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Biomedical subjects

O Nakamura

Publications and source records attributed to O Nakamura.

At least 37 records · Page 2Linked to original sources

Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases.

The authors analyzed 153 cases of histologically verified intracranial germ cell tumors. The histological diagnosis was germinoma in 63 patients (41.2%), teratoma in 30 (19.6%), and other types of tumors in 60 patients (39.2%). The patients were treated by a consistent policy of surgical removal with histological verification followed by radiation therapy with or without chemotherapy. The 10- and 20-year survival rates of patients with pure germinoma were 92.7% and 80.6%, respectively. The 10-year survival rates of patients with mature teratoma and malignant teratoma were 92.9% and 70.7%, respectively. Patients with pure malignant germ cell tumors (embryonal carcinoma, yolk sac tumor, or choriocarcinoma) had a 3-year survival rate of 27.3%. The mixed tumors were divided into three subgroups: 1) mixed germinoma and teratoma; 2) mixed tumors whose predominant characteristics were germinoma or teratoma combined with some elements of pure malignant tumors; and 3) mixed tumors with predominantly pure malignant elements. The 3-year survival rates were 94.1% for the first group, 70% for the second group, and 9.3% for the third group, and the differences were statistically significant. Twenty-six patients with malignant tumors received chemotherapy that consisted of cisplatin and carboplatin combinations with or without radiation therapy. However, chemotherapy was not significantly more effective than radiation therapy alone. From these treatment results, the authors classified tumors into three groups with different prognoses and proposed a treatment guideline appropriate for the subgroups.

Adolescent↗

Usefulness of Ga-67 brain SPECT in patients with CNS malignant lymphoma.

The efficacy of Ga-67 SPECT imaging of CNS malignant lymphoma was investigated in 14 studies of 11 patients. As compared with planar images, the SPECT imaging improved the detectability of the focus of CNS malignant lymphoma. All untreated cases showed L/N ratios higher than 3.0. And the L/N ratios also changed according to remission or relapse of CNS malignant lymphoma.

Adult↗

Effect of hepatocyte growth factor/scatter factor on lipogenesis in adult rat hepatocytes in primary culture.

Hepatocyte growth factor (HGF)/scatter factor is known to be the most potent mitogen for hepatocytes. In this paper, we report that lipogenesis in primary cultured rat hepatocytes treated with 10 ng/ml of recombinant human HGF (rhHGF) for 24 h was stimulated, as measured by the incorporation of 3H2O into long-chain fatty acids, to more than twice as much as the control. Insulin (0.1 microM) was more effective than rhHGF but rhHGF did not show an additive or synergistic effect when added to insulin. We also showed that treatment with rhHGF increased the activities of glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme, key enzymes which supply NADPH for lipogenesis, and acetyl-CoA carboxylase, the rate-limiting enzyme of lipogenesis. The increase in G6PDH and acetyl-CoA carboxylase activities was accompanied by increases in the levels of mRNA for the enzymes. These results suggest that HGF is involved in liver regeneration not only by stimulation of cell proliferation but also by acceleration of differentiation of hepatocytes.

Acetyl-CoA Carboxylase↗

Comparison of whole brain radiation therapy and locally limited radiation therapy in the treatment of solitary brain metastases from non-small cell lung cancer.

The benefit and risk of whole brain radiation therapy (WBRT) compared to locally limited radiation therapy was assessed in 61 patients with solitary brain metastases from non-small cell lung cancer without an unresectable active primary lesion or systemic dissemination in the other organs. Twenty-three patients received local irradiation (Group A), and 38 patients received whole brain irradiation with or without local irradiation (Group B). The survival was significantly better in Group A than in Group B (p < 0.05), with median survivals of 83.1 and 30.7 weeks, respectively. One-year local recurrence rates were 7% in Group A and 21% in Group B, but the difference was not statistically significant. The 1-year distant recurrence rate was similar at 18%. Radiation-induced dementia occurred in two patients in Group A (8.7%) and seven in Group B (18.4%), but was not statistically significant (p = 0.30). There is no obvious benefit and possible disadvantages of WBRT compared to local irradiation for the population of patients investigated in this study. Intraoperative radiation therapy or stereotactic radiosurgery without WBRT should be considered in the patients with solitary brain metastases.

