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Biomedical subjects

T Shimura

Publications and source records attributed to T Shimura.

At least 37 records · Page 2Linked to original sources

The effect of caffeine on p53-dependent radioresponses in undifferentiated mouse embryonal carcinoma cells after X-ray and UV-irradiations.

The effect of caffeine was studied on the radioresponses of undifferentiated mouse embryonal carcinoma cells (EC cells) with or without the functional p53. The radioresponses studied included radiosensitivity, the activation of p53, apoptosis with characteristic DNA ladder formation and cell cycle progression. An undifferentiated mouse EC cell line, ECA2, and a newly established p53-deficient EC cell line, p53 delta, were used in the present study. The status of the p53 gene did not significantly affect the colony survivals of undifferentiated EC cells to X-rays and UV. Although a post-irradiation treatment with caffeine sensitized both lines to X-rays marginally, the sensitization was prominent for UV regardless of the p53 status of the cells. The activation of a p53 responsible lacZ reporter construct was observed in stably transfected ECA2 cells after X-ray and UV irradiations. Caffeine suppressed the X-ray induced activation of the lacZ reporter, while it drastically enhanced the activation after UV irradiation. X-rays and UV readily triggered the apoptosis of ECA2 cells with the characteristic DNA ladder. Although UV-induced DNA ladder formation was enhanced by caffeine, that induced by X-rays was unaffected. Therefore, the effects of caffeine on the p53-dependent radioresponses were found to be agent specific: suppression for the X-ray induced and augmentation for the UV induced. In contrast to p53-proficient ECA2 cells, smear-like DNA degradation was observed for irradiated p53 delta cells, suggesting the presence of a mode of cell death without DNA ladder formation. UV induction of the smear-like DNA degradation was enhanced in the presence of caffeine. Regardless of the state of the p53 gene, G1/S arrest was not observed in X-ray and UV irradiated EC cells. X-ray induced G2/M arrest in both lines, which was abrogated by caffeine, while G2/M arrest after UV was unaffected by a caffeine treatment. These results indicate that the radioresponses of undifferentiated EC cells differ considerably from those of somatic cells, and that these radioresponses were modulated by a post-irradiation treatment with caffeine.

Animals↗

[The usefulness of fluconazole administration and beta-D-glucan measurement in neurosurgical patients with deep-seated mycosis].

The diagnostic usefulness of beta-D-glucan values and the efficacy of flconazole (FLCZ) were investigated in 20 patients with deep-seated mycosis treated in our neurosurgical department from Oct 1, 1997 to May 31, 1998. The diagnosis of deep-seated mycosis was carried out using mycological and serological methods. When the serological beta-D-glucan value was above 10 pg/ml, the patient was considered to have deep-seated mycosis. In 13 patients (65%), the definite diagnosis of deep-seated mycosis was established by culture. In 7 patients, diagnosis based on serological examination alone was false positive or false negative. FLCZ 200 or 400 mg per day was administered for 10 days. Three patients were administered 200 mg/day FLCZ for another 10 days. No side effect of FLCZ was noticed among these patients. Three of 13 patients (23%) in whom fungi were isolated became fungi negative after FLCZ administration. The mean beta-D-glucan values before and after the administration of FLCZ were 36.37 mg/ml and 13.75 mg/ml, respectively. The beta-D-glucan values before and after the administration of FLCZ were significantly correlated with statistics (Student's t-test; p < 0.001). It was concluded that FLCZ was useful, and that beta-D-glucan values generally reflected the therapeutic effect of FLCZ. In contrast to the mycological culture tests that provided only a low detection rate, beta-D-glucan values were useful not only as a diagnostic means but also as a means to evaluate the efficacy of FLCZ treatment.

Adult↗

[A case of urinary retention secondary to aseptic meningitis].

