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Biomedical subjects

Y Kono

Publications and source records attributed to Y Kono.

At least 37 records · Page 2Linked to original sources
PubMed2001

Risk factors for persistence of pulmonary arterial branch stenosis in neonates and young infants.

BACKGROUND: Pulmonary arterial branch stenosis (PBS) in neonates is considered to be transient. However, PBS has been found not only in neonates, but also in young infants. Among these patients, we encountered several patients whose PBS was still present after the age of 1 year. METHODS: To clarify the natural history of PBS in neonates and young infants, we retrospectively reviewed the records of 103 patients diagnosed with PBS in the neonatal period and early infancy. RESULTS: The PBS findings were improved in all patients. Pulmonary arterial branch stenosis disappeared in 94 patients by the age of 1 year (group A), but persisted after I year of age in nine patients (group B). Group B patients had a significantly lower mean birth weight and greater deltavelocity (the difference in the peak flow velocity between the main pulmonary artery and stenotic branch) at diagnosis than group A patients. Incidences of low birth weight (< 2,500 g) and deltavelocity above 1.2 m/s were significantly higher in group B than group A patients. There was no significant difference in the frequency of premature infants (gestational age < 36 weeks) between the groups, suggesting that intrauterine growth retardation may be related to developmental abnormalities of the pulmonary arterial branch. CONCLUSIONS: All cases of PBS in neonates and young infants were improved. However, PBS persisted in some patients after the age of 1 year. Low birth weight and deltavelocity above 1.2 m/s are risk factors for persistent PBS. Pulmonary arterial branch stenosis was not present after the age of 1 year in 62 of 63 patients without either of these risk factors.

Age Factors↗
PubMed2001

Effect of lactational exposure to 1,2,3,4- tetrachlorodibenzo-p-dioxin on cytochrome P-450 1A1 mRNA in the neonatal rat liver: quantitative analysis by the competitive RT-PCR method.

BACKGROUND AND METHODS: The aim of this study was to assess the effect of lactational exposure to dioxins in neonates on the cytochrome P450 1A1 (CYP1A1) induction in the level of gene expression. Maternal rats were treated with a single dose of 50 or 100 micromol/kg 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD), a low potent congener of dioxins, on the first day post-partum (day 1). Induction of CYP1A1 mRNA expression was quantitatively analyzed by the competitive reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: The CYP1A1 mRNA was detectable at extremely low amounts in the liver of control neonates and mothers. The mRNA ratios of CYP1A1 to beta-actin in neonates were dose-dependently increased by the treatment of 1,2,3,4-TCDD of their mothers. Its peak occurred on day 6 and was sustained at the same level on day 10. Increases of the ratio with 100 micromol/kg 1,2,3,4-TCDD on day 2, 6 and 10 were 26-, 40- and 40-fold of the appropriate controls, respectively. These levels paralleled the activity of ethoxyresorufin-o-deethylase, representing CYP1A mediated monooxygenase. In the mother, the mRNA ratio was increased only to threefold of the control, 10 days after treatment. CONCLUSION: Current RT-PCR procedure enabled to assess both constitutive and induced levels of CYP1A1 mRNA in the neonatal rat livers. Although the dose of 1,2,3,4-TCDD selected in this study was about 5000 times higher than the daily intake of dioxins in breast-fed infants, CYP1A1 mRNA was highly induced for a longer period of time in neonatal rats receiving 1,2,3,4-TCDD via lactation than the treated maternal rats.

Actins↗
PubMed2001

Infantile cholestatic jaundice associated with adult-onset type II citrullinemia.

Adult-onset type II citrullinemia, characterized by a liver-specific argininosuccinate synthetase deficiency, is caused by a deficiency of citrin that is encoded by the SLC25A13 gene. Three patients with infantile cholestatic jaundice were found to have mutations of the SLC25A13 gene. Adult-onset type II citrullinemia may be associated with infantile cholestatic disease.

Biopsy↗
PubMed2001

Effects of testosterone on production of perivitelline membrane glycoprotein ZPC by granulosa cells of Japanese quail (Coturnix japonica).

