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Biomedical subjects

K Kojima

Publications and source records attributed to K Kojima.

At least 91 records · Page 5Linked to original sources
PubMed2001

Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells.

BACKGROUND & AIMS: Because short-chain fatty acids (SCFAs) and heat shock proteins (hsps) confer protection to intestinal epithelia cells (IECs), we studied whether SCFAs modulate IEC hsp expression. METHODS: Hsp 25, hsp72, and hsc73 protein expression in rat intestinal tissues and IEC-18 cells were determined by Western blot and immunohistochemistry. Cell survival under conditions of oxidant stress (monochloramine) was determined using (51)Cr release in hsp25 cDNA anti-sense and sense-transfected cells expressing minimal and increased hsp25, respectively. RESULTS: Butyrate induces a time- and concentration-dependent increase in hsp25, but not hsp72 or hsc73, protein expression in rat IEC-18 cells but not 3T3 fibroblasts. Other SCFAs, including the poorly metabolized isobutyate, also induced selective expression of hsp25. Butyrate treatment significantly improved the ability of IEC-18 cells to withstand oxidant (monochloramine) injury. This effect could be blocked in cells in which hsp25 induction by butyrate was blocked by stable hsp25 antisense transfection. Additionally, hsp25-transfected overexpressing IEC-18 cells showed increased resistance to monochloramine. In vivo, increasing dietary fiber increased colonic, but not proximal, ileal hsp25 while having no effect on hsp72 or hsc73 expression. CONCLUSIONS: SCFAs, the predominant anions of colonic fluid derived from bacterial flora metabolism of luminal carbohydrates, protect IECs against oxidant injury, an effect mediated in part by cell-specific hsp25 induction.

3T3 Cells↗
PubMed2001

Survival of neural stem cells in the cochlea.

Adult rat hippocampus-derived neural stem cells (NSCs) have been reported to have been successfully grafted in several brain regions. To evaluate the possibility of treatment of sensorineural hearing loss using NSCs, survival of NSCs in the cochlea was estimated. NSCs were grafted into newborn rat cochleas. Within 2-4 weeks of grafting to the cochlea, some NSCs survived in the cochlear cavity. Some of them had adopted the morphologies and positions of hair cells. This suggests that NSCs can adapt to the environment of the cochlea and gives hope for treatment of the damaged cochlea and sensorineural hearing loss.

Animals↗
PubMed2001

Transvaginal ultrasound-guided embryo transfer improves pregnancy and implantation rates after IVF.

BACKGROUND: Attempts are constantly being made to improve clinical pregnancy rates after IVF and embryo transfer. Since November 1998, we have gradually been adopting transvaginal ultrasound guidance during embryo transfer. We retrospectively examined the efficacy of this method on pregnancy and implantation rates. METHODS: The results of 846 cycles from our IVF-embryo transfer programme were analysed and comparisons were made between those carried out using ultrasound guidance and those by the clinical touch method. RESULTS: Higher pregnancy and implantation rates (28.9 and 15.2% respectively) were found in the group using the transvaginal ultrasound guidance during embryo transfer compared with those in the group using the clinical touch method (13.1 and 7.0% respectively). The differences were statistically significant (P < 0.01). There was no significant difference in ectopic pregnancy rates between the two groups. CONCLUSION: The use of transvaginal ultrasound-guided embryo transfer significantly improved both pregnancy and implantation rates. Although technically difficult, we suggest its use may maximize the chances of achieving a successful pregnancy outcome.

Adult↗
PubMed2001

Recognition of mitochondrial protein precursor lacking arginine at position -2 by mitochondrial processing peptidase: processing of bovine cytochrome P450(SCC) precursor.

