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Biomedical subjects

R Harada

Publications and source records attributed to R Harada.

At least 55 records · Page 3Linked to original sources

Effects of Chinese herbal drug, dai-saiko-to on plasma lipids, lipoproteins and liver lipid contents in guinea pig.

Effects of Chinese herbal drug, Dai-saiko-to, on plasma lipids, lipoproteins and liver lipid contents were investigated in guinea pig with/without cholesterol feeding. Guinea pigs were divided into 4 groups (Group 1: normal chow (N) diet, Group 2: N + 1% Dai-saiko-to (D) diet, Group 3: 1% cholesterol (C) diet, Group 4: 1% C+ 1% D diet), and were treated for 5 weeks. Significant body weight reductions were observed in Groups 3 and 4 compared to Groups 1 and 2. Significant reductions of plasma triglyceride (TG) and very low and low density lipoproteins [(V) LDL]-TG were found in Group 3 compared to Groups 1, 2, and 4. (HDL)-TG significantly decreased in Groups 3 and 4 compared to Groups 1 and 2, but no significant difference was noted between Groups 1 and 2, and Groups 3 and 4. Liver lipid contents analysis showed no significant changes between Groups 1 and 2, and Groups 3 and 4, respectively, but the distribution of lipid droplets as pathologically determined using a computer program showed Group 4 had less lipid deposition compared to Group 3. These data suggest that Dai-saiko-to acts on triglyceride metabolism in hypercholesterolemic guinea pigs.

Alanine Transaminase↗

Putative mechanisms of action of probucol on high-density lipoprotein apolipoprotein A-I and its isoproteins kinetics in rabbits.

Probucol is a widely prescribed lipid-lowering agent, the major effects of which are to lower cholesterol in both low- and high-density lipoproteins (LDL and HDL, respectively). The mechanism of action of probucol on HDL apolipoprotein (apo) A-I kinetics was investigated in rabbits, with or without cholesterol feeding. 125I-labeled HDL was injected intravenously, and blood samples were taken periodically for 6 days. Kinetic parameters were calculated from the apo A-I-specific radioactivity decay curves. Fractional catabolic rate (FCR) and synthetic rate (SR) of apo A-I in rabbits fed a normal chow and normal chow with 1% probucol were similar. Apo A-I FCR of the rabbits fed 0.5% cholesterol was significantly increased but there were no changes in SR, compared to findings in the normal chow-fed group. Apo A-I FCR of the rabbits fed 1% probucol with 0.5% cholesterol (both 1 month and 2 months) was significantly increased compared to findings in rabbits fed the normal chow as well as 0.5% cholesterol diet group, while SR of apo A-I was significantly reduced in the former groups. Kinetics at 1 month after discontinuation of 1% probucol (under cholesterol feeding) showed a similar FCR of HDL-apo A-I to that of the rabbits fed 0.5% cholesterol, but the SR of apo A-I remained lower. Apo A-I isoproteins kinetics assessed by autoradiography of isoelectric focusing slab gels showed that the synthesis of proapo A-I was significantly reduced in the 1% probucol with 0.5% cholesterol administered, compared to the 0.5% cholesterol group. Thus, the action of probucol on HDL apo A-I kinetics was only prominent in case of higher serum cholesterol levels. The decreased HDL or apo A-I seen with probucol was apparently the result of an increase in FCR and a decrease in SR of HDL-apo A-I. A decreased synthesis of apo A-I remained evident even 1 month after discontinuing probucol. The action of probucol on the intracellular synthetic processes of apo A-I was revealed by the reduced synthesis of proapo A-I.

Animals↗

High idiotypic connectivity of the VH7183-encoded antibodies directed to a murine embryonic carbohydrate antigen, Lewis Y, as ascertained by syngenic anti-idiotype monoclonal antibodies.

