Diagnostic management of orthostatic intolerance in the workplace.

OBJECTIVE: Orthostatic intolerance (OI) is a syndrome that is characterised by headache, concentration difficulties, palpitation of the heart, dizziness associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high when the sufferer is in the upright posture. In contrast to other forms of orthostatic dysregulation - orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS) - OI, hitherto, could be diagnosed only by a tilt table examination, with high expenditure. In this paper we examine the reliability and validity of a questionnaire as a screening instrument for OI. METHODS: We studied 138 young men (mean age 21.6 years) who were undergoing military service. After a medical check and filling in the questionnaire, the participants underwent a tilt table test including monitoring of blood pressure, heart rate and plasma catecholamines, in the supine position and during 30 min of standing. The questionnaire consisted of ten items registering presence and frequency of typical OI symptoms. RESULTS: Probands (104) showed normal tilt table test results. OI was diagnosed in 14 probands, OH in 6 and POTS in 14. The OI participants scored significantly higher in the questionnaire than the healthy subjects did: the mean score of the OI group was 22.6, the healthy participants had a mean score of 3.9. Participants with POTS had a mean score of 13.5 and subjects with OH had a mean score of 17.0. Reliability analysis showed a Cronbach's alpha of 0.888. Validity analysis showed that 93.5% of the probands with any kind of orthostatic dysregulation can be detected. CONCLUSIONS: We were able to establish a short questionnaire as a reliable and valid screening instrument for OI. Usage of this questionnaire can simplify enormously the diagnostic management of patients with suspected OI.

Eukaryotically encoded and chloroplast-located rubredoxin is associated with photosystem II.

We analyzed a eukaryotically encoded rubredoxin from the cryptomonad Guillardia theta and identified additional domains at the N- and C-termini in comparison to known prokaryotic paralogous molecules. The cryptophytic N-terminal extension was shown to be a transit peptide for intracellular targeting of the protein to the plastid, whereas a C-terminal domain represents a membrane anchor. Rubredoxin was identified in all tested phototrophic eukaryotes. Presumably facilitated by its C-terminal extension, nucleomorph-encoded rubredoxin (nmRub) is associated with the thylakoid membrane. Association with photosystem II (PSII) was demonstrated by co-localization of nmRub and PSII membrane particles and PSII core complexes and confirmed by comparative electron paramagnetic resonance measurements. The midpoint potential of nmRub was determined as +125 mV, which is the highest redox potential of all known rubredoxins. Therefore, nmRub provides a striking example of the ability of the protein environment to tune the redox potentials of metal sites, allowing for evolutionary adaption in specific electron transport systems, as for example that coupled to the PSII pathway.

Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc.

BACKGROUND: Necrolytic acral erythema is a recently described necrolytic erythema that is unique in its exclusive acral location and strong association with hepatitis C. OBSERVATION: We report the first case of necrolytic acral erythema in the United States. The patient is a 43-year-old black woman who presented with a 4-year history of tender, flaccid blisters localized to the dorsal aspect of her feet. Serum zinc and glucagon levels were normal. Serum antibodies were positive for hepatitis C, and a liver biopsy specimen showed chronic hepatitis. She was successfully treated with interferon alfa-2b and zinc. We review all previously reported cases. CONCLUSIONS: Necrolytic acral erythema is a distinct entity. In a review of the literature, most patients were between 35 and 55 years of age, although 1 patient was 12 years old. Five of 8 patients were female. Four of 7 patients described previously were treated with variable success using oral zinc sulfate and amino acids, whereas 2 were successfully treated with interferon alfa. All patients were infected with hepatitis C. Necrolytic acral erythema appears to be a skin disorder linked to infection with hepatitis C virus that responds to treatment with interferon alfa and oral zinc.

X-ray absorption spectroscopy on layered photosystem II membrane particles suggests manganese-centered oxidation of the oxygen-evolving complex for the S0-S1, S1-S2, and S2-S3 transitions of the water oxidation cycle.

