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Biomedical subjects

C York

Publications and source records attributed to C York.

At least 19 recordsLinked to original sources

Glycyl-glutamine inhibits the respiratory depression, but not the antinociception, produced by morphine.

Glycyl-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide that is synthesized through the posttranslational processing of beta-endorphin in brain stem regions that control respiration and autonomic function. This study tested the hypothesis that Gly-Gln administration to conscious rats will prevent the respiratory depression caused by morphine without affecting morphine antinociception. Rats were administered Gly-Gln (1-100 nmol) or saline (10 microl) intracerebroventricularly followed, 5 min later, by morphine (40 nmol icv). Arterial blood gases and pH were measured immediately before Gly-Gln and 30 min after morphine injection. Gly-Gln pretreatment inhibited morphine-induced hypercapnia, hypoxia, and acidosis significantly. The response was dose dependent and significant at Gly-Gln doses as low as 1 nmol. In contrast, Gly-Gln (1-300 nmol) had no effect on morphine-evoked antinociception in the paw withdrawal test. When given alone to otherwise untreated animals, Gly-Gln did not affect nociceptive latencies or blood gas values. These data indicate that Gly-Gln inhibits morphine-induced respiratory depression without compromising morphine antinociception.

Acidosis↗

Vitamin D receptor polymorphisms are associated with altered prognosis in patients with malignant melanoma.

Calcitriol [1,25(OH)2D3], the hormonal derivative of vitamin D3, is an antiproliferative and prodifferentiation factor for several cell types, including cultured melanocytes and malignant melanoma (MM) cells. Several polymorphisms of the vitamin D receptor (VDR) gene have been described including a FokI RFLP in exon 2, BsmI, and ApaI polymorphisms in intron 8 and an adjacent TaqI RFLP in exon 9. Alterations in vitamin D/1,25(OH)2D3 levels and polymorphisms of the VDR have been shown to be associated with several systemic malignancies. We hypothesize that polymorphism in this gene may be associated with altered susceptibility and outcome in patients with MM. A hospital-based case-control study, using 316 MM cases and 108 controls, was used to assess associations with MM susceptibility. Breslow thickness, the most important single prognostic factor in MM, was used as the outcome measure. Polymorphisms at the FokI and TaqI restriction sites were determined using PCR-based methods. Polymorphism at the FokI, but not TaqI, RFLP was associated with an altered risk of MM (P = 0.014). More importantly, variant alleles were associated with increased Breslow thickness. Thus, homozygosity for variant alleles at both RFLP (ttff genotype combination) was significantly associated with thicker tumors. (> or = 3.5 mm; P = 0.001; odds ratio = 31.5). Thus, polymorphisms of the VDR gene, which would be expected to result in impaired function, are associated with susceptibility and prognosis in MM. These data suggest that 1,25(OH)2D3, the ligand of the VDR, may have a protective influence in MM, as has been proposed for other malignancies.

Case-Control Studies↗

Managing the quality effort in a health care setting: an application.

Recent marketplace realities and trends have forced health care institutions to adopt strategic orientations that stress a customer focus. Central to such strategic orientations is the effective utilization of service quality practices and philosophies. Toward that end, this research offers health care institutions an affordable methodology. A real-life application of the rapid assessment methodology (RAM) in a health care operational setting is presented. Finally, a framework to guide the implementation of the RAM methodology is outlined and explored.

Consumer Behavior↗

Using the World Wide Web to answer clinical questions: how efficient are different methods of information retrieval?

BACKGROUND: The World Wide Web (Web) has the potential to revolutionize information retrieval in medicine. However, the best method of information retrieval from the Web is not known. The purpose of our study was to compare medical search engines, general-purpose search engines, medical meta-lists, and commercial sites on the Web with regard to their efficiency in retrieving medical information. METHODS: Ten questions were identified from a database of questions posed by primary care clinicians. Authoritative answers were identified. Searches were performed using 1 commercial site, 4 general search engines, 9 medicine-specific search engines, and 2 medical meta-lists. The main outcome measures were the number of questions answered by each Web site, the correctness of the answers, the number of links followed to get an answer, and how well documented the answer was using the Health on the Net criteria. RESULTS: MD Consult, a commercial site, answered 6 of 10 questions. Hardin MD (a meta-list) and Excite and HotBot (general search engines) each answered 5 questions. The medicine-specific search engines performed poorly, answering an average of only 1 question. MD Consult and HotBot required the least number of links to find an answer. MD Consult and Hardin MD had the best documented answers. CONCLUSIONS: Medicine-specific search engines on the Web fare poorly in answering clinical questions when compared with general search engines. MD Consult, Excite, HotBot, and Hardin MD found the greatest number of answers.