Avian perivitelline membrane, an investment homologous to the zona pellucida of mammalian oocytes, is composed of at least two glycoproteins. Previous studies have indicated that one of the components, a glycoprotein homologous to mammalian ZPC, is produced and secreted by the granulosa cells of developing follicles of the chicken ovary. In the present study, we evaluated the expression and regulation of ZPC in Japanese quail (Coturnix japonica) granulosa cells both in vivo and in vitro. Western blot analysis of the SDS-solubilized granulosa layer using anti-quail ZPC antiserum showed that the amount of ZPC increased in parallel with follicular development. Northern blot analysis of total RNA using cDNA of quail ZPC showed that the increase in mRNA expression was also correlated with follicular development. To investigate the regulation of ZPC production, the granulosa cells were cultured in a medium containing steroid hormones such as progesterone, estradiol-17ss, or testosterone. By measuring ZPC protein and mRNA with Western and Northern blot analyses, respectively, we found that addition of testosterone maintained ZPC contents in the culture of the granulosa cells, and that ZPC mRNA expression was high in the culture with testosterone compared to the control. These results suggest that testosterone stimulates ZPC protein production at the gene transcription level.

Animals↗
PubMed2001

Effect of cicletanine on the nitric oxide pathway in human umbilical vein endothelial cells.

The purpose of this study was to evaluate the effects of cicletanine, a slightly diuretic antihypertensive drug, on human vascular endothelial cells with regard to nitric oxide, intracellular calcium concentration ([Ca2+]i), cyclic nucleotide, inositol 1,4,5-trisphosphate (IP3), and prostacyclin generation. Primary cultured human umbilical vein endothelial cells were used in this study. [Ca2+]i was measured by fura-2/AM. Cyclic adenosine monophosphate (AMP), cyclic guanosine monophosphate (GMP), IP3, and prostacyclin were measured by radioimmunoassay. Nitric oxide was measured by the Griess method. Cicletanine had no effect on [Ca2+]i. Cicletanine (10(-6)-10(-4) M) increased cyclic GMP but decreased prostacyclin generation. Cicletanine had no stimulating effect on cyclic AMP or IP3 generation. IP3 increased 45Ca release from storage sites. Cicletanine decreased prostacyclin generation via increase in cyclic GMP. Cicletanine had no stimulating effect on nitrogen oxides for 2 h after incubation but increased it after 3-24 h. Pretreatment with L-N(G)-monomethyl-arginine (L-NMMA) prevented this increase. The inhibitory effect of L-NMMA was prevented by pretreatment with L-arginine. These results indicate that nitric oxide and cyclic GMP may contribute to the antihypertensive action of cicletanine.

Antihypertensive Agents↗
PubMed2001

Glucosylceramide synthesis inhibitors block pharmacologically induced dispersal of the Golgi and anterograde membrane flow from the endoplasmic reticulum: implication of sphingolipid metabolism in maintenance of the Golgi architecture and anterograde membrane flow.

PDMP (D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) and PPMP (D,L-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol), inhibitors of glucosylceramide synthesis, blocked brefeldin A (BFA)- and nordihydroguaiaretic acid-induced dispersal of the Golgi and trans Golgi network, and Golgi-derived vesicles were retained in the juxtanuclear region. PDMP and PPMP did not stabilize microtubules but blocked nocodazole-induced extensive fragmentation and dispersal of the Golgi, and large Golgi vesicles were retained in the juxtanuclear region. PPMP is a stronger inhibitor of glucosylceramide synthesis than PDMP, but PDMP showed a stronger activity against BFA-induced retrograde membrane flow. However, PPMP showed a stronger activity for Golgi disruption and inhibition of anterograde trafficking from the endoplasmic reticulum, and rebuilding of the Golgi architecture. Cumulatively, these results suggest that sphingolipid metabolism is implicated in maintenance of the Golgi architecture and anterograde membrane flow from the endoplasmic reticulum but not in Golgi dispersal induced by BFA.

Adenosine Triphosphate↗
PubMed2001

Characterization of clofibrate-induced retrograde Golgi membrane movement to the endoplasmic reticulum: clofibrate distinguishes the Golgi from the trans Golgi network.

Clofibrate-induced retrograde Golgi membrane movement was blocked or retarded when NRK cells were treated with sodium azide/2-deoxyglucose, nocodazole, taxol, and destruxin B, indicating that it depends on energy, and the dynamic state of microtubules, and being acidic or vacuolar-type ATPase function. PDMP and phospholipase A2 inhibitors also blocked it. These characteristics are similar to those of brefeldin A (BFA) and nordihydroguaiaretic acid (NDGA), inducers of retrograde Golgi membrane movement. However, clofibrate was distinguished from BFA in that BFA action was insensitive to phospholipase A2 inhibitors and from NDGA in that NDGA stabilized microtubules against nocodazole and its action was almost insensitive to taxol. The trans Golgi network (TGN) was resistant to clofibrate, while BFA and NDGA dispersed it. To our knowledge, clofibrate is the first drug to show such different effects on the Golgi and TGN and, therefore, is expected to be a useful tool to distinguish their architecture and/or membrane dynamics.

