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Biomedical subjects

H Take

Publications and source records attributed to H Take.

At least 19 recordsLinked to original sources
PubMed2001

Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in children with acute lymphoblastic leukemia: results obtained by the Kyushu-Yamaguchi Children's Cancer Study Group.

We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and 63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.

Adolescent↗
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↗
PubMed2000

Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes.

CIN85 is an 85-kDa adaptor protein whose functions in signaling pathways are presently unknown. Using the yeast two-hybrid screen, the B cell linker protein (BLNK) was identified as a binding partner of CIN85. Coimmunoprecipitation experiments using mammalian cells revealed that CIN85 directly bound to BLNK through its SH3 domains. Immunostaining analysis showed that CIN85 and BLNK were colocalized in the cytoplasm. These results indicate a potential role of CIN85 in the B cell receptor-mediated signaling pathway. It was also found that Crk-I, Crk-II, p130(Cas), p85-PI3K, Grb2, and Sos1 were components of CIN85 complexes. CIN85 interacted with itself through its coiled-coil region, resulting in formation of a tetramer. Both the coiled-coil region and SH3 domains of CIN85 were responsible for its subcellular localization. Our data suggest that CIN85 may serve for regulation of various signaling events through formation of its diverse complexes.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Cloning and characterization of a novel adaptor protein, CIN85, that interacts with c-Cbl.

The c-Cbl protooncogene product is a prominent substrate of protein tyrosine kinases and is rapidly tyrosine-phosphorylated upon stimulation of a wide variety of cell-surface receptors. We have identified a novel c-Cbl-interacting protein termed CIN85 with a molecular mass of 85 kDa which shows similarity to adaptor proteins, CMS and CD2AP. CIN85 mRNA is expressed ubiquitously in normal human tissues and cancer cell lines analyzed. CIN85 was basally associated with c-Cbl. For interaction of CIN85 with c-Cbl, the second SH3 domain of CIN85 was shown to serve as a central player. The CIN85-c-Cbl association was enhanced shortly after stimulation of 293 cells with epidermal growth factor (EGF) and gradually diminished to a basal level, which correlated with a tyrosine phosphorylation level of c-Cbl. Our results suggest that CIN85 may play a specific role in the EGF receptor-mediated signaling cascade via its interaction with c-Cbl.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Key amino acids of vasopressin V1a receptor responsible for the species difference in the affinity of OPC-21268.

A non-peptide, vasopressin V1a receptor-selective antagonist, OPC-21268, exhibited a markedly higher affinity for the rat V1a receptor (Ki = 380 nM) than for the human V1a receptor (Ki = 140 microM). To delineate the region responsible for the high affinity binding of OPC-21268 for the rat V1a receptor, we have constructed a series of chimeric human and rat V1a receptors, and examined the chimeric and point-mutated receptors by competitive radioligand binding analysis. The results showed that the transmembrane domain (TMD) VI-VII of the vasopressin V1a receptor, in particular the amino acid residue Ala-342 in TMD VII, is the major component conferring the rat-selective binding of OPC-21268 to the V1a receptor.

Amino Acid Sequence↗
PubMed1999

Restricted diversification of T-cells in chronic active Epstein-Barr virus infection: potential inclination to T-lymphoproliferative disease.

To assess the abnormal T-cell expansion in chronic active Epstein-Barr virus infection (CAEBV), T-cell antigen receptor (TCR) repertoire was analyzed in four patients with the disease. All fulfilled the diagnostic criteria of CAEBV, presenting with fever, hepatosplenomegaly, cytopenia, abnormal high titers of anti EBV-antibodies, and positive EBV genome of unknown cause. Southern blotting probed with EBV-terminal repeats and TCR Cbeta gene indicated clonal expansion of the infected cells in 3 and 2 patients, respectively. The number of CD4+ HLA-DR+ cells appreciably increased in patients 1 (59%) and 2 (24%), who had a coronary aneurysm and central nervous system involvement, respectively. TCR gene expression examined by the inverse polymerase chain reaction methods revealed that Vbeta gene usages were preferential in all patients (Vbeta7 and Vbeta12: patient 1, Vbeta4: patient 2, Vbeta13: patients 3 and 4), compared with those in healthy controls. Valpha18 gene expression was remarkably high in patients 1 and 2. Moreover, Jbeta gene expression was skewing in the reigning Vbeta clones in all patients. Vbeta4-Jbeta1.5 and Vbeta13-Jbeta1.5 genes were clonally expressed in patients 2 and 4, respectively. These results suggest that CAEBV is associated with the restricted diversity of T-cells, which may stem from the sustained expansion of oligoclonal T-cells possibly driven by conventional viral antigens, but not, superantigens. Although the study is limited by the small number of patients, the unbalanced T-cell repertoire might contribute to the evolution of T-lymphoproliferative disease, otherwise, imply the innate defective immunity to EBV in CAEBV patients.

