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Biomedical subjects

F Shimizu

Publications and source records attributed to F Shimizu.

At least 127 records · Page 7Linked to original sources
PubMed1991

Nephrotoxic serum nephritis in nude rats: the roles of host immune reactions.

A description is made of renal lesions in rats induced by heterologous (rabbit) nephrotoxic serum with or without subsequent host immune reactions against it and the effects of immune reactions on the course of classical nephrotoxic serum (Masugi) nephritis are discussed. The disease was induced by injecting congenitally athymic ACI nude rats (rnu/rnu) and their normal heterozygous littermates (rnu/+) with rabbit anti-rat glomerular basement membrane (GBM) antiserum. In the autologous phase, rat IgG and immunoglobulins were localized in a linear pattern along capillary walls only in nephritic heterozygous rats. In the indirect plaque-forming cell (PFC) assay against rabbit immunoglobulins in the autologous phase, significantly more PFC could be detected in nephritic heterozygous rats than in nephritic nude rats. The nude and heterozygous rats were essentially the same with respect to the amount of urinary protein, histological change and clinical course. At least in classical nephrotoxic serum nephritis in rats, host immune reactions against GBM bound heterologous nephrotoxic serum were concluded to have no effect on the course of the disease.

Animals↗
PubMed1991

Modulation of mesangial cell proliferation by endothelial cells in coculture.

The effects of direct cell contact between endothelial (ECs) and mesangial cells (MCs) on MCs proliferation were examined in a coculture system in vitro. Mitomycin C treated ECs (M-ECs) were plated on culture dishes and MCs were cocultured with these M-ECs. Cell number was measured at the end of days 1, 3, and 5. In the coculture system with direct contact, the growth of cocultured MCs was modulated as follows: 1) the growth of MCs was inhibited up to day 3, and 2) a high level of proliferation was observed between days 3 and 5. This biphasic pattern of growth could not be detected in coculture of fibroblasts with MCs. In coculture without direct contact, using intercup chambers, the kinetics in cell proliferation between cocultured MCs and MCs alone were essentially the same. Conditioned media derived from cocultures up to day 3 in a contact-dependent manner inhibited the 3H-thymidine uptake of MCs. From these results, it would thus appear that MCs proliferation is regulated by intercellular contact with ECs.

Animals↗
PubMed1990

Auditory brain stem response (ABR) in eating disorder.

Auditory brain stem responses were recorded in 10 eating disorder patients and 10 normal control subjects. Absolute latencies, interwave latencies, absolute amplitudes, and amplitude ratios were investigated. A nonsignificant difference was found between the eating disorder group and the normal control group as far as the absolute latencies and interwave latencies were concerned. But the eating disorder patients had significantly smaller amplitude ratios (III/I, IV-V/I) and absolute amplitude (V) than did the control subjects. These findings suggest that some dysfunction exists in the region of brain stem. It may be related with the pathophysiology in patients with eating disorder.

Adolescent↗
PubMed1990

Application of a ribosomal DNA integration vector in the construction of a brewer's yeast having alpha-acetolactate decarboxylase activity.

An integration plasmid, pIARL28, containing the ribosomal DNA gene as a homologous recombination sequence was constructed for introduction of the alpha-acetolactate decarboxylase gene into brewer's yeast. The transformation efficiency of pIARL28 was 20- to 50-fold higher than those of the other YIp vectors, as yeast cells had approximately 140 copies of the ribosomal DNA gene. All transformants showed very high alpha-acetolactate decarboxylase activity due to the multiple integrated copies of the plasmid. The transformants were grown in nonselective conditions, and segregants which had maintained the alpha-acetolactate decarboxylase expression cassette but no other vector sequences were isolated. Southern analysis showed that these marker-excised segregants contained more than 20 copies of the alpha-acetolactate decarboxylase gene and were stably maintained under nonselective conditions. Fermentation tests confirmed that the diacetyl concentration was considerably reduced in wort fermented by these marker-excised segregants. The degree of reduction was related to the copy number of the alpha-acetolactate decarboxylase gene.

Carboxy-Lyases↗
PubMed1990

Genetic regulation of the development of glomerular sclerotic lesions in the BUF/Mna rat.

