New version of brief depression scale.
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Aged↗
Biomedical subjects
K Moore
Publications and source records attributed to K Moore.
Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo.
Nitric oxide is reportedly involved in the regulation of several ovarian processes, yet the isoforms of nitric oxide synthase (NOS) expressed in the ovary are unknown. Our purpose was to identify and localize NOS isoenzymes in the rat ovary and to examine++ if mRNA expression of NOS isoenzymes change after gonadotropin stimulation. Using reverse transcriptase-PCR, we demonstrated that inducible (iNOS) and endothelial (eNOS), but not neuronal, NOS mRNAs are expressed in the ovary. In a gonadotropin-stimulated rat model, unstimulated ovaries had the highest levels of iNOS mRNA as quantified by ribonuclease protection assay. After gonadotropin injection, iNOS mRNA declined to undetectable levels in ovaries containing ovulatory follicles before increasing slighty in ovaries containing copora lutea. In situ hybridization studies localized iNOS to granulosa cells of secondary follicles and small antral follicles. Western blots of unstimulated ovaries demonstrated iNOS protein. In contrast to iNOS, eNOS mRNA levels, determined by quantitative PCR, increased after gonadotropin stimulation and peaked in ovaries containing ovulatory follicles before declining in the luteal phase. eNOS protein was localized to blood vessels in the ovary by immunohistochemistry. We conclude that two isoforms of NOS are expressed in the ovary and the mRNA levels for these isozymes are differentially regulated.
Animals↗
Breastfeeding outcomes for women with insulin dependent diabetes.
The incidence of breastfeeding among women with insulin dependent diabetes mellitus (IDDM) has received little attention. During a 17-month period, 19 pregnant women with IDDM attending the prenatal clinic of the Royal Women's Hospital (Brisbane) were recruited into a prospective study to compare their breastfeeding outcomes with a control group of 18 women who were not diabetic (non-IDDM). The incidence of breastfeeding was monitored. At discharge, 63 percent of IDDM and 78 percent of non-IDDM mothers were breastfeeding. At eight weeks, the proportion of each were nearly identical (58 percent and 56 percent respectively), and at three months of age, 47 percent of IDDM mothers and 33 percent of non-IDDM women continued to breastfeed. We conclude that women with IDDM breastfeed at least as commonly and for as long as women without diabetes, despite the fact that infants of the IDDM women were artificially fed more often and began breastfeeding later than infants in the control group. In addition, the IDDM women were more likely to be delivered by Caesarean section (p < 0.0005), to be delivered earlier (p < 0.0002), and their babies more likely to be admitted to the special care nursery (p < 0.0005).
Adult↗
The urethral sphincter: an update.
The urethral sphincter is a single mechanism capable of forming a watertight barrier to urinary leakage during bladder filling while changing its shape to serve as an effective conduit for bladder emptying during micturition. By abandoning traditional concepts of the two muscular sphincters, urologic clinicians are better able to assess and manage sphincter dysfunction causing SUI or bladder outlet obstruction.
Female↗
Clinical and immunological effects of treatment with murine anti-CD3 monoclonal antibody along with interleukin 2 in patients with cancer.
Anti-CD3 mAb and interleukin 2 (IL-2) were used in a Phase I study to treat 29 patients with cancer. The anti-CD3 was given as an i.v. bolus infusion over 10 min followed by two i.v. 96-h continuous infusions of IL-2 at 3 x 10(6) units/m2/day with a 3-day rest between the IL-2 infusions. Four patients were treated with 6, 18, 60, and 300 microgram/m2 anti-CD3. One patient received 3000 microgram/m2 anti-CD3. This patient developed profound hypotension and the IL-2 infusions were delayed for 2 weeks. Two patients were treated at an intermediate dose of 600 microgram/m2. These patients developed dose-limiting toxicities including hypotension, dyspnea and increased blood urea nitrogen, creatinine, and bilirubin. They were unable to complete their first course of therapy. In an effort to achieve a dose of anti-CD3 which would activate T cells in vivo, pentoxifylline was given to blunt the toxicities seen with anti-CD3 thought to be due predominantly to the cytokine syndrome and tumor necrosis factor release. Four patients received p.o. pentoxifylline to cover an anti-CD3 dose of 600 microgram/m2. The IL-2 infusion was initiated 1 week after the mAb. While there was an anti-CD3 dose-dependent increase in serum tumor necrosis factor level 1 h after mAb infusion, pentoxifylline did not reduce the serum tumor necrosis factor level. There was also an anti-CD3 dose-dependent increase in the serum soluble IL-2 receptor levels. Other immune parameters monitored, including in vitro cytotoxic and proliferative responses and lymphocyte count, were similar to treatment courses with IL-2 alone. Fourteen of 26 patients examined developed human anti-murine antibodies following a single dose of anti-CD3. There were no objective antitumor responses. We conclude that in vivo treatment with anti-CD3 did not enhance T cell activity or expansion with subsequent IL-2 infusion and that the combination of anti-CD3 followed by IL-2 did not improve upon the antitumor activity previously seen with IL-2 alone.
Antibody-Dependent Cell Cytotoxicity↗
Increased sensitivity of diagnostic latex agglutination tests in an ultrasonic standing wave field.
A technique is described which increases the sensitivity of latex agglutination tests for soluble and particulate antigens. The levels of detection of tests for C-reactive protein and E. coli O157 respectively have been improved by x256 and x1024 compared with the standard test procedure of sample rotation on a test-card. This new method combines dilution of the test latex particles, a 2 min sample treatment in the ultrasonic standing wave field of a tubular piezo-electric transducer and subsequent examination by video-microscopy. Ultrasonic treatment is required to achieve increased localised concentrations of the latex particles in the standing wave field, and dilution of the latex is a critical requirement to allow agglutination to occur at low antigen concentrations.
Antigens, Bacterial↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Stroke: the first critical days.
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Cerebrovascular Circulation↗
Stroke: the long road back.
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Activities of Daily Living↗
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↗
Illustrations from the Wellcome Institute Library. Some recently acquired papers of Robert Whytt (1714-1766), FRS.
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History, 18th Century↗