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Biomedical subjects

Y Matsui

Publications and source records attributed to Y Matsui.

At least 145 records · Page 8Linked to original sources

Simple mixing of IFN with a polysaccharide having high liver affinity enables IFN to target to the liver.

Interferon (IFN) therapy is only one method that is clinically effective in controlling disease activity in patients with chronic hepatitis. A chelating residue (diethylenetriamine pentaacetic acid, DTPA) was introduced to pullulan, which is a polysaccharide with high liver affinity. This DTPA-pullulan could conjugate with IFN through Zn2+ coordination on mixing these three components. Intravenous injection of the IFN-DTPA-pullulan conjugate with Zn2+ coordination induced activity in the liver of an antiviral enzyme. 2',5'-oligoadenylate synthetase at IFN doses lower than those used for free IFN injection. In addition, synthetase induction by the conjugate continued for a longer time than did induction by free IFN. Liver targeting of IFN by this conjugation technique based on Zn2+ coordination opens a new method of IFN therapy.

2',5'-Oligoadenylate Synthetase↗

Combined effects of vancomycin and imipenem against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo.

Infectious disease caused by methicillin-resistant Staphylococcus aureus (MRSA) often develops in compromised hosts in whom a single administration of vancomycin is usually not effective. We assessed the combined antimicrobial effects of vancomycin and imipenem against MRSA growth in vitro as well as in vivo using a neutropenic mouse thigh infection model. Synergic and additive effects of the two drugs were observed for 34 and two, respectively, of the 36 clinical isolates of MRSA, as determined by the chequerboard method. For MRSA strain N, postantibiotic effect (PAE) values obtained in vitro were 1.9-2.6 h for vancomycin and 2.6-3.5 h for imipenem, while higher values of 2.7-4.4 h were obtained for the combination of vancomycin and imipenem. In vivo, a single administration of vancomycin at 1 or 2 mg/kg or of imipenem/cilastatin at 5 mg/kg produced growth curves similar to those in controls, with a suppressive time of 0 h. Imipenem/cilastatin at 10 mg/kg demonstrated a suppressive time of 3.1 h. Combinations of vancomycin 1 mg/kg plus imipenem/cilastatin 5 mg/kg, vancomycin 1 mg/kg plus imipenem/cilastatin 10 mg/k and vancomycin 2 mg/kg plus imipenem/cilastatin 10 mg/kg demonstrated suppressive times of 2.9, 3.9 and 5.2 h, respectively, indicating that combined administration was effective. Simultaneous administration of the two drugs was more effective than sequential administration. Thus, combined administration of vancomycin and imipenem/cilastatin proved effective for MRSA in vivo. The combined effects seemed to be synergic, since a single administration of either drug did not show anti-MRSA effects at the doses used in the combined regimen.

Animals↗

Rho3 of Saccharomyces cerevisiae, which regulates the actin cytoskeleton and exocytosis, is a GTPase which interacts with Myo2 and Exo70.

The Rho3 protein plays a critical role in the budding yeast Saccharomyces cerevisiae by directing proper cell growth. Rho3 appears to influence cell growth by regulating polarized secretion and the actin cytoskeleton, since rho3 mutants exhibit large rounded cells with an aberrant actin cytoskeleton. To gain insights into how Rho3 influences these events, we have carried out a yeast two-hybrid screen using an S. cerevisiae cDNA library to identify proteins interacting with Rho3. Two proteins, Exo70 and Myo2, were identified in this screen. Interactions with these two proteins are greatly reduced or abolished when mutations are introduced into the Rho3 effector domain. In addition, a type of mutation known to produce dominant negative mutants of Rho proteins abolished the interaction with both of these proteins. In contrast, Rho3 did not interact with protein kinase C (Pkc1), an effector of another Rho family protein, Rho1, nor did Rho1 interact with Exo70 or Myo2. Rho3 did interact with Bni1, another effector of Rho1, but less efficiently than with Rho1. The interaction between Rho3 and Exo70 and between Rho3 and Myo2 was also demonstrated with purified proteins. The interaction between Exo70 and Rho3 in vitro was dependent on the presence of GTP, since Rho3 complexed with guanosine 5'-O-(3-thiotriphosphate) interacted more efficiently with Exo70 than Rho3 complexed with guanosine 5'-O-(3-thiodiphosphate). Overlapping subcellular localization of the Rho3 and Exo70 proteins was demonstrated by indirect immunofluorescence. In addition, patterns of localization of both Exo70 and Rho3 were altered when a dominant active allele of RHO3, RHO3(E129,A131), which causes a morphological abnormality, was expressed. These results provide a direct molecular basis for the action of Rho3 on exocytosis and the actin cytoskeleton.

Actins↗

Selective ablation of porcine and rabbit liver tissue using radiofrequency: preclinical study.

