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The first discovery of a complete skeleton of a fossil orang-utan in a cave of the Hoa Binh Province, Vietnam.

Here we provide a description of the first complete adult fossil orang-utan skeleton from the Asian mainland. This specimen, and remains of a juvenile orang, were collected in a late Pleistocene cavern in the Hoa Binh Province of The Socialist Republic of Vietnam. The results confirm the suggestions by Hooijer (1948) Zool. Meded. Leiden29, 175-301 and later by Schwartz et al. (1995) Anthrop. Pap. Am. Mus. Nat. Hist.76, 1-24, that ancient orang-utans had bigger teeth than those of modern Pongo pygmaeus (P. p. pygmaeus and P. p. abelii), while the dental morphology is similar. Body proportions of the adult individual of Hoa Binh show a large skull with very large teeth but proportionally a small body. This individual is also singular in having high intermembral and brachial indices, in comparison with those of modern subspecies.

Animals↗

Bone density in medieval skeletons.

We studied the most complete skeletons found in an excavation from the 14th and 15th century in central Stockholm. One hundred eighty-seven were from men and 156 from women: 241 individuals were estimated to be between 20 and 39 and 102 between 40 and 59 years old at death. We examined the bones radiographically and by dual photon absorptiometry. The bone mineral density (BMD) was similar to the finding in North America and Northern Europe today as was the relationship between men and women. However, there appeared to be a higher diaphyseal bone density in the lower extremities, especially in men. The femur score was higher and the BMD of the femoral and tibial shafts was higher than today. In the upper extremities the diaphyseal bone density was lower. Meema's index, as well as the metacarpal score, was smaller than in individuals in this century and the BMD of the humeral shaft was also lower than seen today. Overall, the metaphyseal bone density was similar to what we now consider normal; i.e., the mean BMD of the femoral neck was 0.96 g/cm2 in men and 0.90 g/cm2 in women and of the distal radius 0.43 and 0.32 g/cm2, respectively. The low diaphyseal density and in the upper extremities may be related to the nutritional status, whereas the greater need for walking and standing in the 14th and 15th century might have led to the high diaphyseal density in the lower extremities. There was no evidence of bone loss after 40 years of age in either sex in our study. The average expected lifespan for an adult individual was less than 50 years and we suggest that the relatively high bone density in the older age group may be due to selection of the most physically fit. The activity pattern, therefore, may be considered the most important determinant for the differences.

Adult↗

Effect of Nocardia rubra cell wall skeleton and/or cyclophosphamide on leukemogenesis induced by N-ethyl-N-nitrosourea in Donryu rats.

The effect of Nocardia rubra cell wall skeleton (N-CWS) and/or cyclophosphamide (CP) on chemical carcinogenesis was examined in female Donryu rats exposed to N-ethyl-N-nitrosourea (ENU) in the drinking water for 6 weeks. Five administrations of N-CWS following ENU treatment caused a slight prolongation of the average survival of rats but did not reduce the incidence of leukemia. CP given on two occasions after ENU treatment caused a moderate prolongation of average survival period and a moderate reduction of the incidence of leukemia, but significant differences from ENU-treated control group values were not observed after statistical analysis. Combined treatment with N-CWS and CP after ENU treatment caused prolongation of the average survival period of rats and a statistically significant reduction in the incidence of leukemia. The present experiment indicates that combined treatment with N-CWS and CP effectively reduces induction of leukemia by ENU in rats, although other types of tumors were not affected.

Animals↗

Malformations of the axial skeleton in cranioschisis aperta and exencephaly in rat fetuses induced after neural tube closure.

Single doses of cyclophosphamide were administered (IP) to groups of Wistar rats, on different days of gestation after neural tube closure (days 12-15) and fetuses were collected on day 20. A very large number of the fetuses treated during days 12-14 exhibited cranioschisis and exencephaly. Ethanol fixed, alizarin red stained specimens were observed for axial skeletal abnormalities. The exencephalic ones lacked ossified skulls. The basicranial bones were either under ossified or had undergone extensive fusion resulting in reduction in cranial volume. The basicraniovertebral angle was obtuse. The vertebral bodies and arches showed varying degrees of hypoplasia, fusion and/or agenesis. The development of ribs and sternebrae was also extensively affected. Treatment on day 15 did not induce exencephaly but the axial skeleton was hypoplastic. Wavy ribs were a remarkable feature of these fetuses. All exencephalic fetuses had subcutaneous haemorrhages; many of them were obviously oedematous. These data indicate that the susceptible period for induction of these anomalies does not stop at neuropore closure.