Adult↗

Neural activity of chorda tympani mechanosensitive fibers during licking behavior in rats.

The chorda tympani nerve, supplying the anterior two-thirds of the tongue, contains gustatory and mechanosensitive afferent fibers. We have analyzed discharge patterns in rats of various fibers recorded from dissected nerve filaments during licking behavior of which 4 were taste-sensitive and 12 mechanosensitive. The incidence of these two types were estimated electrophysiologically under anesthesia and their conduction velocity measured. Recordings in freely moving animals showed that the mechanosensitive fibers innervating the dorsal part of the tongue gave two burst discharges per lick, suggesting that contact of the tongue with the upper incisors and/or lip occurred during tongue protrusion and retraction. The fibers from the tip of the tongue showed one burst discharge per lick, which was the response to contact with a drinking spout. No rhythmical discharges synchronized with lick signals were observed in the fibers from the lateral part of the tongue or the taste-sensitive fibers. Such mechanoreceptor discharges were difficult to detect in recordings from the whole chorda tympani nerve. This masking of responses was due mainly to activation of a small number of mechanosensitive fibers by licking-induced mechanical stimulation. The lubricating action of saliva also decreased mechanoreceptor sensitivity. Despite their small number, the mechanosensitive fibers had axons with faster conduction velocities (larger diameter) than the taste-sensitive fibers. This was probably the reason why dissected nerve bundles more frequently showed mechanical than taste responses in conscious rats.

Action Potentials↗

Steroidal saponins from the bulbs of Triteleia lactea and their inhibitory activity on cyclic AMP phosphodiesterase.

The chemical compounds in the bulbs of Triteleia lactea have been analysed as a part of our systematic study of plants of the subfamily Allioideae in Liliaceae. Thirteen steroidal saponins, seven of which appeared to be new compounds, were isolated. The structures of the new saponins were elucidated on the basis of the spectroscopic analysis, including two-dimensional NMR techniques, and hydrolysis. Inhibitory activity of the isolated saponins on cyclic AMP phosphodiesterase was evaluated to identify new compounds with medicinal potential.

3',5'-Cyclic-AMP Phosphodiesterases↗

Structures of steroidal saponins from the tubers of Brodiaea californica and their inhibitory activity on tumor promoter-induced phospholipid metabolism.

Phytochemical examination of the fresh tubers of Brodiaea californica resulted in the isolation of four new steroidal saponins. Their structures were determined, by extensive spectral analysis including two-dimensional (2D) NMR spectroscopy and acid-catalyzed hydrolysis, to be (25S)-spirost-5-ene-1 beta,3 beta-diol [(25S)-ryscogenin] 1-O-[O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)- beta-D-glucopyranoside] (1), (25S)-ruscogenin 1-O-[O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-O -[beta-D-xylopyranosyl-(1-->3)]-beta-D-glucopyranoside] (2), the C-20 and C-22 isomer of 2 (3) and the 6'-O-acetyl derivative of 2 (4), respectively. The conformations of the tetrasaccharide moiety of 2 and 4 were inspected through molecular mechanics and molecular dynamics calculation studies, showing that the acetyl group attached to C-6 of the inner glucose was near the C-21 methyl of the aglycon in the calculated preferred conformation of 4, which must cause the downfield shift of 21-Me by 0.07 ppm in comparing the 1H-NMR of 4 with that of 2. The inhibitory activity of the isolated saponins on 12-O-tetradecanoylphorbor-13-acetate (TPA)-stimulated 32P-incorporation into phospholipids of HeLa cells was evaluated to identify new antitumor-promoter compounds.

