Large cell carcinoma of lung with osteoclast-like giant cells

This is the first reported case of a laryngocoele developing after laryngeal trauma. A 26-year-old man sustained a shotgun injury to his larynx. A large number of shotgun pellets was removed from his left vestibular fold. He subsequently developed a left-sided laryngocoele, probably due to fibrosis around the neck of the saccule. The laryngocoele was removed by an external approach.     

Proliferation of synovial tissue cells in rats with adjuvant disease

Proliferation of synovial lining cells and fibroblasts in adjuvant arthritis of rats was investigated by autradiographic methods. As manifestation of the generalized experimental disease increased labelling rates of both cell types were found in all joints. While in the knee joint this cellular proliferation was of a short duration, it progressed in the ankle joint until the joints were destroyed. It is concluded that increased cellular proliferation is an important mechanism leading to joint destruction in adjuvant arthritis.     

Increased osteoclast-like cells formation in long-term bone marrow cultures from patients with a spinal cord injury

A simple and sensitive method for analysis of three tetracyclic antidepressants, maprotiline, mianserin, and setiptiline, in human whole blood was developed using headspace-solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). A vial containing a blood sample, sodium hydroxide, and imipramine as an internal standard was heated at 120 degrees C. The extraction fiber of the SPME was exposed for 45 min in the headspace of the vial. The compounds absorbed on the fiber were desorbed by exposing the fiber in the injection port of a GC-MS. The calibration curves, using an internal standard method, demonstrated good linearity throughout the concentration range from 0.005 to 5.0 microg/g for mianserin and setiptiline and from 0.025 to 25 microg/g for maprotiline. No interferences were found, and the time for analysis was 60 min for one sample. In addition, this proposed method was applied to a medicolegal case in which the cause of death was suspected to be acute setiptiline poisoning. Setiptiline was detected in the left and right heart blood samples of the victim at concentrations of 1.77 and 0.78 microg/g, respectively.     

Circular forms of unintegrated human immunodeficiency virus type 1 DNA and high levels of viral protein expression: association with dementia and multinucleated giant cells in the brains of patients with AIDS

Thirty-one histologically abnormal brains from patients with AIDS were studied in order to establish the relationship between multinucleated giant cells, viral protein expression, the various forms of human immunodeficiency virus type 1 (HIV-1) DNA, and clinical evidence of dementia. Unintegrated HIV-1 DNA of 2 to 8 kb was found in 22 of the 31 brains. Multinucleated giant cells without any other pathology were found in 14 cases; unintegrated 1-long terminal repeat (1-LTR) circular forms of HIV-1 DNA and strongly positive immunohistochemistry for gp41 and p24 were found in most of these brains. Most of these patients had a clinical diagnosis of HIV-1-associated dementia and cerebral atrophy. In all the other brains studied, 1-LTR circles were absent and immunohistochemistry for gp41 and p24 was usually negative. Very few of these patients had a clinical diagnosis of dementia. Sequence comparison of the LTR region from integrated HIV-1 DNA with that from unintegrated 1-LTR circular forms of HIV-1 DNA in 12 cases showed no significant differences. A further comparison of these brain-derived LTR sequences with LTR sequences derived directly from lymphoid tissue also showed strong sequence conservation. The V3 loop of the virus from the brain was sequenced in 6 cases and had a non-syncytium inducing-macrophage-tropic genotype. Our results show that (i) although unintegrated HIV-1 DNA was present in most brains from patients with AIDS, molecular evidence of high levels of viral replication was associated with the presence of multinucleated giant cells and dementia, and that (ii) the HIV-1 LTR is not a determinant of neurotropism. These observations suggest that replication of HIV-1 and not just the presence of HIV-1 DNA within giant cells makes the important contribution to central nervous system damage.     

Markers of bone turnover in patients with nephrolithiasis

A total of 19 patients with active nephrolithiasis, 14 patients with non-active nephrolithiasis and 17 healthy subjects were examined under standardized intake of calcium, phosphorus, purine and protein. In patients with both active and non-active renal stone disease the following abnormalities were found: elevated plasma levels of PTH and osteocalcin, increased activity of the bone isozyme of alkaline phosphatase, low plasma levels of phosphate and increased urinary excretion of calcium and oxalic acid. These abnormalities were more marked in patients with active than non-active nephrolithiasis. No correlation was found between plasma PTH levels and parameters of bone turnover as well as calciuria and oxaluria. Results presented in this paper suggest that (a) Smith's criteria of active renal stone disease are of minor pathogenetic and therapeutic value and (b) patients with active nephrolithiasis differ from non-active renal stone formers by more elevated oxaluria and markers of bone turnover and more marked abnormalities in calcium-phosphate metabolism related parameters.     