The Lewis Y Ag is a carbohydrate Ag which is closely related to a well-known murine embryonic Ag, the stage-specific embryonic Ag-1 (SSEA-1), in its biochemical structure. It is expressed at the surface of murine embryonic cells as well as many murine cancer cells. For the analysis of idiotopes carried by the anti-Lewis Y antibodies, we generated two syngenic anti-idiotypic mAb, Id-A1 and Id-B4 (both BALB/c IgG1), which are directed to the idiotypic determinants carried by the anti-Lewis Y mAb, AH-6 (BALB/c IgM). Both Id-A1 and Id-B4 (Ab2) recognized paratope-related idiotopes carried by the AH-6 antibody (Ab1); they specifically inhibited the binding of AH-6 to the Lewis Y Ag. The high idiotypic connectivity of anti-Lewis Y antibodies was noted; the polyclonal anti-idiotype antibody, produced in the sera of BALB/c mice by immunizing AH-6 antibody, cross-reacted with several anti-Lewis Y mAb which has been established in different laboratories. Id-B4 and Id-A1 seem to represent such cross-reactive anti-idiotypic antibodies. Id-A1 recognized an idiotope carried by two out of six panel Ab1 mAb directed to the Lewis Y Ag. Id-B4 reacted with four out of the six panel antibodies, and was considered to recognize a recurrent idiotope of anti-Lewis Y antibodies which occurs more commonly than the idiotope recognized by Id-A1. All of the anti-Lewis Y antibodies which carry idiotopes that react with Id-A1 or Id-B4 were encoded by the VH genes of the VH7183 family; the most D-J proximal VH gene family in BALB/c mice, which is known to be preferentially expressed in embryonic B cells. Immunization of BALB/c mice with keyhole limpet hemocyanin-conjugated Id-B4 and/or Id-A1 induced a significant titer of anti-Lewis Y antibodies (Ab1-like Ab3) in the sera.

Animals↗

Purification of 1F5 antigen that prevents complement attack on homologous cell membranes.

A mAb, 1F5, has the ability to cause hemolysis by human serum of human E treated with neuraminidase via the alternative C pathway. By Western blotting, this mAb reacts with a glycoprotein having a molecular mass of 20 kDa (1F5Ag). 1F5Ag was isolated from human E by affinity chromatography with mAb-coupled Sepharose. Purified 1F5Ag was then adsorbed to guinea pig E rendering them resistant to human C attack by both the classical and the alternative pathways. Furthermore, experiments with isolated C components revealed that 1F5Ag interferes with both homologous human C8 and C9 in the terminal stage of the C reaction, whereas it has little effect on hemolysis by rabbit C8 and C9. Therefore, 1F5Ag can be called HRF20, which stands for homologous restriction factor of 20 kDa.

Amino Acid Sequence↗

Biosynthesis, processing, and intracellular transport of lysosomal acid phosphatase in rat hepatocytes.

The biosynthesis, processing, and intracellular transport of lysosomal acid phosphatase was studied using an in vitro cell-free translation system, pulse-chase experiments with primary cultured rat hepatocytes and subcellular fractionation techniques of rat liver after pulse-labeling with [35S]methionine in vivo. The single polypeptide of 45 kDa translated in the cell-free system from membrane-bound polysomal RNAs was converted to the 64 kDa form when the translation was carried out in the presence of microsomal vesicles. Pulse-chase experiments using cultured rat hepatocytes showed that acid phosphatase is initially synthesized as an endo-beta-N-acetylglucosaminidase H (Endo H)-sensitive form of 64 kDa, and processed via an Endo H-sensitive intermediate form of 62 kDa to an Endo H-resistant form with a 67 kDa mass. Phase separation with Triton X-114 showed that both the 64 and 67 kDa forms have hydrophobic properties. Treatment of the cells with chloroquine or tunicamycin, drugs which enhance the secretion of lysosomal hydrolases, had no effect on the normal transport of acid phosphatase to lysosomes. Acid phosphatase did not contain the phosphorylated high mannose type of oligosaccharide chains observed in cathepsin D. Subcellular fractionation experiments in conjunction with pulse-labeling in vivo showed that the acid phosphatase of the 67 kDa form was present in the Golgi heavy fraction (GF3) and the Golgi light fraction (GF1+2) enriched in cis and trans Golgi elements, respectively, at 30 min after the administration of [35S]methionine. Simultaneously, this polypeptide was also found in the lysosomal membrane fraction, thereby indicating that acid phosphatase is delivered to lysosomes in a membrane-bound form, immediately after reaching the trans-Golgi region.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Erythrocytes of patients with paroxysmal nocturnal haemoglobinuria acquire resistance to complement attack by purified 20-kD homologous restriction factor.

