Effect of the thiazolidinedione antihyperglycaemic agent BRL 49653 on liver fatty acid binding protein gene expression.
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Animals↗
Biomedical subjects
S A Smith
Publications and source records attributed to S A Smith.
Reduced insulin sensitivity of isolated skeletal muscle but enhanced lipogenic capacity of adipocytes in both spontaneously hypertensive and Wistar Kyoto rats.
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Adipocytes↗
Physical activity, trauma, and ALS: a case-control study.
AIMS: The association of trauma and physical activity with ALS is controversial. We explored the relation in a pilot case-control study. MATERIAL AND METHODS: ALS patients were selected from a university muscle disease clinic and paired with two matched controls: one from the clinic, but having different diseases, and one from the community. RESULTS: We found several strong and statistically significant differences between ALS cases and the matched controls. These included severe head, neck and back injury (OR = 5.3), the frequency of sweating in work (OR = 1.6) or leisure activity (also OR = 1.6), and earning a school letter (OR = 3.1). Other measures of trauma and activity, while not achieving statistical significance (p < 0.05), were in accord with these findings. DISCUSSION: Possible explanations include trauma and vigorous exercise precipitating ALS; trauma as an early sign of disease; or a third factor associated with ALS predisposing to injury. CONCLUSIONS: Severe head, neck, and back injury and frequency of sweating both in work and leisure activity showed a strong association with ALS. Further study could test narrower and less common exposures with greater statistical power.
Amyotrophic Lateral Sclerosis↗
Effect of foscarnet on quantities of cytomegalovirus and human immunodeficiency virus in blood of persons with AIDS.
Four intravenous dosages of foscarnet given for 10 days were compared with no therapy in persons with AIDS who had asymptomatic cytomegalovirus (CMV) viremia. CMV viremia was quantitated by endpoint cell dilution microcultures, pp65 antigenemia assay, and measurement of CMV DNA in peripheral blood leukocytes by a quantitative-competitive PCR. Human immunodeficiency virus type 1 (HIV-1) viremia was quantitated by endpoint cell dilution microculture, serum p24 antigen assay, and PCR for HIV-1 RNA in plasma. Twenty-seven subjects who had received a median of 22 months of nucleoside antiretroviral therapy were enrolled. Twenty-two subjects received foscarnet, which was well tolerated and decreased the CMV burden, as reflected by all three indicator assays. During the 10 days of dosing, the level of CMV viremia, as measured by 50 percent tissue culture infective doses, decreased from 117.5 to 12.7 (P = 0.001), the amount of CMV DNA decreased from 20,328 copies to 622 copies per 150,000 leukocytes (P = 0.02), and the level of CMV pp65 antigenemia decreased from 14.9 to 1.6 positive peripheral blood mononuclear cells per 50,000 leukocytes (P = 0.008). A significant pharmacodynamic relationship was found between the peak foscarnet concentration and a decrease in the level of CMV antigenemia (P < 0.05). Foscarnet had no effect on quantitative HIV-1 microcultures during the 10 days of treatment, but the HIV-1 p24 antigen level in serum decreased significantly, from 454 to 305 pg/ml (P = 0.01). Also, a significant pharmacodynamic relationship was seen between plasma HIV-1 RNA concentrations and both peak foscarnet concentration (P < 0.01) and the area under the foscarnet time-concentration curve (P < 0.05). Reductions in the levels of CMV and HIV-1 viremia correlated quantitatively with systemic exposure to foscarnet, whereas control subjects actually experienced an increase in CMV and HIV-1 burdens. The dual antiviral activity of foscarnet shown in this trial encourages investigation of its use in combination with other antiretroviral therapies for persons with AIDS.
AIDS-Related Opportunistic Infections↗
Toxicity and tolerability of recombinant human ciliary neurotrophic factor in patients with amyotrophic lateral sclerosis.
We examined the toxicity of both single and multiple subcutaneous injections of recombinant human ciliary neurotrophic factor (rhCNTF) in 72 patients with ALS, in doses ranging from 2 to 100 micrograms/kg. Adverse events were generally dose related and ranged from mild to severe. The tolerability of daily subcutaneous rhCNTF was equivalent to placebo at doses < or = 5 micrograms/kg/day. At higher doses, anorexia, weight loss, reactivation of herpes simplex virus (HSV1) labialis/stomatitis, cough, and increased oral secretions occurred.
Adult↗
Central projections of persistent larval sensory neurons prefigure adult sensory pathways in the CNS of Drosophila.