Anticarcinogenic Agents↗

[IgD-lambda type multiple myeloma associated with IgG-kappa type benign monoclonal gammopathy].

A 76-year-old man was admitted to Kisen hospital because of lumbago and chest pain. Laboratory examinations revealed a chronic renal failure with marked elevation of the serum BUN (48.8 mg/dl) and creatinine levels (8.2 mg/dl). The serum electrophoresis demonstrated a hypergammaglobulinemia with M peaks. An immunoelectrophoresis demonstrated monoclonal IgD-lambda and IgG-kappa proteins in the serum, and lambda-type Bence Jones protein in the urine (0.4 g/day). Bone marrow smears revealed an abnormal proliferation of atypical plasma cells (43%). A systemic X-ray examination of the skeletal system showed systemic osteoporosis without punched out lesion. The patient was diagnosed as having IgD-lambda type multiple myeloma and IgG-kappa type benign monoclonal gammopathy by quantifying concentration of two M proteins (1,160 mg/dl in IgD, 1,179 mg/dl in IgG, respectively). A combination chemotherapy with melphalan and prednisolone was administered monthly for multiple myeloma, and hemodialysis for the renal failure was performed 3 times a week. A marked improvement of his laboratory findings including a diminution of the serum IgD-lambda M-protein was obtained. On the other hand, IgG-kappa M-protein level was unchanged. Two M-protein levels showed a different behavior after the combination chemotherapy. Although the patient died of congestive heart failure, the partial remission of multiple myeloma has been maintained for 16 months with chemotherapy.

Aged↗

Evidence for the presence of an inactive precursor of human hepatocyte growth factor in plasma and sera of patients with liver diseases.

Human hepatocyte growth factor (hHGF), which is now known to be the same protein as the scatter factor and the tumor cytotoxic factor, is a heterodimeric protein with one heavy chain and one light chain linked together by a disulfide bond, and is thought to be involved in liver regeneration. Using an enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, we found that a significant amount of single chain precursor of hHGF (pro-hHGF) was present in plasma of patients with fulminant hepatic failure (FHF) and that normal human serum contained a protease or proteases that convert pro-HGF to a heterodimeric (mature) form of hHGF. We also showed that the processing protease activity for hHGF was suppressed by such serine protease inhibitors as leupeptin, antipain, and aprotinin, and that sera of patients with liver diseases such as fulminant hepatic failure, acute hepatitis, chronic hepatitis, and cirrhosis contained not only pro-hHGF but also the protease. This is the first report showing the presence of pro-hHGF in human blood, and our observations suggest that hHGF is synthesized and secreted from the hHGF-producing cells as an inactive pro-hHGF after hepatic injuries, and the pro-hHGF is then converted to an active heterodimeric form of hHGF in the blood. It is also suggested that plasma of patients with liver diseases contains an active protease or proteases that convert pro-hHGF to a mature form of hHGF.

Animals↗

Prediction of survival in patients with suspected recurrent cerebral tumors by quantitative thallium-201 single photon emission computed tomography.

PURPOSE: To assess whether quantitative 201Tl single photon emission computed tomography (SPECT) can be used as a prognostic test in patients with suspected recurrent cerebral tumor, regardless of various combined therapies given. METHODS AND MATERIALS: The study population consisted of 22 patients with grade 4, 3, or 2 glioma and 7 patients with solitary cerebral metastasis. All patients had undergone combined radiotherapy and chemotherapy after or during surgical debulking. Each patient underwent 201Tl brain SPECT to differentiate recurrent tumor from cerebral radiation necrosis, because the prior computed tomography and/or magnetic resonance imaging showed a mass lesion with an irregularly enhanced rim in the irradiation field. RESULTS: Higher values of 201Tl index (L/N ratio) showed a tendency for shorter survival (r = -0.502, p < 0.05). In patients with grade 3 glioma or solitary cerebral metastasis, survival time was definitely dependent upon 201Tl index values, that is, above or below the baseline index of 2.5. Grade 4 glioma patients, however, had a very short-term survival independent of 201Tl index values. CONCLUSION: Quantitative 201Tl SPECT may be a useful tool for predicting survival of patients with suspected recurrent cerebral tumor and may be used in place of fluorine-18-2-deoxy-2-fluoro-D-glucose (18F-FDG) scan.

