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Biomedical subjects

M Field

Publications and source records attributed to M Field.

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

Antinuclear antibody determination methods.

Screening rheumatology patients for anti-nuclear and anti-cytoplasmic antibodies is easily done in a qualitative manner using the IF, CIE and ID assays. The immunoblot is of use for anti-La and anti-RNP assays but gives anomalous results for Sm binding by anti-RNP sera and is not easily quantitated. These deficiencies of the immunoblot do not apply to the ELISA. Advances in cloning of autoantigens will enable standardisation of antigen preparations used for these ELISAs. The quantitation of autoantibody appears significant since disease flares occur together with elevations in specific autoantibody. IgM anti-Sm autoantibody was detected with a different disease distribution to IgG anti-Sm but the prognostic implications for this remain to be determined.

Antibodies, Antinuclear↗
PubMed1990

Epithelial K channel expressed in Xenopus oocytes is inactivated by protein kinase C.

K homeostasis is maintained in higher animals by epithelia of the kidney and intestine. Little is known regarding the molecular regulation of K secretion. We injected Xenopus oocytes with mRNA from teleost intestine, a K-secreting epithelium with apical membrane K channels. Oocytes expressed a conductance that displayed whole-cell current properties with the following characteristics: marked selectivity for K over Na and Cl, voltage-independent kinetics, Ca insensitivity, tonic activation, and inward rectification in symmetrical K. Barium, quinine, and tetraethylammonium blocked the conductance, whereas apamin, charybdotoxin, and 4-aminopyridine did not. The K conductance was rapidly (t1/2 = 10 min) and completely inactivated by 4 beta-phorbol 12-myristate 13-acetate but not by 4 alpha-phorbol 12,13-didecanoate. Sucrose density gradient fractionation revealed that mRNA required for expression is in the 1- to 2-kilobase size range, suggesting the possibility that a single subunit encodes the channel. The K conductance expressed from injection of size-fractionated mRNA was identical in all respects to that seen using unfractionated mRNA, including response to 4 beta-phorbol 12-myristate 13-acetate. The results suggest that protein kinase C regulates K secretion in epithelia by modulation of apical K channels.

Animals↗
PubMed1990

Predicting IQ change in preschoolers with developmental delays.

This study examined IQ change over a 2-year period in 291 young children (mean age 39 months) referred to a pediatric developmental clinic for evaluation of developmental problems. Although correlation between initial and follow-up IQ was very high (0.78), there was also a significant increase in mean IQ score, from 67.12 to 74.06. Moreover, 26% of the subjects showed IQ increase of 16 points or more. Variables making some contribution to IQ change were initial clinical diagnosis, etiology, and intervention. Children diagnosed with a developmental language disorder made significantly greater gains than those diagnosed as mentally retarded. Sex, family status, initial age, and test interval were not significantly correlated with IQ change. We concluded that prediction for individual children is difficult, but that initial diagnosis may be useful in differentially predicting IQ change in young children with developmental delays.

Affective Symptoms↗
PubMed1989

Inhibition of HIV-1 proviral DNA synthesis and RNA accumulation by mismatched dsRNA.

The antiviral activity of mismatched dsRNA of the form poly(I):poly(C12-U)n (Ampligen) against the human immunodeficiency virus type 1 (HIV-1) was investigated by RNA-RNA and RNA-DNA hybridizations. Mismatched dsRNA delayed the appearance of newly transcribed HIV-1 RNA as detected by liquid dot-blot hybridization in cultures of H9 T-lymphoblastoid cells following virus challenge. The appearance of proviral DNA as detected by Southern hybridization following virus challenge in H9 cells was also delayed. Mismatched dsRNA had no effect in syncytium inhibition assays performed by fusing MT-2 cells with H9/HTLV-IIIB cells. These results suggest that the in vitro anti-HIV-1 activity of mismatched dsRNA occurs, at least in part, at an early stage in the viral replication cycle following initial gp120-CD4 binding.

Antiviral Agents↗
PubMed1989

Induction of intestinal glucose carriers in streptozocin-treated chronically diabetic rats.

The maximal transport capacity (Vmax) for intestinal glucose absorption is increased in experimentally induced chronic diabetes mellitus. Using [3H]phlorizin radioautography, we examined the relation between this increase in transport Vmax and the number and distribution of sodium-glucose co-transporters on the luminal surface of rat ileum. Male Lewis rats were made diabetic with streptozocin. Ninety days later we measured 3-O-methyl-D-glucopyranose absorption and specific [3H]phlorizin binding to the ileal mucosa of the same rats. Net 3-O-methyl-D-glucopyranose flux was 6.9-fold greater in diabetic rats compared with age-matched controls. Specific binding of [3H]phlorizin to the luminal surface was 7.2-fold greater in the diabetic rats. Radioautography revealed that, in chronic diabetes, specific phlorizin binding extends into the midvillus region of the ileum, whereas in age-matched controls, it is confined to villus tips. We believe that, in untreated diabetes, a larger fraction of intestinal villus epithelial cells participate in glucose absorption.

