Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 289 records · Page 16Linked to original sources

PubMed1998

Autoantibody inhibits binding of von Willebrand factor to glycoprotein Ib and collagen in multiple myeloma: recognition sites present on the A1 loop and A3 domains of von Willebrand factor.

A 49-year-old man with multiple myeloma (IgG-lambda Bence-Jones protein positive) presented a bleeding tendency: characterized intramuscular hemorrhage. Coagulation studies showed a von Willebrand factor (vWF) defect (Duke bleeding time > 20 min; ristocetin cofactor activity [vWF:RC] < 6%; significant reduction of large multimers of vWF. Mixing study suggested the presence of inhibitor directed against vWF:RC activity and collagen binding activity of vWF. The inhibitor was identified as an antibody of the IgG class. The inhibitor blocked the interaction of vWF with glycoprotein Ib in the presence of ristocetin, as did the pepsin-digested fragment of the inhibitor [F(ab)2'], but neither blocked botrocetin-mediated interaction of vWF with glycoprotein Ib. They also inhibited the binding of vWF to immobilized collagen type I. The inhibitor and the F(ab)2' reacted strongly with native vWF and fragment I (amino acids 911-1365) and with the 39/34 kDa fragment (amino acids 480/481-718), but not with fragment II (amino acids 1366-2050) and fragment III-T2 (heavy chains, amino acids 273-511; light chains, amino acids 674-728). We conclude that the IgG antibody inhibits both vWF:RC activity and the binding of vWF to collagen by reacting with the epitopes present on the A1 loop and A3 domains of vWF.

Autoantibodies↗

PubMed1998

The role of endothelin-1 in regulation of rat mesenteric microcirculation.

Immunocytochemistry of endothelin-1 (ET-1) and the ETA receptor, and scanning electron microscopy using cast resin after treatment with ET-1, were carried out in the rat mesenteric microvasculature. Immunoreaction of ET-1 was preferentially seen along the endothelium of the proximal portion of the anterior mesenteric artery, the endothelial cells of which contain abundant Weibel-Palade (WP) bodies. However, the arterioles and small veins distal to the artery showed little immunoreactivity but showed heavy immunoreaction of ETA receptors in the media. By scanning electron microscopy after treatment with ET-1, the mesenteric microvasculature became slightly narrower compared to the control exhibited of localized constricted areas, especially in the region of the small veins. Light microscopy of such areas revealed localized thickening of the medial muscle cells. Because the release of ET-1 from endothelial cells depends in part on extracellular discharge of the WP bodies, the results indicate that ET-1, discharged from the proximal portion of the anterior mesenteric artery, induces vasoconstriction of the arterioles and small veins, mediated by ETA receptors. The localized thickening in areas in the media of the small veins may participate in the maintenance of blood flow through the portal circulation.

Animals↗

PubMed1998

The significance of endothelin for generation of endocochlear potential.

The role of intermediate cells (ICs) in the stria vascularis (SV) of the cochlear ducts in the generation of endocochlear potential (EP) is clear because certain mutants cannot generate EP. Recent reports have shown that endothelin (ET) stimulates or inhibits the function of Na+, K(+)-ATPase in various organs. This study was designed to examine the immunocytochemical localization of ET and its receptor in the SV. The cochlear ducts of WBB6F1 (+/+) mice and mutants (W/Wv) devoid of the ICs were used for light and electron microscopic immunocytochemistry using rabbit anti-ET-1, ET-3, and ETA receptor antisera. The location of Na+, K(+)-ATPase using rabbit anti-rat Na+, K(+)-ATPase was also examined. Immunoreactivity to Na+, K(+)-ATPase was seen in the marginal cells (MCs) in both species. Immunoreactivity to ET-1 and ET-3 was preferentially localized in the rough endoplasmic reticulum and cytoplasmic vesicles of the ICs and along the plasma membrane of the ICs and in the MCs apposed to the ICs. Immunoreactive sites for ETA were almost identical to those of ET-1 and ET-3. Because Na+, K(+)-ATPase activities also exist in the MCs of the mutants, it appears likely that ET, synthesized and released by the ICs, may participate in generation of EP by regulating the function of Na+, K(+)-ATPase for production of the endolymph of the MCs.

