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Biomedical subjects

T Isshiki

Publications and source records attributed to T Isshiki.

At least 55 records · Page 3Linked to original sources
PubMed1997

Use of synchrotron radiation microangiography to assess development of small collateral arteries in a rat model of hindlimb ischemia.

BACKGROUND: Current methods of angiography cannot provide images of arteries measuring < 200 microns in diameter. We have recently developed a new angiography system that uses monochromatic synchrotron radiation and a high-definition video system with a spatial resolution of 30 microns. In the present study, we applied this microangiography system to visualize small arteries in normal and ischemic rat limbs and investigated the development of collateral arteries. METHODS AND RESULTS: Microangiography was performed in the normal and the ischemic limb 4 weeks after the excision of the femoral artery. In the normal limb, up to the fourth branches of the iliac and/or femoral arteries (diameter < 100 microns) were readily identified. Some of these branches were found to perfuse the distal thigh area. In the ischemic limb, an extensive structural remodeling of the vascular network was observed. Numerous small arteries had developed from the branches of the iliac artery to constitute a fine arterial network, the so-called "midzone," which was composed of linear, normal appearing arteries and those with an undulating, unbranched appearance. CONCLUSIONS: The small collateral artery network was angiographically visualized with a resolution limit < 100 microns. The linear collaterals appeared to result from an opening of preexisting vessels. The undulating, unbranched vessels were not observed in the normal limbs and seemed to be vessels that were newly formed after limb ischemia. Synchrotron radiation microangiography appears to be a powerful means of assessing the development of small collateral arteries, which may help to provide a basis for understanding of the collateral circulation.

Angiography↗
PubMed1997

Microangiographic assessment of collateral vessel formation following direct gene transfer of vascular endothelial growth factor in rats.

OBJECTIVE: The development of collateral microvessels following therapeutic angiogenesis with vascular endothelial growth factor (VEGF) was investigated using a new system of microangiography that employs monochromatic synchrotron radiation (SR) and a high definition video system to visualize arteries with a spatial resolution of 30 microns. METHODS: Ischemia was induced in the hindlimb of 20 rats by excision of the femoral artery, followed by transfection of the plasmid (400 micrograms) encoding VEGF or beta-galactosidase (control) into limb muscles. Microangiography was used to assess the development of collaterals in the ischemic limb four weeks after treatment. RESULTS: Gene transfer of VEGF produced morphologically similar, but significantly more extensive, collateral networks at the microvascular level as compared with the naturally occurring collateral arteries in the control animals (angiographic score: 0.88 +/- 0.08 versus 0.54 +/- 0.05, p < 0.01). No adverse vascular effects such as hemangiomas and/or arteriovenous (AV) fistulae were observed following VEGF treatment. The vasodilator effect of papaverine was evident in relatively large vessels in both groups. At the microvascular level (diameter < 100 microns), however, papaverine induced significant vasodilation in the VEGF-treated animals, and almost no vasodilation in the controls. CONCLUSIONS: SR microangiography allowed us to assess the development of small collateral arteries following VEGF-gene transfer. The information obtained may provide new insights regarding the collateral microcirculation and therapeutic angiogenesis.

Angiography↗
PubMed1997

Systemic inflammatory responses in acute coronary syndrome: increased activity observed in polymorphonuclear leukocytes but not T lymphocytes.

BACKGROUND: Local inflammation within the coronary arteries is involved in the pathogenesis of acute coronary syndrome. However, the contribution of a systemic inflammatory response to the pathogenesis of this syndrome has not been well characterized. Accordingly, we investigated systemic inflammatory responses in patients with acute coronary syndrome. METHODS: A total of 83 patients with ischemic heart disease (15 with stable exertional angina and 68 with acute coronary syndrome) were studied. The luminol-dependent chemiluminescence (CL) response of polymorphonuclear leukocytes (PMNs), which reflects their ability to generate oxygen species, was used as a marker for PMN activation. Soluble interleukin-2 receptor (sIL-2R) levels were measured to assess T-lymphocyte activation. RESULTS: CL counts of whole blood from patients with acute coronary syndrome were twice those of patients with stable angina (2.38 +/- 0.22 vs 1.10 +/- 0.17 x 10(6) counts, P < 0.05). A comparison of CL counts between patients with unstable angina and those with acute myocardial infarction revealed no significant differences. T-lymphocyte activity, measured by serum sIL-2R, was significantly lower in patients with acute coronary syndrome than those with stable angina (214.3 +/- 11.5 vs. 358.3 +/- 115.7 U/ml, P < 0.05). CONCLUSIONS: This investigation shows that there is a systemic increase in PMN activity and a decrease in T-lymphocyte activity in patients with acute coronary syndrome. This contrasts with the pattern of cellular activation seen at sites of local inflammation within atherosclerotic plaques, suggesting that two independent inflammatory processes (local and systemic) may be involved in the pathogenesis of this syndrome.

