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Biomedical subjects

S Koike

Publications and source records attributed to S Koike.

At least 91 records · Page 5Linked to original sources

A comparison of biological effects of modulated carbon-ions and fast neutrons in human osteosarcoma cells.

PURPOSE: To compare the biological effects of a 135 MeV/u carbon-ion beam and 13 MeV fast neutron beam using human osteosarcoma cells. METHODS AND MATERIALS: We have studied the clonogenic cell survival, recovery of potentially lethal damage (PLD) in plateau phase cells, and spheroid cure in multicellular spheroid after irradiation at various positions in the plateau and spread out Bragg peak (SOBP) of a 135 MeV/u carbon-ion beam and with 13 MeV neutrons. The carbon beam had a 4-cm range in water and a range filter was used to produce a 3-cm extended-peak region. The reference radiation was 137Cs gamma-rays. RESULTS: The relative biological effectiveness (RBE) values for 10% survival level of plateau phase cells for carbon-ions at the position of plateau, proximal peak, midpeak, and distal peak within the SOBP, and neutrons were 1.71, 2.48, 2.63, 3.47, and 2.29, respectively. Corresponding RBE values at 1% level were 1.64, 1.93, 2.06, 2.49, and 2.05. The extent of recovery from PLD was reduced after carbon-ions at proximal peak, midpeak, and distal peak, and neutrons, although not substantially reduced after carbon-ions at plateau. The RBE values for 50% spheroid cure level of spheroids for carbon-ions at the position of plateau, proximal peak, midproximal peak, middistal peak, and distal peak within the SOBP, and neutrons were 1.69, 1.88, 1.87, 1.94, 2.03, and 1.90, respectively. CONCLUSIONS: The biological parameters measured all indicate an approximately comparable biological effectiveness between 75-80 KeV/microns carbon-ions of the SOBP and 13 MeV neutrons in the human tumor model studied in vitro.

Carbon↗

Immunohistochemical detection of the expression of the alpha subunit of inhibin, TGF-beta, basic-FGF and IGF-II in fetal ovarian grafts grown with fetal testes beneath the kidney capsule of adult castrated male rats.

In order to characterize the participation of growth factors in gonadal differentiation and development, we examined patterns of expression of the alpha subunit of inhibin, transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (basic FGF) and insulin-like growth factor-II (IGF-II) immunohistochemically in experimentally induced ovotestes. Ovotestes were derived from ovaries of fetal rats on gestational day (GD) 13 that had been co-crafted with fetal testes (GD 17) beneath the kidney capsule of adult castrated males and examined on the 7th, 14th and 21st days after transplantation (TD). Reactivity with antibodies against the alpha subunit of inhibin and basic FGF was observed in the Sertoli cells in both ovotestes and testes on TD 14 and on TD7, 14 and 21, respectively. Expression of IGF-II was also recognized in the Leydig/interstitial cells in both types of graft on TD 14 and 21. Therefore, the gonadal somatic cells in the testicular region of the ovotestes had immunohistochemical properties similar to those in the cografted testes. However, the somatic cells in the ovarian region of the ovotestes had immunohistochemical profiles different from those in solitary grafted ovaries. The germ cells in the ovotestes showed some differences in patterns of expression when compared with those in cografted testes and solitary grafted ovaries: expression of basic FGF was recognized in the germ cells in ovotestes on TD 21 but not in co-grafted testes; expression of IGF-II was recognized in the germ cells in ovotestes on TD 21 but not in solitary grafted ovaries. These results indicate that the immunohistochemical properties that reflect expression of growth factors in female gonadal somatic cells were changed to properties that resemble those of male gonads by the co-grafted fetal testes.

Animals↗

Neurovirulence test for oral live poliovaccines using poliovirus-sensitive transgenic mice.

