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Biomedical subjects

T Nakashima

Publications and source records attributed to T Nakashima.

At least 199 records · Page 11Linked to original sources
PubMed1998

Family aggregation of carcinoma of the hypopharynx and cervical esophagus: special reference to multiplicity of cancer in upper aerodigestive tract.

The role of family history in the multiple occurrence of cancer in the upper aerodigestive tract (UADT) remains unclear. The family histories of close relatives were examined in 167 patients with either hypopharyngeal or cervical esophageal cancer (PhCe cancer) and in 167 control subjects with benign diseases. The odds ratio for PhCe cancer was 2.6 in relation to family history of UADT cancers. Based on the family histories of close relatives, 167 cases with PhCe cancer were divided into 3 groups (Group I, 18 cases with a family history of UADT cancer; Group II, 37 cases with a family history of other cancers; Group III, 112 cases with no family history of any cancers). The mean age of the cases in group I was 59.4, which was younger than in group III (64.2). Second primary squamous-cell carcinomas in the UADT were more frequently recognized in group I (39%) than in group III (11%). However, no differences were observed in the smoking and drinking habits of male patients between each group. These results thus suggest that a family history of UADT cancers appears to be associated with the multiple occurrence of UADT cancers as well as the development of PhCe cancer.

Aged↗
PubMed1998

Direct transfer of bovine embryos frozen-thawed in the presence of propylene glycol or ethylene glycol under on-farm conditions in an integrated embryo transfer program.

An integrated bovine embryo transfer program was conducted in collaboration with 11 Japanese prefectural livestock experiment stations. The program was conducted to evaluate the practicability of the direct transfer method for bovine embryos frozen-thawed in the presence of propylene glycol (PG) or ethylene glycol (EG) under on-farm conditions. Embryos at the compacted morula to expanded blastocyst stages were collected from superovulated donors on Day 7 or 8 after estrus and equilibrated in 1.6 M PG or 1.8 M EG in Dulbecco's phosphate-buffered saline (DPBS) supplemented with 20% heat-inactivated calf serum. Embryos were then loaded individually into a 0.25-ml straw and placed directly into a cooling chamber of a programmable freezer precooled to -7 degrees C. After 2 min, the straw was seeded, maintained at -7 degrees C for 8 min more, and then cooled to -30 degrees C either at 0.3 degree C/min or 0.5 degree C/min before being plunged into liquid nitrogen. Embryos at the same stages were also frozen in the presence of 1.4 M glycerol (GLY) by a conventional method, which served as a control. The frozen embryos were thawed by allowing the straws to stand in air for 5 to 10 sec and then immersing them in a 30 degrees C water bath. Embryos frozen-thawed in the presence of PG or EG were nonsurgically transferred into the uterine horn without diluting the cryoprotectant. Embryos frozen-thawed in the presence of GLY were nonsurgically transferred after removing GLY either by the stepwise method (GLY-I) or by in situ dilution with 0.3 M sucrose solution (GLY-II). A total of 1,273 (PG: 400, EG: 418, GLY-I: 177, GLY-II; 278) frozen-thawed embryos was transferred into recipients, yielding 545 pregnancies (overall: 42.8%, PG: 36.0%, EG; 44.7%, GLY-I; 48.6%, GLY-II; 46.0%). The pregnancy rate with PG was significantly lower than that with EG or GLY-II (P < 0.05). The pregnancy rate was affected by the type of cryoprotectant, the region where the embryo transfer program was carried out, the developmental stage of the embryos, the parity of the recipients, and corpus luteum (CL) quality of the recipients. There were no differences in rates of abortion and stillbirth among the 3 cryoprotectants. The present study demonstrates that EG can be effectively used as a cryoprotectant for freezing and direct transfer of bovine embryos, and that the direct transfer method is applicable under on-farm conditions.

Animals↗
PubMed1998

Metabolic mapping of the brain in pregnant, parturient and lactating rats using fos immunohistochemistry.

