Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 127 records · Page 7Linked to original sources

PubMed2001

The practical synthesis of a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246).

The synthetic route for a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246), was established by the coupling of optically active components, the bromohydrin 14 and the amine 24. We now describe the practical synthesis of these two optically active components. Bromohydrin 14 was obtained by the asymmetric borane reduction of the prochiral phenacyl bromide 13 using a catalyst prepared from aluminum triethoxide and a chiral amino alcohol. The other optically active component 24 was prepared from (S)-AMT.

Acetamides↗

PubMed2001

The practical synthesis of (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthylamine via optical resolution of 2-(3-methoxybenzyl)succinic acid.

We describe the practical synthetic route for (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthylamine 1(2S)-2-amino-7-methoxytetraline; (S)-AMT]. (2R)-2-(3-Methoxybenzyl)succinic acid [(R)-1] was obtained by the optical resolution of 2-(3-methoxybenzyl)succinic acid (1) as the salt of (1R,2S)-2-(benzylamino)cyclohexylmethanol (7), and (R)-1 was converted to the optically active (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthoic acid [(S)-2] by the intramolecular Friedel-Crafts reaction followed by catalytic hydrogenation. (S)-AMT was obtained from the acid (S)-2 by Hofmann rearrangement without racemization.

Adrenergic beta-Agonists↗

PubMed2001

Existence of retinoic acid-receptor-independent retinoid X-receptor-dependent pathway in myeloid cell function.

We previously reported that ER-27191 (4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid) is a potent antagonist of retinoic acid receptor (RAR), and ER-35795 ((2E,4E,6E)-7-[1-(1-methylethyl)-8-chloro-1,2,3,4-tetrahydroquinolin-6-yl]-6-fluoro-3-methyl-2,4,6-nonatrienoic acid) is a novel retinoid X receptor (RXR)-specific agonist. By using these compounds, we investigated whether distinct RAR-dependent and RXR-dependent pathways operate to mediate the diverse activities of retinoids, particularly, the effects of the RXR pathway on cellular function. ER-27191 completely antagonized HL60 cell differentiation induced by all-trans-retinoic acid (atRA). However, the differentiation induced by the ER-35795 was not antagonized at all by the RAR antagonist, but was inhibited by an RXR homodimer antagonist (LGD100754, (2E,4E,6Z)-7-(3-n-propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid). Its agonistic action on RXR/RAR heterodimer, on the other hand, was neutralized by the RAR antagonist. During HL60 cell differentiation, atRA induced RARbeta mRNA, while the RXR had no effect. Interestingly, a functional RXR-pathway was also seen in lipopolysaccharide-induced inhibition of mouse splenocyte proliferation. These results strongly suggest the existence of a pharmacological RXR-dependent pathway that is activated by a ligand that can bind to RXR.

Animals↗

PubMed2001

Proteolytic activity and recombinant protein production in virus-infected Sf-9 insect cell cultures supplemented with carboxyl and cysteine protease inhibitors.

In insect cell-baculovirus expression systems for recombinant protein production, it is sometimes necessary to supplement cultures with protease inhibitors to protect recombinant proteins against proteolysis. To date, however, there is no information available concerning protease activities in inhibitor-supplemented cultures. The aim of the present study was to investigate intracellular and extracellular protease activities in cultures of virus-infected Sf-9 insect cells which were supplemented with inhibitors against carboxyl and cysteine proteases produced during culture. Prior to the supplementation culture, the cell toxicity of several protease inhibitors was determined. As a result, pepstatin A (carboxyl protease inhibitor) and E64, cystatin, leupeptin, and antipain (cysteine protease inhibitors) tested in this study showed no apparent negative effects on the growth and viability of noninfected Sf-9 insect cells at low concentrations. In addition, E64 and pepstatin A could rapidly permeate virus-infected Sf-9 cells and inhibit the respective intracellular protease activities. A virus-infected culture with a multiplicity of infection of 1 was carried out with E64 and pepstatin A which were added to the culture medium at 2 d post-infection. As a result of inhibitor supplementation, the cellular activity for recombinant protein biosynthesis was reduced by 5-30%. However, a significant reduction in carboxyl and cysteine protease activities was observed not only in the medium but also intracellularly. This is the first study that directly demonstrates a reduction in extracellular and intracellular protease activities in protease inhibitor-supplemented cultures of virus-infected insect cells.

Journal Article↗

PubMed2001

Transmission electron microscopy studies of the zona reaction in pig oocytes fertilized in vivo and in vitro.

