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Biomedical subjects

T Green

Publications and source records attributed to T Green.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pharmacological properties of the potent epileptogenic amino acid dysiherbaine, a novel glutamate receptor agonist isolated from the marine sponge Dysidea herbacea.

Dysiherbaine (DH) is a marine sponge-derived amino acid that causes seizures upon injection into mice. In this report we investigate the behavioral effects and characterize the pharmacological activity of DH. DH induced convulsive behaviors in mice with ED(50) values of 13 pmol/mouse, i.c.v. and 0.97 mg/kg, i.p. In rat brain synaptic membranes DH displaced binding of [3H]kainic acid (KA) and [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) with K(i) values of 26 and 153 nM, respectively; in contrast, DH did not displace the N-methyl-D-aspartic acid (NMDA) receptor ligand [3H]CGS-19755. DH displaced [3H]KA from recombinant GluR5 and GluR6 kainate receptor subunits expressed in HEK293 cells with K(i) values of 0.74 and 1.2 nM, respectively. In whole-cell voltage-clamp recordings from cultured rat hippocampal neurons, DH evoked inward currents from both AMPA and KA receptors with EC(50) values of 9.7 microM and 210 nM, respectively. AMPA receptor currents were blocked by GYKI 53655, whereas KA receptor currents were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Surprisingly, in calcium imaging experiments we found that DH also activated recombinant mGluR5 receptors but did not activate mGluR1 receptors. DH did not activate glutamate transporters or gamma-aminobutyric acid A (GABA(A)) receptors. These results indicate that DH is a potent non-NMDA-type agonist with very high affinity for KA receptors, as well as a subtype-selective mGluR agonist. DH possesses the most potent epileptogenic activity among the amino acids yet identified. This novel excitatory amino acid may prove useful for evaluating the physiological and pathological roles of non-NMDA receptors, especially KA receptors, in the central nervous system.

ATP-Binding Cassette Transporters↗
PubMed2001

A randomized controlled trial of a passive accessory joint mobilization on acute ankle inversion sprains.

BACKGROUND AND PURPOSE: Passive joint mobilization is commonly used by physical therapists as an intervention for acute ankle inversion sprains. A randomized controlled trial with blinded assessors was conducted to investigate the effect of a specific joint mobilization, the anteroposterior glide on the talus, on increasing pain-free dorsiflexion and 3 gait variables: stride speed (gait speed), step length, and single support time. SUBJECTS: Forty-one subjects with acute ankle inversion sprains (<72 hours) and no other injury to the lower limb entered the trial. METHODS: Subjects were randomly assigned to 1 of 2 treatment groups. The control group received a protocol of rest, ice, compression, and elevation (RICE). The experimental group received the anteroposterior mobilization, using a force that avoided incurring any increase in pain, in addition to the RICE protocol. Subjects in both groups were treated every second day for a maximum of 2 weeks or until the discharge criteria were met, and all subjects were given a home program of continued RICE application. Outcomes were measured before and after each treatment. RESULTS: The results showed that the experimental group required fewer treatment sessions than the control group to achieve full pain-free dorsiflexion. The experimental group had greater improvement in range of movement before and after each of the first 3 treatment sessions. The experimental group also had greater increases in stride speed during the first and third treatment sessions. DISCUSSION AND CONCLUSION Addition of a talocrural mobilization to the RICE protocol in the management of ankle inversion injuries necessitated fewer treatments to achieve pain-free dorsiflexion and to improve stride speed more than RICE alone. Improvement in step length symmetry and single support time was similar in both groups.

Acute Disease↗
PubMed2000

Building a "brain attack" team to administer thrombolytic therapy for acute ischemic stroke.

Before tissue plasminogen activator (tPA) was licensed for use in Canada, in February 1999, the Calgary Regional Stroke Program spearheaded the development and organization of local resources to use thrombolytic therapy in patients who had experienced acute ischemic stroke. In 1996 special permission was obtained from the Calgary Regional Health Authority to use intravenously administered tPA for acute ischemic stroke, and ethical and scientific review boards approved the protocols. After 3 years our efforts have resulted in improved patient outcomes, shorter times from symptom onset to treatment and acceptable adverse event rates. Areas for continued improvement include the door-to-needle time and broader education of the public about the symptoms of acute ischemic stroke.

