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Biomedical subjects

M Koivusalo

Publications and source records attributed to M Koivusalo.

At least 19 recordsLinked to original sources
PubMed2001

Mass spectrometric analysis reveals an increase in plasma membrane polyunsaturated phospholipid species upon cellular cholesterol loading.

Here we used electrospray ionization mass spectrometry for quantitative determination of lipid molecular species in human fibroblasts and their plasma membrane incorporated into enveloped viruses. Both influenza virus selecting ordered domains and vesicular stomatitis virus (VSV) depleted of such domains [Scheiffele, P., et al. (1999) J. Biol. Chem. 274, 2038-2044] were analyzed. The major difference between influenza and VSV was found to be a marked enrichment of glycosphingolipids in the former. The effect of chronic cholesterol loading on viral lipid composition was studied in Niemann-Pick type C (NPC) fibroblasts. Both NPC-derived influenza and VSV virions contained increased amounts of cholesterol. Furthermore, polyunsaturated phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine were enriched in NPC-derived virions at the expense of the monounsaturated ones. When normal fibroblasts were acutely loaded with cholesterol using cyclodextrin complexes, an adjustment toward increasingly unsaturated phospholipid species was observed, most clearly for phosphatidylcholine and sphingomyelin. Our results provide evidence that (1) glycosphingolipids are enriched in domains through which influenza virus buds, (2) chronic cholesterol accumulation increases the cholesterol content of both glycosphingolipid-enriched and intervening plasma membrane domains, and (3) an increase in membrane cholesterol content is accompanied by an increased level of polyunsaturated species of the major membrane phospholipids. We suggest that remodeling of phospholipids toward higher unsaturation may serve as both an acute and a long-term adaptive mechanism in human cellular membranes against cholesterol excess.

Carrier Proteins↗
PubMed2001

Quantitative determination of phospholipid compositions by ESI-MS: effects of acyl chain length, unsaturation, and lipid concentration on instrument response.

Electrospray ionization-mass spectrometry (ESI-MS) is a very promising tool for the analysis of phospholipid compositions, but is hampered by the fact that not all molecular species are detected with equal efficiency. We studied this and other issues that need to be taken into account to obtain truly quantitative compositional data. The key findings were as follows: First, the instrument response for both saturated and unsaturated phospholipid species decreased with increasing acyl chain length. This effect became increasingly prominent with increasing overall lipid concentration. Second, the degree of acyl chain unsaturation also had a significant effect on instrument response. At the highest concentration studied (10 pmol/microl), polyunsaturated species gave 40% higher intensity than the fully saturated ones. The effect of unsaturation diminished and nearly disappeared with progressive dilution. Third, the instrument response for the different head group classes varied markedly depending on the infusion solvent used. Notably, inclusion of ammonia in the infusion solvent eliminated sodium adduct formation in the positive ion mode, thus greatly simplifying the interpretation of the spectra. The fact that instrument response is dependent on many structural features, overall lipid concentration, solvent composition, and instrument settings makes it necessary to include several internal standards for each phospholipid class to obtain accurate data. Preferably, both unsaturated and saturated standards should be used. Finally, we quantified the major phospholipid classes of BHK cells using ESI-MS. The data agreed closely with those obtained with thin-layer chromatography and phosphorus analysis. This study indicates that quantitative compositional data can be obtained with ESI-MS, provided that proper attention is paid to experimental details, particularly the choice of internal standards.

Animals↗
PubMed2000

International actors and population policies in India, with special reference to contraceptive policies.

The international population policy agenda has traditionally been dominated by demographically driven population control policies. However, in the population policy development that preceded the International Conference on Population and Development in 1994, people's reproductive needs and rights received more emphasis. The aim of this study was to analyze how the new emphasis in population policies has been interpreted at the country level. In analyzing population policy rhetoric and its practical interpretations in India in 1994, the authors found that the rhetoric was broadening to encompass women's empowerment and reproductive health and that the use of direct method-specific monetary incentives and disincentives for accepting family planning methods was disapproved. However, population policy options were still considered mainly in terms of their ability to reduce fertility. Furthermore, the increased emphasis on the general market agenda was more important than that on reproductive needs and rights in molding population policies, as was evident in the greater stress on cost-recovery systems and nongovernmental actors. The findings suggest that the broader agenda for population policies and reproductive rights has been interpreted so that it can serve the aims of population-growth control and be implemented in the context of more market-oriented social policies and trade liberalization.

