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Biomedical subjects

L M Harrison

Publications and source records attributed to L M Harrison.

At least 55 records · Page 3Linked to original sources
PubMed1994

The opiate system in invertebrates.

The presence in diverse species of a similar mode of communication, that of a soluble messenger binding to a receptor, raises the question as to whether the specific components of this system are equally widespread. Do invertebrates use the same hormones and receptors as vertebrates do? Invertebrates ranging from unicellular organisms to insects have been shown to contain opiate-like peptides and binding sites, and they exhibit biological responses to opiates. However, critical genetic data are lacking. It is not known how signal systems arise phylogenetically, but it is conceivable that signal molecules that are already present cause the formation of their own receptors from membrane proteins.

Animals↗
PubMed1994

Differential regulation of mu and delta opiate receptors by morphine, selective agonists and antagonists and differentiating agents in SH-SY5Y human neuroblastoma cells.

Mu and delta opiate receptor regulation by opiate agonists and antagonists was studied in the human neuroblastoma cell line SH-SY5Y. Morphine down-regulated both mu and delta receptors, but its effects on each subtype could be dissociated by use of specific antagonists. The selective mu antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Pen-Thr-NH2 (CTAP) blocked the down-regulation of mu, but not delta receptors. Conversely, the delta antagonist (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH([N,N-diallyl-Tyr1, Aib2,3]Leu- enkephalin)] ICI 174,864 blocked morphine-induced down-regulation of delta but not mu receptors. These selective antagonists also were studied alone for their effects on both receptors. CTAP alone at doses of 0.1 microM and higher up-regulated mu receptors. CTAP did not affect delta receptors at 0.3 microM or less, but it down-regulated them at doses of 1 microM or more, apparently due to its delta agonist activity at higher doses, which was reversed by ICI 174,864. ICI 174,864 alone also showed complex effects on the two subtypes, up-regulating both mu and delta sites. Its effects were most selective at a low dose (0.1 microM), which upregulated delta sites with minimal effects on mu sites. The nonselective antagonist naloxone provided a more robust upregulation (> 40%) of both mu and delta receptors than either selective antagonist alone or in combination. The mu-to-delta ratio (1.4 to 1) was not altered by differentiation of the cells with retinoic acid, which up-regulated both mu and delta receptors. Differentiation with the phorbol agent 12-O-tetradecanoyl-phorbol-13-acetate, however, up-regulated mu, but not delta receptors. The selective mu agonist Tyr-Pro-MePhe-D-Pro-NH2 (PL017) down-regulated mu receptors with a half-maximal effect at 180 nM, but was without effect on delta receptors at concentrations up to 10 microM. Conversely, the selective delta agonist Tyr-D-Pen-Gly-Phe-D-Pen([D-Pen2,5]-enkephalin) (DPDPE) potently down-regulated delta receptors, producing half-maximal decreases at 0.5 nM. At doses above those that reduced the maximum binding of [3H]pCl-DPDPE binding to the delta site, DPDPE also induced an apparent loss of affinity (increased Kd) at the delta site. It was without effect on mu receptors, however, at doses up to 10 microM. Thus, down-regulation of mu and delta receptors was homologous, because selective agonists down-regulated their respective receptors without effect on the heterologous opiate receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1993

Effects of neonatal treatment with Tyr-MIF-1, morphiceptin, and morphine on development, tail flick, and blood-brain barrier transport.

Morphine and endogenous peptides can alter developmental processes, inducing changes that can endure into adulthood. Morphiceptin binds to mu opiate receptors and to non-opiate sites labeled by Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), an endogenous brain peptide known to modulate opiate effects. Morphine, morphiceptin, Tyr-MIF-1, morphine + Tyr-MIF-1, and morphiceptin+Tyr-MIF-1 (50 micrograms, s.c.) were given to rats during their first week of life. Animals given morphine alone or in combination with Tyr-MIF-1 had significantly lower body weights for the first 3 weeks of life and delayed eye opening on day 16. Rats given morphine had hypersensitive tail flick responses on day 9 while those given morphine + Tyr-MIF-1 were hypersensitive on days 3, 8, and 9. Locomotor, passive avoidance, and rotorod behaviors were not altered by the neonatal treatments. Transport of [125I]Tyr-MIF-1 out of the brain was tested on day 23 and found to be increased by neonatal morphine, an effect that was significantly potentiated by neonatal Tyr-MIF-1. The results indicate that neonatal administration of peptides and opiates can affect later peptide transport across the blood-brain barrier as well as selected developmental characteristics.

