Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 145 records · Page 8Linked to original sources

PubMed2000

Popliteal amyloidoma presenting with leg ischemia in a chronic dialysis patient.

The authors report a case of bilateral popliteal amyloidoma causing stenosis of the popliteal artery and vein. This patient had been treated with hemodialysis for 26 years. The diagnosis was made with MR angiography. A popliteal tumor of the right knee was resected surgically and the histologic examination showed deposition of amyloid. After resecting the popliteal tumor, the severe leg pain and intermittent claudication improved. This report suggests that popliteal amyloid tumors should be considered in a patient undergoing long-term hemodialysis who complains of leg pain and intermittent claudication.

Adult↗

PubMed2000

GM-CSF gene therapy using adenoviral vector in hamster pancreatic cancer.

The aim of this study was to examine the antitumor effect of irradiated granulocyte macrophage-colony-stimulating factor (GM-CSF)-gene-transduced hamster pancreatic cancer cells and its relationship to the amount of GM-CSF produced by transduced tumor cells. Hamster pancreatic adenocarcinoma cells, HPD1NR, which spontaneously secrete 15.0+/-0.4 pg/106 cells per 24 h of GM-CSF, and HPD2NR cells, which do not secrete GM-CSF, were used. When these cells were infected with recombinant adenovirus harboring the GM-CSF gene, HPD1NR and HPD2NR secreted 624.2+/-9.9 and 157.8 +/-5.7 pg/106 cells per 24 h, respectively. Vaccination with irradiated GM-CSF-secreting HPD2NR completely protected syngeneic hamsters challenged with live parental cells. On the other hand, vaccination with irradiated HPD1NR protected 60% of hamsters from tumor development after challenge with parental cells. None of the tumor-free hamsters initially vaccinated with irradiated GM-CSF-producing HPD2NR cells developed tumor upon repeated challenge with parental cells during the entire observation period. Irradiated GM-CSF-gene-transduced hamster pancreatic cells are promising as a novel adjuvant cancer therapy after surgery for primary and metastatic pancreatic cancer. The results indicate the necessity for a therapeutic strategy for cancer based on the cytokine status of tumors.

Adenoviridae↗

PubMed2000

Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations.

Holocarboxylase synthetase (HCS) deficiency is a rare autosomal recessive disorder of biotin metabolism. Including three new Japanese patients we diagnosed in this study, ten Japanese families have, so far, been accumulated. In these families, the mutations 237Leu > Pro (seven alleles) and 1067delG (five alleles) were predominant; 508Arg > Trp and 55(Val > Met mutations were identified in three families in the heterozygous form and in one patient in the homozygous form, respectively. To determine the origin of these mutations, we identified new polymorphic microsatellite markers in the HCS gene and analyzed the haplotypes of the patients. All the 237Leu > Pro and the 1067delG alleles were associated with haplotype 2-2. This finding is consistent with the notion that these mutations are founder mutations in the Japanese population. Three Japanese 508Arg > Trp alleles were associated with several haplotypes, including 2-3 and 1-4. The haplotype of a Taiwanese patient homozygous for the 508Arg > Trp mutation was 2-3/2-3. The haplotype of one Japanese patient homozygous for the 550Val > Met mutation was 1-4/1-4, whereas that of a Jewish patient with the same homozygous mutation was 2-3/2-3. Both mutations were associated with at least two haplotypes and were found in several ethnic groups. The changes 508Arg > Trp and 550Val > Met occurred at CpG dinucleotide. The data suggest that these two mutations represent a mutational hot-spot.

Biotin↗

PubMed2000

An automated assay for measuring serum ascorbic acid with use of 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy, free radical and o-phenylenediamine.

