Global disease burden of COPD from 1990 to 2019 and prediction of future disease burden trend in China.

OBJECTIVES: This study aimed to assess and predict the disease burden attributable to chronic obstructive pulmonary disease (COPD) in a timely, comprehensive, and reliable manner, thereby mitigating the health hazards of COPD. STUDY DESIGN AND METHODS: Data on the disease burden owing to COPD from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study 2019. Linear regression analysis was used to calculate the estimated annual percentage change (EAPC) in the age-standardized rates. Non-parametric tests were used for subgroup analysis. The Bayesian age-period-cohot (BAPC) model integrated nested Laplace approximations to predict the disease burden over the next 25 years. Sensitivity analysis was performed using the Norpred APC model. RESULTS: Globally, the COPD-related age-standardized incidence rate decreased from 216.48/100,000 in 1990 to 200.49/100,000 in 2019, with an EAPC of -0.33. But the number of new cases increased from 8,722,966 in 1990 to 16, 214, 828 in 2019. Trends in prevalence, deaths, and disability-adjusted life years (DALYs) were the same as incidence. There were significant differences in disease burden between the genders and all age groups (P < 0.05) in China. The projections suggested that the COPD-related number of new cases and deaths in China would increase by approximately 1.5 times over the next 25 years. CONCLUSIONS: The number of incidence, prevalence, deaths, and DALYs had all increased in China in the past and would continue to grow over the next 25 years. Therefore, measures should be taken to target risk factors and high-risk groups.

[Role of probiotics in treatment of nonalcoholic fatty liver disease].

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in China and manifests as simple fatty liver, non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Studies have shown that intestinal flora can affect the development and progression of NAFLD via the "gut-liver axis" . Probiotics are active microorganisms with beneficial effects on the host, and more and more studies have found that probiotics play a positive role in improving NAFLD. They are cheaper, less harmful, and safer compared with antibiotics and surgery, and therefore, it may become a new method for the prevention and treatment of NAFLD. This article reviews the research advances in probiotics in the treatment of NAFLD, in order to provide a basis for the treatment of NAFLD using probiotics.

Candidate genes for the development of hair follicles in Hu sheep.

The aim of this study was to detect candidate genes for the development of hair follicles in the Hu sheep breed. Seven genes have been detected in large, medium, and small wave follicles of Hu sheep using gene chip technology. The histological features of the follicles of newborn Hu-lambs were combined with fluorescence quantitative PCR technology to detect the correlation between the expression of the seven genes and hair follicle development. Among the genes studied, matrix metalloproteinase 2 (MMP2), bone morphogenetic protein-7 (BMP7), and sideroflexin 1 (SFXN1) showed a significantly different pattern of expression in large, medium, and small wave follicles (P < 0.05). The expression of MMP2 had a significant positive correlation with secondary follicles in large waves (P < 0.05), while the expression of BMP7 had a significant correlation with primary follicle diameter in small wave follicles, and a highly significant positive correlation with the number of secondary follicles in the small waves (P < 0.01). The expression of SFXN1 was significantly and positively correlated with the diameters of small wave primary follicles; it also showed a highly significant positive correlation with secondary follicle diameters. Although other genes are associated with hair follicles, their expression in large, medium, and small wave follicles was not significant. We propose that BMP7, MMP2, and SFXN1 genes could be important candidate genes for use in breeding Hu lambs with early coat development.

Anesthesia management for open fetal intrauterine surgery.

OBJECTIVE: Open fetal surgery is usually performed during the second trimester in a fetus suffering from severe congenital diseases, thus enabling the pregnancy to continue until delivery. MATERIALS AND METHODS: The key of this treatment is to promote uterine relaxation enough to maintain both maternal and fetal circulation stable and once surgery is completed, to offer a perfect analgesic to avoid the contractions due to pain, and finally to reduce preterm delivery. RESULTS: Successful anesthesia is fundamental to this surgery. CONCLUSION: The authors have performed three cases under inhalation anesthesia combined with successful epidural anesthesia.