Analgesics↗
PubMed1993

Analysis of uroporphyrinogen decarboxylase complementary DNAs in sporadic porphyria cutanea tarda.

BACKGROUND: Sporadic porphyria cutanea tarda (S-PCT) has been considered an acquired disease because of the generation of liver-specific inhibitors of uroporphyrinogen decarboxylase (URO-D) activity. Several families have been described with S-PCT in multiple generations, raising the possibility of an inherited basis for the disease. To determine if S-PCT is associated with mutant URO-Ds that might be sensitive to liver-specific inhibitors, a molecular analysis of genomic and hepatocellular URO-Ds was undertaken. METHODS: Total RNA from lymphoid cell lines from three unrelated patients with S-PCT and poly A+ RNA from liver biopsy samples from two additional patients was used as a template for single-stranded cDNA synthesis, and URO-D sequences were amplified and sequenced. DNA prepared from peripheral blood leukocytes was used as a template to polymerase chain reaction (PCR) amplify the promoter region of the URO-D gene. Sequencing of PCR products was performed completely in both directions by the chain termination method using a variety of custom oligonucleotide primers. RESULTS: Ten URO-D alleles were sequenced, and no mutations were found. The promoter region of the URO-D gene was also normal. CONCLUSIONS: It is concluded that S-PCT is not due to mutations at the URO-D locus. If inherited factors are involved, other loci must be affected.

Adult↗
PubMed1993

Patterns of central motor reorganization in hemiplegic cerebral palsy.

Central motor reorganization was studied in 33 subjects with hemiplegic cerebral palsy. Corticospinal projections were investigated using focal magnetic stimulation of the motor cortex. Reflex pathways were examined with digital nerve stimulation. Cross-correlation analysis of multi-unit EMG was used to detect activity in branched common stem last order presynaptic inputs to motor neuron pools. The neurophysiological findings were related to the clinical outcome. In 21 of the subjects studied (64%), there was evidence for reorganization of central motor pathways. The clinical and neurophysiological findings revealed two different forms of reorganization. In both forms focal magnetic stimulation demonstrated novel ipsilateral motor pathways from the undamaged motor cortex to the hemiplegic hand. Ipsilateral projections were not demonstrated from the damaged motor cortex. Eleven subjects had intense mirror movements. In these subjects cross-correlation analysis and reflex testing suggested that corticospinal axons had branched abnormally and projected bilaterally to homologous motor neuron pools on both sides of the spinal cord. The remaining 10 subjects did not have intense mirror movements and in these subjects there was no evidence for last order branching of corticospinal axons. It was found that good function of the hemiplegic hand was associated with the presence of EMG responses in that hand following magnetic stimulation of the contralateral motor cortex. When EMG responses were absent, hand function was poor unless the subject had intense mirror movements.

Adolescent↗
PubMed1991

Cross-correlation analysis of multi-unit EMG recordings in man.

This paper discusses the measurement of synchrony between 2 multi-unit EMG recordings. The suitability of a number of previously described indices of synchrony is reviewed. A new index of synchronisation is proposed. This index is independent of the number of units contributing to the correlogram but is dependent upon their firing frequency and upon the bin width of the correlogram. The autospectral density function calculated from each multi-unit record is used to estimate motor unit firing rates. The relationship between the frequency of firing and the chosen index of synchronisation is reciprocal such that if the firing rate is doubled, the index is halved. This may be explained if the proportion of events that is synchronized remains constant and is independent of the firing rate. It is argued that this in turn indicates that the proportion of common and non-common sources driving the neurons also remains unchanged in these experiments. In these circumstances, and to take into account changes in unit firing that may be present in different recordings, it is convenient to normalize an experimentally determined index E/M at a frequency f to some standard frequency fs. The problem of superimposition of spikes that occurs as the contraction strength is increased is discussed.

