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Biomedical subjects

T Shimura

Publications and source records attributed to T Shimura.

At least 19 recordsLinked to original sources
PubMed1992

Absorptive-mediated endocytosis of an adrenocorticotropic hormone (ACTH) analogue, ebiratide, into the blood-brain barrier: studies with monolayers of primary cultured bovine brain capillary endothelial cells.

The internalization of a neuromodulatory adrenocorticotropic hormone (ACTH) analogue, [125I]ebiratide (H-Met(O2)-Glu[125I]His-Phe-D-Lys-Phe-NH(CH2)2NH2), was examined in cultured monolayers of bovine brain capillary endothelial cells (BCEC). HPLC analysis of the incubation solution showed that [125I]ebiratide was not metabolized during the incubation with BCEC. The acid-resistant binding of [125I]ebiratide to BCEC increased with time for 120 min and showed a significant dependence on temperature and medium osmolarity. Pretreatment of BCEC with dansylcadaverine or phenylarsine oxide, endocytosis inhibitors, and 2,4-dinitrophenol, a metabolic inhibitor, decreased significantly the acid-resistant binding of [125I]ebiratide. The acid-resistant binding of [125I]ebiratide was saturable in the presence of unlabeled ebiratide (100 nM-1 mM). The maximal internalization capacity (Bmax) at 30 min was 7.96 +/- 3.27 pmol/mg of protein with a half-saturation constant (Kd) of 15.9 +/- 6.4 microM. The acid-resistant binding was inhibited by basic peptides such as poly-L-lysine, protamine, histone, and ACTH but was not inhibited by poly-L-glutamic acid, insulin, or transferrin. These results confirmed that ebiratide is transported through the blood-brain barrier via an absorptive-mediated endocytosis.

Adrenocorticotropic Hormone↗
PubMed1992

C-fos expression in the rat brain after intraperitoneal injection of lithium chloride.

The distribution of evoked expression of the proto-oncogene c-fos was immunohistochemically examined in the rat brain after intraperitoneal injection of isotonic LiCl, which is commonly used to induce internal malaise in the conditioned taste aversion paradigm. C-fos-like immunoreactive neurones (c-fos neurones) were most densely observed in the central amygdaloid nucleus, external lateral subnucleus of the parabrachial nucleus (PBN), posteromedial and commissural parts of the nucleus of the tractus solitarius (NTS) and area postrema (AP). Experiments including vagotomy, intravenous injection of LiCl and lesions of the area postrema suggest that NTS neurones are activated via both sides of the vagus nerves, while AP neurones, humorally as well as neurally via the vagal nerve with a right side predominance. The activated NTS and AP neurones project mainly to the external lateral subnucleus of the PBN and lightly to the central lateral subnucleus of the PBN. These results are discussed in terms of the role of LiCl in the formation of conditioned taste aversion.

Animals↗
PubMed1992

In-vivo blood-brain barrier transport of a novel adrenocorticotropic hormone analogue, ebiratide, demonstrated by brain microdialysis and capillary depletion methods.

The transport of ebiratide, a novel adrenocorticotropic hormone (ACTH) analogue, [H-Met-(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], through the blood-brain barrier was directly demonstrated in-vivo. [125I]Ebiratide (16.9 MBq mL-1) or [14C]sucrose (29.2 MBq mL-1) known to be restrictively transported through the blood-brain barrier was infused into the rat internal carotid artery at a flow rate of 50 microL min-1 for 10 min, and after 15 min infusion the distribution volume of each compound in the brain parenchyma was determined by the capillary depletion method. The distribution volume of [125I]ebiratide was 167.8 +/- 62.2 microL (g brain)-1, which was about seven times higher than that of [14C]sucrose (24.9 +/- 4.0 microL g brain)-1, indicating the uptake of ebiratide into brain parenchymal cells. During the infusion into the internal carotid artery, brain microdialysis was simultaneously performed to directly collect the brain interstitial fluid as the dialysate. Radioactivity was detected in the dialysate during the [125I]ebiratide infusion and HPLC analysis of the dialysate revealed that the intact ebiratide accounted for greater than or equal to 80% total radioactivity. The concentrations of [125I]ebiratide and [14C]sucrose in the brain interstitial fluid were estimated based on the relative recovery obtained in the in-vitro recovery study. The brain interstitial fluid/internal carotid arterial blood concentration ratio for [125I]ebiratide was determined to be 1.47 x 10(-2) +/- 0.17 x 10(-2) and was about eight times higher than that for [14C]sucrose (1.92 x 10(-3) +/- 0.36 x 10(-3)), indicating significant transport of ebiratide to the brain interstitial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Inhibition of deoxyribonucleic acid synthesis in vitro by anticancer platinum pyrimidine greens against Daudi cells.

