Shigeo Kanazawa

VEGF, basic-FGF, and TGF-β in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation

OBJECTIVE:Inflammatory bowel disease (IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation; ulcerative colitis (UC) and Crohns disease (CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assessed serum concentration levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), and plasma level of endothelin-1 (ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-β1,2,3 (TGF-β1,2,3) in tissue by immunostaining.METHODS:Blood samples were obtained from 11 patients with UC, 11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemical study.RESULTS:The concentration levels (in picograms per milliliter) were as follows: for ET-1, UC: 127 ± 47.0, CD: 167.3 ± 35.1, and controls (asthma: 38.5 ± 23.8, p < 0.01; diverticulitis: 40.5 ± 25.6, p < 0.01), for b-FGF, UC: 9.2 ± 1.9, CD: 9.1 ± 1.5, and controls (asthma: 5.0 ± 0, p < 0.01; diverticulitis: 5.0 ± 0, p < 0.01), for VEGF, UC: 659.8 ± 181.0, CD: 740.0 ± 182.3, and controls (asthma: 193.7 ± 58.7, p < 0.01; diverticulitis: 199.6 ± 59.7, p < 0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF and the plasma level of ET-1; that is, elevated VEGF, b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-β2 and TGF-β3 were found in inflammatory cells of active IBD, but no change was observed around the vessels in the controls.CONCLUSIONS:It is suggested that the reciprocal reaction of these cytokines may contribute to angiogenesis in IBD by inducing intestinal ischemia through vasoconstriction.

Analysis of flow characteristics in poststenotic regions of the human coronary artery during bypass graft surgery.

Poststenotic blood flow velocities were evaluated in nine patients with 75% to 99% stenosis of the left anterior descending coronary artery (LAD) during coronary artery bypass graft surgery. We used the 20 MHz 80-channel pulsed Doppler velocimeter developed in our laboratory. An operator placed a specially designed probe on the native LAD with his fingers. Before induction of extracorporeal circulation, LAD blood velocities were measured at several locations distal to the stenosis. The poststenotic flow velocities were rich in systolic flow component with reduced diastolic component. The velocity configuration in the poststenotic portions was characterized by the presence of reverse flow velocities and/or irregularity of the velocity pattern near the vessel wall, indicating the existence of flow separation and recirculation in the regions. The broadening of the velocity spectrum observed at central axial regions suggested the occurrence of flow disturbances. After grafting, the velocity waveform in the LAD beyond a vein bypass graft changed to a diastolic-predominant pattern with a relatively small systolic component. A transient bypass graft occlusion caused a marked reduction in diastolic flow velocity. The systolic-to-diastolic velocity ratio increased from 0.27 +/- 0.07 to 1.50 +/- 0.50 (p less than .01) by the graft occlusion.

Comparison of blood-flow velocity waveforms in different coronary artery bypass grafts. Sequential saphenous vein grafts and internal mammary artery grafts.

Characteristics of blood-flow velocities were investigated at different sites in two types of coronary artery bypass grafts, sequential saphenous vein grafts (SSVG) and internal mammary artery grafts (IMAG). The latter appear to have the longest life span. The patency rate of the side-to-side anastomosis of the SSVG is better than that of the end-to-side anastomosis. The SSVG was anastomosed to the major diagonal branch by side-to-side anastomosis and to the left anterior descending coronary artery (LAD) by end-to-side anastomosis in 13 patients who had 75-100% and 75-90% stenoses in the LAD and major diagonal branch, respectively. IMAG anastomoses were performed to the LAD in 10 patients with 75-100% stenoses of the artery. The blood-flow velocities were measured by the 20-MHz, eighty-channel ultrasound pulsed Doppler method during surgery. In six patients in the SSVG group, we investigated the configuration of velocity profiles at the region just proximal to the side-to-side anastomosis and at the bridge portion between the side-to-side and end-to-side anastomosis. In the other seven patients, we measured the blood-flow velocity at several centimeters proximal to the side-to-side anastomosis and compared it with that in the IMAG. At the region just proximal to the side-to-side anastomosis, the velocity profile skewed toward the anastomosis side wall in all patients, and the flow velocity near the wall opposite to the side-to-side anastomosis was reversed in five of six patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A granulomatous liver abscess which developed after a toothpick penetrated the gastrointestinal tract: Report of a case

Abstract.An unusual case of a toothpick perforating the stomach, then penetrating the liver, and thereafter forming a liver abscess is reported. A 48-year-old woman who had ingested a toothpick 1 month earlier was admitted to our hospital because of severe epigastralgia which had progressively worsened. A laparotomy was performed because a granulomatous abscess in the liver due to this ingested foreign body was suspected. We found a granulomatous abscess in the liver due to the penetration of the toothpick through the stomach. The toothpick had become completely embedded about 2 cm deep in the left lobe of the liver. When dissecting the tumor, a 5.5-cm toothpick was removed, and a partial lateral resection of the liver was performed. The histological diagnosis was a hepatic abscess with granulomatous change. This was a rare case of a migration of an ingested toothpick into the liver through the stomach.

