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Biomedical subjects

T Irie

Publications and source records attributed to T Irie.

At least 55 records · Page 3Linked to original sources
PubMed2000

Alteration of a p53 gene status affects outcome of patients with recurrent ovarian cancer.

The aim of this longitudinal study was to examine whether and how the p53 gene is altered in patients with recurrent ovarian cancer and to determine the significance of p53 mutation in recurrent tumors. The primary and recurrent tumors were examined in 15 patients who had recurrent epithelial ovarian cancer, and whose primary tumor contained a wild-type p53 gene. The interval between cytoreductive surgery and the appearance of recurrence ranged from 5. 2 to 63.6 months (mean 23.4 months). Mutations in the p53 gene were screened by polymerase chain reaction single strand conformation polymorphism analysis and determined by cycle sequencing. Mutation of the p53 gene in the recurrent tumor was found in 7 of the 15 patients (46.7%). Estimated 3- and 5-year survival rates were 57.1 and 0%, respectively, for patients with p53 gene mutation detected in the recurrence tumor, and 75.0% and 37.5% for patients without the mutation (p = 0.0155). The interval between cytoreductive surgery and the appearance of recurrence did not differ between those groups (549.7 +/- 102.2 vs. 832.9 +/- 283.8 days). Mean survival time after recurrence was significantly better in the patients without mutation (438.6 +/- 56.4 vs. 873.0 +/- 157.5 days, p = 0.0125). The present study suggests that p53 gene mutation frequently occurs in recurrent ovarian cancer and that alteration of p53 gene status affects salvage chemotherapy. This phenomenon affects the prognosis of recurrent disease and may predict outcome.

Aged↗
PubMed2000

Improvement of subcutaneous bioavailability of insulin by sulphobutyl ether beta-cyclodextrin in rats.

The objective of this study was to examine and compare how hydrophilic beta-cyclodextrin derivatives (beta-CyDs) improve the bioavailability of insulin following subcutaneous injection of insulin solution in rats. When insulin solutions in the absence of beta-CyDs were injected into the dorsal subcutaneous tissues of rats, the absolute bioavailability of insulin calculated from plasma immunoreactive insulin (IRI) levels was approximately 50%. When maltosyl-beta-cyclodextrin was added to the solutions, there was no change in the plasma IRI levels and hypoglycaemia compared with those of the insulin-alone solution. Dimethyl-beta-cyclodextrin decreased the bioavailability of insulin, although it increased the maximal concentration of IRI in plasma and the capillary permeability of the fluorescein isothiocyanatedextran 40, a non-degraded permeation marker. When insulin solutions containing sulphobutyl ether-beta-cyclodextrin with a degree of substitution of the sulphobutyl group of 3.9 (SBE4-beta-CyD) were injected, the IRI level rapidly increased and maintained higher IRI levels for at least 8 h. The bioavailability of the insulin/SBE4-beta-CyD system was about twice that of insulin alone and approached 96%. The enhancing effects of SBE4-beta-CyD may be in part due to the inhibitory effects of SBE4-beta-CyDs on the enzymatic degradation and/or the adsorption of insulin onto the subcutaneous tissue at the injection site, although this does not apparently facilitate capillary permeability. These results suggest that SBE4-beta-CyD in aqueous insulin injection for subcutaneous administration is useful for improving the bioavailability and the hence the pharmacological effects of insulin.

Animals↗
PubMed2000

Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer's disease: a positron emission tomography study.

