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Biomedical subjects

J K Young

Publications and source records attributed to J K Young.

At least 37 records · Page 2Linked to original sources

Immunoreactivity for diazepam binding inhibitor in Gomori-positive astrocytes.

A polypeptide termed diazepam binding inhibitor (DBI), capable of binding to receptor sites on glial mitochondria, is known to be present in glial cells and is particularly abundant in areas near circumventricular organs of the brain such as the arcuate nucleus of the hypothalamus. DBI appears to stimulate steroid synthesis and/or transport in glial mitochondria. The arcuate nucleus also contains large numbers of specialized glia, termed Gomori-positive astrocytes, that are estrogen-sensitive and which possess highly stained, heme-containing cytoplasmic granules. This study was performed to determine if these Gomori-positive astrocytes are immunoreactive for DBI. A rabbit antibody to DBI, but not pre-immune serum, stained Gomori-positive glia and suggests that these glia are partly responsible for the high levels of DBI in circumventricular organs. DBI in these glia may be related to functional responses of the hypothalamus to steroid hormones.

Animals↗

Hypothalamic lesions increase levels of neuropeptide Y mRNA in the arcuate nucleus of mice.

A recent study demonstrated that hypothalamic lesions induced by goldthioglucose (GTG) in mice produced an increase in neuronal immunoreactivity for neuropeptide Y (NPY) in the hypothalamic arcuate nucleus. Since NPY is a potent stimulator of feeding, this increase represented a potential explanation for the hyperphagia seen after GTG lesions. To examine whether or not this increase in NPY immunoreactivity was accompanied by an increase in the mRNA for NPY, in situ hybridization histochemistry for NPY mRNA in control and in lesioned mice was performed. A 47% increase in NPY mRNA levels in the arcuate nucleus was observed in lesioned mice compared with controls, suggesting that an increased expression of the gene for NPY contributes to elevations in hypothalamic NPY after lesioning. This elevation in NPY may, in turn, relate to mechanisms provoking hyperphagia.

Animals↗

Nmr and molecular modeling investigations of the neuropeptide bradykinin in three different solvent systems: DMSO, 9:1 dioxane/water, and in the presence of 7.4 mM lyso phosphatidylcholine micelles.

The linear nonapeptide hormone bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) is involved, either directly or indirectly, in a wide variety of physiological processes, particularly pain and hyperanalgesia. Additional evidence suggests that bradykinin also plays a major role in inflammatory response, asthma, sepsis, and symptoms associated with the rhinoviral infection. It has long been speculated that a beta-turn at the C-terminus of bradykinin plays a major role in the biological activity of the neuropeptide. The beta-turn forming potential of bradykinin in three vastly different local chemical environments, DMSO, 9:1 dioxane/water, and in the presence of 7.4 mM lyso phosphatidylcholine micelles, was investigated using two-dimensional homonuclear nmr experiments coupled with simulated annealing calculations. The results of these investigations show that in all three systems residues 6-9 of the C-terminus adopt very similar beta-turn like structures. These results suggest that the beta-turn at the C-terminus of bradykinin is an important secondary structural feature for receptor recognition and binding.

Amino Acid Sequence↗

NMR and molecular modeling investigations of the neuropeptide substance P in the presence of 15 mM sodium dodecyl sulfate micelles.

To better understand the structural basis of the biological activity of the neuropeptide substance P SP; (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2), two-dimensional nmr spectroscopy experiments and simulated annealing calculations were used to investigate the conformation adopted in the presence of the membrane model system sodium dodecyl sulfate. It was determined that SP in the presence of SDS micelles undergoes a conformational equilibrium between an alpha- and a 3(10)-helix involving the midregion (Pro4-Gln5-Gln6-Phe7-Phe8) of the peptide. The C-terminus adopts an extended conformation while the N-terminus remains quite flexible. The conformation adopted by SP in the presence of SDS micelles yields a structure that is consistent with the model of a neurokinin-1 selective ligand proposed by Convert.

Amino Acid Sequence↗

Atrial natriuretic peptide-like (ANP-LIR) and ANP prohormone immunoreactive astrocytes and neurons of human cerebral cortex.

