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Biomedical subjects

S Konishi

Publications and source records attributed to S Konishi.

At least 73 records · Page 4Linked to original sources
PubMed1996

Increased level of neurokinin-1 tachykinin receptor gene expression during early postnatal development of rat brain.

Substance P is known to elicit diverse actions via activating multiple subtypes of tachykinin receptors, and these actions appear to be involved not only in synaptic transmission but also in synaptic plasticity during development of the mammalian central nervous system. The availability of sensitive quantitation of individual tachykinin receptor subtypes is crucial for elucidating the physiological function specifically mediated by activation of a particular receptor subtype. We thus attempted to develop an assay to determine the level of messenger RNA molecule encoding the neurokinin-1-type tachykinin receptor and apply it for assessment of developmental changes in the neurokinin-1 receptor gene expression in the rat brain to explore the role of tachykinin receptors during ontogeny. The assay was designed to use a competitive reverse transcription-polymerase chain reaction co-amplifying endogenous neurokinin-1 receptor messenger RNA and internal standard, which enabled specific quantification of the number of neurokinin-1 receptor transcripts, ranging from 3.1 x 10(3) to 1.3 x 10(5) molecules/microgram total RNA. The levels of neurokinin-1 receptor gene expression were examined in three different brain regions of the rat aged 0-56 days after birth. The order of neurokinin-1 receptor messenger RNA expression was hippocampus > cerebral cortex > > cerebellum at all ages examined except postnatal day 0, where its expression was more abundant in the cerebral cortex than in the hippocampus. From postnatal day 3 onward, the hippocampus contained 140-160% of the cortical levels. Although the tachykinin receptor expression in the cerebellum was too low to be accurately assessed by conventional techniques, our assay enabled us to determine the amount of cerebellar neurokinin-1 receptor messenger RNA that changed in the range 7-23% of the cortical level during postnatal development. A prominent feature revealed by this assay is that the neurokinin-1 receptor gene expression in the rat brain is developmentally regulated. The hippocampus displayed a transient peak of neurokinin-1 receptor messenger RNA at postnatal day 3 and a subsequent gradual decrease. In the cerebral cortex, the amount of the message was highest at birth, and was followed by a moderate decrease during postnatal development. At 56 days after birth, the expression levels in both brain regions were down-regulated to approximately 50% of their maximal levels. The transitory pattern of gene expression was also observed in the cerebellum. The results of this study demonstrate that the reverse transcription-polymerase chain reaction-based assay is useful to quantitate precisely the neurokinin-1 tachykinin receptor message in limited tissue samples derived from discrete brain regions. Together with previous findings, the increased level of neurokinin-1 receptor messenger RNA expression in immature rat brain shown by the present analysis suggests that the neurokinin-1-type tachykinin receptor may play a role in the synaptic plasticity associated with morphological and functional development of the mammalian CNS.

Aging↗
PubMed1996

Effect of induced hypertension with angiotensin II infusion on biodistribution of 111in-labeled monoclonal antibody.

We investigated whether induced hypertension could enhance tumor uptake of monoclonal antibody. 111In-DTPA-A7 (IgG1 against 40kD tumor associated glycoprotein) was injected into colon carcinoma xenografted mice which were subcutaneously implanted with micro-osmotic pump containing angiotensin II (AT-II). Biodistribution was observed in groups of mice infused with AT-II at rate of 0.5 micrograms/kg/min (L) or 1 microgram/kg/min (H) and compared with a group of mice infused with saline (S). Tumor uptake of 111In-A7 in L and H was 1.32 and 1.57 times greater than S at 48 h after intravenous injection of A7. Normal organ uptakes also tended to be increased by AT-II infusion. Further study is needed to get optimum effect of hypertensive treatment on biodistribution of radiolabeled MoAb.

Angiotensin II↗
PubMed1996

201Tl and 99Tcm-human serum albumin for assessment of the effect of hypertensive treatment with angiotensin II infusion on tumour circulation.

