Biomedical subjects

H Kamei

Publications and source records attributed to H Kamei.

At least 73 records · Page 4Linked to original sources

PubMed1996

(+)-SKF-10,047 and dextromethorphan ameliorate conditioned fear stress via dopaminergic systems linked to phenytoin-regulated sigma 1 sites.

Mice exhibited a marked suppression of motility when they were re-placed in the same environment in which they had previously received an electric footshock. (+)-SKF-10,047 ([2S-(2 alpha, 6 alpha, 11R*)]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-me tha no-3-benzazocin-8-ol hydrochloride; (+)-N-allylnormetazocine hydrochloride) and dextromethorphan, putative sigma receptor agonists, have been reported to reserve this psychological stress-induced motor suppression, defined as conditioned fear stress, through phenytoin-regulated type sigma 1, receptors. In the present study, we investigated the involvement of dopaminergic neurons in the ameliorating effects of (+)-SKF-10,047 and dextromethorphan on conditioned fear stress. (+)-SKF-10,047 and dextromethorphan attenuated conditioned fear stress at low doses (4 and 20 mg/kg, respectively) when they were co-administered with phenytoin (10 mg/kg), an anticonvulsant drug. The effects were antagonized by the sigma receptor antagonists. NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride) and BMY-14802 (a-(4-fluoro-phenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol hydrochloride). Furthermore, the effects of (+)-SKF-10,047 or dextromethorphan in combination with phenytoin were blocked by the dopamine D1 receptor antagonist. SCH 23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine), and the dopamine D2 receptor antagonist, (-)-sulpiride, and they were also attenuated by 6-hydroxydopamine-induced lesions of dopaminergic neurons. The ameliorating effects of (+)-SKF-10,047 and dextromethorphan on conditioned fear stress at high doses (5 and 30 mg/kg, respectively) were also blocked by both the dopamine receptor antagonists. These results suggest that the stress-induced motor suppression is restored by the activation of dopaminergic neuronal systems as a result of the stimulation of phenytoin-regulated type sigma 1 receptors.

Animals↗

PubMed1996

Reversible large-body formation from nuclear bodies upon amino acid(s) starvation in T24 cells.

AP435 dot, a nuclear dot-like structure that is recognized by a monoclonal antibody AP435 MAb and that seems to correlate with perinuclear intermediate filaments, was identified as a nuclear body by double immunofluorescent staining with AP435 MAb and the nuclear-body-specific antibody alphaSp100 or mAb 5E10. In T24 cells, nuclear bodies usually appear as small entities with an apparent diameter ranging from 0.2 to 0.7 microm, and several to 20 or more of them are present per nucleus. After long culture without a change in the medium, however, nuclear bodies disappeared while one or more large doughnut-shaped bodies appeared, which had apparent outer diameters of 0.7-1.8 microm. When the medium was changed or medium components were added, large bodies disappeared and many nuclear bodies of normal size reappeared within several hours. Large-body formation was not related to the arrest of DNA synthesis, as revealed by double labeling with AP435 MAb and anti-cyclin antibody. Among the medium components, only an amino acid mixture induced the change from large bodies to nuclear bodies. Large-body formation was also observed in long-cultured HeLa cells. These results suggest that nuclear bodies reversibly aggregate or reorganized to form large bodies upon amino acid(s) starvation.

Adenocarcinoma↗

PubMed1996

(+)-SKF-10,047 and dextromethorphan ameliorate conditioned fear stress through the activation of phenytoin-regulated sigma 1 sites.

Mice exhibited a marked suppression of motility when they were replaced in the same environment in which they had previously received an electric footshock. This psychological stress-induced motor suppression, known as conditioned fear stress, was dose dependently attenuated by (+)-N-allylnormetazocine ((+)-SKF-10,047) and by dextromethorphan, putative sigma receptor agonists, but not by other sigma receptor ligands, (+)-pentazocine and 1,3-di-(2-tolyl)guanidine (DTG). Unlike (+)-SKF-10,047 and dextromethorphan, the non-competitive NMDA receptor antagonists, phencyclidine and dizocilpine, attenuated the conditioned fear stress only at high doses that induced marked hypermotility in non-stressed mice. The effects of (+)-SKF-10,047 and dextromethorphan, but not phencyclidine and dizocilpine, on the conditioned fear stress were antagonized by the sigma receptor antagonists, NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2- phenylethoxy)phenyl]-ethylamine monohydrochloride) and BMY-14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine- butanol hydrochloride). Interestingly, the effects of (+)-SKF-10,047 and dextromethorphan on the stress response were enhanced by combination with phenytoin, an anticonvulsant drug, whereas those of (+)- pentazocine, DTG, phencyclidine, and dizocilpine were not. These results suggest that activation of phenytoin-regulated type sigma 1 receptors, but not of phencyclidine receptors, is involved in the ameliorating effects of (+)-SKF-10,047 and dextromethorphan on stress-induced motor suppression.

