Biomedical subjects

M Akimoto

Publications and source records attributed to M Akimoto.

At least 73 records · Page 4Linked to original sources

PubMed1999

The short-term effects of tamsulosin in Japanese men with benign prostatic hyperplasia.

We evaluated the short-term effects of tamsulosin in treating benign prostatic hyperplasia. Twenty-seven patients, aged 57 to 86 years (mean 68.4); complaining of obstructive urinary symptoms who had received no previous treatment for such symptoms were orally administered 0.2 mg of tamsulosin for 4 weeks. Symptoms (total AUA symptom score and AUA symptom subscores) and objective parameters including peak and average flow rate, and post-void residual urine rate were evaluated before and after 1, 2 and 4 weeks of treatment. The mean total AUA symptom score and the mean AUA symptom subscores for incomplete emptying and weak stream were significantly decreased after only 1 week of treatment. The mean AUA symptom subscores for intermittency, urgency and nocturia were significantly decreased after 4 weeks of treatment. The mean AUA symptom subscores for frequency and hesitancy were unchanged after 4 weeks of treatment. The mean peak and average flow rate, and post-void residual urine rate were significantly improved after only 1 week of treatment. In conclusion, tamsulosin improved not only objective parameters but also symptoms only 1 week after the start of treatment.

Administration, Oral↗

PubMed1999

A kinetic study on lipase-catalyzed interesterification of soybean oil with oleic acid in a continuous packed-bed reactor.

To provide a mathematical basis for the design and operation of a continuous, packed-bed reactor for the interesterification of soybean oil, soybean oil that contains 22.7% oleoyl and 54.3% linoleoyl moieties as molar acyl moiety composition was interesterified in hexane with oleic acid, using an immobilized sn-1,3-specific lipase (Lipozyme IM) from Mucor miehei. The reaction was carried out in a U-shaped Pyrex glass-made packed-bed reactor at 37 degrees C in the following system: concentration of soybean oil in the feed stream = 12.5 wt%, molar ratio of fatty acid to soybean oil = 3.0, and water content in the feed stream = 1340-2340 ppm. At these water contents, Lipozyme IM gave practically the same catalytic activity, and the content of triacylglycerols in the product oil was 91-94 wt%. Rate equations for the change in oleoyl and linoleoyl moiety compositions in soybean oil were derived and their validity was confirmed experimentally. On the other hand, the catalytic activity of Lipozyme IM decayed in the first-order fashion. Based on these deactivation kinetics, the flow rate of the feed stream is simulated for the operation of a continuous, packed-bed reactor at 37 degrees C that produces an oil of a fixed composition of oleoyl moiety.

Journal Article↗

PubMed1999

Identification of human cytochrome P-450 isoforms involved in metabolism of R(+)- and S(-)-gallopamil: utility of in vitro disappearance rate.

Isoforms of cytochrome P-450 (CYP) involved in the metabolism of gallopamil enantiomers were identified by measuring the disappearance rate of parent drug from an incubation mixture with human liver microsomes and recombinant human CYPs. Mean (+/- S.D.) intrinsic clearances (CL(int)) of R(+)- and S(-)-gallopamil in human liver microsomes were 0.320 +/- 0.165 and 0.205 +/- 0.107 ml/min/mg protein, respectively. These values were highly correlated with the 6beta-hydroxylation activity of testosterone, a marker substrate of CYP3A4 (r = 0.977 and 0.900 for R(+)- and S(-)-gallopamil, respectively, p <.001). Ketoconazole and troleandomycin, selective inhibitors of CYP3A4, and polyclonal antibodies raised against CYP3A4/5 markedly reduced the CL(int) of gallopamil enantiomers in human liver microsomes. Among the 10 recombinant human CYP isoforms, CYP3A4 exhibited the highest CL(int) of gallopamil enantiomers, and CYP2C8 and CYP2D6 also exhibited appreciable activity. When the contribution of CYP3A4 to the total metabolic clearance of gallopamil enantiomers in human liver microsomes was estimated by relative activity factor, the mean (+/- S.D.) contributions were 92 +/- 18 and 68 +/- 19% for R(+)- and S(-)-gallopamil, respectively. These values were comparable to the rates of immunoinhibition by antibodies raised against CYP3A4/5 observed in human liver microsomes. The present study suggests that CYP3A4 is a major isoform involved in the overall metabolic clearance of gallopamil enantiomers in the human liver, and that the present approach based on disappearance rate may be applicable to identify major isoforms of CYP involved in the metabolism of a drug in human liver microsomes.

