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Biomedical subjects

G Sanders

Publications and source records attributed to G Sanders.

At least 37 records · Page 2Linked to original sources

Sexual orientation differences in cerebral asymmetry and in the performance of sexually dimorphic cognitive and motor tasks.

With each of the tasks in the present studies we expected to find the reported sex difference between heterosexual women and heterosexual men and we predicted a sexual orientation effect with the performance of homosexual men being similar to that of heterosexual women and different from that of heterosexual men. Study 1 aimed to replicate earlier findings by recording the performance of a group of homosexual men on a visuospatial task, the Vincent Mechanical Diagrams Test (VMDT), a dot detection divided visual field measure of functional cerebral asymmetry, and on five subtests of the Wechsler Adult Intelligence Scale (WAIS). For each task the profile of scores obtained for the homosexual men was similar to that of heterosexual women in that they scored lower than heterosexual men on the VMDT, they showed less asymmetry, and they recorded a higher Verbal than Performance IQ on the WAIS. In Study 2, a male-biased targeted throwing task favored heterosexual men while, in contrast, on the female-biased Purdue Pegboard single peg condition heterosexual men were outperformed by heterosexual women and homosexual men. On neither of these two tasks did the performances of homosexual men and heterosexual women differ. One task, manual speed, yielded neither sex nor sexual orientation differences. Another, the Purdue Pegboard assemblies condition, revealed a sex difference but no sexual orientation difference. Failure to obtain a sexual orientation difference in the presence of a sex difference suggests that the sexual orientation effect may be restricted to a subset of sexually dimorphic tasks.

Adult↗

Characteristics of individuals with Huntington disease in long-term care.

This is a retrospective review of 97 Huntington disease (HD) patients living in long-term care facilities in the Twin Cities. The purpose of the study was to describe the demographic features, patterns of behavior, weight change, nursing issues, medication use, and hospitalization in this population. On admission to the nursing home, the "average" HD patient was of either sex, 45 years old, previously employed, a high school graduate, and not married. One third had severe behavior problems. Half gained and half lost weight; weight loss was not a predictor of death. Almost all used central nervous system-active drugs, most commonly neuroleptics. Eighty-four percent were ambulatory on admission, but 88% of those who died were nonambulatory at the time of death. We concluded that (a) HD patients are demographically different from other residents of long-term care facilities, (b) weight gain can occur in some late-stage patients, (c) negative behavior is a significant problem but is restricted to a subset of patients, and (d) adapting creatively to increasing multifaceted disability is the greatest challenge to the staff in facilities caring for HD patients.

Adult↗

Polychlorinated biphenyls (PCBs) in the British environment: sinks, sources and temporal trends.

