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Biomedical subjects

K Kadomatsu

Publications and source records attributed to K Kadomatsu.

At least 91 records · Page 5Linked to original sources
PubMed1997

Le(X) structure enhances myocardial differentiation from embryonic stem cells.

alpha-1,3-Fucosyltransferase (Fuc T IV) cDNA was placed under the control of beta-actin, cytomegalovirus enhancer/promoter and transfected into embryonic stem cells. The transfected cell clones with integrated cDNA (positive clones) differentiated more efficiently into myocardial cell clones without integrated cDNA (negative clones) or parental cells. Furthermore, myocardial cells differentiated from the positive clones survived longer than those differentiated from the negative clones or parental cells. These results indicate that Lewis X structure, the product of Fuc T IV, enhances myocardial differentiation. The mechanism of the phenomenon is discussed on relation to integrin action.

Animals↗
PubMed1997

Expression of syndecan-1 and -3 during embryogenesis of the central nervous system in relation to binding with midkine.

Midkine (MK) is a 13-kDa heparin-binding growth/differentiation factor, and its interaction with heparan sulfate proteoglycan is important in promotion of neurite outgrowth. This study was performed to reveal the species of syndecans that interact with MK during embryogenesis of the central nervous system in the rat. Northern blot analysis and immunohistochemical staining using antibodies to syndecans showed that syndecan-1 was strongly expressed in the brain and spinal cord of the 10-day rat fetus, and the expression became weak as embryogenesis proceeded. On the other hand, syndecan-3 expression was stronger both in the brain and spinal cord in the later developmental period (day 14-16 of gestation). No significant expression of ryudocan (syndecan-4) was detected in fetal brains by Northern blot analysis. Syndecan-3 isolated from 16-day rat fetus bound to MK strongly, as did syndecan-1 isolated from 10-day rat fetus. Thus, both syndecan-1 and syndecan-3 were considered to be involved in interaction with MK during construction of the central nervous system; syndecan-1 is expected to play important roles in the earlier periods, and syndecan-3 in the later periods.

Animals↗
PubMed1996

Regulation of apoptosis induced by transforming growth factor-beta1 in nontumorigenic rat prostatic epithelial cell lines.

Transforming growth factor-beta1 (TGF-beta1), which is induced in the prostate following castration, has been speculated to mediate apoptosis of epithelial cells during prostatic involution. Here, we report the first evidence of a direct effect of TGF-beta on induction of apoptosis in prostatic epithelial cells in vitro, using NRP-152 nontumorigenic and NRP-154 tumorigenic rat prostatic epithelial cell lines. TGF-beta1 induces apoptosis of both cell lines within 24 h, as shown by a decrease in cell viability, in situ DNA nick-end labeling, and internucleosomal DNA fragmentation. Moreover, the ability of TGF-beta to induce apoptosis of NRP-152 is strictly dependent on culture conditions, because dexamethasone enhances while insulin and insulin-like growth factor-I specifically block apoptosis induced by TGF-beta. We suggest that TGF-betas are direct physiological regulators of apoptosis of prostatic epithelial cells.

Animals↗
PubMed1996

Roles of basigin, a member of the immunoglobulin superfamily, in behavior as to an irritating odor, lymphocyte response, and blood-brain barrier.

Basigin is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Using the knockout mouse lacking the basigin gene (Bsg), we analyzed the function of basigin in adult mice lacking the gene [Bsg (-1-)]. Although histochemical studies on the localization of basigin (also called HT7 and neurothelin) strongly indicated that it is involved in the function of the blood-brain barrier, basigin knockout mice showed only a little difference, if any, to wild-type mice in the function of the blood brain-barrier. The mitogenic response of lymphocytes upon mixed lymphocyte reaction was greater in Bsg (-1-) mice. Finally, Bsg (-1-) mice repeatedly visited filter paper impregnated with acetic acid or isozine, indicating an abnormality in either reception of the odor or behavior as to it.

Animals↗
PubMed1996

The expression of truncated MK in human tumors.

Midkine (MK) is a heparin binding growth/differentiation factor different from fibroblast growth factors (FGFs), and is largely composed of two domains which are found by a folded polypeptide chain interconnected by disulfide bridges. Polymerase chain reaction revealed the presence of a short MK mRNA in 7 among 12 human tumor cells which expressed MK mRNA. All of 4 pancreatic carcinoma cell lines expressed the short species in addition to the full size mRNA. The short mRNA lacked an exon and resulted in the lack of a more N-terminally located domain. The truncated form of MK was found also in some surgically removed specimens of human tumors, but not in noncancerous tissue.

