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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 577 records · Page 32Linked to original sources

High reproducibility of regional abnormalities on interictal 123I-IMP SPECT brain scans in adults with partial epilepsy.

The reproducibility of two N-isopropyl-(iodine 123) p-iodoamphetamine (123I-IMP single photon emission computed tomography (SPECT) scans both taken during interictal periods was studied in 13 adult patients with partial epilepsy who had normal CT scans. The frequency of the seizures and the nature of the ictal symptoms were virtually unchanged during the interval between the two SPECT scans performed in each case. In 8 (72.7%) of 11 patients who had abnormal images consisting of focal hypofixation images of 123I-IMP, i.e. zones of decreased regional cerebral blood flow on the first scans, complete or partial regional reproduction of the SPECT abnormalities was observed. This high reproducibility supports the usefulness of SPECT scans in the regional diagnosis of epileptic foci.

Amphetamines↗

Specific cytotoxic effect of neocarzinostatin conjugated to monoclonal antibody A7 on human pancreatic carcinoma.

The anti-cancer drug neocarzinostatin (NCS) was bound covalently to the monoclonal antibody A7 to form the conjugate A7-NCS. This antibody was produced by fusing the spleen cells of a mouse immunized against human colonic carcinoma with murine myeloma cells and reacts with a high percentage of human pancreatic carcinoma cell lines and with no normal human pancreas tissue by immunoperoxidase staining. The cytotoxic effect of A7-NCS was tested by measuring the inhibition of 3H-thymidine incorporation into human pancreatic carcinoma cells. The A7-NCS was approximately 2.7 times as effective as free NCS against human pancreatic carcinoma cells which reacted with the monoclonal antibody A7. A7-NCS had almost the same cytotoxicity a free NCS on human pancreatic carcinoma cells which did not react with the monoclonal antibody A7. A7-NCS appeared to be potentially useful as a conjugate for immunotargeting chemotherapy against pancreatic carcinoma.

Antibiotics, Antineoplastic↗

Structural comparison of murine T-cell (B151K12)-derived T-cell-replacing factor (IL-5) with rIL-5: dimer formation is essential for the expression of biological activity.

T-cell-replacing factor (TRF)/IL-5 is a T-cell-derived glycoprotein which has pleiotropic activity on lymphoid and myeloid cells. IL-5 polypeptide translated into Xenopus oocytes are heterogeneous in molecular size (40,000 to 60,000 under nonreducing conditions) and yields a monomeric form (Mr of 25,000 to 30,000) under reducing conditions (J. Immun., 140, 1175-1181, 1988). We purified T-cell-derived TRF and rIL-5 using anti-TRF/IL-5 antibody-coupled affinity column from supernatants of a T-cell hybridoma B151K12 and supernatants of HeLa cells, respectively, which had been transfected with murine IL-5 cDNA, and determined their partial N-terminal amino acid sequence (27 residues for B151-TRF and 13 residues for rIL-5). A single amino acid sequence of each sample obtained beginning from methionine that was identical to that predicted from IL-5 cDNA. This finding supports the notion that secreted B151-TRF polypeptide consists of 113 amino acids. Purified B151-TRF supported eosinophilopoiesis of human bone marrow cells as effective as mouse rIL-5 and human rIL-5. B151-TRF competitively inhibited 35S-labeled rIL-5 binding to target cells to the same extent at rIL-5. Treatment of purified rIL-5 and B151-TRF with reducing reagents such as 2-ME, sodium borohydride or dithiothreitol produced a monomeric form of IL-5 which did not exert a biological activity. Reduction and alkylation of rIL-5 caused the loss of binding to its target cells. These results strongly suggest that B151-TRF exists as a homodimer and its primary structure and secondary structures are identical to those of rIL-5. Moreover, the formation of inter-molecular disulfide bond(s) linked by two pairs of cystein residues is essential for the expression of the biological activity of mouse IL-5.

Amino Acid Sequence↗

Alpha 2-adrenoceptor modulation of catecholamine and neuropeptide Y responses during haemorrhagic hypotension in anaesthetized dogs.

