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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 19 recordsLinked to original sources

A 13-week subchronic toxicity study of dietary administered morin in F344 rats.

A subchronic toxicity study of a flavonoid morin was performed in both sexes of F344 rats with dietary administration at concentrations of 0%, 0.625%, 1.25%, 2.5% and 5% (w/w) for 13 weeks. No mortality or abnormal clinical signs were observed throughout the experimental period in any group. Although a slight tendency for increase in food intake was noted in both sexes of the 2.5% and 5.0% groups, slight non-significant body weight decrease was observed in 5.0% males. Significant increases in alanine transaminase (ALT; over 2.5%), alkali phosphatase (ALP; 1.25% and 5.0%) and relative liver weights (1.25% and 2.5%) in males and in gamma-glutamyl transpeptidase (gamma-GT), aspartate transaminase (AST), ALT, relative liver weights in the 2.5% and 5.0% females and ALP in 5.0% females were noted. Increased urea nitrogen and relative kidney weights at dose of 1.25% and above and creatinine at 5.0% were observed also in females. On histopathological observation, hepatocyte hypertrophy was detected in 3 of 10 5.0% females. Based on the above findings, the no-observed-adverse-effect level (NOAEL) for both sexes was estimated to be 0.625% (299 and 356 mg/kg b.w./day for males and females, respectively).

Alanine Transaminase↗

[Surgical indication for non-small cell lung cancer with synchronous distant metastases].

From 1989 to 2004, 20 patients with synchronous distant metastases [intrapulmonary metastases (n=10) and extrapulmonary metastases (n=10)] underwent surgery for primary lesion of non-small cell lung cancer (NSCLC). Complete resection of the primary tumor and metastases was achieved in 5 patients. Overall 1- and 2-year survival rates were 48 and 11%, respectively, and mean survival was 21 months. The corresponding figures for patients with pulmonary metastasis to another lobe were 78, 23%, and 35 months, and those for patients with distant metastasis to a site other than another pulmonary lobe were 20, 0%, and 7 months. Two patients with pulmonary metastasis survived more than 5 years. With pulmonary metastasis to another lobe prognosis was better than that with distant metastasis to another site. Survival was not affected by histology or N factor. Complete resection tended to be a factor contributing to a better clinical outcome. This study suggests that surgery for NSCLC with synchronous distant metastasis should be indicated only for patients who could be expected to undergo complete excision of both the primary and metastasis lesion, as a clinical study under informed consent.

Adult↗

[Pulmonary benign metastasizing leiomyoma from uterine myoma; report of a case].

A 46-year-old female with benign metastasizing leiomyoma was reported. The patient had undergone a lobectomy of thyroid for adenomatous goiter at the age of 30, and a myomectomy for uterine myoma and a modified radical masmectomy for breast cancer at the age of 32. The chest X-ray on health screening revealed multiple nodules in the bilateral lung. Computed tomography (CT) revealed 6 nodules in the right side and 3 nodules in the left side of the lung. The tumors of the right lung were resected under thoracoscopic surgery. Pathologically these lesions were diagnosed as benign metastasizing leiomyoma. Left lung nodules have been followed-up.

Combined Modality Therapy↗

[Blunt tracheal transection].

Blunt tracheobronchial injuries are rare, but can be life-threatening. A precise preoperative diagnosis and well recognized plan of surgical treatment, which may be unique for each patient are needed to restore the continuity of tracheobronchial tree in a one-stage intervention. We encountered 2 patients with complete tracheal transection of neck and 1 patient with complete tracheal transection in mediastinum and 15 cm tear in the posterior membranous trachea, whose tracheal injury was difficult to repair using direct intubation of distal airway by bronchoscopy. We achieved a good result of repair using a percutaneous cardiopulmonary support system (PCPS).

Adult↗

[Mediastinal recurrence of breast cancer suspecting mediastinal fibrosis].

A 63-year-old female, who had undergone a modified radical mastectomy for breast cancer at the age of 45, was suffered from trachyphonia due to left recurrent nerve paralysis at the age of 53. She presented left phrenic nerve paralysis and dysphagia at the age of 61. Computed tomography (CT) revealed mediastinal fibrosis, stenosis of esophagus and superior vena cava, and slight lymph nodes swelling. Video-assisted thoracoscopic mediastinal biopsy was performed and the mediastinal fibrosis was diagnosed as recurrence of breast cancer 17 years after the breast cancer operation. She underwent mediastinal radiation and chemotherapy for mediastinal recurrence and stenting for esophageal stenosis.

