A new allele at the lpr gene on mouse chromosome 19 expresses properties different from the original recessive mutation.
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Alleles↗
Biomedical subjects
Y Sakai
Publications and source records attributed to Y Sakai.
Long-term culture of primary rat hepatocytes with high albumin secretion using membrane-supported collagen sandwich.
Primary cultured rat hepatocytes in a membrane-supported collagen sandwich maintained their normal cell morphology and high level of albumin secretion for over 56 days. It was found that the existence of an upper layer of collagen gel is crucial for long-term culture and that the transference of cellular nutrients between the culture media and hepatocytes from both the upper and the lower sides of gel layers promotes albumin secretion. These facts suggest that the membrane-supported collagen sandwich mimics well the in vivo environment of hepatocytes. This method has great potential for the long-term culture of primary cells.
Albumins↗
Longitudinal changes of plasma pancreatic enzymes and hormones in experimental pancreatolithiasis in dogs.
Plasma pancreatic enzymes and hormones were longitudinally observed after producing partial obstruction of the major pancreatic duct in dogs to study an initial state of chronic pancreatitis or pancreatolithiasis. Fasting plasma immunoreactive cationic trypsin was elevated during the first six months and then decreased in a subgroup with pancreatic calculi, marked fibrosis, or duct dilatation when compared with the corresponding opposite at the end of the 12-month period. Similar but less prominent changes were found in fasting plasma immunoreactive pancreatic polypeptide (IRPP). Plasma amylase, glucose, or immunoreactive insulin or glucagon (IRG) show no significant variation. Plasma IRG and IRPP responses to intravenous insulin were reduced in the subgroups with marked pancreatic changes towards the end of the 12-month period. These results suggest that plasma pancreatic enzymes and hormones remain elevated as long as pancreatic damage is mild and then start to decline as the damage progresses in chronic pancreatitis or pancreatolithiasis.
Amylases↗
Necrotizing chorioretinitis in mice inoculated with herpes simplex virus type 1 with or without glycoprotein C: anterior chamber-associated immune deviation does not persist.
BALB/c mice developed contralateral necrotizing retinitis following intracameral inoculation with herpes simplex virus type 1 (HSV-1). The animals showed a positive delayed-type hypersensitivity (DTH) response at 10 days postinoculation, indicating that the anterior chamber-associated immune deviation was transient after HSV-1 inoculation. Since glycoprotein C (gC) of HSV-1 is a major immunogen, we examined DTH and the antibody response induced by a gC-deficient strain TN-1 and compared them with those induced by the recombinant gC-positive mutants. We found that gC was not required for DTH reaction, and that gC was neither necessary for nor protective against the contralateral retinal necrosis. Serial lymphocyte subset analyses of the draining lymph nodes revealed an absolute increase of B cells, CD4-positive T cells, and CD8-positive T cells. CD4-positive T cells but not CD8-positive T cells increased in the contralateral eyes during the inflammation and necrosis. The coincident emergence of the positive DTH and contralateral retinal necrosis of HSV-1-inoculated mice, together with the presence of CD4-positive cells in the retina, indicated that CD4-positive T cells responsible for DTH induction may participate in the retinal necrosis.
Animals↗
Induction of bilateral retinal necrosis in mice by unilateral intracameral inoculation of a glycoprotein-C deficient clinical isolate of herpes simplex virus type 1.
Herpes simplex virus can cause acute retinal necrosis, a blinding retinal disease in man. A unilateral intracameral inoculation of herpes simplex virus type 1 (HSV-1) in mice induces retinal necrosis primarily in the contralateral eye and provides an experimental model for the disease. Previous studies suggested that a major envelope glycoprotein of HSV-1, glycoprotein C (gC), is required for retinal necrosis. We studied HSV-1 strain TN-1, a gC-deficient clinical isolated from a lesion of herpetic keratitis, for its pathogenicity in mice with an intracameral inoculation of the virus and found that TN-1 could induce severe necrotizing retinitis in both inoculated and uninoculated eyes of BALB/c mice. Inoculation with a lower dose of TN-1 resulted in a unilateral necrotizing retinitis in the uninoculated eyes. Tissue virus titration of infected mice killed at various times after inoculation detected an infectious virus in various organs including the eyeballs, trigeminal ganglia, brain and adrenal glands. Anterior chamber-associated immune deviation (ACAID) was observed in TN-1-inoculated mice as well as in mice inoculated with gC-positive laboratory strain KOS 7 days postinoculation. Our findings suggested that gC of HSV-1 is not necessary for either the induction of retinal necrosis, neural spread of the virus, or ACAID.
