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Biomedical subjects

H Hatano

Publications and source records attributed to H Hatano.

At least 37 records · Page 2Linked to original sources

[Effectiveness of DeVIC chemotherapy for recurrent primary central nervous system lymphoma].

Six cases with recurrent or refractory primary central nervous system lymphoma were treated with a new chemotherapeutic regimen "DeVIC (dexamethasone, VP16, ifosfamide, carboplatin)". Five recurrent cases had a remission period for an average of 18 months after initial treatment, but relapse occurred. One refractory case had no response after initial treatment. Then these 6 cases were treated with 1-3 courses of DeVIC chemotherapy at intervals of 4 weeks. Two cases achieved complete remission, and 3 cases attained partial remission (response rate was 83%). One case showed no response after 1 course of DeVIC chemotherapy. However, in all cases re-relapse occurred 1-5 months after remission, and only 1 case is still alive. DeVIC chemotherapy produced a high response rate for recurrent central nervous system lymphoma, but re-relapse occurred after only a few months. The establishment of maintenance chemotherapy is required.

Adolescent↗

In vivo drug release behavior in dogs from a new colon-targeted delivery system.

The colon-targeted delivery capsule (CTDC), a new capsule-type dosage form for colonic delivery of drugs, was investigated for the in vivo drug release behavior in dogs. A CTDC formulation with prednisolone as a model drug and theophylline as a marker substance for gastric emptying was prepared for this study. The enteric-coated capsule (ECC) formulation with a similar composition was also prepared as the reference. Both formulations were administered to four beagle dogs, and the drug release behavior thereof was compared. Under fasted condition, ECC released prednisolone and theophylline at the same time within 1 h after the gastric emptying. On the other hand the CTDC released prednisolone at 3.2 h after the gastric emptying. Such release behavior of CTDC was approximately consistent with the results obtained from the in vitro dissolution study, suggesting that the pH-sensing and timed-release functions imparted to the CTDC can work in the gastrointestinal tract of dogs as programmed. Under non-fasted condition, however, the gastric emptying of CTDC was found to be considerably delayed, up to about 14 h, and in this case the in vivo dissolution lag time of prednisolone at the small intestine was shortened to about 1.5 h.

Administration, Oral↗

Expression of metalloproteinase-13 (Collagenase-3) is induced during fracture healing in mice.

In fracture healing, a large amount of cartilage is formed, then rapidly replaced by osseous tissue. This process requires the transition of extracellular matrix component from type II to type I collagen. We investigated the expression of matrix metalloproteinase-13 (MMP-13), which has a high potential to cleave type II as well as type I collagen, during fracture repair in mouse ribs. In situ hybridization demonstrated that MMP-13 mRNA was present throughout the healing process. It was detected in the cells of the periosteum at day 1. As fracture callus grew, strong MMP-13 mRNA signals were detected in cells of the cartilaginous callus. In the reparative and remodeling phases, both hypertrophic chondrocytes and immature osteoblastic cells in the fracture callus expressed MMP-13 mRNA strongly. These cells were located adjacent to tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts at the sites of cartilage/bone transition. In osteoclasts, MMP-13 expression was not detected. The level of MMP-13 mRNA peaked at day 14 postfracture by northern blotting. Immunohistochemical staining showed that MMP-13 was detected primarily in hypertrophic chondrocytes. These results indicate that MMP-13 is induced during fracture healing. The site- and cell-specific expression of MMP-13 and its enzymatic property suggest that MMP-13 initiates the degradation of cartilage matrix, resulting in resorption and remodeling of the callus. In conclusion, MMP-13 plays an important role in the healing process of fractured bone in mice.

Acid Phosphatase↗

Origin of histiocyte-like cells and multinucleated giant cells in malignant fibrous histiocytoma: neoplastic or reactive?

