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Biomedical subjects

I Adachi

Publications and source records attributed to I Adachi.

At least 145 records · Page 8Linked to original sources
PubMed1995

Staurosporine potentiates cAMP-mediated promoter activity of the vasoactive intestinal polypeptide gene in rat pheochromocytoma PC12 cells.

The potent protein kinase inhibitor staurosporine enhances cAMP-mediated responses in human neuroblastoma cells as represented by neurite extension and induction of tyrosine hydroxylase. To explore how staurosporine regulates cAMP signaling pathway, we examined transcriptional activity of the human vasoactive intestinal polypeptide (VIP) gene promoter carrying a cAMP-responsive element. In PC12 cells stably transfected with a reporter plasmid, staurosporine alone had little effect; however, in combination with forskolin or dibutyryl cAMP, staurosporine dose-dependently (1-50 nM) enhanced cAMP-mediated transcription from the VIP gene promoter, which was comparable to that maximally induced by cAMP plus 12-O-tetradecanoylphorbol-13-acetate. This is the first report of potentiation of cAMP-mediated promoter activity by staurosporine in neuroendocrine cells.

Adrenal Gland Neoplasms↗
PubMed1995

Preparation and characterization of dextran magnetite-incorporated thermosensitive liposomes: an on-line flow system for quantifying magnetic responsiveness.

PURPOSE: Dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs), were prepared and characterized in order to investigate their possibility for magnetic drug targeting. METHODS: TMs containing calcein were prepared at various DM concentrations by reverse-phase evaporation of dipalmitoylphosphatidylcholine (DPPC). They were evaluated for their physicochemical properties including size, DM capture, magnetite distribution within liposomes, and temperature-dependent calcein release. Moreover, a novel on-line flow apparatus with a sample injector, a coil of tubing placed in an electromagnet, and a fluorescence detector was developed for quantifying the magnetic responsiveness of TMs. This device allowed us a real-time measurement of percentage holding of TMs by magnetic field. RESULTS: Due to water-soluble property of DM, higher contents of magnetite up to 490 mg per mmol DPPC were successfully incorporated into the liposomes with DM than with conventional magnetite (Fe3O4). Thermosensitivity and lipid integrity of TMs were not influenced by inclusion of DM. Using the on-line flow system, percentage holding of TMs by magnetic field was shown to vary with several factors; it increases as the magnetic field strength increases, the fluid flow rate decreases, the magnetite content increases, and the liposome concentration increases. Typically, at 490 mg incorporated magnetite per mmol DPPC, 0.5 ml/min-fluid flow rate, and high magnetic field strength (> or = 10 kiloGauss), approximately 100% of TMs were found to be held. CONCLUSIONS: The TMs were suggested to be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Tc-99m sestamibi uptake by malignant lymphoma and slow washout.

Tc-99m sestamibi has been used to detect primary brain tumors, lung tumors, and breast cancers. The authors report a patient who had superior vena cava (SVC) syndrome and underwent Tc-99m sestamibi and Tl-201 SPECT to differentiate the tumor from thrombus in the mediastinum because of an abnormal mass lesion on a contrast enhanced CT scan. An abnormal area of increased Tc-99m sestamibi uptake in the supra azygos area was demonstrated on early and delayed SPECT imaging. The washout of tumor uptake was slow. The removed tumor was confirmed to be malignant lymphoma.

Aged↗
PubMed1995

Blueberry juice: preliminary evaluation as an oral contrast agent in gastrointestinal MR imaging.

PURPOSE: To evaluate the use of blueberry juice as an oral contrast agent in magnetic resonance (MR) imaging. MATERIALS AND METHODS: MR imaging of phantoms of blueberry juice and of manganese chloride solutions with different manganese concentrations were conducted. Patient trials were conducted to evaluate manganese blood levels and signal intensity changes on MR images of the abdomen. T1- and T2-weighted conventional spin-echo MR imaging was performed at various field strengths. Six radiologists graded image contrast; signal intensities were calculated. RESULTS: T1 and T2 relaxation curves for blueberry juice and manganese chloride showed similar signal intensity profiles as a function of manganese concentration. Blood concentrations of manganese were unchanged before and after an oral dose of blueberry juice that contained 18 mg of manganese. The results of patient studies indicated that the optimal oral dose of manganese in blueberry juice was 3-4 mg/dL. T1 and T2 shortening were apparent at field strengths of 0.2-1.5 T. CONCLUSION: At appropriate concentrations, blueberry juice has the potential to be an effective oral contrast agent for MR imaging.