BUF/Mna strain rats spontaneously develop renal glomerular sclerotic lesions (RSL) at a nearly 100% incidence, diagnosed by hyperalbuminuria (greater than 500 mg/dl) and glomerular lesions morphologically resembling one type of human focal glomerular sclerosis (FGS). Genetic segregation of RSL development was studied by crossing the BUF/Mna strain with two other rat strains, WKY/NCrj and ACI/NMs, which were free of RSL. Two autosomal recessive genes in the BUF/Mna rats were found to determine the susceptibility to RSL in both combinations of crosses.

Albuminuria↗
PubMed1990

Mechanism of formation of subepithelial electron-dense deposits in active in situ immune complex glomerulonephritis.

The influences of the epitope density on cationic antigens on the fate of immune reactants and the formation of subepithelial electron dense deposits (EDD) were studied in a model of active in situ immune complex glomerulonephritis (ICGN), using a hapten-carrier system. Three weeks after immunization with trinitrophenol conjugated bovine serum albumin (TNP17.3-BSA), the left kidneys of rats were perfused with 500 micrograms of TNP6.2-cationized human immunoglobulin G (C-HIgG) or TNP31.3-C-HIgG. The renal tissues were then examined at intervals by light, immunofluorescence, and electron microscopies. The perfused kidneys of rats given high-valency antigens (TNP31.3) showed marked subepithelial EDDs with foot process retraction associated with proteinuria. In contrast, those of rats given low-valency antigens (TNP6.2) showed only small subepithelial EDDs beneath the slit membrane, which consisted of apparently normal epithelial cells, and did not develop proteinuria. Kinetic studies on immunofluorescence showed that glomerular depositions of immune reactants (TNP-carrier conjugate, rat IgG, and C3) were present longer in rats treated with high-valency antigens than in those treated with low-valency antigens. We conclude that the epitope density on cationic antigens strongly influences the retention of immune reactants and the formation of subepithelial EDDs, as well as development of glomerular injury.

Animals↗
PubMed1990

The charge-dependent materno-fetal barrier in the rat.

The charge-dependent materno-fetal barrier of near-term rats was examined with two pairs of radiolabelled proteins differently charged. When the proteins were injected intra-arterially, the maternal blood concentrations of the two cationized proteins (BSA and human IgG) exceeded those of native proteins in the chorioallantoic placenta and fetus during the period of examination (15-180 min). In the yolk sac placenta, these percentages were essentially the same as those of native proteins. Following intra-placental injection, the amounts of the cationized proteins in the chorioallantoic placenta and fetus were significantly (p less than 0.01) greater than those of native proteins at the particular times examined (5 and 60 min). In contrast, the amounts of cationized proteins in the yolk sac placenta were basically the same as those of native proteins. The data presented above indicate the charge on proteins that considerably influenced their materno-fetal transfer, particularly via the chorioallantoic placenta.

Animals↗
PubMed1989

Effects of porcine pancreastatin on postprandial pancreatic exocrine secretion and endocrine functions in the conscious rat.

The inhibitory effect of a newly discovered polypeptide, pancreastatin, on postprandial pancreatic exocrine secretions and endocrine functions was examined in the conscious rat with a chronic external bile, pancreatic and gastric fistula. The infusion of 100 and 200 pmol/kg/h of pancreastatin significantly inhibited meal-stimulated pancreatic secretion of fluid and protein but not bicarbonate in a dose-dependent manner. The infusion of 100 and 200 pmol/kg/h of pancreastatin increased plasma pancreastatin concentrations (mean +/- SE) up to 133.5 +/- 15.9 and 209.8 +/- 14.5 pM, respectively. However, the same doses of pancreastatin failed to inhibit postprandial insulin and gastrin releases and did not affect blood glucose levels. It is suggested that pancreastatin may be an inhibitor of postprandial pancreatic exocrine secretion. However, the doses used in the present study may not have been high enough to affect endocrine functions.

Animals↗
PubMed1989

Establishment of latent ganglionic infection with herpes simplex virus via maxillary gingiva and viral re-activation in vivo after trauma.

