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T Katafuchi

Publications and source records attributed to T Katafuchi.

At least 55 records · Page 3Linked to original sources
PubMed1995

Roles of cytokines in the neural-immune interactions: modulation of NMDA responses by IFN-alpha.

Several lines of evidence have indicated that interferon-alpha (IFN-alpha) induces a variety of central actions; e.g., fever anorexia, slow wave sleep and depression. However, little is known about the cellular mechanisms by which IFN-alpha affects neuronal activity. In the present article, the effects of recombinant human IFN-alpha on N-methyl-D-aspartate (NMDA)-induced responses of rat medial preoptic (MPO) neurons were examined by means of slice patch method as an in vitro model of neural-immune interactions. The results suggest that IFN-alpha suppresses the NMDA responses through its action on opioid receptors and the production of free radicals such as hydroxyl radicals and nitric oxide (NO) due to the neuron-glial cell interactions.

Animals↗
PubMed1994

The biphasic changes in splenic natural killer cell activity following ventromedial hypothalamic lesions in rats.

The cytotoxic activity of natural killer (NK) cells in the spleen was measured by a standard 4-h chromium release assay following electrical lesioning of the ventromedial hypothalamic nucleus (VMH) in rats. The splenic NK cell activity of VMH lesioned rats was found to be significantly suppressed at effector:target cell ratios of 100:1 and 50:1 compared with that of sham lesioned rats on day 4 after the lesion. On the other hand, on day 49, the VMH lesioned animals that had become hyperphagic and obese showed an enhancement of splenic NK cell activity compared with sham lesioned animals. The mechanisms of the biphasic change in NK cell activity following the VMH lesions are discussed.

Animals↗
PubMed1994

Cloning and expression of eel natriuretic-peptide receptor B and comparison with its mammalian counterparts.

A comparative study of the natriuretic-peptide receptor NPR-B was performed by cloning and expressing, in COS-1 cells, the NPR-B receptor subtype from the eel gill which exhibited a strong C-type-natriuretic-peptide (CNP)-induced guanylate cyclase activity. Like other mammalian NPR-B receptors, the eel NPR-B receptor consisted of a ligand-binding extracellular domain, a hydrophobic transmembrane domain, a kinase-like domain and a guanylate cyclase domain. Sequence comparison among the eel and mammalian receptors revealed a relatively low similarity (approximately 44%) in the extracellular domain compared to a very high similarity (approximately 84%) in the cytoplasmic regulatory and catalytic domains. This low similarity allowed identification of the amino acid residues or candidate regions important for the ligand-binding activity. RNase protection analysis of the eel NPR-B mRNA demonstrated that the message was predominantly expressed in the liver and atrium as well as in the gill with moderate-to-small amounts in the brain, ventricle, esophageal sphincter, stomach, posterior intestine and kidney. The high NPR-B mRNA levels in the liver, atrium and gill were found to decrease markedly when eels were transferred from fresh water to seawater and kept there for 2 weeks. Since similar changes are known to occur in the ligand CNP levels when eels are facing osmotic challenges, the CNP/NPR-B system appears to play an important role in their successful adaptation to salinity changes.

Amino Acid Sequence↗
PubMed1994

Central interleukin-1 beta enhances splenic sympathetic nerve activity in rats.

The central administration of immune cytokines such as interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) results in the suppression of peripheral cellular immunity, which depends, at least partly, on the sympathetic nervous activity. An intrathird cerebroventricular (I3V) infusion of recombinant human IL-1 beta (rhIL-1 beta) (1-5 ng/rat) elicited a dose-dependent increase in the electrical activity of the splenic sympathetic nerve in urethane and alpha-chloralose anesthetized rats. The effect of rhIL-1 beta (1 ng/rat) was completely blocked by pretreatment with an IL-1 receptor antagonist (1 microgram/rat, I3V 10 min before rhIL-1 beta), sodium salicylate (1 microgram/rat), or alpha-melanocyte stimulating hormone (alpha-MSH) (400 ng/rat). Furthermore, an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF9-41 (2 micrograms/rat), completely abolished the rhIL-1 beta-induced increase in the splenic nerve activity, although an I3V infusion of CRF (1 microgram/rat) excited it. These results suggest that IL-1 beta in the brain activates splenic sympathetic activity by its receptor-mediated and prostaglandin-dependent action that is sensitive to alpha-MSH, depending on CRF system. Our findings, together with the previous results, suggest that the splenic sympathetic nerve represents one of the communication channels from the brain to the immune system.

