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Biomedical subjects

S Konishi

Publications and source records attributed to S Konishi.

At least 55 records · Page 3Linked to original sources

Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI.

Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

Adaptation, Physiological↗

Early response of tumour to radiotherapy should be assessed by both uptake and retention of single photon tracers: in vitro analysis with 201Tl-chloride, 99Tcm-sestamibi and 99Tcm-tetrofosmin in human bladder cancer cells and human leukocytes.

The uptake and retention of single photon tracers in irradiated tumour cells was observed in an attempt at the early evaluation of the effect of radiation. T24 human bladder cancer cells were exposed to a single dose of 10 Gy or 20 Gy or a fractionated dose of 10 Gy (2 Gy for 5 days). The uptake of 201Tl chloride, 99Tcm-sestamibi and 99Tcm-tetrofosmin was observed by incubating in vitro for 60 min. The retention of the tracers was observed at 60 min after changing the incubation medium for a tracer-free medium. Uptake per culture well of all tracers in the cells exposed to 20 Gy declined as viable cell number decreased, but uptake per cell increased progressively. Uptake per cell of all tracers in the cells exposed to either a single dose or a fractionated dose of 10 Gy also increased, while a delay in growth was observed. The retention of these tracers decreased during this period and recovered thereafter. A binding assay with purified human leukocytes indicated that assessment with 99Tcm-sestamibi and 99Tcm-tetrofosmin is influenced by inflammatory cells. In conclusion, the effect of radiation may be underestimated if assessed by tracer uptake alone because of the increase in tracer uptake in viable irradiated cells. Observation of the retention of tracers may provide additional information.

Humans↗

Preoperative assessment of residual hepatic functional reserve using 99mTc-DTPA-galactosyl-human serum albumin dynamic SPECT.

UNLABELLED: Preoperative assessment of residual hepatic functional reserve offers important strategic information for hepatic resection. To predict the postoperative residual liver function, we assessed the value of hepatic 99mTc-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) clearance estimated by dynamic SPECT analysis. METHODS: We investigated 114 consecutive patients with liver disease, including 55 hepatectomy cases. One minute after injection of 185 MBq 99mTc-GSA, 15 serial dynamic SPECT images were obtained every minute. The initial five sets of SPECT images were analyzed by Patlak plot to estimate the sequential initial hepatic 99mTc-GSA clearance (mL/min) as an index of hepatic function. The sum of hepatic 99mTc-GSA clearance of the segments immune from resection was categorized as predicted residual 99mTC-GSA clearance. In the hepatectomy cases, scintigraphy was performed before and 37 +/- 10 d after the operation. RESULTS: Good correlation was observed between the total hepatic 99mTc-GSA clearance and conventional hepatic function tests: plasma retention rate of iodocyanine green (ICG) at 15 min (ICG R15), r = -0.600, P < 0.0001, n = 94; plasma disappearance rate of ICG (K ICG), r = 0.670, P < 0.0001, n = 83; cholinesterase, r = 0.539, P < 0.0001, n = 121; serum albumin, r = 0.421, P = 0.0001, n = 123; and hepaplastin test, r = 0.456, P < 0.0001, n = 120. There was good correlation between the predicted residual 99mTc-GSA clearance and the postoperative total hepatic 99mTc-GSA clearance in patients who underwent segmentectomy or lobectomy (r = 0.84, P < 0.0001, n = 28) and between the pre- and postoperative total hepatic 99mTc-GSA clearance in patients who underwent subsegmentectomy (r = 0.91, P < 0.0001, n = 25). Five patients who had postoperative complications due to hepatic insufficiency (2 patients died of postoperative hepatic failure within 2 mo after operation) showed significantly lower predicted residual 99mTc-GSA clearance compared with the patients without complications (90.3 +/- 37.2 versus 320.9 +/- 158.8 mL/min; P < 0.005). CONCLUSION: The total hepatic 99mTC-GSA clearance reflected hepatic function. In addition, preoperative predicted residual hepatic 99mTc-GSA clearance was a good indicator of postoperative hepatic function and early prognosis. 99mTc-GSA dynamic SPECT is assumed to be a useful method for determining the surgical strategy in patients with hepatic tumor and especially in patients with hepatic dysfunction.

