Molecular network modeling and data analysis
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Journal Article↗
Biomedical subjects
H Kitano
Publications and source records attributed to H Kitano.
[A case of effective bisphosphonate therapy of sequential pamidronate and incadronate for bone metastases from breast cancer].
A 55-year-old woman complained of neck pain ten years after undergoing surgery. She was diagnosed as having bone metastases and treated using pamidronate therapy with doxifluridine, tamoxifen and fadrozole, which was assessed as effective. She complained of neck pain 32 months after pamidronate infusion. CT revealed that the sclerosis had continued but new lytic lesions were detected in the cervical vertebra. Thus, we attempted incadronate and medroxyprogesterone acetate (MPA) administration. After 2 months, incadronate therapy with MPA relieved her neck pain. CT revealed lytic lesions of cervical vertebra showing sclerosis 3 months after this treatment and the sclerosis has continued. Bisphosphonate therapy of sequential pamidronate and incadronate with MPA administration is a useful treatment for bone metastasis from breast cancer.
Antineoplastic Combined Chemotherapy Protocols↗
[A case of effective chemotherapy using CAF followed by docetaxel for advanced breast cancer].
A huge mass measuring 13 x 12 cm and wide cutaneous edema were detected in the right breast of a 51-year-old woman. Under a diagnosis of locally advanced breast cancer (T4bN2M1, stage IV) with liver metastases, we attempted sequential neoadjuvant chemotherapy. After three courses of CAF therapy (cyclophosphamide, doxorubicin (DXR), 5-FU), the primary tumor was decreased by 56% and the liver metastases had disappeared. A minor pathologic response was observed. Subsequently, three courses of docetaxel (TXT) administration were carried out. The primary tumor was then decreased by 75% and the axillary metastases had disappeared. Histopathological examination showed gross viable tumor cells in the residual tumor and positive axillary lymph nodes. The only toxic effect was nausea (grade 1) and no major adverse effects were observed. Neoadjuvant chemotherapy with sequential DXR followed by TXT is a useful treatment for locally advanced breast cancer.
Antineoplastic Agents, Phytogenic↗
[Two bedridden patients with bone metastases from breast cancer effectively treated with pamidronate therapy].
Case 1: A 43-year-old woman underwent mastectomy because of locally advanced breast cancer with multiple bone metastases. She was treated with CMF therapy but developed a compression fracture of a thoracic vertebra after 10 months and received pamidronate therapy. Pamidronate administration relived her back pain after 2 months and she was able to walk again after 3 months. However, she developed a resistance to the treatment, and then refused another treatment. She was found to have hypercalcemia 6 months later and received pamidronate again, but died 9 months after the treatment. Case 2: A 52-year-old woman underwent mastectomy because of breast cancer (T2) and was diagnosed as having multiple bone metastases 24 months after the operation. She could not turn over in bed due to progressing bone pain and received pamidronate therapy with CMF therapy at home 23 months after the diagnosis. After 2 months, pamidronate administration relieved her bone pain and she was free of pain after 4 months. After 5 months, X-rays revealed that lytic lesions showed sclerosis, and the pamidronate therapy was assessed as producing a PR. Pamidronate therapy improved her quality of life and activities of daily living, and she continues to receive it this time as an outpatient. Pamidronate therapy is promising as an effective treatment for bedridden patients with bone metastasis from breast cancer.
Adult↗
A gene network inference method from continuous-value gene expression data of wild-type and mutants.
In this paper we introduce a new inference method of a gene regulatory network from steady-state gene expression data. Our method determines a regulatory structure consistent with an observed set of steady-state expression profiles, each generated from wild-type and single deletion mutant of the target network. Our method derives the regulatory relationships in the network using a graph theoretic approach. The advantage of our method is to be able to deal with continuous values of steady-state data, while most of the methods proposed in past use a Boolean network model with binary data. Performance of our method is evaluated on simulated networks with varying the size of networks, indegree of each gene, and the data characteristics (continuous-value/binary), and is compared with that of predictor method proposed by Ideker et al. As a result, we show the superiority of using continuous values to binary values, and the performance of our method is much better than that of the predictor method.