Self-assembly of a colloidal interstitial solid with tunable sublattice doping.

We determine the phase diagram of a binary mixture of small and large hard spheres with a size ratio of 0.3 using free-energy calculations in Monte Carlo simulations. We find a stable binary fluid phase, a pure face-centered-cubic (fcc) crystal phase of the small spheres, and binary crystal structures with LS and LS(6) stoichiometries. Surprisingly, we demonstrate theoretically and experimentally the stability of a novel interstitial solid solution in binary hard-sphere mixtures, which is constructed by filling the octahedral holes of an fcc crystal of large spheres with small spheres. We find that the fraction of octahedral holes filled with a small sphere can be completely tuned from 0 to 1. Additionally, we study the hopping of the small spheres between neighboring octahedral holes, and interestingly, we find that the diffusion increases upon increasing the density of small spheres.

Simulation of nucleation in almost hard-sphere colloids: the discrepancy between experiment and simulation persists.

In this paper we examine the phase behavior of the Weeks-Chandler-Andersen (WCA) potential with ßε = 40. Crystal nucleation in this model system was recently studied by Kawasaki and Tanaka [Proc. Natl. Acad. Sci. U.S.A. 107, 14036 (2010)], who argued that the computed nucleation rates agree well with experiment, a finding that contradicted earlier simulation results. Here we report an extensive numerical study of crystallization in the WCA model, using three totally different techniques (Brownian dynamics, umbrella sampling, and forward flux sampling). We find that all simulations yield essentially the same nucleation rates. However, these rates differ significantly from the values reported by Kawasaki and Tanaka and hence we argue that the huge discrepancy in nucleation rates between simulation and experiment persists. When we map the WCA model onto a hard-sphere system, we find good agreement between the present simulation results and those that had been obtained for hard spheres [L. Filion, M. Hermes, R. Ni, and M. Dijkstra, J. Chem. Phys. 133, 244115 (2010); S. Auer and D. Frenkel, Nature 409, 1020 (2001)].

Expression of aquaporin-4 in human supratentorial meningiomas with peritumoral brain edema and correlation of VEGF with edema formation.

Peritumoral brain edema is a common complication of meningiomas. It is believed that vascular endothelial growth factor (VEGF), as an angiogenic factor, plays a vital role in edema formation. Aquaporin-4 (AQP4) is a small integral membrane protein that regulates water in the normal brain. However, the expression of AQP4 and its relationship to VEGF in edematous meningiomas are not well known. We studied tumor specimens of 59 human supratentorial meningiomas. Western blot analysis was used to detect the expression of AQP4, and double-labeling immunofluorescence histochemical staining was performed to determine the relationship between AQP4 and VEGF. The AQP4 expression was significantly higher in the edema group, in which the protein level was correlated with the extent of edema. Greater VEGF expression was also observed in the edema group, and a relationship between AQP4 and VEGF was found. We conclude that AQP4 is involved in peritumoral brain edema formation in meningiomas and is also closely related to the expression of VEGF.

Crystal nucleation of hard spheres using molecular dynamics, umbrella sampling, and forward flux sampling: a comparison of simulation techniques.

Over the last number of years several simulation methods have been introduced to study rare events such as nucleation. In this paper we examine the crystal nucleation rate of hard spheres using three such numerical techniques: molecular dynamics, forward flux sampling, and a Bennett-Chandler-type theory where the nucleation barrier is determined using umbrella sampling simulations. The resulting nucleation rates are compared with the experimental rates of Harland and van Megen [Phys. Rev. E 55, 3054 (1997)], Sinn et al. [Prog. Colloid Polym. Sci. 118, 266 (2001)], Schätzel and Ackerson [Phys. Rev. E 48, 3766 (1993)], and the predicted rates for monodisperse and 5% polydisperse hard spheres of Auer and Frenkel [Nature 409, 1020 (2001)]. When the rates are examined in units of the long-time diffusion coefficient, we find agreement between all the theoretically predicted nucleation rates, however, the experimental results display a markedly different behavior for low supersaturation. Additionally, we examined the precritical nuclei arising in the molecular dynamics, forward flux sampling, and umbrella sampling simulations. The structure of the nuclei appears independent of the simulation method, and in all cases, the nuclei contains on average significantly more face-centered-cubic ordered particles than hexagonal-close-packed ordered particles.