Coloring Agents↗

Phospholipase C-independent group I metabotropic glutamate receptor-mediated inward current in mouse purkinje cells.

The mGluR agonist 1S,3R-ACPD induces a potent excitatory inward current in various central neurons, but the underlying mechanism is not fully understood. Thus, we explored the signal transduction mechanism underlying the 1S,3R-ACPD-induced inward current in mouse cerebellar Purkinje cells. Iontophoretic application of 1S,3R-ACPD produced a group I mGluR antagonist-sensitive inward current. This current closely resembled a slow synaptic inward current evoked by repetitive stimulation of parallel fibers. Although phosphoinositide hydrolysis is shown to be coupled with group I mGluRs, we found that intracellular injections of various PLC inhibitors and an IP3 receptor antagonist heparin only partially inhibited the 1S, 3R-ACPD-induced current. Moreover, intracellular injection of the Ca2+ chelator BAPTA or a selective Na+/Ca2+ exchange inhibitor KB-R7943 affected slightly the inward current. In contrast, infusion of GDPbetaS and GTPgammaS markedly suppressed the 1S,3R-ACPD-induced current. These results suggest that activation of mGluR1 in mouse cerebellar Purkinje cells by 1S,3R-ACPD application or by repetitive stimulation of parallel fibres induces an inward current with a minor contribution from intracellular Ca2+ or Na+/Ca2+ exchange.

Animals↗

A novel protein containing Cdc10/SWI6 motifs regulates expression of mRNA encoding catecholamine biosynthesizing enzymes.

Catecholaminergic (dopaminergic, noradrenergic, and adrenergic) transmitter phenotypes require the cooperative actions of four biosynthetic enzymes: tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase. Mechanisms that control expression of these enzymes in a transmitter phenotype-specific manner, however, are poorly understood. Here, we provide evidence that overexpression of a novel cdc10/SWI6 motif-containing protein, V-1, elicits the coordinate up-regulation of tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine beta-hydroxylase mRNAs in the neuronal cell line PC12D, and as a result, catecholamine levels are increased. Furthermore, V-1 is strongly expressed in the cytoplasm of rat chromaffin cells of adrenal medulla. Thus, V-1 may act as a cytoplasmic protein/protein adapter and be involved in control of the catecholaminergic phenotype expression via an intracellular pathway signaling to the nucleus.

Adrenal Medulla↗

Down-regulation of RFL, the FLO/LFY homolog of rice, accompanied with panicle branch initiation.

FLORICAULA (FLO) of Antirrhinum and LEAFY (FLY) of Arabidopsis regulate the formation of floral meristems. To examine whether same mechanisms control floral development in distantly related species such as grasses, we isolated RFL, FLO-LFY homolog of rice, and examined its expression and function. Northern analysis showed that RFL is expressed predominantly in very young panicle but not in mature florets, mature leaves, or roots. In situ hybridization revealed that RFL RNA was expressed in epidermal cells in young leaves at vegetative growth stage. After the transition to reproductive stage, RFL RNA was detected in all layers of very young panicle including the apical meristem, but absent in the incipient primary branches. As development of branches proceeds, RFL RNA accumulation localized in the developing branches except for the apical meristems of the branches and secondary branch primordia. Expression pattern of RFL raised a possibility that, unlike FLO and LFY, RFL might be involved in panicle branching. Transgenic Arabidopsis plants constitutively expressing RFL from the cauliflower mosaic virus 35S promoter were produced to test whether 35S-RFL would cause similar phenotype as observed in 35S-LFY plants. In 35S-RFL plants, transformation of inflorescence meristem to floral meristem was rarely observed. Instead, development of cotyledons, rosette leaves, petals, and stamens was severely affected, demonstrating that RFL function is distinct from that of LFY. Our results suggest that mechanisms controlling floral development in rice might be diverged from that of Arabidopsis and Antirrhinum.

