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PubMed1977

'Malignant lymphoepithelial lesions' (undifferentiated ductal carcinomas of the parotid gland). Three case reports and review of the literature.

Three cases of the so-cassed malignant lymphoepithelial lesion occurring in women are described. The authors, however, prefer to label the lesion 'undifferentiated carcinoma of the parotid'. From an accurate review of the world literature it appears that 23 cases of such lesion have been reported, 22 arising in the parotid and 1 in the submandibular gland. The malignant lymphoepithelial lesion has been mainly encountered in Eskimos and the three cases of the present report are the first to have been evidenced in Europe. The malignant lymphoepithelial lesion is discussed from the taxonomic, nosologic, pathogenetic, diagnostic and therapeutic points of view. The lesion does not seem to be of an autoimmune nature, unlike the benign lymphoepithelial lesion which is generally regarded as an autoimmune disease.

Adult↗

PubMed2000

HLA genes in Mexican Mazatecans, the peopling of the Americas and the uniqueness of Amerindians.

The HLA allele frequency distribution of the Mexican Mazatecan Indians (Olmec culture) has been studied and compared with those of other First American Natives and worldwide populations (a total of 12,100 chromosomes; 6,050 individuals from 59 different populations). The main conclusions are: 1) An indirect evidence of Olmec and Mayan relatedness is suggested, further supporting the notion that Olmecs may have been the precursors of Mayans; 2) Language and genetics do not completely correlate in microenvironmental studies; and 3) Peopling of the Americas was probably more complex than postulated by Greenberg and others (three peopling waves). Significant genetic input from outside is not noticed in Meso and South American Amerindians according to the phylogenetic analyses; while all world populations (including Africans, Europeans, Asians, Australians, Polynesians, North American Na-Dene Indians and Eskimos) are genetically related. Meso and South American Amerindians tend to remain isolated in the Neighbor-Joining, correspondence and plane genetic distance analyses.

Alleles↗

PubMed2003

Origin of Mayans according to HLA genes and the uniqueness of Amerindians.

The HLA allele frequency distribution of the Mayans from Guatemala was studied and compared with those of other First American Natives and worldwide populations (a total of 12,364 chromosomes and 6182 individuals from 60 different populations). The main conclusions were (1): the closest Amerindian group to Mayans is the Arhuacs, who were the first recorded Caribbean Islands' inhabitants (2). Mayans are not so close to Mesoamerican Zapotec, Mixe and Mixtec Amerindians, who genetically cluster together. Mixe had been related to Mayans only on linguistic bases (3). DRB1*0407 and DRB1*0802 alleles are found in 50% of Mayans; these alleles are also found in other Amerindians, but the Mayans' high frequencies may be showing a founder effect for this Mesoamerican-Caribbean population (4). Extended Mayan specific HLA haplotypes are described for the first time (5). Language and genes do not completely correlate in microgeographical studies (6). Significant genetic input from outside is not noticed in Meso and South American Amerindians according to the genetic analyses; while all world populations (including Africans, Europeans, Asians, Australians, Polynesians, North American Na-Dene Indians and Eskimos) are genetically related. Meso and South American Amerindians tend to remain isolated in the neighbour joining analyses.

Alleles↗

PubMed2002

Exfoliation syndrome: frequency, gender distribution and association with climatically induced alterations of the cornea and conjunctiva.