Fibrinogen controls human platelet fibronectin internalization and cell-surface retention.

BACKGROUND: We recently demonstrated that platelet aggregation occurred in fibrinogen-deficient mice. In these animals, platelet fibronectin (Fn) content was increased 3-5 fold, suggesting that Fn may also be involved in platelet aggregation. METHODS AND RESULTS: We compared platelet Fn content from a severe hypofibrinogenemic patient (with approximately 0.5% of normal fibrinogen levels) with his parents (heterozygous) and healthy donors. A significant increase in the patient's platelet Fn content was detected by immunoblot, flow cytometry, and immunoelectron microscopy (IEM). To examine the possible contribution of platelet Fn to platelet aggregation, we examined cell-surface Fn expression after thrombin treatment. Unexpectedly, IEM detected only trace amounts of Fn retained on the patient's platelet surface, and flow cytometry indicated that surface Fn was approximately 6-fold lower than that of his parents and tenfold lower than that of healthy donors. An ELISA further confirmed that the patient's platelet Fn was primarily released into the extracellular medium. To test whether retention of surface Fn was due to fibrin formation on the platelet surface, an antifibrin antibody (T2 G1) was employed. Fibrin was detected on platelets from healthy donors and from the father, but was negligible on the patient's platelets. Consistent with these data, when gel-filtered platelets of healthy donors were treated with thrombin receptor activation peptide (SFLLRN-NH(2); no conversion of fibrinogen to fibrin), little surface Fn was detected. CONCLUSION: Fibrinogen not only competitively inhibits human platelet Fn internalization but also controls platelet-surface Fn retention via fibrin formation. The Fn-fibrin interaction is one possible mechanism to promote Fn interaction with platelets.

Overexpression of dishevelled 2 is involved in tumor metastasis and is associated with poor prognosis in hepatocellular carcinoma.

PURPOSE: Although hepatocellular carcinoma (HCC) is one of the most common malignant tumors, its molecular mechanism is still unknown. Dishevelled 2 (Dvl2) is one of the downstream targets of non-canonical Wnt signaling, which has been demonstrated to be of great importance in the progression of cancers. Nevertheless, the expression mechanisms and physiological significance of Dvl2 in HCC remain unclear. METHODS: Western blotting and immunohistochemistry were used to measure Dvl2 protein expression in HCC and adjacent normal tissues of 101 patients. Wound healing and transwell assays were used to determine cell migration and invasion. RESULTS: Dvl2 expression was upregulated in HCC tissues compared to the adjacent normal tissues. Moreover, its expression level was significantly correlated with histological grade (P = 0.042), metastasis (P = 0.005) and vein invasion (P = 0.009) in patients with HCC. Wound healing and transwell assays showed that knockdown of Dvl2 reduced cell migration and invasion in HepG2 cells. Finally, we confirmed that Dvl2 could regulate the migration and invasion of HCC cells by interacting with P62 in non-canonical Wnt signaling. CONCLUSIONS: Our data showed that Dvl2 was overexpressed in HCC tissues and was also correlated with poor prognosis, suggesting that Dvl2 is a novel therapeutic target for HCC.

Comparison of the effect of dabigatran and dalteparin on thrombus stability in a murine model of venous thromboembolism.

