Search PubMed⌕ Search

Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 631 records · Page 35Linked to original sources

The protective effect of the trypsin inhibitor urinastatin on cerulein-induced acute pancreatitis in rats.

We examined the protective effects of the trypsin inhibitor, urinastatin, extracted from human urine in experimental acute pancreatitis in conscious rats. Acute pancreatitis was induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Urinastatin at a dose of 50,000 U/kg body weight/6.5 h was given by continuous i.v. infusion beginning 0.5 h before the first cerulein injection and continuing until 3 h after the last one, for a total of 6.5 h. Urinastatin significantly reduced serum levels of amylase, lipase, and anionic trypsin(ogen) but did not affect pancreatic wet weight or protein or enzyme content. Urinastatin also significantly reduced the degree of acinar cell vacuolization, interstitial edema, and cellular infiltration. These results suggest that urinastatin does not block the induction of acute pancreatitis by cerulein but does substantially reduce its severity.

Acute Disease↗

Selective inhibition of high- but not low-affinity interleukin 2 binding by lectins and anti-interleukin 2 receptor alpha antibody.

The present study demonstrated that various reagents can specifically reduce the affinity of high-affinity interleukin 2 receptor (IL-2R) but not that of low-affinity IL-2R. They included lectins such as wheat germ agglutinin (WGA), concanavalin A and phytohemagglutinin, and a chemical cross-linker, glutaraldehyde, in addition to anti-IL-2R monoclonal antibodies, HIEI and H-47. The affinity of the high-affinity IL-2R was reduced when the cells were treated with WGA or H-47 before, but not after, addition of 125I-labeled interleukin 2 (IL-2). Their inhibitory effects were also demonstrated by the chemical cross-linking method. On treatment with the reagents, the IL-2 binding to both IL-2R alpha and beta chains was inhibited and these inhibitory effects were seen only when the reagents were added before IL-2 addition, like their high-affinity reducing effects. These results support a supposition that the high affinity IL-2R is generated by assembly of the alpha and beta chains, and suggest that the IL-2 binding to IL-2R alpha and beta chains could induce stable constitution of the high-affinity state of IL-2R, but these affinity modulating reagents could perturb the optimum association between alpha and beta chains to generate the high-affinity IL-2R.

Antibodies, Monoclonal↗

Albumin gene transcription is enhanced in liver of nephrotic rats.

The level of albumin mRNA and the transcription rate of the albumin gene were studied in the liver of control rats and rats with nephrosis induced by injection of the aminonucleoside of puromycin. Total RNA was extracted from liver by the guanidium thiocyanate method. The albumin mRNA level was measured by cDNA-RNA dot-blot hybridization, and the transcription rate of the albumin gene was measured by the "run-on" transcription assay using isolated nuclei. Urinary protein excretion in nephrotic rats was significantly higher than in control rats (258 +/- 132 vs. 12 +/- 2 mg/day), and the serum albumin concentration in nephrotic rats was significantly lower. There was no difference in body weight, liver weight, serum creatinine, or urea nitrogen between the two groups. Both the level of albumin mRNA and the transcription rate of the albumin gene in the nephrotic liver were about twice as high as those in the control liver. There was no difference in the level of beta-actin mRNA between the two groups. Northern blot analysis showed that both putative precursor RNA and the mature form of albumin mRNA were increased in nephrotic rats. We conclude that albumin synthesis is increased in the liver of nephrotic rats and a transcriptional process is responsible for this increase.

Actins↗

Effect of salicylic acid on mitochondrial-peroxisomal fatty acid catabolism.

To understand the possible role of salicylic acid in the pathogenesis of Reye's syndrome, we examined its effect on the oxidative metabolism of fatty acids in the rat liver mitochondrial-peroxisomal fraction. Fatty acids of different chain lengths are oxidized in different organelles. Octanoic acid is oxidized in mitochondria, lignoceric acid in peroxisomes, and palmitic acid in both mitochondria and peroxisomes. Salicylic acid (up to 1 mM concentration) had no effect on the oxidation of [1-14C]lignoceric acid. However, at the same concentration it inhibited the oxidation of [1-14C]palmitic acid by 26% and [1-14C] octanoic acid by 42%. The apparent Ki for the oxidation of [1-14C] octanoic acid, [1-14C]palmitic acid and [1-14C]lignoceric acid were 0.27, 6.0, and 14.8 mM, respectively. This selective inhibition of mitochondrial oxidation of medium-chain (octanoic acid) and long-chain (palmitic acid) fatty acids by salicylic acid may potentiate the accumulation of fatty acids in plasma in Reye's syndrome patients.

Animals↗

Physical properties of flowing blood.

