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Biomedical subjects

T Sakakura

Publications and source records attributed to T Sakakura.

At least 127 records · Page 7Linked to original sources
PubMed1986

Cloning and expression of cDNA encoding mouse tyrosinase.

We have isolated a pigment cell-specific cDNA clone from a B16 mouse melanoma cDNA library by differential hybridization. The mRNA of isolated cDNA is highly expressed in B16 melanoma cells and in black mouse (C57BL/6) skin, but is not detectable in mouse neuroblastoma cells nor in K1735 mouse amelanotic melanoma cells. The protein sequence deduced from the nucleotide sequence of the cloned cDNA shows significant similarity to the entire region of Neurospora tyrosinase. To know the identity of cDNA, we transfected K1735 amelanotic melanoma and COS-7 cells with the cDNA carried in a simian virus 40 vector (pKCRH2). We confirmed that the isolated cDNA encodes mouse tyrosinase by immunofluorescence staining of transfected cells using two different anti-T4-tyrosinase monoclonal antibodies. Tyrosinase is composed of 513 amino acids with a molecular weight of 57,872 excluding a hydrophobic signal peptide of 24 amino acids.

Amino Acid Sequence↗
PubMed1985

A pituitary-salivary mixed gland induced by tissue recombination of embryonic pituitary epithelium and embryonic submandibular gland mesenchyme in mice.

Renal subcapsular syngrafts of Day 9 to 11 mouse embryonic pituitary epithelium with Day 14 mouse embryonic submandibular gland mesenchyme produced mixed organs that include residual cleft structure surrounded by anterior pituitary cells some which are stained by anti-ACTH antiserum and submandibular gland-like structure with differentiated acinar cells which are stained by anti-alpha-amylase antiserum. However, when Day 8.5 or 12 embryonic pituitary epithelium was recombined with submandibular gland mesenchyme and syngrafted, development of submandibular gland-like or anterior pituitary tissues resulted, respectively. Thus, during organogenesis of the mouse anterior pituitary, there exists a developmental stage (Day 8.5-11 in utero), when prospective pituitary epithelium can respond to heterotypic submandibular gland mesenchyme with the development of a submandibular gland-like tissue.

Animals↗
PubMed1985

Participation of two different mesenchymes in the developing mouse mammary gland: synthesis of basement membrane components by fat pad precursor cells.

Two different types of mesenchyme, fat pad precursor cells (FP) and fibroblastic cells (MM) are involved in the morphogenesis of mammary gland epithelium of mouse embryo. Especially, an interaction between FP and the epithelium is necessary for its characteristic shaping of ductal branching structure. To assess the relative participations of the mesenchymes, we have analysed the extracellular matrix products by immunofluorescent staining method using antibodies to laminin, proteoheparan sulphate, and fibronectin. The staining patterns suggested that, after the 16th day of gestation when fatty substances first appeared in FP and the epithelial rudiments started to elongate and branch rapidly, FP initiated synthesis of laminin and proteoheparan sulphate, while MM synthesized fibronectin at all times. Attention was also paid to differences in the epithelial basement membranes (BM) concomitant with ones in the mesenchyme. BM were always stained with antibodies to laminin and proteoheparan sulphate. However, topographical differences in thickness were observed: the one facing FP, often seen at the tip region of the end bud, was thin, while the other surrounded by MM, often at the flank region of the duct, was thick. Specific elaboration of BM-like extracellular matrix products by FP may attribute to observed differences in BM thickness which are related to the characteristic shaping of the mammary gland.

Adipose Tissue↗
PubMed1984

Polyester wax embedding and sectioning technique for immunohistochemistry.

We have developed a method useful for immunohistochemical studies by combining tissue fixation with buffered neutral formalin and polyester wax embedding. Buffered neutral formalin fixation preserves cell and tissue fine structure, and also the antigenicity of unstable enzymes. Polyester wax embedding makes possible thin serial sections of various tissues and preserves antigenicities for at least 6 months. We have demonstrated using this technique the localization of alpha-amylase in mouse salivary gland, parietal-cell specific antigen in mouse glandular stomach, and DNA polymerase alpha and beta in chick tissue.

Animals↗
PubMed1984

Intestine-like remodeling of adult mouse glandular stomach by implanting of fetal intestinal mesenchyme.