Adult↗
PubMed1991

Cutaneomuscular reflexes recorded from the first dorsal interosseous muscle of children with cerebral palsy.

Cutaneomuscular reflexes were recorded from the first dorsal interosseous muscles of 21 children with spastic cerebral palsy. The reflex responses in children with cerebral palsy were consistent with dysfunction of the pyramidal system, but differed from those seen in adults with central nervous lesions. This provides further evidence that the effect of a central nervous lesion on the reflex control of movement is dependent on whether it occurs in early or adult life.

Adolescent↗
PubMed1991

Plasticity of central motor pathways in children with hemiplegic cerebral palsy.

To obtain neurophysiologic evidence for a reorganization of central motor pathways in children who had suffered a cerebral lesion at birth, we performed cross-correlation analyses of multiunit EMG recordings obtained from children with hemiplegic cerebral palsy and marked mirror movements. We found that the motoneuron pools of homologous left and right hand muscles received common synaptic input from abnormally branched presynaptic axons. The results of electromagnetic brain stimulation, cutaneomuscular, and tendon reflex testing suggested that these common inputs are provided by abnormally branched corticospinal tract fibers whose origin is the undamaged motor cortex.

Cerebral Palsy↗
PubMed1991

Microtechnique for quantifying phenol in plasma by gas chromatography-mass spectrometry.

Methods for detection and quantification of phenol have been developed primarily for use in environmental and industrial monitoring, given the widespread use of phenol as a disinfectant and antiseptic. Little information is available regarding concentrations of phenol in the blood of patients treated with phenol in regional nerve blocks (e.g., intrathecal) for temporary relief of pain or spasticity. We report a specific and sensitive method for quantifying phenol in plasma, using chemical derivatization and high-resolution capillary column gas chromatography in conjunction with mass spectrometry. The assay we describe was developed to monitor plasma concentrations of phenol in children given motor point nerve blocks with dilute phenol.

Contraindications↗
PubMed1990

Rates of lipogenesis and plasma insulin concentrations in inbred lines of mice differing in fatness.

Rates of lipogenesis de novo and plasma concentrations of insulin were compared during post-natal growth in two inbred lines of mice (VL/fDk (VL) and SWR/fNIMR (SWR] in which differences in growth and fatness are probably due to multiple not single gene effects. Irrespective of sex, the lipogenic rate/g was higher in the fatter VL mice in the liver and all other tissues except the head, where it was lower, and the gonadal fat pad, where it was not different. Adult mice in general had lower lipogenic rates than those measured soon after weaning. In both lines the lipogenic rate/g of tissue was higher in males in the liver and in females in the gonadal fat pad. Plasma insulin concentrations were higher in VL mice and tended to rise with age. These results demonstrate that metabolic differences associated with differences in fatness in inbred lines of mice in which fatness is controlled by more than one gene, are qualitatively but not quantitatively similar to those observed by other workers in lines of mice differing in fatness due to a single gene mutation.

Adipose Tissue↗
PubMed1990

Methandrostenolone metabolism in humans: potential problems associated with isolation and identification of metabolites.

