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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 73 records · Page 4Linked to original sources
PubMed2001

Safety evaluation of lipase produced from Candida rugosa: summary of toxicological data.

The toxicity of lipase AY, an enzyme preparation used in lipid hydrolysis to produce flavors, was evaluated in a series of studies. A 13-week dietary toxicity study in Sprague-Dawley (Crj:CD) rats was conducted in which animals received lipase AY in the feed at concentrations of 0, 625, 1250, or 2500 mg/kg body wt. No adverse treatment-related effects were observed. Lack of genotoxic potential was demonstrated by the results of an in vitro reverse mutation assay in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and in Escherichia coli strain WP2 uvrA, by an in vitro forward mutation assay in L5178Y mouse lymphoma cells, and by an in vitro chromosome aberration test in CHL/IU cells derived from fibroblasts of the lungs of Chinese hamsters. Finally, the particular strain of Candida rugosa, the yeast strain used to prepare lipase AY, has been shown to be nonpathogenic upon a single injection into the tail vein of rats of viable spores at doses up to 1.5x10(7) colony-forming units per animal. The results of these studies demonstrate that the enzyme preparation may be considered safe to workers and consumers when employed in the production of flavors from fats.

Animals↗
PubMed2001

The cell surface-expressed HSC70-like molecule preferentially reacts with the rat T-cell receptor Vdelta6 family.

We previously showed that the cell surface-expressed Mr 70,000 heat shock cognate (hsc70, a constitutively expressed member of the hsp70 family) protein-like molecule (#067 molecule) interacts with rat CD3+, CD4-, CD8-, T-cell receptor (TCR)alphabeta-, natural killer recetor-P1- T cells. This 70hsc-like molecule was also suggested to present cellular peptide antigens to these T cells. In the present study, we identified the genetic structure of the TCR by establishing T-cell hybridomas between these T cells and mouse BW5147 cells. Our data indicated that these T cells preferentially used TCRs with the Vdelta6 family. Analysis of the nucleotide sequence of the CDR3 junctional portion showed that there are substantial diversities, with insertion of seven to nine amino acid residues. These data provide indirect evidences for our hypothesis that an hsc70-like molecule could be presented together with cellular peptide antigens to particular T cells with TCR gammadelta chains. Since the expression of this hsc70-like #067 antigen on the cell surface is usually induced along with cell transformation by activated oncogenes, T cells with the TCR Vdelta6 family are likely to contribute to host resistance to tumor cells.

Amino Acid Sequence↗
PubMed2001

Acute idiopathic blind spot enlargement syndrome: prolonged retinal dysfunction revealed by multifocal electroretinogram technique.

PURPOSE: To report the multifocal electroretinographic findings of a patient with acute idiopathic blind spot enlargement syndrome recorded at 2 weeks and 4 months after the onset. METHODS: A 35-year-old patient underwent static visual field (Humphrey, 30-2) and multifocal electroretinogram testing at 2 weeks and 4 months after the onset of acute idiopathic blind spot enlargement. The stimulus array for the multifocal electroretinogram consisted of 61 hexagons, and the total recording time was about 4 minutes. RESULTS: At 2 weeks, the patient had a large, well-demarcated scotoma centered on the blind spot, and its margin extended to within 5 degrees of fixation. The multifocal electroretinograms were depressed in the areas corresponding to the scotoma. At 4 months, her visual symptoms disappeared and static visual fields showed normal sensitivities at almost all locations. However, the multifocal electroretinograms still revealed reduced focal responses in a broad area around the blind spot. CONCLUSION: These results suggest that multifocal electroretinograms may be used to detect subclinical retinal dysfunction in patients with acute idiopathic blind spot enlargement.

Acute Disease↗
PubMed2001

Multifocal pupillary light response fields in normal subjects and patients with visual field defects.

The optimal conditions for recording focal pupillary light responses with a multifocal stimulation technique were determined, and the technique was applied to normal subjects and patients with visual field defects. Thirty-seven hexagonal stimuli were presented on a TV monitor with a visual field of 40 degrees diameter under a constant background illumination. Using a slow (4.7 Hz) m-sequence, reliable focal responses were obtained in both normal subjects and patients. The pupillary field and visual field were well correlated in patients with retinal diseases, but the correlation was not strong in patients with optic-nerve diseases. Pupillary light responses were reduced in the blind hemifield in patients with post-geniculate lesions. These results indicate that the multifocal stimulation technique can be used clinically to obtain a pupillary field for objective visual field testing.