3-O-Methylglucose↗
PubMed1989

Cerebral dysfunction with evidence of cerebral HIV infection amongst asymptomatic HIV seropositive subjects.

Twelve asymptomatic HIV seropositive subjects ages 21 to 40 years were examined for serologic evidence of cerebral HIV infection, for cerebral structural abnormalities, and for neuropsychologic evidence of cerebral dysfunction using standard methods. Eleven of the 12 had antibody to HIV in the cerebrospinal fluid (CSF). Nine subjects had oligoclonal immunoglobulins in the CSF, of whom five had some for which there were no corresponding serum oligoclonal immunoglobulins ('unique' oligoclonal immunoglobulins). Intracerebral synthesis of HIV specific antibodies was demonstrated for four subjects. Significant deficits of memory and frontal lobe function were found in five of the 12 subjects. Subjects who had oligoclonal immunoglobulins unique to the CSF all had significant neuropsychological abnormalities. No structural cerebral abnormalities were demonstrated using CT scanning for any subject tested. These results support other evidence that HIV is neurotropic and capable of directly inducing brain damage even in immunologically normal subjects. Tests of memory and frontal lobe function are frequently abnormal in patients with early HIV infection, and identify as abnormal a similar group of patients to immunological or biochemical tests which might indicate cerebral HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

K-independent Na-Cl cotransport in bovine tracheal epithelial cells.

Uptakes of 22Na, 36Cl, and 86Rb into isolated bovine tracheal epithelial cells were measured in the presence and absence of 10 microM bumetanide. Preincubation with ouabain (0.5 mM) did not alter initial rates of Na and Cl uptakes but prolonged from 0.5 or less to 2 min the period in which Na uptake is linear with time. Initial rates of bumetanide-inhibitable Na and Cl uptakes (influxes), measured for 2 min in identical solutions, were similar in magnitude (bumetanide-sensitive Cl influx/bumetanide-sensitive Na influx = 1.2). Omission of K did not affect bumetanide-sensitive Na or Cl influx. Cl influx was not affected by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid. Amiloride (0.1 mM) partially inhibited the bumetanide-insensitive Na influx but had no effect on the bumetanide-sensitive Na influx. Rb influx was not affected by bumetanide but was markedly reduced by ouabain and slightly reduced by Ba, the combination being additive. Half-maximally inhibitory concentration values for inhibition of Cl influx by 4 sulfamoylbenzoic acid derivatives were as follows (in mumol/l): 0.125 benzmetanide; 0.64 bumetanide; 16 piretanide; and 26 furosemide. Affinities of Na and Cl for the bumetanide-inhibitable cotransport process were determined by measuring bumetanide-sensitive Cl influx at varying [Na] and bumetanide-sensitive Na influx at varying [Cl]. Both plots were hyperbolic, and the K0.5 values for Na and Cl were 4.1 and 53.9 mM, respectively. Bumetanide-inhibitable Cl influx was not altered by secretory stimuli (epinephrine, A23187) but was more than doubled by osmotic shrinkage (200 mM mannitol or sucrose).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1989

Rapid clearance of the lupus antigen Sm is delayed by autoantibody: a possible mechanism of autoimmunity perpetuation.

Sm ribonucleoprotein complex was immunopurified and labelled with 125I. After i.v. injection into normal mice 125I-Sm was cleared with a half life of less than 3 min, mainly to the liver (54% at 15 min). With time there was a progressive reduction in liver uptake (13.3% at 1 h), and this was associated with the appearance of increasing amounts of trichloroacetic acid soluble 125I in serum, suggesting complete Sm catabolism. Injection of 125I-Sm as a preformed immune complex with human anti-Sm antibody was associated with slower antigen removal from the circulation (half life 15 min), more gradual liver uptake (27% at 1 hr), and less degradation products in the serum than after injection of antigen alone. These data suggest that release of 125I-Sm into the circulation is followed by specific organ uptake and antigen degradation. In the form of an immune complex, the rapid removal mechanism is impaired, and antigen persists in the circulation in an undegraded form. Simultaneous production of anti-Sm antibody and Sm antigen release following tissue destruction could lead to amplification of any primed immune response as a result of autoantigen drive in systemic lupus erythematosus.

