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Biomedical subjects

T Inaba

Publications and source records attributed to T Inaba.

At least 325 records · Page 18Linked to original sources

[Relapsed stage I neuroblastoma successfully treated by allogeneic bone marrow transplantation in second remission: case report of a 7-year-old girl].

Stage I neuroblastoma in a seven-year-girl have had local recurrence with bone metastasis. Second surgery was performed after the aggressive chemotherapy including cisplatin, VP16, cyclophosphamide, vincristine and doxorubicin. She underwent allogeneic bone marrow transplantation from her HLA identical brother, following the preparative regimen consisting of high-dose melphalan and total body irradiation (12 Gy). Clinical course after the transplantation was uneventful. She is still alive with no evidence of disease for twenty-eight months after the transplantation. It is suggested that bone marrow transplantation is an effective way of therapy even in a patient with relapsed neuroblastoma.

Adrenal Gland Neoplasms↗

[Myelodysplastic syndrome in a child which developed into megakaryocytic leukemia with late appearing Ph1 chromosome and rearrangement of breakpoint cluster region].

A 3-year-old boy was referred to our hospital in September 1985, because of pancytopenia. His bone marrow was normocellular with 18% blasts, which had Auer rod and were positive for peroxidase staining. A diagnosis of refractory anemia with excess blasts in transformation was made according to FAB criteria. Chromosome analysis of bone marrow cells showed normal male karyotype. He attained complete remission with aclarubicin and BH-AC and continued it until August 1987 when pancytopenia and hypoplastic bone marrow developed. Chromosome analysis of bone marrow cells showed normal male karyotype and gene analysis revealed germ-line configuration of breakpoint cluster region (bcr). Overt leukemia developed in May 1988 when his WBC count increased to 60, 600/microliters with 91% blasts, which were negative for peroxidase staining, positive for anti-Ia and CDw 41 by cell surface analysis, and positive for ultrastructurally demonstrable platelet peroxidase. A diagnosis of megakaryocytic leukemia was made. Chromosome analysis of bone marrow cells showed 46, XY, t(9;22) (q34;q11) and gene analysis revealed rearrangement of bcr. He died in November 1988. Our results and review of literature suggest that late appearing ph1 chromosome and rearrangement of bcr may occur in a variety of hematologic malignancies and influence the course of disease.

Anemia, Refractory, with Excess of Blasts↗

[Effect of combination therapy with carumonam and clindamycin on severe infections in patients with hematologic malignancies].

We evaluated the efficacy of a combination therapy with carumonam (CRMN) and clindamycin (CLDM) on severe infections in patients with hematologic malignancies. Fifty three patients were included in this study. The efficacy of the combination therapy was evaluated according to the criteria by TAKAKU et al. Fourteen cases were evaluated as excellent, and 24 cases were as good, with a total rate of effectiveness of 71.7% (38/53). It should be noted that the rate of effectiveness in patients having less than 100/microliters neutrophils was 77.3% (17/22). Adverse effects were observed in 2 patients (3.7%). One case was hepatotoxicity and the other was nephrotoxicity. Both were mild and transient, however. These observations suggested that the combination therapy with CRMN and CLDM was effective and safe for the treatment of severe infections in patients with hematologic malignancies.

Adult↗

cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver.

A cDNA designated hIIB1, representing the entire coding sequence of a P450 in the IIB gene family, was isolated from a human liver lambda gt11 library by using the rat IIB1 cDNA as a probe. The hIIB1 protein, deduced from the cDNA sequence, contained 491 amino acids, had a calculated molecular weight of 56,286, and displayed 76% amino acid similarity with the rat IIB1 protein. Expression of this cDNA, using the vaccinia virus system, yielded a P450 that had a reduced CO-binding spectrum with an absorption maximum of 452 nm. The expressed human enzyme was able to catalyze the deethylation of 7-ethoxy-coumarin. Total RNA from 13 livers was probed for levels of hIIB mRNA. Two livers had high levels, four contained moderate levels, and eight contained very low, or no detectable, mRNA. These data suggest either that defective hIIB1 genes exist in humans or that the hIIB1 gene is regulated and variably induced in our liver specimens. To search for mutant mRNA transcripts, libraries were constructed from livers expressing low levels of hIIB1 mRNA. A cDNA, designated hIIB2, was isolated that was identical with the hIIB1 cDNA except for the presence of an unusual alteration of the DNA near its 5' end corresponding to the putative exon 4. This alteration was caused by a deletion of 29 bp and an insertion of 44 bp of nonhomologous DNA. This sequence replacement occurs at the junction of the third and fourth exons as predicted from the structure of the rat IIB1 gene, suggesting that a faulty splice might have given rise to the variant hIIb2 transcript.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine.

