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Biomedical subjects

M A Collins

Publications and source records attributed to M A Collins.

At least 37 records · Page 2Linked to original sources
PubMed2000

Increased beta-carboline 9N-methyltransferase activity in the frontal cortex in Parkinson's disease.

Enzymatic beta-carboline N-methyltransferase activities generate N-methylated beta-carbolinium cations that are analogs of the parkinsonian-producing neurotoxin MPP+. We measured beta-carboline-2N-methyltransferase and beta-carboline-9N-methyltransferase activities in the supernatant and particulate fractions from postmortem human brains. These N-methyltransferase activities were assessed in the substantia nigra, putamen, and frontal cortex from control and Parkinson's disease cases. No significant differences were measured in any brain region in particulate and supernatant fraction beta-carboline 2N-methyltransferase activity or particulate fraction beta-carboline 9N-methyltransferase activity. Likewise, supernatant fraction beta-carboline 9N-methyltransferase activity was similar in the putamen and substantia nigra from Parkinson's disease and control cases. Unexpectedly, supernatant fraction beta-carboline 9N-methyltransferase activity was increased fourfold in Parkinson's disease frontal cortex (P < 0.05), suggesting that beta-carboline N-methylation may play a role in Parkinson's disease.

Aged↗
PubMed1999

Contrasting effects of catecholic and O-methylated tetrahydroisoquinolines on hydroxyl radical production.

Tetrahydroisoquinolines (TIQs) are intraneuronal, catecholamine-derived alkaloids that have been implicated in the etiology of Parkinson's disease and in alcohol related disorders. The in vitro production of the cytotoxic hydroxyl radical (*OH) was recorded during the autoxidation of salsolinol (SAL) and salsolinol-1-carboxylic acid (SAL-1C), but not when these two catecholic TIQs were oxidized by tyrosinase. Significantly higher levels of the radical were produced when these catecholic TIQs were incubated with *OH generating complexes, or with chelated iron. In contrast, mono-O-methylated TIQs such as salsoline (SLN) and salsoline-1-carboxylic acid (SLN-1C) did not generate *OH during autoxidation or when incubated with chelated iron or tyrosinase. Radical production by *OH-generating complexes was reduced in the presence of O-methylated TIQs. The neurotoxicity of TIQs may result from their propensity to autoxidize and generate reactive quinoids and ensuing oxygen radicals. The functional significance of the replacement of a hydroxyl group attached to C-7 of SAL or SAL-1C with a methoxyl group remains to be determined. This single structural modification may prevent mono-O-methylated TIQs from participating in catalytic redox cycling reactions that would otherwise augment *OH production. If true, then O-methylation and other cellular mechanisms that circumvent the autoxidation of catecholamine-derived TIQs may reduce the likelihood of these substances forming cytotoxic quinoids and influencing endogenous *OH-generating reactions.

Catechols↗
PubMed1999

Complete sequence of plasmid pLH1 from lactobacillus helveticus ATCC15009: analysis reveals the presence of regions homologous to other native plasmids from the host strain.

The complete sequence for plasmid pLH1 from Lactobacillus helveticus ATCC15009 has been determined. Analysis of the 19,360-bp primary sequence revealed a putative replication origin and initiation protein, information that could provide the basis for the construction of cloning vectors for L. helveticus. Evidence that pLH1 is theta-replicating could be deduced from the plasmid size, from the homology to the replication protein of the Bacillus natto theta-replicating plasmid pLS32, and from the identification of a putative resolvase gene (orf-195). Although 14 open reading frames capable of encoding polypeptides longer than 100 amino acids were identified, none, on the basis of homology with known sequences, appeared to encode a well-characterized trait relevant to milk fermentation. Plasmid pLH1 revealed regions of identity with the smaller cryptic plasmids (pLH2 and pLH3) from the same strain and with other tracts of DNA, including insertion sequence elements, from a variety of other lactic acid bacteria. The presence of such regions provides a basis for developing an explanation of the phenotypic variability observed in these bacteria. The plasmid also appears to possess a number of genetic elements present in other lactic acid bacterial plasmids, conservation of which would be consistent with an important functional or evolutionary role. It could be argued that the plasmid complement of L. helveticus ATCC15009 consists of parasitic entities concerned only with their own replication and survival.