Base Sequence↗
PubMed1996

Enzyme-linked immunoassay for midkine, and its application to evaluation of midkine levels in developing mouse brain and sera from patients with hepatocellular carcinomas.

Midkine (MK) is a growth factor that promotes neurite outgrowth and survival of neurons, and enhances the plasminogen activator in endothelial cells. A highly sensitive enzyme-linked immunoassay for MK was developed, involving affinity-purified anti-MK antibodies, their biotinylated form, and avidin-beta-galactosidase. The amount of bound avidin-beta-galactosidase was determined using a fluorogenic substrate, 4-methylumbelliferyl-beta-D-galactoside. This method allowed the detection of human and mouse MK in the range of 50 pg-10 ng. Pleiotrophin, which is related to MK in its amino acid sequence, did not show any cross reactivity. Employing this method, the MK levels in the developing mouse brain were determined. The MK level was 2 micrograms/g of wet tissue on the 12th day of gestation, and then steadily decreased during embryogenesis and postnatal development to 30 ng/g two months after birth. The assay method can also be applied to serum samples. Although the MK levels in the sera of normal human subjects were low or undetectable, 0.6-8 ng/ml of MK was detected in samples in the majority of cases of hepatocellular carcinomas.

Animals↗
PubMed1995

Restricted expression of Xenopus midkine gene during early development.

Midkine (MK) is a heparin-binding growth factor and forms a novel protein family together with another member, pleiotrophin (PTN)/heparin-binding growth-associated molecule (HB-GAM). A cDNA clone isolated from Xenopus laevis specifies for the Xenopus counterpart of MK (XMK), and the mode of XMK expression was studied by in situ hybridization and Northern blot analysis. XMK was first expressed at stage 11 (middle gastrula) and was located in the neural anlage at stage 12 (late gastrula). Through stage 13 to 15 (early neurula), XMK expression was restricted to the neural folds. At stage 23 (tailbud stage), XMK was predominantly localized in the brain and neural tube. At the larva stage, XMK expression was again restrictedly observed in the brain, the optic vesicles, the otic vesicle, and the spinal cord, all of which are derivatives of the neural tube, as well as in the branchial arches, derivatives of the cranial neural crest. Comparing the mode of MK expression between Xenopus and the mouse, we propose that MK plays evolutionally conserved roles in neurogenesis and development of the craniofacial architecture of ectomesenchymal origin. We also found that XMK was expressed in various adult organs; strong expression was observed in the brain, the eye and the spinal cord, all of which showed intense MK expression at the larva stage.

Amino Acid Sequence↗
PubMed1995

Increased midkine gene expression in human gastrointestinal cancers.

Midkine (MK) is a product of a retinoic acid-responsive gene, and is a novel growth differentiation factor. We examined the expression of the MK gene in specimens of 47 surgically removed human carcinomas of the gastrointestinal organs, namely, gastric, colorectal, hepatocellular, pancreatic, esophageal, ampullary duodenal and bile duct carcinomas. In most cases, the MK mRNA level was higher in cancer specimens than in the corresponding non-cancerous tissues. Furthermore, MK mRNA was more highly expressed in the colon adenocarcinoma lesion than in the adenoma lesions, in the two familial polyposis cases. While MK mRNA was not detected in the normal liver, it became detectable in cirrhotic tissues in 2 of 4 cases, and its expression was increased in the cancerous tissues. Thus, the increase of MK mRNA level is a phenomenon seen in many human gastrointestinal carcinomas. The increased expression of the MK gene in gastric carcinoma was significantly more prominent in well and moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas and signet ring cell carcinomas.

Adult↗
PubMed1995

[Beneficial effect of a retinoic acid responsive gene product, midkine, on constant light-induced retinal damage in albino mice].

