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Biomedical subjects

K Marutsuka

Publications and source records attributed to K Marutsuka.

At least 37 records · Page 2Linked to original sources

Intravenous injection of sonicated blood induces pulmonary microthromboembolism in rabbits with ligation of the splenic artery.

Pulmonary thromboembolism (PTE) is found in long hospitalized patients. Chronic PTE has been reported to play an important role in cardiac failure in thalassemic patients after splenectomy. However, the mechanism of PTE in these patients remains unclear. In this study, we attempted to establish an animal model of PTE. We divided New Zealand white rabbits into three groups: Group I was injected sonicated blood, II was injected non-sonicated blood after ligation of the splenic artery, and III was injected sonicated blood after ligation of the splenic artery. After injection of the sonicated blood, we examined the platelet counts every 10 minutes until 1 hour and the rabbits were sacrificed for histological examination. Platelets significantly decreased in number immediately after the injection of sonicated blood in Groups I and III. Many pulmonary thromboemboli composed mainly of platelets were found in Group III but not in other groups. These pathological changes seem to be partly similar to those of thalassemic patients after splenectomy. This animal model is thought to be useful to study the pathogenesis of pulmonary thromboembolism, especially in thalassemic patients after splenectomy.

Animals↗

Localization and activity of tissue factor in human aortic atherosclerotic lesions.

Tissue factor (TF) is a transmembrane protein that serves as the major initiator of the blood coagulation cascade. The overexpression of TF antigen and mRNA has previously been reported in advanced atherosclerotic lesions. Recently TF procoagulant activity has also been identified in these lesions. However, localization and activity of TF in various stages of atherosclerosis have not yet been reported. We studied TF localization and its activity in three stages of the human atherosclerotic lesions (diffuse intimal thickening, fatty streak, and atheromatous plaque). The thoracic aortas were obtained from 23 autopsy cases and were examined immunohistochemically using an anti-human TF polyclonal antibody and biotinylated factor VIIa (FVIIa) as a probe to test the FVIIa-binding ability of TF. In addition, the TF-mediated activation of factor X (FX) was quantitatively assessed using a chromogenic assay. In lesions of the diffuse intimal thickening and the fatty streak, almost all of intimal smooth muscle cells (SMCs), macrophages, and endothelial cells were positive for TF. In the atheromatous plaques, TF antigen was detected extensively in the extracellular matrix as well as in the intimal cells. TF in all stages of atherosclerotic lesions had the ability to bind biotinylated FVIIa. TF activity was detected in each lesion and was more prominent in fatty streaks and atheromatous plaques than in the diffuse intimal thickening. These results indicate that active TF is expressed in the early stage of atherosclerotic lesions as well as in the advanced stage, and it contributes to the thrombotic property of human atherosclerotic lesions.

Adolescent↗

Tissue factor pathway inhibitor inhibits aortic smooth muscle cell migration induced by tissue factor/factor VIIa complex.

Tissue factor (TF), a transmembrane glycoprotein, forms a high affinity complex with factor VII/VIIa (FVIIa) and thereby initiates blood coagulation. Tissue factor pathway inhibitor (TFPI) is an endogenous protease inhibitor of TF/FVIIa-initiated coagulation. We previously reported that TF was a strong chemotactic factor for cultured vascular smooth muscle cells (SMCs). In this study, we examined the contribution of FVIIa and the effect of TFPI to TF-induced cultured SMC migration. TF/FVIIa complex showed a strong migration ability, however, neither TF alone nor FVIIa induced SMC migration. TF/FVIIa treated by a serine protease inhibitor and the complex of TF and inactivated FVIIa (DEGR-FVIIa) did not stimulate SMC migration. Pretreatment with hirudin and the antibodies to alpha-thrombin and factor X had no effect on TF/FVIIa-induced SMC migration, although alpha-thrombin and factor Xa also induced SMC migration respectively. TFPI markedly inhibited TF/FVIIa-induced SMC migration in a concentration-dependent manner, but did not affect the SMC migration induced by platelet-derived growth factor (PDGF)-BB, basic fibroblast-growth factor (bFGF), or alpha-thrombin. These results indicate that the catalytic activity of TF/FVIIa complex is important on SMC migration, and TFPI can reduce SMC migration as well as thrombosis.