Cytochrome P-450 Enzyme System↗

PubMed1999

[A case of extragonadal germ cell tumor with inferior vena caval tumor thrombus].

We report a case of retroperitoneal extragonadal germ cell tumor with tumor thrombus in the inferior vena cava. The patient referred to our hospital with lumbago. Computed tomography (CT) showed a bulky mass in the retroperitoneum. The levels of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-HCG) in the serum were elevated. Histological examinations indicated embryonal cell carcinoma. Bilateral testicles did not contain any palpable mass upon careful palpation. No tumor mass was detected in the bilateral testicles on ultrasonography. Clinically, the diagnosis was a retroperitoneal extragonadal germ cell tumor associated with para-aortic lymph-node involvement. After the combination chemotherapy (BEP 1 course and EP 3 courses), the tumor mass was reduced in size and the tumor marker was normalized. Retroperitoneal lymph node dissection (RPLND) was performed and tumor thrombus in the inferior vena cava was resected. There was no involvement of the viable cells in the resected tumor. The patient has been in good condition with no evidence of disease.

Adult↗

PubMed1999

Adenovirally expressed basic fibroblast growth factor rescues photoreceptor cells in RCS rats.

PURPOSE: To evaluate the abilities of recombinant adenovirus carrying the basic fibroblast growth factor (bFGF) gene to (1) produce bFGF protein in vitro and (2) rescue retinal photoreceptors in Royal College of Surgeons (RCS) rats in vivo. METHODS: Cultured human retinal pigment epithelial cells were infected with one of the following two replication-deficient adenoviral vectors that drive inserted genes by beta-actin promoter with cytomegalovirus enhancer: AxCAJSbFGF, which expresses the human bFGF gene, and AxCAlacZ, carrying the cDNA of bacterial beta-galactosidase as a viral control. These viruses and recombinant bFGF protein were also injected into the subretinal space of RCS rats at the age of 21 days. The production of bFGF was evaluated by an immunohistochemical method in vitro and in vivo. The secretion of bFGF produced in vitro was quantified by an enzyme-linked immunosorbent assay. The thickness of the outer nuclear layer (ONL) as a marker of photoreceptor cell rescue was estimated at 2, 28, and 56 days after the injections. RESULTS: AxCAJSbFGF produced human bFGF protein effectively both in vitro and in vivo. The semiquantitative analysis of ONL thickness revealed a significant protective effect of AxCAJSbFGF and the recombinant bFGF protein injection up to 56 days after injection. CONCLUSIONS: These results demonstrate that a recombinant adenoviral vector can achieve the transfer of bFGF gene in vitro and have a protective effect for photoreceptor cells in vivo. Gene therapy with a bFGF-expressing recombinant adenoviral vector may provide a new strategy with which to target retinal degenerative diseases.

Adenoviridae↗

PubMed1998

Growth inhibition of cultured human Tenon's fibroblastic cells by targeting the E2F transcription factor.

The transcription factor E2F regulates the expression of several genes concerned with cell growth. The ability to inhibit transcription by blocking E2F expression has great potential in the treatment of proliferative disorders. The effect of double-stranded phosphorothioate oligonucleotides containing E2F transcription factor cis element, a so called 'decoy' has examined on the growth of cultured human Tenon's fibroblastic cells. Human Tenon's fibroblastic cells were cultured and challenged by E2F decoy coated with the Hemagglutinating virus of Japan (HVJ) cationic liposomes (HVJ-CL). The outcome was evaluated using fluorescence microscopy, RT-PCR and growth assays. HVJ-CL facilitated the transfer of external oligonucleotides to cultured human Tenon's fibroblastic cells. The E2F decoy, transferred by HVJ-CL, inhibited simultaneously the expression of the mRNAs of several cell cycle related genes such as c-myc, cdc2, proliferative cell nuclear antigen, and dehydrofolate reductase. Entry into S phase was also reduced to 42.7% of the positive control by the E2F decoy. The total increase of DNA at four days was reduced to 59.7% of the positive control by 5 microM and 29.9% by 15 microM of E2F decoy. It is concluded that gene therapy using the E2F transcription factor offers a potential therapeutic modality for the treatment of proliferative disorders such as proliferative vitreoretinopathy and fibrosis following filtering surgery.