Amino Acid Sequence↗
PubMed1999

Dental anomalies associated with amelogenesis imperfecta: a radiographic assessment.

Amelogenesis imperfecta, a group of hereditary conditions primarily affecting the enamel, has been associated with dental anomalies, including taurodontism, congenitally missing teeth, delayed eruption, crown resorption, and abnormal enamel density. The purpose of this study was to assess the prevalence of these anomalies in an amelogenesis imperfecta population. The study group consisted of members of 9 unrelated families--22 family members with amelogenesis imperfecta and 13 unaffected family members. Panoramic radiographs were evaluated for taurodontism, congenitally missing teeth, delayed tooth eruption, pathologic dental resorption, pulp calcification, and radiographic enamel density. The prevalence of taurodontism was similar in people with amelogenesis imperfecta and normal people; all of the remaining parameters were more commonly observed in people with amelogenesis imperfecta. The radiographic enamel density was quantitatively reduced in teeth affected by amelogenesis imperfecta in comparison with teeth with normal enamel. These findings suggest that some of the features associated with amelogenesis imperfecta result from abnormal enamel formation (eg, decreased enamel density, crown resorption) whereas others may occur as a result of expression of the genetic mutation in cells other than ameloblasts (eg, abnormal eruption, pulp calcification).

Adolescent↗
PubMed1999

Multiplicity of glutamic acid decarboxylases (GAD) in vertebrates: molecular phylogeny and evidence for a new GAD paralog.

The evolution of chordate glutamic acid decarboxylase (GAD; EC 4.1.1.15), a key enzyme in the central nervous system synthesizing the neurotransmitter gamma-amino-butyric acid (GABA) from glutamate, was studied. Prior to this study, molecular data of GAD had been restricted to mammals, which express two distinct forms, GAD65 and GAD67. These are the products of separate genes and probably are derived from a common ancestral GAD following gene duplication at some point during vertebrate evolution. To enable a comprehensive phylogenetic analysis, molecular information of GAD forms in other vertebrate classes was essential. By reverse transcriptase-polymerase chain reaction (RT-PCR), partial nucleotide sequences of GAD were cloned from brains of zebra finch (Taeniopygia guttata), turtle (Trachemys scripta), goldfish (Carassius auratus), zebrafish (Danio rerio), and armoured grenadier (Coryphaenoides (Nematonurus) armatus, a deep-sea fish), and from the cerebral ganglion plus neural gland of Ciona intestinalis, a protochordate. Whereas GAD65 and GAD67 homologs were expressed in birds, reptiles, and fish, only a single GAD cDNA with equal similarities to both vertebrate GAD forms was found in the protochordate. This indicates that the duplication of the vertebrate GAD gene occurred between 400 and 560 million years ago. For both GAD65 and GAD67, the generated phylogenetic tree followed the general tree topology for the major vertebrate classes. In turtle, an alternative spliced form of GAD65, putatively encoding a truncated, nonactive GAD, was found. Furthermore, a third GAD form, which is equally divergent from both GAD65 and GAD67, is expressed in C. (N.) armatus. This third form might have originated from an ancient genome duplication specific to modern ray-finned fishes.

Alternative Splicing↗
PubMed1999

Evaluation of the BOD POD for assessing body fat in collegiate football players.

