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Biomedical subjects

J Madden

Publications and source records attributed to J Madden.

At least 55 records · Page 3Linked to original sources

Clonality of cell populations in refractory anaemia using combined approach of gene loss and X-linked restriction fragment length polymorphism-methylation analyses.

We have used X-linked restriction fragment length polymorphism (RFLP)-methylation and gene deletion analyses to investigate the nature of the progenitor cell of origin in the myelodysplastic syndromes (MDS). Gene deletion studies were performed on the granulocyte and T-lymphocyte fractions of six women with refractory anaemia (RA) and either a partial deletion of the long arm of chromosome 5 (5q-) or monosomy 7. All six showed gene loss in the granulocyte but not the T-lymphocyte fractions, indicating monoclonality of the granulocytes but not the T-lymphocytes. In order to further investigate this finding, we subsequently performed X-RFLP-methylation studies using the probe M27 beta, and also a probe for the phosphoglycerate kinase (PGK) gene. These studies have confirmed the monoclonality of the granulocytes and the polyclonality of the T-lymphocytes in these cases. Our findings suggest that in this group of patients with MDS the T-lymphocytes were not involved in the disorder, and furthermore, in the one case where B-lymphocytes were also available, that the progenitor cell of origin was restricted to the myeloid lineage.

Anemia, Refractory↗

Isolation and characterization of opioid peptides from rabbit cerebellum.

The rabbit cerebellum has been shown to contain significant quantities of opioid receptors consisting of both mu- and kappa-subtypes. To determine the nature of the endogenous opioid ligands in this tissue, extracts from rabbit cerebellum were separated by various chromatography techniques and fractions were assayed initially for opioid peptides with a radioimmunoassay capable of detecting all peptides with an amino-terminal Tyr-Gly-Gly-Phe sequence. This sequence is common to all mammalian opioid peptides and is critical for recognition by all known opioid receptors. Each of the three immunoreactive opioid peptide peaks detected was purified to homogeneity and subjected to amino acid composition and sequence analysis. One peak was analyzed further by mass spectrometry. This identified the major opioid peptides in the cerebellum as [Met5]enkephalin, [Leu5]enkephalin, and heptapeptide [Met5]enkephalyl-Arg6-Phe7. The comprehensiveness of this initial detection scheme in identifying biologically active opioid peptides was substantiated through subsequent analysis. Using specific radioimmunoassays for representative opioid peptides of the three opioid systems currently known, no other peptides of either the proenkephalin, proopiomelanocortin, or prodynorphin series were detected in any appreciable amounts. Collectively, these results are consistent with the position that rabbit cerebellar opioids are derived from proenkephalin. However, given that no appreciable quantities of either [Met5]enkephalyl-Arg6-Arg7-Val8-NH2 (metorphamide) or [Met5]enkephalyl-Arg6-Gly7-Leu8 were detected suggests that rabbit proenkephalin may have a slightly altered sequence and/or is differentially processed relative to other mammalian species studied.

Amino Acid Sequence↗

Characterization of implants from Dupuytren's contracture tissue into the nude (athymic) mouse.

Dupuytren's contracture tissues were obtained from six patients as excess surgical material. Pieces of these tissues (a total of 38 implants) were placed into subcutaneous pockets in the suprascapular area of nude (athymic) mice. The objective was to determine whether the implant tissues would be maintained in the mouse with the characteristics of Dupuytren's tissue. The implants were removed for study at 14-179 days after implantation. Microvascular anastomosis between implant and host skin was established within the first 14 days. Histologic character and electron microscopic structure of the implants did not change during the course of the study. The implants became reduced in size with time. However, neither the spatial pattern of collagen nor the appearance of fibroblast cells changed. The original high levels of chondroitin-4-sulfate were significantly decreased in the 66- to 179-day postimplantation group, but were not significantly different from the values for normal fascial bands. The hyaluronic acid of the implants increased significantly with time of implantation, but never reached the level found in the normal fascial bands. The use of implants into nude mice may be useful for further experimental studies of Dupuytren's contracture.

Animals↗

Pharmacological analysis of the magnocellular red nucleus during classical conditioning of the rabbit nictitating membrane response.

Previous experiments have suggested that the red nucleus is an essential structure in the neural pathways subserving the conditioned responses (CRs) elicited in several simple associative learning paradigms. The present investigation confirms the involvement of the magnocellular red nucleus in production of the classically conditioned nictitating membrane response in the rabbit and suggests that gamma-aminobutyric acid (GABA) processes within this structure are involved in expression of the CR. Specifically, these studies demonstrate that microinfusion of a GABA antagonist (either picrotoxin or bicuculline methiodide) into the magnocellular red nucleus can selectively and reversibly reduce or abolish retention of the CR, without altering the unconditioned reflex response. Furthermore, these pharmacological manipulations that disrupt the CR are both anatomically and pharmacologically specific, and demonstrate a predictable dose-dependent function. These findings suggest that GABAergic processes within the magnocellular red nucleus are part of the critical circuitry subserving the CR.

Animals↗

Cerebellar GABAergic processes: evidence for critical involvement in a form of simple associative learning in the rabbit.

Converging evidence from electrophysiological recording and lesion studies suggests an essential role for the cerebellum in classical conditioning of the nictitating membrane response in the rabbit. The present study begins to delineate within this structure neurotransmitter systems that appear critical for the expression of this form of simple associative learning. Experiments reported here demonstrate that microinfusion of gamma-aminobutyric acid (GABA) antagonists (either bicuculline methiodide or picrotoxin) into specific areas of the medial dentate/lateral interpositus nuclei or into the cerebellar cortex of lobule HVI can selectively and reversibly abolish conditioned responding, while leaving the unconditioned reflex response intact. The results are consistent with the suggestion that GABAergic synapses play an essential role in the circuitry that mediates the conditioned response.

