PubMed Health⌕ Search

Biomedical subjects

O Nakamura

Publications and source records attributed to O Nakamura.

At least 73 records · Page 4Linked to original sources

Purification, characterization, and studies on biosynthesis of a 59-kDa bone sialic acid-containing protein (BSP) from rat mandible using a monoclonal antibody. Evidence that 59-kDa BSP may be the rat counterpart of human alpha 2-HS glycoprotein and is synthesized by both hepatocytes and osteoblasts.

A monoclonal antibody was raised against a mineralized tissue-specific sialoprotein containing no phosphorus using partially purified noncollagenous bone matrix proteins from rats as antigen. Then the sialoprotein was purified by high performance liquid chromatography from rat mandibulae using the monoclonal antibody as a marker. The sialoprotein (59-kDa bone sialoprotein (BSP)) with a molecular weight of 59,000 contained 1.4% sialic acid but no detectable phosphorus. Immunohistochemical studies with the antibody showed that the protein was specific to mineralized tissues such as bone and dentin, and present in osteoblasts, osteocytes, and bone matrix. No other soft tissues, such as the cartilage, liver, kidney, and periosteum, were stained. However, Western blot analysis showed that plasma contained immunoreactive 59-kDa BSP. The quantitative amino acid composition of 59-kDa BSP resembled that of human alpha 2-HS glycoprotein (alpha 2-HSG) (Lee, C.-C., Bowman, B.H., and Yang, F. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4403-4407; Kellermann, J., Haupt, H., Auerswald, E.-A., and Muller-Esterl, W. (1989) J. Biol. Chem. 264, 14121-14128) and rat 64-kDa protein (Franzén, A., and Heinegård, D. (1985) in The Chemistry and Biology of Mineralized Tissues (Butler, W.T., ed), p. 132, EBSCO Media, Birmingham, AL). Amino acid sequence analyses of the amino-terminal region and four peptide fragments of 59-kDa BSP revealed that about 50% of the amino acids were homologous with those of human alpha 2-HSG, which is known to be synthesized by the liver, transported in the bloodstream, and incorporated into calcified tissues. But when newborn rat calvaria, primary cultures of osteoblast-rich cells, and adult rat hepatocytes were incubated with radioactive leucine, immunoreactive 59-kDa BSP was detected in their conditioned medium by fluorography. Several characteristics, including the amino acid sequence, suggest that 59-kDa BSP may be the rat counterpart of human alpha 2-HSG. However, rat 59-kDa BSP is a single peptide and synthesized by both osteoblasts and hepatocytes, whereas human alpha 2-HSG is known to be a heterodimer and to be synthesized by the liver.

Amino Acid Sequence↗

[Differential diagnosis between recurrence of brain tumor and radiation necrosis by 201Tl SPECT].

In order to differentiate recurrence of brain tumor from radiation necrosis, we performed 201Tl brain SPECT in 16 post-operative patients. Five of them had residual anaplastic astrocytoma. Final diagnosis of the other 11 patients was recurrent astrocytoma (n = 6), cerebral radiation necrosis (n = 5), based on re-operation (n = 9) and more than one year follow-up finding (n = 2). Early and delayed images were obtained at 10-15 min. and 4 hrs. after i.v. injection of 111 MBq of 201Tl chloride. Counts ratio of a lesion to the normal brain (L/N) was calculated by creating rectangular ROI over each area. All of the patients with recurrent or residual tumor showed L/N ratios of more than 2.5 on the early images (mean 4.70 +/- 2.65). On the other hand, L/N ratios on the early images were less than 2.5 in patients with radiation necrosis (mean 2.05 +/- 0.25, p less than 0.001). In conclusion, a quantitative assessment using 201Tl brain SPECT may be useful in differentiating recurrence of brain tumor from radiation necrosis.

Adult↗

Correlation between bromodeoxyuridine-labeling indices and patient prognosis in cerebral astrocytic tumors of adults.

Bromodeoxyuridine (BUdR), a nonradioactive thymidine analogue, is taken up by cells in S-phase, and the ratio of BUdR-positive nuclei to the total number of cells counted is defined as the labeling index (LI). In this study, BUdR LI and the clinical course of 50 cerebral astrocytic tumors in adults were analyzed. The obtained LI distributed continuously in a broad range from 0% to 19%. The mean LI of 28 glioblastomas, 12 anaplastic astrocytomas, and ten astrocytomas were 8.5%, 4.2%, and 1.2%, respectively, and these differences were statistically significant (P = 0.05). In the analysis of LI and the recurrence-free period (RFP), regardless of the histologic findings, 23 patients with LI more than 5% had a median RFP of 9.0 months; the median RFP of nine patients with LI of 3% to 5% was 14.7 months. Nine of 13 patients with LI less than 3% have not yet recurred after a median follow-up of 36 months. These differences were also statistically significant by the generalized Wilcoxon test (P = 0.05). The proliferative potential reflected by the BUdR LI is a good clinical indicator for predicting the rate of tumor growth in cerebral astrocytic tumors. In combination with histologic diagnosis, BUdR LI could help in determining a patient's prognosis more precisely.

