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Biomedical subjects

K Moore

Publications and source records attributed to K Moore.

At least 163 records · Page 9Linked to original sources
PubMed1994

A lag in intracellular degradation of mutant alpha 1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha 1-antitrypsin deficiency.

Liver injury in PiZZ alpha 1-antitrypsin (alpha 1-AT) deficiency probably results from toxic effects of the abnormal alpha 1-AT molecule accumulating within the ER of liver cells. However, only 12-15% of individuals with this same genotype develops liver disease. Therefore, we predicted that other genetic traits that determine the net intracellular accumulation of the mutant alpha 1-AT molecule would also determine susceptibility to liver disease. To address this prediction, we transduced skin fibroblasts from PiZZ individuals with liver disease or without liver disease with amphotropic recombinant retroviral particles designed for constitutive expression of the mutant alpha 1-AT Z gene. Human skin fibroblasts do not express the endogenous alpha 1-AT gene but presumably express other genes involved in postsynthetic processing of secretory proteins. The results show that expression of human alpha 1-AT gene was conferred on each fibroblast cell line. Compared to the same cell line transduced with the wild-type alpha 1-AT M gene, there was selective intracellular accumulation of the mutant alpha 1-AT Z protein in each case. However, there was a marked delay in degradation of the mutant alpha 1-AT Z protein after it accumulated in the fibroblasts from ZZ individuals with liver disease ("susceptible hosts") as compared to those without liver disease ("protected hosts"). Appropriate disease controls showed that the lag in degradation in susceptible hosts is specific for the combination of PiZZ phenotype and liver disease. Biochemical characteristics of alpha 1-AT Z degradation in the protected hosts were found to be similar to those of a common ER degradation pathway previously described in model experimental cell systems for T-cell receptor alpha subunits and asialoglycoprotein receptor subunits, therefore, raising the possibility that the lag in degradation in the susceptible host is a defect in this common ER degradation pathway. Thus, these data provide evidence that other genetic traits that affect the fate of the abnormal alpha 1-AT Z molecule, at least in part, determine susceptibility to liver disease. These data also validate a system for elucidating the biochemical/genetic characteristics of these traits and for examining the relevance to human disease of pathways for protein degradation in the ER.

Amino Acid Sequence↗
PubMed1994

Cholecystokinin inhibits gastric emptying and contracts the pyloric sphincter in rats by interacting with low affinity CCK receptor sites.

The aim of these experiments was to characterize the receptor affinity state through which CCK produces pyloric contraction and inhibits gastric emptying in the rat using the novel CCK heptapeptide analog CCK-JMV-180. CCK-JMV-180 has been demonstrated to act as a functional agonist at high affinity pancreatic CCKA receptors but as a functional antagonist at CCKA low affinity receptors. CCK-8 (1, 3.2 and 10 nM) induced dose dependent tension increases in isolated pyloric segments. CCK-JMV-180 (3.2 microM) or vehicle failed to mimic this action when administered alone but blocked the ability of CCK-8 (3.2 nM) to induce tension increases. CCK-8 (2 micrograms/kg) also inhibited the gastric emptying of physiological saline. CCK-JMV-180 (320 and 1000 micrograms/kg) failed to inhibit emptying when administered alone but dose dependently antagonized CCK induced inhibition of gastric emptying. Thus, in both preparations CCK-JMV-180 acted as a functional CCK antagonist. This profile is consistent with the interpretation that the actions of CCK in pyloric contraction and the inhibition of gastric emptying are mediated through CCK's interactions with receptors functionally similar to pancreatic low affinity sites.

Animals↗
PubMed1994

Long-term changes in urodynamic studies of voiding in the elderly.

Urodynamic studies were conducted in 80 incontinent elderly patients (27 men and 53 women; mean age, 77 years) and repeated 2-4 weeks later after patients had been subject to interventions. Interpretable voiding studies were performed in 84% of sessions. Interpretable initial and repeat studies were performed in 74% of patients. For detrusor pressure at maximum flow the intra-individual, between-sessions variability was +/- 11.7 cm H2O (SD) and the initial-repeat correlation coefficient was 0.61. For maximum flow rate the corresponding figures were +/- 4.7 ml/s and 0.44. Mean residual urine volume was 195 ml, with a between-sessions variability of +/- 113 ml (SD). These results suggest that there is substantial long-term variability in voiding function, including urethral resistance. Of the mean, 5% showed a change in obstruction classification (unobstructed/obstructed) between sessions. This variability and the modest proportion of interpretable studies should be taken into account when assessing urethral obstruction and designing clinical trials.

Aged↗
PubMed1994

Cerebral aetiology of urinary urge incontinence in elderly people.