The present study was designed to investigate Fos-positive neurons of the female rat brain at various reproductive states in order to analyze the metabolic map connected with pregnancy, parturition and lactation. The number of Fos-positive neurons in each brain nucleus was analyzed with a quantitative immunohistochemical method in virgin, pregnant, parturient, lactating and arrested lactating rats. In parturient rats, a significant number of Fos-positive neurons was observed as compared to virgin or pregnant females in the following brain regions; the bed nucleus of the stria terminalis (BST), lateral septal nucleus (LS), medial preoptic area (MPA), periventricular hypothalamic nucleus (Pe), parvocellular paraventricular hypothalamic nucleus (PaPVN), magnocellular paraventricular hypothalamic nucleus (MaPVN), supraoptic nucleus (SON), paraventricular thalamic nucleus (PV), anterior hypothalamic area (AHA), lateral hypothalamic area (LH), amygdaloid nucleus (AM), supramammillary nucleus (SuM), substantia nigra (SN), central grey (CG), microcellular tegmental nucleus (MiTg), subparafascicular thalamic nucleus (SPF), posterior hypothalamic area (PH), dorsal raphe nucleus (DR), locus coeruleus (LC), dorsal parabrachial nucleus (DPB), nucleus of solitary tract (Sol), and ventrolateral medulla (VLM). Significant differences were found in the number of Fos-positive neurons between parturient and lactating females, although localization of Fos-positive neurons in lactating females was quite similar to parturient ones. Between parturient and lactating rats: (1) In the MPA, PaPVN, AHA, arcuate hypothalamic nucleus (Arc), ventromedial hypothalamic nucleus (VMH), MLT, and Ge, the number of Fos-positive neurons of lactating females were significantly higher than those of parturient ones; (2) In the LS, Pe, PV, LH, AM, SuM, CG, MiTg, SPF, PH, DR, LC, and VLM, there was no significant differences in the number of Fos-positive neurons; (3) In the BST, MaPVN, SON, SN, DPB and Sol, the number of Fos-positive neurons of lactating rats were significantly lower than those of parturient ones. These different patterns of Fos expression among many brain regions may be owing to the functional differences in each region. Fos expression in lactating rats was apparently induced by suckling stimulation because the removal of their litters immediately after parturition completely eliminated expression of Fos protein in each nucleus. These results suggest that the localization of Fos-positive neurons in a number of neural populations throughout the brain may be revealing the neural circuits in response to parturition or lactation.

Animals↗
PubMed1998

Expression of bcl-2-, p53, and Ki-67 and outcome of patients with primary nasopharyngeal carcinomas following DNA-damaging treatment.

BACKGROUND: Recent studies suggest that apoptosis is important in the cell death induced by treatment that damages deoxyribonucleic acid (DNA). We assessed the correlation between the expression of the apoptosis-related proteins, p53 and bcl-2, and the clinical outcome of patients with nasopharyngeal carcinomas (NPCs) who were treated with both DNA-damaging treatments. We also assessed the level of Ki-67, a marker of cell proliferation, in these tumors. METHODS: We evaluated statistically the relationships among the expression of p53, bcl-2, and Ki-67 and clinicopathologic factors, the sensitivity to radiation, the incidence of distant metastases, and survival. RESULTS: The group that was positive for p53 tended to be resistant to radiotherapy and to have a significantly poorer prognosis (p = .05). CONCLUSIONS: The enhanced expression of p53 may be a prognostic factor in patients with NPCs whose tumor is resistant to therapy that damages DNA.

Adult↗
PubMed1998

Expression and function of Fas and Fas ligand on peripheral blood lymphocytes in normal subjects.

We investigated the expression and function of Fas and Fas ligand (FasL) on peripheral blood lymphocytes (PBLs). The cells were stimulated with various cytokines or 12-0-tetradecanoyl phorbol 13-acetate (PMA) plus ionomycin. About 30% of unstimulated PBLs expressed Fas, and the expression was augmented by interleukin-1beta (IL-1beta), IL-2, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), or PMA plus ionomycin. Although only minimal FasL expression was detected on unstimulated PBLs, FasL expression was markedly induced by IL-2 or PMA plus ionomycin, suggesting that Fas and FasL were both expressed on IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs. Although IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs were positive for both Fas and FasL, no significant increase in apoptosis was demonstrated in these activated PBLs. In addition, treatment of PBLs with IL-2 or PMA plus ionomycin did not change anti-Fas-induced apoptosis, although these activated PBLs expressed Fas strongly when compared with unstimulated PBLs. Only IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs killed Fas+ target cells efficiently via the interaction of Fas on target cells with FasL of PBLs. Bcl-2 was constitutively expressed on unstimulated PBLs, but its expression was significantly augmented by IL-2 or PMA plus ionomycin. The expression of Bax was clearly induced only on IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs and that of other Bcl-2 family proteins such as Bcl-x and Bad could not be detected on human PBLs, including IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs. Our results suggest that PBLs activated by IL-2 or PMA plus ionomycin express both Fas and FasL and that they kill Fas+ target cells by using FasL on the surface. The resistance of these activated PBLs to Fas-mediated apoptosis may be due to the augmented Bcl-2 expression or the presence of Bcl-2:Bax heterodimers on these cells.