Carrier Proteins↗

PubMed1998

Stress coping and social support in glucose tolerance abnormality.

We examined coping with stress, including social support, dealing with illness, and mood states, in a sample of 600 persons who underwent primary health-care screening. Subjects were not yet diagnosed as having glucose tolerance abnormality and considered themselves healthy before the examination. Although no significant differences on the existence and perception of social support were found, the utilization of social support was significantly and negatively correlated with the level of glucose tolerance abnormality. The results suggest that poor utilization of social support is associated with the onset of glucose tolerance abnormality.

Adaptation, Psychological↗

PubMed1998

Perception and utilization of social support in diabetic control.

This study examined the influence of social support (perception and utilization) on diabetic control. Subjects were 178 patients with diabetes mellitus [insulin dependent diabetes mellitus (IDDM) = 26, non-insulin dependent diabetes mellitus (NIDDM)= 152]. HbA1c values was used as an indicator of diabetic control. Assessment of social support was performed using the Stress and Coping Inventory. HbA1c values were significantly related to the presence or absence of participation in a diabetic education program as well as scores on perception and utilization of social supports. The participation in the diabetic education program was not significantly associated with the two social supports, however, the two social support factors interacted significantly with one another. As for type of DM, these findings were stronger in IDDM patients. These results suggest that, in particular patients with NIDDM, although diabetes education is effective for decreasing HbA1c, a combination of the two social supports also decrease the HbA1c value, independent of diabetic education.

Adolescent↗

PubMed1998

Primary cutaneous Langerhans cell histiocytosis in an adult.

A 76-year-old man with Langerhans cell histiocytosis was admitted with an asymptomatic, dark red nodule on his left buttock. Histologic examination of the nodule showed a dense dermal infiltrate of histiocytic cells with bean-shaped nuclei; these cells reacted with antibodies to S-100 and CD1a. Ultrastructural analysis showed Birbeck granules in the cytoplasm of the histiocytic cells. Inguinal lymph node involvement subsequently developed in the patient and cutaneous nodules recurred three times in the inguinal area. Four years have passed since he first was admitted to our hospital with the cutaneous nodule on his buttock, and he is doing well without any intensive treatment except wide excision of the nodules and inguinal lymph nodes. We believe this case should be classified as one of "benign" primary cutaneous Langerhans cell histiocytosis based on the clinical course.

Aged↗

PubMed1998

Relationship between recurrence of gastric ulcer and the microcirculation.

We investigated the relationship between microcirculatory disturbance and the host response to Helicobacter pylori infections in gastric ulcer scars to determine the role of endothelin-1 (ET) in ulcer recurrence. The subjects were divided into three groups. The GuS group consisted of patients who had red scarring (S1 stage) at the gastric angle with H. pylori, the gast+ group who had gastritis with H. pylori, and the gast- group who had gastritis without H. pylori. During endoscopic examination, biopsies were taken from the gastric angle. Mucosal ET, nitric oxide (NO), interleukin-8 (IL-8), and RANTES were measured. ET, inducible NO synthase (iNOS), and endothelial constitutive NOS (ecNOS) were immunostained. Mucosal ET and oxides of nitrogen (NOx) were significantly higher in the GuS group than in the other groups. IL-8 was elevated in the GuS and gast+ groups, and RANTES was elevated in the gast+ group (p < 0.01). There was prominent inflammatory cell infiltration in the GuS group. ET-positive cells were found in vascular smooth muscle, gastric epithelium, and gastric smooth muscle. iNOS-positive cells were found in vascular smooth muscle, gastric epithelium, gastric smooth muscle, and inflammatory cells. In conclusion, local inflammation and microcirculatory disturbance persist at the center of the ulcer scar (S1). Decreased cytokine levels and increased ET and NO (mainly synthesized by iNOS) levels suggested that microcirculatory disturbance is a more important factor than immune response in ulcer recurrence.