Adult↗
PubMed2001

Unilateral cone dysfunction with bull's eye maculopathy.

OBJECTIVE: To report a Japanese subject who presented with an acute-onset, unilateral cone dysfunction with bull's eye maculopathy and to describe the functional changes determined by psychophysical and electrophysiologic tests. DESIGN: A single observational case report. METHODS: In addition to a complete ophthalmic examination, the subject underwent some electrophysiologic and psychophysical tests. MAIN OUTCOME MEASURES: Kinetic visual field test, cone and rod perimetry (two-color perimetry), full-field electroretinograms (ERGs), focal macular ERGs, and multifocal ERGs. RESULTS: The full-field ERGs and two-color perimetry showed a predominant loss of cone function in the right eye, whereas the left eye was normal. Cone perimetry and multifocal ERGs revealed that there were small regions functioning normally and other retinal areas that were severely altered in the right eye. CONCLUSIONS: The topographical function analysis suggested that the disorder affected the retina unevenly. The cause of this rare case of unilateral cone dysfunction with bull's eye maculopathy still remains unknown.

Acute Disease↗
PubMed2001

A 10-year-old boy with Marfan syndrome exhibiting cerebrovascular abnormalities.

A young male with Marfan syndrome, diagnosed at the age of 10 years, presented with conspicuous elongation and tortuosity of the internal carotid, middle cerebral, vertebral and basilar arteries on cranial magnetic resonance and computed tomography angiography. There is a little mention of cerebral blood vessel examinations in the guidelines of the American Academy of Pediatrics for Marfan syndrome. Guidelines may be provided for the evaluation of cerebrovascular system for the patients with Marfan syndrome who have family history of Marfan syndrome as well as a family history of death from subarachnoid hemorrhage.

Cerebrovascular Disorders↗
PubMed2001

Lymphocyte development from hematopoietic stem cells.

The recent application of new techniques, such as multi-color cell sorting and the production of transgenic and gene-knockout mice, has contributed to a better understanding of lymphocyte development from hematopoietic stem cells. Now that we can purify progenitors at different maturational stages during lymphocyte development, the challenge is to understand the processes that govern each developmental stage transition.

Animals↗
PubMed2001

Differences in recombination frequencies during female and male meioses of the sex chromosomes of the medaka, Oryzias latipes.

In the medaka, Oryzias latipes, sex is determined chromosomally. The sex chromosomes differ from those of mammals in that the X and Y chromosomes are highly homologous. Using backcross panels for linkage analysis, we mapped 21 sequence tagged site (STS) markers on the sex chromosomes (linkage group 1). The genetic map of the sex chromosome was established using male and female meioses. The genetic length of the sex chromosome was shorter in male than in female meioses. The region where male recombination is suppressed is the region close to the sex-determining gene y, while female recombination was suppressed in both the telomeric regions. The restriction in recombination does not occur uniformly on the sex chromosome, as the genetic map distances of the markers are not proportional in male and female recombination. Thus, this observation seems to support the hypothesis that the heterogeneous sex chromosomes were derived from suppression of recombination between autosomal chromosomes. In two of the markers, Yc-2 and Casp6, which were expressed sequence-tagged (EST) sites, polymorphisms of both X and Y chromosomes were detected. The alleles of the X and Y chromosomes were also detected in O. curvinotus, a species related to the medaka. These markers could be used for genotyping the sex chromosomes in the medaka and other species, and could be used in other studies on sex chromosomes.

Animals↗
PubMed2001

Preferential binding of polyethylene glycol-coated liposomes containing a novel cationic lipid, TRX-20, to human subendthelial cells via chondroitin sulfate.

