Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 181 records · Page 10Linked to original sources

PubMed1999

[A case of traumatic aneurysm of innominate artery with occlusion of right subclavian artery].

A 42-year-old woman with history of chest blunt trauma from an automobile accident 250 days earlier had suffered easy fatigability of the right upper extremity. She had difference of blood pressure between upper extremities, 94/60 mmHg in the right and 126/70 mmHg in the left. Chest CT showed dilation of the innominate artery which compressed the trachea. Aortography showed an aneurysm of the innominate artery and occlusion of the right subclavian artery at its origin. The aneurysm of the innominate artery was resected and replaced with a 6 mm Dacron graft with aid of the external shunt. The right subclavian artery was also reconstructed with same graft. The aneurysm of the innominate artery should be suspected as a rare complication in blunt trauma of the chest.

Adult↗

PubMed1999

[Detection of early hilar lung cancers with fluorescence bronchoscopy].

The development of fluorescence bronchoscopy has made it possible to diagnose locally superficial hilar lung cancers such as carcinoma in situ, and in some cases atypical squamous metaplasia thought to be precancerous lesions. The selection of a treatment modality can be difficult for early hilar lung cancers due to problems associated with multiple lung carcinomas and the large number of heavy smokers afflicted. Many patients also have decreased pulmonary function. If carcinoma in situ and microinvasive carcinomas can be detected early, it may be possible to treat them radically with a less invasive method than surgery, such as endoscopic laser therapy. Centrally arising squamous cell carcinoma of the tracheobronchial tree, especially in heavy smokers, is thought to develop in multiple stages from squamous metaplasia, to atypical squamous metaplasia, followed by carcinoma in situ, and finally invasive cancer. However, it is hoped that preventive medicine for lung cancer will be established whereby patients with localized atypical squamous metaplasia detected by fluorescence bronchoscopy can be carefully monitored and motivated to stop smoking, and also administered chemopreventive agents.

Adult↗

PubMed1999

Reverse transcriptase (RT)-independent as well as RT-dependent HIV-1 replication exists in syncytia following cell fusion.

We studied the role of reverse transcriptase (RT) in human immunodeficiency virus (HIV)-1 replication in syncytia following cell fusion. A chronically HIV-1-infected MOLT-4 (MOLT-4/IIIB) cells allow HIV-1 replication and induce syncytium formation between uninfected MOLT-4 cells. AZT (3'-azido-3'-deoxythymidine, 1 microM) inhibited neither HIV-1 replication in MOLT-4/IIIB cells nor the syncytium formation induced by concultivation of MOLT-4/IIIB cells with uninfected MOLT-4 cells. In the supernatant of the syncytium containing culture a remarkably higher titer of p24 antigen was produced than in that of MOLT/IIIB cell culture. AZT inhibited p24 antigen production by HIV-1 in the syncytia to levels to comparable to that in MOLT-4/IIIB cells which were treated with AZT. In addition, p24 production by HIV-1 in the syncytia formed by cocultivation of CL-2 cells, which are chronically infected with HIV-1 but lack functional RT, with uninfected MOLT-4 cells was not different from that in CL-2 cells alone. The results suggest that HIV-1 RT plays an important role in HIV-1 replication within the syncytia but an RT-independent replication process which is essential for syncytium formation also exists in the syncytia. These results indicate that not only RT inhibitors but also inhibitors of syncytium formation are essential for anti-HIV therapy.

Cell Line↗

PubMed1999

Elevated levels of circulating plasma matrix metalloproteinase 9 in non-small cell lung cancer patients.