Methandrostenolone dose (amount and duration) and methods of isolation from urine can influence the identification and quantitation of methandrostenolone metabolites. Long-term use of methandrostenolone at high dosages led to the appearance of unmetabolized drug in the urine and contributed to the identification of a previously unreported metabolite, 3 beta, 6 section, 17 beta-trihydroxy-17 alpha-methyl-5 section-1-androstene. Exposure of methandrostenolone in vitro to acid conditions induced a retropinacol rearrangement in the D-ring of the methandrostenolone molecule, causing the formation of 18-nor-17,17-dimethyl-1,4,13(14)-androstatrien-3-one in large amounts. The same acidic conditions led to the addition of a hydroxyl at the 6 position of the B-ring of either the retropinacol rearrangement products or native methandrostenolone resulting in the formation of 6 beta-hydroxy-18-nor-17,17-dimethyl-1,4,13(14)-androstatrien-3-one, 6 alpha- hydroxy-18-nor-17,17-dimethyl-1,4,13(14)-androstatrien, 6 beta-17 alpha-methyl-1,4-androstadien-3-one and 6 alpha,17 beta-dihydroxy-17 alpha-methyl-1,4-androstadien-3-one. Hydroxylation of native methandrostenolone at the 6 position also occurs endogenously. However, no evidence of an endogenous retropinacol rearrangement was found. Silylating agents alone can induce the formation of small amounts of 6 beta-17 beta-dihydroxy-17 alpha-methyl-1,4-androstadien-3-one. Discrepancies between previously published reports on methandrostenolone metabolism in man are discussed and compared with an animal model.

Androgens↗
PubMed1990

Maturation of the cutaneomuscular reflex recorded from the first dorsal interosseous muscle in man.

1. Cutaneous reflexes have been recorded from the first dorsal interosseous muscle following electrical stimulation of the digital nerves of the index finger in man. Recordings have been obtained from 127 children, aged from 3 to 18 years while each performed an isometric abduction of the index finger and whole hand grips. 2. In the adult, reflexes recorded while subjects performed an isometric abduction of the index finger consisted of three readily identifiable components within the first 100 ms. These were an initial short spinal latency increase in EMG (E1), followed by a decrease (I1), followed by a prominent longer-latency increase (E2) which was normally larger in size than the shorter-latency increase. 3. The configuration of the reflex changed during development. When recorded during an abduction, the E1 component was present in all children and showed a small but progressive reduction in size with age. With increasing age, both the I1 and E2 components were present in an increasing proportion of children and increased in size until the adult configuration was reached at 14-15 years. 4. Comparison of reflexes recorded during sustained whole hand grips with reflexes recorded during an isometric index finger abduction revealed differences in all three components. When recorded during those grips used in the present study the E1 component was generally significantly larger while the I1 component was generally significantly smaller than when recorded during index finger abduction. At all ages the E2 component was significantly smaller when recorded during a grip. 5. The configuration of the reflex during an isometric index finger abduction was compared with the ability of the child to perform rapid finger movements. Those children who had no E2 component tended not to perform well in the tests of rapid finger movement. However, there was no simple relationship between the size of the E2 component and ability to produce rapid finger movements.

Adolescent↗
PubMed1990

Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda.

Uroporphyrinogen decarboxylase (URO-D) is a cytosolic heme-biosynthetic enzyme that converts uroporphyrinogen to coproporphyrinogen. Defects at the uroporphyrinogen decarboxylase locus cause the human genetic disease familial porphyria cutanea tarda. A splice site mutation has been found in a pedigree with familial porphyria cutanea tarda that causes exon 6 to be deleted from the mRNA. The intron/exon junctions on either side of exon 6 fall between codons, so the resulting protein is shorter than the normal protein, missing only the amino acids coded by exon 6. The shortened protein lacks catalytic activity, is rapidly degraded when exposed to human lymphocyte lysates, and is not detectable by Western blot analysis in lymphocyte lysates derived from affected individuals. The mutation was detected in five of 22 unrelated familial porphyria cutanea tarda pedigrees tested, so it appears to be common. This is the first splice site mutation to be found at the URO-D locus, and the first mutation that causes familial porphyria cutanea tarda to be found in more than one pedigree.

Amino Acid Sequence↗
PubMed1989

Effect of extended use of single anabolic steroids on urinary steroid excretion and metabolism.