Mitochondrial processing peptidase (MPP) specifically cleaves off the N-terminal presequence of the mitochondrial protein precursor. Previous studies demonstrated that Arg at position -2 from the cleavage site, which is found among many precursors, plays a critical role in recognition by MPP. We analyzed the structural elements of bovine cytochrome P450 side-chain cleavage enzyme precursor [pre-P450(SCC)], which has Ala at position -2, for recognition by MPP. Replacement of Ala position -2 of pre-P450(SCC) with Arg resulted in an increase in the cleavage rate. Replacement with Gly caused a reduction in the cleavage rate and the appearance of an additional cleavage site downstream of the authentic site. A pre-P450(SCC) mutant with Met at position -2 retained cleavage efficiency equal to that of the wild type. These results indicate that -2 Ala of pre-P450(SCC) is recognized by MPP as a determinant for precise cleavage, and that the amino acid at -2 is required to have a straight methylene chain for interaction with the S(2) site. The preference for distal basic residues, a hydrophobic residue at +1, and hydroxyl residues at +2 and +3, was almost the same as those of the precursors with Arg at -2, indicating that the recognition mechanism of pre-P450(SCC) by MPP is essentially the same as that of the precursors with Arg at position -2.

Amino Acid Motifs↗
PubMed2001

Inhibition of the light-independent synthesis of chlorophyll in pine cotyledons at low temperature.

Cotyledons of Japanese black pine (Pinus thunbergii) were yellow when they developed in darkness at 8 degrees C since the light-independent synthesis of chlorophyll was almost completely inhibited in these cotyledons. The level of chlorophyll in dark-grown cotyledons was less than one-twentieth of that in light-grown cotyledons at the same temperature. In the yellow cotyledons, levels of transcripts of cab, rbcS, rbcL and psbA genes were quite high. The large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase were also detected at relatively high levels in yellow cotyledons. However, the accumulation of the two apoproteins of the light-harvesting chlorophyll a/b-binding protein of PSII was limited because of the limited supply of chlorophyll.

Chlorophyll↗
PubMed2001

Proper regulation of cyclic AMP-dependent protein kinase is required for growth, conidiation, and appressorium function in the anthracnose fungus Colletotrichum lagenarium.

Colletotrichum lagenarium, the casual agent of anthracnose of cucumber, forms specialized infection structures, called appressoria, during infection. To evaluate the role of cAMP signaling in C. lagenarium, we isolated and functionally characterized the regulatory subunit gene of the cAMP-dependent protein kinase (PKA). The RPK1 gene encoding the PKA regulatory subunit was isolated from C. lagenarium by polymerase chain reaction-based screening. rpk1 mutants, generated by gene replacement, exhibited high PKA activity during vegetative growth, whereas the wild-type strain had basal level activity. The rpk1 mutants showed significant reduction in vegetative growth and conidiation. Furthermore, the rpk1 mutants were nonpathogenic on cucumber plants, whereas they formed lesions when inoculated through wounds. A suppressor mutant showing restored growth and conidiation was isolated from a rpk1 mutant culture. The rpkl-suppressor mutant did not show high PKA activity, unlike the parental rpk1 mutant, suggesting that high PKA activity inhibits normal growth and conidiation. The suppressor mutant, however, was nonpathogenic on cucumber and failed to form lesions, even when inoculated through wounds. The rpk1 and suppressor mutants formed melanized appressoria on the host leaf surface but were unable to generate penetration hyphae. These results suggest that proper regulation of the PKA activity by the RPK1-encoded regulatory subunit is required for growth, conidiation, and appressorium function in C. lagenarium.

Amino Acid Sequence↗
PubMed2001

Association of Mycoplasma genitalium persistence in the urethra with recurrence of nongonococcal urethritis.