Adrenal Glands↗
Nucleolar and dispersed nucleolar organiser regions (NORs) in differentiating neoplastic from atypical non-neoplastic lesions of the pancreas.
Our objective was to compare the accuracy of differentiation of pancreatic carcinoma from the benign ductular aggregation of chronic pancreatitis using two methods, nuclear morphometric analysis and modified argyrophilic nucleolar organiser region (AgNOR) staining for nucleoli and dispersed NORs (AgNU staining). We evaluated 35 metastatic or invasive lesions of pancreatic carcinoma with low-grade atypia, 16 lesions of ductular aggregation and 12 lesions of proper epithelium. Four parameters, consisting of the size of nucleus: mean area, mean minor axis, mean major axis and mean perimeter, and two parameters of AgNu staining: mean number of AgNu-stained dots per nucleus (equal to mean number of nucleoli and dispersed NORs) and mean area of the largest AgNu-stained dot (equal to mean area of the largest nucleolus) of pancreatic carcinomas were significantly larger than those of ductular aggregations and of proper epithelia. In the discriminant analysis of four parameters of nuclear size, the discrimination of carcinomas was correct in 82.9% and that of ductular aggregations in 81.3%. Discriminant analysis by two parameters of AgNu staining showed 2 correct discrimination of lesions in 88.6% and 100%. Thus, AgNu staining was more accurate than nuclear morphometric analysis in discriminating a pancreatic carcinoma from ductular aggregation.
Carcinoma, Intraductal, Noninfiltrating↗
Serum pancreatic stone protein in pancreatic diseases.
Serum pancreatic stone protein (PSP) was determined in sera of pancreatic and nonpancreatic diseases using enzyme immunoassay specific to human PSP to study the diagnostic and pathophysiological significance of PSP. Serum PSP in acute pancreatitis (mean +/- SD = 1075.4 +/- 2849.1 ng/mL, n = 33) was significantly higher than that in controls (78.6 +/- 31.8 ng/mL, n = 37, p < 0.01), chronic pancreatitis (156.8 +/- 82.8 ng/mL, n = 32, p < 0.05), and pancreatic cancer (148.468.8 ng/mL, n = 26, p < 0.05). No significant difference was found between noncalcified and calcified chronic pancreatitis. Serum PSP levels were significantly higher in chronic renal failure under hemodialysis (1796.0 +/- 1492.9 ng/mL) than in other diseases such as peptic ulcer, liver cirrhosis, gallstone, and diabetes mellitus. Low but significant correlation was obtained between serum PSP and serum immunoreactive trypsin (r = 0.22, p < 0.05). Increased serum PSP levels in acute pancreatitis and chronic renal failure suggest that serum PSP levels reflect reflex from pancreatic secretion, release from damaged pancreatic acinar cells, or retention in circulation, and can be useful for diagnosis of acute pancreatitis, but not chronic calcified pancreatitis.
Acute Disease↗
Effect of lymphoblastoid alfa-interferon in patients with chronic hepatitis C having different genotypic subtype of hepatitis C virus.
Five subtypes of hepatitis C virus (Pt[I], K1[II], K2a[III], K2b[IV] and Tr[V]) have been suggested based on the nucleotide sequence of the non-structural five region. To assess the susceptibility of each subtype to interferon therapy, we developed a one-step method which allows quick determination of subtype using polymerase chain reaction with a mixed primer set deduced from the sequence of each subtype. We were able to determine the subtype of 69 of 80 (86.3%) Japanese patients who received natural alfa-interferon treatment. The incidence of each subtype was K1: 53 (76.8%), K2a: 14 (20.3%), K2b: 3 (4.3%) and Tr: 1 (1.4%). Interferon was administered to these patients and found to be effective in 28 of 51 (54.9%) patients with K1 subtype and in 16 of 18 (88.9%) patients with other subtypes (P < 0.01). These data show that K1 is a major subtype in Japan and relatively resistant to interferon treatment.
