Seasonal variation in serum cholesterol levels in health screening populations from the U.K. and Japan.

We have performed time series analyses on data from 140,000 men and 32,000 women in the U.K. and 30,000 men and 12,000 women in Japan, seen over periods ranging from 4 to 6 1/2 years, in order to test for seasonal variation in serum cholesterol levels. In both countries and both sexes we found a strong seasonal effect, with mean cholesterol levels being some three to five percent higher in winter than in summer. Mean monthly cholesterol levels were negatively correlated with mean monthly air temperatures (r = -0.60 to -0.71). The seasonal differences observed were independent of changes in body weight, and have important implications both for long-term epidemiological or follow-up studies, and for the interpretation of patient data.

Defining normality--art or science?

The problem of defining normality, and in particular the establishment of reference ranges, is discussed. A so-called "objective" method of determining such ranges is described. It is suggested, however, that all currently used methods for defining "normal" ranges rely ultimately on a subjective choice. We propose the use of "How Often That Happens" (HOTH) graphs as an alternative to the conventional reference range. Such graphs show the frequency of results at least as extreme as any observed value. We have used such graphs, along with computer simulation models, in an attempt to describe how the frequency distribution of a given parameter changes as a population ages. Finally, an analogy is drawn between the states of "health", "illness" and "death", and the attractors which arise in non-linear dynamic systems. We conclude that the definition of normality is in fact more of an art than a science.

Seasonal variation in serum cholesterol levels--evidence from the UK and Japan.

Using data from 140,000 men and 32,000 women in the UK and 30,000 men and 12,000 women in Japan, we performed spectral analyses to test for seasonal variation in serum cholesterol levels. In both countries and both sexes we found a strong seasonal effect, cholesterol levels being some 3-5% higher in winter than in summer. This was independent of seasonal changes in body mass. Mean monthly cholesterol levels were negatively correlated with mean monthly air temperatures (r = -0.60 to -0.71). The observed seasonal differences were larger than the inter-assay coefficient of variation for the cholesterol determination method employed and have important consequences for long-term epidemiological or intervention studies.

Cloning of the HIS3 gene of Yarrowia lipolytica.

The HIS3 gene of the yeast Yarrowia lipolytica has been cloned from a genomic library by complementation of the his3 mutation of Saccharomyces cerevisiae. The gene was subsequently subcloned in Escherichia coli and characterized by restriction enzyme mapping.

Defects in diagnostic kits for determination of urate in serum.

Certain diagnostic kits that measure serum urate by the Barham and Trinder principle of enzymic liberation of oxygen and its combination with chromogens can give results for urate in fresh serum that are approximately 20% lower than results from serum stored at ambient temperature for 72 h. In fresh serum, antioxidants compete with chromogen for liberated peroxyl-oxygen. We postulate that during storage the interfering antioxidant substances are destroyed. In some diagnostic kits, L-ascorbate oxidase is added to the reaction, eliminating some but not all of this effect. We discuss defects of several commercially available kits for determination of serum urate and recommend comparing results of these kits with results from the phosphotungstic acid method as a precaution against falsely low results.

A genetic analysis of glucoamylase activity in the diastatic yeast Saccharomyces cerevisiae NCYC 625.

The wild diastatic yeast Saccharomyces cerevisiae NCYC 625 has been shown to be homozygous for the glucoamylase-specifying gene STA2. spoII-1-mapping has positioned STA2 on chromosome II. Expression of STA2 is suppressed in some but not all diploids capable of sporulation, and is also inhibited by unlinked nuclear suppressor genes (SGL) found in some S. cerevisiae tester strains. EMS-induced glucoamylase-negative mutants often contain STA2-suppressor mutations. Depending on the allelic status of GEP1, a nuclear gene which also appears able to antagonise SGL-mediated suppression, STA2 expression can be blocked in petite mutants.

Purification and properties of an extracellular glucoamylase from a diastatic strain of Saccharomyces cerevisiae.

The extracellular glucoamylase from certain strains of Saccharomyces cerevisiae can be purified from culture medium by a simple chromatographic procedure. The native enzyme is heavily glycosylated and has an Mr of about 250,000, but gel filtration indicates the existence of oligomers of larger size. Dissociation yields a form of Mr about 70,000. The glucoamylase is rich in serine and threonine and in aspartic acid plus asparagine, and has a pI of 4.62 and a pH optimum of 4.5-6.5. The thermostability and resistance to denaturants of the yeast enzyme is compared with those of two other fungal glucoamylases. Kinetic data for the yeast enzyme and a variety of substrates is presented; the enzyme is particularly ineffective in cleaving alpha-(1----6)-glycosidic bonds.

High density lipoprotein subfractions and coronary risk factors in normal men.