We studied the protective effects of midkine, a growth factor produced by a retinoic acid responsive gene, on constant light-induced retinal damage in albino BALB/C adult mice. Two days before exposure to constant light, midkine was injected into the vitreous of the left eye and a phosphate buffer saline into the right eye (control eyes). After 7 days of constant light, control eyes exhibited shortening of the photoreceptor outer segments and decreased thickness of the outer nuclear layer, whereas in midkine-treated eyes photoreceptor cells were virtually intact. Although midkine-treated eyes also showed photoreceptor damage after longer light exposure of up to 21 days, the damage was significantly less than in control eyes. Measurement of the thickness of the outer nuclear layer showed the protective effect of intravitreous midkine on the constant light-induced retinal damage. These findings suggest that midkine is a potential agent for the prevention of photoreceptor degeneration.

Albinism, Ocular↗
PubMed1994

Development and characterization of nontumorigenic and tumorigenic epithelial cell lines from rat dorsal-lateral prostate.

We have established two new epithelial cell lines (NRP-152, NRP-154), with markedly different properties, from the dorsal-lateral prostate of Lobund/Wistar rats treated with N-methyl-N-nitrosourea and testosterone propionate. NRP-152 cells do not form tumors in athymic mice and retain many of the properties of normal prostatic epithelial cells. They produce prostatic acid phosphatase, have functional androgen receptors, and require the combination of several growth factors in addition to serum for optimal growth. Their growth is stimulated by epidermal growth factor, insulin, dexamethasone, cholera toxin, dihydrotestosterone, and testosterone, and their growth is inhibited by transforming growth factor beta s and retinoic acid. These cells also respond to 1,25-dihydroxyvitamin D3 with an early growth stimulation followed by growth inhibition at later times. In contrast, tumorigenic NRP-154 cells lack detectable androgen receptor mRNA and have less stringent growth factor requirements for optimal growth. Growth of NRP-154 cells is stimulated by dexamethasone and insulin, inhibited by transforming growth factor beta 1, but not significantly altered by epidermal growth factor, cholera toxin, dihydrotestosterone, retinoic acid, or 1 alpha,25-dihydroxyvitamin D3. Our data suggest that the NRP-152 and NRP-154 cell lines are suitable systems for analysis of normal prostate growth and prostatic carcinogenesis.

Acid Phosphatase↗
PubMed1994

Histogenesis of induced prostate and seminal vesicle carcinoma in Lobund-Wistar rats: a system for histological scoring and grading.

We have developed a grading system for the evaluation of the histogenesis of neoplastic lesions of the prostate and seminal vesicle of the laboratory rat. Prostatic and seminal vesicle carcinomas were induced in Lobund-Wistar rats by initiation with 30 mg/kg N-nitroso-N-methylurea i.v., followed by promotion with 40 mg testosterone propionate implants 1 week later and at 3-month intervals thereafter. Experimental and control groups were sacrificed at various time points between 5 and 11 months after dosing with N-nitroso-N-methylurea in order to visualize progressive stages of carcinogenesis of the dorsolateral prostate, the anterior prostate, and the seminal vesicle. A system of staging was created which allows three different categories (in situ change, invasion, desmoplasia) of tumor development to be ranked progressively in a manner conducive to nonparametric analysis. Each category was then further subdivided to create a total of six stages. This system can be used to evaluate agents which modify tumor induction or suppression. The application of this staging system to the measurement of the effects of the synthetic retinoid, 4-hydroxyphenyl retinamide, on prostatic carcinogenesis in the Lobund-Wistar rat is described.

Animals↗
PubMed1993

Expression of sulfated glycoprotein 2 is associated with carcinogenesis induced by N-nitroso-N-methylurea in rat prostate and seminal vesicle.

To understand the molecular mechanism of carcinogenesis in androgen-dependent tumors, we have searched for new markers which are associated with this process. In normal rat prostate and seminal vesicle, sulfated glycoprotein 2 (SGP-2) messenger RNA is barely detectable. However, we have found high levels of SGP-2 expression in the epithelial component of carcinomas of the prostate and seminal vesicle after initiation with N-nitroso-N-methylurea and promotion with testosterone propionate. We have also observed induction of SGP-2 expression in epithelial cells at early stages in carcinogenesis when cytologically malignant cells first begin to appear. SGP-2 has been reported previously to be associated with a variety of models of programmed cell death (apoptosis), including the prostate following castration. Our present findings provide a novel marker for carcinogenesis in the rat prostate and seminal vesicle.

Animals↗
PubMed1993

A new family of heparin-binding growth/differentiation factors: increased midkine expression in Wilms' tumor and other human carcinomas.