Contraception↗
PubMed2000

Joining together to combat poverty.

The International Poverty and Health Network (IPHN) was created in December 1997 following a series of conferences organized by the World Health Organization, with the aim of integrating health into plans to eradicate poverty. Around 1.3 billion people live on less than US$1 per day. Of the 4.4 billion people in developing countries nearly 60% lack access to sanitation, 30% do not have clean water, 20% have no health care, and 20% do not have enough dietary energy and protein. Even among rich nations there are gross socioeconomic inequalities. Many children are robbed of their physical and mental potential through poverty. Expressed in constant 1963 US dollars, an average Croatian family needed the annual income of US$894 to meet the poverty line in 1960 and US$9,027 in 1995. Accordingly, 9-25% of Croatian households were below the poverty line between 1960 and 1995. The increase in the poverty rate after 1991 was compounded by the war that destroyed almost a third of industrial capacity and infrastructure. Dissipation of the communist economy and inadequate privatization have contributed to the increase in unemployment rate, corruption, and other social ills. IPHN invited Croatian Medical Journal to publish this editorial to help push the issue of poverty up political and medical agendas on a global level. We argue that a factor contributing to the failure of most large-scale programs against poverty to date is the excessive emphasis on material and infrastructure assistance at the expense of spiritual, moral, and intellectual development.

Croatia↗
PubMed1998

Drinking water mutagenicity and urinary tract cancers: a population-based case-control study in Finland.

The detection of mutagenic and carcinogenic chlorination by-products in chlorinated drinking water has raised concern in many countries over the potential health effects of long-term exposure to these products. The relation between estimated exposure to historical drinking water mutagenicity and cancer was studied in Finland by using a population-based case-control study comprising 732 bladder cancer cases, 703 kidney cancer cases, and 914 controls. The cases were obtained from the nationwide Finnish Cancer Registry for the years 1991-1992. The controls, frequency matched by age and sex, were randomly selected from the national population registry. Information on past drinking water sources and confounding factors was acquired through a questionnaire. Historical exposure to drinking water mutagenicity was estimated by using information on past residence, past water source, and historical data on water quality and treatment. Odds ratios were calculated for an increase of 3,000 net revertants per liter (net rev/liter) in average exposure from 1950 to 1987, adjusting for age, sex, socioeconomic status, and smoking in logistic regression models. A small, statistically significant, exposure-related excess risk was found for kidney cancer for men (odds ratio = 1.49, 95 percent confidence interval (CI) 1.05-2.13) for 3,000 net rev/liter exposure level. For women, the association remained nonsignificant, with a lower odds ratio of 1.08 (95% CI 0.69-1.68). For bladder cancer, the odds ratio for both men and women was 1.22 (95% CI 0.92-1.62) for 3,000 net rev/liter exposure. However, a higher odds ratio of 2.59 (95% CI 1.13-5.94) for 3,000 net rev/liter exposure was observed for male nonsmokers.

Adult↗
PubMed1998

Aryl hydrocarbon receptor-associated genes in rat liver: regional coinduction of aldehyde dehydrogenase 3 and glutathione transferase Ya.