Adenocarcinoma↗

Effect of salivation on neural taste responses in freely moving rats: analyses of salivary secretion and taste responses of the chorda tympani nerve.

The outer surface of the mammalian taste receptor cell is usually covered with saliva, which may affect the initial process of gustation. To ascertain the interaction between salivation and gustation, salivary secretion from the submandibular and parotid glands and taste responses to the chorda tympani nerve were analyzed in the rat, during grooming, eating, and licking of the four standard taste stimuli (sucrose, NaCl, HCl, and quinine hydrochloride). Regions of the tongue surface bathed by saliva secreted from the each gland were examined, and it was found that: (1) Rats frequently groomed, and the anterior part of the tongue, innervated by the chorda tympani nerve, was usually covered with a mixture of submandibular saliva and substances on the body surface. (2) Licking of acceptable sucrose and NaCl solutions elicited initial phasic and long-lasting tonic taste responses, and did not evoked saliva enough to wash away the stimuli from the oral cavity. Licking of rejectable quinine evoked only a small phasic taste response and was followed by taste rejection behavior, accompanied by maximum salivation which could wash out the stimuli. (3) When taste responses were compared under awake and anesthetized (the tongue adapted to water) condition, sucrose response was larger, while responses to other taste stimuli were smaller under the awake condition. Rise time of the phasic NaCl response was longer under the awake condition. These taste response alterations may reflect the effects of prolonged adaptation of the tongue to the mixture of submandibular saliva and body surface substances, and flow rate of licked taste stimuli on the tongue surface.

Animals↗

Effects of cytokines and growth factors on phosphorylated fetuin biosynthesis by adult rat hepatocytes in primary culture.

Recently, we showed that a 59 kDa non-phosphorylated sialoprotein purified from rat bone matrix is the rat counterpart of bovine fetuin and human alpha 2-HS glycoprotein and that fetuin synthesized and secreted by adult rat hepatocytes in primary culture is mostly phosphorylated (phosphofetuin), though fetuin is known to contain no phosphorus. Here we report that the rate of synthesis of phosphofetuin by hepatocytes in culture was reduced by inflammatory cytokines such as human interleukin (hIL)-6, human tumor necrosis factor-alpha and hIL-1 alpha, but dose-dependently stimulated by growth factors of hepatocytes, such as hepatocyte growth factor (HGF)/scatter factor (SF), epidermal growth factor and insulin, as determined by metabolic labeling and Northern blot analysis using cDNA for rat fetuin as a probe. We also showed that administration of HGF/SF stimulated gene expression of rat fetuin in vivo.

Animals↗

CT and MRI features of intracranial germ cell tumors.

The computed tomographic (CT) and magnetic resonance imaging (MRI) features of 73 histologically proven primary intracranial germ cell tumors were analysed. CT images were available for all 73 patients, and 22 of them were also examined by MRI. The tumors were classified as germinoma, mature teratoma, immature or malignant teratoma, yolk sac tumor, choriocarcinoma, embryonal carcinoma and mixed type. Germinoma was revealed as a high- or slightly high-density area on plain CT scan, and was enhanced homogeneously. MRI revealed iso- or slightly low signal intensity on T1-weighted images, and iso- or high intensity on T2-weighted images. Mature teratoma, which had a clear margin on neuroradiological images, was characterized by mixed density on CT scans, often showing large cysts and area of calcification. Immature or malignant teratoma had a similar pattern to that of mature teratoma, but the cystic components and area of calcification tended to be less and smaller respectively. The tumor margin was obscure in malignant teratoma, and perifocal edema was observed in some cases. The shape of yolk sac tumors was irregular. Plain CT scan revealed an iso- or low-density mass with good heterogeneous enhancement. Perifocal edema was observed in some cases. In mixed germ cell tumors, MRI imaging was useful for detecting teratomatous components, particularly fatty components. Although definite histological diagnosis cannot be achieved by CT and/or MRI alone, detailed analysis of neuroradiological images are useful for predicting the histological diagnosis.

