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Biomedical subjects

T Shimura

Publications and source records attributed to T Shimura.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effects of different absorption enhancers on the permeation of ebiratide, an ACTH analogue, across intestinal membranes.

The permeation of ebiratide (H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8NH2), a novel ACTH analogue, across the intestinal mucosae has been examined by use of isolated intestinal membranes from rats in a modified Ussing chamber. Regional differences were observed in the permeation of ebiratide across intestinal membranes; the order of membrane permeability was jejunum > ileum > duodenum > colon. Overall, the permeation of ebiratide was relatively poor. The effects of various absorption enhancers were examined to increase the intestinal permeability to ebiratide. Sodium glycocholate and sodium caprate had no significant enhancing effect on the permeability of the jejunal membrane, but significantly enhanced the permeation of ebiratide through the colonic membrane. On the other hand, N-dodecyl-beta-D-maltopyramoside (LM) significantly enhanced the permeation of ebiratide through both jejunal and colonic membranes. In general, the absorption-enhancing effects of these agents were more predominant in the colon than in the jejunum. Membrane damage by the absorption enhancers was evaluated by measuring the amount of protein released from the intestinal membrane. It was found that all the absorption enhancers slightly increased the amount of protein released, but that the amounts of protein released in the presence of these enhancers were much less than in the presence of ethylenediaminetetraacetic acid (EDTA), used as a positive control. These findings suggest that the absorption enhancers, especially LM might be useful adjuvants for improving the intestinal absorption of peptide and protein drugs, including ebiratide.

Adrenocorticotropic Hormone↗
PubMed1997

Docosahexanoic acid (DHA) improved glucose and lipid metabolism in KK-Ay mice with genetic non-insulin-dependent diabetes mellitus (NIDDM).

The hypoglycemic and hypolipidemic effect of docosahexaenoic acid (DHA; C22: 6omega-3) ethyl ester was examined in KK-Ay mice and neonatal streptozotocin-induced diabetic (NSZ) which are respectively obese and lean animal models of non-insulin-dependent diabetes mellitus (NIDDM), and in ddY normal mice. Single administration of DHA (500 mg/kg body weight) to KK-Ay mice significantly reduced (p<0.05) the blood glucose levels (BG) (p<0.05) and plasma free fatty acid levels (FFA) (p<0.05) at 10 h after oral administration when compared with control group. DHA (500 mg/kg body weight)-treated NSZ and normal mice, however, showed no change in these parameters. In addition, repeated administration of DHA (100 mg/kg) to KK-Ay mice significantly suppressed the increment of BG (p<0.05) and plasma triglyceride levels (TG) (p<0.01), and significantly decreased FFA (p<0.05) at 30 d compared with control group. DHA also significantly decreased the blood glucose at 60 and 120 min on insulin tolerance test (ITT). From these findings, it seems likely that DHA exhibits its hypoglycemic effects by increasing insulin sensitivity. It is concluded that DHA would be useful for treatment of obese type NIDDM with insulin resistance.

Animals↗
PubMed1997

[A lateral fluid percussion model for the experimental severe brain injury and a morphological study in the rats].

Few morphological studies have been reported on fluid-percussion experimental models using mechanically induced severe brain injury have been reported. This study was initiated to evaluate microscopic and immunohistochemical findings in severe brain injury models using rats. The experimental rats and the methods used were the same as described for a fluid-percussion model. Fluid-percussion models of traumatic brain injury were produce by rapidly injecting fluid volume into the epidural space of the temporal lobe. We used 5 rats which sustained various degrees of injury by high (7.0 atm), medium (5.6 atm) and low (3.5 atm) magnitudes of impact and sham control. The rats were sacrificed and perfused transcardially with buffer solution followed by 2.5% glutaraldehyde at intervals of 24 hours, 3 days, and 7 days, and there were normal and sham control groups. In this immunohistochemical study, monoclonal antibody to 70 kilodalton neurofilament subunit was used in a standard Avidin-Biotin Complex Kit (DAKO). Microscopic findings revealed subarachnoid hemorrhage, lateral IIIrd ventricular hemorrhage, and rarefaction and petechial hemorrhage of the local contusional lesion. In the medium level injury, there was a marked petechial hemorrhage in the corpus callosum and subependymal area. In the high level injury, there was marked edema in the white matter of the ipsi- and contralateral cerebral hemisphere, and multiple petechial hemorrhage in the brain stem and cerebellum. Microscopic findings in the corpus callosum, subependyma and brain stem in the vicinity of petechial hemorrhage revealed a large number of axonal swellings, but in these specimens only a few typical axonal retraction balls were seen with Bodian and immunohistochemical stains. In conclusion, this experimental model seems to simulate local and diffuse shearing injury, showing various morphological characteristics of diffuse axonal injury.

Animals↗
PubMed1997

Brainstem lesions and gustatory function: I. The role of the nucleus of the solitary tract during a brief intake test in rats.

