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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 55 records · Page 3Linked to original sources
PubMed2000

Determination of titanium NMR parameters of ATiO3 compounds: correlations with structural distortion.

Solid state 47,49Ti NMR spectra have been obtained for a number of perovskite and ilmenite ATiO3 compounds. The 49Ti quadrupole coupling constant varies from 2.75 MHz (CaTiO3) to 15.5 MHz (MgTiO3) and the electric field gradient at the titanium site was found to correlate well with the shear strain, independent of structure. The chemical shift in the perovskite structures varies by approximately 160 ppm and correlates well with the mean Ti-O distance. The 25Mg and 113Cd NMR parameters are also reported for the relevant compounds.

Barium↗
PubMed2000

Chemoenzymatic synthesis of PSGL-1 glycopeptides: sulfation on tyrosine affects glycosyltransferase-catalyzed synthesis of the O-glycan.

PSGL-1 is the primary glycoprotein ligand for P-selectin during the inflammatory response. Interestingly, the N-terminal sequence, containing both a site of tyrosine sulfation and an O-glycan, has been shown to bind to P-selectin with an affinity similar to full-length PSGL-1. To further characterize this system, the synthesis of glycopeptides from PSGL-1 was undertaken. The synthesis involved both solution- and solid-phase synthesis, as well as enzymatic transformations. During the synthesis, notable reactivity differences of the glycosyltransferases toward sulfated and unsulfated versions of the same glycopeptides were observed.

Amino Acid Sequence↗
PubMed2000

Test-retest reliability of cognitive EEG.

OBJECTIVE: Task-related EEG is sensitive to changes in cognitive state produced by increased task difficulty and by transient impairment. If task-related EEG has high test-retest reliability, it could be used as part of a clinical test to assess changes in cognitive function. The aim of this study was to determine the reliability of the EEG recorded during the performance of a working memory (WM) task and a psychomotor vigilance task (PVT). METHODS: EEG was recorded while subjects rested quietly and while they performed the tasks. Within session (test-retest interval of approximately 1 h) and between session (test-retest interval of approximately 7 days) reliability was calculated for four EEG components: frontal midline theta at Fz, posterior theta at Pz, and slow and fast alpha at Pz. RESULTS: Task-related EEG was highly reliable within and between sessions (r0.9 for all components in WM task, and r0.8 for all components in the PVT). Resting EEG also showed high reliability, although the magnitude of the correlation was somewhat smaller than that of the task-related EEG (r0.7 for all 4 components). CONCLUSIONS: These results suggest that under appropriate conditions, task-related EEG has sufficient retest reliability for use in assessing clinical changes in cognitive status.

Adolescent↗
PubMed2000

Expression of nitric oxide synthase isoforms in spinal cord in amyotrophic lateral sclerosis.

METHODS: Autoradiography with [3H]nitro-L-arginine (3HL-NNA) was used to quantify nitric oxide synthase (NOS), and immunocytochemistry to identify NOS isoforms, in spinal cord in amyotrophic lateral sclerosis (ALS) and controls. RESULTS: In controls NOS binding was marked only in the superficial dorsal horn, but in ALS tissue it was intense throughout the grey and white matter. A single population of binding sites was indicated in controls, but two populations in ALS. In the controls intense neuronal NOS (nNOS) immunoreactivity was present in numerous cells in the dorsal horn, and faint immunoreactivity in small and medium-sized cells in the ventral horn. Only weak immunoreactivity for inducible NOS (iNOS) and endothelial NOS (eNOS) was detectable in control tissue. In ALS, the pattern was broadly similar in the grey matter, but immunoreactivity for both nNOS and iNOS was present in white matter. CONCLUSION: Expression of abnormal variants of nNOS or increased expression of iNOS may have a role in motoneuron death in ALS.

Aged↗
PubMed2000

Neurophysiological measures of working memory and individual differences in cognitive ability and cognitive style.

The capacity to deliberately control attention in order to hold and manipulate information in working memory is critical to higher cognitive functions. This suggests that between-subject differences in general cognitive ability might be related to observable differences in the activity of brain systems that support working memory and attention control. To test this notion, electroencephalograms were recorded from 80 healthy young adults during spatial working memory tasks. Measures of task-related neurophysiological and behavioral variables were derived from these data and compared to scores on a test battery commonly used to assess general cognitive ability (the WAIS-R). Subjects who scored high on the psychometric test also tended to respond faster in the experimental tasks without any loss of accuracy. The amplitude of the late positive component of the event-related potential was larger in high-ability subjects, and the frontal midline theta component of the EEG signal was also selectively enhanced in this group under conditions of sustained performance and high working memory load. These results suggest that subjects who scored high on the WAIS-R were better able to focus and sustain attention to task performance. Changes in the EEG alpha rhythm in response to manipulations of task practice and load were also examined and compared between frontal and parietal regions. The results indicated that high-ability subjects developed strategies that made relatively greater use of parietal regions, whereas low-ability subjects relied more exclusively on frontal regions. Other analyses indicated that hemispheric asymmetries in alpha band measures distinguish between individuals with relatively high verbal aptitude and those with relatively high nonverbal aptitude. In particular, subjects with a verbal cognitive style tended to make greater use of the left parietal region during task performance, and subjects with a nonverbal style tended to make greater use of the right parietal region. These results help clarify relationships between task-related brain activity and individual differences in cognitive ability and style.