PURPOSE: To investigate exfoliation syndrome (ES) in order to elucidate gender distribution and the roles of genetic and climatic factors in its manifestation. MATERIAL AND METHODS: We studied the gender distribution of ES and the association between ES and the appearance of certain climatically induced disorders (pterygium, climatic droplet keratopathy) and the size of pingueculae in populations living in the Arctic region, in temperate regions and in tropical regions. This involved a total of 11 samples taken in eight different countries, comprising 2206 persons of both genders over the age of 50 years. RESULTS: A total of 1051 males were investigated for ES and 147 of them (14.0%) were found to have it. The corresponding figures for females were 1093 and 177 (16.2%). After standardization according to age, no systematic difference between the genders was found in the study. The frequency of ES varied greatly. It was not observed at all in the Inuit (Eskimos) but was found most frequently (about 30%) among the Saami (Lapps), Aland Islanders, Finns, Icelanders and Russians over 70 years of age. After the age of 50, the frequency of ES increases rapidly with age in all populations. However, the curves for ES in people living in the tropics show a delay of about 10 years. In contrast, the frequency of climatically caused changes (pterygium, climatic keratopathy and pronounced pinguecula) mostly peaks at the age of 50 years and is highest in the tropics and in the Arctic. Males in these regions tended to be more affected by climatically caused changes than females. Likewise, in tropical climates, where radiation from the sun is strong, and in Lapland and Novosibirsk, where there is radiation from snow, males showed more evidence of ES than females. However, examination of 506 patients from a private practice in South Finland, who were under observation for glaucoma or for risk of glaucoma, showed females to be in the majority of those with ES. CONCLUSIONS: As a rule, climate does not appear to influence the occurrence of ES. However, in tropical countries, where radiation from the sun is strong, ES was more common among males than among females. In the light of its peculiar population distribution, even when climatic factors are considered, there would appear to be an important genetic factor involved in the manifestation of ES.

Age Distribution↗

PubMed1987

Cancer pattern among Greenlandic Inuit migrants in Denmark, 1968-1982.

For several cancer sites the incidence among Inuit (Eskimos) in Alaska, Canada and Greenland differs markedly from that in non-Inuit in adjacent areas. This is the first study of Inuit migrants. Among 11,571 Inuit Greenlandic people living in Denmark in the period 1968-1982 we found 69 cases of cancer. Significantly increased risks compared to the Danish population were found for cancer of the rectum (RR = 5.5) in males and for nasopharyngeal cancer (RR = 185.2) and cancer of the cervix uteri (RR = 1.9). The significance of these findings in relation to the role of environmental factors in the aetiology of cancer in Inuit is discussed.

Adult↗

PubMed1991

Population genetics of human glyoxalases.

The gene for glyoxalase I (E.C. 4.4.1.5), Glo, has two alleles, Glo1 and Glo2, which are autosomally inherited in a co-dominant manner. Glo1 allele-frequency is highest in native Alaskan-Eskimo and Indian populations and decreases geographically south and east, to minimum levels in Aboriginal-Australian populations and native tribes in Papua New Guinea. There was no correlation between Glo1 frequency and incidence of insulin-dependent diabetes mellitus (IDDM). The frequencies of GLO phenotypes, Glo 1-1, Glo 1-2 and Glo 2-2, are disturbed in IDDM and there is a suggestion that IDDM patients with or without chronic, clinical complications have characteristic phenotype frequencies.

Alleles↗

PubMedDate not supplied

Analysis of FMR1 (CGG)n alleles and FRAXA microsatellite haplotypes in the population of Greenland: implications for the population of the New World from Asia.

The fragile X syndrome is caused by the expansion of a polymorphic (CGG)n tract in the promoter region of the FMR1 gene. Apparently the incidence of fragile X syndrome is rare in the population of Greenland. In order to examine population-related factors involved in stability of the (CGG)n sequence, DNA samples obtained randomly from the Greenlandic population were analysed for size and AGG interspersion pattern of the FMR1 (CGG)n region and associated DXS548-FRAXAC1 haplotypes. In addition a large Greenland family with unstable transmission in the premutation range was analysed. The (CGG)n allele sizes in the Greenland population showed a narrow distribution similar to that reported for Asian populations. DNA sequencing of alleles with 36 CGG repeats revealed an AGG(CGG)6 insertion previously reported exclusively in Asian populations and a high frequency of alleles with a (CGG)10AGG(CGG)9AGG(CGG)9 or (CGG)9AGG(CGG)9AGG(CGG)6AGG(CGG)9 sequence pattern was found. Thus the data confirm the Asian origin of the Greenlandic (Eskimo) population and indicates that some (CGG)n alleles have remained stable for 15-30,000 years, since the population of the New World arrived from Asia via the Bering Strait.

Alleles↗

PubMed2002

Age at acquisition of Helicobacter pylori in a pediatric Canadian First Nations population.