We have examined 73 elderly incontinent patients (mean age 79 years) and 27 continent subjects (mean age 78 years) of similar cognitive status. Among the incontinent patients, 20 were shown objectively to have urge incontinence with normal bladder filling sensation, 14 had objectively demonstrated urge incontinence with reduced bladder sensation, and 39 had other types of incontinence. We compared cognitive function (by Mini-mental State Examination: MMSE) and regional brain perfusion (by SPECT scanning) in these four groups. Patients with objectively demonstrated urge incontinence and reduced bladder sensation stood out as being different from the rest: their mean MMSE score was significantly lower than that of any of the other three groups; perfusion of the frontal cortex was significantly poorer than that in the continent and other incontinent groups; global cortical perfusion was significantly poorer than in the other incontinence groups. This was not found in patients with urge incontinence and normal bladder sensation. The observations support the hypothesis that in elderly people urge incontinence with reduced bladder sensation can be a consequence of cortical neuropathy, especially in the frontal lobes.

Aged↗
PubMed1994

Induction of nitric oxide synthase in cultured vascular smooth muscle cells: the role of cyclic AMP.

1. Interleukin-1 beta (IL-1 beta) is a potent stimulant of inducible nitric oxide synthase (iNOS) mRNA and nitric oxide (NO) production in vascular smooth muscle (VSM) cells in culture. These studies investigate the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in this process. 2. Dibutyryl cyclic AMP (db cyclic AMP, 0.1-1 mM), forskolin (1-10 microM) and the phosphodiesterase inhibitor, Ro 20-1724 (1-10 microM), all of which increase intracellular cyclic AMP, had no effect on NO production when added alone but markedly enhanced NO production by IL-1 beta-stimulated VSM cells in a dose-dependent manner. Consistent with a cyclic AMP-mediated action, isoprenaline (1-10 microM) increased NO production from IL-1 beta-stimulated cells. Dibutyryl cyclic GMP (db cyclic GMP) had no effect at concentrations up to 1 mM. 3. Pursuing these observations, iNOS protein levels were examined by Western blot analysis and iNOS mRNA levels were measured by reverse transcription and amplification of the resultant cDNA using the polymerase chain reaction. In addition to enhancing NO production, db cyclic AMP increased iNOS protein and mRNA above that produced by IL-1 beta alone. 4. These data demonstrate a major effect of cyclic AMP on cytokine-induced NOS activity in VSM cells, mediated at least in part by regulating synthesis of iNOS, and has implications for the pathogenesis and management of septic shock.

Amino Acid Oxidoreductases↗
PubMed1994

Crystallization of the EGF receptor ectodomain on US space mission STS-47.

Although biochemists working in the field of biological signal transduction have characterized cell surface receptors for numerous growth factors within the past ten years, none of the three-dimensional structures could be obtained for these important proteins which represent major components of the cells' growth control system. Now, the extracellular ligand binding domain of the EGF receptor was crystallized in the presence of EGF under microgravity on US Shuttle mission STS-47. In 8 out of 9 experiments prepared under different conditions crystal growth was observed. One of these space-grown crystals showed higher diffraction quality than all crystals previously obtained in the laboratory. It allowed, for the first time, evaluation of the real space group by partial data collection.

Crystallization↗
PubMed1994

Protein crystal growth in microgravity-temperature induced large scale crystallization of insulin.

One of the major stumbling blocks that prevents rapid structure determination using x-ray crystallography is macromolecular crystal growth. There are many examples where crystallization takes longer than structure determination. In some cases, it is impossible to grow useful crystals on earth. Recent experiments conducted in conjunction with NASA on various Space Shuttle missions have demonstrated that protein crystals often grow larger and display better internal molecular order than their earth-grown counterparts. This paper reports results from three Shuttle flights using the Protein Crystallization Facility (PCF). The PCF hardware produced large, high-quality insulin crystals by using a temperature change as the sole means to affect protein solubility and thus, crystallization. The facility consists of cylinders/containers with volumes of 500, 200, 100, and 50 ml. Data from the three Shuttle flights demonstrated that larger, higher resolution crystals (as evidenced by x-ray diffraction data) were obtained from the microgravity experiments when compared to earth-grown crystals.

Animals↗
PubMed1994

Development of a user-defined surgical database using a personal computer network.

Advances in personal computer technology have made powerful methods for the collection and analysis of patient information available to clinical users. This report details the development of a multi-user database distributed across a network of personal computers that facilitates operative scheduling, and collection and analysis of operative data. Clinicians from each surgical service in our medical center developed customized data entry programs that contribute information centrally through a telephone-line network to prepare the daily operative schedule. Subsequently, information from the operating rooms is added to the preoperative database to form an operative log, which is distributed to client services for further analysis and modification. This system has improved the efficiency and accuracy of operative scheduling and information management and shifted the burden of data collection away from the physician. Widespread availability of these data has contributed to the development of an effective quality improvement program and facilitated effective management of personnel and resources.

Computer Communication Networks↗
PubMed1993

Expression of the human neuropeptide tyrosine Y1 receptor.