Herpes simplex virus can remain latent for months or years in sensory and automatic ganglia of animals and man, and can be re-activated in vivo by several procedures such as neurectomy, irritation of epithelial surfaces, and administration of immunosuppressive agents. The objective of this study was to determine whether dental stimuli can cause re-activation of the latent herpes simplex virus. Homogenization and explanation of ganglia from mice showed that herpes simplex virus (type 1) traveled from maxillary gingiva to trigeminal ganglia, and remained latent. It was also shown that mice passively immunized with rabbit antibody to herpes simplex virus, following the inoculation of herpes simplex virus by the maxillary gingiva route, developed a latent infection in the trigeminal ganglia. Neutralizing antibody was cleared from the circulation and could not be detected in most of these animals after five weeks. A neutralizing test showed that antibody-negative mice with latent infection were able to produce antibody to re-infection with herpes simplex virus, suggesting that re-activation can be identified by measurement of serum antibody. By use of this mouse model system, it was shown that when maxillary gingiva was traumatized with dry ice, viral re-activation occurred in 58% of these animals, as demonstrated by the appearance of neutralizing antibody. Irradiation by a Stomalaser beam had no effect on the re-activation of latent herpes simplex virus. Our mouse model system may serve as a useful model for obtaining new information on re-activating or inhibitory factors in dentistry.

Animals↗
PubMed1989

Hapten-specific cellular immune response producing glomerular injury.

A new model of experimental glomerulonephritis (GN) in which a cell-mediated (delayed-type) reaction predominated was established. Cationized TNP-BSA conjugates were planted in the kidney of rats by perfusion via the renal artery. Rats which had been sensitized with the TNP hapten 7 days previously revealed marked exudative and proliferative changes in their glomeruli, accompanied by transient proteinuria. A cellular influx was seen without deposition of any autologous antibody. The resulting data are compatible with the idea that cell-mediated immune reactions can participate in tissue damage in glomerular disease.

Animals↗
PubMed1988

Massive proteinuria induced in rats by a single intravenous injection of a monoclonal antibody.

A single i.v. injection of a mAb 5-1-6 to rats was found to cause massive though transient proteinuria. This mAb 5-1-6, IgG1 was produced by immunization of BALB/c mice with collagenase-treated Wistar rat glomeruli and was highly organ and species specific. Immunoelectron microscopy using immunoperoxidase with the avidin-biotin complex and immunogold staining indicated mAb 5-1-6 to bind in vitro to the surface of glomerular epithelial foot processes, mainly to slit diaphragms. The recognized antigenic molecule was not susceptible to neuraminidase treatment and its Mr was about 51 kDa by immunoprecipitation. A one-shot i.v. injection of this mAb induced proteinuria in rats starting immediately, reaching the peak on day 8 (mean value of 150 mg/24 h), then gradually decreasing to normal level on day 18. The in vivo localization of administrated mAb 5-1-6 changed with time. Linear binding along glomerular capillary walls was observed 2 h after injection. However, 3 days later, it partially shifted to a fine granular pattern. The linear pattern disappeared and the size as well as intensity of the fluorescent granules decreased on day 12 to trace positive on day 18. Immunoelectron microscopy revealed the binding pattern of in vivo injected mAb 5-1-6 after 2 h to be similar to that in vitro. Three days later, injected mAb was observed within multivesicular bodies in glomerular epithelial cells as well as along the surface of foot processes and around slit diaphragms. Twelve days after injection, mAb along the surface of the foot processes and around slit diaphragms decreased but those in multivesicular bodies were observed more frequently. Rat IgG and C3 could not be detected throughout the period of observation. No histologic abnormalities were noted except for partial retraction of epithelial foot processes at the peak of proteinuria on day 8. This mAb thus provides a valuable means for examining the mechanism of proteinuria.

Animals↗
PubMed1988

Monoclonal antibodies to human glomerular antigens.

