PubMed Health⌕ Search

Biomedical subjects

M Mitchell

Publications and source records attributed to M Mitchell.

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

Physical mapping of deletion breakpoints in patients with X-linked ichthyosis: evidence for clustering of distal and proximal breakpoints.

Previous studies have shown that approximately 80% of patients with X-linked ichthyosis have a total deletion of the steroid sulphatase (STS) locus which lies in Xp22.3-Xpter. We show by Southern analysis that a common core of sequences are absent in 78.6% of our cases, suggesting that the deletion breakpoints may be highly clustered. To characterize the region in more detail a long-range physical map of over 3 megabases (Mb) surrounding the STS locus was constructed using pulse-field gel electrophoresis. The map enabled the order of sequences tel-SI19-GMGXY3-[STS,GMGXY19]-GMGX9-[dic56 ,SIII2]-cen and the localization of the deletion breakpoints to be established. In ten cases the pulse-field evidence supports the clustering of breakpoints and indicates a deletion size of 2 Mb in most patients. Five CpG islands have been positioned around the STS locus and may be associated with other loci in the region involved in mental retardation and Kallman's syndrome. The map will be instrumental in an attempt to isolate and characterize the deletion breakpoints and to access other genes located in the region.

Arylsulfatases↗
PubMed1990

Mannostatin A, a new glycoprotein-processing inhibitor.

Mannostatin A is a metabolite produced by the microorganism Streptoverticillium verticillus and reported to be a potent competitive inhibitor of rat epididymal alpha-mannosidase. When tested against a number of other arylglycosidases, mannostatin A was inactive toward alpha- and beta-glucosidase and galactosidase as well as beta-mannosidase, but it was a potent inhibitor of jack bean, mung bean, and rat liver lysosomal alpha-mannosidases, with estimated IC50's of 70 nM, 450 nM, and 160 nM, respectively. The type of inhibition was competitive in nature. This compound also proved to be an effective competitive inhibitor of the glycoprotein-processing enzyme mannosidase II (IC50 of about 10-15 nM with p-nitrophenyl alpha-D-mannopyranoside as substrate, and about 90 nM with [3H]mannose-labeled GlcNAc-Man5GlcNAc as substrate). However, it was virtually inactive toward mannosidase I. The N-acetylated derivative of mannostatin A had no inhibitory activity. In cell culture studies, mannostatin A also proved to be a potent inhibitor of glycoprotein processing. Thus, in influenza virus infected Madin Darby canine kidney (MDCK) cells, mannostatin A blocked the normal formation of complex types of oligosaccharides on the viral glycoproteins and caused the accumulation of hybrid types of oligosaccharides. This observation is in keeping with other data which indicate that the site of action of mannostatin A is mannosidase II. Thus, mannostatin A represents the first nonalkaloidal processing inhibitor and adds to the growing list of chemical structures that can have important biological activity.

Animals↗
PubMed1990

Kifunensine, a potent inhibitor of the glycoprotein processing mannosidase I.

Kifunensine, produced by the actinomycete Kitasatosporia kifunense 9482, is an alkaloid that corresponds to a cyclic oxamide derivative of 1-amino mannojirimycin. This compound was reported to be a weak inhibitor of jack bean alpha-mannosidase (IC50 of 1.2 x 10(-4) M) (Kayakiri, H., Takese, S., Shibata, T., Okamoto, M., Terano, H., Hashimoto, M., Tada, T., and Koda, S. (1989) J. Org. Chem. 54, 4015-4016). We also found that kifunensine was a poor inhibitor of jack bean and mung bean aryl-alpha-mannosidases, but it was a very potent inhibitor of the plant glycoprotein processing enzyme, mannosidase I (IC50 of 2-5 x 10(-8) M), when [3H]mannose-labeled Man9GlcNAc was used as substrate. However, kifunensine was inactive toward the plant mannosidase II. Studies with rat liver microsomes also indicated that kifunensine inhibited the Golgi mannosidase I, but probably does not inhibit the endoplasmic reticulum mannosidase. Kifunensine was tested in cell culture by examining its ability to inhibit processing of the influenza viral glycoproteins in Madin-Darby canine kidney cells. Thus, when kifunensine was placed in the incubation medium at concentrations of 1 microgram/ml or higher, it caused a complete shift in the structure of the N-linked oligosaccharides from complex chains to Man9(GlcNAc)2 structures, in keeping with its inhibition of mannosidase I. On the other hand, even at 50 micrograms/ml, deoxymannojirimyucin did not prevent the formation of all complex chains. Thus kifunensine appears to be one of the most effective glycoprotein processing inhibitors observed thus far, and knowledge of its structure may lead to the development of potent inhibitors for other processing enzymes.