PURPOSE: The purpose of this investigation was to evaluate the accuracy of a new air displacement plethysmograph, BOD POD Body Composition System, for determining %fat in collegiate football players. METHODS: Body fatness was estimated from body density (Db), which was measured on the same day using the BOD POD and hydrostatic weighing (HW) in 69 Division IA football players. In addition, 20 subjects were whole body scanned using dual-energy x-ray absorptiometry, DXA (Lunar DPX-L) to assess total body mineral content and %fat. Mineral content and HW determined Db were used to compute %fat from a three-component model (3C; fat, mineral, and residual). RESULTS: Test-retest reliability for assessing %fat using the BOD POD (N = 15) was 0.994 with a technical error of measurement of 0.448%. Mean (+/- SEM) Db measured with the BOD POD (1.064 +/- 0.002 g x cc(-1) was significantly greater (P < 0.05) than HW (1.060 +/- 0.002 g x cc(-1)), thus resulting in a lower %fat for the BOD POD (15.1 +/- 0.8%) compared with HW (17.0 +/- 0.8%). Similar results (N = 20) were found for DXA (12.9 +/- 1.2%) and the 3C (12.7 +/- 0.8%) where %fat scores were significantly higher (P < 0.05) than scores determined using the BOD POD (10.9 +/- 1.0%). CONCLUSIONS: Db measured with the BOD POD was higher than the criterion HW, thus yielding lower %fat scores for the BOD POD. In addition, BOD POD determined %fat was lower than DXA and 3C determined values in a subgroup of subjects. Assessment of %fat using the BOD POD is reliable and requires minimal technical expertise; however, in this study of collegiate football players, %fat values were underpredicted when compared to HW, DXA, and the 3C model.

Absorptiometry, Photon↗
PubMed1999

Impact of bone mineral estimates on percent fat estimates from a four-component model.

PURPOSE: The primary purpose of this study was to determine the impact of bone mineral content (BMC) from QDR 1000/W and DPX-L dual-energy x-ray absorptiometers (DXA(QDR) and DXA(DPX-L) on percent fat (%fat) estimates from a four-component model. A secondary purpose was to test the accuracy of %fat estimates from DXA(QDR) and DXA(DPX-L) using %fat estimates from a four-component model as the criterion. METHODS: Percent fat, fat mass, and fat-free mass (FFM) were determined from DXA(QDR) and DXA(DPX-L) and from a four-component model based on measures of body density from underwater weighing, body water from deuterium dilution, and BMC from DXA(QDR) (4C(QDR)) or DXA(DPX-L) (4C(DPX-L)) in young men (N = 14) and women (N = 10). RESULTS: BMC was significantly lower using DXA(QDR) compared with DXA(DPX-L) (approximately 11%), resulting in slightly lower estimates of %fat and fat mass and slightly higher estimates of FFM from 4C(QDR) than 4C(DPX-L). Although estimates of %fat, fat mass, and FFM from DXA(QDR) and DXA(DPX-L) were not different than those from a four-component model, there was considerable individual variability between methods. Furthermore, %fat from DXA(QDR) was lower than %fat from 4C(DPX-L). CONCLUSIONS: We conclude that using BMC from different DXA instruments has a minimal impact on %fat, fat mass, and FFM estimates from a four-component model. The large variability in %fat estimates between the two DXA instruments and those from a four-component model does not support DXA as a criterion method of body composition. Further studies involving larger sample sizes and specific population groups are needed to assess the validity of body composition measurements from DXA.

Absorptiometry, Photon↗
PubMed1999

Driving drug discovery and patient therapy via the encapsulation and fusion of knowledge.

Knowledge and Knowledge Management are becoming common senior management parlance in the Pharmaceutical Industry in the late 1990s. This perspective article will address exactly what is knowledge and the various techniques available to harness and use it to drive the pharmaceutical business process. The impact of knowledge on this process to provide a better service to the industry's customers (the patient) are discussed with respect to the key business problems facing the industry as it enters the new millennium.

Artificial Intelligence↗
PubMed1998

(3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol: a conformationally restricted analogue of the NR2B subtype-selective NMDA antagonist (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)- 1-propanol.