Animals↗

PubMed1998

Intracranial aneurysms associated with aortitis syndrome: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Aortitis syndrome is a systemic vasculitis of unknown etiology, affecting mainly the major branches of the aorta and leading to stenosis or occlusion. Intracranial aneurysms are rarely associated with this syndrome. Only 15 cases have been previously reported. CLINICAL PRESENTATION: A 54-year-old woman with a 10-year history of aortitis syndrome demonstrated nonruptured cerebral aneurysms in the left internal carotid and anterior communicating arteries, with decreased flow in the right internal carotid artery and ipsilateral A1 segment. INTERVENTION: The patient underwent clipping of the aneurysms through a left pterional craniotomy and transsylvian approach. CONCLUSION: In our review of 16 reported cases, including the present case (13 with ruptured aneurysms and 3 with nonruptured aneurysms), there were 25 saccular aneurysms, and we noted the following clinical characteristics: 1) patient age was 26 to 64 years, with an average of 50.2 years; 2) aneurysms arose predominantly along the course of collateral flow, especially in the vertebrobasilar system (13 of 25 aneurysms, 52.0%); 3) there was a high incidence of multiplicity (7 of 16 cases, 43.8%). These characteristics suggest that increased hemodynamic stress, produced by stenosis or occlusion of the major branches of the aorta and systemic hypertension, plays an important role in the development of cerebral aneurysms in patients with this syndrome.

Aortitis↗

PubMed1998

Spirochaete-like swimming mode of Campylobacter jejuni in a viscous environment.

The swimming patterns of Campylobacter jejuni in environments of low and high viscosity were examined by a video tracking method. In media of low viscosity, C. jejuni swam with an average velocity of 39.3 microm/s with frequent changes in direction. The velocity of C. jejuni increased in a medium at a little higher viscosity than that of a low viscosity buffer. In addition to this, C. jejuni showed a second increase of velocity in media of a high viscosity of about 40 centipoise. The swimming patterns at these two velocity peaks were compared. In the second peak the wild-type C. jejuni exhibited repeated back and forth swimming patterns which were more like the swimming pattern of spirochaetes than that of monotrichous bacteria. Thus C. jejuni may presumably use a different swimming mode in media of high viscosity than the original swimming mode mediated by the propelling force of the flagella. The spiral shape of this bacterium like that of spirochaetes may strongly influence its swimming ability in media of high viscosity such as the mucous layer of the intestinal tract.

Animals↗

PubMed1998

Heterogeneity in expression of lipopolysaccharide and major outer-membrane proteins by strains of Escherichia coli O157 with different H-serotypes.

A total of 11 strains of Escherichia coli (E. coli) belonging to serogroup O157 were examined for the expression of long-chain lipopolysaccharide (LPS) and major outer-membrane proteins (OMPs) by means of SDS-PAGE. The strains belonged to either one of four different flagellar (H) types or did not express flagella. Four of the eleven strains carried genes encoding Shiga-like toxins (SLTs). All the strains exhibited one of four LPS profiles, designated A, B, C or D. Electron microscopic analysis with the freeze-substitution technique demonstrated the differences in the cell surface structures of strains with each LPS profile. Strains with LPS profile A, B or C had layers of thin fibers 10, 20 and 20 nm long, respectively, on the outer membrane but strains with LPS profile D had no such structure. An analysis of the OMPs showed that all the strains had one of four OMP profiles, designated I, II, III or IV. Both LPS and OMP profiles were dependent on H-serotypes, and the combination pattern of LPS and OMP profiles of the strains was unique for each H-serotype. These data support the existence of heterogeneous groups of O157 strains.

Bacterial Outer Membrane Proteins↗

PubMed1998

Schedule-dependent and -independent antitumor activity of paclitaxel-based combination chemotherapy against M-109 murine lung carcinoma in vivo.