Using cultured human fetal kidney cortical cells as antigen, two monoclonal antibodies (moAbs) against human glomeruli were produced. One of these moAbs, H-4, recognized the cell surface of glomerular epithelial cells, and the other, H-13, recognized the extracellular matrix present in the mesangial area. Both also reacted with liver, H-4 recognizing antigen present on the hepatocyte, and H-13 recognizing antigen distributed along the sinusoid. Species specificity for these moAbs was examined using mouse, rat, guinea pig and rabbit glomeruli, which revealed that H-4 reacted with rat glomerular epithelial cells and H-13 stained guinea pig glomerular mesangium. In the human fetal kidney, H-13 reacted with the mesangium, glomerular and tubular basement membrane and Bowman's capsule, and H-4 with the glomerular and tubular epithelial cells. Dot immunobinding assay of fibronectin purified from glomerular culture supernatant and plasma revealed that H-13 recognized both plasma and cellular fibronectin. Immunoblot analysis of 2.0 M guanidine HCl extract after dissociation in sodium dodecyl sulfate and electrophoresis demonstrated binding of H-4 to a 125 kd polypeptide. Immunoblot analysis of thermolysin-digested fibronectin exhibited binding of H-13 to 145 kd and 110 kd fragments, but not to 38 kd-29 kd fragments. In renal biopsy specimens from patients with membranous nephropathy. H-13 stained the glomerular basement membrane (GBM), but not the mesangium, whereas anti-fibronectin antisera stained both the GBM and the mesangium. In those from patients with minimal change nephrotic syndrome (MCNS), IgA glomerulonephritis (IgAGN) and membranoproliferative glomerulonephritis (MPGN), the staining pattern with H-13 was similar to that with polyclonal anti-fibronectin antisera. These results indicate that H-4 recognizes a 125 kd polypeptide constituent of the glomerular epithelial cell membrane and that H-13 recognizes the cell binding domain of fibronectin as well as revealing structural alterations in the mesangium and GBM.

Animals↗
PubMed1988

Nucleotide sequence and expression of the Enterobacter aerogenes alpha-acetolactate decarboxylase gene in brewer's yeast.

The nucleotide sequence of a 1.4-kilobase DNA fragment containing the alpha-acetolactate decarboxylase gene of Enterobacter aerogenes was determined. The sequence contains an entire protein-coding region of 780 nucleotides which encodes an alpha-acetolactate decarboxylase of 260 amino acids. The DNA sequence coding for alpha-acetolactate decarboxylase was placed under the control of the alcohol dehydrogenase I promoter of the yeast Saccharomyces cerevisiae in a plasmid capable of autonomous replication in both S. cerevisiae and Escherichia coli. Brewer's yeast cells transformed by this plasmid showed alpha-acetolactate decarboxylase activity and were used in laboratory-scale fermentation experiments. These experiments revealed that the diacetyl concentration in wort fermented by the plasmid-containing yeast strain was significantly lower than that in wort fermented by the parental strain. These results indicated that the alpha-acetolactate decarboxylase activity produced by brewer's yeast cells degraded alpha-acetolactate and that this degradation caused a decrease in diacetyl production.

Base Sequence↗
PubMed1988

The electrophoretic pattern of urinary protein in in situ immune complex glomerulonephritis.

Urinary protein excreted in active in situ immune complex glomerulonephritis (ICGN) was qualitatively analyzed by the comparison of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns of urinary proteins from rats with Masugi GN, active Heymann GN (AHGN), and chronic serum sickness GN (CSSGN). In the SDS-PAGE analysis of urinary protein excreted in the active in situ ICGN and Masugi GN models, 200- and 145-kD macromolecules and low molecular weight components around 12 kD were excreted in large quantities at the full development stage (greater than 100 mg/24 h urinary protein). These findings, however, were obscure or lacking in CSS-GN and AHGN at the peak of proteinuria. Electrophoretic patterns of urinary proteins including lower molecular weight proteins could be divided into two groups: either active in situ ICGN and Masugi GN or AHGN and CSSGN. These two groups corresponded to the differences of morphologic expression such as proliferative changes rather than degree of proteinuria. The location of immune complex formation and deposition, probably different among the experimental models, may play an important role for determining the mediation and nature of glomerular injury.

Animals↗
PubMed1988

Active in situ immune complex glomerulonephritis using the hapten-carrier system: role of epitope density in cationic antigens.

The role of epitope density in cationic antigen was investigated in an active model of in situ immune complex glomerulonephritis (ICGN) using the hapten-carrier system. Trinitrophenol (TNP) was conjugated with variable density to cationic human immunoglobulin (C-HIgG) to yield TNP6.2-C-HIgG (low-valency antigen) and TNP31.3-C-HIgG (high-valency antigen). In rats preimmunized with TNP17.3-bovine serum albumin (BSA), endocapillary proliferative GN with proteinuria developed in rats receiving high-valency antigen. In contrast, no significant abnormalities in renal histology or urinalysis were observed when a low-valency antigen was injected. These results indicate that glomerular injury produced by hapten-specific immune reaction is affected by the number of haptenic groups conjugated to the carrier molecule (epitope density) in active in situ ICGN.

Animals↗