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Biomedical subjects

S Kitamura

Publications and source records attributed to S Kitamura.

1,362 records · Page 76Linked to original sources

Effects of double-filtration plasmapheresis and a platelet-activating factor antagonist on the prolongation of xenograft survival.

Xenotransplantation may be considered a possible solution to the clinical donor-organ shortage. We studied the effects of the removal of preformed natural antibodies against donor tissue by double-filtration plasmapheresis (DFPP) and the administration of a platelet-activating factor antagonist on the prolongation of xenograft survival using the pig-to-dog model. The porcine hearts were perfused with the blood of mongrel dogs. Pairs of animals were divided into four groups: group I (n = 3) was given no pretreatment before perfusion; group II (n = 6) was pretreated by DFPP; group III (n = 3) was given a platelet-activating factor antagonist intravenously at a dose of 0.1 mg/kg 5 minutes before and after perfusion; group IV (n = 5) was pretreated by DFPP and then given a platelet-activating factor antagonist. The titer of natural antibodies was measured by lymphocytotoxicity and hemagglutination. Heart specimens were examined by immunohistochemical staining for deposits of dog antibodies. No immunosuppressive drugs were given in this study. The porcine hearts resumed beating immediately after perfusion in all groups. The mean duration of the graft beating was 17.0 +/- 2.0 minutes for group I, 215.2 +/- 22.6 minutes for group II (p < 0.001 compared with group I), 18.3 +/- 2.1 minutes for group III, and 317.0 +/- 26.5 minutes for group IV (p < 0.001 compared with group II). Immunoglobulin (Ig) M, IgG, complements (C3, C4), and fibrinogen were removed significantly from the perfusing blood, and natural antibody titer was scarcely detectable in groups II and IV after DFPP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The roles of platelet-activating factor (PAF) in pulmonary vasoconstriction during venous air embolism in anesthetized mongrel dogs.

Chemical mediators play minor roles in the acute lung injury caused by venous air embolism. The function of PAF in this condition was examined. Eight open chest mongrel dogs, mechanically ventilated, received air at an infusion rate of 0.1 ml/kg per min for 15 min. In addition, four dogs received air under continuous infusion of PAF at 10 ng/kg per min, the other four dogs under pretreatment with the PAF antagonist, CV-3988, at 10 mg/kg. In conclusion, PAF did not mediate pulmonary vasoconstriction but did modulate it and might possibly modulate cardiac deterioration in air embolism.

Anesthesia↗

Left ventricular function and coronary morphology with anomalous origin of the left coronary artery from the pulmonary artery.

Reconstructive surgery of the left coronary artery system was performed in two adult patients with anomalous origin of the left coronary artery from the pulmonary artery. Postoperative studies were carried out at 2 months and at 49 months. Left ventricular volume, left ventricular myocardial mass, and ejection fraction were normal postoperatively in one patient. In the second patient, the left ventricular volume was markedly reduced, but the decrease in left ventricular mass was less pronounced. Dilatation and tortuosity of the right coronary artery disappeared postoperatively in both patients. However, the dilatation and tortuosity of the left coronary artery persisted on coronary arteriogram.

Adolescent↗

Direct communication between the pulmonary artery and the left atrium. A case report and review of the literature.

A case of direct communication between the right pulmonary artery and the left atrium is presented. Twenty-two cases from the literature and our case are analyzed. Complete cure can be obtained by simple ligation, division, or intracardiac repair with cardiopulmonary bypass. This anomaly involves the risk of serious complications such as cerebral abscess and systemic embolization and should be accurately diagnosed and treated by surgery.

Angiography↗

Early and late results of the Bentall operation for annulo-aortic ectasia.

Our experience is reported with 20 consecutive patients undergoing the Bentall operation during the past 10 years for ascending aortic aneurysms with aortic regurgitation due to idiopathic medical necrosis with a resultant annulo-aortic ectasia. Concomitant aortic dissection was present in 45% of the patients. In the earlier period from 1972 to 1976, the operative and hospital mortality rates were 40%, and it was reduced to 0% (p less than 0.08) in the later period from 1977 to 1981. Operative survivors showed the mean clinical improvement from the NYHA class 3.0 to 1.3. The LVEDP and the left ventricular dimension were significantly reduced toward normal (p less than 0.05 and p less than 0.001). The actuarial survival rate at 6 years after operation was 71% in this series. The Bentall operation can now be performed with a low risk, and can improve the clinical and hemodynamic states significantly. However, in patients with chronic type I aortic dissection, a false lumen remained patent after surgery regardless of the types of graft-distal aorta anastomosis. The fate of the remaining dissection is undetermined, but some may require further surgery.