Atrial natriuretic peptide (ANP) represents a family of related peptides originally isolated from cardiac atria that have potent natriuretic, diuretic, and vasorelaxant properties. ANP has previously been localized in neurons of the rat brain in regions subserving cardiovascular functions and fluid/electrolyte balance and has been localized in astroglia of the canine brain. To determine whether ANP is present in astrocytes of the human brain and to validate the canine model for future studies, human brain tissue was obtained from autopsy cases with no brain damage or neurological or vascular disease. Human brains were obtained less than 3 h postmortem, and anterior cingulate and striate cortices were dissected following perfusion or immersion fixation. Immunohistochemical processing utilized antibodies against the processed form of ANP (ANP IV, ANP104-128) and against rat proANP (amino terminus) and the avidin-biotin-peroxidase technique. Isolated, strongly ANP-immunoreactive protoplasmic astrocytes were observed in all layers of the cingulate and striate cortex gray matter. ANP-positive fibrous astrocytes were observed in the white matter. Additionally, distinctive immunopositive astrocytes were found both within and immediately subjacent to the glia limitans. Antibody against the prohormone stained only protoplasmic astrocytes and sublimitans astrocytes and processes. In addition to the astroglia, ANP was detected in scattered multipolar neurons in the cerebral gray matter. These results provide additional evidence for diversity of peptide localization in astrocytes and suggest roles for ANP in the local regulation of cerebral blood flow, blood-brain barrier permeability, or cerebrospinal fluid volume.

Adult↗

A three-dimensional reconstruction of the human hypothalamus.

A previous three-dimensional reconstruction of the rat hypothalamus revealed an organization of nuclei into three major clusters. This clustering may relate to the presence of three hypothalamic anlagen in the embryo and to a restriction of marker proteins and transcription factors to specific regions of the hypothalamus during development. To see if a similar clustering was apparent in the human hypothalamus, a reconstruction of the hypothalamus from a male cadaver was prepared. The reconstruction showed a clustering of nuclei into three anterior-posterior groups. With reference to the well-defined human supraoptic nucleus, the suprachiasmatic and lateral mammillary nuclei were proportionately smaller in this single human specimen than would be expected from data in the rat. A high degree of homology between hypothalamic structures in the rat and human were generally observed.

Animals↗

CQI and technology: partnership drives improvement.

CQI plus technology equals increased financial success, according to Parkview Episcopal Medical Center. For this Pueblo, Colo., community hospital, the results of this equation are impressive--time saved, a motivated workforce and last but not least, more revenue.

Colorado↗

Contrasting approaches aim at similar network goals.

At any node on the network implementation timeline, whether in the first planning stages or after the bottom-line benefits are stacking up, networking is a compelling idea. So compelling, with flexibility, cost-cutting results and strengthened community resources, that it extends its influence into the future of the organizations it serves. Two institutions, University Hospital in Denver and the Medical Center of Delaware in Wilmington, Del., illustrate networking's tempting benefits. University Hospital disabled its mainframe, switching to an Ungermann-Bass Access One smart hub in January of this year. Their systems are added to the network one-at-a-time, with plans for complete integration once everything is working online. In contrast, the Medical Center of Delaware shifted to networking in 1987, following a five-year implementation plan. The completed, integrated network is now a strategic tool for containing costs an MCD.

Colorado↗

Industry leaders earn Pioneer Award.

Computers in Healthecare announces four new Pioneers for 1993. They join a distinguished list of 17 CIH Pioneers who have received this honor since 1990. These new Pioneers, along with their Pioneer colleagues, will be honored May 12 at the 1993 Computers in Healthcare Conference and Exposition in Hilton Head, S.C.

Awards and Prizes↗

The interactions of neuropeptides with membrane model systems: a case study.

The interactions between the positively charged neuropeptides substance P (SP), bradykinin (BK), and zwitterionic Met-enkephalin (ME) neuropeptides, and negatively charged SDS and zwitterionic lysophosphatidylcholine (LPC) membrane model systems, have been investigated using one- and two-dimensional nmr experiments. Proton longitudinal relaxation studies were used to characterize these interactions as intrinsic or extrinsic. An extrinsic interaction are similar to those observed for extrinsic membrane proteins. An intrinsic interaction are similar to those observed for intrinsic membrane proteins, and would require that the hydrophobic residues penetrate or insert into the hydrophobic core of the membrane. The interactions between both SP and BK and SDS, based on nmr results, may be characterized as intrinsic, and the interaction between ME and SDS may be characterized as extrinsic. Two-dimensional nuclear Overhauser enhancement spectroscopy experiments proved the insertion of the phenylalanine residues on both SP and BK into the hydrophobic core of SDS micelles. The interaction between SP and BK with LPC based on nmr results are characterized as extrinsic, with the interaction between ME and SDS characterized as weakly intrinsic.