The transgenic mice, ICR-PVRTg21, carrying the human poliovirus receptor gene, were intraspinally inoculated with oral poliovirus vaccine viruses and the viruses that had been derived from a vaccine preparation by passagings at 38 degrees. Dose-dependent incidence of paralysis was observed in the transgenic mice inoculated with any of the viruses used. All transgenic mice showing histopathological lesions in the central nervous system appeared to display clinical signs that resembled those observed in human poliomyelitis. These suggest that relative neurovirulence levels of individual virus preparations can be estimated by values of 50% paralysis dose. Indeed, the parameter correlated well with monkey lesion scores of viruses used. Histopathological changes such as degeneration of neurons resemble those displayed by monkeys and were observed in the spinal cord, medulla oblongata, and pons. Thus, the transgenic mice, ICR-PVRTg21, may become a new animal model in place of monkeys for safety testing of oral poliovirus vaccine preparations.

Animals↗

Preoperative intraperitoneal chemotherapy for gastric cancer, with special reference to delayed peritoneal complications.

Preoperative intraperitoneal (IP) chemotherapy was performed in 23 patients with gastric malignancies to inhibit peritoneal recurrence. Cis-diamminedichloroplatinum (CDDP) and mitomycin C (MMC) were administered intraperitoneally 3 days prior to surgery, at which time a very viscid peritoneum and mucinous intraperitoneal fluid were found in 100% and 83% of the patients, respectively. Inflammatory changes were microscopically observed in the subserosal layer of the resected stomachs and in the intraperitoneal fluid, but degenerative changes characteristic of cancer cells could not be seen. The 3-year survival rate of the stage III patients was 55.6%, and peritoneal recurrence was found in three of six patients with recurrence. Extensive adhesions were found in eight patients (34.8%) as a delayed peritoneal complication, and chronic bowel obstruction resulting from the adhesion developed in five patients (21.7%). Thus, we conclude that the administration of this IP chemotherapy demonstrated no definite antitumor effects or survival benefits, but was frequently associated with delayed peritoneal complications.

Adult↗

The influence of excess body weight on the surgical treatment of patients with gastric cancer.

Sixty-two overweight gastric cancer patients were compared with 201 normal-weight patients to clarify the influences of excessive weight on the surgical treatment of gastric cancer. The frequencies of hypertension and diabetes mellitus were significantly higher in the overweight group (P < 0.01), but no pathologic differences in the resected tumor were found between the two groups. The operative times were longer (P < 0.01) and the number of lymph nodes extirpated and examined was smaller (P < 0.01) in the overweight group. The incidence of postoperative complications was not higher in the overweight group. The postoperative survival rate of patients with nodal metastasis was statistically lower in the overweight group (P < 0.05). Regarding the causes of death in patients with nodal metastasis, 61.1% of overweight patients and 43.8% of normal-weight patients died of recurrence of gastric cancer. In conclusion, surgical treatment of overweight patients with gastric cancer was found to be technically more difficult and the prognosis of such patients with nodal metastasis may thus be worse than that of their normal-weight counterparts.

Body Weight↗

Regional ventilatory evaluation using dynamic SPET imaging of xenon-133 washout in obstructive lung disease: an initial study.

Regional ventilatory abnormalities in obstructive lung disease were evaluated by dynamic single-photon emission tomography (SPET) of pulmonary washout of xenon-133 (133Xe) gas. The subjects included seven healthy volunteers. 17 patients with obstructive lung disease, and seven patients with restrictive lung disease. Following 6 min of inhalation of 133Xe gas (60-72 MBq/l), equilibrium and subsequent washout SPET images during spontaneous breathing were sequentially acquired every 30 s for 6-7 min, using a triple-head SPET system with the return mode of continuous repetitive rotating acquisition. A gravity-induced gradient of ventilation was demonstrated in the volunteers' lungs. Compared with the normal subjects, all the patients with obstructive disease showed abnormal 133Xe retention on the washout SPET images, with or without abnormalities on chest X-ray computed tomography, whereas the patients with restrictive disease did not show any significant delays in washout. This modality may assist in the evaluation of the three-dimensional dynamic process of ventilatory abnormalities in obstructive lung disease.

Adult↗

Neurotransmitters for the canine inferior pharyngeal constrictor muscle.