Alberta↗
PubMed2000

Trichloroethylene induced vitamin B(12) and folate deficiency leads to increased formic acid excretion in the rat.

Exposure of rats to trichloroethylene induces a sustained excretion of large amounts of formic acid in urine. Both of the major metabolites, trichloroethanol and trichloroacetic acid, were found to induce this response, but not the minor metabolite S-(1, 2-dichlorovinyl) cysteine. Other polychlorinated solvents, including carbon tetrachloride and chloroform, also increased urinary formate excretion. Addition of folic acid either to diet or drinking water modulated the response indicating that these rats were folate deficient. Two markers of vitamin B(12) deficiency, methylmalonic acid and 5-methyltetrahydrofolate, were also markedly increased in urine and plasma respectively. The increase in 5-methyltetrahydrofolate is consistent with a folate deficiency caused by an inhibition of the vitamin B(12) dependent methionine salvage pathway. Since both vitamin B(12) and chemicals containing polychlorinated carbon atoms readily form free radicals, it is suggested that trichloroacetic acid and trichloroethanol interact with vitamin B(12) through a free radical mechanism inducing a B(12) deficiency and, as a consequence, a folate deficiency. As a result of the folate deficiency, excess formic acid, which is normally utilised through this pathway, is excreted in urine.

Anesthetics, Inhalation↗
PubMed2000

Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.

The chronic inflammatory bowel diseases (IBDs)-Crohn disease (CD) and ulcerative colitis (UC)-are idiopathic, inflammatory disorders of the gastrointestinal tract. These conditions have a peak incidence in early adulthood and a combined prevalence of approximately 100-200/100,000. Although the etiology of IBD is multifactorial, a significant genetic contribution to disease susceptibility is implied by epidemiological data revealing a sibling risk of approximately 35-fold for CD and approximately 15-fold for UC. To elucidate the genetic basis for these disorders, we undertook a genomewide scan in 158 Canadian sib-pair families and identified three regions of suggestive linkage (3p, 5q31-33, and 6p) and one region of significant linkage to 19p13 (LOD score 4.6). Higher-density mapping in the 5q31-q33 region revealed a locus of genomewide significance (LOD score 3.9) that contributes to CD susceptibility in families with early-onset disease. Both of these genomic regions contain numerous genes that are important to the immune and inflammatory systems and that provide good targets for future candidate-gene studies.

Age of Onset↗
PubMed2000

Acetochlor-induced rat nasal tumors: further studies on the mode of action and relevance to humans.

The herbicide acetochlor, and its analogue alachlor, have similar toxicological properties, the most significant being the induction of nasal adenomas in rats in 2-year feeding studies. Previous investigations have proposed a mode of action involving metabolism to a quinone-imine, the formation of protein adducts, cell death, and compensatory hyperplasia leading to the observed adenomas. Comparisons between rats and humans of the metabolic cascade leading to the quinone-imine indicate that these chemicals do not pose a threat to humans. Further investigations with acetochlor, presented here, have revealed an additional activation pathway in which a sulfoxide metabolite of acetochlor plays a key role. The sulfoxide was found to be the major plasma metabolite in rats dosed with acetochlor. Whole-body autoradiography studies established that this metabolite selectively accumulates and persists in the olfactory epithelium of rats. Radiolabeling of the sulfoxide molecule in the phenyl ring and in the sulfoxide side-chain demonstrated that the metabolite accumulating in nasal tissues retains the sulfoxide side-chain. The formation of a quinone-imine from the sulfoxide was facilitated by hydroxylation of the phenyl ring by a cytochrome P450 isoenzyme which was specific to the nasal epithelium in the rat. This metabolic conversion could not be detected in 33 fresh human nasal tissue samples, supporting the earlier view that the acetochlor-induced rat nasal tumors do not represent a hazard for humans.

Adenoma↗
PubMed2000

Psychiatric manifestations of systemic illness.

Many behavioral manifestations of systemic disease exist, including delirium, psychosis, mania, catatonia, depression, and anxiety. The features and medical causes of each of those manifestations are described. The indications from history and physical examination that suggest underlying medical illness are reviewed. The psychiatric presentations of several specific conditions are discussed in detail.

