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Biomedical subjects

K Tachibana

Publications and source records attributed to K Tachibana.

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

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

Journal Article↗
PubMed2001

Regulation of Ras and Rho small G proteins by SHP-2.

BACKGROUND: Hepatocyte growth factor/scatter factor (HGF/SF) induces cell scattering through the tyrosine kinase-type HGF/SF receptor, c-Met. We have previously shown that SHP-2, a protein tyrosine phosphatase, positively regulates the HGF/SF-induced cell scattering through modulating the activity of Rho to form stress fibres and focal adhesions. To further investigate the role of SHP-2 in HGF/SF-induced cell scattering, we have now examined the effect of a dominant active mutant of SHP-2 (SHP-2-DA). RESULTS: Expression of SHP-2-DA markedly increased the formation of lamellipodia with ruffles, while it decreased the accumulation of E-cadherin and beta-catenin at cell-cell adhesion sites in MDCK cells. In addition, expression of SHP-2-DA markedly enhanced cell scattering of MDCK cells in response to HGF/SF. Expression of SHP-2-DA induced the activation of MAP kinase without HGF/SF stimulation, whereas an inhibitor of MEK partly reversed the SHP-2-DA-induced morphological phenotypes. Furthermore, expression of either a dominant-active mutant of Rho or Vav2 also reversed the SHP-2-DA-induced morphological phenotypes. CONCLUSION: These results indicate that SHP-2 plays a crucial role in the HGF/SF-induced cell scattering through the regulation of two distinct small G proteins, Ras and Rho.

Animals↗
PubMed2001

The use of ultrasound for drug delivery.

Ultrasound has been in use for the last three decades as a modality for diagnostic imaging in medicine. Recent studies have shown that nonthermal ultrasound energy could be applied for targeting or controlling drug release. This new concept of therapeutic ultrasound combined with drugs has induced interest in various medical fields. Enhanced effects of thrombolytic agents such as urokinase and TPA with acoustic energy have been demonstrated. Ultrasound transducer-tipped catheters are being developed for treatment of cardiovascular diseases. Other devices with ultrasound transducers implanted in transdermal drug patches are also being evaluated for possible delivery of insulin through the skin. Echo contrast microbubbles could also be used to carry and release genes to various tissues and lesions. Chemical activation of drugs by ultrasound energy for treatment of cancers is another new field recently termed "sonodynamic therapy." Various examples of ultrasound application are under investigation that could lead to revolutionary drug delivery systems of the future.

Drug Delivery Systems↗
PubMed2001

Congenital absence of the portal vein and role of liver transplantation in children.

BACKGROUND/PURPOSE: Congenital absence of the portal vein (CAPV) is a subtype of congenital portosystemic shunt, which can cause a broad spectrum of clinical manifestations. The authors report on 4 patients with CAPV including a boy with CAPV-associated encephalopathy, which was resolved effectively by liver transplantation (LT). METHODS: The case records of 4 pediatric patients with CAPV who were referred to the author's institution between 1984 and 1999 were reviewed. RESULTS: The patients (3 boys and 1 girl) ranged in age at diagnosis from 0.8 to 14 years. Two patients had growth retardation or disturbed consciousness, and the other 2 had no specific manifestations. Not only high serum levels of bile acids, ammonia, and transaminases but also low plasma levels of branched-chain amino acids were common laboratory findings. The absent portal vein was replaced by a large portosystemic shunt, which connected the splanchnic vein to the inferior vena cava or the left renal vein. Two patients survived without any symptoms, but 1 with growth retardation died of hepatic failure. The other with encephalopathy did not respond to medical therapy and underwent LT, which resolved symptoms and metabolic disorders effectively. CONCLUSIONS: Patients with CAPV do not always have a good prognosis. They should be followed up with careful observation of their symptoms, hepatic function, and metabolic abnormalities. LT might be indicated for patients with symptomatic CAPV unresponsive to medical therapy.

Adolescent↗
PubMed2001

Graves' disease in patients with 22q11.2 deletion.

