[Hereditary protein S deficiency].
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Biomedical subjects
Publications and source records attributed to K Dohi.
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To clarify the role of locally secreted humoral factors in coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA), we studied the effects of coronary circulation-derived plasma from patients with and without restenosis on the growth of coronary artery smooth muscle cells (CASMC) in culture. Specific coronary plasma-dependent growth stimulation/inhibition of cells (CASMC and human umbilical venous endothelial cells) was estimated by subtracting the stimulatory activity, determined by bromodeoxyuridine incorporation, of the pre-coronary plasma from that of the post-coronary plasma. Coronary-specific plasma from five patients with restenosis showed a stimulatory effect on the growth of CASMC, whereas that from four patients without restenosis showed an inhibitory effect. On the other hand, they showed the opposite effects on the growth of endothelial cells. These findings suggested that the local environment is closely associated with the development of restenosis and may play a crucial role. Analysis of coronary circulation-derived plasma may facilitate clarification of the mechanism of restenosis.
We report a 63-year-old male patient with purpura nephritis, which appeared 7 days after extracorporeal shock wave lithotripsy (ESWL). He was referred to our clinic because of a petechial rash on both lower extremities, pretibial edema and massive proteinuria. Urinalysis showed proteinuria and hematuria and some hyaline casts. A 24-hour urine sample contained 5.0 g of protein. Renal function on admission was decreased: serum creatinine was 1.5 mg/dl and creatinine clearance, 21 ml/min. Immunoserological tests demonstrated an increase in serum IgA (424.3 mg/dl). A skin biopsy revealed leukocytoclastic vasculitis. A renal biopsy showed endocapillary proliferation in a diffuse, but segmental fashion. However, no crescent formation was seen. Immunofluorescence microscopy disclosed mesangial staining for IgA and C3. Electron microscopy demonstrated severe injury to endothelial and epithelial cells: detachment of endothelial and epithelial cells, foot process effacement and macrophage infiltration. Electron-dense deposits were observed in the subendothelial and paramesangial areas. Because renal function was deteriorating rapidly, methylprednisolone pulse therapy and immunosuppressive treatment were implemented. Treatment was effective and the patient's renal function and proteinuria improved remarkably. The electron microscopic findings in this case of purpura nephritis seemed to be more severe than usual, suggesting that ESWL may aggravate glomerular damage.
UNLABELLED: Histopathological findings were examined in the models of chronic pancreatitis. Using mongrel dogs, we prepared a control group (group C), a chronic ischemic group (group I), an alcohol administration group (group A), a duct obstruction group (group O), and an alcohol + obstruction group (group AO). Group I showed severe inflammatory cell infiltration, fibrosis, fat replacement and loss of acinar cells. Group A showed no change. In group O, mild periductal fibrosis was recognized. Group AO showed moderate inter-lobular fibrosis and inflammatory cell infiltration, resembling those of human chronic alcoholic pancreatitis. CONCLUSION: 1) Histological findings of chronic ischemic group is severer than that of group O and AO. 2) The model of alcohol administration with incomplete duct obstruction is a useful model of human chronic alcoholic pancreatitis.
We analyzed microsatellite instability, alterations of the polyadenine tract in TGF-beta RII (transforming growth factor beta type II receptor gene), and mutations of hMSH2 and hMLH1 in 32 patients with familial colorectal cancer (29 kindreds) fulfilling the clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC), defined at the 34th Annual Meeting of Japanese Society for Cancer of the Colon and Rectum (Tokushima, Japan, 1991), including five kindreds fulfilling the Amsterdam criteria. Eighteen of 32 (56%) cases were replication error positive (RER+) at two or more microsatellite loci analyzed. The clinicopathological characteristics of RER+ cases corresponded well with those reported previously. Eleven of 18 RER+ cases showed RER+ at most of the microsatellite loci examined. Among these 11 cases (10 kindreds), 3 kindreds fulfilled the Amsterdam criteria and 7 kindreds did not. For these 10 kindreds, germ-line mutations in hMSH2 and hMLH1 were detected for 6 kindreds by PCR-SSCP analysis and direct sequencing. Only two of these six fulfilled the Amsterdam criteria; more than one germ-line mutation was detected in hMSH2 and/or hMLH1. Specifically, two point mutations of hMSH2 were detected in two kindreds, one point mutation of both hMSH2 and hMLH1 was detected in one kindred, two point mutations of hMSH2 and one point mutation of hMLH1 were detected in one kindred, and two point mutations of hMLH1 and one point mutation of hMSH2 were detected in one kindred. In addition, 19 of 26 (74%) cancer lesions of these 11 cases with the RER phenotype showed alterations of the polyadenine tract in TGF-beta RII. From our data, although seven kindreds did not fulfill the Amsterdam criteria, we considered them as HNPCC. Therefore, we suggest that the "Japanese criteria" have the advantage of being able to detect more HNPCC kindreds from borderline HNPCC kindreds.
