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Biomedical subjects

M Fukasawa

Publications and source records attributed to M Fukasawa.

At least 127 records · Page 7Linked to original sources

Identification of feline immunodeficiency virus rev gene activity.

We constructed 16 deletion mutants from an infectious molecular clone of feline immunodeficiency virus (FIV) and a reporter plasmid carrying the bacterial chloramphenicol acetyltransferase (CAT) gene to identify the rev transactivator activity of the virus. Cotransfections of various mutants and the rev reporter clone bearing a portion of FIV env in addition to the CAT gene revealed that the sequence important for the augmentation of CAT production was located in three separate parts of the virus genome. This enhancement was FIV specific in that the human retrovirus rev and rex gene products did not activate the reporter. The phenotypic properties of an FIV proviral mutant containing a small deletion in the genome were similar to those of rev mutants derived from primate immunodeficiency viruses. These results indicate that FIV, like the other lentiviruses, contains the rev gene in its genome.

Animals↗

[A role of postsurgical macrophage activation by peritoneal injury].

At a site of peritoneal injury after abdominal surgery, macrophages are thought to be a principle type of inflammatory cells. Therefore, we determined the metabolic activities of postsurgical peritoneal exudate macrophages using standardized rabbit model. Rabbits underwent midline laparotomy followed by resection and reanastomosis of the ileum. At various days after surgery, peritoneal exudate macrophages were recovered from lavage fluid. Postsurgical Day-5 macrophages expressed significantly high potential to produce superoxide anion even without PMA stimulation compared to non-surgical control macrophages, although an activity of Day-10 macrophages was similar to control. The conditioned media from postsurgical Day-1 macrophage culture strongly inhibited urokinase type plasminogen activator (PA) and this plasminogen activator inhibitor (PAI) activities decreased following the extension of postsurgical time. Conversely, PA activities of macrophage-conditioned media decreased by day 1 and then gradually increased reaching control levels by day 10. Elastase activities of macrophage-conditioned media gradually decreased until postsurgical day 10. These data suggest that surgical injury activates postsurgical exudate macrophages. However, a time course of metabolic activities of these cells was dependent upon each secretory products. This differential secretion might express the stage of activation and differentiation of postsurgical macrophages. Moreover, postsurgical activated macrophages may control the tissue repair through a digestion of injured matrix and fibrinolytic process.

Animals↗

[Preventive effect of post-ischemic reperfusion injury by terminal Nicorandil-Mg cardioplegia].

In this study, we evaluated the postischemic myocardial tissue blood flow, specific enzymes, and functional recovery infused with a Nicorandil vasodilator-magnesium solution (Nico.: 8 mg/L, Mg: 20 mEq/L) given just prior to reperfusion (Terminal Cardioplegia, TCP). 27 patients undergoing valve replacement were divided into two groups; the hearts of group non-TCP (nTCP) (n = 15) were reperfused after ischemia without TCP, and in the other hearts of group TCP (n = 12), TCP was given for 2 min prior to reperfusion. During the reperfusion period, myocardial tissue blood flow (TBF) on the anterior wall of left ventricle were monitored by a laser blood flow-meter. Thereafter, serum CK-MB levels, MM3/MM1 values by CK-MM subbands (MM1, MM2, MM3) levels and LVSWI were measured until 24 hours after surgery. At 5 and 10 min of reperfusion, Group TCP had a significantly greater TBF than Group nTCP (5 min; G-TCP: 69.9 +/- 19.0 ml/100 g.min, G-nTCP: 47.5 +/- 20.9, p less than 0.05, 10 min; G-TCP: 74.9 +/- 22.8, G-nTCP: 56.1 +/- 23.4, p less than 0.05). At 3 hrs after surgery, an increase of MM3/MM1 values was significantly suppressed in Group TCP compared to Group nTCP (G-TCP: 2.6 +/- 0.6, G-nTCP: 3.4 +/- 1.0, p less than 0.05). Also, Group TCP had better recovery of LVSWI. These results indicate that the TCP might reduce the postischemic reperfusion injury by the improvement of myocardial TBF and metabolism.

Heart Arrest, Induced↗

[Mechanical factors of a severe type of ventricular arrhythmia after Cabrol's operation].