Adolescent↗
PubMed1999

Blood dolichols in a patient with abetalipoproteinaemia.

Dolichol and dolichyl derivatives have an important function as glycosyl carriers in the assembly of the N-asparaginyl-linked oligosaccharide core region of glycoproteins. Dolichols are synthesized through the cholesterol biosynthesis pathways in all mammalian organs and are present in all tissues, and are also associated with lipoproteins in the blood circulation. However, the origin and metabolic pathway of blood dolichols remain unknown. Abetalipoproteinaemia is a disorder of the secretion of very low-density lipoprotein (VLDL) from the liver and of chylomicrons from the intestine into the blood circulation. Therefore, examination of blood dolichols in this disorder may provide valuable information on their origin and metabolic pathway. Dolichols were exclusively associated with the high-density lipoprotein (HDL) fraction (80.7 +/- 6.3% of total dolichols) in control human blood. Serum from a patient also contained dolichols in the HDL fraction (82.8% of total dolichols). The total amount of dolichols was higher in the patient (207.0 ng/mL) than in the controls (106.2 +/- 22.7 ng/mL, n = 14). The compositions of dolichols were very similar to each other. These results indicated that, at least in the patient with abetalipoproteinaemia, the HDL-associated dolichols were possibly derived from the liver not through other lipoproteins but through dolichol transfer protein, or were possibly taken up and carried by HDL from peripheral tissues.

Abetalipoproteinemia↗
PubMed1999

Identification of the binding site for an alloantibody to von Willebrand factor which inhibits binding to glycoprotein Ib within the amino-terminal region flanking the A1 domain.

An alloantibody to von Willebrand factor (vWF) which developed in a Japanese boy with type 3 von Willebrand disease has been characterized. The antibody was non-precipitating IgG and the main subclasses were IgG2 and IgG4. The antibody inhibited completely ristocetin-induced platelet aggregation (RIPA) and high shear stress-induced platelet aggregation (SIPA). Its predominant inhibitory role was focused, therefore, on the interaction between vWF and platelet gycoprotein Ib. The antibody reacted with a 52/48 kDa tryptic fragment of vWF (residues 449-728). No reaction was seen, however, with either a 39/34 kDa dispase fragment (480-718) or a recombinant vWF fragment (residues 465-728). These findings suggested that the essential epitope resided in the amino-terminal flanking region of the Al domain. We synthesized overlapping peptides corresponding to the region containing D3/A1 boundary. A peptide, residues 458-472, bound to the antibody and dose-dependently blocked the antibody binding to the 52/48 kDa fragment. The same peptide neutralized the inhibitory effect of the alloantibody on SIPA. The data are consistent with the presence of an epitope within residues 458-472 which reacted with the 52/48 kDa fragment. Furthermore, the specific component of the antibody, directed against residues 458-472, blocked vWF binding to GPIb in absence of exogenous agonist. Our results suggest that the region flanking the Al domain plays an important role in regulating vWF binding to GPIb.

Antibody Specificity↗
PubMed1998

Vascular alpha1-adrenoceptor subtype selectivity and alpha1-blocker-induced orthostatic hypotension.

