PubMed Health⌕ Search

Biomedical subjects

K Mitsumori

Publications and source records attributed to K Mitsumori.

At least 19 recordsLinked to original sources
PubMed2005

Chronic toxicity and carcinogenicity of dietary administered ammonium sulfate in F344 rats.

Chronic toxicity and carcinogenicity studies of ammonium sulfate, used as a food additive in fermentation, were performed in male and female Fisher 344 rats at dietary concentrations of 0%, 0.1%, 0.6% and 3.0% in a 52-week toxicity study and 0%, 1.5% and 3.0% in a 104-week carcinogenicity study. Treatment with ammonium sulfate caused significant increase in kidney and/or liver weights in males and females of the 3.0% diet group, but no effects were found on survival rate, body weights, and hematological, serum biochemical or histopathological parameters at any dose levels in the chronic toxicity study. Regarding carcinogenicity, ammonium sulfate did not exert any significant influence on the incidences of tumors in any of the organs and tissues examined. It was concluded that the no observed adverse effect level of ammonium sulfate was the 0.6% diet, which is equivalent to 256 and 284 mg/kg b.w./day in males and females, respectively, and the compound is non-carcinogenic under the conditions of the study.

Administration, Oral↗
PubMed2005

Thyroid lesions and dioxin accumulation in the livers of jungle crows (Corvus macrorhynchos) in urban and suburban Tokyo.

Wild jungle crows (Corvus macrorhynchos) captured from three different areas of Tokyo were examined to evaluate environmental contamination of dioxins. In addition to the pathologic examination of their whole body, accumulation of dioxins, mRNA expression of the aryl hydrocarbon receptor (AhR), and pentoxyresorufin-O-depenthylase (PROD) activity in the liver were determined. Marked histopathologic changes were observed in the thyroid glands, especially in the crows from the urban downtown area. Levels of dioxins and their toxic equivalents (TEQs) and AhR mRNA expression in the livers of the crows from the urban area were higher than those from the suburban area. There was a high correlation between the levels of TEQs and PROD activity. The results of the present study demonstrated that jungle crows possess AhR-mediated toxicologic pathways similar to those of mammals and suggest the possibility that the thyroidal changes observed in the adult crows from the urban areas are one of the toxic manifestations resulting from exposure to dioxins and other environmental chemicals.

Age Factors↗
PubMed2005

A histological study of the cardiac conduction system in a heifer with complete atrioventricular block.

A case of complete atrioventricular (AV) block of congenital origin in a 16-month-old Holstein heifer was studied histologically with serial sectioning of the cardiac conduction system. The heart was enlarged and showed moderate dilatation of the left and right ventricles. Histologically, the abnormally placed and poorly formed AV bundle was observed in association with abnormality in the tricuspid extension of the central fibrous body, suggesting that the pathological state of the AV bundle had been responsible for the complete AV block. This type of anatomical fault in the AV bundle is considered to be part of an embryological, developmental malformation of the central fibrous body.

Animals↗
PubMed2004

Evaluation of the toxicity of enzymatically decomposed rutin with 13-weeks dietary administration to Wistar rats.

The subchronic toxicity of enzymatically decomposed rutin, which consists mainly of isoquercitrin, was investigated in male and female Wistar rats with dietary administration at concentrations of 0, 0.2, 1 and 5% for 13 weeks. No mortality or abnormal clinical signs were observed throughout the experimental period in any groups. Body weight gain was reduced from week 10 to the end of the experiment in the 5% dosed males as compared to the 0% controls. Decreased erythrocytic parameters, i.e. red blood cell count, hemoglobin concentration and hematocrit, and significantly lowered serum triglyceride levels were also detected in the 5% males. Organ weight measurement, macro and microscopic observation revealed no test substance-related toxicological changes. Based on the above findings, no-observed-adverse-effect levels (NOAELs) for male and female rats were estimated to be 1 and 5%, respectively, translating into 539 and 3227 mg/kg b.w./day.

Animals↗
PubMed2004

Smooth muscle hamartoma of the abomasum in a calf.