Adult↗
Coronary flow reserve in patients with dilated cardiomyopathy.
Coronary flow reserve was studied in patients with dilated cardiomyopathy. A 3F coronary Doppler catheter was placed in the proximal left anterior descending artery in each of 10 patients with dilated cardiomyopathy (CDM group), seven patients with coronary artery disease that involved only the left anterior descending artery (CAD group), and seven patients with chest pain syndrome and normal hearts (control group). Coronary flow reserve was calculated as the ratio of the maximum mean coronary blood flow velocity after intracoronary administration of papaverine (10 mg) to resting flow velocity (M/R). The time until maximum flow velocity was reached after papaverine administration (Tmax) was also measured. M/R was lower in the DCM (p < 0.001) and CAD (p < 0.001) groups when compared with the control group. Tmax was not abnormal in the DCM group but was prolonged in the CAD group (p < 0.05). In the DCM group, the M/R ratio correlated with the left ventricular end-diastolic pressure (r = -0.69; p < 0.05), the left ventricular end-diastolic volume index (r = -0.7; p < 0.05), the ejection fraction (r = 0.82; p < 0.01), the left ventricular mass (r = -0.7; p < 0.05), and the left ventricular end-diastolic wall stress (r = -0.84; p < 0.001). These results indicate that coronary flow reserve was decreased in patients with dilated cardiomyopathy and that the mechanism of its reduction may differ from that in patients with coronary artery disease.
Adult↗
Cholangioscopic extraction of intrahepatic stones associated with biliary strictures using a rendezvous technique.
Two patients with a severe biliary stricture of one intrahepatic duct and associated intrahepatic stones were successfully treated after dilatation of their stricture by a new endobiliary rendezvous technique with the aid of percutaneous transhepatic cholangioscopy (PTCS). The strictured bile duct was approached from a contralateral percutaneous tract via PTCS and from the diseased duct by introducing a guidewire. This guidewire was then extracted through the other side using a PTCS-guided biopsy forceps to form a communication between both sides which could be used as a pathway for subsequent dilatation. Our technique allows the extraction of intrahepatic stones even in the presence of biliary strictures.
Adult↗
Production and characterization of specific asialoglycoprotein receptor antibodies.
Monoclonal antibodies (MoAbs) were produced by immunizing BALB/c mice with asialoglycoprotein receptor (AGPR) purified from human liver. The purity of AGPR was confirmed by SDS-polyacrylamide gel electrophoresis and by amino acid sequence. An enzyme-linked immunoassay revealed 24 monoclonal antibodies which reacted with human AGPR. By Western blot analysis, all antibodies recognized the 46 kDa human AGPR under the non-reduced conditions and four MoAbs recognized reduced protein. Two MoAbs reacted with AGPR derived from rat, rabbit and mouse liver under both non-reduced and reduced conditions, suggesting that we could obtain antibodies which reacted with AGPR epitopes shared by different species. In immunohistochemical studies, 30201-MoAb reacted with human liver tissue but not with other tissues. This antibody immunoprecipitated two major bands of 46 kDa and 39 kDa from [35S]-methionine metabolically labeled human hepatoma HepG2 cells. The determinant recognized by 30201-MoAb is a common epitope of AGPR which is present in different species and in both the precursor and maturation forms of the receptor.
Amino Acid Sequence↗
Hepatitis C virus infection in alcoholic liver cirrhosis in Japan: its contribution to the development of hepatocellular carcinoma.