The origin of histiocyte-like cells in malignant fibrous histiocytoma (MFH) remains controversial. To determine whether histiocyte-like cells and multinucleated giant cells show reactive or neoplastic proliferation, we transplanted human storiform-pleomorphic MFH to nude mice and investigated the origin of histiocyte-like cells using the DNA in situ hybridization (ISH) system. In addition, we analyzed the mRNA expression of mouse c-fms and human colony stimulating factor-1 (CSF-1); immunohistochemical expression of markers detectable in cells of monocyte/macrophage lineage. The DNA ISH revealed neoplastic proliferation of fibroblastic cells and bizarre multinucleated giant cells of human origin. Monocyte/macrophage lineage cells were seen in parental tumors, whereas they did not participate in neoplastic proliferation in transplanted tumors. The parental tumors expressed human CSF-1 mRNA and the histiocyte-like cells in transplanted tumors expressed 'mouse' c-fms mRNA. These results suggest that MFH induce infiltration of monocyte/macrophage and CSF-1 is one of the mediators involved in this phenomenon, because the human CSF-1 can act as a ligand to the mouse c-fms. Histiocyte-like cells in MFH should be considered as a reactive monocyte/macrophage lineage rather than as an element of neoplasm.

Aged↗

Differences in umbilical cord serum lipid levels with mode of delivery.

OBJECTIVE: To investigate whether umbilical cord serum lipid levels differ with mode of delivery. DESIGN: Retrospective observation study. POPULATION: Two hundred and ninety mothers aged 29.1 years (SD 4.7) who had vaginal delivery, and 44 mothers aged 30.4 years (SD 4.7) who had elective caesarean section were enrolled. MAIN OUTCOME MEASURES: Maternal and umbilical cord blood were obtained immediately after delivery. Serum lipid levels including total cholesterol, high density lipoprotein cholesterol, saturated fatty acid, mono-unsaturated fatty acid and polyunsaturated fatty acid were measured. Obstetric variables and serum lipid levels were compared between the two groups. In each group the correlations of fetal serum lipid levels with maternal serum lipid levels were investigated. RESULTS: There were no significant differences in maternal age, neonatal weight, gestational duration, placental weight and neonatal gender distribution between the two groups. Only the two fetal serum lipid levels (including total cholesterol and non-high density lipoprotein cholesterol) showed a correlation with maternal fetal lipid levels with correlation coefficients > 0.3 in the caesarean section group. However, saturated fatty acid, mono-unsaturated fatty acid and total fatty acid levels in the non-high density lipoprotein low density lipoprotein, very low density lipoprotein, intermediate density lipoprotein and free fatty acid fraction in the umbilical cord serum were significantly higher in the vaginal delivery cases (P < 0.01). CONCLUSIONS: Umbilical cord serum levels of saturated and mono-unsaturated fatty acids increase during vaginal delivery.

Adolescent↗

Asthma-like disease in the children living in the neighborhood of Mt. Sakurajima.

We conducted self-administered questionnaire surveys of school children living in the vicinity of Mt. Sakurajima using ATS-DLD questionnaire. In this paper, we report the results of analysis comparing the proportion of children with asthma-like disease in the area exposed to the volcanic ash and gases released by Mt. Sakurajima and control areas. Asthma-like disease was ascertained using ATS-DLD questionnaire and the definition proposed by the study group established by Environmental Protection Agency in Japan. The proportion of children with asthma-like disease was not different between the exposed and control groups. The odds ratio of asthma-like disease comparing the exposed and control groups was 1.1 and its 95% confidence interval was 0.7-1.8 (P = 0.583). When the exposed area was divided into Tarumizu city. Sakurajima town and Kagoshima city, none of them showed an elevated proportion of children with asthma-like disease when compared with the control area. In the entire study population including both the exposed and control groups, the proportion of children with asthma-like disease was 6 and 3% in boys and girls, respectively. These values were quite similar to those obtained from a survey of 45,674 school children in western districts in Japan in 1992. In conclusion, the present study indicates that the proportion of children with asthma-like disease is not elevated in the exposed area. Further investigations are necessary to confirm our conclusions.

Air Pollutants↗

[Evaluation of restenosis after percutaneous transluminal coronary angioplasty using a Doppler index, the Tei index].

