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Biomedical subjects

N Zempo

Publications and source records attributed to N Zempo.

At least 19 recordsLinked to original sources

Prolonged survival of xenograft fetal cardiomyocytes by adenovirus-mediated CTLA4-Ig expression.

BACKGROUND: Experimental allografting of fetal cardiomyocytes has been performed successfully. In this study, we attempted to transplant rat fetal cardiomyocytes into the hearts of mice by blocking the CD28/B7 costimulatory pathway via CTLA4-Ig gene transfer. METHODS: Fetal cardiomyocytes derived from Dark Agouti rat were infected with CTLA4-Ig-expressing adenovirus vectors (AdCTLA) and injected directly into the normal myocardium of C3H/He mice (n=15). For control, cells infected with beta-Gal-expressing adenovirus vector (AdRL) and cells without infection were injected into additional mice (n=30). Mice were killed at 2 (n=5), 4 (n=5), and 8 (n=5) weeks after xenotransplantation. Transplanted fetal cardiomyocytes were examined for survival by immunostaining with anti-rat atrial natriuretic peptide and anti-CTLA4-Ig antibodies. RESULTS: Fetal cardiomyocytes were successfully infected by AdCTLA and AdRL. The cardiomyocytes infected with AdCTLA expressed CTLA4-Ig and survived to 8 weeks after xenotransplantation in all of these mice. However, cardiomyocytes infected with AdRL and noninfected cells were not detected even 2 weeks after xenotransplantation. CONCLUSION: Survival of xenografted fetal cardiomyocytes is prolonged by adenovirus-mediated CTLA4-Ig expression.

Abatacept↗

Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model.

BACKGROUND: Bone marrow possesses endothelial progenitor cells that secrete several growth factors and can contribute to the formation of new capillaries. In the present study, we investigated the extent of angiogenesis induced by implantation of autologous bone marrow cells (BMCs) in a rat ischemic hindlimb model and studied whether the increased collateral vessels can improve deteriorated physical function. MATERIALS AND METHODS: Ischemic hindlimb was created by ligation of the femoral artery and its branches in Dark Agouti (DA) rats. BMCs (1 x 10(7)) were injected percutaneously at six points into the gastrocnemius muscle. To assess angiogenesis, histologic evaluation and microangiography were performed at 2 weeks postligation. Severity of the ischemic insult was evaluated by measuring blood flow in the adductor and gastrocnemius muscles using nonradioactive colored microspheres and by determining the femoral arteriovenous oxygen difference (AVDO(2)) at 2 weeks postligation. Running time on a motor-driven treadmill was used to represent exercise capacity. RESULTS: The histologic evaluation and microangiogram showed that the implanted BMCs induce angiogenesis. Blood flow to the adductor muscle on the treated side in the bone marrow cell implantation (BMI) group was significantly restored to 77.3 +/- 19.3% of that of the normally perfused limb in comparison to that in control groups (P < 0.05). AVDO(2) in the BMI group significantly decreased when compared with AVDO(2) in control groups. Rats in the BMI group ran approximately 1.5 times longer than rats in control groups at 2 and 4 weeks postligation (P < 0.01). CONCLUSIONS: Implantation of autologous BMCs induced angiogenesis and improved deteriorated exercise capacity in our rat ischemic hindlimb model.

Angiography↗

Stress caused by minimally invasive cardiac surgery versus conventional cardiac surgery: incidence of systemic inflammatory response syndrome.

The present study was conducted to evaluate the degree of stress in patients induced by minimally invasive cardiac surgery (MICS) in comparison with that caused by conventional cardiac surgery. We did this by assessing the incidence of systemic inflammatory response syndrome (SIRS). A total of 48 adult patients who underwent surgery for single valve disease were included in this study, 27 of whom underwent conventional surgery and 21 MICS. We evaluated the stress inflicted on the patients in these two groups by analyzing the duration and degree of SIRS and the level of C-reactive protein (CRP). SIRS was assessed by measuring body temperature, heart rate, respiratory rate, and white blood cell counts. There were no significant differences in the operating times, perfusion times, or aorta clamp times between the two groups; and the mean volume of blood transfusion did not differ significantly either. There was no significant difference in the incidence of SIRS or the mean duration of SIRS between the two groups. The CRP levels did not differ significantly between the two groups. Thus although MICS is superior to conventional cardiac surgery in that only a small skin incision is required, the stress experienced by the patient may be the same as that experienced by the patient undergoing conventional cardiac surgery.

