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Biomedical subjects

H Hemilä

Publications and source records attributed to H Hemilä.

At least 19 recordsLinked to original sources

Physical activity and the risk of pneumonia in male smokers administered vitamin E and beta-carotene.

It has been proposed that moderate exercise may enhance the immune system. We evaluated whether physical activity at work or at leisure is associated with the risk of pneumonia, and whether the antioxidants vitamin E and beta-carotene affect pneumonia risk in physically active people. A cohort of 16 804 male smokers aged 50-69 years and working at study entry was drawn from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which examined the effect of vitamin E, 50 mg/day, and beta-carotene, 20 mg/day, on lung and other cancers. Physical activity at work, and the type of leisure-time exercise, were recorded at study entry. We retrieved the first occurrence of hospital-treated pneumonia during a 3-year follow-up from the National Hospital Discharge Register (133 cases). Physical activity at work and at leisure had no association with the risk of pneumonia. In participants with physically loading jobs, neither vitamin E nor beta-carotene affected the risk of pneumonia. In participants carrying out moderate or heavy exercise at leisure, beta-carotene had no effect, but vitamin E reduced the risk of pneumonia by 50% (95% CI: 16-70%). Previously, exercise has been shown to affect diverse laboratory measures of the immune system which are, however, only surrogate markers for the resistance to infections. The lack of association between physical activity and the risk of pneumonia observed in our study emphasizes the problem of drawing conclusions from surrogate end points. The finding that vitamin E reduced the risk of pneumonia in persons carrying out leisure-time exercise warrants further study.

Aged↗

Vitamin C and other compounds in vitamin C rich food in relation to risk of tuberculosis in male smokers.

To examine whether vitamin C rich food consumption and related vitamin C intake are associated with the risk of tuberculosis, the authors analyzed 167 incident cases of tuberculosis during a median follow-up time of 6.7 years in a clinical trial cohort of 26,975 Finnish men for whom they had baseline dietary data. A highly statistically significant inverse association between calculated vitamin C intake and the incidence of tuberculosis was found, but adjustment for non-dietary factors weakened the association to nonsignificant. Furthermore, the risk of tuberculosis decreased with increasing intake of fruits, vegetables, and berries independent of vitamin C intake. Subjects who had dietary vitamin C intake >90 mg/day and who consumed more than the average amount of fruits, vegetables, and berries had a significantly lower risk of tuberculosis (adjusted relative risk = 0.40; 95% confidence interval 0.24, 0.69). Associations between dietary vitamin C intake and occurrence of various diseases without proper control of confounding have often been interpreted as causal. These findings show that such associations can be confounded even by some other dietary components. Lower tuberculosis incidence in subjects who consumed more fruits, vegetables, and berries poor in vitamin C suggests that other compounds in such a diet may reduce the risk of tuberculosis.

Aged↗

Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit.

Placebo-controlled trials have shown that vitamin C supplementation decreases the duration and severity of common cold infections. However, the magnitude of the benefit has substantially varied, hampering conclusions about the clinical significance of the vitamin. In this paper, 23 studies with regular vitamin C supplementation (> or = 1 g/day) were analyzed to find out factors that may explain some part of the variation in the results. It was found that on average, vitamin C produces greater benefit for children than for adults. The dose may also affect the magnitude of the benefit, there being on average greater benefit from > or = 2 g/day compared to 1 g/day of the vitamin. In five studies with adults administered 1 g/day of vitamin C, the median decrease in cold duration was only 6%, whereas in two studies with children administered 2 g/day the median decrease was four times higher, 26%. The trials analyzed in this work used regular vitamin C supplementation, but it is conceivable that therapeutic supplementation starting early at the onset of the cold episode could produce comparable benefits. Since few trials have examined the effects of therapeutic supplementation and their results have been variable, further therapeutic trials are required to examine the role of vitamin C in the treatment of colds.

Adult↗

Vitamin C and acute respiratory infections.

