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Biomedical subjects

W Muir

Publications and source records attributed to W Muir.

At least 19 recordsLinked to original sources
PubMed1994

Methodological considerations in measurement of the P300 component of the auditory oddball ERP in schizophrenia.

Twenty-three schizophrenic patients and 26 age-matched control subjects were studied using the P300 recorded during the auditory oddball task, with counting. Our aim was to assess the most suitable method of measurement and analysis of P300 amplitude and latency for use in clinical studies of schizophrenia. The effect of high-pass filtering, peak definition method and recording electrode site were all investigated. We have developed a technique, based on a least-mean-squares approximation to data, which seems particularly well suited to dealing with multi-peak P300 complexes. We have also investigated the spectral composition of the P300 and have found some evidence to support a proposed 2-frequency model of the P300 complex.

Acoustic Stimulation↗
PubMed1994

Induction of specific IgA responses in rats after oral vaccination with biodegradable microspheres containing a recombinant protein.

Diseases which affect mucosal surfaces cause considerable mortality and morbidity. New vaccine technologies are now available which justify a reappraisal of oral delivery not only for infectious disease control but also to control mucosal physiological processes such as fertility. Biodegradable microspheres have been investigated for their use as an oral delivery vehicle in rats using a recombinant antigen derived from fox sperm. Unencapsulated antigen administered in saline by the oral route produced a negligible response although an improved response was obtained if administered directly into the duodenum. This response was considerably enhanced if Peyer's patch (PP) priming was performed by direct injection of antigen in Freund's complete adjuvant (FCA) prior to intraduodenal (ID) delivery. In contrast, microencapsulated antigen given orally produced a substantial response, which was predominantly IgA specific, and almost equal in magnitude to that obtained by PP priming and ID boosting with native antigen. Direct ID delivery produced a similar response but when PP were primed with microencapsulated antigen in FCA the response to ID boosting was greater than with any of the other protocols investigated. These data demonstrate the efficacy of biodegradable microspheres in producing an IgA antibody response following oral vaccination.

Administration, Oral↗
PubMed1994

Cytokine regulation of mucosal responses: a rational basis for new vaccine delivery strategies.

In this review, cytokine regulation of mucosal responses is discussed in relation to the mucosal immune network and regulation of IgA responses. Based on this understanding, aspects of gene therapy for manipulation of the host environment and vaccine delivery systems are discussed. Although evidence obtained in vitro is briefly reviewed the general focus of this article is on evidence obtained from models in vivo.

Animals↗
PubMed1994

Screening schizophrenic patients for mutations in the amyloid precursor protein gene.

A limited number of rare missense mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene have been reported. They are associated with a variety of phenotypes including cerebral haemorrhage, multi-infarct dementia and Alzheimer's disease. We recently reported an alanine to valine mutation in codon 713 in a single case of chronic familial schizophrenia with cognitive deficits. Using denaturing gradient gel electrophoresis (DGGE) we have screened a cohort of 250 chronic schizophrenics for further mutations of exons 7, 16 and 17. None were found. Nevertheless recent evidence suggests that the 713 mutation is indeed pathogenic for the clinical phenotype observed; the mechanisms involved are outlined.

Amyloid beta-Protein Precursor↗
PubMed1993

Human olfactory marker protein maps close to tyrosinase and is a candidate gene for Usher syndrome type I.

Olfactory marker protein (OMP) shows olfactory neuron-specific expression in rodents. We recently reported tight linkage on mouse chromosome 7 of OMP to the shaker-1 deafness mutant, between the tyrosinase and globin loci. Here we isolate and map the human homologue. Our results show that OMP maps immediately centromeric to tyrosinase on the long arm of human chromosome 11. Genetic linkage to this region has recently been established for Usher Syndrome Type I, an autosomal recessive blindness and deafness disorder and a putative homologue of the shaker-1 mutant. OMP is thus a candidate gene for both congenital deafness defects.

Animals↗
PubMed1993

Schizophrenia-associated chromosome 11q21 translocation: identification of flanking markers and development of chromosome 11q fragment hybrids as cloning and mapping resources.