PURPOSE: To design novel cationic liposomes, polyethylene glycol (PEG)-coated cationic liposomes containing a newly synthesized cationic lipid, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20) were formulated and their cellular binding and uptake investigated in vitro in the following cells: human subendothelial cells (aortic smooth muscle cells and mesangial cells) and human endothelial cells. METHODS: Three different PEG-coated cationic liposomes were prepared by the extrusion method, and their mean particle size and zeta potential were determined. Rhodamine-labeled PEG-coated cationic liposomes were incubated with smooth muscle cells, mesangial cells, and endothelial cells at 37 degrees C for 24 h. The amounts of cellular binding and uptake of liposomes were estimated by measuring the cell-associated fluorescence intensity of rhodamine. To investigate the binding property of the liposomes, the changes of the binding to the cells pretreated by various kinds of glycosaminoglycan lyases were examined. Fluorescence microscopy-is used to seek localization of liposomes in the cells. RESULTS: The cellular binding and uptake of PEG-coated cationic liposomes to smooth muscle cells was depended strongly on the chemical species of cationic lipids in these liposomes. Smooth muscle cells bound higher amount of PEG-coated TRX-20 liposomes than other cationic liposomes containing N-(1-(2.3-dioleoyloxy) propyl)-N, N, N-trimethylammonium salts or N-(alpha-(trimethylammonio)acetyl)-D-glutamate chloride. Despite of the higher affinity of PEG-coated TRX-20 liposomes for subendothelial cells, their binding to endothelial cells was very small. The binding to subendothelial cells was inhibited when cells were pretreated by certain kinds of chondroitinase, but not by heparitinase. These results suggest that PEG-coated TRX-20 liposomes have strong and selective binding property to subendothelial cells by interacting with certain kinds of chondroitin sulfate proteoglycans (not with heparan sulfate proteoglycans) on the cell surface and in the extracellular matrix of the cells. This binding feature was different from that reported for other cationic liposomes. CONCLUSIONS: PEG-coated TRX-20 liposomes can strongly and selectively bind to subendothelial cells via certain kinds of chondroitin sulfate proteoglycans and would have an advantage to use as a specific drug delivery system.

Aorta, Thoracic↗
PubMed2001

Combination of HLA-A and HLA class II alleles controls the susceptibility to rheumatoid arthritis.

Two hundred and four unrelated Japanese patients with rheumatoid arthritis (RA) were typed for HLA by serological typing and DNA typing. The serological typing revealed that frequencies of HLA-A11, DR4, DR53 and DQ4 were increased and those of DR8 and DQ1 were decreased in the patients. The DNA typing has precisely defined the disease-associated HLA class II alleles; DRBl*0405, DQAl*03 and DQBl*0401 showed positive associations, while negative associations were found with DRBl*0803, DQAl*0103 and DQBl*0601. The risk for RA was found to be closely associated with particular amino acid sequences of DR-beta chain, including glycine residue at the 86th position in addition to those between 70 and 74, which are known to confer binding specificity and affinity to antigenic peptides. The observation that the frequency of HLA-A11 was increased in the DRBl*0405-positive patients suggested the interaction of these two alleles in the susceptibility to RA. On the other hand, the frequency of DPB1*0201 was increased in the DRBl*0405-negative patients and the frequency of HLA-A2 was increased in the DPBl*0201-positive patients, especially in the younger onset group. These findings suggested that the combination of HLA-A2 and DPBl*0201 may confer the susceptibility in the DRBl*0405-negative patients. Our results suggested the possibility that the susceptibility to RA is controlled by the interaction of HLA-A and DRBl genes or by that of HLA-A and DPBl genes in different patient subgroups.

Adult↗
PubMed2001

Nrl is required for rod photoreceptor development.

The protein neural retina leucine zipper (Nrl) is a basic motif-leucine zipper transcription factor that is preferentially expressed in rod photoreceptors. It acts synergistically with Crx to regulate rhodopsin transcription. Missense mutations in human NRL have been associated with autosomal dominant retinitis pigmentosa. Here we report that deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, mediated by S cones. The photoreceptors in the Nrl-/- retina have cone-like nuclear morphology and short, sparse outer segments with abnormal disks. Analysis of retinal gene expression confirms the apparent functional transformation of rods into S cones in the Nrl-/- retina. On the basis of these findings, we postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3.

Animals↗
PubMed2001

Risk factors for chronic graft-versus-host disease after allogeneic stem cell transplantation in children.