Elevated expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 have been implicated as playing important roles in tumor invasion and metastasis in various tissues. We investigated the relationship between circulating plasma MMP-9, its expression in tumor samples, and other clinical features in patients with non-small cell lung cancer (NSCLC). A series of 73 patients (45 men and 28 women) who underwent surgery for NSCLC was used in this study. Preoperative plasma concentrations of MMP-9 were examined using a one-step sandwich enzyme immunoassay. Expression levels of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were measured in 24 tumor samples by immunohistochemistry. The plasma concentration of MMP-9 in NSCLC patients (71.0 +/- 60.2 ng/ml) was significantly elevated compared to that of healthy volunteers (P < 0.0001). MMP-9 concentrations were elevated in 33 of 73 cases (45.2%), compared with a cutoff value of the mean +/- 2 SD in healthy volunteers. There were statistically significant differences in MMP-9 concentration in adenocarcinoma versus squamous cell carcinoma (P = 0.014) and adenocarcinoma versus large cell carcinoma (P = 0.014). Five of 24 patients (20.8%) had positive immunohistochemical MMP staining of the tumor cell cytoplasm, and two cases had positive staining in the surrounding stromal cells. Plasma MMP-9 concentrations were elevated in 45.2% of NSCLC patients; however, this elevation did not seem to correlate with MMP-9 production by cancer and stromal cells. We concluded that the MMP-9 ELISA could be a beneficial adjunct for assessing the tumor burden of NSCLC, especially for types of squamous cell carcinoma and large cell carcinoma.

Aged↗

PubMed1998

Pivotal role of TARC, a CC chemokine, in bacteria-induced fulminant hepatic failure in mice.

Thymus and activation-regulated chemokine (TARC) is a recently identified lymphocyte-directed CC chemokine which specifically chemoattracts T helper type 2 CD4(+) T cells in human. To establish the pathophysiological roles of TARC in vivo, we investigated whether a monoclonal antibody (mAb) against TARC could inhibit the induction of hepatic lesions in murine model using Propionibacterium acnes and lipopolysaccharide (LPS). P. acnes-induced intrahepatic granuloma formation in the priming phase is essential to the subsequent liver injury elicited by a low dose of LPS. The priming phase appears to be dominated by Th1 type immune responses determined by the profile of chemokine and chemokine receptor expression. TARC was selectively produced by granuloma-forming cells, and CC chemokine receptor 4 (CCR4)-expressing CD4(+) T cells migrated into the liver after LPS administration. In vivo injection of anti-TARC mAb just before LPS administration protected the mice from acute lethal liver damage, which was accompanied by a significant reduction of both CCR4 mRNA expression and IL-4 production by liver-infiltrating CD4(+) T cells. Moreover, both TNF-alpha and Fas ligand expressions in the liver were decreased by anti-TARC treatment. These results suggest that recruitment of IL-4-producing CCR4(+) CD4(+) T cells by granuloma-derived TARC into the liver parenchyma may be a key cause of massive liver injury after systemic LPS administration.

Animals↗

PubMed1998

Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid, cepharanthine, in chronically infected monocytic cells.

Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have antiinflammatory, antiallergic, and immunomodulatory activities in vivo. As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection, we investigated the inhibitory effects of cepharanthine on tumor necrosis factor alpha (TNF-alpha)- and phorbol 12-myristate 13-acetate (PMA)-induced HIV-1 replication in chronically infected cell lines. Two chronically HIV-1-infected cell lines, U1 (monocytic) and ACH-2 (T lymphocytic), were stimulated with TNF-alpha or PMA and cultured in the presence of various concentrations of the compound. HIV-1 replication was determined by p24 antigen level. The inhibitory effects of cepharanthine on HIV-1 long terminal repeat (LTR)-driven gene expression and nuclear factor kappaB (NF-kappaB) activation were also examined. Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA-stimulated U1 cells but not in ACH-2 cells. Its 50% effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in PMA-stimulated U1 cells, respectively. Cepharanthine was found to suppress HIV-1 LTR-driven gene expression through the inhibition of NF-kappaB activation. These results indicate that cepharanthine is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line. Since biscoclaurine alkaloids, containing cepharanthine as a major component, are widely used for the treatment of patients with various inflammatory diseases in Japan, cepharanthine should be further pursued for its chemotherapeutic potential in HIV-1-infected patients.

Alkaloids↗

PubMed1998

Anti-tumor and anti-metastatic effects of human-vascular-endothelial-growth-factor-neutralizing antibody on human colon and gastric carcinoma xenotransplanted orthotopically into nude mice.