So far over 60 studies have examined the effects of vitamin C on the common cold. No effect on common cold incidence was observed in the six largest studies, indicating that vitamin C has no preventive effects in normally nourished subjects in the Western countries. There are, however, smaller studies reporting benefit. In three trials of subjects under heavy acute physical stress, common cold incidence decreased by on average 50%, and in four trials of British males common cold incidence decreased by on average 30% in the vitamin C groups. The dietary vitamin C intake in the UK is low, and consequently the benefit may be due to the correction of marginal deficiency, rather than high vitamin doses. Regular vitamin C supplementation (> or =1 g/day) has quite consistently reduced the duration of colds, but the size of the benefit has varied greatly. In the four largest studies the duration of colds was reduced only by 5%. In two of these studies, however, absence from school and work was reduced by 14-21% per episode, which may have practical importance. Three controlled studies recorded a reduction of at least 80% in the incidence of pneumonia in the vitamin C group, and one randomised trial reported substantial treatment benefit from vitamin C in elderly UK patients hospitalized with pneumonia or bronchitis. It seems that the preventive effects of supplementation are mainly limited to subjects with low dietary vitamin C intake, but therapeutic effects may occur in wider population groups. Further carefully designed trials are needed to explore the effects of vitamin C.

Ascorbic Acid↗

Vitamin C intake and susceptibility to the common cold.

Although the role of vitamin C in common cold incidence had been studied extensively, the level of vitamin C intake has not been unequivocally shown to affect the incidence of colds. In the present study the six largest vitamin C supplementation (> or = 1 g/d) studies, including over 5000 episodes in all, have been analysed, and it is shown that common cold incidence is not reduced in the vitamin C-supplemented groups compared with the placebo groups (pooled rate ratio (RR) 0.99; 95% CI 0.93, 1.04). Consequently these six major studies give no evidence that high-dose vitamin C supplementation decreases common cold incidence in ordinary people. Nevertheless, the analysis was continued with the hypothesis that vitamin C intake may affect common cold susceptibility in specific groups of people. It was assumed that the potential effect of supplementation might be most conspicuous in subjects with low dietary vitamin C intake. The average vitamin C intake has been rather low in the UK and plasma vitamin C concentrations are in general lower in males than in females. In four studies with British females vitamin C supplementation had no marked effect on common cold incidence (pooled RR 0.95; 95% CI 0.86, 1.04). However, in four studies with British male schoolchildren and students a statistically highly significant reduction in common cold incidence was found in groups supplemented with vitamin C (pooled RR 0.70; 95% CI 0.60, 0.81). Thus, these studies with British males indicate that vitamin C intake has physiological effects on susceptibility to common cold infections, although the effect seems quantitatively meaningful only in limited groups of people and is not very large.

Adolescent↗

Vitamin C supplementation and the common cold--was Linus Pauling right or wrong?

In 1970 Linus Pauling claimed that vitamin C prevents and alleviates the episodes of the common cold. Pauling was correct in concluding from trials published up till then, that in general vitamin C does have biological effects on the common cold, but he was rather over-optimistic as regards the size of benefit. His quantitative conclusions were based on a single placebo-controlled trial on schoolchildren in a skiing camp in the Swiss Alps, in which a significant decrease in common cold incidence and duration in the group administered 1 g/day of vitamin C was found. As children in a skiing camp are not a representative sample of the general population, Pauling's extrapolation to the population at large was too bold, erring as to the magnitude of the effect. Nevertheless, Pauling's general conclusion that vitamin C has physiological effects on the common cold is of major importance as it conflicts with the prevailing consensus that the only physiological effect of vitamin C on human beings is to prevent scurvy.

Ascorbic Acid↗

Vitamin C, the placebo effect, and the common cold: a case study of how preconceptions influence the analysis of results.

