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Biomedical subjects

K Hamano

Publications and source records attributed to K Hamano.

At least 19 recordsLinked to original sources

The detection of chronic heart graft rejection by 31P NMR spectroscopy.

The usefulness of phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMRS) for detecting heart graft rejection after transplantation has been investigated by several researchers, and it has thus been demonstrated to be a valid technique for detecting acute myocardial rejection. In this study, we investigated the value of 31P NMRS to assess chronic cardiac allograft rejection. Lewis rat hearts were transplanted into the femoral region of F-344 rat recipients which were treated with cyclosporine, 5mg/kg body weight, by a daily intramuscular injection for 30 days beginning on the day of transplantation. The control isografts employed Lewis donors and recipients not given cyclosporine. The ratios of phosphocreatine (PCr) to inorganic phosphate (Pi), beta-adenosine triphosphate (beta-ATP) to Pi, and PCr to beta-ATP were monitored using surface coil 31P NMRS. 31P NMRS was performed 3, 30, and 60 days after transplantation, and the degree of the rejection and arteriosclerosis of the coronary arteries were then assessed histologically. The PCr:Pi and beta-ATP:Pi ratios for the allografts demonstrated a significant decrease on postoperative day (POD) 60 from that on POD 30 (PCr:Pi, P < 0.001; beta-ATP:Pi, P < 0.01). Although a significant difference existed between the isografts and allografts on POD 60 (PCr: Pi, P < 0.01; beta-ATP:P, P < 0.01), no significant difference was found in the PCr:beta-ATP ratio between the allografts and the isografts. On POD 60, the allografts showed significant graft rejection and arteriosclerotic changes in the coronary arteries. These findings therefore demonstrated the effectiveness of 31P NMRS for detecting chronic graft rejection in a rat model.

Adenosine Triphosphate

An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.

Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in Japan (incidence is 0.7-1.2 per 10,000 births), is characterized by congenital muscular dystrophy associated with brain malformation (micropolygria) due to a defect in the migration of neurons. We previously mapped the FCMD gene to a region of less than 100 kilobases which included the marker locus D9S2107 on chromosome 9q31. We have also described a haplotype that is shared by more than 80% of FCMD chromosomes, indicating that most chromosomes bearing the FCMD mutation could be derived from a single ancestor. Here we report that there is a retrotransposal insertion of tandemly repeated sequences within this candidate-gene interval in all FCMD chromosomes carrying the founder haplotype (87%). The inserted sequence is about 3 kilobases long and is located in the 3' untranslated region of a gene encoding a new 461-amino-acid protein. This gene is expressed in various tissues in normal individuals, but not in FCMD patients who carry the insertion. Two independent point mutations confirm that mutation of this gene is responsible for FCMD. The predicted protein, which we term fukutin, contains an amino-terminal signal sequence, which together with results from transfection experiments suggests that fukutin is a secreted protein. To our knowledge, FCMD is the first human disease to be caused by an ancient retrotransposal integration.

Amino Acid Sequence

A quantitative study of the progress of myelination in the rat central nervous system, using the immunohistochemical method for proteolipid protein.

The temporal changes in intensity of myelination of the nervous pathways in 0 to 42-day-old Wistar rats were quantitatively analyzed by immunohistochemistry with anti-proteolipid protein and compared with that obtained by immunohistochemistry with anti-myelin basic protein. Immunohistochemistry was performed on paraffin-embedded tissue according to the standard ABC technique. Intensity of myelination was examined by an image analyzing system. We analyzed nine nervous pathways: corpus callosum, optic tract, internal capsule, spinal tract of the trigeminal nerve, inferior cerebellar peduncle, cerebellar white matter, pyramidal tract, medial longitudinal fasciculus, and cuneate fasciculus. The presence of immunoreactive fibers for proteolipid protein (PLP) in the spinal tract of the trigeminal nerve, medial longitudinal fasciculus and cuneate fasciculus was noted on postnatal day 0. Those of the corpus callosum, inferior cerebellar peduncle, cerebellar white matter, pyramidal tract and internal capsule were noted on day 7, and that of optic tract on day 14. The time required to reach the intensity of myelination of day 42 was day 14 for the cuneate fasciculus, day 21 for the spinal tract of the trigeminal nerve, inferior cerebellar peduncle and medial longitudinal fasciculus, day 28 for the optic and pyramidal tracts, day 35 for the corpus callosum and day 42 for the internal capsule and cerebellar white matter. The appearance of immunoreactive fibers for PLP was usually earlier than that for myelin basic protein (MBP) and the pattern of difference between PLP and MBP can be classified into three groups: (1) their time of appearance and progress are almost the same, as in the optic tract; (2) the appearance and progress of PLP occurs earlier than those of MBP, as in the pyramidal tract; (3) the appearance of PLP occurs earlier than that of MBP, but their progress is the same. Our findings revealed that the time of appearance and progress of myelination as measured by PLP are different among the nervous pathways, and that there is also a difference between PLP and MBP. This difference between PLP and MBP may indicate a functional difference between them.