In order to determine whether the inhibition of vascular-endothelial-growth-factor (VEGF) activity by administration of an immunoneutralizing antibody could suppress tumor growth and metastasis in spontaneous metastatic models of human colon and gastric carcinoma, 4 human carcinoma xenografts, 2 human colon carcinomas (TK4 and TK 13) and 2 gastric carcinomas (MT2 and MT5) were transplanted orthotopically into nude mice. The anti-VEGF antibody (MV833, 100 microg/mouse) or the same volume of saline was administered i.p. on alternative days from day 10 after transplantation. With each of the 4 xenografts, administration of MV833 significantly inhibited not only primary tumor growth but also macroscopic liver metastasis, although the growth rate varied. The inhibitory effect of MV833 on primary tumor growth appeared to have no correlation with the level of VEGF in tumor. Body-weight gain in each treated group was comparable with that in the control group. No toxicity of the antibody was observed. These results suggest that an anti-VEGF antibody can be effective against a wide variety of cancers, and that VEGF may be a possible target for cancer therapy.

Adenocarcinoma↗

PubMed1998

T-cell-receptor signalling in inositol 1,4,5-trisphosphate receptor (IP3R) type-1-deficient mice: is IP3R type 1 essential for T-cell-receptor signalling?

Stimulation of T-cells via the T-cell receptor (TCR) complex is accompanied by an increase in intracellular Ca2+ concentration ([Ca2+]i). Recently, it was reported that a stable transformant of the human T-cell line, Jurkat, expressing an antisense cDNA construct of inositol 1,4,5-trisphosphate receptor (IP3R) type 1 (IP3R1), failed to demonstrate increased [Ca2+]i or interleukin-2 production after TCR stimulation and was also resistant to apoptotic stimuli. This cell line lacked IP3R1 expression, but expressed the type-2 and -3 receptors, IP3R2 and IP3R3 respectively [Jayaraman, Ondriasova, Ondrias, Harnick and Marks (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 6007-6011, and Jayaraman and Marks (1997) Mol. Cell. Biol. 17, 3005-3012]. The authors concluded that IP3R1 is essential for TCR signalling and suggested that Ca2+ release via IP3R1 is a critical mediator of apoptosis. To establish whether a loss of IP3R1 function in T-cells occurred in vivo and in vitro, we investigated Ca2+ signalling after TCR stimulation and the properties of T-cells using IP3R1-deficient (IP3R1-/-) mice. As IP3R1-/- mice die at weaning, we transplanted bone marrow cells of IP3R1-/- mice into irradiated wild-type mice. Western blot analysis showed that the recipient IP3R1-containing (IP3R1+/+) lymphocytes were replaced by the donor IP3R1-/- lymphocytes after transplantation and that expression of IP3R2 and IP3R3 was unaltered. In contrast with the previous reports, T-cells lacking IP3R1 were able to mobilize Ca2+ from intracellular Ca2+ stores after stimulation via the TCR. We observed no significant differences between IP3R1+/+ and IP3R1-/- T-cells in terms of the number of thymocytes and splenocytes, the proportion of the T-cell phenotype, proliferative response to anti-CD3 monoclonal antibody (mAb) stimulation and cell viability. Therefore IP3R1 is not essential for T-cell development and function.

Animals↗

PubMed1998

Prevention of murine AIDS development by (R)-9-(2-phosphonylmethoxypropyl)adenine.

LP-BM5 murine leukemia virus (MuLV) infection causes severe immunodeficiency termed murine AIDS (MAIDS). The acyclic nucleoside phosphonates, (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were examined, in comparison with zidovudine (AZT), for their inhibitory effect on the development of MAIDS. Although no significant difference in inhibition of LP-BM5 MuLV replication was identified between PMPA and PMEA in cell cultures, PMPA was obviously less cytotoxic to the host lymphocytes. None of the mice treated in vivo with 5 or 25 mg/kg of PMPA or 25 mg/kg of PMEA developed MAIDS at 5 weeks after viral infection. However at 9 weeks, none of the 25 mg/kg PMPA-treated mice progressed to MAIDS, except for one that developed mild MAIDS, whereas PMEA, even at 100 mg/kg, could not prevent disease progression. MAIDS-associated activation of lymphocytes and viral replication were drastically inhibited by PMPA treatment. These results indicate that PMPA is a highly effective antiretroviral agent in vivo.

