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PubMed1985

Effects of Nocardia rubra cell wall skeleton on lymphocyte subsets in former poison gas factory workers.

Peripheral blood lymphocyte subsets were determined in former workers of the Okunojima Poison Gas Factory (poison gas workers) having a high incidence of lung cancer, and the effect of administration of Nocardia rubra cell wall skeleton (N-CWS) was studied. In poison gas workers not receiving N-CWS, both the percentage and absolute number of Leu-2a+ cells were significantly increased as compared with normal controls, while both the percentage and absolute number of Leu-7+ cells as well as the Leu-3a/Leu-2a ratio were significantly decreased. In poison gas workers receiving N-CWS, the percentage of Leu-2a+ cells was significantly decreased when compared with poison gas workers not receiving N-CWS, while the percentage of Leu-1+ cells and both the percentage and absolute number of Leu-7+ cells as well as the Leu-3a/Leu-2a ratio were significantly increased. When N-CWS was administered to poison gas workers, the percentage of Leu-2a+ cells significantly decreased, with a minimum two weeks after administration, while the percentage of Leu-3a+ and the Leu-3a/Leu-2a ratio significantly increased and the percentages of Leu-1+ and Leu-7+ cells also increased. Furthermore, the absolute number of Leu-3a+ cells increased markedly with a peak two weeks after administration. The absolute numbers of both Leu-1+ cells and Leu-7+ cells as well as total lymphocytes also significantly increased, but that of Leu-2a+ cells showed hardly any change. It is considered that a single administration of N-CWS transiently corrects the abnormality of lymphocyte subsets, and that repeated administration of N-CWS once every three months may maintain the lymphocyte subsets of poison gas workers at normal levels.

Aged↗
PubMed1979

Antitumor activity of cell-wall skeleton of Propionibacterium acnes C7 in mice and guinea pigs.

The antitumor activity of the cell-wall skeleton (CWS) of Propionibacterium acnes C7 was examined by using transplantable tumors in syngeneic mice and in guinea pigs, and autochthonous tumors in mice. P. acnes-CWS was shown to suppress the growth of fibrosarcomas, EL4 leukemia, and MH134 hepatoma in syngeneic mice, and to regress the established tumors of a fibrosarcoma (MC104) in C57BL/6J mice, and a hepatoma (line-10) in strain-2 guinea pigs. The oil-attached P. acnes-CWS mixed with fructose mycolate was effective for suppression of the autograft of fibrosarcoma in mice. The repeated intralesional injections of suspension of P. acnes-CWS in phosphate-buffered saline was effective for prolongation of survival period of mice bearing 3-methylcholanthrene-induced fibrosarcoma. The test results on the cell fractions of P. acnes indicated that the CWS, but not the cytoplasmic or glucan fraction, of P. acnes had anti-tumor activity. The activation of peritoneal macrophages of mice was observed when P. acnes-CWS, but not the cytoplasmic fraction, was injected intraperitoneally 4 days before. The relationship between the cytolytic activity of peritoneal macrophages and antitumor activities of P. acnes-CWS was also discussed.

Animals↗
PubMed1985

Postnatal somatometry of the rat facial skeleton.

Growth of the rat facial skeleton over a 40 day period from birth was examined relative to 8 length and 4 width parameters of animals subject to somatic growth retardation experimentally induced by overtaxing the maternal lactational capacity by means of excessively large cross-fostered litters. Least squares regression lines were calculated for the preweaning period (day 1-20); the postweaning period (day 21-40) and the total period (day 1-40), thereafter being recalculated into segmented regression lines relative to the physiological growth phases. Specific phases of growth activity were noted throughout the 40 days with those in the preweaning period showing a marked consistency concomitant with the maternal lactational ability and subsequent emergence of biological weaning. A consistent phasic growth spectrum with definitive breaks in continuity supports the original postulate (Brody, 1927) that growth curves consist of phases of exponential activity delineated by changes in growth rate. Due to the inclusion of both control and experimental samples, the breakage points of the phases marking the change of growth rate different and were therefore reciprocated by alterations of phasic duration. Phasic growth occurred in the postweaning period with some degree of variance which did not permit an assessment of the causation factors with sufficient validity. The postweaning period of the experimental sample exhibited varying degrees of growth recovery (catch-up) in the majority of the facial parameters. Covariance analysis of the parameters in most instances showed that the parameters, as defined, and the bone units incorporated within them manifested a characteristic growth response in each sample irrespective of the modifying influence of the environmental factors.