Efficiency↗

The Costello syndrome.

In 1971 and again in 1977, Costello reported on two unrelated children with multiple congenital malformations associated with growth and developmental retardation and nasal papillomata (Costello, NZ Med J 74:397, 1971; Costello, Aust Paediatr J 13:114-118, 1977). Subsequently, two similar cases were described (Der Kaloustian et al., Am J Med Genet 41:69-73, 1991; Martin and Jones, Am J Med Genet 41:346-349, 1991). Costello syndrome is now a distinct entity. We describe another patient who additionally had hitherto unreported malformations, such as hydrocephalus, seizures, atrial fibrillation, and flutter with atrial septal defect. Although no nasal lesions were found he had laryngeal papillomata associated with a congenital web. A skin biopsy showed no evidence of lipid or mucopolysaccharide storage disease and muscle biopsy was normal by gross and electron microscopic examination.

Abnormalities, Multiple↗

Erythrocyte membrane structure in bipolar affective disorder: a non-replication.

Fifteen bipolar patients were compared with sixteen controls in an attempt to replicate the findings of Pettegrew et al. in 1982 of decreased fluidity in the hydrocarbon core of the erythrocyte membrane. No significant differences were seen between groups. The present control group shows very similar membrane characteristics to the original control series; however, the bipolar patient group is not similar. Possible explanations are discussed.

Adult↗

Aerosol infection of rhesus macaques with Junin virus.

The purpose of our work was to determine if aerosols of Junin virus can infect rhesus macaques and if the disease is the same as that produced by virus inoculated parenterally. The 6 macaques exposed to the virus by aerosol became acutely ill during the 3rd week after exposure, and all died. Three died by day 21, while the remainder died after 1 month. Junin virus was found primarily in visceral organs of those animals dying before 21 days after infection and in the central nervous system tissues from animals dying later. Histological changes were similar to those reported in rhesus monkeys after parenteral Junin viral infection. Gastrointestinal necrosis, however, was less severe in aerosol-infected animals and the associated septicemia was not seen. High levels of alpha interferon were detected by the 3rd day in all infected macaques. Experimental Argentine hemorrhagic fever induced by aerosol infection in rhesus macaques was similar to that seen after parenteral challenge and mimicked closely the clinical syndrome observed in humans.

Aerosols↗

Mesenteric artery embolization by an unsuspected aortic tumor: diagnostic evaluation and operative management.

Malignant tumor embolus recovered at the time of superior mesenteric artery embolectomy is an uncommon experience. A report of such a case is presented and the literature is reviewed. In this clinical setting, guidelines for further diagnostic evaluation are not well defined. We suggest an algorithm for the evaluation and management of these patients. In the near future, use of intraoperative angioscopy and the intravascular laser to eradicate the tumor may represent the optimal method of treatment.

Algorithms↗

Comparison of noninvasive and direct measurements of intracranial pressure.

After creating "fontanelles" in infant rhesus monkeys, we measured intracranial pressure of these monkeys directly with an indwelling cannula and indirectly with a Ladd 1700 sensor. Values obtained with the Ladd sensor placed over the shaven fontanelle closely approximate directly measured pressure in acute experiments in these animals and in human cadavers. Application of the device is simple and application pressure need not always be the same for multiple determinations. The response time is 1.6 cm H2O/sec, which is adequate to record changes in intracranial pressure caused by changes in the partial pressure of CO2 in arterial blood.

Animals↗

Biochemical maturation of the non-innervated chick optic lobe.

The development of the chick optic lobe was impaired following removal of the optic cup of the early embryo. Tectal cell number is reduced but cell size may be relatively normal. Ther was evidence of neuronal cell death and several neuron-associated proteins and enzymes (nerve-specific protein and acetylcholinesterase) showed selectively impaired maturation. However, other nerve-specific enzymes (choline acetyltransferase, tyrosine hydroxylase), develop normally on a per cell basis. The noninnervated optic lobe had a normal blood-brain barrier but a depressed ability to accumulate amino acids from plasma. Levels of 3':5'-cyclic GMP were also reduced in the nonafferented lobe.

Animals↗

Comparative studies on parenteral and intranasal inoculation of an attenuated feline herpes virus.