This paper estimates the present UK environmental loading of polychlorinated biphenyls (PCBs). Of the estimated approximately 40,000 t SigmaPCB sold in the UK since 1954, only an estimated 1% (400 t) are now present in the UK environment. Comparisons of estimated production and current environmental loadings of congeners 28, 52, 101, 138, 153 and 180 suggest that PCB persistence broadly increases with increasing chlorination. Those PCBs that are not now present in the UK environment are considered to have been destroyed--by natural or anthropogenic mechanisms, to be still in use, to reside in landfills or to have undergone atmospheric and/or pelagic transport from the UK. The dramatic fall in PCB levels in archived UK soils and vegetation between the mid-1960s and the present is evidence that the latter mechanism is the most important and that a significant proportion of PCBs released into the UK environment in the 1960s have subsequently undergone environmental transport away from the UK. The bulk (93.1%) of the estimated contemporary UK environmental burden of SigmaPCBs is associated with soils, with the rest found in seawater (3.5%) and marine sediments (2.1%). Freshwater sediments, vegetation, humans and sewage sludge combined account for 1.4% of the present burden, whilst PCB loadings in air and freshwater are insignificant. Although consideration of individual congeners does not reveal any major deviations from the relative partitioning of Sigma PCBs, the importance of sinks other than soils is enhanced for individual congeners, particularly 138 and 180. In particular, around 2% of the total UK burden of congener 180 is present in humans, implying that biodata as a whole may constitute an important sink for the higher chlorinated congeners. The contemporary flux of SigmaPCBs to the UK surface is estimated at 19 t yr(-1), compared with an estimated annual flux to the atmosphere of 44-46 t. This implies that the major sources of PCBs to the UK atmosphere have been identified and that there is currently a net loss of these compounds from the UK. These sources are: volatilisation from soils (88.1%), leaks from large capacitors (8.5%), the production of refuse-derived fuel (RDF) (2.2%), leaks from transformers (0.6%), the recovery of contaminated scrap metal (0.5%) and volatilisation from sewage sludge-amended land (0.2%). Interestingly, whilst large excesses of estimated annual fluxes to the atmosphere over deposition fluxes for individual congeners exist for congeners 28, 52 and 101, estimates of fluxes in both directions across the soil-atmosphere interface agree closely for congeners 138, 153 and 180. This suggests that lower chlorinated congeners are more susceptible to both long-range environmental transport beyond the UK and to atmospheric degradation. Retrospective analysis of dated sediment cores, vegetation and soils indicates that environmental transport from North America and continental Europe introduced PCBs into the British environment well before the onset of their commercial production in the UK in 1954. Since that time, the input of PCBs to the UK environment has essentially reflected temporal trends in UK use. After peaking in the 1960s they declined rapidly through the 1970s following restrictions on PCB use. Recent evidence, however, is that the rate of decrease has diminished and that further significant reductions in fresh environmental input will take some time to occur. Such reductions will be especially slow for humans and other biota with long life-spans. This stems partly from cross-generational transfer from parents to offspring and also because the persistence of PCBs in biota means that present body burdens will reflect past as well as current exposure.

Journal Article↗

Estimation of arterial stiffness, compliance, and distensibility from M-mode ultrasound measurements of the common carotid artery.

BACKGROUND AND PURPOSE: Arterial stiffness may indicate early vascular changes that predispose to the development of major vascular disease. The repeatability of a variety of indices of arterial stiffness calculated from a standard carotid arterial M-mode ultrasound image was investigated. METHODS: Twenty-six asymptomatic normal subjects were imaged and had blood pressure recordings on each of two separate occasions at least 1 day apart. Using a computer-assisted method, the maximum and minimum internal diameter and average wall thickness of the right common carotid artery were measured over several cardiac cycles, and the following indices of arterial stiffness and distensibility (compliance) were derived: the pressure-strain elastic modulus (Ep), Young's modulus (E), cross-sectional compliance (CC), and the distensibility coefficient (DC). RESULTS: The repeatability of these measures, expressed as coefficients of variation, was as follows: Ep, 18%; E, 24%; CC, 14%; and DC, 13%. In another group of 20 subjects, the coefficient of variation for repeat examination by different sonographers was Ep, 19%; E, 20%; CC, 14%; and DC, 17% and for the one sonographer using two ultrasound machines was Ep, 13%; E, 13%; CC, 11%; and DC, 13%. These values indicate a moderate level of repeatability. In a univariate analysis each of these indices was significantly related to increasing age (Ep = 1.0 + 12.9 x AGE, r = .80; E = 314.5 + 13.9 x AGE, r = .48; CC = 22.6-0.26 x AGE, r = -.63; DC = 64.0-0.65 x AGE, r = -.78) but not to wall thickness (all P > .47). Using multiple regression techniques to adjust for age, wall thickness is a significant predictor of distensibility (P = .017), cross-sectional compliance (P < .001), and the pressure-strain elastic modulus (P = .019). Because Young's modulus is calculated from wall thickness, it could not be included in the multivariate analysis. CONCLUSIONS: We conclude that estimates of carotid artery distensibility and cross-sectional compliance derived from M-mode ultrasound recordings are moderately repeatable and may provide useful additional end points for trials of atherosclerotic progression.

Adult↗

The role of methotrexate in the management of steroid-dependent asthma.

