Variation in limb proportions between Jomon foragers and Yayoi agriculturalists from prehistoric Japan

Variation in limb proportions between prehistoric Jomon and Yayoi people of Japan are explored by this study. Jomon people were the descendents of Pleistocene nomads who migrated to the Japanese Islands around 30,000 yBP. Phenotypic and genotypic evidence indicates that Yayoi people were recent migrants to Japan from continental Northeast Asia who likely interbred with Jomon foragers. Limb proportions of Jomon and Yayoi people were compared using RMA regression and "Quick-Test" calculations to investigate relative variability between these two groups. Cluster and principal components analyses were performed on size-standardized limb lengths and used to compare Jomon and Yayoi people with other groups from various climatic zones. Elongated distal relative to proximal limb lengths were observed among Jomon compared to Yayoi people. Jomon limb proportions were similar to human groups from temperate/tropical climates at lower latitudes, while Yayoi limb proportions more closely resemble groups from colder climates at higher latitudes. Limb proportional similarities with groups from warmer environments among Jomon foragers likely reflect morphological changes following Pleistocene colonization of the Japanese Islands. Cold-derived limb proportions among the Yayoi people likely indicate retention of these traits following comparatively recent migrations to the Japanese Islands. Changes in limb proportions experienced by Jomon foragers and retention of cold-derived limb proportions among Yayoi people conform to previous findings that report changes in these proportions following long-standing evolution in a specific environment.     

Paleopathological study on a case of osteosarcoma

This report concerns a probable case of osteosarcoma found in a precontact Hawaiian skeleton from the east coast of Oahu Island, Hawaii. A young adult female showed a tumorous bone proliferation with a coarse, corallike appearance at the distal metaphyseal area of the left femur. In gross observation, a profusion of coalescing bone was extended to the surrounding space and also invaded the marrow space. X-ray films revealed spotted and ringed shadows in the shaft and a "sunburst appearance" in the lesion. Histological examination of the tumor bone fragment showed a great deal of primitive bone tissue formation without any systemic Haversian structure. The diagnosis of osteogenic osteosarcoma is much more compatible than other primary malignant bone tumors such as Ewing's sarcoma, fibrosarcoma, and chondrosarcoma or osteoplastic metastatic carcinoma of the bone when the location and morphology of the tumor are considered along with the age of the decedent.     

Patterns of systemic stress during the agricultural transition in prehistoric Japan

This study documents and interprets systemic stress during the agricultural transition in prehistoric Japan using linear enamel hypoplasia (LEH) defects and cribra orbitalia (CO) lesions. Middle to Final Jomon cultures (5000–2300 BP) from Honshu Island represent the foraging samples, while Yayoi cultures (2500–1700 BP) represent the early agricultural samples. Jomon foragers from eastern Japan had broad‐based, intensive economies. Jomon foragers from western Japan had a greater focus on seasonally available, nutritionally poor resources, while Yayoi people were descendents of migrants from the East Asian continent and introduced wet rice economies to Japan. This study tests the hypotheses that wet rice economies will be associated with a lower prevalence of teeth/individuals affected by LEH defects in western Japan, while few differences in the prevalence of teeth/individuals with LEH defects will be observed between eastern Jomon people and Yayoi farmers. It is further predicted that similar CO prevalence will be observed between Jomon and Yayoi people given environmental similarities. Significantly greater frequencies of teeth affected by LEH defects are observed among western Jomon compared to Yayoi people. The prevalence of teeth with LEH defects is slightly elevated among eastern Jomon foragers compared to Yayoi agriculturalists. Significant differences in CO prevalence are not observed. Systemic stress prevalence in western Japan likely declined following wet‐rice agriculture because this crop provided a predictable, renewable resource base. Systemic stress prevalence was similar between eastern Jomon and Yayoi people because both groups practiced intensive subsistence strategies. Similar CO prevalence reflects infectious diseases associated with living conditions. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc.     

Role of osteoblast suppression in multiple myeloma

Multiple myeloma is the most common form of plasma cell dyscrasia and virtually all cases of myeloma exhibit osteolytic lesions, which result in bone pain, pathological fractures, spinal cord compression, and hypercalcaemia. Malignant plasma cells disrupt the delicate balance between bone formation and bone resorption, which ultimately leads to the debilitating osteolytic lesions. This review focuses principally on mechanisms of osteoblast inhibition by malignant plasma cells with emphasis placed on our experimental findings, which support a model for abnormal Wnt signaling in osteoblast suppression. We describe how excessive amounts of soluble Wnt inhibitors secreted by malignant plasma cells in multiple myeloma could promote osteolytic lesions, tumor growth, suppress hematopoiesis, prevent proper engraftment, and expansion of transplanted stem cells. Finally, we detail current therapies shown to disrupt the interaction between the myeloma cell and the microenvironment, leading to activation of osteoblasts.     