Platinum pyrimidine greens inhibited the deoxyribonucleic acid (DNA) synthesis of tumor cells in the S phase of the cell cycle and exerted antitumor activity. Clear differences were observed in the activity between the samples prepared at 40 degrees C and at 75 degrees C. Using 3H-thymidine incorporation assay and cell cycle analysis we confirmed that the former had much stronger and more specific inhibitory activity against DNA synthesis than the latter. Reactivity of the 40 degrees C sample with deoxyguanosine monophosphate (dGMP) and deoxyadenosine monophosphate (dAMP) was, respectively, two and three times larger than that of the 75 degrees C sample.

Antineoplastic Agents↗
PubMed1992

[Cyst formation following local chemotherapy of malignant brain tumor: a clinicopathological study of two cases].

This paper reports clinicopathological findings concerning an enlarged bulky cyst and the tumor cavity following local administration of an anticancer agent combined with radiotherapy in two patients suffering from malignant glioma. Case 1: This 69 year-old man who had been diagnosed as having glioblastoma in the right parietal lobe had received local chemotherapy after the first operation. Simultaneously radiotherapy of 69 Gy in total dose was performed. At the second operation for the tumor, cyst formation was clinically confirmed and necrotomy as well as evacuation of the large cyst was performed after adjuvant therapy. The patient died at a time ten months after the first surgical operation. Case 2: This is the case of a 48 year-old man who was diagnosed as having gemistocytic astrocytoma in the left frontal lobe. The first surgical operation was performed and was followed by local chemotherapy as well as radiotherapy (total dose of 90 Gy in two sessions). The second surgical operation of the recurrent tumor, with necrotomy and evacuation of the large cyst were performed after adjuvant therapy. The patient expired at a time sixty-five months after the first surgical operation. Relevant to the chemotherapy, adriamycin (ADM) (0.5mg) and methotrexate (MTX) (1mg) were administered through the Ommaya's reservoir into the tumor bed at craniotomy. The usual doses of ADM and MTX amounted to 5.0mg respectively. Through conventional CT and MRI, formation of a cyst including abundant membranous debris or septi was identified in both cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Modification of male rat copulatory behavior by lateral midbrain stimulation.

Effects of electrical stimulation of the lateral midbrain tegmentum (LMT) on the copulatory behavior of male rats were examined in our investigation of the role of the LMT in this behavior. Sexually experienced male rats (n = 15) that had been implanted with chronic electrodes under sodium pentobarbital anesthesia were individually tested for copulation with a receptive female under a 30 s on, 30 s off pattern of stimulation. The ejaculation latency, and mount and intromission frequencies decreased significantly during the stimulation tests, indicative of facilitation of copulation. In contrast, a strong stimulus-bound inhibition of copulation was found in 12 males (80%). Six animals who showed accelerated copulation also depressed the lever for self-stimulation at an identical current during the copulation tests. These results suggest that the LMT functions in ejaculation, in the normal expression of intromission and in sexual reward, thereby regulating the copulatory behavior of male rats.

Animals↗
PubMed1991

[Hypothalamic and pituitary function in brain death].

Hypothalamic and pituitary hormone levels were measured in 56 patients meeting the criteria of brain death proposed by the Japanese Ministry of Welfare. Pituitary hormone releasing tests were carried out in 39 patients. In addition, cerebral angiography and transcranial Doppler (TCD) were performed in 13 and six patients, respectively, just after hormone measurements. Serum hypothalamic and pituitary hormone levels were inconsistently high based on the half life time in the presumed absence of cerebral blood flow shown by angiography. The responses to releasing hormones were normal in 16 patients. TCD detected cerebral blood flow in the middle cerebral artery or ophthalmic artery in three patients who showed non-filling on angiography. Postmortem microscopic examination of the hypothalamus and anterior pituitary lobe revealed normal structure and cells intermingled with lytic changes and necrosis. This series suggests that some part of the hypothalamus and hypophysis may still be alive after brain death, although the function of these regions may be clinically insignificant.