We developed a novel, cost-effective, and automated assay for ascorbic acid (AsA) in serum using a COBAS MIRA S analyzer (Roche Diagnostic System). Our method has a wide dynamic range and covers AsA concentrations from well below the lower reference interval to well above it. AsA is oxidized by 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy, free radical (TEMPO) to dehydroascorbic acid (DAsA). The latter condenses with o-phenylenediamine (OPDA) to form a quinoxaline derivative that absorbs light at 340 nm. The change in absorbance at 340 nm is proportional to the concentration of AsA in the specimen. The automated system permitted the assay of 65 specimens per hour at a cost of approximately US$ 0.01 per specimen for reagents. The assay can be applied directly to serum specimens (direct method) and also to sera with a prior deproteinization step with metaphosphoric acid. The detection limit for the direct serum assays is 0.8 vs. 0.4 mg/l with the deproteinization method. The recovery of AsA from a supplemented serum pool was of >95% for both procedures. We used four distinct methods on 66 patients sera. The direct method for AsA correlated well with an HPLC method (r=0.964, P<0.001); the direct method also correlated well with a method that uses AsA oxidase (r=0.975, P<0. 001). The deproteinization method correlated well with HPLC (r=0.981, P<0.001), and with the AsA oxidase procedure (r=0.994, P<0.001). Ten within-day determinations on a serum pool gave a C.V. <4.3% for both the direct and deproteinization procedures. The between-day assays of the same serum pool over 10 days gave a C.V. of <6.7% by both methods.

Artifacts↗

PubMed2000

Use of the abdominal wall fat index determined ultrasonographically for assessing the risk of post-operative pulmonary embolism.

OBJECTIVE: To assess the usefulness of the abdominal wall fat index (AFI) for predicting pulmonary embolism (PE) after gynecologic surgery. METHOD: The subjects were 115 female patients who underwent laparotomy for gynecologic disease. They were divided into low-dose heparin therapy (n=28) and control, without heparin (n=87) groups. The AFI ratio of the maximum preperitoneal fat thickness to the minimum subcutaneous fat thickness was determined using ultrasonography. RESULT: Post-operative PE occurred in four control patients. If the cut-off value of the AFI for predicting PE development was set at more than or equal to 0.85, the sensitivity was 1.00 and the specificity was 0.60 (P=0.03). If we restricted the criteria, and set the cut-off value of the AFI to more than or equal to 0.85 in patients with hypertension [systolic blood pressure (BP)>/=140 mmHg, diastolic BP>/=90 mmHg or patients were taking antihypertensive medication], the sensitivity and specificity were 0. 75 and 0.92, respectively (P=0.001). CONCLUSION: Visceral fat obesity is a risk factor for PE after gynecologic surgery, and the AFI is useful for predicting PE and for whom post-operative low-dose heparin therapy may be indicated.

Abdomen↗

PubMed2000

A single institutional outcome analysis of Gamma Knife radiosurgery for single or multiple brain metastases.

Although Gamma Knife stereotactic radiosurgery (SRS) is widely used for metastatic brain tumors, optimal patient selection and treatment strategy continue to be investigated. The aim of this study was to provide treatment results with Gamma Knife SRS and to establish prognostic factors. Of the 54 patients treated from 1990 to 1997, 51 patients were evaluable. There were 28 males and 23 females, with a median age of 60 years. Median Karnofsky Index was 80. There were 19 non-small cell lung cancers, eight colon cancers, six renal cell cancers, five ovarian cancers, four gastric cancers, three breast cancers, and six others. Primary tumors were controlled in 33 patients, and extracranial tumors were absent in 25 patients. Sixty-eight metastatic brain tumors in 37 patients underwent SRS as an initial treatment for the brain metastasis. Brain metastasis was solitary in 32 patients. Conventional radiation was combined with SRS in 29 patients, 24 of whom received whole brain radiotherapy. Eight patients had some form of surgical resection. Median survival time was 7.4 months. Five-year actuarial survival and local control rates were 16 and 52%, respectively. Median duration time of keeping pretreatment quality of life was 6.9 months. On a multivariate analysis, uncontrolled primary tumor, combined conventional radiotherapy, and performance status were statistically significant prognostic factors. Four patients who underwent whole brain radiation developed low grade dementia.

Adult↗

PubMed2000

An application of PCR-single strand conformation polymorphism to MN genotyping.