The biodistribution of 201Tl and of 99Tcm-human serum albumin (99Tcm-HSA) was observed in tumour-bearing mice to investigate if tissue blood circulation could be evaluated in groups of mice infused with angiotensin II at a rate of 0.5 micrograms kg-1 min-1 (L) or 1 microgram kg-1 min-1 (H). Ten minutes after tracer injection, tumour uptake of 201Tl in the angiotensin II infused group showed a 2.20- and a 3.18-fold increase in the L and H groups, respectively, when compared to a group of mice infused with saline (P = 0.0478 and 0.0029, respectively). The effect of angiotensin II infusion on 201Tl uptake was minimal in normal organs. Decreased normal organ uptake of simultaneously injected 99Tcm-HSA in the L and H groups indicated the contraction of normal organ vessels, while increased tumour uptake of the tracer indicated mechanical dilatation of tumour vessels. We conclude that the effect of angiotensin II or other vasoactive agents can be non-invasively assessed by 201Tl and 99Tcm-HSA scintigraphy.

Angiotensin II↗
PubMed1996

Tachykininergic synaptic transmission in the coeliac ganglion of the guinea-pig.

1. The responses of coeliac ganglion neurones of the guinea-pig to electrical stimulation of the mesenteric nerves and applications of tachykinin receptor agonists were investigated by use of intracellular recording techniques. 2. Ganglion neurones were classified into three groups based on firing patterns in response to a depolarizing current pulse: phasic (38% of the population), tonic (39%) and atypical (23%). In the majority of phasic neurones (91%) a long after-hyperpolarization (LAH) lasting 5-8 s followed action potentials induced by a train of depolarizing current pulses. In contrast, LAH was rarely observed in tonic neurones (5%). 3. In most of tonic neurones (90%) slow excitatory post-synaptic potentials (e.p.s.ps) lasting 3-10 min were evoked by repetitive electrical stimulation of the mesenteric nerves. Prolonged depolarizations were also evoked in most tonic neurones by applications of substance P (SP), neurokinin A (NKA) or senktide, a tachykinin NK3 receptor agonist. 4. In most of phasic neurones (73%), mesenteric nerve stimulation did not induce an obvious depolarization but induced a prolonged inhibition of LAH lasting 3-10 min. Bath-applied tachykinin receptor agonists similarly induced an inhibition of LAH without causing depolarization in most of the phasic neurones. 5. GR 71251 (5 microM), a tachykinin NK1 receptor antagonist, partially depressed the nerve-evoked slow e.p.s.ps in tonic neurones and the nerve-evoked LAH inhibition in phasic neurones. 6. Capsaicin (0.1-5 microM) induced a prolonged depolarization in tonic neurones and an inhibition of LAH in phasic neurones. 7. A mixture of peptidase inhibitors potentiated the depolarization and the LAH inhibition evoked by nerve stimulation, SP and NKA, but not those evoked by senktide. 8. It is concluded that tonic neurones respond to repetitive mesenteric nerve stimulation preferentially with slow e.p.s.ps and that phasic neurones respond preferentially with LAH inhibition. The present study further suggests that SP and NKA, released from axon collaterals of primary afferent neurones, produce slow e.p.s.ps in tonic neurones and the LAH inhibition in phasic neurones via NK1 receptors.

Animals↗
PubMed1995

Three-dimensional solution structure of the calcium channel antagonist omega-agatoxin IVA: consensus molecular folding of calcium channel blockers.

The three-dimensional solution structure of omega-agatoxin IVA, which is a specific blocker of the P-type calcium channel isolated from funnel web spider venom and has a molecular mass of 5.2 kDa, was determined by two dimensional 1H NMR spectroscopy, combined with simulated annealing calculations. On the basis of 563 experimental constraints, including 516 distance constraints obtained from the nuclear Overhauser effect, 21 torsion angle (phi, chi 1) constraints, and 26 constraints associated with hydrogen bonds and disulfide bonds, a total of 14 converged structures were obtained. The atomic root mean square difference for the 14 converged structures with respect to the mean coordinates is 0.42 (+/- 0.07) A for the backbone atoms (N, C alpha, C) and 0.95 (+/- 0.15) A for all heavy atoms of the central part (residues 4 to 38) constrained by four disulfide bonds. The N- and C-terminal segments (residues 1 to 3 and 39 to 48, respectively) have a disordered structure in aqueous solution. The molecular structure of omega-agatoxin IVA is composed of a short triple-stranded antiparallel beta-sheet, three loops, and the disordered N- and C-terminal segments. The overall beta-sheet topology is +2x, -1, which is the same as that reported for omega-conotoxin GVIA, an N-type calcium channel blocker. Irrespective of differences in the number of disulfide bonds and low primary sequence homology, these two peptide toxins show a significant structural similarity in three dimensions. The whole-cell voltage-clamp recording using rat cerebellar slices suggests that the hydrophobic C-terminal segment of omega-agatoxin IVA, which does not exist in omega-conotoxin GVIA, plays a crucial role in the blocking action of omega-agatoxin IVA on the P-type calcium channel in rat cerebellar Purkinje cells. The present study provides a molecular basis for the toxin-channel interaction, and thereby provides insight into the discrimination of different subtypes of calcium channels.

