Search PubMed⌕ Search

Biomedical subjects

S Koike

Publications and source records attributed to S Koike.

At least 109 records · Page 6Linked to original sources

Characterization of three different transgenic mouse lines that carry human poliovirus receptor gene--influence of the transgene expression on pathogenesis.

Three transgenic mouse lines, ICR-PVRTg1, ICR-PVRTg5, and ICR-PVRTg21, which are susceptible to poliovirus, have been established by introducing the human gene for poliovirus receptor (PVR) into the genome of mouse strain ICR. Genetic characterizations of the PVR gene were carried out on these mouse lines to define the approximate copy number, insertion site, and expression of the transgene in the central nervous system (CNS). The transgene was integrated in the chromosome 4, 12, and 13 of ICR-PVRTg1, ICR-PVRTg5 and ICR-PVRTg21 mice, respectively, and was stably transmitted to progeny mice. ICR-PVRTg1 appeared to have the most abundant copy numbers of the transgene and showed the highest level of PVR mRNA and membrane associated PVR protein in the CNS among the three mouse lines. Those in ICR-PVRTg21 and ICR-PVRTg5 were at intermediate and lowest levels, respectively. In the CNS, PVR mRNA was detected at high levels only in neurons of the spinal cord and brain stem where poliovirus can replicate, suggesting that the PVR mRNA expression confers cell specificity to poliovirus in the CNS. ICR-PVRTg1 and ICR-PVRTg5 showed the highest and the lowest sensitivity to poliovirus, respectively, whereas ICR-PVRTg21 was in-between. These results may suggest that poliovirus sensitivity of the mice is attributed to relative levels of PVR expression.

Animals↗

A murine model for bone marrow metastasis established by an i.v. injection of C-1300 neuroblastoma in A/J mice.

A reproducible tumor model for bone marrow metastasis has been developed by an injection of murine C-1300 neuroblastoma (C-1300 NB) cells into the tail vein of syngeneic A/J mice. The animals died with liver metastases at 18-21 days after an injection of 10(5) tumor cells and often had bone marrow metastasis in the femur. N-methylformamide (NMF), a maturational agent, was administered to inhibit liver metastases and to extend survival in mice with advancing bone metastasis. Histological examination of bone marrow metastasis, demonstrated lesions varying from a few small colonies of C-1300 NB cells either in metaphysis or diaphysis to large foci replacing normal hematopoietic bone marrow, simultaneously invading epiphysis or cortex of bone as bone metastasis. This assay demonstrated the ability to detect neuroblastoma cells in the bone marrow histologically and could determine bone marrow TD50 by extraction of bone marrow cells after treatment with various doses of drug. Fifty per cent of mice injected with cyclophosphamide (CY) developed bone marrow metastasis without liver metastasis. Treatment with tamoxifen, an anti-calmodulin drug, suppressed tumor takes in the recipient mice with tamoxifen-dose-dependent fashion. This experimental system allows for investigations into the therapeutic response and biology of neuroblastoma metastases in the bone marrow.

Animals↗

Tissue tropism and species specificity of poliovirus infection.

Paralytic poliomyelitis is caused by the destruction of neurons in the central nervous system during the lytic replication of poliovirus. The human gene for the poliovirus receptor has been cloned recently, and transgenic mice generated that are susceptible to this virus. This has allowed the critical amino acids that determine the specificity of poliovirus to be identified.

Amino Acid Sequence↗

Repopulation of tumour cells following irradiation with X-rays or low energy neutrons.

The repopulation of C3H mouse mammary carcinoma cells following X-ray or fast neutron irradiation was investigated in vivo using TCD50 as an endpoint. Tumours in the C3H mouse leg were irradiated in air with an X-ray dose of 9.6, 28.8 or 48.0 Gy, or a neutron dose of 2.6 or 5.2 Gy, and, various times thereafter, graded X-ray doses were given under hypoxic conditions to determine TCD50. Substantial recovery from sublethal and potentially lethal radiation damages was observed within 48 h following X-ray irradiation, and less recovery was found after neutrons. The effective number of tumourigenic cells was calculated at the time of the second irradiation using the TCD50 equation based on the multitarget model. The effective cell doubling time following X-rays depended on radiation dose. Repopulation appeared to be faster after small and intermediate X-ray doses (9.6 and 28.8 Gy) than after the largest dose, but substantial division delay was observed after the largest X-ray dose. A significant finding was that the tumour cells treated with a neutron dose, either 2.6 or 5.2 Gy, appeared to repopulate slightly more rapidly than those irradiated with X-rays, and the doubling times following two different neutron doses were not significantly different. These results suggest the use of a short overall treatment time for the high LET radiotherapy, and that caution must be exercised if the high LET radiation is given before photon doses.