A 46-year-old male was admitted to our hospital with headache, high fever and subsequent consciousness disturbance. Spinal fluid examination intimated aseptic meningitis. Not only these symptoms but bladder dysfunction was presented. The patient was treated with conservative therapy and bladder dysfunction was resolved a month and a half later. We report a case of urinary retention secondary to aseptic meningitis and review the clinical presentation and treatment.

Acyclovir↗

Cavernous hemangioma of the skull in a neonate.

Cavernous hemangiomas rarely occur in the calvarium and most commonly present in middle-age. Although a congenital vascular disorder can theoretically cause a diploic lesion in any age group, a calvarial cavernous hemangioma has not been reported in newborn. A 4-month-old male infant presented with a large left parietal mass that had been present since birth. Total resection was performed. Pathological examination revealed a cavernous hemangioma developing within the diploic space adjacent to prior hemorrhages. Surgery was performed in this case because of the size and persistence of the lesion. Removal of tumors of a benign nature from the calvarium can be done safely. Cavernous hemangioma of the skull in a neonate should be considered as one of the differential diagnoses in the case of suspected ossified cephalohematoma.

Hemangioma, Cavernous↗

Serum soluble HLA-DR antigens in autoimmune hepatitis.

To investigate the significance of HLA-class II, especially DR antigens, in autoimmune hepatitis (AIH), the serum concentrations of soluble HLA-DR antigen (sDR) were measured in 16 patients with AIH. The expression of HLA-DR antigens in the liver tissues of AIH patients was also studied by immunohistochemistry. AIH at diagnosis showed markedly higher serum sDR levels than controls, in which the liver tissues exhibited positive staining of HLA-DR antigens. Seven patients received corticosteroid therapy, in whom the serum sHLA-DR concentration was reduced dramatically from activated to remission stage. In sequentially follow-up cases, sDR correlated well with the disease activity, and also with the change of surface DR expression in the liver. A single major band with a molecular size of 60 kDa was detected, both in patient's sera and in normal control sera, by Western blotting. In conclusions, serum sHLA-DR level could be a marker reflecting immunological activity of the disease.

Alanine Transaminase↗

Roles of chemical mediators in the taste system.

Recent advances in neural mechanisms of taste are reviewed with special reference to neuroactive substances. In the first section, taste transduction mechanisms of basic tastes are explained in two groups, whether taste stimuli directly activate ion channels in the taste cell membrane or they bind to cell surface receptors coupled to intracellular signaling pathways. In the second section, putative transmitters and modulators from taste cells to afferent nerves are summarized. The candidates include acetylcholine, catecholamines, serotonin, amino acids and peptides. Studies favor serotonin as a possible neuromodulator in the taste bud. In the third section, the role of neuroactive substances in the central gustatory pathways is introduced. Excitatory and inhibitory amino acids (e.g., glutamate and GABA) and peptides (substance P and calcitonin gene-related peptide) are proved to play roles in transmission of taste information in both the brainstem relay and cortical gustatory area. In the fourth section, conditioned taste aversion is introduced as a model to study gustatory learning and memory. Pharmacobehavioral studies to examine the effects of glutamate receptor antagonists and protein kinase C inhibitors on the formation of conditioned taste aversion show that both glutamate and protein kinase C in the amygdala and cortical gustatory area play essential roles in taste aversion learning. Recent molecular and genetic approaches to disclose biological mechanisms of gustatory learning are also introduced. In the last section, behavioral and pharmacological approaches to elucidate palatability, taste pleasure, are described. Dopamine, benzodiazepine derivatives and opioid substances may play some roles in evaluation of palatability and motivation to ingest palatable edibles.

Animals↗

Malignant fibrous histiocytoma in the parietal bone.