We have used a GAL4 enhancer-trap line driving the expression of a lacZ construct to examine the reorganisation of an identified group of proprioceptive sensory neurons during metamorphosis in Drosophila. The results show that whilst most larval sensory neurons degenerate during the first 24 hours of metamorphosis a segmentally repeated array of 6 neurons per segment persists into the adult stages to become functional adult neurons. These sensory neurons retain their axonal projections in the central nervous system intact and unchanged throughout. The adult sensory neuron axons enter the central nervous system at around 44 hours after puparium formation. Most of these axons grow along the pathways defined by the persistent larval sensory axons. The ordering of the adult sensory projections is, therefore, established upon the larval pattern of projections. The possibility that the larval neurons act as guidance cues for organising the ordered arrays of sensory neurons is discussed.
Animals↗
Comparison of two screening tests of competency to stand trial for defendants with mental retardation.
Scores for the four terms found by Smith and Hudson to predict competency to stand trial in defendants with mental retardation correlated significantly (r = .65) with scores on the Competency Screening Test (N = 34). Agreement between sets of scores was 84%.
Adult↗
Fine structure of the retinal pigment epithelium of the barred owl (Strix varia).
The retinal pigment epithelium (RPE) as well as the choriocapillaris and Bruch's membrane (complexus basalis) have been studied by light and electron microscopy in the barred owl (Strix varia). The RPE consists of a single layer of cuboidal cells joined laterally by a series of tight junctions that forms part of the blood-ocular barrier. Basally (sclerally) the retinal epithelial cells display numerous deep infoldings while apically (vitreally) microvillar processes interdigitate with the photoreceptor outer segments. Internally the RPE cells show a large vesicular nucleus, plentiful smooth endoplasmic reticulum (SER) and polysomes but very little rough endoplasmic reticulum (RER). Numerous pleomorphic (including ring-shaped) mitochondria are basally located. In the light-adapted state the small melanosomes are almost exclusively located within the apical process indicating that retinomotor movements probably occur. Phagosomes and lysosome-like bodies are present as are myeloid bodies which may show ribosomes on their outer surface. Bruch's membrane is typical of avian species in that it is pentalaminate and the central lamina densa is displaced towards the choroid. The choriocapillaris endothelium is thin but only minimally fenestrated facing Bruch's membrane. Most fenestrations present show a single-layered diaphragm while others display a double-layered diaphragm as noted in other avian species.
Animals↗
Fine structure of the retinal photoreceptors of the barred owl (Strix varia).
The photoreceptors of the barred owl (Strix varia) consist of rods, single cones and unequal double cones present in a ratio of about 35:1:3. In the light-adapted condition the rods are of uniform diameter along their entire length and are therefore not felt to undergo photomechanical changes. The rod outer segment consists of a stack of scalloped bimembranous discs enclosed in a limiting membrane. The rod inner segment displays an ellipsoid of mitochondria, much rough endoplasmic reticulum (RER), numerous polysomes, Golgi zones and autophagic vacuoles, but no hyperboloid of glycogen. Single cones show a slightly tapered outer segment and a heterogeneous oil droplet along with an ellipsoid of mitochondria at the apex of the inner segment. Double cones consist of a larger chief member which also displays a heterogeneous oil droplet and a slightly smaller accessory member which does not. Both members of the double cone as well as the single cones show plentiful polysomes and RER as well as Golgi zones in the inner segment, but none of the cones possessed a condensed paraboloid of glycogen. The contiguous membranes of the chief and accessory cones displayed a few presumed junctional complexes. Judging by their elongated shape in the light-adapted state, cones in this species do not undergo retinomotor movements. Rods and both types of cones have both invaginated (ribbon) and superficial (conventional) synaptic sites.
Animals↗
Fine structure of the pecten oculi of the barred owl (Strix varia).
The pecten oculi of the barred owl (Strix varia) has been examined by light and transmission electron microscopy. The pecten in this species is of the pleated type and is small in comparison to the size of the ocular globe. The pecten consists of 8-10 accordion-like folds that are linked apically by a pigmented tissue bridge. Each fold contains numerous capillaries, larger supply and drainage vessels, and abundant pleomorphic melanocytes. Most of these capillaries are extremely specialized vessels that possess plentiful microfolds on both the luminal and abluminal surfaces. Some capillaries however display only a few microfolds. The endothelial cell bodies are extremely attenuated, with most organelles located near the nucleus. All capillaries are surrounded by a very thick fibrillar basal lamina, which is thought to provide structural support to these small vessels. Pericytes are commonly found within these thickened basal laminae. Numerous melanocytes are also present, with processes that form an incomplete sheath around the capillaries. These processes are also presumed to provide structural support for the capillaries. As in other avian species, the morphology of the barred owl pecten is indicative of extensive involvement in substance transport. When compared to the pecten of more visually-oriented species, this pecten is smaller, has fewer folds, and displays a reduced number of microfolds within the capillaries. In these and other features, the barred owl pecten is similar to the pecten of the great horned owl (Bubo virginianus).