BACKGROUND: Most patients with recurrent symptomatic nongonococcal urethritis receive negative test results for Chlamydia trachomatis and Ureaplasma urealyticum, and the cause of such recurrence usually is unknown. GOAL: To assess the association of Mycoplasma genitalium with recurrent nongonococcal urethritis. STUDY DESIGN: In this study, 72 men with nongonococcal urethritis were treated with levofloxacin. Before and after treatment, symptoms and signs were assessed and first-pass urine was examined for C trachomatis, M genitalium, U urealyticum, and Mycoplasma hominis by polymerase chain reaction-based assays. RESULTS: In 6 of 45 men who had no symptoms and no evidence of inflammation after treatment, nongonococcal urethritis recurred. Of these 6 men, 5 had positive test results for M genitalium before levofloxacin treatment, which remained positive afterward. After the second treatment for recurrent nongonococcal urethritis, one man was still had a positive test result for the mycoplasma and experienced a subsequent recurrence. CONCLUSIONS: This study suggests that the persistence of M genitalium in the urethra may be associated with recurrence of nongonococcal urethritis.

Adolescent↗
PubMed2001

Phenytoin intoxication induced by fluvoxamine.

A patient had phenytoin intoxication after administration of fluvoxamine, a selective serotonin reuptake inhibitor. The serum concentration of phenytoin increased dramatically from 16.6 to 49.1 microg/mL when fluvoxamine was coadministered, although the daily dosage of phenytoin and other drugs had not changed. During phenytoin and fluvoxamine treatment, ataxia, a typical side effect of phenytoin, was observed. The genotypes of CYP2C9 and 2C19, the enzymes responsible for phenytoin metabolism, were homozygous for the wild-type alleles (CYP2C9*1/*1 and 2C19*1/ *1). The interaction may be a result of inhibition of both CYP2C9 and 2C19 by fluvoxamine.

Alleles↗
PubMed2001

Sesquiterpenoid derivatives from Ferula ferulaeoides [correction of ferulioides]. V.

Nine novel prenyl-dihydrofurocoumarin-type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4-methyl-5- (4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo-[3,2-c]coumarin, and 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, were isolated from the roots of Ferula ferulaeoides [corrected]. The structures were established by comprehensive spectral analysis. The biosynthetic pathway leading to these prenyl-furocoumarin-type sesquiterpenoids is proposed based on their structures.

Ferula↗
PubMed2001

Postprandial hyperlipidemia in Zucker diabetic fatty fa/fa rats, an animal model of type II diabetes, and its amelioration by acyl-CoA:cholesterol acyltransferase inhibition.

Postprandial hyperlipidemia (PH) is frequently observed in diabetic patients. We performed an oral fat-loading test in Zucker diabetic fatty (ZDF) fa/fa rats, a model for type II diabetes, to determine whether PH was induced in the rats. Post fat-loading changes in serum cholesterol and triglyceride levels were significantly greater in the fa/fa rats than those seen in their lean littermates and an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor significantly reduced these levels by 24% and 31%, respectively. Therefore, we confirmed that PH appeared in ZDF fa/fa rats by fat loading and ACAT inhibition may be a potential treatment for PH.

Animals↗
PubMed2001

Intraarterial corticosteroid infusion following radiotherapy for primary central nervous system lymphoma: feasibility and preliminary result.

To utilize the high lympholytic effect of corticosteroids with minimal systemic adverse effects, we used intraarterial corticosteroid infusion in the treatment of 8 patients with primary central nervous system lymphoma (PCNSL). One patient had recurrent PCNSL, while the other patients had primary disease. Following standard radiotherapy with or without some systemic or intrathecal chemotherapy, prednisolone (60-100 mg in total) or dexamethazone (12 mg in total) was rapidly infused through the carotid arteries in all patients and also through the left vertebral artery in 5 patients. No acute or late complications of this treatment were observed. All 8 patients achieved complete or partial response. Four patients died of the disease, while the other 4 were alive with (1 patient) or without (3 patients) disease at 8-37 months after treatment, giving a 2-year survival rate of 55%. Intraarterial administration of high-dose corticosteroids appears to be a feasible treatment modality. This method may be used in preradiotherapy setting to evaluate response of PCNSL in future studies.

Adrenal Cortex Hormones↗
PubMed2001

[Treatment of phimosis with betamethasone ointment in children].