Animals↗

Expression of tissue factor and tissue factor pathway inhibitor in rats lungs with lipopolysaccharide-induced disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a frequent complication of endotoxin shock, and modulation of endothelial cell hemostatic properties has been proposed to play an important role in its onset. We examined the in vivo expression of tissue factor (TF) and TF pathway inhibitor (TFPI) in rat lungs of a lipopolysaccharide (LPS)-induced DIC model. Light and electron microscopic studies showed that fibrin-rich thrombi were present in the pulmonary microvasculature 3 hours after intraperitoneal injection of LPS (7.5 mg/kg) and increased in number at 6 hours. In an immunohistochemical study, an increase in number of monocytes in the microvasculature was observed after LPS injection, and many of these cells (> 90%) were positive for TF antigen. However, no TF expression in endothelial cells was detected. Pulmonary endothelial cells showed positive reaction for TFPI antigen before LPS injection, but TFPI-positive endothelial cells markedly decreased in number after LPS injection. mRNA expression of TF increased and that of TFPI decreased in the lung tissue 3 and 6 hours after LPS injection. High values of TF activity were detected in the lung tissue and plasma, whereas TFPI activities decreased after LPS injection. These results indicate that imbalance between TF and TFPI, overexpression of TF, and underexpression of TFPI in the lung may contribute to thrombus formation in this LPS-induced DIC model.

Animals↗

Pulmonary microthromboembolism by injection of sonicated autologous blood in rabbits with splenic artery ligations.

Chronic pulmonary thromboembolism (PTE) has been reported to play an important role in cardiac failure in thalassemic patients after splenectomy. However, the mechanism of PTE in these patients remains unclear. In this study, we attempted to establish an animal model of PTE seen in thalassemic patients after splenectomy. We divided New Zealand white rabbits into three groups: Group 1 was injected sonicated blood, II was injected non-sonicated blood after ligation of the splenic artery, and III was injected sonicated blood after ligation of the splenic artery. After injection of the sonicated blood, we counted the platelet number until 1 hour and the rabbits were sacrificed for histological examination. Platelets significantly decreased in number immediately after injection of the sonicated blood in Groups I and III. Many pulmonary thromboemboli composed mainly of platelets were found in Group III but not in other groups. These pathological changes seem to be partly similar to those of thalassemic patients after splenectomy. This animal model is thought to be useful to study the pathogenesis of pulmonary thromboembolism, especially in thalassemic patients after splenectomy.

Animals↗

Effects of inflation pressure of balloon catheter on vascular injuries and subsequent development of intimal hyperplasia in rabbit aorta.

Balloon catheter de-endothelialization is the most popular means of arterial injury in experimental animals and has been used as the model system to investigate atherogenesis and restenosis after percutaneous transluminal coronary angioplasty (PTCA). The aim of this study was to examine the relationship between balloon inflation pressure and vascular damage and also subsequent intimal hyperplasia. Retrograde pullback balloon injury of rabbit aortas was made at three different balloon pressures (1.5, 1.75, and 2.0 atm). The medial injuries, such as necrosis of smooth muscle cells and disruption of elastic lamina, were occasionally found in the injured segment of the aorta by balloon catheter at 1.75 atm and more frequently at 2.0 atm. No prominent medial injury was observed in the aortic segment to balloon catheter injury at 1.5 atm; Intimal hyperplasia developed in each animal and increased with time, 2, 4, and 8 weeks after injury. The intimal hyperplasia followed by balloon injury at 1.75 and 2.0 atm was more prominent than that at 1.5 atm, however, the development of the intimal hyperplasia was not parallel to the degree of inflation pressure. On the other hand, decrease of DNA content of the media and reduction of norepinephrine-induced vasoconstriction were observed in a pressure-dependent manner after balloon injury. These findings indicate that intimal hyperplasia is not proportionally correlated to the severity of the vascular injury. The control of inflation pressure is very important in order to examine vascular injuries, subsequent intimal hyperplasia and vasomotor responses in animal models of balloon catheter injury.

Animals↗

Ganglioneuroblastoma of the thymus: an adult case with the syndrome of inappropriate secretion of antidiuretic hormone.

A 61-year-old woman was admitted to the hospital because of general fatigue. Laboratory examinations showed hyponatremia, plasma hypo-osmolarity, and inappropriate increased concentration of the plasma antidiuretic hormone (ADH) in the presence of concentrated urine. Magnetic resonance imaging revealed a mass lesion in the anterior mediastinum. An extended thymectomy was performed under the diagnosis of thymoma with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Histologically the tumor was located in the thymic tissue and was diagnosed as ganglioneuroblastoma. Immunohistochemical studies showed the existence of ADH in the tumor cells. To the knowledge of the authors, this is the first case of ganglioneuroblastoma of the thymus with SIADH.

Female↗

Prognostic value of urokinase-type plasminogen activator in patients with superficial bladder cancer.