We analyzed the incidence and risk factors for chronic graft-versus-host disease (GVHD) in 265 children undergoing allogeneic stem cell transplantation (SCT) who survived longer than 3 months post SCT. Patients transplanted from HLA-mismatched related donors and matched unrelated donors were included. Fifty-five patients developed chronic GVHD between 1 and 25 months after SCT, and the 5-year cumulative incidence of chronic GVHD was 22%. By multivariate analysis, acute GVHD (P = 0.004), malignant disease (P = 0.004), recipient age (> or =10 years) (P = 0.01) and a female donor to male recipient (P = 0.035) were significant risk factors for chronic GVHD. When acute GVHD was excluded from the multivariate analysis, malignant disease (P = 0.002) and older recipient age (P = 0.007) were identified. The incidence of chronic GVHD in this childhood study was lower than that observed in adults, and recipient age was an important factor in childhood SCT. The high incidence associated with malignant disease may be affected by changes in GVHD prophylaxis in order to ensure graft-versus-tumor effects.

Adolescent↗
PubMed2001

Genetic analysis of pancreatic duct hyperplasia in Otsuka Long-Evans Tokushima Fatty rats: possible association with a region on rat chromosome 14 that includes the disrupted cholecystokinin-A receptor gene.

An Otsuka Long-Evans Tokushima Fatty (OLETF) strain of rat spontaneously developed hyperglycemia, hyperinsulinemia, insulin resistance and mild obesity, which had been studied as animal model for type II diabetes mellitus (T2DM). Recently, we observed that this strain coincidentally developed atypical hyperplasia of the choledocho-pancreatic ductal epithelium with a complete incidence. In an effort to locate genes responsible for this hyperplasia, we prepared 288 backcross progeny from a mating between OLETF rats and BN rats (which do not develop hyperplasia), and performed a genome-wide scan using 207 polymorphic genetic markers. We observed a prominent association of hyperplasia with a region involving a marker locus D14Mit4 (P = 0.00020, Fisher's exact test) and Cckar (the cholecystokinin-A receptor gene; P = 0.00025, Fisher's exact test) which is known to be disrupted in an OLETF strain. Our findings indicated that epithelial hyperplasia of the choledocho-pancreatic duct is associated with a region on rat chromosome 14 around the Cckar gene in an additive fashion with another two susceptible loci, each on chromosome 9 and 7. This implied the possibility that Cckar deficiency could result in a predisposition towards pancreatic duct hyperplasia.

Animals↗
PubMed2001

New quinolone, grepafloxacin, inhibits Cl- secretion across bovine airway epithelium in culture.

OBJECTIVE: Transepithelial ion transport plays an important role in the regulation of the amount and the rheological properties of bronchial secretion. The effect of grepafloxacin (GPFX), a new quinolone agent, on bioelectrical properties of airway epithelium was determined. METHODOLOGY: Electrical properties of bovine tracheal epithelium cultured under an air-liquid interface condition were measured by the short-circuit technique. RESULTS: Addition of GPFX (100 microg/mL) to the mucosal side decreased short-circuit current (Isc) from 14.4 +/- 1.3 to 5.6 +/- 0.6 microA/cm2 (P < 0.001), and the response was accompanied by corresponding decreases in transepithelial potential difference and cell conductance. This effect was concentration dependent, and a similar response was also noted when GPFX was added to the submucosal side. The GPFX-induced decrease in Isc was not altered by the Na+ channel blocker amiloride, but was inhibited by the Cl- channel blocker diphenylamine-2-carboxylate or Cl(-)-free medium (P < 0.001, in each case). Furthermore, GPFX reduced Cl- conductance (P < 0.01) without affecting Na+ conductance of the epithelium. CONCLUSIONS: Grepafloxacin selectively inhibits Cl- secretion across tracheal epithelial cells, which may result in the inhibition of water secretion and, hence, the reduction of airway secretion.

Animals↗
PubMed2001

Differences in transcutaneous bilirubin readings in Japanese term infants according to feeding method.

