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Biomedical subjects

T Araki

Publications and source records attributed to T Araki.

At least 271 records · Page 15Linked to original sources

Effect of rolipram on age-related changes in cyclic AMP-selective phosphodiesterase in the rat brain: an autoradiographic study.

Rolipram is a clinically effective antidepressant with cyclic AMP-selective phosphodiesterase (cyclic-AMP PDE) inhibiting action. In this study, we investigated the effect of chronic treatment with rolipram on age-related changes in cyclic-AMP PDE in the rat brain visualized and quantitated by in vitro [3H]rolipram autoradiography. Rolipram (0.01 mg/kg and 0.1 mg/kg) or its vehicle was administered orally to 15-week-old (young) and 80-week-old (aged) Wistar rats once a day for 4 weeks. In control young rats, high [3H]rolipram binding was seen in the hippocampus, the cerebellum and the neocortex. In control aged rats, the [3H]rolipram binding decreased strikingly in almost all brain regions. Chronic treatment of the young rats with rolipram reduced the [3H]rolipram binding in a dose-dependent manner. By contrast, the same treatment of the aged rats induced no or minimal changes. These results suggest that 1) cyclic-AMP PDE in the rat brain is subject to age-associated decline, and 2) the response to rolipram treatment is different between young and aged rats.

3',5'-Cyclic-AMP Phosphodiesterases↗

Age-related effects of rolipram on [3H]quinuclidinyl benzilate and [3H]phorbol 12,13-dibutyrate binding in the rat brain.

Cholinergic neurotransmission and protein kinase C (PKC) in the brain play important roles in the processes of cognitive function. In this study, we examined the effect of chronic treatment with rolipram, a 3',5'-cyclic adenosine monophosphate (cyclic AMP)-selective phosphodiesterase inhibitor, on age-related changes in [3H]quinuclidinyl benzilate (QNB) and [3H]phorbol 12,13-dibutyrate (PDBu) binding, which labeled brain muscarinic cholinergic receptors and PKC, respectively. Rolipram was administered per os to young (15 weeks old) and old (80 weeks old) Wistar rats at dosage of 0.01 mg/kg and 0.1 mg/kg once a day over 4 weeks. Then, quantitative in vitro autoradiography was performed. Control old rats showed elevations in [3H]PDBu binding in the hippocampus and the cerebellum compared to young rats, but [3H]QNB binding was largely unchanged. Chronic treatment of the old rats with the higher dose of rolipram led to reductions in [3H]QNB and [3H]PDBu binding in many brain regions. However, the same treatment of the young rats induced no or minimal effect. Thus, the response of the brain to rolipram was different between young and old rats. These results suggest that the cyclic AMP-selective phosphodiesterase system in the brain is modified during aging, modulating subsequently cholinergic neurotransmission and PKC activity exclusively in old rat brains.

Aging↗

Mutual relation between the cell-cycle progression and prespore differentiation in Dictyostelium development.

In Dictyostelium discoideum Ax-2, the cell-cycle progression from the early aggregate to mound stage has been proposed to have some connection with prespore differentiation. Hereupon, we examined the role of cell-cycle progression during the development on cell differentiation, using two kinds of cell-cycle inhibitors. Nocodazole, an inhibitor of microtubule formation, was found to inhibit greatly cell division around the mound stage as well as during the vegetative growth phase, when applied to exponentially growing Ax-2 cells. Essentially the same inhibition was attained by treatment of starved Ax-2 cells with calyculin A, an inhibitor of serine/threonine protein phosphatases. It is noteworthy that the nocodazole- or calyculin A-treated cells exhibit abnormal morphogenesis to form a stick-like multicellular structure on non-nutrient agar, and also that prespore differentiation as exemplified by the prespore-specific Dp87 gene expression and prespore specific vacuole (PSV) formation was greatly suppressed. In contrast, the differentiation of prestalk (pstA) cells was scarcely affected by the drug treatments. Taken together these results seem to indicate that the cell-cycle progression around the mound stage is important for prespore differentiation.

Animals↗

Diffusion-weighted MR imaging with a single-shot echoplanar sequence: detection and characterization of focal hepatic lesions.