Amino Acid Sequence↗
PubMed1995

Effects of auricular acupuncture stimulation on nonobese, healthy volunteer subjects.

Effects of auricular acupuncture stimulation on nonobese healthy volunteers were investigated. Subjects (n = 35) averaged 34.5 years old, and BMI was 25.3 kg/m2. Small (0.15 x 2.0 mm) auricular needles were applied intracutaneously into the bilateral cavum conchae that was identified by having less than 100 k omega resistance. Body weight was measured four times a day and charted by the subjects themselves. Results showed that, in the period 11-2, in which only body weight was measured, without auricular acupuncture stimulations, 57.1% of the subjects reduced their body weight. This indicates that charting body weight themselves might be useful to maintain their weight. In the auricular acupuncture treated period, 19 (70.4%) out of 27 decreased (p < 0.01), 5 (18.5%) was increased, and 3 (11.1%) had no change in body weight. In conclusion, the results suggest that success in maintaining weight reduction can be attributed to graphic illustration of one's weight pattern. Bilateral auricular acupuncture stimulation can also reduce body weight of healthy non-obese subjects. This is consistent with the suggestion that it might be effective in the treatment of obese patients.

Acupuncture Points↗
PubMed1995

Immunoglobulin free light chain assay using latex agglutination.

Under normal biological conditions, immunoglobulin light chains are generally formed in conjunction with heavy chains; however, small quantities of free light chains are also produced. Thus, two types of immunoglobulin light chains may be identified; immunoglobulin-bound light chains and free light chains. In mature neoplastic B cells, immunoglobulin synthesis, including that of the free light chain, is generally increased. Furthermore, elevated free light chain levels also occur in the presence of renal glomerular and tubular impairment. Thus, the quantitative and qualitative measurement of free light chains is of considerable clinical benefit. Although methods for measurement of free light chains do exist they are technically complicated and time consuming. Previously, we have reported a quantitative nephelometric immunoassay for measuring free light chain levels. We report here a refinement of this method using latex agglutination techniques. This new method enables quantitative measurement of free light chains in serum at levels as low as 1 mg/l and may allow the clinical application of serum free light chain estimation.

Adult↗
PubMed1995

The endocrine pancreas of spontaneously diabetic db/db mice: microangiopathy as revealed by transmission electron microscopy.

Abnormalities in ultrastructures of islet capillaries were detected in db/db mice, with the visual inspection and morphometry of electron micrographs. The observed changes are: (1) capillary scarcity; (2) increase in the mean and diversity of capillary size; (3) pericapillary edema and fibrosis; (4) hypertrophy of the pericyte and abundance therein of actin-like microfilaments; and (5) luminal irregularity. Changes (2), (3) and (4) are conceived to indicate hyperperfusion, capillary hypertension and secondary vascular response. In particular, such pericyte changes were found to be shared by other organs whose capillaries are susceptible to diabetic complications.

Animals↗
PubMed1995

Subtypes of tachykinin receptors on tonic and phasic neurones in coeliac ganglion of the guinea-pig.