BACKGROUND: Controversy has existed for many years over whether infant feeding methods are related to serum bilirubin concentrations during the first few days of life. Differences in initial jaundice patterns according to the feeding method until 72 h after birth have not been elucidated hitherto. The difference may become clear in Japanese neonates because jaundice shows a much higher peak bilirubin concentration and a later peak in Japanese neonates than in Caucasian neonates. METHODS: In the present study, we investigated variations in the transcutaneous bilirubin reading (TcB) obtained within 72 h after birth among 177 breast-fed and 494 formula-fed healthy Japanese term neonates. RESULTS: There was no difference between TcB in formula-fed and breast-fed infants until the first 30 h, after which time the rate of increase in TcB was lower in formula-fed infants. Among breast-fed neonates, a good linear regression between time after birth and TcB was maintained. Similarly, weight losses in breast-fed infants at 24-48 h and 48-72 h after birth were greater than those in formula-fed infants. CONCLUSIONS: The jaundice pattern in Japanese neonates from 30 to 72 h after birth according to the feeding method was different from that in Caucasian neonates.

Asian People↗
PubMed2001

Cerebral metabolism and regional cerebral blood flow during moderate systemic cooling in newborn piglets.

BACKGROUND: Clinical trials of hypothermic therapy in asphyxiated infants have started recently. However, clinical studies have been delayed by the difficulty in selecting infants with a bad neurological prognosis and by the concern regarding adverse effects of hypothermia. The purpose of this study is to examine the effects of systemic cooling on cerebral metabolism (CMR) and the regional cerebral blood flow (rCBF) in newborn piglets. METHODS: The rCBF in the seven parts of the brain were measured with colored microspheres. The blood samples for the measurement of cerebral oxygen consumption (CMRO2) and cerebral glucose consumption (CMRglc) was collected from the umbilical artery and the superior sagittal sinus. RESULTS: Reductions of cerebral cortex temperature to 32 degrees C decreased blood flow in all brain regions. In particular, blood flow in the brainstem decreased more significantly than in any other region. The total cerebral blood flow (CBF), CMRO2 and CMRglc, respectively, decreased to 32.3+/-3.9 mL/100 g per min, 2.8+/-1.0 mLO2/100 g per min and 22+/-12 mmol/100 g per min at 32 degrees C (41, 53 and 46% of the initial value). The CBF decreased in parallel with CMRO2 and CMRglc down to 35 degrees C, but CBF decreased to a greater extent than CMRO2 and CMRglc at below 35 degrees C. CONCLUSIONS: The indication of hypothermic therapy and the degree of cooling have to be performed very carefully. Systemic cooling is especially dangerous for the total asphyxiated infants who might have damage to the brainstem because the blood flow in the brainstem has significantly decreased during hypothermia.

Animals↗
PubMed2001

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm.

It is well known that chronic inflammatory conditions involving the bile ducts predispose to the development of bile duct carcinoma, although the relationship between chronic inflammation and malignant transformation is unclear. In this study, by combining immunohistochemistry and computer imaging techniques, we quantified and compared the cyclooxygenase-2 (COX-2) protein expression levels of epithelial cells according with their histopathological backgrounds. This technique revealed that the highest levels of COX-2 were expressed in bile duct carcinoma cells, mainly in cytoplasm, and the expression pattern was homogenous and abundant. Moderate levels of COX-2 protein expression were also observed in noncancerous epithelial cells with inflammatory reaction, but the staining intensity was heterogeneous among the positive cells exhibiting inflammation. In contrast, only scattered weak reactivity of COX-2 protein was observed in the noncancerous bile duct epithelial cells without inflammatory reaction. Moreover, bile duct epithelial cells in primary sclerosing cholangitis (PSC) showed very strong expression of COX-2 protein, that was comparable with carcinoma cells. On the other hand, primary biliary cirrhosis (PBC) epithelial cells showed moderate levels of COX-2 expression. In addition, specific COX-2 inhibitors, JTE-522 and NS-398, directly inhibited the growth of 4 bile duct carcinoma and 1 gall bladder carcinoma cell lines that expressed COX-2 protein, in vitro. These data suggest that COX-2 expression might regulate carcinogenesis of bile duct epithelial cells in inflammatory regions and tumor progression in this cancer. The data also suggest that COX-2 selective inhibitors might have therapeutic effects not only on bile duct carcinoma, but other hepatobiliary carcinomas.

Animals↗