Cytokines↗

PubMed1998

Retention mechanism of imidazoles in connective tissue. II. Activation of imidazoles in cupro-ascorbate system for irreversible binding formation with aortic tissue in vitro.

In order to obtain an insight into the retention mechanism of drugs with imidazole moiety in the connective tissue, the in vitro characteristics of the interaction between 14C-labeled imidazoles (imidazole and its 2-methyl derivative) and slices of dog aorta were studied. We found that cupro-ascorbate-catalyzed oxidative reactions for the imidazoles led to their irreversible binding with connective tissue, and that, from a study using protein modifiers, the aldehydic function intrinsic to the tissue protein was involved in the binding formation. This characteristic in vitro was observed under physiological conditions, hence it can be extrapolated to the in vivo situation and could also give a clue to the nature of the retention of imidazole-containing drugs in connective tissue.

Animals↗

PubMed1998

Retention mechanism of imidazoles in connective tissue. III. Aldehyde adduct formation of a 4(5H)(or5(4H))-imidazolone product in vitro.

2-Methylimidazole (2MI), as well as imidazole, has been thought to undergo cupro-ascorbate (Cu-VC)-catalyzed oxidative transformation in vitro to become a reactive species capable of combining with aldehydes intrinsic to connective-tissue proteins. We attempted to seize the essence of the above reaction through obtaining the structural information of an aldehyde-bonding species. As major products from 2MI in the in vitro Cu-VC system, 2-hydroxymethylimidazole (2(OH)MI) and 2-methyl-4(5H)(or 5(4H))-imidazolone (2MIone) were identified by mass-spectral and chromatographic comparison with the corresponding authentic standards synthesized. The in situ addition of acetaldehyde or propionaldehyde as a simple protein-aldehyde model to the system resulted in the deducible formation of an aldol condensate, 2-methyl-4(or 5)-ethylidene-4(5H)(or 5(4H))-imidazolone (2MEIone) or its possible analogue with a propylidene moiety, respectively. The authentic compound of 2MIone directly reacted with acetaldehyde and easily afforded the products assignable to the isomers of 2MEIone through the ethylidene moiety at physiological pH and temperature, whereas neither 2MI or 2(OH)MI reacted at all. These results suggest that a 4(5H)(or 5(4H))-imidazolone product, although simply a monooxygenated form, is sufficiently reactive to give aldol condensation-typed covalent adducts with aldehydes, even under physiological conditions, probably having an activated methylene moiety in the ring structure. Based on the present results, we discussed the mechanism of the retention of imidazole-containing drugs in connective tissue.

Acetaldehyde↗

PubMed1998

[Adrenal pheochromocytoma associated with renal cell carcinoma: report of two cases].

Two cases of adrenal pheochromocytoma associated with renal cell carcinoma are reported. The first case was in a 56-year-old woman who had been treated for hypertension. Computerized tomography (CT) scan revealed a right renal tumor and a right adrenal mass. Endocrinological examination and 131I-MIBG scintigraphy confirmed the diagnosis of pheochromocytoma. Right radical nephrectomy was performed under stable blood pressure. The second case was in a 45-year-old man who had been treated for gastric ulcers. CT scan incidentally revealed a right renal tumor and a left adrenal mass. He was normotensive and endocrinologically normal. Right radical nephrectomy and left adrenalectomy were performed, followed by corticosteroid supplementation. In both cases, histopathological diagnosis was renal cell carcinoma and adrenal pheochromocytoma. Both patients had no clinical evidence for von Hippel-Lindau disease such as tumorous lesions of the central nervous system, spinal cord and retina, and cystic lesions of the kidney and pancreas.

Adrenal Gland Neoplasms↗

PubMed1998

Mapping of a new target region of allelic loss to a 6-cM interval at 21q21 in primary breast cancers.

A detailed analysis of loss of heterozygosity (LOH) in breast cancers was performed with 11 microsatellite markers on the long arm of chromosome 21. Among the 142 tumors examined, 44 (31%) showed LOH at one or more loci. Peak LOH frequency was observed on band 21q21. Deletion mapping identified a new commonly deleted region in a 6-cM interval of 21q21 between loci D21S1432 and D21S1437, and raised the possibility that one or more tumor suppressor genes associated with breast cancer may exist in this region. Comparison of these alterations with clinicopathological parameters revealed an association of LOH on 21q with loss of progesterone receptor (P = 0.0013).