OBJECTIVE: We evaluated the efficacy of betamethasone ointment in the treatment of childhood phimosis and determined the most effective concentration of betamethasone. MATERIAL AND METHODS: Between August 1996 and May 2000, 69 patients (median age 3.0, range 0-12) presented to our department with severe phimosis (grade 4, Tsugaya's classification), and were enrolled in this study and treated with betamethasone ointment for 4 weeks. The ointment was applied on the narrowed preputial skin twice a day by parents. During the first week, parents were asked not to retract the foreskin. After this period, parents were encouraged to retract the foreskin gently and without intense tension. The concentration of betamethasone were 0.12%, 0.05% and 0.025%. If the patients become to be able to retract foreskin satisfactory, we consider the state as complete response. If he become to be able to retract to allow partial exposure of the glans, we consider the state as partial response. We compared the efficacy among each of the concentrations, and at 3 months after the end of the treatment, we also assessed the adverse effects and recurrence. RESULTS: The overall success rate was 85.5%. Success rates with 0.12%, 0.05% and 0.025% ointment were 96.8%, 82.8% and 55.6%, respectively (p = 0.0001). The 0.12% ointment was most effective. Recurrence was observed in 3 patients (4.3%). No adverse effects were observed in any of the patients. CONCLUSIONS: Treatment with betamethasone ointment is very effective, easy and safe. We recommend betamethasone ointment as the first treatment of choice for childhood phimosis.

Betamethasone↗
PubMed2001

[Comparison of digital subtraction angiography, CT angiography, and ultrasonic Doppler examination in the evaluation of penile arterial lesions].

BACKGROUND: CT angiography reconstructed by a multidetector-row helical CT scanner is a newly developed form of imaging. We compared CT angiography and ultrasonic Doppler examination with digital subtraction angiography (DSA) in the diagnosis of arterial lesion. METHOD: Eighteen patients with arteriogenic erectile dysfunction (ED) underwent color Doppler study, DSA, and CT angiography after providing informed consent. The CT angiography images were obtained by a multidetector-row helical CT scanner, Asteion TSX021A (TOSHIBA). We injected prostaglandin E1 into the penile cavernous body, and then rapidly infused nonionic contrast medium into the antecubital vein. DSA and CT angiography images of the bilateral internal pudendal arteries and cavernous arteries were examined for stenotic lesions or occlusion. We also compared the peak systolic blood flow velocity in the cavernous artery measured by color Doppler ultrasound with CT angiography and DSA. RESULTS: The CT angiography and color Doppler studies were performed on an outpatient basis, but DSA required hospitalization. In the 36 internal pudendal arteries, DSA represented 22 normal arteries and 14 stenosis or occlusions. CT angiography showed 15 normal arteries and 21 occlusions. For the diagnosis of stenosis or occlusion in the internal pudendal artery, the CT angiography image had a good agreement, with a sensitivity of 1.00, specificity of 0.68, and accuracy of 0.81. For diagnosis in the cavernous artery, CT angiography image also showed a good agreement with DSA; however, the quality of the images of fine arteries was better in the DSA images. The inferior view and internal view of the pelvis in CT angiography were helpful for visualizing the internal pudendal artery, especially at the pubic bone. There was insufficient correlation between peak systolic blood flow velocity and DSA findings. There were no serious complications involved in either examination. CONCLUSIONS: CT angiography has not yet reached the same level as DSA in the evaluation of fine arteries. However, CT angiography can produced images sufficient for the diagnosis of arteriogenic ED with some advantages. We believe that with improvement, CT angiography will become an adequate replacement for DSA in the diagnosis of penile arterisl lesion.

Adult↗
PubMed2001

Synthesis and antibacterial activity of novel 1beta-methyl carbapenems with cycloalkylamine moiety at the C-2 position.

Novel 1beta-methyl carbapenems with a cycloalkylamine moiety as a side chain were synthesized and their structure-activity relationships were studied. These carbapenems showed potent antibacterial activities against a wide range of Gram-positive and Gram-negative bacteria, and moderate urinary recovery when administered intraperitoneally in mice.