This report describes a case of smooth muscle hamartoma of the abomasum in a 6-month-old steer humanely killed because of severe pneumonia. At necropsy, marked thickening of the abomasal wall in the area of the pylorus was found. On cut section, the thickness of the submucosal layer, extending from the submucosa to the muscularis propria, was seen to be increased to 3 cm. The upper (i.e., nearest to the gut lumen) half of the sectioned thickening was composed mainly of adipose-like tissue and the lower half mainly of muscle-like tissue. Histologically, the submucosal layer was composed of fibroadipose tissue, within which were embedded, to varying degrees, numerous well-defined, haphazardly oriented, thin to thick bundles of smooth muscle fibres. This appears to be the first report of smooth muscle hamartoma of the stomach or abomasum in animals, including man.

Abomasum↗
PubMed2004

Sequential analysis of testicular lesions and serum hormone levels in rats treated with a Psoralea corylifolia extract.

In order to clarify pathogenetic targets for the testicular toxicity of a extract of Psoralea corylifolia (P. corylifolia), F344 rats were fed diet containing 3% P. corylifolia extract for up to 12 weeks and subjected to hormone assays and histopathological examination on the testis and epididymis at weeks 1, 2, 4, 8 and 12 (Exp 1). Similar analyses were performed on 1, 3, 7 and 14 days after a single gavage administration of the P. corylifolia extract at a dose of 10 g/kg b.w. (Exp 2). In Exp 1, increase in the numbers of degenerated and exfoliated germ cells and loss of elongated spermatids beyond steps 7 or 8 were initially observed in the seminiferous tubules at week 1, followed by more pronounced degeneration of germ cells with depletion of post-meiotic populations from week 2. The tubular degeneration was associated with Leydig cell atrophy and persistent reduction of serum testosterone and FSH levels throughout the treatment period and a slight reduction of serum LH in later stages. In Exp 2, reduction of serum testosterone and FSH levels preceded degeneration of germ cells in stage VII and VIII tubules at 3 and 7 days after the administration. The results suggest that rapid androgen deprivation reflecting direct interference with Leydig cell function and simultaneous disturbance of the pituitary-testicular axis play pivotal roles in P. corylifolia extract-induced germ cell injury in seminiferous tubules.

Animals↗
PubMed2003

Transgenic tumor models for carcinogen identification: the heterozygous Trp53-deficient and RasH2 mouse lines.

Genetically altered mouse models (GAMM) for human cancers have been critical to the investigation and characterization of oncogene and tumor suppressor gene expression and function and the associated cancer phenotype. Similarly, several of the mouse models with defined genetic alterations have shown promise for identification of potential human carcinogens and investigation of mechanisms of carcinogen-gene interactions and tumorigenesis. In particular, both the B6.129N5-Trp53 mouse, heterozygous for a p53 null allele, and the CB6F1-RasH2 mouse, hemizygous for the human H-ras transgene, have been extensively investigated. Using 26-week exposure protocols at or approaching the maximum tolerated dose, the summary results to date indicate the potential for GAMM to identify and, possibly, classify chemicals of potential risk to humans using short-term carcinogenicity experiments. This IWGT session focused on: (1) the development of recommendations for genetic/molecular characterization required in animals, tissues, and tumors before and after treatment for identification of presumptive human carcinogens based on the current state of knowledge, (2) identification of data gaps in our current state of knowledge, and (3) development of recommendations for research strategies for further development of our knowledge base of these particular models. By optimization of protocols and identification of significant outcomes and responses to chemical exposure in appropriate short-term mechanism-based genetically altered rodent models, strategies for prevention and intervention may be developed and employed to the benefit of public health.

Animals↗
PubMed2003

Primary malignant mixed mesenchymal tumour of the heart in a dog.

A case of primary malignant mixed mesenchymal tumour of the heart in an 8-year-old golden retriever is described. The cardiac tumour, measuring 2.5 x 3 x 5 cm, was located in the posterior part of the atrial septum, extending into the surrounding region. Histologically, the tumour was composed of multiple mesenchymal elements of fibrosarcoma, rhabdomyosarcoma, liposarcoma and chondrosarcoma. No previous reports of such a tumour occurring in the heart of the dog were found in the literature.