Cardiac function and restenosis were evaluated after percutaneous transluminal coronary angioplasty (PTCA) using a Doppler index (the Tei index). Thirty-eight patients, 31 men and 7 women (mean age 57 years) with ischemic heart disease were studied. The underlying heart diseases were angina pectoris without left ventricular asynergy in 16 patients and old myocardial infarction (OMI) with left ventricular asynergy in 22 . Ejection fraction was measured by M-mode echocardiography and deceleration time, and the interval between cessation and onset of the mitral inflow velocity (a), ejection time at aortic valve (b), and the Tei index [(a-b)/b] were measured by M-mode echocardiography performed before and 6 months after PTCA. The ejection fraction, deceleration time and Tei index showed no changes after PTCA in patients with angina pectoris with or without restenosis. In patients with OMI with restenosis, the Tei index increased slightly after PTCA, from 0.56 +/- 0.15 to 0.61 +/- 0.13. The deceleration time changed from 0.23 +/- 0.03 to 0.24 +/- 0.02 msec, and the ejection fraction from 0.46 +/- 0.11 to 0.51 +/- 0.17, neither significantly. However, in patients with OMI without restenosis (15 out of 22 patients), the Tei index significantly improved after PTCA, from 0.55 +/- 0.13 to 0.48 +/- 0.12 (p < 0.05). In patients with left ventricular asynergy due to old myocardial infarction, without restenosis, the Tei index significantly improved after PTCA. The Tei index is useful for evaluating restenosis after PTCA in patients with OMI.

Angina Pectoris↗

Origin of bone-forming cells in human osteosarcomas transplanted into nude mice--which cells produce bone, human or mouse?

Osteosarcomas are malignant tumours producing osteoid and/or bone. It is difficult to distinguish tumour bone formation from reactive, based on their morphological features alone. The objective of this study was two-fold: to clarify the origins of bone-forming cells in human osteosarcoma transplanted into nude mice; and to examine the role of bone morphogenetic proteins (BMPs) in the tumour-induced osteogenesis. DNA in situ hybridization was carried out with digoxigenin (DIG) polymerase chain reaction (PCR) labelled DNA probes for human-specific 'Alu' and mouse-specific 'mouse L1 (m-L1)' genes. Human osteosarcoma cells, established cell lines of NOS-1, NOS-2, and HuO9, were transplanted separately into nude mice. Bone-forming cells of the bone in the NOS-1 or NOS-2 tumours were positive for Alu, while they were negative for m-L1. The cells lining the surface of trabeculae in the HuO9 tumour were positive for Alu, but a few of them were also positive for m-L1. The m-L1-positive cells expressed mouse osteocalcin and type 1 collagen mRNAs. These facts suggest that the mouse cells were involved in osteoid synthesis of the HuO9 tumour. The NOS-1 or NOS-2 tumours expressed human BMP 2-7 mRNAs, whereas the HuO9 tumour expressed human BMPs 2, 4, 5, and 7. The osteogenetic potential of the tumours may depend on the expression patterns of BMPs. These results demonstrate two distinct types of bone formation, by tumour cells and by an admixture of tumour and non-tumour cells. The present study showed that the HuO9 tumour produces chimeric bone formation. This is the first report to demonstrate the relationships between tumour cells and non-tumour cells in bone formation, using genetic markers.

Alkaline Phosphatase↗

Periosteal chondrosarcoma invading the medullary cavity.

We present a case of periosteal chondrosarcoma of the femur, in which a tumor invaded the medullary cavity and the lesion was clearly demonstrated only on MRI. To the best of our knowledge, there have been no previous reports of an intramedullary lesion caused by periosteal chondrosarcoma demonstrated on MRI.

Adult↗

Apoptosis in cultured human colon cancer cells induced by combined treatments with 5-fluorouracil, tumor necrosis factor-alpha and interferon-alpha.

