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Low frequency of the delta F508 mutation in Finno-Ugrian and Baltic populations.

The frequency of carriers of the delta F508 mutation at the cystic fibrosis (CF) locus was studied in population samples of Finns, Lithuanians, Saamis (Lapps) and Swedes from northern Sweden. The carrier frequencies in northern Sweden (1:200) and in Lithuanians (1:143) were significantly lower than in southern Scandinavia (Denmark; 1:38). No delta F508 carriers were found in Finns (n = 171) and Saamis (n = 151). The results indicate that the frequency of delta F508 is low in Finno-Ugrian and Baltic populations, and the decreased frequency of delta F508 in northern Sweden may be due to Finnish and Saamish admixture.

Baltic States↗

Concentration and subcellular distribution of trace elements in liver of small cetaceans incidentally caught along the Brazilian coast.

Concentrations of trace elements (V, Cr, Mn, Fe, Co, Cu, Zn, Ga, As, Se, Rb, Sr, Mo, Ag, Cd, Sb, Cs, Ba, T-Hg, Org-Hg, Tl and Pb) were determined in liver samples of estuarine dolphin (Sotalia guianensis; n = 20), Franciscana dolphin (Pontoporia blainvillei; n = 23), Atlantic spotted dolphin (Stenella frontalis; n = 2), common dolphin (Delphinus capensis; n = 1) and striped dolphin (Stenella coeruleoalba; n = 1) incidentally caught along the coast of Sao Paulo State and Parana State, Brazil, from 1997 to 1999. The hepatic concentrations of trace elements in the Brazilian cetaceans were comparable to the data available in literature on marine mammals from Northern Hemisphere. Concentrations of V, Se, Mo, Cd, T-Hg and Org-Hg increased with increasing age in liver of both estuarine and Franciscana dolphins. Very high concentrations of Cu (range, 262-1970 microg/g dry wt.) and Zn (range, 242-369 microg/g dry wt.) were observed in liver of sucklings of estuarine dolphin. Hepatic concentrations of V, Se, T-Hg, Org-Hg and Pb were significantly higher in estuarine dolphin, whereas Franciscana dolphin showed higher concentrations of Mn, Co, As and Rb. Ratio of Org-Hg to T-Hg in liver was significantly higher in Franciscana dolphin than estuarine dolphin, suggesting that demethylation ability of methyl Hg might be lower in liver of Franciscana than estuarine dolphins. High hepatic concentrations of Ag were found in some specimens of Franciscana dolphin (maximum, 20 microg/g dry wt.), and 17% of Franciscana showed higher concentrations of Ag than Hg. These samples with high Ag concentration also exhibited elevated hepatic Se concentration, implying that Ag might be detoxified by Se in the liver. Higher correlation coefficient between (Hg+0.5 Ag) and Se than between Hg and Se and the large distribution of Ag in non-soluble fraction in nuclear and mitochondrial fraction of the liver also suggests that Ag might be detoxified by Se via formation of Ag2Se in the liver of Franciscana dolphin.

Animals↗

Prostate cancer mortality trends in Mexico, 1980-1995.

BACKGROUND: In Mexico, prostate cancer (PC) is the second highest cause of mortality by cancer in men. In 1991, there were 2,473 deaths, with a crude rate of 5.66 cases per 100,000 men age 40 or over. For this same year, the ratio of proportional mortality to the total number of malignant tumors was 12.6%. Our objectives were to determine the trends and geographic distribution of mortality for PC in Mexico for 1980-1995. METHODS: Crude and adjusted mortality rates were carried out for 1980-1995. A test for trend was done using the simple lineal regression method. The standardized mortality ratio (SMR) was calculated for 1980-1995 for each Mexican state. RESULTS: The total number of deaths by PC in Mexico for 1980-1995 was 32,349. The crude mortality rate increased during that period from 3.16 to 6.75 cases per 100,000 men over age 40. The statistical trend test with respect to time was significant (P<0.0001). The state of Southern Baja California showed a higher SMR, and a smaller SMR was shown for the state of Quintana Roo. CONCLUSIONS: The mortality trends for PC increased for the period studied. It represents a serious problem for public health. We find that the central and northern states of the country, characterized by a greater industrial and socioeconomic development, are those with a higher SMR.

Adult↗

A heterozygous 4-bp deletion mutation in the Gs alpha gene (GNAS1) in a patient with Albright hereditary osteodystrophy.