Brain Neoplasms↗

Radiation therapy combined with radiosensitizing agents for cerebral glioblastoma in adults.

We analyzed our treatment results of 71 operated patients with cerebral glioblastoma treated by conventional external radiation therapy (mean dose 60.2 Gy) combined with radiosensitizing agents. More than 50% reduction of tumor volume was obtained in 20 patients (28.2%). A response rate of at least 40% was obtained in patients treated with combined ACNU-vincristine-nicardipine, ACNU-5FU-hydroxyurea, or cisplatin alone. The combination of ACNU and vincristine with or without nicardipine resulted in significantly longer survival. The median survival in this group was 101.1 weeks and the two-year survival rate was 45.9%; these results were significantly better than those achieved with other ACNU combinations or other combinations without ACNU. In the analysis of survival, factors correlated to longer survival were a patient age of younger than 45 years, wide resection of the tumor, a good postoperative performance status (KS > or = 70%), a radiation dose of 68-72 Gy, small postoperative tumor remnants (< 20 cm3), no visible tumor after radiation therapy, and the administration of adjuvant chemotherapy. Maximum resection of the tumor and localized irradiation with a dose of 70 Gy combined with ACNU and vincristine appears to be the most effective treatment at present.

Adolescent↗

Intra-operative radiation therapy for malignant brain tumors: rationale, method, and treatment results of cerebral glioblastomas.

In radiation therapy for malignant brain tumours, the dose of radiation that can be safely delivered to a tumour is limited by the radiation tolerance of the adjacent normal brain tissue. Among various radiation modalities to produce local tumour eradication without unacceptable complications, we chose a large, single irradiation dose during the operation (intra-operative radiation therapy, IORT). In contrast to X-ray or Cobalt-60 gamma ray irradiation, IORT with a high-energy electron beam delivered by the Shimadzu 20 MeV betatron provides acceptable dose homogeneity with rapid fall-off of the radiation dose beyond the treatment volume. Thus, IORT has the advantage of precise demarcation of the target volume, minimum damage to surrounding normal tissues, and a high absorbed target dose (15-25 Gy in 5-10 min). On the basis of our experience with 170 patients treated by IORT, we established the treatment indications and method in patients with malignant brain tumours. IORT with a dose of 15-25 Gy was delivered to widely resected tumours followed by external radiation therapy. No acute or subacute complications were observed. Treatment results of 30 patients with glioblastoma treated by IORT (mean 18.3 Gy) combined with external radiation therapy (mean 58.5 Gy) resulted in a median survival of 119 weeks and a 2-year survival rate of 61%.

Adolescent↗

New treatment protocol by intra-operative radiation therapy for metastatic brain tumours.

In patients with brain metastasis from lung cancer, we have been able to control local recurrence in approximately 80% of cases. But many of them tend to show brain atrophy with mental deterioration developing a few months after whole brain radiation. To prevent brain atrophy, we have attempted treating patients, whose metastasis was diagnosed as single, by intra-operative radiotherapy (IOR) alone following surgical resection. Among 43 patients, 19 patients who had no metastases other than the brain metastases, were chosen as subjects for active treatment (surgical resection+IOR). Their 1-year survival rate was 75%. Fourteen out of 27 patients with brain metastases from lung cancer received active treatment and their 1-year survival rate was 74%. This result was not inferior to our result of 71 patients who received surgical resection and whole brain irradiation. When no preventive whole brain irradiation was performed, patients were observed every 8 weeks by CT scan in order to ascertain tumour recurrence limited to the treated site or appearance of any new metastatic lesion remote from the treated site. Among all 43 patients, local recurrence was recognized in 7 cases and remote recurrence was observed in 7 cases. Within 6 months, local and remote recurrence was found in 3 cases each. These results were almost the same as those for the usual therapy (surgery plus whole brain irradiation). If such a new lesion is detected, additional radiation can be performed with the possibility of achieving complete remission.