The established antitumor efficacy of paclitaxel against a variety of human tumors has led to pre-clinical and clinical studies to develop the paclitaxel-based combination regimens. We examined in vivo the antitumor activity and toxicity of the combination of paclitaxel and each of 8 antitumor agents, currently in clinical use, against M-109 murine lung carcinoma implanted subcutaneously into male CDF1 mice. Paclitaxel given intravenously at 24 mg/kg/day on a schedule of consecutive daily injections for 5 days (d1-5) induced reproducibly, in 6 experiments, a significant (37-82%) increase in the survival time of tumor-bearing mice over saline-treated control mice. Cisplatin at 4 and 2 mg/kg/day given intravenously on the same treatment schedule showed no significant antitumor activity when given alone; however, the combination of paclitaxel at 24 mg/kg/day (d1-5) followed by cisplatin at a dose of 2 mg/kg/day (d6-10) induced a significant (P < 0.05) prolongation of the survival time of tumor-bearing mice compared with the group given paclitaxel alone. On the other hand, treatment with these drugs on the reverse sequence caused toxic deaths of all mice. Such sequence-dependent toxic death of mice was also observed with the combination of paclitaxel and carboplatin, etoposide or methotrexate. The combination of paclitaxel and adriamycin, cyclophosphamide, ranimustine or vinblastine (VLB) showed a sequence-independent antitumor activity and a more-than-additive therapeutic effect was observed with the combination of paclitaxel and either VLB or ranimustine. Although the drug administration schedules used here may not be directly applicable to the clinic, knowledge of the nature of the sequence-dependency in paclitaxel-based combination chemotherapy should be useful in the design of clinical trials.

Animals↗

PubMed1998

Sequential T cell response involved in tumor rejection of sarcoma, Meth A, in syngeneic mice.

We investigated the type of T cell response involved in Meth A tumor rejection in primary immune and hyperimmune syngeneic mice. It was found that a CD4+ T cell-mediated delayed-type hypersensitivity (DTH) response activating non-specific killer cells such as macrophages, NK and LAK cells, without a specific CD8+ cytotoxic T lymphocyte (CTL) response, was the major immune response leading to Meth A tumor rejection in primary immune mice. In contrast, the specific CD8+ CTL response was the major response leading to the tumor rejection, in addition to CD4+ T cell-mediated DTH response, in hyperimmune mice. Analysis of CD4+ T cell clones established from primary immune and hyperimmune spleen cells indicated that a CD4+ T cell clone (C9) of primary immune mice (although only one clone was established) was of Th1 type, and induced cytotoxicity in accessory cells by classic DTH in vitro. Eight CD4+ T cell clones were established from hyperimmune spleen cells. Six out of the eight clones were of the Th2 type and two were Th0-like. However, no Th1-type CD4+ T cell clone was established from hyperimmune spleen cells. All of these CD4+ T cell clones, even the Th2-type clones, were capable of inducing cytotoxicity in vitro in T cell-depleted accessory cells, as in an in vitro DTH response. We postulate on the basis of these results that the T cell response leading to Meth A tumor rejection in vivo sequentially changed from a CD4+ T cell-mediated classic DTH response to a CD8+ CTL response, in addition to a cellular response mediated probably by Th2-type cells, during the process of repeated immunization.

Animals↗

PubMed1998

National survey of periventricular leukomalacia in Japan.

BACKGROUND: Clarification of the present status of periventricular leukomalacia (PVL) in Japan. METHODS: Questionnaires were mailed to the leading neonatal intensive care units (NICU) and rehabilitation centers for children. RESULTS: The incidence of PVL in the group of surviving preterm infants of gestational ages less than 33 weeks was 4.8-4.9% on ultrasound and 7.7-7.9% on magnetic resonance imaging and/or computed tomography. The incidence of PVL did not decrease between 1990 and 1994. The incidence of PVL in the NICU varied from 0 to 47.1%. Infants from multiple pregnancies had a higher incidence (9.1%) of PVL than those from single pregnancies (6.2%). The proportion of PVL in all patients in rehabilitation centers with cerebral palsy (CP) has increased recently. CONCLUSIONS: It was roughly calculated that about 750 cases of CP with PVL occurred annually in Japan, thus accounting for about one-third of the total number of cases of CP.

Cerebral Palsy↗

PubMed1998

Silent premature rupture of membranes, detected and monitored serially by an AFP kit.

