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Biomedical subjects

M Edwards

Publications and source records attributed to M Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1990

On the mechanism by which midazolam causes spinally mediated analgesia.

The electrical current thresholds for pain (ECTP) in the skin of the neck and tail were measured in rats with chronically implanted lumbar subarachnoid catheters. The effects of a benzodiazepine antagonist and a gamma-aminobutyric acid (GABA) antagonist on the analgesic effects of equivalent doses of midazolam, fentanyl, and ketocyclazocine were studied. These were the minimum doses producing maximal segmental analgesia when given intrathecally (i.e., they all caused a significant and maximum increase in ECTP in the tail, which was similar for all three drugs, but no significant change in the ECTP in the neck). Flumazenil (Ro 15-1788) administration caused a parallel shift to the right of the dose-response curve for midazolam spinal analgesia. Segmental analgesia following midazolam was also significantly attenuated (P less than 0.05) when the selective GABA antagonist bicuculline was given intrathecally at the same time as midazolam. The highest dose of bicuculline used (50 pmol) caused no significant attenuation of the segmental analgesic effects of either ketocyclazocine or fentanyl. The authors concluded that the segmental analgesia produced by intrathecal midazolam is mediated by the benzodiazepine-GABA receptor complex that is involved in other benzodiazepine actions.

Analgesia, Epidural↗
PubMed1990

Expression of the human carbonic anhydrase I gene is activated late in fetal erythroid development and regulated by stage-specific trans-acting factors.

Using flow cytometric analysis of red cells from different stages of ontogeny with anti-CAI antibody, it was shown that the human carbonic anhydrase I (HCAI) gene product appears in a developmental stage-specific manner. Virtually no CAI protein was detectable in fetal red cells prior to birth. However, at about the time of normal delivery (40 weeks gestation) CAI production is switched on. The proportion of cells containing CAI reaches adult levels during the second half of the first year of life. Northern analysis suggests that the appearance of CAI protein results directly from the activation of the gene and the production of new mRNA. A transient heterokaryon system was set up by fusing the erythroleukaemic cell lines MEL C88 (a mouse cell line in which CAI is expressed) and K562 SAI (a human cell line with an embryonic/fetal phenotype, not expressing CAI). SP6 RNAase mapping of RNA from the fused cells showed activation of the human CAI gene. This shows the developmental stage-specific expression of HCAI to be regulated by trans-acting factors.

Adult↗
PubMed1989

Multiple GF-1 binding sites flank the erythroid specific transcription unit of the human carbonic anhydrase I gene.

Six potential GF-1 sites which bind an erythroid factor are present in the 5' and 3' regions flanking the erythroid-specific transcription unit of the human carbonic anhydrase I (HCAI) gene. When two of these sites are placed upstream of a minimal eukaryotic promoter they confer up-regulated expression in erythroid over non-erythroid cells. The presence of the erythroid factor in TPA-treated HEL cells in which the level of HCAI transcript has greatly decreased and in non-HCAI-expressing K562 cells suggests that in these cases the presence of the factor is not sufficient for HCAI expression.

Base Sequence↗
PubMed1989

Crystallization and preliminary X-ray studies of an aspartate aminotransferase mutant from Escherichia coli.

Mutant aspartate aminotransferase V39L (Val39 replaced by Leu) from Escherichia coli has been crystallized into a monoclinic cell from a polyethylene glycol solution (pH 7.5) by vapor diffusion. The space group and the unit cell dimensions have been determined using a precession camera, a CAD4 diffractometer and a Nicolet Xentronics area detector to be P2(1) with a = 86.8 A, b = 79.9 A, c = 89.4 A, beta = 118.74 degrees. The crystals diffract to better than 2.3 A and are suitable for X-ray structure analysis.

Aspartate Aminotransferases↗
PubMed1989

Transformation of murine melanocytes by basic fibroblast growth factor cDNA and oncogenes and selective suppression of the transformed phenotype in a reconstituted cutaneous environment.

Constitutive expression of basic fibroblast growth factor (bFGF), a common characteristic of metastatic melanomas, was reproduced in vitro by infection of normal murine melanocytes with a recombinant retrovirus carrying a cDNA for bFGF. Expression of bFGF in these cells conferred autonomous growth in culture and extinguished differentiated functions, such as the synthesis of melanin and formation of dendrites. Independence from exogenous bFGF and loss of differentiated functions in vitro were induced also by transformation of melanocytes with the oncogenes myc, Ela, ras, and neu, although bFGF was not expressed by the respective transformants. As shown in skin reconstitution experiments onto syngeneic mice and subcutaneous injections into nude mice, the various transformants differed in their behavior in vivo. The bFGF transformants did not form tumors. They reverted to having a normal, melanotic phenotype and restricted growth. Myc and Ela transformants grew as tumors in nude mice but not in syngeneic, immunocompetent animals. Ras-transformed melanocytes were always tumorigenic, whereas the formation of tumors by neu transformants was suppressed by the concomitant grafting of keratinocytes in reconstituted skin of syngeneic mice. These data show that melanocytes genetically manipulated to produce bFGF acquire properties in vitro similar to those of metastatic melanoma cells or those induced by various oncogenes but that constitutive production of bFGF by itself is insufficient to make melanocytes tumorigenic. The experiments also show that melanocytes transformed by the selected oncogenes respond differentially to various environments in vivo.

