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.     

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.     

Asialoglycoprotein receptor and hepatic blood flow using technetium-99m-DTPA-galactosyl human serum albumin

The decades just before and after the founding of the American Public Health Association in 1872 saw an efflorescence of political cartooning and caricature in national-circulation weeklies. Part of the political and social critique that cartoonists and their editors provided the public focused on needs or opportunities for preventing illness and accidents. This paper presents a small selection of editorial cartoons that agitated in support of public health activities over 4 decades. The goals are to illustrate several concerns that rose to national prominence in that era, to examine the kinds of imagery that newspapers and magazine editors offered their readers, and to observe how frequently the public was encouraged to see politicians and commercial interests as responsible for preventable health problems. This discussion focuses exclusively on propagandistic images, leaving aside the reportorial depictions of events in the news and the neutral illustrations of methods and machines in scientific and technical publications.     

A system for measuring magnetic core noise as a function of themagnetization level

The problem of magnetic core noise is considered in terms of non-repeatability of the hysteresis loop trace for any repetition of the magnetization process. The examination condition is that the effect of eddy currents is reduced to as low a level as possible. Based on such premises, this paper presents a system which periodically extracts the fluctuation voltage, induced at an arbitrary but specified point of the impressed magnetic field, as an instantaneous value. The minimum extraction interval is mainly determined by the integration time of the digital voltmeter used to measure the voltage and by the time required for transferring the extracted data to a personal computer. Therefore, the upper limit of the repetition frequency for the magnetization is restricted to less than 1 Hz. The serially extracted time data is dealt with in a statistical manner and is arranged in order as a magnitude distribution. Two kinds of cores are tested, one is a Fe-Ni-based amorphous core and the other a supermalloy. The results reveal that each core has distinctive noise features     

Identification of tethering domains for protein kinase A type Ialpha regulatory subunits on sperm fibrous sheath protein FSC1

The fibrous sheath is a unique cytoskeletal structure in the sperm flagellum believed to modulate sperm motility. FSC1 is the major structural protein of the fibrous sheath. The yeast two-hybrid system was used to identify other proteins that contribute to the structure of the fibrous sheath or participate in sperm motility. When FSC1 was used as the bait to screen a mouse testis cDNA library, two clones were isolated encoding the type Ialpha regulatory subunit (RIalpha) of cAMP-dependent protein kinase. Deletion analysis using the yeast two-hybrid system and in vitro binding assays with glutathione S-transferase-FSC1 fusion proteins identified two RIalpha tethering domains on FSC1. A domain located at residues 219-232 (termed domain A) corresponds to the reported tethering domain for a type II regulatory subunit (RII) of cAMP-dependent protein kinase, indicating that this binding domain has dual specificity to RI and RII. Another RIalpha tethering site (termed domain B) at residues 335-344 shows specific binding of RIalpha and had no significant sequence homology with known RII tethering domains. However, helical wheel projection analysis indicates that domain B is likely to form an amphipathic helix, the secondary structure of RII tethering domains of protein kinase A anchoring proteins. This was supported by the finding that site-directed mutagenesis to disrupt the amphipathic helix eliminated RIalpha binding. This is apparently the first report of an RIalpha-specific protein kinase A anchoring protein tethering domain.