Adult↗
PubMed1995

Pharmacokinetic and pharmacodynamic studies of a thromboxane synthetase inhibitor, ozagrel, in rabbits.

The pharmacokinetic and pharmacodynamic (PK/PD) characteristics of ozagrel, a new potent and selective thromboxane synthetase inhibitor, were investigated in rabbits after its intravenous, oral, and rectal administration. Serum level of TXB2 (the stable metabolite of TXA2), a direct pharmacological marker, was measured after each dosing. A marked reduction of serum TXB2 within 30 min was shown after the three routes of administration, reflecting rapid onset of action. Due to rapid and complete absorption (i.e., Tmax; 20 min, bioavailability; 100%) and longer duration of pharmacological action after rectal dosing, the rectum offers a practical delivery route for ozagrel. An Emax model was employed to fit the pharmacological data, and IC50 and Emax for thromboxane synthetase inhibition were estimated to be 56.0 ng/ml and 94%, respectively. These pharmacodynamic parameters were incorporated into an integrated mathematical model to simulate the PK/PD profiles of ozagrel after i.v., oral, and rectal administration at lower (50 mg) and higher (200 mg) doses, and good agreement between the experimental and calculated values was achieved. The present PK/PD model may be useful for optimizing the therapeutic regimens of ozagrel.

Administration, Oral↗
PubMed1995

Regional differences of CGRP-immunoreactive nerve fibers in nasal epithelium of the rat.

The regional distribution of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the epithelium throughout the nasal cavity was determined using semiserial cryostat sections and whole mount preparations. Both respiratory and olfactory epithelia displayed, in their basal portion, an extensive nerve plexus projecting beaded nerve fibers toward the luminal surface. However, the density of the intraepithelial CGRP nerve fibers conspicuously varied according to regions. They were abundant on the septal mucosa, the ventromedial side of the nasoturbinates and the dorsal surface of the maxilloturbinates, while less numerous on the lateral side of the naso- and maxilloturbinates and on the lateral nasal wall. Another difference in the regional distribution of nerves was recognized between the anterior and posterior portions of the respiratory area: the anterior portion received a denser supply of intraepithelial CGRP fibers than the posterior portion. Characteristically, the transepithelial CGRP-immunoreactive nerve fibers were densest on the anteroventral aspect of the nasoturbinates and on the anterodorsal surface of the maxilloturbinates. Some of them appeared to penetrate through the epithelium to come into contact with the lumen of the nasal cavity. These results suggest that the CGRP fibers in the epithelium display a region-specific distribution, apparently disposed more densely over the areas which are more directly exposed to inhaled air, possibly that containing irritants and toxicants.

Animals↗
PubMed1995

Nitric oxide synthase in rat nasal mucosa; immunohistochemical and histochemical localization.

The localization of nitric oxide synthase (NOS) and its cofactor, nicotinamide-adenine dinucleotide hydrogen phosphate (NADPH)-diaphorase, was examined in the nasal mucosa of the rat by immunohistochemical and histochemical methods. In addition to cryostat sections, whole mount preparations were used to examine the distribution of nerves. Both in the nasal mucosa and in associated ganglia, the distribution of NOS-immunoreactive nervous structures essentially corresponded to that of NADPH-diaphorase-positive ones. The NOS-immunopositive nerve fibers in the respiratory area of the nasal mucosa were distributed around blood vessels and in submucosal glands. Part of the respiratory area was supplied with intraepithelial arborizations of the immunopositive fibers. The epithelial cells in the respiratory area were NADPH-diaphorase positive but NOS immunoreactivity negative. In the olfactory area, the NADPH-diaphorase- and NOS-positive nerve fibers were restricted to blood vessels located deep in the submucosa. Throughout the nasal mucosa, arterial endothelium was NADPH-diaphorase positive but NOS immunoreactivity negative. Both NOS immunoreactivity and NADPH-diaphorase activity were found in major populations of neuronal somata in the sphenopalatine ganglion. The present study provides the direct evidence supporting the notion that nitric oxide is richly produced in autonomic nerves of the nasal mucosa derived from the sphenopalatine ganglion.

