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[Host mediated anti-tumor effect of Nocardia rubra cell wall skeleton on syngeneic tumor in mice].

The mode of action of Nocardia rubra cell wall skeleton (N-CWS) on Meth A fibrosarcoma (Meth A) was studied in BALB/c mice. N-CWS suppressed or regressed the intradermal growth of syngeneic Meth A cells in normal BALB/c and athymic BALB/c mice. The intradermally and subcutaneously infiltrated cells harvested from injection sites of N-CWS in normal mice showed in vitro cytotoxic activity against Meth A cells. Pretreatment of normal BALB/c mice with immunosuppressing agents such as hydrocortisone, carrageenan, or silica particles significantly reduced the anti-tumor effect of N-CWS. The growth of Meth A cells, rechallenged into BALB/c mice in which Meth A cells had once been suppressed or regressed by N-CWS treatment, was also inhibited, but not in similarly treated athymic nude mice. This resistant mechanism was shown to be dependent out cellular components but not on humoral components by the Winn Assay. The present results suggest that N-CWS exerts its anti-tumor activity by mediation of the immune system of the host and that the main effector cells in the early stage of tumor rejection are macrophages; T cells may also be involved in the later stage.

Animals↗

Genetic analysis of a Scytho-Siberian skeleton and its implications for ancient Central Asian migrations.

The excavation of a frozen grave on the Kizil site (dated to be 2500 years old) in the Altai Republic (Central Asia) revealed a skeleton belonging to the Scytho-Siberian population. DNA was extracted from a bone sample and analyzed by autosomal STRs (short tandem repeats) and by sequencing the hypervariable region I (HV1) of the mitochondrial DNA. The resulting STR profile, mitochondrial haplotype, and haplogroup were compared with data from modern Eurasian and northern native American populations and were found only in European populations historically influenced by ancient nomadic tribes of Central Asia.

Asia↗

Greatly increased cancellous bone formation with rapid improvements in bone structure in the rat maternal skeleton after lactation.

There is a decrease in cancellous bone mass and strength during lactation but these are partially or completely reconstituted in the postlactational period. The purpose of this study was to determine changes in cancellous bone structure and formation after lactation in established breeder rats. For this, rats were taken at the end of the second pregnancy (Preg-2) and second lactation (Lac-2) and 2, 4, and 6 weeks after weaning. Nulliparous (NP) groups were included for comparisons. Bone structure was measured using morphometric methods and bone dynamics by histomorphometry. Tibial metaphyseal cancellous bone was lost during the first reproductive cycle, as expected, and again depleted during the Lac-2. Bone formation indices were elevated at the end of Lac-2, compared with those at the end of the second pregnancy or in the nulliparous animals. Within 2 weeks after the second weaning, the amount of double-labeled surface (dLS) increased approximately 800%, the mineralizing surface (MS) increased >400% with similar increases in bone formation rates (BFRs), compared with already elevated bone formation measured at the end of Lac-2. From 2 to 4 weeks after lactation, there were commensurate increases in cancellous bone mass and structural indices with essentially complete restoration of cancellous bone volume and structure compared with that measured at the end of Preg-2. The results show rapid and substantial increases in bone formation with reconstitution of cancellous bone mass and structure after lactation in rats. The skeletal changes that occur during the postlactational period may serve to prepare and protect the maternal skeleton for subsequent reproductive cycles.

Animals↗

Permanent preservation of whole alizarin red S skeletons by clearing and embedding in polyester resins.

A one-step clearing and embedding procedure for alizarin red S stained skeletons is described. Embryos are fixed in formalin, skinned and eviscerated. After staining in a 10 mg/liter solution of alizarin red S in 5% aqueous KOH, specimens are dehydrated in a graded series of acetone-polyester monomer solutions. Finally, the specimens are embedded at room temperature in the polyester resin. A special reusable metallic mold is described for embedment of large fetuses. Specimens previously cleared in glycerol can be processed with this method.

Anthraquinones↗

Osteochondroma in a skeleton from an 11th century Croatian cemetery.