Animals↗
Suppression of the heterotrimeric G protein causes abnormal morphology, including dwarfism, in rice.
Transgenic rice containing an antisense cDNA for the alpha subunit of rice heterotrimeric G protein produced little or no mRNA for the subunit and exhibited abnormal morphology, including dwarf traits and the setting of small seeds. In normal rice, the mRNA for the alpha subunit was abundant in the internodes and florets, the tissues closely related to abnormality in the dwarf transformants. The position of the alpha-subunit gene was mapped on rice chromosome 5 by mapping with the restriction fragment length polymorphism. The position was closely linked to the locus of a rice dwarf mutant, Daikoku dwarf (d-1), which is known to exhibit abnormal phenotypes similar to those of the transformants that suppressed the endogenous mRNA for the alpha subunit by antisense technology. Analysis of the cDNAs for the alpha subunits of five alleles of Daikoku dwarf (d-1), ID-1, DK22, DKT-1, DKT-2, and CM1361-1, showed that these dwarf mutants had mutated in the coding region of the alpha-subunit gene. These results show that the G protein functions in the formation of normal internodes and seeds in rice.
Base Sequence↗
Regulation of inner ear fluid in the rat by vasopressin.
The anti-diuretic hormone vasopressin has been shown to be important in regulating inner ear fluid. The diuretic hormone, CNP, and its receptor, ANP-B receptor, may also function in the regulation of inner ear fluid. To determine whether vasopressin directly affects the fluid level, we infused this hormone to rat and assay of V2-AVP receptor mRNA by semiquantitative RT-PCR demonstrated a significantly lower level of this transcript in vasopressin-infused animals than in saline-infused animals. The levels of CNP and ANP-B receptors mRNA, however, were the same in both groups of rats. Results suggest that high plasma levels of vasopressin may be a principal causal factor of endolymphatic hydrops in Meniere's disease, perhaps by down-regulating the number of vasopressin receptors.
Animals↗
Temperature-Responsiveness of A-B-A Block Telomers at Solid-Liquid Interfaces.
Macroinitiators were prepared by coupling disuccinimidyl ester of 4,4'-azobis(cyanovaleric acid) with poly(N-isopropylacrylamide) (PIPA), which had an amino group at its end. Styrene was telomerized with the initiators in THF. When the styrene content in the A-B-A block telomer obtained (PIPA-b-PSt-b-PIPA) was high, the telomer formed an irreversible aggregation resulting in microspheres, whereas the telomer with a much shorter styrene block could be dispersed monomolecularly. The telomers dispersed in water were aggregated by raising the temperature above 32 degrees C due to a coil-globule transition of PIPA moieties. The PIPA-b-PSt-b-PIPA could be strongly adsorbed to polystyrene (PSt) solid surfaces to form a layer, and the PSt blocks might lay on the PSt surface and the PIPA blocks might direct to the solution phase. The contact angle of air bubbles on the surface of telomer-coated PSt in the air-in-water system was dependent on temperature; that is, with the increase in temperature the contact angle of air bubbles largely decreased and leveled off above the coil-globule transition temperature (Tc). Correspondingly, the amount of protein Concanavalin A adsorbed to the telomer layer deposited on the PSt surface increased gradually with an increase in temperature and leveled off above the Tc. These phenomena were attributed to the changes in hydrophobicity of the telomer layer below and above the Tc. The usefulness of macroinitiators in preparing various kinds of block telomers which have responsiveness to external stimuli was strongly suggested. Copyright 1999 Academic Press.
Journal Article↗
Recognition of Amphiphiles with Many Pendent Galactose Residues by Ricinus communis Agglutinin.
