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Biomedical subjects

S Shindo

Publications and source records attributed to S Shindo.

At least 55 records · Page 3Linked to original sources

Hepatocyte growth factor in bronchoalveolar lavage fluids and cells in patients with inflammatory chest diseases of the lower respiratory tract: detection by RIA and in situ hybridization.

Pulmonary fibrosis is a chronic inflammatory disorder characterized by diffuse fibrous remodeling of alveolar spaces. Although much interest is focused on mechanisms of the inflammatory process in pulmonary fibrosis, little is known about the repair and regenerative process. Hepatocyte growth factor (HGF), originally discovered as a mitogen for hepatocyte regeneration, is now recognized as a multifunctional mesenchymal factor for epithelial regeneration, including the regeneration of alveolar type II epithelial cells. Involvement of HGF and its receptor (c-met) is evident in animal models of acute lung injury produced by hydrochloride inhalation. We studied the role of HGF in patients with idiopathic pulmonary fibrosis (IPF) (25 cases), lung fibrosis associated with rheumatoid arthritis (22 cases), and sarcoidosis (39 cases). Immunohistochemical evaluation demonstrated that hyperplastic alveolar type II epithelial cells, as well as alveolar macrophages, were strongly stained with anti-HGF antibody in tissues of patients with IPF. The concentration of HGF in bronchoalveolar lavage fluid (BALF) was significantly higher than in normal controls (0.23 +/- 0.09 pg/microg) in patients with IPF (0.77 +/- 0.88 pg of HGF/microg of albumin, P < 0.001), lung fibrosis associated with rheumatoid arthritis (0.50 +/- 0.64 pg/microg, P < 0.01), and sarcoidosis (0.41 +/- 0.61 pg/microg, P < 0.05). In situ hybridization revealed mRNA for HGF in alveolar macrophages (especially small monocytelike macrophages). These results indicate that the increase in HGF concentration in patients' peripheral air spaces is due to augmented HGF production by alveolar epithelial cells and alveolar macrophages. HGF, through a paracrine mechanism, may play an important role in the repair and healing of the inflammatory lung damage in pulmonary fibrosis.

Adult↗

[Sairei-to may inhibit the synthesis of endothelin-1 in nephritic glomeruli].

In order to clarify the antinephritic mechanisms of Sairei-to (TJ-114), its effects on the synthesis and expression of endothelin-1 were evaluated in rats with anti-glomerular basement membrane (GBM) nephritis. TJ-114 was administered orally once daily from the 20th day after anti-GBM serum injection and was continued throughout the experiment. TJ-114 prevented proteinuria and histopathological changes in the glomeruli of nephritic rats. TJ-114 inhibited elevation of the endothelin-1 concentration in the supernatant from cultured glomeruli of nephritic rats and the endothelin-1 positive area in the glomeruli. TJ-114 inhibited the elevation of systolic blood pressure and the number of proliferating cell nuclear antigen (PCNA)-positive cells per glomeruli. We also found that the constitutive Kampo medicine in TJ-114, Gorei-san (TJ-17), inhibited the synthesis and expression of endothelin-1. In addition, the constitutive herbs TJ-17, alismatis rhizoma (Japanese name "Takusha") and hoelen (Japanese name "Bukuryou") inhibited the synthesis and expression of endothelin-1. These results indicate that the antinephritic actions of TJ-114 may be due partially to the inhibition of endothelin-1 synthesis in the glomeruli.

Animals↗

[Protective effect of onpi-to (TJ-8117) on the expression of apoptosis in 5/6 nephrectomized rats].

The present study was designed to clarify the effects of TJ-8117 on apoptosis in the glomeruli of 5/6 nephrectomized rats. TJ-8117 (400 mg/kg/day), captopril (50 mg/kg/day) and nicardipine (50 mg/kg/day) were administered as drinking water from the 56th day after renal ablation, and continued throughout the experiment. All rats were sacrificed at 13 weeks and renal tissues were removed to quantify histopathological and apoptotic parameters in glomeruli. TJ-8117 inhibited proteinuria, matrix index and decrease in the number of total cells in glomeruli of nephrectomized rats. In addition, the increase in apoptotic body and DNA fragmentation was significantly inhibited in the TJ-8117-treated group. Captopril and nicardipine failed to inhibit both parameters. In 400 mg/kg of the TJ-8117 treated group, the number of Bcl -2 positive cells in the glomeruli was elevated compared with the 5/6 nephrectomized control group. In addition, the number of Bax positive cells in the TJ-8117 group was significantly suppressed in a dose-dependent manner. These results suggest that TJ-8117 may inhibit apoptosis in the late stage of this model by suppressing matrix accumulation and progression of glomerulosclerosis. The apoptosis-preventing effect may be mediated by decreased expression of Bax in the glomerular cells.

