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Biomedical subjects

T Inaba

Publications and source records attributed to T Inaba.

At least 343 records · Page 19Linked to original sources

Selective in vivo inhibition by quinidine of methoxyphenamine oxidation in rat models of human debrisoquine polymorphism.

1. Lewis and Dark Agouti (DA) rat strains (n = 4), models of human extensive and poor metabolizer phenotypes of debrisoquine/sparteine, respectively, were dosed with methoxyphenamine with and without prior administration of quinidine. Methoxyphenamine and its three metabolites, namely N-desmethylmethoxyphenamine, O-desmethylmethoxyphenamine and 5-hydroxymethoxyphenamine were quantified in 0-24 h urine. 2. The oxidative metabolic routes of methoxyphenamine which had been previously shown to involve the debrisoquine/sparteine isozyme, namely O-demethylation and aromatic 5-hydroxylation, were both significantly inhibited by quinidine in the two rat strains. 3. The oxidative metabolic route of methoxyphenamine which had been previously shown to not involve the debrisoquine/sparteine isozyme, namely N-demethylation, was not significantly inhibited by quinidine in either rat strain. 4. The Lewis strain pretreated with quinidine resembled the DA strain without such pretreatment in terms of O-desmethylmethoxyphenamine and 5-hydroxymethoxyphenamine in that the mean percentages of the dose excreted as these two metabolites and the mean O-desmethylmethoxyphenamine/methoxyphenamine and 5-hydroxymethoxyphenamine/methoxyphenamine ratios were similar to one another. 5. Ten days after quinidine administration to the Lewis strain of rat, all parameters of methoxyphenamine and its metabolites returned to normal. 6. A protocol involving substrate administration to Lewis strain rats with and without prior administration of quinidine could be developed as an attractive approach to screen substrates for metabolism in vivo by the debrisoquine/sparteine isozyme. Such an approach obviates interstrain differences.

Amphetamines↗

Suppression of lactation by pregnancy-dependent mammary tumors in GR/A mice.

Pregnancy-dependent mammary tumors (PDMT) in GR/A mice appear during pregnancy, disappear soon after parturition, and appear again during subsequent pregnancies. The retardation of pup growth, an indication of the level of milk production, was also observed with the advance of lactation numbers in this strain. This study was performed to elucidate the relationship between PDMT and lactational performance. At the end of the second pregnancy, mice were divided into two groups according to the presence of PDMT [PDMT(-) and PDMT(+) groups]. Although all PDMT disappeared within a day after parturition, the weight and growth of pups on Day 12 of lactation were significantly less in the PDMT(+) group than in the PDMT(-) group. Associated with this, the DNA and RNA contents of the mammary glands were apparently lower in the former than in the latter, although the differences were not statistically significant. There was little difference in mammary RNA/DNA ratio between groups. No difference was also observed between groups in endocrine organ weights, mother body weights, morphology of the mammary glands, adrenals and ovaries and plasma prolactin and progesterone levels. These results suggest that PDMT suppression of lactation is principally due to the retardation of mammary gland growth. Furthermore, no significant correlations were obtained between the size of PDMT and the parameters for mammary gland function. The data suggest that the development of PDMT per se is important for the retarded mammary gland growth.

Animals↗

Renal blood volume vs. glomerular filtration rate: evaluation with C15O and 88Ga-ethylenediaminetetraacetic acid (EDTA) study.

68Ga-EDTA (ethylenediaminetetraacetic acid) is simply and economically obtained without a cyclotron. We used renal blood volume (RBV) values obtained by C15O studies for blood activity subtraction on renal time activity curves using a positron emission tomography for the determination of the glomerular filtration rate (GFR) by intravenous 68Ga-EDTA administration. Positive correlation was revealed between the GFR and RBV values, where the ratio of blood activity in whole renal activity increased relatively as GFR value decreased. The estimation using a correction equation derived from the correlation curve was possible without a C15O study.