Amino Acid Sequence↗

Prevalence of mutations in core promoter/precore region in Japanese patients with chronic hepatitis B virus infection.

We examined the frequency and significance of mutations in the core promoter and precore region in 103 Japanese patients with chronic hepatitis B virus (HBV) infection. HBV DNAs from the patients' sera were amplified by polymerase chain reaction and were directly sequenced. A double mutation (T1762 A1764) in the core promoter was frequently observed in the patients regardless of HBeAg status except for asymptomatic carriers with HBeAg. Furthermore, a mutation at nucleotide 1753 from T to C or G was frequently found in anti-HBe positive patients and was often accompanied by the double mutation. The A1896 mutation was found in only about one fourth of the patients with anti-HBe. These data suggest that the patients with chronic liver diseases frequently had a double mutation regardless of HBeAg status and a mutation at nucleotide 1753 might be associated with HBeAg-negative chronic hepatitis B virus infection.

Amino Acid Sequence↗

Transient activation of inferior prefrontal cortex during cognitive set shifting.

The Wisconsin Card Sorting Test, which probes the ability to shift attention from one category of stimulus attributes to another (shifting cognitive sets), is the most common paradigm used to detect human frontal lobe pathology. However, the exact relationship of this card test to prefrontal function and the precise anatomical localization of the cognitive shifts involved are controversial. By isolating shift-related signals using the temporal resolution of functional magnetic resonance imaging, we reproducibly found transient activation of the posterior part of the bilateral inferior frontal sulci. This activation was larger as the number of dimensions (relevant stimulus attributes that had to be recognized) were increased. These results suggest that the inferior frontal areas play an essential role in the flexible shifting of cognitive sets.

Attention↗

No-go dominant brain activity in human inferior prefrontal cortex revealed by functional magnetic resonance imaging.

We investigated the response inhibition function of the prefrontal cortex associated with the go/no-go task using functional magnetic resonance imaging in five human subjects. The go/no-go task consisted of go and no-go trials given randomly with roughly equal probability. In go trials a green square was presented and the subjects had to respond by promptly pushing a button using their right or left thumbs, but in no-go trials a red square was presented and subjects were instructed not to respond. When brain activity in no-go trials is dominant over that in go trials in areas in the prefrontal cortex, this no-go dominant brain activity would reflect the neural processes for inhibiting inherent response tendency. We used a new strategy of image data analysis by which transient brain activity in go or no-go trials can be analysed separately, and looked for the prefrontal areas in which the brain activity in no-go trials is dominant over that in go trials. We found the no-go dominant foci in the posterior part of the right inferior frontal sulcus reproducibly among the subjects. This was true whether the right or left hand was used. These results suggest that this region in the prefrontal cortex is related to the neural mechanisms underlying the response inhibition function.

Adult↗

Rhenium-186-mercaptoacetyltriglycine-labeled monoclonal antibody for radioimmunotherapy: in vitro assessment, in vivo kinetics and dosimetry in tumor-bearing nude mice.