Abnormalities, Drug-Induced↗

Augmentative effect of Nocardia rubra cell-wall skeleton on the induction of human lymphokine-activated killer (LAK) cells by the production of LAK cell helper factor(s).

Nocardia rubra cell wall skeleton (N-CWS) was found to synergistically augment lymphokine-activated killer (LAK) cell generation from human peripheral blood mononuclear cells (PBMC) in the presence of a suboptimal dose of recombinant interleukin-2 (rIL-2). N-CWS increased the number of PBMC expressing IL-2 receptor on their surfaces, and the presence of N-CWS at the early stage of the culture period was essential for the exertion of its augmentative activity on the LAK induction. The predominant phenotype of LAK precursor cells responding to N-CWS and rIL-2 was CD3- CD16+. Culture supernatant from N-CWS-stimulated PBMC was found to act as a substitute for N-CWS in the induction of LAK generation in the presence of rIL-2, suggesting that these cells produced a factor capable of augmenting LAK cell induction (LAK helper factor, LHF). LHF was found to have a molecular mass of 29 kDa by gel filtration, and could also function as a killer helper factor to augment allo-antigen-specific cytotoxic T lymphocyte generation from human peripheral blood T cells as well as murine thymocytes. LHF showed no species specificity, indicating that it is different from IL-4. The enhancing activity of LHF was not neutralized with anti-TNF alpha, anti-IL-1 alpha, or anti-IL-1 beta antibodies. Furthermore, no tumor necrosis factor-alpha (TNF alpha), TNF beta, IL-1 alpha, beta, IL-2, IL-5, IL-6 or interferon activity was detected in semi-purified LHF during enzyme-linked immunosorbant assay and biological assays. The present findings indicate that LHF produced from N-CWS-stimulated PBMC is a molecule distinct from TNF alpha, TNF beta, interferon, IL-1, -2, -4, -5, and -6, and suggest that LHF might be a novel lymphokine involved in LAK generation.

Adjuvants, Immunologic↗

Effects of periodic administration of Nocardia rubra cell-wall skeleton on immunoglobulin production and B-cell-stimulatory factor activity in vitro in workers at a poison gas factory.

The former workers at the Okunojima poison gas factory (poison gas workers) are a high-risk group for malignant neoplasms and show abnormalities in cellular immunity. At the same time, poison gas workers often have chronic respiratory diseases, such as chronic bronchitis, and are highly susceptible to respiratory infections. To explore the possibility of immunological cancer prevention, we have periodically administered 200 micrograms Nocardia rubra cell-wall skeleton (N-CWS) to poison gas workers once every 3 months since December 1978. During this period, we noted a significantly lower incidence of influenza among poison gas workers receiving N-CWS than in those not receiving the drug during the influenza epidemic. This finding suggested that the administration of N-CWS enhanced the resistance of these workers to infections. Therefore, periodical administration of N-CWS to poison gas workers was considered to enhance the reduced T-cell function of normalizing antibody production by stimulating the production of B-cell-stimulatory factor (BSF). In the present study, to clarify the mechanism of immunosuppression in the poison gas workers and to examine the effects of continual administration of N-CWS on this condition, we compared the immunoglobulin production and the proliferative and differentiative activities of B-cell-stimulatory factor (BSF) of peripheral blood mononuclear cells (PBMC), in poison gas workers treated or not treated with N-CWS. Comparisons were also made with age-matched healthy controls. In the untreated poison gas workers, immunoglobulin and BSF production of PBMC were reduced as compared with the control group. On the other hand, in the poison gas workers receiving N-CWS, immunoglobulin and BSF production of PBMC were restored nearly to the control level. These results show that in vitro antibody production in the poison gas workers was reduced and that a reduction in BSF production of T cells was one of its causes.

Adjuvants, Immunologic↗

Effect of Nocardia rubra cell-wall skeleton on cancer prevention in humans.