Animals↗
PubMed1989

Posterior cortical atrophy.

Two patients had a steadily progressive disorder of higher cortical function dominated by the early development of cortical visual deficits. In one, a right visual inattention progressed over a period of 2 years to a complete right homonymous hemianopia and relative left inferior quadrantanopia. In the second case, blind in the left eye for unrelated reasons, a temporal field loss was noted at presentation in the right eye, with the subsequent development of field loss in the inferior nasal quadrant on that side. Features of Balint's syndrome developed in both patients, with sticky fixation, ocular dysmetria and simultanagnosia. Prominent associated features were progressive dysmnesia, dyscalculia, ideomotor apraxia and spatial disorientation. Abstract reasoning, speech function and insight were all well preserved. MRI and CT scans revealed no focal abnormalities. These cases are similar to the 5 recently described by Benson et al. The pathological basis is unknown but may be an atypical form of Alzheimer's disease.

Atrophy↗
PubMed1988

A revised potential-energy surface for molecular mechanics studies of carbohydrates.

A revised CHARMM-type molecular mechanics potential-energy function has been developed for use in the dynamical simulation of simple carbohydrates in aqueous solution. Atomic charges used in this parameterization were taken to be those previously determined to be appropriate for hydrogen-bonded systems, and the various force-constants were selected by the nonlinear least-squares matching of the calculated normal-mode frequencies and minimum-energy structure to experiment as a function of the parameter set. The new function was found to represent the vibrational spectrum and ring pucker of alpha-D-glucopyranose as well as previously studied potentials, while incorporating the charges necessary for the simulation of condensed phases. Molecular dynamics simulations of the motions of alpha-D-glucopyranose in vacuo in both the 1C4 and 4C1 conformation were conducted, and compared to the results of previous simulations using another potential-energy function. The revised potential function was found to produce a D-glucose molecule less flexible in vacuo than had been previously observed.

Carbohydrates↗
PubMed1988

Specificity of anti-Sm antibodies by ELISA for systemic lupus erythematosus: increased sensitivity of detection using purified peptide antigens.

Sm antigen was purified by immunoaffinity chromatography using a murine monoclonal anti-Sm antibody and was confirmed to be free from contaminating polypeptides. This was then used to detect anti-Sm antibodies in patients' sera by enzyme linked immunosorbent assay (ELISA). Antibodies against Sm were detected in only 9/52 (17%) patients with systemic lupus erythematosus (SLE) by immunodiffusion, but 15/52 (29%) were positive for IgG anti-Sm antibodies by ELISA. The presence of anti-Sm antibodies remained disease specific despite the increase in sensitivity of this assay and validates its potential use for clinical application. There was no correlation between the presence of anti-Sm antibodies and any clinical features of SLE. In 23 renal biopsies a membranous component to the glomerulonephritis correlated with anti-Sm antibodies (p less than 0.05). Patients from West Africa, the Carribean Islands, and Asia had a higher prevalence of anti-Sm antibodies than the local Caucasian population.

Antibody Specificity↗
PubMed1988

Cyclic nucleotide-dependent protein kinase inhibition by H-8: effects on ion transport.

We explored the potential role of cyclic nucleotide-dependent protein phosphorylation in regulating ion transport across flounder intestinal mucosa by studying the effects of N-[2(methylamino)-ethyl]-s-isoquinolinesulfonamide (H-8), a selective inhibitor of cyclic nucleotide-dependent protein kinase in vitro. Addition of H-8 reversed the inhibitory effects of 8-bromoguanosine 3',5'-cyclic-monophosphate (8-BrcGMP), 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), atriopeptin III (AP III), and vasoactive intestinal peptide (VIP) on the short-circuit current (Isc) and transepithelial potential difference (PD). Flux measurements established that these changes in Isc and PD directly reflected changes in Na and Cl absorption by the intestine. H-8 was unable, however, to reverse the inhibitory effects on Isc and PD of the Ca ionophore ionomycin and of substance P at dosages exceeding those needed to reverse the effects of AP III, VIP, and the cyclic nucleotides. We conclude that 1) H-8 (100 microM or less) does not exert toxic effects, 2) exogenously added cyclic nucleotide analogues inhibit ion transport through activation of cyclic nucleotide-dependent kinases resulting in protein phosphorylation, 3) activation of these kinases is an essential intermediate step in the inhibitory action of AP III and VIP on ion transport, and 4) the Ca ionophore ionomycin and substance P appear to inhibit ion transport by a mechanism that is independent of cyclic nucleotide-dependent protein phosphorylation.

8-Bromo Cyclic Adenosine Monophosphate↗