Blood Volume↗

[Acute myelomonocytic leukemia (M4) with CD19 antigen expression, eosinophilia and basophilia in bone marrow].

A 12-year old boy was admitted to Saitama Children's Medical Center because of fever and epistaxis. He had leukocytosis (WBC 40,800/microliters, blast 75%), anemia, thrombocytopenia and high levels of serum LDH, lysozyme, Vitamin B12, and plasma histamine. Bone marrow aspiration revealed hypercellular marrow with 31.2% blasts, 15.2% eosinophils, and 14.2% basophils. Blasts had Auer rods and were positive for peroxidase and negative for alpha-naphthyl butyrate esterase and PAS stainings. Ia, CD13 (My7), and CD19 (B4) antigens were expressed on his leukemic cells. Chromosomal study showed 46, XY, t(7;8) (q35;q22), del(9) (q13q22). Southern blot analysis using immunoglobulin constant region (C) probes revealed germline patterns of C mu, C kappa, C lambda, and breakpoint cluster region. A diagnosis of acute myelomonocytic leukemia (AMMoL, M4) was made. He attained a complete remission with daunorubicin and cytarabine, and 6 months later he received bone marrow transplantation from HLA-identical sister. This case had the common breakpoint 8q22 with ANLL with t(8;21) (q22;q22), and was unique AMMoL with proliferation of eosinophils and basophils in bone marrow.

Antigens, CD19↗

[Conversion of acute leukemia from a T-lymphoid to a myeloid phenotype].

A 7-year-old girl with an acute leukemia was reported whose blasts showed conversion from a T-lymphoid to a myeloid phenotype. At the onset of the disease, the blasts were negative for peroxidase and displayed FAB L1 morphology. Surface marker analysis revealed only CD7 antigen. Although complete remission was achieved, an extramedullary relapse was identified as having a several subcutaneous tumors 15 months later. Tumor cells showed the same marker expression as that of the blasts at the onset. After short term culture without an addition of any differentiation stimulators, the blast cells expressed CD2, CD3, CD4, CD8, and CD25 antigens. The karyotype was 46, XX, t(12; 21) (p11; q22). The intensive chemotherapy and radiation therapy were carried out, however, a hematological relapse occurred 12 months later. At this time, the blasts were strongly positive for peroxidase and expressed HLA-DR and CD33 antigens with disappearance of the CD7 antigen. Chromosome analysis revealed the additional abnormalities (del (7) (p15), -17, +der (17) t (17;?) (p13;?].

Child↗

[Effect of high-dose cyclophosphamide plus high-dose etoposide in malignant brain tumors of children followed by autologous bone marrow rescue].

Four pediatric patients with malignant brain tumors were treated with very high-dose etoposide plus very high-dose cyclophosphamide (HD-VP 16/CPM) followed by autologous bone marrow rescue. There were two brain stem gliomas, which were refractory to radiation therapy, ACNC, and beta-interferon and two relapsed malignant brain tumors. Both of the two with brain stem gliomas achieved response, one with clinical improvement and decrease of tumor size on CT scanning, the other with clinical improvement. Overall response duration was three months and nine months. Two patients with relapsed brain tumors received HD-VP 16/CPM as adjuvant chemotherapy. Low but significant levels of VP 16 and CPM were detected in CSF. Further investigation of HD-VP 16/CPM is needed as a chemotherapy for malignant brain tumors in children.

Antineoplastic Combined Chemotherapy Protocols↗

[Surgical resection of pulmonary metastasis from genitourinary cancers].

Three patients who underwent surgical resection for pulmonary metastases were reviewed. The primary lesion was testicular tumor, bladder cancer and renal cell carcinoma. One of these patients is alive without disease at 30 months after the pulmonary resection, while the others died of recurrence at 3 and 7 months after the surgical resection, respectively. As a factor affecting prognosis, characteristics of the primary lesion, especially its chemosensitivity, was thought to be important. The surgical resection of pulmonary metastasis may be effective, if the indication is assessed carefully.