The retired workers at the chemical weapons plant in Japan are regarded as a high-risk group for cancers. Under the Cancer Preventive Program, Nocardia rubra cell-wall skeleton (N-CWS) was administered to 80 workers directly involved in the production of sulfur mustard and 66 workers engaged in work related to sulfur mustard production. Untreated workers whose age, sex, duties and duration of work at this factory were individually matched to the N-CWS-treated workers were used as controls. During a 4.5-year observation period, development of cancers was found in 7 treated workers and 17 untreated controls. After elimination of the influence of the difference in smoking level, the incidence of subjects who developed cancers was compared statistically between the N-CWS-treated workers and the untreated controls and a significant suppression of development of cancers was noted in the N-CWS-treated workers. Thus, it was concluded that the administration of N-CWS could prevent cancer development in humans.

Aged↗

Clinical usefulness of continuous administration of Nocardia rubra cell wall skeleton (N-CWS) in diffuse panbronchiolitis (DPB).

Eight patients with diffuse panbronchiolitis (DPB) who had repeated intractable airway infections were continuously treated with Nocardia rubra cell wall skeleton (N-CWS), a biological response modifier. As a result, subjective symptoms were reduced in 6 patients. Antibiotics therapy could be discontinued completely in two patients and the dose of antibiotics could be reduced considerably in two other patients. No adverse reactions in relation to N-CWS were observed. These results suggest that N-CWS is effective in treating erythromycin-resistant DPB.

Adult↗

Human blood monocyte activation by Nocardia rubra cell wall skeleton for productions of interleukin 1 and tumor necrosis factor-alpha.

Human blood monocytes were obtained from peripheral blood of healthy donors by counter-flow centrifugal elutriation. Functional integrity of monocytes for production of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) in response to Nocardia rubra cell wall skeleton (N-CWS) was examined by bioassay and enzyme immunoassay. Monocytes treated with N-CWS at more than 0.5 microgram/ml produced IL-1 and TNF-alpha extracellularly. Extracellular TNF activity appeared within 4 h, and maximally, 16 h after N-CWS stimulation, whereas longer time was needed for IL-1 activity to appear, the peak production being at 24 h. The neutralizing experiment also showed that anti TNF-alpha antibody did not affect IL-1 production by the monocytes treated with N-CWS, suggesting independency of IL-1 production of TNF-alpha. These results suggest that the therapeutic antitumor effect of N-CWS is due, in part at least, to the augmented production of these monokines.

Bacterial Proteins↗

Non-radiological technique for 3D imaging of intestinal endoscopes: computerised graphical 3D representation of endoscope and skeleton.

Colorectal cancer is a common malignancy but as yet there is no agreement regarding the optimal method for screening. Colonoscopy is theoretically the investigation of choice. The examination can, however, be difficult to perform and the average trainee requires at least 200 supervised examinations to become proficient. Colonoscopy takes on average about half an hour per patient and sedation is normally required because of painful instrument looping. The authors previously developed a non-radiological method of visualising the path of the endoscope using magnetic drive coils under the patient and a chain of sensors in the biopsy channel of the instrument. The computer-generated grey-scale images produced in real time were deemed unsatisfactory and the anatomical markers confusing. A new computer graphics system is described in which a much more realistic endoscope and, if necessary, skeleton can be produced. The wire-frame octagonal representation should help in the detailed analysis of colonoscopy using existing endoscopes and aid in future computer design and testing of novel instruments incorporating worm or snake-like properties.

Colonoscopy↗

Morphological study of cytotoxicity produced by PSK-induced polymorphonuclear leukocytes (PMNs) and Nocardia rubra cell wall skeleton.