The tumor-associated aldehyde dehydrogenase 3 (ALDH3) and the glutathione transferase (GST)Ya form are coded by members of the Ah (aryl hydrocarbon) battery group of genes activated in the liver by polycyclic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The physiological role of the Ah receptor (AHR), its gene-activating mechanism and its endogenous ligands are still poorly clarified. We had previously observed that 3-methylcholanthrene (3MC) and beta-naphthoflavone (betaNF) induced the AHR-associated CYP1A1/1A2 pair in different liver regions, an effect not explained by the acinar distribution of the AHR protein. Here, we investigated AHR-associated regional induction by comparing the expression patterns of ALDH3 and GSTYa. Analysis of samples from periportal and perivenous cell lysates from 3MC-treated animals revealed that ALDH3 mRNA, protein and benzaldehyde-NADP associated activity were all confined to the perivenous region. In contrast, such regio-specific induction was not seen after beta-NF induction. Immunohistochemically, a peculiar mono- or oligocellular induction pattern of ALDH3 was seen, consistently surrounding terminal hepatic veins after 3MC but mainly in the midzonal region after betaNF. A ligand-specific difference in regional induction of GSTYa1 mRNA was also observed: The constitutive perivenous dominance was preserved after 3MC while induction by betaNF was mainly periportal. A 3MC-betaNF difference was also seen by immunohistochemistry and at the GSTYa protein level, in contrast to that of the AHR-unassociated GSTYb protein. However, experiments with hepatocytes isolated from the periportal or perivenous region to replicate these inducer-specific induction responses in vitro were unsuccessful. These data demonstrate that the different acinar induction patterns by 3MC and betaNF previously observed for CYP1A1 and CYP1A2 are seen also for two other Ah battery genes, GSTYa1 and ALDH3, but in a modified, gene-specific form. We hypothesize that unknown protein(s) operating in vivo and modifying the Ah-mediated response at the common XRE element located upstream of these genes is affected zonespecifically by 3MC and betaNF.

Alanine Transaminase↗
PubMed1997

Drinking water chlorination and cancer-a historical cohort study in Finland.

Chlorination of water rich in organic material is known to produce a complex mixture of organochlorine compounds, including mutagenic and carcinogenic substances. A historical cohort study of 621,431 persons living in 56 towns in Finland was conducted in order to assess the relation between historical exposure to drinking water mutagenicity and cancer. Exposure to quantity of mutagenicity was calculated on the basis of historical information of raw water quality and water treatment practices using an empirical equation relating mutagenicity and raw water pH, KMnO4 value and chlorine dose. Cancer cases were derived from the population-based Finnish Cancer Registry and follow-up time in the study started in 1970. Age, gender, time period, social class, and urban residence were taken into account in Poisson regression analysis of the observed numbers of cases using expected numbers of cases standardized for age and gender as a basis. Excess risks were calculated using a continuous variable for mutagenicity for 3,000 net rev/l exposure representing an average exposure in a town using chlorinated surface water. After adjustment for confounding, a statistically significant excess risk was observed for women in cancers of the bladder (relative risk [RR] = 1.48, 95 percent confidence interval [CI] = 1.01-2.18), rectum (RR = 1.38, CI = 1.03-1.85), esophagus (RR = 1.90, CI = 1.02-3.52), and breast (RR = 1.11, CI = 1.01-1.22). These results support the magnitude of excess risks for rectal and bladder cancers found in earlier epidemiologic studies on chlorination by-products and give additional information on exposure-response concerning the mutagenic compounds. Nevertheless, due to the public health importance of water chlorination, uncertainty related to the magnitude of observed risks, and the fact that excess risks were observed only for women, the results of the study should be interpreted with caution.

Adolescent↗
PubMed1996

Trends in the concentrations of mercury, copper, zinc and selenium in inhabitants of north-eastern Finnish Lapland in 1982-1991. A pilot study.

