The first identified case of thalassemia?

The spread of thalassemia among prehistoric populations of the Mediterranean basin has been linked to the increased risk to early agriculturalists posed by thePlasmodium falciparum parasite. We here present the earliest case, to our knowledge, of thalassemia diagnosed on the basis of long bone remains. We further discuss the value of this finding for our understanding of the transition from foraging to agriculture.     

Anemia,genetic diseases,and malaria in prehistoric mainland southeast Asia

The analysis of a sample of skeletons from the 4,000-year-old site of Khok Phanom Di on the coast of central Thailand has identified a number of individuals with skeletal evidence suggestive of severe anemia. The differential diagnosis of the lesions is discussed and the presence of one of the thalassemia syndromes is proposed. The implications of this for southeast Asian prehistory are discussed. The presence of these conditions has been suggested in previous analyses of prehistoric southeast Asian populations, but this is the first population in which the evidence, including post-cranial responses, is presented in detail. © 1996 Wiley-Liss, Inc.     

A case of megacolon in Rio Grande valley as a possible case of Chagas disease

We have been searching for evidence of Chagas disease in mummified human remains. Specifically, we have looked for evidence of alteration of intestinal or fecal morphology consistent with megacolon, a condition associated with Chagas disease. One prehistoric individual recovered from the Chihuahuan Desert near the Rio Grande exhibits such pathology. We present documentation of this case. We are certain that this individual presents a profoundly altered large intestinal tract and we suggest that further research should focus on confirmation of a diagnosis of Chagas disease. We propose that the prehistoric activity and dietary patterns in Chihuahua Desert hunter/gatherers promoted the pathoecology of Chagas disease.     

Paleodemography and evolution

Data on porotic hyperostosis (usually from thalassemia or sicklemia) and on morphology as related to differential survival and fertility in Early Neolithic Nea Nikomedeia (N over 90) and Middle Bronze Age Lerna (N = 234) show (a) the importance of disease, mainly falciparum malaria, in determining fertility, (b) the irregular fit between prediction from fertile family groups and observed prehistoric microevolutionary change in Greece, (c) the probable effects of nutrition and disease.     

Human treponematosis and tuberculosis: evidence from the New World.

The purpose of this study has been first, to critically review the evidence for the presence of human treponematosis and tuberculosis in the skeletal remains of prehistoric natives in the New World, and second, to report on nine new cases dated to before contact and suggesting the presence of these two disease conditions. A review of the medical history and findings by human paleopathologists leaves little doubt that both diseases originated in the Old World. The findings of this study lend further support to the fact that, although rare, human treponematosis and tuberculosis were indeed endemic in the pre-Columbia New World before contact. There is no evidence that these two diseases could have arisen independently and de novo, especially during the relatively short time since man's arrival in the New World. Where a disease has been endemic for quite some time as appears to be the case with human treponematosis and tuberculosis, milder forms of the disease and improved host response could have developed in which only the most severe cases would be observable. This explains the rarity of skeletal lesions suggestive of these two human disease conditions in prehistoric human populations.     

Evidence for prehistoric cardiovascular disease of syphilitic origin on the Northern Plains

The identification of the treponemas among prehistoric Amerindian populations is problematic. This paper presents the evidence for the presence of cardiovascular disease of syphilitic origin on the Plains of North America during prehistoric times. Comparative data from modern populations is used to arrive at a diagnosis.     

Histological examination of experimentally mummified tissues

Tissue mummified by desiccation can be examined histologically after rehydration with Ruffer's solution, and a number of natural mummies have been studied by this technique. In order to study the efficacy of the rehydration process, and to evaluate the degree of artefact introduced, normal human tissues were desiccated, rehydrated, and examined histologically. There was generally good preservation of architecture and moderate preservation of cellular detail, with some organ specific variability. The prospect of an atlas of mummified pathological lesions is discussed, as an aid to the determination of disease patterns in prehistoric populations.     

Genetic aspects of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

The variability of clinical and biological expression of the 21 OH hydroxylase deficiency is likely to be related to genetical variability. Beside the well known autosomic recessive mode of inheritance the frequencies of the different forms of the disease, especially the classical and late onset form, have been more precisely defined through neonatal screening programs for the classical form which lead to a frequency of about 1 case/20,000 with a calculated gene frequency around 1/140. The linkage with the major histocompatibility complex allows the location of the putative locus of the 21 OH ase on the short arm of the chromosome 6 in the class III of the MHC. This linkage has made possible a better fetal diagnosis even if some pitfalls as recombination must be kept in mind. On the basis of clinical conditions the abnormal genes are likely to be considered as an allelic series with a least two main types of pathological alleles: the "severe" and "moderate". During the last two years, taking advantages of molecular gene biology, the structure of the normal human 21 OH ase gene has been studied. It exists as duplicate genes in close relation with the gene of the fourth component of the complement. A deletion of one of the copy has been demonstrated in the form associated with the BW47 MHC haplotype. It is likely that during the coming years genetical heterogeneity will be demonstrated as it has been for other genetic diseases as thalassemia.     

