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Biomedical subjects

S Konishi

Publications and source records attributed to S Konishi.

At least 19 recordsLinked to original sources
PubMed2005

Randomized, double-blind, placebo-controlled crossover trial of famotidine in patients with functional dyspepsia.

BACKGROUND: Histamine 2-receptor antagonists were used as a first therapy against functional dyspepsia. However, few clinical studies with famotidine for functional dyspepsia have been reported. AIM: To evaluate the effectiveness of famotidine for functional dyspepsia patients. METHODS: A multicentre, randomized, double-blind, placebo-controlled crossover trail was conducted. Patients diagnosed with functional dyspepsia by the Roma II criteria were included. Subjects were randomized into two groups, and received either famotidine or placebo as the first 4 weeks medication. After a 1-week washout period, they were switched to the other regimen for another 4 weeks. Evaluation was made prior to the start of study, upon completion of the first drug cycle, and the second drug cycle, by Gastrointestinal Symptoms Rating Scale for the seriousness of abdominal symptoms, and by Short Form-36 for the level of quality of life. RESULTS: Nineteen of 21 enrolled patients successfully completed this study. Significant improvement in Gastrointestinal Symptoms Rating Scale scores was observed in abdominal pain (P = 0.007), indigestion and reflux syndrome after famotidine treatment. Also quality of life scores showed significant improvement in body pain, vitality and general health perceptions after famotidine treatment. There was no improvement of symptoms and quality of life scores after administration of placebo. CONCLUSIONS: Famotidine was effective for improving symptoms and quality of life in functional dyspepsia patients.

Adult↗
PubMed2003

Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death.

OBJECTIVE: To investigate the clinical outcome, ECG characteristics, and optimal treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), a malignant and rare ventricular tachycardia. PATIENTS AND METHODS: Questionnaire responses and ECGs of 29 patients with CPVT were evaluated. Mean (SD) age of onset was 10.3 (6.1) years. RESULTS: The initial CPVT manifestations were syncope (79%), cardiac arrest (7%), and a family history (14%). ECGs showed sinus bradycardia and a normal QTc. Mean heart rate during CPVT was 192 (30) beats/min. Most cases were non-sustained (72%), but 21% were sustained and 7% were associated with ventricular fibrillation. The morphology of CPVT was polymorphic (62%), polymorphic and bidirectional (21%), bidirectional (10%), or polymorphic with ventricular fibrillation (7%). There was 100% inducement of CPVT by exercise, 75% by catecholamine infusion, and none by programmed stimulation. No late potential was recorded. Onset was in the right ventricular outflow tract in more than half the cases. During a follow up of 6.8 (4.9) years, sudden death occurred in 24% of the patients, 7% of whom had anoxic brain damage. Autosomal dominant inheritance was seen in 8% of the patients' families. beta Blockers completely controlled CPVT in only 31% of cases. Calcium antagonists partially suppressed CPVT in autosomal dominant cases. CONCLUSIONS: CPVT may arise in certain distinct areas but the prognosis is poor. The onset of CPVT may be an indication for an implanted cardioverter-defibrillator.

Adolescent↗
PubMed2001

Multiple G-protein-coupled receptors mediate presynaptic inhibition at single excitatory synapses in the rat visual cortex.

Modulation of excitatory synaptic transmission by agonists for several neurotransmitter receptors was investigated at intrinsic cortical synapses derived from single presynaptic neurons. Excitatory postsynaptic currents (EPSCs) were recorded from layer 5 pyramidal neurons in the rat visual cortex in response to minimal stimulation within the same layer. 5-hydroxytryptamine, adenosine, baclofen, carbachol and DCG-IV all suppressed EPSCs with an increase in paired-pulse ratio. These agonists reduced the frequency of miniature EPSCs without significantly affecting their amplitude distribution. These results suggest that glutamatergic excitatory transmission in the neocortex is under the control of presynaptic inhibition mediated by multiple neuromodulator receptors co-expressed in single presynaptic terminals.