We report 4 female patients and 1 male patient with a 22q11.2 deletion and Graves' disease diagnosed at age 27 months, 7, 10, 17, and 16 years, respectively. The clinical presentations were typical for hyperthyroidism, but 1 female infant had seizures in addition to symptoms of hyperthyroidism. All patients had elevated serum levels of thyroid hormones in association with suppressed thyroid-stimulating hormone levels. From these observations, we suggest that Graves' disease may be a part of the clinical spectrum associated with the 22q11.2 deletion syndrome.

Adolescent↗
PubMed2001

alpha-catenin-independent recruitment of ZO-1 to nectin-based cell-cell adhesion sites through afadin.

ZO-1 is an actin filament (F-actin)-binding protein that localizes to tight junctions and connects claudin to the actin cytoskeleton in epithelial cells. In nonepithelial cells that have no tight junctions, ZO-1 localizes to adherens junctions (AJs) and may connect cadherin to the actin cytoskeleton indirectly through beta- and alpha-catenins as one of many F-actin-binding proteins. Nectin is an immunoglobulin-like adhesion molecule that localizes to AJs and is associated with the actin cytoskeleton through afadin, an F-actin-binding protein. Ponsin is an afadin- and vinculin-binding protein that also localizes to AJs. The nectin-afadin complex has a potency to recruit the E-cadherin-beta-catenin complex through alpha-catenin in a manner independent of ponsin. By the use of cadherin-deficient L cell lines stably expressing various components of the cadherin-catenin and nectin-afadin systems, and alpha-catenin-deficient F9 cell lines, we examined here whether nectin recruits ZO-1 to nectin-based cell-cell adhesion sites. Nectin showed a potency to recruit not only alpha-catenin but also ZO-1 to nectin-based cell-cell adhesion sites. This recruitment of ZO-1 was dependent on afadin but independent of alpha-catenin and ponsin. These results indicate that ZO-1 localizes to cadherin-based AJs through interactions not only with alpha-catenin but also with the nectin-afadin system.

Animals↗
PubMed2001

Hic-5-reduced cell spreading on fibronectin: competitive effects between paxillin and Hic-5 through interaction with focal adhesion kinase.

Hic-5 is a paxillin homologue that is localized to focal adhesion complexes. Hic-5 and paxillin share structural homology and interacting factors such as focal adhesion kinase (FAK), Pyk2/CAKbeta/RAFTK, and PTP-PEST. Here, we showed that Hic-5 inhibits integrin-mediated cell spreading on fibronectin in a competitive manner with paxillin in NIH 3T3 cells. The overexpression of Hic-5 sequestered FAK from paxillin, reduced tyrosine phosphorylation of paxillin and FAK, and prevented paxillin-Crk complex formation. In addition, Hic-5-mediated inhibition of spreading was not observed in mouse embryo fibroblasts (MEFs) derived from FAK(-/-) mice. The activity of c-Src following fibronectin stimulation was decreased by about 30% in Hic-5-expressing cells, and the effect of Hic-5 was restored by the overexpression of FAK and the constitutively active forms of Rho-family GTPases, Rac1 V12 and Cdc42 V12, but not RhoA V14. These observations suggested that Hic-5 inhibits cell spreading through competition with paxillin for FAK and subsequent prevention of downstream signal transduction. Moreover, expression of antisense Hic-5 increased spreading in primary MEFs. These results suggested that the counterbalance of paxillin and Hic-5 expression may be a novel mechanism regulating integrin-mediated signal transduction.

3T3 Cells↗
PubMed2001

Compound heterozygous mutations in the gamma subunit gene of ENaC (1627delG and 1570-1G-->A) in one sporadic Japanese patient with a systemic form of pseudohypoaldosteronism type 1.

The systemic form of pseudohypoaldosteronism type 1 (PHA1) is a rare autosomal recessive disorder with salt-wasting, hyperkalemia, metabolic acidosis, and multiorgan aldosterone unresponsiveness. Recently, this form of PHA1 was found to be caused by the loss-of-function mutations in the gene of each subunit (alpha, beta, and gamma) of the epithelial sodium channel (ENaC). To investigate the molecular basis of one sporadic Japanese patient with a systemic form of PHA1, we determined the nucleotide sequence of the genes of every subunit of ENaC of this patient. The patient was found to be a compound heterozygote for one base deletion in exon 12 (1627delG) in combination with 1570-1-->GA substitution at the 5' splice acceptor site of intron 11 in the gamma subunit gene of ENaC. The 1627delG mutation altered a reading frame, resulting in a premature stop codon in exon 12. Messenger RNA from the allele harboring the splice site mutation was not identified by RT-PCR. In conclusion, two novel mutations in the gamma subunit gene of ENaC caused systemic PHA1 in the sporadic Japanese patient. Identification of the molecular basis of PHA1 is helpful for early diagnosis and understanding the pathophysiology of the disease.