Animals↗

PubMed1996

Nuclear antigens, as DNA, of DSB389 MAb and some other anti-desmin monoclonal antibodies.

The anti-desmin monoclonal antibodies (MAbs) DSB389, AC54, and DSB860 recognize intermediate filaments (IFs) and nuclear antigens that appear granular, locate around chromosomes, and are insoluble following 0.5% Triton X-100 and cetyltrimethylammonium bromide (CTAB) extraction. Nuclear antigens of the MAbs were searched for in an IFs-deficient clone of SW13 cells. Reactive materials specific to DSB389, AC54, and DSB860 MAbs were trapped at the top of the gel of SDS-agarose-PAGE. The reactivity of the materials disappeared after treatment with DNase I. The reactivity, or trapping of this material at the top of the gel, required previous heat treatment of the sample before application to the gel. The MAbs recognized both single-stranded and double-stranded DNA in ELISA. These results indicate that at least the main nuclear antigens of DSB389, DSB860 and AC54 MAbs are DNA.

Adenocarcinoma↗

PubMed1996

Flavonoid-mediated tumor growth suppression demonstrated by in vivo study.

Many of flavonoids as well as bioflavonoids extracted from higher plants, which were earlier revealed to have tumor cell growth suppression activity in vitro, were examined for their effect on tumors in vivo. Balb/c mice were inoculated i.p. with syngeneic tumor cells, meth/a, and then provided with flavonoids dissolved in their drinking water during the course of their survival time. Many flavonoids were effective in prolonging the survival period. Furthermore, flavonoids that did not show suppressive activities in the in vitro experiments were effective in the in vivo assay. The data suggested that sugar bonded to the A ring, which suppresses tumor growth inhibition in vitro, plays an important role. Many aglycones that were effective in the in vitro assay on the tumor growth suppression were not effective in the in vivo assay. The reason for this seems to be that most aglycones are unstable and thus break down in vivo. No acute nor chronic toxicity of flavonoids was observed in the mice.

Animals↗

PubMed1996

Influence of OH group and sugar bonded to flavonoids on flavonoid-mediated suppression of tumor growth in vitro.

Many flavonoids extracted from higher plants, synthesized or purified flavonoids, and their aglycones showed anti-tumor activity. Using purified or synthesized flavonoids, we studied the effect of the chemical structure of 2-benzoic flavone on the growth of human tumor cells (HCT-15 in vitro. The type of sugar combined with the A phenol of flavonoids played an important role in the tumor suppression; i.e., glucose attachment at the A phenol caused suppression of tumor cell growth, but other sugars such as rhamnose and lutinoside at that position did not suppress the growth of the cells. OH groups bonded to the B phenol also had a great effect on the growth. Flavonoids with OH groups conjugated to the 3', 4', and 5' of B phenol were stronger in anti-tumor effect than those with the OH groups attached at the 3' and 4' or 4' only, although anthocyanins were generally more effective than the other flavonoids.

Antineoplastic Agents, Phytogenic↗

PubMed1996

Antitumor effect of hydrolyzed anthocyanin from grape rinds and red rice.

When Balb/C mice that were fed with red glutinous rice, white ordinary rice, or commercially available standard food were inoculated with syngeneic Meth/A lymphoma cells i.p., the group fed the red rice survived longer than the other two groups. In order to determine if the anthocyanins contained in red-coloured seeds and fruit rinds were responsible for the tumor suppressive effect, we added anthocyanins extracted from grape rinds and glutinous red rice to petri dishes that had been seeded with HCT-15 cells. After 4 days of culture, cell counts were made. These anthocyanins were not effective in suppressing the tumor growth. However, anthocyanidins, which were generated by keeping anthocyanins in 5 to 6% HC1 methanol for 5 to 6 hours, were effective in the suppression of tumor growth. Flowcytometric histograms were made after 2 days of culture with these bioflavonoids. The histogram of cells treated with crude anthocyanin was similar to that of the control. Hydrolyzed anthocyanidins gave the elevation of S phase, suggesting a block in the step from S-phase to G2-phase. It seemed that the anthocyanidins contained in the grape rinds and red rice were effective on the suppression of cell growth as observed previously for anthocyanins extracted from the petals of higher plants.

