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I Kondo

Publications and source records attributed to I Kondo.

At least 55 records · Page 3Linked to original sources
PubMed2000

Protein kinase C potentiates capacitative Ca2+ entry that links to steroidogenesis in bovine adrenocortical cells.

I investigated the role of protein kinase C (PKC) in regulation of the capacitative Ca2+ entry and steroidogenesis in bovine adrenocortical (BA) cells. Thapsigargin (TG)-treatment depleted intracellular Ca2+ stores followed by induction of Ca2+ influx from the extracellular pool and also increasing of Mn2+ influx as an indicator of divalent cation influx in BA cells. Calphostin C, a PKC inhibitor, inhibited the TG-induced [Ca2+]i elevation dose-dependently (0.1-1 microM) and attenuated Mn2+ entry. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, potentiated the elevation of [Ca2+]i and enhanced Mn2+ entry by TG treatment. These results suggest that PKC may modulate capacitative Ca2+ entry in BA cells. In the presence of extracellular Ca2+, TG enhanced cortisol production in BA cells. Calphostin C attenuated the TG-induced steroidogenesis dose-dependently (0.25-1 microM). PMA enhanced the steroidogenesis dose-dependently (1-100 nM). These results suggested that PKC may have a modulatory effect on the capacitative Ca2+ entry that links to steroidogenesis in BA cells.

Adenosine Triphosphate↗
PubMed2000

Capacitative calcium entry is involved in steroidogenesis in bovine adrenocortical fasciculata cells.

Capacitative Ca(2+) entry into bovine adrenocortical fasciculata cells was investigated by using the mobilization of intracellular Ca(2+) concentration ([Ca(2+)](i)) and Ca(2+)-induced steroidogenesis as the indicators. Bovine adrenocortical fasciculata cells on a glass coverslip were loaded with fura-2. The [Ca(2+)](i) mobilization was detected by a change of fura-2 fluorescence intensity. In the intracellular Ca(2+) store depleted cells, the addition of Ca(2+) to the incubation medium elicited a marked and sustained increase in [Ca(2+)](i). In the intracellular Ca(2+) store non-depleted cells, the addition of thapsigargin, an endoplasmic reticulum Ca(2+)-ATPase inhibitor, in the absence of extracellular Ca(2+), induced a slight and transient increase in [Ca(2+)](i), but an extensive and sustained increase in [Ca(2+)](i) was obtained by adding Ca(2+) to the incubation medium after the thapsigargin treatment. The sustained increase induced by thapsigargin was not inhibited by nifedipine, but was inhibited by Zn(2+) and Cd(2+) in a concentration-dependent manner. The effect of Zn(2+) was more potent than that of Cd(2+). Thapsigargin stimulated steroidogenesis in the presence of extracellular Ca(2+). The steroidogenic effect of thapsigargin was inhibited by Zn(2+) and Cd(2+) but not by nifedipine. These results suggest that there is, in bovine adrenocortical fasciculata cells, a steroidogenesis-linked Ca(2+) entry process other than that involving voltage-operated Ca(2+) channels and that the process might be capacitative Ca(2+) entry.

Analysis of Variance↗
PubMed2000

[Nation-wide survey on hemimegalencephaly in Japan].

We report here 38 Japanese patients with hemimegalencephaly collected by a national survey study. All the patients were sporadic. There was no familial occurrence or sex difference. Some patients had basic diseases: hypomelanosis of Ito in 3 cases and organic nevus syndromes in 8. Most patients had hemiparesis, and 11 were bed-ridden. All except for 3 patients had mental retardation, being profound in half of them. There was no correlation between the side of hemimegalencephaly and clinical symptoms. All patients had epileptic seizures, which first appeared within 24 hours after birth in 4 cases, within 7 days in 7, within a month in 2, within 6 months in 10, and within a year in 4. Antiepileptic drugs were not very effective for controlling seizures. In 7 patients, however, functional hemispherectomy resulted in seizure control and improved development. The patients whose epileptic symptom occurred earlier tended to be more severe in clinical symptoms.

Adolescent↗
PubMed2000

[5'-DFUR chemoprophylaxis in superficial bladder cancer. Kanagawa Urology 5'-DFUR Study Group].