Adult↗

Steroidal saponins from the bulbs of Lilium longiflorum and their antitumour-promoter activity.

Two new spirostanol saponins and two new furostanol saponins were isolated from the fresh bulbs of Lilium longiflorum together with several known saponins. The structures of new compounds were determined to be (25S)-spirost-5-ene-3 beta, 27-diol 3-O-(O-alpha-L-rhamnopyranosyl-(1-->2)-O- [alpha-L-arabinopyranosyl-(1-->3)]-beta-D-glucopyranoside), (25R)-27-O-[(S)-3-hydroxy-3-methylglutaryl]-spirost-5-ene-3 beta,27 diol 3-O-(O-alpha-L-rhamnopyranosyl-(1-->2)-O-[alpha-L-arabinopyranosyl -(1-->3)] - beta-D-glucopyranoside), 22-O-methyl-26-O-beta-D-glucopyranosyl-(25R)-furost-5-ene-3 beta,22 xi, 26-triol 3-O-(O-alpha-L-rhamnopyranosyl-(1-->2)-O-[alpha-L- arabinopyranosyl-(1-->3)]-beta-D-glucopyranoside) and 22-O-methyl-26-O-beta-D-glucopyranosyl-(25R)-furost-5-ene-3 beta, zeta, 26-triol 3-O-(O-alpha-L-rhamnopyranosyl-(1 --> 2)- O-[beta-D-xylopyranosyl-(1 --> 3)]-beta-D-glucopyranoside). The isolated saponins and their derivatives were examined for inhibitory activity on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32P-incorporation into phospholipids of HeLa cells as the primary screening test to find new antitumour-promoter compounds.

Antineoplastic Agents, Phytogenic↗

Steroidal saponins from the bulbs of Lilium speciosum x L. nobilissimum 'Star Gazer' and their antitumour-promoter activity.

The fresh bulbs of the oriental hybrid lily, Lilium speciosum x L. nobilissimum 'Star Gazer' yielded a new steroidal saponin, (25R,26R)-26-methoxyspirost-5-en-3 beta-ol 3-O-[O-alpha-L-rhamnopyranosyl-(1-->2)-O-[6-O-acetyl-beta-D-glucopyranos yl- (1-->4)]-beta-D-glucopyranoside], along with four known steroidal saponins, (25R,26R)-26-methoxyspirost-5-en-3 beta-ol 3-O-[O-alpha-L-rhamnopyranosyl-(1-->2)-O-]beta-D-glucopyranosyl-(1-->4)] - beta-D-glucopyranoside], (25R)-27-O-[(S)-3-hydroxy-3-methylglutaryl]- spirost-5-ene-3 beta, 27-diol 3-O-[O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D- glucopy-ranoside] and (25R)-27-O-[(S)-3-hydroxy-3-methylglutaryl]- spirost-5-eene-3 beta, 27-diol 3-O-[O-alpha-L-rhamnopyranosyl-(1-->2)-O- O-[beta-D-glucoyranosyl-(1-->4)]-beta-D-glucoyranoside]. The structure of The structure of the new saponin was determined by means of spectroscopic analysis and hydrolysis. The methyl ester of 5 showed potent inhibitory activity on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32P incorporation into phospholipids of HeLa cells.

Antineoplastic Agents, Phytogenic↗