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Biomedical subjects

A Warren

Publications and source records attributed to A Warren.

At least 55 records · Page 3Linked to original sources

Basal ganglia volume in adults with Down syndrome.

This study was designed to determine the effects of aging on the volume of the basal ganglia in individuals with Down syndrome (DS) and to examine the relationship between basal ganglia volumes, neuropsychological test performance, and dementia status in this population. Subjects were 32 adults with DS. Basal ganglia volumes from 22 of these subjects were compared with those of 22 cognitively-normal individuals, who were individually matched on age, sex, and race. Performance on neuropsychological tests was correlated with basal ganglia volumes for 32 individuals with DS, and basal ganglia volumes of five demented DS subjects were compared with those of 14 non-demented DS subjects. Results indicated larger putamen volumes in the DS subjects, despite significantly smaller total brain volumes. Volumes of caudate and globus pallidus did not differ between DS and control subjects. Although there were some significant correlations between basal ganglia volumes and age, neuropsychological test performance, and dementia status in the DS subjects, these associations appeared to be a reflection of neurodevelopmental or atrophic reductions in overall brain volume rather than a reflection of specific basal ganglia abnormality. Correlations between age and volumes of basal ganglia and total brain were not significantly greater in non-demented DS subjects than in control subjects. Results suggest that volume reductions of the basal ganglia are not a salient feature of aging or of the dementia associated with DS.

Adult↗

Protistan communities in aquifers: a review.

Eukaryotic microorganisms (protists) are a very important component of microbial communities inhabiting groundwater aquifers. This is not unexpected when one considers that many protists feed heterotrophically, by means of either phagotrophy (bacterivory) or osmotrophy. Protistan numbers are usually low (< 10(2) per g dw of aquifer material) in pristine, uncontaminated aquifers but may increase by several orders of magnitude in aquifers subject to organic pollution. Small flagellates (typically 2-3(5) microns in size in situ) are by far the dominant protists in aquifers, although amoebae and occasionally ciliates may also be present in much lower numbers. Although a wealth of new taxonomic information is waiting to be brought to light, interest in the identity of aquifer protists is not exclusively academic. If verified, the following hypotheses may prove to be important towards our understanding of the functioning of microbial communities in aquifers: (1) Differences in swimming behavior between species of flagellates lead to feeding heterogeneity and niche differentiation, implying that bacterivorous flagellates graze on different subsets of the bacterial community, and therefore play different roles in controlling bacterial densities. (2) Bacterivorous flagellates grazing on bacteria capable of degrading organic compounds have an indirect effect on the overall rates of biodegradation.

Animals↗

Development of a modified paediatric coma scale in intensive care clinical practice.

James' adaptation of the Glasgow coma scale (JGCS) was designed for young children. Intubated patients are not allocated a verbal score, however, so important changes in a patient's conscious level may be missed. A grimace score was therefore developed and assessed for use in intubated children. Two observers made a JGCS observation within 15 minutes of each other. One observer was the patient's nurse and the other a trained investigator. Interobserver reliability was determined between the first and second observation for each component of the scale. Reliability was measured using kappa and weighted kappa statistics. Seventy three children had 104 sets of observations. Interobserver reliability was moderate to good for all components, with the grimace score better than the verbal score. It is concluded that the grimace score is more reliable than the verbal score and may be useful in intubated patients in whom the verbal score cannot be used.

Adolescent↗

Small planum temporale volume in Down's syndrome: a volumetric MRI study.

OBJECTIVE: Down's syndrome is associated with structural brain abnormalities and language deficits. The aim of this study was to investigate whether the superior temporal gyrus and the planum temporale, both parts of the anatomic substrate for language, are abnormal in Down's syndrome. METHOD: The authors examined volumetric magnetic resonance imaging (MRI) measures of the superior temporal gyrus and the planum temporale for 17 community-dwelling patients with Down's syndrome and 17 matched healthy comparison subjects. For the subjects with Down's syndrome, the correlations of the superior temporal gyrus and planum temporale volumes with performance on tests of language function were examined. RESULTS: The planum temporale volume of the patients with Down's syndrome was smaller than that of the healthy subjects, even after differences in whole brain volume were controlled for. The volume of the superior temporal gyrus in the Down's syndrome patients was proportionally similar to that of the comparison group. For the subjects with Down's syndrome, neither superior temporal gyrus nor planum temporale volume was significantly correlated with performance on language tests after total brain volume was controlled for. CONCLUSIONS: In Down's syndrome, planum temporale volume may be selectively smaller than normal, although the effect of this volume deficit on language is not clear.

