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Biomedical subjects

N Morioka

Publications and source records attributed to N Morioka.

At least 19 recordsLinked to original sources

Nocturnal changes in pineal melatonin synthesis during puberty: relation to estrogen and progesterone levels in female rats.

Our objective was to evaluate the changes in melatonin synthesis during the peripubertal period in the female rat and to determine the effects of ovarian steroid hormones on melatonin synthesis. Pineal levels of tryptophan, 5-hydroxytryptamine (5-HT), melatonin and norepinephrine were determined in female Sprague Dawley rats (between 2 and 12 weeks of age) in the mid-dark during the daily light/dark cycle. Melatonin levels increased with age, parallel to pineal growth, until 6 weeks of age, when the vaginal opening was found in 66.7% of rats, and significantly decreased until 8 weeks of age, when the vaginal opening was found in all rats. Norepinephrine began to increase earlier and reached a mature level at 4 weeks of age. Treatments with bilateral ovariectomy at 4, 6, and 8 weeks of age resulted in significant increases in melatonin and 5-HT levels, and significant decrease in tryptophan level at 2 weeks after ovariectomy. Treatments with ovariectomy at 6 weeks of age produced a consistent increase in 5-HT level and a consistent decrease in tryptophan level until 6 weeks after ovariectomy. However, melatonin levels increased until 2 weeks after ovariectomy, then decreased and reached a control level at 6 weeks after ovariectomy. Subcutaneous implantation of estradiol-17 beta capsule and daily subcutaneous injection of estradiol benzoate (E2B) (1.0 microgram, 20 micrograms) for two weeks in the rats ovariectomized at 4, 6, and 8 weeks of age resulted in significant decreases in melatonin and 5-HT levels and a significant increase in tryptophan level at 2 weeks after ovariectomy. A smaller dose of E2B (0.1 microgram) produced the same effects in the rats ovariectomized at 4, but not at 6 and 8 weeks of age. Administration of progesterone (200 micrograms/day) for 2 weeks did not produce any significant changes in melatonin, 5-HT, and tryptophan levels. Norepinephrine levels were not changed by any of the above treatments. These results suggest that estrogen, but not progesterone, can modulate nocturnal pineal melatonin synthesis in peripubertal female rats, and that the decline in the melatonin synthetic activity during the pubertal period might be related to the increasing levels of endogenous estrogen, which is secreted from the maturing ovary. The sites of action of the inhibitory effect of estrogen on the pineal melatonin synthesis may be multiple.

Age Factors

Cytotoxic T cell recognition of a human melanoma derived peptide with a carboxyl-terminal alanine-proline sequence.

Recently, we defined the antigenic epitope recognized by the human monoclonal antibody L94 to be a protein with a C-terminal sequence of alanine-proline (AP). An antigenic peptide no. 707 (RVAALARDAP), which was identified by the use of cDNA libraries of an antigen positive melanoma cell line M14, was evaluated for cellular immune responses in melanoma patients. PBMC from 16 of 19 melanoma patients were shown to lyse autologous B lymphoblastoid cell lines (BCL) pulsed with synthetic peptide no. 707 (hereafter no. 707). This specific cytotoxicity to the peptide significantly increased in 84% of melanoma patients after in vivo immunization with a melanoma cell vaccine (MCV). In contrast, peptide specific cytotoxicity was observed in only one of 19 normal volunteer donors. In vitro restimulation of MCV treated patients' PBMC with no. 707 augmented cytotoxicity against autologous no. 707-pulsed BCL. This cytotoxicity was specific to the C-terminal sequence AP, since the removal of C-terminal AP completely abolished the specific lysis. no. 707 restimulation of PBMC enhanced cytotoxicity against autologous melanomas. Autologous melanoma and peptide-pulsed BCL targets were lysed by CD8+CTL in a HLA class I-restricted manner. The strong cytotoxicity was obtained from patients of HLA A24. CTL lysis of autologous no. 707-pulsed BCL was partially blocked by unlabeled autologous melanomas in a cold target inhibition test. This suggested that the epitope identical or cross-reactive to no. 707 may be presented on the melanoma cell surface by HLA class I antigens. Our findings suggest that peptide no. 707 presented on human melanoma cells is recognized by CTL and that C-terminal AP plays a critical role in both antibody and T cell recognition.

Alanine

[Physical properties of Strecker stents].