Analysis of Variance↗
PubMed1993

Roles of sympathetic nervous system in the suppression of cytotoxicity of splenic natural killer cells in the rat.

1. We previously demonstrated that a central injection of interferon-alpha in rats induced a suppression of cytotoxicity of splenic natural killer cells which depended upon intact splenic sympathetic innervation, suggesting the important role of the splenic nerve in immunosuppression. To further study the mechanisms of this phenomenon, we investigated: (1) the effects of a central injection of recombinant human interferon-alpha on the electrical activity of the splenic nerve, and (2) the responses of splenic natural killer cytotoxicity on the electrical stimulation of the splenic nerve in urethane with alpha-chloralose anaesthetized rats. 2. An injection of recombinant human interferon-alpha (1.5 x 10(3) and 6.0 x 10(3) units (u) per rat) into the third cerebral ventricle produced a sustained and long lasting (at least for more than 60 min) increase in the electrical activity of splenic sympathetic nerve filaments in a dose-dependent manner. Following an intra-third-ventricular injection of recombinant human interferon-alpha at a dose of 6.0 x 10(3) u, the efferent discharges were elevated 2-6 times that of the pre-injection level with a mean onset latency of 12 min (8-16 min). No changes in the arterial blood pressure and body temperature were observed after injections of recombinant human interferon-alpha. 3. The excitation of the nerve activity induced by intra-ventricular recombinant human interferon-alpha was reversibly suppressed by an intravenous injection of an opioid antagonist, naloxone (1 mg/kg in 0.1 ml saline), whereas the injection of naloxone alone did not affect either the baseline level of the nerve activity or the systemic blood pressure. 4. The cytotoxicity of natural killer cells in the spleen measured by a standard chromium release assay was reduced 20 min after the laparotomy alone in anaesthetized rats. The reduced natural killer activity then recovered significantly when the splenic nerve was cut immediately after the laparotomy. When the peripheral cut end of the splenic nerve was subsequently stimulated (0.5 mA, 0.5 ms, 20 Hz for 20 min), a further suppression of natural killer cytotoxicity was observed. 5. The reduction of natural killer cytotoxicity produced by the stimulation of the splenic nerve was completely blocked by an intravenous injection of nadolol (a peripherally acting beta-adrenergic receptor antagonist), but not by that of prazosin (an alpha-antagonist). 6. These results indicate that a central injection of recombinant human interferon-alpha activates the splenic sympathetic nerve through brain opioid receptors and thereby suppresses the natural killer cytotoxicity by beta-adrenergic mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Hypothalamic modulation of splenic natural killer cell activity in rats.

1. The cytotoxic activity of splenic natural killer cells measured by a standard chromium release assay in urethane and alpha-chloralose-anaesthetized rats was significantly suppressed 20 min after bilateral ablation of the medial part of the preoptic hypothalamus (MPO). The suppression was completely blocked by prior splenic denervation. The splenic natural killer cell activity of MPO sham-lesioned rats or thalamus-lesioned rats, both having an intact splenic innervation, were not different from that of a non-treated control group. 2. Electrical stimulation of the bilateral MPO (0.1 ms, 0.1-0.3 mA, 5-100 Hz) suppressed the efferent activity of the splenic nerve in all six rats examined. The reduction of the nerve activity was accompanied by a transient fall in blood pressure. An I.V. injection of phenylephrine (3 micrograms/0.3 ml) also evoked a suppression of the nerve activity, which was accompanied by transient hypertension, suggesting that the suppressive effect of the MPO stimulation was independent of changes in blood pressure. On the other hand, a bilateral lesion of the MPO resulted in a sustained increase in the electrical activity of the splenic sympathetic nerve filaments which lasted for more than 2 h. 3. Microinjection of monosodium-L-glutamate (0.1 and 0.01 M in 0.1 microliters saline) unilaterally into the MPO evoked a transient suppression of the efferent discharge rate of the splenic nerve activity within 1 min, which was also accompanied by a decrease in blood pressure. The injection of saline (0.1 microliter) into the MPO had no effect. The microinjection of recombinant human interferon-alpha (200 and 2000 U in 0.1 microliter saline) into the MPO dose dependently increased the splenic nerve activity without any change in blood pressure. 4. In contrast, microinjection of interferon-alpha into the paraventricular nucleus of the hypothalamus (PVN) had no effect on splenic nerve activity, although an injection of glutamate increased the nerve activity. 5. The present results, taken together with previous reports, suggest that the neuronal networks between the MPO and the splenic sympathetic nerve, which may be activated by centrally administered interferon-alpha, are important in the suppression of the splenic cellular immunity.