Several heterozygous mutations within the gene encoding the alpha-subunit of Gs (GNAS1), the G protein that stimulates adenylyl cyclase, have been previously identified in patients with Albright hereditary osteodystrophy (AHO). We have now identified a fourth GNAS1 mutation from an AHO patient. Amplification by the polymerase chain reaction (PCR) of a genomic fragment encompassing GNAS1 exons 7 and 8 from one patient resulted in a product with aberrant migration on nondenaturing polyacrylamide and agarose gels. Direct DNA sequencing identified a 4-bp deletion in one allele of exon 7 encoding a frameshift with a premature stop codon. Analysis of lymphocyte RNA by reverse transcription-PCR and direct sequencing showed that the GNAS1 allele bearing the mutation is not expressed as mRNA. Consistent with this, Northern analysis revealed an approximate 50% deficiency in steady-state levels of GNAS1 mRNA. These findings further illustrate the heterogeneity of GNAS1 gene defects in AHO.

Amino Acid Sequence↗

Activation of protein kinase-C inhibits vitamin D receptor gene expression.

The abundance of 1,25-dihydroxyvitamin D3 receptors (VDR) in cultured cells has been shown to vary in direct relation to the rate of cell proliferation. This study examines the question of whether the growth-factor mediated up-regulation of VDR is due to direct modulation of VDR gene expression or is secondary to the stimulation of cell cycle events. Mitogenic agents, such as basic fibroblast growth factor and phorbol esters, were found to cause significant decreases in VDR abundance, while substantially stimulating proliferation of NIH-3T3 cells. Potent phorbol esters, such as phorbol myristate acetate (PMA) and phorbol-12,13-dibutyrate, whose biological actions have been shown to be mediated through the activation of protein kinase-C, down-regulated VDR in a time- and dose-dependent manner. An inactive phorbol ester, 4 alpha-phorbol-12,13-didecanoate, which does not activate protein kinase-C, did not alter VDR levels. Desensitization of protein kinase-C by prolonged exposure of cells to phorbol esters eliminated the PMA-mediated down-regulation of VDR. Staurosporine, an inhibitor of protein kinase-C, blocked the actions of PMA. Oleoyl acetyl glycerol, a synthetic diacyl glycerol, and A23187, a calcium ionophore, were both able to suppress VDR abundance alone and were additive in combination. The results suggest that activation of the protein kinase-C pathway and elevation of intracellular Ca2+ lead to significant down-regulation of VDR. The inhibitory effect of PMA appears to be exerted at the level of VDR mRNA expression. Northern blot analysis revealed significant decreases in steady state levels of VDR mRNA species that qualitatively corresponded to the decrease in VDR protein concentration seen on a Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

Environmental health in the Baltic region--toxic metals.

Recent reports on concentrations of lead, cadmium, methylmercury, arsenic and nickel in some biological media in populations in the Baltic region are reviewed. In particular, children in parts of Poland, the Czech Republic, and Germany have uptakes of lead sufficient to cause adverse effects on the central nervous system and kidneys. Cadmium exposure is also high in Poland. Slight cadmium-induced effects on the kidneys have been reported from Germany and Sweden. Methylmercury uptake is dependent upon the intake of fish, in particular from contaminated lakes and rivers in Sweden and Finland, as well as the eastern coast of the Baltic Sea. There are some indications of immunotoxic effects associated with the intake of such fish. However, fish also contain other immunomodulating agents. Exposure to arsenic seems to be low everywhere in the Baltic region. There is high nickel exposure in northern Russia.

Adolescent↗

Surveillance of Escherichia coli O157 isolation and confirmation, United States, 1988.

In 1989, to examine patterns of testing for Escherichia coli O157:H7 in state public health laboratories (SPHLs), CDC conducted a survey to determine the availability and type of Escherichia coli O157:H7 testing in SPHLs during 1988 and the number of isolates confirmed at SPHLs if such testing was available. The results were compared with information on isolates submitted for confirmatory testing at CDC in 1988. Thirty-nine (78%) of the 51 SPHLs were testing for E. coli O157:H7 in 1988; 26 confirmed at least one E. coli O157 isolate in that year. CDC confirmed isolates from three additional states. A total of 489 E. coli O157:H7 or E. coli O157:NM isolates were identified, with the largest numbers being reported from Washington (156), Oregon (64), Minnesota (63), and Massachusetts (36). These results show that E. coli O157 has been detected in most areas of the United States. Infections are apparently concentrated in northern states; however, improved surveillance data are needed to determine regional incidence and trends.

Child↗

[The risk of breast cancer in Catalonia].