BACKGROUND: Few data exist regarding the epidemiology of Helicobacter pylori infections in aboriginal, including the First Nations (Indian) or Inuit (Eskimo) populations of North America. We have previously found 95% of the adults in Wasagamack, a First Nations community in Northeastern Manitoba, Canada, are seropositive for H. pylori. We aimed to determine the age at acquisition of H. pylori among the children of this community, and if any association existed with stool occult blood or demographic factors. MATERIALS AND METHODS: We prospectively enrolled children resident in the Wasagamack First Nation in August 1999. A demographic questionnaire was administered. Stool was collected, frozen and batch analyzed by enzyme-linked immunosorbent assay (ELISA) for H. pylori antigen and for the presence of occult blood. Questionnaire data were analyzed and correlated with the presence or absence of H. pylori. RESULTS: 163 (47%) of the estimated 350 children aged 6 weeks to 12 years, resident in the community were enrolled. Stool was positive for H. pylori in 92 (56%). By the second year of life 67% were positive for H. pylori. The youngest to test positive was 6 weeks old. There was no correlation of a positive H. pylori status with gender, presence of pets, serum Hgb, or stool occult blood. Forty-three percent of H. pylori positive and 24% of H. pylori negative children were < 50th percentile for height (p = 0.024). Positive H. pylori status was associated with the use of indoor pail toileting (86/143) compared with outhouse toileting (6/20) (p = 0.01). CONCLUSIONS: In a community with widespread H. pylori infection, overcrowded housing and primitive toileting, H. pylori is acquired as early as 6 weeks of age, and by the second year of life 67% of children test positive for H. pylori.

Age of Onset↗

PubMed2001

The aetiology of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is a disease with a remarkable racial and geographical distribution. In most parts of the world it is a rare condition and in only a handful of places does this low risk profile alter. These include the Southern Chinese, Eskimos and other Arctic natives, inhabitants of South-East Asia and also the populations of North Africa and Kuwait.

Adolescent↗

PubMed1997

Lymphoepithelioma-like salivary gland carcinoma in Taiwan: a clinicopathological study of nine cases demonstrating a strong association with Epstein-Barr virus.

AIMS: Lymphoepithelioma-like carcinoma (LELC) of the salivary glands is a rather rare tumour. Previous studies have shown its strong association with Epstein-Barr virus (EBV) among Chinese and Eskimos. We tested this observation with nine Chinese patients with salivary gland LELC in Taiwan including one with coexisting nasopharyngeal carcinoma (NPC) and studied the prognostic significance of their histopathological features. METHODS AND RESULTS: This series showed a predilection for female patients and parotid glands with a median age of 50 years. Three patients died 18.5-26 months after the diagnosis including the case with NPC. Six patients were alive without recurrence for 14-45 months with a median follow-up of 34.5 months. Histopathologically, the tumours showed either lobular or diffuse growth pattern. Granulomas and/or germinal centres were observed in most cases and both B- and T-cells were found in the lymphoid infiltrates, indicating that the salivary gland LELC was capable of inducing a strong host immune reaction. Microscopic growth pattern, lymph node metastasis, and presence or absence of granulomas and/or germinal centres seemed to be important prognostic factors. Both salivary gland LELC and NPC shared similar histopathological appearance and positive immunostaining for epithelial membrane antigen and cytokeratin AE1 but not AE3. Granulomas and amyloid might occur in both tumours. A nasopharyngeal examination is indicated in patients with salivary gland LELC to exclude the possibility of coexisting or metastatic NPC. All nine cases showed positive nuclear signals for EBV-encoded RNA by in situ hybridization including the case with NPC. CONCLUSIONS: Our study and the previously published studies show that the association of salivary gland LELC and EBV is strongly related to racial and geographical factors.

Adolescent↗

PubMed1998

Geographic differences in bacterial meningitis: less may be as interesting as more.

Many reports in the last decade have described populations with a high incidence of bacterial meningitis, especially amongst indigenous groups in industrialised countries, such as North American Eskimos and Apache Indians and Australian Aborigines, particularly with meningitis due to Haemophilus influenzae type b (Hib). Lack of evidence that invasive Hib disease, including meningitis, is a significant health problem has been attributed to lack of appropriate data, either due to lack of laboratory and clinical facilities, such as in most less industrialised countries, or lack of study. Host differences in immune response, though known to be important for individual susceptibility to Hib disease and bacterial meningitis, have not been thought important on a population level. Good quality epidemiologic data now available from Hong Kong and Japan, based on sound laboratory methods, have shown bacterial meningitis, particularly due to Hib and Neisseria meningitidis, to be significantly less common than in predominantly Caucasian populations in various industrialised countries. Differences in host immune response to these capsular polysaccharides seems the most likely explanation for this observation. It is interesting that other immunologically mediated disorders such as Kawasaki disease and systemic lupus erythematosis have a relatively high incidence in Sino Japanese populations, lending plausibility to inherited differences in immune response as a mechanism for these observations.