The aim of this study was to determine the ultrastructure of cross-sectioned zonae pellucidae of in vitro-matured and ovulated pig oocytes before or after sperm penetration in vitro and in vivo, respectively. The in vitro and in vivo (ovulated) oocytes and zygotes (fertilized in vitro and in vivo) were fixed with glutaraldehyde either directly or after pretreatment with ruthenium red and saponin, processed and then examined using transmission electron microscopy. The thickness of the zona pellucida, as measured on the section of the specimens with largest diameter fixed with glutaraldehyde, differed between the in vivo (9.19 +/- 0.47 microm) and in vitro (5.95 +/- 0.51 microm) oocytes. The in vivo oocytes had a rather thick external mesh-like structure, whereas it was much thinner in the in vitro oocytes. This mesh-like external rim was less apparent in both in vivo and in vitro zygotes. Obvious differences in the density of the lattice formed by the fixed zonae pellucidae were visible between the outer and inner (ad-oolemmal) zonae. The outer area always formed a concentrically arrayed fibrillar network, whereas the inner area showed a much more compact, trabecule-like mesh. However, both areas, but particularly the outer network, were much more compacted after the zona reaction. Clear differences in the degree of fibrillar aggregation of the inner zona area were also observed between in vitro and in vivo zygotes, being much higher in the latter. This fibrillar network was more clearly visible in the zygotes pretreated with ruthenium red and saponin; the in vitro zygotes had a fibrillar, radially oriented set of parallel fibrils, whereas it was much more aggregated and trabecule-like in the in vivo zygotes. These results demonstrate that the fine structure of the zona pellucida and the zona reaction at sperm penetration differ between pig oocytes fertilized in vivo and in vitro. Moreover, the ultrastructure of the outer and inner pig zonae pellucidae has a different network organization.

Animals↗

PubMed2001

Spontaneous rupture of the amyloid spleen in a case of usual interstitial pneumonia.

We describe a rare case of secondary amyloidosis associated with usual interstitial pneumonia (UIP), who died from spontaneous rupture of the amyloid spleen. A 68-year-old man was admitted to evaluate to his interstital lung disease. Chest radiography showed reticular shadow in bilateral lower lung fields. Two years later, he suddenly felt severe abdominal pain. In spite of maximum therapy, he died from hypovolemic shock. Postmortem examination revealed massive intraabdominal hemorrhage. The diagnosis of lung disease was UIP and amyloid A type deposits were observed in various organs including the ruptured spleen.

Aged↗

PubMed2001

Discrimination of brain abscess and cystic tumor by in vivo proton magnetic resonance spectroscopy.

Proton magnetic resonance (MR) spectroscopy was evaluated for the differentiation of brain abscesses and cystic brain tumors. Proton MR spectroscopy was performed in vivo in two patients with brain abscess and eight patients with various cystic brain tumors (anaplastic astrocytoma, glioblastoma, and metastatic brain tumor). MR imaging with contrast medium demonstrated ring-like enhanced mass lesions in all patients. The various resonance peaks in proton MR spectra were assigned to metabolites according to chemical shifts. Treatment of the cystic brain lesions was based on the information from proton MR spectroscopy. Aspirated pus from one patient with brain abscess was examined using ex vivo proton MR spectroscopy. The in vivo spectra of brain abscess contained resonance peaks attributed to acetate, lactate, alanine, amino acids, and lipids in both cases, and an additional peak of succinate in one case. In vivo spectra of the neoplasms contained resonance peaks corresponding to lactate, lipids, choline, creatine, and N-acetyl aspartate. Proton MR spectroscopy is useful for discriminating brain abscess from cystic tumors with similar neuroimaging appearance, which is very important for determining the treatment strategy.

Acetates↗

PubMed2001

Lightning injury as a blast injury of skull, brain, and visceral lesions: clinical and experimental evidences.

The present study attempts to better understand the mechanism of injuries associated with direct lightning strikes. We reviewed the records of 256 individuals struck by lightning between 1965 and 1999, including 56 people who were killed. Basal skull fracture, intracranial haemorrhage, pulmonary haemorrhage, or solid organ rupture was suspected in three men who died. Generally these lesions have been attributed to current flow or falling after being struck. However, examination of surface injuries sustained suggested that the true cause was concussion secondary to blast injury resulting from vaporization of water on the body surface by a surface flashover spark. To investigate this hypothesis, an experimental model of a lightning strike was created in the rat. Saline-soaked blotting paper was used to simulate wet clothing or skin, and an artificial lightning impulse was applied. The resultant lesions were consistent with our hypothesis that the blast was reinforced by the concussive effect of water vaporization. The concordance between the clinical and experimental evidence argues strongly for blast injury as an important source of morbidity and mortality in lightning strikes.