Adolescent↗
PubMed2000

A 278 bp region just upstream of the human CYP19 (aromatase) gene mediates ovary-specific expression in transgenic mice.

In humans, the CYP19 gene, which encodes aromatase P450, is expressed in a number of tissues including gonads, adipose, bone, and placenta. The 5'-untranslated regions (UTR) of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are alternatively spliced onto a common site just upstream of the start site of translation in exon II. In ovary, the 5'-UTR of CYP19 transcripts is encoded by exon IIa, which lies just upstream of exon II. To map genomic sequences required for ovary-specific CYP19 expression, fusion genes containing 2700, 278 and 43 bp of exon IIa 5'-flanking DNA linked to the human growth hormone (hGH) gene, as reporter, were introduced into mice. CYP19(IIa)-2700:hGH and CYP19(IIa)-278:hGH transgenes were expressed at high levels in ovaries of transgenic mice, whereas, ovarian expression of CYP19(IIa)-43:hGH was undetectable. In the majority of mice carrying the CYP19(IIa)-2700:hGH and CYP19(IIa)-278:hGH fusion genes, transgene expression was ovary-specific, indicating that genomic sequences within 278 bp region mediate ovary-specific expression. Expression of CYP19(IIa)-2700:hGH and CYP19(IIa)-278:hGH fusion genes was detected in ovarian granulosa and luteal cells, as well as in luteinized interstitial cells in mice during the estrous cycle. The most intense hGH immunostaining was observed in corpora lutea. This pattern of transgene expression is similar to that of aromatase in women where both granulosa and luteal cells express aromatase during the menstrual cycle. These findings suggest that transgenic mice provide an excellent model for analyzing genomic regions that mediate ovary-specific expression of the human CYP19 gene.

Alternative Splicing↗
PubMed2000

Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women.

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.

Absorptiometry, Photon↗
PubMed2000

Increased chylomicron triglyceride hydrolysis by connective tissue flow in perfused rat hindlimb. Implications for lipid storage.

Skeletal muscle has two circulatory routes, nutritive (in contact with muscle) and non-nutritive (part of which is located in the connective tissue), and the balance of flow between the two is controlled by neural input and circulating vasomodulators. The purpose of this study was to assess muscle triglyceride hydrolysis given that the two circuits may have a differing vascular distribution of hydrolytic activity. The isolated rat hindlimb was perfused with 6% Ficoll((R)) and a radiolabeled chylomicron;-lipid emulsion containing apolipoprotein C-II. Serotonin (0.5-1 micrometer), a model vasoconstrictor previously shown to preferentially increase connective tissue flow, inhibited hindlimb oxygen uptake (from 16.7 +/- 0.6 to 10.2 +/- 1.0, mean +/- SE, n = 7 (P <0.001)) and stimulated [(14)C]-labeled fatty acid uptake into muscles (from 184 +/- 28 to 602 +/- 132, mean +/- SE, n = 7 (P = 0.009)). These effects were reversed by the vasodilator carbamyl choline. Vasopressin resulted in increased oxygen consumption but no change in triglyceride hydrolysis. Cholesteryl oleate uptake (an indicator of endocytosis of the chylomicron or remnant particle) was unaltered by serotonin. It is concluded that chylomicron triglyceride hydrolysis is enhanced by vasoconstrictors that increase connective tissue flow in the perfused rat hindlimb. Increased hydrolysis appears to be primarily due to an increased access of triglyceride to hydrolytic enzymes, presumably lipoprotein lipase associated with the fat cells commonly observed interlaced amongst bundles of muscle fibers.

Animals↗
PubMed1999

NMDA and AMPA glutamate receptor subtypes in the thoracic spinal cord in lean and obese-diabetic ob/ob mice.

Quantitative autoradiography was used to characterise the binding of selective radiolabelled antagonists for the N-methyl-D-aspartate (NMDA) receptor and the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor in the dorsal, intermediate and ventral subregions of the grey matter of the upper thoracic spinal cord in male and female lean and obese-diabetic (ob/ob) mice. The density of binding sites for both receptor subtypes was greater in diabetic mice, in all three subregions of the grey matter, than the corresponding subregions in the lean mice. The affinity of the binding site for the NMDA antagonist was significantly higher in obese mice than lean mice, consistent with the presence of two subpopulations of NMDA receptors with different ligand binding affinities in obese mice. The increase in expression of the glutamate receptor subtypes, and altered ligand affinity for the NMDA receptor subtype in the obese mice may be causally involved in the peripheral neuropathies which can accompany diabetes mellitus.