OBJECTIVES: A number of studies have demonstrated that urokinase-type plasminogen activator (u-PA) is one of the major enzymes in the development of cancer invasion and metastasis. We examined the possibility that u-PA content is an independent prognostic marker for superficial bladder cancer. METHODS: The u-PA content was estimated in superficial bladder cancer from 52 patients undergoing transurethral resection for the first time. The survival rates of the patients were calculated and the prognostic values for u-PA content (less than 8 ng/mg protein versus more than 8 ng/mg), Stage (pTa or pT1), grade (1 and 2 versus 3), number (single versus multiple), and size (less than 1 cm versus more than 1 cm) of tumor were determined by a multivariate regression model. RESULTS: Development of cancer invasion and metastasis was observed in 3 and 8 patients, respectively. The survival rate of the patients with high u-PA content was significantly lower than those with low u-PA content (P < 0.005). In the multivariate regression analysis, u-PA content was the most important risk factor for the prognosis, compared with the other factors: tumor stage, grade, multiplicity, and size. CONCLUSIONS: We have first shown that u-PA content is a new independent prognostic marker in patients with superficial bladder cancer.

Aged↗

Tissue factor induces migration of cultured aortic smooth muscle cells.

Tissue factor (TF) plays a key role as a primary initiator on the extrinsic coagulation cascade. Recently, upregulation of TF has been reported in human atherosclerotic lesions. We investigated the effects of TF on migration and proliferation of cultured smooth muscle cells (SMCs) from rabbit aortas. We tested three kinds of recombinant human TF (L-TF: the full length of TF with relipidation, NL-TF: the full length of TF without relipidation, and S-TF: a soluble form of TF1-219). Only L-TF had coagulant activity. All kinds of TF showed the chemotactic migration activity for SMCs. The migration ability of TFs was comparable to those of platelet-derived growth factor (PDGF)-BB and basic fibroblast-growth factor (bFGF), and was inhibited by anti-TF polyclonal and monoclonal antibodies. On the other hand, none of the forms of TF induced SMC proliferation. These results indicate that TF is not only a coagulation factor but also a strong chemotactic factor for vascular SMCs, and suggest that TF could play an important role in atherogenesis as well as in hemostasis and thrombosis.

Animals↗

Effects of suramin on metastatic ability, proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6.

Effects of suramin, a polysulfonated naphthylurea compound, on metastatic ability, proliferation, and production of plasminogen activators and plasminogen activator inhibitors were studied using the highly metastatic human renal cell carcinoma cell line, SN12C-PM6. After renal subscapular implantation of tumor cells in nude mice, suramin significantly inhibited metastasis of tumor cells to the lungs and liver. In vitro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID50 = 105 micrograms/ml). Plasminogen activator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 micrograms/ml), whereas urokinase-type plasminogen activator (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be beneficial for the treatment of patients with an early stage of renal cancer with potential risk of metastasis.

Animals↗

Pulmonary tumor thrombotic microangiopathy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is characterized by widespread fibrocellular intimal proliferation of the small pulmonary arteries and arterioles in patients with metastatic carcinoma. Microscopic pulmonary tumor emboli have frequently occurred in patients with malignant tumors; however, few cases of PTTM have been reported. A rare case of a patient with gastric adenocarcinoma who presented with acute dyspnea and lethal respiratory failure is described. Histologically, diffuse fibromuscular intimal thickening causing luminal stenosis and obstruction but containing rather few cancer cells was observed in the small pulmonary arteries and arterioles. These findings were consistent with PTTM. Although PTTM is a rare phenomenon, PTTM should be considered in the differential diagnosis of acute dyspnea or pulmonary hypertension in patients with carcinoma.

Adenocarcinoma↗

[Acute necrotizing gastritis associated with adult T-cell leukemia in the course of chemotherapy].

A 63-year-old man with smoldering adult T-cell leukemia (ATL) which became acute was admitted. During chemotherapy, he experienced epigastric pain and fever due to neutropenia. The combination therapy of antimicrobials and rhG-CSF was ineffective and he died. Autopsy revealed systemic invasion of ATL cells. The stomach findings resembled those of phlegmonous gastritis, a rare form of bacterial gastritis, along with diffuse, mucosal necrosis with hemorrhage. The pathogenesis of necrotizing gastritis remains to be elucidated. The patient had also received histamine H2 antagonist for gastric ulceration, which might have influenced the gastric bacterial flora.

Aged↗

Relationship between serum prostate specific antigen and histological prostatitis in patients with benign prostatic hyperplasia.

The relationship between the serum values of prostate specific antigen (PSA) and the extent of histological prostatitis was investigated in 42 patients undergoing transurethral resection of the prostate for benign hyperplasia (BPH) without clinical evidence of prostatitis. Histological prostatitis was divided into three groups: acute, chronic-active, and chronic-inactive inflammation. The extent of histological prostatitis was expressed as the number of prostatic acinar and ductal glands with inflammatory infiltrate per total number of glands (%). The serum PSA values significantly correlated with the extent of acute and chronic-active prostatitis (correlation coefficient r = 0.765 and 0.656, P < 0.01). A relationship between PSA values and the extent of chronic-inactive prostatitis was not found. In the immunohistochemical study, prostatic epithelial cells with acute and chronic-active inflammation showed negative staining for PSA antigen. These results indicate that histological acute and chronic-active prostatitis is considered an important factor for inducing the high increase in serum PSA values via the leak phenomenon.