Adult↗

PubMed2001

[A Case of central venous catheter-related infection with Malassezia sympodialis].

We report a 63-year-old male with central venous catheter-related infection caused by Malassezia sympodialis after total gastrectomy for a gastric cancer. He had fever and his leukocyte counts and C-reactive protein were elevated 14 days after his operation. After his central venous hyperalimentation catheter was removed, the inflammatory signs immediately disappeared, suggesting an intravenous catheter-related infection. A yeast-like fungus was cultured in brain-heart infection semi-solid agar ten days later, and was diagnosed morphologically as Malassezia sp. This strain was identified as M. sympodialis by Tween assimilation test and was confirmed by whole-sequence of internal transcribed spacer 1 regions (ITS1). This is the first report of catheter-related infection caused by M. sympodialis. This strain grew and was subcultured on CHROMagar Candida, potato dextrose agar and Sabouraud agar. There have been no reports of such a lipid-independent Malassezia sp. except for M. pachydermatis. The mechanism of lipid independence of this strain is undetermined and future work is needed. Malassezia sp. is receiving increased attention as an etiologic pathogen of catheter-related fungemia in clinical microbiology laboratories and infectious disease sections.

Catheterization, Central Venous↗

PubMed2001

Measurement of cerebral hemodynamics with perfusion-weighted MR imaging: comparison with pre- and post-acetazolamide 133Xe-SPECT in occlusive carotid disease.

BACKGROUND AND PURPOSE: We generated regional cerebral blood volume (rCBV) and regional cerebral blood flow (rCBF) studies from dynamic susceptibility contrast-enhanced MR images after an intravenous bolus injection of contrast agent (perfusion-weighted imaging [PWI]) by applying indicator dilution theory. We used a multishot echo-planar imaging (EPI) sequence to obtain adequate arterial input function (AIF). Our purpose was to compare the cerebral hemodynamics measured by PWI with the rCBF values and cerebral perfusion reserve obtained by xenon-133 single-photon emission CT (133Xe-SPECT). METHODS: Eight patients with chronic internal carotid artery occlusion or stenosis were examined. PWI data were acquired using a multishot EPI sequence, and the AIF was determined automatically. Our procedure was based on indicator dilution theory and deconvolution analysis. To eliminate the effect of superficial vessels, the automatic threshold selection method was used. RESULTS: AIF was adequate to generate rCBF and rCBV images. The rCBF and rCBV images by PWI were superior to 133Xe-SPECT scans in spatial resolution, and the rCBF values obtained by PWI correlated well with those obtained by 133Xe-SPECT. The regions with severely decreased perfusion reserve, which were determined by pre- and post-acetazolamide 133Xe-SPECT, showed significantly lower rCBF and higher rCBV by PWI than did regions with normal and moderately decreased perfusion reserve. CONCLUSION: The rCBF and rCBV images generated by our procedure using PWI data appear to provide important clinical information for evaluating the degree of cerebral perfusion reserve impairment in patients with chronic ischemia.

Acetazolamide↗

PubMed2001

[A case of adenoid cystic carcinoma of the left main bronchus, which was performed carinal resection and reconstruction while the aortic arch is pulled down].

A 55-year-old woman, who had treated as bronchial asthma for eight months, was admitted to our hospital. Chest CT scan showed a mass in the left main bronchus. Bronchoscopic examination revealed a tumor obstructing the left main bronchus and invading the left lower portion of the trachea. The pathologic diagnosis was adenoid cystic carcinoma. Primary resection of the left main bronchus and the carina with the objective and one-stoma-type carinal reconstruction were performed by the left thoracotomy. We pulled down the aortic arch to obtain an operative field, and carried out the operative procedure at the upper side of the aortic arch. As the resection margin contained residual tumor, the postoperative irradiation (50 Gy) was added.

Aorta, Thoracic↗

PubMed2001

[Relationship between keeping a companion animal and instrumental activity of daily living (IADL). A study of Japanese elderly living at home in Satomi Village].