Animals↗
PubMed1999

Effect of sympathectomy on the expression of NMDA receptors in the spinal cord.

The expression of NMDA receptors in the intermediolateral (IML) region of the upper thoracic spinal cord, was studied in 3 week old rats. The effect of section of the cervical sympathetic nerve on neuronal cell number and receptor expression was examined up to two weeks after the operation. Age-matched sham-operated and unoperated animals were used as controls. It was shown using quantitative autoradiography with the NMDA receptor antagonist [(3)H]MK-801 (dizocilpine maleate), that there was a marked downregulation of receptors in all groups of animals, beginning at approximately 4 weeks of age. However after sympathectomy, which resulted in the death of 44% of neurones in the IML by 7 days, there was a significant increase in receptor density per neurone compared to sham-operated controls. In the control animals there was a significant increase in the Kd value of the binding between 21 and 24 days after birth indicating an increased expression of a low affinity receptor, but no such increase was seen after axotomy. The results are consistent with two populations of NMDA receptors being transiently expressed in the IML in developing animals, and the higher affinity receptor being down-regulated between 4 and 5 weeks of age. The presence of the high affinity receptor subtype may predispose neurones to die after axotomy.

Animals↗
PubMed1999

Effect of open label pulse cyclophosphamide therapy on MRI measures of disease activity in five patients with refractory relapsing-remitting multiple sclerosis.

OBJECTIVE: To evaluate the response to cyclophosphamide (CTX) of five patients who failed an average three treatments with multiple other therapeutic agents, using serial monthly MRI measures. METHODS: Five patients with relapsing-remitting multiple sclerosis (MS) and documented MRI disease activity were started on monthly pulse intravenous CTX at a dose of 1 g/m2. CTX was administered without an induction phase according to the protocol similar to the treatment of lupus nephritis. The five patients were followed with monthly MRI and clinical evaluation for a mean of 28 months. RESULTS: All the patients showed a rapid reduction in the contrast-enhancing lesion frequency and in three patients there was a decrease in the T2 lesion load within the first 5 months after starting CTX treatment. The administration of CTX during overnight hospitalization was safe and well tolerated. CONCLUSIONS: These findings suggest that aggressive immunosuppressive therapy may be useful in some rapidly deteriorating refractory patients and further controlled study should be considered in order to full evaluate this type of treatment as a potential therapy in MS.

Adult↗
PubMed1999

Electroencephalographic imaging of higher brain function.

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Brain↗
PubMed1999

A 500-bp region, approximately 40 kb upstream of the human CYP19 (aromatase) gene, mediates placenta-specific expression in transgenic mice.

In humans, aromatase P450 (product of CYP19 gene), which catalyzes conversion of C19 steroids to estrogens, is expressed in a number of tissues, including ovary, adipose, and syncytiotrophoblast of the placenta. The 5' untranslated regions of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are spliced onto a common site just upstream of the translation initiation site in exon II. In placenta, the 5' untranslated region of CYP19 mRNA transcripts is encoded by exon I.1, which lies approximately 40 kb upstream of exon II. To map genomic sequences required for placenta-specific CYP19 expression, fusion genes containing 2,400 and 501 bp of placenta-specific exon I.1 5' flanking DNA linked to the human growth hormone gene (hGH), as reporter, were introduced into transgenic mice. Expression of CYP19(I.1):hGH fusion genes containing as little as 501 bp of 5' flanking DNA was placenta-specific and developmentally regulated. Furthermore, transgene expression occurred specifically in the labyrinthine trophoblast of the mouse placenta, which contains syncytial cells that may be analogous to the human syncytiotrophoblast. We show that a relatively small segment of DNA (approximately 500 bp) >40 kb upstream of the protein coding region of a human gene is able to direct expression in an appropriate tissue- and cell-specific manner in transgenic mice. These findings suggest that 5' flanking DNA within 501 bp of exon I.1 of the human CYP19 gene contains cis-acting elements that bind placenta-specific transcription factors that are conserved between humans and mice.

Animals↗
PubMed1999

Inhibition of autoreactive antibody effects with antibody feedings: a pilot study.

This study seeks to determine if tolerance to autoreactive antibody can be achieved by exposing gut-associated lymphocytic tissue (GALT) to the protein. The method involved immunizing rats with AchR after feeding anti-AchR purified from myasthenic plasma or non-specific, pooled human immunoglobulins. Both feedings improved the neuromuscular block of EAMG, the commercial preparation requiring a tenfold increase in protein concentration. Despite its protective effect, antibody feeding was associated with late levels of serum anti-AchR considerably above those in immunized controls. The hypothesis presented is that the tolerance results from enhanced anti-idiotype production.

Administration, Oral↗