After resection of a non-invasive thymoma, two metastatic lung tumors were found in the left upper lobe and the left lower lobe. There were differences in tumor doubling time (TDT) and invasion between the metastatic tumor in the lower lobe and the one in the upper lobe. The TDTs of the tumors were 834.1 days and 328.3 days, and the tumor of the left lower lobe invaded the left lateral basal segmental bronchus (B9). The differences in the two tumors were determined by pathological findings and nuclear DNA pattern. Pathologically, the resected thymoma and both of the metastatic tumors were mixed type, which consisted of epithelial cells and lymphocytes. But by epithelium form, the resected thymoma and the tumor in the lower lobe were classified as cortex type, and only the slow growing tumor in the upper lobe contained a spindle-cell component. The DNA pattern of the resected thymoma was aneuploid and the two metastatic tumors were diploid. As this case is very interesting clinically and pathologically, we reported it.
A gene has been identified by mRNA differential display whose expression is reduced in the renal cortex of MRL/lpr mouse. The nucleotide sequence of the cDNA contains an open reading frame that encodes a protein of 338 amino acids (termed LN1). In situ hybridization showed that LN1 mRNA is present in glomeruli, and a 39 kDa protein was detected in the kidney by immunoblot. A human LN1 cDNA was also isolated, the deduced amino acid sequence of which is 78% identical to that of mouse LN1. Although the function of LN1 remains to be elucidated, its reduced expression may contribute to the pathogenesis of lupus nephritis.
Preservation with University of Wisconsin (UW) solution can maintain liver graft function and produces survival rates of recipients higher than that with Euro Collins (EC) solution. To explore the underlying mechanisms, we transplanted rat livers following cold preservation with EC or UW solution for 18 hr, and measured hepatic adenine nucleotide levels, the percentage of water content, lactate levels, and endogenous antioxidant levels (alpha-tocopherol [alpha-Toc], reduced coenzyme Q9 [CoQ9H2], reduced coenzyme Q10, [CoQ1OH2] and reduced glutathione [GSH] during preservation and after transplantation. The adenosine triphosphate levels of the liver grafts preserved with UW solution recovered after reperfusion more rapidly and reached a higher level than those preserved with EC solution. UW solution caused a reduction in hepatic water content during preservation. Conversely, EC solution induced remarkable tissue edema. In addition, UW solution reduced the rate of hepatic lactate production both during preservation and after reperfusion. The concentrations of hepatic GSH, alpha-Toc, CoQ9H2, and CoQ1OH2 immediately after the graftectomy, and after the 18 hr of preservation with both EC and UW solutions, did not differ from those in the normal liver, and decreased only after transplantation. However, UW solution suppressed significantly the reduction in hepatic GSH, alpha-Toc, and CoQ9H2 after reperfusion, compared with EC solution. These results suggest that long-term cold storage induces tissue edema, reflecting a disturbance of the microcirculation during preservation, followed by parenchymal cell damage mediated by free radicals after reperfusion. The protective effects of UW solution could be attributable to the inhibition of free radical production after reperfusion.
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We investigated the efficacy of a new rinse solution containing nafamostat mesilate (NM) (a serine protease inhibitor) for liver preservation with modulation of Kupffer cell function. Orthotopic liver transplantation (OLT) was performed in male Lewis rats after 24 h of cold storage in University of Wisconsin organ preservation solution. After OLT, survival was determined, together with assays of blood chemistry, tissue NM metabolites, and histology 3 h after OLT. NM rinse was found to have a cytoprotective effect on liver parenchymal cells, based on enzyme data showing that NM rinse reduced the release of serum alanine aminotransferase significantly in comparison with saline rinse (P < 0.05). However, the effect was not sufficient to improve the survival rate. In contrast, when the donor was treated with gadolinium chloride 24-30 h before graft harvest, NM rinse improved the survival rate to around 80% compared with 25% for saline. The assay of NM metabolites in grafted liver tissue showed that pretreatment of the donor rats with GdCl3 delayed the degeneration of NM in the liver tissue. These data demonstrate that NM rinse and Kupffer cell blockade exert synergistic effects, leading to increased survival after cold-preserved liver transplantation.