Asian People↗
PubMed2001

Turner syndrome and Xp deletions: clinical and molecular studies in 47 patients.

Although clinical features of Turner syndrome have primarily been explained by the dosage effects of SHOX (short stature homeobox-containing gene) and the putative lymphogenic gene together with chromosomal effects leading to nonspecific features, several matters remain to be determined, including modifying factors for the effects of SHOX haploinsufficiency, chromosomal location of the lymphogenic gene, and genetic factors for miscellaneous features such as multiple pigmented nevi. To clarify such unresolved issues, we examined clinical findings in 47 patients with molecularly defined Xp deletion chromosomes accompanied by the breakpoints on Xp21-22 (group 1; n = 19), those accompanied by the breakpoints on Xp11 (group 2; n = 16), i(Xq) or idic(X)(p11) chromosomes (group 3; n = 8), and interstitial Xp deletion chromosomes (group 4; n = 4). The deletion size of each patient was determined by fluorescence in situ hybridization and microsatellite analyses for 38 Xp loci including SHOX, which was deleted in groups 1-3 and preserved in group 4. The mean GH-untreated adult height was -2.2 SD in group 1 and -2.7 SD in group 2 (GH-untreated adult heights were scanty in group 3). The prevalence of spontaneous breast development in patients aged 12.8 yr or more (mean +/- 2 SD for B2 stage) was 11 of 11 in group 1, 7 of 12 in group 2, and 1 of 7 in group 3. The prevalence of wrist abnormality suggestive of Madelung deformity was 8 of 18 in group 1 and 2 of 23 in groups 2 and 3, and 9 of 18 in patients with spontaneous puberty and 1 of 23 in those without spontaneous puberty. The prevalence of short neck was 1 of 19 in group 1 and 7 of 24 in groups 2 and 3. Soft tissue and visceral anomalies were absent in group 1 preserving the region proximal to Duchenne muscular dystrophy and were often present in groups 2 and 3 missing the region distal to monoamine oxidase A (MAOA). Multiple pigmented nevi were observed in groups 1-3, with the prevalence of 0 of 7 in patients less than 10 yr of age and 15 of 36 in those 10 yr or older regardless of the presence or absence of spontaneous puberty. Turner phenotype was absent in group 4, including a fetus aborted at 21 wk gestation who preserved the region distal to MAOA. The results provide further support for the idea that clinical features in X chromosome aberrations are primarily explained by haploinsufficiency of SHOX and the lymphogenic gene and by the extent of chromosome imbalance in mitotic cells and pairing failure in meiotic cells. Furthermore, it is suggested that 1) expressivity of SHOX haploinsufficiency in the limb and faciocervical regions is primarily influenced by gonadal function status and the presence or absence of the lymphogenic gene, respectively; 2) the lymphogenic gene for soft tissue and visceral stigmata is located between Duchenne muscular dystrophy and MAOA; and 3) multiple pigmented nevi may primarily be ascribed to cooperation between a hitherto unknown genetic factor and an age-dependent factor other than gonadal E.

Adult↗
PubMed2001

Relationship between doppler-derived left ventricular diastolic function and exercise capacity in patients with myocardial infarction.

Doppler echocardiographic indices of left ventricular (LV) diastolic function are widely used to evaluate the cardiac function of patients with cardiac disease. However, there have been few reports about the relationship between Doppler indices and exercise capacity and so 44 patients with myocardial infarction were investigated by cardiopulmonary exercise testing and 2-D and Doppler echocardiography. Diastolic performance was assessed using Doppler transmitral flow velocity and pulmonary venous flow velocity. The ratio of peak E wave velocity and peak A wave velocity (E/A) correlated with peak oxygen consumption (peak Vo2) (R=0.72), and there was a negative correlation between the deceleration time of E velocity (Dct) and peak Vo2 or anaerobic threshold (AT) (R=-0.65, -0.62, respectively). The ratio of peak S wave velocity and peak D wave velocity (S/D) negatively correlated with peak Vo2 (R=-0.58). Left ventricular ejection fraction did not correlate to exercise capacity. These results suggest that the Doppler echocardiographic indices of LV diastolic function correlate with exercise capacity in patients with mild cardiac dysfunction.