Newly developed alpha1-adrenoceptor antagonists including naftopidil are free from the "prazosin-like" side effect of orthostatic hypotension and associated symptoms. We investigated the mechanism for the differential effects of naftopidil and prazosin on the development of postural hypotension, with special attention on their selectivity for the alpha1-adrenoceptor subtype. We observed that head-up tilt caused a similar extent of drop in mean arterial pressure in control, naftopidil (1 mg/kg)- or prazosin (10 microg/kg)-treated rats; however, the tilt-induced postural hypotension was recovered within 2 min in the naftopidil-treated group, but not in the prazosin-treated group. Comparing an inhibitory effect on noradrenaline-induced contraction in the rat aorta and portal vein, we found that naftopidil was sixfold less potent in the portal vein, while prazosin showed similar potency in both tissues. Reverse transcription-polymerase chain reaction analysis showed that the expression of alpha1d-adrenoceptor mRNA predominated in the aorta, while that of alpha1b-adrenoceptor mRNA predominated in the portal vein. Using cloned rat alpha1-adrenoceptor subtypes, we found that naftopidil was selective for the alpha1d-subtype with approximately ninefold higher affinity than at the other subtypes. These results show that the pharmacological character of naftopidil, combined with the differential expression of the alpha1-adrenoceptor subtype in the artery and the vein, may partly explain the differential effect of naftopidil and prazosin on head-up tilt-induced hemodynamic responses.

Adrenergic alpha-Antagonists↗
PubMed1997

Effects of hyperthermal stress on the ultrastructure of platelets with reference to the localization of platelet peroxidase and fibrinogen in vivo.

Ultrastructure of platelets with the localization of platelet peroxidase and fibrinogen through 3-min 47 degrees C hot-spring bathing was investigated in eight healthy volunteers. The mean sublingual temperature rose about 1.8 degrees C 5 min after the start of bathing. The frequencies of fold, pseudopods, vacuoles, and centralization were increased after bathing. Platelet peroxidase activity was decreased after bathing. Furthermore, fibrinogen was decreased in alpha-granules after bathing. Thus, hyperthermal stress in vivo may activate platelets, resulting in consumption of platelet peroxidase and fibrinogen.

Adult↗
PubMed1997

Ultrastructure of myeloma cells producing parathyroid hormone-related peptide.

We examined the ultrastructure of myeloma cells producing parathyroid hormone-related peptide. The nucleus was mature and the cytoplasm was well-developed, being classified into the mature type with slight nucleo-cytoplasmic asynchrony. Although various nuclear and cytoplasmic abnormalities commonly observed in myeloma cells were recognized, a multilamellar body-like structure which has not been reported previously in myeloma cells was characteristically observed. Numerous nuclear and cytoplasmic abnormalities observed in the myeloma cells of this case were considered to have resulted from increased and aberrant proliferation of myeloma cells. We reported previously that the immature nucleus and various nuclear and cytoplasmic abnormalities are related to poor prognosis. Thus, the ultrastructural findings of myeloma cells in this case is not inconsistent with the short survival time.

Aged↗
PubMed1997

Breast milk is not a significant source for early Epstein-Barr virus or human herpesvirus 6 infection in infants: a seroepidemiologic study in 2 endemic areas of human T-cell lymphotropic virus type I in Japan.

In order to evaluate the possibility of Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) transmission via breast milk, a total of 331 serum specimens collected from bottle-fed and breast-fed children and their mothers, in 2 endemic areas of human T-cell lymphotropic virus type I (HTLV-I) in Japan, were assayed for antibodies to EBV and HHV-6. The seroprevalences of EBV and HHV-6 were over 95% both in the mothers of bottle-fed children and in those of breast-fed children. The seroprevalence of EBV at 12-23 months of age was 54.5% (36/66) and 55.8% (24/43) in breast-fed children and bottle-fed children, respectively. The seroprevalence of HHV-6 at 12-23 months of age was 90.9% (60/66) and 93.0% (40/43) in breast-fed children and bottle-fed children, respectively. No difference was observed between the seroprevalences of EBV and HHV-6 in breast-fed and bottle-fed children at 12-23 months of age. Our seroepidemiologic data indicate that breast milk is not a significant source of early EBV or HHV-6 infection in infancy.

Antibodies, Viral↗
PubMed1997

Treatment of refractory cases of atopic dermatitis with acidic hot-spring bathing.

The incidence of refractory atopic dermatitis has increased in teenagers and young adults. The purpose of this study was to control the skin symptoms of such patients in daily life. Seventy patients repeatedly took a 10-min 42 degrees C acidic hot-spring bath twice daily. The skin symptoms were improved in 76% of cases. In 30 of 42 responders examined Staphylococcus aureus, detected on the skin surface, disappeared or decreased through balneotherapy. In contrast, S. aureus remained unchanged in 8 of 10 non-responders examined. Thus, the balneotherapy using acidic hot-spring water may be useful for controlling the skin symptoms of acute flares of refractory cases of atopic dermatitis.