Animals↗

[Effects of onpi-to (TJ-8117) and (-)epicatechin-3-O-gallate on the proliferating changes in glomeruli of 5/6 nephrectomized rats].

Onpi-to (TJ-8117) is a herbal medicine composed of five crude drugs (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber). Our previous experiments have demonstrated that TJ-8117 suppressed the development of glomerulosclerosis and retarded the deterioration of renal function in 5/6 nephrectomised rats. In the present study, the effects of TJ-8117 and (-)Epicatechin-3-O-gallate (ECG), which is a component of Rhei Rhizoma, on glomerular cell proliferation, extracellular matrix accumulation and glomerular hypertrophy were investigated in 5/6 nephrectomized rats. Male Wistar rats (170-180 g) were subjected to 5/6 nephrectomy, and TJ-8117 (0.32%, 0.64%) or angiotensin-converting enzyme inhibitor, captopril (CAP 0.08%) was administered daily by mixing in normal chow and ECG (2 mg, 8 mg/100 ml) by drinking water from the day after 5/6 nephrectomy. Following 5/6 nephrectomy, glomerular cell poliferation was increased and reached a maximum at 1 week in the untreated control rats, but was suppressed significantly at 1 and 2 weeks after treatment with TJ-8117 and at only 1 week after treatment with CAP. Extracellular matrix accumulation was detected after 1 week and increased gradually until 4 weeks in the control rats, whereas it was significantly inhibited in both the TJ-8117- and CAP-treated rats. In addition, immunohistochemistry revealed that TJ-8117 significantly inhibited the increase of fibronectin, and tended to reduce type I and type IV collagen at 4 weeks. Furthermore, TJ-8117 suppressed glomerular hypertrophy at 4 weeks. Systolic blood pressure (SBP) and urinary protein excretion (UP) were higher in the control rats than sham-operated rats. TJ-8117 prevented this increase of SBP and UP at 1 week. ECG also suppressed glomerular cell proliferation and the increase of SBP and UP at 1 week after 5/6 nephrectomy. These findings suggest that ECG was one of active components of TJ-8117. These results suggest that TJ-8117 suppressed proliferating changes in glomeruli at an early stage in 5/6 nephrectomized rats, and inhibited the development of glomerulosclerosis.

Animals↗

Localised thrombus in the distal aortic arch: its aetiology analysed by three-dimensional mould model of the thoracic aorta.

Isolated thrombus of the thoracic aorta without aneurysmal change or dissection is a relatively rare event. A case presenting with aortic thrombus and successive distal embolism is reported herein and the aetiology of the thrombus of the distal aortic arch is analysed by a three dimensional aortic model. A 61-year-old man suffered acute ischaemia in his right leg on January 26, 1994. Enhanced computed tomography (CT) showed a localized thrombus in the distal aortic arch expanding towards the descending aorta, and partial infarction of the left kidney and the spleen. Angiography demonstrated abrupt occlusion of the right superficial femoral artery. Immediate anticoagulation with heparin and coumadin was administered, and the thrombus in the aorta disappeared following 1 month of this medical treatment, leaving the renal and splenic infarction unchanged. The unresolved occlusion of the superficial femoral artery and the popliteal artery was treated with a bypass from the right superficial femoral artery to the peroneal artery using a reversed saphenous vein graft. The mould model of the thoracic aorta was reconstructed from CT, and the thrombus was found to be at the most distal and medial site of the lesser curvature of the aortic arch. This specific location is referred mostly as the site for thrombus formation in the literature. The case is reported briefly and the risk of this specific region of the thoracic aorta for thrombus formation is discussed using this mold model.

