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Biomedical subjects

H Gross

Publications and source records attributed to H Gross.

139 records · Page 8Linked to original sources

Acetylcholine receptor antibodies in myasthenia gravis.

A multivariate statistical analysis of levels of serum acetylcholine receptor antibody (AChR Ab) obtained from 197 patients with various clinical forms of myasthenia gravis (MG) was performed. Elevated AChR Ab levels are specific for MG, but normal AChR Ab levels do not rule out MG. Patients in remission or with purely ocular MG had the lowest incidence of elevation of serum AChR Ab levels, while patients with generalized, severe MG, particularly in the presence of thymoma, tended to have the greatest antibody elevations. Corticosteroids depressed AChR Ab levels, but thymectomy did not exert a consistent effect on antibody levels within a 24- to 30-month postoperative period. The relatively low 55% positivity of antibody elevations in all 197 patients probably reflects the use of heterologous (rat) AChR.

Adrenal Cortex Hormones↗

Imaging the asymmetrical DNA bend induced by repressor activator protein 1 with scanning tunneling microscopy.

The yeast Repressor Activator Protein 1 (RAP1) binds a 13-bp consensus found in many transcriptional regulatory regions, in silencer elements, and in telomeric repeat DNA of Saccharomyces cerevisiae. Gel retardation assays suggest that RAP1 bends DNA as it binds, with the vertex of the angle located 5' of the consensus. We show that removal of 230 aa in the N-terminus of RAP1 reduces the aberrant electrophoretic mobility of the protein-DNA complex, while removal of a C-terminal domain of RAP1 causes even greater distortion. To demonstrate that the aberrant electrophoretic mobility is really due to a bend in the double helix, the RAP1-DNA complex was analyzed by Scanning Tunnelling Microscopy (STM). The efficiency and accuracy of binding is checked in parallel by standard Transmission Electron Microscopy (TEM). Due to the use of high-angle shadowing of freeze-dried samples at low temperatures, the STM images allow us to confirm that RAP1 binding induces a DNA bend > 50 degrees, while the binding of the minimal DNA-binding domain shows significantly less distortion of the DNA helix.

DNA↗

Localization of reactive cysteine residues by maleidoyl undecagold in the mitochondrial creatine kinase octamer.

Octamers of mitochondrial creatine kinase (Mi-CK) were modified with the thiol-specific reagents N-ethylmaleimide or the gold-coupled derivative, maleidoyl undecagold. The kinetics of inhibition of the Mi-CK catalysis was shown to be comparable for both reagents, suggesting that the large gold cluster complex is accessible to the reactive cysteines. SDS-PAGE analysis revealed that two of eight cysteines per Mi-CK monomer were labeled with maleidoyl undecagold with a similar affinity for the functional maleimide group. Gel exclusion chromatography of labeled molecules showed that the octameric structure of Mi-CK was preserved after thiol modification. Freeze-dried gold-labeled octamers visualized by electron microscopy under cryo-conditions were enhanced in contrast and showed a well-preserved fourfold symmetry of the end-on view. Image analysis of gold-labeled Mi-CK exhibited an averaged end-on view with four strong contrast signals located at the periphery of the octamer, whereas the center of the molecule remained electron translucent. We conclude that the two cysteine residues per monomer labeled with maleidoyl undecagold are located at the octamer's perimeter and we discuss the possible role of these reactive cysteines in enzyme catalysis.

Animals↗

Activity patterns and time allocation during pregnancy: a longitudinal study of British women.

OBJECTIVE: Few studies provide data regarding the integrated everyday activities of Western pregnant women. The study aimed to quantify changes in the daily activity of women during pregnancy and to examine whether pregnancy has a differential impact on different activity domains. DESIGN: A prospective, longitudinal study of maternal time allocation and activity was carried out. METHODS: The time allocation patterns of 57 healthy nulliparous pregnant women were assessed at 16, 25, 34 and 38 weeks gestation by semi-structured interview. Mean total daily activity levels (DALs) were estimated according to the intensity and duration of each activity reported. Self-reported activity was sub-divided into occupational, recreational, domestic and nocturnal activity ratios. RESULTS: From 16 to 34 weeks gestation mean self-reported DAL declined significantly from 1.54 to 1.40 METS (Metabolic Equivalent TEE Score, where TEE is total energy expenditure) (p < 0.001). In the different activity domains, mean occupational activity ratio decreased (p < 0.002) whilst nocturnal activity ratio increased (p < 0.002) from 16 to 34 weeks. Mean recreational activity ratio decreased significantly between 25 and 38 weeks (p < 0.001) but no significant changes were observed in mean domestic activity ratio. CONCLUSIONS: Low-risk pregnancy has a differential impact on occupational, recreational and domestic domains. Economies in energy expenditure appear to be made in occupational and recreational activity while domestic activities are largely maintained during pregnancy. Changes in physical activity may be influenced more by the type of activity rather than the intensity of activity.