1-Deoxynojirimycin↗
PubMed1990

Improved carrier detection of haemophilia A using novel RFLPs at the DXS115 (767) locus.

Two novel restriction fragment length polymorphisms (RFLPs) around the DXS115 (767) locus, detectable with the restriction enzymes MspI, are described. Since DXS115 is closely linked to the factor VIII gene (F8C), the MspI RFLP was employed in haemophilia A carrier detection. The utility of these RFLPs lies in the increased applicability and accuracy of diagnoses carried out in cases where available intragenic markers are uninformative.

Deoxyribonuclease HpaII↗
PubMed1990

Detection of restricted predominant epitopes of Theiler's murine encephalomyelitis virus capsid proteins expressed in the lambda gt11 system: differential patterns of antibody reactivity among different mouse strains.

Intracerebral injection of mice with Theiler's murine encephalomyelitis virus results in chronic demyelination in susceptible strains, and serves as a model system for the study of multiple sclerosis. The role of individual epitopes in the disease process remains to be elucidated. Random fragments of DNA from the viral capsid protein genome covering the coding regions from VP1, VP2, and VP3 have been expressed in the lambda gt11 vector system. Fusion proteins from the clones were expressed and probed with antibodies from both resistant and susceptible strains of mice. Each strain displays a distinctive pattern with certain fusion proteins recognized by all of the strains and others recognized uniquely by either the susceptible or the resistant strains.

Animals↗
PubMed1990

A comparison of two doses of nizatidine versus placebo in the treatment of reflux oesophagitis.

Three-hundred and twenty-five patients with endoscopically verified oesophagitis entered a double-blind, randomized multicentre study that compared 300 mg nizatidine b.d., 300 mg nocte and placebo. The 6- and 12-week treatment responses were studied. Healing was defined as complete epithelialization of all oesophageal lesions. The healing rates were 40% in the 300 mg nizatidine b.d. group, 30% in the 300 mg nocte group and 26% in the placebo group at 6 weeks. The corresponding figures after 12 weeks of treatment were 50%, 44% and 34%, respectively. The healing rates were significantly different (P less than 0.05) between the high-dose nizatidine group and placebo only, both at 6 and 12 weeks. Despite a trend at both 6 and 12 weeks in favour of 300 mg nizatidine nocte compared to placebo, this was not significantly different. The most important factor for the outcome, apart from the treatment group, was the pre-entry severity of oesophagitis. The differences observed between treatment groups in healing rates, symptomatic relief, and antacid consumption appear to result mainly from the patients with moderate and severe oesophagitis upon entry. Nizatidine (300 mg) b.d. appeared to be safe and effective in the treatment of reflux oesophagitis.

Adult↗
PubMed1990

Remoxipride and haloperidol in the acute phase of schizophrenia: a double-blind comparison.

The efficacy and safety of remoxipride in the treatment of schizophrenia were compared with those of haloperidol in a multicentre double-blind 6-week study which was randomized with a parallel group design and was preceded by a washout period. Eighty-nine consecutively admitted men and women meeting the Research Diagnostic Criteria for schizophrenia in an acute phase of the illness were treated with remoxipride 75-300 mg twice daily or haloperidol 5-20 mg twice daily. The efficacy assessments were the Brief Psychiatric Rating Scale, Krawiecka Rating Scale, and Clinical Global Impression. Both antipsychotic drugs produced clinical improvement with no significant differences between the efficacy of the two drugs. There were relatively few side effects. There were significantly fewer extrapyramidal symptoms and instances of blurred vision with remoxipride and less constipation with haloperidol. The results indicate that remoxipride is as effective an antipsychotic as haloperidol. Remoxipride has an advantage over haloperidol in respect to extrapyramidal side effects.

Acute Disease↗
PubMed1990

Glomerular hemodynamic alterations during renal nerve stimulation in rats on high- and low-salt diets.