Adult↗

Depression, delusions, and hallucinations in Alzheimer's disease: no relationship to apolipoprotein E genotype.

The apolipoprotein E (APOE) locus on chromosome 19 has been shown to modify risk, and age at onset, of Alzheimer's disease (AD). The authors hypothesized that the phenotypic expression of different psychiatric symptoms in patients with AD would be associated with variability in APOE locus. Neuropsychiatric and genetic testing of 120 probable AD patients revealed 28% had major depression, 17% had minor depression, 30% had delusions, and 14% had hallucinations; 69% were carriers of at least one APOE E4 allele (14% homozygous E4/E4, 49% heterozygous E3/E4, 6% heterozygous E2/E4, 29% homozygous E3/E3, 2% heterozygous E2/E3). Prevalence of the various psychiatric disturbances did not differ significantly in AD patients with different APOE genotypes. Apolipoprotein E does not appear to modify the risk of developing AD-associated psychiatric symptomatology.

Aged↗

Major and minor depression in Alzheimer's disease: prevalence and impact.

One hundred nine outpatients with Alzheimer's disease (AD) were neuropsychiatrically evaluated and rated on standardized measures of depression, activities of daily living (ADL), nonmood behavioral disturbance, and burdensome events such as serious wandering, falls, and accidents. Distribution of depression scores revealed three patient groups: very few depressive symptoms (51%), minor depression (27%), and major depression (22%). Major depression was associated with substantially greater impairment in ADL, worse nonmood behavioral disturbance (such as aggression), and more frequent serious wandering, even after adjusting for severity of dementia or comorbid health problems. Minor depression was also associated with nonmood behavioral disturbance and wandering. The authors conclude that both major and minor depression are common in AD and produce considerable mood and nonmood morbidity affecting both patients and caregivers. Efforts are warranted to identify and treat depression in AD.

Aged↗

Chromosomal translocations and leukaemia: a role for LMO2 in T cell acute leukaemia, in transcription and in erythropoiesis.

The LMO2 gene associated with T cell acute leukaemia has been used as an example of a gene activated by association with the T cell receptor genes after chromosomal translocations. The gene is shown to encode a LIM protein which is involved in protein interactions and during normal haematopoiesis is necessary for erythroid development. LMO2 has been shown to cause tumours when aberrantly expressed and to be able to heterodimerise with TAL1 to facilitate tumour development.

Adaptor Proteins, Signal Transducing↗

Some methods for dynamic analysis of the scalp recorded EEG.

This paper describes methods for quantifying the spatiotemporal dynamics of EEG. Development of these methods was motivated by watching computer-generated animations of EEG voltage records. These animations contain a wealth of information about the pattern of change across time in the voltages observed across the surface of the scalp. In an effort to quantify this pattern of changing voltages, we elected to extract a single quantifiable feature from each measurement epoch, the highest squared voltage among the various electrode sites. Nineteen channels of EEG were collected from subjects using an electrode cap with standard 10-20 system placements. Two minute records were obtained. Each record was sampled at a rate of 200 per second. Thirty seconds of artifact-free data were extracted from each 2 minute record. An algorithm then determined the location of the channel with the greatest amplitude for each 5 msec sampling epoch. We quantified these spatio-temporal dynamics as scalars, vectors and cluster analytic plots of EEG activity for finger tapping, cognitive effort (counting backwards) and relaxation to illustrate the utility of the techniques.

Algorithms↗

Clinical features of early onset, familial Alzheimer's disease linked to chromosome 14.

Early onset familial Alzheimer's disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the beta-amyloid precursor protein (beta APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with beta APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val-->Ile) or a valine to glycine (Val-->Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the beta APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the beta APP717 Val-->Ile and beta APP717 Val-->Gly encoded families that have been previously described.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Genetic manipulation of insect vectors as a strategy for the control of vector-borne disease.