(1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606, 1) is a recently described antagonist of N-methyl-D-aspartate (NMDA) receptors containing the NR2B subunit. In the present study, the optimal orientation of compounds of this structural type for their receptor was explored. Tethering of the pendent methyl group of 1 to the phenolic aromatic ring via an oxygen atom prevents rotation about the central portion of the molecule. Several of the new chromanol compounds have high affinity for the racemic [3H]CP-101,606 binding site on the NMDA receptor and protect against glutamate toxicity in cultured hippocampal neurons. The new ring caused a change in the stereochemical preference of the receptor-cis (erythro) compounds had better affinity for the receptor than the trans isomers. Computational studies suggest that steric interactions between the pendent methyl group and the phenol ring in the acyclic series determine which structures can best fit the receptor. The chromanol analogue, (3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1- yl]chroman-4,7-diol (12a, CP-283,097), was found to possess potency and selectivity comparable to CP-101,606. Thus 12a is a new tool to explore the function of the NR2B-containing NMDA receptors.

Animals↗
PubMed1998

Bright, bad, babyfaced boys: appearance stereotypes do not always yield self-fulfilling prophecy effects.

Three studies tested the hypothesis that babyfaced adolescent boys would compensate for the undesirable expectation that they will exhibit childlike traits by behaving contrary to it. Studies 1 and 2 revealed that babyfaced boys from middle- and lower class samples, including a sample of delinquents, showed higher academic achievement than their mature-faced peers, refuting the stereotype of babyfaced people as intellectually weak. In the lower class samples, this compensation effect was moderated by IQ and socioeconomic status (SES), variables that influence the ability to overcome low expectations. Study 3 showed that babyfaceness also can produce negative compensatory behaviors. Low-SES babyfaced boys were more likely than their mature-faced peers to be delinquent, and babyfaced delinquents committed more crimes, refuting the stereotype of babyfaced people as warm, submissive, and physically weak.

Achievement↗
PubMed1998

Brain damage due to episodic alcohol exposure in vivo and in vitro: furosemide neuroprotection implicates edema-based mechanism.

Adult rats intubated with a single dose of ethanol (alcohol; approximately 5 g/kg) for 5 to 10 successive days incur neurodegeneration in the entorhinal cortex, dentate gyrus, and olfactory bulbs accompanied by cerebrocortical edema and electrolyte (Na+, K+) accumulation. The brain damage is not lessened by cotreatment with the NMDA receptor antagonist MK-801; also, as reported elsewhere, MK-801 as well as non-NMDA receptor and Ca2+ channel antagonists are not neuroprotective in a similar, but more compressed, intoxication protocol. However, cotreatment with the electrolyte transport inhibitor/diuretic furosemide reduces alcohol-dependent cerebrocortical damage by 75-85% while preventing brain hydration and electrolyte elevations; olfactory bulb neurodegeneration is not attenuated. In parallel in vitro studies, rat organotypic entorhinal/hippocampal slice cultures exposed to alcohol (50-200 mM) 15 h/day for 6 days, mirroring episodic intoxication in vivo, demonstrate concentration-related release of the cytotoxic indicator, lactate dehydrogenase. Analogous to the in vivo findings, furosemide blocks this alcohol-induced in vitro cytotoxicity. Our results showing neuroprotection by furosemide indicate that brain edema and swelling are essential events in the brain damage induced by episodic alcohol exposure. Furosemide and related agents might be useful as neuroprotective agents in alcohol abuse. We suggest that the neurodegeneration is elicited in part by edema-dependent oxidative stress, but the regional selectivity of the damage may be best explained by physical (mechanical) compression of the limbic cortex against the adjacent tympanic bulla and subsequent neuronal cytoskeletal collapse. A scheme for these apparently nonexcitotoxic metabolic and mechanical pathways initiated by repeated alcohol exposure is proposed.

Alcoholic Intoxication↗
PubMed1998

Effect of weight training exercise and treadmill exercise on post-exercise oxygen consumption.