Renal adrenergic nerve activity exerts a major influence on glomerular hemodynamics and tubular fluid reabsorption. Modulation of the functional expression of adrenergic activity in the kidney can be mediated, in part, by the renin-angiotensin system and by prostanoid activity. Alterations in dietary salt intake have been previously shown to modify the activity of various vasoactive systems, including angiotensin and prostaglandin activity and thereby have a potential of modifying the glomerular hemodynamic response to a given renal adrenergic stimulus. Munich-Wistar rats were fed either a high-, low-, or normal salt diet for 2 wk before the day of the study. Measurements of glomerular hemodynamics were performed in both unstimulated with basal renal nerve traffic eliminated and during exogenous renal nerve stimulation (RNS) (3 Hz). RNS decreased glomerular capillary hydrostatic pressure and single-nephron plasma flow to a similar extent in all three dietary conditions via increases in afferent arteriolar resistance. The data demonstrated that dietary preconditioning does not alter the glomerular hemodynamic response to an exogenous, fixed RNS. Glomerular prostaglandin E2 production and plasma renin activity were significantly greater in rats fed a low-salt diet compared with either normal- or high-salt diet. The constancy of glomerular hemodynamic responses to RNS in spite of wide variations in dietary salt intake indicates that functional renal hemodynamic differences observed as a result of NaCl intake must be primarily the consequence of differences in renal nerve traffic and not hormonal alterations.

Absorption↗
PubMed1990

Research attitudes and activities of occupational therapy clinicians.

Two hundred and seventy occupational therapy clinicians, whose primary or secondary employment function was in direct patient service, were surveyed to determine their perceived roles and attitudes regarding research. Results showed a strong belief in the importance of research in the profession, yet minimal involvement in research due to limited time, money, and skill. The role of collaborator with experienced researchers was rated as highly desirable. Few clinicians indicated no interest in research. Implications of the results and suggestions for strategies to increase clinicians' involvement and satisfaction in research through mutual experiences and continuing education are given.

Attitude of Health Personnel↗
PubMed1990

Reconstituted basement membrane enhances neurite outgrowth in PC12 cells induced by nerve growth factor.

Rat pheochromocytoma cells (PC12) respond to nerve growth factor (NGF) by elaborating neurites. We have studied the effect of extracellular matrix proteins on responsiveness of PC12 cells to NGF. NGF elicited neurite outgrowth in cells plated on collagen, fibronectin, or laminin within 48-72 h. In contrast, cells entrapped in reconstituted basement membrane prepared from the Engelbreth-Holm-Swarm tumor (EHS-BM) responded within 24 h. Cells plated on collagen or fibronectin required a minimal dose of 50 ng/ml NGF to achieve the same effect as cells entrapped in EHS-BM at 1 ng/ml NGF. Neurites displayed by cells plated in EHS-BM were more extensively branched and remained intact up to 21 days following a single administration of NGF.

Adrenal Gland Neoplasms↗
PubMed1990

Outcomes of research consortium project.

In previous articles, 1-3 the authors described the evolution and activities of the consortium project, a unique collaborative model for facilitating the conduct of nursing research in service settings. The authors' aim in these articles was to provide information useful to nursing administrators as they fulfill their professional obligation to support and foster the involvement of their staff in nursing research activities. Now, after five years of funding, the chronicle of this project's development, its successes, and difficulties would be incomplete without a final report of the experience. Therefore, this article describes the last two years of the consortium project.

Clinical Nursing Research↗
PubMed1989

Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing.

Australine [(1R,2R,3R,7S,7aR)-3-(hydroxymethyl)-1,2,7-trihydroxypyrrolizid ine] is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis [Molyneux et al. (1988) J. Nat. Prod. (in press)]. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, we tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the alpha-glucosidase amyloglucosidase (50% inhibition at 5.8 microM), but it did not inhibit beta-glucosidase, alpha- or beta-mannosidase, or alpha- or beta-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc3Man7-9(GlcNAc)2-oligosaccharides.

Alkaloids↗
PubMed1989

Differences between the sexes and the effects of surgery and anesthesia on the urinary excretion rate of eicosinoids in the rat.

Measurements were made of PGE2, PGF2 and TXB2 in the urine of male and female Munich-Wistar rats. Initial urine were collected in the awake state in metabolic cages and were followed by collections of ureteral urine during surgery and anesthesia both before and during cyclooxygenase inhibition with indomethacin. The excretion rate of all eicosinoids in the awake state was similar between the sexes. PGE2 excretion remained unaffected after anesthesia/surgery in both sexes indicating that providing plasma volume is maintained, the PGE2 system is not activated by the stress of anesthesia/surgery. Near complete inhibition of PGE2 was observed during indomethacin administration in both sexes. TXB2 excretion rates rose in both males and females with anesthesia/surgery and were slightly suppressed during indomethacin in males only. PGF2 excretion rose following surgery/anesthesia and was statistically significant in female rats. During indomethacin, TXB2 excretion was moderately reduced in male rats and unaffected in the female. Near complete inhibition of PGF2 was observed during indomethacin in both sexes. The urinary eicosinoid responses to indomethacin seen in these studies failed to provide an explanation for our earlier observations of a fall in renal vascular resistance in the female rat, studied under anesthesia and during indomethacin administration.