Population-based genetic screening.

A preventive genetic programme aimed to control beta-thalassemia in the Sardinian population is based on a combination of increased awareness of the population, carrier screening, genetic counselling and prenatal diagnosis. As a result, the registry of thalassemia major demonstrated a profound decline in the incidence of this disease from 1 per 250 to 1 per 1200 live births, with 90% of cases effectively prevented.     

Heterogeneity of haplotypes among patients with severe Cooley disease in Eastern Sicily

Summary There is a large variation of clinical severity among thalassemic patients in Sicily. A heterogeneous molecular basis has already been demonstrated among the patients presenting with thalassemia intermedia. The same approach, based mostly on linked haplotypes of the gene cluster polymorphisms and in some cases on the demonstration of the molecular defect itself, was used to investigate 55 patients presenting with severe Cooley anemia, all maintained under permanent transfusion regimen. A large heterogeneity was demonstrated in the observed haplotypes, and only a limited overlap with those already found in thalassemia intermedia. It has been noted that many of the patients are compound heterozygotes, the various observed associations making the antenatal diagnosis at the DNA level difficult in the near future.     

βLCR对β地中海贫血基因在转基因小鼠体内表达的影响

目的:明确在转基因小鼠体内,βLCR对β地中海贫血基因表达的影响。方法：将完整人β-IVSⅡ-654地中海贫血基因,与串连了人βLCR的β-IVSⅡ-654地中海贫血基因分别经显微注射法制作转基因小鼠;荧光定量RT-PCR法检测β-IVSⅡ-654地贫基因在转基因小鼠体内的表达;采用统计分析比较2类转基因鼠中外源基因的表达量。结果：成功建立2类整合了人β-IVSⅡ-654地贫基因的转基因小鼠模型。荧光定量RT-PCR分析结果表明,在整合了串连人βLCR的β-IVSⅡ-654地贫基因的小鼠体内,外源基因mRNA的表达量远高于仅整合β-IVSⅡ-654地贫基因的小鼠（统计分析P值 ）。结论：βLCR核心片段的存在可以使β-珠蛋白基因家族（包括β-地贫基因）在转基因小鼠体内获得高效表达的必要条件。     

史前人类对动物骨骼油脂的开发和利用

动物骨骼油脂的开发和利用是史前人类生存活动的重要组成部分.西方学者的研究表明,这一过程可能包含了敲骨取髓和骨脂提取两种不同的人类行为.相较于敲骨取髓,骨脂提取更为复杂,不仅要将骨骼砸碎成较小尺寸,还要加水煮沸骨骼碎片,过程中不断添冷水使水保持温和沸腾的状态,才能获得浮于水面的骨脂.目前,国内学者在此领域的研究多关注于前...     

Pathoecology of Chiribaya parasitism

The excavations of Chiribaya culture sites in the Osmore drainage of southern Peru focused on the recovery of information about prehistoric disease, including parasitism. The archaeologists excavated human, dog, guinea pig, and llama mummies. These mummies were analyzed for internal and external parasites. The results of the analysis and reconstruction of prehistoric life from the excavations allows us to interpret the pathoecology of the Chiribaya culture.     

Chagas' disease in pre-Columbian South America

The quest for the origin and dispersion of Chagas' disease, the second most important vector-borne disease in Latin America, has epidemiological, immunological, and genetical implications. Conjectures based on accounts of chroniclers, reviews of the archaeological literature and the present distribution of triatomine bugs, the vectors of the disease, held that the origin of the adaptation of Triatoma infestans (aspecies of the subfamily Triatominae) to human dwellings occurred in prehistoric times. The autopsy of 35 mummies exhumed in the Chilean desert, dated between 470 B.C. and 600 A.D., revealed the presence of clinical manifestations of Chagas' disease and put earlier speculations on a factual basis.     

