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Biomedical subjects

H Kitano

Publications and source records attributed to H Kitano.

At least 73 records · Page 4Linked to original sources

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↗

[A case of adriamycin and methotrexate-resistant recurrent breast cancer treated with doxifluridine and mitomycin C].

A 49-year-old woman was diagnosed with local recurrence and cervical lymph node and bone metastases 55 months after surgery for breast cancer. She was treated with goserelin acetate and tamoxifen but the disease was assessed as progressive after 8 months. Five courses of CMF therapy were performed but lung, pleural and mediastinal lymph node metastases were detected. Then, five courses of CAF therapy were carried out, but a contralateral breast metastasis was detected and the patient complained of shortness of breath. The CAF therapy was assessed as PD. We attempted administration of doxifluridine (5'-DFUR) and mitomycin C (MMC) on an outpatient basis. After 6 months, no progressive disease was detected and she was relieved of her shortness of breath. The combination therapy was assessed as long NC. Combination therapy with 5'-DFUR and MMC is thus a useful treatment for adriamycin- and methotrexate-resistant breast cancer, especially in terms of quality of life.

Antimetabolites, Antineoplastic↗

Bio-calculus: Its Concept and Molecular Interaction.

The way for expressing biological systems is a key element of usability. Expressions used in the biological society and those in the computer science society have their own merits. But they are too different for one society to utilize the expressions of the other society. In this paper, we design the bio-calculus that attempts to bridge this gap. We provide syntax which is similar to conventional expressions in biology and at the same time specifies information needed for simulation analysis. The information and mathematical background of bio-calculus is what is desired for the field of computer science. We show the practicality of bio-calculus by describing and simulating some molecular interactions with bio-calculus.

Journal Article↗

Towards Automatic Construction of Cell-Lineage of C. elegans from Nomarski DIC Microscope Images.

This study aims at automatic construction of a cell lineage from 4D (multi-focal, time-lapse) images, which are taken using a Nomarski DIC (differential-interference contrast) microscope. A system with such abilities would be a powerful tool for studying embryo genesis and gene function based on mutants, whose cell lineage may differ from that of wild types. We have designed and implemented a system for this purpose, and examined its ability through computational experiments. The procedure of our system consists of two parts: (1) Image processing which detect the positions of the nuclei from each 2D microscope image, and (2) Constructing a hypothetical cell lineage based on the information obtained in (1). We have also developed a tool which allows a human expert to easily filter out erroneous nuclei candidates generated in (1). We present computational results and also discuss other ideas which may improve the performance of our system.

Journal Article↗

RT-PCR analysis of mRNA expression of natriuretic peptide family and their receptors in rat inner ear.

To assess the possible physiological role of the atrial natriuretic peptide (ANP) family, we investigated the expression of mRNA of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and their receptors in rat inner ear using the reverse transcription-polymerase chain reaction method. ANP and CNP message bands were detected in the inner ear, but the BNP message band was not. Amplification products of the expected sizes of ANP-A, ANP-B and ANP-C receptors were detected in the inner ear. These results suggest that natriuretic peptide family may influence the function of the inner ear through the ANP-A, ANP-B, and ANP-C receptors.

Animals↗

The distribution of neurons in the substantia nigra pars reticulata with input from the motor, premotor and prefrontal areas of the cerebral cortex in monkeys.

We investigated the distribution of neurons in the substantia nigra pars reticulata (SNr) which received cortical input. The activities of single SNr neurons were studied extracellulary in awake monkeys. SNr neurons showed excitatory and/or inhibitory responses to cortical stimulation. These responses were considered to be mediated by the subthalamic nucleus and striatum, respectively. The neurons receiving inhibitory input from the motor, premotor and supplementary motor areas (Motor-related cortical areas) were located in the lateral part of the SNr, whereas those with input from the medial, dorsal and orbital areas of the prefrontal cortex (PFmdo) were frequently found in the rostro-medial part of this nucleus. SNr neurons with inhibitory input from the ventral periprincipal area (PSv) were mainly distributed in the intermedio-lateral portion, with some degree of overlap with input from other cortical areas. The distribution of the excitatory input was almost similar to that of inhibitory one, but the excitatory input from the PSv was much stronger than that from the PFmdo. Some SNr neurons receiving cortical input were proved to project to the thalamus. Our results support the existence of several parallel organization of the cortico-basal ganglia loop circuits [G.E. Alexander, M.R. DeLong, P.L. Strick, Parallel organization of functionally segregated circuits linking basal ganglia and cortex, Ann. Rev. Neurosci., 9, 1986, pp. 357-381.], but interaction between the loops can not be ignored.

Animals↗

Negative association between asthma and variants of CC16(CC10) on chromosome 11q13 in British and Japanese populations.

The gene encoding Clara cell-derived inflammatory molecule CC16 has been cited as a candidate gene for atopic asthma on chromosome 1lq13. A genetic association study was performed with variants of the CC16 gene on chromosome 1lq13 in relation to asthma in British (n=275) and Japanese (n=300) populations. No significant association was found between asthma and CC16 genotypes, irrespective of atopic status in these two populations. These data suggest that CC16 might not be the major locus for asthma on 11q13.

Asthma↗

Presence of mRNA for vasoactive intestinal polypeptide (VIP) and its receptor in the rat inner ear.

Although mechanisms regulating inner ear fluid have not been yet elucidated, control of blood flow has been thought to be of great importance. Vasoactive intestinal polypeptide (VIP) was the first neuropeptide demonstrated in cerebrovascular nerves. To study the possible role of VIP in regulation of inner ear fluid, we investigated the presence of mRNA for VIP and VIP receptor in the rat inner ear using a reverse transcription-polymerase chain reaction (RT-PCR) method. A single band of the size expected for VIP and its receptor was detected in mRNA from the rat inner ear by using primers specific for VIP and the receptor. The nucleotide sequences of the subcloned RT-PCR products were identical to those of rat VIP and the rat lung VIP receptor. These results indicate that both VIP and VIP receptor are expressed in the inner ear of the rat and suggest that VIP may be implicated in regulation of fluid in the inner ear.

Animals↗

The two-process model of cellular aging.

To understand the mechanism of aging at the cellular level, cellular senescence has been extensively studied as an experimental model of aging in vitro. Although several hypotheses have been proposed for the mechanism of cellular senescence, none of them could give a comprehensive framework to the mechanism. In this study, we showed our results of extensive computer simulation designed to identify possible molecular models of cellular senescence. By examining representative cases of various molecular models, we elucidated the requirements for the plausible mechanism of cellular senescence. Based on these simulation results, we proposed a new molecular model of cellular senescence--the two-process model. In this model, we assumed that two independent, but time-aligned regulatory processes functioned in individual cells. We defined these two processes as S- and C-processes. The S-process mainly determines the rate of decline in the proliferative potential of the cell population. The simulation results suggested that the growth-inhibitory cell-to-cell interaction was required to drive the S-process. The C-process determines the latent proliferative potential of individual cells. The effector genes for the C-process are suggested to be regulated by a certain threshold-type mechanism. Both growth kinetics and senescence-associated gene expression were generated with high accuracy by the combined effect of these two processes. We also succeeded in simulating the effects of simian virus 40 large T antigen and its inducible variant on cellular senescence. From these theoretical considerations, we discuss the validity of the two-process model and the possible involvement of the heterochromatin structure as a determinant of the replicative lifespan of cells.

Cell Division↗