Animals↗
PubMed1993

A dramatic pH-dependent alteration in ANP receptor density: a note for using cultured cells.

Culture media tend to become acidic when rapidly growing cells are cultured under batch conditions using a CO2/HCO3- buffer system. The effects of this inherent lowering of pH on cellular makeup of cultured cells, which have long been ignored, were examined by monitoring the pH and number of the atrial natriuretic peptide (ANP) receptors expressed on the cultured bovine endothelial cells. The Eagle's minimum essential medium was adjusted to three different pH values of 7.0, 7.4, and 7.7 and used for 48-h batch cultures. After this 48-h incubation, the pH values of the media were found to be 7.0, 7.1, and 7.4, respectively. These pH shifts had unexpectedly strong influences on the ANP receptor levels without affecting the affinity. Cells maintained in the slightly higher pH medium had a trace amount of the receptor (< 10 sites/cell), while those in the lower pH environment exhibited a large number of binding sites (40,000 sites/cell). Similar situations might occur in other cellular components and in other types of cells, and therefore, such possibilities should be kept in mind when cultured cell systems are used.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Central interferon-alpha inhibits natural killer cytotoxicity through sympathetic innervation.

The brain has been known to produce high levels of interferon-alpha (IFN-alpha) during viral infections. We investigated the central and peripheral mechanisms of the brain IFN-alpha-induced suppression of natural killer (NK) cytotoxicity in the rat. The activity of NK cells in the spleen and the peripheral blood decreased 30-120 min after intracerebroventricular (icv) injection of recombinant human IFN-alpha of > 1,000 U but not after its intraperitoneal injection. This effect was antagonized by pretreatment with icv naltrexone (NLTX). Splenic denervation was observed to completely abolish the IFN-alpha-induced suppression of NK activity, whereas bilateral adrenalectomy did not. Furthermore, this immunosuppression was blocked by an icv injection of an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF-(9-41). The icv injection of CRF resulted in reduced NK activity, which was not affected by NLTX. The results suggest that brain IFN-alpha activates the CRF system through central opioid receptors and thereby suppresses the NK cytotoxicity predominantly through splenic sympathetic innervation.

Adrenalectomy↗
PubMed1993

High-density localization of ANP receptors in chondrocytes of eel gill cartilage.

Very high levels of atrial natriuretic peptide (ANP) receptor were found in a quite unexpected tissue, i.e., the chondrocyte of the eel gill cartilage. 125I-labeled ANP binding assay indicated that the eel gill contains large amounts of the receptor and its levels are much higher (> 10-fold) than those in the other tissues examined, including the brain, kidney, head kidney including steroidogenic interrenal cells, and gut. Autoradiography using gill sections revealed dense localization of ANP receptors in the chondrocytes of the cartilage as well as moderate localization in the parenchymal cells. Biochemical and pharmacological characterization of the chondrocyte receptor indicated that most of the receptors are type C receptors, having a broad ligand specificity and a reduced M(r) of 68,000. Because a hyaline cartilage in which chondrocytes reside lacks blood vessels, and all metabolic exchange is by slow diffusion through the matrix, the chondrocyte localization of the type C ANP receptor is notable and may stimulate not only chondrocyte research but also studies on physiological significance of the type C receptor, which is generally considered to be merely a clearance (silent) receptor.

Animals↗
PubMed1993

[Increased lung uptake and transient left ventricular dilatation at stress myocardial scintigraphy with 99mTc-MIBI].