Adenine↗

PubMed1998

Alpha1-adrenoceptor stimulation enhances experimental gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged administration of the norepinephrine-mimicking agent metaraminol, the alpha1-adrenergic agonist phenylephrine and the alpha2-adrenergic agonist clonidine on the incidence of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the ornithine decarboxylase activity of the gastric cancer and the labeling index of the gastric mucosa were investigated in Wistar rats. Rats received s.c. injections of metaraminol, phenylephrine or clonidine every other day after 20 weeks of oral treatment with MNNG. At week 52, administration of metaraminol and phenylephrine at the higher dose significantly increased the incidence of gastric cancers, the ornithine decarboxylase activity of the gastric cancers and the labeling index of the antral epithelial cells. Administration of phenylephrine at the lower dose and clonidine at both doses had no significant effect on the incidence of gastric cancers, the ornithine decarboxylase activity of the gastric cancers or the labeling index of the gastric mucosa. Our results suggest that adrenoreceptor stimulation enhances gastric carcinogenesis and that such enhancement is mediated through alpha1-adrenoceptors without alpha2-adrenoceptor involvement.

Adrenergic alpha-Agonists↗

PubMed1998

Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases.

A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1), beta-homonojirimycin (2), alpha-homomannojirimycin (3), beta-homomannojirimycin (4), alpha-3,4-di-epi-homonojirimycin (5), beta-4,5-di-epi-homonojirimycin (6), N-methyl-alpha-homonojirimycin (7), and N-butyl-alpha-homonojirimycin (8). Compound 1 was a potent inhibitor of a range of alpha-glucosidases with IC50 values of 1 to 0.01 microM. Compounds 2, 3, and 4 were surprisingly inactive as inhibitors of beta-glucosidase and alpha- and beta-mannosidases but were moderately good as inhibitors of rice and some mammalian alpha-glucosidases. Compound 4 was active in the micromolar range toward all alpha-glucosidases tested. Furthermore, compound 4, which superimposes well on beta-l-fucose, was a 10-fold more effective inhibitor of alpha-l-fucosidase than 1-deoxymannojirimycin (12) and 3, with a Ki value of 0.45 microM. Only compounds 5 and 6 showed inhibitory activity toward alpha- and beta-galactosidases (6with an IC50 value of 6.4 microM against alpha-galactosidase). The high-resolution structure of 1 has been determined by X-ray diffraction and showed a chair conformation with the C1 OH (corresponding to the C6 OH in 1-deoxynojirimycin) predominantly equatorial to the piperidine ring in the crystal structure. This preferred (C1 OH equatorial) conformation was also corroborated by 1H NMR coupling constants. The coupling constants for 7 suggest the axial orientation of the C1 OH, while in 8 the C1 OH axial conformation was not observed. The C1 OH axial conformation appears to be responsible for more potent inhibition toward processing alpha-glucosidase I than alpha-glucosidase II. It has been assumed that the anti-HIV activity of alkaloidal glycosidase inhibitors results from the inhibition of processing alpha-glucosidase I, but 1, 7, and 8 were inactive against HIV-1 replication at 500 microg/mL as measured by inhibition of virus-induced cytopathogenicity in MT-4 cells. In contrast, the EC50 value for N-butyl-1-deoxynojirimycin (11), which also inhibits processing alpha-glucosidase I, was 37 microg/mL. Compound 7 has been shown to be a better inhibitor of alpha-glucosidase I than 1 and 8 both in vitro and in the cell culture system. These data imply that inhibition of HIV by glycosidase inhibitors can be due to factors other than simply inhibition of processing alpha-glucosidase I.

1-Deoxynojirimycin↗

PubMed1998

Design and testing of a new cisplatin form using a base material by combining poly-D,L-lactic acid and polyethylene glycol acid against peritoneal metastasis.