Cultural ecology of prehistoric parasitism on the Colorado Plateau as evidenced by coprology

The study of coprolites (desiccated feces) is recognized as a viable method for analyzing parasitism of prehistoric peoples. Eight species of helminth parasites, including nematodes, cestodes, and acanthcephalans, have been recovered from archaeological sites on the Colorado Plateau. The comparative analysis of parasitological findings illustrates the effects of changing subsistence strategies and varying life-style on prehistoric human parasitism. This comparative study is based on the analysis of coprolites recovered from one Archaic hunter-gatherer site and two Anasazi agricultural villages. Hunter-gatherers are represented by coprolites from Dust Devil Cave in south-eastern Utah. Coprolites of prehistoric agriculturalists from Antelope House in Canyon de Chelly, Arizona, and from Salmon Ruin in northwestern New Mexico were studied. The results demonstrate that helminth parasitism increased with the advent of agriculture. Between the agricultural sites, differences in patterns of excreta disposal, foraging behavior, and local ecology resulted in pronounced variations in both percentage of coprolites containing parasite remains and the number of parasite species represented.     

Treponematosis: a possible case from the late prehistoric of North Carolina

The skeleton of an adult female exhibiting evidence of treponemal infection was recently recovered from the Hardin site in the piedmont region of North Carolina. Archaeological indicators suggest a late prehistoric affiliation. The skeleton is affected by a diffuse process resulting in surface changes, both destructive and appositional, node formation and shaft expansion, medullary encroachment and filling, cortical thickening, and fracture. There is both cranial and postcranial involvement. While treponemal infection is indicated, the atypical nature of the total pattern raises the possibility of multiple pathological processes operating simultaneously. The significance of this case is threefold. It provides information on the ability of prehistoric peoples to cope with disease. It reminds the paleopathologist of the dangers inherent in attempts at singular and specific diagnoses. It sheds new light on the epidemiology of the treponemal diseases.     

Mouse beta thalassemia, a model for the membrane defects of erythrocytes in the human disease

The present study describes the pathophysiology, at the cellular level, of the mouse beta thalassemia and shows the pertinence of this model for the human disease. The homozygous state of mouse beta thalassemia is characterized by a clinical syndrome similar to the human beta thalassemia intermedia, but it cannot be explained by the small deficiency in beta chain synthesis. The small pool of unpaired and soluble alpha chains present in mouse reticulocytes contrasts with the large amount of insoluble alpha chains in erythrocytes which is induced by the high instability of mouse alpha chains and the absence of significant proteolysis. The amount of insoluble alpha chains associated with red cell ghosts is similar in human and mouse disease of similar severity. The study of membrane protein defects showed a decreased amount of spectrin (alpha and beta chains) and dramatic changes in the distribution of the most reactive thiol groups of membrane proteins. These results were similar to that previously described in the human disease (Rouyer-Fessard, P., Garel, M. C., Domenget, C., Guetarni, D., Bachir, D., Colonna, P., and Beuzard, Y. (1989) J. Biol. Chem. 264, 19092-19098). Abnormal density distribution curves of erythrocytes and oxidant-induced lysis of red blood cells used as functional tests were similar in the human and mouse beta thalessemia. We conclude from the present study that 1) mouse beta thalassemia is an excellent model for the membrane defects occurring in the human disease; 2) disease expression is not the reflection of the globin chain unbalance only nor of the soluble pool of alpha hemoglobin chain but mainly is a reflection of insoluble alpha chains; and 3) the rate of proteolysis and instability of alpha chains are important factors which must be taken into consideration in the pathophysiology and the clinical heterogeneity of the disease.     

Stable nitrogen and carbon isotope ratios in bone collagen as indices of prehistoric dietary dependence on marine and terrestrial resources in southern California

The ratios of 15N to 14N and 13C to 12C tend to be higher in marine than in terrestrial organisms. The concentrations of these isotopes in human bone collagen consequently can be used to make inferences about the contribution of marine and terrestrial resources to prehistoric diets. The utility of studying 15N/14N and 13C/12C ratios in conjunction with each other is illustrated by our analysis of 40 human burials from archaeological sites in the Santa Barbara Channel area of southern California. The mean delta 13C and delta 15N values (in per mil) of collagen from these skeletons decrease progressively from the Channel Islands (delta 13C = -14.0, delta 15N = +16.3) to the mainland coast (delta 13C = -14.5, delta 15N = +14.9) to the interior (delta 13C = -17.2, delta 15N = +10.9). These data suggest that Indians living on the Channel Islands during the late prehistoric period were heavily dependent on marine resources. The inhabitants of the mainland interior, in contrast, had a diet composed largely of terrestrial foods. From their isotope ratios, it appears that the Indians who lived on the mainland coast consumed a mixed diet containing substantial quantities of both marine and terrestrial resources. Differences in 15N/14N and 13C/12C ratios of individuals from mainland sites dating from the early and late prehistoric periods show that the marine component of the diet increased substantially through time. These isotopic data are consistent with pathological, faunal, and artifactual evidence of increased marine resource exploitation during the late prehistoric period.