Anti-Bacterial Agents↗
PubMed2001

[T-cell prolymphocytic leukemia complicated by diffuse large B-cell lymphoma of the stomach].

We describe a case of T-cell prolymphocytic leukemia (T-PLL) in a 76-year-old man, who developed diffuse large B-cell lymphoma (DLBL) of the stomach, a previously unreported occurrence. The patient was referred to our hospital because of marked leukocytosis (40,000/microliter) without clinical symptoms. He was diagnosed as having T-PLL on the basis of the characteristic cell morphology and immunophenotype (CD2+, CD3+, CD4+, CD5+, CD7+, CD8-, CD25-, TCR alpha/beta+), but cytogenetic analysis showed no abnormalities. Fifteen months later, he developed a gastric tumor. Biopsy of the tumor revealed DLBL without features of MALT lymphoma; Helicobacter pylori was not detected. Chemotherapy eradicated the tumor, whereas the T-PLL was resistant to the therapy. The disease showed an indolent course for about 2 years thereafter. Immunological derangement due to T-PLL might have potentiated the development of DLBL in this case.

Aged↗
PubMed2001

ACAT inhibitor F-1394 prevents intimal hyperplasia induced by balloon injury in rabbits.

Acyl-CoA:cholesterol acyltransferase (ACAT) is thought to contribute significantly to lipid deposition in macrophages, which subsequently leads to the initiation and progression of atherosclerosis. The aim of the present study was to examine the influence of hypercholesterolemia on arterial hyperplasia induced by endothelial denudation and the direct effect of ACAT inhibition on lesion formation. Rabbits were fed either a cholesterol diet or a regular diet for 4 weeks, and then the left common carotid arteries were denuded of endothelium. After the operation, all rabbits were kept on the regular diet for 2;-6 weeks. Two weeks after the denudation, the degree of intimal thickening and the number of proliferating cells (which were immunohistologically identified to be smooth muscle cells) were similar in hypercholesterolemic and normolipidemic rabbits. After that, both parameters progressively increased in hypercholesterolemic rabbits but declined in normolipidemic rabbits. Macrophages were apparent in the lesions only in hypercholesterolemic rabbits. Next, the effect of the ACAT inhibitor, (1S,2S)-2-[3-(2,2-dimethylpropyl)-3-nonylureido] cyclohexane-1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate (F-1394), on neointimal formation in hypercholesterolemic rabbits was examined. Oral administration of F-1394 significantly reduced neointimal thickening and the extent of macrophages in lesions without affecting serum cholesterol levels. These results suggest that hypercholesterolemia causes macrophage-derived foam cell accumulation in lesions, and that the progression of lesions is accelerated by the presence of macrophages. Moreover, the study shows that F-1394 prevents neointimal formation even in the presence of hypercholesterolemia, indicating that F-1394 may be useful for treating restenosis after percutaneous translumenal coronary angioplasty in hyperlipidemic patients.

Animals↗
PubMed2001

[Allogeneic bone marrow transplantation for refractory multiple myeloma: presence of a graft-versus-myeloma effect].

We investigated the graft-versus-myeloma effect (GVM) after allogeneic bone marrow transplantation (allo-BMT). Three patients with refractory multiple myeloma (MM) underwent related allo-BMT. Two of the patients showed disappearance of serum M protein 4 and 5 months after transplantation, respectively. One of them has remained in complete remission for more than 22 months after allo-BMT, with accompanying chronic GVHD. Two patients with relapse and disease progression after allo-BMT underwent donor lymphocyte infusion (DLI). Although one patient did not respond to DLI, the other developed acute GVHD after 4 weeks and achieved a 75% reduction in serum M protein. DLI did not produce severe acute GVHD or myelosuppression. These findings suggest the presence of a GVM effect. DLI may be an effective therapy for patients with MM who have relapsed after allo-BMT. Furthermore, non-myeloablative stem cell transplantation (mini-transplantation) for refractory MM should be investigated further as a potentially curative option.

Adult↗