Animals↗
PubMedDate not supplied

Drugs and the developing skeleton.

The skeleton develops from early embryonal stages until the end of the second decade. Normal morphogenesis requires integrated growth, differentiation and morphogenetic movement over prolonged periods of time. The complexity of the processes involved ensures that the potential for drugs to affect the system is very large, and that a number of metabolic pathways may be disturbed. Skeletal abnormalities are thus an important component of many malformation syndromes and are produced by varied genetic mechanisms combined with environmental effects.

Abnormalities, Drug-Induced↗
PubMed1985

Effector mechanism in concomitant immunity potentiated by intratumoral injection of Nocardia rubra cell wall skeleton.

Primary growth of AMC 60 fibrosarcoma inoculated into the hind leg of ACI/N rats resulted in occasional generation of concomitant resistance to growth of a second graft of the same tumor cells in the peritoneal or pleural cavity. Using this syngeneic tumor-host system, experiments were carried out to elucidate the effect of intratumoral injections of an immunomodulator, Nocardia rubra cell wall skeleton (N-CWS), on concomitant immunity. Rats bearing a solid tumor into which N-CWS was repeatedly injected showed a significant inhibitory effect on the proliferation of the tumor cells inoculated secondarily into the peritoneal cavity, i.e., concomitant immunity, as compared to control groups of normal, N-CWS-treated and solid tumor-bearing rats. Peritoneal macrophages, when harvested after i.p. tumor inoculation into the N-CWS treated solid tumor-bearing rats, were found to be significantly potentiated for tumoricidal activity against [5-125I]iodo-2'-deoxyuridine-labeled AMC tumor cells. These potentiated macrophages were induced tumor specifically by i.p. inoculation of AMC tumor cells but not by unrelated syngeneic reticulosarcoma SL 1 tumor cells; nevertheless their tumoricidal activity was observed tumor nonspecifically for the SL 1 tumor cells. Additional experiments revealed that nonadherent peritoneal cells were only weakly tumoricidal and that the macrophage tumoricidal activity was completely abolished in the presence of carrageenan. Thus in the model presented here, it is possible to conclude that the augmentation of concomitant immunity by injection of N-CWS into a primary solid tumor is mainly due to potentiation of the tumoricidal activity of tumor-associated macrophages in the peritoneal cavity. Although the underlying mechanism by which concomitant resistance can be augmented by intratumoral injection of N-CWS remains undetermined, the existence of a tumor-specific trigger for induction of potentiated tumoricidal macrophages may indicate that N-CWS when injected repeatedly into the tumor tissue plays an important role in augmenting a pre-existing, weak, tumor-specific cell-mediated immune response leading to activation of macrophages.

Animals↗
PubMed1979

Effect of Nocardia rubra cell-wall skeleton on the induction of lung cancer in ACI/N rats.

Administration of oil-attached Nocardia rubra cell-wall skeleton (N. rubra-CWS) was evaluated for the effect of the induction of lung cancers in ACI/N rats. Lung cancers were induced by 15 weekly intratracheal instillations of 3 mg benzo[a]-pyrene with 3 mg ferric oxide. After the 10th instillation of the carcinogen, rats received seven subcutaneous injections of 100 microgram of N. rubra-CWS at 2-week intervals. In the observation period of 56 weeks, the cumulative incidence of lung cancer was 71.4% in the control group and 48.0% in the N. rubra-CWS treated group. The latent period of tumor induction was prolonged in the group treated with N. rubra-CWS.

Animals↗
PubMed1979

[Chondrocyte differentiation and bone growth during the development of the cartilaginous skeleton of chickens].