Temperature changes and their distribution induced by 13.56-MHz radiofrequency (RF) heating of agar phantom and porcine and rabbit liver were investigated. It was possible to produce selective local heating of approximately 50 degrees C in the RF field of 2 x 2 x 2 cm(3) of the pig or rabbit liver. Coagulation necrosis after heating became pronounced and the margin between the coagulated lesion and normal tissue became clearer with time. Within 1 week after RF heating at 50 degrees C for 20 min, the coagulated area was replaced selectively and totally by necrotic tissue.

Animals↗

[Effect of compression with aerosolized fibrin sealant on surgical hemostasis].

In order to decrease complications following incomplete hemostasis after surgery, especially in the case of arterial bleeding, we experimentally investigated an effective way of applying fibrin glue as a sealant. Using white rabbits as a model, in which arterial bleeding from the abdominal aorta was induced, fibrin glue and a related hemostatic agent were tested to evaluate the hemostatic effectiveness. Group I (n = 9): Fibrin glue was applied by spraying it on the fingertip and then placing the fingertip on the bleeding part and pressing. Group II (n = 9): Fibrin glue was applied with oxycellulose on the fingertip and then placing the fingertip on the bleeding part and pressing. The results demonstrated that: 1) Although complete hemostasis could not be obtained with finger-pressing alone in 30 second, it could be obtained in 9/9 cases 100%) in Group I but in only 3/9 cases (33%) in Group II. 2) Pressure-resistant force was higher for Group I at an earlier time after hemostasis (p < 0.05). 3) Pathological study reconfirmed the predominance of Group I. We conclude from this study that ideal hemostasis can be obtained with fibrin glue applied simply by spraying it on the fingertip and then placing the fingertip on the bleeding part and pressing.

Aerosols↗

Abdominal aortic aneurysms in aged patients: analysis of risk factors in non-ruptured cases.

BACKGROUND AND METHODS: A retrospective analysis of 304 patients (274 males and 30 females) surgically treated for non-ruptured, infrarenal abdominal aortic aneurysm (AAA) to determine the relative contribution of preoperative, operative, and postoperative factors to mortality and to the development of postoperative complications. 1) Risk factors, hospital mortality and long-term survival rate were compared between patients aged 75 or older (- group I; n=79) and those under 75 years of age (group II; n=225). 2) These risk factors were subjected to univariate and multivariate analysis to determine their relative contribution to patient hospital mortality and to the development of major postoperative complications in aged patients. RESULTS: Maximum diameter of AAA, the prevalence of respiratory dysfunction, diabetes mellitus and the total volumes of intraoperative blood loss were significantly different between the two groups. A higher hospital mortality was noted in the aged patients (10.1% versus 3.1%, p<0.05). The majority of deaths in group I resulted from organ dysfunctions, especially involved with respiratory failure. The long term survival rate at 3 and 5 years was not different between operative survivors in the two groups. Incremental risk factors for hospital death in aged patients included the presence of symptomatic AAA, the maximum diameter of AAA, the postoperative development of myocardial infarction, respiratory complications and gastrointestinal bleeding. Operation time and the volumes of intraoperative blood loss significantly correlated with the postoperative development of respiratory failure, renal failure and multiple organ failure. CONCLUSIONS: 1) A higher operative mortality and higher prevalence of postoperative complications were noted in aged patients with AAA. 2) To reduce operation time and the volumes of intraoperative blood loss would be essential to improve surgical results of AAA in aged patients.

Adult↗

[Long-term results of mitral valve regurgitation after surgical repair of incomplete atrioventricular septal defect].

Although the postoperative outcome in patients with incomplete atrioventricular septal defect (iAVSD) is excellent, deterioration of mitral valve regurgitation (MR) is still remained to be resolved. Therefore, this study was undertaken to compare surgical procedures for mitral cleft repair with their long-term results of MR. From 1991 to 1996, 52 patients underwent surgical repair of iAVSD. Age at operation ranged from 2 months to 62 years old with mean age of 14.2 years. Mean follow-up period was 8.6 +/- 4.4 years. All patients underwent patch closure of ostium primum defect. Two patients did not have cleft (Group A). Seven patients did not close the cleft at all (Group B), while 40 patients had the repair of valve by closing cleft near septal attachment only (Group C). The latest 3 patients had the complete closure of cleft from annulus to margin of leaflet where chorda is attached. MR was evaluated by echocardiography grading 0 to IV and regurgitation more than grade II was considered to be significant. In Group A, MR remained grade I. In Group B, MR was deteriorated in 5 patients (71%). Consequently, 6 patients (86%) had grade II or more regurgitation and 4 patients (57%) revealed grade III/IV regurgitation including one (14%) reoperation. In Group C, MR was deteriorated in 10 patients (55%). Consequently, 22 patients (86%) had grade II or more regurgitation and 5 patients (13%) had grade III/IV regurgitation including 3 (7.5%) reoperations. In Group D, no deterioration of MR was noted and all had grade I or less regurgitation. These results suggest that the closure of cleft near septal attachment is not sufficient to prevent MR in late phase and the complete closure of cleft from annulus to margin of leaflet, where chorda is attached, would be useful to prevent the deterioration of MR in late phase.