Biochemical analysis using nick end-labeling was performed to investigate the effect of various combinations of 5-fluorouracil, natural human tumor necrosis factor-alpha and natural human interferon-alpha on the induction of apoptosis in RPMI 4788 human colon cancer cells. After treatment with 5-fluorouracil (1 mM) for 48 h, the number of nick end-positive cells was significantly increased in comparison to the situation without treatment. When tumor cells were treated with 1 mM 5-fluorouracil, 2.86 Japan Reference Units (JRU)/ml natural human tumor necrosis factor-alpha and 1 x 10(3) IU/ml natural human interferon-alpha in combination for 48 h, the number of nick end-positive cells was significantly higher than that after treatment with 5-fluorouracil alone. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay revealed a significant decrease of relative viability, as compared to treatment with 5-fluorouracil (1 mM), 5-fluorouracil + natural human tumor necrosis factor-alpha, or 5-fluorouracil + natural human interferon-alpha for 48 h. Pretreatment with 5-fluorouracil (1 mM) for 24 h prior to treatment with natural human tumor necrosis factor-alpha (2.86 JRU/ml) and natural human interferon-alpha (10(3) IU/ml) for 24 h resulted in a significant increase of nick end-positive cells compared to pretreatment with natural human tumor necrosis factor-alpha and natural human interferon-alpha prior to treatment with 5-fluorouracil for 24 h (p < 0.05). These results suggest that 5-fluorouracil alone can induce apoptosis in RPMI 4788 tumor cells and that this effect can be enhanced by combination with natural human tumor necrosis factor-alpha and natural human interferon-alpha.

Antimetabolites, Antineoplastic↗

The sex differences in cord-blood cholesterol and fatty-acid levels among Japanese fetuses.

We examined serum cholesterol and fatty-acid levels of cord blood and maternal blood samples collected from 193 Japanese fetuses and their mothers. Our study, which is the largest study of this kind ever conducted in Japan, is the first Japanese study reporting that total, high density lipoprotein (HDL) and non-HDL cholesterol levels in females were statistically significantly higher than those in males; the sex differences of total, HDL and non-HDL cholesterol levels were 8.5 mg/dl (P = 0.002), 4.5 mg/dl (P = 0.004) and 4.1 mg/dl (P = 0.045), respectively. The sex difference of total cholesterol was attributable to both HDL and non-HDL cholesterol. The sex of fetuses didn't show evident differences in cholesterol levels in maternal sera. Fatty-acid levels in cord blood were also higher in female fetuses than in male fetuses. However, none of the differences except for monoene fatty acids were statistically significant. Further investigations seem warranted to elucidate the mechanisms involved in our results.

Adult↗

Genetic controls of susceptibility and resistance to 4-nitroquinoline 1-oxide-induced tongue carcinomas in rats.

We analyzed the incidence of infiltrative mass-type tongue carcinomas (IMTC) induced in 550 rats by continuous oral administration of 0.001% 4-nitroquinoline 1-oxide solution for 180 days. The study included various crosses of susceptible Dark-Agouti rats (DA) and resistant Wistar/Furth rats (WF). DA showed a 93.6% incidence of IMTC measuring more than 5 mm in their largest diameter, while WF showed only a 4% incidence. Reciprocal F1 and F2 hybrids mated by DA and WF showed 47.5% and 45.8% incidences, respectively. Meanwhile, reciprocal backcrossed hybrids to DA and WF showed 73.7%, and 24.6% incidences, respectively. Segregation of the incidences suggests that there are two autosomal dominant genes, one linked to the susceptibility of DA and the other to the resistance of WF.

4-Nitroquinoline-1-oxide↗

Effectiveness and toxicity screening of various absorption enhancers in the large intestine: intestinal absorption of phenol red and protein and phospholipid release from the intestinal membrane.

The effectiveness and local toxicity of absorption enhancers on the absorption of phenol red (PR) from the large intestine of rats were examined using an in situ loop method. The absorption enhancers used in this study were sodium glycocholate (GC-Na), sodium taurocholate (TC-Na), sodium deoxycholate (DC-Na), EDTA, sodium salicylate (Sal-Na), sodium caprate (Cap-Na), diethyl maleate (DM), N-lauryl-beta-D-maltopyranoside (LM) and mixed micelles (MM), all used at a concentration of 20 mM. Local toxicity was also investigated by assessing protein and phospholipid release as biological markers. DC-Na and MM were the most effective absorption enhancers, but they caused considerable release of proteins and phospholipids. GC-Na, TC-Na and LM, which caused little or only slight membrane damage, promoted PR absorption. Sal-Na, DM and EDTA did not enhance PR absorption. Overall, a correlation exists between the area under the curve of PR and protein and phospholipid release in the presence of absorption enhancers. However, GC-Na, TC-Na and LM promoted the absorption of PR with low toxicity. From these results, we concluded that GC-Na, TC-Na and LM are effective absorption enhancers which have low levels of toxicity at a concentration of 20 mM.