BACKGROUND: To evaluate the risk of developing breast cancer among Catalan women and to estimate the number of new cases of this tumor that appear annually in Catalonia (north-east of Spain). MATERIAL AND METHODS: The incidence rates of breast cancer were used in the period 1985-1989 proceeding from the population-based cancer registries of Tarragona and Girona. The age-specific rates (ASR) in Catalonia were estimated by an ASR average of Girona and Tarragona, that were adjusted by the standardized mortality ratio (SMR) of these health regions in relation to Catalonia. The cumulative rate and the risk of developing breast cancer were calculated, considering the probability of death by other causes. The temporal trend of breast cancer incidence was analysed by the Poisson's regression model. RESULTS: The cumulative risk (0-74 years) for breast cancer among Catalan women was 5.17% (1 out of 19 women). The highest risk of developing breast cancer is in the group of age between 60 and 79 years old. Tarragona and Girona had both a moderate increase that was not statistically significant. About 2,550 new cases of breast cancer have been estimated in 1994 and 2,600 in 1996. CONCLUSION: The risk of developing breast cancer in Catalonia after adjusting for the probability of dying by other causes, is lower than in other countries of Northern Europe and the United States.

Adult↗

Cloning and molecular characterisation of the trout (Oncorhynchus mykiss) vacuolar H(+)-ATPase B subunit.

The current model of transepithelial ion movements in the gill of freshwater fish incorporates an apically oriented vacuolar H(+)-ATPase (H(+)V-ATPase; proton pump) that is believed to facilitate both acid excretion and Na(+) uptake. To substantiate this model, we have cloned and sequenced a cDNA encoding the B subunit of the rainbow trout (Oncorhynchus mykiss) H(+)V-ATPase. The cloning of the B subunit enabled an examination by northern analysis of its tissue distribution and expression during external hypercapnia. Degenerate oligonucleotide primers to the B subunit of the H(+)V-ATPase were designed and used in a semi-nested polymerase chain reaction (PCR) to amplify an 810 base pair (bp) product from a trout gill/kidney cDNA library. This PCR product was cloned and sequenced and then used to screen the same cDNA library. The assembled 2262 bp cDNA included an open reading frame coding for a deduced protein of 502 amino acid residues. A BLAST search of the GenBank nucleotide database revealed numerous matches to other vertebrate and invertebrate H(+)V-ATPase B subunits. Protein alignment demonstrated that the trout H(+)V-ATPase B subunit is more than 85 % identical and more than 90 % similar to those in other vertebrate species. An initial analysis of H(+)V-ATPase mRNA tissue distribution revealed significant expression in blood. Although a comparison of perfused tissues (blood removed) with non-perfused tissues demonstrated no obvious contribution of the blood to total tissue H(+)-ATPase mRNA levels, all subsequent experiments were performed using perfused tissues. Levels of H(+)V-ATPase mRNA expression were high in the gill, kidney (anterior or posterior), intestine, heart and spleen, but lower in liver and white muscle. Exposure of the fish to 12 h of external hypercapnia (water P(CO2)=7. 5 mmHg; 1 kPa) was associated with a transient increase (at 2 h) in the levels of H(+)V-ATPase B subunit mRNA in gill and kidney; liver mRNA levels were unaffected. These results are consistent with the hypothesis of an apically localised plasma membrane H(+)V-ATPase in the freshwater trout gill and that the expression of this proton pump is increased during periods of acidosis, at least in part because of an increased steady-state level of H(+)V-ATPase mRNA.

Amino Acid Sequence↗

Dietary intake of vegetables and fruits among adults in five regions of Spain. EPIC Group of Spain. European Prospective Investigation into Cancer and Nutrition.

OBJECTIVE: To assess the consumption of vegetables and fruits (V&F) in adults from five regions in Spain according to sex, age and educational level. DESIGN: Cross-sectional study within the members of the EPIC cohort in Spain. SETTING: Three regions of the north of Spain (Asturias, Guipúzcoa and Navarra) and two regions of the south of Spain (Granada and Murcia). SUBJECTS: 41448 healthy volunteers (15365 men, 25813 women), aged 29-69 y. INTERVENTIONS: Information on habitual diet during the previous year was collected by means of a computerised version of a diet history questionnaire. RESULTS: Among men, the mean daily consumption of vegetables and of fruits was 273.7 g (3.4 servings) and 348.3 g (4.4 servings) respectively. Among women, the corresponding vegetables and fruit intakes per day were 244.4g (3.1 servings) and 349.4g (4.4 servings). The total V&F intake tended to increase with age and educational level. Overall, 74% of subjects consumed 400 g/d (5 servings) of vegetables and fruit. CONCLUSIONS: Consumption of vegetables and fruits in healthy adults in Spain is considerably higher than in most European countries and the United States; this complies with what is considered to be the Mediterranean diet. Despite some regional differences, there were no clearly differentiated patterns of V&F intake between southern and northern regions within Spain.

Adult↗

[Nasofacial zygomycosis in the state of Pará: the registration of 2 cases].

Two new cases of nasofacial zygomycosis from the state of Pará, Brazil, are reported. Both cases were treated with ketoconazole and the response to the drug was considered to be good; the patients improved rapidly and the nasal obstruction was the first manifestation to disappear. As five cases have been described in recent years from the state of Pará, this form of zygomycosis can no longer be considered as a rare disease in northern Brazil.