Global Health↗

PubMedDate not supplied

Effect of randomized supplementation with high dose olive, flax or fish oil on serum phospholipid fatty acid levels in adults with attention deficit hyperactivity disorder.

Dietary intake of omega-3 fatty acids has been positively correlated with cardiovascular and neuropsychiatric health in several studies. The high seafood intake by the Japanese and Greenland Inuit has resulted in low ratios of the omega-6 fatty acid arachidonic acid (AA, 20:4n-6) to eicosapentaenoic acid (EPA, 20:5n-3), with the Japanese showing AA:EPA ratios of approximately 1.7 and the Greenland Eskimos showing ratios of approximately 0.14. It was the objective of this study to determine the effect of supplementation with high doses (60 g) of flax and fish oils on the blood phospholipid (PL) fatty acid status, and AA/EPA ratio of individuals with Attention Deficit Hyperactivity Disorder (ADHD), commonly associated with decreased blood omega-3 fatty acid levels. Thirty adults with ADHD were randomized to 12 weeks of supplementation with olive oil (< 1% omega-3 fatty acids), flax oil (source of alpha-linolenic acid; 18:3n-3; alpha-LNA) or fish oil (source of EPA and docosahexaenoic acid; 22:6n-3; DHA). Serum PL fatty acid levels were determined at baseline and at 12 weeks. Flax oil supplementation resulted in an increase in alpha-LNA and a slight decrease in the ratio of AA/EPA, while fish oil supplementation resulted in increases in EPA, DHA and total omega-3 fatty acids and a decrease in the AA/EPA ratio to values seen in the Japanese population. These data suggest that in order to increase levels of EPA and DHA in adults with ADHD, and decrease the AA/EPA ratio to levels seen in high fish consuming populations, high dose fish oil may be preferable to high dose flax oil. Future study is warranted to determine whether correction of low levels of long-chain omega-3 fatty acids is of therapeutic benefit in this population.

Adolescent↗

PubMed2000

Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how?

Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Though this is an attractive explanation, there could be other actions as well. N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease. These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function. Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias. Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18. Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus. TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids. Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter. Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids. This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.

Acetylcholine↗

PubMed1992

Mechanisms of adaptation to cold.

The animal model used the most frequently for understanding the mechanisms of adaptation to cold in humans has been the rat. It has been established that rats kept in the cold for a few weeks stop shivering while preserving a normal internal temperature because of an enhanced thermogenic capacity of the brown adipose tissue (BAT) mediated by the sympathetic nervous system. Studies on groups of humans exposed to cold have shown that shivering is also attenuated but without compensatory increased in heat production possibly because of non-significant contribution of the BAT. However when humans and laboratory animals are exposed repeatedly to short severe cold evidence for adaptation has been described. This adaptation is not metabolic; instead it is related to the phenomenon of habituation. When exposed to a novel stress such as cold, the alarm reaction is initiated as evidenced by the activation of the sympathetic nervous system which opposes the stressing situation. However with time, when it is realized that the normal functioning of the body is not endangered the responses are attenuated and enhanced tolerance is observed. This type of adaptation was observed in Eskimos, fishermen, outdoor workers, etc.

Adaptation, Physiological↗

PubMed1992

The different types of general cold adaptation in man.

Different types of general cold adaptation have been described over the last 50 years. Metabolic adaptation (Alacaluf Indians, Arctic Indians Eskimos), insulative adaptation (coastal Aborigines of tropical northern Australia), hypothermic adaptation (bushmen of the Kalahari desert, Peruvian Indians) and insulative hypothermic adaptation (Central Australian Aborigines, nomadic Lapps, Korean and Japanese diving women). These different types of cold adaptation are related to the intensity of the cold stress and to individual factors such as diet, the level of physical fitness and body fat content. Thus, in natural environments, man develops a strategy of adaptation to cold, which takes into account environmental and individual factors. This strategy is susceptible to be modified when these conditions change. Caloric intake deficit could have been responsible for the hypothermic adaptation observed after J.-L. Etienne's journey to the North Pole. Physiological responses were adapted to maintain an acceptable level of energetic reserves with a moderate hypothermia, which was not life threatening for the climatic conditions encountered by the polar explorer.