We measured brain acetylcholinesterase activity in 30 patients with Alzheimer's disease (AD) and 14 age-matched controls by positron emission tomography (PET) and using a carbon 11-labeled acetylcholine analogue. Seven AD patients had repeat PET scans. The k3 values were calculated as an index of acetylcholinesterase activity in a three-compartment analysis using the metabolite corrected arterial input function. Twenty-eight of the 30 AD patients (14 each in the early and late onset subgroups) were retained in the study so as to equalize the range and average severity of cognitive impairment within the early and late onset subgroups. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala in the early onset AD patients, although the k3 values were significantly reduced only in the temporoparietal cortex and amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat AD patients showed further reduction of cortical k3 values in the second PET scans, with a mean interval of 2 years, suggesting a progressive loss of the ascending cholinergic system from the nucleus basalis of Meynert in AD. In 37 AD patients, there was a highly significant correlation between the cortical k3 values and Mini-Mental State Examination scores, supporting the cholinergic hypothesis in AD.

Acetylcholinesterase↗
PubMed2000

Transcatheter embolization of mycotic aneurysm of the subclavian artery with metallic coils.

Mycotic aneurysms of the subclavian artery are rare. This report describes an experience of 2 rare cases in which transcatheter embolization with metallic coils was performed for the management of these lesions alternative to surgery. Two patients who had been treated with chemotherapy for malignant neoplasms were diagnosed as having mycotic aneurysms of the left subclavian artery. The causes of these lesions were presumed to be the invasion of the arterial wall by the pulmonary abscess in case 1, and wound infection after placement of the reservoir for intraarterial chemotherapy in case 2. In both cases, proximal and distal sites of the aneurysm were embolized with metallic coils. In case 1, the vertebral artery was also embolized with Guglielmi detachable coils to avoid retrograde blood flow. Both aneurysms were completely occluded by a single embolization. In case 1, although weakness and paresthesia of the left hand remained, lethal hemoptysis due to aneurysmal fistulization to the lung parenchyma ceased. In case 2, no neurological deficit except for mild paresthesia in the left thumb had been observed. Both patients died of primary disease 10 and 5 months after the procedure. Transcatheter embolization is technically feasible and effective enough to treat the mycotic aneurysm of the subclavian artery even in the situation in which the surgical option seems to be difficult or risky.

Aneurysm, Infected↗
PubMed2000

Metastatic carcinoma in a transposed ovary after radical hysterectomy for a stage 1B cervical adenosquamous cell carcinoma. Case report.

A 41-year-old multigravida woman presented with a cervical stage 1b adenosquamous cell carcinoma with metastasis in a transposed ovary. Twenty-four months following a radical hysterectomy for cervical cancer a CT scan revealed a mass measuring 7x6x4 cm in size lateral to the ascending colon. The pathological diagnosis showed the mass to be metastatic adenocarcinoma in the transposed ovary which was considered to be adenocarcinoma from the previous cervical adenosquamous cell carcinoma. Thereafter, she was administered a combination of mitomycin C, etoposide and cisplatin (MEP) three times. One year following the completion of the chemotherapy she is still alive without any definitive recurrence. It is important to clarify whether or not ovarian transposition is safe and effective in helping surgeons determine whether or not to preserve the ovarian function for a young patient likely to undergo postoperative irradiation for early invasive cervical cancer. In the present report, we also review the current literature on this subject and discuss our findings.

Adult↗
PubMed2000

[Rapid production of gelatin sponge particles for transcatheter arterial embolization: pumping method].

We devised a simple "pumping" method to make gelatin sponge particles for transcatheter arterial embolization. As the frequency of pumping increased, the number of particles 0.2-1.6 mm in diameter increased, whereas no particles of more than 3.2 mm in diameter were present after 20 pumpings. After passing through the microcatheter, particles of less than 0.2 mm in diameter were relatively increased by about 10 points in both the pumping and cutting methods. It was histologically demonstrated that the size of embolized arteries corresponded well to the size of particles. These results suggest that our "pumping" method offers sufficient quality for transcatheter arterial embolization.

Animals↗
PubMed1999

Factors affecting membrane-controlled drug release for an osmotic pump tablet (OPT) utilizing (SBE)(7m)-beta-CD as both a solubilizer and osmotic agent.