The inferior pharyngeal constrictor muscle plays an important role at the pharyngeal phase of deglutition and is anatomically composed of the thyropharyngeal muscle and cricopharyngeal muscle. In this study we investigated the distribution pattern of neuropeptidergic and catecholaminergic nerve fibers in the thyropharyngeal muscle and cricopharyngeal muscle of seven puppies by immunohistochemistry. Some of the calcitonin gene-related peptide-, substance P-, vasoactive intestinal polypeptide-, and tyrosine hydroxylase-immunoreactive nerve fibers were found to lie parallel to the muscle fibers in both the thyropharyngeal muscle and cricopharyngeal muscle. Nerve fibers with immunoreactivity to all substances examined were found to be associated with blood vessels in both the thyropharyngeal muscle and cricopharyngeal muscle, and the number of calcitonin gene-related peptide, neuropeptide Y, and tyrosine hydroxylase nerve fibers was higher than the number of substance P, vasoactive intestinal polypeptide, and galanin nerve fibers. Motor end plate-like structures with calcitonin gene-related peptide immunoreactivity were found in both the thyropharyngeal muscle and cricopharyngeal muscle. These structures in the cricopharyngeal muscle were clearly less than those in the thyropharyngeal muscle. Some clusters of neurons were detected only in the cricopharyngeal muscle of all dogs examined. Substance P-, vasoactive intestinal polypeptide-, galanin-, and neuropeptide Y-immunoreactive neurons were found in this ganglion, and the vasoactive intestinal polypeptide-immunoreactive neurons were the most abundant. Abundant calcitonin gene-related peptide- and vasoactive intestinal polypeptide-immunoreactive nerve fibers, and some substance P- and galanin-immunoreactive nerve fibers were distributed in the ganglion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Radiosensitivity and cell cycle redistribution of cultured human tumour cells during fractionated daily 2-Gy irradiations.

Exponentially growing SQ-5 human lung squamous cell carcinoma cells were irradiated in vitro at 2-Gy per fraction per day continuously for 14 days. The number of total cells continued to increase exponentially till day 5, and reached a plateau level thereafter. The cell cycle distribution changed marginally for the first 5 days, and showed a prominent G2/M accumulation at day 7. Plating efficiencies decreased exponentially with increasing fractionation while the total clonogenic cell number remained constant until day 4. Radiosensitivity at each fraction was stable until day 9, but significantly increased at day 11. A comparison of plating efficiencies between the immediate and 24-h delayed assays revealed that the capacity of cells to spare 2-Gy damage increased with the number of 2-Gy fractions. These results suggest that sublethal damage could accumulate during multifraction daily irradiations, while repair of potentially lethal damage and/or proliferation could rather increase.

Carcinoma, Squamous Cell↗

[Evaluation of regional pulmonary 133Xe-gas washout with dynamic SPECT imaging obtained by a triple-headed SPECT system with continuous repetitive rotating acquisition mode].

The clinical potential of the dynamic SPECT in studying pulmonary washout of Xenon-133 (133Xe), using a triple-headed SPECT system (Toshiba GCA 9300A/HG, Japan) with continuous repetitive rotating acquisition mode, was preliminarily investigated in 6 healthy volunteers and 23 patients with various lung diseases. The equilibrium image was initially acquired for 1 min after breathing 133Xe gas (370 MBq) in a closed circuit for 6 min, and subsequently serial 133Xe-washout SPECT images were continuously acquired every 60 sec for 5-6 min. As the ventilation index, the real half time of regional activity was evaluated. The SPECT study demonstrated the gravity-induced gradient on ventilation in the normal subjects. In the various lung diseases, it allowed us to demonstrate visually and quantitatively the dynamic process and three-dimensional distribution of ventilation abnormalities, with or without chest radiographic abnormalities. These results indicate clinical potential of pulmonary dynamic SPECT of 133Xe-washout for elucidating the distribution and nature of ventilation abnormalities in various lung diseases.

Adult↗

[Hypothalamic-adenohypophysial function of corticotropin releasing hormone (CRH)-ACTH system in brain death].