Adenosine↗
PubMed2001

Complete cysteine-scanning mutagenesis and site-directed chemical modification of the Tn10-encoded metal-tetracycline/H+ antiporter.

Bacterial Tn10-encoded metal-tetracycline/H(+) antiporter was the first found drug exporter and has been studied as a paradigm of antiporter-type major facilitator superfamily transporters. Here the 400 amino acid residues of this protein were individually replaced by cysteine except for the initial methionine. As a result, we could obtain a complete map of the functionally or structurally important residues. In addition, we could determine the precise boundaries of all the transmembrane segments on the basis of the reactivity with N-ethylmaleimide (NEM). The NEM binding results indicated the presence of a transmembrane water-filled channel in the transporter. The twelve transmembrane segments can be divided into three groups; four are totally embedded in the hydrophobic interior, four face a putative water-filled channel along their full length, and the remaining four face the channel for half their length, the other halves being embedded in the hydrophobic interior. These three types of transmembrane segments are mutually arranged with a 4-fold symmetry. The competitive binding of membrane-permeable and -impermeable SH reagents in intact cells indicates that the transmembrane water-filled channel has a thin barrier against hydrophilic molecules in the middle of the transmembrane region. Inhibition and stimulation of NEM binding in the presence of tetracycline reflects the substrate-induced protection or conformational change of the Tn10-encoded metal-tetracycline/H(+) antiporter. The mutations protected from NEM binding by tetracycline were mainly located around the permeability barrier in the N-terminal half, suggesting the location of the substrate binding site.

Amino Acid Sequence↗
PubMed2001

Transient activation during block transition.

Functional MRI (fMRI) data analysis of blocked-task paradigms typically considers brain activity present across a temporally extended task block relative to a reference block. An open question remains as to whether processes evolving with distinct temporal profiles are also present and can inform us about further functional-anatomic processes underlying task performance. To explore this question, a meta-analysis of data from these separate studies was performed. The meta-analysis specifically focused on detecting transient activation occurring at the onset and offset of task blocks. The composite data set from 39 subjects included four distinct task conditions (from various intentional encoding paradigms) that had equivalent block timing. Task block activation included a network of regions consistent with prior analyses of intentional encoding. Activation related to the block transitions included a set of transiently activated regions, consistent across all four separate task conditions. The most prominent activation was found in right frontal cortex along the dorsal extent of inferior frontal gyrus (near BA 6/44). Importantly, in one condition, this transient activation was present in the absence of a response across the task block suggesting dissociation between processes in support of ongoing task demands and those associated with transitions between blocks. Other prominent transient activations included posterior superior temporal sulcus, medial occipitoparietal sulcus, anterior insula, and anterior cingulate sulcus in the right hemisphere. These findings are discussed in relation to models of set shifting and competitive interactions between brain regions.

Brain↗
PubMed2001

A case of double cancers with myocardial metastasis mimicking acute myocardial infarction both on an electrocardiogram and on Tc-99m-MIBI myocardial SPECT.

We report a rare case of double cancers with myocardial metastasis presenting acute myocardial infarction (AMI)-like findings both on an electrocardiogram (ECG) and on Tc-99m-MIBI myocardial SPECT. The ECG showed abnormal Q-waves and ST-segment elevation in leads V1-V4, and Tc-99m-MIBI SPECT showed a photon deficient area in the anteroseptum. These findings were suggestive of AMI, but the patient had been simultaneously suffering from two adenocarcinomas, which were lung cancer and gastric cancer, and consecutive ultrasonic cardiography (UCG) demonstrated a growing mass lesion in the septal aspect of the left ventricle. After a month he died of severe heart failure. The histological diagnosis of a specimen of the cardiac mass lesion was invasive adenocarcinoma infiltrating to the heart, which revealed that the myocardial metastasis had mimicked AMI. This case shows that it is difficult to distinguish between myocardial infarction and myocardial metastasis with myocardial perfusion SPECT. It is necessary to consider the possibility of myocardial metastasis when a patient with malignancy presents AMI-like findings.