A PCR-based genotyping of MN blood group system was investigated for DNA samples taken from a population of 409 northern Japanese. DNA fragment (257bp) including exon 2 of glycophorin A (GPA) gene, in which encodes the determinants of MN antigens, was specifically amplified. On the analysis of PCR-single-strand conformation polymorphism (PCR-SSCP) for M alleles, band patterns of M(G) and M(T) were easily discriminated each other. For N alleles, three band patterns were observed, and we tentatively named these alleles as N(1), N(2) and N(V). The N(1) allele appeared predominantly and N(2) had two base substitutions at 1st (C-->A) and 56th (C-->T) in exon 2 of N(1). The other N(V), which was detected from a pair of a mother and her child, possessed a single base substitution at 23rd (A-->G) in intron 2. The allele frequencies of M(G), M(T), N(1) and N(2) were 0.4450, 0.0978, 0.4303 and 0.0269, respectively. The polymorphism information content and the probability of paternity exclusion by this MN genotyping were estimated to be 0.5252 and 0.3219, respectively.

Journal Article↗

PubMed2000

In vitro antifilarial activity of extracts of the medicinal plant Cardiospermum halicacabum against Brugia pahangi.

The in vitro effects of ethanol and aqueous extracts of the medicinal plant Cardiospermum halicacabum on adult worms and microfilariae of Brugia pahangi were investigated. With or without the plant extracts in culture medium, the motility of adult worms, microfilariae and microfilarial release from female worms were monitored daily. After 7 days of culture, viability or tissue damage of adult worms was assessed using the MTT assay. At > 500 microg ml-1, the aqueous extract significantly reduced motility of adult females after 24 h of exposure and adult males after 3 days. The aqueous extract, at > 500 microg ml-1, also significantly reduced microfilarial release from female worms, starting on day 2. The reduction in the motility of adult worms and the pattern of microfilarial release from female worms were concentration and time dependent. The MTT assay results revealed that adult worms cultured in the presence of aqueous extracts at > 500 microg ml-1 were damaged. However, the aqueous extract did not affect the motility of microfilariae with the exception of those in higher concentration extracts. Higher concentrations of ethanol extracts (2 mg ml-1) inhibited both the motility of adult worms and the release of microfilariae from females. Little effect of ethanol extracts was detected by the MTT assay, as only slight damage was caused to worms exposed only to the highest concentration (2 mg ml-1). However, ethanol extract at 500 microg ml-1 rapidly reduced the motility of microfilariae on day 2. The present study revealed that an aqueous extract of C. halicacabum has mild but definite direct macrofilaricidal action on B. pahangi.

Animals↗

PubMed2000

Determination of medullasin levels for the diagnosis of multiple sclerosis.

OBJECTIVES: To obtain a simple and reliable clinical parameter for the diagnosis of multiple sclerosis among patients with neurological diseases. PATIENTS AND METHODS: Heparinized peripheral blood was obtained from patients with multiple sclerosis and those with non-inflammatory neurological diseases and healthy volunteers. A new enzyme immunoassay method determining medullasin levels in human granulocytes was developed by using mouse monoclonal antibody against medullasin. RESULTS: A newly developed enzyme immunoassay method for medullasin can detect as little as 1 ng/ml medullasin and results can be obtained within 2 h. Eighty-five out of 112 patients with multiple sclerosis (75.8%) showed positive results (above means of normals + 2 SD) in the medullasin test, while 15.4% (12/78) of patients with non-inflammatory neurological disease had positive results. CONCLUSION: This newly developed enzyme immunoassay method for medullasin is considered to be a useful paraclinical test for the diagnosis of multiple sclerosis.

Adolescent↗

PubMed2000

The liver in collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver.

AIMS/BACKGROUND: Among patients with collagen diseases, liver enzyme abnormalities are a relatively common phenomenon. To establish the liver pathology in collagen diseases, detailed pathologic studies were performed on the hepatic diseases in many patients, including various kinds of collagen diseases. METHODS: The livers from 160 patients (120 autopsy and 40 liver biopsy patients) were examined pathologically: 73 with systemic lupus erythematosus (SLE), 32 with rheumatoid arthritis (RA), 18 with polymyositis and dermatomyositis (PM and DM), 15 with systemic sclerosis (SSc), 11 with mixed connective tissue disease (MCTD) and 11 with polyarteritis nodosa (PAN). RESULTS: Liver diseases were divided into three groups: hepatic arteritis, liver diseases associated with collagen diseases (primary biliary cirrhosis, PBC; autoimmune hepatitis, AIH; nodular regenerative hyperplasia of the liver, NRH) and other liver diseases. Hepatic arteritis presenting the features of the PAN type of necrotizing arteritis was found in 27 autopsy patients. The incidence of arteritis in autopsy patients was 100% in PAN and 8.3-25% in other collagen diseases. Primary biliary cirrhosis was observed in 9 patients, 7 of whom (3 with SSc, 2 with RA, 1 with PM and DM, and 1 with MCTD) had antimitochondrial antibodies (AMA)-positive PBC, and 2 SLE patients had AMA-negative PBC. Three patients (2 with SLE and 1 with MCTD) were diagnosed clinicopathologically as having AIH. However, 3 patients (1 with SLE, 1 with MCTD and 1 with PM and DM) with clinical, biochemical and serologic data indicating probable AIH were excluded from the group with AIH association because of the liver histology (no characteristic features of AIH) and clinical course. These results indicated that data without histologic assessments of the liver are not adequate for diagnosing AIH in collagen diseases. Nodular regenerative hyperplasia of the liver was observed in 7 patients (5 with SLE, 1 with SSc and 1 with PAN). CONCLUSION: The present study offers data that are useful for the diagnosis and treatment of patients with collagen diseases and liver abnormalities.