To determine risk factors for hepatocellular carcinoma (HCC) in Japan, we studied 575 patients with liver cirrhosis (LC) who presented to our out-patient clinics in a month; 217 patients with habitual drinking with or without viral infections (AL-LC), 235 with hepatitis C virus (HCV) infection, 40 with hepatitis B virus (HB) infection, and 82 with liver diseases from other aetiologies such as primary biliary cirrhosis (PBC). HCC was found in 28% of AL-LC, 27% of HCV-LC, and 18% of HB-LC. HCV antibody examined by the second-generation HCV antibody assay (HCV II) was positive in 49% of AL-LC without HCC, and 84% of AL-LC with HCC. HCV was significantly associated with the development of HCC with an odds ratio of 1.90 by multivariate analysis, whereas alcohol alone did not become a risk factor, with an odds ratio of 0.65. When both variables were combined (HCV+AL), however, the odds ratio was increased twice to 3.65. One-hundred and thirteen patients who had a history of blood transfusion more than 10 years ago were selected to assess the interaction between alcohol and HCV in hepatocarcinogenesis. A year-adjusted disease occurrence rate calculated by the Kaplan-Meyer method showed that HCV+AL had a significantly higher disease occurrence rate than HCV alone. These results suggest that although alcohol alone may not become a risk factor for HCC, it may potentiate the development of HCC caused by HCV. HCV+AL is considered to be the highest risk group; strict abstinence is necessary for these patients.
Adult↗
Effect of a new synthetic trypsin inhibitor on taurocholate-induced acute pancreatitis in rats.
The effect of a novel synthetic trypsin inhibitor, 4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate (ONO-3307), on severe acute pancreatitis was studied by changing its timing, frequency, and dose in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of ONO-3307 administration: group A, 2 mg/0.5 ml of ONO-3307 s.c. 1 h before and after induction of pancreatitis; group B, 2 mg/0.5 ml s.c. 1 and 3 h after; group C, 4 mg/1 ml s.c. 1 h before; group D, 4 mg/1 ml s.c. 1 h after. The survival rate at 24 h was significantly improved in group A (75% in A vs. 17% in control; p < 0.01) and in group B (57 vs. 29%; p < 0.05), but not in group C or D. Amylase and immunoreactive trypsin in serum and ascites of the treated were significantly lower than those of controls in both groups A and B. The survival rates were improved dose dependently when ONO-3307 was administered 1 h before and after induction of pancreatitis. ONO-3307 showed favorable effects on the initial stage of severe acute pancreatitis when given in divided doses to maintain the effective serum levels.
Acute Disease↗
Tolerance by old livers of prolonged periods of preservation in the rat.
To determine the tolerance of old livers to prolonged preservation, livers from aged rats (corresponding to humans in the sixth to seventh decades of life) were transplanted after specific periods of cold preservation. Male BN/BiRij rats received orthotopic, arterialized liver grafts from either young (5 months) or old (25 to 28 month) donor rats after liver storage for 12 (n = 6), 24 (n = 6) or 30 (n = 10) hours in University of Wisconsin solution. Outcome was assessed by survival, liver enzymes after transplantation, and histology of the grafts. There were no significant differences in survival rates between recipients of old and young grafts. All rats survived after 12-hr and 24-hr preservation except one recipient of an old graft preserved for 24 hr. After 30-hr preservation recipients of old and young livers had identical survival rates (60%). There was a strong correlation between the highest postoperative AST and ALT and the duration of preservation in all groups (P < 0.0001), but only in the 24-hr preservation experiments was the ALT significantly higher in recipients of old grafts than in recipients of young livers (P = 0.025). Age of the donor did not significantly affect the peak AST, but there was a correlation between donor age and the highest postoperative ALT (P = 0.007). Although intracellular vacuolization was a prominent histological finding in more than half of the old livers at the end of preservation, it was not associated with an increase in mortality. It is concluded that under the ideal conditions provided in the experiments, old rat livers tolerate long preservation periods with satisfactory graft survival compared with young livers.
Age Factors↗
The effect of donor-recipient strain combination on rejection and graft-versus-host disease after small bowel/liver transplantation in the rat.
The initial clinical experience with simultaneous small bowel/liver transplantation (SBL) suggests that liver grafting may protect the small bowel from rejection. A pilot study of SBL in DA (RT1a) rats with Lewis (RT1l) allografts in our laboratory provided experimental support for this concept. However, the clinical applicability of the data was questioned because the transplants were performed in a low-immune-responder rat strain combination. This study examined the outcome of SBL in several rat strain combinations. Isolated small bowel transplants (SB) and SBL were performed in three groups: DA-->PVG (low immune responder), BN-->LEW (intermediate immune responder) and ACI-->LEW (high immune responder). Lewis-->Lewis isografts were used as controls. All of the rats with SB rejected their allografts, whereas all of the rats with simultaneous liver grafts had minimal or no signs of intestinal rejection. The outcome of SBL was profoundly affected by the donor-recipient strain combination. The low immune responders developed severe graft-versus-host disease. The intermediate immune responders developed mild-to-moderate GVHD and moderate liver rejection. The high immune responders developed severe liver rejection. In this study, the outcome of small bowel transplantation depended upon the strain combination used and whether or not a simultaneous liver graft was transplanted. The immune interactions that occur after multi-visceral transplantation are complex and cannot be easily predicted.