PURPOSE: The purpose of this study was to define membrane controlling factors responsible for drug release from a controlled-porosity osmotic pump tablet (OPT) that utilizes a sulfobutyl ether-beta-cyclodextrin, (SBE)(7m)-beta-CD, as both a solubilizing and osmotic agent. METHOD: The OPT was spray coated with cellulose acetate solutions varying the amount and size of micronized lactose, the amount of triethyl citrate (TEC) and the composition ratio of dichlormethane to ethanol. Chlorpromazine (CLP) was used as a model drug. The release of CLP from the OPTs was studied using the Japanese Pharmacopoeia dissolution method. The membrane surface area of the OPTs were measured with multi-point analysis by the gas absorption method. RESULTS: The release rate of CLP from OPTs containing (SBE)(7m)-beta-CD increased with increasing amounts of micronized lactose and decreasing amounts of TEC and lactose particle size in the membrane. Also, the CLP release rates from the spray-coated OPTs using mixtures of varying ratios of dichlormethane to ethanol were almost identical. The membrane surface area of the OPTs following release of membrane components had a linear relationship to CLP release rates from the OPTs. CONCLUSION: The present results confirmed that the membrane controlling factors responsible for the drug release were the amount and size of micronized lactose and the amount of TEC in the membrane.

Antipsychotic Agents↗
PubMed1999

Mitochondrial DNA replication in human T lymphocytes is regulated primarily at the H-strand termination site.

The most unique feature in the replication of mitochondrial DNA (mtDNA) is that most of the newly synthesized heavy strands (H-strands) terminate prematurely, resulting in the formation of displacement loop (D-loop) strands. Only the H-strand which proceeds past the termination site is a true nascent H-strand leading to the overall replication on a circular mtDNA molecule. The physiological significance of the D-loop formation has long been unclear. To examine the role of premature termination in mtDNA replication, we therefore developed a method for selectively measuring both the total amount of nascent H-strands and the amount of true nascent H-strands using ligation-mediated polymerase chain reaction, which, for the first time, enabled us to estimate the frequency of premature termination. The stimulation of cell proliferation with interleukin 2 and phytohemagglutinin in human peripheral T lymphocytes caused an increase in the net replication rate of mtDNA. In stimulated cells, in comparison to resting ones, the amount of true nascent H-strands increased approx. 2.6-fold while the total amount of nascent H-strands remained unchanged, indicating that premature termination decreased while the initiation of replication remained the same. Our findings thus demonstrate the first clear example that premature termination plays a primary role in the up-regulation of the net rate of mtDNA replication in human cells.

Aphidicolin↗
PubMed1999

Characterization of itraconazole/2-hydroxypropyl-beta-cyclodextrin inclusion complex in aqueous propylene glycol solution.

The interaction of itraconazole, a triazole antifungal agent, with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) in water and 10% v/v propylene glycol/water solution at pH 2.0 was investigated by the solubility method and ultraviolet and 1H-nuclear magnetic resonance (NMR) spectroscopies. The solubility of itraconazole in water significantly increased as the concentrations of HP-beta-CyD were augmented, showing an AP type phase solubility diagram. The upward curvature closely corresponded to the simulation curve which was calculated on the basis of the 1:2 (guest:host) complexation model. The 1:2 complex was formed even in the presence of 10% v/v propylene glycol, although the co-solvent system made the interaction with HP-beta-CyD weaker due to the competitive inclusion. The ultraviolet spectroscopic studies also supported the 1:2 complex formation of itraconazole with HP-beta-CyD in 10% v/v propylene glycol/water solution at pH 2.0. The 1H-NMR spectroscopic studies suggested that the triazole and triazolone moieties of itraconazole are involved in the 1:2 inclusion complexation.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1999

Lithium decreases Cl--ATPase activity and increases intracellular Cl- concentration in cultured rat hippocampal neurons.

