Tired,weak, or in need of rest: fatigue among general practice attenders.

OBJECTIVES--To determine the prevalence and associations of symptoms of fatigue. DESIGN--Questionnaire survey. SETTING--London general practice. PARTICIPANTS--611 General practice attenders. MAIN OUTCOME MEASURES--Scores on a fatigue questionnaire and reasons given for fatigue. RESULTS--10.2% Of men (17/167) and 10.6% of women (47/444) had substantial fatigue for one month or more. Age, occupation, and marital status exerted minor effects. Subjects attributed fatigue equally to physical and non-physical causes. Physical ill health, including viral infection, was associated with more severe fatigue. Women rather than men blamed family responsibilities for their fatigue. The profile of persistent fatigue did not differ from that of short duration. Only one person met criteria for the chronic fatigue syndrome. CONCLUSIONS--Fatigue is a common complaint among general practice attenders and can be severe. Patients may attribute this to physical, psychological, and social stress.     

A third class I major histocompatibility complex antigen encoded by a gene in the D region of the H-2 d haplotype recognized by cytotoxic T lymphocytes

The D region of the H-2 ^d haplotype contains five class I genes: H-2D ^d , D2 ^d , D3 ^d , D4 ^d and H-2L ^d . Although previous studies have suggested the presence of D-end encoded class I molecules in addition to H-2D^d and H-2L^d, segregation of genes encoding such molecules has not been demonstrated. In this report we have used cãtotoxic T lymphocytes (CTL) to examine the D region of the H-2 ^d haplotype for the presence of additional class I molecules. CTL generated in (C3H × B6.K1)F₁ (K ^k D ^k , K ^b D ^b ) mice against the hybrid class I gene product Q10^d/L^d expressed on L cells cross-react with H-2L^d but not H-2D^d molecules, as determined by lysis of transfected cells expressing H-2L^d but not H-2D^d. Although H-2L^d-specific monoclonal antibodies (mAb) completely inhibit H-2L^d-specific CTL from killing B10.A(3R) (K ^b D ^d L ^d ) target cells, only partial inhibition of anti-Q10 CTL-mediated lysis was observed, suggesting the presence of an additional D-end molecule as a target for these latter CTL. To identify the region containing the gene encoding the Q10 cross-reactive molecule, we show that anti-Q10 CTL lyse target cells from a D-region recombinant strain B10.RQDB, which has H-2D ^d , D2 ^d , D3 ^d , D4 ^d , and H-2D ^b but not the H-2L ^d H-2 ^d , and H-2L ^d (including D2 ^d , D3 ^d , and D4 ^d , lacks this anti-Q10 CTL target molecule. Together, these data demonstrate that a class I gene mapping between H-2D ^d and H-2L ^d encodes an antigen recognozed by anti-Q10 CTL. A likely candidate for this gene is D2 ^d , D3 ^d or D4 ^d .     

Blood lipid concentrations and other cardiovascular risk factors: distribution,prevalence, and detection in Britain