Animals↗

PubMed1996

[Moderately differentiated adenocarcinoma of the lung presenting as multiple intrapulmonary metastases with thin-walled cavities].

A 63-year-old woman complaining of a non-productive cough was referred to our hospital. A chest X-ray film and computed tomographic scan showed a large mass in the S9 region of the right lung, and many intrapulmonary nodules with thin-walled cavities. A transbronchial biopsy specimen revealed moderately differentiated adenocarcinoma of bronchial gland origin. By the end of four cycles of chemotherapy with vindesine, ifosfamide, and cisplatin, the primary mass had markedly regressed, the many metastases had disappeared, and a few bullous lesions remained. On the second admission, many intrapulmonary metastases and cavities were seen again. Although some of the cavities may have been associated with regrowth of residual cancer cells around the remaining bullae, some nodules showed newly-developed thin-walled cavities, and in others bullous lesions developed again. These observations indicate that a check valve mechanism may operate in the formation of the thin-walled cavities.

Adenocarcinoma↗

PubMed1995

Activation of both dopamine D1 and D2 receptors necessary for amelioration of conditioned fear stress.

Mice exhibited a marked suppression of motility when they were re-placed in the same environment in which they had previously received an electric footshock. This psychological stress-induced motor suppression, known as conditioned fear stress, was dose dependently attenuated by apomorphine, a non-selective dopamine receptor agonist. Combined treatment with the dopamine D1 receptor agonist, SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1-H-3-benzazepine), and the dopamine D2 receptor agonist, quinpirole, also synergistically attenuated the conditioned fear stress although, alone, neither SKF 38393 nor quinpirole did so at the doses used. The effects of apomorphine and of the coadministration of SKF 38393 and quinpirole on the conditioned fear stress were completely blocked by the dopamine D1 receptor antagonist, SCH 23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H- 3-benzazepine), and by the dopamine D2 receptor antagonist, (-)-sulpiride. These results suggest that a dysfunction in the dopaminergic neuronal system is responsible for the conditioned fear stress, and that the activation of both dopamine D1 and D2 receptors is necessary to attenuate this stress-induced motor suppression.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

A nuclear dot-like structure that has a relationship with perinuclear intermediate filaments.

A new type of nuclear dot-like structure was found that seems to associate with perinuclear intermediate filaments (IFs). A monoclonal antibody AP435 MAb (IgM), reactive with desmin and vimentin, recognized from several to dozens of small nuclear dots (AP435 dots) as well as cytoplasmic IFs in various mammalian cells under immunofluorescence microscopy. AP435 dots were sensitive to treatment with 0.5% Triton X-100 while IFs were resistant. The dots disappeared during mitosis in some cells. They colocalized with neither centromeres nor structures involved in RNA processing. Many AP435 dots seem to associate with perinuclear IFs, though they were observed even in cells with no IFs. In cells possessing IFs AP435 dots separated from the bulk of the IFs and remained in the nuclear region both after treatment with colchicin and after treatment with cytochalasin B followed by centrifugation. Confocal laser-scanning fluorescence microscopy revealed the dots to be inside the nucleus. AP435 dots are small intranuclear structures that seem to interact directly or indirectly with perinuclear IFs.

Animals↗

PubMed1995

Suppression of tumor cell growth by anthocyanins in vitro.

Bioflavonoids, extracted from flower petals, were examined for their growth inhibitory effect on cells in culture. They were found to significantly suppress the growth of the cultured cells. Anthocyanins tended to show greater inhibitory effect than other flavonoids. Commercially synthesized or purified aglycones of flavonoids were also studied for their suppression of tumor cells. The anthocyanins were more effective than other flavonoid aglycones, although the aglycones were easily inactivated under the culture conditions.

Anthocyanins↗

PubMed1994

SKF-10,047 reverses stress-induced motor suppression: interaction with dopaminergic system.