Central Nervous System Neoplasms↗
PubMed2000

Lipoprotein subpopulation distributions in lean, obese, and type 2 diabetic women: a comparison of African and white Americans.

OBJECTIVE: Abnormal subpopulation distributions of plasma lipoproteins have been reported in white American (WA) women with obesity and type 2 diabetes that explain part of the elevated rate of cardiovascular disease in these patients. This study examined if these perturbations also occur in obese and diabetic African American (AA) women and compared the lipoprotein profiles with WA counterparts. RESEARCH METHODS AND PROCEDURES: We determined the lipoprotein subpopulation distribution in the plasma of 51 lean women (29 WA, 22 AA, body mass index [BMI] < 30), 50 obese women (27 WA, 23 AA, BMI > 30), and 43 obese women with type 2 diabetes (27 WA, 16 AA), by nuclear magnetic resonance spectroscopy. RESULTS: AA diabetic women, like WA diabetic women, had a larger average very low density lipoprotein (VLDL) size, elevated levels of small low density lipoprotein cholesterol (LDL-C), and lower levels of small high density lipoprotein cholesterol (HDL-C), when compared to lean controls (p<0.05). These differences were accompanied by higher VLDL-triglycerides (TG) and LDL-C in WA (p<0.05), but not in AA. Although the effects of obesity and diabetes on lipoprotein subpopulation were fairly similar for AA and WA, some racial differences, particularly with respect to HDL, were observed. DISCUSSION: The atherogenic perturbations in lipoprotein profiles of obese AA women, particularly those with diabetes, were relatively similar to those found in WA women and may be contributing to the increased rate of cardiovascular disease (CVD) in AA with obesity and diabetes. The parameters of subpopulation distribution may provide better markers for CVD than lipid concentrations alone, particularly in AA women. Furthermore, subtle racial differences in lipoprotein profiles suggest that race-specific criteria may be needed to screen patients for CVD.

Adult↗
PubMed2000

Exploring the sexual histories of older GUM clinic attenders.

Little is known either of the factors motivating clinic attendance in later life, or the sexual health histories of older clinic attenders. A self-administered questionnaire study linked to patient note data aiming to explore these issues was undertaken within 3 genitourinary medicine (GUM) clinics in the Trent region. Participants comprised 224 individuals aged 50 years and older attending the 3 clinics during the study period. The majority of study participants were attending the clinic with a suspected sexually transmitted infection (STI) (n = 145, 64.7%) and approximately half (n=119, 53.1%) were first-time GUM clinic attenders. Data available for participants recruited from the Sheffield clinic indicated that, although the majority of participants reported having had only one sexual partner during the last 12 months, a significant minority reported considerably higher numbers of partners, including those classed 'higher risk' for STI acquisition. These data indicate that older people engage in behaviours that place them at risk of STI acquisition and many attend GUM clinics for the first time in later life.

Age Factors↗
PubMed2000

Pulmonary toxicity and carcinogenicity of trichloroethylene: species differences and modes of action.

Trichloroethylene (TCE) is both acutely toxic and carcinogenic to the mouse lung following exposure by inhalation. In contrast, it is not carcinogenic in the rat lung and is markedly less toxic following acute exposure. Toxicity to the mouse lung is confined almost exclusively to the nonciliated Clara cell and is characterized by vacuolation and increases in cell replication. Chloral, a metabolite of TCE that accumulates in Clara cells and has been shown to be the cause of the toxicity, also causes aneuploidy in some test systems. Cytotoxicity, increased cell division, and aneuploidy are known risk factors in the development of cancer and provide a plausible mode of action for TCE as a mouse lung carcinogen. All acute and chronic effects of TCE on the mouse lung are believed to be a direct consequence of high cytochrome P450 activity and impaired metabolism of chloral in Clara cells. Comparisons between species suggest that the ability of the human lung to metabolize TCE is approximately 600-fold less than that in the mouse. In addition, the human lung differs markedly from the mouse lung in the number and morphology of its Clara cells. Thus, the large quantitative differences between the metabolic capacity of the mouse lung and the human lung, together with the species differences in the number and morphology of lung Clara cells, suggest that the risks to humans are minimal and that other tumor sites should take precedent over the lung when assessing the potential risks to humans exposed to TCE.