OBJECTIVE: The purpose of this study was to determine the usefulness of diffusion-weighted MR imaging with single-shot echoplanar imaging in characterizing focal hepatic lesions by apparent diffusion coefficient (ADC) and contrast-to-noise ratio (CNR) measurements. MATERIALS AND METHODS: Diffusion-weighted imaging on a 1.5-T MR unit was performed in 46 patients with 74 known focal hepatic lesions (11 hemangiomas, 15 metastases, and 48 hepatocellular carcinomas [HCCs]). Mean values for ADCs and CNRs of all lesions were calculated. Mean values for CNRs with diffusion-weighted imaging were also compared with those for breath-hold T2-weighted fast spin-echo images. RESULTS: The mean values for ADCs were different for each type of tumor (5.39 x 10(-3) mm2/sec +/- 1.23 in hemangiomas, 2.85 x 10(-3) mm2/sec +/- 0.59 in metastases, and 3.84 x 10(-3) mm2/sec +/- 0.92 in HCCs), and each of them was significantly greater than the mean values for ADCs of the normal liver (2.28 x 10(-3) mm2/sec +/- 1.23 in normal liver [p < .05] except metastasis versus normal liver [p < .1]). Also, the mean values for ADCs were based on differences of ADC values. Only four (6%) of 63 malignant tumors (three HCCs and one metastasis) could not be differentiated from hemangiomas. The mean value for CNRs with diffusion-weighted images (14.4 +/- 8.54 in HCC and 29.0 +/- 6.79 in metastasis) was significantly higher than the mean values for CNRs obtained with T2-weighted fast spin-echo images in both metastases and HCCs (p < .05), whereas no significant difference was seen for hemangiomas. CONCLUSION: Mean values for ADCs differed for the three types of the hepatic lesions and were higher than ADCs of the normal liver. We suggest that diffusion-weighted imaging may be useful for increased detection of HCCs and metastases and in distinguishing these entities from hemangiomas.

Carcinoma, Hepatocellular↗

Characterization of hepatic lesions by perfusion-weighted MR imaging with an echoplanar sequence.

OBJECTIVE: The purpose of this study was to examine the usefulness of perfusion-weighted MR imaging with a single-shot gradient echoplanar sequence in characterizing hepatic tumors. SUBJECTS AND METHODS: Perfusion-weighted imaging was performed in 61 patients with 91 confirmed hepatic tumors (14 hemangiomas, 19 metastases, and 58 hepatocellular carcinomas). The perfusion-weighted imaging was started at the time of administration of 0.1 mmol/kg of gadolinium, and images were continuously obtained every 2 sec for 88 sec. Time-intensity curves for all the tumors were created for quantitative analysis. Patterns of enhancement were also evaluated. RESULTS: Changes in signal intensity that occurred throughout examination differed in three types of tumor. Transient signal intensity decreases in the perfusion phase significantly differed in three types of tumors (46% in hepatocellular carcinoma, 48% in hemangioma, and 15% in metastasis, p < .05 for hepatocellular carcinoma versus metastasis and for hemangioma versus metastasis). Signal intensity recovered rapidly for hepatocellular carcinoma and metastasis, whereas recovery was slower for hemangioma. Final signal intensity recovery was 94% in hepatocellular carcinoma, 91% in metastasis, and 54% in hemangioma compared with their initial signal intensities. (p < .05 for hepatocellular carcinoma versus hemangioma and for hemangioma versus metastasis.) The enhancement patterns also differed in three types of tumor. CONCLUSION: Perfusion-weighted imaging with a gradient echoplanar sequence provides real-time mapping of many points along the enhancement profile curves because of its excellent temporal resolution. Therefore, it accurately characterizes hepatic tumors based on their different negative-enhancement patterns.

Adult↗

Technetium-99m-tetrofosmin, technetium-99m-MIBI and thallium-201 uptake in rat myocardial cells.

