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Biomedical subjects

K Furusho

Publications and source records attributed to K Furusho.

At least 37 records · Page 2Linked to original sources
PubMed1998

Combination therapy with GH and cyproterone acetate does not improve final height in boys with non-GH-deficient short stature.

BACKGROUND AND OBJECTIVE: Recently, we reported that GH therapy without gonadal suppression (GS) decreased the final height of boys with non-GH-deficient short stature by decreasing the height standard deviation score (SDS) for bone age (BA) during puberty. Combination therapy with GH and GS has been reported to suppress bone maturation and improve final height in some cases. We evaluated the effects of combination therapy with GH and GS using cyproterone acetate on the final height of boys with non-GH-deficient short stature. PATIENTS: Fifty nine boys with non-GH deficient short stature were observed retrospectively until they reached their final height. The boys were divided into 3 groups: Group A consisted of 26 boys who were not treated with GH, group B consisted of 13 boys who were treated with GH alone, and group C consisted of 20 boys who were treated with combination therapy with GH and GS using cyproterone acetate. At the start of observation, the height SDS for BA and projected height were matched among these three groups. RESULTS: The mean +/- SDS of the final height for groups A, B, and C were 162.7 +/- 5.3 cm, 155.4 +/- 4.9 cm, and 161.9 +/- 3.2 cm, respectively. GH therapy did not affect the height SDS for BA during the prepubertal period. GH therapy without GS decreased the height SDS for BA during puberty in group B. Combination therapy with GH and cyproterone acetate increased the height SDS for BA between 12 and 14 years BA in group C. However, after GS therapy was discontinued at 14 years BA, the height SDS for BA gradually decreased and eventually reached the same value as that in group A. CONCLUSIONS: GH therapy during the prepubertal period did not improve the final height of boys with non-GH-deficient short stature. GH therapy without GS decreased pubertal height gain, resulting in reduced final height. Combination therapy with GH and GS using cyproterone acetate decelerated the bone maturation during puberty which might be accelerated by GH therapy, but did not improve the final height which might have been attained without treatment.

Androgen Antagonists↗
PubMed1998

Liver transplantation in a case of hypoproteinemia and coagulopathy.

A female infant with hypoproteinemia and coagulopathy associated with hypertyrosinemia was successfully treated with living-related liver transplantation (LRLT). On the 12th day of life plasma amino acid analysis revealed a marked elevation of tyrosine, so the patient was fed on a low-tyrosine and low-phenylalanine diet. However, hepatosplenomegaly, hypotonia, alopecia, eczema and psychomotor delay did not improve and recurrent episodes of disseminated intravascular coagulation (DIC) caused her condition to deteriorate. Liver biopsy on the 230th day revealed marked fatty change accompanied by mild to moderate cholestasis. Therefore, LRLT from her father was performed on the 286th day resulting in improvement of all the aforementioned signs and symptoms. Despite a thorough examination, no diagnosis of a known disorder could be established. However, her elder brother had also been born with severe hypoproteinemia and coagulopathy, and died of DIC on the second day of life. Thus, the disorder is designated as a new entity, namely 'congenital hypoproteinemia and coagulopathy associated with hypertyrosinemia'.

Disseminated Intravascular Coagulation↗
PubMed1998

Uniparental and functional X disomy in Turner syndrome patients with unexplained mental retardation and X derived marker chromosomes.