Biopsy↗

Lack of chemopreventive effects of alpha-eleostearic acid on 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH)-induced mammary and colon carcinogenesis in female Sprague-Dawley rats.

alpha-Eleostearic acid is one of the conjugated linolenic acids from tung oil, which is obtained from the seeds of Aleurites fordii. The effects of dietary alpha-eleostearic acid (18:3, n-5) on the post-initiation period of 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH)-induced mammary and colon carcinogenesis were examined using female Sprague-Dawley (SD) rats. For initiation, rats were given subcutaneous injections of 40mg/kg body weight (5 times) and 20mg/kg body weight (3 times) of DMH during the age of 6-8 weeks and a single intragastric administration of 50mg/kg body weight of DMBA at 9 weeks. Then, the animals were treated with 0%, 0.01%, 0.1% or 1.0% alpha-eleostearic acid for 34 weeks. Control rats received the basal diet alone or 1.0% alpha-eleostearic acid without prior initiation treatment. All surviving animals were killed at week 37 of the experiment. There were no statistically significant alterations in any of the parameters for either mammary or colon tumors. These results thus indicate that alpha-eleostearic acid does not exert clear modification effects on DMBA and DMH-induced mammary and colon carcinogenesis, at least under the present experimental conditions.

1,2-Dimethylhydrazine↗

A subchronic toxicity study of dunaliella carotene in F344 rats.

Dunaliella carotene, extracted from dunaliella alga (Dunaliella bardawil or Dunaliella salina), for use as a food-coloring agent, has beta-carotene as its mainly constituent. As there have been no reports of toxicological evaluation, a 90-day subchronic toxicity study was here performed in F344 rats at dose levels of 0 (control), 0.63%, 1.25%, 2.5% and 5% in powdered basal diet. The average daily intakes of dunaliella carotene were 352, 696, 1420 and 2750 mg/kg/day, respectively, for males, and 370, 748, 1444 and 2879 mg/kg/day for females. No mortality or treatment-related clinical signs were observed throughout the experimental period in any of the groups. Body weight gain was slightly but significantly (p < 0.05) reduced from week 5 to the end of the experiment in 2.5% and 5% males. Increased PLT were observed in 1.25% and 5% males, and 2.5% and 5% females. Significant elevations or tendencies for increase in serum T. Cho and Ca were observed in all treated males and females, with clear dose-dependence in males. Organ weight measurement and histopathological observation revealed no toxicological changes. Based on growth suppression, no-observed-adverse-effect-levels (NOAELs) were estimated to be 1.25% (696 mg/kg/day) for males and 5% (2879 mg/kg/day) for females. As increases in serum Ca were observed in the lowest group in both sexes, a no-observed-effect level (NOEL) could not be determined in this study.

Administration, Oral↗

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↗

Promotion of thyroid carcinogenesis by para-aminobenzoic acid in rats initiated with N-bis(2-hydroxypropyl)nitrosamine.

Sulfonamide analogues of para-aminobenzoic acid (PABA), a precursor of folate synthesis, have beneficial effects as antifolate, but thyroid peroxidase inhibition has been reported as a side effect that results in promotion of rat thyroid carcinogenesis. In the present study, effects of PABA itself on F344 rat thyroid carcinogenesis after initiation with N-bis(2-hydroxypropyl)nitrosamine (DHPN) were evaluated. In experiment 1, rats in groups 1-4 received a single subcutaneous injection of DHPN at 2800 mg/kg, and groups 5 and 6 received vehicle saline alone. From 1 week after DHPN initiation, rats in groups 2, 3, 4, and 6 were fed basal diet containing 0.25%, 0.5%, 1.0%, and 1.0% PABA, respectively, for 40 weeks. Rats in groups 1 and 5 received basal diet alone throughout the experiment. The final incidence of thyroid follicular cell adenomas and adenocarcinomas was significantly (p < 0.05 or 0.01) increased in groups 3 and 4 as compared to group 1. No thyroid tumors were found in groups 5 and 6. In experiment 2, animals in group 1 were fed basal diet alone, while groups 2 and 3 were given 0.5% and 1.0% PABA in the diet, respectively, for 2 weeks. Thyroid weights in group 3, and serum thyroid stimulating hormone level and proliferative activity of follicular cells in groups 2 and 3 were significantly (p < 0.05 or 0.01) elevated. In addition, the serum thyroxine level in group 3 was significantly (p < 0.05) depressed. These results clearly indicate that PABA exerts promotion/progression effects on rat thyroid carcinogenesis as a result of hypothyroidism followed by negative-feedback via the thyroid-pituitary axis.