Aged↗
PubMed2001

Development of growth hormone and adrenocorticotropic hormone deficiencies in patients with prenatal or perinatal-onset hypothalamic hypopituitarism having invisible or thin pituitary stalk on magnetic resonance imaging.

A gradual loss of anterior pituitary hormones is suspected in patients treated with irradiation due to brain tumors. Development of growth hormone deficiency (GHD) with age has been documented in patients with idiopathic GHD. A gradual loss of adrenocorticotropic hormone (ACTH) secretion has been also shown in a patient with severe GHD and an invisible pituitary stalk on magnetic resonance imaging (MRI). The purpose of this longitudinal and cross-sectional study was to evaluate the gradual loss of growth hormone (GH) and ACTH in a homogeneous group of patients with hypopituitarism. Twenty-eight patients (23 males, 5 females) from four hospitals were diagnosed as having prenatal or perinatal-onset hypothalamic hypopituitarism. They had an abnormal pituitary stalk on MRI (invisible in 18 patients, thin in 10 patients) without any other organic disease of the brain. Each patient had GHD upon initial evaluation. Height (n=20) was analyzed as standard deviation score (SDS). Longitudinal (n=8) and cross-sectional (n=28) GH secretion capacity was evaluated by GH peaks, in response to insulin tolerance test (ITT) and growth hormone releasing factor test (GRF test). Longitudinal (n=10) and cross-sectional (n=28) ACTH secretion capacity was evaluated by cortisol peaks in response to ITT. Height SDS decreased each year in all the untreated patients after birth. GH peaks decreased gradually with age. Longitudinal data showed decreased GH peaks with age in seven out of eight patients using ITT and in all four patients using GRF tests. Cortisol peaks also decreased gradually together with signs and symptoms for adrenal deficiency such as general fatigue. Cortisol peaks of less than 414 nmol/L (15 microg/dl) in response to ITT were seen in 24% of the tests before age 10 and 56% before age 25. In conclusion, GHD and ACTH deficiency developed gradually in patients with prenatal or perinatal-onset hypothalamic hypopituitarism who had invisible or thin pituitary stalks examined by MRI.

Adolescent↗
PubMed2001

[Assessment of general movements at routine medical examination of one-month-old infants].

On routine medical examination of one-month-old infants, general movements (GMs) were video-recorded for about 5 minutes of 252 infants born at Kyoto City Hospital or other hospitals, including the infants discharged from the NICU. Their ages ranged from 39 postmenstrual to 8 post-term weeks. One of the experimenters assessed 181 infants among 252 available for assessment of their GMs twice at intervals of more than one month without being informed about their clinical histories. The subjects included 19 low-birthweight infants, and their average age was 3.5 post-term weeks. The assessment was carried out in comparison to the "gold standard" GMs depicted in a demonstration video produced by the GMs Trust. The Kappa value for intra-observer concordance was 0.85. Twenty (11.0%) out of the 181 infants were judged abnormal because of their poor repertoire of GMs in both the first and second assessment. Neither cramped synchronized GMs nor chaotic ones were observed. Meanwhile, 155 (85.6%) out of the 181 infants were found to be normal. The incidence of abnormal GMs was significantly higher among infants with history of asphyxia and/or respiratory distress than among low-risk infants. There of the experimenters independently assessed GMs of 50 infants among 181 which had been video-recorded between June and September 1998. The inter-observer concordance was higher among the low-birth weight infants than among full-term ones. In conclusion, qualitative assessment of GMs by an experienced observer at routine medical examination of one-month old infants is a useful method for the follow-up of high-risk infants.

Female↗
PubMed2001

[Two pediatric cases of malignant hyperthermia caused by sevoflurane].