Immunoblotting analysis of human liver microsome preparations revealed that human cytochrome P-450 PCN1 (hPCN1, Mr approximately 52,000) was expressed in each of 40 individual specimens examined. In about 10-20% of the livers, an immunologically related protein having a lower electrophoretic mobility (Mr approximately 52,500) was also detected. A single liver was found that expressed only the lower mobility protein, designated hPCN3, and RNA isolated from this liver was used to construct a lambda gt11 library. The library was screened with an hPCN1 cDNA probe resulting in the isolation of a unique full-length cDNA that was sequenced and shown to encode hPCN3. The deduced amino acid sequence of this cDNA contained 502 residues, a calculated molecular mass of 57,115 daltons, and displayed 84% similarity with hPCN1. The deduced amino-terminal sequence of hPCN3 was identical to that of HFLa, a major cytochrome P-450 expressed in human fetal liver that is immunologically cross-reactive with several family III cytochrome P-450s. hPCN1 and hPCN3 cDNAs were expressed in Hep G2 cells using a vaccinia virus expression system and shown to encode active enzymes, both characterized by reduced CO-binding spectra with lambda max at 450 nm. Enzymatic analysis revealed that both cytochrome P-450s were similarly active in catalyzing oxidation of the calcium channel blocking drug nifedipine. Both enzymes also catalyzed 6 beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione, although hPCN1 exhibited several-fold higher expressed activity than hPCN3. Several minor oxidation products of these steroids (e.g. 15 beta-hydroxytestosterone), comprising up to approximately 20% of the total metabolites, were formed by hPCN1 but not hPCN3, indicating that hPCN3 is a more highly regiospecific monooxygenase catalyst with steroid substrates. Clear differences were also detected in their catalytic activities toward the immunosuppressive drug cyclosporine, with two hydroxylated metabolites (M1 and M17) and one demethylated metabolite (M21) formed by hPCN1 but only one metabolite (M1) formed by hPCN3. These studies establish that hPCN3 is a newly described cytochrome P-450 that is differentially expressed in the adult human population and that has overlapping substrate specificity compared to hPCN1 for metabolism of steroid and drug substrates.

Amino Acid Sequence↗

Cytogenetic findings and prognosis in neuroblastoma with emphasis on marker chromosome 1.

The relationship between cytogenetic findings and prognosis in 51 pediatric patients with neuroblastoma is described. Patients were classified into the following four groups based on karyotypic findings: (1) near diploidy, 42 to 47 chromosomes (n = 11); (2) hyperdiploidy, 50 to 56 chromosomes (n = 4); (3) near triploidy, 60 to 77 chromosomes (n = 33); and (4) hypotetraploidy, 80 to 83 chromosomes (n = 3). Patients with near diploid or hypotetraploid karyotypes also had several structural abnormalities including marker chromosome 1, with or without double minutes (DM) or homogeneously staining regions (HSR). Most of these patients were 1 year of age or older and had advanced tumors. The patients who were in the hyperdiploid or near triploid category had few structural abnormalities; all of them, except one, were younger than 1 year of age, had localized tumors, and are long-term, disease-free survivors. Kaplan-Meier analysis of survival rates disclosed a significant difference favoring the latter group (P less than 0.001). N-myc gene amplification was found in five patients of the former group but in no patients of the latter group. The presence or absence of DM or HSR in the former group had no statistically demonstrable effect on survival. However, the presence of marker chromosome 1 appears to indicate a poor prognosis. Five patients with Stage IV-S disease had near triploid abnormalities similar to findings in patients with localized tumors. We propose that localized and Stage IV-S neuroblastomas can be classified as one disease category, and that patients with near diploid or hypotetraploid karyotypes are clinically distinct from those having hyperdiploid or near triploid karyotypes. We consider that chromosomal pattern is a more influential prognostic factor than age, disease stage, or N-myc gene amplification.