Microspheres containing cisplatin (CDDP) embedded in poly-d,l-lactic acid (PLA) and polyethylene glycol acid (CDDP-PPMS) were developed to improve treatment of malignant effusions. In vitro studies demonstrated that CDDP was released continuously for more than 4 weeks from CDDP-PPMS without initial burst. CDDP-PPMS was compared with CDDP aqueous solution (CDDP-SOL) by i.p. administration in rats for 1) tissue distribution, 2) toxicity and 3) therapeutic effects against Yoshida sarcoma. We found that the CDDP concentration in the omentum was maintained at a higher level than in the CDDP-SOL group, while the particles of CDDP-PPMS were observed in the stomata of the omentum by electron microscopy. Concentrations of CDDP in the lung, liver, kidney and blood were lower in the CDDP-PPMS group than in the CDDP-SOL group. All rats given CDDP-PPMS containing < or = 28 mg/kg were alive, whereas in the CDDP-SOL group, all rats given > or = 16 mg/kg died from side effects. The LD50 of CDDP-PPMS and CDDP-SOL were 32.8 and 14.8 mg/kg, respectively. The survival of rats with peritoneal metastasis was better in the CDDP-PPMS group than in the CDDP-SOL group.

Animals↗

PubMed1998

Attenuation by methionine of monochloramine-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

Helicobacter pylori appears to play a major role in the development of gastric cancer in humans. The mechanism behind the carcinogenic or co-carcinogenic effects of H. pylori has not been established. Ammonia, generated by urea from H. pylori, has been studied as a possible cause. However, the ammonia-monochloramine system has been shown to play a more important role in H. pylori-associated mucosal injury. Therefore, the effects of combined administration of monochloramine and methionine, singly or together, on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar rats. After receiving oral MNNG and regular chow pellet for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without a subcutaneous injection of methionine, until the end of the experiment (week 52). Treatment with both ammonium acetate and sodium hypochlorite, which produce monochloramine, significantly increased the incidence of gastric cancers in week 52, whereas the concomitant administration of methionine with ammonium acetate and sodium hypochlorite significantly attenuated such enhanced gastric carcinogenesis. Spectrophotometric examination revealed that methionine scavenged monochloramine. Our findings suggest that H. pylori-associated gastric carcinogenesis may be mediated by monochloramine.

Animals↗

PubMed1998

Inhibition by galanin of experimental carcinogenesis induced by azaserine in rat pancreas.

The effects of galanin on pancreatic carcinogenesis induced by azaserine and on the norepinephrine concentration in the pancreas were investigated in male Wistar rats. Rats were given weekly injections of 10 mg/kg body weight of azaserine for 25 weeks and 8 microg/kg body weight of galanin in depot form every other day for 62 weeks. Azaserine-induced pancreatic lesions were examined with hematoxylin and eosin and histochemical techniques. In week 62, quantitative histological examination showed that prolonged administration of galanin significantly reduced the number and size (as percent of parenchyma) of adenosine triphosphatase-positive pancreatic lesions, which are correlated closely with the ultimate development of pancreatic cancer. The number of pancreatic adenocarcinomas in rats treated with galanin was significantly less than in controls. Galanin also significantly decreased the bromodeoxyuridine-labeling index of azaserine-induced pancreatic lesions and the norepinephrine concentration in the pancreas. Our findings indicate that galanin inhibits pancreatic carcinogenesis and that such inhibition may be related to the suppression of sympathetic nervous system activity and subsequently to the inhibition of cell proliferation in neoplastic lesions of the pancreas.

Animals↗

PubMed1998

Promotion by the alpha-adrenoceptor agonist phenylephrine, but not by the beta-adrenoceptor agonist isoproterenol, of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of prolonged administration of the alpha-adrenoceptor agonist phenylephrine and the beta-adrenoceptor agonist isoproterenol on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and on the labeling index of gastric mucosa were compared in Wistar rats. Rats received subcutaneous injections of 3 or 6 mg/kg body weight of phenylephrine or 0.1 or 0.2 mg/kg body weight of isoproterenol every other day after 25 weeks of oral treatment with the carcinogen. Long-term administration of phenylephrine at a high dose, but not at a low dose, significantly increased the incidence of gastric cancers and the labeling index of antral epithelial cells at the end of the experiment in week 52. However, administration of isoproterenol at either dosage had no significant effect on the incidence of gastric cancers and the labeling index of antral epithelial cells. These findings indicate that increased activity of the sympathetic nervous system enhances gastric carcinogenesis through alpha-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1998

Concanavalin A-immobilized polystyrene nanospheres capture HIV-1 virions and gp120: potential approach towards prevention of viral transmission.