Animals↗
PubMed1995

Low-dose granulocyte colony-stimulating factor enables the efficient collection of peripheral blood stem cells after disease-oriented, conventional-dose chemotherapy for breast cancer, malignant lymphoma and germ cell tumor.

Peripheral blood stem cells (PBSCs) were collected from 29 adult patients (median age 42 years, range 14-59 years) with breast cancer, germ cell tumor and malignant lymphoma after disease-oriented, conventional-dose chemotherapy combined with daily subcutaneous injections of low-dose (50 micrograms/m2 or 2 micrograms/kg) granulocyte colony-stimulating factor (G-CSF). The median number of colony-forming units-granulocyte macrophage (CFU-GM) collected in an apheresis was 2.37 (range 0-60.6) x 10(4)/kg body weight. Taking into consideration the minimum number of CFU-GM for hematopoietic reconstitution (at least 1 x 10(5) CFU-GM/kg), it was suggested that sufficient PBSCs could be collected by a few leukaphereses, although the cell yields of PBSCs tended to differ among the chemotherapeutic regimens. Twelve patients subsequently received high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT), including four receiving PBSCT alone and eight both PBSCT and autologous bone marrow transplantation (BMT). When compared with the 20 patients who received high-dose chemotherapy followed by autologous BMT alone, the median day of recovery of a neutrophil count > 0.5 x 10(9)/l and a platelet count > 20 x 10(9)/l was significantly shortened in those who received PBSCT (9 vs 12 days; P < 0.01 and 14 vs 30.5 days; P < 0.001), resulting in a lower platelet transfusion requirement (4.5 vs 9; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[In vitro uptake and release of 201Tl and 99mTc-MIBI in HeLa cell].

201Tl is useful in the diagnosis of tumor malignancy determined by the grade of washout rate to the normal tissue especially in lung tumors and thyroid tumors. 99mTc-MIBI, a tracer of myocardial blood flow is also a tumor tracer. We determined whether the growth of the tumor cell is related to the uptake and release of the these tracers in cultured cells (HeLa cell). Cultured HeLa cells were incubated for 1 hr with 10 kBq of either tracer for the kinetic study of cellular uptake and additionally incubated for 90 min with cold medium for the kinetic study of cellular release. These cells cultured with various concentrations of actinomycin D (ACD) were used to examine the correlation between cellular growth and kinetics of these tracers. The uptake in the cell reached a plateau at about 60 min and the uptake at 60 min correlated with the number of the cells and was identified for specific accumulation in the cell. The uptake of 201Tl and 99mTc-MIBI at 60 min was 5.17% and 1.32% respectively of the given dose. The release for 90 min showed almost the same tendency for these tracers. The cellular release of 201Tl with the addition of ACD was increased in association with the concentration of ACD. On the other hand, the cellular release of 99mTc-MIBI showed no change by the addition of ACD. In conclusion, 201Tl showed slower washout in high growth cells than in low growth cells, and could act as an indicator of tumor malignancy by assessment of its washout by the tumor.

Culture Media↗
PubMed1995

Eyelid metastasis from breast cancer showing marked response to chemotherapy.