Child↗

Heterogeneity in the breakpoints of chromosome 19 among acute leukemic patients with the t(11;19)(q23;p13) translocation.

Gene probes for insulin receptor (INSR) and c-ets-1 were hybridized to metaphase cells from three leukemic patients with the t(11;19)(q23;p13) translocation. Patients 1 and 2 were diagnosed as acute lymphocytic leukemia (ALL) (L2), and patient 3, as acute myelogenous leukemia (AML) (M4). The c-ets-1 gene was demonstrated to have translocated from chromosome 11 to the short arm of the rearranged chromosome 19 (19p+) in all three patients. On the other hand, the INSR gene translocated from chromosome 19 to the rearranged chromosome 11 (11q-) in the AML case, but remained on the rearranged chromosome 19 in the two ALL cases. Thus, the breakpoints of chromosome 19 are different among the patients studied, proximal to the INSR gene locus in the AML case and distal in the two ALL cases. Consequently, the c-ets-1 gene and the INSR gene remain separated in the AML case, whereas they become close to each other in the two ALL cases. Rearrangement of these two genes was studied in the two ALL patients, with no positive data being obtained. The results suggest that there may be heterogeneity in the breakpoints of chromosome 19 among the t(11;19)-associated acute leukemias.

Chromosomes, Human, Pair 11↗

Similar chromosomal patterns and lack of N-myc gene amplification in localized and IV-S stage neuroblastomas in infants.

Chromosome analysis was performed on 33 neuroblastomas in infants. Near triploid chromosome abnormalities (range, 60 to 77) were found in 29 patients with localized and IV-S stage neuroblastoma, and hyperdiploidy (range, 50 to 56) in 3 patients with localized neuroblastoma. No marker chromosome 1, homogeneously staining region (HSR), or double minutes (DMS) was observed in these patients, all of which have been previously reported in advanced neuroblastomas. N-myc gene amplification was not detected in any of these patients. All the patients were completely free of disease 4-45 months after diagnosis. Only one patient with stage IV neuroblastoma had a marker chromosome 1 (mode 46) and N-myc gene amplification and relapsed. Five patients with IV-S neuroblastoma lacking N-myc gene amplification had near triploid chromosomal abnormalities similar to those seen in localized neuroblastoma in infants. We consider that, cytogenetically, localized and IV-S neuroblastoma may be within the same disease category and different from advanced neuroblastoma.

Chromosome Aberrations↗

Enzyme-linked immunosorbent assays for human tissue kallikrein and analysis of immunoreactive kallikrein in the plasma by them.

In order to study immunoreactive tissue kallikrein (TK) in human plasma, three kinds of enzyme-linked immunosorbent assay (ELISA) systems for human urinary kallikrein (HUK) were developed. All three types of TK in the plasma, i.e., active kallikrein, prokallikrein and kallikrein-alpha 1 antitrypsin (alpha 1 AT) complex, could be measured by the competitive ELISA (C-ELISA). However, the sandwich ELISA (S-ELISA) showed more strict specificity. Namely, both active and prokallikreins were able to be measured by the S-ELISA, while kallikrein-alpha 1 AT complex was hardly measurable. Measurement of this kallikrein-alpha 1 AT complex was made possible by using horseradish peroxidase (HRP)-labeled anti-alpha 1 AT IgG instead of HRP-labeled anti-HUK Fab' as the second antibody (HS-ELISA). Using these ELISAs we studied TK in plasma and the following observations were made. 1) The greater part of TK in the plasma was found in a form of a complex with alpha 1 AT. 2) The amount of free type TK was very small and the most part of this type TK in normal plasma was prokallikrein.

Chromatography, Affinity↗

Fatal infectious mononucleosis with staphylococcal pyoderma in a girl with hereditary immunological dysregulations.