Pulmonary sequestration associated with aspergillosis.

Pulmonary sequestration involves an abnormal pulmonary tissue separated from the normal pulmonary parenchyma, not connected to the tracheobronchial tree and supplied by a systemic artery. A case of intralobar pulmonary sequestration is presented. Case; a 49-year-old male was admitted to our hospital complaining of fever, cough and sputum production. Sputum culture resulted in a large growth of Aspergillus niger. Angiography showed an abnormal blood supply from the abdominal aorta to the right lower lobe. Right lower lobectomy was performed. The postoperative courses are uneventful.

Coronary flow characteristics of left coronary artery in aortic regurgitation before and after aortic valve replacement

In 6 patients with pure aortic regurgitation, the velocity waveform in the left anterior descending coronary artery (LAD) was measured using an 80-channel 20-MHz-pulse Doppler velocimeter before and immediately after aortic valve replacement. All patients showed normal coronary angiograms. Flow velocity was analyzed by both zero-cross and fast Fourier transform methods in real time. The LAD flow in severe aortic regurgitation was characterized by an increase in the systolic flow component, a small and rapidly decreased diastolic flow, an irregular velocity profile across the vessel, and a wider velocity spectrum. After aortic valve replacement, systolic flow decreased by 36.3 +/- 21.7% (p less than 0.01), whereas diastolic flow increased by 81.4 +/- 51.8% (p less than 0.05). The ratio of diastolic flow to total LAD flow increased from 63 +/- 13% to 82 +/- 7% (p less than 0.05). The velocity profile became more parabolic and had a narrow spectrum. These results suggest that operation for aortic regurgitation induces beneficial effects on the myocardial inflow immediately after valve replacement.

Intralobar Pulmonary Sequestration Supplied by Multiple Anomalous Arteries : Report of a Case

Abstract Pulmonary sequestration is abnormal pulmonary tissue that has separated from the normal pulmonary parenchyma, is not connected to the tracheobronchial tree, and is supplied by a systemic artery. We describe herein a case of intralobar pulmonary sequestration found in a 66-year-old man who was admitted to our hospital with hemoptysis, coughing, and fever. Angiography showed that the branches of the 11th left intercostal artery and a bronchial artery had formed a hypervascular area in the lower part of the left lung. Bronchial artery embolization and subsequent embolization of the left 11th intercostal artery were performed in an attempt to control the recurrent hemoptysis. These treatments were unsuccessful, and he was transferred to our department of surgery after coughing up about 400 ml of fresh blood. A left lower lobectomy was performed. The resected lung contained a large feeding artery, some acute and partly organizing inflammatory lesions within collapsed lung parenchyma, and massive intra-alveolar hemorrhage in the peripheral area. The patient had an uneventful recovery and was discharged 22 days after his operation.

MALIGNANT MESOTHELIOMA OF THE TUNICA VAGINALIS TESTIS : REPORT OF A CASE

We describe herein the case of a 68-year-old man with malignant mesothelioma of the tunica vaginalis testis. The pathological diagnosis was based upon the clinical findings, gross and microscopic morphology, and special stains. Malignant mesothelioma is a rare tumor associated with asbestos exposure that can be effectively treated with orchidectomy via an inguinal approach.

Forskolin-stimulated adenylylcyclase activity: a marker to assess islet cell viability following cold storage in different solutions and to predict islet cell function following transplantation.

For clinical islet cell transplantation, short-term storage of islet cells is likely to be necessary, and it is imperative that the islet cells be kept as viable as possible during the period. However, there are little data on which preservative solutions are most suitable for the storage of islet cells after isolations or before transplantation. To estimate islet cell viability and transplantation success rate in the present study, adenylylcyclase activity was measured with a rapid new fluorometric assay in rat islet cells prior to transplantation, because cAMP plays an essential role in determining islet β-cell viability and responsiveness to various hormonal stimuli. Adenylylcyclase activity was measured in islet cells stored for different periods of time (0, 3, 16, 24, 48, 96 h) and in different preservative solutions. Approximately 1,000 islet cells from each preservation group using University of Wisconsin (UW) solution were transplanted to streptozotocin-induced diabetes mellitus (DM) rats. Transplant success was evaluated by measuring blood glucose levels. Preoperative adenylylcyclase activity was compared with posttransplant islet cell function. The adenylylcyclase activity of UW solution was significantly higher than that of Euro-Collins solution and lactate-Ringers solution through the different preservation time periods. Preoperative adenylylcyclase activity correlated well with posttransplant islet cell function in a rat model of DM. We conclude that adenylylcyclase activity can be used as a marker to assess islet cell viability as well as differences in preservation media and may predict islet cell transplant success.

Non-Penetrating Traumatic Tricuspid Regurgitation after Mitral Valve Replacement

A case of traumatic rupture of the tricuspid chordae tendineae with severe regurgitation in a patient who previously had mitral valve replacement is presented. In this case, it is strongly suggested that a firm pericardial adhesion of the anterior right ventricular wall became a factor of the disruption of the tricuspid valve under a slight precordial blow.