Angiography↗

Temperatures measured by a deep body thermometer (Coretemp) compared with tissue temperatures measured at various depths using needles placed into the sole of the foot.

Continuous monitoring of body temperature during anaesthesia is a widely accepted clinical practice for which a variety of techniques are used. In this study, the accuracy of the deep body thermometer (Coretemp) was compared with temperatures measured by needle thermocouples. With IRB approval and informed consent, seven ASA physical status I and II patients undergoing otolaryngeal surgery were studied. General anaesthesia and neuromuscular blockade were induced with thiamylal and vecuronium. Anaesthesia was maintained with isoflurane at an end-tidal concentration of 1.0-2.0% and 66% nitrous oxide in oxygen. After induction of general anaesthesia, subcutaneous temperature was measured at the sole of the left foot using a Coretemp. Additionally 8-, 18-, and 38-mm-long needle thermocouples were inserted into the the sole of the left foot close to Coretemp and skin-surface temperature was also recorded adjacent to the needles. The Coretemp measurement (Tc) correlated best with 18-mm-deep needle temperature (r2 = 0.87). There was also a good correlation between Tc and 38-mm-deep needle temperature (r2 = 0.83). Skin and 8-mm-deep needle temperatures correlated poorly or only moderately with Tc (r2 = 0.67, 0.75, respectively). These results indicate that temperatures measured by Coretemp well reflect the temperatures at a depth of 18 mm or more from the skin into the foot.

Anesthesia, General↗

Effect of acteoside on mesangial proliferation in rat anti-Thy 1 nephritis.

We investigated whether acteoside can inhibit mesangial matrix expansion or mesangial cell proliferation in mesangioproliferative anti-Thy 1 nephritis. Untreated control rats were compared to the rats treated with acteoside either during early (day 1 to 8) or late (day 4 to 12) period after the induction of anti-Thy 1 nephritis. The result showed that acteoside and prednisolone treatments (in either early or late period) significantly reduced proteinuria, mesangial matrix expansion (the index of matrix expansion) and mesangial proliferation as determined by the number of proliferating nuclear cell antigen (PCNA)-positive cells. Acteoside also reduced glomerular macrophage infiltration and ICAM-1 expression in glomeruli of anti-Thy 1 nephritic rats. Furthermore, acteoside treatment markedly increased the activities of matrix metaloproteinases (MMP) in glomeruli. These results suggest that acteoside can inhibit mesangial cell proliferation and extracellular matrix overproduction by either inhibiting ICAM-1 expression or increasing activities of MMP.

Animals↗

[Reconstruction of the crural artery in atherosclerotic occlusive arterial disease].

Limb threatening ischemia in patients with atherosclerotic occlusive disease is frequently induced by the association of crural artery occlusion. To improve the patency of distal bypass grafts, we developed a "non-dissection method" for reconstruction of these lesions. This method involves following procedures; an adventitial dissection limited to the frontal surface of the artery at the anastomotic site, complete evacuation of blood from the lower leg using a Esmarch's rubber bandage or a pneumatic tourniquet under systemic heparinization, and distal anastomosis with vein graft in end to side fashion with long arteriotomy (20 mm in length) without use of vascular clamps. This method has several advantages to the conventional method, such as easiness of suturing for accurate anastomosis, preservation of the muscular branches around the anastomosis, avoidance of surgery-induced injury to the artery and prevention of postoperative cicatrization around the anastomosis which may affect natural enlargement of the bypassed native artery. The technical details are described. Since 1982, 76 tibial bypass surgeries were performed using this method. Whenever stenotic lesions were recognized, the grafts were revised and counted as a primary occlusion. The primary patency rates at 1 year, 3 years, 5 years and 10 years are 82.2%. 75.8%, 63.9% and 63.9% respectively. The secondary patency rates are 89.1%, 84.8%, 80.8% and 80.8% respectively at the same term.

Arterial Occlusive Diseases↗

Experiences of postcardiotomy assist: pneumatic ventricular assist device or venoarterial bypass with percutaneous cardiopulmonary support.