A 24-year-old woman underwent conization and cervical cerclage during pregnancy. After she later complained of fluid leakage, a premature rupture of the membranes (PROM) was suspected, because of positive results on a test for nitrazine, the intra-amniotic dye injection method (PSP test), and an AFP-kit test at 22 weeks of gestation. The nitrazine and PSP tests later turned negative. However, during the period from the 22nd through 26th weeks of gestation, the results of AFP-kit tests fluctuated, with repeated positive indications for bacterial cultures and elevated granulocyte elastase activity in the cervical mucus. The pregnancy was well maintained with administration of antibiotics and ritodrine hydrochloride until 34 weeks of gestation. The presence of chorioamnionitis, local inflammation of the fetal membranes, was found by pathological examination after the delivery. We propose a new clinical entity--to be referred to as silent PROM--the premature chemical rupture of the membranes.

Adult↗

PubMed1998

Peptic ulcers after the Hanshin-Awaji earthquake: increased incidence of bleeding gastric ulcers.

OBJECTIVE: Although physical stresses are known to induce peptic ulcers in the upper gastrointestinal tract, it remains controversial whether emotional stress can cause peptic ulcers. Therefore, we examined retrospectively the influence of the Hanshin-Awaji earthquake that occurred in Japan in January 1995 on the occurrence of peptic ulcer disease among noninjured residents. METHODS: Sixty-one hospitals, covering 70% of all endoscopy examinations performed in this area, joined the study and were divided into three areas according to the severity of the damage. A comparison was made between a group of 10,831 patients who underwent upper gastrointestinal endoscopy within 2 months after the earthquake and 16,100 who did so in the same hospitals during the corresponding period in 1994. RESULTS: In the most devastated area, in spite of a dramatic decrease in the total number of endoscopies (50.0%), patients with gastric ulcer (GU) were increased in 1995, whereas those with duodenal ulcer were decreased, resulting in a higher ratio of gastric to duodenal ulcers than in 1994 (3.07 vs 1.88). In particular, there was a marked increase in bleeding GU. The mean age of patients with GU was significantly higher in 1995 than in 1994. CONCLUSION: The Hanshin-Awaji earthquake-induced life event stress not only triggered but also exacerbated GU, particularly in the elderly.

Adult↗

PubMed1998

Analysis of the expression of CagA and VacA and the vacuolating activity in 167 isolates from patients with either peptic ulcers or non-ulcer dyspepsia.

OBJECTIVES: The goals of this study were: 1) to examine the prevalence of cytotoxin-associated protein (CagA), vacuolating cytotoxin (VacA), and the vacuolating cytotoxin activity (VCA) in vitro of infecting Helicobacter pylori isolates and 2) to clarify the relation between the expression of these virulence factors and the occurrence of peptic ulceration. METHODS: One hundred sixty-seven clinical isolates of H. pylori from patients with peptic ulcer disease (gastric ulcer, 62 cases; duodenal ulcer, 48 cases) and nonulcer dyspepsia (57 cases) were studied regarding their genetic and phenotypic properties. RESULTS: Type 1 bacteria, which had both CagA and VCA, and type 2 bacteria, which did not express either CagA or VCA, represented 62.9% and 7.8%, respectively; the remaining 29.4% had an intermediate phenotype, expressing either CagA independent of the presence of VCA (CagA+VCA-) or vice versa (CagA-VCA+). CagA+VCA- and CagA-VCA+ bacteria represented 17.4 % and 12.0%, respectively, both of which were more numerous than the type 2 category. The proportion of the CagA-positive isolates was significantly higher in both the duodenal ulcer (97.9%) and gastric ulcer (83.9%) patients than in the non-ulcer dyspepsia patients (61.4%) (p < 0.01). On the other hand, the proportion of VacA/VCA-positive isolates was not significantly different between peptic ulcer disease and non-ulcer dyspepsia. CONCLUSIONS: The currently used classification of this bacterium based on the concomitant expression of CagA and VacA/VCA into the two major types is not adequate. The CagA-positive phenotype thus may be important as a virulence marker for peptic ulcer disease independent of the presence of VacA/VCA.