Adenosine Triphosphatases↗
PubMed2001

Genetic variation and correlations among responses to five insecticides within natural populations of Drosophila melanogaster (Diptera: Drosophilidae).

To investigate the genetic basis of cross-resistance to insecticides, natural populations of Drosophila melanogaster (Meigen) were first collected from four different locations in Japan. After 10-80 isofemale lines of each population had been established in a laboratory, the susceptibility of each line to each of the insecticides permethrin, malathion, fenitrothion, prothiophos, and DDT was examined. Broad ranges of continuous variation in susceptibility to all the chemicals were observed within each natural population as a whole. In addition, highly significant correlations among responses to organophosphates were observed. However, based on the coefficients of determination, about less than half of variation in responses to one insecticide could be explained by variation in responses to another insecticide, suggesting that not only a common resistance factor but also other factors could be involved in a natural population. Genetic analyses by using resistant and susceptible inbred lines from the same natural population demonstrated that resistance to organophosphates in some resistant lines could be due to a single or tightly linked factors, and that resistance in the other line may be due to more than one major factor. These observations could suggest that several resistance factors may be involved within each natural population, and that some of major factors could contribute to correlations among responses to organophosphates. These major factors could then contribute to the broad ranges of continuous variation observed at the level of the populations.

Animals↗
PubMed2001

Fipronil modulation of gamma-aminobutyric acid(A) receptors in rat dorsal root ganglion neurons.

The gamma-aminobutyric acid (GABA) receptor is an important site of action of a variety of chemicals, including barbiturates, benzodiazepines, picrotoxin, bicuculline, general anesthetics, alcohols, and certain insecticides. Fipronil is the first phenylpyrazole insecticide introduced for pest control. It is effective against some insects that have become resistant to the existing insecticides. To elucidate the mechanism of fipronil interaction with the mammalian GABA system, whole-cell patch-clamp experiments were performed using rat dorsal root ganglion neurons in primary culture. Fipronil suppressed the GABA-induced whole-cell currents reversibly in both closed and activated states. The IC(50) values and Hill coefficients for fipronil block of the GABA(A) receptor were estimated to be 1.66 +/- 0.18 microM and 1.23 +/- 0.14 for the closed receptor, respectively, and 1.61 +/- 0.14 microM and 0.96 +/- 0.06 for the activated receptor, respectively. The association rate and dissociation rate constants of fipronil effect were estimated to be 673 +/- 220 M(-1) s(-1) and 0.018 +/- 0.0035 s(-1) for the closed GABA(A) receptor, respectively, and 6600 +/- 380 M(-1) s(-1) and 0.11 +/- 0.0054 s(-1) for the activated GABA(A) receptor, respectively. Thus, both the association and dissociation rate constants of fipronil for the activated GABA(A) receptor are approximately 10 times as large as those for the closed receptor. Experiments with coapplication of fipronil and picrotoxinin indicated that they did not compete for the same binding site to block the receptor. It is concluded that although fipronil binds to the GABA(A) receptor without activation, channel opening facilitates fipronil binding to and unbinding from the receptor.

Animals↗
PubMed2000

Replication ability in vitro and in vivo of equine infectious anemia virus avirulent Japanese strain.

An attenuated equine infectious anemia virus (EIAV), V26, was previously prepared by 50 passages of the Japanese virulent strain V70 in primary horse macrophage culture. The horses inoculated with this V26 virus were shown to raise neutralizing antibodies against V70 without any viremia. Here, we investigated the in vitro and in vivo replication ability of V26. Comparison of the long-terminal repeat (LTR) sequences between V26 and V70 revealed a large insertion within the LTR U3 hypervariable region of V26. V26 with the mutation in the LTR showed much higher promoter activity in vitro than V70. This is consistent with the much higher replication rate of V26 in horse primary macrophage cultures compared with V70. In sharp contrast, we failed to identify the V26-specific LTR sequence by PCR, at least in sequential samples of plasma or peripheral blood mononuclear cells derived from three horses until day 62 after V26 inoculation. In contrast, antibody responses to EIAV were observed in all horses. The results suggest that the replication ability of V26 in vivo is extremely low. When one of the horses was subsequently challenged with cell-associated V70, it was found that the horse became PCR positive for EIAV. There was no LTR mutation in EIAV genome in samples periodically prepared from the V70-challenged horse. Thus it was suggested that the LTR mutation in EIAV, which occurs during serial passage in vitro, affects EIAV replication in vitro and in vivo.