Adolescent↗
PubMed1997

[Acute myocardial infarction and cerebral infarction at Kusatsu-spa].

From January 1989 to June 1995, 31 patients were admitted to our hospital with acute myocardial infarction (15 were tourists and 16 were Kusatsu residents) and 40 were admitted with cerebral infarction (15 tourists and 25 Kusatsu residents). We examined the possibility that hot hot-spring bathing was related to the occurrence of their illness. Fifteen patients with acute myocardial infarction (9 tourists and 6 Kusatsu residents) and 27 patients with cerebral infarction (11 tourists and 16 Kusatsu residents) had a hot hot-spring bath within 24 hours before the onset of symptoms. In 12 of the 15 with acute myocardial infarction (6 tourists and 6 Kusatsu residents) and in 15 of the 27 with cerebral infarction (9 tourists and 6 Kusatsu residents), symptoms began within 3 hours after they began bathing. In 2 of the remaining 3 patients with acute myocardial infarction and in 8 of the remaining 12 patients with cerebral infarction, bathing at night was followed by the onset of symptoms the next morning (more than 3 hour later). Acute myocardial infarction and cerebral infarction within 3 hours after hot hot-spring bathing may be attributable to transient change in blood pressure, heart rate, blood viscosity, fibrinolytic activity, and platelet function. We described previously that hot hot-spring bathing at night can accentuate the nocturnal decrease in blood pressure and can make the early morning increase in blood viscosity more abrupt. These phenomena may account for the occurrence of acute myocardial infarction and cerebral infarction early in the morning.

Aged↗
PubMed1997

Juvenile systemic granulomatosis manifesting as premature aging syndrome and renal failure.

We describe a case of juvenile systemic granulomatosis in a 22-year-old woman. The rash consisted of purple papules and first appeared at the age of one year. She had persistent symmetrical painless boggy tenosynovitis with minimal roentgenographic changes and chronic granulomatous symptoms. Uveitis resulted in visual impairment. She also had granulomatous changes in her vessels. Renal impairment developed; however, neither renal artery stenosis nor hypercalcemia was found. Clinical features included the development of premature aging with alopecia, which differed from the previously reported progeria syndrome. Poikiloderma may cause a prematurely aged appearance. Our report expands the clinical spectrum of systemic granulomatosis to include the development of premature aging with alopecia.

Adult↗
PubMed1997

Effects of repeated hyperthermal stress on blood cells in vivo.

The effects of repeated hyperthermal stress on blood cells were examined in seven healthy subjects who took three 3-minute 47 degrees C hotspring baths daily for three consecutive weeks. After a 3-minute 47 degrees C bath, the sublingual temperature was transiently increased about 1.8 degrees C, returning to the baseline level within 60 min. Two weeks after completing the 3-week bathing period, monocytes were increased and eosinophils were decreased significantly. Total lymphocytes and CD3+ cells tended to be decreased. Interestingly, CD4+ cells were decreased significantly at the time of completing the 3-week bathing period and returned to the baseline level two weeks later. These findings suggest that repeated hyperthermal stress may induce alteration of the blood cells.

Adult↗
PubMed1996

Activation of circulating platelets by hyperthermal stress.

To determine the involvement of activated platelets in the frequent thrombosis after hot hot-spring bathing, we examined effects of a hyperthermal stress on platelets in vivo. Plasma levels of beta-thromboglobulin (beta-TG) began to rise at 5 minutes and elevated significantly 10 minutes after the start of traditional 47 degrees C hot-spring bathing. In contrast, there was no significant factor 4 change in plasma beta-TG level through a control 10-minute bath in the same water at 42 degrees C. A beta-TG to platelet factor 4 ratio, a value suggested to be useful for evaluating clinical studies for in vitro versus in vivo granule release, was sufficiently high in each sampling, indicating that the experiment was performed without being influenced by artificial platelet activation. These data show that only a few minutes' hyperthermal stress can induce granule release from platelets in vivo.

Adult↗