A 20-kD homologous restriction factor (HRF20) which is a membrane inhibitor of the terminal stage of human complement action can be detected by the monoclonal antibody 1F5, and is deficient on abnormal erythrocytes as well as leucocytes from patients with paroxysmal nocturnal haemoglobinuria (PNH). The erythrocytes of PNH patients significantly improved their resistance to homologous complement after adsorption of purified HRF20.

CD59 Antigens↗

Lupus nephritis with adult T cell leukemia.

A 64-year-old Japanese male patient with lupus nephritis associated with adult T cell leukemia (ATL) is described. Percutaneous renal biopsy demonstrated findings consistent with membranous lupus nephritis. To our knowledge, this is the first case of lupus nephritis complicated by ATL, suggesting that human T cell leukemia virus type I may be correlated not only to outbreaks of ATL but also to lupus nephritis/systemic lupus erythematosus.

Humans↗

[The removal efficiency of beta 2-microglobulin, alpha 1-microglobulin and alpha 1-acid glycoprotein by using dialyzers in the bloodstream and transference of endotoxin through membranes].

Retention of beta 2-microglobulin (beta 2-MG) has been indicated as one of the causes of hemodialysis-associated amyloidosis. Membranes with higher permeability (high-performance membrane) have recently been developed accordingly. Several dialyzers were tested by us in an attempt to study their removal efficiency of beta 2-MG and higher molecular substances of alpha 1-microglobulin (alpha 1-MG) and alpha 1-acid glycoprotein (alpha 1-AG), as well as transferring of endotoxin (ET) through membranes into bloodstream. The membranes subjected to our study were PMMA, CTA, PS, EVAL-C and CA. Removal efficiency of beta 2-MG through EVAL-C and CA was lower as compared with that through other membranes (P less than 0.05), while the EVAL-C showed relatively higher removal efficiency for alpha 1-MG and alpha 1-AG. Permeability for ET was not observed with all membranes studied herein.

Alpha-Globulins↗

[A case of Fabry's disease detected by renal biopsy findings].

A 39 year-old man was found to have mild proteinuria by urinary examination since one year ago. He was for the first time diagnosed as having Fabry's disease by histopathological and electronmicroscopic findings of the renal biopsy specimens, which showed the presence of numerous vacuolated cells and electron dense bodies inside the cells. The level of WBC alpha-galactosidase was significantly lower than normal level. The pedigree of this patient showed a familial history of various types of renal disease. One of the patient's brothers also showed decreased level of WBC alpha-galactosidase, who has been treated by maintenance hemodialysis for 2 years. It is concluded that early diagnosis of this disease through renal biopsy and WBC alpha-galactosidase level is important to manage the future course of patients with Fabry's disease.

Adult↗

[A case of acute potassium bromate intoxication].

We experienced a case of a 44 year old man who had ingested potassium bromate solution for suicide attempt. Soon after the ingestion, nausea, vomiting, abdominal pain and diarrhea developed in him. Several hours later, he began to complain of auditory disturbance and, in addition, anuric acute renal failure occurred. Direct hemoperfusion and hemodialysis was performed on the patient for the treatment purpose. Five weeks later, he was released from hemodialysis procedure. Gradually, on the other hand, progressing anemia was observed until 90th hospital day, which slowly improved thereafter. Further, pruritus, lower leg pain, headache, tinnitus and loss of sense of taste, etc. were observed in the clinical course. Renal biopsy was performed on the 119th hospital day and the specimen showed the regenerative stage of acute tubular necrosis. In our case, acute renal failure was reversible and, many other clinical manifestations were observed. However slight anemia and irreversible severe auditory disturbance remained unimproved.

Acute Kidney Injury↗

[A case of blue rubber-bleb nevus syndrome with CAPD].

The first case of blue-rubber-bleb nevus syndrome treated with CAPD in Japan was presented. As operation for A-V fistula construction could not be performed due to the skin lesions, she was obliged to have CAPD treatment. She has been visiting our hospital for regular check-ups.

Female↗

[Disturbance of the autonomic nerve system in patients with chronic renal failure--represented by variation coefficient of R-R intervals in the ECG as a parameter].