Adolescent↗

Surface topography of microtubule walls decorated with monomeric and dimeric kinesin constructs.

The surface topography of opened-up microtubule walls (sheets) decorated with monomeric and dimeric kinesin motor domains was investigated by freeze-drying and unidirectional metal shadowing. Electron microscopy of surface-shadowed specimens produces images with a high signal/noise ratio, which enable a direct observation of surface features below 2 nm detail. Here we investigate the inner and outer surface of microtubules and tubulin sheets with and without decoration by kinesin motor domains. Tubulin sheets are flattened walls of microtubules, keeping lateral protofilament contacts intact. Surface shadowing reveals the following features: (i) when the microtubule outside is exposed the surface relief is dominated by the bound motor domains. Monomeric motor constructs generate a strong 8 nm periodicity, corresponding to the binding of one motor domain per alpha-beta-tubulin heterodimer. This surface periodicity largely disappears when dimeric kinesin motor domains are used for decoration, even though it is still visible in negatively stained or frozen hydrated specimens. This could be explained by disorder in the binding of the second (loosely tethered) kinesin head, and/or disorder in the coiled-coil tail. (ii) Both surfaces of undecorated sheets or microtubules, as well as the inner surface of decorated sheets, reveal a strong 4 nm repeat (due to the periodicity of tubulin monomers) and a weak 8 nm repeat (due to slight differences between alpha- and beta-tubulin). The differences between alpha- and beta-tubulin on the inner surface are stronger than expected from cryo-electron microscopy of unstained microtubules, indicating the existence of tubulin subdomain-specific surface properties that reflect the surface corrugation and hence metal deposition during evaporation. The 16 nm periodicity visible in some negatively stained specimens (caused by the pairing of cooperatively bound kinesin dimers) is not detected by surface shadowing.

Freeze Drying↗

An arm phantom: a digital simulation system for testing sphygmomanometers.

An arm phantom for testing non-invasive blood pressure measuring instruments under reproducible and real conditions has been developed. Signal records, recorded on patients and validated by a reference method, are played into the instruments to be tested using a combination of an electro-pneumatic and an electro-acoustic converter. For each of 90 patients a database contains records of at least three different kinds of signal: cuff pressure oscillations, Korotkoff sounds (except in neonates) and cuff pressure. As the inflation and deflation rate varies between different sphygmomanometers the control and synchronization of the signal output are ensured as a function of the instantaneous cuff pressure, measured continuously by the system. A segmented output procedure synchronizes the data flow during the test procedure. The records of blood pressure signals are separated in different signal groups, containing only one pressure oscillation and Korotkoff sound respectively, whereas the instantaneous cuff pressure determines the signal group to be selected. Suitable interfaces to the sphygmomanometers under test consist of two specifically developed signal converters, an electro-pneumatic converter and an electro-acoustic converter. The system generates both cuff pressure oscillations and Korotkoff sounds from real data earlier recorded on human subjects. It allows any inflation and deflation rate of the cuff pressure to be applied, considers the variability of the pulse rate occurring in the same data record and finally it allows the superposition of artefacts. The arm phantom can replace clinical trials. The possibility of testing the limits of the performance of sphygmomanometers has been considerably extended.

Arm↗

Eleven years of experience with depot neuroleptics.

The authors prescribe depot neuroleptics almost exclusively to chronic schizophrenics; the minimum duration of treatment is 6 months; 63% of long-acting neuroleptics are fluphenazine decanoate or flupentixol decanoate (main indication: inactive schizophrenics), 37% are clopentixol decanoate (main indication: productive and agitated schizophrenics). Safety, compliance and pharmacokinetics are much better with long-acting neuroleptics (LANs) than with oral medications, but the authors question the reality of a dose reduction as compared to oral neuroleptics since the latter are taken irregularly. The lowest possible dose and an increase of intervals between injections are advocated, because of less cumulative effects and less tardive dyskinesias. LANs bring about a quantitative reduction of symptomatology, but not a cure of the schizophrenic process: most patients relapse upon discontinuation.

Antipsychotic Agents↗