A patient with recurrent breast cancer, who was diagnosed with eyelid metastasis as a part of systemic metastases and in whom systemic chemotherapy was markedly effective, is reported. A 50-year-old woman underwent a radical mastectomy for stage II breast cancer in October, 1988. Histologically, the tumor was invasive lobular carcinoma. In October, 1993, the patient consulted our hospital complaining primarily of swelling of the left eyelid and restriction of movement in the left eye. Metastasis from breast cancer was diagnosed on eyelid biopsy. On further examination, metastases were detected in the liver, bone, orbit, peritoneum and pleura. Systemic combined chemotherapy consisting of cyclophosphamide, adriamycin and 5-fluorouracil was administered intravenously at intervals of three weeks. Complete responses were obtained in the eyelid and peritoneal metastases after three courses, and in the liver metastasis after five courses. Partial responses were also observed in the bone and pleural metastases. The incidence of eyelid metastasis from breast cancer is very low, one case only having been previously reported in Japan and 34 cases abroad. Most of these cases were treated locally by surgical resection or radiotherapy, but the mean survival period was only 14 months, ranging from two months to four years. Eyelid metastasis from breast cancer should be regarded as a manifestation of systemic spread of the tumor and, in principle, treated by systemic therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Clinical usefulness of dipyridamole loading 99mTc-tetrofosmin myocardial scintigraphy].

This study performed to establish the most suitable method in one-day protocol and to evaluate clinical usefulness of 99mTc-tetrofosmin myocardial scintigraphy after dipyridamole infusion. Image quality and liver overlapping of the myocardial SPECT were evaluated in 107 patients with old myocardial infarction (42 cases), angina pectoris (53 cases) and others (12 cases). Left ventricular wall motion and coronary artery stenosis were compared to myocardial uptake score in 55 patients who received cardiac catheterization. The suitable image quality was acquired in early SPECT images using 259 MBq of 99mTc-tetrofosmin. The overlapping between inferior wall and liver uptake was able to minimize over 45 minutes interval from injection of 99mTc-tetrofosmin to data acquisition. The segments of normal wall motion had no perfusion defect of the myocardial SPECT in all cases (100% (148/148)). The segments of abnormal wall motion had decreased myocardial uptake of the myocardial SPECT (77% (24/31)). The agreement between coronary artery stenosis and decreased myocardial uptake was 96% (24/25) in right coronary artery, 87% (26/30) in left anterior descending coronary artery and 83% (19/23) in left circumflex coronary artery. These data suggests that image quality of dipyridamole loading 99mTc-tetrofosmin myocardial scintigraphy. Myocardial perfusion in the 99mTc-tetrofosmin myocardial scintigraphy is good correlation to both left ventricular wall motion and coronary artery stenosis.

Adult↗
PubMed1994

Tumor-associated Fever in Recurrent Breast Cancer with Liver Metastases.

Of 67 patients with recurrent breast cancer accompanied by liver metastases admitted to our facility between January 1990 and August 1993, 8(12%) were found to have tumor-associated fever. We examined the characteristics of these patents. These patients had fever (over 38 degrees C) for more than one week. Their leukocyte counts did not exceed 10000/mm(3), and C-reactive protein (CRP) was below 5 mg/dl in 6 patients. ALL 8 patients had extensive liver metastases. Six patients had massive metastatic lesions, while the remaining 2 had diffuse metastases. Following systemic chemotherapy, 3 patients showed a reduction in tumor size and remission of fever; they remain alive at 14, 16 and 19 months after treatment. Of the remaining 5 patients who did not respond to systemic chemotherapy, 4 died within 6 months. The results of this study suggest that unexplained fever in patients with recurrent breast cancer is closely related to liver metastases.

Journal Article↗
PubMed1994

Bilateral Breast Cancer in a Patient with a Strong Family History of Cancer: Analysis of p53 Germ Line Mutations.

We report a case of bilateral breast carcinoma in a patient with a strong family history, including 4 cases of breast carcinoma, 1 case of prostate carcinoma (father), 1 case of hepatocellular carcinoma (mother), 2 cases of gastric carcinoma, 1 case of lung carcinoma, and 1 case of lingual carcinoma, in second degree relatives, together with analysis of germ line p53 mutations. The patient was a 51-year-old female who had undergone mastectomy 9 years previously for an invasive ductal carcinoma of the right breast. Lymph nodes were free of metastases and the tumor had negative estrogen receptor (ER) status. Bone and lung metastases developed 18 months after surgery, and had been well controlled with chemoendocrine therapy. She subsequently underwent a modified radical mastectomy for carcinoma in the contralateral breast. This was an invasive lobular carcinoma with negative lymph node metastasis, negative p53 immunoreaction, negative c-erbB-2 protein and positive ER status. In this breast-prostate carcinoma-type cancer family there was a high incidence of breast carcinoma; the father, who had prostate carcinoma, was possibly a carrier of a breast carcinoma susceptible gene. We have however detected to p53 germ line mutations in the lymphocytes DNA of the patient and her niece. The accumulation of cancers in this family line remains to be elucidated further using other genetic markers.