The acute effects of oxymetazoline, an alpha 2-adrenoceptor agonist, and idazoxan, an alpha 2-adrenoceptor antagonist, on the release of neuropeptide Y were evaluated during haemorrhage in pentobarbital-anaesthetized dogs. Plasma concentrations of neuropeptide Y and catecholamines (adrenaline, noradrenaline, and dopamine) were determined in samples simultaneously collected from aorta, portal vein, and adrenal veins. In control dogs, adrenal catecholamine output, aortic concentrations neuropeptide Y and catecholamines markedly increased during the hypotension period. However, adrenal neuropeptide Y output decreased significantly during this period. Portal venous noradrenaline and neuropeptide Y concentrations increased significantly. In dogs treated with idazoxan, catecholamine output from the adrenals increased to an extent similar to that observed in control dogs. However, the increase in noradrenaline and neuropeptide Y in aortic or portal venous blood during haemorrhage was significantly potentiated in the presence of idazoxan. Administration of oxymetazoline abolished this increase, but did not alter adrenal catecholamine or neuropeptide Y output. The present study demonstrates that neuropeptide Y is co-released with noradrenaline from sympathetic nerve fibers during haemorrhage. Since the release of neuropeptide Y appeared to follow a similar time course to that of noradrenaline release, the present observations suggest that haemorrhagic hypotension enhances both neuropeptide Y and noradrenaline release presumably through a common releasing mechanism. These results also indicate that, in peripheral sympathetic nerves but not in the adrenal gland, neuropeptide Y release is also modulated presynaptically by the inhibitory alpha 2-adrenoceptors in conjunction with the noradrenaline release.

Adrenergic alpha-Antagonists↗

Effect of a novel anticonvulsant, zonisamide (AD-810, CI-912), in an experimental model of photosensitive epilepsy.

The effects of a novel anticonvulsant, zonisamide (3-sulfamoylmethyl-1,2-benzisoxazole), on photically induced seizures were studied in the lateral geniculate-kindled cat. Zonisamide was found to reduce the behavioral severity of seizure responses to photic stimulation in a dose-related manner. This anticonvulsant effect was only observed with doses that caused behavioral toxicity, but anticonvulsant action outlasted behavioral effects. The present results suggest that zonisamide may be effective in the treatment of human photosensitive epilepsy.

Animals↗

Comparative experimental study of antiepileptics--regional specificity of antiepileptic action of carbamazepine, phenobarbital and valproate sodium.

The antiepileptic action of carbamazepine (CBZ), phenobarbital (PB), and valproate sodium (VPA) was examined in 109 adult male rabbits during steady state serum levels produced on the basis of the pharmacokinetics of each drug. The duration and discharge pattern of electrically induced focal and secondarily generalized after-discharges (ADs) in the motor, visual cortices and hippocampus were compared before and after administration of doses of each drug. A CBZ level of 3-30 micrograms/ml shortened the duration of both neocortical and hippocampal ADs. CBZ at levels above 5 micrograms/ml suppressed the spread in the secondarily generalized ADs originating from the neocortical areas, but not that originating from the hippocampus. PB levels of 10-80 micrograms/ml shortened the duration of both neocortical ADs, especially motor ADs, whereas they had little or no effect on the hippocampal ADs. VPA showed inhibitory effects on both the neocortical and hippocampal AD durations only at high levels of 400-1,100 micrograms/ml. However, the inhibitory effects were more marked on the latter than the former, and further, the effects were enhanced as time elapsed. These results suggest that the action of each drug on focal seizures is region-specific.

Animals↗

Anticonvulsant effects of zonisamide and phenytoin on seizure activity of the feline visual cortex.

The acute anticonvulsant effects of zonisamide (ZNS) and phenytoin (PHT) on seizure activity produced by electrical stimulation of the feline visual cortex were studied. The intravenous administration of ZNS 60 mg/kg reduced kindled generalized seizures into partial seizures, with marked reduction in the afterdischarge duration. ZNS also suppressed focal seizure activity of the visual cortex and produced a dose-related increase in the afterdischarge threshold. The anticonvulsant effect of ZNS (60 mg/kg) was comparable to that of PHT (15 mg/kg) and was observed in the absence of neurological toxicity and background EEG changes. The present findings demonstrated that ZNS possesses potent anticonvulsant action against focal seizure and its secondary generalization from the visual cortex.

