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Biomedical subjects

A Sumiyoshi

Publications and source records attributed to A Sumiyoshi.

At least 91 records · Page 5Linked to original sources

[The use of cultured endothelial cells in studies of pathophysiology of diseases].

The endothelial cells comprise a single layer of polygonal cells lining the entire length of blood vessels and the heart. It plays a pivotal role in modulating a number of physiological and pathophysiological processes. This review focuses on the endothelial cell function. To obtain information on endothelial cell functions and its biological behavior, a critical step is studying endothelial cells separated from other types of cells. Methods of isolation, culture and identification of endothelial cells are briefly described. Moreover, there is described a wide variety of applications of cultured endothelial cells in the study of pathophysiology of diseases, and are picked up several points to be solved on this.

Animals↗

[Intimal injury and thrombus formation].

One of the most important factor of thrombosis is intimal injury. We examined the morphology of thrombogenesis in the large artery using the rabbit as an experimental animal. When the intima was injured by a balloon catheter, we observed the adhesion of platelets onto the denuded area of the intima with various degrees of aggregation. Fibrinogen, fibronectin and vWF were observed on the surface of the aggregated platelets. In the raised thrombi induced by a polyethylene tubing fibrin thread formation was observed among the aggregated platelets. In the injured site showing interruption of internal elastic lamina by polyethylene tubing or wire tubing prominent fibrin formation was observed. The intima showing fibrous thickening which was induced by polyethylene tubing 3 weeks before the second injury also revealed prominent fibrin formation after the second injury. These thickened intima is considered to have an availability of a large amount of tissue factor for the activation of coagulation system than the normal intima.

Animals↗

[Clinicopathologic study of adult-onset membranoproliferative glomerulonephritis].

We analyzed clinicopathologic characteristics of adult-onset membranoproliferative glomerulonephritis (MPGN) by comparing two tentatively-classified subgroups. Group A consisted of 9 patients in whom more than 50% of glomeruli showed mixed segmental and global duplication of glomerular basement membrane (GBM), and Group B 9 patients with global duplication of GBM. Group A showed a tendency for more favorable clinical course and outcome than Group B. Nephrotic syndrome was present in 33% of Group A and 100% in Group B, hypertension in 22% and 44%, hypocomplementemia in 44% and 67% at the time of renal biopsy. Deterioration of renal function, at comparable durations of follow-up of 62 +/- 12 (M +/- SE) and 53 +/- 13 months, was observed in 22% of Group A and 56% in Group B, respectively. Histologically, mesangial proliferation and tubulointerstitial change were more pronounced and frequency of sclerosing glomeruli was greater in Group B. There was also a negative correlation between the extent of global double contour and renal function as assessed by creatinine clearance at the time of renal biopsy (r = -0.55, P less than 0.05). These results indicate that the high incidence of global double contour, in addition to the presence of marked tubulointerstitial change and sclerosing glomeruli, may relate to progressive deterioration of renal function in MPGN. That outcomes for Group A and Group B may be different when clinical parameters, including the durations from onset of symptoms to the time of biopsy and length of follow-up periods, are comparable also indicates that these two groups should be considered separate entities, at least on the basis of clinical results.

Adolescent↗

Aortic endothelial cell damage induced by beta-VLDL and macrophages in vitro.

We performed an in vitro study to assess damage to swine aortic endothelial cells by rabbit beta-VLDL and/or rabbit peritoneal macrophages. Incubation of cultured aortic endothelial cells with beta-VLDL, macrophages, or macrophage lysate induced endothelial cell damage time- and dose-dependently as estimated by [3H]adenine release. Incubation of endothelial cells with both beta-VLDL and macrophages produced a synergistic effect on the increase of [3H]adenine release. Pretreatment of the endothelial cells with some kinds of antioxidants (probucol 50 micrograms/ml, vitamin E 50 microM, superoxide dismutase-polyethylene glycol 0.5 mg/ml, or catalase-polyethylene glycol 0.5-1.0 mg/ml) significantly prevented the endothelial damage by beta-VLDL or macrophage lysate. We conclude that beta-VLDL and/or macrophages could induce endothelial cell damage and that some kinds of antioxidants could prevent it.

Adenine↗

A new method for simultaneous measurement of endogenous noradrenaline release and vascular responsiveness in perfused rabbit carotid arteries in vitro.