Adenocarcinoma↗
PubMed2001

Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment.

A methylxanthine, pentoxifylline (PTX), has the potential to improve tumour microcirculation and oxygenation in vivo. We aimed to determine whether this agent would enhance the response of tumours to experimental radioimmunotherapy (RIT). Balb/c nu/nu mice with xenografts of LS180 human colon cancer were treated with 4.63 MBq of 131I-A7 anti-colorectal monoclonal antibody. A dose of 50 mg/kg of PTX was administered i.p. immediately after the 131I-A7 injection and daily thereafter for 7 days. The effect of PTX administration on 131I-A7 targeting in tumours was assessed with biodistribution and radioluminography on day 2. Intratumoural pO2 was measured with microelectrodes. The administration of PTX alone did not suppress tumour growth, but the efficacy of RIT with 131I-A7 was significantly improved by PTX: tumour volumes on day 15, relative to the initial volume, were 16.8+/-3.60 in the nontreated controls, 13.9+/-2.17 with PTX, 3.43+/-0.44 with RIT, and 1.86+/-0.59 with RIT+PTX (P<0.05). PTX administration did not alter the biodistribution or intratumoural distribution of 131I-A7. However, intratumoural pO2 was significantly improved by PTX administration: 16.9+/-9.75 mmHg in control tumours versus 25.6+/-11.3 mmHg in PTX-treated tumours (P<0.01). These results indicate that PTX-induced radiosensitisation of tumour cells due to better oxygenation is responsible for the better RIT outcomes, because the net radiation absorbed dose to the tumours did not appear to be changed.

Animals↗
PubMed2001

GABA(B) receptor activation enhances mGluR-mediated responses at cerebellar excitatory synapses.

Metabotropic gamma-aminobutyric acid type B (GABAB) and glutamate receptors (mGluRs) are postsynaptically co-expressed at cerebellar parallel fiber (PF)-Purkinje cell (PC) excitatory synapses, but their functional interactions are unclear. We found that mGluR1 agonist-induced currents and [Ca2+]i increases in PCs were enhanced following co-activation of GABAB receptors. A GABAB antagonist and a G-protein uncoupler suppressed these effects. Low-concentration baclofen, a GABAB agonist, augmented mGluR1-mediated excitatory synaptic current produced by stimulating PFs. These results indicate that postsynaptic GABAB receptors functionally interact with mGluR1 and enhance mGluR1-mediated excitatory transmission at PF-PC synapses. The interaction between the two types of metabotropic receptors provides a likely mechanism for regulating cerebellar synaptic plasticity.

Animals↗
PubMed2001

Technetium-99m-tetrofosmin would be a substrate for multidrug resistance-associated protein (MRP): comparison between a leukemia cell line with high MRP gene expression and its parental cell line.

UNLABELLED: The kinetics of cellular accumulation and retention of technetium-99m-tetrofosmin (99mTc-TF) were investigated in wild type HL60/WT cell line and in its doxorubicin-resistant HL60/DOX cell line with multidrug resistance-associated protein (MRP), but without P-gp overexpression, to determine whether 99mTc-TF is a substrate for MRP. METHODS: The accumulation and washout of 99mTc-TF were observed in both cell lines at 37 degrees C. The effect of verapamil on the kinetics was also assessed. RESULTS: 99mTc-TF net accumulation was significantly lower in HL60/DOX (1.35 +/- 0.23%) than in HL60/WT (12.79 +/- 0.47%) at 60 min (P < 0.001). Three minutes after exchanging the incubation solution to the tracer-free medium, only 18.20 +/- 0.34% of 99mTc-TF remained in HL60/DOX, whereas 84.74 +/- 0.65% did in HL60/WT (P < 0.001). In the presence of 10 microM verapamil, 99mTc-TF net accumulation in HL60/DOX was 302% of the control and the washout was significantly delayed. CONCLUSION: 99mTc-TF would be a substrate for MRP and 99mTc-TF may be used as a functional imaging agent of MRP in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Use of folded vascularized rib graft in anterior fusion after treatment of thoracic and upper lumbar lesions. Technical note.