Acclimatization↗

PubMed1992

Cold and the airways.

Physiological and pathological respiratory responses are triggered by various conditions of exposure to cold climates. Beside airway smooth muscle, both the pulmonary and the tracheobronchial vasculatures are major effectors of respiratory responses to cold. General exposure to cold causes pulmonary vasoconstriction known as "Raynaud's phenomenon of the lung" in subjects with primary Raynaud syndrome and favors acute pulmonary oedema in subjects with congestive heart failure. In healthy subjects acute hyperventilation of very cold air has led to acute respiratory failure closely similar to hypoxic pulmonary oedema. In outdoor exercising people years long repetition of hyperventilation of subfreezing air causes "eskimo lung" made of obstructive lung disease and increased wall thickness of pulmonary arteries. At a lesser degree hyperventilation of dry air cools the central airways and triggers subclinical bronchial obstruction in healthy subjects. In asthmatic subjects hyperventilation of dry air causes asthma attacks. Results of recent animal and human experiments point to a key role of mucosal vessels in thermal balance of the airways. Simultaneously, there is increasing evidence that hyperventilation-induced asthma is triggered by a thermal stimulus.

Acute Disease↗

PubMed1998

Epidemiology of factor V Leiden: clinical implications.

Inherited resistance to activated protein C (APC) has been recently recognized as a novel cause underlying venous thrombophilia. In most cases APC resistance is due to a single point mutation in the factor V gene leading to a replacement of Arg506 with Gln (factor V Leiden). Factor V Leiden allele is present in about 5% of the Caucasian individuals (Europeans, Jews, Israeli Arabs, and Indians) and is virtually absent in Africans, Asians, and races with Asian ancestry such as Amerindians, Eskimos, and Polynesians; this suggests a single origin of the mutation, which has been proven by haplotype analysis. A low prevalence of the mutation (1%) was noticed in African-Americans for recent racial admixture. Factor V Leiden presents not a major role as risk factor for arterial thrombosis, while it is present in 18% of Caucasian patients with venous thrombosis. This high incidence prevalence mirrors the incidence in the corresponding general populations and can be even higher in some areas according to the ethnic background. Conversely, factor V Leiden is usually not found in non-Caucasian thrombotic patients; this could give reason of the lower incidence of venous thrombotic disease in Africa and Asia in comparison with Europe. Therefore, screening for factor V Leiden is suggested for all Caucasian individuals with previous venous thrombosis; inclusion criteria for the screening should not be stringent because clinical manifestations associated with the mutant genotype can be also mild or secondary to circumstantial risk factors or manifesting at advanced age. Factor V Leiden can act also as concurrent risk factor in individuals with deficiency of natural inhibitors or mild hyperhomocysteinemia. So far, screening for the mutation in individuals with no history of thrombosis is recommended only for relatives of proband patients identified as carriers; the available data do not justify indiscriminate screening before risk situations such as oral contraceptives intake, pregnancy, or high-risk surgery.

Factor V↗

PubMed1985

The inverse relation between fish consumption and 20-year mortality from coronary heart disease.

The low death rate from coronary heart disease among the Greenland Eskimos has been ascribed to their high fish consumption. We therefore decided to investigate the relation between fish consumption and coronary heart disease in a group of men in the town of Zutphen, the Netherlands. Information about the fish consumption of 852 middle-aged men without coronary heart disease was collected in 1960 by a careful dietary history obtained from the participants and their wives. During 20 years of follow-up 78 men died from coronary heart disease. An inverse dose-response relation was observed between fish consumption in 1960 and death from coronary heart disease during 20 years of follow-up. This relation persisted after multiple logistic-regression analyses. Mortality from coronary heart disease was more than 50 per cent lower among those who consumed at least 30 g of fish per day than among those who did not eat fish. We conclude that the consumption of as little as one or two fish dishes per week may be of preventive value in relation to coronary heart disease.

Age Factors↗