Severe type of ventricular arrhythmia was noticed after Cabrol's operation more frequently than usual reperfusion arrhythmia. Nine patients received Cabrol's operation and 2 of Bentall's were divided into 2 groups according to the occurrence of postsurgical ventricular arrhythmia (Lown's classification grade 0-3: 5 cases, grade 4 A-5: 6 cases), and then the factors contributed to the arrhythmia were analyzed. There were no significant differences between the 2 groups on the point of the characteristics of the cases with or without emergent surgery for, such as ruptured or dissecting thoracic aortic aneurysms or other complicated lesions, the degree of surgical damage, or preoperative cardiac function. The only significant difference between the groups was the angle overheading to the central point of left coronary orifice anastomosed with intermediate tube from the extensive line of the prosthetic flange obtained in the left anterior oblique views on the angiography. The mean value of the angle of the severe group (grade 4 A-5) was 41 +/- 6.8 degrees (mean +/- SD) and significantly acute than the angle of the other group (grade 0-3: 57 +/- 6.4 degrees). This fact suggested that the main reason of the ventricular arrhythmia was coronary ischemia caused by compression of the intermediate tube after formation of massive hematoma within the aneurysmal capsule wrapped over the composite graft.

Adult↗

[A successful case of double outlet right ventricle accompanied with complete endocardial cushion defect].

Surgical correction of a case of double outlet right ventricle accompanied with complete endocardial cushion defect was completed successfully. No other complicated anomaly existed in this case. Correction was done by using two patch method. The patch for VSD was designed to be comma-like shape. For ensuring the left ventricular out tract, the patch was sutured with bulging at the circumference of the aortic orifice and the suture line of the patch with atrio-ventricular valve was deviated to the right. There was no stenosis in the left ventricular out tract and tricuspid valve.

Child, Preschool↗

Molecular cloning of feline leukemia provirus genomes integrated in the feline large granular lymphoma cells.

Feline leukemia virus (FeLV) is a horizontally transmitted agent of the domestic cat which is known to be associated with wide spectrum of diseases of the hematopoietic system. In the present study, proviral DNAs of FeLV proviruses were examined in the tumor cells of natural killer cell lineage which is very rare in cats. In the chromosomal DNA of the tumor cells, 5 distinct bands corresponding to exogenous FeLV provirus genomes were detected by digestion with EcoRI which does not cut most FeLV isolates. Five clones of pLC1, pLC2, pLC3, pLC4, and pLC5 obtained from the 5 respective bands were analysed by restriction endonuclease mapping and Southern blot hybridization using gene-specific probes of FeLV. The results have clearly demonstrated that pLC4 and pLC5 contained large deletions in the pol and part of gag regions, while the full-length proviruses could be observed in pLC1 and pLC2. Furthermore, pLC3 contained part of a variant FeLV genome having an EcoRI site in its gag region. The molecular clones of defective and variant FeLV in this study may be useful for the further examination of tumorigenesis of large granular lymphoma in the cat.

Animals↗

Regulation of proliferation of peritoneal tissue repair cells by peritoneal macrophages.

Macrophages produce soluble mediators which modulate fibroblast growth during tissue repair. Interaction between tissue repair fibroblasts (TRC) and regulatory proteins from surgically elicited macrophages is important for peritoneal reepithelialization. In this study, we compared the effects of an extract from postsurgical macrophage spent medium with those of known growth factors on TRC collected from injured peritoneum to evaluate certain characteristics of macrophage secretory products on peritoneal healing. Rabbits underwent a midline laparotomy followed by resection and reanastomosis of the ileum or abrasion of the abdominal wall. TRC were then collected at various times after surgery. Peritoneal macrophages recovered from nonsurgical or postsurgical rabbits were cultured for 2 days in vitro. The peak of thymidine incorporation by TRC occurred on day 5 after surgery; this gradually decreased with extended postsurgical times. Fibroblast growth factor and epidermal growth factor stimulated, whereas TGF-beta inhibited, [3H]thymidine incorporation into TRC. Maximal thymidine incorporation occurred when TRC from Postsurgical Day 5 were cultured with an extract from postsurgical macrophage spent medium. However, when TRC recovered from Postsurgical Days 2 and 10 were cultured with an extract of postsurgical macrophage spent medium, they showed greater stimulation than Day 5 TRC. These data suggest that postsurgical macrophages may produce an array of factors that stimulate fibroblast growth and differentiation and may in turn affect tissue repair throughout the wound healing process.

Animals↗

Establishment of a phylogenetic survey system for AIDS-related lentiviruses and demonstration of a new HIV-2 subgroup.