Long-term use of single anabolic steroids by weightlifters and body builders at dosages greater than or equal to 25 mg per 24 h resulted in reduced excretion of urinary androgen metabolites, androsterone and etiocholanolone, compared to values prior to anabolic use. The excretion of major urinary metabolites of glucocorticoids was not affected by anabolic use. Urinary excretion of anabolic steroids or anabolic metabolites averaged 20-25% of total anabolic steroid administered. The major excreted metabolites of methandrostenolone, nandrolone, oxandrolone and oxymetholone were identified by gas chromatography-mass spectrometry based on the major mass spectral ion peaks.

Anabolic Agents↗
PubMed1989

Task-dependent changes in cutaneous reflexes recorded from various muscles controlling finger movement in man.

1. Cutaneous reflex responses have been recorded from muscles involved in the control of finger movement following electrical stimulation of the digital nerves of the fingers in man. 2. Recordings have been made while subjects performed various manual tasks. 3. Reflexes recorded while subjects performed a relatively isolated finger movement consisted of an initial short-latency increase in muscle electrical activity, followed by a decrease, followed by a prominent longer-latency increase. The long-latency excitatory component was smaller or absent during those grips used in the present study. 4. The short-latency excitatory (E1) and inhibitory (I1) components of the cutaneomuscular reflex response are mediated via spinal pathways. The second longer-latency excitatory component (E2) is of supraspinal origin, requiring the integrity of the dorsal columns, sensorimotor cortex and corticospinal tract (Jenner & Stephens, 1982). The results of the present study suggest that one or more of these supraspinal pathways is more active when a finger is used in a relatively isolated manner than when the same finger participates in any of the gripping manoeuvres used in the present experiments.

Adolescent↗
PubMed1989

Task-dependent changes in the size of response to magnetic brain stimulation in human first dorsal interosseous muscle.

1. Electromyographic responses have been recorded from human first dorsal interosseous muscle (FDI) in response to magnetic and transcutaneous electrical stimulation of the brain. 2. Following magnetic but not electrical stimulation of the brain, the recorded EMG response was larger when FDI was active during voluntary isometric index finger abduction than during a power grip. 3. In the same experiment, cutaneous reflex responses have been recorded from FDI following electrical stimulation of the digital nerves. The long-latency excitatory component at about 60 ms (E2) was larger when recorded during voluntary finger abduction than during a power grip. This difference in size of E2 with task bore no simple relationship to the difference in size with task of the motor response to magnetic brain stimulation. 4. The results are discussed in relation to the presumed site of action of magnetic and electrical brain stimulation. It is concluded that the results may best be interpreted by assuming a higher level of cortical activity during a voluntary index finger abduction than during a grip and that this could in part explain the task-dependent changes in the long-latency response to cutaneous stimulation.

Adult↗
PubMed1989

A point mutation in the coding region of uroporphyrinogen decarboxylase associated with familial porphyria cutanea tarda.

Familial porphyria cutanea tarda (PCT) is inherited as an autosomal dominant trait caused by decreased activity of uroporphyrinogen decarboxylase (URO-D). In most families with PCT, URO-D mRNA levels are normal but both catalytic activity and immunologic reactivity of URO-D are half normal. We have cloned and sequenced 8 URO-D cDNA transcripts derived from a pedigree member with familial PCT. Three of the cDNAs had sequences encoding normal URO-D but five cDNA's contained a point mutation resulting in a gly----val substitution at amino acid position 281. An oligonucleotide probe complementary to the mutant sequence hybridized to DNA from affected individuals within the pedigree, but not to DNA from normal individuals. Measurements of pulse labeled URO-D in Epstein-Barr virus transformed lymphocytes indicated that the mutant protein has a half-life in vivo of less than four hours. In vitro measurements utilizing labeled URO-Ds generated in a reticulocyte lysate system revealed a 12-hour half-life for the mutant protein compared with a 102-hour half-life for normal URO-D. This is the first URO-D mutation to be characterized in a pedigree with familial PCT. This mutation was not detected in affected individuals from seven other PCT pedigrees, suggesting that PCT can result from different mutations.

Carboxy-Lyases↗