Adult↗

[Patterns in the epidemic process of scarlet fever in various territories differing in respect of climate and geography].

Observations carried out in Ashkhabad and Petrozavodsk permitted to reveal specific features of the epidemic process in scarlet fever at the territories differing in climato-geographic respect. This was expressed in a different level of morbidity, differences in the character of periodicity, seasonality and age structure of morbidity. Along with this there were noted differences in the spread of the carrier state of hemolytic streptococcus and of their biological properties, and also in the process of immunity formation in the population. The data obtained suggest that one of the causes of epidemiological differences in scarlet fever detected in the southern and the northern districts were peculiarities of the immunological reactivity of the population and a difference in the carrier state of the highly toxigenic streptococci.

Adolescent↗

Evidence for HIV type 1 strains of U.S. intravenous drug users as founders of AIDS epidemic among intravenous drug users in northern Europe.

To establish an epidemiological link between HIV-1 epidemics in U.S. and European homosexual men and intravenous drug users (IVDUs) we analyzed the HIV-1 gp120 V3 sequences in both risk groups. Signature pattern analysis revealed that the V3 sequences of viruses from IVDUs in Northern Europe are distinguishable from those of homosexual men on the basis of one amino acid and two synonymous nucleotide substitutions, which the most conserved was a synonymous nucleotide substitution in the second glycine codon at the tip of the gp120 V3 loop (GGC). This substitution was seen in 17 of 20 (85%) viruses of IVDUs in Northern Europe, in none of 41 homosexual men in either Europe or the United States, and in 5 of 11 (45%) U.S. IVDUs sequences analyzed. Subsequent phylogenetic and multivariate principal coordinate (PCOORD) analyses showed that 16 of 20 (80%) of the Northern European IVDU sequences clustered together with the 5 U.S. IVDU sequences carrying the GGC substitution and away from the sequences of homosexual men from either Europe or the United States. Taken together with the higher level of heterogeneity of U.S. IVDU sequences compared to the Dutch IVDU sequences taken at the same time, these data present suggestive evidence for a U.S. instead of a European origin of the AIDS epidemic among Northern European IVDUs.

Acquired Immunodeficiency Syndrome↗

Increase by tri-iodothyronine of endothelin-1, fibronectin and von Willebrand factor in cultured endothelial cells.

Hyperthyroidism is associated with elevated plasma levels of endothelium-derived proteins such as von Willebrand factor (vWF), fibronectin (FN) and endothelin-1 (ET-1). This study was designed to characterize the mechanisms involved in this phenomenon at the cellular level. vWF, FN and ET-1 secretion and mRNA expression were measured in human umbilical vein endothelial cells (HUVECs) exposed to tri-iodothyronine (T3) for 13 +/- 1 days, using ELISA, Western blot, RIA and Northern blot analysis respectively. Exposure of HUVECs to T3 significantly increased vWF secretion (50 ng T3/ml: 117 +/- 5%, P < 0.01; 100 ng T3/ml: 127 +/- 26%, P < 0.01) as well as vWF mRNA expression (50 ng/ml: 116 +/- 13%, P < 0.001; 100 ng/ml: 136 +/- 30%, P < 0.002) (results are means +/- S.D. analysed by the Wilcoxon signed rank test). FN secretion was significantly affected by 50 (145 +/- 42% of control, P < 0.05) and 100 (116.8 +/- 16% of control, P < 0.05) ng T3/ml, and FN mRNA expression by 50 ng T3/ml (123 +/- 20%, P < 0.05). Long-term incubation with T3 increased both ET-1 secretion (25 ng/ml: 124 +/- 25%, P < 0.001; 50 ng/ml: 165 +/- 53%, P < 0.05; 100 ng/ml: 116 +/- 17%, P < 0.05) and prepro-ET-1 mRNA expression (25 ng/ml: 112 +/- 16%, P < 0.05; 50 ng/ml: 134 +/- 43%, P < 0.02; 100 ng/ml: 120 +/- 20%, P < 0.02). Protein kinase C (PKC) isoforms epsilon and beta II were not significantly affected by T3, whereas PKC alpha was increased in whole cell lysates and in membrane fractions of cells incubated with 100 but not 50 ng T3/ml. Prepro-ET-1 mRNA stability, cell numbers and proliferation, measured by [3H]thymidine assays, remained unaffected in HUVECs after exposure to T3. These data indicate thyroid hormone-induced upregulation of mRNA expression and protein synthesis of vWF, FN and ET-1, by PKC alpha-, beta II- and epsilon-independent pathways, explaining, at least in part, increased plasma concentrations of endothelial proteins and peptides in the hyperthyroid state.

Blotting, Northern↗