To establish the distribution of blood lipid concentrations and the prevalences of other risk factors for cardiovascular disease in Britain 12 092 men and women aged 25-59 in Glasgow, Leicester, London, and Oxford were studied. Subjects were selected by opportunistic case finding, in which patients consulting their general practitioner for any reason were offered a health check by appointment, or random selection from age-sex registers, in which an invitation for a health check was posted. The overall rate of response was 73%, being 91-94% by opportunistic case finding and 36-63% by random selection. At the health check subjects answered a brief questionnaire about risk factors for cardiovascular disease, and their height, weight, and blood pressure were recorded; a blood sample was taken for measuring plasma concentrations of cholesterol, triglyceride, high density lipoprotein cholesterol, and glucose.The mean cholesterol concentrations were 5·9 (SD 1·2) and 5·8 (1·2) mmol/l in men and women, respectively. In London the mean value was 5·5 (1·2) mmol/l for both men and women and was significantly lower than mean values in the three other centres, among which there were no significant differences. In men and women aged 25-29 concentrations were similar but they increased in men until the age of 45-49, after which they showed no further increase; in women concentrations did not increase until the age of 40-44 and by the age of 50-59 values were higher than in men. Mean triglyceride concentrations were significantly higher in men than in women (1·8 (1·4) v 1·3 (0·9) mmol/l, respectively), and trends with age were similar to those for cholesterol concentrations, except that at no age were values higher in women than in men. Mean triglyceride values overall were higher in Glasgow and London than in Oxford and Leicester. Body mass index was higher in Glasgow and London than in the other two centres and correlated with systolic and diastolic blood pressures and triglyceride concentration. In addition, subjects in Glasgow smoked significantly more than those in the other centres. These observations could contribute to the higher rate of coronary heart disease in Glasgow. Plasma lipid concentrations and the prevalences of other risk factors for cardiovascular disease were similar in subjects selected by opportunistic case finding and by random selection.In Britain cholesterol values have changed little during the past 12 years despite dietary recommendations and health education. Identifying subjects at particularly high risk of coronary heart disease is required to supplement advice to the general population to reduce the prevalence of this disease. Opportunistic case finding would be an appropriate method of identifying such subjects in general practice, although none of the potential markers for hyperlipidaemia was particularly useful in identifying all subjects at high risk.     

Histone H3 N-terminal mutations allow hyperactivation of the yeast GAL1 gene in vivo.

Recent work has shown that the yeast histone H4 N-terminus, while not essential for viability, is required for repression of the silent mating loci and activation of GAL1 and PHO5 promoters. Because histone H3 shares many structural features with histone H4 and is intimately associated with H4 in the assembled nucleosome, we asked whether H3 has similar functions. While the basic N-terminal domain of H3 is found to be non-essential (deletion of residues 4-40 of this 135 amino acid protein allows viability), its removal has only a minor effect on mating. Surprisingly, both deletions (of residues 4-15) and acetylation site substitutions (at residues 9, 14 and 18) within the N-terminus of H3 allow hyperactivation of the GAL1 promoter as well as a number of other GAL4-regulated genes including GAL2, GAL7 and GAL10. To a limited extent glucose repression is also alleviated by H3 N-terminal deletions. Expression of another inducible promoter, PHO5, is shown to be relatively unaffected. We conclude that the H3 and H4 N-termini have different functions in both the repression of the silent mating loci and in the regulation of GAL1.     

The cytochrome oxidase II gene in mitochondria of the sugar-beetBeta vulgaris L.

We have cloned and analyzed the sugar-beet mitochondrial gene for cytochrome oxidase subunit II (coxII). The sugar-beet and its deduced amino acid sequence were compared to its homologouscoxII gene sequences from both monocot and dicot plants. It was found to be highly conserved (89–95%) compared to homologue in other plant species. The 780 bp coding sequence of the sugar beetcoxII gene is interrupted at position 383 by a 1463 bp intron. This intron contains an additional 107 bp sequence that is not found in any of the plantcoxII genes studied thus far. The structure of the intron suggests that a large intron existed in an ancestralcoxII gene before monocots and dicots diverged in evolution. Three CGG codons in the sugar-beetcoxII coding sequence align with conserved tryptophan residues in the homologous gene of other species, suggesting that RNA editing takes place also in sugar-beet mitochondria. In 13 out of 24 codons ofcoxII mRNA that were found to be edited in four other plants, the sugar-beet gene already utilizes the edited codons. This phenomenon may indicate that the mitochondrial genome in sugar-beet is phylogenetically more archaic relative to these plants. An additional sequence of 279 bp that is identical to the first exon ofcoxII was identified in the mtDNA of the sugar-beet. This pseudo-gene is transcribed and its existence in the mitochondrial genome is unexplained.     

N-terminal amino-acid sequence of pig kidney dipeptidyl peptidase IV solubilized by autolysis.

The N-terminal amino-acid sequence of the intrinsic membrane protein dipeptidyl peptidase IV (DP IV) was determined. The protein was isolated from pig kidney and solubilized by autolysis at pH 3.8. The first 34 amino acids were sequenced and indicated approximately 78% identity to the N-terminal sequence of rat liver DP IV.     

