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Biomedical subjects

F Shimizu

Publications and source records attributed to F Shimizu.

At least 145 records · Page 8Linked to original sources
PubMed1988

The effect of thymectomy on the development of nephropathy in spontaneous thymoma rats of the BUF/Mna strain.

A close relationship was assumed between the developments of nephropathy and thymoma in the previous study, in which the effect of introduction of the rat nude gene was studied in high thymoma BUF/Mna rats. In this paper, the effect of neonatal thymectomy on the development of nephropathy was examined to clarify the relationship between these two lesions in BUF/Mna rats. The average amount of urinary protein excreted from sham-operated and thymectomized BUF/Mna rats was 30.8 +/- 17.1 and 40.0 +/- 20.0 mg/day, respectively, and the number of affected glomeruli per 100 glomeruli 4.9 +/- 1.0 and 5.3 +/- 2.0, respectively. There were no significant differences in the urinary protein content, the number of the affected glomeruli, and immunofluorescence findings. In a control group, ACI/NMs rats exhibited 8.9 +/- 2.6 mg/day protein in urine and 0.8 +/- 0.4% affected glomeruli, which were significantly different from that of sham-operated and thymectomized BUF/Mna rats. These results indicate that nephropathy in BUF/Mna rats results neither from thymoma itself nor from the immunological abnormality secondary to it, and suggest that this lesion might be ascribed to a genetic factors.

Animals↗
PubMed1987

Nephritogenicity of anti-Engelbreth-Holm-Swarm sarcoma antibody.

We have examined the antibody activity and nephritogenicity of anti-Engelbreth-Holm-Swarm (EHS) sarcoma antiserum in order to analyze the pathogenesis of the EHS nephropathy which has already been reported by us. An increased amount of urine protein was not recognized in rats injected with a large quantity of anti-EHS sarcoma antiserum. In addition, rats immunized with rabbit IgG before anti-EHS sarcoma antiserum injection developed no abnormal proteinuria, despite positive fluorescent staining for rat IgG as well as rabbit IgG in the glomeruli. From these results we concluded that nephritogenic antibodies could not be produced in rabbits by immunization with EHS sarcoma, which could induce the EHS nephropathy in an active model.

Animals↗
PubMed1987

Effects of combined treatment with nimustine hydrochloride and radiation on solid FM3A tumor in mice.

Female C3H/HeN mice bearing solid FM3A tumors were treated with a combination of ACNU (or Nimustine hydrochloride) and radiation in order to investigate the antitumor effects and also to determine the optimal treatment schedule of ACNU in such combined therapy. ACNU was intravenously injected either twice with an interval of 2 weeks and a dose of 30 mg/kg (intermittent large-dose treatment), or as 4 weekly doses of 15 mg/kg (fractionated small-dose treatment). Local irradiation (5 Gy) at the tumor site was performed twice with an interval of 2 weeks between the doses. Synergistic effects were obtained by the combination of ACNU and radiotherapy in terms of tumor growth inhibition and prolongation of survival. Histology also revealed much greater reduction of viable tumor cells in the case of combination treatment. With either treatment with ACNU alone or in combination with irradiation, the intermittent large-dose injections resulted in better inhibition of tumor growth than did the fractionated small-dose injections, but the survival times with the intermittent treatments were not as prolonged as would be expected from the direct effects. Loss of body weight and depression of WBC number were also much more severe in the intermittent treatment group. Thus, it may be concluded that when ACNU is combined with radiotherapy, the intermittent large-dose regimen is not necessarily superior to the fractionated small-dose one.

Animals↗
PubMed1987

Protective effect of nimustine hydrochloride against radiation-induced pulmonary injury in mice.

Female C3H/HeN mice were irradiated in the thorax at a dose ranging from 10 to 25 Gy with or without ACNU (nimustine hydrochloride) treatment in order to determine whether the chemotherapeutic agent would lead to an enhancement of radiation-induced lung damage. ACNU given intravenously at 15 mg/kg immediately prior to irradiation reduced the mortality of mice irradiated with a low dose; mortality with either radiation alone or radiation plus ACNU was 4/10 (40%) or 0/10 (0%) at 13.1 Gy, and 9/10 (90%) or 6/10 (60%) at 15 Gy, respectively. The presence of ACNU during thoracic irradiation also prolonged the survival time of mice approximately 2-fold over that of animals given radiation alone. Histological examination of mice sacrificed 80 days after treatments revealed that the combination of drug and irradiation produced no radiation pneumonitis, which was predominant in mice given radiation alone. It is unexpectedly concluded that ACNU may have a protective effect against radiation-induced lung injury.

Animals↗
PubMed1987

A long-term cortical blindness after head trauma.