4-Aminobenzoic Acid↗

Lack of subchronic toxicity of an aqueous extract of Agaricus blazei Murrill in F344 rats.

Agaricus blazei Murrill, an edible mushroom, is widely used as a functional food due to its possible medicinal effects. Aqueous extracts are also used as food additive to provide an agreeable bitter taste. As a part of its safety assessment, the present 90-day subchronic toxicity study was performed in F344 rats. To establish a no-observed-adverse-effect level (NOAEL), rats were fed powder diet containing A. blazei Murrill aqueous extract at dose levels of 0 (basal diet), 0.63, 1.25, 2.5 and 5% (maximum) for 90 days. During the experiment, there were no remarkable changes in general appearance and no deaths occurred in any experimental group. Although serum blood urea nitrogen was slightly but significantly increased in males of the 2.5 and 5% groups, no related histopathological changes were observed in the kidney, and serum creatinine levels were rather reduced, suggesting the increase of blood urea nitrogen to be of little toxicological significance. Hematology, organ weight measurement and histopathological observation revealed no test compound-related toxicological changes. In conclusion, A. blazei Murrill extract even at 5% in the diet (2654 mg/kgb.w./day for male rats and 2965 mg/kgb.w./day for female rats) did not cause remarkable adverse effects in F344 rats. Thus, the NOAEL was concluded to be 5% in the diet.

Agaricus↗

Lack of carcinogenicity of D-xylose given in the diet to F344 rats for two years.

The two year carcinogenicity of D-xylose was examined in groups of 50 male and 50 female F344 rats at dietary doses of 0% (control), 2.5% and 5%. The doses were selected on the basis of results from a 13-week subchronic toxicity study. Growth suppression and soft feces were observed in male and female rats of the 5% group. However, no significant differences from the controls were noted with regard to clinical signs, mortality and hematological findings. Decrease in absolute weight and increase in relative weight of the brain in males, and decrease of absolute kidney weight in females were observed in the 5% group, but there were no remarkable histopathological changes. A variety of tumors developed in all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any type of neoplastic lesion was found for either sex in the treated groups. Thus, it was concluded that, under the present experimental conditions, D-xylose is not carcinogenic to F344 rats.

Animals↗

[Abdominal organ infarction encountered immediately after surgery of primary lung cancer].

Very rare cases of abdominal organ infarction after surgery of primary lung cancer were reported. Case 1: Patient 1 was a 70-year-old man who underwent left upper lobectomy and ND 2a in June 1999 based on the clinical diagnosis of stage IA lung cancer. On the 4th postoperative day, the patient developed fever and right flank pain. Abdominal computed tomography (CT) demonstrated a specific finding compatible with renal infarction. The etiology could not be determined. The patient was treated conservatively. However, severe atrophy of right kidney was demonstrated by following CT performed 3 years later. Case 2: Patient 2 was a 70-year-old woman who underwent left upper lobectomy and ND 2a in December 2002 based on the clinical diagnosis of stage IA lung cancer. On the 4th postoperative day, the patient developed abdominal pain in the left upper quadrant, nausea and vomiting which had lasted for 10 days. Abdominal CT demonstrated a wedge-shaped filling defect at spleen compatible with splenic infarction. The etiology could not be determined. The patient was treated conservatively with prophylactic antibiotic therapy and followed closely. Partial atrophy of spleen was demonstrated by following CT performed 4 months later.

Adenocarcinoma↗

Existence of a threshold for induction of aberrant crypt foci in the rat colon with low doses of 2-amino-1-methyl-6-phenolimidazo[4,5-b]pyridine.

