Suppression of interleukin-2 receptor expression on mouse CD4+ T cells by bovine kappa-caseinoglycopeptide

Bovine kappa-caseinoglycopeptide (residues 106-169, CGP) completely inhibited the PHA-induced proliferation of mouse splenocytes when CGP was added simultaneously with PHA. The inhibitory effect, however, was reduced to about one-half when CGP was added after 24 h of cultivating the splenocytes with PHA or when anti-IL-1ra antibody was added simultaneously with PHA and CGP. On the other hand, CGP bound to mouse CD4+ T cells but not to CD8+ T cells. CGP suppressed IL-2 receptor expression of the PHA-stimulated mouse CD4+ T cells.     

Vertical seismic response of overhead crane

Vertical seismic response behavior is an important issue for the seismic design of equipments. The equipment, which is comparatively soft and unrestrained vertically, may resonate and its response is significantly magnified under vertical seismic excitation. Overhead crane is an example of equipment that is unrestrained vertically. The dynamic behavior of an 150-ton-capacity overhead crane under vertical seismic excitation was investigated by scale model excitation test and nonlinear time history analysis. The excitation tests were performed with several input levels and the vertical response with each input level was obtained. The simulation analysis approximately corresponded to the results of the excitation test.     

Clinical evaluation of the efficacy of an antithrombin agent "Argatroban" combined with exercise therapy on increase of the skeletal muscle blood flow

Argatroban has selective antithrombin activity and widely used for treatment of ASO. In this study we investigated vasodilating activity of Argatroban besides antithrombin activity in ASO patients. Three patients who have undergone F-P bypasses previously which were all occluded received 10 mg or 20 mg of Argatroban per day intravenously for 4 weeks. Skin temperature were measured before and after administration of Argatroban at the point of 1, 2, 4 weeks which increased 2.3-6.0 degrees C after administration of Argatroban. Subjective symptoms were also improved and these patients became to be able to walk 1.5-3.3 km. These patients were also given PGE, intravenously, however, temperature increase was less than 1.1 degrees C. These results showed that Argatroban has not only antithrombin activity but also significant vasodilating activity resulting in increase of skeletal muscle blood flow.     

Long-term results of mitral valvuloplasty for mitral regurgitation

From July 1979 to February 1995, 126 patients, including 4 reoperations, aged between 6 months and 77 years underwent mitral valve repair for mitral regurgitation. The patients were divided in two groups, 46 patients aged less than 16 years in pediatric age group and the other 80 patients in a dult group. The methods consisted of asymmetric annuloplasty (Kay-Reed method) in 98 patient, Carpentier-Edwards ring annuloplasty in 14, quadrangular resection of the posterior leaflet with annuloplasty in 9, and chordal and leaflet repair in 5. There was no hospital nor late death in pediatric age group. Three hospital deaths and one late death were in adult group. Follow-up was 96% complete and totaled 812.1 patient years. Reoperations underwent in 3 pediatric patients and 9 adults. At 15 years' follow-up, freedom from reoperation was 91.5 +/- 4.7% in pediatric age group and 67.1 +/- 12.7% in adults. Freedom from event was 63.5 +/- 12.1% in adult group. These results suggest that mitral repair with Kay-Reed method in pediatric age group is favorable for long-term. In contrast, indications for mitral reconstraction with other methods including ring annuloplasty should be extended for aged patients with severely dilated annuls and degenerated leaflets.     

Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines

CNTF rescues various types of lesioned neurons in vivo, and it needs to be released from astrocytes into the extracellular space to have the effect. However, direct evidence for CNTF release has not been unequivocally demonstrated. We hypothesized that the rapid sequestration by CNTF receptor present on cultured astrocytes might be the cause of the inability to detect CNTF released into astrocyte-conditioned medium (ACM). Therefore, we measured CNTF immunoreactivity in medium conditioned by astrocytes treated with phosphatidylinositol-specific phospholipase C (PI-PLC) which was used to prevent released CNTF from binding to the CNTF receptor, since PI-PLC cleaves glycosyl-phosphatidylinositol anchor of CNTFR alpha, the unique component involved in CNTF binding. CNTF was not detectable in untreated ACM, but was detectable in PI-PLC-treated ACM. These results together with the evidence that PI-PLC treatment did not have a toxic effect on astrocytes prove the fact that CNTF can be released from astrocytes without cell lysis. Subsequently, the effect of cytokines such as IL-1 beta, TNF-alpha, and EGF on CNTF release was examined. These cytokines increased CNTF protein levels in ACMs without increasing CNTF protein levels in astrocyte-extracts, indicating that they enhanced CNTF release from astrocytes.     