The effects of clodronate on increased bone turnover and bone loss due to ovariectomy in rats

The present study was carried out to investigate the ability of clodronate to inhibit ovariectomy-induced bone loss and increased bone turnover in rats. Estradiol was administered as a reference compound. Seventy Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (Sham) at the age of 90 days and divided into seven groups. Two Sham and two OVX groups received subcutaneously either the vehicle of clodronate or the vehicle of estradiol. Other OVX groups were given s.c. either disodium clodronate at two dose levels (5 mg/kg or 12.5 mg/kg twice a week) or 17 beta-estradiol (10 micrograms/kg five times a week) for 8 weeks. Femur length, volume, dry weight, and ash weight were determined, and proximal ends of tibiae were used for bone histomorphometry. Markers of bone metabolism were measured from urine and serum. A significant loss of 54% of trabecular bone area of proximal tibial metaphysis was found at 8 weeks after ovariectomy. Clodronate and estradiol inhibited (p < 0.001) this osteopenia. Both drugs prevented the decrease in ash weight/volume of the femur. The inhibitory effect of clodronate and estradiol on bone resorption in OVX rats could be detected also in decreased urinary excretion of hydroxyproline and lysylpyridinoline (p < 0.001). Clodronate and estradiol decreased (p < 0.001) the ovariectomy-induced enhanced tibial endocortical mineral apposition rate (Ec.MAR) on the lateral cortex to the level of the Sham group. In contrast, periosteal MAR analyzed on the medial side of tibial cortical bone did not change significantly in the OVX/Veh group. Estradiol decreased periosteal MAR to below the level in the Sham group (p < 0.01). These results suggest that ovariectomy of growing rats resulted in tibial and femoral osteopenia two months later. Clodronate as well as estradiol can suppress bone resorption and turnover in ovariectomized rats, inhibiting the development of osteopenia. Both clodronate doses (5 and 12.5 mg/kg) had beneficial effects in ovariectomized animals.     

Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.     

Efferent targets of osseous CGRP-immunoreactive nerve fiber before and after bone destruction in adjuvant arthritic rat: an ultramorphological study on their terminal-target relations

We report the ultramorphological characterization of the terminal-target relation of sensory peptidergic nerve fibers in healthy and diseased osseous tissues. Bone tissue sections were immunoelectronmicroscopically investigated for calcitonin gene-related peptide (CGRP), a neuropeptide widely distributed in sensory peptidergic fibers. Ultramorphological relation of the osseous CGRP-immunoreactive (ir) nerve terminals and their target cells was comparatively analyzed using healthy, arthritic, and postarthritic bone specimens from control and adjuvant-induced arthritic rats. Terminal-like profiles of the osseous CGRP-ir axons were evidenced in direct contact with the metaphyseal osteoblasts and osteoclasts of the control animals. Terminal-like profiles were also noted in the vicinity of the periosteal lining cells. Nonterminal-like profiles did not make intimate spatial relation to the cells/structures surrounding the nerve. Osseous CGRP-ir terminals and axons, which are either uncovered or thinly ensheathed by the supportive tissues, were extensively degenerated in adjuvant-induced infiltration, whereas larger fibers were relatively resistant. Numerous CGRP-ir axons with distinctive features reinnervated the postarthritic, ossifying periosteum. CGRP-ir axons appeared to reinnervate the eroded surface of metaphyseal bone and cartilage as early as the recruited osteoblasts resume osteogenesis in the postarthritic metaphysis. The observed terminal-target relations in the healthy and diseased bone tissues give an ultramorphological basis for the putative trophic, modulatory actions of CGRP innervation of the bone cells.     