Until recently it has been generally considered that genotoxic carcinogens have no threshold in exerting their potential for cancer induction. However, the nonthreshold theory can be challenged with regard to assessment of cancer risk to humans. In the present study we show that a food derived, genotoxic hepatocarcinogen, 2-amino-1-methyl-6-phenolimidazo[4,5-b]pyridine (PhIP), does not induce aberrant crypt foci (ACF) as preneoplastic lesions at low dose (below 50 ppm) or 8-hydroxy-2'-deoxyguanosine (below 400 ppm) in the rat colon. Moreover PhIP-DNA adducts were not formed at the lowest dose (below 0.01 ppm). Thus, the dose required to initiate ACF is approximately 5000 times higher than that needed for adduct formation. The results imply a no-observed effect level (existence of a threshold) for colon carcinogenesis by a genotoxic carcinogen.

8-Hydroxy-2'-Deoxyguanosine↗

Successful intrauterine treatment with radiofrequency ablation in a case of acardiac twin pregnancy complicated with a hydropic pump twin.

Twin reversed arterial perfusion sequence is a serious complication of monochorionic twin pregnancy, as the pump twin that perfuses blood to the acardiac twin may experience heart failure and fetal hydrops resulting in a poor perinatal outcome. A woman with an acardiac twin pregnancy complicated by a hydropic pump twin underwent intrauterine treatment with radiofrequency ablation (RFA) at 27 weeks of gestation. Obliteration of blood flow to the acardiac twin from the pump twin was successful. Fetal hydrops resolved by the time of delivery at 32 weeks of gestation, in spite of transient deterioration, and a good postnatal outcome was achieved for the pump twin. We found that RFA was an effective intrauterine treatment for acardiac twin pregnancy and suggest that it could be introduced in cases complicated by a hydropic pump twin.

Adult↗

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↗

Three-dimensional finite element analysis of human temporomandibular joint with and without disc displacement during jaw opening.

The aim of this study was to evaluate the differences of stress distribution in the temporomandibular joint (TMJ) disc during jaw opening between the subjects with and without internal derangement of TMJ (TMJ-ID). Three symptom-free volunteers and three symptomatic patients with anterior disc displacement were selected as normal and TMJ-ID subjects, respectively. For each subject, magnetic resonance images (MRI) were taken in the axial, sagittal and coronal directions. Using MRI taken, six three-dimensional finite element models of TMJ were developed. For each subject, the condylar movements during jaw opening were recorded and used as the loading condition for stress analysis. By comparing the calculated disc displacement to the measured one from MRI, the frictional coefficients were mu = 0.001 for the normal subjects, but mu = 0.01-0.001 for the TMJ-ID subjects. For the normal subjects, relatively high stresses were found at the anterior and lateral portions of the disc throughout jaw opening. In the connective tissues, the stress level was higher in the TMJ-ID than in the normal subjects. It is suggested that the disc displacement induces the change of stress distribution in the disc and the increase of frictional coefficients between articular surfaces, resulting in the secondary tissue damage.

Adult↗

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↗

Influence of microcatheter length on flow rates of disposable infusion kits.

BACKGROUND AND OBJECTIVE: Continuous spinal analgesia (CSA) offers considerable pain relief, and has been used in various procedures such as for surgery and cancer pain control. In Japan, portable and disposable infusion kits are increasingly employed for continuous epidural analgesia and CSA. In CSA, the use of a microcatheter is expected to reduce the incidence of spinal headache previously encountered with larger catheters. However, the flow rate of disposable infusion kits is reduced when used in conjunction with a microcatheter. METHODS: This study aimed to investigate the influence of catheter length on the flow rate of two different devices: 20- or 91-cm 28-G microcatheters connected to balloon- or syringe-type infusion pumps were examined (50 mL, 1 mL h(-1)). There were four groups each of 10 experiments: Group A: balloon-type infuser, 91 cm catheter; Group B: balloon-type infuser, 20 cm catheter; Group C: syringe-type infuser, 91 cm catheter; Group D: syringe-type infuser, 20 cm catheter. RESULTS: The mean flow rate in Group A was significantly less than that in Group B and the mean flow rate in Group C was significantly less than Group D (P < 0.05). CONCLUSION: These results indicated that the use of a shorter microcatheter achieves a better flow rate during CSA.

Analgesia, Epidural↗