Animals↗

Effect of total adipose weight and systemic hypertension on left ventricular mass in children.

To investigate the effect of obesity and hypertension on left ventricular (LV) mass in children, we performed echocardiography and measured the height, weight, and blood pressure of 267 healthy children (145 boys and 122 girls) aged 12 years. The percentage of body fat was estimated using bioelectric impedance to derive the total adipose weight and lean body weight. End-diastolic measurements of LV parameters were obtained from M-mode echocardiograms. The LV mass was calculated by using the formula of Devereux et al. A strong positive correlation was demonstrated between non-normalized LV mass and height or other measures of body size. Systolic blood pressure was weakly correlated with non-normalized LV mass in boys. The impact of height on LV mass differed between boys and girls. Thus, different allometric formulas to normalize the LV mass for height were determined, using the height to the 3.1 and 1.9 powers for boys and girls, respectively. Regression analysis revealed that only total adipose weight affected the normalized LV mass, and that the effect of total adipose weight was greater in girls than in boys. The obese children had a significantly greater normalized LV mass than the nonobese children. The increase in the LV mass due to obesity appeared to be eccentric, because of the lack of an association between the indices of obesity and relative wall thickness. Our data indicate that appropriate normalization of LV mass is necessary for each study population, and that LV hypertrophy due to obesity begins in childhood.

Adipose Tissue↗

Comparative study on topical and oral administration of ofloxacin for Pseudomonas corneal ulcer in rabbits.

Pseudomonas aeruginosa is one of the most frequently isolated microorganisms in bacterial corneal ulcers in Japan and other countries. We evaluated a topical application of 0.3% ofloxacin (OFLX) for Pseudomonas corneal ulcer in rabbits and compared it to the clinical effects of OFLX in topical and oral applications. All corneas in the control groups of both experiments showed total leukoma with a score of 4 on the seventh day. On the other hand, in the preventive experiment, all the scores in the OFLX-treated group were 0, and those in the therapeutic experiment were smaller than those of both the control and oral groups. The results indicate that topical OFLX is effective on Pseudomonas corneal ulcer in rabbits.

Administration, Oral↗

Systemic amyloidosis following ankylosing spondylitis associated with congestive heart failure. A case report.

We report the case of a 38-year-old man who developed fatal, systemic amyloidosis following ankylosing spondylitis. He was admitted for symptoms of congestive heart failure. Based on parotid gland biopsy and echocardiography, he was diagnosed as having systemic amyloidosis following active ankylosing spondylitis. However, the clinical course was rapidly progressive and eventually the patient died of acute necrotizing pancreatitis. The association has been reported thus far in a limited number of cases worldwide. The literature has featured localized lesions and a benign clinical course of the amyloidosis. This case, the first report from Japan, indicates that the amyloidosis associated with ankylosing spondylitis might exhibit a rapidly progressive clinical course, thereby suggesting that in such a case, meticulous treatment is required.

Acute Disease↗

[Normal-sized ovary carcinoma syndrome: histopathological analysis of 14 cases].

Fourteen cases of "normal-sized ovary carcinoma syndrome" (diffuse metastatic malignant disease of the abdominal cavity of the female, with normal-sized ovaries, with no origin assigned definitively by intraoperative or preoperative evaluation, Feuer et al., 1989) were analyzed histologically, histochemically, immunohistochemically and ultrastructurally. Through these studies, 14 cases were divided into 11 primary peritoneal tumors (4 diffuse malignant mesotheliomas and 7 serous surface papillary carcinomas) and 3 metastatic peritoneal tumors (2 ovarian tumors and 1 appendicular tumor). To distinguish serous surface papillary carcinomas from epithelioid diffuse malignant mesotheliomas, examinations such as hyaluronidase digestion test, electron microscopy, and immunohistochemical studies using antibodies for Ber-EP4 and Vimentin were found to be useful. In order to achieve an accurate prognosis of normal-sized ovary carcinoma syndrome, it seems necessary for us to accumulate more information on this syndrome.

Carcinoma, Papillary↗