Adult↗
PubMed1998

Effects of an endothelin ET(A)-receptor antagonist, S-0139, on cerebral vasospasm and behavioral changes in dogs intracisternally administered endothelin-1.

The effects of an endothelin ET(A)-receptor selective antagonist, S-0139, were examined using dogs given endothelin-1 (ET-1) into the subarachnoid space. ET-1 at 40 pmol apparently constricted the basilar artery in anesthetized dogs and caused various grades of ataxia, facial clonus, nystagmus and other features in conscious dogs, partially mimicking those which have been reported for conscious rats. S-0139 could completely inhibit both the vasoconstriction and behavioral changes. It could also alleviate the behavioral changes caused by ET-1 in conscious dogs when given after the severe ataxia. We concluded that ET-1 in the subarachnoid space produces behavioral changes via endothelin ET(A)-receptor mediation similar to its cerebral vasoconstricting action, at least, in dogs.

Animals↗
PubMed1998

Profiles of an intravenously available endothelin A-receptor antagonist, S-0139, for preventing cerebral vasospasm in a canine two-hemorrhage model.

We examined the prophylactic effect of a novel nonpeptide endothelin (ET) A-receptor selective antagonist, S-0139, using a canine two-hemorrhage model and an ET-1-induced cerebral vasospasm model. The agent markedly prevented cerebral vasospasm in the canine two-hemorrhage model when given intracisternally or intravenously by continuous daily dosing. An efficacious intravenous method was to apply a relatively high initial dose followed by daily sustaining administration at a much lower dose, which alone would have been ineffective. The need for sustaining dosing may imply daily successive attacks of ETs in the cerebral vessel compartment after the introduction of autologous blood into the subarachnoid space. A small amount of S-0139 was detected from the cerebrospinal fluid (CSF) with an apparent lag time after its disappearance from the plasma following intravenous dosing of 0.83 mg/kg/min for 12 min, however, cerebral vasoconstriction induced by ET-1 dosing from the adventitial side was clearly inhibited during such a lag period. Moreover, its movement into the CSF was greatly enhanced after the application of autologous blood to the animals. From these results, we conclude that ET-1 play a major role in producing delayed cerebral vasospasm in this canine two-hemorrhage model, and S-0139 effectively antagonizes the action of ET-1 even by intravenous treatment because it moves easily into the cerebral vessel compartment from plasma.

Animals↗
PubMed1998

Methamphetamine-induced neurotoxicity in BALB/c, DBA/2N and C57BL/6N mice.

Repeated administration of methamphetamine (METH; 2 and 4 mg/kg, s.c. four times every 2 h) caused hyperthermia and a dose-dependent depletion of striatal dopamine levels 3 days after the METH-treatment in both BALB/cAnNCrj (BALB) and DBA/2NCrj (DBA) mice, but these responses were lower in C57BL/6NCrj (C57BL) mice. An acute decrease of striatal dopamine levels 30 min after the last injection of METH (4 mg/kg) was observed in both BALB and DBA mice, while an increase in dopamine was observed in C57BL mice. Striatal 3-methoxytyramine levels were drastically increased in both DBA and C57BL mice after this same treatment. Moreover, pretreatment with the superoxide dismutase inhibitor, diethyldithiocarbamate (200 mg/kg, i.p.) exacerbated the METH (4 mg/kg)-induced striatal dopamine-depletion in BALB mice. In addition, pretreatment with an inhibitor of poly(ADP-ribose) polymerase, benzamide (160 mg/kg, s.c.), significantly attenuated the METH (4 mg/kg)-induced striatal dopamine depletion in both BALB and DBA mice. These results suggest that both BALB and DBA mice possess a higher sensitivity to the METH-induced striatal dopaminergic neurotoxicity compared to C57BL mice. In addition, the striatal dopaminergic neurons of BALB mice may be more vulnerable to METH-induced oxidative stress as compared to that in C57BL mice.

Animals↗
PubMed1998

Different effect of oxytocin on membrane potential of supraoptic oxytocin neurons in virgin female and male rats in vitro.

The effects of oxytocin on membrane potential were investigated in the supraoptic nucleus (SON) neurons of rats using whole-cell patch-clamp technique. SON neurons were electrophysiologically identified as oxytocin (OT) or vasopressin (VP) neurons. Application of OT (1 x 10[-7] M) hyperpolarized membrane potentials of OT neurons in virgin female rats but depolarized membrane potentials of putative OT neurons in male rats. The membrane conductance of SON neurons were increased by treatment of OT in both sexes, suggesting that OT increased the opening of channels on SON neurons. The reversal potential of OT neurons in virgin female rats and putative OT neurons in male rats under OT effective conditions were -66 +/- 1 mV (n = 4) and -46 +/- 2 mV (n = 5), respectively. These data suggest that OT released within the SON suppresses the activity of OT neurons in virgin female rats while it excites putative OT neurons in male rats.