For lesions involving the anterior and/or middle column of the spine, an anterior approach is adequate for curetting the lesion and restoring spinal stability. Materials such as autogenous bone grafts, cages with bone chips, some artificial materials, or allografts are used as strut materials. Rib material is usually removed when the anterior approach is conducted for thoracic or thoracolumbar lesions. A rib itself is not rigid enough to support the load, and a bone union is not easily obtained. The purpose of this paper is to describe a method of grafting vascularized rib in folded form to fill the defects left after removal of a spinal lesion. The rib, with the artery and vein at two levels cranial to the involved vertebral body, was isolated from surrounding tissues such as the intercostal nerve, muscles, and pleura. After curetting the lesion, the rib was folded into three or four pieces to a length adequate to fill the defect and inserted as a pedicled vascularized graft. A total of 23 cases, including 14 men and nine women, underwent surgery in which this grafting technique was used. The pathological conditions requiring anterior decompression and fusion were spinal trauma in nine cases, spinal infection in six cases, osteoporotic fracture in seven cases, and spinal metastasis in one case. In all cases a solid bone union was obtained and all infections resolved. With vascularized rib graft folded into three to four pieces, solid bone union can be obtained without use of any other grafted materials even in cases of infection and osteoporosis.

Adolescent↗
PubMed2001

[Quantitative evaluation of esophageal scintigraphy in systemic sclerosis].

BACKGROUND: Esophageal involvement by systemic sclerosis (SSc) is frequent. The purpose of this study was to evaluate esophageal motility disorders quantitatively. METHODS: We investigate esophageal scintigraphy in 22 patients with SSc. Esophageal scintigraphy was obtained with swallowing physiological saline in supine position, and swallowing soup in supine and sitting positions. Data was acquired with 0.5 sec per frame for 192 frames in the anterior view. We employed a condensed image as a visual evaluation, half-life and retention rate as a quantitative evaluation, which were obtained from time-activity curves generated from regions of interest on the whole esophagus. The half-life and retention rate were compared with classification of Barnett, stages of SSc, and modified Rodnan total skin score (TSS). RESULTS: No significant differences were seen in classification of Barnett and the stages of SSc. No significant difference was seen between swallowing water and soup in the supine position. The retention rate was significantly prolonged in the supine position than in the sitting position. The retention rate of soup study in the sitting position correlated with TSS (r = 0.61). CONCLUSION: Esophageal scintigraphy in the sitting position is useful in evaluation of esophageal motility in SSc.

Adult↗
PubMed2000

Cysteine-scanning mutagenesis around transmembrane segments 1 and 11 and their flanking loop regions of Tn10-encoded metal-Tetracycline/H+ antiporter.