A variety of very effective methods have been employed for suppressing insect vector populations, including the application of biological control agents and the elimination of breeding sites, with a continuing and heavy reliance on the use of chemical insecticides. However, the development of insecticide resistance by vector insects, the cost of developing and registering new insecticidal compounds, and the increase in legislation to combat the detrimental effects of insecticidal residues on the environment, have emphasized the need to assess alternative strategies for vector control. What is required is a completely novel approach to either suppress vector populations, or to alter their ability to transmit disease-causing organisms in such a way as to have a profound and long-lasting effect on disease transmission. Genetic manipulation of insect vectors may provide just such an approach. The major requirements for genome manipulation in insects and the progress which has been made to create transgenic vector insects are reviewed. The potential applications of this methodology are then explored in the context of its future use for the control of vector-borne diseases.

Animals↗

Endometrial lymphoid tissue in the timed endometrial biopsy: morphometric and immunohistochemical aspects.

OBJECTIVES: The purpose of this study was to provide a morphometric profile of endometrial granulated lymphocytes and to investigate qualitative and quantitative differences in leukocyte subsets in precisely timed luteal phase endometrial biopsies. STUDY DESIGN: Endometrial biopsies were obtained from 24 normal fertile women at 4, 7, 10, and 13 days after the luteinizing hormone surge. Endometrial granulated lymphocytes were assessed morphometrically in 2 microns resin sections. Eleven monoclonal antibodies were used to characterize leukocytes in frozen sections. Semiquantitation was performed with a Quantimet 970 image analyzer. Data were analyzed with one-way analysis of variance. RESULTS: CD8+ (T suppressor-cytotoxic) cells increased significantly from 4 to 7 days after the luteinizing hormone surge, whereas CD68+ macrophages increased from days 10 to 13. Lymphocytes with an unusual phenotype (CD56+, CD38+, CD2+) increased dramatically after 7 days. The volume fraction of endometrium occupied by the nuclei of endometrial granulated lymphocytes did not alter, but their mean nuclear diameter and axial ratio decreased from days 7 to 13. CONCLUSION: The morphometric findings indicate in situ proliferation of endometrial granulated lymphocytes rather than migration from the peripheral circulation. T lymphocytes, macrophages, and endometrial granulated lymphocytes increase significantly between certain stages of the luteal phase.

Adult↗

An analysis of the variation of plasma concentrations of placental protein 14 in artificial cycles.

OBJECTIVE: To analyze the factors affecting the variation of plasma concentration of placental protein 14 (PP14) in artificial cycles. DESIGN: The effects of different hormone replacement therapy (HRT) regimens were examined in a crossover design. SETTING: Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Eighteen women with premature ovarian failure: 6 associated with Turner's syndrome and 12 with idiopathic premature ovarian failure. INTERVENTIONS: Four different HRT regimens; 36 study cycles. MAIN OUTCOME MEASURES: Plasma PP14 concentrations on days 1, 15, 19, and 29 of the artificial cycles. RESULTS: In cycles treated with a standard HRT, the levels were similar to those of the natural cycle. Subjects with Turner's syndrome did not have elevated PP14 levels, whereas the majority (9/12 [75%]) of those with idiopathic premature ovarian failure had elevated levels on day 29 of the cycle. Levels of PP14 were reduced when either the doses of estradiol valerate were reduced to 1/3 or the doses of progesterone (P) were reduced to 1/5 of the standard HRT. CONCLUSIONS: Plasma levels of PP14 are dependent not only on P stimulation but also on adequate estrogen priming.

Adult↗

Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene.

Several families with an early-onset form of familial Alzheimer's disease have been found to harbour mutations at a specific codon (717) of the gene for the beta-amyloid precursor protein (APP) on chromosome 21. We now report, a novel base mutation in the same exon of the APP gene which co-segregates in one family with presenile dementia and cerebral haemorrhage due to cerebral amyloid angiopathy. The mutation results in the substitution of alanine into glycine at codon 692. These results suggest that the clinically distinct entities, presenile dementia and cerebral amyloid angiopathy, can be caused by the same mutation in the APP gene.