Adult↗

PubMed1998

Induction of endometriosis and adenomyosis by transvaginal pituitary transplantation in mice with and without natural killer cell activity.

PROBLEM: The aims of this study were to establish a mouse model of endometriosis and adenomyosis and to elucidate the necessity of reduced natural killer (NK)-cell and T-cell activities in the establishment of endometriosis and adenomyosis. METHOD OF STUDY: Pituitary glands, submandibular glands, a hypothalami were transvaginally inoculated into the uteri of syngeneic female mice. Twenty weeks later, the recipient mice were sacrificed and examined. RESULTS: Cysts, adhesion of the uteri to surrounding tissues, and adenomyosis had formed in the uteri of 7 (29.2%), 14 (58.3%), and 22 (91.7%) mice, respectively, out of 24 BALB/c mice after the transplantation of pituitary glands. Similar findings were obtained by experiments with C3H/He and C57BL/6 mice. In NK-cell-deficient C57BL/6-bgJ and T-cell-deficient BALB/c nu/nu mice, an increase in the formation of cysts, adhesion, and adenomyosis was not observed. CONCLUSIONS: These findings indicate that transvaginal pituitary transplantation specifically induces cysts, adhesion, and adenomyosis. Reduced NK-cell activities may not be necessary in the primary development of endometriosis and adenomyosis.

Animals↗

PubMed1998

Efficient transfer of the pheromone-independent Enterococcus faecium plasmid pMG1 (Gmr) (65.1 kilobases) to Enterococcus strains during broth mating.

Plasmid pMG1 (65.1 kb) was isolated from a gentamicin-resistant Enterococcus faecium clinical isolate and was found to encode gentamicin resistance. EcoRI restriction of pMG1 produced five fragments, A through E, with molecular sizes of 50.2, 11.5, 2.0, 0.7, and 0.7 kb, respectively. The clockwise order of the fragments was ACDEB. pMG1 transferred at high frequency to Enterococcus strains in broth mating. pMG1 transferred between Enterococcus faecalis strains, between E. faecium strains, and between E. faecium and E. faecalis strains at a frequency of approximately 10(-4) per donor cell after 3 h of mating. The pMG1 transfers were not induced by the exposure of the donor cell to culture filtrates of plasmid-free E. faecalis FA2-2 or an E. faecium strain. Mating aggregates were not observed by the naked eye during broth mating. Small mating aggregates of several cells in the broth matings were observed by microscopy, while no aggregates of donor cells which had been exposed to a culture filtrate of E. faecalis FA2-2 or an E. faecium strain were observed, even by microscopy. pMG1 DNA did not show any homology in Southern hybridization with that of the pheromone-responsive plasmids and broad-host-range plasmids pAMbeta1 and pIP501. These results indicate that there is another efficient transfer system in the conjugative plasmids of Enterococcus and that this system is different from the pheromone-induced transfer system of E. faecalis plasmids.

DNA, Bacterial↗

PubMed1998

Seminoma in a postmenopausal woman with a Y;15 translocation in peripheral blood lymphocytes and a t(Y;15)/45,X Turner mosaic pattern in skin fibroblasts.

We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses. The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history. A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass. Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13). Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype. Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome. An androgen receptor binding assay of cultured genital skin fibroblasts was negative. Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence. These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation.

Blotting, Southern↗

PubMed1998

Metabolic inhibition impairs ATP-sensitive K+ channel block by sulfonylurea in pancreatic beta-cells.

The effect of metabolic inhibition on the blocking of beta-cell ATP-sensitive K+ channels (KATP channels) by glibenclamide was investigated using a patch-clamp technique. Inhibition of KATP channels by glibenclamide was attenuated in the cell-attached mode under metabolic inhibition induced by 2,4-dinitrophenol. Under a low concentration (0.1 microM) of ATP applied in the inside-out mode, KATP channel activity was not fully abolished, even when a high dose of glibenclamide was applied, in contrast to the dose-dependent and complete KATP channel inhibition under 10 microM ATP. On the other hand, cibenzoline, a class Ia antiarrhythmic agent, inhibits KATP channel activity in a dose-dependent manner and completely blocks it, even under metabolic inhibition. In sulfonylurea receptor (SUR1)- and inward rectifier K+ channel (Kir6.2)-expressed proteins, cibenzoline binds directly to Kir6.2, unlike glibenclamide. Thus, KATP channel inhibition by glibenclamide is impaired under the condition of decreased intracellular ATP in pancreatic beta-cells, probably because of a defect in signal transmission between SUR1 and Kir6.2 downstream of the site of sulfonylurea binding to SUR1.