Adult↗

Ganglioside GD3 shedding by human gliomas.

The proportion of ganglioside GD3 increases in glioma tissue and GD3 content is correlated with malignancy of gliomas. This ganglioside can be detected in the sera of patients with glioma by thin-layer chromatographic analysis. Ganglioside GD3 was not detected in the sera of healthy donors and astrocytoma grade 2 patients. However, serum GD3 was detected in one of three astrocytoma grade 3 patients and seven of nine glioblastoma patients. These results show that shedding of GD3 increases in proportion to the degree of malignancy of gliomas. Nevertheless, all of the glioblastoma patients in this study were advanced cases. Considering the high reliability of radiological diagnostic techniques in the neurosurgical field, further study will be necessary to clarify the relationships between the GD3 level in serum and the properties of tumours.

Antibodies, Monoclonal↗

[Advances of surgery and radiation therapy of glioblastoma and metastatic tumor].

On the surgery for malignant gliomas, most cases are beyond the stage for desirable removal of tumors, because of the risk of damage to the normal function of surrounding brain tissue. The restriction of the surgical treatment has inevitably required postoperative radiation therapy. With a protocol aiming at removing tumors extensively and delivering high dose radiation to the tumor area, we treated 107 patients with cerebral glioblastoma. Wide removal of the tumor combined with intraoperative radiation therapy (IORT) was applied to expected resectable cases at the first surgery or at the second salvage surgery after conventional external radiation therapy. Thirty patients underwent extensive removal with IORT and demonstrated a 2-year survival rate of 60%. Fifty six patients were treated only by postoperative radiation therapy and a two-year survival rate was only 6.8%. The results apparently indicate that areas adjacent to the margin of almost complete removal should be irradiated with a sufficient dose to sterilize the remaining malignant remnants. As metastatic brain tumors without systemic metastasis seldom develop to multiple lesions, surgical removal followed by local radiation therapy would be ideal in order to prevent brain atrophy and dementia induced by whole brain irradiation. IORT would be also useful for its strong local effect to tumors and for shortening the hospital stay of patients.

Brain Neoplasms↗

Inhibition of angiogenesis by vitamin D3 analogues.

The effects of vitamin D3 and two analogues on embryonic angiogenesis were studied in 4.5-day-old chick embryo chorioallantoic membranes. The active metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3, and a synthetic vitamin D3 analogue, 22-oxa-1 alpha,25-dihydroxyvitamin D3, inhibited angiogenesis in a dose-dependent manner, the inhibition occurring in the picomolar range. In contrast, vitamin D3 was not effective. The results suggest that these two vitamin D3 analogues might be promising anti-angiogenic agents for controlling the angiogenesis which occurs in several pathological conditions, including tumor development.

Animals↗

Stimulation of proteoglycan and DNA syntheses in chondrocytes by centrifugation.

So that the effects of biomechanical forces on the proliferation of chondrocytes and their proteoglycan synthesis could be studied, growth-plate and articular chondrocytes were maintained separately as packed masses in centrifuge tubes in the presence of 10% serum. In these conditions, the cells became re-organized into cartilaginous tissue in seven days. After ten days, they were centrifuged at gravities (g) of 1.3-27 for 24 h in a CO2 incubator. Control cells were maintained in the CO2 incubator without centrifugation. Centrifugation of growth-plate chondrocytes at 3 g resulted in a two-fold increase in incorporation of [35S]sulfate into proteoglycans, but had little effect on their [3H]thymidine incorporation into DNA. On the other hand, centrifugation of articular chondrocytes at 3 g for 24 h caused 1.5-fold increases in both [35S]sulfate incorporation into proteoglycans and [3H]thymidine incorporation into DNA. These results suggest that biomechanical forces have different effects on the growth and differentiation of articular and growth-plate chondrocytes.

Animals↗

Inhibition of angiogenesis by bleomycin and its copper complex.