Binding of soluble fibronectin and its subsequent incorporation into the extracellular matrix by early and late passage human skin fibroblasts

The specific binding of soluble 125I-labeled human plasma fibronectin (125I-HFN-P) to confluent cultures of early and late passage human skin fibroblasts was investigated. Previous studies of HFN-P bound to fibroblast cell layers indicated that HFN-P was present in the cultures in two separate pools, distinguishable on the basis of their solubility in 1% deoxycholate. Pool I contained deoxycholate-soluble fibronectin (cell-associated), whereas Pool II contained deoxycholate-insoluble fibronectin (matrix-associated). Time course studies indicated that HFN-P was initially incorporated into Pool I and then accumulated into Pool II (McKeown-Longo, P.J., and Mosher, D.F. (1983) J. Cell Biol. 97, 466-472). Examination of the kinetics of 125I-HFN-P binding to Pool I of early and late passage cultures revealed that both cultures required 2-4 h to approach steady-state conditions. Other kinetic studies showed that the rates of loss of 125I-HFN-P from either Pool I or Pool II were similar for both cultures. However, the late passage cultures bound greater than twice as much fibronectin into Pool I, per cell, than the early passage cultures. This difference was not related to a difference in the level of endogenously produced fibronectins accumulating in the medium. Late passage cultures incorporated 125I-HFN-P into the deoxycholate-insoluble Pool at an average rate 2.6 times greater than early passage cultures. The late passage cultures also chased a greater percent of their Pool I-bound fibronectin into Pool II and a lower percent into the chase medium. These results indicate that early and late passage cultures of human fibroblasts exhibit differences in the binding of soluble fibronectin and in the extent to which they incorporate soluble fibronectin into the extracellular matrix.     

M?ssbauer spectroscopic studies of the cores of human, limpet and bacterial ferritins

Ferritin cores from human spleen, limpet (Patella vulgata) haemolymph and bacterial (Pseudomonas aeruginosa) cells have been investigated using 57Fe M?ssbauer spectroscopy. The M?ssbauer spectra were recorded over a range of temperatures from 1.3 to 78 K, all the spectra are quadrupole-split doublets with similar quadrupole splittings and isomer shifts, characteristic of iron(III), while at sufficiently low temperatures the spectra of all the samples show well-resolved magnetic splitting. At intermediate temperatures, the spectra from the human ferritin exhibit typical superparamagnetic behaviour, while those from the bacterial ferritin show behaviour corresponding to a transition from a magnetically ordered to a paramagnetic state. The spectra from the limpet ferritin show a complex combination of the two effects. The results are discussed in terms of the magnetic behaviour of small particles. The data are consistent with magnetic ordering temperatures of about 3 and 30 K for the bacterial and limpet ferritin cores, respectively, while the data indicate that the magnetic ordering temperature for the human ferritin cores must be above 50 K. These differences are interpreted as being related to different densities of iron in the cores and to variations in the composition of the cores. The human ferritin cores are observed to have a mean superparamagnetic blocking temperature of about 40 K, while that of the limpet ferritin cores is about 25 K. This difference is interpreted as being due not only to different mean numbers of iron atoms in the two types of core but also to the higher degree of crystallinity in the cores of the human ferritin.     

Genetic Analysis of a Mouse t Complex Locus That Is Homologous to a Kidney Cdna Clone

A mouse kidney cDNA clone, pMK174, identifies restriction fragment length polymorphisms (RFLPs) that map to two unlinked loci. One, designated D17Rp17, has been mapped near quaking, (qk), on chromosome 17 using three sets of recombinant inbred (RI) strains. A study of several t haplotypes resulted in the identification of t-specific alleles of D17Rp17 that map to the proximal half of the t complex. Neither t-specific nor wild-type D17Rp17 alleles are present in chromosomes carrying either the T Orleans (TtOrl) or the T hairpin tail (Thp) deletions. Comparison with other molecular markers indicates that pMK174 identifies a new proximal t complex locus, Rp17. The second locus identified by pMK174, termed D4Rp18, is tentatively assigned to chromosome 4 by mouse-Chinese hamster somatic cell hybrid analysis.