Animals↗
PubMed2002

Iron lactate induction of pancreatic and endometrial proliferative lesions and a lack of increased tumors in a 104-week carcinogenicity study in F344 rats.

Iron lactate has been used as a food additive for iron supplementation. The present study was conducted to determine whether it might have carcinogenic potential. A total of 150 male and 150 female Fischer 344 rats were divided into three groups and fed basal diet containing 0, 1 or 2% of iron lactate for 104 weeks. No iron lactate-induced tumors were observed in any groups, although the incidences of pancreatic acinar cell and endometrial gland hyperplasias were increased in males and females, respectively, in the 2% group. Thus our in vivo animal data indicate that iron lactate lacks carcinogenicity in male and female F344 rats. However, estrogenic effects might be concluded based on the data for endometrial lesions. In a second experiment, an estrogen responsive rat pituitary tumor cell line, MtT/Se, and a human breast cancer cell line, MCF-7, were therefore employed to examine the estrogenic potential of iron lactate with regard to receptor binding affinity and ERE-reporter gene activation. Results in both cases were negative. Further investigations are needed to elucidate the mechanisms of induction of pancreatic and endometrial proliferative lesions by iron lactate.

Animals↗
PubMed2002

Non-secretor status is associated with female acute uncomplicated pyelonephritis.

OBJECTIVE: To retrospectively analyse the secretor status in women with acute uncomplicated pyelonephritis, as non-secretors of histo-blood group antigens are reportedly at risk of recurrent urinary tract infections (UTIs). PATIENTS AND METHODS: The study included 245 women who had been diagnosed as having acute uncomplicated pyelonephritis in affiliated hospitals over the past 5 years. All women were sent antiseptic swabs, to collect saliva, and a questionnaire to survey their past UTI episodes and menstrual status. Responses with written informed consent were obtained from 106 women (median age 50.5 years, range 17-85). The secretor status was determined using the haemagglutination inhibition assay from the saliva on the swabs. RESULTS: Forty-four (41%) of the women were non-secretors, a significantly higher frequency than in the (control) Japanese population (217 of 960, 22.6%; P< 0.001). The incidence of non-secretors was significantly higher (P < 0.01) in premenopausal (26 of 46, 57%) than in postmenopausal women (18 of 60, 30%). CONCLUSION: These results suggest that non-secretor status is associated with a genetic susceptibility to acute uncomplicated pyelonephritis, especially in premenopausal women.

ABO Blood-Group System↗
PubMed2002

Myocardial hamartoma of the right atrium in a dog.

A myocardial hamartoma of the right atrium is described in an 8-year-old dog that died from pneumonia. At necropsy, a firm, mottled, dark-brown right atrial appendage, of normal shape but slightly enlarged, was found incidentally. On section, the right atrial appendage was composed of a grey-tan, solid mass. Histological features of the mass were as follows: the component cells were mature cardiac muscle cells; the mass contained all of the components of the normal heart wall (i.e., epicardium, myocardium and endocardium), but the arrangement of the component tissues was disorganized; growth of the mass was non-invasive, and continuity of the component cells with adjacent normal myocardial cells was evident, suggesting a congenital origin. This appears to be the first report of congenital myocardial hamartoma in any animal other than man.

Animals↗
PubMed2001

Testicular toxicity in F344 rats by aminophenylnorharman, formed from norharman and aniline.

9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole [aminophenylnorharman (APNH)] is a novel mutagenic heterocyclic amine, produced by the reaction of norharman with aniline in the presence of S9 mix. In the present study, the acute toxicity of this compound was investigated in male F344 rats. Ten-week-old animals were treated with a single intragastric injection of APNH at doses of 45 or 90 mg/kg body wt and euthanized 1, 3, or 6 days afterward. When APNH was administered at a dose of 90 mg/kg, vacuolation of Sertoli cells in the testis was seen at 1 day after treatment. The testicular damage had markedly progressed by day 6, with multinucleated giant cells and loss of round spermatids in the seminiferous tubules observed in groups 1 and 2 of the four histological categories of spermatogenesis. Numbers of spermatogonia were also decreased by APNH treatment. No toxic changes were observed in Leydig cells under these conditions and serum follicle-stimulating hormone and luteinizing hormone concentrations were also unchanged from control values. Such severe testicular damage was not observed at any time point at the 45 mg/kg dose level of APNH. Moreover, neither norharman nor aniline alone exerted acute testicular toxicity at doses equivalent to 90 mg/kg of APNH. In addition to the testicular lesions, erosive changes of urinary bladder, thymic atrophy, and panmyelophthisis were evident in rats given APNH at 90 mg/kg.