Neuropeptide tyrosine (NPY) is the predominant peptide in the innervation of many human tissues and is considered to play a role in the regulation of blood flow, gastrointestinal secretion and motility, and renal function. Three NPY receptors have been identified (Y1, Y2, and Y3) and the cDNAs encoding the human Y1 and bovine Y3 receptors have recently been cloned. We have demonstrated the expression of the Y1 receptor subtype in several fetal and adult human tissues, including the colon, kidney, adrenal gland, heart, and placenta. A single transcript was identified (approximately 2.2 kb) and localized in tissue sections by in situ hybridization. In the colon the receptor is expressed in the mucosa and basal glands, as well as the myenteric and submucous plexuses. Y1 receptor mRNA was detected in renal collecting ducts, loop of Henle, and juxtaglomerular apparatus and in the syncytiotrophoblast layer of placental villi. Fetal aorta and adult intramyocardial, colonic, and renal blood vessels also exhibited receptor expression, localized to the intima as well as the media. The distribution of Y1 receptor expression correlates with that of NPY-immunoreactive nerves and the apparent actions of NPY in the intestine, kidney, and heart. Although the placenta is devoid of nerves, an NPY-like transcript was detected in the villous trophoblast layer. The results indicate a tissue-specific regulation of NPY Y1 receptor expression.

Adult↗
PubMed1993

Glycine and alanine supplementation of culture medium enhances development of in vitro matured and fertilized cattle embryos.

One-cell cattle embryos were prepared by in vitro oocyte maturation and fertilization (IVM/IVF) and cultured with or without oviductal cells. Embryos were evaluated after 7 days in culture to determine the percentage developing from the 1-cell stage to the morula or blastocyst stage. The combination of glycine (2 mM) and alanine (1 mM) with oviductal cells (experiment 1) improved embryo development over that in control culture (29 vs. 13%; p < 0.05). An optimum response was obtained with 10 mM glycine and 1 mM alanine in coculture (experiments 2 and 3). In experiment 4, the effects of glycine (0 or 10 mM), alanine (0 or 1 mM), and the presence or absence of oviductal cells were tested. In the absence of oviductal cells, the addition of glycine, alanine, or glycine and alanine combined improved embryonic development over that in control medium (45, 33, 42 vs. 24%, p < 0.001, p < 0.05, p < 0.001, respectively). However, the effect of the combination of glycine and alanine was not different from that of glycine alone when oviductal cells were absent (42 vs. 45%, p > 0.10). In the presence of oviductal cells, glycine or the combination of glycine and alanine improved embryonic development over that in the control medium with cells (47, 55 vs 37%, p < 0.01, respectively). However, supplementation with alanine alone gave no improvement over controls when oviductal cells were present (40 vs. 37%, p > 0.10). These results indicate that glycine and alanine, when used independently, directly affect cattle embryo development, but in combination affect embryo development indirectly, possibly by altering oviductal cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1993

Critical care unit design: a collaborative approach.

Determining a critical care unit design can be a complex and sometimes overwhelming task. Even so, through group participation the project can be an opportunity for developing collaborative relationships and having fun as well. Collaborative decision making can prevent unnecessary duplication, promote greater staff satisfaction, and improve overall cost containment. The article describes the collaborative approach used at Elizabeth Community Health Center in Lincoln, Nebraska to plan the design of the critical care unit, staff orientation, the open house, and the move process.

Decision Making, Organizational↗
PubMed1993

Bacterial ventriculitis and duration of ventriculostomy catheter insertion.

Invasive monitoring of intracranial pressure (ICP) plays an important role in managing many neurosurgical patients. While there are several techniques available to monitor ICP, the ventricular catheter is most commonly used and the most accurate. ICP monitoring poses potential risks to the patient. The most common and one of the most devastating complications is infection. This research study examined the rate of bacterial ventriculitis in relation to duration of ventricular catheter insertion as well as other factors which may contribute to ventriculitis. Data were collected prospectively on 78 patients with a ventriculostomy who were 14 years of age or older and admitted to the neuroscience intensive care unit. Patients were followed from the time of ventricular catheter placement to two weeks after the catheter was removed or until the patient was discharged from the hospital. A significantly higher ventriculitis rate was found in patients with a mean catheter duration of 11 days or longer (p = .004). In the group that developed ventriculitis there was a significant rise (means = 6.03592, p = .014) in the cerebrospinal fluid (CSF) lactate prior to the onset of ventriculitis. Neuroscience nurses should be aware of the factors which may increase the rate of ventriculitis, such as duration of catheter placement and factors which may indicate impending infection such as a rise in the CSF lactate. Future studies should compare various methods of ventriculostomy site care for efficacy of infection prevention, cost and caregiver time.

Adolescent↗
PubMed1993

A multicentre double blind trial of fluoxetine versus amitriptyline in the treatment of depressive illness.

The antidepressant efficacy and side effect profile of a fixed dose of 20 mg/day of fluoxetine, a specific serotonin reuptake inhibitor, were compared to those of amitriptyline. Fifty-eight patients with DSM-III-R depression were randomly assigned to receive either fluoxetine or amitriptyline. Fifty-six patients (fluoxetine N = 23, amitriptyline N = 23) completed the 6 week study. Comparable antidepressant efficacy was demonstrated for the two drugs. Patients taking fluoxetine reported less side-effects than those taking amitriptyline.

Adult↗