To establish an effective tool for the prevention of HIV-1 transmission, lectin-immobilized polystyrene nanospheres were synthesized and examined for their HIV-1 capture activity. When concanavalin A (Con A) was immobilized on the surface of polystyrene nanospheres (400 nm in diameter) with poly(methacrylic acid) branches and incubated with HIV-1 suspension at room temperature for 60 min, the nanospheres (Con A-NSs) achieved a >3.3 log and a 2.2 log reduction of viral infectivity in HIV-1 (IIIB strain) suspension at a concentration of 2 and 0.5 mg/ml, respectively. Meanwhile, Con A-free nanospheres, which were not immobilized with Con A, achieved only a 0.29 log reduction at 0.5 mg/ ml. Con A-NSs (2 mg/ml) could also reduce the gp120 level of III(B) and HE strains to <7.1% and 5.5% of each control, respectively. The combination of Con A-NS treatment followed by filtration with a microporous membrane efficiently removed virion-free gp120 as well as infectious viral particles from HIV-1 suspension. Electron microscopic examination demonstrated that HIV-1 virions were trapped on the surface of Con A-NSs. Thus, Con A-NSs can capture HIV-1 virions and gp120 with high affinity, and may have potential as an effective tool for the prevention of HIV-1 transmission.

Concanavalin A↗

PubMed1998

A lymphocyte-specific CC chemokine, secondary lymphoid tissue chemokine (SLC), is a highly efficient chemoattractant for B cells and activated T cells.

Secondary lymphoid tissue chemokine (SLC) is a CC chemokine expressed mainly in lymph nodes, appendix and spleen, and specifically chemotactic for lymphocytes (Nagira et al., J. Biol. Chem. 1997. 272: 19518-19524). Here, we carried out transendothelial migration assays to determine the classes and subsets of lymphocytes migrating toward SLC. SLC attracted freshly isolated B cells with high efficiency and T cells modestly. Thus, SLC is the first CC chemokine with a strong chemotactic activity on fresh B cells. Among T cell types and subsets, SLC broadly attracted CD4+ and CD8+ cells, CD45RO- (naive) and CD45RO+ (memory) cells, and CD26high (activated) and CD26low- (resting) cells. SLC also attracted both L-selectin+ and L-selectin- subpopulations of various T cell subsets and B cells. Furthermore, mitogenic stimulation strongly enhanced migratory responses of T cells and B cells toward SLC. By in situ hybridization, SLC mRNA was detected in the cortical parafollicular regions (the T cell areas) of a lymph node and an appendix. Collectively, SLC may be a basic chemokine supporting homeostatic migration of a broad spectrum of lymphocytes into the secondary lymphoid tissues. SLC may also be involved in immune responses by inducing highly efficient migration of T and B cells following antigenic stimulation.

Adult↗

PubMed1998

Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein.

Recently, alpha-synuclein was shown to be a structural component of the filaments in Lewy bodies (LBs) of Parkinson's disease (PD), dementia with LBs (DLB) as well as the LB variant of Alzheimer's disease, and this suggests that alpha-synuclein could play a mechanistic role in the pathogenesis of these disorders. To determine whether alpha-synuclein is a building block of inclusions in other neurodegenerative movement disorders, we examined brains from patients with multiple system atrophy (MSA) and detected alpha-synuclein, but not beta- or gamma-synuclein, in glial cytoplasmic inclusions (GCIs) throughout the MSA brain. In MSA white matter, alpha-synuclein-positive GCIs were restricted to oligodendrocytes, and alpha-synuclein was localized to the filaments in GCIs by immunoelectron microscopy. Finally, we demonstrated that insoluble alpha-synuclein accumulated selectively in MSA white matter with alpha-synuclein-positive GCIs. Taken together with evidence that LBs contain insoluble alpha-synuclein, our data suggest that a reduction in the solubility of alpha-synuclein may induce this protein to form filaments that aggregate into cytoplasmic inclusions, which contribute to the dysfunction or death of glial cells as well as neurons in neurodegenerative disorders with different phenotypes.

Actin Cytoskeleton↗