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Biomedical subjects

T Sawamura

Publications and source records attributed to T Sawamura.

157 records · Page 9Linked to original sources

Hyperasialoglycoproteinemia in patients with chronic liver diseases and/or liver cell carcinoma. Asialoglycoprotein receptor in cirrhosis and liver cell carcinoma.

The pathogenesis of hyperasialoglycoproteinemia in cirrhosis and liver cell carcinoma was investigated by measuring the amount of asialoglycoprotein receptor in hepatic tissues from 30 patients with either cirrhosis or a malignancy. The asialoglycoprotein receptor activity in the cirrhotic liver was 770 +/- 423 U/g liver, i.e., 28% of the control value (2770 +/- 731 U/g liver). Receptor activity was negligible in tissues from patients with either liver cell carcinoma or metastatic tumor. The receptor levels in noncirrhotic and cirrhotic tissues in close proximity to liver cell carcinoma were 2281 +/- 659 and 1134 +/- 473 U/g liver, respectively. There was a close correlation between serum asialoglycoprotein levels and the size of the tumor mass in patients with liver cell carcinoma. Our results suggest that decreases in the asialoglycoprotein receptor levels may lead to an accumulation of serum asialoglycoproteins in patients with cirrhosis or liver cell carcinoma, or both.

Asialoglycoprotein Receptor↗

[Studies of red cell deformability and lipid composition of red cell membrane in chronic arterial occlusive diseases].

Red cell deformability (RCD), by a filtration method, was studied on patients with chronic arterial occlusive diseases: Arteriosclerosis obliterans (ASO) and Buerger's disease (TAO). RCD decreased significantly in both ASO and TAO. Furthermore, RCD decreased in patients with gangrene and complications in other organs much more than in those without them in ASO. In ASO positive correlation was observed between RCD and serum HDL-cholesterol level, while negative correlation between RCD and serum lipid peroxide level. The deformability of the red cells resuspended in a standard plasma protein fraction was also studied to assess the influences of plasma factors on RCD. As the result decreased RCD was considered probably due to a change in red cells rather than plasma factors in ASO.

Adult↗

Distribution of an asialoglycoprotein receptor on rat hepatocyte cell surface.

Direct ferritin immunoelectron microscopy was applied to visualize the distribution of the hepatocyte cell surface of the asialoglycoprotein receptor which is responsible for the rapid clearance of serum glycoproteins and lysosomal catabolism. For this purpose, rabbit antibody against the purified hepatic binding protein specific for asialoglycoproteins was prepared and coupled to ferritin by glutaraldehyde. The specific antibody conjugates were incubated with the hepatocytes, which were isolated from rat liver homogenate after fixation by glutaraldehyde perfusion. These cells preserved well the original polygonal shape and polarity, and it was easy to identify the sinusoidal, lateral, and bile canalicular faces. The surface density of the ferritin particles bound to the sinusoidal face was about four times higher than that of particles bound to the lateral face, while the bile canalicular face was hardly labeled and almost at the control level. Using the surface area of hepatocyte measured by morphometrical analyses, it was estimated that approximately 90% of bound ferritin particles were at the sinusoidal face, approximately 10% at the lateral face, and approximately 1% at the bile canalicular face. Nonhepatic cells such as endothelial and Kupffer cells had no receptor specific for asialoglycoproteins.

Animals↗

Biosynthesis and insertion of a hepatic binding protein specific for asialoglycoproteins into endoplasmic reticulum membranes.

Biosynthesis of a hepatic binding protein specific for asialoglycoproteins and its subsequent insertion into microsomal membrane were studied by using antibody monospecific for the binding protein. 125I-Labeled antibody binds much more preferentially with membrane-bound ribosomes than with free ribosomes, and nascent binding protein labeled with [3H]puromycin was detected exclusively on tightly membrane-bound ribosomes, which can be detached from the membrane by puromycin treatment in the presence of high salt buffer. When rough microsomes labeled in vivo with 14C-amino acid mixture were digested with protease, nascent binding protein was effectively protected from the digestion like nascent albumin (approximately 90%). When rough microsomes labeled in vitro with [3H]puromycin were digested with protease, the degree of protection of albumin was again approximately 90%, whereas that of the binding protein was only approximately 50%. The carbohydrate moieties of the binding protein and the bulk of glycoproteins in the microsomes labeled in vivo with [3H]glycosamine and [3H]mannose were also effectively protected from the protease digestion (approximately 90%). These results indicate that the binding protein is exclusively synthesized on the membrane-bound ribosomes and spans the microsomal membrane probably exposing the carboxyl-terminal segment on the cytoplasmic surface and the amino-terminal segment charged with carbohydrate moieties on the luminal surface, respectively.

Animals↗

Decrease of a hepatic binding protein specific for asialoglycoproteins with accumulation of serum asialoglycoproteins in galactosamine-treated rats.