Animals↗

Occlusion time dependency of regional noradrenaline release and cardiac arrhythmias during reperfusion of acutely ischaemic heart in the dog in vivo.

STUDY OBJECTIVE: The aim was to study the occlusion time dependency of reperfusion induced increases in regional cardiac noradrenaline release from the ischaemic area in relation to the incidence of ventricular arrhythmias. DESIGN: The left anterior descending coronary artery was ligated for 15, 30 and 60 min in three separate groups of dogs (n = 10 per group). Each occlusion period was followed by a 30 min reperfusion period. The coronary sinus and the epicardial vein running in parallel with the left anterior descending coronary artery were cannulated for measurement of noradrenaline and lactate. EXPERIMENTAL MATERIAL: 30 adult mongrel dogs, 22.5(SEM 1.1) kg, were used for the study. The animals were anaesthetised with sodium pentobarbitone. MEASUREMENTS AND MAIN RESULTS: During occlusion, epicardial venous blood noradrenaline concentrations remained unchanged up to 30 min, but increased from 0.133(0.027) ng.ml-1 to 0.289(0.069) ng.ml-1 after 60 min of occlusion (p less than 0.05). However, epicardial venous blood lactate concentrations increased immediately upon occlusion, and remained elevated (p less than 0.05) during the whole period of occlusion in all groups. Neither noradrenaline nor lactate concentrations in coronary sinus blood increased during occlusion. During reperfusion, nine dogs showed early ventricular fibrillation. The highest incidence of fibrillation (n = 5/10) was found in the 15 min occlusion group, but the difference was not significant between groups. Epicardial venous blood noradrenaline concentrations increased to 0.371(0.076) ng.ml-1, 0.470(0.178) ng.ml-1, and 1.824(0.713) ng.ml-1 upon reperfusion following 15, 30 and 60 min occlusion, respectively (each p less than 0.05). Maximum increases in epicardial venous blood noradrenaline concentrations during reperfusion were correlated with duration of preceding occlusion (r = 0.60, n = 21, p less than 0.01). Maximum increases in mean arrhythmic ratios observed during the first 10 min of reperfusion were proportionally related to mean epicardial venous blood noradrenaline concentrations. The increases in epicardial venous blood noradrenaline concentrations and the incidence of ventricular arrhythmias in the 60 min occlusion group were greater (p less than 0.05) than in the other two groups. CONCLUSIONS: This study shows that noradrenaline is released progressively from the ischaemic area during occlusion for 60 min. The amount of noradrenaline washed out upon reperfusion and the incidence of reperfusion ventricular arrhythmias both appear to be dependent upon duration of preceding occlusion. The results suggest that cardiac noradrenaline released locally from the ischaemic region may contribute to the genesis of reperfusion ventricular arrhythmias, but not to that of reperfusion ventricular fibrillation.

Animals↗

Characterization of the murine interleukin 5 receptor by using a monoclonal antibody.

Murine interleukin 5 (IL-5), a lymphokine produced by helper T cells, is involved in the regulation of growth and differentiation of B cells and other hematopoietic cells. The receptor for IL-5 has been identified as two cross-linked complexes on T88-M cells (a murine IL-5-dependent early B cell line). In this study the IL-5 receptor was directly characterized by utilizing an immobilized IL-5 column and a rat monoclonal antibody, designated H7, directed against the IL-5 receptor. H7 completely inhibited specific binding of 35S-labeled IL-5 to T88-M cells, and bound to IL-5-responsive cells, e.g. T88-M, BCL1-B20 (a chronic B-cell leukemia), and MOPC104E (a myeloma), whereas H7 did not bind to IL-5-non-responsive cells, e.g. X5563 (a myeloma), FDC-P1 (an IL-3-dependent line), and MTH (an IL-2-dependent CTLL). H7 could barely bind to T88-M cells in the presence of IL-5, and immunoprecipitated a major band with an Mr of approximately 60 kd from the extract of surface-radioiodinated T88-M cells. The precipitation of this 60 kd molecule was inhibited by the addition of IL-5. Analysis with immobilized IL-5 also revealed that a 60 kd molecule bound specifically to IL-5-coupled beads compared with control beads. Furthermore, no additional molecule with a higher Mr that was recognized by H7 appeared under non-reducing, compared with reducing, conditions. The 60 kd molecule recognized by H7 could be digested with N-glycanase to yield a protein band of approximately 55 kd.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Radiation necrosis of the optic chiasm, optic tract, hypothalamus, and upper pons after radiotherapy for pituitary adenoma, detected by gadolinium-enhanced, T1-weighted magnetic resonance imaging: case report.