We analysed parental origin and X inactivation status of X derived marker (mar(X)) or ring X (r(X)) chromosomes in six Turner syndrome patients. Two of these patients had mental retardation of unknown cause in addition to the usual Turner syndrome phenotype. By FISH analysis, the mar(X)/r(X) chromosomes of all patients retained the X centromere and the XIST locus at Xq13.2. By polymorphic marker analysis, both patients with mental retardation were shown to have uniparental X disomy while the others had both a maternal and paternal contribution of X chromosomes. By RT-PCR analysis and the androgen receptor assay, it was shown that in one of these mentally retarded patients, the XIST on the mar(X) was not transcribed and consequently the mar(X) was not inactivated, leading to functional disomy X. In the other patient, the XIST was transcribed but the r(X) appeared to be active by the androgen receptor assay. Our results suggest that uniparental disomy X may not be uncommon in mentally retarded patients with Turner syndrome. Functional disomy X seems to be the cause of mental retardation in these patients, although the underlying molecular basis could be diverse. In addition, even without unusual dysmorphic features, Turner syndrome patients with unexplained mental retardation need to be investigated for possible mosaicism including these mar(X)/r(X) chromosomes.

Base Sequence↗
PubMed1998

Prospective study of mutant frequencies at the hprt and T-cell receptor gene loci in pediatric cancer patients during chemotherapy.

Mutant frequencies (MFs) at the hypoxanthine phosphoribosyl transferase gene and the T-cell receptor (TCR) gene loci were evaluated in nine pediatric cancer patients before and during anticancer chemotherapy. The study population consisted of three patients with Hodgkin's disease, four patients with neuroblastoma, and two patients with Wilms' tumor. Except for one patient with neuroblastoma and one patient with Wilms' tumor, MFs at the hypoxanthine phosphoribosyl transferase locus tended to increase during the early cycles of treatment. The elevation was most striking and persistent in patients with Hodgkin's disease. The clonal relationship was determined in mutant cells derived from Hodgkin's disease patients by TCR-gamma gene rearrangement pattern and showed that the elevation of MFs resulted from increased mutational events rather than from clonal expansion of mutants. An increase in TCR MF was also found during chemotherapy in most patients, but the time of TCR MF elevation was variable among patients. Among the chemotherapeutic agents used in this study, cyclophosphamide was considered to be the most mutagenic. Our present study clearly demonstrates that anticancer chemotherapy can induce mutagenesis in vivo in various pediatric cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Re-evaluation of multi-allergen skin prick test for infants with atopic dermatitis--clinical relevance and evaluation by mothers].

We performed skin-prick tests (SPT) for 8 food and inhalant allergens on 55 infants (between 3 months and 2 years of age) with atopic dermatitis (AD) at their initial visit to our allergy clinic. SPT results were compared with those of radioallergosorbent tests (RAST) and the severity of AD symptoms. We also administered a questionnaire-based survey of 46 patients mothers to see how they evaluated SPT compared to blood tests. SPT for egg white had the highest positive rate (91%) and far exceeded that for other allergens. More than two allergens showed positive in more than half of the patients, and about 30% of them showed positive reactions to more than three allergens. Concordance rate between SPT and RAST was 78.6%. Patients showing positive reactions to multi-allergens tended to have more severe AD symptoms. Mothers appreciated the SPT test and felt that quick results for multi-allergens was the greatest advantage of SPT. More than 90% of the mothers wanted the allergic status of their next children to be evaluated with SPT. Especially, more than 30% of the mothers preferred SPT than RAST as initial screening test. As SPT is harmless, easy to administer even in infancy, and has different advantages for those of RAST, this method deserves further re-evaluation as a means of identifying allergic status especially among infants.

Child, Preschool↗
PubMed1997

NADH dehydrogenase deficiency in an apoptosis-resistant mutant isolated from a human HL-60 leukemia cell line.

An apoptosis-resistant mutant (VC-33) was selected from HL-60 by alternating exposure to camptothecin and etoposide. VC-33 cells demonstrated resistance to apoptosis as induced not only by camptothecin and etoposide but by a variety of other agents as well, including 1-beta-D-arabinofuranosylcytosine, hydroxyurea, calcium ionophore (A23187), cycloheximide, and UV irradiation. In an effort to identify the mechanism of such apoptosis resistance, a mRNA differential display analysis was used. Among a total of 12 bands with reduced expression in VC-33 cells, 1 cDNA clone was isolated that was hybridized to the wild-type transcript but not to the VC-33 transcript on Northern blotting. Partial sequence of this gene revealed 98% homology to mitochondrial NADH dehydrogenase subunit 5. When cell growth and intracellular ATP levels under glucose starvation were measured, VC-33 cells were found to be more sensitive than wild-type cells. Thus, NADH dehydrogenase deficiency may contribute, at least in part, to the mechanism of resistance to apoptosis in VC-33 cells.

