Biomedical subjects
Publications and source records attributed to M Gotoh.
A rare case of the pituitary apoplexy was presented in this paper. Computerized tomography clearly showed a blood-fluid level in the pituitary adenoma.
In order to understand the mechanism of clinical worsening in patients with cerebral infarction, attention was focused on the changes in cerebral angiograms obtained repeatedly before and after neurological deterioration. Among 212 stroke patients with minor neurological deficits, incomplete hemiparesis progressed to complete hemiplegia in 15 patients several days after the beginning of symptoms. On admission, 3 had internal carotid artery occlusion, 2 had stenosis of the internal carotid artery, 5 had occlusion of the middle cerebral arterial trunk, 2 had occlusion of the middle cerebral arterial branch, and 3 had no angiographically visible occlusion. The changes between the first and the second angiograms were of different varieties: another recurrent occlusion, progression of occlusion, new occlusion in the cerebral arteries opacified through the collateral pathway, recanalization of the initially occluded artery, and no change. Such different patterns of pathophysiological events show that the mechanism of neurological worsening in infarcted patients is not uniform. Based on the results from the present study, several problems which arose during the investigation and the somewhat vague definition of "progressing stroke" currently in use are discussed.
In the study of cardiac abnormalities responsible for the development of cerebral embolism two-dimensional echocardiography was performed on 350 patients with ischemic cerebrovascular disease. The results were compared with those obtained from 350 controls without any history of stroke. Atrial fibrillation was detected on ECG in 115 cases (33%) of the patients and in 35 cases (10%) of the controls (p less than 0.001). The structural cardiac diseases observed in stroke patients were: rheumatic heart disease (RHD) in 37, congestive cardiomyopathy (CCM) in 7, hypertrophic cardiomyopathy (HCM) in 19, mitral annulus calcification (MAC) in 29, mitral valve prolapse (MVP) in 9, and myocardial infarction (MyI) in 10 patients. Controls were found to have these lesions in 11, 2, 3, 12, 4 and 9 patients respectively. RHD (p less than 0.001), HCM (p less than 0.01) and MAC (p less than 0.01) were significantly more frequent in patients with ischemic cerebrovascular disease, but not MyI, CCM or MVP. Intracardiac thrombi were diagnosed in 29 cases of patients and in 4 cases of controls (p less than 0.001). Our data suggested that nonrheumatic heart diseases such as MAC and HCM could also be considered as causes of embolic stroke. The reasons for the variable frequencies of cardiac abnormalities reported in the literature for stroke patients are discussed.
We have previously shown that mitomycin C (MMC) treatment of donor tissue resulted in significant prolongation of graft survival in allo- and xenotransplantation models. However, the mechanisms involved in this prolongation are not clearly understood. This study aims to shed light on the immune responses to MMC-treated islet xenografting under the kidney capsule. Collagenase-digested WS (RT1k) rat islets incubated for 30 min with MMC and subsequently cultured for 20 h were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 (B6;H-2b) mice. The grafts were harvested on postgrafting day 7 and sections were prepared and stained by hematoxylin and eosin (H&E). Histological study of the grafts in a group not treated with MMC showed marked cellular infiltration and destruction of islet clusters, whereas that of MMC-treated grafts demonstrated a bleb formation under the kidney capsule, in which islet cell clusters were reorganized, creating a layer of cells fixed to the interior of the bleb. Minimal invasion by inflammatory cells was observed only at the edge of the bleb, and most islet cells were protected from these infiltrating cells. In conclusion, MMC treatment induces remodeling of islet structure and forms a bleb under the kidney capsule, where no inflammatory cell infiltration occurs, suggesting that this site is a kind of immunologically privileged environment for xenografted islets.
The liver is thought to be an immunologically privileged organ in the response to inoculated antigens. We previously demonstrated that it is possible to localize inoculated antigens to the liver alone or only to extrahepatic tissue using orthotopic syngeneic liver transplantation (OSLT). In this study, we analyzed more detailed mechanisms of the anti-alloimmune response in the liver. DA rat spleen cells were systemically injected into WS rats (donor spleen cell inoculation, DSI). In the sensitized liver-grafted (SLG) group, after DSI, liver grafts were retrieved from sensitized WS rats, then transplanted into naive WS rats. In the sensitized liver-removed (SLR) group, after DSI, WS rats were totally hepatectomized and given livers transplanted from naive WS rats. All the rats were challenged with heterotopic heart grafts 10 days after DSI. Mean heart graft survival in the control, DSI, SLG, and SLR groups were 11.6+/-1.6, 10.7+/-2.4, 4.4+/-1.0, and 24.6+/-6.3 days, respectively. Accelerated rejection in the SLG group as well as graft prolongation in the SLR group disappeared when OSLT was performed 2 days after DSI or later. Irradiation of DA splenocytes before inoculation did not alter graft survival in SLG. However, pretreatment with gadolinium chloride prior to DSI attenuated the antidonor response in the SLG group. In conclusion, a vigorous antidonor response occurred in the liver after systemic inoculation of spleen cells. It peaked I day after DSI and disappeared rapidly. Kupffer cells seemed to play an important role in this phenomenon.