Age Factors

Recovery after prolonged cross-clamping tepid blood cardioplegia: report of a case.

Despite a prolonged repetitive aortic cross-clamp time of 411 min, a patient who suffered a left ventricular rupture after undergoing mitral valve replacement following mitral valvuloplasty and Maze procedure recovered without any permanent residual left ventricular dysfunction. During the aortic cross-clamping we used tepid blood cardioplegia for myocardial protection. This case report serves to demonstrate the potential of tepid blood cardioplegia as an effective method of myocardial protection.

Aged

[Experimental study of coronary artery anastomosis using VCS clips].

The experiment was intended to test the feasibility of VCS clips for coronary anastomosis during minimally invasive direct coronary artery bypass grafting (MIDCAB). Six dogs were anesthetized under endotracheal intubation and were placed on right lateral position. Three 10.5-mm ports were placed on the left lateral chest wall (3rd, 5th and 7th intercostal space) and the left internal thoracic artery (LITA) was dissected completely from its root to bifurcation under thoracoscope. Chest was opened through the left 6th intercostal space. The anastomotic site of LAD was dissected and was then occluded temporally for 5 minutes to obtain ischemic preconditioning. The anastomosis was performed by the following procedure; horizontal mattress sutures of 8-0 polypropylene were placed on heel, toe and the center of both lateral sides. Two VCS clips (8 in total), 0.9-mm in size, were applied between every two sutures. After the measurement of graft flow, the pedicle was transected and an angiography was done. Graft flow was 12-17 ml/min (mean 14.7 +/- 2.1 ml/min) and cineangiogram showed good patency of LITA and no anastomotic stenosis. VCS clips were supposed to have a potential for facilitating port access coronary artery bypass grafting.

Anastomosis, Surgical

Increased serum interleukin-8: correlation with poor prognosis in patients with postoperative multiple organ failure.

This study investigated whether cytokines and colony-stimulating factors can predict prognosis in patients with postoperative multiple organ failure (MOF). We evaluated 14 patients with postoperative MOF who underwent operation for cardiovascular disease. Seven patients recovered from MOF (survivors) and seven did not recover and died (nonsurvivors). The white blood cell (WBC) count, granulocyte colony-stimulating factor, monocytic colony-stimulating factor, interleukin-6 (IL-6), and IL-8 were measured on the day the patients were judged to be in MOF and each week thereafter until the patients recovered or died. Survivors and nonsurvivors were equivalent in terms of age, gender, proportion of use of extracorporeal circulation, operation time, volume of blood transfusion, time from operation to the onset of MOF, the MOF score, proportion of bacteremia, duration of MOF, and number of failed organs. The mean duration of MOF was less than 2 weeks in both groups; therefore the measurements were compared on the first day of MOF and 1 week later. No significant differences between the two groups in terms of WBC counts, colony-stimulating factors, and IL-6 levels were noted. However, the serum level of IL-8 was significantly higher in nonsurvivors than in survivors. Patients with a high serum levels of IL-8 at the time of MOF had a poor prognosis.

Aged

Granulocyte elastase release and pulmonary hemodynamics in patients with atrial septal defect.

BACKGROUND: In patients with increased pulmonary artery pressure, the pulmonary vascular endothelium is morphologically and functionally abnormal and may be vulnerable to neutrophil-mediated injury induced by cardiopulmonary bypass (CPB). We investigated the relation between levels of granulocyte elastase (GEL), interleukin-6, or interleukin-8 after CPB and preoperative pulmonary hemodynamics or changes in pulmonary function after the operation. METHODS: We measured plasma levels of GEL, interleukin-6, and interleukin-8 before and after CPB in patients who underwent closure of an atrial septal defect. Preoperative and postoperative respiratory index were evaluated. Preoperative pulmonary hemodynamics were determined within 1 month before the operation. RESULTS: The level of GEL rose significantly after CPB from baseline (164.8 +/- 81.3 versus 819.4 +/- 320.3 microg/L; p < 0.01). Levels of interleukin-6 and interleukin-8 showed no significant changes after CPB. Peak level of GEL was significantly correlated with preoperative systolic pulmonary artery pressure (r = 0.76; p = 0.017), mean pulmonary artery pressure (r = 0.75; p = 0.021) and pulmonary-to-systemic arterial pressure ratio (r = 0.77; p = 0.016), but not with the hemodynamic variables for pulmonary blood flow or pulmonary resistance. Moreover, the value of (postoperative respiratory index - preoperative respiratory index)/preoperative respiratory index was positively correlated with the peak level of GEL (r = 0.72; p = 0.030). CONCLUSIONS: The increase in GEL level after CPB is proportional to the increase in preoperative pulmonary artery pressure, which may cause the accordant pulmonary vascular damage.