Severe asthma often requires high-dose corticosteroid therapy. However, steroid therapy is fraught with many side effects. There are conflicting reports in the literature regarding the role of methotrexate in reducing the steroid requirements of these patients. This study examined the role of low-dose methotrexate in the management of steroid-dependent asthma. Eleven subjects with stable steroid-dependent asthma were enrolled in a placebo-controlled double-blind crossover trial. Patients received methotrexate, 15 mg/wk, or placebo each for two 12-week periods. There was significant improvement of pulmonary function and reduction of prednisone requirement in both placebo and methotrexate treatment periods. However, methotrexate was not superior to placebo. Only 3 of 11 patients responded to methotrexate. Although low-dose methotrexate therapy may have a role in a small select group of steroid-dependent asthmatics, it provided no additional benefit overall.

Adolescent↗

B-mode ultrasound images of the carotid artery wall: correlation of ultrasound with histological measurements.

B-mode ultrasound is being used to assess carotid atherosclerosis in epidemiological studies and clinical trials. Recently the interpretation of measurements made from ultrasound images has been questioned. This study examines the anatomical correlates of B-mode ultrasound of carotid arteries in vitro and in situ in cadavers. Twenty-seven segments of human carotid artery were collected at autopsy, pressure perfusion fixed in buffered 2.5% glutaraldehyde and 4% paraformaldehyde and imaged using an ATL UM-8 (10 MHz single crystal mechanical probe). Each artery was then frozen, sectioned and stained with van Gieson or elastin van Gieson. The thickness of the intima, media and adventitia were measured to an accuracy of 0.01 mm from histological sections using a calibrated eye graticule on a light microscope. Shrinkage artifact induced by histological preparation was determined to be 7.8%. Digitised ultrasound images of the artery wall were analysed off-line. The distance from the leading edge of the first interface (LE1) to the leading edge of the second interface (LE2) was measured using a dedicated programme. LE1-LE2 measurements were correlated against histological measurements corrected for shrinkage. Mean values for the far wall were: ultrasound LE1-LE2 (0.97 mm, S.D. 0.26), total wall thickness (1.05 mm, S.D. 0.37), adventitia (0.35 mm, S.D. 0.16), media (0.61 mm, S.D. 0.18), intima (0.09 mm, S.D. 0.13). Ultrasound measurements corresponded best with total wall thickness, rather than elastin or the intima-media complex. Excision of part of the intima plus media or removal of the adventitia resulted in a corresponding decrease in the LE1-LE2 distance of the B-mode image. Furthermore, increased wall thickness due to intimal atherosclerotic thickening correlated well with LE1-LE2 distance of the B-mode images. B-mode images obtained from the carotid arteries in situ in four cadavers also corresponded best with total wall thickness measured from histological sections and not with the thickness of the intima plus media. In conclusion, the LE1-LE2 distance measured on B-mode images of the carotid artery best represents total wall thickness of intima plus media plus adventitia and not intima plus media alone.

Adult↗

An immunoplaque assay distinguishing between cytopathogenic and noncytopathogenic biotypes of bovine viral diarrhoea virus.

Cytopathogenic (cp) and noncytopathogenic (ncp) biotypes of bovine virus diarrhoea virus (BVDV) could be clearly distinguished by hollow plaques with peripheral immunostaining in infected fetal calf kidney (FCK) monolayers cultures or the appearance of homogenously stained immunoplaques (IPs), respectively. Of 70 BVDV isolates formerly classified as cytopathogenic according to microscopic observations in FCK cell cultures, 46 produced IPs of both types while the remaining 24 isolates induced only the IP type characteristic of the ncp BVDV biotype. The same was true for 24 additional isolates classified by light microscopy as ncp after ten blind passages in FCK cell cultures. Thus it appeared that in 1/3 of the cases changes in FCK cell cultures had been formerly misinterpreted as BVDV induced cytopathic effects (CPE). Of the 46 isolates which produced both ncp and cp immunoplaques 5 BVDV isolates were selected and successfully subjected to cloning. Clones of the cp biotype were developed by picking native plaques from unfixed FCK cell monolayers. In case of ncp IP, cloning was attempted by picking randomly in the spaces between visible native plaques. Pairs of clones from each of the field isolates proved to consist of pure plaque populations of cp BVDV and ncp BVDV biotypes, respectively, at the dilution of viral suspension which allowed the classification of a single IP according to morphology. Analysis of the clones using 15 monoclonal antibodies against the major viral glycoprotein revealed far-reaching antigenic homogeneity for each pair with only few but distinct exceptions.