Acute Disease↗
PubMed1997

The role of the msh homeobox gene during Drosophila neurogenesis: implication for the dorsoventral specification of the neuroectoderm.

Development of the Drosophila central nervous system begins with the delamination of neural and glial precursors, called neuroblasts, from the neuroectoderm. An early and important step in the generation of neural diversity is the specification of individual neuroblasts according to their position. In this study, we describe the genetic analysis of the msh gene which is likely to play a role in this process. The msh/Msx genes are one of the most highly conserved families of homeobox genes. During vertebrate spinal cord development, Msx genes (Msx1-3) are regionally expressed in the dorsal portion of the developing neuroectoderm. Similarly in Drosophila, msh is expressed in two longitudinal bands that correspond to the dorsal half of the neuroectoderm, and subsequently in many dorsal neuroblasts and their progeny. We showed that Drosophila msh loss-of-function mutations led to cell fate alterations of neuroblasts formed in the dorsal aspect of the neuroectoderm, including a possible dorsal-to-ventral fate switch. Conversely, ectopic expression of msh in the entire neuroectoderm severely disrupted the proper development of the midline and ventral neuroblasts. The results provide the first in vivo evidence for the role of the msh/Msx genes in neural development, and support the notion that they may perform phylogenetically conserved functions in the dorsoventral patterning of the neuroectoderm.

Animals↗
PubMed1997

[Female autopsy case of Seitelberger's connatal form of Pelizaeus-Merzbacher disease].

We report here an autopsy case of connatal Pelizaeus-Merzbacher disease, the second from Japan. Her clinico-pathological findings were essentially the same as those of the first case that we reported previously. The clinical course of this patient was 19 years in duration. Pathologically myelin had disappeared from the entire central nervous system, whereas that of the peripheral nervous system was preserved. Axons appeared also intact except for torpedo formation in the cerebellum. Demyelinated areas showed isomorphic gliosis. Recent studies have revealed impairment of proteolipid protein synthesis in classical Pelizaeus-Merzbacher disease, the causative gene of which being located on the X chromosome. Thus, this disease is inherited as an X-linked recessive trait. However we report herein a sporadic female case in a non-consanguineous family. Therefore, we propose that this disease might have another causative gene and/or another mode of inheritance.

Adult↗
PubMed1996

Effects of competitive blood flow on arterial graft patency and diameter. Medium-term postoperative follow-up.

To identify predictors of arterial graft patency, we followed up 30 internal thoracic arterial grafts and 23 right gastroepiploic arterial grafts in situ with patency documented during postoperative angiography. After 24 months of follow-up on average, repeat angiography detected that one internal thoracic artery and two gastroepiploic arteries were anatomically occluded and that the other three gastroepiploic arteries were nonfunctioning. The logistic regression model identified a relationship between graft patency and competitive flow, which was detected as stenosis in the recipient coronary arteries (coefficients, p < 0.05; model, Hosmer-Lemeshow chi2 statistic 3.59, p = 0.89). The linear regression model demonstrated that changes in graft luminal diameter correlated with competitive flow (p < 0.01), smoking history (p < 0.05), and type of arterial grafts (p < 0.001) (R2 = 0.40, adjusted R2 = 0.36). The findings suggest a temporal relationship between competitive flow and prognosis of arterial graft.

Abdominal Muscles↗
PubMed1996

ST reelevation at reperfusion is associated with the occurrence of late potentials in patients with acute anterior infarction.