A 26-year-old woman was treated for a prolactin secreting pituitary adenoma by surgery and radiotherapy (5860 rads). Fourteen months later, she developed right hemiparesis and dysarthria. A T1-weighted magnetic resonance imaging scan using gadolinium contrast showed a small, enhanced lesion in the upper pons. Seven months later, she had a sudden onset of loss of vision, and radiation optic neuropathy was diagnosed. A T1-weighted magnetic resonance imaging scan showed widespread gadolinium-enhanced lesions in the optic chiasm, optic tract, and hypothalamus. Magnetic resonance imaging is indispensable for the early diagnosis of radiation necrosis, which is not visualized by radiography or computed tomography.

Adenoma↗

Elevated expression of proto-oncogenes during interleukin-5-induced growth and differentiation of murine B lineage cells.

Interleukin 5 (IL-5), a lymphokine produced by helper T cells, is involved in the regulation of growth and differentiation of B cells and other hematopoietic cells. To elucidate IL-5-mediated intracellular mechanisms, we have established IL-5-dependent and -independent murine early B cell lines, J6 and MJ88-1, respectively, and examined the effect of IL-5 on the expression of proto-oncogenes during proliferation. Two- to 3.5-fold increases in the levels of c-myb, c-myc, c-fos, and c-fms mRNA were observed in J6 cells, compared with those in MJ88-1 cells. Further, a role of IL-5 in the proto-oncogene expression during differentiation was examined by using thymidine-treated murine B-cell chronic leukemia BCL1-B20 cells with growth arrest. After 4-day culture, the amount of IgM secreted from BCL1-B20 cells was augmented 4-6 fold in the presence of IL-5. Although expression of c-myb, c-fos, and c-fms mRNA did not change, only c-myc mRNA expression was elevated within 30 min of stimulation with IL-5 and reached a maximal level by 1 hr. Addition of phorbol 12-myristate 13-acetate (PMA) or IL-4 to the culture of BCL1-B20 cells inhibited both the IL-5-mediated augmentation of IgM secretion and the elevated expression of c-myc mRNA. These findings suggest that the IL-5 signal may be associated with the up-regulation of c-myc expression.

Animals↗

Analysis of stomach cancer incidence by histologic subtypes based on a mathematical model of multistage cancer induction and exponential growth.

A mathematical model incorporating the processes of both cancer induction and subsequent tumor growth has been developed. The model was applied to incidence data of stomach classified into histologic subtypes: papillary adenocarcinoma (PAP), well and moderately differentiated tubular adenocarcinomas (WEL and MOD), poorly differentiated adenocarcinoma (POR), mucinous adenocarcinoma (MUC) and signet-ring cell carcinoma (SIG). The multistage theory was assumed for cancer induction as in the Armitage-Doll model. For the period of growth, exponential growth was assumed and clinical surfacing was formulated as a stochastic process related to tumor diameter. The number of stages in cancer induction and the tumor growth rate were simultaneously estimated for each histologic subtype using the maximum likelihood procedure. The present model showed better fits than the Armitage-Doll model in most histologic subtypes except WEL, PAP, WEL and MOD, which are characterized as differentiated subtypes with less mucous production, showed different features from POR, MUC and SIG: 1) the number of stages was estimated to be larger, 2) the differences in incidence rates between males and females were more marked, and 3) males tended to have larger growth rates in PAP and MOD, while in POR, MUC and SIG, females had larger values. The present study showed that an analysis by histologic subtypes is of importance in stomach cancer and that the period of tumor growth should not be ignored when formulating a model of the natural history of stomach cancer.