Adult

The lack of type III collagen in a patient with aneurysms and an aortic dissection.

We analyzed 79 consecutive patients with aneurysms and found a patient who lacked type III collagen. Collagen was extracted from the skin, and the lack of type III collagen was determined by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Only 1 of the 79 patients was found to lack type III collagen. This patient was a 55-year-old man who had sustained an abdominal aortic aneurysm and aortic dissection. He did not show any of the typical clinical symptoms of Ehlers-Danlos syndrome type IV, such as hyperextensible skin and joints. He had none of the usual risk factors nor any clear family history of the syndrome. Furthermore, his collagen fibrils demonstrated a homogeneous appearance. This case may represent a new form of type III collagen deficiency.

Aortic Dissection

Changes in the morphology and components of the coronary arteries during the progression of coronary arteriosclerosis following cardiac transplantation in rats.

In order to examine the changes in coronary artery morphology following cardiac transplantation, the intimal and medial areas and vascular components were measured 30 and 60 days postoperatively in rats receiving both iso- (n = 5, each time) and allotransplantations (n = 7, each time). Although cyclosporine A was administered intramuscularly (10 mg/kg per day) for 20 days following transplantation, graft rejection progressed gradually in the allotransplanted group. There were no clear changes in the intimal or medial areas following transplantation in the isotransplanted group. The intimal area of the coronary arteries in the allograft group was significantly thicker 30 and 60 days following transplantation, while the medial area of the coronary arteries in this group was significantly thinner than that of the isotransplantation group at these same time points. In the thickened intimal areas in the allotransplantation group, only the density of smooth muscle cells was higher following transplantation. In the thinned medial areas in the allotransplantation group, the densities of the smooth muscle cells and collagen were less than those in the isotransplantation group. These changes suggest that following transplantation, smooth muscle cells proliferate in the intimal areas, while smooth muscle cells and collagen are degraded in the medial areas.

Animals

Late postoperative respiratory function in adults after surgical correction of atrial septal defects. Analysis of respiratory dysfunction patterns.

Respiratory function after repair of atrial septal defect (ASD) was analysed in 44 adults (> 40 years), 21 of whom had preoperative respiratory dysfunction, 14 of restrictive type, defined as % vital capacity (% VC) less than 80% of predicted value, 3 with an obstructive pattern, defined as % forced expiratory volume/1 s (% FEV1) less than 70% of predicted value, and 4 patients with a mixed pattern. Increased % VC was found postoperatively in all 14 patients with restrictive respiratory dysfunction, with normal values in 8 out of the 14. Although the three patients with obstructive, and the four with mixed-pattern respiratory dysfunction improved preoperatively in % VC or % FEV1, or both, none had normalized values. We conclude that preoperative restrictive respiratory dysfunction in ASD patients frequently normalizes postoperatively, but not dysfunction of obstructive or mixed restrictive-obstructive type.

Adult

Correlations among expression of intercellular adhesion molecule 1, cellular infiltration, and coronary arteriosclerosis during chronic rejection using the rat heart transplantation model.

Immunologic mechanisms contribute to the development of coronary arteriosclerosis. In this study the rat heart transplantation model was used to investigate correlations among the expression of intercellular adhesion molecule 1, cellular infiltrate, and coronary arteriosclerosis during chronic rejection. Lewis rats served as heart donors and F-344 rats as recipients. Heart transplantations were performed heterotopically. The recipients were treated with cyclosporin A (5 mg/kg/day) by daily intramuscular injection for 30 days, beginning on the day of transplantation. Rejection grade and the intimal area were measured. The expression of intercellular adhesion molecule 1 and the numbers of infiltrating CD4- and CD8-positive cells and macrophages were examined immunohistochemically. The area of the intima was significantly increased in the allograft group after transplantation. In the allograft group, the level of expression of intercellular adhesion molecule 1 was considerably increased over the same time period. There was increased cellular infiltration in the 60-day group, and many expressed intercellular adhesion molecule 1. The expression of intercellular adhesion molecule 1 in vascular endothelium, infiltrating cells, and the sarcolemmal membrane of myocytes remained constant up to 120 days in the allograft group. In the allograft group, the number of infiltrating CD4- and CD8-positive cells and macrophages increased significantly between 30 and 60 days, and the infiltration of these cells remained constant. Continuous expression of intercellular adhesion molecule 1 induces the infiltration of T cells and macrophages, and the inflammation caused by such cells and their soluble products contributes to the arteriosclerotic process.

Animals

Direct vasoconstrictor action of homologous angiotensin II on isolated arterial ring preparations in an elasmobranch fish.