Stability and immunoreactivity of 186Re-labeled monoclonal antibody were examined, and its in vivo kinetics was investigated in tumor-bearing Balb/c nu/nu female mice to assess the feasibility of using it in radioimmunotherapy (RIT). A murine IgG1, A7, against a 45 kD glycoprotein in human colon cancer was radiolabeled with 186Re by using a chelating method with a mercaptoacetyltriglycine (MAG3). 186Re-MAG3 complex was conjugated to A7 after esterification of 186Re-MAG3 with tetrafluorophenol (TFP). The efficiency of 186Re-MAG3-TFP production and the labeling efficiency of A7 were 51-59% and 57-60%, respectively. Immunoreactivity of purified 186Re-MAG3-A7 was 68.2% at infinite antigen excess. In 0.9% NaCl at 4 degrees C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from 186Re-MAG3-A7 as a small molecular weight moiety because of autoradiolysis. The addition of ascorbic acid, 5 mg/ml, as a radioprotectant or storage at -80 degrees C could effectively prevent the radiolysis of 186Re-MAG3-A7 for 7 days. Immunoreactivity of 186Re-MAG3-A7, 6.70 MBq/mg (6.66 MBq/ml), stored in the presence of ascorbic acid was well retained up to 8 days after the preparation. In colon cancer xenografted mice, 31.0% of the injected dose/g of 186Re-MAG3-A7 had accumulated in the tumors at 24 h postinjection. Estimated radiation dose to tumors was 14.9 cGy/37 kBq up to 8 days postinjection which was 12-fold greater than the whole-body radiation dose. These in vivo characteristics were superior to those of A7 labeled with radioiodine, affording greater therapeutic ratios than 131I-A7. Because of the better image quality of 186Re-MAG3-A7 as well as more favorable dosimetry, 186Re-MAG3-A7 would be a better choice for RIT of colon cancer than 131I-A7. These results indicated the feasibility of RIT with 186Re-MAG3-A7, though the prevention of radiolysis of the labeled antibody should be considered.

Animals↗

Patient background of the Pokemon phenomenon: questionnaire studies in multiple pediatric clinics.

Many children in Japan developed various neuropsychological problems, including seizures, while watching the program Pocket Monster, televised on 16 December 1997. To examine the basis for this incident, we have performed a survey of volunteering children and their parents who visited our pediatric clinics for other reasons from 8 January to 28 February 1998. Children and their parents filled out questionnaires. Among the total of 662 children surveyed, the great majority (603, 91.1%) was found to have watched the Pocket Monster program and 30 individuals (5.0% of viewers) complained of variable degrees of neuropsychological abnormalities. These included seizures (two cases), headache (nine cases), nausea (eight cases), blurred vision (four cases), vertigo (two cases), dysthymia (two cases) and vomiting (one case). Nearly half (14) of these children developed symptoms during or immediately after watching the program, while the remainder did so later. Representative cases are reported and other statistical aspects are discussed.

Adolescent↗

Persistent distension and enhanced diffusive extravasation of tumor vessels improved uniform tumor targeting of radioimmunoconjugate in mice administered with angiotensin II and kininase inhibitor.

Induced hypertension with angiotensin II (AT-II) and the inhibition of kininase with enalapril maleate may increase the tumor targeting of radiolabeled monoclonal antibodies (MAbs). We previously found that short-period infusion of 2.0 microg/kg/min of AT-II enhanced tumor targeting of MAb without an impact on normal tissue distribution. In this study, we aimed to optimize the manipulation with these agents, and examine the possible mechanism of their effects on MAb distribution. Effect of the manipulation on tissue circulation was assessed in mice bearing colon cancer xenografts by 201Tl and 99mTc-human serum albumin (HSA) as markers of tissue blood flow and tissue blood volume and/or vascular permeability. A dose finding study of enalapril ranging from 3 to 300 microg showed that 30 microg of enalapril in combination with AT-II infusion produced the best improvement in tumor uptake of 99Tc-HSA without altering 201Tl distribution, suggesting that the increase of vascular permeability was caused by enalapril. AT-II infusion for longer than 1 h affected renal blood flow and caused subcutaneous edema. Tumor uptake of (111)In-A7, a murine IgG1, was 1.62-fold improved 72 h postinjection (P < 0.001) and intratumoral distribution became uniform with 2.0 microg/kg/min of AT-II for 1 h and 30 microg of enalapril. Vessels in manipulated tumors were distended even 48 h after the cessation of AT-II infusion. In conclusion, it was suggested that persistent distension of tumor vessels and the increase of diffusive extravasation of MAb caused by short-period-induced hypertension and inhibition of bradykinin degradation produced favorable effect for the MAb distribution in tumors.