Strecker stent is a balloon-expandable metallic stent that is made of knitted tantalum wire mesh in order to Maintain flexibility. Therefore, the prosthesis is well suited to irregular and tortuous tube organs. We performed several physical experiments using 8 mm and 6 mm diameter stents made of 0.1 mm diameter wire filament. The bearing power of the 8 mm diameter stent against the circumferential compression pressure was divided into two groups, that is, 77-100% and under 66% of expansile rate. The capacity bearing the circumferential compression pressure of the latter group was greater than that of the former. Further, the bearing power of the 6 mm diameter stent was greater than that of the 56% expansile rate of the 8 mm diameter stent. The smaller the expansile rate of the stent, the smaller the minimum radius of curvature within the limits of the stent's plastic. To evaluate the suitability of the stent in clinical use, we made two projections on the inner surface of rubber tubes, and the stents were placed into the rubber tubes at different expansile rates. We evaluated the degree of contact of the stents against the rubber wall by taking soft X-ray photographs. The stents showed good suitability under the condition of incomplete expansion. For the above reasons, we concluded that, from the view-point of bearing power, the stent should be placed in the full expansile state. From the viewpoint of contact against the vessel wall, the stent should be placed in the incomplete expansile state.

Physical Phenomena

[Percutaneous placement of intraluminal stent-graft for aortic dissection: experimental study].

Highly porous fabric vascular grafts fabricated of ultrafine polyester fibers (UFPF-graft; porosity, 7,000 ml, 9,000 ml, 11,000 ml at 120 mmHg) were attached between two Gianturco stents connected with two stainless steel struts. UFPF-grafts with two Gianturco stents were placed into the aortas of six adult mongrel dogs without firm contact with the luminal surface. From two days to four months after placement, all the UFPF-grafts were completely sealed with fresh thrombus or neointima. Within two months, complete endothelialization was observed on both surfaces of the neointima. In three dogs, aortic dissections were created experimentally. Then an UFPF-graft (porosity, 9,000 ml) with two Gianturco stents was placed at the site of entry of the dissection, followed by additional Gianturco stents to expand the UFPF-graft. X-ray angiography showed that the entries were closed immediately after placement, and false lumens disappeared within one hour after placement. These results indicated that the method has the possibility of treating aortic dissection with complete sealing of the fabric by the neointima.

Aortic Dissection

A decapeptide (Gln-Asp-Leu-Thr-Met-Lys-Tyr-Gln-Ile-Phe) from human melanoma is recognized by CTL in melanoma patients.

The decapeptide 810 (QDLTMKYQIF) contains the antigenic epitope (KYQI) recognized by human mAb L92. This sequence is found in a 43-kDa protein associated with human melanoma M14. We examined the expression of 810 in human cells and its involvement in the cellular immune responses of melanoma patients. Nineteen stage III melanoma patients and 19 normal donors were studied for their responses to 810. All patients were immunized in vivo with an allogeneic melanoma cell vaccine. PBMC cytotoxicity was tested on autologous EBV-transformed B lymphoblastoid cell lines (BCL) pulsed with 810 and autologous melanomas. Proliferative responses of PBMC to 810 were evaluated by using [3H]Tdr incorporation assays. Western blotting revealed that the 43-kDa protein was not specific to melanoma but was common to various cells. However, the percentage of cytotoxicity of PBMC against autologous 810-pulsed BCL was significantly greater in melanoma patients than in normal controls (p < 0.005). Cytotoxicity was increased after melanoma cell vaccine immunization in 15 patients (78%). Proliferative responses to 810 were observed only in melanoma patients and were enhanced in 12 patients (63%) after vaccination. Restimulation of PBMC from vaccinated patients with 810 increased cytotoxicity against both autologous 810-pulsed BCL and melanomas. These targets were lysed by CD8+ T lymphocytes in an HLA class I-restricted manner. HLA-A2 and -A11 seemed to serve as the 810-presenting molecule. Our findings indicate that 810 may function as an epitope for CTL on human melanoma and can be used as a vaccine.

Amino Acid Sequence

[Percutaneous radiofrequency coagulation therapy for liver tumor: experimental study].

We invented a newly devised local thermal therapy using radiofrequency energy for treating liver tumors. This method was investigated for evaluating its safety and effectiveness. In vitro study, the maximum size of coagulated albumen was 5.5 to 6.2mm in diameter, and 9.8 to 11.3mm in length. In vivo study using rabbit's liver, the range of coagulated tissue by radiofrequency energy was localized around the tip of the needle. Percutaneous radiofrequency coagulation therapy will be the effective therapy for liver tumor regardless of tumor vascularity.

Animals

Intraarterial occlusion by radiofrequency.

Arterial occlusion using radiofrequency energy was performed. The length of the noninsulated part of the guidewire was 10 mm and the duration of radiofrequency supply was 20 s. Animal experiments were carried out in 17 canine arteries; 4 out of 6 arteries less than 2.3 mm in diameter were completely occluded during the 20 s radiofrequency supply. A clinical application was also successfully performed without any complications. Arterial occlusion with radiofrequency can be applied to vessels less than about 2 mm in diameter.