Animals↗
PubMed1998

Infant cold exposure changes Fos expression to acute cold stimulation in adult hypothalamic brain regions.

It is known that cold exposure as an infant results in a permanent cold tolerance which is accompanied by a reduced rate of colonic temperature decline and increased metabolic heat production to cold stimulation. The present study was aimed to elucidate the central mechanism of cold tolerance of adult rats with cold exposure as infants. Newborn infants were exposed to cold ambient (4 degrees C) daily for 2 weeks, and when they were 15-weeks old, Fos expression to acute cold stimulation (10 degrees C) in whole brain regions was investigated using quantitative immunohistochemistry. Acute cold stimulation induced a significant increase of Fos-positive neurons in many nuclei of whole brain areas in adult rats both with and without cold exposure as infants. However, the number of Fos-positive neurons was significantly less in the rats with cold exposure than without cold exposure as infants, particularly in the hypothalamic nuclei such as the lateral septal nucleus (LS), preoptic area (POA), parvocellular paraventricular nucleus (pPVN0, ventromedial hypothalamic nucleus (VMH) and supramammillary nucleus (SuM). However, there was no significant difference in the number of Fos-positive neurons in the extra-hypothalamic regions between the rats with and without cold exposure as infants. These results suggest that the central mechanism of cold tolerance with cold exposure as infants is due to metabolic changes of the hypothalamic brain regions.

Animals↗
PubMed1998

Comparison of the expression of two immediate early gene proteins, FosB and Fos in the rat preoptic area, hypothalamus and brainstem during pregnancy, parturition and lactation.

Medial preoptic area (MPA), supraoptic nucleus (SON), magnocellular (MaPVN) and parvocellular (PaPVN) paraventricular hypothalamic nuclei, and mesencephalic lateral tegmentum (MLT) are involved in maternal behavior, parturition and lactation. This study investigated the FosB and Fos immunoreactivity in these regions of virgin, pregnant, parturient, lactating, and lactating-arrested rats. The patterns of FosB and Fos expression were compared between the sections taken from the same animals. Quantitative immunohistochemistry revealed a significant increase in the numbers of FosB-positive neurons in the MPA, SON, MaPVN, and MLT of parturient and lactating females as compared with pregnant or virgin animals. In lactating rats, the numbers of FosB-positive neurons in the MPA, PaPVN, and MLT were increased, but the numbers in the SON and MaPVN were decreased as compared with parturient females. Many Fos-positive neurons were also seen in parturient and lactating rats, and the patterns of Fos expression in each region were quite similar to those of FosB. Moreover, double-labeling immunohistochemistry revealed that: (1) many FosB-positive nuclei were observed in oxytocin and vasopressin neurons of the SON and PVN in parturient rats; (2) within FosB-positive neurons, 89.5% in the MPA, 86.8% in the MLT of parturient rats, and 92% in the MPA and 90.8% in the MLT of lactating animals were also Fos-positive. Only a small number of FosB and Fos-positive neurons were seen in females that were killed in the early stage of parturition. Removal of the litters immediately after parturition completely eliminated FosB and Fos expression in each region in the dams. Taken together, the present results suggest that FosB expression is co-involved with Fos in the neural activation during parturition and lactation in rats.

Animals↗
PubMed1998

Methamphetamine-induced changes in activity and water intake during light and dark cycles in rats.

1. The authors investigated the ambulatory activity and water intake of rats during each 12 hr light and dark cycle for one week following four s.c. injections of 4 or 8 mg/kg of methamphetamine (METH). 2. Administration of the higher METH dose caused an increase in activity during the dark cycle on days 1 through 6 with the maximal increase on day 3 while the increase in activity during the light cycle was observed only on day 1. 3. Water intake increased the first day after administration of both METH doses, but returned to baseline by day 3. 4. Administration of both METH doses induced hyperthermia and the 8 mg/kg dose produced depletions of striatal dopamine and striatal, hippocampal and hypothalamic serotonin on day 3 but only in hippocampal serotonin by day 7. 5. These results demonstrate that high doses of METH produce a long-lasting increase in activity during the dark cycle and a transient increase in water intake. The behavioral changes which occurred during the dark cycle appear to be related to the depletion of central dopamine and/or serotonin.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

CD4+ T-cell-mediated cytotoxicity against staphylococcal enterotoxin B-pulsed synovial cells.