Animals↗
Comparison of hematologic reference intervals between culture system and type of hybrid striped bass.
OBJECTIVE: To determine and compare hematologic reference intervals for hybrid striped bass from different culture systems and for 2 types of hybrid. DESIGN: Observational comparison study. ANIMALS: Clinically normal sunshine bass (reciprocal hybrid striped bass, female Morone chrysops X male M saxatilis) raised in high-density recirculating systems, sunshine bass raised in tanks with biofilters, and palmetto bass (original hybrid striped bass, female M saxatilis X male M chrysops) raised in tanks with biofilters. PROCEDURES: Hematologic reference intervals were determined for fish from the different production systems, following the National Committee for Clinical Laboratory Standards guidelines. Reference intervals from the 3 groups were compared. RESULTS: Reference intervals were significantly different between sunshine bass in the 2 culture systems and between sunshine and palmetto bass. Many of the differences were slight, but notable differences were observed. Sunshine bass in recirculating systems had higher total leukocyte, lymphocyte, neutrophil, and monocyte counts than did either hybrid in tanks. Palmetto bass had a greater number of neutrophils than monocytes, whereas sunshine bass had more monocytes than neutrophils. Additionally, palmetto bass had a lower PCV and hemoglobin value than did either group of sunshine bass. CONCLUSIONS: Separate reference intervals should be developed for hybrid striped bass in different culture systems and for different types of hybrids. CLINICAL RELEVANCE: Determining reference intervals for hybrid striped bass provides a tool to assess the health status of these fish.
Animals↗
Blood biochemical reference intervals for sunshine bass (Morone chrysops x Morone saxatilis) in three culture systems.
OBJECTIVE: To determine and compare biochemical reference intervals for sunshine bass (hybrid striped bass) from 3 culture systems. DESIGN: Observational comparison study. ANIMALS: Clinically normal sunshine bass (reciprocal hybrid striped bass, female Morone chrysops x male M saxatilis raised in high-density recirculating systems (80 g/L), low-density tanks (5 g/L) with biofilters, and cages (70 g/L) in a fresh water pond. PROCEDURE: Biochemical reference intervals were determined for fish from the different production systems following the National Committee for Clinical Laboratory Standards guidelines. Reference intervals from the 3 groups were compared. RESULTS: Reference intervals were significantly different between sunshine bass in the various culture systems. Though most of the differences in reference intervals were minor, fish in the high-density recirculating system had higher concentrations of total protein, albumin, globulin, creatinine, and phosphorus, and lower chloride values. There were no significant differences in glucose concentrations among the 3 groups of fish, and no differences in cortisol concentrations between fish in tanks and cages. CONCLUSIONS: Separate reference intervals should be developed for hybrid striped bass in different culture systems. CLINICAL RELEVANCE: Determining biochemical reference intervals for hybrid striped bass provides a tool to assess the health status of these fish.
Alkaline Phosphatase↗
Esotropia and epileptic eye deviation.
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Child↗
alpha-Hydroxy phosphinyl-based inhibitors of human renin.
The design and application of alpha-hydroxy phosphonates, a new class of transition state analogs, toward the discovery of novel and potent inhibitors of the aspartyl protease renin is described. Tripeptidic alpha-hydroxy diethyl phosphonate 3, the first example in this series, was found to be a good inhibitor of human renin (IC50 = 29 nM), and preliminary studies led to the choice of alpha-hydroxy dimethyl phosphonate 15 (IC50 = 16 nM) as a base-line compound for further structure-activity relationship study. Corresponding phosphinate (28-30) and phosphine oxide (23 and 24) analogs of 15 were prepared to assess the steric and electronic requirements around the phosphorus center. Evaluation of these analogs suggested that the presence of at least one alkoxy group on phosphorus was a critical requirement for good activity. Inhibitors with leucine at P2 possessed better in vitro activity than the corresponding P2 histidine analogs (15, IC50 = 16 nM vs 37, IC50 = 220 nM; 33, IC50 = 8.5 nM vs 40, IC50 = 41 nM). Compound 34 (IC50 = 31 nM), the P3 aminocaproic analog of 15, showed complete and long-lasting inhibition of plasma renin activity while eliciting a 10-15 mmHg drop in mean arterial pressure when administered intravenously at 1 mumol/kg in conscious, sodium-depleted, cynomolgus monkeys. In summary, the alpha-hydroxy phosphonates represent a promising and structurally novel class of transition state analog inhibitors of human renin.