Arterial rings were prepared from the branchial artery, coeliac artery and ventral aorta of the Japanese dogfish Triakis scyllia and used to determine arterial contraction in a myograph. Noradrenaline caused a dose-dependent contraction (10(-9)-3 x 10(-6) M) that was completely inhibited by pre-treatment with 10(-7) M phentolamine. Homologous dogfish angiotensin II (ANG II) ([Asn1, Pro3, Ile5]-ANG II) also caused dose-dependent contraction (10(-9)-3 x 10(-6) M), but phentolamine had no effect on this response. Administration of dogfish angiotensin I (ANG-I) ([Asn1, Pro3, Ile5, Gln9]-ANG I) resulted in a contraction similar to that produced by ANG II and the effect could be blocked with 10(-7) M captopril. The mammalian ANG II receptor antagonists [Sar1, Ile8]-ANG II and [Sar1, Ala8]-ANG II caused dose-dependent contractions of coeliac artery rings, but were less potent than homologous ANG I and ANG II. These results show that the contractile effect of [Asn1, Pro3, Ile5]-ANG II is not mediated by the alpha-adrenergic system and contractions of arterial rings by noradrenaline and elasmobranch ANG II are mediated by separate vascular receptors. The elasmobranch ANG II vascular receptor may have co-evolved with the unusual structure of this peptide.

Adrenergic alpha-Antagonists

[Minimally invasive cardiac surgery for aortic valve disease].

Recent surgical advances leading to good operative results have contributed to the trend to useminimally invasive approaches, even in cardiac surgery. Smaller incisions are clearly more cosmetically acceptable to patients. When using a minimally invasive approach, it is most important to maintain surgical quality without jeopardizing patients. A good operative visual field leads to good surgical results. In the parasternal approach, we use a retractor to harvest an internal thoracic artery in coronary artery bypass surgery. Retracting the sternum upward allows for a good surgical view and permits the use of an arch cannula rather than femoral cannulation. When reoperating for aortic valve repair, the j-sternotomy approach requires less adhesiolysis compared with the traditional full sternotomy. No special technique is necessary to perform aortic valve surgery using the j-sternotomy approach. However, meticulous attention must be paid to avoiding left ventricular air embolisms to prevent postoperative stroke or neurocognitive deficits, especially when utilizing a minimally invasive approach. Transesophageal echo is useful not only for monitoring cardiac function but also for monitoring the persence of air in the left ventricle and atrium. This paper compare as the degree of invasion of minimally invasive cardiac surgery and the traditional full sternotomy. No differences were found in the occurrence of systemic inflammatory response syndrome between patients undergoing minimally invasive cardiac surgery and the traditional technique. Therefore it is concluded that minimally invasive surgery for patients with aortic valve disease may become the standard approach in the near future.

Aortic Valve

[Repair of left ventricular free wall rupture with GRF glue associated with acute myocardial infarction: report of a case].

Histopathological examination of a repair of left ventricular free wall rupture associated with acute myocardial infarction using GRF glue was reported. A 63-year-old male with cardiac rupture due to LMT total occlusion was referred to our ward after unsuccessful PTCA with institution of IABP and PCPS. Left ventricular rupture repair by GRF glue and xenograft pericardial patch with concomitant myocardial revascularization (SVG-LAD, CX) was performed under cardiopulmonary bypass. Hemostasis around the ventricular rupture was easily accomplished. Unfortunately, the patient died at 14 POD because of low output syndrome caused by broad myocardial infarction. At autopsy, rupture site was examined histologically and was revealed that GRF glue made a tight adhesion between patch and myocardium. Neither abnormal inflammatory cells nor giant cells were found. We concluded that GRF glue might be a effective histocompatibly in hemostasis for left ventricular rupture associated with acute myocardial infarction.

Cardiac Surgical Procedures

[Surgery for the treatment of infective endocarditis in the active and inactive stages].

Twenty-eight patients (16 M, 12 F, age 11 approximately 72 yr, mean 52.8 yr) underwent surgery for infective endocarditis. Of the 27 patients, 16 were in the active stage and 11 were in the inactive stage. In patients in the active stage, aortic valve replacement (AVR) was performed in 5, mitral valve replacement (MVR) in 7, AVR + MVR in 1, AVR + MVR + tricuspid valve plasty (TVP) in 1 and other procedures in 2. In patients in the inactive stage, AVR was performed in 3, MVR in 4, AVR + MVR in 2, and other procedures in 2. Causative organisms were detected in 56.3% of the patients in the active stage and 54.5% in the inactive stage. Also in patients in the active stage, infection was not prolonged. No deaths occurred among patients in the inactive stage but five patients (31%) died postoperatively; 4 of the five also died, for had severe heart failure before surgery, three died of multiple organ failure and one died of subarachnoid hemorrhage due to infective aneurysm. We recommend surgery for the treatment of infective endocarditis even in the active stage before emergence of heart failure.

Adolescent