The changes of viscosity, optical reflection and electrical resistivity of blood due to flow are dependent on the orientation and deformation of red cells. From electrical point of view, it can be assumed that blood is suspension of small insulating particles (red cells) in conductive fluid (plasma) when the frequency of supplied voltage is lower than several hundreds KHz. When blood flows, red cells deform and orient in flow direction. Therefore, flowing blood shows anisotropic electrical and optical properties. In steady flow, blood resistivity longitudinal to flow decrease with flow rate, and transverse one increases. Blood flow in living body is not steady but pulsatile. We measured both longitudinal and transverse resistivity changes, optical reflection change and viscosity change of sinusoidally flowing blood in a rectangular conduit. The results are 1) during one period of sinusoidal flow the longitudinal resistivity change is opposite to that of transverse one, 2) the waveform of reflection light change is similar to that of resistance change, and 3) minimum points of both longitudinal resistivity and viscosity changes do not appear at the moment when flow is zero but are delayed. When the amplitude of sinusoidal flow is small and oscillation frequency is high, the phase difference between the zero crossing period of flow and the period of minimum change in resistivity, increases up to 90 degrees. Viscosity of blood decreases with increase of amplitude and frequency of sinusoidal flow.

Animals↗

[Combined radiotherapy and chemotherapy for head and neck cancer].

There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neoadjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary.

Animals↗

[Transcatheter hepatic arterial chemoembolization using microencapsulated mitomycin C (MMCmc)].

Thirty-six patients with hepatocellular carcinoma were treated by hepatic arterial chemoembolization of microencapslated mitomycin C (MMCmc). The infusion cannulae were placed in the hepatic artery by the Soldinger method, and 10 to 40 mg of MMCmc was injected 1 to 4 times (total doses, 10-110 mg). The evaluation of anti-tumor effects revealed 12 partial responses in 27 evaluable lesions and response rates were 44%. The serum AFP levels were decreased in 70% of patients. The survival rate for 12 months was 35% in all patients, but 67% at Stage III. The control of liver function is also important, because the hepatic failure and esophageal varices were the main causes of death. Side effects such as fever and pain were seen in 70%, but they were mild.

Adult↗

[Induction of endogenous antitumor activities in the portal vein by using a subcutaneously-imbedded pediculated spleen in the rat; experimental study of adjuvant immunotherapy in liver metastases].

For the purpose of inducing the antitumor effect in the portal vein, the intrasplenic serial biological response modifier (BRM) administration was performed by using our original subcutaneously-imbedded pediculated spleen in the rats. In a view point of endogenous tumor necrosis factor (TNF) production, lipopolysaccharide, BCG and OK-432 were chosen and injected into the spleen frequently. The study of the portal blood serum revealed that intrasplenic (i.s.) BRM administration group gained higher TNF and interferon (IFN) activity than control group. On the other hand, the study of the mononuclear cells in the portal vein and splenocyte after i.s. BRM administration showed higher cytotoxic activity against YAC-1 cells than control group significantly. Compared with intravenous and intraperitoneal administration groups, i.s. group showed more effective antitumor effects in the portal vein significantly. The experimental liver metastases by intraportal transplantation of AH60C could be cured with i.s. BRM administration, which could increase % survival significantly. According to the result of this study, it is prospective that i.s. serial BRM administration could be new process for suppression of transportal hepatic metastases.

Animals↗

Simultaneous production of natural human tumor necrosis factor-alpha, -beta and interferon-alpha from BALL-1 cells stimulated by HVJ.

B-cell human lymphoblastoid cell line, BALL-1, produced interferon-alpha (IFN-alpha) and cytotoxic factors by the stimulation of hemagglutinating virus of Japan (HVJ). These cytotoxic factors were identified to be tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) on the basis of molecular level analysis. In the kinetic study, it was found that the maximum production of IFN-alpha was reached at 16-20 hr and that of TNF-alpha was at 10-16 hr after the stimulation by HVJ, whereas the maximum production of TNF-beta was at 40-50 hr, suggesting that the regulation of TNF-alpha and TNF-beta genes are different. These cytokines were purified by monoclonal antibody linked column chromatography, respectively. IFN-alpha was further separated into 9 subspecies on the basis of the difference of isoelectric point by FPLC chromatofocusing method. From the N-terminal amino acid sequence analyses of the 7 species of 9 subspecies, these subspecies were classified into 3 subtypes according to the Weissmann's notation. On the other hand, the amino acid sequence of the tryptic peptides of purified TNF-alpha and TNF-beta coincided well with the parts of the complete amino acid sequences which had been deduced from complementary DNA of TNF-alpha and TNF-beta of BALL-1 cell.

Amino Acid Sequence↗

Germanium-induced nephropathy: report of two cases and review of the literature.

We report two cases of renal failure following long-term ingestion of germanium dioxide (GeO2) and comment on eight other cases reported in Japan. Ge-induced nephropathy is characterized by insidious onset of renal failure without proteinuria or hematuria after oral intake of Ge-containing compounds for more than several months, and by degeneration of renal tubular cells with minor glomerular abnormality in histology. When patients ceased to ingest Ge compounds, renal function gradually recovered but never returned to the normal range. Serious extrarenal complication can contribute to an unfavorable prognosis.

Acute Kidney Injury↗