Adult↗

Molecular biological approaches to the study of vectors in relation to malaria control.

To a large extent, control of malaria vectors relies on the elimination of breeding sites and the application of chemical agents. There are increasing problems associated with the use of synthetic insecticides for vector control, including the evolution of resistance, the high cost of developing and registering new insecticides and an awareness of pollution from insecticide residues. These factors have stimulated interest in the application of molecular biology to the study of mosquito vectors of malaria; focussing primarily on two aspects. First, the improvement of existing control measures through the development of simplified DNA probe systems suitable for identification of vectors of malaria. The development of synthetic, non-radioactive DNA probes suitable for the identification of species in the Anopheles gambiae complex is described with the aim of defining a simplified methodology which is suitable for entomologist in the field. The second aspect to be considered is the development of completely novel strategies through the genetic manipulation of insect vectors of malaria in order to alter their ability to transmit the disease. The major requirements for producing transgenic mosquitoes are outlined together with the progress which has been made to date and discussed in relation to the prospects which this type of approach has for the future control of malaria.

Animals↗

Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene.

A mutation at codon 717 of the beta-amyloid precursor protein gene has been found to cosegregate with familial Alzheimer's disease in a single family. This mutation has been reported in a further five out of approximately 100 families multiply affected by Alzheimer's disease. We have identified another family, F19, in which we have detected linkage between the beta-amyloid precursor protein gene and Alzheimer's disease. Direct sequencing of exon 17 in affected individuals from this family has revealed a base change producing a Val----Gly substitution, also at codon 717. The occurrence of a second allelic variant at codon 717 linked to the Alzheimer's phenotype supports the hypothesis that they are pathogenic mutations.

Alzheimer Disease↗

Persistent vaginal discharge in a sexually active adolescent female.

With the high prevalence of unprotected sexual activity among adolescents, health-care providers are frequently called upon to evaluate patients with abnormal vaginal discharges. Usually, thorough pelvic and laboratory examinations will identify offending organisms which can be promptly eradicated with the judicious use of antibiotics. Occasionally, however, an abnormal discharge may persist despite these interventions. Health-care providers need to be aware of the fact that anal intercourse may be a common practice among sexually active teenagers. Penile-vaginal contact after anal intercourse may cause vaginal discharge due to contamination. Health-care providers should make it a routine part of their history-taking of adolescent patients to inquire about anal intercourse. Not only might it reveal useful clinical information, but it may indicate the need for additional health education and counseling.

Adolescent↗

Lectin binding of endometrium in women with unexplained infertility.

OBJECTIVE: To investigate whether peri-implantation phase endometrium in women with unexplained infertility differs from the endometrium of normal fertile women. DESIGN: Assessment of the function of the endometrium by using endometrial biopsy specimens and lectin histochemistry. SETTING: Infertility Clinic, Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Eighteen normal fertile women (group I) and 18 women with unexplained infertility (group II). INTERVENTIONS: Endometrial biopsies were obtained from both groups at 5, 7, and 9 days after the luteinizing hormone (LH) surge. MAIN OUTCOME MEASURES: Five biotinylated lectins, concanavalin A (ConA), wheat germ agglutinin (WGA), soybean agglutinin, Peanut, and Ulex europaeus I were used as analytical probes to study endometrial glycoconjugates. Histochemical staining was performed using the avidin-biotin peroxidase method. The lectin binding by endometrial glands, surface epithelium, stromal cells, and vessels was assessed. RESULTS: In group I, ConA stained the subnuclear glandular cytoplasm, glandular lumen, stroma cells, and surface epithelium. In group II, ConA binding to glandular or surface epithelium was none or equivocal. In group I, WGA bound to glandular cytoplasm and stroma cells on days LH + 5 and LH + 7. In group II, WGA binding was absent in glands but present in stroma. CONCLUSIONS: Reproductive failure of women with unexplained infertility may be associated with defective biosynthesis and distribution of glycoconjugates that subsequently results in an unfavorable endometrial environment during the peri-implantation phase.

Adult↗