OBJECTIVE: The purpose of this study was to clarify the relationship between the companionship of an animal and the level of Instrumental Activity of Daily Living (IADL) of elderly people living at home, and to consequently determine beneficial effects on the overall health of the elderly. METHODS: For this study, 400 elderly people aged 65 years and over were randomly selected from among the 1,345 citizens of Satomi Village, Ibaraki Prefecture. Self-administered questionnaires were mailed to the selected subjects in March of 1999. In the survey, the respondents were asked if they could accomplish all seven IADL activities. Subjects for whom this was the case were classified as having no IADL disability. Elderly who answered "No" for even one were listed as having an IADL disability. Using the existence of an IADL disability as a dependent variable and various factors related to companion animals as independent variables, a logistic regression analysis was performed. RESULTS: Out of the 400 individuals, 84.8% responded. With respect to the possession of a companion animal, the number of participants who never had a companion animal was 115 (35.8%); while 118 (36.8%) possessed a companion animal in the present. With regard to factors relevant to IADL of elderly people, the odds ratio (OR) adjusted for age and sex for participants who owned dogs was 0.53 (95% confidence interval [CI] 0.27-0.99) relative to those who never had a companion animal: The difference was significant. For those respondents who indicated that their companion animals were their best friends, the OR was 0.48 (95% CI 0.23-0.99), and again significant. The OR tended to decrease with increase in the duration of owning a companion animal. CONCLUSION: In this study, owning a dog and everyday contact with the companion animal were related to the IADL of the elderly living at home. It is possible that keeping a companion animal may be linked to better overall health in the elderly.

Activities of Daily Living↗

PubMed2001

[Complete response of a massive hepatocellular carcinoma with lung metastasis to UFT (DPD inhibitory fluoroprymidines: DIF)].

A 77-year-old man was referred to our hospital because a periodic examination for hepatitis C cirrhosis and diabetes mellitus at a nearby clinic had revealed an elevated AFP level. Abdominal ultrasound and CT scan revealed a giant tumor in the right hepatic lobe, and a diagnosis of hepatocellular carcinoma was made with a biopsy. A pulmonary CT scan also revealed a diffuse granular shadow in the right lung field, leading to a diagnosis of multiple pulmonary metastases from the hepatocellular carcinoma. Arterial infusion chemotherapy was performed, but was ineffective. Thus, the administration of 600 mg/day of UFT was initiated. Both the AFP and PIVKA-2 levels, which had been increasing, returned to normal 3 months later. Ultrasound and CT scan showed that the hepatocellular carcinoma and lung metastatic foci had disappeared completely. The administration of UFT therefore appears promising for the treatment of hepatocelluar carcinoma and can be used safely, even with patients in poor general condition.

Aged↗

PubMed2001

[Mupirocin resistant MRSA in Japan].

Mupirocin is a unique antibiotic that is produced by Pseudomonas fluorescens, and is available for elimination of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). However, there have been many reports that high level mupirocin resistant S. aureus were discovered in Europe, South or North American countries. In Japan, mupirocin has been only available for nasal ointment of MRSA eradication since 1996. After introduction of mupirocin, we have screened mupirocin resistance routinely in our hospital. On January 1998, we had high level mupirocin-resistant MRSA isolated from a nose of a neonate with severe nephrotic syndrome. The mupA was detected by PCR and the mupirocin-resistance could transfer to S. aureus RN2677 by filter-mating with co-transfer of gentamicin, tobramycin, kanamycin and erythromycin. This strain was eradicated after prophylactic use of vancomycin for her nephrectomy. To our knowledge, this is the first isolate of high level mupirocin-resistant MRSA in Japan.

Anti-Bacterial Agents↗

PubMed2001

[Management of hypertension in patients with coronary artery disease].

The management of hypertensive patients with coronary artery disease (CAD) should be started with lifestyle modification for reduction of coronary risk factors. As the principle of drug therapy, rapid decrease in blood pressure below the limits of coronary auto-regulation must be avoided. Clinical trials showed J-curved relationship between diastolic pressure and mortality was not found above 75 mmHg. The current desired goal of blood pressure in patients with CAD might be suggested as 125-140/85-75 mmHg. Pulse pressure should be recognized as a strong predictor for CAD as well as systolic and diastolic blood pressure, especially in elderly patients. The choice of drug therapy have to be based on efficiency in clinical trials, side effects, and also particular condition of each patient.

Antihypertensive Agents↗

PubMed2001

[The pollen survey and dynamic statistics of patients with allergic rhinitis in Hakodate].