Animals↗
PubMed1989

Oculogyric crisis after metoclopramide therapy.

Oculogyric crisis developed in a 21-year-old girl after 5 oral doses of 10 mg of metoclopramide. The symptoms were relieved by i.v. administration of diphenhydramine hydrochloride. Although ocular side effects of metoclopramide are rare, it can induce an alarming oculogyric crisis in some sensitive subjects. The mechanism of oculogyric crises is unclear but the characteristics of the condition and some known causes are discussed. Advice is given on optometric management.

Adult↗
PubMed1989

Neurofibromatosis types 1 and 2: cranial MR findings.

Neurofibromatosis 1 (NF-1) (von Rekhlinghausen disease) and neurofibromatosis 2 (NF-2) (bilateral acoustic neurofibromatosis) have been recently recognized to be distinct disorders through genetic linkages. The authors compared the cranial magnetic resonance (MR) images of 53 patients with NF-1 and 11 with NF-2. In the NF-1 group, MR imaging revealed 19 patients with optic gliomas and eight with parenchymal gliomas. In 32 patients, foci of prolonged T2, similar to those reported previously as hamartomas, were identified in the cerebellar peduncles, globus pallidus, midbrain, and other locations. The frequency of these foci was related to both age and the presence of optic gliomas. In the NF-2 group, MR imaging revealed eight patients with cranial nerve schwannomas and six with meningiomas (in addition to acoustic schwannomas in all 11). These findings demonstrate that NF-1 and NF-2 are different diseases requiring different imaging protocols. NF-1 seems to be associated with tumors of astrocytes and neurons and NF-2 with tumors of meninges and Schwann cells.

Adolescent↗
PubMed1989

MR imaging in the tethered spinal cord syndrome.

MR examinations of the spine were reviewed in 25 patients with a clinical diagnosis of tethered spinal cord. In 21 patients (84%), the level of the tip of the conus was below the mid L2 vertebral body. The causes of the tethering were spinal lipomas (72%), tight filum terminale syndrome (12%), diastematomyelia (8%), and myelomeningocele (8%). These entities were readily identified in all instances. Bony dysraphisms were well demonstrated by MR. Interestingly, cavitary lesions/myelomalacia of the conus or the cord adjacent to the tethering lesion were seen with appropriate images in nine of 20 patients. This unexpected finding may have diagnostic and/or prognostic significance. Spinal MR was found to be extremely useful in the evaluation of the suspected tethered spinal cord. It was able to visualize the conus medullaris, assess the thickness of the filum terminale, identify traction lesions, and evaluate associated bony dysraphisms.

Adolescent↗
PubMed1989

Transvaginal sonography in the evaluation of normal early pregnancy: correlation with HCG level.

Transvaginal sonography (TVS) is the procedure of choice in evaluating the viability of embryos early in pregnancy. However, viability based on TVS can be assessed more accurately when the exact gestational age from the last menstrual period is known or when the findings are correlated with beta human chorionic gonadotropin (HCG) levels. No large series has been reported with correlative data between early pregnancy findings, HCG, and gestational age. We performed 75 transvaginal examinations in 53 patients with proved normal pregnancy in the fifth through seventh weeks of gestation. The presence and size of the gestational sac, presence of a yolk sac, and identification of embryonic heart activity were correlated with the level of HCG. Sac size was correlated with yolk sac and heart activity and the three parameters correlated with gestational age in days. When the level of HCG reached 1000 mIU/ml by using the first International Reference Preparation, a gestational sac was seen sonographically in each patient. When the HCG level reached 7200 mIU/ml, a yolk sac was seen in every patient. Ten of 22 patients with HCG between 1000 and 7200 mIU/ml had a visible yolk sac. Every patient with an HCG level greater than 10,800 mIU/ml had a visible embryo with a heartbeat. A discriminatory level of 32 days was found for the presence of a gestational sac. A yolk sac was first seen in every patient between 36 and 40 days. Every patient with accurate dates greater than 40 days had an embryo with a heartbeat identified. When correlating sac size with structures within the sac, a yolk sac was first seen in a gestational sac between 6 and 9 mm and a heartbeat seen in every patient with a 9-mm or greater gestational sac diameter. These data allow identification of normal intrauterine pregnancy and distinction of normal from ectopic gestation at least 1 week earlier than is possible with transabdominal techniques.