The effects of bleomycin (BLM) and its copper complex on embryonic angiogenesis were studied in the chorioallantoic membranes of 4.5-day-old chick embryos. Copper-free BLM inhibited embryonic angiogenesis in a dose-dependent manner, with activity detectable at 1 ng/egg and maximal at 1000 ng/egg. Also, treatment with copper-BLM complex dose-dependently caused inhibition of embryonic angiogenesis in a lower dose range. Since tumor growth is believed to depend on angiogenesis, the present results may indicate that the antiangiogenic activity of BLM is, at least in part, implicated in the antitumor activity of the drug.

Animals↗

[Drug sensitivity test against malignant gliomas].

In treating brain tumors with chemotherapy, the choice of drug is most important since human tumors have different drug sensitivities and growth rates. We have been studying the therapeutic effect of anticancer drugs against malignant brain tumors in the following in vivo models. 1) Human glioma-bearing nude mice. 2) Methylcholantrene-induced 203Gl mouse glioma-bearing immunocompetent C57BL/6 mice. 3) Human gliomas transplanted into the chorioallantoic membrane of chick embryos. We evaluated the advantages of each model for anti-cancer drug sensitivity tests. 1) Human glioma-bearing nude mice were found to be most useful in predicting the direct effects of anticancer drugs. We evaluated the effects of several drugs such as ACNU or interferons in six glioma strains transplanted into nude mice. 2) Immunocompetent C57BL/6 mice models were found useful in predicting the therapeutic effects of biological response modifiers. In this model, we can also evaluate changes in immunological parameters such as NK activities or T cell subsets. 3) In the drug sensitivity test using the CAM of chick embryos, various kinds of gliomas could be grafted with a high rate of success. The tumor reduction rate of the sensitivity test using this system tended to agree with that using nude mice. This test was found to be useful in predicting the effect of drugs against gliomas directly resected from individual patients.

Animals↗

[Clinical diagnosis of gliomatosis cerebri by radioimages].

Gliomatosis cerebri (GC) is a rare clinical entity characterized by diffuse and infiltrative overgrowth of the tumor cells. Most of the previously reported cases of GC were autopsy cases because the clinical diagnosis of GC has been difficult. The authors report four cases diagnosed clinically as GC. Cases 1 and 2 are females aged 19 and 69. Cases 3 and 4 are males aged 47 and 50. In the first three cases, CT findings were almost normal. MRI study, especially on its T2 weighted image (T2W1), clearly demonstrated the wide extent of the infiltration of the tumor cells along the white matter. The last case occurred in the pre-MRI era, but contrast enhanced CT showed a bilateral periventricular high density area accompanied by diffuse low density white matter. Three of them underwent echo-guided needle biopsy, and one underwent partial excision of the lesion. Histological diagnosis was glioblastoma in Cases 1 and 4, and anaplastic astrocytoma in Cases 2 and 3. Difficulty in the clinical diagnosis of GC has been based on the fact that traditional imaging studies, including CT, can not clearly show the extent of tumor cell infiltration. MRI study is a very sensitive imaging technique which can easily demonstrate the area infiltrated by glioma cells. So we may be able to make clinical diagnosis of GC, coupling the data from MRI study and brain biopsy. The authors expect that accumulation of clinical experiences of GC may give useful information for the investigation of "invasion", which is one of the major problems in the treatment of malignant gliomas.

Adult↗

A highly potent antiangiogenic activity of retinoids.

Four retinoids, i.e. retinol (vitamin A), retinoic acid, retinyl acetate and synthetic chalcone carboxylic acid (Ch 55), were examined for their effects on embryonic angiogenesis using 4.5-day chorioallantoic membranes of chick embryo. The effects of these retinoids were compared with that of antibiotic herbimycin A, which was the most powerful inhibitor of the angiogenesis reported previously. The four retinoids strongly inhibited embryonic angiogenesis; the order of inhibitory activity was Ch 55 greater than retinoic acid greater than herbimycin A greater than retinyl acetate based on the dose required for the half-maximal inhibitory effect. The present results suggest that retinoids are effective inhibitors of angiogenesis, and can be applied for the management of certain diseases accompanied by aberrant angiogenesis, particularly that which occurs during progressive growth of solid tumors.

Animals↗

Subacute brain atrophy after radiation therapy for malignant brain tumor.

Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

Aged↗

[Regrowth pattern of glioblastoma multiforme after radiotherapy].