Animals↗

Hair fibrous protein compositions in some hereditary hair abnormalities determined by two-dimensional polyacrylamide gel electrophoresis.

S-carboxymethylated (SCM) fibrous proteins (FPs) from the scalp hairs of the three different hereditary hair abnormalities (trichorrhexis invaginata in Netherton's syndrome, pili trianguli et canaliculi in uncombable hair syndrome, and fine hair in anhidrotic ectodermal dysplasia) were analyzed by two-dimensional polyacrylamide gel electrophoresis. Comparison of the SCM FP compositions of the three hair abnormalities with that of the normal revealed that the SCM FP compositions of these three abnormal hairs were all electrophoretically different from each other and that of the normal.

Child↗

Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence.

Recombinant viruses between the virulent Mahoney and attenuated Sabin 1 strains of poliovirus type 1 were subjected to neurovirulence tests using a transgenic (Tg) mouse line, ICR-PVRTg1, that carried the human poliovirus receptor gene. The Tg mice were inoculated intracerebrally with these recombinant viruses and observed for clinical signs, histopathological lesions, and viral antigens as parameters of neurovirulence of the viruses. These parameters observed in the Tg mice were different for different inoculated viruses. Dose-dependent incidences of paralysis and of death were observed in the Tg mice inoculated with any viruses used. This indicates that values of 50% lethal dose are useful to score a wide range of neurovirulence of poliovirus. The neurovirulence of individual viruses estimated by the Tg mouse model had a strong correlation with those estimated by monkey model. Consequently, the mouse tests identified the neurovirulence determinants on the genome of poliovirus that had been identified by monkey tests. In addition, the mouse tests revealed new neurovirulence determinants, that is, different nucleotides between the two strains at positions 189 and 21 and/or 935 in the 5'-proximal 1,122 nucleotides. The Tg mice used in this study may be suitable for replacing monkeys for investigating poliovirus neurovirulence.

Animals↗

The response of quiescent cell populations in murine solid tumors to irradiation with fast neutrons.

5-bromo-2'-deoxyuridine (BUdR) was injected into SCC VII tumor-bearing mice intraperitoneally to label all proliferating tumor cells. The mice were irradiated with fast neutrons or x-rays. Immediately, or 24 h after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis blocker). The micronucleus frequency was determined using immunofluorescence staining to BUdR. The cells that were not labeled with BUdR could be regarded as the quiescent cells. The micronucleus frequency in total tumor cells was determined from the irradiated tumors that were not pretreated with BUdR. The difference in radiosensitivity between total and quiescent cells was markedly reduced with fast neutrons, especially at higher doses of radiation. Potentially lethal damage repair by total and quiescent cells was inhibited more strongly with neutrons than with x-rays. When using fast neutrons, the radiosensitivity of solid tumors depends on their heterogeneity less critically than for x-rays.

Animals↗

[Mandibular reconstruction using a vascularized osteocutaneous scapular flap].

Composite tissue defect of the mandible following the surgical resection of head and neck neoplasma or osteoradionecrosis causes functional and cosmetic disorders. Mandibular reconstruction is, therefore, necessary to obtain satisfactory results. The introduction of microvascular surgery has made it possible to transfer various types of vascularized bone grafts and this technique is considered one of the most reliable procedures for mandibular reconstruction. Recently it has been reported that an osteocutaneous scapular flap is useful for mandibular reconstruction. We have performed, over the last 2.5 years, 13 mandibular reconstructions using a vascularized osteocutaneous scapular free flap, and successful results have been achieved. The features of this flap are as follows: 1) it provides a consistent blood supply to the bone and the skin and has a constant vascular pedicle; 2) since the skin island and bone flap have separate pedicles, three-dimensional reconstructions are facilitated; 3) if needed, two skin flaps can be elevated; 4) the skin island is not so bulky; 5) the lateral border of the scapula provides highly vascularized bone of thick cortical density and osteotomies are safely performed; 6) using an angular branch based on thracodorsal artery, a bi-pedicled scapula bone can be raised and two completely vascularized bone segments can be transferred with a single pedicle. Thus, a vascularized osteocutaneous scapular flap has proven very useful for complex mandibular reconstructions.

Adult↗

[Thyroid function in patients with anorexia nervosa and depression].