Adolescent↗

PubMed2000

Transgenic zebrafish for detecting mutations caused by compounds in aquatic environments.

We have established a transgenic zebrafish line carrying a shuttle vector plasmid (pML4) for detecting mutagens in aquatic environments. The plasmid contains the rpsL gene of Escherichia coli as a mutational target gene, and the kanamycin-resistance gene for recovering the plasmid from the chromosomal DNA. To evaluate the system, we treated embryos of the transgenic fish with N-ethyl-N-nitrosourea (ENU), which induces a dose-dependent increase in the mutation frequency of the target gene. The mutation spectrum was consistent with the proposed mechanism of ENU mutagenesis. Similarly, treating the embryos with benzo[a]pyrene or 2-amino-3, 8-dimethylimidazo[4,5- f]quinoxaline, which are found in naturally polluted water, significantly increased the frequency of mutations in the target gene.

Animals↗

PubMed2000

Effect of activated human protein C on experimental venous thrombosis induced by stasis with operative invasion in mice.

Protein C (PC) is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating blood coagulation and fibrinolysis by inhibiting not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). In this study, it was reported that the antithrombotic effect of a human APC product (designated as CTC-111) compared with that of heparin and human PC on the deep venous thrombosis (DVT) model induced in mice by stasis caused by inferior vena cava ligation and operative invasion. Drugs were injected into a tail vein at -2, 30, 60, and 120 min after the inferior vena cava ligation. One-fifth amount of the total dosage of a given drug was injected at each time point. The wet weight of thrombus formed was reduced by APC or heparin administration, however, PC, which was equal to APC in protein amount, did not show any antithrombotic effect. To confirm whether human PC could be activated by mouse thrombin, PC was treated with mouse or human thrombin to measure the amount of APC formed. Mouse thrombin could activate human PC at a similar activation rate as human thrombin. These results suggest that externally administrated PC cannot exhibit antithrombotic effect in this DVT model due to slow activation rate to APC and that APC is a better antithrombic agent than PC for treating thrombotic diseases.

Animals↗

PubMed2000

Effect of activated human protein C on disseminated intravascular coagulation induced by lipopolysaccharide in rats.

Protein C is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating coagulation and fibrinolysis by inactivating not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). The aim of the present study was to examine the effect of a human APC product (designated as CTC-111), compared with that of heparin, on the disseminated intravascular coagulation (DIC) induced by lipopolysaccharide (LPS) in rats. LPS (1 mg/kg/h) infusion was performed through a femoral vein for 4 h. One-fifth amount of the total dosage of CTC-111 or heparin was injected into the other femoral vein, followed by a 4-h infusion of the remainder. Both CTC-111 (10,000-100,000 U/kg) and heparin (400-800 IU/kg) inhibited the decrease in platelet count and fibrinogen level equally. The prolonged activated partial thromboplastin time and prothrombin time observed in DIC rats were further elongated in both CTC-111- and heparin-treated rats. But, this prolongation was less in CTC-111-treated rats than in the heparin-treated ones. Heparin inhibited the increase in fibrin and fibrinogen degradation products more prominently than CTC-111. On the other hand, CTC-111 strongly inhibited the increase in PAI-1 activity but heparin did not. These results suggest that CTC-111 may enhance fibrinolysis through its direct inhibitory effect on PAI-1. The parameters for liver or renal damage, i.e., plasma glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), creatinine (Cre) and blood urea nitrogen (BUN), were significantly increased by LPS infusion. Both CTC-111 (100,000 U/kg) and heparin (800 IU/kg) decreased the increase in GOT and GPT levels significantly, whereas neither affected the increase in Cre or BUN. From these results, the activation of the blood coagulation system might partially contribute to the progression of liver damage caused by LPS, and might be less involved in the progression of renal damage in this model. In conclusion, CTC-111 showed both anticoagulant and profibrinolytic activity in the LPS-induced DIC model without excessive prolongation of coagulation time. From these results, CTC-111 is expected to be a useful remedy for DIC without the risk of bleeding.

