Biomedical subjects

M K Hahn

Publications and source records attributed to M K Hahn.

6 recordsLinked to original sources

PubMed2002

Monoamine transporter gene structure and polymorphisms in relation to psychiatric and other complex disorders.

The norepinephrine, dopamine and serotonin transporters (NET, DAT and SERT, respectively), limit cellular signaling by recapturing released neurotransmitter, and serve as targets for antidepressants and drugs of abuse, emphasizing the integral role these molecules play in neurotransmission and pathology. This has compelled researchers to search for polymorphisms in monoamine (MA) transporter genes. Studies support linkage and association of MA transporter genetic variation in psychiatric and other complex disorders. Understanding the contribution of MA transporter polymorphisms to human behavior, disease susceptibility and response to pharmacotherapies will involve further progress in linkage and association that will be aided by both definition of highly selective phenotypes and utilization of a large number of polymorphic markers. The relationship of polymorphisms to alterations in transport capacity, likely a complex interaction, involving genetic background, disease state, and medication, will elucidate the means by which MA transporter genetic variability contributes to our individuality.

Biogenic Monoamines↗

PubMed2000

Analysis of tyrosine hydroxylase gene transcription using an intron specific probe.

The nuclear run-on assay is the most commonly used technique to determine transcription rates of specific genes such as tyrosine hydroxylase. Its application to studies in the nervous system is problematic, however, as a result of limitations in sensitivity and the loss of anatomical integrity. We observed that the relative levels of tyrosine hydroxylase intron 2-containing RNA using a ribonuclease protection assay in the adrenal medulla changed in response to pharmacological treatments consistently with changes shown by the nuclear run-on assay. Our results indicate that measures of tyrosine hydroxylase primary transcript levels offer an alternative to the nuclear run-on assay and validate the application of intron-specific in situ hybridization as a means of assessing the relative transcriptional activity of the tyrosine hydroxylase gene. Similar quantitative results were obtained using intron-specific in situ hybridization with oligonucleotide probes specific for rat tyrosine hydroxylase intron 2. Furthermore, we observed that intron-specific in situ hybridization could be used to measure tyrosine hydroxylase transcription rates in the locus coeruleus, providing resolution at the level of single neurons. Thus, measuring the levels of tyrosine hydroxylase intron 2 provides a sensitive measure of tyrosine hydroxylase transcription rate that can be applied to the study of brain catecholaminergic neurons.

Adrenal Medulla↗

PubMed1999

Stress-induced C-fos expression in the rat locus coeruleus is dependent on neurokinin 1 receptor activation.

These experiments examined the role of substance P-selective neurokinin 1 receptors in the restraint-induced activation of the rat locus coeruleus. Immunohistochemistry revealed high levels of neurokinin 1 receptor expression in the plasma membrane of tyrosine hydroxylase-positive locus coeruleus neurons. The selective neurokinin 1 receptor antagonists, RP 67580 (5 nmol) and L-760,735 (3.4 nmol), were administered intracerebroventricularly prior to restraint stress, and c-fos protein was measured as an index of locus coeruleus activation. Both antagonists attenuated the restraint-induced increase in locus coeruleus c-fos expression, whereas their inactive enantiomers were ineffective. These results suggest that neurokinin 1 receptors may mediate activation of locus coeruleus neurons during stress. Neurokinin 1 receptor antagonists may prove to be novel therapeutic compounds in the treatment of anxiety and depression.

Animals↗

PubMed1998

Tachykinin NK1 receptor antagonists enhance stress-induced c-fos in rat locus coeruleus.

These experiments tested the hypothesis that substance P neurotransmission at tachykinin NK1 receptors in the locus coeruleus is involved in stress-induced activation of the locus coeruleus, using c-fos as an index of activation. Selective tachykinin NK1 receptor antagonists administered systemically did not result in substantial locus coeruleus c-fos expression. Restraint stress resulted in a large number of locus coeruleus c-fos expressing cells. Administration of two selective tachykinin NK1 receptor antagonists prior to restraint resulted in an increase in the number of locus coeruleus c-fos expressing cells, compared to restraint alone. These results suggest that the enhanced c-fos expression observed in response to tachykinin NK1 receptor antagonists combined with stress, could be due to the blockade of tachykinin NK1 receptor-mediated activity at sites other than the locus coeruleus, resulting in an overall activation of the locus coeruleus.

Acetamides↗

PubMed1995

Microvascular techniques in limb-sparing surgery.

Microvascular techniques allowing free tissue transfer have expanded the indications for limb salvage in tumor patients. Preoperative planning should predict the type of deficit anticipated. Specific techniques for soft tissue, skeletal, neurovascular, and composite tissue transfer are discussed. While demanding, the use of living autogenous tissue gives the potential for biologic adaptivity and life-long durability.

Adult↗

PubMed1991

Determination of benzyl alcohol and its metabolite in plasma by reversed-phase high-performance liquid chromatography.

A study undertaken following recent reports of deaths in neonatal children associated with the use of benzyl alcohol resulted in the development of a stability-indicating high-performance liquid chromatographic assay of benzyl alcohol in plasma using benzocaine as internal standard. Thawed plasma samples were diluted and subjected to solid-phase extraction using Extrelut and eluted with ethyl acetate. The evaporated eluate was reconstituted with mobile phase and chromatographed on a C18 column with water-acetonitrile-glacial acetic acid as mobile phase and detection at 254 nm. Baseline separation was achieved within 12 min for benzyl alcohol, benzaldehyde, benzoic acid, hippuric acid and benzocaine. Peak-height ratios were linear over 80-640 ng of benzyl alcohol injected (r = 0.998) and over 10-80 ng of benzoic acid injected (r = 0.999). Benzaldehyde and hippuric acid were not quantitated because these compounds were not detectable in actual dog plasma. Validation studies by spiking dog plasma with benzyl alcohol and benzoic acid gave overall percent recoveries (+/- relative standard deviation, n = 4) of 98.3 +/- 3.0 and 101.4 +/- 7.6%, respectively. The method was applied to the assay of actual plasma samples. Since benzyl alcohol is very susceptible to oxidation to benzaldehyde and benzoic acid, its purity in bulk liquid samples can be determined by this method.

Animals↗