UNLABELLED: The mechanisms of uptake and intracellular distribution of 99mTc-tetrofosmin, 99mTc-MIBI and 201TI and the behaviors of 99mTc-tetrofosmin and 99mTc-MIBI in relation to Na+ were studied with primary cultures of myocardial cells. METHODS: Both the uptake and the washout of the tracers were sequentially measured. The cells were treated with ouabain, bumetanide, tetrodotoxin, dimethyl amiloride (DMA), nigericin and carbonyl cyanide m-chlorophenylhydrazone (CCCP) to observe the effects of the uptake and intracellular distribution of the traders. Cells equilibrated in buffers with or without Na+ were treated with monensin and DMA to evaluate the effect of Na+ on the accumulation of the tracers. RESULTS: Despite the similarities in uptake kinetics, there was a higher level of retention of 99mTc-tetrofosmin inside the cells. Ouabain, bumetanide and tetrodotoxin did not show any inhibitory effect on the uptake of 99mTc-tetrofosmin and 99mTc-MIBI, whereas they produced various degrees of inhibition of 201TI uptake. DMA produced approximately 35% inhibition of 99mTc-tetrofosmin uptake and 50% inhibition of 99mTc-MIBI uptake. Nigericin increased the uptake of 99mTc-MIBI by the cells. The addition of CCCP produced the release of 38% of the accumulated 99mTc-tetrofosmin and 52%-70% of the accumulated 99mTc-MIBI, indicating that these percentages of accumulation were related to mitochondrial uptake. Neither Na+-free buffer nor monensin had any significant effect on 99mTc-tetrofosmin accumulation, but they both caused increased accumulation of 99mTc-MIBI. CONCLUSION: The uptake of both 99mTc-tetrofosmin and 99mTc-MIBI through the cell membrane is partly related to the Na+/H+ antiporter system. Only part of the accumulated 99mTc-tetrofosmin inside the cells enters into mitochondria; most of the accumulated 99mc-MIBI is related to mitochondrial uptake. This uptake may be related to Na+.

Amiloride↗

Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCA1.

We analyzed the clinical features of 25 ovarian cancer patients who were associated with germ-line mutations of BRCA1 from four site-specific ovarian cancer families and seven breast-ovarian cancer families in Japan. The average age at diagnosis was 51.1 years (range, 38-77 years). Histological examination revealed 24 serous cyst adenocarcinomas in 25 patients. In 23 patients with clear clinical records, 3 patients had stage I disease, 17 had stage III disease, and 3 had stage IV disease. Thirteen patients with stage III disease who were treated with cisplatin-containing chemotherapy following tumor reduction surgery showed more favorable outcomes in both the survival rate and disease-free intervals, compared with age- and treatment course-matched controls (5-year survival rate, 0.786 versus 0.303; median disease-free interval, 91.43 versus 40.92 months; P < 0.05 for both, by logarithmic rank test). Our statistical model for the inheritance of susceptibility to ovarian cancer was derived from the analysis of 26 patients and 19 healthy carriers of 12 families. The expected lifetime risk of ovarian cancer is about 80% for women with mutations of BRCA1. These results suggest that the clinical outcome of ovarian cancer with germ-line mutations of BRCA1 appears to be more favorable than that with sporadic cases and that the disease penetrance among pedigrees with germ-line mutations of the BRCA1 gene is substantially high.

Adult↗

Velocity-coded color MR angiography.

We developed a method of velocity-coded color MR angiography using a color code from the data obtained from velocity-phase images of phase-contrast MR angiography in order to add flow direction information to MR angiograms. Phase-contrast MR angiography with reconstruction of velocity-phase images was performed in 30 patients. Two projection images from velocity-phase images of each phase-contrast MR angiogram were obtained and assigned color according to flow direction. We then superimposed the two color images onto the maximum intensity projection image of the MR angiogram. The velocity-coded color MR angiogram clearly showed flow direction from the data on the phase-contrast MR angiogram of the neck. Veins were readily distinguishable from arteries, and flow changes, such as a subclavian steal, were also identified.

Blood Flow Velocity↗

Optimization of parameters for isolation of protoplasts from Gracilaria verrucosa (Rhodophyta).

A systematic method was designed for the isolation of a large number of protoplasts from an agarophyte alga Gracilaria verrucosa using agarase from a marine bacterium Vibrio sp. PO-303 and commercial enzymes (Cellulase Onozuka RS and Macerozyme R-10). Pretreatment of the tissue with 5% papain at 22 degreesC for 30 min before digestion with polysaccharide-degrading enzymes increased the protoplast yield. Suitable pH and temperature for the polysaccharide-degrading enzyme reaction were 6.5 and 22 degreesC, respectively. Mannitol (0.7 M) was found to be an excellent osmotic stabilizer. When the tissue (1 g, fresh wt.) of G. verrucosa pretreated with 5% papain solution (20 mM MES buffer, pH 7.5, containing 0.7 M mannitol) was digested with an enzyme mixture consisting of 4 units of agarase, 4% Cellulase Onozuka, 2% Macerozyme, and 0.7 M mannitol in 20 mM MES buffer (pH 6.5) with gentle agitation for 150 min at 22 degreesC, 1.03 x 10(8) protoplasts were obtained.

Journal Article↗

[Pituitary enlargement in spontaneous intracranial hypotension on MRI].