A large number of placebo-controlled studies have shown that vitamin C supplementation alleviates the symptoms of the common cold, but widespread skepticism that vitamin C could have any significant effect remains. One of the most influential common cold studies, published in 1975, was carried out by Thomas Karlowski et al, at the National Institutes of Health. Their placebo consisted of lactose, which can easily be distinguished from ascorbic acid by taste. Karlowski et al, found a 17% decrease in the duration of cold episodes in the group administered vitamin C (6 g/day); however, they suggested that the decrease was entirely due to the placebo effect. In this article it will be shown that the placebo effect is not a valid explanation for the results of the Karlowski study, as it is inconsistent with their results. This is an important conclusion for two reasons. First, the placebo explanation becomes even more unreasonable as regards the reported benefits found in several other studies with valid placebo tablets. Second, as the results from the Karlowski study are not due to the placebo effect, their results can be used to assess the quantitative effects of vitamin C supplementation. The most important conclusions from Karlowski's study are that therapeutic vitamin C supplementation during a common cold episode appears to be as effective as regular supplementation, and that there appears to be linear dose dependency at least up to 6 g/day. These findings suggest that large therapeutic vitamin C doses might alleviate the symptoms of the common cold substantially.

Ascorbic Acid↗

Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress.

Several studies have observed an increased risk of respiratory infections in subjects doing heavy physical exercise. Vitamin C has been shown to affect some parts of the immune system, and accordingly it seems biologically conceivable that it could have effects on the increased incidence of respiratory infections caused by heavy physical stress. In this report the results of three placebo-controlled studies that have examined the effect of vitamin C supplementation on common cold incidence in subjects under acute physical stress are analyzed. In one study the subjects were school-children at a skiing camp in the Swiss Alps, in another they were military troops training in Northern Canada, and in the third they were participants in a 90 km running race. In each of the three studies a considerable reduction in common cold incidence in the group supplemented with vitamin C(0.6-1.0 g/day) was found. The pooled rate ratio (RR) of common cold infections in the studies was 0.50 (95% CI: 0.35-0.69) in favour of vitamin C groups. Accordingly, the results of the three studies suggest that vitamin C supplementation may be beneficial for some of the subjects doing heavy exercise who have problems with frequent upper respiratory infections.

Ascorbic Acid↗

Vitamin C and the common cold: a retrospective analysis of Chalmers' review.

In 1975 Thomas Chalmers analyzed the possible effect of vitamin C on the common cold by calculating the average difference in the duration of cold episodes in vitamin C and control groups in seven placebo-controlled studies. He found that episodes were 0.11 +/- 0.24 (SE) days shorter in the vitamin C groups and concluded that there was no valid evidence to indicate that vitamin C is beneficial in the treatment of the common cold. Chalmers' review has been extensively cited in scientific articles and monographs. However, other reviewers have concluded that vitamin C significantly alleviates the symptoms of the common cold. A careful analysis of Chalmers' review reveals serious shortcomings. For example, Chalmers did not consider the amount of vitamin C used in the studies and included in his meta-analysis was a study in which only 0.025-0.05 g/day of vitamin C was administered to the test subjects. For some studies Chalmers used values that are inconsistent with the original published results. Using data from the same studies, we calculated that vitamin C (1-6 g/day) decreased the duration of the cold episodes by 0.93 +/- 0.22 (SE) days; the relative decrease in the episode duration was 21%. The current notion that vitamin C has no effect on the common cold seems to be based in large part on a faulty review written two decades ago.

Ascorbic Acid↗

Hormone-sensitive lipase is closely related to several bacterial proteins, and distantly related to acetylcholinesterase and lipoprotein lipase: identification of a superfamily of esterases and lipases.

We have sequenced a gene from Bacillus acidocaldarius which encodes an open reading frame (ORF3) of 310 amino acids. The ORF3 was found to be related to the mammalian hormone-sensitive lipase (HSL). Searching the protein data base revealed five other bacterial proteins related to the HSL. Upon further sequence comparisons this HSL-group was found to be related to the family of carboxylesterases, and to a family of lipases (lipoprotein, hepatic and pancreatic lipases). The evolutionary relationship of these serine-dependent hydrolytic enzymes has not been studied previously, and it has not been known that these proteins belong to the same superfamily. Finally, the alignment of the HSL with the bacterial proteins allowed us to infer the location of the hormone-sensitive regulatory domain of the HSL-protein.