Autonomic nerve dysfunction in patients with chronic renal failure has of late become an issue to be investigated. R-R intervals in resting electrocardiograms were measured to evaluate activities of the cardiac parasympathetic nerve system. A total of 140 patients with chronic renal failure were studied to be compared with 20 normal controls (cont.) and 39 with diabetes mellitus (DM). Of these patients 15 were subjected to conservative treatment (CRF), while 125 patients were undergoing hemodialysis due to chronic renal failure-100 of them derived from chronic glomerulonephritis (HD) and 25 from diabetes mellitus (DM.HD). The variation coefficient of the R-R interval (CVRR) was measured after the subject patients had rested for over 15 minutes before a dialysis session. The mean CVRR were 2.15 +/- 1.25% in CRF group, 2.36 +/- 1.37% in HD and 1.37 +/- 0.99% in DM.HD. These values were significantly lower than in control group (4.70 +/- 2.64%). On the other hand, the value in DM.HD group, as shown above, was significantly lower than in HD. In CRF group the CVRR values lowered as residual renal functions decreased. No significant correlations between CVRR S and the duration of hemodialysis treatment were noted among the groups. In HD group the CVRR S were significantly lower in patients with hypotensive tendency during hemodialysis than in those who enjoyed good control of blood pressure. These results suggest that the measurement of CVRR S can be of help in evaluating autonomic nerve dysfunction in patients with chronic renal failure.

Adult↗

Cardiac function of WHHL rabbit, an animal model of familial hypercholesterolemia.

To investigate the cardiac function of WHHL rabbit (WHHL), an animal model of familial hypercholesterolemia, electrocardiography (ECG) and echocardiography (UCG) were taken from this species of homozygous type and normolipidemic Japanese White rabbits (controls). In WHHL, two of four had intraventricular conduction disturbances (IVCD) in ECG. UCG study showed that the ejection fraction significantly increased (p less than 0.05) and deceleration time was shortened (p less than 0.01) in WHHL compared to normal controls.

Animals↗

Complete deficiency of 20 KDa homologous restriction factor (HRF20) and restoration with purified HRF20.

20 KDa homologous restriction factor (HRF20) is a membrane glycoprotein which inhibits formation of membrane attack complexes of homologous complement. Erythrocytes from a patient who is completely deficient in HRF20 were readily hemolyzed by homologous complement activated by sucrose or by acidification as in paroxysmal nocturnal hemoglobinuria (PNH). After incubating PNH erythrocytes (PNH-E) with purified HRF20, the cells were analyzed by flow cytometry using a monoclonal antibody to HRF20 and shown to have the antigen absorbed. These PNH-E acquired resistance to hemolysis by homologous complement suggesting that HRF20 may be successfully used for treatment of these patients.

Adult↗

Monoclonal antibodies capable of causing hemolysis of neuraminidase-treated human erythrocytes by homologous complement.

As human E (HuE) treated with neuraminidase (Neu) are resistant to hemolysis by human serum but are readily lysed by heterologous serum via the alternative C pathway, we attempted to produce mAb which might modify Neu-treated HuE (Neu-HuE) so as to render them sensitive to homologous C. A hybridoma, clone -1F5, was obtained by screening for antibody which caused hemolysis of Neu-HuE by human serum via the alternative C pathway. We have shown that this antibody (1F5) of IgG1 isotype blocks the action of a 20-kDa membrane inhibitor capable of interfering with the terminal step in the homologous C cascade. The antigenic molecule can be termed HRF20, which stands for homologous restriction factor (HRF) with m.w. 20,000, because its function is essentially the same as that of HRF (68,000) reported by others.

Animals↗

A novel membrane glycoprotein capable of inhibiting membrane attack by homologous complement.

Neuraminidase-treated human erythrocytes become sensitive to haemolysis by heterologous serum via activation of the alternative complement pathway (ACP), while remaining insensitive to homologous serum because of the presence of inhibitors on the cell membrane. We obtained a monoclonal antibody which renders the neuraminidase-treated erythrocytes sensitive to haemolysis by homologous human serum via the ACP. This antibody reacts with a 20 KDa membrane glycoprotein which interferes with the terminal stage of complement action on cell membranes. The 20 KDa protein is anchored to the membrane via phosphatidylinositol.

Antibodies, Monoclonal↗