Certain local alterations in functional and reproductive activity of chondrocytes were stated at the development of the cartilage skeleton. In epiphyses chondrocytes gradually pass into the phase of rest (G0) with subsequent multiplication during the process of skeletal development. In these structures biosynthesis of nonsulfated proteoglycans predominate, in time, while in other cartilage zones--that of sulfated ones. Proofs are furnished on gradual transition of epiphyseal chondrocytes into the state peculiar for cells of the proliferative zone accompanied by an intensified biosynthesis of sulfated proteoglycans and collagenous proteins. Owing to these peculiarities they can be compared with the cells of the reserve zone in the mammalian metaepiphyseal cartilage. It was stated that intensity of chondrogenesis and growth of bones are affected by several processes: intensity of chondrocyte multiplication, the rate of their repeated division in the proliferative zone, the velosity with which the cells transfer into the state of hypertrophy and the rate of the periostal bone formation at the border-line of metaphysis and diaphysis.

Animals↗
PubMed1979

Association of macrophage activation with antitumor effect on rat syngeneic fibrosarcoma by Nocardia rubra cell wall skeleton.

The antitumor activities of the cell wall skeleton (CWS) of Nocardia rubra were demonstrated for syngeneic fibrosarcoma (AMC-60) in ACI/N rats in regard to macrophage activation. In the 24-hr cytolytic test, activated macrophages which were fractionated from peritoneal exudate cells induced by i.p. injection of Nocardia CWS showed significant cytolytic activity for [125I]iododeoxyuridine-labeled tumor cells. Activated macrophages also strongly inhibited [3H]thymidine incorporation into the tumor cells during the 24-hr cytostatic test. When tumor cells were inoculated s.c. with activated macrophages in the Winn-type transfer assay, subsequent tumor growth was significantly inhibited. Repeated i.p. injection of the CWS seemed to enhance these antitumor activities of macrophages. The therapeutic effect of Nocardia CWS was assessed with the ascites tumor and with the solid tumor inoculated i.m. into the hind leg. In the former treatment, repeated i.p. injections completely prevented the accumulation of ascites fluid and resulted in prolongation of the survival period. The peritoneal macrophages harvested from these survivors had a strong cytolytic activity for tumor cells in the cytolytic test. In the latter treatment, repeated intratumoral injections inhibited the growth of primary tumor and prevented metastasis. Furthermore, peritoneal resident macrophages from these tumor-bearing rats treated intratumorally with the CWS were found to be cytolytic for tumor cells in the cytolytic test.

Animals↗
PubMed1978

[Roentgenographic changes of the skeleton in a case of tuberous sclerosis (morbus Bourneville-Pringle) (author's transl)].

Increasing sclerosis in the thoracolumbar spine has been followed up in a boy suffering from tuberous sclerosis. The earlist abnormality appearing as an irregular density in the radix of the posterior arch of the first lumbar vertebra has been detected at the age of one year. Until the ninth year of life the disease process has involved the vertebral column from T-8 to L-2. During the course roentgenograms revealed several diffuse areas of opacification with ill-defined outlines which tended to merge. As a rule all vertebrae were affected asymmetrically. Neither deformities of the vertebrae nor functional impairment of the axial skeleton have been found. Based on X ray appearance classification of characteristic and accessory bone abnormalities in tuberous sclerosis was discussed.

Bone Diseases↗
PubMed1983

[Late results of Küntscher medullary nailing of femoral and tibial fractures in the still growing skeleton].

This is a report about the clinical and roentgenological results of 11 patients who had single lower-leg fractures (average age at times of operation 15.6 years) average 4.8 years after medullary nailing, and about 11 patients with single femoral fractures (average age at times of operation 13.3 years) average 6.4 years after the operation. The Küntscher-nail had already been removed. Beside inquiring subjective statements we checked the possible influence of medullary nailing on the still growing skeleton. We did not find any severe faults in axis or rotation. Acceleration or retardation of bone growth were mainly found in younger patients (10-12 years of age at first operation), in distal localised fractures or in case of longer pre- or intraoperative bone reduction. We did not find essential differences in length of the legs in cases where the fractures had been nailed during the final period of bone growth (15-17 years).