We designed a universal primer (UNIPOL) for DNA amplification of AIDS-related viruses. The phylogenetic tree constructed from the presumed sequences amplified with UNIPOL was representative of the tree calculated from whole pol gene sequences so far reported. UNIPOL was able to amplify the sequences of all four major groups of primate lentiviruses and also that of a distinct virus from a Ghanaian patient with an AIDS-related complex, designated GH-2. This strain scarcely hybridizes with known HIV/simian immunodeficiency virus (SIV) DNA probes. Sequence analysis of the only amplified fragment revealed rapidly that GH-2 was quite similar to the recently reported HIV-2ALT(D205) and that these two viruses form a new subgroup distint from known HIV-2 and SIVmac/SIVsm in the large HIV-2 group. This system will be useful for further phylogenetic study of various primate lentiviruses.

Acquired Immunodeficiency Syndrome↗

Affinities of SM-7338 for penicillin-binding proteins and its release from these proteins in Staphylococcus aureus.

SM-7338, a carbapenem antibiotic, had high affinities for penicillin-binding proteins (PBPs) 1, 2, and 4 of Staphylococcus aureus but not for PBP 3 when a competition assay with [14C]benzylpenicillin was used. However, binding of [14C]SM-7338 was saturated for PBP 3 at a concentration of 1 microgram/ml. These results were due to the rapid release of SM-7338 from PBP 3-SM-7338 complexes with a half-life of 2 min.

Bacterial Proteins↗

Comparison of two carbapenems, SM-7338 and imipenem: affinities for penicillin-binding proteins and morphological changes.

We investigated the binding affinities of SM-7338 for penicillin-binding proteins (PBPs) and the morphological changes induced by it compared with those of imipenem. Both SM-7338 and imipenem had the highest binding affinities for PBP-2 of Escherichia coli, which were in good agreement with the primary morphological response of spherical cell formation. SM-7338 also showed high affinities for PBP-1A, -1Bs, and -3, and imipenem showed high affinities for PBP-1A and -1Bs but not for PBP-3. At 4-fold MIC, SM-7338 induced a indeterminate form, whereas imipenem did not. This may be due to the higher affinity of SM-7338 for PBP-3 compared to that of imipenem. Against Pseudomonas aeruginosa, SM-7338 had very high affinities for PBP-2 and -3, and imipenem had higher affinities for PBP-2 and -1A. SM-7338 induced this organism to filamentous cells at a concentration lower than its MIC, bulge cells at 2-fold MIC, and spherical cells at 4-fold MIC, while imipenem principally induced round cell formation at each concentration. These morphological differences in P. aeruginosa may be due to the differences in binding profiles to PBPs. We also studied the affinities for PBPs using radioactive SM-7338. The data obtained supported these results.

Bacterial Proteins↗

A novel carbapenem antibiotic, SM-7338 structure-activity relationships.

A series of new carbapenem compounds, which have a pyrrolidin-3'-ylthio group substituted with various aminocarbonyl group at C-5' position as C-2 side chain, have been prepared. The antibacterial activity and the stability to renal dehydropeptidase-I of these compounds were investigated, and the structure-activity relationships were discussed. In this series, SM-7338; (1R,5S,6S)-2-[(3S,5S)-5-dimethylaminocarbonylpyrrolidin-3-ylthi o]-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid (5a) was the most interesting compound.

Bacteria↗

[Preventive effect of post-ischemic reperfusion injury by terminal Nicorandil-Mg cardioplegia].

In this study, we evaluated the preventive effect of post-ischemic reperfusion injury by Nicorandil-Mg cardioplegia (Nic: 8 mg/l, Mg: 20 mEq/l) given just prior to reperfusion as "terminal cardioplegia". Nineteen dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 90 min under hypothermic (17-19 degrees C) cardioplegic arrest. The hearts of ten dogs were reperfused without terminal cardioplegia (Group A). In the other nine dogs, terminal cardioplegia was given for 2 min prior to reperfusion (Group B). During and after a period of ischemia, myocardial tissue calcium ion (t-Ca) and PCO2 (t-PCO2) were continuously monitored by ISFET (ion sensitive filed effective transistor) sensor. Myocardial tissue blood flow, oxygen consumption and lactate flux were calculated at 5, 10, 20, 40 min of reperfusion. And myocardial function was evaluated at 45 min of reperfusion. In the initial reperfusion period, Group B showed an improved myocardial tissue blood flow compared to group A (at 5 min of reperfusion in group A: 29.4% of control, in group B: 42.7% of control, p less than 0.025). T-Ca and T-PCO2 in Group B were rapidly and significantly decreased at 5 min of reperfusion (t-Ca in group A: 2.8 +/- 0.5 mM----1.7 +/- 0.5 mM, in group B: 3.1 +/- 0.6----1.2 +/- 0.4, p less than 0.05; t-PCO2 in group A: 117.5 +/- 23.0 mmHg----82.5 +/- 17.4 mmHg, in group B: 127.5 +/- 22.5----42.5 +/- 9.7, p less than 0.001), and group B had better metablic recovery evaluated by myocardial oxygen consumption and lactate flux.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Secondary tricuspid insufficiency and right atrial myosin ATPase activity].