Acute liver injury was induced experimentally in rats by a single injection of a large amount of D-galactosamine. Hepatocellular damage was apparent from decrease of total serum proteins, marked release of transaminases into the circulation, precipitous decrease of total microsomal proteins, and intracellular enzymes such as cytochrome P450 and 5'-nucleotidase. In parallel with such hepatocellular damage, serum asialoglycoproteins accumulated markedly, reaching a maximum level 4 days after the injection and then decreased to the control level. In contrast to this increase, hepatic binding protein, a receptor in the liver which specifically recognizes asialoglycoproteins, decreased very much. At the same time, survival time of [125I]asialoorosomucoid intravenously administered into rats was much prolonged in inverse proportion to the decrease of the binding protein. From these results it was concluded that the decrease of the hepatic binding protein induced by galactosamine treatment is probably responsible for the marked accumulation of serum asialoglycoproteins.

Animals↗

Localization of nascent NADPH-cytochrome c reductase in rat liver microsomes.

Rat liver microsomes incubated with [3H] puromycin in high salt buffer were digested with a mixture of protease, trypsin and chymotrypsin, in both the presence and absence of 1 % deoxycholate. Our observations revealed that the proteolysis of peptidyl puromycin labeled with [3H] puromycin was at least partially protected by the presence of microsomal membrane. Immuno-chemical analyses have further shown that most of the nascent NADPH-cytochrome c reductase in the microsomes was digested with the proteases while serum albumin was effectively protected from the digestion. It is thus proposed that NADPH-cytochrome c reductase synthesized on the membrane bound ribosomes is not transported to the vesicular cavity but directly to the outer surface of the microsomal membrane in a form which is accessible to the proteases.

Acyltransferases↗

Hormone profiles and testicular histology in azoospermic men with sex chromosome aberrations, autosomal anomalies and normal karyotype.

Hormone profiles and testicular histology were studied in azoospermic men with sex chromosome aberrations, autosomal anomalies, and normal karyotype. In patients with sex chromosome aberrations, levels of plasma gonadotropins were significantly higher than those with autosomal anomalies and normal karyotype. The testosterone level in plasma was considerably lower in those with sex chromosome aberrations than in other groups. The prolactin level in plasma was not significantly different among the three groups. The administration of LH-RH resulted in a remarkably lower response of plasma gonadotropins in sex chromosome anomalies than in other groups. The response of plasma testosterone to the administration of hCG was also significantly decreased in those with sex chromosome aberrations compared with other groups. Johnsen score count and diameter of the seminiferous tubules were considerably reduced in those with sex chromosome anomalies compared with other groups, while wall thickness and Leydig cells per seminiferous tubule were significantly increased. It would appear that hormone disturbances and testicular alterations are less marked in azoospermic men with autosomal anomalies than in those with sex chromosome aberrations.

Adult↗

Gonadal function and testicular histology in Noonan's syndrome with bilateral cryptorchidism.

Testicular histology and gonadal function were studied in 2 patients with Noonan's syndrome accompanied by bilateral cryptorchidism. Plasma FSH level was elevated above the normal range, but plasma levels of LH, prolactin, and testosterone were within normal ranges in both cases. The administration of LH-RH resulted in abnormally high response of plasma gonadotropins in both cases. The response of plasma testosterone to the administration of LH-RH was poor in case 2, but case 1 showed normal response. Testicular histology showed reduction of tubular diameter, Leydig cells per seminiferous tubules, and spermatogonia per tubule in both cases. The results indicate that bilateral cryptorchid patients with Noonan's syndrome have an abnormality in the hypothalamo-pituitary-gonadal axis.

Child↗

Hormone profiles and testicular histology in cryptorchid boys with marker chromosome.

Hormone profiles and testicular histology were studied in two cryptorchid boys with marker chromosome. Plasma testosterone levels were abnormally low in both cases. Plasma levels of gonadotropins and prolactin were within normal ranges in case 1, but case 2 showed decreased concentration of plasma gonadotropins and normal level of plasma prolactin. The administration of LH-RH induced low response of plasma gonadotropins in case 1 and exaggerated response in case 2. The response of plasma testosterone to the administration of hCG was poor in both cases. Testicular histology showed maturation arrest and reduction of tubular diameter and Leydig cells per seminiferous tubules in both cases. Although testicular histology in these cases were similar to those in prepubertal or pubertal boys with cryptorchidism, hormonal disturbances were more severe. It would appear that marker chromosome enhances hormonal alterations.

Adolescent↗

Serum levels of total and free testosterone in men undergoing hemodialysis.

Serum concentrations of total and free testosterone were measured in 102 hemodialysis male patients and 45 healthy men. In hemodialysis patients, serum levels of total and free testosterone were significantly reduced compared to the controls (p < .001). Neither serum total nor free testosterone correlated with age in the controls. In contrast, both total and free testosterone in serum negatively correlated with age in hemodialysis patients (p < .05-.001). It would appear that testicular dysfunction becomes more severe with increasing age in hemodialysis patients.

Adult↗