1. Intracellular recording techniques were used to investigate the characteristics of tachykinin receptors and their subtypes in tonic and phasic neurones, which constituted two major neuronal populations in the coeliac ganglion of the guinea-pig. 2. In 95% of phasic neurones a long-lasting after-hyperpolarization (LAH), 5-8 s in duration and 10-20 mV in amplitude, was observed following action potentials evoked by passing a train of depolarizing current pulses into the neurones. In contrast, LAH was observed in only 4% of tonic neurones. 3. In most tonic neurones, substance P (SP), neurokinin A (NKA) and senktide induced depolarizations, whereas in phasic neurones they usually inhibited LAH but rarely induced depolarization. 4. Tonic and phasic neurones were further classified into three groups based on their responses (depolarization for tonic neurones and LAH inhibition for phasic neurones) to these tachykinin receptor agonists: (1) neurones responsive to SP, NKA and senktide (71-78%); (2) those responsive to senktide but not to SP and NKA (12-23%) and (3) those not responsive to any of the three agonists (7-11%). 5. GR71251 (5 microM), an NK1-selective tachykinin receptor antagonist, depressed the depolarization in tonic neurones and the LAH inhibition in phasic neurones induced by SP and NKA, but not those induced by senktide. 6. Selective NK2 receptor agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, were without effect in both tonic and phasic neurones. Furthermore, an NK2 receptor antagonist, L659,877, did not inhibit the depolarization induced by NKA, SP or senktide in tonic neurones. 7. It is suggested that NK1 and NK3 receptors are present on a large proportion of coeliac ganglion neurones. In tonic neurones both subtypes of tachykinin receptors are coupled to membrane depolarization,whereas in phasic neurones activation of these receptors leads to inhibition of LAH. The present study also suggests that NKA evokes the depolarization in tonic neurones and the LAH inhibition in phasic neurones via NK1, but not NK2 receptors.

Animals↗
PubMed1995

Utility of iodine-123-BMIPP in the diagnosis and follow-up of vasospastic angina.

UNLABELLED: Myocardial damage caused by vasospastic angina (VSA) may be detected by [123I]BMIPP, a beta-methyl-branched fatty acid. We investigated whether BMIPP could be used in the diagnosis and follow-up of patients with VSA. METHODS: Thirty-two patients with VSA were studied with resting BMIPP-SPECT in comparison to stress perfusion imaging with either 201Tl or 99mTc-MIBI. During coronary arteriography, spasm was induced by provocative testing with acetylcholine or ergonovine, and only total or subtotal occlusion was considered positive. Decreased BMIPP uptake was semiquantitatively evaluated segmentally aided by polar map display. RESULTS: Reduced BMIPP uptake was observed in 25 of 32 patients (78%), with complete or partial agreement between the BMIPP abnormality and coronary territory seen in 23 patients (72%). In contrast, a perfusion abnormality was seen in only 10 patients (31%). In the repeat BMIPP study (n = 23) during the follow-up period (average 206 days), 11 of 14 patients who showed BMIPP improvement also had improved angina attacks. Conversely, two of nine patients with nonimproved BMIPP showed improved symptoms (p < 0.05). CONCLUSION: BMIPP can detect myocardial injury associated with VSA and may be useful in monitoring response to treatment.

Acetylcholine↗
PubMed1995

[Intratumoral pharmacokinetics following intraarterial administration of MCNU in patients with malignant gliomas].

This clinical study was undertaken to examine intratumoral (i.t.) pharmacokinetics after intraarterial (i.a.) administration of MCNU (80mg/m2) in 5 patients with glioblastoma (GB) and 2 with anaplastic astrocytoma (AA). After resection or stereotactic biopsy of the cystic lesion, an Ommaya reservoir was placed into the tumor cavity in all patients. The distribution of MCNU in blood was compatible with a two-compartment model, and the half life of the alpha-phase and beta-phase was 4.1 minutes and 160.4 minutes, respectively. MCNU was detected in the i.t. fluid in 5 cases, 4 of GB and 1 of AA. The concentration of i.t. MCNU gradually increased during the 5 to 30 minutes after i.a. injection to a level about 20.0% of its blood concentration. However, no MCNU was detected in patients showing partial response (3 of GB and 1 of AA) or no change (1 of GB) after the i.a. infusion of MCNU during maintenance chemotherapy. These results suggests that MCNU may transfer into the tumor tissues. Further investigation is warranted.