Growth-related changes in prehistoric Jomon and modern Japanese mandibles with emphasis on cortical bone distribution

Cortical bone distribution of the anthropoid mandibular symphysis has been addressed in relation to mechanical stress generated by mastication. To examine whether or not bone mass and distribution patterns of the human mandibular symphysis could be interpreted as an example of functional adaptation, we compared the skeletal growth series of two populations, prehistoric Jomon, considered to represent a "robust" mandibular morphology associated with a presumed heavier masticatory load, and modern Japanese. Results showed that the adult Jomon symphysis possessed significantly greater bone mass and thicker cortical bone compared to the modern Japanese condition. However, the second moments of area did not differ significantly between the two, indicating comparable rigidity against bending. Furthermore, the Jomon mandibles of the infant to juvenile stages exhibited most of the adult characteristics, in both bone mass/distribution of the symphysis and in mandibular corpus/ramus morphologies. The present study also demonstrated the presence of a growth pattern of symphyseal cortical thickness, common to both the Jomon and the modern Japanese series. In both populations, subsequent to deciduous molar occlusion, cortical bone tends to be thickest at the inferolingual symphysis, at the location where the highest tensile stresses presumably occur during mastication. These findings suggest that the "robust" characteristics of the Jomon mandible are initially manifested early in development, and that the effect of mechanical stimulus to bone mass formation in the human symphysis is largely confined to a regulatory role during growth modeling.     

Problems of differential diagnosis in a case of bone lesions caused by myelosclerosis associated with hyperparathyroidism

The authors present a report on the case of a female patient with myelofibrosis where X-ray examinations of the bone skeleton predominantly showed such osteolytic changes which are no typical of myelosclerosis. Morphological criteria rather would have corresponded to osteitis fibrosa cystica generalisata. Laboratory examinations partially indicated primary hyperparathyroidism, this assumption could not be confirmed by other examinations. Also histological findings of repeated bone biopsies did not lead to a uniform diagnosis. Autopsy confirmed the presence of both diseases. The authors consider the synergistic effect of both diseases to be the cause for the development of those bone changes mentioned above.     

Probable destructive meningioma in an archaeological adult male skull from Alaska

Several intracranial pathological conditions can affect the bones of the skull. The most common cause of these conditions is tumor, but infection and other diseases are also known to affect the bones of the skull. Distinguishing between the various causes of intracranial skeletal pathology in archaeological human remains is usually a challenging exercise, and a specific diagnosis will often be impossible. Meningiomas are tumors that arise in arachnoid tissues embedded in the outer layer of the dura. Because of this association, they occur almost exclusively in the skull and vertebral column. Usually meningiomas are slow-growing tumors that do not metastasize to other organs and tissues of the body. However, rare cases can be malignant and, even when meningiomas are benign, their presence and growth can adversely affect the nervous and vascular supply to other tissues in the skull and vertebral column. Their effect on adjacent bone tissue varies from stimulating bone-forming lesions to causing highly destructive lesions. A few examples of meningioma have been described in the paleopathological literature. Most of these cases are bone-stimulating meningiomas. The case presented here is a probable example of a highly destructive meningioma of the skull base, with unilateral extension into the left side of the cranium. This case is compared with a modern clinical case of destructive intracranial meningioma that was documented both radiographically and pathologically. Destructive meningiomas can be confused with other pathological conditions, including benign and malignant tumors. Criteria for differentiating the diagnostic options are reviewed.     