Aged↗

Enhanced expression of matrix metalloproteinase-9 in abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are characterized by structural alterations of the aortic wall resulting from degradation of collagen and elastin. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, show strong elastinolytic activity. We examined the levels of mRNA for MMP-2, MMP-9, membrane type (MT)-MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in AAAs (n = 8), atherosclerotic occlusive diseases (AOD) (n = 8), and normal subjects (n = 8) using the reverse transcription-polymerase chain reaction (RT-PCR). We also analyzed the gelatinolytic activity of these metalloproteinases using gelatin zymography. The levels of MMP-2 and MMP-9 mRNA were increased in the AAA group compared with those in the AOD group and normal subjects. The levels for TIMP-1 and TIMP-2 mRNA in the AAA group were also higher than those in the AOD and normal groups. Only in the case of MT-MMP-1 was the difference between AAA and AOD not statistically significant. By gelatin zymography with the same samples used for RT-PCR, gelatinolytic activity of MMP-9 was elevated in all AAA tissues. The 62-kDa form of MMP-2 was elevated in both the AAA and AOD groups and did not differ significantly between them. Linear regression analysis demonstrated a significant positive correlation between mRNA levels of MMPs and those of TIMPs. These observations suggest that aneurysm formation in patients with atherosclerosis is related to the degree of MMP-9 expression.

Aged↗

Surgically treated primary lung cancer associated with Brugada syndrome: report of a case.

A 71-year-old man with primary lung cancer associated with Brugada syndrome was safely operated on following the placement of an implantable cardioverter defibrillator (ICD). During examinations for Brugada syndrome, a tumor in the apicoposterior segment of the left lung was incidentally detected by chest computed tomography. Following the implantation of an ICD, surgical treatment of the left lung tumor was scheduled. A lung biopsy was thoracoscopically performed and adenocarcinoma was diagnosed based on a frozen section analysis. A left upper lobectomy with lymph node dissection was performed through a standard posterolateral thoracotomy. Ventricular fibrillation, which occurred during the night of the first day following surgery, was successfully managed by the ICD.

Adenocarcinoma↗

Fatal diffuse atheromatous embolization following endovascular grafting for an abdominal aortic aneurysm: report of a case.

A 78-year-old woman with an abdominal aortic aneurysm, 57 mm in diameter, was admitted to our hospital for endovascular grafting. Preoperative computed tomography and angiography showed friable mural thrombus in the suprarenal and infrarenal aorta, and a diagnosis of shaggy aorta was made. Postoperatively, the patient suffered cerebral infarction, and disseminated intravascular coagulopathy with multiple organ failure developed, resulting in early death on the third day after surgery. An autopsy revealed diffuse atheromatous embolization into the celiac, superior mesenteric, bilateral renal, bilateral hypogastric (trash buttock), and peripheral arteries. This case report serves to demonstrate that an abdominal aortic aneurysm with a shaggy aorta in the proximal neck is a contraindication to endovascular grafting, and that predicting the possibility of diffuse atheromatous embolization by detecting a shaggy aorta is the best way to prevent this catastrophic complication.

Aged↗

Digitonin enhances the antitumor effect of cisplatin during isolated lung perfusion.