Acetylcholinesterase↗

Does vitamin C alleviate the symptoms of the common cold?--a review of current evidence.

Since 1971, 21 placebo-controlled studies have been made to establish whether vitamin C at a dosage of > or = 1 g/day affects the common cold. These studies have not found any consistent evidence that vitamin C supplementation reduces the incidence of the common cold in the general population. Nevertheless, in each of the 21 studies, vitamin C reduced the duration of episodes and the severity of the symptoms of the common cold by an average of 23%. However, there have been large variations in the benefits observed, and clinical significance cannot be clearly inferred from the results. Still, the consistency of the results indicates that the role of vitamin C in the treatment of the common cold should be reconsidered.

Ascorbic Acid↗

Cloning and sequencing of a gene encoding acidophilic amylase from Bacillus acidocaldarius.

Two starch-degrading enzymes produced by Bacillus acidocaldarius (renamed as Alicyclobacillus acidocaldarius) were identified. According to SDS-PAGE, the apparent molecular masses of the enzymes were 90 and 160 kDa. Eight peptide fragments and the N-terminal end of the 90 kDa polypeptide were sequenced. An oligonucleotide, based on the amino acid sequence of a peptide fragment of the 90 kDa protein, was used to screen a lambda gt10 bank of B. acidocaldarius, and the region encoding the 90 kDa protein was cloned. Unexpectedly, the ORF continued upstream of the N terminus of the 90 kDa protein. The entire ORF was 1301 amino acids (aa) long (calculated molecular mass 140 kDa) and it was preceded by a putative ribosomal binding site and a promoter. Computer analysis showed that the 1301 aa protein was closely related to an alpha-amylase-pullulanase of Clostridium thermohydrosulfuricum. We suggest that the starch-degrading 160 kDa protein of B. acidocaldarius is an alpha-amylase-pullulanase, and the 90 kDa protein is a cleavage product of the 160 kDa protein. Another ORF, apparently in the same transcription unit, was found downstream from the amylase gene. It encoded a protein that was closely related to the maltose-binding protein of Escherichia coli.

ATP-Binding Cassette Transporters↗

Sequence encoding ribosomal protein L33 of Lactococcus lactis.

A cloned fragment from Lactococcus lactis chromosome encoding the L33 ribosomal protein was sequenced. Two incomplete open reading frames (ORFs) were also found: the upstream ORF shows similarity to the tetracycline-resistance protein (Tet) of Bacillus stearothermophilus, and the downstream ORF shows homology to a protein of Bacillus subtilis participating in sporulation (SpoVE), and to proteins of Escherichia coli involved in cell division (FtsW) and the maintenance of cell shape (RodA).

Amino Acid Sequence↗

Expression of the Erwinia carotovora polygalacturonase-encoding gene in Bacillus subtilis: role of signal peptide fusions on production of a heterologous protein.

The pehA gene encoding an endopolygalacturonase (pectinase) of Erwinia carotovora subsp. carotovora has been cloned previously [Saarilahti et al., Mol. Microbiol. 4 (1990) 1037-1044]. We expressed pehA in Bacillus subtilis using a secretion vector based on the promoter and signal sequence of the alpha-amylase (Amy)-encoding gene, amyE, from Bacillus amyloliquefaciens. To test whether the location of the junction between the secretion vector and pehA affects the protein yield, we made four different junctions. Two constructs contained an intact Amy signal sequence, whereas the other two were fusions between the Amy signal sequence and the polygalacturonase (PG) signal sequence. There was approximately fourfold variation in the production efficiency of B. subtilis strains carrying the different constructs. The most efficient construct contained the N-terminal and hydrophobic regions of the Amy signal peptide joined to the C terminus of PG signal peptide. This construct produced, in a shake flask culture, 0.8 g of polygalacturonase per liter of growth medium. In a pulse-chase experiment, the signal peptide of the most efficient construct was rapidly cleaved while cleavage was slow in the other constructs. Our results suggest that fusions containing intact signal peptides, which are common when producing foreign proteins, are not necessarily the most efficient.

Amino Acid Sequence↗