Animals↗
PubMed1999

Effects of reduced ankle dorsiflexion following lateral ligament sprain on temporal and spatial gait parameters.

Partial rupture of the lateral ligament complex of the ankle is the commonest soft tissue injury affecting the lower limb. The effect of the limitation of motion at the ankle, particularly of dorsiflexion, on gait is unclear. In this study, 34 subjects were measured during their recovery from a partial rupture of the lateral ligament for both range of dorsiflexion and the temporal and spatial parameters of walking. Consistent relationships were identified between the range and the gait variables which were in concordance with the characteristics expected from an antalgic gait pattern.

Adolescent↗
PubMed1999

Comparison of the internal transcribed spacer, ITS-1, from Sarcocystis falcatula isolates and Sarcocystis neurona.

The genetic diversity among 6 Sarcocystis falcatula isolates derived from geographically distinct regions in the U.S.A. was detected using the first internal transcribed spacer region 1 (ITS-1) of the rRNA gene. These sequences were then compared to the full sequence from a Sarcocystis neurona isolate obtained from a California horse diagnosed with equine protozoal myeloencephalitis. No nucleotide differences were detected over partial sequence analysis of 2 additional S. neurona isolates: however, the complete nucleotide sequence for the ITS-1 region was not compared. Twelve nucleotide differences were consistently detected when aligned sequences of S. neurona were compared to those of the S. falcatula isolates. Additional nucleotide base changes were detected among the S. falcatula isolates, but these changes were not consistent in all the S. falcatula isolates. These results indicate that S. falcatula may be comprised of a heterogeneous population and that the ITS-1 region can be used to distinguish S. neurona from S. falcatala used in this study.

Animals↗
PubMed1998

Increased bioactivation of dihaloalkanes in rat liver due to induction of class theta glutathione S-transferase T1-1.

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3. 5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.

Animals↗
PubMed1998

Direct effects of metabotropic glutamate receptor compounds on native and recombinant N-methyl-D-aspartate receptors.

The actions of glutamate in the central nervous system are mediated through interaction with fast activating ionotropic receptors and G protein-coupled metabotropic glutamate receptors (mGluRs). Studies of these receptors have relied on the availability of agonists and antagonists selective for each receptor class. Compounds that were thought to be selective for mGluRs have been extensively used to study the role of these receptors in the brain. Their use has implicated mGluRs in a wide range of physiological and pathological processes including the modulation of N-methyl-D-aspartate (NMDA) receptors and NMDA receptor-dependent processes. We report that some of the most commonly used mGluR compounds act as antagonists on NMDA receptors at concentrations commonly used to activate or block mGluRs. In addition, several of the drugs also act as agonists at higher concentrations due at least in part to high levels of contaminant amino acids. Our results indicate that caution should be used when using these drugs to study the roles of mGluRs in various NMDA-dependent processes. The antagonist effects were dependent on the concentration of the NMDA receptor coagonists, preventing reappraisal of previously published work.

Animals↗
PubMed1998

Formic acid excretion in rats exposed to trichloroethylene: a possible explanation for renal toxicity in long-term studies.

Rats exposed to trichloroethylene, either by gavage or by inhalation, excreted large amounts of formic acid in urine which was accompanied by a change in urinary pH, increased excretion of ammonia, and slight increases in the excretion of calcium. Following a single 6-h exposure to 500 ppm trichloroethylene, the excretion of formic acid was comparable to that seen after a 500 mg/kg dose of formic acid itself, yet the half-life was markedly different. Formate excretion in trichloroethylene treated rats reached a maximum on day 2 and had a half-life of 4-5 days, whereas urinary excretion was complete within 24 h following a single dose of formic acid itself. Formic acid was shown not to be a metabolite of trichloroethylene. When rats were exposed to 250 or 500 ppm trichloroethylene, 6 h/day, for 28 days, the only significant effects were increased formic acid and ammonia excretion, and a change in urinary pH. There was no evidence of morphological liver or kidney damage. Long-term exposure to formic acid is known to cause kidney damage suggesting that excretion of this acid may contribute to the kidney damage seen in the long-term studies with trichloroethylene.

Administration, Inhalation↗