Here is a case of long-term cortical blindness after a head trauma. Its etiology is ascribed to the cerebral vascular occlusion caused by the head trauma. From the findings of both a computerized tomography (CT) and magnetic resonance image (MRI), the lesions of our case are assumed to be in the bilateral areas 17 (Brodmann), some part of the bilateral areas 18, 19 (Brodmann) and bilateral optic radiations. On determination of the areas of these lesions, the location of the lesion in the bilateral areas 17 has been especially done by using the MRI. The MRI findings in our case have a full significance on this point.

Adult↗
PubMed1986

Sclerotic lesions in the glomeruli of Buffalo/Mna rats.

Spontaneously developing focal and segmental glomerulosclerosis (FGS) in Buffalo/Mna rats was studied. There were no differences in the occurrence of the disease between male and female rats. Plasma macromolecules were detected in the urine samples of 2-month-old rats using sodium dodecyl sulphate polyacrylamide gel electrophoresis. All 4-month-old animals had proteinuria in excess of 30 mg/24 h. At the age of 4 months, sclerotic glomeruli were rarely observed. At the age of 6 months, all animals had a few sclerotic glomeruli in every kidney section examined. Animals which were 22 months old had sclerotic lesions in 37.8-52.1% of the glomeruli. Ultrastructural examination revealed that alterations in epithelial cells, such as effacement of foot processes, vacuolization, and a podocytic membrane-like structure, were found at the age of 2 months. The animals examined were neither uremic nor hypertensive. Our present study showed that female as well as male Buffalo/Mna rats had an earlier onset of the disease than the other strains of rats and that alterations in glomerular epithelial cells were first detected in the early stage of the disease.

Aging↗
PubMed1986

Immunoelectron microscopic demonstration of Thy-1 antigen on the surfaces of mesangial cells in the rat glomerulus.

Mesangial cells of F344 rats degenerated and then disappeared within 2 days after the intravenous administration of rabbit antirat thymocyte serum (ATS). Rabbit IgG and rat C3 were identified in the mesangium in the rat glomeruli. To establish the glomerular binding site of ATS administered intravenously into rats, one kidney of each rat given ATS intravenously 12 h earlier was perfused ex vivo through the renal artery with peroxidase-labeled antirabbit IgG followed by sequential glutaraldehyde and diaminobenzidine perfusions to minimize the ultrastructural damage. The other kidney was removed before the perfusion for histologic study to examine the glomerular injury. The rabbit IgG identified by peroxidase-reaction product was present diffusely in the glomerular mesangium when viewed by light microscopy and exclusively on the surfaces of most mesangial cells by electron microscopy. Immunofluorescence microscopy showed rabbit IgG essentially in the mesangium, and electron microscopy revealed the degeneration of mesangial cells in the kidneys that had been removed before the surgical perfusion. However, no histological abnormalities were found in the kidneys from control rats given ATS absorbed with rat thymocytes. The present study showed that the intravenous administration of ATS into rats induced the extensive mesangial cell damage by the binding of ATS to Thy-1 antigens on the mesangial cells.

Animals↗
PubMed1986

The effect of protamine sulfate on the course of immune complex glomerulonephritis in the rat.

In vivo studies in rats demonstrated that the binding of a highly cationic antigen (cationized human IgG, pI greater than 9.5) to glomerular polyanion could be significantly reduced by prior application of a small polycation, protamine sulfate. The degree of inhibition was dose dependent and the highest dose used, 4 mg/100 g body weight, reduced antigen binding by approximately 70%. In further experiments the ability of protamine sulfate to enhance elimination of cationic antigen-antibody immune complexes from the glomerular capillary wall was examined. Daily treatment with protamine sulfate, starting after induction of nephritis, produced a significant but only moderate reduction in the persistence of the antigen, without having any effect on proteinuria. Proteinuria could only be prevented when protamine sulfate was given immediately before induction of nephritis. Protamine sulfate had little influence on the course of established renal disease in the model employed. These results do not substantiate the concept of charge competition as a potentially useful therapeutic strategy.

Animals↗
PubMed1986

Monoclonal autoantibodies in Heymann nephritis.

We have developed hybridoma cell lines, each of which secretes a monoclonal antibody (MoAb) to rat renal and hepatic tissue antigens, from Lewis rat with Heymann's nephritis. Three antibodies bind to the brush border of proximal tubular epithelium (BB), one in a fine net-like pattern (no. 3-11), another one in a coarse granular pattern (no. 1-8) and the third one in a typical pattern (no. 3-9). Three antibodies bind to glomerulus in characteristic patterns but not to BB. After repeated intravenous injections of MoAb (no. 3-11), granular mesangial deposits of rat IgG were observed and of MoAb (no. 1-8), fine granular deposition along capillary walls. These monoclonal autoantibodies should be of value in research on the mechanism of autoimmune membranous nephropathy.

Animals↗
PubMed1986

Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines.