Animals↗

PubMed2000

Biphasic effects of dopamine on 86rubidium uptake in rat renal proximal tubules.

The mechanism(s) by which dopamine inhibits Na+-K+-ATPase activity in the renal proximal tubule is still controversial. We studied the short-term effects of dopamine on the sodium pump in rat renal proximal tubule suspensions with the 86Rb uptake method. Dopamine and the D1-like agonist, SKF81297, initially stimulated Na+-K+-ATPase activity at 5 min and subsequently inhibited it at 10 min and 20 min; the inhibition by 10 microM dopamine at 20 min was 21.3 +/- 4.5%. The inhibitory effect of dopamine on Na+-K+-ATPase activity was mimicked by thymeleatoxin (a classical protein kinase C [PKC] agonist) while Sp-8-CPT-cAMPS (a protein kinase A [PKA] agonist) had no effect. However, the combination of the PKC and PKA agonists mimicked the biphasic effects of dopamine and SKF81297. Rp-8-CPT-cAMPS (a PKA inhibitor), U-73122 (a phospholipase C inhibitor), or calphostin C (a PKC inhibitor), blocked the dopamine-mediated biphasic effects on Na+-K+-ATPase activity. It is suggested that the biphasic effects of dopamine on Na+-K+-ATPase activity (an initial stimulation and a subsequent inhibition) are transduced by activating both PKA and PKC through a D1-like receptor.

Animals↗

PubMed2000

Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6.

Since the discovery of the virus in 1994, the rapid pace with which Karposi's sarcoma-associated herpesvirus (KSHV) research has progressed has quickly led to a broad understanding of the structure of the virus and its biology and pathology in humans. Molecular piracy of potentially useful cellular genes has emerged as a characteristic feature of this virus. The viral homolog of human IL-6, vIL-6 is an example in kind. Studies in vitro and in vivo have shown that vIL-6 can stimulate the growth of KSHV-infected primary infusion lymphoma (PEL) cells, can promote hematopoiesis, and act as an angiogenic factor through the induction of vascular endothelial growth factor (VEGF). It is not difficult to envision how vIL-6, through these properties and perhaps others yet to be identified, can contribute to KSHV survival and spread in the human population.

Hematopoiesis↗

PubMed2000

Increase in mutation frequency in lung of Big Blue rat by exposure to diesel exhaust.

Exposure to diesel exhaust (DE) is known to cause lung tumors in rats. To clarify the mutagenicity of DE, we estimated mutant frequency (MF) and determined the mutation spectra in rat lung after exposure to DE using lambda/lacI transgenic rats (Big Blue system). Male Big Blue rats (6 weeks old) were exposed for 4 weeks to 1 or 6 mg/m(3) DE, which contains suspended particulate matter. Control rats were maintained in filtered clean air. After exposure to 6 mg/m(3) DE, MF in lung was 4.8-fold higher than in control rats (P < 0.01), but no increase in MF was observed in rats exposed to 1 mg/m(3) DE. Sixty-nine mutants were identified after exposure to 6 mg/m(3) DE. The major mutations were A:T-->G:C (18 mutations) and G:C-->A:T (19 mutations) transitions. Remarkably, G-->T transversion of the lacI gene at site 221 was a hot-spot induced by exposure to DE, and there were complex mutations in which multiple mutations occurred in a single mutant, especially in the rats exposed to 6 mg/m(3) DE. DNA adducts formed by DE were analyzed using a (32)P-post-label TLC method and the amount of 8-hydroxydeoxyguanosine (8-OHdG) was measured using HPLC. Relative adduct level and amount of 8-OHdG were significantly increased in the rats exposed to 6 mg/m(3) DE compared with the controls (3.0- and 2.2-fold, respectively; P < 0.01). The level of cytochrome P450 1A1 mRNA was shown by northern blot analysis to be significantly increased in the lungs of rats exposed to 6 mg/m(3) DE (5.5-fold; P < 0.01). These results indicate that DE causes lesions in genomic DNA and acts as a mutagen in rat lung.