To evaluate the hypothalamic-adenohypophysial function of corticotropin releasing hormone (CRH)-ACTH system in brain death, basal serum values of ACTH and cortisol was measured, and in addition, insulin-tolerance test (ITT) and CRH stimulation test was performed is 28 brain death cases. Basal levels of ACTH were low-normal, whereas those of cortisol were high-normal, and no correlation was observed between them. There was no correlation between these levels and the age, sex, cause of the brain death, and the incidence of hypotention. However, basal ACTH value significantly decreased within a few days (p < 0.01), and ACTH was undetectable in all cases 5 days after the diagnosis of the brain death. On the other hand, ITT and CRH test was negative in all cases. These results suggest that some degree of adenohypophysial function of ACTH secretion remains for a few days after the diagnosis of the brain death. Compared with other adenohypophysial hormones of the brain death cases in previous reports, however, ACTH was lower, decreased more rapidly, and did not response to the direct pituitary stimulation test, the CRH test. These results further suggest that disturbance of ACTH secretion occurs from an early stage in the brain death cases.

Adolescent↗

Immunohistochemical localization of insulin-like growth factor-II in the perinatal rat gonad.

To clarify the participation of insulin-like growth factor type-II (IGF-II) in rat gonadal differentiation, immunohistochemical localization of IGF-II was chronologically studied in Sprague-Dawley rat gonads from gestational day (GD) 13 to postnatal day (PD) 21 by using avidin-biotin complex technique. In male gonads, most cells were negative to IGF-II immunostaining during the perinatal period. Only Leydig/interstitial cells expressed positive reactivity from GD 21 to PD 11: the intensity of staining and the number of positive cells were gradually increased until PD 11. In female gonads, almost all cells showed negative immunoreactivity. Mesonephric tubules in both sexes exhibited slight or moderate reactivity on GD 13. These results indicate that IGF-II is likely to participate in the regression of fetal-type Leydig cells and/or the proliferation of adult-type Leydig cells around birth, and in the development of mesonephric tubules in the initial stage of gonadal differentiation.

Aging↗

Radioprotection by WR-151327 against the late normal tissue damage in mouse hind legs from gamma ray radiation.

PURPOSE: To evaluate the protective effect of WR-151327 on late radiation-induced damage to normal tissues in mice. METHODS AND MATERIALS: The right hind legs of mice with or without WR-151327 administration (400 mg/kg) were irradiated with 137Cs gamma rays. Leg contracture and skin shrinkage assays were performed at 380 days after irradiation. The mice were killed on day 400 postirradiation and histological sections of the legs were made. The thickness of the dermis, epidermis, and skin (dermis plus epidermis) was measured. The muscular area of the legs and the posterior knee angle between the femur and tibia were also measured. The left hind legs were similarly assessed as nonirradiated controls. Group means and standard deviations were calculated and dose-response curves were drawn for every endpoint. Then, the dose modifying factor (DMF) for each endpoint and the correlations among endpoints were determined. RESULTS: Late damage assayed by leg contracture and skin shrinkage progressed with increasing radiation dose. However, it was reduced by drug treatment. The significant effect was indicated for skin shrinkage by a DMF of 1.8 at 35%. The DMF for leg contracture was 1.3 at 6 mm. In the irradiated legs, epidermal hyperplasia and dermal fibrosis in the skin, muscular atrophy, and extension disturbance of the knee joint were observed. These changes progressed with increasing radiation dose. Skin damage assayed by the present endpoints was also reduced by drug treatment by DMFs of 1.4 to 1.7. However, DMFs for damage to the muscle and knee were not determined because no isoeffect was observed. There were good correlations between leg contracture or skin shrinkage and the other endpoints in both untreated and drug-treated mice. CONCLUSIONS: WR-151327 has the potential to protect against radiation-induced late normal tissue damage.

Animals↗

Accelerated bone marrow recovery from radiation damage in etoposide-pretreated mice.