Aged↗

The content of urokinase-type plasminogen activator and tumor recurrence in superficial bladder cancer.

The contents of urokinase-type plasminogen activator were estimated in superficial bladder cancer from 42 patients undergoing transurethral resection for the first time. Tumor recurred in 11 of 16 patients (68.8%) with high urokinase-type plasminogen activator content (8 ng. urokinase-type plasminogen activator per mg. protein and more) and in 12 of 26 (46.2%) with low urokinase-type plasminogen activator content. In the high content group 8 patients (50%) had disease progression compared to 2 (7.7%) in the low content group (p < 0.01). The progression rates in the high urokinase-type plasminogen activator group with stage pTa disease or tumors more than 1 cm. large were significantly higher than those in the low urokinase-type plasminogen activator group (p < 0.05). The recurrence and progression rates in the high content group with stage pT1, grades 2 and 3, single and multiple tumors, and tumors less than 1 cm. large were higher than those in the low content group. The progression-free survival rate in the high content group was significantly lower than that in the low content group (p < 0.005). In conclusion, urokinase-type plasminogen activator content may be a useful marker to predict recurrence and progression of superficial bladder cancer.

Aged↗

Suramin inhibits intimal thickening following intimal injury in the rabbit aorta in vivo.

OBJECTIVE: Proliferation of vascular smooth muscle cells is a major event in atherogenesis. Several growth factors have been well documented to control this proliferation. Inhibition by suramin of the binding of some growth factors to their receptors has recently been reported. The aim of this study was to examine the effects of this agent on neointimal thickening following intimal mechanical injury, as well as on platelet function. METHODS: Intimal thickening was induced by indwelling of polyethylene tubing for 24 h in the rabbit aorta. Rabbits were killed 10 d after drawing out the tubing. Throughout the experiment, suramin (15 mg.kg-1) was injected intravenously every 24 h. Morphological and morphometrical studies were performed in the suramin treated group (n = 6) and in a control group (n = 6). Platelet-rich plasma was prepared from animals before and 3 h after injection of suramin. Platelet aggregation and ATP release induced by collagen were examined. Platelet adhesion on the de-endothelialised area of the rabbit aorta was also examined in the two groups. RESULTS: The mean intimal thickening in the suramin treated group was significantly less than in the control group. Smooth muscle cell replication and cell density in the thickened intima of the suramin treated group were less than in control. Suramin did not affect collagen induced platelet aggregation, ATP release, or platelet adhesion. CONCLUSIONS: Suramin has an inhibitory effect on the neointimal thickening and intimal smooth muscle cell proliferation after intimal injury in the rabbit aorta, but has no effect on platelet function.

Animals↗

Expression of dipeptidyl aminopeptidase IV activity in human lung carcinoma.

Dipeptidyl aminopeptidase IV (DAP IV) staining was examined in various histological types of lung carcinomas to evaluate this enzyme activity. A total of 45 lung carcinomas were examined for their enzyme activity. Almost all (93.1%) cases of adenocarcinoma were positive for DAP IV activity, whereas all cases of squamous cell carcinoma, small cell carcinoma, large cell carcinoma and carcinoid were negative. DAP IV activity of microsomes in lung carcinomas was significantly higher in papillary adenocarcinomas than in squamous cell carcinomas. These data suggest that DAP IV may be a good marker to distinguish adenocarcinoma from other histological types of lung carcinoma.

Adenocarcinoma↗

Autopsy findings in 47 cases of adult T-cell leukemia/lymphoma in Miyazaki prefecture, Japan.

To identify factors that might improve the prognosis of adult T-cell leukemia/lymphoma (ATL), we reviewed data on 47 autopsied cases of ATL with reference to the complications and cause of death. The primary cause of death was respiratory insufficiency due to pulmonary infection. Respiratory insufficiency was also attributed to the diffuse alveolar damage and pulmonary fibrosis resulting from chemotherapy given and oxygen. About 90% of the cases had infections with one or more pathogens. Cytomegalovirus (CMV) was the most frequent pathogen involved in 35/47 (74.5%) while fungal infections were also commonly seen in 25 of the 47 cases (53.2%). Of these, 17 (70%) had pulmonary aspergillosis. Other neoplasias were present in 10 of the 47 cases, while hypercalcemia was evident in 21 patients. These findings suggest that the prevention and treatment of nosocomial infections and of drug-induced pulmonary toxicity may improve the prognosis and quality of life of ATL patients.

Adult↗