Putative transmembrane helices (TM) 1 and 11 in the metal-tetracycline/H(+) antiporter are predicted to be close to each other on the basis of disulfide cross-linking experiments of the double-cysteine mutants in the periplasmic loop regions (Kubo, Y., Konishi, S., Kawabe, T., Nada, S., and Yamaguchi, A. (2000) J. Biol. Chem. 275, 5270-5274). In this study, each amino acid from Asn-2 to Gly-44 in the putative TM1 and loop1-2 regions or that from Ser-328 to Gly-366 in TM11 and its flanking regions was individually replaced with cysteine. With respect to the TM1 region, 10 mutants, from T5C to L14C, were all not reactive with N-ethylmaleimide (NEM), and from D15C to I22C, NEM-reactive and non-reactive mutations periodically appeared every two residues. Three mutants, M23C to V25C, were all NEM-reactive, but the degree of the latter two mutants was very low. Seven mutants, from L26C to E32C, were all highly reactive with NEM. Therefore, the region of TM1 is composed of the 21 amino acid residues from Thr-5 to Val-25. It is a partially amphiphilic helix, that is, the N-terminal (cytoplasmic) half is embedded in the hydrophobic interior, and the C-terminal (periplasmic) half faces a water-filled channel. With respect to TM11, nine mutants, from S328C to G336C, and six mutants, from L361C to G366C, were all reactive with NEM. On the other hand, out of the 24 mutants, from L337C to S360C, 17 were not reactive with NEM, and the 7 NEM-reactive mutants were scattered, indicating that this region is a transmembrane segment. The 7 residues from Val-347 to Phe-353 including Pro-350 formed a central hydrophobic core, and the 7 NEM-reactive mutations were periodically distributed in its flanking regions, indicating that both ends of TM11 face a water-filled channel. Ala-354 is located at about 1/3 of the length from the periplasmic end of TM11. Disulfide cross-linking experiments on double-cysteine mutants having the combination of A354C and a cysteine-scanning mutation in the loop1-2 region indicated that loop1-2 is very flexible and close to the periplasmic end of TM11. Tetracycline prevented the cross-linking formation between the periplasmic ends of TM1 and TM11; however, it did not affect the cross-linking between loop1-2 and TM11, indicating that the substrate-induced conformational change involves a shift in the relative locations of TM1 and TM11.

Amino Acid Sequence↗
PubMed2000

Proximity of periplasmic loops in the metal-Tetracycline/H(+) antiporter of Escherichia coli observed on site-directed chemical cross-linking.

Our previous study on second-site suppressor mutations of the Tn10-encoded metal-tetracycline/H(+) antiporter suggested that Leu(30) and Ala(354), located in periplasmic loop 1-2 and 11-12, respectively, are conformationally linked to each other (Kawabe, T., and Yamaguchi, A. (1999) FEBS Lett. 457, 169-173). To determine the spatial proximity of these two residues, cross-linking gel-shift assays of the L30C/A354C double mutant were performed after the mutant had been oxidized with Cu(2+)/o-phenanthroline. The results indicated that Leu(30) and Ala(354) are close to each other but that Gly(62), which is located in cytoplasmic loop 2-3, and Ala(354) are distant from each other, as a negative control. Then, a single Cys residue was introduced into each of the six periplasmic loop regions (P1-P6), and eleven double mutants were constructed. Of these eleven double Cys mutants, the L30C/A354C and L30C/T235C mutants showed a mobility shift on oxidation, indicating that P1 is spatially close to P4 as well as P6. In contrast, the other nine mutants, L30C/S92C, L30C/S156C, L30C/S296C, S92C/S296C, S92C/T235C, S92C/A354C, S156C/T235C, S156C/S296C, and S156C/A354C, showed no mobility shift under oxidized conditions on intramolecular cross-linking. The S92C and S296C mutants showed dimerization on intermolecular cross-linking, indicating that P2 and P5 are located at the periphery of the helix bundle.

Amino Acid Sequence↗
PubMed2000

An experimental study of the effects of nerve root retraction on the posterior ramus.