Malignant fibrous histiocytomas (MFHs) are mesenchymal tumors, usually arising in soft tissue of the extremities and are remarkably resistant to radiation and chemotherapy. A 45-year-old female presented with a rare case of MFH originating in the cranial bone manifesting as a lump in the left parietal region with no neurological abnormality. Neuroimaging revealed the presence of an osteolytic tumor in the left parietal bone invading into muscle and subdural region, penetrating through the dura. Selective external carotid angiography disclosed a marked tumor stain. Examination of the whole body excluded neoplastic disease elsewhere. The patient was treated by surgical excision, radiation, and two courses of multi-drug chemotherapy using cyclophosphamide, doxorubicin, vincristine, and prednisolone. Since there is no established treatment against this malignancy, a longer follow-up is necessary to determine whether cure has been achieved.

Combined Modality Therapy↗

Ibotenic acid lesions of the parabrachial nucleus and conditioned taste aversion: further evidence for an associative deficit in rats.

Rats with extensive ibotenic acid lesions centered in the gustatory zone of the pontine parabrachial nucleus (PBN) failed to acquire a conditioned taste aversion (CTA) induced by lithium chloride (LiCl) toxicosis (Experiments 1 and 4). This deficit cannot be explained as an inability to either perceive or process gustatory information because lesioned rats that failed to acquire a CTA readily acquired a conditioned flavor preference (Experiment 2). Similarly, the CTA deficit cannot be attributed to an inability to experience or process visceral input because PBN-lesioned rats that failed to acquire a CTA successfully learned an aversion to a trigeminal stimulus, capsaicin, when paired with LiCl-induced illness (Experiment 3). This pattern of results supports the view that cell bodies within the PBN are essential for the associative processes that govern CTA learning.

Animals↗

Acute sodium deficiency reduces gustatory responsiveness to NaCl in the parabrachial nucleus of rats.

Sodium-deprived rats ingest excessive amounts of salt solutions at high concentrations which are normally avoided. This phenomenon, salt appetite, is known to be controlled by the sense of taste. In the present study, a possible involvement of the parabrachial nucleus (PBN) in sodium appetite was examined by recording PBN neuron responses to 12 different taste stimuli in sodium-deprived and control groups of urethane anesthetized rats. Sodium deficiency was induced by two injections of furosemide 24 and 22 h before the recording. Taste responses to 0.3 and 0.5 M solutions of NaCl were significantly lower in the sodium-deprived rats than in controls. In gustatory responses to other taste solutions except for quinine hydrochloride solution, no differences were detected between the two groups of the rats. Correlation coefficients of responses among sodium salts and those between 0.5 M NaCl and sweeteners were larger in the sodium-deprived rats than in controls. The results indicate that PBN neurons in sodium-deprived rats are critically implicated in induction of quantitative and qualitative changes of gustatory sense to sodium salts.

Animals↗

Serum concentrations of soluble HLA-class I and CD8 forms in patients with viral hepatic disorders.

Soluble HLA-class I and CD8 molecules were determined by sandwich ELISA in patients with viral-induced hepatic disorders. As a whole, the patients with hepatic disorders (acute hepatitis: AH; chronic hepatitis: CH; liver cirrhosis: LC; hepatocellular carcinoma: HCC) showed higher sHLA-class I and sCD8 levels than normal controls (P < 0.001). AH patients had the highest sHLA-class I levels (mean, 3513 +/- 2112 ng/ml), followed by CH (2896 +/- 1290 ng/ml), LC (2293 +/- 1266 ng/ml), and HCC (2221 +/- 1212 ng/ml) sCD8 levels wer highest in AH, followed by HCC, LC, and CH, in that order. Among histologically defined C virus-positive patients, sHLA-I levels were higher in those with chronic active hepatitis (CAH) 2A (3802 +/- 1124 ng/ml) than in those with chronic persistent hepatitis (CPH; 2200 +/- 711 ng/ml; P < 0.01), the levels then decreased as the disease progressed (CAH2B, 3564 +/- 1783 ng/ml, LC, 2376 +/- 1265 ng/ml). In contrast, sCD8 values showed little difference among the disorders. sHLA-class I levels showed a positive correlation with sCD8 values both in whole patients and in patients with AH (P < 0.01), but no correlation was shown, in any patients, with biochemical parameters such as GPT and GOT. These findings, taken together, suggest that hepatic destruction is not the only cause of sHLA-class I production, but that sHLA-class I levels, together with sCD8 levels, may reflect immunological activity in hepatic disorders.