Paleopathological Description and Diagnosis of Metastatic Carcinoma in an Early Bronze Age (4588+34 Cal. BP) Forager from the Cis-Baikal Region of Eastern Siberia

Extensive osteolytic and osteoblastic lesions were observed on the skeletal remains of an adult male excavated from an Early Bronze Age cemetery dated to 4556+32 years BP, located in the Cis-Baikal region of Siberia (Russian Federation). Lytic lesions ranged in size from several mm to over 60 mm in diameter and had irregular, moth-eaten borders. Many of these lesions destroyed trabecular bone, though a hollowed shell of cortical bone often remained observable. Radiographic analysis revealed numerous lytic lesions within trabecular bone that had not yet affected the cortex. Blastic lesions were identified as spiculated lines, bands, or nodules of mostly immature (woven) bone formed at irregular intervals. Anatomical elements with the greatest involvement included those of the axial skeleton (skull, vertebrae, sacrum, ribs, and sternum) as well as proximal appendicular elements (ossa coxae, proximal femora, clavicles, scapulae, and proximal humeri). Osteocoalescence of destructive foci was observed on the ilium and frontal bone, with the largest lesion found on the right ilium. Differential diagnoses include metastatic carcinoma, mycotic infections, tuberculosis, Langerhan''s cell histiocytosis, and multiple myeloma. Based on lesion appearance and distribution, age and sex of the individual, as well as pathogen endemism, the most likely diagnostic option for this set of lesions is metastatic carcinoma. The age and sex of this individual and appearance of the lesions may reflect carcinoma of the lung or, possibly, prostate. This represents one of the earliest cases of metastatic carcinoma worldwide and the oldest case documented thus far from Northeast Asia.     

Secretory products from PC-3 and MCF-7 tumor cell lines upregulate osteopontin in MC3T3-E1 cells

Tumor cells frequently have pronounced effects on the skeleton including bone destruction, bone pain, hypercalcemia, and depletion of bone marrow cells. Despite the serious sequelae associated with skeletal metastasis, the mechanisms by which tumor cells alter bone homeostasis remain largely unknown. In this study, we tested the hypothesis that the disruption of bone homeostasis by tumor cells is due in part to the ability of tumor cells to upregulate osteopontin (OPN) mRNA in osteoblasts. Conditioned media were collected from tumor cells that elicit either osteolytic (MCF-7, PC-3) or osteoblastic responses (LNCaP) in animal models and their effects on OPN gene expression were compared using an osteoblast precursor cell line, MC3T3-E1 cells. Secretory products from osteolytic but not osteoblastic tumor cell lines were demonstrated to upregulate OPN in osteoblasts while inhibiting osteoblast proliferation and differentiation. Signal transduction studies revealed that regulation of OPN was dependent on both protein kinase C (PKC) and the mitogen-activated protein (MAP) kinase cascade. These results suggest that the upregulation of OPN may play a key role in the development of osteolytic lesions. Furthermore, these results suggest that drugs that prevent activation of the MAP kinase pathway may be efficacious in the treatment of osteolytic metastases.     

Multiple myeloma; a review of 26 cases

Multiple myeloma is a rare, malignant disease of bone marrow which affects principally the vertebrae, ribs, pelvis and skull but may involve any part of the skeleton. Severe demineralization and destructive lesions of bones, producing severe pain and debility, are distinctive features. The disease is further distinguished by abnormalities of blood proteins and in some cases by the excretion in the urine of Bence-Jones protein, which seldom, if ever, is found in association with any other disease.X-ray examination is frequently helpful. In 22 of 24 cases (of a series of 26 cases) in which films were available, definite abnormalities were noted. Spontaneous fractures, particularly of vertebrae, are common. The diagnosis of the disease rests on the identification of the myeloma cell. This is best accomplished by aspiration of bone marrow. In several of the 26 cases in the series diagnosis was made by a neurosurgeon at the time of operation to relieve pressure on the spinal cord. The myeloma cell has a very characteristic appearance. In the present series the average duration of life after the onset of symptoms was only nine months. One patient, however, survived for at least ten years.     

MULTIPLE MYELOMA—A Review of 26 Cases

Multiple myeloma is a rare, malignant disease of bone marrow which affects principally the vertebrae, ribs, pelvis and skull but may involve any part of the skeleton. Severe demineralization and destructive lesions of bones, producing severe pain and debility, are distinctive features. The disease is further distinguished by abnormalities of blood proteins and in some cases by the excretion in the urine of Bence-Jones protein, which seldom, if ever, is found in association with any other disease.X-ray examination is frequently helpful. In 22 of 24 cases (of a series of 26 cases) in which films were available, definite abnormalities were noted. Spontaneous fractures, particularly of vertebrae, are common.The diagnosis of the disease rests on the identification of the myeloma cell. This is best accomplished by aspiration of bone marrow. In several of the 26 cases in the series diagnosis was made by a neurosurgeon at the time of operation to relieve pressure on the spinal cord. The myeloma cell has a very characteristic appearance.In the present series the average duration of life after the onset of symptoms was only nine months. One patient, however, survived for at least ten years.     