Adult↗

Comparison of cardiac rejection in heart and heart-lung concordant xenotransplantation.

Clinical observations indicate that in heart-lung grafting the heart is less frequently rejected than in heart grafting alone. In addition, our results of allograft experiments indicated that the graft survival period is longer in the former (11.8 +/- 0.8 days versus 6.6 +/- 0.5 days, p < 0.05), suggesting that the simultaneous grafting of the lung in heart-lung allografts suppressed the rejection of the grafted heart. We assessed the effect of simultaneous lung xenografting, splenectomy, and FK506 treatment on the survival of the xenografted heart in a concordant model. With Wistar rats as recipients and golden hamsters as donors, cardiac survival was compared between en bloc heart-lung and heart heterotopic xenografts. The cardiac survival of heart-lung and heart xenografts was not prolonged by FK506 treatment alone but was prolonged by splenectomy. Splenectomy plus FK506 (1.0 mg/kg/day) showed suppression of antibody production and a remarkable synergistic effect in prolongation (33.2 +/- 7.4 days versus 36.8 +/- 8.1 days) in heart-lung and heart xenografts. Simultaneous lung xenografting significantly shortened the survival period of the xenografted heart in splenectomy plus FK506 (0.5 mg/kg/day) recipients (4.8 +/- 0.8 days versus 9.0 +/- 3.5 days, p < 0.05), in contrast to the prolongation of the survival period of the grafted heart in heart-lung allografting.

Animals↗

The effect of excipients on glass transition temperatures for FK906 in the frozen and lyophilized states.

FK906, a tripeptide, has been used as a model compound to study the effect of excipients on the glass transition temperature for peptides and related compounds in the frozen solution and lyophilized states. Three kinds of excipients were chosen for study, low molecular weight sugars, high molecular weight polymers and salts. Our results indicate that the Gordon-Taylor equation can be used to predict the glass transition temperature of FK906 in the presence of sucrose, lactose, trehalose and maltose in the frozen solutions and in lyophilized products. Dextrans having different molecular weights can have different effects on the glass transition temperature of FK906 in the frozen state. Cooling rate can also have an effect on the glass transition temperature for FK906 frozen solutions in the presence of dextran. Finally, salts have a significant effect on the glass transition temperature of FK906 in the frozen state but not in lyophilized FK906.

Antihypertensive Agents↗

Some physicochemical properties of FK906: glass transition and relaxation.

FK906, a tripeptide antihypertensive agent, was used as a model compound to study some physicochemical properties of peptides and peptide-related compounds. Our results indicate that lyophilization, grinding and melting or storing the samples under conditions of high relative humidity affect chemical stability and crystallinity of FK906. In a preliminary study of lyophilization process design, an extended phase diagram for FK906 in aqueous solution was constructed, and the effects of cooling rate and and heating rate on the glass transition temperatures of lyophilized FK906 and the FK906 solution were investigated. Following lyophilization, the DSC thermogram of FK906 exhibits an endothermic peak whose area is storage temperature- and time-dependent. The endothermic peak shifts to higher temperatures as the heating rate is increased. Our results indicate that the endothermic peak is related to structural change during incubation of lyophilized FK906.

Antihypertensive Agents↗

Protection against lipid peroxidation induced during preservation of lungs for transplantation.

The questions of whether oxygen-derived free radicals are induced during preservation of lungs and, if so, how such radicals might relate to reperfusion injury were investigated by means of an isolated canine lung model. Lungs were obtained from 16 mongrel dogs and divided into groups 1 (n = 6), 2 (n = 5), and 3 (n = 5). The lungs of groups 1, 2, and 3 were flushed through the pulmonary artery with Euro-Collins solution alone, the solution with superoxide dismutase (120,000 U/L), and the solution with allopurinol (1 mmol/L), respectively, at 4 degrees C and then stored for 4 hours in the respective solutions at 4 degrees C with clamped bronchi. They were then reperfused for 2 hours by means of an isolated lung model. Lung lipid peroxidation was sequentially determined. The lung functional status was assessed by systolic pulmonary arterial pressure and end-inspiratory airway pressure. The lung edema was assessed by lung wet/dry weight ratio. Lipid peroxidation was induced after 1 hour of preservation and the first 30 minutes of the reperfusion in group 1 and only 2 hours of the reperfusion in group 2, whereas no induction was observed in group 3. Values for systolic pulmonary arterial pressure and end-inspiratory pressure in group 1 were significantly higher than those in group 3 (p < 0.05). The lung wet/dry weight ratio in group 1 was significantly higher than that in groups 2 and 3 (p < 0.05). The present results indicate that the administration of free radical scavengers in the preservation may effectively improve conditions for lung transplantation.