5'-Deoxy-5-fluorouridine (5'-DFUR), an oral fluorinated pyrimidine carbamate, is widely used in patients with gastrointestinal and breast cancers because of its effectiveness. However, in bladder cancer, response rates have only been reported in Phase II clinical trials. Therefore, we conducted a prospective randomized trial to investigate chemoprophylactic effect of 5'-DFUR against recurrence of superficial bladder cancer after transurethral bladder tumor resection (TUR-Bt). The subjects were grouped as follows: 1) 5'-DFUR group (n = 31), received 600 mg/day of 5'-DFUR starting 2-3 weeks after TUR-Bt for 2 years; and 2) control group (n = 31) received no 5'-DFUR. Although there was no significant difference between groups, the cumulative recurrence rates was more favorable in the 5'-DFUR group (p = 0.256) than in the controls. Results according to cancer factors showed that, in patients with G2 based on grading, those in the 5'-DFUR group tended to have a lower recurrence rate than the control group (p = 0.070). There was a 40% incidence of adverse drug reactions (12/30 patients), primarily slight gastrointestinal symptoms which disappeared or improved with drug discontinuation. The results of the present study suggest that 5'-DFUR might be the choice of treatment to prevent recurrence of superficial bladder cancer.

Adult↗
PubMed2000

Inhibition of disease flare with diethylstilbestrol diphosphate and chlormadinone acetate administration for two weeks prior to slow-releasing leuprolide acetate in prostatic cancer patients.

To determine whether administration of estrogen or gestagen prior to luteinizing hormone-releasing hormone (LH-RH) agonist prevents disease flare in prostate cancer patients, we pretreated the patients with either diethylstilbestrol diphosphate (DES-P) 300 mg daily (N = 17) or chlormadinone acetate (CMA) 100 mg daily (N = 16) or none (N = 16) for two weeks before the initial injection of leuprolide acetate (L). Blood samples for prostatic specific antigen (PSA), testosterone (T), and luteinizing hormone were collected before CMA and DES-P administration, before and at 2, 7, 14, 28, 56, and 84 days after the first administration of leuprolide. The treatment with DES-P and CMA prior to LH-RH agonist induced an early decline of PSA. The mean PSA level showed no significant secondary rise in those patients with pretreatment after L administration. In the patients pretreated with DES-P or CMA, the mean serum T level never exceeded the pretreatment baseline after L administration. On the other hand, in the patients without DES-P or CMA, both serum T and PSA levels increased after the first administration of L. These results clearly demonstrate that pretreatment with DES-P 300 mg daily or CMA 100 mg daily for 2 weeks is quite effective to prevent disease flare after the first administration of L in patients with prostatic cancer.

Aged↗
PubMed2000

[Cohen syndrome].

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Abnormalities, Multiple↗
PubMed2000

[Rett syndrome].

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Chromosomal Proteins, Non-Histone↗
PubMed1999

Genetic localization of the familial adult myoclonic epilepsy (FAME) gene to chromosome 8q24.

OBJECTIVE: To identify the genetic locus for the familial adult myoclonic epilepsy (FAME) gene. BACKGROUND: Idiopathic generalized epilepsy (IGE) represents a collection of disorders in which affected individuals present with recurring seizures that have diffuse onset on EEG. These individuals have no known structural cerebral lesions or other identifiable etiology. IGE accounts for approximately 40% of all epilepsies. FAME is a type of IGE characterized by autosomal dominant inheritance, adult onset, varying degrees of myoclonus in the limbs, rare tonic-clonic seizures, and a benign course. METHODS: We investigated four previously reported Japanese kindreds and performed a genome-wide screen with genetic linkage analysis. RESULTS: Clinical characterization and sampling of 30 individuals in four families revealed that 21 had the FAME phenotype. We defined a 4.6-cM region on chromosome 8q24 (maximum lod score of 4.86 at theta = 0) that contains the FAME gene. CONCLUSIONS: The identification and characterization of the FAME gene allows us to better understand the molecular basis of FAME. Such knowledge may provide clues to understanding the molecular basis of the clinically similar, and more common, juvenile myoclonic epilepsies, and other generalized seizure disorders that have thus far eluded genetic approaches.