Adolescent↗
PubMed1983

Changes in natural killer cell, antibody-dependent cell-mediated cytotoxicity and interferon activities with administration of Nocardia rubra cell wall skeleton to subjects with high risk of lung cancer.

Changes in natural killer (NK) cell, antibody-dependent cell-mediated cytotoxicity (ADCC) and interferon activities after administration of Nocardia rubra cell wall skeleton (N-CWS) to a group of subjects with high risk of lung cancer (retired workers of the Okunojima poison gas factory) were studied. No difference in NK cell activity against K-562 derived from chronic myelogeneous leukemia was observed among normal controls, non N-CWS-injected workers and N-CWS-injected workers. None of the normals or N-CWS-injected retired workers showed low NK cell activity (less than 10% cytotoxicity), but among the non N-CWS-injected workers 6.3% showed reduced activity. Following injection of N-CWS, NK cell activity against K-562 and T-24 derived from bladder cancer was significantly elevated by the second week and then gradually reverted to the preinjection level. When a second injection was administered at the twelfth week, a similar elevation was noted. Further, a significant increase was noted in ADCC activity two weeks after N-CWS injection. There was a significant elevation of interferon at the second week after N-CWS injection. It was considered that N-CWS affects the NK cell activity enhancement by serum interferon.

Adjuvants, Immunologic↗
PubMed1982

The restoration of suppressed T cell activities induced by 7,12-dimethylbenz[a]anthracene with an anti-tumor immunomodulator, BCG-cell wall skeleton.

The restoring effect of Bacille de Calmette et Guérin (BCG)-cell wall skeleton (CWS) on the suppressed T cell reactivities in mice treated with 7,12-dimethylbenz[a]anthracene (DMBA) was studied using a system involving the induction of hapten-reactive cytotoxic T cells and mixed lymphocyte reaction in vitro. When the mice were treated with DMBA, the reactivity of lymphoid cells to generate cytotoxic T cells and proliferative T cell responses against allogeneic spleen cells was markedly suppressed. When BCG-CWS was administered to mice by intravenous injection before and after the treatment with DMBA, these depressed T cell functions reverted completely to the normal level. However, the restoration of the immune functions by BCG-CWS varied depending on the strain of mice. Namely, the reactivity of C57BL/6 mice was restored by BCG-CWS, whereas that of C3H/He mice was not. This strain difference correlates very well with the strain difference in effectiveness of the prevention of the DMBA-induced tumorigenesis by BCG-CWS. The possible relation between the restoration of T cell reactivities by BCG-CWS and prevention of tumorigenesis by BCG-CWS is discussed in the context of the role of host immune surveillance in the regulation of tumor development.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

[Paget disease of the skeleton. Internal medicine aspects].

Paget's disease of bone seems to be a slow virus infection of a single or several areas of the skeleton. Pagetic lesions are rather common among elderly people, but the disease does not manifest itself very often. Compared to the incidence of Paget's disease in England it seems to be rarer in this country. The pelvis is most frequently involved, followed by bones of the leg, skull, lumbar spine. The patients suffer from pain and deformities, arthroses of the adhering ankles, increased temperature of the area, nerve irritation and nerve damage due to increased bone growth (e.g. hearing loss due to Paget's disease of the skull). The development of sarcoma is rare and is only seen in severe cases. Diagnosis is made by X-ray, confirmed by bone biopsy, if necessary. Asymptomatic lesions are detected by bone scintigraphy. The activity of the disease is expressed by increased alkaline serum phosphatase and urinary hydroxyproline excretion. For treatment calcitonins and diphosphonates (especially EHDP, Diphos) are used. Both inhibit the overactive osteoclasts, and the increased bone turnover is normalized. The patients feel considerable relief; the elevated biochemical parameters fall to about 50% of initial values after calcitonin or EHDP monotherapy. In severe cases the combination of both substances may be profitable. The cytostatic drug mithramycin which can also be effective is only needed in exceptional cases.