Adolescent↗
PubMed1991

Transport mechanism of a new behaviorally highly potent adrenocorticotropic hormone (ACTH) analog, ebiratide, through the blood-brain barrier.

The binding and internalization of a novel adrenocorticotropic hormone (ACTH) analog having a potent neuromodulating effect, ebiratide (H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8NH2), by isolated bovine brain capillaries, were examined. Metabolism of [5-125I-His]ebiratide occurred during a 30-min incubation with bovine brain capillaries at 37 degrees C. In the presence of 20 mM EDTA, added to inhibit this metabolism, the medium, after 30 min of incubation, contained 82.3 +/- 0.5% of the unchanged ebiratide. The total binding and acid-resistant binding of [125I]ebiratide increased with time and reached an equilibrium at about 15 min. The total binding and acid-resistant binding at 30 min (as the cell/medium ratios corrected with [14C]sucrose) were 13.07 +/- 0.86 and 5.00 +/- 0.18 microliters/mg of protein, respectively. The acid-resistant binding showed significant dependence on temperature and medium osmolarity. The [125I]ebiratide binding was significantly inhibited by dansylcadaverine, an endocytosis inhibitor. The saturable acid-resistant binding was obtained by the addition of unlabeled ebiratide (100 nM-5 mM), and the maximal internalization capacity (Bmax) at 30 min was 144.2 pmol/mg of protein, with the half-saturation constant (KD) of 62.1 microM. The nonsaturable acid-resistant binding [cell/medium ratio in the presence of the unlabeled compound (1 mM or more)] was 2.2 microliters/mg of protein. The acid-resistant binding was significantly inhibited by human ACTH, poly-L-lysine, protamine and E-2078, a basic peptide, but was not inhibited by poly-L-glutamate, insulin or transferrin. These results demonstrate that ebiratide is transported through the blood-brain barrier via a basic peptide-specific absorptive-mediated endocytosis.

Adrenocorticotropic Hormone↗
PubMed1990

Involvement of the lateral mesencephalic tegmentum in copulatory behavior of male rats: neuron activity in freely moving animals.

Single unit activity was recorded from the lateral mesencephalic tegmentum (LMT) during free copulatory activity by male rats. Twenty-four (89%) of 27 units showed changes in the firing rate during at least one of the three phases of copulatory behavior: pursuit of the female, pelvic thrusting and genital grooming. The activity of 16 units (59%) increased during pursuit of the female, and the activity of 3 units (11%) increased markedly during pelvic thrusting accompanied by intromission. In contrast, 6 units (22%) were suppressed during thrusting with intromission. Whereas the activity of 10 units (37%) increased during genital grooming, 7 units (26%) were suppressed below the baseline during this behavior. The specific firing patterns of the LMT units that are correlated with the particular copulatory movements are a strong indication that the LMT may have an important function in the execution of male copulatory behavior. Some LMT units may mediate sensory information from the genitals that is needed to display a series of copulatory movements. Other units may be more directly related to reflex-like copulatory movements.

Animals↗
PubMed1990

[Dural arteriovenous malformation in the posterior fossa presenting with multiple intracerebral hematomas. Case report].

A 59-year-old female was hospitalized because of disturbance of consciousness and convulsive seizures. She had taken a hormonal drug for 15 months after breast cancer surgery. A computed tomography scan revealed multiple high-density areas in the left temporal and frontal and the right parietal lobes. Angiography showed a dural arteriovenous malformation (AVM) in the posterior fossa fed by the occipital and the middle meningeal arteries and draining into the transverse sinus. It also demonstrated occlusion of the left sigmoid sinus in the venous phase. She complained of headache in the occipital region and dizziness. On day 13, the left occipital artery was ligated and cut, and then abnormal arterial anastomoses around the lesion were coagulated. After surgery, clinical symptoms disappeared. The etiology of dural AVM is controversial, but in this case it is suspected that sinus thrombosis due to the drug caused the dural AVM. The authors discuss the etiology and treatment of dural AVM in the posterior fossa.