Bradykinin↗

The use of UV-visible spectroscopy for the determination of hydrophobic interactions between neuropeptides and membrane model systems.

Ultraviolet-visible spectroscopy has been used as a rapid method to evaluate the hydrophobic interactions between a series of cationic and zwitterionic neuropeptides and dipeptides with the hydrophobic core of two membrane model systems; sodium dodecyl sulfate and lysophosphatidylcholine micelles. If a hydrophobic interaction occurs, a 1-nm bathochromic shift is observed in the uv-visible spectrum of the aromatic side chains when going from aqueous solution to a micellar solution. The aromatic residues of substance P, bradykinin, and Des-Arg9 bradykinin all exhibited the 1-nm bathochromic shift in the presence of sodium dodecyl sulfate while those of Met-enkephalin did not. The opposite effects were observed in the presence of lysophosphatidylcholine micelles.

Amino Acid Sequence↗

Alzheimer's disease and metal-containing glia.

Considerable evidence suggests that in Alzheimer's disease, olfactory bulb damage may be a primary factor, causing degeneration and neurofibrillary tangles primarily in neurons connected with this brain area. Also, deposits of amyloid may involve an improper regulation of the cleavage of a precursor protein by glia. Finally, toxic effects of aluminium may be an etiological factor. This review proposes that all these seemingly unrelated aspects of Alzheimer's disease could be related to a disturbed function of metal-containing glia. Such a disturbance, initiated by or aggravating toxic effects of aluminum, may underlie initial damage in the olfactory bulb and/or other brain areas with a weakened blood-brain barrier and may be responsible for amyloid deposition.

Aluminum↗

Healthcare pioneers lead the way.

Using the Pioneer space program as a metaphor for the spirit of adventure, the vision and the innovation embodied by all Computers in Healthcare Pioneers, CIH names four new Pioneers for 1992. These new Pioneers as well as our 13 current Pioneers will be honored at the Seventh Annual Computers in Healthcare Conference and Exposition May 27 and 28 in San Diego.

Awards and Prizes↗

Information systems help knowledge workers work even harder at productivity.

Information systems are here to stay, but their full benefits continue to elude healthcare users. Multimillion dollar systems--for all of their promise--tend to create more work. Some even require significant additional staffing to maintain them. How can healthcare knowledge workers measure and increase their productivity?

Efficiency↗

Glial immunoreactivity for metallothionein in the rat brain.

A series of frozen and vibratome coronal sections of the rat brain were examined by immunocytochemistry for the presence of a cysteine-rich metal binding protein, metallothionein (MT). Astrocytes throughout the brain and brainstem stained positively for MT; neurons and oligodendroglia were unstained. Ependymal cells and tanycyte processes in the hypothalamus were also immunoreactive, along with a narrow zone of immunopositivity along the margins of the area postrema. Gomori-positive astrocytes in the hypothalamus, identifiable by toluidine blue staining, metal-containing cytoplasmic granules, represented a subset of MT-positive astrocytes that may be involved in reactions to blood-borne metal compounds that penetrate into circumventricular organs of the brain.

Animals↗

A three-dimensional reconstruction of the rat hypothalamus.

Tracings of structures present in serial coronal frozen sections of the rat hypothalamus were entered into an IBM-PC and sections were aligned in space using a program for 3-dimensional reconstruction. The positions and relative volumes of 16 major hypothalamic nuclei were accurately displayed in lateral, medial, and superior views of the hypothalamus. Three major clusters of hypothalamic nuclei were apparent, reinforcing embryological concepts of "neuromeres" from which adult structures develop. A better knowledge of the spatial locations of hypothalamic nuclei, which determine the pathways of intrahypothalamic connections, should be of aid in interpreting studies which disrupt such connections.

Animals↗