Under the conditions of stimulated phosphatidylinositol turnover (0. 1 mM carbachol plus 20 mM KCl), LiCl (0.1-10 mM) reduced the activity of Cl--ATPase in cultured rat hippocampal neurons without affecting Na+/K+- or anion-insensitive Mg2+-ATPase. This inhibition of Cl--ATPase was attenuated by the addition of 0.5 mM inositol to culture media. The intracellular Cl- concentrations of the LiCl-treated neurons increased in an inositol-sensitive manner.

Adenosine Triphosphatases↗
PubMed1999

Cyclodextrins in peptide and protein delivery.

The objective of this contribution is to summarize recent findings on the potential of cyclodextrins (CDs) and their derivatives as carriers for therapeutically important peptides, proteins and oligonucleotides. As one of the indices relevant to bioadaptability of CDs in pharmaceutical uses, their interaction with cellular membranes in vitro is outlined. CDs enable the creation of advanced dosage forms for the next generation of drugs that are difficult to formulate and deliver with the existing pharmaceutical excipients. Furthermore, the diagnostic uses of CDs for the direct measurement of cholesterol in high-density and low-density lipoproteins in serum are discussed on the basis of their ability to recognize the surface properties of each lipoprotein particle.

Journal Article↗
PubMed1999

Human cerebral acetylcholinesterase activity measured with positron emission tomography: procedure, normal values and effect of age.

The regional cerebral metabolic rate of [11C]N-methyl-4-piperidyl acetate, which is nearly proportional to regional cerebral acetylcholinesterase (AChE) activity, was measured by dynamic positron emission tomography in 20 healthy subjects with a wide age range (24-89 years). Quantitative measurement was achieved using a kinetic model which consisted of arterial plasma and cerebral tissue compartments. The plasma input function was obtained using thin-layer chromatography and an imaging phosphor plate system at frequent sampling intervals to catch the rapid metabolism of the tracer in the blood. The distribution of the rate constant k3, an index of AChE activity, agreed well with reported post-mortem AChE distribution in the cerebral cortex (0.067-0.097 min-1) and thalamus (0.268 min-1), where AChE activity was low to moderate. The k3 values in the striatum and cerebellum, where AChE activity was very high, did not respond linearly to AChE activity because of increased flow dependency. No significant effect of age was found on AChE activity of the cerebral cortex, suggesting that the ascending central cholinergic system is preserved in normal aging. This study has shown that quantitative measurement of enzyme activity in the living brain is possible through appropriate modelling of tracer kinetics and accurate measurement of the input function. The method should be applicable to patients with Alzheimer's disease and those with other kinds of dementia whose central cholinergic system has been reported to be disturbed.

Acetates↗
PubMed1999

Design and evaluation of an osmotic pump tablet (OPT) for chlorpromazine using (SBE)7m-beta-CD.

PURPOSE: The purpose of this study was to develop a controlled-porosity osmotic pump tablet (OPT) which exhibits pH-independent release profiles for a basic drug using a sulfobutyl ether-beta-cyclodextrin, (SBE)7m-beta-CD, which acts as both a solubilizer and as an osmotic agent. METHODS: Chlorpromazine free base (CLP) was chosen as a model drug for this study. The release of CLP from osmotic pump tablets was studied in vitro. In vivo absorption of CLP from the OPT was evaluated in male beagle dogs. RESULTS: The CLP release profile from an OPT prepared from a core tablet composed of a 1:10 molar ratio of CLP to (SBE)7m-beta-CD was pH-independent, and was controlled by modulating the membrane thickness of the OPT. Another cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and a sugar mixture of lactose and fructose resulted in pH-dependent release at the same molar ratio. An in vivo absorption study in dogs with an OPT containing (SBE)7m-beta-CD correlated very well with the in vitro release profiles using the Japanese Pharmacopoeia dissolution method. CONCLUSIONS: In addition to serving as a solubilizer and osmotic agent, (SBE)7m-beta-CD can also serve as the controlling agent for pH independent release of CLP from OPTs. This system successfully modified the in vivo input rate of CLP without compromising oral bioavailability.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1999