The morphologic changes in PMNs induced by an i.p. injection of PSK, a polysaccharide from the mycelia of Coriolus versicolor, and tumor cells undergoing cell death, were evaluated by immunohistochemical staining and electron microscopy. Male C3H/He mice, 8-10 -weeks old, received an i.p. injection of 125 mg/kg of PSK. Their PMNs were obtained 6 h after the PSK injection by peritoneal lavage. N-CWS (Nocardia rubra cell wall skeleton) was added at the start of the chromium release assay using the MM46 mammary carcinoma cell line, which is syngeneic to C3H/He mice, as target cells. During the cytotoxic assay, the cells were fixed at various time points. The MM46 cells expressed ICAM-1 while the PMNs expressed both ICAM-1 and LFA-1 as determined by immunohistochemical staining and immunoelectron microscopy using anti-ICAM-1 and anti-LFA-1 antibodies. PMNs with ruffle-like microvilli adhered to the MM46 tumor cells 30 min after the addition of N-CWS. Immunoelectron microscopic findings suggested that the adhesion molecules were LFA-1 on the PMNs and ICAM-1 on the MM46 tumor cells, but cell fusion between the PMNs and tumor cells was not observed. The MM46 tumor cells gradually lost their microvilli, which showed cell damage, and died 6-7 h after the addition of the N-CWS. This time course of tumor cell death is compatible with the results of the cytotoxic assay. Pretreatment of PMNs by anti-LFA-1 antibody suppressed 1% lysis of MM46 tumor cells from 90% to 10% (p < 0.01). These data suggest that adhesion molecule on the surface of PMNs such as LFA-1 might play an important role on signal transduction of these PMNs cytotoxic function in this experimental system.

Adjuvants, Immunologic↗

[Paleopathology of ancient Egyptian mummies and skeletons. Investigations on the occurrence and frequency of specific diseases during various time periods in the necropolis of Thebes-West].

The scientific investigation of mummies and skeletons provides considerable data for the reconstruction of the living conditions and diseases of past populations. We describe the data on four completely analyzed tomb complexes from the huge necropolis of Thebes-West in Upper Egypt dating to different time periods. A total of 211 individuals from the so-called "Middle Kingdom" (MK, c. 2050-1750 BC) were compared to 273 individuals from the "New Kingdom" (NK) to "Late Period" (LP, in total 1550-500 BC). The age at death and the sex ratio were comparable between both groups. There was a high rate of early death with a maximum between the 2nd and 3rd decade of life but infant/adolescent burials were comparably rare. This early death is assumed to be due to an elevated prevalence of various infectious diseases. Likewise, a high rate of tuberculosis infections was seen in those individuals regardless of which time period they came from. Metabolic disorders with osseous manifestations, such as scurvy, osteomalacia and chronic anemia (cribra orbitalia, porotic hyperostosis) were found with a high frequency in the MK populations but significantly less in the NK-LP populations. On the other hand signs of trauma were comparably high, and lesions due to degenerative joint and vertebral diseases were significantly higher in LP than in MK or NK individuals suggesting a higher mechanical load in the later populations. Cases of malignant (secondary) bone tumors and various soft tissue/organ diseases indicate that "civilization" disorders were present when the living conditions assured survival into advanced age. In summary, we provide circumstantial evidence that the systematic and concise analysis of mummy and skeletal remains can allow a reconstruction of major aspects of life and disease in historic populations, although a complete reconstruction is not possible.

Bone Diseases↗

Regression of bovine lymphosarcoma by treatment with cell-wall skeleton of Nocardia rubra.

Five bovine-leukaemia-virus-positive cattle with enlarged subcutaneous lymphatic nodules and having tumour-associated antigens (TAA) in their peripheral blood lymphocytes (PBL) were treated by injection of the cell-wall skeleton of Nocardia rubra (N-CWS) into the nodules. All treated animals received two or three injections of N-CWS (each 0.5-4 mg per nodule) at 2 or 4-week intervals. The effect of the treatment was evaluated by the size of the nodules. Complete regression of nodules was observed in seven out of ten nodules treated in five animals. Decrease of TAA-positive cells was also observed in their peripheral blood lymphocytes for all five treated animals. In one cow, the TAA-positive cells remained low for at least 280 days after treatment.

Adjuvants, Immunologic↗

New forensic anthropological approachment for the age determination of human fetal skeletons on the base of morphometry of vertebral column.

The anthropometrical study was carried out on 107 human fetal/newborn skeletons (54 male, 43 female, and 9 of unknown sex). The age of the individuals ranged from 4 to 10 lunar months. Each fetal or newborn vertebral region (cervical, thoracal and lumbar) has its own distinguishing features that are easily identifiable even in fragmentary bones. With our large sample size and extension of the age range studied, we are able to determine the fetal age with a considerable degree of accuracy from measurements defined in the vertebral ossification centers using regression equations. A simple rapid method for the identification and classification of fetal vertebral column bones has been contributed. The identification and classifications were carried out using discriminant functions. Knowledge of changes in vertebral column bones during fetal development is important in applied contexts of forensic and anthropology researches.