Anesthesia↗
PubMed1989

The use of an emergency department observation unit in the management of abdominal trauma.

Diagnostic peritoneal lavage (DPL) is a valuable triage tool in the evaluation of patients with abdominal trauma. Observation after a negative lavage is necessary to detect injuries not well discerned by DPL performed in the early postinjury period. We evaluated the use of 12 hours of monitoring in an emergency department observation unit in the management of 230 patients with abdominal trauma and a negative initial DPL. One hundred five of the patients had blunt and 125 had penetrating trauma. One hundred eighty-seven patients (81%) were discharged home from the observation unit without any reported significant complications. Thirty-eight patients (17%) required admission to our hospital; four of the 38 underwent necessary laparotomy. In the 230 patients evaluated, no deaths or complications could be assigned to the use of 12 hours of observation in the unit. The use of an observation unit in our study resulted in the potential savings of $51,329. Our study supports the concept that selected patients with significant abdominal trauma and a negative DPL can be managed safely and cost effectively in an ED observation unit.

Abdominal Injuries↗
PubMed1989

Abnormal diurnal weight gain among chronically psychotic patients contrasted with acutely psychotic patients and normals.

We found diurnal weight gain to be abnormal among 28 institutionalized chronically psychotic patients. They were weighed daily for 15 days at 7 a.m. and 4 p.m. We normalized the diurnal weight gain (NDWG) as a percentage by subtracting the 7 a.m. weight from the 4 p.m. weight, multiplying the difference by 100, and then dividing the result by the 7 a.m. weight. NDWG was 2.8 +/- 1.3% for the 28 study patients, 0.631 +/- 0.405% for 16 acutely psychotic controls, and 0.511 +/- 0.351% for 29 normals. Ninety-three per cent of the study sample had NDWG values above the upper limit of normal. Sex, diagnosis, smoking, baseline weight, blood pressure, and pulse did not explain these observations. NDWG related (N = 28, r = 0.552, P = 0.002) to antipsychotic drug dose. The implications of our findings are discussed.

Adult↗
PubMed1989

Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance.

To evaluate the possibility of administering therapeutic proteins via the respiratory route, we administered an aerosol of recombinant DNA-produced human alpha 1-antitrypsin (rAAT) to anesthetized sheep and measured levels of the protein in epithelial lining fluid (ELF), lung lymph, blood, and urine. Using a nebulizer that generated aerosol droplets with a mass median aerodynamic diameter of 2.7 micron (55% of droplets were less than 3 micron, a particle size optimal for deposition on the alveolar epithelium), in vitro studies demonstrated that the aerosolized rAAT remained intact and fully functional as an inhibitor of neutrophil elastase. When aerosolized to sheep, the 45-kDa rAAT molecule diffused across the alveolar epithelium, as evidenced by its presence in lung lymph and in blood. Comparison of ELF, lymph, blood, and urine rAAT levels demonstrated that the process was concentration dependent, with highest levels in ELF and in descending concentrations with approximately 10-fold concentration differences in each consecutive compartment, respectively. Importantly, evaluation with aerosolized 125I-labeled rAAT demonstrated that the rAAT molecules that reached the lung lymph and the systemic circulation remained intact as a 45-kDa protein. These results demonstrate the feasibility of using aerosolization to the pulmonary epithelial surface to administer sizeable proteins of therapeutic interest, thus circumventing the necessity of the traditional parenteral modes of administration of such molecules.

Absorption↗
PubMed1989

Localization of murine X and autosomal sequences homologous to the human Y located testis-determining region.

Recently a candidate gene for the primary testis-determining factor (TDF) encoding a zinc finger protein (ZFY) has been cloned from the human Y chromosome. A highly homologous X-linked copy has also been identified. Using this human sequence it is possible to identify two Y loci, an X and an autosomal locus in the mouse (Zfy-1, Zfy-2, Zfx and Zfa, respectively). Suprisingly ZFY is more homologous to the mouse X and autosomal sequences than it is to either of the Y-linked loci. Both Zfy-1 and Zfy-2 are present in the Sxr region of the Y but Zfy-2 is absent in the Sxr deletion variant Sxrb (or Sxr") suggesting it is not necessary for male determination. Extensive backcross analyses map Zfa to mouse chromosome 10 and Zfx to a 5-cM interval between anonymous X probe MDXS120 and the tabby locus (Ta). We also show that the mouse androgen receptor locus (m-AR) believed to underlie the testicular feminization mutation (Tfm) shows complete linkage to Zfx. Comparative mapping indicates that in man these genes lie in separate conserved DNA segments.

Animals↗