Effect of weight training exercise and treadmill exercise on postexercise oxygen consumption. Med. Sci. Sports Exerc., Vol. 30, No. 4, pp. 518-522, 1998. To compare the effect of weight training (WT) and treadmill (TM) exercise on postexercise oxygen consumption (VO2), 15 males (mean +/- SD) age = 22.7 +/- 1.6 yr; height = 175.0 +/- 6.2 cm; mass = 82.0 +/- 14.3 kg) performed a 27-min bout of WT and a 27-min bout of TM exercise at matched rates of VO2. WT consisted of performing two circuits of eight exercises at 60% of each subject's one repetition maximum with a work/rest ratio of 45 s/60 s. Approximately 5 d after WT each subject walked or jogged on the TM at a pace that elicited an average VO2 matched with his mean value during WT. VO2 was measured continuously during exercise and the first 30 min into recovery and at 60 and 90 min into recovery. VO2 during WT (1.58 L.min-1) and TM exercise (1.55 L.min-1) were not significantly (P > 0.05) different; thus the two activities were matched for VO2. Total oxygen consumption during the first 30 min of recovery was significantly higher (P < 0.05) as a result of WT (19.0 L) compared with that during TM exercise (12.7 L). However, VO2 values at 60 (0.32 vs 0.29 L.min-1), and 90 min (0.33 vs 0.30 L.min-1) were not significantly different (P > 0.05) between WT and TM exercise, respectively. The results suggest that, during the first 30 min following exercise. WT elicits a greater elevated postexercise VO2 than TM exercise when the two activities are performed at matched VO2 and equal durations. Therefore, total energy expenditure as a consequence of WT will be underestimated if based on exercise VO2 only.

Adult↗
PubMed1998

Brain neuronal degeneration caused by episodic alcohol intoxication in rats: effects of nimodipine, 6,7-dinitro-quinoxaline-2,3-dione, and MK-801.

Rats repeatedly intoxicated with alcohol (ethanol, three times daily) over a 4-day period display neuronal degeneration in the dentate gyrus; entorhinal, piriform, insular, orbital, and perirhinal cortices; and in the olfactory nerve fibers and terminals in the olfactory bulb. Postulating a role for excitotoxicity, we have attempted to prevent the degeneration using antagonists that are neuroprotective in this type of brain damage. In an initial study, continuous subcutaneous infusion of a high dose of the glutamate/NMDA receptor antagonist MK-801 (2 mg/kg/day) by itself caused extensive neuronal degeneration in several brain regions and severe behavioral intoxication that precluded survival if combined with high blood alcohol levels (approximately 300 mg/dl). Moreover, the lower, nonneurotoxic blood alcohol levels (approximately 150 mg/dl) that were compatible with survival worsened the MK-801-induced brain damage. In a subsequent experiment, daily intraperitoneal injections of a lower dose of MK-801 (1 mg/kg/day) resulted in no MK-801 toxicity and, when combined with neurotoxic levels of alcohol, no reduction in alcohol-induced neurotoxicity. Nimodipine, a voltage-gated Ca2+ channel blocker, reduced the neuronal damage in the dentate gyrus, but greatly increased it in the piriform cortex when administered intragastrically at 600 mg/kg/day; it provided no protection from alcohol-dependent degeneration when given intragastrically at 100 mg/kg/day. Continuous intracerebroventricular delivery of 0.24 to 0.29 mg/day of 6,7-dinitro-quinoxaline-2,3-dione, a glutamate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor antagonist, failed to diminish alcohol-dependent neuronal damage in any brain region. We conclude that brain damage from episodic "binge" alcohol intoxication is not primarily mediated by excitotoxic mechanisms, implying that other, nonexcitotoxic pathophysiological mechanisms, are involved. Furthermore, MK-801, far from protecting from the alcohol-induced damage, at high doses causes widespread neuropathology that is significantly potentiated by alcohol.

Alcoholic Intoxication↗
PubMed1997

Characterization of brain beta-carboline-2-N-methyltransferase, an enzyme that may play a role in idiopathic Parkinson's disease.