Probable evidence of scurvy in subadults from archeological sites in Peru

Subadult scurvy is not well documented in archeological human remains despite the existence of many biomedical references indicating that bone changes do occur in some cases and, because of this, should be observable in human burials. There are several potential reasons for this gap in our knowledge of scurvy. Not all children who suffered from scurvy died of the disease or from other causes when they had scurvy. Scurvy may not leave characteristic bone changes in every case of the disease. Some of the pathological conditions associated with scurvy have been known for many years, but these features may be rare or difficult to differentiate from other pathological conditions. Recently a lesion of the skull has been described that is probably pathognomonic for scurvy, specifically porous and sometimes hypertrophic lesions of the greater wing of the sphenoid. This lesion is bilateral and highly associated with evidence of inflammation at other anatomical sites in the skull. A survey of subadult skulls (N = 363) in the human skeletal collection from Peru at the National Museum of Natural History, Smithsonian Institution, reveals a prevalence of 10% of skulls that exhibit plausible evidence of scurvy. Some cases of scurvy also have cribra orbitalia that has been attributed to anemia. In most of the Peruvian scurvy cases, anemia is an unlikely possibility because there is no evidence of marrow hyperplasia. This highlights the need for caution in using lesions of the orbit as an indicator of anemia when there is no other evidence of this disease elsewhere in the skeleton. Anatomical evidence of scurvy offers the potential of providing new and important evidence of diet in archeological human populations.     

The role of the BMP signaling antagonist noggin in the development of prostate cancer osteolytic bone metastasis

Members of the BMP and Wnt protein families play a relevant role in physiologic and pathologic bone turnover. Extracellular antagonists are crucial for the modulation of their activity. Lack of expression of the BMP antagonist noggin by osteoinductive, carcinoma-derived cell lines is a determinant of the osteoblast response induced by their bone metastases. In contrast, osteolytic, carcinoma-derived cell lines express noggin constitutively. We hypothesized that cancer cell-derived noggin may contribute to the pathogenesis of osteolytic bone metastasis of solid cancers by repressing bone formation. Intra-osseous xenografts of PC-3 prostate cancer cells induced osteolytic lesions characterized not only by enhanced osteoclast-mediated bone resorption, but also by decreased osteoblast-mediated bone formation. Therefore, in this model, uncoupling of the bone remodeling process contributes to osteolysis. Bone formation was preserved in the osteolytic lesions induced by noggin-silenced PC-3 cells, suggesting that cancer cell-derived noggin interferes with physiologic bone coupling. Furthermore, intra-osseous tumor growth of noggin-silenced PC-3 cells was limited, most probably as a result of the persisting osteoblast activity. This investigation provides new evidence for a model of osteolytic bone metastasis where constitutive secretion of noggin by cancer cells mediates inhibition of bone formation, thereby preventing repair of osteolytic lesions generated by an excess of osteoclast-mediated bone resorption. Therefore, noggin suppression may be a novel strategy for the treatment of osteolytic bone metastases.     

Dimensional variation in the proximal ulna: evaluation of a metric method for sex assessment

We examined nutritional and developmental instability in prehistoric Japan, using data from 49 individuals across 13 archaeological sites. Hypoplasia incidence was used as a measure of nutritional stress, and fluctuating asymmetry (of upper facial breath, orbital breadth, and orbital height) as an indirect assessment of developmental instability. Abundant resources due to a stable climate during the Middle Jomon (5,000-3,000 BP) encouraged population growth, which led to regional cultural homogeneity and complexity. A population crash on Honshu in the Late/Final Jomon (roughly 4,000-2,000 BP) led to regionally divergent subsistence economies and settlement patterns. We find that the nutritional stress was consistent between periods, but developmental instability (DI) decreased in the Late/Final Jomon. While the DI values were not statistically significant, the higher values for Middle Jomon may result from sedentism, social stratification, and differential access to resources. On Hokkaido, Jomon culture persisted until the Okhotsk period (1,000-600 BP), marked by the arrival of immigrants from Sakhalin. Nutritional stress was consistent between Middle and Late/Final Jomon, but DI increased in the Late/Final. Nutritional and developmental instability decreased from Late/Final to Okhotsk, suggesting a positive immigrant effect. We expected to find an association between stress markers due to the synergistic relationship between nutrition and pathology. The data support this hypothesis, but only one finding was statistically significant. While high critical values from small sample sizes place limits on the significance of our results, we find that the impact of environmental and cultural change to prehistoric Japanese populations was minimal.     

NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF

Advanced breast cancers frequently metastasize to bone, resulting in osteolytic lesions, yet the underlying mechanisms are poorly understood. Here we report that nuclear factor-kappaB (NF-kappaB) plays a crucial role in the osteolytic bone metastasis of breast cancer by stimulating osteoclastogenesis. Using an in vivo bone metastasis model, we found that constitutive NF-kappaB activity in breast cancer cells is crucial for the bone resorption characteristic of osteolytic bone metastasis. We identified the gene encoding granulocyte macrophage-colony stimulating factor (GM-CSF) as a key target of NF-kappaB and found that it mediates osteolytic bone metastasis of breast cancer by stimulating osteoclast development. Moreover, we observed that the expression of GM-CSF correlated with NF-kappaB activation in bone-metastatic tumor tissues from individuals with breast cancer. These results uncover a new and specific role of NF-kappaB in osteolytic bone metastasis through GM-CSF induction, suggesting that NF-kappaB is a potential target for the treatment of breast cancer and the prevention of skeletal metastasis.     

Japanese tooth size: past and present

Mesial-distal and buccal-lingual crown measurements were made on male and female samples of recent Japanese teeth from three locations, Fukuoka, Kyoto, and Tokyo, and for Hokkaido Ainu and Koreans. Similar data were collected for prehistoric Middle-to-Late Jomon Japanese and from Yayoi specimens representing the first agriculturalists to appear in Japan. From a tooth-by-tooth comparison of cross-sectional areas, it was shown that the modern Japanese samples did not differ from one part of Japan to another. Korean tooth size also is not significantly different from Japanese, while Ainu have the smallest teeth recorded in Asia. The Yayoi who brought rice to Japan about 300 B.C. came in with teeth that were the same size as Chinese Neolithic teeth. They encountered a resident Jomon population whose teeth were 10% smaller. From tooth size measures alone, it is most economical to suggest that, if the rates of reduction observed elsewhere in the world applied in Japan, the recent Ainu would best be regarded as the direct descendants of the Jomon, while the modern Japanese are the results of in situ reduction from the incoming Yayoi. Other aspects of craniofacial morphology suggest that some Jomon was incorporated by the Yayoi. The modern Japanese, then, while predominantly derived from the Yayoi, would include a Jomon component.     

Reflections on the face of Japan: a multivariate craniofacial and odontometric perspective

Craniofacial variables for modern and prehistoric Japanese were subjected to multivariate analysis to test the relationships of the people of Japan with mainland Asian and Oceanic samples. The modern Japanese are tied to Koreans, Chinese, Southeast Asians, and the Yayoi rice agriculturalists who entered Japan in 300 B.C. Together they make up a Mainland-Asia cluster of related populations. The prehistoric Jomon foragers, the original inhabitants of the Japanese archipelago, are the direct ancestors of the modern Ainu, who made a recognizable contribution to the warrior class--the Samurai--of feudal Japan. Together, they are associated with Polynesians and Micronesians in a Jomon-Pacific cluster of related populations. Jomon-to-Ainu tooth size reduction proceeded at the same rate as that observable in the post-Pleistocene elsewhere in the Old World.     

Importance of <Emphasis Type="Italic">Rhus verniciflua</Emphasis> Stokes (lacquer tree) in prehistoric periods in Japan,deduced from identification of its fossil woods

In Japan, lacquered artifacts and remains of lacquer processing became common items in the early Jomon period beginning at ca. 6300 b.p. (ca. 5300 cal b.c.). However, there was no archaeobotanical evidence that Rhus verniciflua (lacquer tree), which is thought to be a prehistoric introduction from China on botanical grounds, grew in Japan until its distinction in wood structure from those of native Rhus species was clarified in 2004. Based on this new refinement in identification, 573 Rhus fossil woods so far reported from various archaeological sites in Japan were re-identified. The results showed that R. verniciflua commonly grew in middle to northern Honshu since the early Jomon period and that it may have been introduced from China with other cultivated plants before that time. During the Jomon period, R. verniciflua trees were used not just for lacquer collection, but also for building in the lowland which exploited their durability in waterlogged conditions.