Rhizoxin, isolated from a plant pathogenic fungus which causes rice seedling blight, inhibits the mitosis of the tumor cells in a manner similar to that of Vinca alkaloids as revealed by morphological study and flow cytometry analysis. This new 16-membered macrocyclic lactone showed similar chemotherapeutic effects to those of vincristine against L1210 and P388 leukemia-bearing mice. The drug is also effective against B16 melanoma inoculated i.p. or s.c. Rhizoxin, in contrast to the ansamacrolide, maytansine, was effective against human and murine tumor cells resistant to vincristine and Adriamycin in vitro and in vivo. A maximum 60% increase in life span was obtained in mice inoculated with P388 leukemia resistant to vincristine. Rhizoxin showed greater cytotoxicity in cultured tumor cells than did vincristine. Rhizoxin seems to bear consideration for further development as a new chemotherapeutic agent.

Animals↗
PubMed1986

[Clinicopathological study on minute- and small-gastric cancer--growing pattern in incipient phase of gastric cancer development and its clinical significance].

A clinicopathological study was performed on 13 cases of minute gastric cancer (14 lesions) with a diameter less than 5.0 mm and 33 cases of small gastric cancer (34 lesions) with a diameter between 5.1 mm and 10.0 mm. The incidence of flat lesions, multiple cancer and differentiated adenocarcinoma was more frequent in minute and small gastric cancer than in ordinary early gastric cancer with a diameter greater than 11 mm. The incidence of submucosal invasion in single cancer case (30.6%, 11/36) was significantly higher than that in multiple cancer case (8.3%, 1/12). The size of the smallest lesion invading the submucosal layer was 3.2 mm in diameter. Histological examination of the cancer lesions revealed that differentiated adenocarcinoma began to develop at the deeper mucosal layer, while undifferentiated adenocarcinoma did at the superficial mucosal layer. It was also demonstrated that the differentiated adenocarcinoma invaded the submucosal layer through the natural crevices of lamina muscularis mucosa. Pathological and mucohistochemical analysis of both the cancer cells and the surrounding mucosal tissue showed that intestinal metaplasia of the mucosa, especially mucohistochemically incomplete type metaplasia seemed to have close relation with the histogenesis of the differentiated adenocarcinoma.

Adenocarcinoma↗
PubMed1985

A simple method for efficiently establishing 8-azaguanine-resistant mutant human leukemia and myeloma cell lines.

A simple and convenient method for efficiently establishing 8-azaguanine-resistant mutant leukemia and myeloma cell lines (for example, the T cell lines Jurkat and CCRF-CEM, human myeloid/macrophage-like cell lines HL60 and U937, Burkitt lymphoma line Raji and the human myeloma line RPMI 8226), is described. The method relies on culturing the cell lines in RPMI 1640 medium containing 8-azaguanine and supplemented with 15% heat-inactivated fetal calf serum and large amounts of amino acids and vitamins, and removes the necessity for pretreatment with mutagenic reagents such as ethyl methylsulfonate or X-irradiation. The possibility of obtaining mutant cell lines using the method described here is about 15 times greater than using media without high levels of amino acids and vitamins. Hybridomas produced between mitogen-activated human peripheral blood lymphocytes and an 8-azaguanine-resistant Jurkat mutant cell line (established by this method) were shown to produce soluble T cell-derived macrophage activating factor (MAF)-like material.

Antigens, Surface↗
PubMed1985

Ultramicroscopic localization of cationized antigen in the glomerular basement membrane in the course of active, in situ immune complex glomerulonephritis.

The sequence of antigen localization and the interaction of immune deposits with the anionic sites of the glomerular basement membrane (GBM) were investigated in an active model of in situ immune complex glomerulonephritis using a cationized ferritin. Three weeks after immunization with native horse spleen ferritin, the left kidneys of rats were perfused with 500 micrograms of cationized ferritin through the left renal artery. One h after renal perfusion, most of ferritin particles localized subendothelially, corresponding to the anionic sites of the lamina rara interna. In the glomerular capillary loops, infiltrating polymorphonuclear leukocytes and monocytes were seen. Some of these monocytes were in direct contact with immune complexes containing ferritin aggregates associated with anionic sites of the lamina rara interna. At 24 h, numerous ferritin aggregates were present subepithelially, preferentially beneath the slit membrane. The subepithelial location of ferritin did not always correspond to the anionic sites of the lamina rara externa. From days 3 to 7, there was remarkable endocapillary cell proliferation in some loops and pronounced effacement of epithelial foot processes. Focal detachment of epithelium from the GBM was observed occasionally. From days 14 to 28, most of ferritin aggregates were located intramembranously and subepithelially. Membranous transformation has already begun around the subepithelial deposits. This morphological study provides insight into the fate of immune deposits and injury to the GBM in the glomerulonephritis.

Animals↗