Animals↗

Triplex formation inhibits HER-2/neu transcription in vitro.

Triplex-forming oligonucleotides (TFOs) have been shown to bind to target DNA sequences in several human gene promoters such as the c-myc oncogene, the epidermal growth factor receptor, and the dihydrofolate reductase genes. TFOs have been shown to inhibit transcription in vitro and gene expression in cell culture of the c-myc and other genes. The HER-2/neu oncogene, which is overexpressed in breast cancer and other human malignancies, contains a purine-rich sequence in its promoter, which is favorable for purine:purine:pyrimidine (R:R:Y) triplex formation. Although its function in the HER-2/neu promoter is unknown, this purine-rich site is homologous to a protein-binding sequence in the promoter of the epidermal growth factor receptor that is necessary for efficient transcription of this gene. We have shown that this sequence is a site for nuclear protein binding by incubation with a crude nuclear extract. We describe the formation of an interstrand triplex using a purine-rich oligonucleotide antiparallel to this purine-rich target sequence of the HER-2/neu promoter. Triplex formation by the oligonucleotide prevents protein binding to the target site in the HER-2/neu promoter in vitro. We have shown that this oligonucleotide is a potent and specific inhibitor of HER-2/neu transcription in an in vitro assay. The triplex target site contains a single pyrimidine base that does not conform to the R:R:Y triplex motif. In an attempt to abrogate the potentially destabilizing effects of this pyrimidine base on triplex formation, we have substituted an abasic linker for the pyrimidine residue in the triplex forming oligonucleotide. Triplex formation with the modified oligonucleotide appears to occur with approximately equivalent binding affinity. Triplex formation in the HER-2/neu oncogene promoter prevents transcription in vitro and may represent a future modality for specific inhibition of this gene in vivo.

Base Sequence↗

cDNA encoding the chicken ortholog of the mouse dilute gene product. Sequence comparison reveals a myosin I subfamily with conserved C-terminal domains.

We report the cDNA-deduced primary structure of the chicken counterpart of the murine dilute gene product, a member of the myosin I family. Comparison of the chicken and mouse sequences reveals a distinct pattern of domains of high and low sequence conservation. An internal deletion of 25 amino acids probably reflects differential mRNA processing. Compared with other myosin heavy chain molecules, sequence similarity is highest with the MYO2 gene product of Saccharomyces cerevisiae. The MYO2 protein, implicated in vectorial vesicle transport, is homologous to the dilute protein over practically its entire length. In addition, the C-terminal domain of the dilute protein is highly similar to a putative glutamic acid decarboxylase sequence cloned from mouse brain. Alternatively, this closely related clone might represent an isoform of the dilute protein derived from a second gene, potentially involved in genetic conditions related to dilute.

Amino Acid Sequence↗

Factors influencing default at a hospital colposcopy clinic.