1-Methyl-4-phenylpyridinium ion (MPP+) selectively inhibits the replication of mitochondrial DNA.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine is known to cause Parkinsonism in its neurotoxic form, 1-methyl-4-phenylpyridinium ion (MPP+). We have previously reported that MPP+ decreases the content of mitochondrial DNA (mtDNA) independently of the inhibition of complex I in human cells [Miyako, K., Kai, Y., Irie, T., Takeshige, K., and Kang, D. (1997) J. Biol. Chem. 272, 9605-9608]. Here we study the mechanism causing the decrease in mtDNA. MPP+ inhibits the incorporation of 5-bromo-2'-deoxyuridine into mtDNA but not into nuclear DNA, indicating that MPP+ inhibits the replication of mtDNA but not that of the nuclear genome. The replication of mtDNA is initiated by the synthesis of the heavy strand switched from the transcription of the light strand. MPP+ decreases the nascent heavy strands per mtDNA and increases the transcript of the ND6 gene, encoded on light strand, per mtDNA. The amount of mitochondrial transcription factor A is not decreased. These data suggest that the transcription is not inhibited and therefore the transition from transcription to replication of mtDNA is lowered in the MPP+-treated cells. Electron microscopy shows that the number of mitochondria is not decreased in the MPP+-treated cells, suggesting that MPP+ does not affect the overall biogenesis of mitochondria. Thus, MPP+ selectively inhibits the replication of mtDNA.

1-Methyl-4-phenylpyridinium↗
PubMed1999

Prognostic significance of the PC10 index for patients with stage II and III oesophageal cancer treated with radiotherapy.

The monoclonal antibody PC10 is used for immunohistochemical staining of the proliferating cell nuclear antigen (PCNA). The percentage of PC10-positive cancer cells is defined as the PC10 index. We evaluated the relationship between the PC10 index in pretreatment endoscopic biopsies and the prognoses of 47 patients with Stage II-III oesophageal squamous cell carcinoma treated with radiotherapy. The patients with a PC10 index > 40% had significantly poorer prognoses than the other patients (p = 0.0007). Proportional hazards model analysis indicated that only the PC10 index was a prognostic factor (p = 0.0009). The patient group of complete responders showed significantly lower PC10 indices compared to patients with a partial response or no change (p = 0.049). The PC10 index can be a good predictive indicator of the prognosis in patients with Stage II-III oesophageal cancer treated with radiotherapy.

Aged↗
PubMed1999

Significance of cytoreductive surgery including bowel resection for patients with advanced ovarian cancer.

The aim of this study was to determine the significance of bowel resection in advanced ovarian cancer. A total of 64 women with stage IIIc or IV epithelial ovarian cancer, who consecutively received primary treatment between 1991 and 1995, were entered in this prospective study. The outcome of the patients undergoing bowel resection was evaluated. Thirty-nine patients underwent cytoreductive surgery at initial surgery. Of them, 16 patients could undergo optimal operation without bowel resection. Twenty-three patients received bowel resection at initial surgery. Of these 23 patients, 16 underwent optimal operation and 7 did not. Among 25 patients judged as inoperable cases at initial surgery, 21 responded to chemotherapy and underwent second surgery. Of 21 patients receiving second surgery, 15 underwent optimal operation (7 without bowel resection and 8 with bowel resection). The 3-year survival rate for 24 patients undergoing optimal operation with bowel resection (46.8%) was not significantly different from that for 23 patients without bowel resection (59.1%). Postoperative complications were seen in 8 patients (21.6%) of the patients receiving bowel resection and 3 (13.0%) of those without bowel resection. Cytoreductive surgery including bowel resection is effective for an improvement of the survival in patients with advanced ovarian cancer, if an optimal operation can be performed.

Adult↗