Adenocarcinoma↗

Method to determine the enantiomers of ibuprofen from human urine by high-performance liquid chromatography.

By means of ethyl chloroformate, ibuprofen enantiomers were coupled to 4-methoxyaniline. The resulting amides were resolved from each other and from urinary constituents on a Pirkle column using an isocratic mobile phase with ultraviolet detection at 254 nm. Applicability of this method for the determination of inter-individual differences in urinary metabolic profiles of ibuprofen enantiomers is demonstrated. The chromatographic behavior of the corresponding amide derivatives of two ibuprofen metabolites is also described.

Biotransformation↗

Non-identity of human plasma lysozyme and 4-methylumbelliferyl-tetra-N-acetyl-beta-D-chitotetraoside hydrolase.

1. Using 4-methylumbelliferyl-tetra-N-acetyl-beta-D-chitotetraoside (MU-TACT) as substrate, it is possible to measure the activity of purified lysozyme and to demonstrate lysozyme activity in the urine of patients with acute monocytic leukemia, characterized by massive lysozymuria. 2. Notwithstanding this observation, we present evidence that in normal human plasma another acid endoglucosaminidase is hydrolyzing the substrate. 3. The following data support the hypothesis of the existence of a separate hydrolase: (a) Thermoinactivation is different for MU-TACT hydrolase and lysozyme. (b) In plasma and many other biological samples, the concentration of lysozyme is too low to be measured with the artificial substrate and there is no correlation between MU-TACT hydrolase and lysozyme. (c) Serum of lysozyme deficient rabbits has normal MU-TACT hydrolase activity. (d) On Sephadex G-200 and DEAE cellulose chromatography, lysozyme and MU-TACT hydrolase are eluted separately. (e) Immunoremoval of lysozyme from human plasma does not affect the activity towards MU-TACT. (f) The effect of N-acetylglucosamine and N-acetylmuramic acid on the activity of lysozyme and MU-TACT hydrolase is different.

Animals↗

Childhood myelodysplastic syndromes with 11p15 translocation.

Two cases of childhood myelodysplastic syndrome with chromosome abnormalities involving band 11p15 are described. The first case, with inv(11)(p15q23), had a complex clinical course; the initial diagnosis was aplastic anemia, then refractory anemia with excess of blasts in transformation (RAEB-t), and finally, before death, chronic myelomonocytic leukemia with hematologic features similar to those of chronic myelogenous leukemia (CML). The second case, with t(4;11)(p13;p15), progressed from RAEB to acute myelogenous leukemia (M2). In the literature, we found 12 patients with nonlymphocytic leukemia and chromosome abnormalities involving band 11p15, including seven cases with t(7;11)(p13-p15;p15); four cases (including the present case 1) showed CML-like hematologic features. It is suggested that translocations involving 11p15 are a nonrandom chromosome abnormality in nonlymphocytic leukemia.

Bone Marrow↗

Oxazepam as a probe of hepatic metabolism in patients with Alzheimer's disease.

1. Hepatic metabolism of oxazepam in Alzheimer's disease (AD) was assessed by measurement of urinary metabolites in a group of hospitalized patients with AD, a hospitalized schizophrenic control group and a normal community based group. 2. A subgroup of six AD patients showed marked elevations of the hydroxylated metabolite. The median excretion of conjugated oxazepam in the AD and schizophrenic patients was almost one third that in normal controls (p less than .005). 3. A relationship between decline in level of conjugated metabolite and increase in the mental confusion score on the London Psychiatric Rating Scale (r = -.5253, p less than .05) was found in the AD patients. 4. Changes in hepatic metabolism in AD may be relevant not only for drug metabolism and the development of side effects, but also for the pathogenesis of AD.

Aged↗

Chromosome findings and prognosis in 15 patients with neuroblastoma found by VMA mass screening.