Journal Article↗
PubMed1994

[Contrast enhancement effect of new oral agent (blueberry juice) for upper abdominal MR imaging].

Manganese is known to affect relaxation times. Blueberry is naturally rich in manganese, and oral contrast effect by its squeezed juice (B. J) was expected. At some appropriate concentration of manganese within daily intake level, B. J worked as positive contrast agent on T1WIs and negative one on T2WIs simultaneously without any side effects. The negative effect on T2WIs could reduce ghost artifacts from motion of high intensity structures. B. J improved confirmation of gastroduodenal tract regardless of field strength and could be adapted for fast SE. We introduced a preliminary examination of B. J as an oral contrast agent for upper abdominal MRI.

Abdomen↗
PubMed1994

[MR imaging findings in patients with epilepsy].

We retrospectively examined the MR imaging (MRI) findings in 144 patients with epilepsy (31 with temporal lobe epilepsy and 113 with other epilepsies). 110 cases (76.4%) showed abnormal findings such as spotty lesions in white matter, hippocampal atrophy and/or signal change, ventricular dilatation and/or deformity, developmental lesions, brain tumors and so on. Hippocampal atrophy and/or signal change was shown in 74.1% of temporal lobe epilepsy, a remarkably high percentage (P < 0.01) compared with the other types of epilepsies (18.1%). This finding means that hippocampal lesions may play a large part in the cause of temporal lobe epilepsy. Investigation of the relationship between clinical term and abnormal findings revealed that the longer the clinical term, the larger the number of hippocampal lesions, regardless of whether it is temporal lobe epilepsy or not. Thus hippocampal lesions may occur as a result of hypoxia accompanied with seizure. Therefore we recommend horizontal and/or vertical sections of hippocampus in MR imaging of all patients with epilepsy. Even though MR findings may reflect some secondary lesions, MRI will shed some light on the proper understanding of epilepsy.

Adolescent↗
PubMed1994

Enhancement of the intestinal absorption of a cyclosporine derivative by milk fat globule membrane.

A cyclosporine derivative, dihydrocyclosporine D, was used for the evaluation of milk fat globule membrane (MFGM) as an emulsifier of lipophilic cyclopeptides. As compared with olive oil formulation, MFGM emulsion significantly enhanced the blood and lymphatic fluid concentrations of the cyclosporine derivative after intraduodenal dosing in rats. Thus, it was suggested that MFGM can be used as an intestinal absorption enhancer of cyclosporines.

Animals↗
PubMed1994

Rectal absorption of ozagrel from suppositories in rabbits.

Rectal absorption of ozagrel (a selective thromboxane synthetase inhibitor) from suppositories was studied in rabbits. Two kinds of suppositories were prepared, one was from ozagrel powder (OPS, ozagrel powder suppository), and the other from ozagrel tablet (OTS, ozagrel tablet suppository). Ozagrel from OPS was absorbed quickly with a Tmax value of 26.3 +/- 7.5 min, and the peak plasma level was significantly higher than that involving intravenous infusion or oral dose (50.3 +/- 6.7 vs. 32.8 +/- 5.4 or 9.9 +/- 1.2 micrograms/ml), indicating that OPS may be a useful dosage form rather than injection. OTS was absorbed less rapidly than OPS, but the AUCs of both suppositories were similar. Because OTS was prepared using an ozagrel tablet, it is fairly easy to get an equal content in each suppository. Therefore, OTS is not only an experimentally interesting dosage form, like OPS, but is also a practical preparation for clinical use.

Absorption↗