UNLABELLED: ESSENTIALS: Does thrombus stability alter the presentation of venous thromboembolism and do anticoagulants alter this? In a murine model, we imaged a femoral vein thrombus and quantified emboli in the pulmonary arteries. Dabigatran decreases thrombus stability via factor XIII increasing embolization and pulmonary emboli. This cautions against the unapproved use of dabigatran for acute initial treatment of deep vein thrombosis. BACKGROUND: Venous thromboembolism (VTE) is a collective term for deep vein thrombosis (DVT) and pulmonary embolism (PE). Thrombus instability possibly contributes to progression of DVT to PE, and direct thrombin inhibitors (DTIs) may alter this. AIM: To develop a model to assess thrombus stability and its link to PE burden, and identify whether DTIs, in contrast to low-molecular-weight heparin (LMWH), alter this correlation. METHODS: Twelve minutes after ferric chloride-induced thrombus formation in the femoral vein of female mice, saline, dalteparin (LMWH) or dabigatran (DTI) was administered. Thrombus size and embolic events breaking off from the thrombus were quantified before treatment and at 10-min intervals after treatment for 2 h using intravital videomicroscopy. Lungs were stained for the presence of PE. RESULTS: Thrombus size was similar over time and between treatment groups. Total and large embolic events and pulmonary emboli were highest after treatment with dabigatran. Variations in amounts of pulmonary embolic events were not attributed to variations in thrombus size. Large embolic events correlated with the number of emboli per lung slice independent of treatment. Embolization in factor XIII deficient (FXIII(-/-) ) saline-treated mice was greater than that in wild-type (WT) saline-treated mice, but was similar to WT dabigatran-treated mice. CONCLUSION: We have developed a mouse model of VTE that can quantify emboli and correlate this with PE burden. Consistent with clinical data, dabigatran, a DTI, acutely decreases thrombus stability and increases PE burden compared with LMWH or saline, which is a FXIII-dependent effect.

Long-term maintenance of functional rat hepatocytes in primary culture by additions of pyruvate and various hormones.

Mature adult rat hepatocytes were cultured as monolayers in serum-free Williams medium E containing 10(-7) M each of insulin (Ins), dexamethasone (Dex) and triiodothyronine (T3) and 30 mM pyruvate. The hepatocytes remained morphologically intact for at least 14 days, during which period they maintained normal liver functions such as the expressions of cytochrome P-450 mRNA and glucokinase and secretion of albumin. They also retained the ability to resume proliferation. Cells cultured with pyruvate had a much higher ATP level than those without pyruvate, suggesting that pyruvate can sustain functional hepatocytes for a long period in culture in the presence of Ins, Dex and T3, probably by producing enough energy for their maintenance.

Molecular cloning of two types of cDNA encoding subunit RC6-I of rat proteasomes.

A new subunit, named RC6-I, of the rat 20 S proteasome was purified and the partial amino acid sequences of several peptide fragments obtained by digestion with lysyl-endopeptidase were determined by Edman degradation. Amplification of cDNAs encoding RC6-I by the polymerase chain reaction (PCR) technique revealed two types of cDNA, tentatively designated as RC6-IL and RC6-IS in order of size. The nucleotide sequences of the two cDNAs are identical except that RC6-IL contains an insertion of 18 nucleotides in the coding region compared with RC6-IS. The polypeptide predicted from the open reading frame of RC6-IS cDNA consists of 248 amino acid residues with a calculated molecular weight of 27,783. These values are consistent with those obtained by protein chemical analyses. Computer-assisted homology analysis showed that RC6-I belongs to the alpha-type subfamily of the proteasome gene family, which shows similarity to the alpha-subunit of the archaebacterium Thermoplasma acidophilum proteasome, and that the 18 nucleotide insert, encoding six amino acid residues, VVASVS, appears to be unique to RC6-IL, because this motif has not been conserved in any other alpha-type subunit. By reverse transcription (RT)-PCR analysis, the mRNAs for both RC6-IL and RC6-IS were found in all the rat tissues examined. These results suggest that proteasomes are present as a heterogeneous population, possibly for acquisition of diversity of functions.