Antineoplastic Agents↗
PubMed1997

Prostaglandin E2 and IL-4 provide naive CD4+ T cells with distinct inhibitory signals for the priming of IFN-gamma production.

We investigated the effects of prostaglandin E2 and IL-4 on the acquisition of cytokine-producing ability by naive CD4(+) T cells in human umbilical cord blood. The presence of PGE2 or IL-4 at primary stimulation inhibited the production of IFN-gamma at secondary stimulation, and the combination of these stimuli resulted in cooperative effects. During primary stimulation with anti-CD3, the intracellular cAMP level was elevated in PGE2-treated cells but not in IL-4-treated or control cells. The signal provided by PGE2, but not by IL-4, was inhibited with RpcAMP, indicating that it was mediated by cAMP. After differentiation into Th2-like cells, cAMP levels in PGE2- and IL-4-treated cells were not different. Our results suggest that both PGE2 and IL-4 play important roles with distinct mechanisms in inhibiting the priming of IFN-gamma production of naive CD4(+) T cells.

CD4-Positive T-Lymphocytes↗
PubMed1997

Apoptosis-resistant phenotype selected by alternating exposure to camptothecin and etoposide.

We selected an apoptosis-resistant subline (VC-33) in a human promyelocytic leukemia cell line, HL-60, by alternating exposure to camptothecin (CPT) and etoposide (VP-16). When wild-type (WT) and VC-33 cells were incubated with various concentrations of either CPT or VP-16 for 4 h, VC-33 showed several-fold resistance to apoptosis induced by these agents in comparison with WT cells. VC-33 cells also exhibited cross-resistance to apoptosis induced by 1-beta-d-arabinofuranosylcytosine, hydroxyurea, a calcium ionophore (A23187), cycloheximide, or UV irradiation. The levels of protein-DNA cross-linking induced by CPT or VP-16, and the amounts of ara-CTP generation, tended to be smaller in VC-33 cells, but the difference was not sufficient to explain the difference in the sensitivity to apoptosis. The initial rise of intracellular calcium ions with A23187 and the expression of P-glycoprotein, Bcl-2, and Bcl-Xl were comparable between WT and VC-33 cells. This mutant may represent a new phenotype of resistance to apoptosis induced by a variety of agents, and may thus be useful in the study of the mechanisms of apoptosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Constitutive endonuclease to induce high molecular weight or internucleosomal DNA fragmentation in freshly isolated leukemia cells.

Using an autodigestion method, we investigated endogenous endonuclease(s) in leukemia cells freshly obtained from pediatric patients with various types of leukemia. Endonucleolytic activity was found to cause both high molecular weight and internucleosomal DNA fragmentation at a neutral pH in whole cell lysates of all common acute lymphoblastic leukemia (cALL) blasts, which was Mg2+-dependent and Ca2+-independent. Whole lysates from most acute myeloblastic leukemia (AML) cells possessed similar endonuclease activity, but both Mg2+ and Ca2+ were required for the activity. Our results suggest that leukemia cells of different lineages have distinct constitutive endonucleases, which may play a role in the occurrence of apoptosis in these cells.

Apoptosis↗
PubMed1997

Myelodysplastic syndrome presenting as third malignancy after non-Hodgkin's lymphoma and osteosarcoma.