Animals↗

Abnormal fetal heart rate pattern associated with severe intrapartum maternal ethanol intoxication. A case report.

Acute intrapartum ethanol intoxication occurred in a chronic ethanol abuser. Continuous fetal heart rate monitoring revealed a pattern of fetal tachycardia, decreased variability and late and variable decelerations in association with a maternal serum ethanol level of 300 mg/dL. This case gives evidence of an association between very high maternal serum ethanol levels and acute fetal distress.

Adult↗

Automating materials management via the computer grey market.

For all but the top 10% of major national corporations who need leading edge computer technology, the "grey market" is an excellent source of first rate equipment at bargain basement prices. But to tap this market profitably, shoppers have to understand how and why it works.

Capital Expenditures↗

Fatty acid composition of human erythrocyte membranes by capillary gas chromatography-mass spectrometry.

Capillary gas chromatographic and gas chromatographic--mass spectrometric methods were employed for profiling total fatty acid content of human erythrocyte membranes. The protocol was designed to efficiently separate, identify, and accurately quantify the fatty acid composition in human erythrocyte membranes. Washed erythrocyte "ghosts" were saponified in aqueous methanolic sodium hydroxide solution and methylated with boron trichloride and acid catalysis. Extracted total fatty acid methyl esters (FAMEs) were analyzed using a highly polar cyanopropylsiloxane SP 2560 fused-silica capillary column. Total run time was 55 min, and 45 FAMEs were tentatively identified by relative retention times compared to those of known FAMEs. Confirmation of identities by mass spectral structure elucidation revealed saturated, mono- and polyunsaturated, and branched-chain FAMEs. The presence of four fatty aldehydes was also confirmed as dimethyl acetal derivatives. Identification of cis/trans isomers was based on relative retention times and characteristic profile of the cis/trans FAME standard. Quantification of FAMEs for normal subjects showed some variation in relative amounts, consistent with expectations based on literature reports on total or phospholipid FAMEs from human erythrocytes. Separation of individual components of fatty acid families (n-3), (n-6), and (n-9) is demonstrated. Losses in relative amounts of polyunsaturated fatty acids upon storing samples were also detectable by this rapid method.

Chromatography, Gas↗

Home again: effects of the Mother-Child Home Program on mother and child.

4 successive cohorts of low-income families were randomly assigned either to a home-based intervention program that focused on modeling verbal interaction between mother and child around selected toys and books or to comparison treatments. Large program effects were found on maternal interaction styles in videotaped observations. Small IQ and program-specific effects were found for children in contrast to much larger IQ effects found in earlier research. IQ effects did not appear to have been mediated by changes in maternal behavior. A variation in which toys and books were supplied without home visits was as effective as the full program on IQ but not on maternal behavior. 3 years postprogram , there were no detectable effects in achievement or IQ tests or in first grade teachers' ratings of school adjustment and performance, but IQ and achievement scores were near national norms. Reasons for discrepancies with earlier results are discussed. The results highlight the need for continued experimental evaluation of early intervention programs with safeguards to insure that samples are educationally at risk.

Achievement↗

Abolition of conditioned heart-rate responses in rabbits following central administration of [N-MePhe3, D-Pro4] morphiceptin.

Rabbits were initially habituated to a tone and then give 15-20 paired trials where the tone was followed by periorbital shock resulting in conditioned heart-rate decelerations to tone onset and an acceleration of heart-rate following shock offset. The animals were matched for learning performance and divided into two groups. Each animal received a microinfusion into the region of the fourth ventricle of either the opiate [N-MePhe3,D-Pro4] morphiceptin, a highly selective mu receptor agonist, or a mixture of the morphiceptin analogue and the opiate antagonist naltrexone. Administration of the morphiceptin analogue eliminated the conditioned bradycardia to the tone but not the acceleration to the shock. Rabbits given the mixture continued to show conditioned heart-rate decelerations. Previous studies have shown that opiates abolish a recently learned conditioned nictitating membrane response. These effects are consistent with the hypothesis that the opiate effect on conditioning is due to an attenuation of conditioned fear.

Acoustic Stimulation↗

Corticosterone: a critical factor in an opioid form of stress-induced analgesia.

The finding that some opioid-mediated forms of stress-induced analgesia are antagonized by hypophysectomy and dexamethasone has led to the suggestion that beta-endorphin, released from the pituitary, may mediate these analgesic reactions. "Long-term analgesia" (an opioid-mediated form of stress-induced analgesia), which is blocked by dexamethasone and hypophysectomy, was also blocked by adrenalectomy and reinstated with corticosterone therapy. Corticosterone is proposed to play a permissive role in long-term analgesia and to be a critical hormone mediating this phenomenon.

Adrenalectomy↗

Opiates and classical conditioning: selective abolition of conditioned responses by activation of opiate receptors within the central nervous system.

It has previously been shown that opiates produce selective abolition of aversively motivated classically conditioned responses in the rabbit. The experiments reported here show that these effects are mediated by specific activation of opiate receptors within the central nervous system in that this central activation is both necessary and sufficient to produce opiate-induced abolition of conditioned responding. Further characterization suggests that selective activation through opiate-mu-receptor interactions within the periaqueductal gray/periventricular region of the fourth ventricle may be critical in mediating this abolition.

Avoidance Learning↗