Arteriovenous Malformations↗
PubMed1989

Interface between the meningioma and the brain.

Though meningiomas are usually well demarcated from the brain, their interfaces with the brain take various forms. Based on 27 nonoperated supratentorial meningiomas from autopsies, the interfaces were classified into four types, that is, smooth, lobular, finger-like expansion, and invasive. Relationships between the types of interfaces and the so-called capsule of the tumor and subarachnoid vessels are discussed. Additionally, three surgical cases which showed more or less the invasive form are presented with neuroradiological findings.

Adult↗
PubMed1989

[Disseminated necrotizing leukoencephalopathy accompanied with multiple calcium deposits following antineoplastic and radiation therapy in a case of intracranial germ cell tumor: computerized tomographical study].

A form of disseminated necrotizing leukoencephalopathy and the shaping process of calcification was observed by CT scan in a 9-year-old boy with intracranial germ cell tumor who had received systemic combined chemotherapy, brain radiation, and intraventricular administration of methotrexate and bleomycin for the meningeal involvement of tumor cells. He was admitted to our hospital complaining of hemiparesis and gait instability. Hormonal examination revealed abnormality of high serum HCG and testosterone. An initial CT scan showed a ring enhancing lesion in the right side of the caudate head. He received a course of irradiation, which was 5,000 rads locally, and combined chemotherapy using cisplatin, vinblastine and bleomycin for ectopic germ cell tumor. Unfortunately, consecutive CT examinations revealed that the tumor recurred with hormonal abnormality and ventricular seeding of tumor cells. Therefore, the patient received two courses of irradiation, which were each 3,000 rads locally, and intraventricular administration of methotrexate and bleomycin via an Ommaya tube at about one year intervals. However, 23 months after the first irradiation, a serial CT scan revealed an abnormal diffuse low density area in the deep white matter of the frontal lobe, predominantly the paraventricular region. Furthermore, 31 months after the first irradiation, a serial CT scan revealed fine and granular calcification in the above mentioned lesion. The Hounsfield number of high density areas was 103.00 in the round calcification of the left parietotemporal lobes. Finally, 34 months after the first irradiation, a serial CT scan revealed large round calcifications in the left temporal lobe and right occipital lobe. The patient died three years and six months after the initial symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Beneficial effects of glucagon-insulin infusion on hepatic protein synthesis and DNA synthesis in partial hepatic ischemia].

To study the effects of glucagon-insulin (G-I) infusion on protein synthesis and DNA synthesis in a condition with partial hepatic ischemia, G-I or saline was infused via portal vein for 40 minutes before and after a period of partial hepatic ischemia or following a period of partial hepatic ischemia. Protein synthesis was measured by 14C-leucine incorporation into proteins in incubated liver slices and DNA synthesis by 3H-thymidine incorporation into DNA. Protein synthesis in the postischemic liver was significantly recovered faster and more completely in G-I treated rats. G-I infusion enhanced the DNA synthesis of postischemic liver significantly, peaking 48 hours after the period of partial hepatic ischemia. However, the dosage of G-I infused in this investigation couldn't increase the hepatic tissue blood flow measured by hydrogen gas clearance method. On the histological examination, mitotic index was significantly higher in G-I treated group than in control. These results suggest that G-I infusion could be beneficial effects on the liver in situation with partial ischemic injury and that G-I infusion could remarkably augment hepatic tissue repair following ischemic damage.

Animals↗
PubMed1989

[A clinical and pathological study of diffuse axonal injury].