Breast Neoplasms↗

PubMed1998

[Chemotherapy of disseminated germ cell tumors].

Current modes and issues of chemotherapy for the patients with disseminated germ cell tumors (GCTs) are described. A review of the literature of prospective randomized trials designed to compare the efficacy and toxicities between induction chemotherapy regimens for patients with either good- or poor-risk disseminated GCTs showed that three cycles of bleomycin, etoposide, and cisplatin (BEP) or four cycles of etoposide and cisplatin (EP) for good-risk GCTs, and four cycles of BEP for poor-risk GCTs, are the most effective regimens even now. A prognostic factor-based staging system can distinguish patients with either good- or poor-risk GCTs, and help make risk-based decisions about therapeutic modes. However, there is a variety of criteria that make intertrial comparison difficult. An internationally accepted prognostic classification of disseminated GCTs reported recently by the International Germ Cell Cancer Collaborative Group will resolve these problems. High-dose chemotherapy (HDCT) with autologous stem cell rescue can cure a relatively small but significant percentage of heavily pretreated patients who are deemed incurable with any other therapeutic strategy. Moreover, HDCT in first-line therapy for patients with poor-risk GCTs is now expected to improve treatment outcome obtained by BEP. Because HDCT has not totally overcome cisplatin-resistance, further investigation should be required.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Severe myopia as a risk factor for progressive visual field loss in primary open-angle glaucoma.

The optic nerve head in severely myopic eyes may be particularly vulnerable to glaucomatous damage. To study this hypothesis, we examined 122 primary open-angle glaucoma eyes with fair to good control of the intraocular pressure and a sign of baseline optic nerve damage. Then, parameters for the progression of the visual field defects were evaluated by multivariate analysis. A high mean intraocular pressure (p = 0.007) and a large refractive error (p = 0.023) were significant risk factors for subsequent visual field loss. A high baseline cup-to-disk ratio (p = 0.100) was a marginal risk factor. Nonsignificant parameters included patient age (p = 0.692), the use of beta-adrenergic antagonists (p = 0.384), gender (p = 0.831) and left versus right side (p = 0.977). When the refractive error was used to subclassify patients into severely myopic (< or = -4 dpt), mildly myopic (-0.25 to -4 dpt), or emmetropic and hyperopic (> or = 0 dpt), only severe myopia was a significant risk factor for progressive visual field loss. Severe myopia, but not mild myopia, is a significant risk factor for subsequent visual field loss in patients with primary open-angle glaucoma.

Adolescent↗

PubMed1997

Development of the eating Attitude Inventory for Diabetes Mellitus.

The authors examined the validity and reliability of the Eating Attitude Inventory for Diabetes Mellitus in a sample of 178 patients with diabetes mellitus. Reliability was supported by factor analysis, adequate internal consistency, and relatively high test-retest correlations. Validity was indicated by correlation with the Eating Attitudes Test designed for eating disorders. This inventory may be useful for assessing eating attitudes of patients with diabetes mellitus.

Adult↗

PubMed1997

[Blood rheological study in rats with fatty liver--with special reference to effects of ethyl icosapentate].

A blood rheological study was conducted using Kikuchi's micro-channel method in rats with fatty liver. Effects of eicosapentaenoic acid (EPA) on blood rheology were also evaluated. Male SD rats given normal feed served as the control. One group was given choline-deficient feed for 4 weeks (EPA (-) group), while another group was daily given EPA (1000 mg/kg) for 4 weeks together with choline-deficient feed (EPA (+) group). The micro-channel passage time was determined using 100 microliters of whole blood. The passage time significantly increased in the EPA (-) group compared to the control (p < 0.01). It significantly decreased in the EPA (+) group compared to the EPA (-) group (p < 0.01). Findings obtained in the present study suggested that blood rheological factors are related to the development of fatty liver and that EPA inhibits fatty changes of the liver by improving these rheological factors.

Animals↗