骨转换标志物在非小细胞肺癌骨转移临床应用价值的研究

Objective:The purpose of this study was to assess the clinical application value of bone turnover markers in non-small-cell lung cancer (NSCLC) patients with bone metastases. Including diagnosing bone metastases, detecting bone metastatic spread. Methods: Alkaline phosphatase (AKP), p-C-terminal telopeptide of type I collagen (B-CTx), osteocalcin (OST) and bone alkaline phosphatase (BALP) were measured in 76 patients with bone metastases from NSCLC and 44 normal people. Results: The level of AKP, B-CTx and BALP in patients with bone metastasis was significantly higher than in the normal people. Significant correlation was observed among bone turnover markers. The levels of BALP and OST were significantly correlated with the extent of bone metastasis. The patients with high-level CTx and low-level BALP had higher risk of pathologic fracture. Conclusion: In NSCLC patients with bone metastases, bone turnover markers can help to make diagnosis and evaluate the severity. It will have a wide range of use in clinical practice.     

In vivo chromosomal aberrations in bone marrow cells of rats treated with Marshal

In this study, the cytogenetic effects of Marshal (insecticide/nematocide) were investigated in bone marrow cells of rats. The results obtained from animals treated with Marshal were compared with the results of animals treated with ethyl carbamate (EC) and with controls. Concentrations of 12.5, 25 and 50 mg/kg b.wt. of Marshal and 100, 200 and 400 mg/kg b.wt. of EC were used and animals were sampled at three different times (6, 12 and 24 h). Marshal increased the number of chromosomal aberrations (CA) per cell, and the number of cells with abnormalities, at all concentrations and treatment times. Generally, Marshal could increase the number of the abnormal cells and the formation of CA as easily as EC. However, Marshal, at 50 mg/kg b.wt. did not increase the frequency of abnormal cells or CA as strongly as EC, at 400 mg/kg b.wt. for 6 h. Marshal also decreased the mitotic index (MI) compared with the control group. The MI was higher in the group treated with Marshal for 6 h than that treated with EC. However, the effects of Marshal and EC on the MI in the groups treated for 12 and 24 h were similar. We found that the effect of Marshal on the formation of abnormal cells and CA was dependent on concentration and treatment time.     

Modulation of bone mass and turnover in growing rats by voluntary weight-bearing exercise and glucose supplementation

Female Sprague-Dawley rats, 9 weeks of age, were assigned to four groups: Group 0 (n = 8) was dissected for base-line control, and the other three groups were fed for 3 mo: Group 1 (n = 9), sedentary controls; Group 2 (n = 6), running rats housed in a cage with a treadmill and pair-fed with Group 1; and Group 3 (n = 7), running rats, pair-fed and allowed free access to additional glucose. The distances of voluntary running did not significantly differ between Groups 2 and 3. Menstrual cycles in these rats were apparently maintained as observed from daily running distances. The amount of glucose taken by rats in Group 3 was 3.5 +/- 0.4 (mean and SE) g/d. Body weight (BW) at the end of the experiment for Groups 1, 2, and 3 were 295.0 +/- 7.9, 211.7 +/- 5.4 (p < 0.001 vs. Group 1), and 259.0 +/- 3.5 g (p < 0.01 vs. Group 2), respectively. The parameters of bone mass such as ash weights of the femur and bone mineral content of the lumbar spine and the tibia in Groups 1 and 2 did not differ, but the values were significantly greater in Group 3 than in Group 2. However, these parameter values corrected for BW were significantly greater in Group 2 than in Group 1 and did not significantly differ between Groups 2 and 3. The parameters of bone formation, such as serum bone alkaline phosphatase activity levels and trabecular bone formation rates corrected for BW, were significantly greater in Group 2 than in Group 1 but did not differ between Group 2 and 3. However, the parameters of bone resorption, such as serum tartrate resistant acid-phosphatase levels, were significantly less in Group 3 than in Group 2. These results suggest that voluntary running augments the age-dependent increase in bone mass by modulating the bone turnover when an adequate energy source is supplied under conditions of normal menstruation, and an adequate supply of energy could be necessary to enhance the age-dependent increase in bone mass.     