Amphiphiles which carry many pendent galactose residues as side chains were prepared by telomerization of 2-methacryloyloxyethyl beta-D-galactopyranoside (MEGal) or 3-(2-methacryloyl aminoethylthio)propyl D-galactopyranoside (MEPGal, alpha:beta = 3.9:1) using a lipophilic radical initiator. The galactose-carrying amphiphiles (DP (degree of polymerization) = 15) incorporated in liposomes were recognized by a lectin from Ricinus communis (RCA120), which was proven by the increase in turbidity of the liposome suspension after mixing with the lectin. The recognition was largely affected by the distance between the galactose residues and the polymer main chain, and the surface density of the amphiphile in the liposomes. The liposomes containing these galactolipids were not taken up by mouse peritoneal macrophages, probably due to a steric hindrance of polymer main chains from the uptake of D-galactose receptors on the macrophages. Copyright 1999 Academic Press.
Journal Article↗
Loss-of-function mutations in the rice homeobox gene OSH15 affect the architecture of internodes resulting in dwarf plants.
The rice homeobox gene OSH15 (Oryza sativa homeobox) is a member of the knotted1-type homeobox gene family. We report here on the identification and characterization of a loss-of-function mutation in OSH15 from a library of retrotransposon-tagged lines of rice. Based on the phenotype and map position, we have identified three independent deletion alleles of the locus among conventional morphological mutants. All of these recessive mutations, which are considered to be null alleles, exhibit defects in internode elongation. Introduction of a 14 kbp genomic DNA fragment that includes all exons, introns and 5'- and 3'- flanking sequences of OSH15 complemented the defects in internode elongation, confirming that they were caused by the loss-of-function of OSH15. Internodes of the mutants had abnormal-shaped epidermal and hypodermal cells and showed an unusual arrangement of small vascular bundles. These mutations demonstrate a role for OSH15 in the development of rice internodes. This is the first evidence that the knotted1-type homeobox genes have roles other than shoot apical meristem formation and/or maintenance in plant development.
Gene Expression Regulation, Plant↗
Squamous Cell Carcinoma of the Breast: Three Case Reports.
Three cases of squamous cell carcinoma of the breast, initially diagnosed by fine needle aspiration cytology, are presented. The first case was a 49-year-old woman with a T1 tumor located in the lower outer quadrant of the left breast. Ultrasonography revealed a cystic tumor. Aspiration cytology suggested squamous cell carcinoma (SCC). Mastectomy was performed. Histological examination revealed a pure SCC. The second case was a 40-year-old woman with a T1 tumor located in the upper outer quadrant of the right breast.Ultrasonography showed a cystic tumor and aspiration cytology revealed SCC. A quad-rantectomy was performed. Histological examination revealed predominant SCC with an adeno-carcinoma component. Estrogen receptor (ER) was negative. The patient received postoperative radiation. Thirteen months after the first operation,a salvage mastectomy was performed because of local recurrence. The third case was a 61-year-old woman with a T1 tumor located in the upper outer quadrant of the right breast. Ultrasonography showed a solid tumor. Aspiration cytology revealed both SCC and adenocarcinoma. Wide excision was performed. Histological examination revealed pre-dominant SCC with foci of adenocarcinoma. ER was negative. She received postoperative radiation. The three patients are alive and disease-free 10 to 54 months after operations
Journal Article↗
Expression of inducible nitric oxide synthase in human thyroid papillary carcinomas.
To evaluate the relationship between nitric oxide (NO) and carcinogenesis, we assayed 4 human thyroid papillary carcinomas (TPC) and 3 normal thyroid glands for the presence of inducible nitric oxide synthase (iNOS). Using an antibody against iNOS, we observed immunohistochemical staining if iNOS in the TPC samples, but not in normal thyroid. When we incubated TPC samples with antibodies against both iNOS and human leukocyte antigen (LCA), a macrophage marker, we found that while most TPC cells were stained with anti-iNOS antibody, only a few were stained with both. Reverse transcription polymerase chain reaction (RT-PCR) showed that iNOS mRNA was expressed in the samples of TPC, but not in normal thyroid. The sequence of iNOS message in the TPC samples was identical to that previously detected in a human colon cancer cell line. These results suggest that iNOS in human TPC is mostly derived from tumor cells, rather than macrophages, and that it may play a direct role in carcinogenesis.