Animals↗

PubMed2000

IL-1 induces expression of p21(WAF1) independently of p53 in high-passage human embryonic fibroblasts WI38.

We tested the effect of IL-1 on the expression of p21(WAF1) in human embryonic fibroblasts WI38. Exposure to IL-1 caused induction of p21(WAF1) protein in high-passage WI38 cells but not in early-passage cells. However, IL-1 did not stimulate the transcription of a CAT-reporter gene having two copies of the p53-responsive element on its promoter or the p53-binding capacity of nuclear extracts, although it increased transcriptional rate of p21(WAF1) in these high-passage cells. These results suggest that the induction of p21(WAF1) by IL-1 occurs at the transcriptional level, but p53 function is not required in these cells. Further studies found that IL-1 did not cause cell-cycle arrest, and the overexpression of p21(WAF1) resulted in only a slight delay of cell growth, while the level of p21(WAF1) coprecipitated with cyclin-dependent kinase-2 (Cdk2) was increased by IL-1. Moreover, a kinase assay of Cdk2 immunoprecipitates showed that IL-1 did not reduce the kinase activity, and IL-1 did not affect the status of phosphorylation of the retinoblastoma gene product (Rb). These findings imply that despite the induction of p21(WAF1), this cannot fully account for the growth arrest in high-passage WI38 cells. Thus, IL-1 mediates p21(WAF1) induction through a p53-independent pathway(s) in high-passage WI38 cells, but the cell cycle is regulated independently of p21(WAF1).

Cell Cycle↗

PubMed2000

Modifying effects of ethinylestradiol but not methoxychlor on N-ethyl-N-nitrosourea-induced uterine carcinogenesis in heterozygous p53-deficient CBA mice.

It is unknown whether endocrine-disrupting chemicals (EDCs) with estrogenic activities have any modifying effects on uterine carcinogenesis. In our previous study, we established a uterine-carcinogenesis model that is useful for detecting tumor-modifying effects of EDCs by the administration of N-ethyl-N-nitrosourea (ENU) to female heterozygous p53-deficient CBA mice [p53 (+/-) mice]. To investigate the effects of ethinylestradiol (EE) and methoxychlor (MXC) on development of ENU-induced uterine tumors, female p53 (+/-) mice and their wild-type littermates [p53 (+/+) mice] received an intraperitoneal injection of 120 mg/kg body weight (bw) of ENU, followed, in Group 1, by no further treatment; in Group 2, by a diet containing 1 ppm EE; in Group 3, by a diet containing 5 ppm EE for 4 weeks and 2.5 ppm EE thereafter; and in Group 4, by a diet containing 2000 ppm MXC for 26 weeks. Uterine proliferative lesions that were induced were composed of both endometrial-stromal and epithelial-cell types. Endometrial stromal sarcomas were induced in p53 (+/-) mice of Groups 1 to 4, and the incidence (87%) in Group 3 was significantly increased compared to Group 1 (47%). Atypical hyperplasias (clear-cell type) of the endometrial gland in p53 (+/-) mice were seen at incidences of 0, 14, 60, and 0% in Groups 1, 2, 3, and 4, respectively, while their incidence in p53 (+/+) mice was 0, 7, 53, and 0%, respectively, with a significant difference between Groups 1 and 3 in both cases. One p53 (+/-) mouse in Group 3 also had an adenocarcinoma consisting of clear cells, and the PCNA labeling indices of the clear-cell atypical hyperplasias, and this endometrial adenocarcinoma, were higher than those of glandular hyperplasias. The present study suggests that 2.5 ppm EE, but not MXC, exerts tumor-promoting effects on stromal and epithelial proliferative lesions of the uteri in p53 (+/-) mice initiated with ENU.

Adenocarcinoma, Clear Cell↗