Animals

[Experimental study with radiofrequency-induced thermal arterial occlusion].

A preliminary experiment on arterial occlusion using radiofrequency energy was performed. A surgitron FFPF was used as a radiofrequency power generator, and a Tracker 18 catheter was used as a probe insulator. A 10 mm length of the guide wire protruding from the tip of catheter was used as the radiofrequency probe. To examine the safety of this procedure within the vessels, the following experiments were performed. A 2.5 mm diameter dimple at the surface of a sausage was filled with human blood. We inserted various lengths of non-insulated guide wire into the dimple and supplied radiofrequency power. We then measured the time until air bubbles appeared in the dimple. With a 10 mm length of non-insulated guide wire, this took over 30 sec. Animal experiments were carried out in 17 canine arteries. The diameter of these arteries ranged from 1.3 to 3.7 mm. Before the procedure, angiograms were taken using a 5 F catheter from the right femoral artery. A tracker 18 catheter and guide wire were inserted to the target position co-axially. The guide wire was attached to the radiofrequency generator. The tip of the guide wire functioned as the convergence point of an electrically conducting induced current. Treatment was performed by supplying radiofrequency power of various durations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[A study of transsplenic CO2 gas enhanced portal angioechography].

Transsplenic CO2 gas enhanced portal angioechography was examined. The spleen of three dogs was punctured by 23 gauge needle with two side holes. From 5 ml to 20 ml of CO2 gas was injected into the splenic vein via the splenic parenchyma, and elevation of echo level of the liver was observed. Hematoma was not seen at the site of puncture. Good image was obtained in the case of 5 ml CO2 injection. In one dog with pseudotumor in the liver, the hyperechoic tumor changed into negative enhanced nodule after CO2 gas enhancement. Transsplenic CO2 gas enhanced portal angioechography is thought to be useful to evaluate hepatic tumors.

Animals

A protein fraction from aged garlic extract enhances cytotoxicity and proliferation of human lymphocytes mediated by interleukin-2 and concanavalin A.

Fraction 4 (F4), a protein fraction isolated from aged garlic extract, enhanced cytotoxicity of human peripheral blood lymphocytes (PBL) against both natural-killer (NK)-sensitive K562 and NK-resistant M14 cell lines. Although F4 treatment alone increased cytotoxicity, the effect was more remarkable when F4 was administered together with suboptimal doses of interleukin-2 (IL-2); combination treatment of 5 micrograms/ml F4 plus 10 U/ml IL-2 for 72 h generated lymphokine-activated killer activity equivalent to that produced by 100 U/ml IL-2 alone against M14. F4 enhanced IL-2-induced proliferation and IL-2 receptor (Tac) expression of PBL without significant increase of IL-2 production. The enhancement of cytotoxicity both by F4 alone and by F4 plus IL-2 was abolished by anti-IL-2 antibody. F4 also enhanced concanavalin-A(ConA)-induced proliferation of PBL. Radiolabeled-ConA binding assays revealed that F4 treatment greatly augmented the affinity and slightly increased the number of ConA binding sites in PBL. F4 also enhanced ConA-induced IL-2 receptor (Tac) expression and IL-2 production of PBL. Anti- IL-2 antibody inhibited the effect of F4 on ConA-induced proliferation. These data suggest that IL-2 is involved in augmentative effects of F4. Our results indicate that F4 is a very efficient immunopotentiator and may be used for immunotherapy.

Concanavalin A

Angiotensin-converting enzyme inhibitors have no effect on ovulation and ovarian steroidogenesis in the perfused rat ovary.

The null hypothesis of this study was that the angiotensin-converting enzyme inhibitors, captopril and teprotide, would not reduce the number of ovulations in vivo and in vitro in the rat. Captopril (in three regimens) was administered continuously beginning prior to pregnant mare's serum gonadotropin and hCG to trigger ovulation. The number of in vivo ovulations were counted. Ovaries similarly primed with pregnant mare's serum gonadotropin were dissected and perfused in media with hCG and captopril (two regimens) or teprotide (one regimen). The number of in vitro ovulations and steroid production in the perfusions were evaluated. The results were evaluated by the Student's t test. Power calculations gave only a 20% chance of missing a 16% difference in ovulations or steroidogenesis. There was no inhibition of ovulation or change in steroid production in angiotensin-converting enzyme treated rats in vivo or in vitro. While angiotensin II has been shown to be an important mediator in the mechanism of ovulation, angiotensin-converting enzyme inhibition via captopril or teprotide does not result in angiotensin II antagonistic effects. Hypothetical mechanisms to explain this paradox are presented.