Hematologic interactions of endotoxin, tumor necrosis factor alpha (TNF alpha), interleukin 1, and adrenal hormones and the hematologic effects of TNF alpha in Corynebacterium parvum-primed rats.

Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose-response-dependent initial neutropenia followed by a monophasic neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophasic neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte-macrophage system and treated with TNF differed from naive rats treated with TNF in that the second peak was as great as the initial peak of neutrophilia, supporting the hypothesis that the second peak of TNF-induced neutrophilia is due to the release of endogenous monokines. In conclusion, exogenous TNF, IL-1, and adrenal hormones affect circulating numbers of lymphocytes and neutrophils in a fashion consistent with their postulated endogenous role in the regulation of leukocyte trafficking during bacterial infection.

Mechanisms of tumor necrosis factor alpha-induced lymphopenia, neutropenia, and biphasic neutrophilia: a study of lymphocyte recirculation and hematologic interactions of TNF alpha with endogenous mediators of leukocyte trafficking.

Tumor necrosis factor alpha (TNF) induces lymphopenia, neutropenia, and biphasic neutrophilia after intravenous injection of 3,000 U TNF in Lewis rats. The mechanism of TNF-induced lymphopenia was investigated by means of thoracic duct cannulation. Hourly measurements of lymphocyte recirculation via the thoracic duct failed to reveal any significant decrease in lymphocyte recirculation in TNF-treated vs. control rats, suggesting that a decrease in lymphocyte recirculation through the thoracic duct is not the mechanism for TNF-induced lymphopenia. The mechanism of TNF-induced neutropenia was investigated by administering TNF to rats in whom a neutrophilia had been induced with interleukin-1 (IL-1). In rats with neutrophilia, TNF resulted in a sharp decrease in the circulating neutrophil pool, demonstrating that TNF induces neutropenia by causing neutrophils to leave the circulating pool rather than decreasing neutrophil release from the marrow. The mechanism of neutropenia was furthermore shown to be due to the transient intravascular margination of neutrophils by administering epinephrine concomitantly with TNF. Epinephrine, which causes neutrophilia solely by demargination, abrogated the TNF-induced neutropenia and actually resulted in a neutrophilia that was greater than the neutrophilia occurring in epinephrine alone-treated rats, demonstrating both that TNF had already caused release of marrow neutrophils at the time of peripheral neutropenia, and that the paradoxical neutropenia was due to the transient intravascular margination of neutrophils. The known property of epinephrine to cause neutrophilia exclusively by demargination was proved by examination of the bone marrow of epinephrine-treated rats in whom no decrease in marrow neutrophils was observed (in contrast to TNF- and IL-1-treated rats in whom neutrophilia is accompanied by a depletion of marrow neutrophils). The mechanism of TNF-induced neutrophilia was investigated by modulating the magnitude of both the first and second peaks of neutrophilia by priming of rats with daily injections of IFN gamma for 2 days prior to administration of TNF. The first peak of neutrophilia in IFN gamma-primed TNF-treated rats was decreased in comparison to TNF alone-treated rats because of the well-known neutropenic and myelosuppressive effect of IFN gamma, which resulted in a decrease in the number of neutrophils that could be recruited to cause neutrophilia.(ABSTRACT TRUNCATED AT 400 WORDS)

The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.

Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal-independent, hemodynamic-independent mechanisms. The possibility that M-PGF2 alpha might be inducing neutrophilia via an endotoxin-like stress reaction was investigated by examining changes in circulating white blood cells in intact and adrenalectomized C3H/HeN (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) mice after prostaglandin administration. No quantitative differences in the prostaglandin-induced neutrophilia were noted in C3H/HeJ mice as compared to the C3H/HeN mice.(ABSTRACT TRUNCATED AT 400 WORDS)

MIF4G domain containing protein regulates cell cycle and hepatic carcinogenesis by antagonizing CDK2-dependent p27 stability.