Base Sequence↗
An ultrashort 1-day protocol of Tc-99m tetrofosmin.
PURPOSE: This study describes a new 1-day protocol with Tc-99m tetrofosmin that requires only 100 minutes to obtain both stress and resting cardiac images by using a double-injection and subtraction method. METHODS: This procedure was performed in 48 consecutive patients. Rest-rest double injections were performed in eight patients (five men, three women; mean age, 69 +/- 9.8 years ) to evaluate count and image reproducibility (subprotocol A), and stress-rest and additional resting perfusion images (true rest) were done on a different day in 11 patients (five men, six women; mean age, 63 +/- 5.9 years) to confirm the validity of the new protocol (subprotocol B). RESULTS: Image quality scores of the resting image were excellent (35 of 48, or 72.9%), good (7 of 48, or 14.6%), fair (3 of 48, or 6.3%), and poor (3 of 48, or 6.3%). The scintigraphic findings with the new protocol corresponded closely with those of angiography in 26 of 34 cases (76.5%), with a tendency for underestimation (in 5 of 34 cases, or 14.7%) rather than overestimation (in 3 of 34 cases, or 8.8%). In subprotocol A, count reproducibility between the two resting images was excellent (r = 0.95; P < 0.0001); and in subprotocol B, the early-rest images were concordant visually and quantitatively with the true rest images (r = 0.89, P < 0.0001). CONCLUSION: Although there are some limitations, this protocol can be used as a routine stress-rest protocol.
Aged↗
Regional expression of the rice KN1-type homeobox gene family during embryo, shoot, and flower development.
We report the isolation, sequence, and pattern of gene expression of members of the KNOTTED1 (KN1)-type class 1 homeobox gene family from rice. Phylogenetic analysis and mapping of the rice genome revealed that all of the rice homeobox genes that we have isolated have one or two direct homologs in maize. Of the homeobox genes that we tested, all exhibited expression in a restricted region of the embryo that defines the position at which the shoot apical meristem (SAM) would eventually develop, prior to visible organ formation. Several distinct spatial and temporal expression patterns were observed for the different genes in this region. After shoot formation, the expression patterns of these homeobox genes were variable in the region of the SAM. These results suggest that the rice KN1-type class 1 homeobox genes function cooperatively to establish the SAM before shoot formation and that after shoot formation, their functions differ.
Amino Acid Sequence↗
Prognostic factors in severe alcoholic liver injury. Nara Liver Study Group.
Severe alcoholic liver injury has been relatively rare, but is gradually increasing in Japan. The clinical features and prognostic factors in severe alcoholic liver injury were retrospectively investigated in 105 patients, consisting of 3 with severe alcoholic hepatitis (SAH), 43 with cirrhosis with superimposed alcoholic hepatitis [liver cirrhosis (LC)+alcoholic hepatitis (AH)], 38 with AH, and 21 with alcoholic cirrhosis. Seven of the 105 patients (6.7%, 2 with SAH and 5 with LC+AH) died of hepatic failure. Patients with SAH showed severe hyperbilirubinemia, reduced hepatic biosynthetic capacity, and marked acute inflammatory reactions, and developed multiple organ failure, such as disseminated intravascular coagulation (DIC), renal failure, acute pancreatitis, or pneumonia. Two SAH patients died within 1 month, whereas five with LC+AH died within 77 days during the second episode of AH. In these nonsurvivors, the serum total bilirubin (T.Bil) level was not normalized, and the hepaplastin test (HPT), serum albumin, cholesterol, and platelet count were not markedly improved after the first episode of AH. In the survivors, elevation of AST lasted longer, and the improvement of T.Bil, hepatic biosynthetic capacity, and the platelet count were much less in patients with LC+AH than in those with AH. Multivariate analysis using the Cox proportional hazards model showed serum C-reactive protein (CRP) and DIC as significant independent prognostic factors among SAH, LC+AH, and AH groups. When factors related to multiple organ failure, such as DIC and renal failure, were excluded, T.Bil and CRP were selected as independent prognostic factors. In patients with LC+AH and AH, CRP, and HPT were shown to be significant independent prognostic factors. These results suggest that SAH with multiple organ failure, and another episode of AH in advanced LC with hyperbilirubinemia and reduced hepatic biosynthetic capacity, are indicative of an extremely poor prognosis in chronic alcoholics.