Thyroid hormone levels were measured in 21 patients with anorexia nervosa, 15 patients with depression and 16 patients with severe depression and were compared with those in 53 normal subjects. In anorexia nervosa and severe depressed patients, serum T3, T4, fT3, fT4 and T3/T4 ratio showed significantly lower values than those in normal subjects. However there was no difference between depressed patients and normal subjects. The serum TSH levels were within normal range in all of the studied subjects. Thus, thyroid hormone levels in severe depressed patients were similar to those in anorexia nervosa and the changes were inversely related to disease conditions. The supplementation of thyroid hormones to antidepressant relieved clinical symptoms in some of the severe depressed patients. These results suggested that the changes in thyroid hormone levels in anorexia nervosa and severe depression were mainly due to impaired conversion of T4 to T3 by increased cortisol secretion through emotional stress.

Adult↗

Cell- and stage-specific expression of basic FGF in the developing rat gonads.

In order to clarify the participation of basic fibroblast growth factor (bFGF) in rat gonadal differentiation and development, immunohistochemical localizations of bFGF were chronologically studied in Sprague-Dawley rat gonads from gestational day (GD) 13 to postnatal day (PD) 21 by using avidin-biotin complex technique. Immunohistochemical reactivity to bFGF antibody was positive in the germ cells. Slight or moderate immunostaining was seen in male germ cells from GD 18 to PD 5, and in female germ cells from PD 5 to 21. Leydig/interstitial cells in male gonads were slightly or moderately stained from GD 16 to PD 21. On the other hand, other types of gonadal cells were not stained during the perinatal period. These results indicate that bFGF shows discrete cell- and stage-specific patterns of expression in gonads during the perinatal period and is likely to participate in control of gonadal development in rats.

Animals↗

[Changes of thyroid hormone levels during ACTH therapy in epileptic children].

To investigate the effect of ACTH on thyroid function, thyroid hormone levels were measured in twelve patients with epileptic children who were treated with ACTH. One week after daily administration of ACTH, serum T3, T4, TSH, thyroglobulin and T3/T4 ratio showed significantly lower values compared with those of pretreatment values (p < 0.001-p < 0.05). Thyroid hormone levels respectively showed negative correlation with cortisol levels before and one week after ACTH treatment respectively. Tapering of ACTH brought a rapid recovery of T3, T4, TSH and thyroglobulin levels with concomitant return of plasma cortisol levels to the normal range. These results suggested that excess ACTH suppressed thyroid hormone secretion mainly through a decreased TSH secretion and a peripheral conversion of T4 to T3 by increased cortisol levels.

Adrenocorticotropic Hormone↗

Microamperometric estimation of photosynthesis inhibition in a single algal protoplast.

The single-cell level inhibition of photosynthesis by some chemicals was investigated from the light-irradiation induced response of intracellular oxygen reduction current at an ultramicroelectrode inserted into a single algal protoplast. The addition of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), an electron-transport inhibitor, decreased a current peak appeared immediately after the light irradiation. The pI50 value (the negative decadic logarithm of the concentration needed for 50% inhibition) was determined from the change in response patterns and found to be 6.9 for DCMU. 2,4-Dichlorophenoxyacetic acid (2,4-D), an auxin herbicide, showed no effect on photosynthesis in the effective concentration range. 2,4-Dinitrophenol (DNP), a proton carrier, accelerated the oxygen production upon light irradiation.

2,4-Dichlorophenoxyacetic Acid↗

Microring-ring electrode for manipulation of a single cell.

Dielectrophoretic manipulation of a single myeloma cell was carried out using microring-ring electrodes (tip radius, 3-5 microns). When a.c. voltages were applied, the cell nearby the electrode tip was forced to move and trapped at the tip due to dielectrophoretic force induced by locally intense electric field.

Cell Movement↗

Molecular mechanisms underlying lymphocyte recirculation. III. Characterization of the LECAM-1 (L-selectin)-dependent adhesion pathway in rats.