Plasma levels of total high density lipoprotein cholesterol (HDL) and its subfractions (HDL2 and HDL3) were measured in 366 healthy Caucasian males; these values were related to a number of coronary risk factors. On univariate statistical analysis, total HDL was negatively correlated with cigarette consumption, body mass index, and serum triglycerides, and positively associated with level of physical activity and alcohol consumption. HDL2 showed an inverse relationship with cigarette consumption, body mass index, triglycerides, and systolic blood pressure and a positive relationship with age. HDL3 was negatively correlated with cigarette smoking, body mass index, and triglycerides and positively associated with exercise level and alcohol consumption. Total HDL and HDL2 were inversely related to coronary risk rating, but HDL3 showed no significant correlation. Many of these relationships became nonsignificant after allowing for the effects of other variables. In particular, none of the HDL measurements correlated significantly with risk score after allowing for the effect of triglycerides. There is insufficient evidence at present to recommend the inclusion of HDL subfractions as routine screening tests for heart disease.

Importance of occult haematuria found at screening.

A retrospective study of the results of dipstick testing and microscopical examination of urine from 10 050 men undergoing health screening showed a prevalence of occult haematuria of 2.5%. Those patients with occult haematuria who were resident in the United Kingdom and registered with a general practitioner were identified and a questionnaire sent to their general practitioners asking what further investigations had been performed. The response rate was 92% (152/165 inquiries). Fifty nine general practitioners (39%) had not instigated any investigations. Among the 76 patients who underwent some further investigations abnormalities were found in 21 (28%); and among those fully investigated by examination of midstream urine, intravenous urography, and cystoscopy abnormalities were found in 12(50%). These included bladder neoplasms (two; one in a patient aged 37), epithelial dysplasia (one), staghorn calculi (one), and chronic reflux nephropathy (one). It is proposed that occult haematuria should be fully investigated regardless of the age of the patient.

Two biochemically and genetically different forms of L dsRNA of Saccharomyces cerevisiae exist: One form, L2, is correlated.

Nucleic acid extracted from killer strains of Saccharomyces cerevisiae and run on agarose gels under sub-optimal conditions for M dsRNA yielded two species of L dsRNA (L1 and L2) which migrated at slightly different rates. L2 dsRNA was shown to be dependent upon MAK3, MAK10 and PES1 but not MAK1 nuclear genes for its maintenance. L1 was shown to be independent of all of these genes.[HOK] a non-Mendelian genetic element which enables a replication-defective M genome, [KIL-sd1], to be maintained in a SKl (+) host (Wickner and Toh-e 1982) was found to be present in an M-o derivative of the strain K7 which possesses L2 but not L1. Curing of L2 at elevated temperatures resulted in a co-curing of [HOK] and it is therefore concluded that either L2 is equivalent to or else it encodes [HOK].

Production and genetic analysis of yeast cybrids.

Data presented here demonstrate that fusion of protoplasts of two different haploid strains of Saccharomyces cerevisiae having the same mating type leads to the formation of "fusants" and "cytoplasmic hybrids". The nuclear and cytoplasmic genome of a "fusant" combine those of the parent haploid strains. The "cytoplasmic hybrid" possesses the haploid genome of one parent and the combined cytoplasmic genomes of both. In mouse cells lines such products have been termed "cybrids" and this term has therefore been adopted here (Bunn and Wallace 1974).

Characterisation of the LdsRNA encoded mRNA of yeast.

Radioactive messenger RNA (mRNA) was isolated from a Saccharomyces cerevisiae strain containing the L double stranded RNA (dsRNA) species. This mRNA was hybridised to LdsRNA isolated from the same strain. Analysis of the hybrid formed shows it to be of a similar size to the LdsRNA. It is concluded from this result that the mRNA complementary to the -ve strand of the LdsRNA is polycistronic.When the total mRNA is fractionated on oligo (dT) cellulose, RNA complementary to the -ve strand of LdsRNA is found only in the non-binding fraction. When LdsRNA is fractionated on oligo (dT) cellulose the majority is found in the non-binding fraction. It is concluded that neither the LdsRNA genome nor the mRNA it encodes have poly(A) tails of a significant length.

The genetic control of DS-RNA virus-like particles associated with Saccharomyces cerevisiae killer yeast.

Previous results have indicated that laboratory strains of yeast possessing two types of dsRNA virus-like particles, V1 and V2, are capable of producing a killer toxin which kills sensitive strains. This paper reports on genetic crosses which correlate the presence of these particles both with a host nuclear gene +/-/mak1 and with the production of a killer toxin. The results show that: (i) V1 particles are inherited independently of the +/-/mak1 gene. (ii) V2 particles are present only in combination with those of V1 and the +/- allele of the +/-/mak1 nuclear gene.