We investigated the correlation between the technique of radiation therapy used and the regrowth pattern of recurrent glioblastoma multiformes of 48 patients who received initial radiation therapy in our clinic from April, 1974 to March, 1988. Three different techniques have been applied to patients with brain tumors: whole brain irradiation, generous local irradiation (the parallel opposing technique or three field technique, in which the treatment field fully covers the peritumoral low density area on CT images), and restricted local irradiation (the rotation technique, in which the treatment field is restricted to within about 2 cm of the tumor margin on CT images). Radiation dose of the treatment field was over 45 Gy in every case. The regrowth pattern was defined as being one of the followings: inside of the treatment field, outside of the treatment field (this includes the boundary zone between the treatment and the non-treatment field), and remote from the treatment field-which mostly due to the tumor spreading through ventricular systems. In all 7 cases that received whole brain irradiation, tumor recurred inside of the treatment field. Two of these 7 cases showed remote recurrence at the same time. Mean duration time to recurrence was 36.3 weeks. In 27 (90%) of 30 cases that received the generous local irradiation, tumor recurred within the treatment field. Only one showed outside recurrence, and two other cases showed remote recurrence. The mean duration time to recurrence in this group was 32.2 weeks. Of 11 cases that received restricted local irradiation, 3 cases (27%) showed recurrence outside of the treatment field, one showed recurrence in a remote area. The mean duration time to recurrence in this group was 38.3 weeks, but was not significantly longer than that of other two groups. These results indicate that restricted local irradiation sometimes fails to cover the tumor invaded area, and that the results of treatment using generous local irradiation are almost the same as those using whole brain irradiation. This suggests that generous local irradiation is advantageous to patients with brain tumors since the incidence of subacute side effects such as mental deterioration is much lower in local irradiation as compared with whole brain irradiation.

Brain Neoplasms↗

[A case of pulmonary alveolar proteinosis associated with fibrotic changes and alveolitis].

A 62-year-old male, who had worked for 20 years as a farmer and who had been exposed to respirable agricultural chemicals apart from silica, was admitted in April, 1987, because of progressed exertional dyspnea. The chest X-ray film on admission showed irregularly-distributed infiltrative shadows in both lung fields. The chest CT also revealed irregular increase of densities in lung fields. Though the TBLB specimen from right B8 indicated only fibrotic changes, the tissues obtained by open lung biopsy from right S3 and S8 revealed PAS-positive proteinaceous deposits in the alveoli as well as alveolitis or fibrotic change of alveolar septum. Bronchoalveolar lavage fluid (BALF) contained phospholipids composed mainly of lecithin. According to these findings, the case was diagnosed as pulmonary alveolar proteinosis associated with alveolitis and patchy fibrotic changes. It is not completely clear whether fibrotic changes are induced by pulmonary alveolar proteinosis itself or fibrosis and proteinosis result coincidentally from direct response to fibrogenic agents. Inhaled agricultural chemicals may play a role for the pathogenesis of this case, for which further studies are required.

Biopsy↗

[Response to antitumoral agents of a human medulloblastoma implanted into the chorioallantoic membrane of a chick embryo].

In a previous study the authors have reported on a correlation between the effects of drugs on gliomas grown in the eggs and in the nude mice, and in this study, they have observed the antineoplastic effects of ACNU or combined chemotherapy (CAP-cyclophosphamide, adriamycin, cisplatin) against a medulloblastoma applied onto the chorioallantoic membrane (CAM) of a chick embryo. In this model, ACNU was thought to be ineffective because of an intracerebral dissemination that occurred in spite of the administration of ACNU. ACNU also proved ineffective against the medulloblastoma that grew on the CAM. There seemed to be correlation between the results of this test and the clinical course of this model. Thus this sensitivity test is thought to be useful in the screening of drugs against gliomas.

Adolescent↗

[The treatment of brain metastasis from breast cancer].

From 1975 through 1988, 25 patients with a brain metastasis from a breast cancer received treatments that varied, according to their systemic condition. Of this number, 13 patients were selected for a surgical removal followed by radiation and inoperable patients (3 of this number had meningeal carcinomatosis) with a serious widespread metastasis were treated by radiation only. The median survival time in the former group was 12 months with a 1-year survival rate of 58.3% and that of the latter group (excluding the meningeal carcinomatous cases) was 7 months with a 1-year survival rate of 20%. The median survival of all 25 patients was 7 months with a 1-year survival rate of 33%. At the diagnosis of the brain metastasis, 88% had metastasis to organs other than intracranial sites and most patients died because of the progression of the metastasis at these other sites. Thus, surgical removal of the brain metastasis, followed by radiation therapy, should be considered for patients without a widespread systemic metastasis. Survival for such cases would be more than 1 year.

Adult↗