The patient was initially diagnosed as having non-Hodgkin's lymphoma and was cured following treatment with prednisolone, vincristine, daunorubicin, 1-asparaginase, and cyclophosphamide. Seven years and two months later, he developed osteosarcoma in his right femur. He received chemotherapy consisting of methotrexate, carboplatin, etoposide, and ifosfamide and again obtained remission. After 2 years and 7 months, however, he was found to have pancytopenia with morphological abnormalities in the erythroid and myeloid series. Diagnosis of myelodysplastic syndrome (MDS) was made. Cytogenetic analysis of bone marrow cells revealed -5 and -7, which is typical for secondary MDS. This is a rare case of third malignancy presumably caused by alkylating agents.

Adolescent↗
PubMed1997

[18F]-fluorodeoxyglucose-positron emission tomography findings in protein infants with severe periventricular leukomalacia and hypsarrhythmia.

UNLABELLED: Two preterm infants with extensive periventricular leukomalacia (PVL) were examined by [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) at the corrected ages of 18 and 34 days. They showed similar clinical courses including oculoclonic seizure, hypsarrhythmia and severe mental retardation, in addition, to spastic quadriplegia. FDG-PET study of these two infants with severe PVL disclosed poorly developed metabolic activity in the primary sensorimotor cortex, while the MRI images displayed only periventricular white matter lesions. CONCLUSIONS: Positron emission tomography may disclose cortical involvement in infants with severe periventricular leukomalacia.

Blood Glucose↗
PubMed1997

PCR-based detection of mosaicism in Turner syndrome patients.

To study the possible role of cryptic mosaicism in phenotypical variations of 45,X Turner syndrome, we analyzed low-level mosaicism by methods based on the polymerase chain reaction. For the detection of Y-chromosome-derived fragments, we used three Y-specific primer pairs representing the centromere, Yp11.3, and Yq12. None of the 18 patients with 45,X had Y-derived chromosomes. For the detection of X chromosome mosaicism, we employed a novel modified HUMARA (human androgen receptor) assay, which proved to be a sensitive method with a detection limit as low as 1 in 960 cells. Using this assay, we detected low frequency cryptic X chromosome mosaicism in 2 of 18 cytogenetically 45,X patients.

Chromosome Mapping↗
PubMed1997

Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy.

OBJECTIVE: To examine the genetic polymorphism of CYP2C9 and CYP2C19 and its effect on the pharmacokinetics of phenytoin among 44 Japanese patients with epilepsy. METHODS: Polymerase chain reaction tests with leukocyte deoxyribonucleic acid were used to detect the mutations for the amino acid substitution (Arg144-->Cys and Ile359-->Leu) in CgammaP2C9 and for the defective allele (m1 and m2) in CgammaP2C19. The pharmacokinetic parameters of phenytoin in individual patients were estimated by means of empirical bayesian analysis, in which the prior information was the population parameters for Japanese patients with epilepsy. RESULTS: Of the 44 patients, none had the CgammaP2C9 mutation for the Cys144 allele, whereas six patients were heterozygous for the wild-type (wt) and Leu359 allele (wt/Leu359) in cgammaP2C9. The maximal elimination rate (Vmax) of phenytoin among patients with heterozygous wt/Leu359 in CgammaP2C9 was 33% lower than that among patients with normal CgammaP2C9. A total of 21 patients were heterozygous for the CgammaP2C19 mutation (wt/m1 or wt/m2), and five patients had the homozygous or heterozygous mutations in CgammaP2C19 (m1/m1 or m1/m2). The Vmax values of phenytoin were slightly decreased (up to 14%) among patients with CgammaP2C19 mutations compared with patients with normal CgammaP2C19. CONCLUSION: The findings indicated that the genetic polymorphisms of CYP2C isozymes play an important role in the pharmacokinetic variability of phenytoin and that the mutation in CYP2C9 proteins (Ile359-->Leu) is a determinant of impaired metabolism of the drug among Japanese persons.

Adolescent↗
PubMed1997

Unfavorable effects of growth hormone therapy on the final height of boys with short stature not caused by growth hormone deficiency.

