educational initiatives and the value of AADS/AoA geriatric dental curricular materials. All schools responded. Compared to previous reports, more schools had geriatric didactic course(s), clinical rotations, and faculty with geriatric dental training. Fifty-eight percent of dental schools support geriatric dentistry in their budgets. The primary barriers to program expansion continue to be the lack of trained faculty members, a crowded curriculum, and fiscal concerns.

Aged↗

PubMed1997

Exposure of tilapian fish to the pesticide lindane results in hypocellularity of the primary hematopoietic organ (pronephros) and the spleen without altering activity of phagocytic cells in these organs.

Tilapia were dosed by intraperitoneal injection for 5 consecutive days with either 20 or 40 mg/kg of the environmental contaminant hexachlorocyclohexane (lindane). The effects of this organochlorine pesticide on morphology and total cellularity of the spleen and pronephros were examined on the second day following termination of dosing. The functional capacity of phagocytic cells isolated from both spleen and pronephros was also evaluated as possible additional indicators of chemical-induced immunotoxicity. A dose-related reduction was found in spleen and pronephros total white blood cell counts in the fish exposed to lindane. In addition, hypocellularity of lymphoid regions in the spleen and pronephros was evident in chemical-exposed animals upon histopathological examination. However, phagocytosis of fluorescent microspheres by phagocytic cells isolated from the spleen and pronephros was not inhibited by the exposure to lindane. Similarly, no decrease in phorbolmyristate acetate (PMA)-stimulated hydrogen peroxide production was observed in phagocytic cells collected from lindane-exposed fish. These results suggest that cellular depletion in tilapia spleen and pronephros may represent a more sensitive indicator of lindane exposure than does the functional capacity of phagocytic cells isolated from these hematopoietic organs. Ultrastructural observations support this hypothesis and, further, suggest that lymphocytic cells may be targeted at the present exposure levels.

Animals↗

PubMed1997

Structure and mechanism of a sub-family of enzymes related to N-acetylneuraminate lyase.

We describe here a sub-family of enzymes related both structurally and functionally to N-acetylneuraminate lyase. Two members of this family (N-acetylneuraminate lyase and dihydrodipicolinate synthase) have known three-dimensional structures and we now proceed to show their structural and functional relationship to two further proteins, trans-o-hydroxybenzylidenepyruvate hydratase-aldolase and D-4-deoxy-5-oxoglucarate dehydratase. These enzymes are all thought to involve intermediate Schiff-base formation with their respective substrates. In order to understand the nature of this intermediate, we have determined the three-dimensional structure of N-acetylneuraminate lyase in complex with hydroxypyruvate (a product analogue) and in complex with one of its products (pyruvate). From these structures we deduce the presence of a closely similar Schiff-base forming motif in all members of the N-acetylneuraminate lyase sub-family. A fifth protein, MosA, is also confirmed to be a member of the sub-family although the involvement of an intermediate Schiff-base in its proposed reaction is unclear.

Amino Acid Sequence↗