The activity of beta-carboline-2-N-methyltransferase results in the formation of neurotoxic N-methylated beta-carbolinium compounds. We have hypothesized that these N-methylated beta-carbolinium cations may contribute to the development of idiopathic Parkinson's disease. This report describes experiments undertaken to optimize assay conditions for bovine brain beta-carboline-2-N-methyltransferase activity. The activity of beta-carboline-2-N-methyltransferase is primarily localized in the cytosol, has a pH optimum of 8.5-9, and obeys Michaelis-Menten kinetics with respect to its substrates, 9-methylnorharman (9-MeNH) and S-adenosyl-L-methionine (SAM). Kinetic constants, KM and Vmax, with respect to 9-MeNH, are 75 microM and 48 pmol/h/mg protein, respectively. The KM for SAM is 81 microM and the Vmax is 53 pmol/h/mg protein. In addition, enzyme activity is inhibited by S-adenosyl-L-homocysteine (SAH) or zinc, and is increased 2-fold in the presence of iron or manganese. Enzyme characterization is a prerequisite to the purification of this N-methyltransferase from bovine brain as well as comparison of its activity in human brain from control and Parkinson's disease individuals.

Animals↗
PubMed1997

Electrotransformation of Lactobacillus plantarum using linearized plasmid DNA.

Evidence is presented that linearized plasmid DNA is capable of electrotransforming Lactobacillus plantarum at a frequency 500-fold lower than with the covalently closed circular molecule. When the linearized plasmid was religated prior to transformation the transformation efficiency was < 10-fold higher, suggesting that open circular plasmid was only slightly more efficient in the transformation of Lact. plantarum than linear DNA. This observation has implications for direct cloning into this species since the high background transformation frequency produced by the linear DNA could potentially obscure the recovery of clones. Nevertheless, using positive selection for enhanced chloramphenicol resistance, cloned fragments of Lact. helveticus DNA were obtained using the shuttle vector pGKV110.

Lactobacillus↗
PubMed1997

Accurate social perception at zero acquaintance: the affordances of a Gibsonian approach.

We review research on accurate social perception at zero acquaintance and apply a Gibsonian ecological approach to redress several shortcomings. We argue that recent use of Brunswik's lens model to determine what physical qualities accurately communicate psychological traits has limited utility because it fails to consider the structured information provided by configural physical qualities that is central to Gibson's (1979) theory. We elaborate a developmental model of relationships between physical and psychological qualities that highlights research needed to identify configural physical qualities that may inform accurate perceptions. This model and tenets of the ecological theory yield several hypotheses regarding such qualities. Finally, we advocate the value of studying perceived affordances (opportunities for acting, interacting, or being acted upon) because this will focus attention on the neglected issue of contextual influences on social perception accuracy, and because affordances may be perceived more accurately than global personality traits.

Journal Article↗
PubMed1997

Antagonistic modulation between the delta opioid agonist BW373U86 and the mu opioid agonist fentanyl in mice.

This study was performed to assess the interactions that occur between delta- and mu opioid receptors by studying effects of the systemically active nonpeptide delta agonist BW373U86 and the mu agonist fentanyl in mice. Concentrations of the compounds were varied, and analgesic responses were determined by 55 degrees C hot-plate assays. BW373U86 produced hot-plate antinociceptive activity along with convulsive side effects. These effects could be antagonized by the selective delta antagonist naltrindole. Fentanyl produced hot-plate antinociceptive activity with Straub tail and hyperactivity as side effects. When BW373U86 and fentanyl were coadministered, BW373U86 convulsive activity was attenuated by fentanyl in a dose-dependent manner and the fentanyl-induced Straub tail effect was antagonized by BW373U86, also in a dose-dependent manner. Hot-plate analgesic activity was additive between the two compounds. The delta antagonist naltrindole partially antagonized the ability of BW373U86 to block the fentanyl-induced Straub tail effect. The mu antagonist beta-funaltrexamine antagonized the fentanyl-induced blockade of the convulsive effects of BW373U86. These data suggest that complex inhibitory interactions take place between mu and delta receptors in mice. Future studies are clearly needed to study the neuromodulatory effects of mu and delta receptors. The widespread use of mu agonists in the clinic indicates that a large number of patients exist who could greatly benefit from the conjunctive use of delta pharmaceuticals.

Analgesics, Opioid↗