Airway Resistance↗

Endoscopic resection of large sessile colorectal polyps using a submucosal saline injection technique.

BACKGROUND/AIMS: Endoscopic removal of sessile colorectal polyps 2 cm or greater in diameter is very difficult. We evaluated the safety and usefulness of submucosal saline injection in endoscopic resection of these polyps. MATERIALS AND METHODS: Under colonoscopic observation, 0.9% NaCl was injected submucosally through needle forceps to elevate polyps, which were then resected by electrocoagulation. Before 1989, the depth and healing status of ulcers produced by endoscopic resection with (N = 12) and without (N = 16) submucosal saline injection were examined in specimens obtained at subsequent colectomies. Between 1990 and 1993, patients were assigned by weighted randomization to undergo colonoscopic polypectomy with (N = 24) or without (N = 5) submucosal saline injection. RESULTS: All 12 ulcers after submucosal saline injection were confined to the submucosal layer while 7 (44%) of 16 ulcers without submucosal saline injection reached the muscle layer or deeper. Seventeen of 24 (71%) polyps were completely removed (14 piecemeal and 3 en bloc) without serious complications after saline injection. Resection without submucosal saline injection was complete, but piecemeal, for two of five polyps; postresection bleeding occurred in one case. CONCLUSIONS: Endoscopic resection after submucosal saline injection is a safe and effective treatment for large, sessile colorectal polyps.

Colectomy↗

Hemodynamic and humoral conditions in stepwise reduction of pulmonary blood flow during venoarterial bypass in awake goats.

The effects of reduced pulmonary arterial blood flow (PAF) during venoarterial bypass (VAB) on hemodynamic and humoral conditions were investigated in a series of experiments in a chronic animal model. A biventricular bypass system was installed in five adult goats weighing 49.8 +/- 1.1 kg. Two weeks later, the extracorporeal circuitry was changed to VAB without anesthesia. The PAF was reduced stepwise from 100% to 50, 25, 10, and 0% of total systemic flow. The mean aortic pressure and systemic vascular resistance decreased from 110 +/- 14 to 66 +/- 3 mmHg and from 1,288 +/- 77 to 740 +/- 73 dyne.sec/cm5, respectively, in proportion to the decrease in PAF from 100 to 0%. The prostaglandin E2 concentration increased from 1.5 +/- 0.6 to 8.8 +/- 0.6 pg/ml following the decrease in PAF from 100 to 0%. The renin-angiotensin system increased in proportion to the decrease in PAF. In contrast, the epinephrine and norepinephrine concentrations (60 +/- 10 and 227 +/- 80 pg/ml, respectively, at 100% PAF) did not change appreciably even at 10% PAF, but were markedly elevated to 335 +/- 117 and 2,088 +/- 1,503 pg/ml at 0% PAF. The antidiuretic hormone level similarly changed. In conclusion, decrease in PAF during VAB exerts significant effects on hemodynamics in a proportional manner and on vasoactive humoral factors in a diverse manner.

Animals↗

Effects of tamoxifen on mammary tumors and bone in 7,12-dimethylbenz-(a)anthracene-treated rats.

We investigated the effects of tamoxifen on the growth of 7,12-dimethylbenz(a)anthracene induced rat mammary tumors, the activity of thymidylate synthetase and thymidine kinase (key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis), and also their gene expression. The effects on immunohistochemistry using bromodeoxyuridine in the tumors and bone mineral density of the femur in rats were also studied. Chronic administration of tamoxifen markedly reduced the expression of thymidylate synthetase mRNA, followed by a reduction in enzyme activity and S-phase cells in the mammary tumors, and significantly enhanced the bone mineral density. Tamoxifen not only attenuated bone loss in aging but also enhanced bone volume in mammary tumor-bearing rats in which tumor growth was suppressed via both the de novo and salvage pathways for pyrimidine nucleotide synthesis.

9,10-Dimethyl-1,2-benzanthracene↗