1. A new preparation for large arteries was tested for the simultaneous measurement of noradrenaline release and vasoconstrictor response induced by nerve stimulation in vitro. 2. Preparations of rabbit carotid artery with an outflow cannula were perfused with a modified Krebs-Ringer bicarbonate solution containing propranolol (3 x 10(-6) M) and cocaine (10(-6) M), to block beta-adrenoceptors and uptake-1, respectively. 3. The perfused carotid arteries were subjected to both transmural field stimulations (TFS) and exogenous noradrenaline administrations. To evaluate the preparation, we carried out the procedures in two control groups and a group with yohimbine (10(-7) M) treatment, respectively. 4. TFS over the range of 1.5-24 Hz caused a frequency-dependent pressor response. Yohimbine significantly increased the TFS-induced pressor responses. 5. TFS also caused frequency-dependent endogenous noradrenaline release. The endogenous noradrenaline release was significantly enhanced by yohimbine treatment. When noradrenaline release was expressed as release per stimulus, it was frequency-dependent in the group with yohimbine treatment but not in control groups. 6. Exogenous noradrenaline induced a dose-dependent pressor response. The exogenous noradrenaline-induced vasoconstrictor response was significantly diminished by yohimbine treatment. 7. It is concluded that this preparation can be effectively used to study drug effects on noradrenergic neurotransmission in relatively large arteries under various pathophysiological states by simultaneously measuring catecholamine release and vascular responsiveness.

Animals↗

Vascular injuries induced by materials released from white mural thrombus and hypercholesterolemia in vivo.

Materials released from platelet-rich white mural thrombi into the arterial circulation and dietary hypercholesterolemia could cause endothelial injury and regeneration, and also smooth muscle cell migration and proliferation in vivo in the intima. In addition, a combination of these two factors showed an additive effect on the endothelial injury in vivo. Further experiments are in progress to clarify how high a level of serum cholesterol and/or oxidized LDL may be sufficient for endothelial injury using this in vivo model for the better understanding of detailed pathogenesis of atherosclerosis.

Animals↗

Isolation of multiple cytomegalovirus strains from a patient with adult T cell leukemia.

A 66-year-old male with adult T cell leukemia had an ulcer on the left medial thigh. The biopsy of the skin lesion revealed enlarged endothelial cells with acidophilic intranuclear inclusion bodies, suggesting cytomegalovirus (CMV) infection. At autopsy, CMV was isolated from a nodular skin lesion of the scrotum. The urine constantly tested positive for CMV. Restriction endonuclease cleavage analysis of DNA of the isolates from the skin and urine indicated that this patient was infected with two different strains of CMV.

Aged↗

[Renal failure associated with polyarteritis nodosa].

We reported 5 patients with renal failure associated with polyarteritis nodosa (PN). In all patients the renal dysfunction became apparent from 2 to 4 weeks after the onset of fever or neuromuscular symptoms with laboratory findings supporting marked inflammatory process and took the course of either acute or rapidly progressive renal failure. The clinical diagnoses on admission were variable; fever of unknown origin, peptic ulcer disease, polyneuritis multiplex, disseminated intravascular coagulation and Buerger's disease. Microscopic examination of the kidneys in 3 by renal biopsy and in 2 by autopsy revealed crescentic glomerulonephritis without immunoglobulin deposit, segmental necrotizing glomerulonephritis, marked inflammatory infiltrate around the glomeruli, granulomatous lesion, tubular necrosis and cortical necrosis other than necrotizing vasculitis. The outcomes were favorable with prednisolone monotherapy in two patients who had biopsy-proven diagnosis and treatment early in the course. Of all PN the prevalence of renal involvement is considered to be about 70%, the prognosis of which has been considered very poor. However it seems possible to alter fatal outcome of this disease by starting treatment with confident histological proof early in the disease process.

Acute Kidney Injury↗

Comparative study of plasminogen activators in cancers and normal mucosae of human urinary bladder.

We have developed a highly sensitive sandwich enzyme immunoassay for determination of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) antigen levels in extracts of human tissues. We determined antigen levels of PAs in extracts of 31 primary cancers and 15 normal mucosal tissues of the urinary bladder using this method. U-PA antigen levels in extracts of bladder cancers were significantly higher than those in normal tissues (p less than 0.005). U-PA antigen levels significantly increased as histological grading of malignancy advanced. There was no correlation between t-PA antigen level and malignancy. These results indicate that an increase of u-PA antigen level may be a parameter of malignant transformation and may play an important role in invasiveness of cancer.

Aged↗

Striated muscle in the biopsy specimen of the prostate.