STUDY DESIGN: The histologic and ultrastructural changes in the posterior ramus after posterior lumbar surgery were studied in rabbits. OBJECTIVE: To investigate the structural changes in the posterior ramus after posterior lumbar surgery that may cause injury to the posterior ramus after the procedure. SUMMARY OF BACKGROUND DATA: Investigators in previous studies have pointed out that low back discomfort after lumbar discectomy relates to neurogenic changes and/or myogenic changes of paravertebral muscle. However, no previous study has demonstrated the effects of excessive nerve root retraction on spinal posterior rami. METHODS: Eighteen male Japanese White rabbits were used. The posterior ramus arising from the S1 nerve root was examined after exposure of the lamina only, fenestration, or retraction of the S1 nerve root, with light microscopy and transmission electron microscopy at 2, 4, and 6 weeks after the procedure. Results were compared with a those in control specimens that did not undergo the procedure. RESULTS: In the exposed group, no distinct difference was found compared with the control specimen. In the fenestration group, especially at 6 weeks, some attenuation and splitting of myelin sheaths was observed. In the retraction group, the structural alteration was most severe. Even at 2 weeks, fragmentation of many myelin sheaths was detected. Examination of specimens by electron microscopy indicated phagocytosis of myelinated fibers at 4 and 6 weeks. CONCLUSIONS: Findings showed that posterior lumbar procedures, including retraction of paravertebral muscle, fenestration of the lamina, and retraction of the nerve root affect the posterior ramus. Excessive retraction of the nerve root has an especially disastrous effect on the posterior ramus. Such a violent maneuver within the spinal canal must be avoided.

Animals↗
PubMed2000

Neural correlates of episodic retrieval success.

Episodic memory retrieval involves multiple component processes, including those that occur when information is correctly remembered (retrieval success). The present study employed rapid-presentation event-related functional MRI that allowed different trial types with short intertrial intervals to be sorted such that the hemodynamic response associated with retrieval success could be extracted. Specifically, in an old/new episodic recognition task, hit trials (correctly recognized old items) and correct rejection trials (correctly rejected new items) were directly compared. The comparison revealed a mostly left-lateralized set of brain regions. Differential activation was most robust in left lateral parietal cortex and medial parietal cortex. Additional regions of differential activation included left anterior prefrontal cortex at or near Brodmann area 10, anterior insula, thalamus, anterior cingulate cortex, frontal cortex along inferior frontal gyrus, premotor cortex, and presupplementary motor area. These results suggest that left frontal and parietal regions modulate activity based on the successful retrieval of information from episodic memory. We discuss these findings in the context of several recent investigations that provide converging results as well as prior studies that have failed to detect these changes.

Adolescent↗
PubMed2000

Increased uptake of 99mTc-HL91 in tumor cells exposed to X-ray radiation.

99mTc-HL91, a hypoxic marker, may be a predictor of tumor response to radiotherapy and an indicator of tumor oxygenation in the course of treatment. In this study, serial changes in 99mTc-HL91 uptake were observed in the normoxic condition in a human bladder cancer cell line exposed to a single dose or a fractionated dose of 10 Gy with an x-ray beam. The uptake per cell increased during cell growth retardation induced by the irradiation. This finding indicates that 99mTc-HL91 uptake is affected by injury to cells due to radiation; it may therefore be difficult to correctly assess the tissue oxygenation status during radiotherapy with 99mTc-HL91.

Cell Division↗
PubMed2000

Intracranial hemorrhage in children with immune thrombocytopenic purpura

We sent questionnaires to hospitals in Japan in order to study the incidence and conditions of intracranial hemorrhage (ICH) in children with immune thrombocytopenic purpura (ITP). From 1980 to 1995, 11 cases of ICH were reported in eight patients with ITP at 35 institutions. One patient had ICH four times, but only one patient died of the condition. From 1990 through 1995, ICH occurred in four (0.52%) of 772 patients with ITP. None of the patients died. The platelet count when ICH occurred was 5.2 +/- 3.7 x 10(9)/l (mean +/- SD) (n = 11). Four of the eight patients (1980-1995) had received active treatment [e.g. intravenous immunoglobulin G (i.v. IgG)] immediately before ICH occurred. In seven cases (1980-1995), possible causes of ICH, including menstruation (n = 2) and viral infections (n = 3), were identified. Systemic lupus erythematosus (SLE) later developed in three patients. Although the incidence of ICH in children with ITP has not decreased compared with the rates in earlier studies, the mortality rate has decreased markedly. Our results suggest that menstruation, infection, and risk factors for progression to SLE may help to predict ICH in children with ITP. Large-scale prospective trials are needed to identify risk factors for ICH.

Acute Disease↗