Angiotensin II↗

Intense Ga-67 uptake in adenosquamous carcinoma of the pancreas.

Gallium-67 citrate (Ga-67) scintigraphy was performed in a patient with adenosquamous carcinoma of the pancreas. Intense and homogeneous uptake was observed in the tumor. Few reports have dealt with Ga-67 findings in pancreatic cancers. Ga-67 uptake in the tumor was assumed to be due to accumulation in the component of squamous cell carcinoma. This case suggested that Ga-67 citrate scintigraphy may be useful in detecting adenosquamous carcinoma of the pancreas. To our knowledge, no report has described findings of Ga-67 citrate scintigraphy of adenosquamous carcinoma of the pancreas. Radiologists should remember adenosquamous carcinoma of the pancreas when encountering such scintigraphic findings.

Aged↗

Short-period-induced hypertension could improve tumor-to-nontumor ratios of radiolabeled monoclonal antibody.

This study was undertaken to find optimum period of hypertensive treatment for the improvement of tumor targeting of 111In-labeled monoclonal antibody. Angiotensin II was infused into tumor-bearing mice at an infusion rate of 2.0 micrograms/kg/min determined by the dose-finding study. The infusion was continued for up to 72 h, and biodistribution of 111In-DTPA-A7, a murine IgG1, was observed 72 h postinjection. Tumor-to-nontumor ratios were best improved with the infusion for 0.5-3 h. However, with the longer infusion, the effect deteriorated by the increase of nontumor uptakes, and body-weight loss became remarkable. It could be concluded that hypertensive treatment for a short period could be safely performed to benefit targeting of radiolabeled monoclonal antibody.

Angiotensin II↗

Transient brain activity used in magnetic resonance imaging to detect functional areas.

Functional areas were detected with short stimuli eliciting transient brain activity using the method of 'transient' regions of interest (ROIs) and functional magnetic resonance imaging (fMRI). This method was validated by comparing the results with sustainedly activated areas identified conventionally. Eighty-eight and 89% of the total areas of transient ROIs derived from 0.2 and 2 s stimulation, respectively, were identified at 5-7 s and 5-9 s, respectively, after stimulus onset. Eighty-eight and 76%, respectively, of these areas overlapped 'conventional' ROIs derived from 20 s stimulation. These results suggest that the delineation of transient ROIs, by targeting a period approximately 7 s after transient neural activity, can be useful for fMRI studies of cognitive functions.

Adult↗

Long-lasting facilitation of inhibitory transmission by monoaminergic and cAMP-dependent mechanism in rat cerebellar GABAergic synapses.

Roles of monoaminergic neurons in synaptic plasticity are not well clarified at mammalian central synapses. We therefore examined the actions of serotonin and noradrenaline on cerebellar excitatory and inhibitory synapses using the whole-cell recording with rat cerebellar slices. Applications of the two amines selectively elicited long-lasting facilitation of gamma-aminobutyric acid (GABA)-mediated inhibitory transmission, possibly through a presynaptic mechanism. The facilitatory action of the amines on GABAergic transmission was mimicked by forskolin and blocked by protein kinase inhibitors, suggesting the involvement of cyclic AMP (cAMP)-dependent mechanism in their action. A monoamine uptake inhibitor, imipramine, enhanced the GABAergic transmission, whereas it was suppressed by monoamine receptor antagonists, propranolol and methiothepin, suggesting that endogenous monoamines released by stimulation enhance the inhibitory transmission at cerebellar GABAergic synapses in sustained and activity-dependent manner. Such monoaminergic facilitation may provide a likely mechanism for synaptic plasticity in motor coordination within the mammalian cerebellar function.

Adenylyl Cyclase Inhibitors↗