Midkine (MK) and heparin-binding growth-associated molecule/pleiotrophin form a new family of heparin-binding growth/differentiation factors. We studied MK gene expression in human tumors. In normal human reference tissues, MK was highly expressed in the mucosal tissue of the small intestine, moderately in the thyroid, weakly in the tissues of the lung, colon, stomach, kidney, and spleen, and not at all in the liver. All of 6 surgically removed specimens of Wilms' tumor highly expressed MK. Also, a moderate to intense level of MK expression was noted in the majority of surgically removed hepatocellular carcinomas. The MK mRNA level was analyzed in a number of cultured and nude mice-transplanted lines of human tumors. In stomach, colon, pancreatic, lung, and esophageal carcinomas, a moderate to high level of MK expression was found in the majority of them. These results suggest an important role of MK in the development and/or biological behavior of tumors and raised a possibility to use MK as a diagnostic marker. Heparin-binding growth associated molecule/pleiotrophin mRNA was low or scarcely detectable in samples analyzed thus far except for significant levels of the expression that were observed in PA-1 teratocarcinoma cells and in some surgical specimens of Wilms' tumor.

Base Sequence↗
PubMed1993

Embigin, a member of the immunoglobulin superfamily expressed in embryonic cells, enhances cell-substratum adhesion.

Embigin is a glycoprotein belonging to the immunoglobulin superfamily, and is preferentially expressed before 10 days of gestation during mouse embryogenesis. To study its function, an embigin cDNA under the control of beta-actin promoter and Rous sarcoma virus enhancer was introduced into L cells. Transfectants expressing embigin were found to have enhanced cell-substratum adhesion activity, which was evident by microscopic observation and could be determined quantitatively by culturing cells on plastic dishes in serum-free medium containing 0.05% bovine serum albumin. After 6 hr of culture about 50% of the transfected cells adhered to the dish, whereas parental cells scarcely adhered. The enhanced cell-substratum adhesion was Ca2+ dependent and inhibited by an arginine-glycine-aspartic acid peptide, which competitively inhibits integrins, and also by anti-integrin antiserum. Thus, one role of embigin appears to be promotion of integrin-mediated cell-substratum adhesion.

Animals↗
PubMed1992

Undifferentiated (embryonal) sarcoma of the liver: report of three cases.

Undifferentiated (embryonal) sarcoma is a rare malignant tumor of the liver. It typically presents in late childhood and its prognosis is poor. We experienced three cases of such a tumor during the period of 1976-1989; two of these patients are still alive without disease. Each case was independently treated with a combination of surgery and pre- and/or postoperative chemotherapy, which was found to be effective. In one surviving patient, cyclophosphamide and vincristine were found to be effective, while in the other a combination of cisplatin, Adriamycin (ADM), vincristine and cyclophosphamide was observed to induce a rapid reduction in the size of the recurrent tumor. Thus, an adequate combination of surgery and chemotherapy may improve the prognosis of this tumor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Genomic structure of human midkine (MK), a retinoic acid-responsive growth/differentiation factor.

Midkine (MK) is a product of a retinoic acid-responsive gene and a new heparin-binding growth/differentiation factor. The coding sequence of human MK was located on 1.5 kb DNA segment. The structure of the cloned human MK gene was determined and compared with that of the mouse gene. The coding sequence was divided into 4 exons, and each exon and exon-intron boundary was highly homologous to those of the mouse. Furthermore, 170 bases in the upstream region of the putative transcription initiation sites and 3 blocks of 200-350 bases in regions further upstream were highly conserved. These sequences are likely to be involved in developmentally regulated expression of MK.

Animals↗
PubMed1991

A new family of heparin-binding factors: strong conservation of midkine (MK) sequences between the human and the mouse.

A retinoic acid responsive gene, MK, specifies for a heparin binding factor termed midkine (MK), which is the initial member of a new protein family involved in regulation of growth and differentiation. A cDNA clone of human MK was isolated from a fetal kidney cDNA library. Human MK mRNA was expressed in PA1 teratocarcinoma cells as well as in the kidney. Sequence analysis of the cDNA clone and of a part of the genomic clone yielded the predicted protein sequence of human MK. Human and mouse MK sequences are highly conserved: 87% of amino acids are identical and all amino acid changes are conservative except for an insertion. Comparison of MK and HB-GAM/pleiotrophin (another member of the family) from various species revealed sequences conserved in the family and those specific for each protein.

Adult↗