Adolescent↗

Ruptured abdominal aortic aneurysms: analysis of factors influencing surgical results in 184 patients.

BACKGROUND: Rupture is often the first manifestation in patients with abdominal aortic aneurysms. Although elective surgery for non-ruptured abdominal aortic aneurysms has provided satisfactory surgical results, operative mortality of ruptured abdominal aortic aneurysms (rAAA) has not improved. The purpose of this study was to identify predictors for early hospital death in patients with rAAA. METHODS DESIGN: A retrospective study. SETTING: A university hospital and 20 affiliated hospitals. PATIENTS: PATIENTS undergoing surgical treatment for rAAA (n=183) between 1968 and 1997. INTERVENTIONS: All patients were surgically treated and divided into operative survivors (n=119) and non-survivors (n=64). MEASURES: The patient-related, procedure-related, and postoperative factors were compared between the two groups. A multivariate analysis was also conducted to determine predictors for hospital deaths. RESULTS: In univariate analysis, age at operation (p=0.004), preoperative hemodynamic conditions (p<0.0001), extent of hematoma (p<0.0001), preexistent renal dysfunction (p=0.001), and volumes of blood loss at operation (p=0.001) were significantly different between the two groups. The morbidity of postoperative renal failure (p<0.0001), gut ischemia (p=0.003), heart failure or ischemic heart disease (p<0.0001), and multiple organ dysfunction syndrome (p<0.0001) was higher in the non-survivors' group. Multivariate analysis also identified preoperative hemodynamic conditions, blood loss volume at operation, pre-existent renal dysfunction, postoperative renal failure, heart failure, and multiple organ dysfunction syndrome as incremental risk factors for hospital deaths. CONCLUSIONS: Every effort to maintain preoperative hemodynamic conditions, to reduce volumes of blood loss at operation, and to minimize deterioration of organ functions postoperatively is all essential to improve patient survival.

Adult↗

Growth factor release from amylopectin hydrogel based on copper coordination.

This paper describes a biodegradable hydrogel matrix releasing basic fibroblast growth factor (bFGF) on the basis of protein metal coordination with the protein drug. The biodegradable hydrogel was prepared from amylopectin by its crosslinking with ethylene glycol diglycidyl ether, followed by introduction of diethylenetriaminepentaacetic acid (DTPA) residues for copper chelation. When bFGF was incorporated into the DTPA-introduced amylopectin hydrogel after chelation with Cu2+, an insignificant amount of bFGF was released from the hydrogel in buffered solution, in contrast to that without Cu2+ chelation. An increased ionic strength in the solution did not affect the bFGF release, indicating the occurrence of coordinate bonding of bFGF to the DTPA-introduced hydrogel through Cu2+ chelation. An implantation study with 125I-labeled amylopectin hydrogels demonstrated that they underwent degradation in the back subcutis of mice. Cu2+ chelation of hydrogels enabled bFGF to remain in the mouse back for a long time period, irrespective of DTPA introduction. However, DTPA residues were necessary to induce significant neovascularization by the Cu2+-chelating hydrogels incorporating bFGF. The DTPA-introduced amylopectin prevented Cu2+-induced deactivation of bFGF, again in marked contrast to DTPA-free amylopectin. It was concluded that biologically active bFGF could be incorporated to DTPA-introduced amylopectin through Cu2+ chelation in a stabilized state and was released as a result of hydrogel biodegradation, resulting in prolonged neovascularization.

Amylopectin↗

Effects of yohimbine on naloxone-induced antinociception in a rat model of inflammatory hyperalgesia.

Effects of the alpha2-adrenoceptor antagonist yohimbine on the antinociception produced by a low dose of naloxone were examined in a rat model of carrageenan-induced inflammation. In rats receiving saline prior to naloxone injection, the low dose of naloxone (5 microg/kg, i.p.) significantly prolonged paw withdrawal latency in response to noxious thermal stimuli for both the inflamed and the non-inflamed paws 4 h after carrageenan injection (6.0 mg in 0.15 ml saline). In rats receiving yohimbine, the low dose of naloxone failed to produce prolongation of paw withdrawal latencies 4 h after carrageenan, whereas naloxone produced antinociception 7 days after carrageenan. The results suggest that noradrenergic mechanisms are involved in naloxone-induced antinociception only in the early phase of carrageenan-induced inflammation.

Adrenergic alpha-2 Receptor Antagonists↗

The involvement of matrix metalloproteinases and inflammation in lumbar disc herniation.