Adult↗
PubMed1999

An AciI polymorphism in the 3' untranslated region of the human phosphomannomutase 2 (PMM2) gene.

We found an AciI polymorphism in the 3' untranslated region of the phosphomannomutase 2 (PMM2) gene located at 16p13. A G-to-C transition at nucleotide position 96 bp downstream from the PMM2 stop codon was detected in polymerase chain reaction (PCR) products after AciI digestion. The heterozygosity of the polymorphic alleles was 0.375 in a Japanese population. This polymorphism is useful for genetic analysis in patients with carbohydrate-deficient glycoprotein syndromes, of which there are four subtypes.

3' Untranslated Regions↗
PubMed1999

Enhancement of ultrasound-accelerated thrombolysis by echo contrast agents: dependence on microbubble structure.

The combination of ultrasound (US) exposure and ultrasound contrast agent (UCA) further increases the amount of drug-mediated thrombolysis. The aim of this study was to examine the efficacy of the combination of US and UCA on tissue plasminogen activator (tPA) thrombolysis, and the dependence on the microbubble structure. A catheter-type transducer capable of US emission (10 MHz, spatial peak temporal average intensity = 1.02 W/cm2 and peak negative pressure = 0.33 MPa) in the continuous-wave mode was employed. In 28 artificial white thrombi, serial changes in acoustic properties monitored by echography and histopathology during the tPA-mediated thrombolysis were analyzed. The thrombi were assorted to 4 groups; UCA nontreated (Control), sonicated albumin (A)-, SH-U508A (SH)- and dodecafluoropentane emulsion (DDFP)-treated groups. Persistence of microbubble opacification and thrombus weight were also measured. After the sample was suspended in a beaker with tPA (8000U) and 100 mL of saline, the UCA was administered and the mixture exposed to US for 10 min. Weight reduction of the thrombus was greatest in the DDFP Group (-49 +/- 8%), and that in the A Group (-8 +/- 5%) was not significantly different from that in the Control Group (-5 +/- 1%). The persistence of the microbubbles expressed as the decay of the time-intensity curve, was longest in the DDFP Group. The echo intensity of the superficial layer of the thrombus exposed to US was high and weight loss was marked. Multiple cavity formation was observed histopathologically. The stability of the microbubbles was an important factor of the US and UCA enhancement effect on tPA-mediated thrombolysis. This combination therapy has potential for clinical application in patients with thrombotic arterial and venous occlusion and left arterial thrombus.

Adult↗
PubMed1999

Missense mutations in the phosphomannomutase 2 gene of two Japanese siblings with carbohydrate-deficient glycoprotein syndrome type I.

Carbohydrate-deficient glycoprotein syndrome type I (CDG1) is an autosomal recessive disorder characterized by severe nervous system involvement and a carbohydrate moiety deficiency in N-linked glycoproteins. Clinical symptoms are psychomotor retardation, stroke-like episodes or hemorrhagic episodes, hepatic dysfunction, polyneuropathy, and cerebellar ataxia. Marked atrophy of the cerebellar hemispheres and pons is recognizable on CT scan or MRI. CDGI has been mapped to human chromosome 16p by linkage studies. Recently, missense mutations in the gene for phosphomannomutase (PMM2) have been detected in Caucasian patients with CDG1. We studied DNA mutations in PMM2 in a Japanese family with CDG1. DNA sequencing of PMM2 in the siblings showed missense mutations of maternal origin in exon 5 and of paternal origin in exon 8. No such mutations were detected in 50 unrelated healthy Japanese. These findings suggest that the PMM2 is responsible for CDG1 in the Japanese as well as in Caucasians, and CDG1 may be the diagnosis in OPCA of neonatal onset, more often than currently thought.

Adolescent↗
PubMed1999

Missense mutations in phosphomannomutase 2 gene in two Japanese families with carbohydrate-deficient glycoprotein syndrome type 1.

Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1) (MIM: 212065) is an autosomal recessive disorder with psychomotor retardation, strokelike episodes, ataxia, and olivopontocerebellar atrophy (OPCA) of neonatal onset. Recently, DNA substitutions in a gene for phosphomannomutase 2 (PMM2), mapped to 16p13, were identified in patients with CDG1. Biochemical findings in previously reported Japanese patients with CDG1 were slightly different from those of Caucasians, suggesting genetic heterogeneity of CDG1 in Japanese patients. We investigated the DNA sequence of PMM2 in two unrelated Japanese families with CDG1. Missense mutations in exon 5 (Phe144Leu) and exon 8 (Tyr229Ser, Arg238Pro) of the PMM2 gene were present in two families, but they were not present in 72 unrelated healthy Japanese individuals. One of the missense mutations, Phe144Leu in exon 5, was common to two families with CDG1. Our findings confirm that mutations in the PMM2 gene account for at least some Japanese patients with CDG1 similar to that seen in Caucasians and that exons 5 and 8 are hot spots of mutations of CDG1 caused by the PMM2 gene.

Adolescent↗
PubMed1999

The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.

Citrullinaemia (CTLN) is an autosomal recessive disease caused by deficiency of argininosuccinate synthetase (ASS). Adult-onset type II citrullinaemia (CTLN2) is characterized by a liver-specific ASS deficiency with no abnormalities in hepatic ASS mRNA or the gene ASS (refs 1-17). CTLN2 patients (1/100,000 in Japan) suffer from a disturbance of consciousness and coma, and most die with cerebral edema within a few years of onset. CTLN2 differs from classical citrullinaemia (CTLN1, OMIM 215700) in that CTLN1 is neonatal or infantile in onset, with ASS enzyme defects (in all tissues) arising due to mutations in ASS on chromosome 9q34 (refs 18-21). We collected 118 CTLN2 families, and localized the CTLN2 locus to chromosome 7q21.3 by homozygosity mapping analysis of individuals from 18 consanguineous unions. Using positional cloning we identified a novel gene, SLC25A13, and found five different DNA sequence alterations that account for mutations in all consanguineous patients examined. SLC25A13 encodes a 3.4-kb transcript expressed most abundantly in liver. The protein encoded by SLC25A13, named citrin, is bipartite in structure, containing a mitochondrial carrier motif and four EF-hand domains, suggesting it is a calcium-dependent mitochondrial solute transporter with a role in urea cycle function.

Adult↗
PubMed1999

Methylene blue, a soluble guanylyl cyclase inhibitor, reduces the sevoflurane minimum alveolar anesthetic concentration and decreases the brain cyclic guanosine monophosphate content in rats.

UNLABELLED: The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signal pathway plays an important role in anesthetic and analgesic effects. We sought to determine the involvement of inhibition of soluble guanylyl cyclase (sGC) in the anesthetic mechanism and site of action of volatile anesthetics. We examined the effect of intracerebroventricular (ICV) administration of methylene blue (MB), a sGC inhibitor, on the minimum alveolar anesthetic concentration (MAC) of sevoflurane and the brain cGMP content in rats in vivo. We also investigated the effect of sevoflurane on NO-stimulated sGC activity in vitro. The rats were divided into three groups. After the ICV administration of MB, sevoflurane MAC and brain cGMP contents were measured in the first group and the second group, respectively. In the third group, brain cGMP contents were determined after sevoflurane anesthesia without the ICV administration of MB to examine the direct effect of sevoflurane on brain cGMP contents. MB significantly decreased sevoflurane MAC and brain cGMP content in a dose-dependent manner. Sevoflurane itself also dose-dependently decreased cGMP contents in brain in vivo and inhibited the NO-stimulated sGC activity in vitro. These results suggest that the inhibition of the NO-cGMP signal pathway at the sGC level could be involved in anesthetic or analgesic effects, and the inhibitory effect of sevoflurane on sGC would be one of the sites of action of this anesthetic. IMPLICATIONS: Because the nitric oxide-cyclic guanosine monophosphate signal pathway mediates nociception and the site of action of halogenated volatile anesthetics in uncertain, we examined the possible involvement of inhibition of soluble guanylyl cyclase in the anesthetic mechanism. The inhibitory effect of sevoflurane on soluble guanylyl cyclase could be one of sites of this anesthetic.

Anesthetics, Inhalation↗
PubMed1999

Biological activities of 1,1,6-trisubstituted indanes: beyond magainin 2.