Induction of Fas ligand in murine bone marrow NK cells by bacterial polysaccharides

Bacterial polysaccharides have a wide range of activities in mammals. We have studied the effect of LPS and poly-beta-(1-->4)-D-mannuronate (mannuronan, poly-M), an exopolysaccharide from Pseudomonas aeruginosa, on the cytotoxicity mediated by murine bone marrow cells (BMC). Addition of LPS or mannuronan to BMC induced a time- and dose-dependent cytotoxicity against Jurkat cells. The LPS- or mannuronan-induced cytotoxicity was due to increased Fas ligand (FasL) expression by BMC, since 1) Fas-transfected L1210-Fas target cells were more susceptible to lysis than the Fas(low)-expressing parent L1210 cells, 2) stimulated BMC from FasL-defective gld/gld mice were not cytolytic and, 3) the cytolytic activity of normal BMC was inhibited by a Fas-Fc fusion protein. Flow cytometry showed an increase in surface FasL in LPS-stimulated BMC. RT-PCR analysis of BMC revealed constitutive expression of FasL mRNA, which was increased after LPS stimulation. Immunomagnetic depletion of NK1.1-, CD2-, or CD32/16-expressing cells from BMC abrogated the LPS-induced BMC cytotoxicity against L1210-Fas cells, suggesting that NK cells were the cytotoxic effector cells. Depletion of CD45R/B220-, Gr-1-, or CD11b/Mac-1-expressing cells only partially decreased BMC-mediated cytotoxicity, and depletion of CD4- or CD8a-expressing cells had no effect. The results support the conclusion that LPS and mannuronan induce expression of cytotoxic FasL on bone marrow NK cells.     

Effects of prednisolone on bone turnover in patients with corticosteroid resistant asthma

Many galactosaemics appear to have neuropsychological and/or linguistic problems in spite of dietary treatment. Because the neonatal screening program in Norway does not include galactosaemia, we have re-examined Norwegian galactosaemics. Of 16 known patients, 8 patients participated in the study. They had been diagnosed between 2 and 11 weeks of age, and were between 9 months and 19 years old at the time of this study. All had very low or 0 activity of galactose-1-phosphate uridyl transferase. As part of the study all were examined neurologically, and had an age-appropriate developmental/IQ test, an ABR and an EEG, and a comprehensive psycholinguistic evaluation. The three youngest patients had normal developmental/IQ tests, while the five older patients had IQ scores in or below low range of normal. The majority had delayed language development and three patients were classified as having verbal dyspraxia. ABR and EEG showed mild pathology in the oldest patient only. Galactosaemia appears to be associated with significant risks of developmental and language delays in this unscreened population.     

Estimation of glucose turnover in rats in vivo with tritium labeled glucoses

Starved and starved-refed rats were injected intravenously with labelled glucose (a mixture of [2-3H]-, [3-3H]- and [U-14C]glucose with either [5-3H]- or [6-3H]glucose), and the decay of the specific activity of [14C]glucose followed. Glucose was degraded to obtain the 3H/14C ratios for 3 isotope combinations in the same sample. The apparent rates of replacements, apparent carbon recycling, and the body glucose mass were calculated for the different tracers. The 3H/14C ratio from [2-3H, -U-14C]glucose declined much faster than that of the other tracers. Apparent recycling as calculated in fasted rats was 28% for [2-3H, U-14C]- 18% for [5-3H,-U-14C]- 17% for [3-3H, U-14C]- and 14% for [6-3H,U-14C]glucoses. The values in fed rats showed a similar pattern. We estimate that in fasted rats 85 to 90% of the 3HOH liberated from injected [2-3H]glucose is formed by catabolism in the periphery and the rest by recycling in the liver between glucose and glucose 6-P. Detritiation of other labels by hepatic recycling accounts for a very small fraction of the total 3HOH yield.     

Metabolism of the sulphated glycosamino-glycans of skin, cartilage and bone of rats with adjuvant arthritis (author's transl)

The time course of the quantitative changes in connective tissue of non-inflamed dorsal skin and of inflamed hind limbs was investigated by means of radioactively-labelled sulphate. Whereas the rate of incorporation of 35SO4 into the skin is reduced, its turnover in the inflamed tissue is greatly accelerated. This increase is observed both in the soft (cartilage) and hard (bone) connective tissue on both hind legs. The citric acid content of affected bone is lower than in healthy animals.     

Identification of metabolic bone disease in patients with endogenous hyperthyroidism: role of biological markers of bone turnover

Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 +/- 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2-L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease.     