We present a case of a well-preserved bone tumor in a skeleton from a Croatian skeletal series dated to the 11th century AD. The tumor is located on the anterior side of the neck of the right femur. The gross morphology of the tumor - a round, lumpy, cauliflower-like appearance with a fairly smooth external surface - is consistent with osteochondroma. The diagnosis is supported by x-ray and CAT-scan findings, which show thickened trabeculae and an internal structure of cancellous bone interspersed with areas of dense compact bone. Comparison with x-rays from a patient surgically treated in 1999 for an osteochondroma with the same localization shows that the characteristics of the tumor have remained unchanged from the 11th century.

Bone Neoplasms↗

Two receptor theory in innate immune activation: studies on the receptors for bacillus Culmet Guillen-cell wall skeleton.

Activation of the innate immune system is a prerequisite for the maturation of dendritic cells (DC) and macrophages (Mphi) followed by clonal expansion of the lymphocytes, targeting cells expressing "non-self' antigens. Microbes usually have a component competent to activate DC/Mphi for antigen presentation. This component has been called adjuvant, but recently renamed "pathogen-associated molecular pattern" (PAMP) or modulin based on its molecular identification. Here, we propose the hypothesis that DC/Mphi express two sorts of receptors for PAMP, whose signaling pathways lead to a sufficient antigen (Ag)-presenting state. In bacterial infection, a Toll-like receptor (TLR) and an uptake receptor participate in DC maturation and Mphi activation. Likewise, with a number of viruses, two of the receptors, with short consensus repeats (SCR), immunoglobulin-like domains or chemokine receptor-like motifs etc. induce functional modulation of DC/Mphi. In immune therapy for cancer, primary activation of the innate system would be essential for tumor Ag-specific T cell augmentation. Cancer cells express tumor-associated Ag but barely co-express PAMP, which situation does not allow for the activation of innate immune responses. Supplementing tumor-associated Ag with PAMP may be an effective therapy for patients with cancer. Here, we discuss the possibility of an innate immune therapy for cancer with reference to bacillus Culmet Guillen cell-wall skeleton (BCG-CWS).

Adjuvants, Immunologic↗

Variability of the pattern of aging on the human skeleton: evidence from bone indicators and implications on age at death estimation.

Age at death assessment of adult skeletons is one of the most difficult problems in forensic and physical anthropology. Two fundamental sources of error are described: the complex variability in the process of skeletal aging and methodological bias. Taking into account these limits, we developed a new scoring system for the auricular surface of the ilium and the pubic symphysis. In order to address a large variability, we examine reference samples from Europe, North America, Africa, and Asia. Data were processed using Bayesian prediction in order to classify specimens in age range categories. Results show that combining indicators do not perform better than the auricular surface used as a single indicator. Morphological changes with aging are variable between Asian, African, and European populations, confirming the necessity to use population-specific standards. Bayesian prediction produces reliable classification and is applicable for subjects over 50 years old, a real methodological improvement.

Age Determination by Skeleton↗

[Anatomical names of Sulcus in skeleton--analysis of Latin names and comparison with Japanese names].

For better understanding of the structures of the human body and for possible revision in the future Latin anatomical names of Sulcus in skeleton were analyzed and compared with Japanese anatomical names. The words that follow after Sulcus indicated: 1) the structure that exists in Sulcus, 2) the structure that contains Sulcus, 3) the location of Sulcus, or 4) the structure of which Sulcus enters into the formation. By the comparison between Latin and Japanese anatomical names, some characteristics of each name were made clear and some problems in Japanese names were pointed out.

Anatomy↗

The core technique in the determination of age at death of skeletons.

This study proposed an histological method of estimating age at death in skeletons that uses a 0.4-cm-diameter core of cortical bone. Age-estimating regression equations were generated from data obtained from the analysis of bone cores taken from femurs, tibiae, humeri, and ulnas of cadavers. When the regression equations generated in this study were applied to eight forensic science cases, accurate ages at death were estimated.

Adult↗

Effect of Nocardia rubra cell wall skeleton on murine interferon production in vitro.