BACKGROUND: The antitumor effect of isolated lung perfusion with cisplatin was limited because the intracellular platinum concentration did not increase sufficiently. To solve this problem, digitonin, a detergent, was chosen to increase cell permeability and enhance intracellular uptake and antitumor effect. This study was designed to investigate toxicity, pharmacokinetics, and efficacy of isolated lung perfusion with the combined use of digitonin and cisplatin in Fischer 344 rats. METHODS: Systemic and local toxicities of isolated lung perfusion treatment were evaluated on the basis of body weight change, survival rate, and histologic findings. The maximal tolerated dose of digitonin was determined by assessing survival on day 21 after contralateral pneumonectomy, body weight change, and histologic findings. Pharmacokinetics were observed in a solitary lung tumor nodule model by measuring platinum concentration in tumor and normal lung tissue. The antitumor effect was evaluated by the number of tumor nodules in the left lung 21 days after isolated lung perfusion. Isolated lung perfusion was performed 7 days after 1.0 x 10(6) methylcholanthrene sarcoma cells were injected into the external jugular vein. RESULTS: The maximal tolerated dose of digitonin was 20 micromol/L. Platinum concentration of tumor nodules in the digitonin-cisplatin-treated rats was 20% higher than in the cisplatin-only group (5.48 +/- 0.64 microg/g tissue versus 4.50 +/- 1.09 microg/g tissue; p = 0.067). The number of pulmonary nodules decreased significantly by digitonin use (1.3 +/- 1.5 versus 9.7 +/- 2; p < 0.0001). CONCLUSIONS: Isolated lung perfusion with digitonin and cisplatin in combination was performed safely and enhanced the antitumor effect. These drugs in combination show promise for enhancing the effect of clinical isolated lung perfusion.

Animals↗

The influence of tumour resection on angiostatin levels and tumour growth--an experimental study in tumour-bearing mice.

The phenomenon of primary neoplasms inhibiting the growth of their metastatic lesions is thought to be related to endogenous angiogenesis inhibitors. The aim of this experiment was to investigate the influence of tumour resection on angiostatin levels and tumour growth using a tumour-bearing mouse model. A primary Lewis lung cancer tumour model was established in C57BL/6 mice and these mice were divided into two groups 10 days after the tumour cells were inoculated. In the surgical resection group (S group) the tumour was resected, but in the control group (C group) a sham operation was performed. The level of angiostatin in the sera was analysed 5 days after the operation by western blotting. To observe tumour growth, four Lewis lung cancer models were established in these mice from both the S and C groups. An immunohistochemical analysis of the tumour tissues was conducted to estimate the proliferation and apoptotic rates of the tumour cells, as well as the amount of neoangiogenesis in the tumours. Angiostatin was observed in the tumour-bearing mice, but disappeared within 5 days after the tumour had been resected. Increased tumour growth was observed in all of the tumour models in the S group compared with the C group and the differences were significant. A significantly higher intratumour vessel density and proliferation cell index, but a significantly lower apoptotic index were also found in the S group compared with the C group. These findings demonstrated that angiostatin was generated directly from the tumour tissue. Furthermore, tumour resection accelerates the growth of other tumours and this is probably related to multiple factors including increased neoangiogenesis, increased tumour cell proliferation, and decreased apoptosis.

Angiostatins↗

Congenital cystic adenomatoid malformation of the lung with an esophageal cyst: report of a case.

The authors report the case of a 7-month-old girl found to have both congenital cystic adenomatoid malformation of the lung (CCAM) and esophageal cyst. She suffered repeated episodes of pneumonia and exhibited signs of respiratory distress on admission to our hospital. Chest radiography and magnetic resonance imaging (MRI) showed 2 different kinds of cystic lesions. Resection of the lower lobe of the right lung and excision of the posterior mediastinal cyst were performed. Histologic examination showed Stocker type I CCAM and esophageal cyst. Coexistence of both CCAM and esophageal cyst is extremely rare. The authors speculate that the pathologies of this case originated from a regional disturbance of common embryologic origin during 2 different phases of lung-bud foregut malformations.

Abnormalities, Multiple↗

Atheromatous plaque in the distal aortic arch creating the potential for cerebral embolism during cardiopulmonary bypass.