Adenocarcinoma↗

Ultrastructure of rectal biopsy specimens in unusual familial ataxia with cerebrospinal fluid abnormality.

The ultrastructure of rectal biopsy specimens from a 60-year-old woman of unusual familial ataxia with cerebrospinal fluid abnormality was investigated. She had two male siblings similarly affected and a close consanguinity in the family. Meissner's plexus neurons, Schwann cells, fibroblasts and smooth muscle cells within the rectum contained intracytoplasmic eosinophilic inclusions (IEIs) with or without intensely eosinophilic granules. Ultrastructurally the IEIs were composed of a membrane-bound, fine granular material with or without dense cores. The IEIs resembled intracytoplasmic inclusions seen in various cells of the central nervous system from a male autopsied sibling. The clinically and morphologically similar finding in the two siblings suggests an autosomal recessive inherited metabolic disorder previously unreported.

Biopsy↗

Absence of prejunctional sympathetic effect of amiodarone in hearts of open-chest anesthetized dogs.

The effect of amiodarone (30 mg/kg p.o. each day for 3 weeks) on noradrenaline (NA) overflow into coronary sinus (CS) blood during left stellate stimulation (15 V, 2-ms square waves, 30 s duration at 1, 2, 4, and 8 Hz in random order) was investigated in an open-chest dog preparation. CS blood samples were taken before and during the stimulation period for plasma NA and hematocrit determinations. CS blood flow was monitored (extracorporal circulation with an electromagnetic flow meter) and used for NA output computation. The right atrium was paced throughout the experimental period. However, because AV block occurred at a high pacing rate in some amiodarone-treated dogs, pacing rate was lower in that group than in control dogs (132 +/- 13 vs. 161 +/- 10 min-1, ns). Mean arterial pressure was also lower in the treated group (95 +/- 9 vs. 110 +/- 13 mmHg, but increased in every dog upon stimulation (p less than 0.05). Basal left ventricular dP/dtmax was comparable in the two groups of dogs and increased in a similar fashion upon stimulation (p less than 0.05). The increase in plasma NA concentration upon stimulation was comparable between the control and the amiodarone-treated group (0.38 +/- 0.08 vs 0.40 +/- 0.12 ng/mL at 1 Hz and 12.7 +/- 3.1 vs 11.3 +/- 2.3 ng/mL at 8 Hz, ns). The increase in NA output was also comparable (7.0 +/- 1.6 vs. 10.7 +/- 5.4 ng/min at 1 Hz and 356 +/- 124 vs. 334 +/- 102 ng/min at 8 Hz, ns). Amiodarone did not alter the myocardial NA content. We conclude that amiodarone, administered orally for 3 weeks, does not interfere with neural NA release, or with the positive inotropic response, following sympathetic nerve stimulation in dogs.

Amiodarone↗

Corelease of neuropeptide Y like immunoreactivity with catecholamines from the adrenal gland during splanchnic nerve stimulation in anesthetized dogs.