OBJECTIVE: To identify factors reducing compliance at diagnosis, treatment, and review stages among women referred with abnormal cervical smears to a hospital colposcopy clinic. DESIGN: Retrospective analysis of sociodemographic data from hospital notes of the attenders and defaulters during one year (1989-90) and prospective collection of information by structured interviews of a sample of defaulters and attenders during five months (May-September 1990). SETTING: One hospital colposcopy clinic. PATIENTS: 238 women defaulting on two consecutive occasions and 188 attending regularly (retrospective analysis) and a subset of 40 defaulters and 24 attenders (interview sample). MAIN MEASURES: Sociodemographic data and interview responses about attitudes, behaviour, choice, accessibility cultural understanding, communications, and emotional response. RESULTS: 22 (12%) women defaulted at diagnosis, 24(13%) at treatment, 39(21%) at the first check up after treatment, and 84(45%) at the review stage; 19(10%) defaulted from the first check up after diagnostic examination revealed no need for treatment. Age and social class differed between the two groups. 181(76%) defaulters were under 30 compared with 91(48%) attenders; 14(6%) compared with 41(23%) were over 40(p < 0.001). The proportion of women in social classes 4 and 5 was 33%(20/60) for defaulters and 21%(25/120) for attenders (p < 0.05) and unemployed was 66%(158/238) and 36%(68/188) respectively. 63(28%) defaulters were pregnant compared with 11(6%) attenders (p < 0.001). More defaulters came from gynaecology or antenatal clinics. Most defaulters (93%) had child care responsibilities and they knew and understood less about colposcopy. Their explicit reasons for defaulting included child care commitments and fear and their implicit reasons lack of understanding, inaccessibility of information, and staff attitudes. CONCLUSIONS: Compliance may be improved by promoting women's understanding of treatment and encouraging health professionals to develop a service more sensitive to the various needs of women in different socioeconomic groups.

Colposcopy↗

Expression of the neuronal noradrenaline transporter in Xenopus laevis oocytes.

RNA isolated from both rat phaeochromocytoma (PC12) cells and bovine adrenal medulla was size-selected and injected into oocytes of Xenopus laevis. Expression of the neuronal noradrenaline transporter was assayed 3 days after injection by measuring the nisoxetine-sensitive noradrenaline uptake. A 2 kilobase fraction of either total RNA derived from both tissues or of polyadenylated mRNA obtained from bovine adrenal medulla caused Na(+)-dependent transport of 3H-noradrenaline in the injected oocytes.

Adrenal Gland Neoplasms↗

Psychological stress of exposure to uncontrollable noise increases plasma oxytocin in high emotionality women.

Oxytocin (OT), arginine-vasopressin (AVP), memory, and mood changes were measured in relation to the psychological stress of exposure to uncontrollable noise (UN), with the physical stress of exposure to the identical, but controllable, noise (CN) as a comparison. Four experiments were performed. In the first, UN but not CN resulted in OT increases in women but not in men; neither treatment altered plasma AVP. No significant changes were detected in the second study, but in the third women again showed an OT response to UN. In both the first and third study the OT response was found in only a proportion of the women exposed to UN. This result was analysed further in the fourth study, in which the stress-induced OT response occurred in high, but not in low, emotionality women. In the fourth, but not in the third, study there was an indication that OT increases may be associated with a general impairment of memory. There was no evidence to support an enhancement of negative memories after exposure to UN. Exposure to noise generally produced a worsening of mood, with no consistent differences between the UN and CN conditions. This is the first report of an OT response to psychological stress in human subjects.

Adult↗

Upper eyelid ptosis correction by a revised tarsal resection technique.

Many techniques have been developed for the correction of eyelid ptosis. A new tarsal plate resection technique is described for use in cases of minimal ptosis with fair to good levator function. The procedure involves a horizontal lenticular excision of the tarsal plate, placed so that equal amounts of tarsus remain above and below the excision. The height of the excision is equal to the amount of ptosis correction desired, as determined in the preoperative examination. This precision in surgical correction is the chief advantage of the procedure. The technique also spares Müller's muscle, thus retaining the lid-elevating action of that muscle. Good results have been achieved in 6 patients, some showing excellent results after nine years.

Adolescent↗

Cerebral lateralization of language in deaf and hearing people.

In Experiment 1 neither hearing nor prelingually deaf signing adolescents showed marked lateralization for lexical decision but, unlike the hearing, the deaf were not impaired by the introduction of pseudohomophones. In Experiment 2 semantic categorization produced a left hemisphere advantage in the hearing for words but not pictures whereas in the deaf words and signs but not pictures showed a right hemisphere advantage. In Experiment 3 the lexical decision and semantic categorization findings were confirmed and both groups showed a right hemisphere advantage for a face/nonface decision task. The possible effect of initial language acquisition on the development of hemispheric lateralization for language is discussed.

Adolescent↗