Animals↗
PubMed2000

The properties of the Kir6.1-6.2 tandem channel co-expressed with SUR2A.

Functional ATP-sensitive K (KATP) channels have an octameric subunit structure with four pore-forming subunits (Kir6.x) and four sulfonylurea receptors (SURx). In the present study, the properties of the heteromeric KATP channel whose pore subunits are composed of Kir6.1 and Kir6.2 were examined using a heterologous expression system. In COS7 cells co-transfected with Kir6.1, Kir6.2 and SUR2A at a ratio of 1:1:2, KATP channels showed various unitary conductances between those of Kir6.1/SUR2A (33.6+/-4.2 pS) and Kir6.2/ SUR2A (67.1+/-1.6 pS). Kir6.1-6.2 tandem protein, constructed by fusing the C-terminus of Kir6.1 to the N-terminus of Kir6.2 with a ten glutamine linker sequence, also formed a channel with an intermediate conductance (58.9+/-1.5 pS). Kir6.2 and Kir6.1-6.2 showed similar sensitivity to ATP4-: half-maximal inhibition (IC50) was obtained at 14.1+/-12.8 microM and 17.6+/-9.6 microM, respectively. In the presence of Mg2+, Kir6. 1-6.2 was significantly less sensitive than Kir6.2 to MgATP (IC50=95.5+/-49.6 microM versus 18.9+/-5.0 microM). These results suggest that Kir6.1 and Kir6.2 are endowed with the potential to form a heteromeric KATP channel, which has a low sensitivity to MgATP.

Adenosine Triphosphate↗
PubMed2000

Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates K(ATP) channels in guinea-pig ventricular myocytes.

Sarcolemmal adenosine 5'-triphosphate-sensitive K+ channels (K(ATP)) are dramatically up-regulated by a membrane phospholipid, phosphatidyl-inositol-4,5-bisphosphate (PIP2). During ischaemia, L-palmitoylcarnitine (L-PC), a fatty acid metabolite, accumulates in the sarcolemma and deranges the membrane lipid environment. We therefore investigated whether alteration of the membrane lipid environment by L-PC modulates the K(ATP) channel activity in inside-out patches from guinea-pig ventricular myocytes. L-PC (1 microM) inhibited KATP channel activity, without affecting the single channel conductance, through interaction with Kir6.2. L-PC simultaneously enhanced the ATP sensitivity of the channel [concentration for half-maximal inhibition (IC50) fell from 62.0+/-2.7 to 30.3+/-5.5 microM]. In contrast, PIP2 attenuated the ATP sensitivity (IC50 343.6+/-54.4 microM) and restored Ca2+-induced inactivation of KATP channels (94.1+/-13.7% of the control current immediately before the Ca2+-induced inactivation). Pretreatment of the patch membrane with 1 microM L-PC, however, reduced the magnitude of the PIP2-induced recovery to 22.7+/-6.3% of the control (P<0.01 vs. 94.1+/-13.7% in the absence of L-PC). Conversely, after the PIP2-induced recovery, L-PC's inhibitory action was attenuated, but L-PC partly reversed the PIP2-mediated decrease in the ATP sensitivity (IC50 fell from 310+/-19.2 to 93.1+/-9.8 microM). Thus, interaction between L-PC and PIP2 in the plasma membrane appears to regulate K(ATP) channels.

Adenosine Triphosphate↗
PubMed2000

Comparison of long-term variability for standard and short-wavelength automated perimetry in stable glaucoma patients.

PURPOSE: To quantify and compare, on a point-by-point basis, the long-term variability of standard and short-wavelength automated perimetry in a group of stable glaucoma patients. METHODS: From a group of 53 glaucoma patients experienced in visual field testing, we identified one eye, randomly chosen, from each of 25 glaucoma patients whose condition was found to be stable, based on both standard and short-wavelength automated perimetry visual field criteria. On each of three visits during a period of up to 3 months, each patient performed one standard and one short-wavelength automated perimetry 24-2 visual field in a random order on a Humphrey visual field analyzer. The long-term variability (also referred to as test-retest variability) was defined as the SD of the three threshold decibel values at each test location. The long-term variability for each test point (mean +/- SD) was determined separately for both standard visual fields and short-wavelength automated perimetry. RESULTS: With all 52 test locations of the 24-2 field averaged, the global long-term variability, mean (+/- SD) for standard visual fields and short-wavelength automated perimetry was 2.37 +/- 2.03 dB (95% confidence interval, 2.26-2.48 dB) and 2.92 +/- 2.03 dB (95% confidence interval, 2.81-3.03 dB), respectively (P <.0001). In 16 of the 52 visual field locations, long-term variability on short-wavelength automated perimetry was significantly higher than long-term variability on standard visual fields. In addition, the long-term variability increased with greater distance from the point of fixation for both standard visual fields and short-wavelength automated perimetry. The long-term variability decreased closer to fixation, more for standard visual fields than for short-wavelength automated perimetry. CONCLUSIONS: In a group of stable glaucoma patients, mean long-term variability was 0.55 dB higher for short-wavelength automated perimetry than for standard visual fields. This needs to be taken into consideration when serial visual fields are evaluated for change.