Myosin of heart muscle shows ATPase activity. In the atrial myocardium, normal isozymic pattern was alpha dominant which converted to being beta dominant in an overloaded hypertrophy. In order to clarify the distribution of myosin isozymes in human heart, ATPase activity of the atrial myosin recovered from the patient underwent open heart surgery was determined. In the present study, ATPase activity of right atrial myosin from the heart with tricuspid regurgitation (TR) (group A (n = 6); 398.1 +/- 67.0 nmol pi/mg/min) was significantly less than that from the heart without TR (group B (N = 7); 533.9 +/- 62.4, p less than 0.05). The myosin ATPase activity showed correlation with systemic RA pressure (y = 0.019x + 19.6, r = -0.68429), systemic RV pressure (y = 0.039x + 58.67, r = 0.73484), SVI (y = 0.05x + 18.1, r = 0.87587) and RV maxDp/Dt (y = 0.42x + 589.9, r = -0.67493) (p less than 0.05). These data suggests that preoperative cardiac function involves in cardiomuscular structure with redistribution of contractile protein.

Adult↗

[A clinical study of cerebral perfusion during pulsatile and nonpulsatile cardiopulmonary bypass].

The purpose of this study was to determine the effect of pulsatile flow on cerebral perfusion under cardiopulmonary bypass (CPB). Twenty-three patients who underwent cardiac operations were divided into two comparable groups: Group A (N = 11) had standard nonpulsatile flow, while in Group B (N = 12), a pulsatile pump was used. The blood flow of left common carotid artery and radial arterial pressure were continuously monitored during cardiac operation in both groups and cerebral vascular resistance was calculated. In Group B, the perfusion pressure of left common carotid artery was monitored and compared with that of radial artery. Arterial and internal jugular venous blood were sampled and the difference of cerebral A.V O2 contents and cerebral oxygen consumption was calculated. Cerebral vascular resistance in Group B (54.0 +/- 11.2% of the value of before-CPB) significantly decreased compared to that in Group A (72.2 +/- 11%) at the end of CPB (p less than 0.05). Pulse pressure following pulsatile CPB flow was 15.1 +/- 5.8 mmHg monitored in radial artery and it reduced to 8.5 +/- 5 mmHg in left common carotid artery. Although there was no significant difference in cerebral oxygen consumption of both groups during and just after CPB, the difference of cerebral A-V O2 contents of Group B was greater than Group A just after CPB. These data suggest that pulsatile flow may minimize the cerebral microcirculatory shunt during CPB, resulting from the reduction of cerebral vascular resistance.

Aged↗

[Right heart bypass operation of complex cardiac anomalies in 4 patients with viscero-atrial heterotaxic syndrome].

Four patients with viscero-atrial heterotaxic syndrome underwent a right heart bypass operation. 2 patients had right isomerism, and two had left isomerism. 3 patients had common atrio-ventricular canal, three had double outlet right ventricle, one had mitral valve hypoplasia, and one had double inlet right ventricle. All patients had anomalous systemic or pulmonary venous drainage. Redirection of systemic venous drainage was accomplished by total cavo-pulmonary shunt (TCPS) (2 patients), atrial baffle (1 patient), and intraatrial conduit (1 patient). In one patient underwent TCPS, regurgitant common atrioventricular valve was replaced with a prosthetic valve. One who had total anomalous pulmonary venous drainage (type Ib) died after cardiac repair. The three survivors are in improved condition. The right heart bypass operation, like total cavopulmonary shunt or connection, simplifies the redirection of systemic venous drainage and offers improved results in the surgical treatment of complex cardiovascular anomalies with viscero-atrial heterotaxic syndrome.

Abdomen↗

[Surgical correction for a case of partial anomalous pulmonary venous drainage with dextrocardia, situs inversus and azygos continuation of inferior vena cava].

An adult case of partial anomalous pulmonary venous drainage of left pulmonary veins with dextrocardia, situs inversus and azygos continuation of inferior vena cava is reported. Surgical repair was accomplished by constructing a baffle to direct the blood flow from left pulmonary veins to the left atrium through the created atrial septal defect. This case is a rare type of PAPVD.

Abnormalities, Multiple↗