LECAM-1 (L-selectin) is thought to play an important role in the binding of lymphocytes to high endothelial venules (HEV) of peripheral lymph nodes (LN), which is an essential process in lymphocyte recirculation. Previously we cloned the rat LECAM-1 cDNA. In this study, by using this probe we have sought to characterize a LECAM-1-dependent adhesion pathway in the rat. We have constructed a cDNA for rat LECAM-1-IgG chimera (rLEC-IgG), expressed it, purified the secreted recombinant chimera molecules, and produced mAb reactive with the rat homologue of LECAM-1 by using the chimera molecules. The use of rLEC-IgG revealed that ligands for LECAM-1 are selectively accumulated in high endothelial (HE) cells in LN, the white matter, neurons, cerebellar Purkinje cells, and choroid plexus of the central nervous system and also distal tubules and capillary blood vessels of the kidney. Binding of lymphocytes to LN HEV on frozen sections was blocked by either rLEC-IgG or the anti-rat LECAM-1 mAb. An HEV-derived cell line, Ax, specifically bound to rLEC-IgG fixed on plastic plate. Consistent with the presence of a C-type lectin domain in the ligand-binding region of LECAM-1, the binding was Ca2+ dependent and inhibitable by either the mannose-6-phosphate-rich polysaccharide polyphosphomannan ester or the anti-rat LECAM-1 mAb. These results indicate that the specific ligand for rat LECAM-1 is expressed on the Ax cells. rLEC-IgG precipitated 55-, 65-, 120-, 190-, and > 250-kDa sulfated glycoproteins from LN lysates and 190-, > 250-, and > 500-kDa proteins from Ax cell lysate. The precipitation was Ca2+ dependent and LECAM-1 specific. These results suggest that a carbohydrate structure on HE cells recognized by LECAM-1 is borne possibly on a limited number of cell surface-sulfated glycoproteins. The ligands were also found to be secreted in LN culture supernatants. rLEC-IgG and Ax cells should prove valuable for studying further the role of LECAM-1 in dynamic interactions between lymphocytes and HE cells.

Animals↗

Antimetastatic activity of lipopolysaccharide against a NK-resistant murine fibrosarcoma.

An intravenous injection of bacterial lipopolysaccharide (LPS) into mice exerted prominent antimetastatic activities against a NK-resistant weakly immunogenic NFSa fibrosarcoma. The number of visible metastases in the lung was increased by a pretreatment of anti-asialoGM1 (asGM1) antibody or silica, but pretreatment of asGM1 antibody or silica scarcely affected the antimetastatic activities of LPS. The pulmonary retention of radiolabeled tumor cells showed that LPS accelerated the detachment of the tumor cells from the lung, and that this acceleration was not suppressed by anti-asGM1 antibody. Sialic acids of lung endothelial cell surface, essential components of various receptors, was diminished by the i.v. injection of LPS. These results suggested that the antimetastatic effect of LPS against NK-resistant NFSa cells was partly the result of modulations of lung endothelial cell surface.

Animals↗

Significance of platelets in an antimetastatic activity of bacterial lipopolysaccharide.

Recently we reported an antimetastatic activity of bacterial lipopolysaccharide (LPS) on a NK-cell-resistant murine fibrosarcoma (NFSa). Here we investigate and report the mechanistic significance of platelets in this activity. The number of circulating platelets was reduced to 63% of the control 3 days after an i.v. injection of 1.0 micrograms LPS, and then recovered to the level of control at day 10. Aggregation efficiency of platelets was impaired by LPS. The number of metastatic lung colonies after an i.v. injection of tumor cells was maximally reduced to 2.2% of the control at day 3 and increased in proportion to the recovery of platelet number. Neuraminidase (Ndase), which caused a non-immunological thrombocytopenia, also inhibited lung metastasis when injected prior to an i.v. tumor cell challenge. LPS and Ndase showed an identical pattern against five other syngeneic tumors; these agents inhibited lung metastases of the FSa fibrosarcoma and the SCC VII squamous cell carcinoma but failed to inhibit those of the NR-S1 squamous cell carcinoma, the MMCa#4 mammary adenocarcinoma and the NR-PG parotid gland tumor. All the three cells which were not responsive to any agents possessed a high aggregating activity of platelets while the other three tumors responsive to both agents did not show a detectable level of this activity. Platelet transfusion failed to modify the antimetastatic activity of LPS. These results suggest that platelets play an important role in the antimetastatic activity of LPS, though whether the role is principal or assistant remains to be seen.

Animals↗

Aberrant retrotracheal goiter: report of a case.

A case of intrathoracic retrotracheal goiter in a 40-year-old woman is herein described. A computed tomographic scan, magnetic resonance imaging and endoscopical ultrasonography all confirmed the existence of a retrotracheal encapsulated lesion, which was suspected to be aberrant mediastinal goiter. Radioiodine scintigraphy, however, demonstrated little uptake in the mass. A large (7 x 6 x 4 cm), encapsulated adenomatous goiter was then easily removed via a right thoracic approach.

Adult↗