Chorionic Gonadotropin↗
PubMed1988

o-(beta-Hydroxyethyl)-rutoside-mediated protection of renal injury associated with cis-diamminedichloroplatinum(II)/hyperthermia treatment.

A bioflavonoid, o-(beta-hydroxyethyl)-rutoside, has been investigated for its potential to increase the therapeutic index of the combined treatment modalities of whole body hypothermia (WBH) (41.5 degrees C) and chemotherapy (cisplatin) in studies utilizing a transplantable fibrosarcoma solid tumor model in Fischer rats. When whole body WBH was induced 45 min after cisplatin administration, a significantly increased tumor growth delay was noted beyond that achieved by either treatment modality alone. The combination of WBH and cisplatin treatments, however, produced an unacceptable increase in renal injury. o-(beta-Hydroxyethyl)-rutoside administration was found to effectively block the renal injury without interfering with the antitumor efficacy of the combined regimen. Potential explanations for the ability of o-(beta-hydroxyethyl)-rutoside to affect the increase in WBH-cisplatin therapeutic regimen are discussed.

Animals↗
PubMed1988

A beta-D-galactosidase from nasturtium (Tropaeolum majus L.) cotyledons. Purification, properties, and demonstration that xyloglucan is the natural substrate.

beta-D-Galactosidase activity has been detected previously in the cotyledons of germinated nasturtium (Tropaeolum majus L.) seeds and has been linked to the hydrolysis in vivo of storage xyloglucan (amyloid) (Edwards, M., Dea, I. C. M., Bulpin, P. V., and Reid, J. S. G. (1985) Planta (Berl.) 163, 133-140). The major beta-D-galactosidase present in extracts from the cotyledons of 9-day seedlings has now been purified to apparent homogeneity. The enzyme (Mr 97,000, no subunits) comprised a range of closely related molecular species ranging in isoelectric point from pH 6.6 to 7.1. Further purification to give a single protein band on isoelectric focusing (pI = 7.1) was achieved by chromatofocusing. The pH optimum of the enzyme (mixed molecular species) was 4.0-5.0 (stable from pH 3-10), and the temperature optimum was 50 degrees C (stable to 50 degrees C). It hydrolyzed lactose and beta-D-galactopyranosides but not melibiose and alpha-D-galactopyranosides. It did not release the terminal nonreducing alpha-D-galactopyranosyl residues from seed galactomannans, but catalyzed the rapid removal of terminal nonreducing beta-D-galactopyranosyl residues from xyloglucans. On the basis of the ability of the enzyme to hydrolyze xyloglucans, the kinetics of xyloglucan hydrolysis, and an experimental demonstration of a clear correlation between xyloglucan depletion and the activity in vitro of this enzyme, it is argued that the cell-wall storage xyloglucan of the nasturtium seed is its natural substrate.

Galactosidases↗
PubMed1988

X-linked recessive inheritance of an orofaciodigital syndrome with partial expression in females and survival of affected males.

We describe a family with clinical features of orofaciodigital (OFD) syndrome type 2 or Mohr syndrome, X-linked recessive inheritance and survival of affected males which has not previously been reported. Four affected males in three generations have survived into infancy and two female heterozygotes have very mild expression. Foetal ultrasonography enabled antenatal diagnosis.

Abnormalities, Multiple↗
PubMed1988

Three-year follow-up of risk factors correlated with new atherothrombotic brain infarction in 708 elderly patients.

A prospective study correlated cigarette smoking, systolic or diastolic hypertension, diabetes mellitus, hypercholesterolemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and obesity with development of new atherothrombotic brain infarction in 192 elderly men and 516 elderly women. Mean follow-up was 36 +/- 6 months (range 19-39). New atherothrombotic brain infarction occurred in 24 of 192 men (13%) and in 63 of 516 women (12%), difference not significant. Risk factors for atherothrombotic brain infarction in elderly men were cigarette smoking (p less than 0.001), systolic or diastolic hypertension (p less than 0.001), and diabetes mellitus (p less than 0.005). Risk factors for atherothrombotic brain infarction in elderly women were systolic or diastolic hypertension (p less than 0.001), diabetes mellitus (p less than 0.001), and obesity (p less than 0.005).

Aged↗
PubMed1987

Cerebral infarction with a single oral dose of phenylpropanolamine.

Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.

Administration, Oral↗