A group of 18 boys with non-growth hormone (GH)-deficient short stature without GH therapy (group A) and another group of 9 boys with non-GH-deficient short stature with GH therapy in doses of 0.5 IU (0.17 mg)/kg per week administered 5 to 6 times weekly (group B) were observed until they reached their final height. The mean duration of GH therapy was 4.2 years (range 3.2 to 5.0 years). These two groups were matched with respect to their standard deviation score (SDS) for bone age at the start of observation. Mean +/- SD of the final height for group A and group B was 162.0 +/- 5.4 cm and 154.2 +/- 4.2 cm, respectively. During the prepubertal period, height SDS for bone age of these two groups was not affected by GH therapy. During the pubertal period, however, height SDS for bone age remained constant for group A but decreased gradually for group B. Our observation indicates that for boys with non-GH-deficient short stature GH therapy does not improve height SDS for bone age during the prepubertal period, and in fact reduces it during the pubertal period, possibly resulting in a shorter final height than might have been attained naturally.

Age Determination by Skeleton↗
PubMed1997

IL-7 induces proliferation, variable cytokine-producing ability and IL-2 responsiveness in naive CD4+ T-cells from human cord blood.

We investigated the effects of IL-7 on the proliferation and acquisition of cytokine-producing ability of naive CD4+ T-cells from human cord blood. Naive CD4+CD45RA+ T-cells from human cord blood expressed CDw127 (IL-7R) at higher levels than adult CD4+ CD45RA+ T-cells and produced IL-2 and a small amount of IFN-gamma upon stimulation with PMA and ionomycin. IL-7 induced IL-2-independent proliferation and both Th1- and Th2-type cytokine-producing abilities in cord blood CD4+CD45RA+ T-cells without stimulation via TCR. These results suggest that this IL-7-induced antigen-independent activation mechanism could contribute to maintaining the clonal size of naive T-cells with the potential to differentiate into either Th1 or Th2 cells at the sites of IL-7-expression.

Adult↗
PubMed1997

Successful bone marrow transplantation from an HLA-identical unrelated donor in a patient with hemophagocytic lymphohistiocytosis.

We report a 3-year-old girl with hemophagocytic lymphohistiocytosis (HLH) who received BMT from an HLA-identical unrelated donor when the disease was active. She had entered remission in response to chemotherapy consisting of etoposide and methylprednisolone. After a relapse, her disease became refractory to chemotherapy, and splenectomy was performed with marginal improvement. She underwent BMT from an HLA-identical unrelated donor, conditioned with CY, TBI and anti-thymocyte globulin (ATG). She has been in complete remission for 18 months since the BMT. This result suggests that BMT from an HLA-identical unrelated donor should be considered for HLH even if the disease is active.

Bone Marrow Transplantation↗
PubMed1997

Inhibition of superoxide production and chemotaxis by methotrexate in neutrophils primed by TNF-alpha or LPS.

We have demonstrated recently that methotrexate (MTX) inhibits superoxide generation and chemotaxis induced by N-formylmethionyl-leucyl-phenylalanine (fMLP) in neutrophils primed by granulocyte colony-stimulating factor (G-CSF). To extend these observations, we examined the in vitro effect of MTX on fMLP-stimulated superoxide generation and chemotaxis in neutrophils primed by either tumor necrosis factor alpha (TNF-alpha) or bacterial lipopolysaccharide (LPS). MTX inhibited superoxide generation and chemotaxis more efficiently in TNF-alpha- or LPS-primed neutrophils than in unprimed neutrophils. When either hypoxanthine or guanosine was added to the culture medium, the effects of MTX were partially counteracted. Furthermore, MTX caused a significant inhibition of both superoxide production induced by phorbol 12-myristate-13-acetate and chemotaxis induced by interleukin 8 in G-CSF-primed neutrophils. These results may support the hypothesis that neutrophils primed by different stimuli are more susceptible to the inhibitory effects of MTX on superoxide generation and chemotaxis irrespective of chemoattractants. Such an effect can be partly attributed to the perturbation of purine nucleotide biosynthesis.

Cells, Cultured↗