The glomerular features of patients with preeclampsia consist of swelling of endothelial cells, subendothelial deposits of incompletely defined material, and thickening of the capillary walls. These abnormalities are thought to resolve in the postpartum period. The distribution of extracellular matrix (ECM) components and integrins was investigated in 10 such patients. Frozen sections and paraffin-embedded sections were stained with antibodies to type IV collagen, laminin (LN), fibronectin (FN), vitronectin (VN), tenascin (TN), fibronectin receptor (FNR), and vitronectin receptor (VNR). In preeclamptic nephropathy, the accumulation of type IV collagen, LN, FN, TN, and FNR was observed in the thickened capillary walls, particularly in the subendothelial layer and, to some extent, in the mesangium. However, deposits of VN were sparse and the distribution of VNR was similar to that in normal kidney. In segmental sclerotic lesions, the amounts of type IV collagen, LN, FN, VN, and TN were increased, whereas those of FNR and VNR were markedly decreased. These results suggest that the materials deposited in the subendothelial space consist of ECM components as well as of plasma-derived proteins, and that the deposition of ECM components and of FNR may be involved in the development and the reparative process of the characteristic glomerular lesions. The formation of sclerotic lesions was linked to the accumulation of ECM components, but not to an interaction with integrins.
It is well known that ischemia causes functional and structural damage to liver cells, and that the status of energy metabolism provides an important means of assessing the functional viability of the ischemic organ. However, the specific sequence leading to ischemic liver cell injury is not yet fully understood; therefore, it is clinically and pathophysiologically important to elucidate the mechanism of cellular injury during hepatic ischemia and subsequent reperfusion. Whereas the conventional view attributes this injury process to the ischemia itself, recent studies have demonstrated that a variable but often substantial proportion of this injury is caused by reactive oxygen metabolites that are generated at the time of reperfusion. This article presents an outline of the mechanism of cellular injury caused during hepatic ischemia and subsequent reperfusion resulting from certain types of surgery, with special reference to the xanthine-xanthine oxidase system and the activation of neutrophils and macrophages.
Controversy exists over how the nutritional condition of the donor liver affects transplant outcome. Some studies suggest that livers from fasted animals (liver glycogen-depleted) are more readily injured than livers from fed animals. Our previous study suggested the opposite, i.e., livers from donors fasted for 4 days were significantly more viable on orthotopic liver transplantation. Fasting may decrease the sensitivity of the liver to an inflammatory response or block Kupffer cell activation following transplantation. Thus, long-term fasting may be beneficial for reasons unrelated to liver glycogen content. In this study we attempted to separate out the roles of fasting and liver glycogen in liver transplant outcome by fasting donors for 2 days and then feeding them only glucose to elevate liver glycogen. Rats (Brown Norway) were fed (standard diet), fasted (4 days), or fasted 2 days and then fed glucose (in water) for 2 days. Livers were preserved for either 30 or 44 h in UW solution and transplanted. Four-day fasting of the donor improved the survival rate in liver transplantation (50%-100% in 30-h cold storage, 29%-83% in 44-h cold storage). However, feeding glucose for 2 days to fasted animals caused a decrease in survival in this series of transplants (40% in 30-h cold storage, 0% in 44-h cold storage). In the glucose-fed group, liver glycogen was 240% of that in the control group. This suggests that the presence of a high concentration of liver glycogen is not beneficial to the preserved and transplanted rat liver.
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A 69-year-old man developed obstructive jaundice 6 months after laparoscopic cholecystectomy. Endoscopic retrograde cholangiography suggested a common bile duct (CD) stone. A second operation was performed, and this revealed a CBD stone with an endoclip as a nidus. Since laparoscopic surgery has become a very common procedure, endoclips are used more frequently. Therefore, careful surveillance and strict follow-up are stressed to avoid CBD stone and various other complications caused by endoclips.
Post-ischemic injury is one of the most important problems affecting successful organ procurement and transplantation. The present study was performed to determine whether alpha-tocopherol can protect the endocrine function of pancreatic grafts against ischemia-reperfusion injury during rat heterotopic pancreatic transplantation. Rats with streptozotocin-induced hyperglycemia were used as recipients. The donor pancreas was removed and subjected to warm ischemia at 37 degrees C for 30, 60, 90 and 120 min, and then transplanted into a recipient. A 30-min period of warm ischemia did not impair the endocrine function of the pancreatic grafts, which was assessed by measuring the blood glucose levels and glucose decay constants (K), and a 60-min period of warm ischemia was considered to be the critical period for reversible tissue damage. Pretreatment with alpha-tocopherol (20 mg/kg/day, i.v.) for seven days before graftectomy significantly decreased blood glucose levels to less than 200 mg/dl and significantly increased K values in the recipient rats after transplantation when compared with placebo pretreatment. These results suggest that alpha-tocopherol pretreatment can protect the endocrine function of pancreatic grafts against injury due to warm ischemia followed by reperfusion.