The present study evaluated the risk in cardiac patients of rupture of a plaque by a jet stream from the arch cannula. The entire thoracic aorta and cardiac function were routinely monitored by transesophageal echocardiography (TEE) in 88 adult patients who underwent coronary artery bypass surgery. The changes in the atheromatous plaque in the distal aortic arch were observed before and after cardiopulmonary bypass. Of the 88 patients, 13 were found to have preoperative atheromatous plaque at the distal aortic arch and 8 (61.5%) of them suffered plaque rupture caused by jet stream from the arch cannula. Only 1 patient experienced apparent embolic episodes manifesting as cerebral and left leg embolisms; the remaining 7 had no clinical embolic symptoms. In order to prevent atheroembolic events, attention should be paid not only to the ascending aorta, but also to the distal arch and in this regard TEE is useful for detecting atheromatous changes of the aorta.

Aged↗

Effects of cardioplegic arrest and reperfusion on rabbit cardiac ryanodine receptors.

Calcium overload is considered to be a primary contributor to ischemia-reperfusion injury. Cardiac sarcoplasmic reticulum (SR), the main regulator of intracellular Ca2+ concentration under normal conditions, is a target for ischemic myocardial injury. The ryanodine receptor (RyR) is the SR Ca2+ release channel. Previous reports have shown that a reduction in RyR activity during global myocardial ischemia correlates with concomitant myocardial dysfunction. Crystalloid cardioplegia, a technique for myocardial protection during heart operations, reduces Ca2+ accumulation during global ischemia. Hence, the effects of cardioplegia on RyR in isolated rabbit hearts was investigated. The study also compared [3H] ryanodine binding before ischemia (control group), after 30 min of ischemia (either global ischemia (GI group) or cardioplegic arrest (CA group)), and after 20 min of reperfusion. The GI group, but not the CA group, showed a significant reduction in the maximum number of binding sites (Bmax) for RyR compared with the control group (Control vs GI group: after ischemia, 1.33+/-0.27 vs 0.83+/-0.12 pmol/mg protein, p<0.05; after reperfusion, 1.33+/-0.27 vs 0.80+/-0.08 pmol/mg protein; p<0.05). CA group: after ischemia, 1.22+/-0.20 pmol/mg protein; after reperfusion, 1.15+/-0.28 pmol/mg protein). The affinity (Kd) values for [3H] ryanodine binding were not different among the 3 groups at any point. The preservation of RyR numbers during cardioplegia correlated with the concomitant preservation of cardiac functions. The results indicate that number of functional RyR was much better preserved during cardioplegia than during global ischemia. It is postulated that cardioplegia-induced protection of cardiac RyR may result in the protection of SR function during ischemia-reperfusion.

Animals↗

[Assessment of stage IIB lung cancer from the pathological factors].

In our experience, the prognosis of patients with pathological T3N0M0 lung cancer is generally poor, the 5-year survival rate being almost the same as that of patients with stage IIIA disease. Thus, we assessed patients with stage IIB disease by examining the pathological factors, lymphatic invasion, vessel invasion, histological type, differentiation, tumor size, and node dissection. Lymphatic invasion was found to be positive in 20 of 21 cases, patients with T3N0M0 lung cancer, and all of those with positive vessel invasion had a significantly poor prognosis. This indicates that positive lymphatic and vessel invasion could be a prognostic factor predicting a poor outcome. Patients with T3N0M0 lung cancer that are found to have this poor prognostic factor may not be diagnosed as having stage IIB disease.

Aged↗

[A coronary artery bypass grafting using cardiopulmonary bypass with intraaortic balloon pumping in patient with low cardiac function combined with cerebral vascular disease].

We reported a 55-year-old man, who had coronary and cerebral vascular disease. Cerebral angiography showed occlusion at left internal carotid artery (ICA) and 50% stenosis at right ICA C4 portion. But acetazolamide reactivity was kept symmetrically. Coronary angiography showed severe three vessel disease, and left ventriculography showed diffuse severe hypokinesis/akinesis, and EF was below 30%. The patient underwent coronary artery bypass grafting using cardiopulmonary bypass with intraaortic balloon pumping to keep intraoperative blood pressure high. After the operation he recovered uneventfully without neurological complication.

Cardiac Output, Low↗

[Recurrent angina due to high grade re-stenosis of the left subclavian artery after coronary artery bypass grafting in a patient on hemodialysis for chronic renal failure: report of a case].