The relationship between ST reelevation at reperfusion and the occurrence of late potentials (LPS) in 35 patients with a first anterior infarction who had single vessel disease was investigated. All patients underwent a successful primary angioplasty and had a patent infarct related artery confirmed angiographically 4 weeks later. Patients were classified into groups based on changes in the ST level at reperfusion: patients with ST reelevation (group A, n = 22) and patients without ST reelevation (group B, n = 13). Signal-averaged ECG was performed 4 weeks after primary angioplasty to detect LPS. Cineventriculography was performed to measure left ventricular ejection fraction (LVEF) and evaluate regional wall motion of the infarct area (SD/chords). LPS were present in eight of the 22 group A patients (36%) and in none of the 13 group B patients (P < 0.05). Left ventricular function was impaired in patients in group A compared with patients in group B (LVEF: 5 1 +/- 12 vs 63 +/- 10, P < 0.01; SD/chords: -2.7 +/- 0.9 vs -1.9 +/- 1.1, P < 0.05). These data suggest that ST reelevation and myocardial damage at reperfusion are associated with the occurrence of LPS in patients with successfully recanalized infarct related arteries after acute anterior infarction.

Action Potentials↗
PubMed1996

Comparison of aortic valve replacement and percutaneous aortic balloon valvuloplasty for elderly patients with aortic stenosis.

The outcome of aortic balloon valvuloplasty (ABV) was compared with that of aortic valve replacement (AVR) in aortic stenosis (AS) patients more than 60 years old. The indications for ABV included low respiratory and renal function, cancer, the patient's refusal of surgery, and low daily activity. Twenty six patients underwent AVR and 13 underwent ABV. Initially, the AVR group was younger and more symptomatic than the ABV group. Two perioperative deaths occurred in the AVR group, while there were none in the ABV group. Twenty-four AVR patients and 12 ABV patients had a successful outcome, with remarkable pressure gradient reduction in both groups. In the follow-up, only 1 death and no cardiac events were detected in the AVR group (mean follow-up of 27 months), whereas 3 deaths, 6 heart failures, 2 repeated ABV, and 4 AVR were seen in the ABV group (mean follow-up of 10 months). The data showed that ABV was safer than AVR, but a higher rate of restenosis limited its efficacy. In the ABV group, a higher ratio of balloon size to aortic diameter correlated with longer event-free survival. We concluded that for elderly AS patients, ABV should be used only in those with high surgical risk as a palliative therapy or a bridge therapy to AVR, and AVR should be primarily recommended under rigid evaluation of the patient's physical status.

Aged↗
PubMed1996

Angiographic and coronary risk factor analyses of Japanese patients with ischemic heart disease before age 40--a multicenter cooperative study.

Coronary angiographic and risk factor (RF) characteristics were analyzed in 133 Japanese patients with ischemic heart disease (IHD) who were less than 40 years old and who had undergone coronary angiography (CAG) during the past 10 years at six university hospitals in the Tokyo area. We compared the coronary angiographic characteristics of the subject group with those of 216 controls with coronary sclerosis detected by CAG who were more than 40 years old (older control group) and the RF characteristics with those of 133 sex- and age-matched volunteers (younger control group). Sixty seven percent of the subjects (89 cases) were diagnosed as having myocardial infarction (MI) and 33% (44 cases) had angina pectoris (AP). Coronary artery disorders in this group consisted of 103 (77%) cases of coronary sclerosis, 20 (15%) cases of coronary spasm and 10 (8%) cases of miscellaneous diseases, eg, possible vasculitis with connective tissue disease, congenital anomalies, etc. The incidences of significant (> or = 75%) sclerotic narrowing in 0 vessels (31%) and 1 vessel (49%) in the subject group were significantly (p < 0.01) higher than those in the older control group, while the incidence of multivessel disease was significantly (p < 0.05) less in the subject group than in the older control group. The incidences of the following coronary risk factors were significantly (p < 0.05) higher in the subjects than in the younger controls: smoking (83% vs 35%), hypercholesteremia (44% vs 10%), obesity (31% vs 9%), hypertension (29% vs 3%), familial IHD (28% vs 7%) and diabetes mellitus (19% vs 2%). Thus, zero- or single-vessel disease predominated in the younger subject group and the prevalence of coronary risk factors was significantly higher in the subject.