Apoptosis of synovial cells in rheumatoid arthritis (RA) synovium determined in vivo is suggested to counteract the overgrowth of synovium. Immunohistological examination has revealed the infiltration of activated CD4+ T cells, which express Fas ligand (FasL), in RA synovium. The presence of a putative antigen (Ag) of autoimmune disorders in a target organ may induce the activation of specific T cells in the inflammatory region such as RA synovium. We examined the possible role of CD4+ T cells activated by synovial cells in a staphylococcal enterotoxin B (SEB)-dependent manner, inducing synovial cell apoptosis. Synovial cells were cultured with or without interferon-gamma (IFN-gamma) and further incubated with CD4+ T cells in the presence of SEB. After the cocultivation, both the cytotoxicity and FasL expression of CD4+ T cells were investigated. Constitutive Fas expression was detected on both unstimulated and IFN-gamma-stimulated synovial cells. CD4+ T cells did not kill SEB-pulsed unstimulated synovial cells efficiently. In contrast, when CD4+ T cells were incubated with IFN-gamma-stimulated synovial cells with SEB whose human leucocyte antigen (HLA)-DR and -DQ expression was markedly induced, significant cytotoxicity by these cells against synovial cells was detected. The addition of anti-HLA-DR and -DQ monoclonal antibodies (mAbs) or human Fas chimeric protein (hFas-Fc) reduced this cytotoxicity. FasL expression of CD4+ T cells cocultured with IFN-gamma-stimulated synovial cells with SEB was significantly induced. Furthermore, the addition of mAbs against CD54, CD58 and CD106 inhibited both the cytotoxicity and FasL expression of CD4+ T cells induced by IFN-gamma-stimulated synovial cells in the presence of SEB, indicating the importance of costimulatory molecules on synovial cells in activating CD4+ T cells. Our results suggest that CD4+ T cells are activated by synovial cells by an SEB-dependent manner and express FasL, inducing Fas-mediated apoptosis of the latter cells. These phenomena may regulate the overgrowth of synovial cells in RA synovium.

Antibodies, Monoclonal↗
PubMed1998

Morphological observation of laryngeal motoneurons by means of cholera toxin B subunit tracing technique.

Gross anatomical and histological studies and immunohistochemical demonstration of cholera toxin B subunit used as a retrograde tracer were performed to investigate distinct muscle fibre bundles (MFBs) in the feline intrinsic laryngeal muscles (ILMs) and to characterize the respective supplying motoneurons in the nucleus ambiguus (AM). Distinct bundles were observed in all ILMs except the lateral cricoarytenoid muscle. Motoneurons supplying MFBs related to phonation located more medially than others. Motoneuron size did not differ between distinct MFBs in the same muscle. Neurodendrites for the cricothyroid muscle (CT) and adductor motoneurons extended dorsomedially, ventrolaterally and ventromedially, while those for the posterior cricoarytenoid muscle (PCA) motoneurons stretched dorsomedially and ventrolaterally. We conclude that distinct MFBs in ILMs play different roles in laryngeal functions, and that corresponding motoneurons have their own specific visceroneural nature allowing regulation of complex laryngeal functions. To receive information from the central nervous system, laryngeal motoneuron dendrites extended to regions locating respiratory, phonatory and swallowing neurons.

Animals↗
PubMed1998

Plexiform schwannoma of the neck extending deeply to the mediastinum.

We describe a 42-year-old man who had tumors occupying the right deep neck through the upper part of the mediastinum. The right vocal cord was fixed and bulgings of the pharyngeal and tracheal wall were observed. At surgery, the masses were subtotally removed as much as possible. Histological examination revealed that they were schwannomas. The postoperative course was uneventful, except for the presence of hoarseness.

Adult↗
PubMed1998

Parvalbumin distribution in the musculature of the pharyngo-oesophageal segment.

The composition and size of muscle fibre types in the hyopharyngeus (HP), thyropharyngeus (TP), cricopharyngeus (CP) and cervical oesophageal muscle (CE) from 6 normal adult cats were investigated using parvalbumin (PA) immunohistochemistry. Fibre types I, IIA and IIB were identified in all muscles. HP and TP revealed predominance of type II fibres (74.8% and 75.2%, respectively), whilst CP and CE showed predominance of type I fibres (72.6% and 82.2%, respectively). The mean diameter of narrow fibres was greater in type II (23.9 microm) than in type I fibres (21.7 microm). The results seem to reflect the physiological features of each muscle, i.e. short rapid contractions of HP and TP, sustained contraction of CP and slow peristaltic movements of CE.

Animals↗