CD8 Antigens↗

Facilitation of glutamate release in the ventromedial division of the globus pallidus during palatable taste stimulation in freely moving rats: real-time measurement.

To make real-time measurements of glutamate in the ventromedial globus pallidus (vGP) in rats during free ingestive behavior, a recently developed dialysis biosensor was employed. The glutamate level in the vGP increased in response to intraoral infusions of various fluids and voluntary ingestion of food pellets. Palatable fluids evoked greater responses than unpalatable fluids did, suggesting that glutamate in the vGP is involved in ingestive behavior.

Animals↗

Salient responsiveness of parabrachial neurons to the conditioned stimulus after the acquisition of taste aversion learning in rats.

The pontine parabrachial nucleus is considered to be one of the most critical regions for the acquisition of conditioned taste aversion which is an associative learning of taste and illness. To further clarify the possible involvement of the parabrachial nucleus in conditioned taste aversion, we recorded neuronal responses to taste stimuli from the parabrachial nucleus of rats under deep urethane anaesthesia. Animals were separated into two groups: the conditioned taste aversion group that had acquired a taste aversion to 0.1 M NaCl (conditioned stimulus) after paired presentations of the taste stimulus with intraperitoneal injection of LiCl (unconditioned stimulus), and the control group that had received only the unconditioned stimulus before experiments. Taste-responsive neurons in the conditioned taste aversion group showed larger responses to NaCl at below 0.1 M, but similar responses to 0.3 M and 0.5 M NaCl when compared with those in the control group. Furthermore, hierarchical cluster analyses revealed a strong similarity among responses to sodium salts in neurons of the conditioned taste aversion group compared with the control group. These results suggest that the aversive conditioning to NaCl modified parabrachial units so that the sodium taste was more salient than other tastes. This modification may reflect a long-term plastic change persisting without support of forebrain structures, and would facilitate the gustatory discrimination of the conditioned stimulus, which is required by conditioned animals.

Animals↗

Serum soluble human leucocyte antigen class I in paediatric liver transplantation with live, related donors.

Serum soluble human leucocyte antigen (HLA) class-I is a useful marker for predicting immunological events in organ transplantation. In cadaver liver transplant cases it is especially the case that high amounts of soluble HLA-I are excreted from the grafts. In Japan, almost all liver transplants have been performed from living parent donors to their children. Therefore, it is interesting to know how soluble HLA-I changes in relation to clinical course. As part of this study we first examined serum concentrations of soluble HLA-I in 33 paediatric patients using enzyme-linked immunosorbent assay. Soluble HLA-I is composed of three different sized molecules (45, 39 and 34-36 kDa); then the change of distribution of these three molecules was demonstrated by Western blot analysis. When donor and recipient have different soluble HLA-I band patterns, the origin of the antigen can be assumed by this method. We found that in a comparison between pre- and post-transplants, the six out of eight (75%) patients that suffered episodes of acute rejection showed a significant elevation of soluble HLA-I, and all patients with infectious episodes had an elevated soluble HLA-I. Meanwhile, 10 out of 22 (45%) patients without any clinical complications still showed increased soluble HLA-I. The Western blot analysis showed that the soluble HLA-I molecules were considerably derived from the grafted liver, from one week to 24 months after grafting. In acute rejection, the band signals of donor origin were significantly increased. These signals were attenuated after immunosuppressive therapy. The grafted liver appears to contribute to the increase of soluble HLA-I following liver transplantation, and this increase is greater with the effects of the host immune system.

Adolescent↗