Nocardia rubra cell wall skeleton (N-CWS) induced alpha- plus beta-interferons (IFN-alpha/beta) in resident peritoneal cells and bone marrow cells from normal mice. N-CWS also induced IFN-alpha/beta and IFN-gamma in the cultures of thioglycollate-elicited peritoneal cells. When induced with N-CWS, the mixed cultures of thioglycollate-elicited macrophages and spleen cells produced high titered IFN-gamma. Both macrophages and lymphocytes present in spleen cells (non-T, non-B, asialo-GM1-positive) were essential for the production. Immunofluorescence staining with anti-IFN-gamma antiserum showed the presence of IFN-gamma in lymphocytes but not in macrophages, suggesting that lymphocytes were producer cells and macrophages were accessory cells. Because IFN-gamma is an important lymphokine in immune response, the ability of N-CWS to stimulate IFN-gamma production may account for a significant portion of the antitumor activity of this agent.

Animals↗

An early twentieth-century skeleton collection.

The collecting of human remains for study in museums and medical schools has been a vital scientific endeavor for many years. In some cases, such as the fetal and neonatal skeletons discussed, surreptitious dealings were involved. However, one must consider the attitudes that prevailed at the time, the high rate of fetal and infant mortality, and the blossoming role of museums as repositories of knowledge.

Attitude to Health↗

[Age and sex diagnosis of the skeleton of immature individuals].

In connection with increasing theory-bound investigations in prehistoric anthropology age and sex diagnosis of children's skeletons is gaining importance. Developmental stages of the tympanic plate are introduced as an additional criterion for ageing infants. Discriminant functions derived from ilium and femur measurements allow preliminary access towards a metric sexual diagnosis of fetal and neonate individuals.

Age Determination by Skeleton↗

Protective effect of Nocardia rubra cell wall skeleton on experimental infection in normal and immunosuppressed mice.

The protective effect of Nocardia rubra cell wall skeleton (N-CWS) on experimental infections was investigated in normal and immunosuppressed mice. Pretreatment with N-CWS provided protection against acute systemic infections due to Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Listeria monocytogenes in normal mice. N-CWS administered before or after challenge also showed protective activity against Herpes simplex virus infection in normal mice. N-CWS was the most effective against extracellular parasitic Pseudomonas aeruginosa infection when administered 1 day before challenge, but displayed the most potent protective activity against infection with Listeria monocytogenes, a facultative intracellular parasite, when administered 7 to 14 days before challenge. In mice with subcutaneous Pseudomonas aeruginosa infection, N-CWS suppressed abscess formation and decreased the viable cell count in the resultant abscess foci when administered either intraperitoneally or subcutaneously to the infected site. In addition, treatment with N-CWS markedly restored host defense ability against pseudomonal infection in mice immunosuppressed with cyclophosphamide, hydrocortisone and X-ray irradiation.

Animals↗

In vivo activation of functional properties in mouse peritoneal macrophages by Nocardia rubra cell wall skeleton.

Exudative cells in the peritoneal cavity of mice, particularly polymorphonuclear leukocytes significantly increased 1 day after intraperitoneal injection of Nocardia rubra cell wall skeleton (N-CWS). Macrophages and lymphocytes significantly increased 4 to 7 days after injection. N-CWS also enhanced peritoneal macrophage functions such as phagocytosis of latex particles, production of superoxide anion, production and secretion of lysosomal enzymes such as beta-glucuronidase, lysozyme and acid phosphatase, phagocytosis and intracellular killing of bacteria, and in vitro chemotaxis. The phagocytic function of the reticuloendothelial system was also enhanced. These results indicate that macrophages were activated in vivo by N-CWS.

Animals↗

Estimating age at death from immature human skeletons: an overview.

Literature on the estimation of age at death of immature human skeletons is critically reviewed. Those estimating age at death for forensic science purposes should consider all available data, but especially rely upon the most appropriate and accurate methods. Estimates should reflect the possible error resulting from the sex differences and population variability known to be associated with the growth process.

Adult↗

[Immunotherapy of acute myelogenous leukemia (AML) in adults with the Nocardia rubra cell wall skeleton].

The effect of immunotherapy with Nocardia rubra cell-wall skeleton (N-CWS) on the remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N-CWS and irradiated allogeneic AML cells. Thirty-four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (p = 0.080) and on survival length (p = 0.098). When the data were analyzed at 42 months after entry, there was a borderline significant difference in remission duration (p = 0.066) between the two groups, prolonging the 50% remission period by 120 days, but no significant differences in survival length (p = 0.306), although the 50% survival was 168 days longer in the chemoimmunotherapy group. Thus, immunotherapy with N-CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy.

Adult↗