We had a chance to see striated muscle fibers in the biopsy specimen of the prostate. We examined the prostate specimens of autopsied cases and biopsy specimens. The distribution of striated muscle fibers was studied with an immunohistochemical method for myoglobin to obtain their anatomical distribution in detail. We showed that the striated external sphincter muscle fibers were present in the peripheral zone of the prostatic gland (9.1%). Therefore, if striated muscle fibers are found in biopsy specimens of prostatic cancer, pathologists and urologists should not diagnose simply that the cancer invades beyond the prostatic capsule.

Adenocarcinoma↗

Comparative study of plasminogen activator antigens in colonic carcinomas and adenomas.

The correlation between malignant transformation and increased PA synthesis or secretion has been examined in a variety of cell lines. To study the relationship between content and composition of PAs and colorectal neoplasms, we measured u-PA and t-PA antigen levels in normal mucosa, tubular adenoma, adenocarcinoma in adenoma, and adenocarcinoma, using a sensitive sandwich enzyme immunoassay. This assay was very sensitive and was not hindered by the presence of serine protease inhibitors. Both adenomas and carcinomas had higher u-PA antigen levels than normal mucosa. The u-PA antigen level of adenomas was lower than that of carcinomas. Antigen level of t-PA, however, was lower in both adenomas and carcinomas compared with that in normal mucosa, the values being lowest in carcinomas. Two cases of carcinoma in adenoma had PA contents similar to those of carcinomas. u-PA antigen level of adenomas with dysplastic epithelium was higher than that of adenomas without dysplastic epithelium. Therefore, the increase of u-PA content in adenomas could be a parameter of malignant changes in adenomas.

Adenoma↗

Renal cell carcinoma associated with acquired renal cystic disease.

A patient with eight years' history of haemodialysis treatment developed gross haematuria. During evaluation severe abdominal pain with dyspnoea developed and he died suddenly. Autopsy revealed spindle cell type renal cell carcinoma (RCC) associated with acquired renal cystic disease and adenoma in the remaining kidney. Multiple embolization of RCC was considered to be linked to the cause of death. Although patients on long-term haemodialysis often have multiple renal cystic lesions, some of which are associated with tumour formation, RCC of this specific cell type in dialysed kidney has not been previously described.

Adult↗

Vascular injuries induced by materials released from platelet-rich thrombus in vivo.

Polyethylene tubing was inserted into the ascending aorta of rabbits via the right common carotid artery and placed for one or four weeks continuously to induce vessel wall injury and thrombotic events, and then the direct non-injured segments from the descending thoracic and abdominal aorta were examined morphologically and for [3H]thymidine incorporation into endothelial cells and smooth muscle cells. The descending aortas of experimental rabbits showed endothelial damage and increased mitosis of endothelial cells. [3H]Thymidine incorporation into the intima and media was significantly increased in the experimental group. This experiment indicates that materials released from activated platelets and/or thrombi into the circulation can cause endothelial damage and smooth muscle cell proliferation at downstream and remote aortic segments.

Animals↗

Diffuse white matter involvement seen in patients in longstanding bedridden state from cerebrovascular dementia.

We report here two autopsied cases of patients who had been in a longstanding bedridden state from cerebrovascular dementia. They showed a clinical history of persistent hypertension, a history of acute strokes, a lengthy clinical course with long plateau periods and a gradual accumulation of focal neurological symptoms and signs, including dementia and prominent motor disturbances and pseudobulbar palsy. They had been in a bedridden state for the last several years and had to be fed. The pathology seemed to predominently affect the perforating vessels to the subcortical gray and white matter. Demyelination, loss of axons, patchy gliosis and infiltration by macrophages were noted in the involved regions. The long penetrating vessels of the white matter showed advanced arteriosclerotic changes. There was a relative sparing of the cortex. The low attenuation of the white matter with moderate to severe atrophy, and an infarction might well be significant features on a CT-scan of these conditions. One of the possible mechanisms on the pathogenesis of chronic vascular disease includes diffuse ischemia related to hypertensive vasculopathy.

Aged↗

Disseminated necrotizing encephalopathy induced by methotrexate therapy alone.

This report describes the autopsy findings in a 62-year-old woman who died of pneumonia and disseminated necrotizing encephalopathy following intrathecal methotrexate (MTX) therapy for meningeal infiltration of lymphoma cells. Radiation therapy was not given. An interesting pathological finding was exudation of fibrin around the small vessels in the demyelinated foci, suggesting increased vascular permeability. This observation and analysis of previous reports of similar cases suggest that primary vascular injury, probably due to the direct effect of MTX, may be involved in the pathogenesis of MTX-related disseminated necrotizing encephalopathy.

Brain↗