Mice exhibited a marked suppression of motility (conditioned suppression) when placed in the same environment in which they had previously received an electric footshock. This stress-induced motor suppression was dose dependently attenuated by (+/-)-SKF-10,047, a sigma receptor agonist, but not by its (-)-optical isomer ((-)-SKF-10,047) and the sigma receptor ligands (+)-pentazocine and 1,3-di-(2-tolyl)guanidine. This effect of (+/-)-SKF-10,047 was antagonized by BMY-14802, a sigma receptor antagonist, and by pimozide, a dopamine receptor antagonist. When dopaminergic neurons were destroyed by pretreatment with 6-hydroxydopamine, the effect of (+/-)-SKF-10,047 on the stress response was also attenuated. Furthermore, (+/-)-SKF-10,047 dose dependently reversed the decrease in striatal dopamine turnover in the conditioned suppression group. These results suggest that stress-induced motor suppression is restored by (+/-)-SKF-10,047 acting through sigma receptors, which are closely linked to the dopaminergic neuronal system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1994

Relationship of nuclear invaginations to perinuclear rings composed of intermediate filaments in MIA PaCa-2 and some other cells.

There have been few investigations of the cause of nuclear invagination and lobule formation. The human pancreatic cancer cells MIA PaCa-2 often show nuclear lobulation and well-developed juxtanuclear aggregates of intermediate filaments with thick bundles of intermediate filaments developed from them. Therefore MIA PaCa-2 cells were used as model cells to examine whether or not there is any relationship between the shape of the nucleus and intermediate filaments. Immunoblotting showed that the intermediate filament proteins in MIA PaCa-2 cells are vimentin, and keratins 8, 18, and 19. Fluorescence microscopy and confocal laser scanning fluorescence microscopy revealed perinuclear rings composed of intermediate filaments, that is, thick bundles of both vimentin and keratin filaments run along deep invaginations in the nucleus and, together with juxtanuclear intermediate filament aggregates, they form closed rings around nuclear invaginated and constricted sites. In other cells such as human bladder carcinoma T24 cells, human melanoma G-361 cells, and human cervix carcinoma HeLa/S3 cells, there were also thick bundles of intermediate filaments cutting into the nucleus at the nuclear invagination site. Thus, it seems that the formation of perinuclear intermediate filament rings may be involved in nuclear invagination and lobule formation in some mammalian cells.

Antibodies, Monoclonal↗

PubMed1993

Pilot study of cyclophosphamide-doxorubicin-vincristine-cisplatin-etoposide hybrid chemotherapy in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is highly sensitive to chemotherapy. Despite the introduction of intensive combination chemotherapy, long-term disease-free survivors are still rare. The emergence of drug-resistant tumor cells during chemotherapy is presumed to be the major cause of poor outcome. METHODS: A pilot Phase II study of hybrid chemotherapy for patients with SCLC was conducted between October 1986 and March 1988. Dose and schedule for each drug in the regimen were as follows: cyclophosphamide, 700 mg/m2 intravenously (IV), day 1; doxorubicin, 30 mg/m2 IV, day 1; vincristine, 1.4 mg/m2 IV, day 1; cisplatin, 60 mg/m2 IV, day 8; and etoposide, 100 mg/m2 IV, days 8 and 9. Courses were repeated every 4 weeks for up to six cycles. Patients with limited disease (LD) received chest irradiation of 5000 cGy when a maximal response was achieved. Only patients with LD who achieved a complete response (CR) received prophylactic cranial irradiation of 3000 cGy. RESULTS: Thirty-six patients were enrolled and fully evaluated for tumor response and toxicity. All 20 patients with LD responded to the regimen, and 14 (70%) of those achieved a CR. Of 16 patients with extensive disease (ED), 7 CR and 7 partial responses were noted, indicating an overall response rate of 88%. The median survival time was 23.6 months for patients with LD and 12.6 months for those with ED. Myelosuppression was the major toxicity, but it was generally well tolerated. CONCLUSIONS: These results indicate that the hybrid regimen is a highly active one for the treatment of patients with SCLC and warrants additional clinical trials.

Adult↗

PubMed1993

MPC-1304, another type of dihydropyridine, possessing highly potent vasodilating action.