By application of microsecond light flashes the oxygen-evolving complex (OEC) was driven through its functional cycle, the S-state cycle. The S-state population distribution obtained by the application of n flashes (n = 0. 6) was determined by analysis of EPR spectra; Mn K-edge X-ray absorption spectra were collected. Taking into consideration the likely statistical error in the data and the variability stemming from the use of three different approaches for the determination of edge positions, we obtained an upshift of the edge position by 0.8-1.5, 0.5-0.9, and 0.6-1.3 eV for the S0-S1, S1-S2, and S2-S3 transitions, respectively, and a downshift by 2.3-3.1 eV for the S3-S0 transition. These results are highly suggestive of Mn oxidation state changes for all four S-state transitions. In the S0-state spectrum, a clearly resolved shoulder in the X-ray spectrum around 6555 eV points toward the presence of Mn(II). We propose that photosynthetic oxygen evolution involves cycling of the photosystem II manganese complex through four distinct oxidation states of this tetranuclear complex: Mn(II)-Mn(III)-Mn(IV)2 in the S0-state, Mn(III)2-Mn(IV)2 in the S1-state, Mn(III)1-Mn(IV)3 in the S2-state, and Mn(IV)4 in the S3-state.

Structure and orientation of the oxygen-evolving manganese complex of green algae and higher plants investigated by X-ray absorption linear dichroism spectroscopy on oriented photosystem II membrane particles.

X-ray absorption spectroscopy at the Mn K-edge has been performed on multilayers of photosystem II-enriched fragments of the native thylakoid membrane prepared from a higher plant (spinach) and a unicellular green alga (Scenedesmus obliquus). Spectra collected for various angles between the prevailing orientation of the thylakoid membrane normal and the X-ray electric field vector contain information on the atomic structure of the tetranuclear manganese complex of photosystem II (PS II) and its orientation with respect to the membrane normal. The previously used approach for evaluation of the dichroism of extended X-ray absorption fine structure (EXAFS) spectra [George, G. N., et al. (1989) Science 243, 789-791] is modified, and the following results are obtained for PS II in its dark-stable state (S1-state): (1) structure and orientation of the PS II manganese complexes of green algae and higher plants are highly similiar or fully identical; (2) two 2.7-A vectors, which, most likely, connect the Mn nuclei of a planar Mn2(mu-O2) structure, are at an average angle of 80 degrees +/- 10 degrees with respect to the thylakoid normal; (3) the plane of the Mn2(mu-O2) structures is rather in parallel with the thylakoid plane than perpendicular. Structural models for the oxygen-evolving manganese complex and its orientation in the thylakoid membrane are discussed within the context of the presented results.

A nontransportable substrate for lactose permease.

A substrate for lactose permease of Escherichia coli was synthesized that binds to the protein with a relatively high affinity, but is not transported to any detectable extent. This substrate, 6'-[(N-phenylalanylphenylalanyl)amino]hexyl 1-thio-beta-D-galactoside, is a peptide galactoside composed of a bulky aromatic dipeptide that is linked to galactose via an aminohexyl spacer. Binding of the peptide galactoside to lactose permease in cytoplasmic membranes was determined in a competition assay yielding a dissociation constant of 150 microM. Transport was measured by a counterflow assay using lipid vesicles with reconstituted lactose permease. An upper limit for the rate constant of transport was obtained as 0.02 s-1, 3 orders of magnitude smaller than the value for lactose.

Contributions of specific cell information to judgments of interevent contingency.

College students considered the possible effect of an experimental drug on a skin rash. The information came from a 2 x 2 contingency table involving receipt or nonreceipt of the drug and improvement or nonimprovement of the rash: Cell A = receipt-improvement; Cell B = receipt-nonimprovement; Cell C = nonreceipt-improvement; Cell D = nonreceipt-nonimprovement. Without numerical information. Ss judged cells to be ordered A greater than B greater than C greater than D. The same order held when the contribution of each cell was derived from the contingency judgments of other subjects given numerical information. No such consistency was seen when one group of Ss made both judgments: whether individual Ss equally or unequally assessed the importance of the four cells, their contingency estimates showed cell use to be ordered A greater than B greater than C greater than D. These findings may result from strong biases that Ss harbor in processing contingency information.