A morphogenetic response of adult glandular stomach grown in contact with implanted fetal intestinal mesenchyme has been demonstrated. Mesenchymal tissues from intestines of 14- to 16-day-old BALB/c mouse fetuses were introduced beneath the epithelial layer of glandular stomach in 2-month-old mice and allowed to develop. Three to 4 weeks later, remodeling of the epithelial architecture had occurred; the characteristic glandular pit structure of normal stomach had been replaced by immature villi and crypts composed of mucus-secreting columnar cells more characteristic of intestinal tissues. Chief and parietal cells had disappeared, but neither goblet nor Paneth cells were observed. Such intestine-like morphogenesis was not induced by similarly implanted mesenchymal controls from fetal glandular stomach, forestomach, and salivary gland. A possible role of the mesenchymal stroma in the pathogenesis of intestinal metaplasia in stomach is discussed.

Aging↗
PubMed1982

Dandy-Walker cyst associated with occipital meningocele.

Two cases of Dandy-Walker cyst associated with occipital meningocele are presented. Only 9 cases with such association have been described in the literature. In our patients computed tomography clearly demonstrated direct communication of a posterior fossa cyst with an occipital meningocele at one end and with the fourth ventricle at the other. Occipital meningocele might simply be an expression of increased intracystic pressure in Dandy-Walker cyst in embryonic life, or such association might suggest its morphogenetic situation during embryogenesis.

Brain↗
PubMed1981

Accelerated mammary cancer development by fetal salivary mesenchyma isografted to adult mouse mammary epithelium.

Transplantation of fetal salivary mesenchyma into adult mammary glands resulted in atypical outgrowths from the mammary duct system. These duct-alveolus nodules (DAN) were distinguishable from hyperplastic alveolar nodules (HAN) that arose from normal mammary duct systems in mice infected with murine mammary tumor virus (MuMTV). DAN displayed a type of ductal branching characteristic of salivary gland rather than of mammary gland, reflecting a tissue-specific perturbation of epithelium-mesenchyma in DAN in milk-transmitted MuMTV-infected C3H/HeN mice and in MuMTV-negative BALB/c mice given 7,12-dimethylbenz[a]anthracene (DMBA) subsequent to transplantation of fetal salivary mesenchyma. Mammary cancers were not increased in milk-transmitted MuMTV-free C3H/HeN and GRS/A mice that received salivary mesenchyma transplants. Salivary mesenchyma accelerated mammary carcinogenesis by increasing the mammary epithelial cell population responsive to MuMTV and DMBA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Earlier appearance of murine mammary tumor virus-associated antigens in duct-alveolus nodules induced by transplantation of fetal salivary mesenchyme into C3H mouse mammary glands.

Mammary epithelium of adult C3H mice in contact with fetal salivary mesenchyme took morphogenetically a salivary gland-like pattern of growth and developed a hyperplastic nodular mass at the site of transplantation. When murine mammary tumor virus-bearing C3H mice were treated in this way, early development and high incidence of mammary cancer were observed from these nodules compared to unstimulated mammary glands of the same host. Since tumor development, the viral antigens in these hyperplastic nodules were examined by means of the immunofluorescence technique. As early as 2 weeks after mesenchyme transplantation, the antigens were observed in the ductular or alveolar structure of these nodules, while surrounding normal tissues were not stained. Positive fluorescence was also observed in the mammary tumors that developed from these stimulated nodules. These results strongly suggested the involvement of murine mammary tumor virus in the early development of mammary cancer induced by fetal mesenchyme transplantation.

Animals↗
PubMed1980

Autoimmune oophoritis in thymectomized mice: detection of circulating antibodies against oocytes.