We investigated the vasodilating action of MPC-1304, one of the most potent dihydropyridines causing hypotension, in anesthetized dogs and compared this with its binding properties. After intraarterial injection, MPC-1304 was 3 times less potent than other dihydropyridines (nitrendipine, nifedipine, nicardipine and nisoldipine) in increasing femoral blood flow. After infusion of these drugs, however, MPC-1304 was the most potent in increasing femoral blood flow. The onset and recovery of the effect of MPC-1304 on femoral blood flow were slower than for nifedipine. Higher doses of Bay K 8644 were needed to antagonize the stimulating activity of MPC-1304 than for nifedipine. In a competition assay of [3H]nitrendipine binding, MPC-1304 and its metabolites bound to the dihydropyridine receptor with lower affinity than the other dihydropyridines. The binding affinity of [3H]MPC-1304 was lower than that of [3H]nitrendipine, consistent with the potency of this drug to increase femoral blood flow by bolus injection. The association and dissociation of [3H]MPC-1304 was slower than those of [3H]nitrendipine, which is consistent with the slow onset and long-lasting vasodilating effects of MPC-1304 on femoral blood flow. Moreover, diltiazem reduced a part of [3H]MPC-1304 binding in a competitive manner. In ex vivo binding assays with serum and aorta obtained after oral administration of the drug in spontaneously hypertensive rats, MPC-1304 inhibited [3H]nitrendipine binding to membrane preparations less potently than nifedipine. From these results, we conclude that MPC-1304 is a different type of dihydropyridine possessing the most potent vasodilating action of the representative dihydropyridines tested. Its activity cannot be explained solely by a slow interaction with voltage-dependent Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1993

Distribution of fluoride in cortical bone of human rib.

We describe a detailed study of fluoride distribution with age in the human cortical rib bone. Human ribs were obtained from 110 subjects (M:68, F;42) aged 20-93 years. The fluoride distribution from the periosteal to endosteal surfaces of the ribs was determined by sampling each specimen using an abrasive micro-sampling technique, and the samples were analyzed using the fluoride electrode, as described by Weatherell et al. [1]. The concentration of fluoride was highest in the periosteal region, decreased gradually towards the interior of the tissue where the concentration of fluoride tended toward the plateau, and then rose again towards the endosteal surface. Patterns of fluoride distribution changed with age, and the difference between periosteal and endosteal fluoride levels increased with age. Although average fluoride concentrations increased with age in both sexes, there was a significant difference between males and females at the age of about 55 years (P < 0.05).

Adult↗

PubMed1993

Comparative study of prophylactic cranial irradiation in patients with small cell lung cancer achieving a complete response: a long-term follow-up result.

Between 1981 and 1986, a total of 46 patients with small cell lung cancer (SCLC) achieving a complete response by chemotherapy with or without chest irradiation were randomized either to receive prophylactic cranial irradiation (PCI) or not. With a median follow-up time of 8.5 years for both groups, only five of 23 patients (22%) in the PCI group developed brain relapse, while 12 out of 23 (52%) in the no PCI group did so (P < 0.05). The frequency of patients developing a sole brain relapse during their whole clinical course was 4% for the PCI group and 17% for the no PCI group, however, the difference was not statistically significant. Patient survival was better for the PCI group (median survival time of 21 months, and 5-year survival rate of 22%) as compared with the no PCI group (median survival time of 15 months, and 5-year survival rate of 13%), showing a marginal significance (P = 0.097). Late neurologic toxicity was infrequent; only one developed a mild deterioration among seven long-term disease-free survivors in the PCI group. These results appear to warrant further clinical trials to clarify the utility of PCI in patients with SCLC achieving a complete response.

Adult↗

PubMed1993

Eisenin (L-pyroGlu-L-Gln-L-Ala), a new biological response modifier.

Eisenin (L-pyroGlu-L-Gln-L-Ala), a tripeptide extracted from a brown marine alga (Eisenia bicyclis Setchell) showed the immunological activity to augment natural cytotoxicity of peripheral blood lymphocytes (PBLs) in humans. This activity could be seen when it was added directly to 51Cr release assay, and also when PBLs alone were incubated with this compound for 0.5-1 h before addition to the 51Cr release assay. The resulting augmented cytotoxicity can be attributed to natural killer cells because treatment of eisenin-stimulated PBLs with anti-Leu 11b monoclonal antibody (mAb) plus complement completely abolished the augmented cytotoxicity, and, moreover, deletion of Leu 19-positive cells with anti-Leu 19 mAb (mouse IgG1) and anti-mouse IgG-coated magnetic beads showed the same effect. Eisenin could not augment natural cytotoxicity of Sephadex G-10 column-eluted cells. Eisenin rendered K-562 target cells resistant to lysis by PBLs stimulated by eisenin. Both amino acids, L-pyroglutamic acid and L-alanine, as well as a mixture of the three component amino acids of eisenin could augment the natural cytotoxicity. Therefore, it is considered that the structure responsible for the augmentation of natural cytotoxicity by eisenin may be that of the amino acids.

Alanine↗