Using a temperature sensitive mutant of feline herpes virus, comparative studies were carried out regarding efficacy of the intramuscular and the intranasal routes of administration of virus in inducing resistance to feline rhinotracheitis disease. Susceptible adult animals and kittens with and without parental immunity were used. Resistance to disease was measured by serological and challenge methods. Results in terms of rapidity or induced resistance or immunity as well as the degree and duration of immunity are discussed.

Administration, Intranasal↗

Axoplasmic transport of a brain-specific soluble protein.

The rate and extent of axoplasmic transport of the brain-specific soluble protein (14-3-2 protein) has been investigated in the avian visual system. 1-day-old chicks were injected monocularly with tritiated proline, Incorporation of the isotope into the 14-3-2 protein synthesized within the retina of the injected eye, as well as the appearance of the labeled protein in the optic lobes was determined at 6 h and 6 days. These time periods were chosen to distinguish between the rapid and slow phases of axophlasmic flowmfollowing preparation of high-speed supernatant fractions, dialysis, chromatography on Sephadex G-150 and immunoprecipitation with specific antiserum, identification of the labeled 14-3-2 protein was carried out by sodium dodecylsulfate-polyacrylamide gel analysis of the radioactive immunoprecipitates; 6 days after isotope administration, approxo% of the 14-3-2 protein synthesized in the chick retina had been transported to the contralateral optic lobe. By contrast, at 6 h no labeled 14-3-2 protein was detectablemthus, transport of this neuronal protein appears to be relatively slow process with little or no rapid component.

Animals↗

Isolation and characterization of the nervous system-specific protein 14-3-2 from rat brain. Purification, subunit composition, and comparison to the beef brain protein.

A procedure is described for the isolation of the nervous system-specific protein designated 14-3-2 from rat brain. The methods utilized are salt precipitation, DEAE-cellulose ion exchange chromatography, Sephadex G-150 gel filtration, and column isoelectric focusing. The native 14-3-2 protein has an isoelectric point of 4.7 in the absence of denaturing agents and 5.0 in the presence of 2.0 M urea. The protein, as isolated, appears homogeneous since it migrates as a single band on Tris-glycine (pH 8.9), sodium dodecyl sulfate (pH 7.2), and 8 M urea (pH 4.0) polyacrylamide gels. Sedimentation velocity and equilibrium data indicate a homogeneous component of molecular weight 78,000. Sedimentation of 14-3-2 in 6 M guanidine HCl containing 0.02% glutathione yielded a molecular weight of 39,000, indicating the dimeric nature of the protein as isolated. The rat brain protein seems to be composed of one subunit type, since polyacrylamide gel electrophoresis in 8 M urea yields a single protein component. Sodium dodecyl sulfate gel electrophoresis of rat brain 14-3-2 produced one sharp band with a relative mobility corresponding to a molecular weight of 48,000. Specific anti-14-3-2 serum has been prepared from both New Zealand white rabbits and goats. Rat 14-3-2 is very similar in amino acid composition to the beef brain protein and to antigen alpha. The antigenic properties of rat and beef 14-3-2 are also similar, since beef 14-3-2 antiserum reacts well with rat 14-3-2 and vice versa. Electrophoretic mobilities of denatured rat and beef 14-3-2 (0.1% sodium dodecyl sulfate and 8 M urea) are identical. Despite these similarities the two proteins are completely resolved on Tris-glycine gels. The sedimentation behavior of the beef and rat proteins are also different, indicating a difference in the association state and conformation of the two preparations.

Amino Acids↗

Synthesis of a brain-specific protein (S100 protein) in a homologous cell-free system programmed with cerebral polysomal messenger RNA.

Polyribosomes, carrying nascent polypeptide chains, were prepared from whole brain, cortex, and hindbrain-medullary white matter of young adult rats. In a homologous cell-free system, a brain-specific protein (S100 protein) was identified in the mixture of polypeptides released from the polyribosomes during incubation for 1 hr at 37 degrees . De novo synthesis of the S100 protein was achieved in a reconstituted cerebral cell-free system containing polysome-derived mRNA and 40S + 60S subunits. The radioactively labeled S100 protein synthesized in vitro was identified by precipitation with antibody to S100 after addition of purified S100 as a carrier, and migration of the solubilized precipitate on acrylamide gels in the presence of sodium dodecyl sulfate. In vitro synthesis of the S100 protein did not occur in analogous cell-free systems derived from hepatic tissue or in a heterologous system containing liver polyribosomes and cerebral enzymes.

Amino Acids↗