Animals↗
Effect of magnetic field on pineal gland volume and pinealocyte size in the rat.
Light microscopic observations on the superficial pineal gland of Wistar-King rats were made to examine whether or not pineal volume and pinealocyte size, expressed as nuclear density, at daytime or nighttime are affected by long-term exposure to 50 Hz rotating magnetic field (MF) at 5.0 microT. Determinations of pineal volume and pinealocyte size were repeated twice (April and October) during the year. Size of pinealocytes in MF-exposed and sham-exposed rats exhibited, in addition to the difference between peripheral and central regions, regional differences in a proximodistal direction; pinealocytes in the distal and middle-peripheral regions were usually larger than those in the proximal and middle-central regions at daytime or nighttime. In October, distal and proximal pinealocytes showed significant day-night changes in size in sham-exposed rats, but not in MF-exposed animals. The situations in the two groups were almost reversed in April. Significant day-night differences were scarcely found in pinealocyte size in the middle region in the two groups. Throughout the study, pineal volume and pinealocyte size in each region were generally the same between MF-exposed and sham-exposed rats at daytime or nighttime. The results suggest that pinealocytes in the distal and proximal regions, but not those in the middle region, are affected by MF-exposure; day-night differences in sizes of distal and proximal pinealocytes appear in April and disappear in October under the influence of MF. MF may exert an effect on mechanisms controlling day-night rhythms of pinealocyte size in the rat.
Animals↗
High-frequency transformation of a methylotrophic yeast, Candida boidinii, with autonomously replicating plasmids which are also functional in Saccharomyces cerevisiae.
We have developed a transformation system which uses autonomous replicating plasmids for a methylotrophic yeast, Candida boidinii. Two autonomous replication sequences, CARS1 and CARS2, were newly cloned from the genome of C. boidinii. Plasmids having both a CARS fragment and the C. boidinii URA3 gene transformed C. boidinii ura3 cells to Ura+ phenotype at frequencies of up to 10(4) CFU/micrograms of DNA. From Southern blot analysis, CARS plasmids seemed to exist in polymeric forms as well as in monomeric forms in C. boidinii cells. The C. boidinii URA3 gene was overexpressed in C. boidinii on these CARS vectors. CARS1 and CARS2 were found to function as an autonomous replicating element in Saccharomyces cerevisiae as well. Different portions of the CARS1 sequence were needed for autonomous replicating activity in C. boidinii and S. cerevisiae. C. boidinii could also be transformed with vectors harboring a CARS fragment and the S. cerevisiae URA3 gene.
Acetates↗
Oxygen demand-supply relationship in peripheral tissues as a therapeutic indicator in acute myocardial infarction with advanced heart failure.
Oxygen demand-supply relationships in peripheral tissues were studied in 14 patients who had acute myocardial infarction with advanced pump failure. Seven patients with acute myocardial infarction but without pump failure were studied as a control. In all patients, a Swan-Ganz catheter and a radial arterial cannula were inserted for the purpose of hemodynamic monitoring, and arterial and mixed venous blood were sampled. Initially, oxygen delivery (DO2) (p < 0.01) was lower, and oxygen extraction ratio (OER) (p < 0.001) and oxygen tension at 50% saturation (P50) (p < 0.01) were higher in patients with pump failure than in the controls. During the therapeutic course, with an increase in the cardiac index and DO2, oxygen uptake (VO2) did not change but OER (p < 0.001) and P50 (p < 0.01) significantly decreased in 6 survivors with pump failure. In contrast, an increased VO2 (p < 0.01) and no change of OER and P50 were observed in 8 nonsurvivors with pump failure. These results suggest that reversibility of oxygenokinetics might be an important factor for recovery from critical heart failure.
Aged↗