Genetic linkage, molecular analysis, and in situ hybridization have identified TYR and D11S388 as markers flanking the chromosome 11 breakpoint in a large pedigree where a balanced translocation, t(1;11)(q43;q21), segregates with schizophrenia and related affective disorders. Somatic cell hybrids, separating the two translocation chromosomes from each other and from the normal homologues, have been produced with the aid of immunomagnetic sorting for chromosome 1- and chromosome 11-encoded cell-surface antigens. The genes for two of these antigens map on either side of the 11q breakpoint. Immunomagnetic bead sorting was also used to isolate two stable X-irradiation hybrids for each cell-surface antigen. Each hybrid carries only chromosome 11 fragments. Translocation and X-irradiation hybrids were analyzed, mainly by PCR, for the presence of 19 chromosome 11 and 4 chromosome 1 markers. Ten newly designed primers are reported. The X-irradiation hybrids were also studied cytogenetically, for human DNA content, by in situ Cot1 DNA hybridization and by painting the Alu-PCR products from these four lines back onto normal human metaphases. The generation of the translocation hybrids and of the chromosome 11q fragment hybrids is a necessary preliminary to determining whether a schizophrenia-predisposition gene SCZD2 is encoded at this site.

Animals↗
PubMed1991

DNA markers and biological vulnerability markers in families multiply affected with schizophrenia.

A family is reported in which the monozygotic co-twin of a schizophrenic proband was diagnosed bipolar 1 and their mother had a history of unipolar major depression. Although their clinical manifestations varied, the ill members of this family shared an abnormality in P300 not found in the asymptomatic siblings. In 14 families, linkage to the 5q11-13 region was excluded when affection status was defined solely by P300 latency independently of the clinical findings. Linkage was also excluded when the analysis was restricted to the families that had no cases of bipolar illness and when the schizophrenic phenotype was narrowly or broadly defined. It is concluded that biological markers such as P300 and eye tracking may help to clarify the overlap of different types of psychosis and help to define the phenotype for linkage analyses.

Arousal↗
PubMed1990

Association within a family of a balanced autosomal translocation with major mental illness.

282 pedigrees in the MRC Cytogenetics Registry, Edinburgh, with familial autosomal anomalies were examined for the presence of associated mental illness. In one large pedigree there were 23 cases of mental and/or behavioural disorders meeting Research Diagnostic Criteria. 34 of the 77 family members available for cytogenetic analysis carried a balanced translocation t(1:11) (q43,q21). Psychiatric diagnoses had been recorded for 16 of the 34 members with the translocation compared with only 5 of the 43 without it. The lod scores (against chance linkage of the translocation with mental illness) were greatest when the mental disorders in the phenotype were restricted to schizophrenia, schizoaffective disorder, recurrent major depression, and adolescent conduct and emotional disorders. Although the mental illness in this family may not be typical of that in the general population, the findings suggest that the q21-22 region of chromosome 11 may be a promising area to examine for genes predisposing to major mental illness.

Adolescent↗
PubMed1989

No linkage of chromosome 5q11-q13 markers to schizophrenia in Scottish families.

Recent work suggests that an autosomal dominant gene for schizophrenia may be located on the 5q11-q13 region of chromosome 5 (refs 1 and 2): a report of schizophrenia associated with trisomy 5q11-q13 in two members of a family of Chinese origin prompted the discovery of linkage with markers p105-599Ha and p105-153Ra in five Icelandic and two English schizophrenic families. The strongest linkage was observed when the phenotype was broadly defined to include minor psychiatric diagnoses not traditionally considered part of the schizophrenia spectrum. By contrast, no evidence was found of linkage in a single multiplex Swedish schizophrenic pedigree. To determine whether these conflicting results arise from genetic and/or uncertainties in defining the schizophrenic phenotype, we examined fifteen Scottish schizophrenic families with restriction fragment length polymorphisms that span this region. We found no evidence for linkage, regardless of how broadly or narrowly the schizophrenic phenotype is defined, and conclude that a susceptibility locus, whose presence awaits confirmation, on the proximal portion of the long arm of chromosome 5 can be responsible for only a minority of cases of familial schizophrenia.

Chromosomes, Human, Pair 5↗
PubMed1989

P300 abnormality in schizophrenic subtypes.