PURPOSE: Etoposide inhibits the activity of Topoisomerase II, and possesses radiosensitizing effects on cultured cells. We showed that pretreatment of mice with etoposide 1 day before whole-body irradiation (WBI) had a protective effect against radiation-induced bone marrow death. The number of endogenous colony-forming units (CFU-S) surviving in WBI mice was significantly increased by pretreatment with etoposide. The purpose of the present study is to clarify mechanisms underlying the protective activity of etoposide against radiation-induced bone marrow damage. METHODS AND MATERIALS: The spleen colony-forming cells (CFU-S) of femoral marrow were assayed by the method of Till and McCulloch. The proliferative state of CFU-S was assessed using the technique of Hodgson. The reduction in exogenous CFU-S after hydroxyurea injection was used to determine the fraction size of S-phase in CFU-S. RESULTS: Etoposide pretreatment did not modify the cell survival parameters of exogeneous CFU-S when bone marrow cells were assayed immediately after WBI. Recovery of CFU-S in femoral marrow started earlier in mice receiving etoposide pretreatment than in the radiation alone group. Administration of hydroxyurea revealed that the accelerated recovery of CFU-S was due to an increased population of S phase cells, suggesting etoposide pretreatment shortened generation time of CFU-S. CONCLUSIONS: The mechanism for the radioprotection appears to be accelerated proliferation of survived bone marrow cells rather than a change in cellular sensitivity to radiation.

Animals↗

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

PURPOSE: We analyzed the characteristics of radiosensitivity and potentially lethal damage repair in the quiescent cell populations of murine SCC VII solid tumors irradiated with fast neutrons, in comparison with those irradiated with 10 MV X rays. METHODS AND MATERIALS: SCC VII tumor-bearing C3H/He mice were irradiated with 30 MeV fast neutrons or 10 MV X rays after receiving 10 injections of 5-bromo-2'-deoxyuridine (BUdR) to label all proliferating tumor cells. Immediately or 24 h after irradiation, the tumors were excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus frequency in cells without BUdR labeling was determined using immunofluorescence staining to BUdR. This micronucleus frequency was then used to calculate the surviving fraction of unlabeled cells from the regression line for the relation between micronucleus frequency and the surviving fraction of all tumor cells. Thus, a cell survival curve could be determined for the cells not labeled by BUdR, which can be regarded as the quiescent cells for all practical purposes. RESULTS: The difference in intrinsic radiosensitivity between all tumor and quiescent cells became smaller by using fast neutrons, compared with X rays, especially when large radiation doses were given. Potentially lethal damage repair by quiescent cells was less evident following irradiation with fast neutrons than with X rays, especially when large doses were delivered. CONCLUSION: By using fast neutrons in clinical radiotherapy, the radiosensitivity of solid tumors is thought to depend on their heterogeneity less critically than for X rays.

Animals↗

Amino acid residues on human poliovirus receptor involved in interaction with poliovirus.

We have previously demonstrated that the N-terminal immunoglobulin-like domain (domain 1; 115 amino acids) of human poliovirus receptor (hPVR) is essential for poliovirus binding and infection to cells. To identify amino acids involved in the interaction with poliovirus, we constructed a number of cDNAs encoding mutant hPVRs whose domain 1 was partially derived from mouse PVR (mPVR) homolog, which does not serve as a binding site for poliovirus. Poliovirus binding and infection assays were performed on mouse L cells that express these chimera cDNAs. Anti-hPVR monoclonal antibodies were employed to confirm the presence of mutant PVRs on the surface of mouse cells and to know conformational alteration of these PVRs. A significant decrease in efficiency of both poliovirus binding and infection to the cells was observed when one or a few amino acids of hPVR at Gly73, Ser74, Gln82, Leu99-Glu102, or Gln130-Ser132 were substituted by the corresponding amino acids of mPVR. Similar results were obtained when a 2-amino acid insertion of mPVR, which was missing in hPVR, was introduced at the corresponding site (between Arg98 and Leu99) of hPVR. These amino acids were highly conserved in functional PVRs of primates but not in unfunctional PVRs of rodents. These results indicate that the amino acids identified may have important roles in interaction of PVR with poliovirus that leads to the establishment of the virus infection. In the three-dimensional model of the domain 1 of hPVR, these amino acids are located on one side of the molecule. This suggests that the interaction with poliovirus occurs on this side of the domain 1.

Amino Acid Sequence↗