A 49-year-old woman on hemodialysis for chronic renal failure was admitted to our hospital with chest pain. She had undergone quadruple coronary artery bypass grafting (CABG) including a left internal thoracic to left anterior descending coronary artery anastomosis 9 months earlier. The blood flow through the left internal thoracic artery had decreased due to high grade stenosis at the proximal portion of the left subclavian artery, and recurrent angina had developed. She was treated by the placement of Palmaz biliary stents in the left subclavian artery, but re-stenosis occurred after 9 months, causing recurrent angina again. There fore, an operation was proposed and bypass grafting from the descending aorta to the left subclavian artery was successfully performed, resulting in complete resolution of her recurrent angina. This case serves to reinforce that patients on dialysis must be carefully followed up after CABG.

Angina Pectoris↗

[Delayed traumatic diaphragmatic hernia diagnosed by magnetic resonance imaging and direct coronal computed tomography: report of a case].

A 59-year-old woman was admitted to our hospital with abdominal symptoms. A diagnosis of delayed traumatic diaphragmatic hernia was made from the findings of a plain X-ray film, magnetic resonance imaging (MRI) and computed tomography (CT). We successfully performed repair of the diaphragm via abdominal approach. Thus, MRI and direct coronal CT can be very useful for establishing a diagnosis of traumatic diaphragmatic hernia.

Female↗

Immunocytochemical analysis of cellular infiltrates in human appendicitis.

This study was conducted to determine the immunologic cellular composition in human appendicitis and its association with the development of perforated appendicitis. Appendiceal specimens from 27 patients with acute appendicitis were immunostained to detect lymphocyte surface markers. Moreover, the lymphocyte surface markers of peripheral blood were analyzed by laser flow cytometry in 12 patients. Helper T lymphocytes (CD4) were present in all the patients, while B lymphocytes (CD19), natural killer (NK) cells (CD56), and cytotoxic T lymphocytes (CD8) were present in 7 (70%), 10 (100%), and 9 patients (90%) with perforated appendicitis, and in 12 (63.2%), 10 (58.8%), and 6 (54.5%) patients without perforation, respectively. There were significant differences between the patients with a perforated appendix and those without perforation, in the positivity rate for CD8 and CD56 cells (P < 0.05). The number of cells positive for CD56, being NK cells, in the blood from the patients with perforation was significantly lower than that in the blood from those without perforation (P < 0.05). The infiltration of a greater number of cytotoxic T lymphocytes and NK cells was observed in the appendices from patients with perforated appendicitis than in those from patients with nonperforated appendicitis.

Adolescent↗

The occurrence of a strangulated ileus due to a traumatic transmesenteric hernia: report of a case.

We report herein the case of a 6-year-old boy in whom a strangulated ileus was caused by a traumatic transmesenteric hernia. The boy had fallen from his bicycle and suffered a severe blow to the abdomen. Abdominal pain and vomiting developed 10 h after the accident and he was admitted to our hospital. Abdominal ultrasonogram and computed tomogram demonstrated ascites, intestinal wall thickening with fluid, and an engorged radiating mesenteric vasculature. Thus, an emergency laparotomy was performed which revealed bloody ascites, a strangulated ileus, and torsion with a transmesenteric hernia. The necrotic intestine was resected and an anastomosis was performed. Macroscopic and microscopic findings revealed a traumatic mesenteric rent. The unusual presentation of this case is discussed.

Abdominal Injuries↗

Right axillary cannulation in the left thoracotomy for thoracic aortic aneurysm.

Perfusion from the femoral artery is commonly used in the open proximal method of performing distal aortic arch aneurysm repair or Stanford type B aortic dissection repair under circulatory arrest through left thoracotomy. However, it is associated with a significant risk of retrograde emboli or malperfusion, and with other problems including a restricted time of circulatory arrest to the brain and difficulties in de-airing from the arch branches and proximal ascending aorta. To overcome these problems, we developed a method of performing right axillary perfusion through left thoracotomy.

Adult↗