STUDY DESIGN: Surgically obtained herniated lumbar disc specimens were stained with hematoxylin-eosin or toluidine blue (for detection of proteoglycans) or were immunostained with monoclonal antibodies (CD68), antihuman interstitial collagenase (matrix metalloproteinase [MMP]-1) and antihuman stromelysin (MMP-3). OBJECTIVE: To investigate the possible correlation of matrix metalloproteinase activity to granulation tissue formation and lumbar disc herniation, depending on the type of herniation. SUMMARY OF BACKGROUND DATA: Interstitial collagenase and stromelysin have been implicated in the degradation of the matrix of articular cartilage in rheumatoid arthritis, osteoarthritis and degenerated disc tissues. However, their role in the herniation of the intervertebral disc has received little study. METHODS: Twenty-one specimens of lumbar disc herniation (classified as protrusions, subligamentous extrusions, transligamentous extrusions, and sequestrations) and four nonherniated discs were stained with hematoxylin-eosin or toluidine blue or were immunostained with monoclonal antibodies to CD20, CD45RO, and CD68, anti-MMP-1, and anti-MMP-3, using the avidin-biotin-peroxidase complex method. The amount of granulation tissue and results of staining were graded to examine differences in histology among the four herniation types. RESULTS: In sequestration and transligamentous extrusion specimens, granulation tissue containing many CD68-positive macrophages was commonly observed. Most cells in granulation tissue, as well as chondrocytes, stained positively with anti-MMP-1 and anti-MMP-3 antibodies. Granulation tissue was less commonly observed in subligamentous extrusions and was absent from most protrusion specimens and all nonherniated specimens. B and T lymphocytes could not be demonstrated in granulation tissue. CONCLUSIONS: The increased staining of MMP-1 and MMP-3 associated with inflammatory cells of granulation tissue in herniated discs suggests a causal correlation of these proteinases to tissue degradation in herniation.

Adolescent↗

Splicing patterns of type XI collagen transcripts act as molecular markers for osteochondrogenic tumors.

Primary transcripts for three distinct alpha chains of the type XI collagen molecule (alpha1(XI), alpha2(XI) and alpha3[XI]) undergo tissue-specific alternative splicing during the process of osteochondrogenesis. In the present study, we analyzed the splicing patterns of type XI collagen genes in osteochondrogenic tumors as well as in various normal tissues using the reverse transcription-polymerase chain reaction method. Analysis of normal subjects revealed the coordinated expression of short alpha1(XI), alpha2(XI) and alpha3(XI) transcripts in the normal differentiated cartilage. Osteochondroma followed this pattern, reflecting the highly chondrogenic phenotype of this benign tumor. Another benign tumor, chondroblastoma, exclusively expressed the long alpha1(XI) transcript, probably reflecting the lack of a chondrogenic nature. Among malignant chondrogenic tumors, the splicing patterns of type XI collagen transcripts were more complex, showing dissociated expression of long alpha1(XI) and short alpha2(XI) mRNAs. This expression pattern may reflect heterogeneous cell populations and may also reflect various levels of cell differentiation in malignant tumors. In addition, short alpha3(XI) expression switched to the long transcript as chondrosarcomas became more aggressive. Thus, the alternative splicing of type XI collagen genes seems to be oncodevelopmentally regulated and splicing analysis may therefore be a useful marker for chondrogenic tumors.

Alternative Splicing↗

Cloning and characterization of developmental endothelial locus-1: an embryonic endothelial cell protein that binds the alphavbeta3 integrin receptor.

We have taken advantage of an enhancer trap event in a line of transgenic mice to identify a unique developmentally regulated endothelial cell locus (Del1). The protein encoded in this locus contains three EGF-like repeats homologous to those in Notch and related proteins, including an EGF-like repeat that contains an RGD motif, and two discoidin I-like domains. Del1 is shown to be a matrix protein and to promote adhesion of endothelial cells through interaction with the alphavbeta3 integrin receptor. Embryonic endothelial-like yolk sac cells expressing recombinant Del1 protein, or grown on an extracellular matrix containing Del1 protein, are inhibited from forming vascular-like structures. Expression of Del1 protein in the chick chorioallantoic membrane leads to loss of vascular integrity and promotes vessel remodeling. Del1 is thus a new ligand for the alphavbeta3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryonic development.

Amino Acid Sequence↗

Myxoma of the mitral valve prolapsing into the left atrium and ventricle: report of a case.

A rare case of myxoma originating from the mitral valve is reported. A 25-year-old woman was found to have a mobile mass around the mitral valve that prolapsed into the left atrium and the left ventricular outflow tract. The mitral valve was approached via the left atrium and aorta, and was excised completely along with the tumor; it was thus replaced with a mechanical prosthesis. The patient recovered and demonstrated no signs of recurrence 16 months postoperatively.

Adult↗