Alkaline Phosphatase↗
PubMed1984

Mechanisms of cartilage precursor replacement by bone in the mammalian skeleton.

The initiation of the endochondral process in ontogenesis is preceded by structural and metabolic preparation of the cells of cartilage anlages of the skeleton as well as the satellite cells of the vascular terminations adjoining the cartilage. In the cartilage anlage, due to a progressive specific biosynthesis, the macromolecular chondroitin-protein complexes capable of binding a large amount of water, are accumulated. As a result the volume of a swelling chondrocyte increases twentyfold or more and a high hydrostatic tension is created within it. At the same time the metabolic situation within the cartilage favours a local concentration, near the hypertrophic chondrocytes, of the perivascular cells possessing an increased resorptive function. The resorption of the cartilage partition walls by these cells leads to the opening of swollen chondrocytes. The blood cells and the cells of the blood capillaries themselves are engulfed through the resulting crater into the emptied lacuna. In the lacuna the conditions of stasis are created which promote local redistribution of the supplied cells and reutilization of the cartilage destruction products. The perivascular cells concentrated along the remnants of the cartilaginous matrix are gradually differentiated into preosteoblasts and osteoblasts. The endosteal bony laminae are built on the remnants of the cartilaginous matrix. The perivascular cells of the apical zone of a lacuna retain their clastic function and continue spreading of the endochondral process on the adjacent chondrocytes. In the course of the successive destruction of hypertrophic chondrocytes, the system of vessels is formed in the endochondral centre, according to the sinusoid pattern.

Animals↗
PubMed1978

Systemic effects of the VX2 carcinoma on the osseous skeleton. A quantitative study of trabecular bone.

The skeleton of rabbits bearing the transplantable VX2 carcinoma has been studied by a combination of radiographic and histomorphometric techniques. It has previously been shown that this tumor produces and secretes large amounts of prostaglandin E2. In vivo experiments, as well as cell and organ culture studies, have led to the conclusion that the hyerpcalcemia observed in tumor-bearing rabbits is due to excessive secretion of prostaglandin E2 by the tumor and its subsequent action on bone throughout the organism. Our new findings reveal (1) no evidence of local invasion of bone by the VX2 tumor or osseous metastases; (2) radiographic evidence of generalized osteopenia; (3) histomorphometric documentation in trabecular bone of reduced volume density of bone matrix, consistent with increased resorption in trabecular bone at sites distant from tumor; and (4) a marked generalized reduction in surface density of osteoblastic layers, volume density of osteoid, osteoid seam thickness, and surface density of osteoid. These findings in trabecular bone of iliac crest and vertebra offer quantitative data in support of the conclusion that VX2 carcinoma affects skeletal metabolism systemically.

Animals↗
PubMed1983

Superoxide anion and hydrogen peroxide release by macrophages from mice treated with Nocardia rubra cell-wall skeleton: inhibition of macrophage cytotoxicity by a protease inhibitor but not by superoxide dismutase and catalase.

Peritoneal macrophages obtained from male BALB/c mice intraperitoneally injected with Nocardia rubra cell-wall skeleton (N-CWS) showed abundant superoxide anion and hydrogen peroxide release in response to opsonized zymosan used as a trigger. These N-CWS-induced macrophages also showed marked cytolytic activity against syngeneic Meth A fibrosarcoma targets. To examine the possible role of superoxide anion and/or hydrogen peroxide in the lysis of Meth A cells, N-CWS-induced macrophages were assayed with Meth A targets in the presence of superoxide dismutase, catalase, or both. However, addition of these agents to the assays, in doses which abolished detectable superoxide anion and/or hydrogen peroxide release from the effector cells, had no inhibitory effects on the cytotoxicity of N-CWS-induced macrophages. In contrast, both a protease inhibitor and actinomycin D could inhibit the cytolysis of Meth A targets by N-CWS-induced macrophages. These data raise the possibility that protease(s) rather than oxygen intermediates might be involved in the cytotoxicity of N-CWS-induced macrophages against tumor cells.

Animals↗