Angiotensinogen↗
A gene (DLG2) located at 17q12-q21 encodes a new homologue of the Drosophila tumor suppressor dIg-A.
We have isolated a novel cDNA that maps distal to BRCA1 at 17q12-q21. The total sequence predicts a protein of 576 amino acids with three conserved regions: a 90-amino-acid repeat domain, a SH3 (src homology region 3) motif, and a guanylate kinase domain. These conserved regions are shared among members of the discs-large family of proteins that include human p55, a membrane protein expressed in erythrocytes, rat PSD-95/SAP90, a synapse protein expressed in brain, Drosophila dIg-A, a septate junction protein expressed in various epithelia, and human and mouse ZO-1 and canine ZO-2, two tight junction proteins. dIg-A has been shown to act as a tumor suppressor, and the other members may all be involved in signal transduction through specialized membrane domains with highly organized cytoskeletons and thus are potential tumor suppressors. Since allelic loss has been reported in the 17q12-q21 region in breast and ovarian cancer and it appears that BRCA1 is not the target of the losses, we looked for somatic alterations in DLG2 in sporadic breast tumors. No evidence for mutation was found, making it unlikely that DLG2 is involved in sporadic breast cancer.
Amino Acid Sequence↗
Isolation and mapping of a gene encoding a novel human ADP-ribosylation factor on chromosome 17q12-q21.
A gene encoding a low-molecular-weight GTP-binding protein was isolated from a retinal cDNA library and mapped to human chromosome 17q12-q21. Comparison of the predicted protein with the protein databases revealed striking homology to the family of ADP-ribosylation factors (ARFs), which are thought to be involved in membrane trafficking and protein secretion. The greatest homology observed was with the rat ARF-like 4 protein (ARL4), with which it shared 58% identity, while the more highly conserved human ARF1 and ARF3 proteins each shared 46% identity. Inspection of the predicted new protein showed that it contained each of the six conserved motifs that are required for guanine nucleotide binding and hydrolysis, and thus it is probably a novel ARF isoform. We have designated the new protein and its corresponding gene ARF4L.
ADP-Ribosylation Factor 1↗
Patella of selected bats: patterns of occurrence or absence and associated modifications of the quadriceps femoris tendon.
BACKGROUND: Having observed the apparent absence of a bony patella in a Madagascar flying fox (Pteropus sp.), other species from the two suborders of bats (Megachiroptera and Microchiroptera) were examined to determine the presence or absence of a bony patella and the distribution of this feature among bats. METHODS: Gross, radiographic, and histologic examination of seven megachiropteran species representing four genera, as well as six microchiropteran species representing six genera, was performed. RESULTS: A bony patella was observed in all six microchiropteran and in three megachiropteran species. The tendon of the quadriceps femoris muscle in Microchiropteran species was composed mainly of dense regular connective tissue. The quadriceps tendon in Megachiropteran species with a patella contained an abundance of fibrocartilage and hyaline cartilage, unlike the quadriceps femoris tendon of the Microchiroptera or a laboratory mouse examined for comparison. CONCLUSIONS: Four species of the megachiropteran genus Pteropus lacking a bony patella displayed a similar occurrence and distribution of fibrocartilage and hyaline cartilage within the quadriceps tendon as seen in the other bats. In reference to this singular feature, Pteropus is unique among the representatives of megachiropteran and microchiropteran genera examined here.
Animals↗
The University of Minnesota Cancer Prevention Research Unit vegetable and fruit classification scheme (United States).
High vegetable and fruit (V&F) intake has been associated with a lower risk of many cancers. However, the specific V&F, the active compounds present in V&F, and the dose at which they confer protection are unknown. Standard methods for assessing, classifying, and quantifying V&F exposures in epidemiologic studies have not been established. Differences among studies occur due to inherent differences among V&F, and across dietary assessment methods, study populations, etiologic hypotheses, and analytic methods. The V&F classification scheme presented here characterizes and quantifies V&F consumption for elucidating risk relationships, identifying chemopreventive compounds present in V&F, and facilitating identification of potential biomarkers of V&F intake. Broad criteria define which plant foods count as V&F. Formation of food groups is based on proposed biological mechanisms of action. Five main groups are included: Total V&F; Total Vegetables; Total Fruits; and two groups orthogonal to these -- the Botanical and Phytochemical groups. Subgroups are specified within each main group. V&F exposure is quantified as the absolute amount consumed (weight) or as the number of household servings. This classification scheme has public health applications and may be used to examine associations with chronic diseases other than cancer.
Eating↗