PURPOSE: To examine whether the pituitary gland enlarges in patients with spontaneous intracranial hypotension (SIH). MATERIALS AND METHODS: All six patients were women ranging in age from 17 to 51 years. They developed severe headache that was completely relieved by lying flat, and MR imaging showed diffuse enhancement of the pachymeninx. They were clinically diagnosed with SIH. The height of the pituitary gland was measured on midsagittal MR image. RESULTS: Pituitary heights ranged from 8 to 11 mm. The measurements were greater than the size of the normal pituitary gland in women described age-matched in the previous report. In one case, follow-up MR images showed that the size of the pituitary gland was decreased from 11 to 5 mm in height. CONCLUSION: The pituitary gland was enlarged in all six patients with SIH on MR images. SIH may cause enlarged pituitary gland.

Adolescent↗

Comparisons of Nitric Oxide Synthases in Normal Human Placenta from 37 to 41 Weeks Gestation: Qualitative and Quantitative Analyses.

> Objective: The purpose of this study was to determine the type of nitric oxide synthase isoform and to measure the quantities of nitric oxide synthase mRNA in the human placenta. Methods: The isoforms of nitric oxide synthase were determined in ten placentas of normal pregnant women using information regarding calcium dependence and inhibition by arginine analogs and findings from Western blot analyses and reverse transcriptase-polymerase chain reaction. Results: The activity of nitric oxide synthase was largely calcium dependent, although a small element of calcium-independent activity was observed. A stronger inhibition was shown with Nomega-nitro-l-arginine than with Nomega-monomethyl-l-arginine. On Western blots endothelial nitric oxide synthase was detected as a band of 140 kilodaltons, without evidence of inducible nitric oxide synthase. Messenger RNA of endothelial nitric oxide synthase was readily detected by reverse transcriptase-polymerase chain reaction, but that of inducible nitric oxide synthase was barely detected. The quantity of mRNA of inducible nitric oxide synthase was about 100-fold less than that of endothelial nitric oxide synthase. Conclusions: These results point to the constitutive endothelial type as the predominant isoform of nitric oxide synthase in human placenta from 37 to 41 weeks gestation, although protein and mRNA of inducible nitric oxide synthase may exist.

Journal Article↗

[Use of the radial artery graft in coronary artery bypass grafting: harvesting technique and spasm prevention].

The use of radial artery (RA) in coronary artery bypass grafting (CABG) has been increasing recently as a revival. In this report, we describe several practical suggestions for improving patency rate of the graft. Between April of 1997 and February of 1998, 41 CABGs were performed using RA graft, totalling 56 anastomoses. The early patency rate of the graft has been 100% (graft: 38/38, anastomosis: 53/53). Harvesting technique: with the use of Harmonic Scalpel, it is possible to atraumatically harvest the vessel in a short time. Although longitudinal fasciotomy of the adventitia has been recently reported to be effective in releasing spasm, the nature of the vessel raise concern that the fasciotomy may even induce spasm. We hypothesize that leaving the adventitia intact, preserving vasa vasorum, rather than performing fasciotomy leads to improvement of long-term patency. Spasm prevention: we consider the body temperature to be the most important factor. Therefore, we utilize normothermic cardiopulmonary bypass (CPB). Another important factor is that the arterial CO2 is kept at a high level during CPB. For dilation of RA graft, milrinone is used instead of papaverine. For the intra- and postoperative management, intravenous continuous administration of diltiazem was changed to nicorandil. Technically, essential resolution for improvement of patency rate is either to allow for large proximal anastomosis, or to make sequential anastomosis with another coronary artery which has a good run off. For these purposes, the proximal anastomosis on the ascending aorta seems to have the advantage over placing it on ITA.

Adult↗

[Breath-hold MR cholangiopancreatography with 2D and 3D-FASE sequence at 0.5 tesla: evaluation based on measurements of signal intensity ratio and contrast-to-noise ratio].

Single-slice 2D-FASE (more than 2 cm) and 3D-FASE images proved to be reliable techniques by which to create high-resolution MRCP images at 0.5 T. In particular, 3D-FASE sequence can provided MIP and its thin source images with sufficient SIR and CNR of the images, which are useful to evaluate detailed structures. Using 3D-FASE sequence, even the non-dilated pancreatobiliary system can frequently be demonstrated because each source image retains satisfactory SIR and CNR of the images due to 3D acquisition and is not affected by motion artifacts of any kind. The most important problem for 3D-FASE sequence is that view-to view amplitude modulation errors may persist, though gradient moment errors can be reduced because of no actual motion during acquisition, resulting in degraded the MIP images due to the different positions of the source images in a few patients with inconstant respiration.

Biliary Tract↗