Administration, Oral↗
PubMed2001

Enhanced late components of AEFs associated with the temporal lobe lesions.

We recorded auditory evoked magnetic fields (AEFs) by presenting pure tone bursts once every 4000 ms in 11 patients with a brain lesion in or in the vicinity of the auditory cortex. AEFs on the damaged side revealed several enhanced deflections in late-latency AEFs (slow AEFs), peaking at approximately 320 (DI), 1030 (D2) and 1600 (D3) ms post-stimulus in eight patients. All the dipoles of slow AEFs were concentrated in the superior temporal regions which were not involved by brain lesions. D1, D2 and D3 dipoles were uniformly upward, downward and upward, respectively. The dipole moment varied from 12 to 122 nAm and had no consistent relationship with latency. This is the first report describing slow AEFs in cases with temporal lobe lesions.

Auditory Cortex↗
PubMed2001

Testicular toxicity of nitrofurazone causing germ cell apoptosis in rats.

In order to clarify the mechanism underlying testicular toxicity of nitrofurazone (NF), two experiments were performed. In experiment 1, sequential histopathological examination of testes after a single oral administration of 100 or 300 mg/kg NF to male rats demonstrated that degeneration of pachytene spermatocytes with an eosinophilic, shrunken appearance in stages VII-VIII and vacuolation of Sertoli cells were first observed 12 h after treatment. By 24 h, degeneration of pachytene spermatocytes in stages VII-XII and diplotene spermatocytes were observed. On post-treatment day 4, neither spermatocytes nor spermatids located inside the pachytene spermatocytes in stage VII were seen anywhere. Generation of seminiferous epithelium progressed with recovery to almost normal morphology after 12 weeks, although some morphological changes were still present. No lesions were apparent in spermatogonia, preleptotene spermatocytes, leptotene spermatocytes, zygotene spermatocytes or Leydig cells. Degenerate pachytene spermatocytes and some round spermatids seen after 24 h showed positive TdT-mediated dUTP-biotin nick end labeling (TUNEL). In addition, DNA laddering patterns were detected with agarose gel electrophoresis, and increased electron density of nuclei and cytoplasm of degenerating spermatocytes with nuclear chromatin focal aggregations were observed by electron microscopy, indicating that cell death was attributable to apoptosis. In experiment 2, sequential serum sex-related hormone levels were assayed after a single oral administration of 300 mg/kg NF to male rats and revealed a significant increase of testosterone and a decrease of progesterone at 6 h, and decreases of luteinizing hormone at 12 h and testosterone at 24 h. Prolactin tended to decrease from 12 h after treatment and the decrease was significant at 48 h. No significant changes were observed in levels of follicle-stimulating hormone or estradiol. The probability that NF damages germ cells by causing a hormonal imbalance is extremely low, since no pattern of hormonal imbalance that could be regarded as the cause of the testicular degeneration was observed until 12 h after NF treatment when pachytene spermatocytes began to degenerate. The present experiments suggest that NF damages Sertoli cells and pachytene spermatocytes in stages VII-XII directly.

Administration, Oral↗
PubMed2001

Primary extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type in the CNS.

Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type has been reported in various internal organs. Here a case is reported of MALT lymphoma developing in the cerebellopontine (CP) angle in a patient with Sjogren syndrome, and the concept of MALT lymphoma of the CNS is introduced. Pathologically, the tumor showed inflammatory features of reactive lymphocytic infiltration with follicle formation, but there were slightly atypical lymphocytes and plasmacytes with B-cell markers. These cells invaded reactive follicles, showing follicular colonization, and showed aberrant expression indicating their neoplastic nature. A review of the literature revealed eight cases of MALT lymphoma originating from the dura mater and one from the CP angle. The average age of patients was 50 years (range 28-66 years), and all patients were female. The tumors were slow to develop and the patients were cured after surgical removal and/or additional therapies. It is proposed that MALT lymphoma should be considered as a differential diagnosis of inflammatory pseudotumor of the CNS.

Adult↗
PubMed2001

Promoting effects of xylazine on development of thyroid tumors in rats initiated with N-bis(2-hydroxypropyl)nitrosamine and the mechanism of action.

To cast light on whether xylazine hydrochloride (XZ), a veterinary medicine commonly used as a sedative agent for food-producing animals, has any promoting potential for thyroid carcinogenesis, the following studies were performed. In Experiment I, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ for 52 weeks with or without initiation with 2400 mg/kg N:-bis(2-hydroxypropyl)nitrosamine (DHPN). Focal follicular cell hyperplasias, adenomas and/or carcinomas were induced in the DHPN alone, XZ alone and DHPN+XZ groups, and the incidences and multiplicities of these lesions in the DHPN+XZ group were significantly increased as compared with the DHPN alone case. In Experiment II, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ and were examined for serum levels of triiodothyronine (T(3)), thyroxine (T(4)) and thyroid-stimulating hormone (TSH) at weeks 1, 2 and 4. In the XZ group, significant increase in thyroid weight and decrease in serum T(4) levels were observed at all time points. Serum T(3) and TSH levels were significantly decreased and increased, respectively, at week 1, but returned to within the control range thereafter. In Experiment III, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ, they were examined for thyroid iodine uptake and organification of XZ after 1 and 2 weeks. The thyroidal iodine uptake per milligram of thyroid and the amount of iodine bound to 1 mg protein showed a tendency for decrease at week 1 and significant decrease at week 2. These results indicate that XZ has tumor-promoting effects on thyroid follicular cells, and suggest an involvement of alterations in thyroid-related hormone levels due to inhibition of thyroid iodine uptake and organification, resulting, provably, in serum TSH stimulation depending on continuous reduction of serum T(4) level through the feedback system in the pituitary-thyroid axis.

Adenoma↗
PubMed2001

Distinct microsatellite alterations in upper urinary tract tumors and subsequent bladder tumors.

PURPOSE: Although synchronous and/or metachronous tumor development is common in urothelial cancer, genetic and biological differences in upper urinary tract and bladder tumors are unclear. We compared the genetic alteration pattern in multifocal disease in patients with upper urinary tract and subsequent bladder tumors, and those with recurrent bladder tumor. MATERIALS AND METHODS: Using 21 microsatellite markers on the 8 chromosomal arms 2q, 4p, 4q, 8p, 9p, 9q, 11p and 17p we analyzed 34 tumors from 15 patients with upper urinary tract and subsequent bladder disease, and 70 tumors from 22 with recurrent bladder disease. RESULTS: Judging from the patterns of genetic alterations multifocal tumors were considered to have derived from an identical progenitor cell in 7 of 13 evaluable patients (54%) with upper urinary tract and subsequent bladder tumors, and 16 of 19 (84%) who were evaluable with recurrent bladder tumor. These data confirm the view that seeding or intraepithelial spread is a major mechanism for the multifocal development of urothelial cancer in general. However, a discordant microsatellite alteration pattern in multifocal tumors was observed in 6 of 7 patients (86%) with upper urinary tract and subsequent bladder lesions but in 2 of 16 (13%) with recurrent bladder cancer (p <0.005). CONCLUSIONS: Our results imply that upper urinary tract neoplasms may be genetically more unstable than bladder neoplasms. The implantation of tumor cells from upper urinary tract to bladder may involve additional and diverse genetic alterations. Furthermore, a considerable number of multifocal upper urinary tract and subsequent bladder lesions may arise independently via field cancerization mechanism. Our study indicates that the factors contributing to multifocal development are different in the 2 groups.

DNA, Satellite↗