The CDK inhibitor p27(kip1) plays crucial roles in cell cycle regulation and cancer progression. Through yeast two-hybrid screening, we identified MIF4G domain containing protein (MIF4GD) as a novel binding partner for p27. The association of MIF4GD and p27 was verified using immunoprecipitation and glutathione S-transferase (GST) pull-down assays. Interaction with MIF4GD led to the stabilization of p27 both in the nucleus and in the cytoplasm in hepatocellular carcinoma (HCC) cells as a result of suppressed phosphorylation of p27 by CDK2 at threonine187. Serum stimulation decreased the levels of MIF4GD and p27 simultaneously. In addition, MIF4GD overexpression resulted in increased p27 levels and reduced cell proliferation, while knockdown of MIF4GD promoted cell cycle progression with decreased p27 levels in cells. Furthermore, overexpression of MIF4GD reduced colony formation and inhibited xenograft tumor growth in nude mice. Finally, we found that both MIF4GD and p27 were expressed at low levels in HCC tissues compared to non-cancerous tissues, and that low expression levels of MIF4GD and p27 were associated with significantly worse prognosis in HCC patients. Our results suggest that MIF4GD is a potential regulator of p27-dependent cell proliferation in HCC. These findings provide a rational framework for the development of potential HCC therapy by targeting the MIF4GD-p27 interaction.

Cloning of a human gene closely related to the genes coding for the c-myc single-strand binding proteins.

Southwestern screening of human fibroblast cDNAs with an upstream element of the alpha2(I) collagen promoter (Box 5A) has led to the identification of a novel gene product (RBMS3). RBMS3 contains two pairs of RNA binding motifs and is very closely related to the structure of the c-myc gene single-strand binding proteins (MSSPs). MSSPs are believed to regulate DNA replication, transcription, apopotosis and cell cycle progression by interacting with the C-MYC protein. Consonant with this postulate, RBMS3 binds in vitro to the minus strand of Box 5A and transactivates transcription in the chimeric GAL4 hybrid system. However, the RBMS3 protein mostly localizes to the cytoplasm of transfected cells, in addition to binding strongly in vitro to synthetic poly-U and poly-A oligoribonucleotides. Finally, overexpression in transfected fibroblasts of RBMS3 with and without a nuclear localization signal has no effect on Box 5A-driven transcription. The results thus exclude RBMS3 involvement in the transcriptional regulation of COL1A2 and strongly suggest a cytoplasmic function of this new member of the MSSP family. As part of the initial characterization of RBMS3 we have also established that the gene resides on human chromosome 3p23-p24 and is widely expressed in the embryo and in the adult organism.

N-methyl-D-aspartate (NMDA) and opioid receptors mediate dynorphin-induced spinal cord injury: behavioral and histological studies.

Both N-methyl-D-aspartate (NMDA) and opioid receptors have been implicated in the pathophysiology of traumatic spinal cord injury and dynorphin-induced paralysis. The present studies compared the effects of the non-competitive NMDA antagonist dextrorphan (Dex) and the kappa-selective opioid antagonist nor-binaltorphimine (nor-BNI) on the acute motor deficits and chronic neuropathological alterations caused by intrathecally administered dynorphin A-(1-17) (Dyn A). Infusion of Dyn A into the rat lower thoracic spinal subarachnoid space produced acute, reversible hindlimb paresis. Histological evaluations of spinal cord sections from these animals at 2 weeks post-infusion revealed ventral grey matter necrosis, neuronal loss and gliosis as well as axonal loss in adjacent white matter; however, there was minimal alteration in serotonin immunocytochemistry caudal to the injury zone. Dex or non-BNI pretreatment each significantly (P less than 0.05) reduced, and to a similar degree, the acute motor deficits and certain histological changes associated with Dyn A administration. These findings further support the hypothesis that dynorphin-induced spinal cord injury involves both NMDA receptors and opioid receptors.