We have investigated the pollen survey (1994-1998) and dynamic statistics of patients with allergic rhinitis (1999-2000) in Hakodate, which is located southern part of Hokkaido. We have noted the pollen dispersion of Cryptomeria japonica, Cupressaceae, white birch, Gramineae and Artemisia. Especially, a lot of dispersion of Cryptomeria japonica has been noted in April. Concerning the dynamic statistics of patients with allergic rhinitis, we have investigated the 192 patients with allergic rhinitis in Hakodate municipal hospital. There has been a lot of pollinosis in March, April, May and September. Frequency of positive reaction to the specific IgE have been 38.0% of house dust, 16.9% of Artemisia, 13.2% of Gramineae, 10.3% of white birch, 9.0% of Cryptomeria japonica and 6.9% of cat in 379 subjects. In conclusion, we have noted that Cryptomeria japonica and white birch in addition to Gramineae and Artemisia are becoming more important antigen in patients with pollinosis in Hakodate, south part of Hokkaido.

Female↗

PubMed2001

Comparison of cardiac sympathetic nervous function with left ventricular function and perfusion in cardiomyopathies by (123)I-MIBG SPECT and (99m)Tc-tetrofosmin electrocardiographically gated SPECT.

UNLABELLED: The objective of this study was to clarify the relationship between cardiac sympathetic nervous function (CSNF) and left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-eight cases (32 males, 6 females; mean age, 56 +/- 15 y), consisting of 5 healthy control subjects, 15 patients with DCM, and 18 patients with HCM, were studied with (123)I-metaiodobenzylguanidine (MIBG) and (99m)Tc-tetrofosmin SPECT. CSNF was evaluated from cardiac uptake and washout of MIBG, whereas LV perfusion and function were evaluated from tetrofosmin uptake and wall thickening on electrocardiographically gated SPECT. As quantitative parameters of global cardiac MIBG uptake and washout, the heart-to-mediastinum ratio (H/M) and percentage washout were calculated from early and delayed planar images. As quantitative regional parameters, the regional uptake and percentage washout of MIBG were calculated from SPECT images dividing the left ventricle into 12 segments. In the tetrofosmin study, the H/M and LV ejection fraction were calculated as the parameters of global LV perfusion and function. As quantitative regional parameters, the regional uptake and wall thickening were also calculated for the 12 myocardial segments using the quantitative gated SPECT software. Multiple linear regression analysis was performed to investigate the correlations between the parameters from the 2 studies. RESULTS: In DCM and HCM, multiple linear regression analysis of the regional parameters showed significant correlations between LV function and CSNF (P < 0.0001) and between LV perfusion and CSNF (P < 0.0001). According to the partial correlation coefficients, washout and early uptake of MIBG were the most significant factors for predicting LV function and LV perfusion, respectively. CONCLUSION: In cardiomyopathies, CSNF was closely related to LV function. The quantitative parameters of MIBG washout could reflect cardiac functional impairment. Early MIBG uptake might be determined by myocardial perfusion in cardiomyopathies.

3-Iodobenzylguanidine↗

PubMed2001

[Prevalence of cervical and cerebral atherosclerosis and silent brain infarction in patients with multivessel coronary artery disease].

OBJECTIVES: This clinical study investigated the prevalence of cervical and cerebral atherosclerosis and silent brain infarction in patients with coronary artery disease. METHODS: Cervical and cerebral magnetic resonance angiography(MRA) was performed in 133 patients (98 males, 35 females, mean age 65.3 years) with suspected coronary artery disease, who were divided into a zero- and one-vessel disease group(n = 71) and a two- and three-vessel disease group(n = 62) depending on the number of major coronary branches with 75% or more stenosis. The MRA lesion was defined as more than 50% stenosis. Magnetic resonance imaging(MRI) of the brain was performed within 1 week of MRA in 78 patients without symptomatic stroke and atrial fibrillation. Silent brain infarction on MRI was defined as a focal high intensity area on T2-weighted images larger than 3 mm. RESULTS: The prevalence of MRA lesions was significantly greater in the two- and three-vessel group than in the zero- and one-vessel group(53% vs 14%, p < 0.01). The prevalence of MRI lesion was significantly higher in the two- and three-vessel group than in the zero- and one-vessel group(77% vs 36%, p < 0.01). The size and number of the MRI lesions were also significantly greater in the two- and three-vessel group than in the zero- and one-vessel group(p < 0.01). Neither age nor percentage of male gender was different between the groups. Diabetes mellitus was the common risk factor for coronary artery disease, MRA lesion and MRI lesion. CONCLUSIONS: Cervical and cerebral atherosclerosis and silent brain infarction are frequently observed in patients with multivessel coronary artery disease.

Adult↗