Adult↗
PubMed1996

Increased expression of direct gene transfer into skeletal muscles observed after acute ischemic injury in rats.

The direct injection of plasmid DNA into skeletal muscles represents a novel strategy that is potentially applicable to lower limb ischemic diseases. Most previous studies that involved skeletal muscle gene transfer have used only normal animals, however, and the efficiency of gene transfer into the ischemic muscles has not yet been well characterized. Accordingly, we sought to determine the extent to which gene expression is altered by performing skeletal muscle transfection under ischemic conditions. The femoral artery was ligated in one limb to induce limb ischemia in rats. The rectus femoris muscle of the ipsilateral limb was transfected 0 to 14 days later with the plasmid pRSVLUC, which contains the firefly luciferase coding sequence. Muscles of the contralateral nonischemic limb also were transfected in an identical fashion to serve as controls. At the end of the study, the rectus femoris muscle of the ischemic limb showed a significant reduction in weight compared with the controls (0.99 +/- 0.02 mg vs 1.07 +/- 0.03 mg, p < 0.0001), which demonstrates that the ligation of the femoral artery created significant limb ischemia in this animal model. Luciferase expression was readily detected in all 98 transfected limb muscles from 49 rats but not in nontransfected muscles or other organs. The relative luciferase activity (ischemic limb to nonischemic limb) calculated for each rat was 1.64 +/- 0.49 at Day 0. It significantly increased after Day 4 (3.76 +/- 1.33), reached its peak at Day 7 (9.00 +/- 3.38, p < 0.05), and declined to the base-line levels by Day 14 (1.44 +/- 0.43). These in vivo results indicate that gene expression after skeletal muscle transfection is significantly augmented by transfecting genes under ischemic conditions, which may have potential implications to increase the efficacy of gene therapy for lower limb vascular occlusive disease.

Animals↗
PubMed1995

Myocardial damage after successful thrombolysis is associated with the duration of ST re-elevation at reperfusion.

The purpose of this study was to investigate the significance of ST re-elevation at reperfusion using strict criteria for patient inclusion and exclusion. Twenty-nine patients who had a first anterior infarction with single-vessel disease, successful recanalization by intracoronary thrombolysis (ICT) with urokinase, and an angiographically confirmed patent infarct-related artery after 4 weeks, were divided into three groups according to the deviation of the ST segment at reperfusion: Group A, 10 patients with sustained ST re-elevation; Group B, 10 patients with transient ST re-elevation; and Group C, 9 patients with ST reduction. Left ventricular (LV) function was evaluated from cineventriculograms performed in the 30 degrees right anterior projection 4 weeks after ICT. LV ejection fraction and regional wall motion of the infarct area, evaluated by the centerline method (SD/chords), were significantly lower in Group A (44 +/- 10%, -3.2 +/- 0.4) than in Group B (61 +/- 9%, -1.9 +/- 0.7) and Group C (60 +/- 5%, -2.0 +/- 0.4) (p < 0.01). Peak creatine kinase (CK) activity was significantly higher in Group A (5848 +/- 2112 IU) than in Group B (2485 +/- 1254 IU) and Group C (1889 +/- 1525 IU) (p < 0.05). These data suggest that a sustained ST re-elevation at reperfusion was strongly associated with marked LV dysfunction and higher peak CK activity. It was concluded that sustained, not transient, ST re-elevation associated with successful reperfusion indicates extensive myocardial damage.

Aged↗
PubMed1995

Initial and subsequent angiographic outcome of percutaneous transluminal angioplasty performed on internal mammary artery grafts.