From October 1982 to the present, 16 patients have been supported by a pneumatic ventricular assist device (VAD). Since April 1990, we have introduced a venoarterial bypass (VAB) with percutaneous cardiopulmonary support (PCPS) system. This PCPS system was used in 12 patients. The long-term survival rate of PCPS cases (41%) was much better than that of VAD cases (19%). The main cause of death in VAD cases was multiple organ failure (MOF). Although VAB was initiated more recently than VAD, the duration on support was longer in the VAD group than in the VAB group. Because of the longer support duration and the presence of many patients with MOF, coagulopathy deteriorated more readily in the VAD group than in the VAB group. In the case of postcardiotomy cardiopulmonary bypass weaning or low-output syndrome (LOS), the VAB with PCPS system should be applied first under intraaortic balloon pumping assist because of its simplicity and low cost. Thereafter, VAD should be applied in cases refractory to VAB support.

Adult↗

Preliminary experimental study about the feasibility of combining pulsatile cardiopulmonary support system and a membrane oxygenator.

A cardiopulmonary support (CPS) device that incorporated a pneumatic ventricular assist device (VAD) and a membrane oxygenator was developed for the support of patients with profound heart and/or respiratory failure. This device has an advantage of being both a pulsatile assist device and membrane oxygenator. A "triple flow" regulator was included in this system to control the blood flow through the oxygenator. The purpose of this study was to clarify the efficacy of this system in supporting an animal model with combined cardiac and respiratory failure. In vitro tests showed 3.7 L/min of pump flow under 1.6 L/min of oxygen supply to the oxygenator even though there was a 50% clamp of a "triple flow" regulator with sufficient pulsatility. In 14 acute canine experiments, cardiogenic shock and acute respiratory failure were introduced by coronary ligation and mechanical hypoventilation simultaneously. The pump flow was maintaned at 1.95-0.6 L/min (average 1.2 L/min) and the driving pressure of the pump was controlled between 200 and 300 mmHg positive pressure and -20 to -50 mmHg negative pressure. The driving rate was fixed at 100 bpm and systolic/diastolic ratio was controlled between 35-50%. The canines were divided into control group (n = 4) and pumped group (drained from the right atrium n = 7, drained from the left atrium n = 3). By using CPS system, flow and aortic pressure recovered to the initial baseline level. Without this support, the canine model could not maintain systemic circulation. In the group drained from right atrium, central venous pressure decreased with the device from 13.9 +/- 2.4 to 5.6 +/- 1.4 cm H2O (p < 0.01), returned to the initial level without this device (p < 0.01). In the group drained from left atrium, pulmonary capillary wedge pressure decreased from 37.9 +/- 4.6 to 20.8 +/- 5.7 mmHG (p < 0.01), and returned to the initial level without the device, arterial oxygen tension levels increased tension levels increased (p < 0.01), and also arterial oxygen saturation levels recovered (p < 0.01). The results suggest that the current model of the pulsatile CPS has a potential to support the animal model with combined cardiac and respiratory failure.

Animals↗

[Effect of Onpi-to (TJ-8117) on TGF-beta 1 in rats with 5/6 nephrectomized chronic renal failure].

We and others have already reported that Onpi-to (TJ-8117), a Kampo medicine composed mainly of Rhei Rhizoma, has a beneficial effect on an adenine-induced renal failure model and 5/6 nephrectomized renal failure. However, little is known about the detailed mechanism of this medicine when used for renal failure. The present study was designed to clarify whether or not TJ-8117 affects TGF-beta 1 production or activation in glomeruli of 5/6 nephrectomized rats. TJ-8117 (400 mg/kg/ day) and captopril (50 mg/kg/day) were administered as drinking water from the day immediately after the operation and continued throughout the experiment. All rats were sacrificed at 4 weeks and renal cortical tissue was removed to quantify the protein and activity of TGF-beta 1 and activities of metalloproteinase. TIMP expression and extracellular matrix (collagen type I, IV) in the glomeruli were analysed histologically. TJ-8117 inhibited proteinuria, and the accumulation of collagen type I and IV in glomeruli of nephrectomized rats. In addition, TJ-8117 inhibited the TGF-beta 1 positive area in the glomeruli and the elevation of mature TGF-beta 1 level in the renal cortex of nephrectomized rats. In the TJ-8117 treated group, activities of metalloproteinase 1, 2 or 9 in the renal cortex were elevated compared with the control group. Captopril failed to affect the TGF-beta 1 level. We also found that the constitutive herbs in TJ-8117, Rhei Rhizoma and Ginseng radix, inhibited the process from inactive TGF-beta 1 to mature TGF-beta 1.