Induction of pre-B lymphoid leukemia following reconstitution of lethally irradiated mice with v-erb-B virus-infected bone marrow progenitor cells

We have previously shown that v-erb-B contained within a recombinant murine retroviral vector is capable of transforming pre-B lymphocytes (M. Miller, A. K. Kennewell, and G. Symonds, Leukemia, 6: 18-28, 1992) and early erythroid precursor cells [blast-forming units (erythroid) (M. Miller, A. Kennewell, Y. Takayama, A. Bruskin, J. M. Bishop, G. Johnson, and G. Symonds, Oncogene, 5: 1125-1131, 1990)] in vitro. To determine the sites and nature of v-erb-B-induced transformation in vivo, the hematopoietic systems of lethally irradiated mice were repopulated with v-erb-B-infected bone marrow. All mice became moribund within 4-12 weeks of reconstitution, with a median onset of disease at 6 weeks. Histopathological and flow cytometric evaluation of tissues from diseased mice, as well as morphological and phenotypic analysis (cytochemical as well as molecular) of the cell lines established from the mice, revealed that all but one of the mice examined at postmortem had developed a pre-B lymphoid leukemia or lymphoma. Abnormally high levels of mast cells in the spleen and bone marrow of the remaining mouse indicated a mast cell disease. The development of pre-B lymphoid malignancy in the majority of the reconstituted mice indicates a marked predisposition of v-erb-B to transform cells of the pre-B lymphoid lineage. The reconstitution of lethally irradiated mice with v-erb-B virus-infected bone marrow provides a model system for the analysis of events involved in the initiation and maintenance of acute lymphoid leukemia.     

艾灸对佐剂性关节炎大鼠免疫介导物质β-内啡肽含量的影响

目的 通过观察艾灸对佐剂性关节炎大鼠免疫介导物质β-内啡肽含量的影响,揭示针灸调节免疫功能的机理.方法 将40只大鼠分为空白组、模型组、灸命门组、灸关元组,灸非穴组,除空白组外,其余大鼠于右后足跖皮内注射弗氏完全佐剂造模,模型组造模后不做任何处理,灸命门组灸命门穴、灸关元组灸关元穴、灸非穴组灸关元穴左侧旁开0.5 cm处.观察足爪肿胀率并观测血浆、下丘脑、垂体和淋巴结中β-内啡肽(β-EP)含量.结果 与模型组比较,灸命门组与灸非穴组右足足爪肿胀率明显降低(P＜0.01);与灸命门组比较,灸关元组与灸非穴组右足足爪肿胀率明显升高(P＜0.05).与空白组比较,模型组左足足爪肿胀率明显升高(P＜0.05),灸命门组与灸关元组左足组爪肿胀率明显升高(P＜0.05);与模型组比较,灸命门组、灸关元组、灸非穴组左足足爪肿胀率明显降低(P＜0.01).与空白组比较,模型组、灸命门组、灸关元组、灸非穴组大鼠血浆中β-EP含量明显降低(P＜0.05);与空白组比较,模型组大鼠下丘脑中β-EP含量明显升高(P＜0.05);与空白组比较,灸关元组、灸非穴组大鼠垂体中β-EP含量明显升高(P＜0.05);与模型组比较,灸关元组、灸非穴组大鼠垂体中β-EP含量明显升高(P＜0.05);与模型组比较,灸命门组、灸关元组、灸非穴组大鼠淋巴结中的β-EP含量明显升高(P＜0.05).结论 灸命门穴和非穴对右足原发性炎症有抑制作用;灸命门穴、关元穴、非穴对左足继发性炎症有抑制作用.推测艾灸上述穴位对机体免疫炎症的调整作用是通过提高淋巴结β-EP含量、调动中枢内β-EP而实现的.     

Region-specific increase in glutamate release from dorsal horn of rats with adjuvant inflammation

Glutamate is considered an important pain transmitter and responsible for inflammatory hyperalgesia, but quantitative and topographical changes in glutamate release in the dorsal horn during peripheral inflammation have not been characterized. To address this issue, image analysis with a confocal laser scanning microscope was performed for quantitatively mapping capsaicin-evoked glutamate release from the lumbar cord slice of rats following unilateral adjuvant inoculation to the hind-paw. Capsaicin induced glutamate release from laminae I, II and X in the spinal cord of the adjuvant-treated and untreated sides, without apparent release from laminae III-V. The concentration of released glutamate in laminae I, II and X was higher on the adjuvant-treated side than on the untreated side. The results suggest that adjuvant inflammation increases glutamate release from capsaicin-sensitive primary afferents in laminae I, II and X.