Using an automated gustometer, licking behavior in rats was evaluated for a range of concentrations of appetitive and aversive stimuli in rats following electrolytic lesions in the rostral nucleus of the solitary tract (NST). Lesions of the NST flattened the concentration-response function for all gustatory stimuli. They attenuated the concentration-response function for MgCl2, QHCI, and NH(4)Cl by shifting it to the right by 0.5 log unit, attenuated the function for citric acid and Polycose by shifting it to the right by 1.5 log units, and fully eliminated the function for sucrose and NaCl. This failure to respond appropriately, however, was specific to gustatory stimuli because all rats reduced ingestive responding when presented with increasing concentrations of capsaicin, a trigeminal stimulus. Together, the data show that the NST is critical for responding appropriately to changes in intensity of a gustatory, but not a trigeminal, stimulus.

Animals↗
PubMed1997

Brainstem lesions and gustatory function: II. The role of the nucleus of the solitary tract in Na+ appetite, conditioned taste aversion, and conditioned odor aversion in rats.

Rats with lesions of the nucleus of the solitary tract (NST) that demonstrated flat concentration-response functions for NaCl and sucrose (T. Shimura, P. S. Grigson, & R. Norgren, 1997) expressed a significant (albeit reduced) salt appetite following sodium depletion, and a normal conditioned taste aversion (CTA) for alanine when paired with lithium chloride-induced toxicosis. Rats with lesions of the NST also could acquire a conditioned odor aversion, but the CTA to alanine was not mediated by odor cues because other rats with NST lesions also demonstrated normal CTA learning even when made anosmic with zinc sulfate. Together, the data suggest that the rostral NST is essential for responding appropriately to increasing concentrations of a tastant, but not for the chemical identification necessary for sodium appetite and CTA learning.

Afferent Pathways↗
PubMed1997

Brainstem lesions and gustatory function: III. The role of the nucleus of the solitary tract and the parabrachial nucleus in retention of a conditioned taste aversion in rats.

Bilateral electrolytic lesions of the nucleus of the solitary tract (NST) or ibotenic acid lesions of the pontine parabrachial nuclei (PBN) failed to disrupt retention of a preoperatively acquired conditioned taste aversion (CTA) to 0.3 M alanine. For both sham- and NST-lesioned rats, the CTA persisted following 3 nonreinforced conditioned stimulus (CS) presentations. For PBN-lesioned rats, retention was more labile. The preoperatively acquired CTA was extinguished by the 3rd nonreinforced CS exposure. When assessed postoperatively using a novel CS, NST-lesioned rats acquired a new CTA, although they were rendered anosmic with zinc sulfate (P. S. Grigson, T. Shimura, & R. Norgren, 1997). Rats with PBN lesions, however, failed to acquire a second CTA postoperatively. Thus, the PBN is essential for the acquisition of a CTA, but neither of the brainstem gustatory nuclei need be intact for the retention of a preoperatively acquired CTA.

Animals↗
PubMed1997

[Histopathological and autoradiographical studies of experimental brain tumors after continuous local chemotherapy--acute stage in rat models].

Continuous local chemotherapy has been evaluated as being an effective administration method and as a possible adjuvant therapy in the sensitivity aspect of the cell cycle for malignant glioma. However, neurotoxicity of anti-cancer agents in the normal brain and non-effective methods for the deeper part of the tumor seem to be the most serious problems. This study was initiated to evaluate histological findings, the uptake distribution, and neurotoxicity of the continuous local administration of isotope labeled anti-cancer agents in the brain tumor of rats. The experimental brain tumor of rats and the method of continuous local chemotherapy were as follows. The tumor was produced by intracerebral inoculation of cultured cells derived from rat brain tumor induced by Rous sarcoma virus (Kumanishi et al. strain). One week later Fluorouracil (5-6-3H) (17.7 Ci/m mol) and methotrexate (L-glutamyl 3-4-3H) (41.0 Ci/m mol) were administered into the brain tumors of rats utilizing a mini osmotic pump (Alzet Model 2001), respectively. We used five rats of various groups. The rats were sacrificed at various time intervals (6 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs and 7 days). The tumor tissues for light microscopic autoradiography were fixed in 10% formalin for 24 hours. Sections for the light microscopic autoradiography were cut at 4 mu thick and coated with Sakura NR-M2 drips. Following exposure for one week at 4 degrees C, the sections were stained with Konidol X. Six hours after administration, slight radioactivity was distributed in the subarachnoid space and subpial brain tissue in the vicinity of the inserted tube. Twenty-four hours after administration, high radioactivity was clearly present in many tumor cells and phagocytes at the tube tip, but no radioactivity was observed in the deeper part of the tumor or normal brain tissue. In the vicinity of necrosis foci, acute toxic inflammation was also observed. In conclusion, this experimental study shows that these anti-cancer agents are capable of direct penetration into the neoplastic cells of an intracerebral tumor following continuous local administration. However, necrotic foci were small in size. The most serious side effect seemed to be the presence of acute toxic inflammation in the vicinity of the necrotic foci.

Animals↗
PubMed1997

[Clinicopathological studies of craniocerebral gunshot injuries].

