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Biomedical subjects

H Hatano

Publications and source records attributed to H Hatano.

At least 19 recordsLinked to original sources

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

Suppressive effect of TNF-alpha on increased production of FdUMP by IFN-alpha.

Interferon-alpha (IFN-alpha) exhibits synergistic antitumor activity when combined with tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo and increases the cytotoxicity of 5-fluorouracil (5-FU) in vitro. Using a colon cancer cell line transplanted into nude mice, we examined the effects of pretreatment for 3 days with IFN-alpha (10(6) IU) and/or TNF-alpha (2.9 x 10(3) JRU) on 5-FU metabolism. 5-FU 30 mg/kg was administered after the pretreatment. IFN-alpha increased the tumor level of 5-fluorodeoxuridine monophosphate (FdUMP), and decreased the free level of thymidylate synthetase. Pretreatment with TNT-alpha alone decreased HUMP whereas TNF-alpha plus IFN-alpha abolished the enhancement of FdUMP production by IFN-alpha. TNF-alpha also suppressed thymidine kinase activity. Neither IFN-alpha nor TNF-alpha altered the incorporation of 5-FU into RNA.

Animals

[Fibronectin].

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Adolescent

A retrospective study of herpes simplex keratitis over the last 30 years.

The clinical features of herpes simplex keratitis seen in 370 eyes of 356 patients (211 males and 145 females) in the outpatient clinic of the Yokohama City University hospital during the last 30 years (1963-1992) were statistically analyzed. The age of patients ranged from 1 to 75 years (mean 38.4 years). Bilateral herpetic keratitis was seen in 11 patients (10.4%) in the period of 1980-1992. Epithelial keratitis, stromal keratitis, and corneal endotheliitis were observed in 67 patients (57.3%), 46 patients (39.3%), and 4 patients (3.4%), respectively, in the period of 1980-1992. There was no significant change in the incidence of the types of corneal lesions during the last 13 years as compared with those in the previous 17 years (1963-1979). Life-table analysis revealed that 5-year recurrence rates were 17.5% in patients treated with acyclovir (ACV) and 52.9% in those treated with idoxuridine (IDU). The recurrence rate in ACV-treated patients was significantly lower than that in IDU-treated patients. Severe cases, such as those complicated by deep corneal ulcers with hypopyon, descemetoceles, or necrotizing keratitis, were decreased in number in ACV-treated patients, as compared with IDU-treated patients.

Acyclovir

Application of topical lomefloxacin against experimental Pseudomonas endophthalmitis in rabbits.

Lomefloxacin is a new quinolone compound with a broad antibacterial spectrum and excellent penetration into the aqueous humor by topical application. Therefore, an experimental study was done to evaluate the efficacy of topical lomefloxacin against experimental endophthalmitis with Pseudomonas aeruginosa. Lomefloxacin eye drops were instilled six times a day onto infected rabbit eyes and gentamicin, sulbenicillin and saline were also tested comparatively in the same manner as lomefloxacin. Clinical observation for 1 week and counting viable pseudomonas cell numbers in the anterior chamber were done. Among all topical eye drops tested, lomefloxacin was shown to be most effective in lowering clinical scores and viable cell numbers in the anterior chamber. In conclusion, lomefloxacin is expected to be a useful ophthalmic solution in the treatment of pseudomonal endophthalmitis.

Animals