OBJECTIVE: To estimate the initial outcome and incidence of restenosis of angioplasty of internal mammary artery grafts in a retrospective study. METHODS: The study population consisted of 46 patients (48 lesions) who underwent first balloon angioplasty within the internal mammary artery graft. Most (37/48) were at the distal anastomosis. A few (8/48) were in the graft body. Six patients with the evidence of angiographic restenosis underwent a second angioplasty. RESULTS: The success rate and the restenosis rate of the first angioplasty was 73% and 30% respectively. Of the 34 patients (35 lesions) with a successful first angioplasty, 30 underwent follow up angiography with a restenosis rate of 30% (9/30). A second angioplasty was performed on six of the nine restenotic lesions, with a success rate of 83% and no restenoses. The percent diameter stenosis of the recipient native coronary artery was significantly greater in the restenosis group, at 75 (SD 27)% v 89 (17)%, p < 0.05. CONCLUSIONS: First angioplasty of 46 patients (48 lesions) within an internal mammary artery graft was performed with a success rate of 73% and a restenosis rate of 30% (follow up rate of 88%). The extent of the stenosis of the recipient native coronary artery may affect the restenosis rate.

Adult↗
PubMed1995

Ischemic cardiomyopathy without significant coronary stenosis. A case report.

The authors present a rare case of myocardial infarction in a fifty-eight-year-old man without significant coronary artery stenosis apparent on the emergency coronary angiogram. However, a second angiogram two days later revealed a total occlusion of the left anterior descending artery. Intracoronary thrombolytic therapy was performed with a successful outcome. The patient was subsequently readmitted with an acute myocardial infarction, and the coronary angiogram again failed to demonstrate significant stenosis. Thereafter, the patient's left ventricular function deteriorated progressively, with the occurrence of another myocardial infarction and frequent bouts of symptoms related to congestive heart failure. He died of ischemic cardiomyopathy about seven years later. Findings including an autopsy report showed that myocardial ischemia was involved in the pathogenesis of what initially appeared to be primary dilated cardiomyopathy, based on emergency angiograms.

Coronary Angiography↗
PubMed1995

[An autopsy case of Down syndrome in an adult patient with multiple senile plaques and systemic amyloidosis].

A rare adult autopsy case of Down syndrome was reported. The patient was a 36-year-old male, whose chromosome analysis revealed 47, XY, +21. He showed typical systemic AA-amyloidosis and numerous senile plaques in the brain. Senile plaques were diffuse or primitive. They were composed of beta-protein, but negative for Congo-red stain. There were few neurofibrillary changes in the para hippocampal gyri. Nucleus basalis Meynert showed no significant lesion. The distribution of these plaques had some characteristics different from that for Alzheimer's disease. In the brain involvement of systemic AA-amyloidosis was restricted to the regions devoid of blood-brain-barrier, such as choroid plexus and pituitary gland. Cerebral beta-amyloid and systemic amyloid A protein were segregated on each side of the blood-brain-barrier. Therefore, we suggested that each amyloid might be synthesized and deposited by its own mechanism. Electronmicroscopically Hirano's body was identified in the hippocampal gyri.

Adult↗
PubMed1994

Glucose repression of fbp1 transcription of Schizosaccharomyces pombe is partially regulated by adenylate cyclase activation by a G protein alpha subunit encoded by gpa2 (git8).

In the fission yeast Schizosaccharomyces pombe, genetic studies have identified genes that are required for glucose repression of fbp1 transcription. The git2 gene, also known as cyr1, encodes adenylate cyclase. Adenylate cyclase converts ATP into the second messenger cAMP as part of many eukaryotic signal transduction pathways. The git1, git3, git5, git7, git8 and git10 genes act upstream of adenylate cyclase, presumably encoding an adenylate cyclase activation pathway. In mammalian cells, adenylate cyclase enzymatic activity is regulated by heterotrimeric guanine nucleotide-binding proteins (G proteins). In the budding yeast Saccharomyces cerevisiae, adenylate cyclase enzymatic activity is regulated by monomeric, guanine nucleotide-binding Ras proteins. We show here that git8 is identical to the gpa2 gene that encodes a protein homologous to the alpha subunit of a G protein. Mutations in two additional genes, git3 and git5 are suppressed by gpa2+ in high copy number. Furthermore, a mutation in either git3 or git5 has an additive effect in strains deleted for gpa2 (git8), as it significantly increases expression of an fbp1-lacZ reporter gene. Therefore, git3 and git5 appear to act either in concert with or independently from gpa2 (git8) to regulate adenylate cyclase activity.

Adenylyl Cyclases↗