Rho-regulated signals induce apoptosis in vitro and in vivo by a p53-independent, but Bcl2 dependent pathway

Rho proteins are a branch of GTPases that belongs to the Ras superfamily which are critical elements of signal transduction pathways leading to a variety of cellular responses. This family of small GTPases has been involved in diverse biological functions such as cytoskeleton organization, cell growth and transformation, cell motility, migration, metastasis, and responses to stress. We report that several human Rho proteins including Rho A, Rho C and Rac 1, are capable of inducing apoptosis in different cell systems like murine NIH3T3 fibroblasts and the human erythroleukemia K562 cell line. Since K562 cells are devoid of p53, apoptosis induced by Rho in this system is independent of p53. Rho-dependent apoptosis is mediated by the generation of ceramides, and it is drastically inhibited by ectopic expression of Bcl2, both under in vitro and in vivo conditions. Furthermore, the human oncogenes vav and ost that have been shown to function as guanine exchange factors for Rho proteins, were also able to induce apoptosis under similar conditions. Finally, we also report that the levels of endogenous Rho proteins are increased when U937 myeloid leukemia cells are exposed to apoptosis-inducing conditions such as TNF alpha treatment. Furthermore, TNF alpha-induced apoptosis in these cells is inhibited by expression of a dominant negative mutant of Rac 1 but it is not affected by a similar mutant of Rho A. These results suggest that Rho proteins play an important role in the physiological regulation of the apoptotic response to stress-inducing agents.     

Responses of dorsal column nuclei neurons in rats with experimental mononeuropathy

During nerve cell degeneration, cholesterol released from the degrading cells is conserved through the formation of a cholesterol-apolipoprotein (apo) E complex which is subsequently taken up by regenerating nerve cells. The aim of the present project was to identify the physiologically relevant lipoprotein receptor for this lipoprotein complex which has remained elusive. HDL was separated into apo E-rich and apo E-poor subfractions and labelled with [14C]-sucrose. Labelled apo E-rich HDL bound to rat brain membranes in a time- and ligand concentration-dependent manner and was a saturable process. Essentially no binding occurred with [14C]-apo E-poor HDL or with free apo E. Binding was partially inhibited by low density lipoprotein (LDL) and by alpha 2-macroglobulin. These results provide new evidence that native apoE-rich HDL particles resembling those present in the brain bind to rat brain membranes and that the binding may be due, at least in part, to the LDL receptor and to the LDL-receptor related protein. Evidence was also provided for the presence of a receptor which binds [14C]-sucrose human apoE-rich HDL in human brain. Characterisation of the receptor which mediates the uptake of cholesterol from HDL-like complexes by brain cells is important in understanding the role of apoE in the central nervous system and of the alterations which occur in disorders such as Alzheimer's disease.     

Comparison of T2 lesion volume and magnetization transfer ratio histogram analysis and of atrophy and measures of lesion burden in patients with multiple sclerosis

A kinetic analysis of degradation of saturated oligoguluronates by poly(alpha-L-guluronate)lyase from Corynebacterium sp. ALY-1 strain was done. The saturated oligoguluronates were prepared by hydrolyzing poly alpha-1,4-L-guluronate from alginate with HCl, and then by gel filtration on a Bio-Gel P-6 column. The saturated pentaguluronate or above were rapidly degraded by the enzyme, while tetraguluronate was slowly degraded. From the dependency of the catalytic rate constant (kcat) on the degree of polymerization of substrates, the enzyme was found to have a subsite size corresponding to hexaguluronate units. The action pattern of the enzyme on hexaguluronate suggested that the catalytic site of the enzyme was matched to the linkage between the second and third uronic residue from the non-reducing end, since the substrate was mainly split into a unsaturated tetramer and a saturated dimer from a HPLC analysis.