UNLABELLED: Gunshot wounds are rare in Japan because of few regulatory laws against the possession of guns. Nevertheless such wounds are increasing in prevalence these days. Reports on the microscopic findings concerning these intracerebral lesions are fewer than those on the macroscopic findings in the scalp, the skull and the intracranial cavity. In this study we evaluated computed tomographical and histopathological findings in craniocerebral gunshot injuries. CASES: Nine patients with gunshot wounds to the head were presented. All were male and the age ranged from 17 to 66 years. Four were suicides and four were attempted murders and the last one was of unknown etiology. Morphological examination was performed on 5 autopsy cases. The distance of the bullet from the cranial cavity was as follows: long distance, 4 cases; close contiguity, 5 cases. The calibers of the weapons were as follows: 38 mm in 6 cases, 45 mm in 1 case and unknown in 2 cases. RESULTS: CT scans were examined in six cases, which revealed a missile track, hemorrhagic contusion, traumatic subarachnoid hemorrhage and marked tension pneumocephalus. In some cases, CT scan also revealed bony and metallic fragments, some deep within the cranial cavity. In the histopathological study, we found marked swollen brain (brain weight over 1500 mg) and hemorrhagic contusion in the vicinity of the missile track and interhemispheric fissure, and widespread traumatic subarachnoid hemorrhage and intraventricular hematoma. We would like to emphasize especially the remote contusion seen in the distant part of the missile track as well as massive exsudation and hemorrhage around the nerve fiber bundles. Remote contusion was observed in the inferior surface of the fronto-temporal lobes, and bilateral hemorrhagic contusion was seen in the vicinity of the superior longitudinal fissure on CT scans and autopsy findings. In one case, the bullet rotated within the intracranial cavity. In conclusion, nine cases of craniocerebral gunshot injuries were examined, while we also reviewed the medical literature concerning the shearing injury produced by gunshot brain wounds. The head injuries were further delineated by the correlation between autopsy and computerized tomography findings.

Adolescent↗
PubMed1996

Xenogeneic iso-skin graft and mixed lymphocyte reaction studies using HLA-DP transgenic mice.

To elucidate the cellular responses against xeno-MHC antigens, in vitro mixed lymphocyte culture (MLC) and in vivo skin grafting (SG) studies were conducted using HLA-DP transgenic mice (B6-DP mice). Xenogenic iso-(B6-DP to B6 mice) MLC showed positive but much lower responses compared to allo-MLC responses. Nevertheless, B6-DP skin grafts were rejected in a similar time course as allo-skin grafts. To examine mechanisms underlining skin graft rejection, both in vitro cytotoxic lymphocyte (CTL) responses and delayed-type hypersensitivity (DTH) reactions were tested. The studies showed that DTH but not CTL reactions were involved for the graft rejection. SG was again conducted after the administration of anti-CD4 and/or CD8 monoclonal antibody (mAb). Mice treated with both CD4 and CD8 mAb accepted B6-DP SG for as long as up to 60 days and those treated with either CD4 or CD8 mAb alone rejected skin grafts on its own most of the time (75% in anti-CD4 mAb treated mice, 88.9% in anti-CD8 mAb treated mice), which suggests that the strict T cell restrictions for xeno-DP antigens do not exist. Even in these finally rejected cases, longer median survival time and final rejection time were observed, and in the other mice (25% in anti-CD4 mAb treated, and 11.1% in anti-CD8 mAb treated mice), graft acceptance was found. Therefore, it was suggested that the immunological reactions leading to the graft rejection occurs most efficiently when both T cell subsets are present. The above results indicate that xenogeneic HLA-DP antigens could act as significant transplantation antigens equivalent to alloantigens despite their lower stimulative activity in vitro, and also support the interpretation that DP antigens act like a minor histocompatibility antigen beyond the difference of species. Monomorphic anti-HLA class II antibodies were detected in recipients' sera as early as 2 weeks and even at 6 months, indicating that xeno-MHC antigens are prone to be memorized to B cells. It was concluded that HLA transgenic mice are useful for the investigation of cellular responses across xeno-MHC barriers.

Animals↗
PubMed1995

Single unit responses of the amygdala after conditioned taste aversion in conscious rats.

Amygdalar neuronal responses to sodium saccharin used as the conditioned stimulus (CS) and to other taste stimuli including sucrose, NaCl, HCl and quinine hydrochloride were recorded before and after the acquisition of conditioned taste aversion (CTA) in freely behaving rats. Of 73 units recorded from the basolateral nucleus of the amygdala (BLA), 17 (23%) and 1 (1%) exhibited facilitatory and inhibitory responses, respectively, to both the CS and sucrose after aversive conditioning to the CS. On the other hand, 3 (5%) and 11 (17%) of 64 units recorded from the central nucleus of the amygdala (Ce) exhibited facilitatory and inhibitory responses, respectively. The responsiveness of these BLA and Ce units to other taste stimuli did not change significantly. These findings that the facilitatory effect was dominant in the BLA, while the inhibitory effect was more frequent in the Ce suggest that the BLA and Ce are differentially involved in CTA.

Amygdala↗