MSI-78 is a peptide analog of naturally occurring magainin 2 isolated from the skin of Xenopus laevis. The peptide is known to have one of the strongest antibacterial activities in magainin 2 analogs against methicillin-resistant Staphylococcus aureus (MRSA). To find novel compounds superior to MSI-78, we have further designed, synthesizing 1,1-di(4-aminobutyl)-6-benzylindane (PM4) and 1,1-dibenzyl-6-(4-aminobutyl) indane (PM5), and tested their inhibitory ability of the growth of S. aureus. In an in vitro assay, PM4 showed the same antibacterial activity against the bacterium as MSI-78, and non-hemolytic activity against human red blood cells (RBCs) at the MIC (minimum inhibitory concentration) value, in contrast to the latter. On the other hand, PM5 showed stronger antibacterial activity than MSI-78, but being still accompanied with hemolysis at the MIC value. Otherwise, stronger decarboxylase activity for oxaloacetate was observed in PM5, rather than magainin 2 analogs or Oxaldie 1 as a control peptide, but not in PM4.

Amino Acid Sequence↗
PubMed1999

Histological observations and the process of ultrasound contrast agent enhancement of tissue plasminogen activator thrombolysis with ultrasound exposure.

Although the enhancement of tissue plasminogen activator (tPA) induced thrombolysis by ultrasound has been reported to be augmented by ultrasound contrast agents (UCA), few data exist regarding its process. The present study evaluated the effect of a galactose based UCA on the efficacy of ultrasonic enhancement of tPA thrombolysis and observed the serial changes in the acoustic property and histopathology. A catheter-type transducer capable of ultrasound emission in both continuous (CW) and pulsed wave (PW) was used. The tPA thrombolysis was studied in 30 artificial white thrombi, which were assigned to 4 study groups based on insonation modes and with and without UCA. Each sample was suspended in 100ml saline in a beaker. Five minutes after tPA (8000U) administration, ultrasound was applied for 10min. For the UCA-treated groups, UCA (0.25g) was added 5 min after the start of ultrasound exposure. The alteration of the thrombus was monitored with echography. Weight reduction of the thrombus was -25+/-6% in PW and -30+/-7% in CW, which was significantly enhanced by UCA treatment, 40+/-3% (p<0.005) in PW+UCA and -43+/-7% (p<0.005) in CW+UCA. The area of thrombus echo image minimally decreased with ultrasound alone (-12+/-6%: PW, -23+/-11%: CW). In the UCA groups, UCA induced a remarkable reduction of size (-36+/-3%: PW+UCA, -43+/-7%: CW+UCA) with a high-echo intensity in the superficial layer of the thrombus, where multiple cavity formation was observed by light microscope. UCA markedly enhanced the effect of ultrasound on tPA thrombolysis. The altered acoustic property and corresponding histological microcavity formation in the shallow layer within the thrombus suggests that UCA augmented infiltration of tPA into the thrombus.

Adult↗
PubMed1999

Analysis of spinocerebellar ataxia type 2 gene and haplotype analysis: (CCG)1-2 polymorphism and contribution to founder effect.

Spinocerebellar ataxia type 2 is a familial spinocerebellar ataxia with autosomal dominant inheritance. The gene responsible was recently cloned and this disorder was found to be the result of a CAG expansion in its open reading frame. We analysed 13 SCA2 patients in seven unrelated families in Gunma Prefecture, Japan. In four of the seven families, we detected CCG or CCGCCG interruptions in only the expanded alleles. Cosegregation of these polymorphisms with SCA2 patients was established within each family. Together with the results of haplotype analyses, we considered that at least two founders were present in our area and that these (CCG)1-2 polymorphisms may make analysis of founder effects easier. By sequencing analysis we found that although the number of the long CAG repeat varied in each subclone of expanded alleles, these polymorphisms did not change their configuration. This finding suggests that CCG or CCGCCG sequences are stable when surrounded by the long CAG repeat and a single CAG. Moreover, the presence of these polymorphisms may lead to miscounting the repeat size by conventional estimation using a size marker such as an M13 sequencing ladder. Therefore we should consider these polymorphisms and accurately determine the repeat size by sequencing.

Alleles↗