2,4-Dinitrophenol↗

PubMed1998

Low in vitro thyrotropic activity of a human chorionic gonadotropin molecule in the first trimester during pregnancy.

Rat thyroid cell strain FRTL-5 is widely used to analyze thyroid stimulators, and responds to purified hCG with increased cyclic AMP production. The aim of this study was to determine the in vitro thyrotropic activity of an immunological hCG molecule according to gestational age during normal pregnancy using the FRTL-5 cell culture system. Sera were collected from 7 normal nonpregnant control and a total of 72 normal pregnant women. Seventy-two pregnant women consisted of 40 women in the first trimester (7-14 weeks' gestational age (GW) (group I)), 16 women in the second trimester (15-28 GW, group II), and 16 women in the third trimester (29-40 GW, group III). Concentrations of serum hCG and FT4 of group I were higher than those of groups II and III (p < 0.001). In the in vitro assay, the supernatants were subjected to radioimmunoassay for cAMP. In order to analyze in vitro thyrotropic activity of an immunological hCG molecule, cAMP accumulation rate expressed as cAMP accumulation (nM) divided by maternal serum concentration of hCG (IU/ml) was determined in all three groups. By regression analyses, a statistically significant positive correlation was observed between serum hCG concentration and cAMP accumulation in group I (r = 0.399; p < 0.05), group II (r = 0.915; p < 0.0001) and group III (r = 0.671; p < 0.01). cAMP accumulation rate in group I (0.355 +/- 0.022, mean +/- SE) was significantly low when compared with group II (0.508 +/- 0.051) (p < 0.01) and group III (0.556 +/- 0.063) (p < 0.001). Thus, it was found for the first time that the in vitro thyrotropic activity of an immunological hCG molecule in the first trimester was lower than those of the second and the third trimesters. In terms of the in vitro thyrotropic activity, an immunological hCG molecule in the first trimester differs from that of the later trimesters.

Animals↗

PubMed1998

Cell proliferation and apoptosis of the glomerular epithelial cells in rats with puromycin aminonucleoside nephrosis.

Injury and repair of the glomerular epithelial cells (GECs) play an important role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). To obtain a better understanding of proliferation and apoptosis of GECs, we examined immunohistochemical and in situ hybridization findings in puromycin aminonucleoside nephrosis (PAN) of rats. The minimal-change nephrotic syndrome model (PAN-MCNS) was induced by administering 5 subcutaneous injections of puromycin aminonucleoside (PA; each 1.5 mg/100 g B/W to one group of rats), whereas the FSGS model (PAN-FSGS) was induced by administering an additional 5 injections of PA to another group of rats. The cell kinetics of the GECs were assessed with labeling 5-bromo 2'-deoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA). To investigate regulation of apoptosis in rats with PAN, we evaluated the expression of p53, Fas antigen, Fas ligand and Bc1-2. Rats with PAN-MCNS exhibited a significantly greater number of BrdU- and PCNA-labeled GECs as compared with control rats. In rats with PAN-FSGS, the number of PCNA-labeled GECs was greater than in rats with PAN-MCNS, but the number of BrdU-labeled GECs was lower. Apoptotic cells were occasionally observed in the sclerotic lesions, with the number being significantly higher in rats with PAN-FSGS than in rats with PAN-MCNS and control. Apoptotic cells were observed in the GECs of PAN-FSGS rats. However, they were negative for p53, Fas antigen, and Fas ligand. Immunohistochemical and in situ hybridization studies revealed a greater intraglomerular overexpression of Bc1-2 protein and bc1-2 mRNA in the PAN-FSGS rats as compared with control rats. These results suggest that insufficient proliferation and apoptosis in GECs may be involved in the progression of FSGS.

Animals↗