It is controversial whether or not microchimerism (MC) is responsible for the induction and maintenance of donor-specific tolerance. We have shown that intraportal injection (i.p.) of donor splenocytes induces a long-term graft survival of liver and heart in rats. In this study, we examined by polymerase chain reaction (PCR) the status of MC in the liver, spleen, and blood of rat cardiac recipients following i.p. or intravenous injection (i.v.) of donor splenocytes. Male DA (RT1a) and Wistar (RT1k) rats were used as donors and recipients, respectively. Heterotopic heart transplantation was performed 10 days after i.p. or i.v. injection of 5 x 10(7) DA spleen cells. DA cardiac allografts were rejected with a mean survival time (MST) of 11.9 +/- 1.6 (n = 10) days in nontreated recipients. Injections (i.v.) led to no significant prolongation of graft survival (MST: 11.2 +/- 1.9 days, n = 6), while i.p. or i.v. injection alone resulted in significant MC in these organs throughout the observation time over 60 days. MC was detected in the spleen, liver, and blood of cardiac recipients 7 days after transplantation and also even after cessation of cardiac heartbeat 21 days after transplantation. This was the case with either i.p. or i.v. group, which showed MC on day 7 after transplantation and persistent MC after cessation of the heartbeat. These data suggests that the presence of MC in the liver, spleen and blood of transplant recipients may not be responsible for immunological unresponsiveness to donor antigens.
In this study, we examined the effect of mitomycin C (MMC) treatment on graft survival and evaluated its efficacy in immunomodulation of islet graft for transplantation. Male WS rats were used as islet donors and streptozotocin-induced diabetic C57BL/6 mice as recipients. The isolated islets were treated with MMC at concentrations of 0, 0.1, 1, 3.2, 10, 32, 100, 320, and 1000 microg/mL for 30 min, and were cultured for 20 h. Then, 300-400 islets were transplanted into the renal subcapsular space of diabetic mice. Significant prolongation of graft survival was obtained when the islets were treated with MMC at a concentration of 10, 32, or 100 microg/mL (MST 23 +/- 7.4, 17.5 +/- 5.4, 29.6 +/- 9.7 days: p < 0.003, p < 0.012, p < 0.001, respectively, vs. 12.3 +/- 2.7 days for culturing alone). Islets treated with MMC at a concentration of 320 microg/mL or more failed to restore normoglycemia in the diabetic recipient mice after transplantation. Viability of islets incubated with doses up to 100 microg/mL, assessed under the confocal microscope after propidium iodide and Hoechst 33342 staining, was maintained well comparable to that of freshly isolated islets, while those treated at 320 microg/mL was significantly decreased. Thus, a therapeutic window for MMC efficacy was found at concentrations from 10 microg/mL to 100 microg/mL. This modality is simple and effective and underlying molecular mechanisms need to be determined in the future.
Alveolar macrophages (AMs) are cells with unique characteristics because of their localization in the aerobic environment and are receiving stimuli by inhalation. To estimate the functional changes of AMs induced by inflammation, a murine model of aspiration pneumonia was made by an intratracheal injection with carragheenan, whose mortality rate was approximately 25%. The cell component which increased predominantly in the inflammatory site was polymorphonuclear leukocytes, and the number of AMs did not show a remarkable increment. Control group showed a high level of intracellular oxidation of 2'7'-dichlorofluorescin (DCFH) by AMs, while that in carragheenan-treated mice decreased significantly (p < 0.05). There were two populations in AMs classified according to the oxidative activity of DCFH; the population showing high oxidative activity of DCFH was asialo GM1 positive, in contrast, that with lower oxidative activity was asialo GM1 negative. Decrease in DCFH-oxidative activity of AMs in control group was observed after a treatment with KCN or deferoxamine. But in the carragheenan-treated group, this decrease was not observed after treatment with KCN. These results show that both oxygen-derived radical produced in mitochondria, which is inhibited by KCN, and cytoplasmic OH radical, which is selectively inhibited by deferoxamine, are concerned with intracellular oxidation of DCFH by AMs, and that a decrease in DCFH-oxidative activity in the carragheenan-treated group was attributed to the depression of mitochondrial respiration. Nevertheless, increased expressions of Ia and F4/80 in AMs of the carragheenan-treated group were observed and phagocytic activity was well preserved at the control level. These results suggest that AMs may play a crucial role, as well as differentiated phagocytes possessing antigen-presenting ability and/or digestive activity against various types of foreign bodies despite showing an obvious decrement in oxidative activity. These results imply that AMs have a strong oxidative activity and deal with various types of antigens in normal states, but in case of acute inflammation they will change into mature type macrophages with high expression of class II molecules which correlates with an antigen-presenting capacity.
Malignant tumors of three types were synchronous in the same patient--sigmoid colon cancer and two extremely rare sarcomas, viz. hepatic leiomyosarcoma and hemangiosarcoma of the spleen. All tumors could be radically resected in one operation.
The relationship between macroscopic growth pattern of main tumor and postoperative survival was retrospectively investigated in 155 patients with resectable hepatocellular carcinoma. The survival of single nodular type (type I, n = 75) was significantly better than that of single nodular type with proliferation into the surrounding area (type II, n = 53) or massive type (type V, n = 13). The frequency of intrahepatic metastasis or portal tumor thrombus in the resected specimens was significantly lower in patients with type I than in those with type II or V (p < 0.05). Patients with type I undergoing segmentectomy (Hr1) had better survival than those with hepatic resections of less than 1 segment (Hr0, p < 0.05). However, such difference was not observed in patients with either type II or V. Moreover, the presence of a cancer-free surgical margin (1 cm or more) significantly affected the long-term prognosis (5-7 years after surgery) in type I but not in type II, suggesting that the intrahepatic spread of tumor might be localized around the main tumor in type I. On the other hand, intrahepatic metastasis and portal involvement were frequently observed in type V and the prognosis was extremely poor even when major hepatic resections were performed. These results indicate that the macroscopic growth pattern of main tumor is an important predictor for hepatocellular carcinoma.