Age Determination by Skeleton↗

Nacholapithecus skeleton from the Middle Miocene of Kenya.

An almost entire skeleton of a male individual of Nacholapithecus kerioi (KNM-BG 35250) was discovered from Middle Miocene (approximately 15 Ma) sediments at Nachola, northern Kenya. N. kerioi exhibits a shared derived subnasal morphology with living apes. In many postcranial features, such as articular shape, as well as the number of the lumbar vertebrae, N. kerioi resembles Proconsul heseloni and/or P. nyanzae, and lacks suspensory specializations characteristic of living apes. Similarly, N. kerioi shares some postcranial characters with Kenyapithecus spp. However, despite the resemblance, N. kerioi and Proconsul spp. are quite different in their body proportions and some joint morphologies. N. kerioi has proportionally large forelimb bones and long pedal digits compared to its hindlimb bones and lumbar vertebrae. Its distinctive body proportions suggest that N. kerioi was more derived for forelimb dominated arboreal activities than P. nyanzae and P. heseloni. On the other hand, it exhibits a mixture of derived and primitive cranio-dental and postcranial features relative to the contemporaneous Kenyapithecus and Early MioceneMorotopithecus. While the phylogenetic position of N. kerioi is unsettled, it seems necessary to posit parallel evolution of cranio-dental and/or postcranial features in fossil and living apes.

Animals↗

Mineralized cartilage in the skeleton of chondrichthyan fishes.

The cartilaginous endoskeleton of chondrichthyan fishes (sharks, rays, and chimaeras) exhibits complex arrangements and morphologies of calcified tissues that vary with age, species, feeding behavior, and location in the body. Understanding of the development, evolutionary history and function of these tissue types has been hampered by the lack of a unifying terminology. In order to facilitate reciprocal illumination between disparate fields with convergent interests, we present levels of organization in which crystal orientation/size delimits three calcification types (areolar, globular, and prismatic) that interact in two distinct skeletal types, vertebral and tessellated cartilage. The tessellated skeleton is composed of small blocks (tesserae) of calcified cartilage (both prismatic and globular) overlying a core of unmineralized cartilage, while vertebral cartilage usually contains all three types of calcification.

Animals↗

Early mammals: teeth, jaws and finally a skeleton!

Suprising new fossils - a skeleton and a jaw - give us a much clearer picture of mammals that lived during the time of non-avian dinosaurs; the new finds illuminate the early evolution of the lineage leading to modern mammals, and challenge traditional understanding of placental mammal evolution and biogeography.

Animals↗

Interferon gamma-producing ability in blood lymphocytes of patients with lung cancer through activation of the innate immune system by BCG cell wall skeleton.

An in vitro assay system was developed to assess the potency of the human innate immune system by measurement of IL-12, IL-18, IL-10 and IFNgamma in the supernatants of bacillus Calmette-Guerin cell wall skeleton (BCG-CWS)-stimulated blood samples. BCG-CWS is a ligand for Toll-like receptor (TLR) 2 and 4, and activates monocytes to macrophages (Mphi), and immature dendritic cells to mature antigen-presenting cells (APC). This system was found to allow the discrimination of immune suppressive states in patients with lung cancer from normal immune states in light of the cytokine profile. The following results were deduced from analyses of BCG-CWS-stimulated blood samples of lung cancer patients with reference to normal subjects. (1) The levels of production of IFNgamma and IL-10 by lymphocytes were decreased. (2) IL-12 p40 production by monocytes/Mphi was upregulated, while that of IL-10 was downregulated. (3) IL-18 was detected in all patients in a range similar to normal subjects. (4) Responses of lymphocytes to IL-2 and IL- 18 in terms of IFNgamma production were diminished. (5) The upregulated IL-12 levels were recovered to within the normal range in most patients after tumor resection. (6) Male patients showed more severe suppression of IL-12/IL-18-mediated IFNgamma production than female patients. Thus, the lesser IFNgamma production observed in patients' blood with high IL-12 p40 levels in response to BCG-CWS may reflect the production of p40 dimers or IL-23 instead of p70, or the presence of some unknown pathways to prohibit the interface between the innate and acquired immune systems. BCG-CWS-mediated Toll signaling may participate in IFNgamma induction for lymphocytes through Mphi/APC IL-12/I-18 modulation.

Adjuvants, Immunologic↗