Animals↗

[Effects of neutralizing antibodies on cytokine treatment for anti-GBM nephritis in mouse].

The process of glomerular injury in nephrotoxic serum nephritis (NTN) is dependent on proinflammatory cytokines. In the present investigation, we assessed the actions of neutralizing antibody against IL-1 beta, TNF-alpha, IL-6 and TGF-beta 1 on glomerular injury. Marked increase in IL-1 beta and IL-6 was detected in cultured glomeruli of NTN in mice throughout the experiments from disease induction. Protein of TNF-alpha and TGF-beta 1 also increased in NTN mice 1 day after disease induction. Treatment with either IL-1 beta or TNF-alpha neutralizing antibody reduced proteinuria from 71 +/- 11.2 m g/24 hr to 32.2 +/- 6.0 (P < 0.01). 34.3 +/- 6.8 mg/24 hr (P < 0.01), respectively. Although the effect of IL-6 neutralizing antibody on proteinuria was not remarkable, the decreased creatinine clearance was improved more than that of IL-1 beta or TNF-alpha. Antibody against TGF-beta 1 had no effect on proteinuria and creatinine clearance. Treatments with IL-1 beta, TNF-alpha and IL-6 neutralizing antibodies inhibited glomerular hypercellularity in NTN mice. TGF-beta 1 neutralizing antibody suppressed the index of mesangial matrix expansion. IL-1 beta and TNF-alpha neutralizing antibodies prevented the increase in the number of macrophages in the glomeruli. The number of PCNA positive cells and alpha-smooth muscle actin expression in glomeruli was significantly reduced in the IL-6 neutralizing antibody-treated group. These results confirm the direct involvement of IL-1 beta, TNF-alpha and IL-6 in mouse NTN. We speculate that TGF-beta 1 may inhibit excessive proliferation in glomerular cells.

Animals↗

[Mondor's disease].

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Diagnosis, Differential↗

Non-genetic group specific component (GC) observed in a patient with acute non-lymphocytic leukemia.

This is the case of a male non-lymphocytic leukemia patient who continuously exhibited non-genetic group specific component (GC). The patient was hospitalized 10 months for treatment. The patient's GC type was GC 2-1A2 upon his admission to the hospital, which was consistent with his parents' type. The additional GC protein isoform appeared during treatment and was detected by polyacrylamide gel isoelectric focusing (PAGIEF). This acquired GC component corresponded to GC 1F in PAGIEF and was thought to have originated from GC 1A2 protein. This phenomenon most probably occurred due to a metabolic abnormality or modification of the GC molecule caused by the disease itself, or by chemotherapy.

Adult↗

Collateral artery bypass in Buerger's disease: report of a novel procedure.

A 25-year-old man was admitted to our hospital for treatment of a painful ulcer on his left fourth toe, 9 years after undergoing lumbar sympathectomy and 4 years after undergoing bypass, both of which had been unsuccessful. Angiography demonstrated diffuse arterial occlusion in the lower extremities except for a persistent sciatic artery and a sural artery, which was the main collateral. Thus, reversed bifurcated saphenous vein bypass from the sciatic artery to the sural artery and the posterior tibial artery was performed utilizing Esmarch's rubber bandage as a substitute for a vascular clamp to control bleeding intraoperatively. The ulcer healed promptly and the patient was discharged symptom-free 1 month postoperatively. This case report demonstrates the advantage of performing collateral arterial bypass and illustrates some of the technical challenges associated with this procedure.

Adult↗

Rupture of an isolated internal iliac artery aneurysm into the rectum: report of a case.

Aneurysmal rupture into the intestinal tract is a rare but disastrous complication of an internal iliac artery aneurysm. We report herein the successful surgical repair of a fistula between a huge aneurysm of the right internal iliac artery and the rectum in an 81-year-old man. After a femoro-femoral cross-over bypass had been performed, the aneurysm was opened and its patent arterial branches were ligated with sutures. The fistula was then intra-aneurysmally sutured and covered with an omental flap. The diagnostic and therapeutic approaches to this severe complication are discussed with a review of the literature following the presentation of this case.

Aged↗