Adult↗
PubMed2000

Mutations occurring during serial passage of Japanese equine infectious anemia virus in primary horse macrophages.

An attenuated equine infectious anemia virus (EIAV), named V26, was previously obtained after 50 passages of the Japanese virulent strain V70 in primary macrophage culture. To clarify the differences between both viruses, their full-length sequences were determined. There were higher mutations in S2 (6.15% amino acid difference) and LTR (10.7% nucleotide difference). The presumed initiation codon of the S2 gene was absent from the sequence of V26. There was a large insertion within the long-terminal repeat (LTR) U3 hypervariable region of V26. In addition, there were minor mutations in gag (1.22% amino acid difference), pol (1.05% amino acid difference) and env (1. 65% amino acid difference) regions, but no mutation in tat region. No mutations were observed in the principal neutralizing domain in the gp90. Thus, the mutations in the S2 and LTR might be the major target sites of mutation in EIAV during serial passages in vitro.

Amino Acid Sequence↗
PubMed2000

Absence of protein polymorphism attributable to insecticide-insensitivity of acetylcholinesterase in the green rice leafhopper, Nephotettix cincticeps.

The cDNA sequence of acetylcholinesterase (AChE) from the green rice leafhopper, Nephotettix cincticeps, was amplified, based on conserved peptide sequences of AChEs. A 2.3 kb contiguous sequence, containing an ORF encoding an AChE precursor with 677 amino acid residues was obtained. The deduced protein sequence showed the most similarity to that of AChE in the Colorado potato beetle, having common features in the primary AChE structure. cDNA sequences of individual leafhoppers from an insecticide susceptible strain and the resistant strain Nakagawara, whose methylcarbamate-insensitive AChEs show 10(2) or more I(50) ratio for propoxur, were compared. No fixed inter-strain difference was identified in the protein sequence, though amino acid substitution polymorphism was found at one position in the susceptible strain. Insecticide-insensitivity of leafhopper AChE does not result from changes in the protein primary structure that is encoded by the AChE gene sequence isolated in this study.

Acetylcholinesterase↗
PubMed2000

Comparative study between pointwise and ranked threshold distribution analyses of change in serial fields for short-wavelength automated perimetry.

PURPOSE: To assess the validity of ranked threshold distribution (RTD) analysis for longitudinal evaluation of short-wavelength automated perimetry (SWAP). METHODS: Eighty-five patients with glaucoma and with three or more SWAP results were examined. An additional 20 patients with glaucoma and 3 stable standard automated visual fields and 3 stable SWAP fields were assessed to calculate variability. An RTD curve was created. For RTD analysis and pointwise analysis, values that decreased more than the SWAP variability were considered to have worsened. Using pointwise analysis, four groups were defined: no change (without any 2 contiguous points decreasing in threshold); focal change (at least 2 contiguous points with decreased thresholds in either hemifield); diffuse change (more than 50% of the entire 52 locations with significant decrease in thresholds); and focal and diffuse change (less than 50%, but crossing both hemifields). RESULTS: Using pointwise analysis, 32 (37.6%) patients did not change; 23 (27.1%) patients had focal worsening; 8 (9.4%) patients had diffuse worsening; and 22 (25.9%) patients had focal and diffuse worsening. Significant differences were found among the groups in the number of deteriorating locations (P < 0.0001, analysis of variance). The ranges of deteriorating locations identified by RTD analysis for focal change and diffuse change did not overlap. A significant correlation was found between the numbers of locations with decreased threshold by both analyzes (r2 = 0.83, P < 0.0001). CONCLUSION: For evaluation of possible SWAP progression, RTD analysis is closely related with pointwise analysis and is useful for visualizing a diffuse component of change in the field.

Adult↗