Adult↗
Simulation of genetic interaction for Drosophila leg formation.
The formation of Drosophila wings and legs are major research topics in Drosophila development, and several hypotheses, such as the polar-coordinate model and the boundary model, has been proposed to explain mechanisms behind these phenomena. A series of recent studies have revealed complex interaction among genes involved in establishing three principal axes (A-P, D-V, and P-D) of leg formation. In this paper, we present a simulation system for leg formation, simulating the genes interactions involved. We use this simulator to investigate a mathematical framework of leg formation which is otherwise well-founded from a molecular perspective. Particularly, we focus on the formation of the expression patterns of dpp, wg, dll, dac, al, en, hh and ci genes, which are involved in the development of the third instar Drosophila leg disc. The most interesting part of this research is showing how the coaxial gene expression patterns behind the P-D axis can be formed, and how positional information, as postulated in the polar-coordinate model, can be conveyed to each cell. Our results suggest that P-D axis can be formed by a set of genes with different activation thresholds; the process involves different chemical gradients of dpp and wg products, forming a bi-polar contour. Interestingly, this combination of chemical gradients can specify unique positions of cells for the hemisphere, leaving the A-P axis determiner to decide only whether the cells are anterior or posterior. All in all, our so-called Bi-Polar Model describes axial formation of the leg disc well.
Animals↗
Initiation of shoot apical meristem in rice: characterization of four SHOOTLESS genes.
The regulatory mechanism of shoot apical meristem (SAM) initiation is an important subject in developmental plant biology. We characterized nine recessive mutations derived from four independent loci (SHL1-SHL4) causing the deletion of the SAM. Radicles were produced in these mutant embryos. Concomitant with the loss of SAM, two embryo-specific organs, coleoptile and epiblast, were lost, but the scutellum was formed normally. Therefore, differentiation of radicle and scutellum is regulated independently of SAM, but that of coleoptile and epiblast may depend on SAM. Regeneration experiments using adventitious shoots from the scutellum-derived calli showed that no adventitious shoots were regenerated in any shl mutant. However, small adventitious leaves were observed in both mutant and wild-type calli, but they soon became necrotic and showed no extensive growth. Thus, leaf primordia can initiate in the absence of SAM, but their extensive growth requires the SAM. An in situ hybridization experiment using a rice homeobox gene, OSH1, as a probe revealed that shl1 and shl2 modified the expression domain of OSH1, but normal expression of OSH1 was observed in shl3 and shl4 embryos. Accordingly, SHL1 and SHL2 function upstream of OSH1, and SHL3 and SHL4 downstream or independently of OSH1. These shl mutants are useful for elucidating the genetic program driving SAM initiation and for unraveling the interrelationships among various organs in grass embryos.
Gene Deletion↗
[A case of pleural and mediastinal lymph node metastases from breast cancer effectively treated with fadrozole hydrochloride in combination with cyclophosphamide].
A 63-year-old woman was diagnosed with pleural and mediastinal lymph node metastases 116 months after operation because of bilateral breast cancer. She was then treated with fadrozole hydrochloride (FH) (2 mg). Adriamycin (30 mg) administration into the pleural cavity was attempted, but did not prove effective. Thus, we tried to combine FH with cyclophosphamide (100 mg). After one month, chemoendocrine therapy relieved her complaints of cough and shortness of breath. CT revealed a remarkable decrease of pleural effusion and disappearance of mediastinal lymph nodes. She was alive 9 months after the treatment. Fadrozole hydrochloride in combination with cyclophosphamide is promising as an effective treatment in postmenopausal patients.
Antineoplastic Combined Chemotherapy Protocols↗