Previous studies from our laboratory described a particular type of ovarian dysgenesis which develops in mice after neonatal thymectomy (Tx) at the critical age of 2-4 days after birth. The present experiment provides evidence which strongly suggests an autoimmune aetiology for this phenomenon. By indirect immunofluorescence (IFL) and horse-radish peroxidase (HRPO) labelled antibody techniques, it was demonstrated that neonatally Tx mice of (C57B1/6Cr x A/JCr)F1 (B6A) and (C3H/HeMs x 129/J)F1 (C31) hybrids produce circulating autoantibody(ies) against ooplasma of oocytes (AOA) in growing follicles, but not against oocytes in primordial follicles. Appearance of AOA was closely correlated with the development of oophoritis which ws characterized by a rapid and complete loss of oocytes at early adulthood. In B6A and C31 mice, oophoritis occurred and AOA appeared in sera after Tx at day 3(Tx -- 3) but not after Tx at days 0 or 7. Also, in athymic B6A and C31 nude mice neither oophoritis or AOA were detectable. Complete absorption of AOA with homogenates of isogeneic normal adult ovaries, but not with homogenates of X-ray-irradiated anovular ovaries or granulosa cell tumour may indicate the specificity of AOA. AOA was first demonstrated at day 30-40 in sera of Tx mice, whose ovaries showed a marked enhancement of follicular degeneration and the death of numerous occytes with or without lymphocyte infiltration. High titres of AOA, detectable in sera of more than 2,000-fold dilutions, were assayed by the IFL technique at day 50-90; however, AOA gradually diminished in titre with age and disappeared at day 150-360 when no oocytes remained in the atrophic ovary. Mice thymectomized at day 3 occasionally produced autoantibodies against zona pellucida and with lesser frequency against steroid-producing cells of the ovary. These data indicate that in the mouse Tx at the critical age shortly after birth produces autoimmune oophoritis, subsequently resulting in early sterility.

Age Factors↗
PubMed1979

Capacity of mammary fat pads of adult C3H/HeMs mice to interact morphogenetically with fetal mammary epithelium.

When rudimentary mammary epithelium from 13- to 17-day female C3H/HeMs fetuses was transplanted into gland-free mammary fat pads of 3-week-old mice, organogenetic development of the grafts occurred, resembling that seen in normal mammary gland morphogenesis. Initial developmental growth did not require the reproductive hormones. Mammary fat pads of juvenile (3-wk-old), young adult (8- to 12-wk-old), and fully matured (40-wk-old) females had equal ability to interact morphogenetically with fetal mammary epithelium. Fetal pulmonary, pancreatic, and salivary gland epithella showed no morphogenetic response within adult mammary fat. An exception was rudimentary hair follicle epithellum, which underwent extensive development toward hair follicles within mammary fat. Mammary glands that developed from rudimentary mammary epithellum transplanted into gland-free fat pads underwent morphologic changes characteristic of lactation when the hosts bore young.

Animals↗
PubMed1979

Acceleration of mammary cancer development by grafting of fetal mammary mesenchymes in C3H mice.

Transplantation of fetal mammary gland mesenchyme into mammary glands of 2-month-old syngeneic virgin mice resulted in focal re-enactment of events that normally occur probably during fetal and early postnatal development of the mammary gland. Portions of the recipient's mammary duct system in contact with the fetal mammary mesenchyme underwent branching and proliferation in a pattern resembling that of rudimentary mammary gland development. This process occurred in C3H mice regardless of whether or not the milk-transmitted mammary tumor virus (MTV-S) was present. In mice carrying MTV-S, mammary cancers of Types A and B appeared earlier and more frequently in the mammary glands that had received transplants of fetal mammary mesenchyme, compared with those in the glands that received no fetal mesenchyme. Some of the smaller cancers were shown to develop directly from portions of the mammary gland interacting with fetal mammary mesenchyme, without preformation of typical hyperplastic alveolar nodules. In C3H mice not carrying MTV-S, cancers did not appear in the similarly treated mammary glands. These facts suggest that non-hormonal and probably nonviral factors that stimulate focal proliferation in the mammary duct system resulting from transplantation of fetal mesenchymes eventually accelerate local development of mammary cancers.

Animals↗
PubMed1979

Prevalent types of tumors developing in neonatally thymectomized mice.

Tumor development was observed for 24 months in neonatally thymectomized (nTx) and normal (C3H/HeMs x 129/J)F1 mice. Thymectomy was performed at 3 days of age. Ovarian (29%, with significant difference from the control at P less than 0.001), pituitary (6%, P less than 0.08), and lymphoreticular tumors (16%, P less than 0.05) were observed in higher incidence in nTx females compared with normal controls, resulting in a significant increase in overall tumor incidence (99 tumors in 114 nTx females vs. 37 tumors in 71 normal females, P less than 0.01). No apparent difference in overall tumor incidence was observed between nTx and non-Tx males. Also, there was no higher risk for lung, liver, and mammary tumors in males and females after neonatal thymectomy. The finding that increased tumor incidence was limited to endocrine and lymphoreticular tissues does not support the concept of immune surveillance of carcinogenesis, but rather suggests the importance of tumor-prone conditioning of endocrine or immune systems as a result of neonatal thymectomy.

Animals↗