P300 and other long latency event-related potentials were recorded in 65 schizophrenic subjects and results were compared to findings in 119 healthy controls. Highly significant differences in P300 latency and amplitude were found between the two groups. Forty six per cent of schizophrenics had P300 latency more than two standard deviations longer than the mean for controls, 35% had a P300 amplitude smaller than the mean for controls by the same amount, and 24% were more than two standard deviations outside the mean for controls on both measures. These differences were independent of chronicity of illness, clinical subtype, family psychiatric history or the effects of neuroleptic medication. They confirm that P300 abnormality is present as a stable trait in a high proportion of schizophrenics. The status of abnormal P300 as a biological vulnerability factor for major mental illness is discussed.

Adult↗
PubMed1989

Effect of sodium bicarbonate infusions on ionized calcium and total calcium concentrations in serum of clinically normal cats.

The effects of sodium bicarbonate (0.5 mEq/kg of body weight, 1.0 mEq/kg, 2.0 mEq/kg, and 4.0 mEq/kg) on ionized and total calcium concentrations were determined in clinically normal cats. Also, serum pH, whole blood pH, and serum albumin, serum total protein, and serum phosphorus concentrations were measured. Intravenous administration of sodium bicarbonate to awake cats decreased serum ionized calcium and serum total calcium concentrations. All dosages of sodium bicarbonate were associated with significant decreases of serum ionized calcium concentration. This effect lasted for greater than 180 minutes when cats were given 2.0 mEq/kg or 4.0 mEq/kg. When cats were given 4 mEq of sodium bicarbonate/kg, serum ionized calcium concentration was significantly decreased, compared with that when cats were given lower doses, but only at 10 minutes after infusion. After sodium bicarbonate infusion, serum total calcium concentration, measured by ion-specific electrode and colorimetry, was lower than baseline values at most of the times evaluated. Decreases in serum ionized calcium and serum total calcium concentrations can be attributed only in part to an increase in serum or whole blood pH and to a decrease in serum protein concentration. Serum total calcium concentrations measured by ion-specific electrode and by colorimetry were positively correlated, but the variability was high. Only 44% of the variability in serum ionized calcium concentration could be predicted when serum total calcium, albumin, total protein, phosphorus, and bicarbonate concentrations and pH were considered.

Animals↗
PubMed1984

Human cervical cancer clearance after 252Cf neutron brachytherapy versus conventional photon brachytherapy.

Tumor clearance pattern was studied for Stage IB carcinoma of the cervix using 252Cf neutron brachytherapy followed by fractionated radiotherapy as compared to conventional therapy using fractionated radiotherapy followed by 137Cs photon low-dose rate (LDR) implant therapy. Reduction in bulk of tumor was assessed by regular and frequent serial clinical observations. The tumor clearance pattern of the neutron-treated patients was greatly accelerated and radically different from those treated using conventional radiation.

Brachytherapy↗
PubMed1983

1,3-bis(2-chloroethyl)-1-nitrosourea treatment of spontaneous radiogenic C57BL mouse leukemia/lymphoma.

Spontaneous radiation-induced or radiation leukemia virus (RadLV)-induced leukemias were treated in vivo in an early-to-advanced lymphomatous state by using 1,3-bis(2-chloroethyl)-1-nitrosouea (BCNU). BCNU was given at various times after the tumor induction procedure. Treatment was based upon the findings that the RadLV-derived transplant lymphosarcoma (LSA) tumor was cured with a frequency of greater than 90% and a tumor-resistant state was produced by tumor cure. Death from RadLV lymphomas which had been initiated in newborn C57BL mice by ip injection of RadLV was scored in untreated or BCNU-treated mice. At 150 days after initiation, control mice had developed extensive thymic lymphomas, whereas BCNU-treated mice had developed less extensive tumors, had a reduced incidence by approximately 50% and had an increased survival time. Similar findings were noted for the radiation (190 rad of cobalt-60 gamma rays weekly X 4)-induced thymic lymphoma-bearing C57BL mice. Injection of 10(6) living LSA cells before BCNU treatment greatly decreased the tumor load for all groups treated but also shortened the mean survival time. Challenge of long-term survivors with small numbers of viable LSA tumor cells did not identify any host resistance of the survivors to the transplant LSA tumor and indicated that the induction procedure, whether RadLV or radiation, was strongly immunosuppressive.

Animals↗