Adolescent↗
PubMed1995

[The efficacy of granisetron as a prophylactic anti-emetic agent used in conjunction with MCNU and VP16 chemotherapeutic regimens in the management of a pediatric case of hypothalamic anaplastic astrocytoma].

The management of a 12-year-old boy with hypothalamic anaplastic astrocytoma is reported herein. The pediatric patient underwent a subtotal removal of his brain tumor, and subsequently received multimodal treatment comprising radiotherapy (30.6 Gy to the whole brain and 50.4 Gy to the local lesion) and immunochemotherapy with MCNU (80 mg/m2, day 1), VP 16 (50 mg/day, days 2 to 6), and interferon-beta (3 x 10(6) units/day, initiating on day 2 for 4 weeks). The immunochemotherapy was given as of 4 weeks after radiotherapy. The administration of anti-cancer drugs caused severe nausea and vomiting, the intra-carotid infusion of MCNU being particularly emetogenic. The multi-modal treatment was then discontinued for a few weeks. A partial response was obtained, and the patient subsequently received 3 courses of maintenance therapy at six-month intervals using the same protocol as for the initial immunochemotherapy. During maintenance therapy, granisetron (40 micrograms/kg) was given intravenously 30 minutes before and one day after the injection of MCNU. Owing to the anti-emetic management of this patient, there were no complications throughout the chemotherapy. The patient has now survived for more than 3 years with a good quality of life, showing a Karnofsky performance score of 90.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Enhancement by serotonin of GABA-mediated inhibitory synaptic currents in rat cerebellar Purkinje cells.

The actions of serotonin (5-HT) on synaptic responses in Purkinje cells were examined using the whole-cell voltage-clamp recording from thin slices of the rat cerebellum. Focal stimulation within the molecular layer elicited synaptic responses: (1) inhibitory postsynaptic currents (IPSCs) that were completely blocked by bicuculline; (2) excitatory postsynaptic currents (EPSCs) that were antagonized by CNQX; and (3) combination of IPSC and EPSC. Application of 5-HT (3-30 microM) increased the amplitude of the stimulation-evoked IPSCs but did not significantly affect the EPSCs. The frequency and the mean amplitude of spontaneous IPSCs were increased in the presence of 5-HT. Neither the sensitivity to exogenously applied GABA nor the holding current of Purkinje cells were noticeably altered by 5-HT. The results indicate that 5-HT differentially enhances the GABA-mediated IPSCs in rat cerebellar Purkinje cells via a presynaptic mechanism. Serotonergic neurons thus appear to play a role in the motor control through selective presynaptic facilitation that modulates the output from the cerebellar cortex.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Characterization of the most frequently encountered Staphylococcus sp. in cats.

Ninety three staphylococci isolated from clinical specimens from cats were characterized and identified. Because the biochemical characteristics of Staphylococcus felis were very similar to those of Staphylococcus simulans, results were submitted to numerical analysis and DNA homology. Forty-two isolates (45%) were identified as S. felis, and 4 isolates (4%) as S. simulans. The other species identified, in order of their frequency were, 12 Staphylococcus aureus (13%), 9 Staphylococcus intermedius (10), 6 Staphylococcus sciuri (6), 6 Staphylococcus epidermidis (6), 2 Staphylococcus haemolyticus (2), 2 Staphylococcus xylosus (2), 1 Staphylococcus capitis (1), 1 Staphylococcus equorum (1), 1 Staphylococcus gallinarum (1) and 1 Staphylococcus lentus (1).

Animals↗
PubMed1994

Effect of fluoride on root resorption caused by mechanical injuries of the periodontal soft tissues in rats.

The present study was carried out to investigate histologically and histometrically the effect of fluoride on root resorption induced by mechanical injuries of the periodontal soft tissues in rats. Resorption lacuna in the root surface of the molar in animals given both mechanical injuries and fluoride administration was significantly smaller in length and area than that in animals given only mechanical injuries. Moreover, resorption lacuna in the former animals contained fewer odontoclasts than that in the latter. The results of the present study might suggest that the administration of fluoride suppressed root resorption induced by mechanical injuries of the periodontal soft tissues.

Animals↗