The release of neuropeptide Y like immunoreactivity (NPY-li) from the adrenal gland was studied in relation to the secretion of catecholamines (CA: NE, norepinephrine; E, epinephrine) during the left splanchnic nerve stimulation in thiopental-chloralose anesthetized dogs (n = 16). Plasma concentrations of NE, E, and NPY-li were determined in the left adrenal venous and aortic blood. Adrenal outputs of NPY-li, NE, and E were 2.4 +/- 0.4, 1.4 +/- 0.2, and 7.3 +/- 1.7 ng/min, under basal conditions, respectively. These values increased significantly (p less than 0.05; n = 8) in response to a continuous stepwise stimulation at frequencies of 1, 3, and 10 Hz given at 3-min intervals during 9 min, reaching a maximum output of 4.6 +/- 0.9 (NPY-li), 240.2 +/- 50.2 (NE), and 1412.5 +/- 309.7 ng/min (E) at a frequency of 10 Hz. Burst electrical stimulation at 40 Hz for 1 s at 10-s intervals for a period of 10 min produced similar increases (p less than 0.05) in the release of NPY-li (4.8 +/- 1.0 ng/min, n = 8), NE (283.5 +/- 144.3 ng/min, n = 8), and E (1133.5 +/- 430.6 ng/min, n = 8). Adrenal NPY-li output was significantly correlated with adrenal NE output (r = 0.606; n = 24; p less than 0.05) and adrenal E output (r = 0.640; n = 24; p less than 0.05) in dogs receiving the burst stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Pancreatic glucagon secretion during a short period of hemorrhage in anesthetized dogs.

Glucagon has been implicated in the hormonal metabolic response to hemorrhage. However, evidence for this has been obtained largely from observations of circulating plasma glucagon concentration. A clear increase in the pancreatic glucagon secretion remains to be demonstrated. Plasma concentrations of pancreatic immunoreactive glucagon (IRG) and insulin (IRI) were determined in portal venous and aortic blood, and plasma glucose in aortic blood. Dogs were bled (approximately 15 mL/kg) until aortic systolic blood pressure dropped to approximately 50% (70.5 +/- 8.1 mmHg, n = 7) (1 mmHg = 133.32 Pa) of its control value (135 +/- 7.1 mmHg, n = 7), and the hemorrhagic hypotension was maintained for 10 min. The net portal venous IRG delivery rate rose significantly and continued to increase during the hemorrhagic hypotension despite a significant fall in the portal venous blood flow. Aortic IRG increased significantly along with the increase in portal venous IRG delivery rate (r = 0.838, n = 42, p less than 0.01). The portal venous delivery rate of IRI decreased significantly in response to hemorrhage. The aortic IRG/IRI concentration ratio increased significantly during the hemorrhage-induced hypotension. Aortic glucose concentration increased significantly 5 min after hemorrhage and continued to rise until the end of the hemorrhagic hypotension. The present study demonstrates that the secretion of pancreatic glucagon actually increases during the early phase of hemorrhage. The results also indicate that the increase in aortic IRG during the hemorrhagic hypotension is due to the increased pancreatic glucagon secretion. It is suggested that the pancreatic glucagon may be involved in the early hyperglycemic response to hemorrhage.

Anesthesia↗

Effect of functional adrenalectomy on glucagon secretion and circulating catecholamines during insulin hypoglycemia in the dog.

The present study was carried out to determine whether an increase in the pancreatic immunoreactive glucagon (IRG) secretion during the acute phase of insulin-induced hypoglycemia depends on circulating catecholamines of adrenal origin. Hypoglycemia was induced by a bolus insulin injection (0.15 IU/kg, i.v.) in dogs anesthetized with sodium pentobarbital (35 mg/kg, i.v.). Plasma aortic epinephrine (E) and norepinephrine (NE) concentrations increased significantly 30 min after the injection of insulin. At this time point, a functional adrenalectomy (diversion of bilateral adrenal venous blood from the systemic circulation) was performed for 5 min. The increased aortic E and NE concentrations significantly decreased reaching, within 5 min, a level below the corresponding preinjection control value. The basal output of pancreatic IRG (6.58 +/- 1.12 ng/min, n = 6) significantly increased (24.93 +/- 2.77 ng/min, p less than 0.05, n = 6) 30 min after insulin injection. During the functional adrenalectomy, the increased pancreatic IRG output diminished rapidly, within 5 min, to approximately 50% (11.73 +/- 3.19 ng/min, p less than 0.05, n = 6) of the value observed 30 min after insulin administration. In the other group of dogs receiving sham adrenalectomy, the increased aortic E and NE concentrations and pancreatic IRG output following insulin injection remained elevated above the levels observed immediately before the sham adrenalectomy. The net decrease in IRG output during the adrenalectomy was significant (p less than 0.05) compared with the corresponding net IRG output observed in the sham group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