We describe a 14-year-old girl with fatal infectious mononucleosis with high fever, pancytopenia, and multiple skin ulcers due to Staphylococcus aureus. Immunological studies revealed low serum IgM, low natural killer (NK) activity, and high CD4/CD8 ratio. Her father had also low NK activity and high CD4/CD8 ratio. It is suggested that she had a dominantly inherited immunodeficiency predisposing to severe Epstein-Barr virus infection.

Adolescent↗

Membrane filters for the concentration of trace elements in water: distribution of ion pairs between membrane filter and aqueous phases.

The sorption of ion pairs on membrane filters (MFs) has been studied by taking the membrane filter as one of the homogeneous phases. The sorbability of some ionic species and the sorption abilities of different types of MF were evaluated in terms of the sorption constant defined by Ksor,CA = [(C+,A-)f]/[C+][A-], where C+, A- and (C+,A-) refer to the cation, anion and the ion pair, respectively, and f refers to the filter phase. The values of Ksor,CA were determined for many combinations of ionic complexes of cobalt(III) with pyridylazophenols, either as cations or anions, and oppositely charged organic ions having different alkyl chain lengths, with MFs made of different materials: nitrocellulose (NC; Toyo Advantec), acetylcellulose (AC; Fuji Film), regenerated cellulose (RC; Toyo Advantec) and polyethersulphone (PS; Toyo Advantec). For a given cobalt complex ion, the value of log Ksor,CA increased linearly with the increasing number of carbons in the counter ion. Membrane filters made of different materials showed different sorption abilities, the order being NC greater than PS greater than RC greater than AC. It was shown that the surface area of the MF is of greater significance than the volume of the matrix of the MF in determining the sorption constant.

Elements↗

Chronic myelomonocytic leukemia with chromosomal changes involving 1p36 and hepatocellular carcinoma in a case of Fanconi's anemia.

A girl with Fanconi's anemia developed chronic myelomonocytic leukemia and hepatocellular carcinoma. At the time that chronic myelomonocytic leukemia was diagnosed, all metaphases of the bone marrow cells revealed a chromosomal translocation involving 1p36. It is suggested that the occurrence of this rare type of leukemia in our patient is related to the chromosomal translocation.

Anemia, Aplastic↗

Cocaine: pharmacokinetics and biotransformation in man.

Pharmacokinetic studies of cocaine have been carried out only in the last decade, although its local anesthetic action and addictive properties have been known for almost 100 years. Elimination half-lives of cocaine in man estimated from serial plasma concentration are relatively short and range from 0.5 to 1.1 h after i.v. and 0.9-1.5 h after administration by the nasal or oral route. The bioavailability after nasal inhalation is about 60%. The bicyclic structure of cocaine is characterized by functional groups including N-methyl, carboxyl methyl ester, and benzoyl ester, which are susceptible to biotransformation. Hydrolysis of the benzoyl group to ecgonine methyl ester is catalyzed by plasma cholinesterase and is thus under monogenic control. The hydrolytic cleavage of the other ester group, methyl ester, to benzoyl ecgonine occurs spontaneously at body temperature. In contrast, N-demethylation of cocaine mediated by microsomal cytochrome P-450 produces norcocaine and this metabolite was shown to be pharmacologically active, the action being similar to cocaine.

Biotransformation↗

Haloperidol reduction can be assayed in human red blood cells.

One metabolite of haloperidol present in plasma is "reduced haloperidol." This study demonstrates that human red blood cells are capable of converting haloperidol to reduced haloperidol in vitro. The reductase involved requires NADPH, as does haloperidol (ketone) reductase in human liver cytosol.

Adult↗

[Clinical consideration for the bridge pontic with the removable plate applying SmCo5 magnet and ferromagnetic alloy].

SmCo5 magnets and ferromagnetic alloy, which were recently developed, have been used to the removable prosthesis, but are not used to the fixed one. We have applied them as a retainer to the bridge pontic with the removable plate. This pontic have following advantage: 1. It is easy to clean and to alter the pontic lower area attached to the alveolar tissue. 2. It is a simple apparatus. Here we propound 2 typical cases with fine result.

Dental Alloys↗