We performed chromosome analysis of 15 neuroblastomas found by mass screening using a vanillymandelic acid spot test. We found near triploid chromosome abnormalities, ranging from 60 to 77 chromosomes, in the tumor cells from 14 patients, and hyperdiploidy with the mode of 50 in cells from one. A structural abnormality was observed in only one patient. We did not find a marker chromosome 1, homogeneously staining region, or double minutes, which have been previously reported in advanced neuroblastomas or in cell lines. All of our patients were completely free of disease 4 to 32 months after diagnosis. We consider that patients with hyperdiploidy or near triploidy are different from those with marker chromosome 1, homogeneously staining region, or double minutes and may constitute a subgroup with a good prognosis in childhood neuroblastoma.

Adrenal Gland Neoplasms↗

A preliminary note on the transient polymorphic oxidation of sparteine in the Ngawbé Guaymí Amerindians: a case of genetic divergence with tentative phylogenetic time frame for the pathway.

The oxidation of sparteine was studied in a total of 121 Ngawbé Guaymí volunteers in Panama, 97 of whom were unrelated. When presented in a frequency histogram, the results of the log10 of the metabolic ratios (LMR) indicated the existence of two modes, the largest of which exhibited a normal distribution (alpha = 0.05; chi 2 = 5.46). A preliminary assignment of an antimode for this population sample is proposed, located within the region of LMR 0.65 to 0.85 vs LMR of 1.3 for white subjects, and results in five poor metabolizers (PMs) (5.2%). This is in contrast to the absence of PMs (0/210) we have reported for the Cuna Amerindians. The microevolution of the sparteine route, corresponding to a tenfold change in the frequency of PMs, is likely to have occurred within their genetic divergence time. These observations of the divergence of a metabolic route of therapeutic importance and the proposal of a time frame for its microevolution constitute the first cases in the literature.

Adolescent↗

The oxidative metabolism of sparteine in the Cuna Amerindians of Panama: absence of evidence for deficient metabolizers.

Sparteine sulfate (50 mg) was administered to 170 Cuna Amerindians, 142 of whom were unrelated, and the drug and its dehydrometabolites were determined in the 0- to 12-hour urine samples. The log10 of the metabolic ratio was unimodally, but not normally, distributed and showed the following values: mean -0.21 +/- 0.26, median -0.24, limits -0.73 and 0.76, skewness 1.00, and kurtosis 4.95. On the basis of these results, it can be concluded that there are no deficient metabolizers in the Cuna sample population studied. However, the similarity of the skewness found between the Cuna sample population studied and the extensive Canadian white group, as well as an inflection point at 6.3 U in the former's probit plot, suggests the existence of at least two subgroups congregating within the same single mode in the frequency distribution curve. The use of the inflection point is discussed thoroughly, concluding that although it does not allow exclusion of the existence of genotypically different subgroups, the limitations of the data do not permit its use to determine the number of heterozygotes and thus the existence of polymorphism. The possibility of an isozyme variant, consistent with the general genetic structure of Amerindians, as suggested by the coexistence of two subgroups within the unimodal curve, is entertained.

Adolescent↗

Effects of pituitary grafting on plasma and milk levels of prolactin, growth hormone and progesterone in mice.

Plasma and milk levels of prolactin, growth hormone (GH) and progesterone on days 12-13 of lactation were compared between C3H/He female mice grafted with isologous anterior pituitaries each under the kidney capsules 2-3 days after placing with males and intact controls. At the 1st lactation, both plasma and milk levels of prolactin were higher in the experimental mice than in the control, however, at the 2nd lactation, milk prolactin level of the former decreased to about 1/8 of that of the latter, whereas plasma prolactin level further elevated in the former. While plasma GH level was increased by pituitary grafting, milk GH level was slightly affected by the treatment at either the 1st or the 2nd lactation. There was only a small difference between the experimental and the control groups in either plasma or milk level of progesterone at the 1st and the 2nd lactations. Progesterone levels in plasma and milk were higher at the 1st lactation than at the 2nd lactation in both the experimental and the control groups. These results suggest that the transfer of plasma hormones into milk is not always free, but there may be any regulatory mechanism(s) in this process.

Animals↗