There is increasing evidence from human and experimental studies that the most important factor governing the outcome in head injury is the severity of diffuse axonal injuries. The authors have experienced 18 cases of severe diffuse axonal injury which showed post-traumatic coma for more than 24 hours and CT findings resembling those of shearing injuries of the cerebral white matter such as have been presented by Zimmerman et al. (1978). The consciousness levels on admission were 6 or less on the Glasgow Coma Scale and all cases were shown clinically to have primary brain stem injury. The main type of head trauma resulted from road traffic accidents (83%). Skull fractures were found in only 5 cases (28%). These findings suggested that acceleration/deceleration injury produce in the patients severe diffuse axonal injury. Initial ICP was below 20 mmHg in 11 cases out of 13 (85%). Parenchymal small hemorrhagic lesions of initial CT were basal ganglia (7 cases), corpus callosum (4 cases), pons (4 cases), midbrain (3 cases) and thalamus (2 cases). Extraparenchymal hemorrhagic lesions included intraventricular hemorrhage (6 cases) and subarachnoid hemorrhage (6 cases). Two autopsied cases of severe diffuse axonal injury (acute case and chronic case) showed remarkable congestion and edema in the deep part of the frontal white matter. Microscopic examination revealed marked axonal degeneration including axonal retraction ball in the corpus callosum, in the internal capsule and in the white matter of the brain stem. Glasgow Outcome Scale of the 18 patients at 3 months after the trauma made us concerned that no patients indicated good recovery or even only moderate disability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Metabolic studies of the edematous cerebral cortex of the pyrithiamine-treated thiamine-deficient rat.

The pyrithiamine-treated rats produced by our method histopathologically exhibited the edematous lesion not only around the third ventricle and at the tegmentum of pons, as expected, but also in the cerebral cortex. These animals were, therefore, used in a biochemical study of the cerebral cortex, in particular, glucose metabolism. The results indicate an accumulation of lactate and severe impairment of the lipid metabolism in the edematous lesion of the cerebral cortex among the pyrithiamine-treated rats. The fact that oxygen consumption was hardly diminished, however, strongly suggested that amino acids were selectively supplied to the tricarboxylic acid cycle from the free amino acid pool.

Amino Acids↗
PubMed1988

[Gas shadow on CT scan following treatment in metastatic brain tumor--an autopsy case].

This is an autopsy case report of a 52-year-old woman with a brain abscess presenting as an intracerebral gas shadow on CT scan. She was admitted to our facility in June 1977, with disorientation and motor weakness of the right upper extremities. CT scan revealed two separate mass lesions in the frontal and occipital lobes on the left side. She was diagnosed as having metastatic carcinoma, and was treated by tumor removal, radiation therapy, and intraneoplastic local chemotherapy. Seventeen months later, she was readmitted with decreased mental activity, hemiconvulsion of the right side and high fever. CT scan revealed a peculiar round gas shadow on the left side of the temporal lobe. Ventricular drainage produced a cloudy cerebrospinal fluid with a protein concentration of more than 400 mg/dl and a leucocyte count of 138,200. An anaerobic culture of the ventricular cerebrospinal fluid revealed Escherichia coli. At that time, the lateral ventricle was irrigated several times with antibiotics. Unfortunately, however, she died one year after readmission. An autopsy was performed shortly after death, at which time serial coronal sectioning of the brain confirmed the CT scan findings presenting as an intracerebral gas shadow, and further demonstrated extension of the brain abscess from the left temporal lobe to the temporal horn of the lateral ventricle. The lesion in the left temporal lobe included yellowish pus with partially brownish capsules. A gas-containing brain abscess confirmed by CT scan and autopsy is rarely seen. The Hounsfield unit obtained from the abscess cavity by utilizing serial CT scan sometimes represents a condition requiring urgent treatment for brain abscess.

Adenocarcinoma↗
PubMed1988

[Histopathological study of a recurrent malignant glioma after an intratumor local injection of adriamycin].

This paper presents interesting morphological findings, which have never been previously reported, on tumor tissues after a local injection of an anticancer agent into three patients with malignant glioma. Following a craniotomy, 0.5 mg of Adriamycin (ADM) was injected through an Ommaya reservoir into the tumor bed. Light microscopy of the recurrent tumor and surrounding necrotic tissue revealed massive coagulation necrosis of the tumor tissues and fibrinoid necrosis of vascular channels, centering at the tip of the Ommaya tube. In the surrounding area of the massive coagulation necrosis, considerable reactive collagenous tissue, infiltrating lymphocytes and foreign body giant cell were found as well as so-called "organized" necrotic tissue. Electron microscopic findings of the same specimens revealed deposits of lipofuscin, lipid droplets, lysosome, abundant myelin figures and fibrous strands. It can therefore be assumed that this or similar anticancer agents, when may be directly incorporated into the residual tumor cells, are apparently reduced by coagulation necrosis and reactive collagenous tissue.

Adult↗