The heavy industry on the Murmansk region in Russia is releasing huge amounts of waste into the air, including heavy metals and sulphur compounds. To investigate the temporal trend in exposure to certain heavy metals among the inhabitants of north-eastern Finland, a pilot study was carried out involving serum and hair samples from group of 11 persons monitored in Ivalo in 1982 and 1991. A further 6 persons residing near the Russian border in Nellim and 10 adults and 2 children residing in the Sevettijärvi-Näätämö area also participated in 1991. In addition, serum and hair samples were also obtained from controls residing in the Helsinki area. Total mercury content, determined by flow injection analysis and the amalgam system, pointed to a decrease in concentrations in the hair of inhabitants of Ivalo, whereas mercury concentrations were found to be higher in those residing near the Russian border. The mercury concentrations in the hair of northern inhabitants were about 4 times greater than those in the hair of the people from southern Finland on average. No trend towards an increase or decrease was found in copper and zinc concentrations in hair and serum as determined by atomic absorption spectrometry in employing the flame technique. Selenium has been thought to act as an antagonist to the heavy metal mercury. The addition of selenium to fertilisers began in Finland in 1984, but such fertilisers have not been used widely in Lapland. Selenium concentrations, determined by flameless atomic absorption spectrometry, showed an increase with time in the inhabitants of northern Finland. Selenium concentrations were higher in the residents of Lapland than in the southern Finns, but this difference occurred after the addition of selenium to fertilisers has begun to be less common.

Adult↗
PubMed1995

Phenethyl isothiocyanate, a new dietary liver aldehyde dehydrogenase inhibitor.

Phenethyl isothiocyanate (PEITC) is found in cabbages and other commonly ingested cruciferous vegetables. Isothiocyanates have anticarcinogenic properties, proposed to be mediated in part by their inhibition of several cytochrome P450 (CYP) forms. We administered PEITC to rats treated chronically with ethanol for 38 days by means of total enteral nutrition model to inhibit CYP2E1. We observed that PEITC not only efficiently prevented the ethanol-induced elevation of CYP2E1 apoprotein and mRNA, but also significantly elevated blood acetaldehyde levels. An elevation also was observed in naive animals acutely administered PEITC and ethanol, an effect found to be associated with marked inhibition of liver aldehyde dehydrogenase (ALDH). PEITC (1 mmol/kg) inhibited total liver ALDH activity by more than 70% and inhibition persisted for at least 24 hr. The inhibition was similar to that caused by an equimolar dose of disulfiram. Experiments using subcellular rat liver fractions revealed that both low- and high-Km ALDH forms were inhibited by low concentrations of PEITC (IC50 = 0.8-6.0 microM). Importantly, the mitochondrial low-Km ALDH activity, which is mainly responsible for detoxification of low aldehyde levels, was strongly inhibited (IC50 = 1.4 microM). In contrast, neither alcohol dehydrogenase nor lactate dehydrogenase activity was inhibited by PEITC. Thus, PEITC inhibits liver ALDH with a potency similar to that of disulfiram, suggesting that, in susceptible individuals, ingestion of large amounts of cruciferous vegetables in combination with alcohol could give rise to antabus-like symptoms. This property of PEITC must be taken into account in experimental alcohol research and in evaluating its proposed anticarcinogenic actions on chemical procarcinogens that are activated into potentially carcinogenic aldehydes.

Acetaldehyde↗
PubMed1994

Drinking water mutagenicity and gastrointestinal and urinary tract cancers: an ecological study in Finland.

OBJECTIVES: The purpose of this study was to investigate the relationship between exposure to mutagenic drinking water and cancers of the gastrointestinal and urinary tract. METHODS: Past exposure to drinking water mutagenicity was assessed in 56 Finnish municipalities for the years 1955 and 1970. The cases of bladder, kidney, stomach, colon, and rectum cancers were derived from two periods (1967 to 1976 and 1977 to 1986). Age, sex, social class, urban living, and time period were taken into account in the Poisson regression analysis. RESULTS: Statistically significant exposure-response association was observed between exposure and incidence of bladder, kidney, and stomach cancers. In an ordinary municipality using chlorinated surface water, this exposure would indicate a relative risk of 1.2 for bladder cancer and of 1.2 to 1.4 for kidney cancer compared with municipalities where nonmutagenic drinking water was consumed. CONCLUSIONS: The acidic mutagenic compounds present in drinking water may play a role in the etiology of kidney and bladder cancers, but, because the results are based on aggregate data, they should be interpreted with caution.

Case-Control Studies↗