We experienced two cases of malignant hyperthermia (MH) triggered by sevoflurane. Case 1 was a six-year-old girl, 15.8 kg, undergoing strabismus repair. She had flat back, elevated diaphragm and high arched palate. Anesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Her trachea was intubated without the use of muscle relaxant. Thirty minutes after the induction of anesthesia, ETco2 was over 60 mmHg despite hyperventilation. Muscle rigidity of legs and the rise in temperature were noted. MH was diagnosed and dantrolene i.v. was administered. Her maximum esophageal temperature was 40.2 degrees C. ETco2 and temperature returned to baseline values after dantrolene administration. Creatine phosphokinase (CK) level was 252 U.l-1 preoperatively, and 1690 U.l-1 next day. Case 2 was a year-and-9-month-old boy undergoing accessory ear resection. Anesthesia was induced with sevoflurane and nitrous oxide in oxygen. His trachea was intubated with an aid of vecuronium. Forty minutes after administration of sevoflurane his temperature rose to 38.6 degrees C with heart rate 191 bpm and Spo2 93%, and muscle rigidity of legs. MH was diagnosed and dantrolene was administered. His highest temperature was 39.3 degrees C and was reduced promptly after dantrolene. Postoperatively he was noted to have downslanting palpebral fissures, micrognathia, low set ears, and a single crease of the fifth finger and diagnosed as King syndrome which is reported to have association with MH. Both patients had no history of anesthesia nor abnormal family history. Both of them were rescued with dantrolene and recovered without sequelae.

Anesthetics, Inhalation↗
PubMed2000

c-Mos forces the mitotic cell cycle to undergo meiosis II to produce haploid gametes.

The meiotic cycle reduces ploidy through two consecutive M phases, meiosis I and meiosis II, without an intervening S phase. To maintain ploidy through successive generations, meiosis must be followed by mitosis after the recovery of diploidy by fertilization. However, the coordination from meiotic to mitotic cycle is still unclear. Mos, the c-mos protooncogene product, is a key regulator of meiosis in vertebrates. In contrast to the previous observation that Mos functions only in vertebrate oocytes that arrest at meiotic metaphase II, here we isolate the first invertebrate mos from starfish and show that Mos functions also in starfish oocytes that arrest after the completion of meiosis II but not at metaphase II. In the absence of Mos, meiosis I is followed directly by repeated embryonic mitotic cycles, and its reinstatement restores meiosis II and subsequent cell cycle arrest. These observations imply that after meiosis I, oocytes have a competence to progress through the embryonic mitotic cycle, but that Mos diverts the cell cycle to execute meiosis II and remains to restrain the return to the mitotic cycle. We propose that a role of Mos that is conserved in invertebrate and vertebrate oocytes is not to support metaphase II arrest but to prevent the meiotic/mitotic conversion after meiosis I until fertilization, directing meiosis II to ensure the reduction of ploidy.

Amino Acid Sequence↗
PubMed2000

A nonproteolytic function of the proteasome is required for the dissociation of Cdc2 and cyclin B at the end of M phase.

Inactivation of cyclin B-Cdc2 kinase at the exit from M phase depends on the specific proteolysis of the cyclin B subunit, whereas the Cdc2 subunit remains present at nearly constant levels throughout the cell cycle. It is unknown how Cdc2 escapes degradation when cyclin B is destroyed. In Xenopus egg extracts that reproduce the exit from M phase in vitro, we have found that dissociation of the cyclin B-Cdc2 complex occurred under conditions where cyclin B was tethered to the 26S proteasome but not yet degraded. The dephosphorylation of Thr 161 on Cdc2 was unlikely to be necessary for the dissociation of the two subunits. However, the dissociation was dependent on the presence of a functional destruction box in cyclin B. Cyclin B ubiquitination was also, by itself, not sufficient for separation of Cdc2 and cyclin B. The 26S proteasome, but not the 20S proteasome, was capable of dissociating the two subunits. These results indicate that the cyclin B and Cdc2 subunits are separated by the proteasome through a mechanism that precedes proteolysis of cyclin B and is independent of proteolysis. As a result, cyclin B levels decrease on exit from M phase but Cdc2 levels remain constant.

Animals↗