Angiotensin-Converting Enzyme Inhibitors

Role of the free radical-scavenger system in aromatase activity of the human ovary.

The present study was undertaken to clarify the physiological role of the free radical-scavenger system in the control of estrogen production in the human ovary with age. Both superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the homogenate of the ovary significantly decreased from the premenopausal period to the menopausal period. The lipid peroxide content, however, showed a small and gradual decrease from the premenopausal to the postmenopausal period. In the premenopausal women, aromatase (Ar) activity in the microsomal fraction of the ovary showed a sharp decline and a significant negative correlation with age. Significant positive correlations were found between SOD and Ar activity, and between GSH-Px and Ar activity. Treatments of homogenate of the ovary with 10, 50 and 100 microM of H2O2 resulted in a decrease in Ar activity in a dose-dependent manner. Moreover, treatment with 10 and 50 microM of H2O2 produced a more significant decrease in the Ar activity in the premenopausal women than that in the postmenopausal women. Treatments with 0.01, 0.1, 1.0 and 10.0 U of GSH-Px before administration of 50 microM of H2O2, on the other hand, induced a recovery of the Ar activity in a dose-dependent manner. The present study showed the inhibitory effect of peroxide on Ar activity, which was attenuated by GSH-Px. These results seem to suggest that these age-related, relatively free radical predominant environments in the human ovary may have an important role in the decrease of estrogen production through the effects on the Ar activity.

Adult

Treatment of tuberculous bronchial stenosis with expandable metallic stents.

Gianturco expandable metallic stents were placed in 5 patients with dyspnea on exercise due to tuberculous bronchial stenosis. The stents were placed after dilatation with a 10-mm diameter high pressure balloon catheter. In all 5 patients, obstructive changes disappeared following the procedure, and dyspnea on exercise improved markedly. No complications related to the procedure were encountered. At follow-up during a period of up to 38 months, 2 patients showed bronchial restenosis at 11 and 17 months, respectively, after stent placement. Restenosis by granulomatous tissue was successfully treated by laser ablation. One patient showed slight one-day hemoptysis 26 months after stent placement.

Adult

Pelgeroid-like anomalous cells in the diagnosis of neutrophilic dermatosis associated with myelodysplastic syndrome.

Neutrophilic dermatoses (ND), with or without accompanying myelodysplastic syndrome (MDS), were examined in terms of nuclear abnormality like pelgeroid anomaly of infiltrating cells into skin lesions. Six ND accompanying MDS showed 1.0 to 13.5% of such anomalous cells among infiltrating cells. In contrast, ND without accompanying myeloproliferative disorders rarely had such anomalous cells. Our findings suggest that pelgeroid-like anomalous cells infiltrating into ND are probably a good marker of underlying MDS.

Aged

[Repeated arterial infusion chemotherapy for inoperable hepatocellular carcinoma using implantable drug delivery system].

We performed a clinical evaluation of repeated arterial infusion chemotherapy using an implantable drug delivery system for 41 patients with inoperable hepatocellular carcinoma (HCC). About half of our patients could not undergo transcatheter arterial embolization (TAE) because of extreme tumor extension and/or accompanying advanced cirrhosis. In most patients we implanted a 5 Fr. catheter non-surgically and connected it to an implanted injection port through a subcutaneous tunnel. The treatment schedule was weekly or biweekly intrahepatic one-shot administration of mitomycin C, adriamycin, 5-fluorouracil and epirubicin. The response rate (CR + PR) was 24.4%. The median survival period was 401.1 days. The 6 month, 1-year and 2-year survival rates were 73%, 48% and 24%, respectively. There were no severe side effects nor complications. The implantable drug delivery system will contribute not only to improved therapeutic efficacy for inoperable HCC but also improve the quality of life for patients.

Adult

[Self-expandable metallic stent for use in arterial occlusive lesions].

Gianturco expandable metallic stents were successfully placed in 4 patients with arterial occlusive disease: aortic obstruction or stenosis due to aortitis (n = 2), dissecting aneurysm (n = 1) and arteriosclerotic obstruction of the iliac artery (n = 1). The length of lesion was from 2 to 15 cm. In one case of aortitis (case 1), eleven stents (5 and 6 stents in tandem connected by wire struts) were inserted through a 12 F Teflon sheath. In another aortitis case (case 2) 4 stents in tandem were inserted through a 10 F sheath. In the two cases the sheaths were introduced by femoral arteriotomy. In case 3 and 4 two or four stents in tandem were placed through a 8 F long sheath which was introduced via the femoral artery by Seldinger method. Symptoms disappeared after placement of stents in all four cases. Our results showed the usefulness of expandable metallic stents in the treatment of arterial occlusive diseases.

Adult