On exercise 201Tl scintigraphy in coronary artery disease, left ventricular transient dilatation (LVTD) and increased lung uptake were noted as a marker of multivessel critical stenosis. To compare the two markers of 99mTc-methoxyisobutyl isonitrile (MIBI) and 201Tl, planar and SPECT myocardial scintigraphy were performed with both radiopharmaceuticals in 27 patients with ischemic heart disease. Lung uptake (lung/max myocardial ratio) of MIBI was significantly lower than that of 201Tl, but the relationship of the lung uptake was linearly correlated (r = 0.77). The LVTD ratio (mean radial ratio = m-RR) was determined by the mean radius of the immediate postexercise short axial image by that of rest (redistribution) image. There was no significant correlation between the m-RR of 201Tl and that of MIBI (r = 0.27). We suggest that the mechanism of LVTD is due to not only subendmyocardial ischemia but also another factors.

Aged↗
PubMed1992

Effects of the opiates on the paraventricular nucleus in genetically polydipsic mice.

The inbred mice, STR/N, are known to possess extreme polydipsia with no known abnormality in vasopressin system and the kidney function. Our previous studies indicate that the opiate antagonists given intracerebroventricularly strongly attenuated spontaneous drinking. To determine the site(s) of action, the present study was undertaken. Microinjections of naltrexone methobromide and a selective kappa-receptor antagonist, nor-binaltorphimine (nor-BNI), into the paraventricular nucleus of the hypothalamus (PVN) greatly attenuated drinking of the STR/N for 0.5 to 16 h after injections, while in the two control groups, non-polydipsic STR/1N and Swiss/Webster strains, drinking was not affected by the injections. Food intake was not much altered in all groups. Studies of PVN neurons in vitro (n = > 160 for each group) showed that basal firing rates and patterns were similar in the STR/N and the control groups. Morphine added to the medium inhibited some but excited none in all strains tested. The threshold for the inhibitory action was higher in the polydipsic STR/N mice (10(-8) M), compared to that in the control, S/W mice (10(-9) M). Further, a proportion of neurons inhibited by morphine in the PVN was significantly smaller (P < 0.01) in the STR/N (41.7%), compared to that in the control (64.9%). Dynorphin had very similar effect to that of morphine, but the proportion of cells inhibited was 25.4% in the STR/N, and 70.4% in the S/W. Prior applications of naloxone to the medium prevented the action of both morphine and dynorphin. Under the synaptic blockade (in a low Ca2+ and high Mg2+ medium) the inhibitory effect of the opiates persisted. We concluded that the PVN is at least one of the possible sites where the opiates are acting to cause the polydipsia in the STR/N mice.

Animals↗
PubMed1992

Modulation by NaCl of atrial natriuretic peptide receptor levels and cyclic GMP responsiveness to atrial natriuretic peptide of cultured vascular endothelial cells.

Type C atrial natriuretic peptide (ANP) receptor levels in cultured vascular endothelial cells were found to be very sensitive to NaCl and shown to be inversely related to the magnitude of ANP-induced cGMP response of the cells. Endothelial cells from bovine carotid artery were subcultured in Eagle's minimum essential medium supplemented with 10% fetal bovine serum (MEM-FBS) and in MEM-FBS plus 25 and 50 mM NaCl. Determination, after several passages, of ANP receptor levels in these cells by 125I-ANP binding assay and affinity labeling revealed a marked reduction in the number of type C receptor in the NaCl-treated cells, whereas type A receptor density was not affected. RNase protection assay to estimate the levels of type C receptor mRNA indicated that the reduction occurred at a pre-translational level. In spite of the decrease in type C receptor number and no significant change in type A receptor (i.e. particulate guanylate cyclase) levels, cGMP response of the NaCl-treated cells to ANP was greatly exaggerated; this sensitization was also observed in membrane preparations. Simple masking of type C ANP receptor with C-ANF (des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP), a ring-deleted ANP analog, did not produce any sensitization of the cGMP response to ANP; therefore, the above phenomenon cannot simply be explained by the clearance function of the type C receptor. Although whether the type C receptor depletion is directly related to the sensitization of the type A receptor/cyclase is not known, the phenomenon reported and characterized here will serve as a useful basis for elucidating ANP receptor regulation and activation.

Affinity Labels↗
PubMed1992

Effects of vasopressin and angiotensin II on neurones in the rat dorsal motor nucleus of the vagus, in vitro.

1. Extracellular recordings were made from 297 spontaneously firing neurones in the dorsal motor nucleus of the vagus (DMV) in slice preparations of rat medulla oblongata. Some of the neurones recorded were identified to be vagal motoneurones by antidromic stimulation. The cells fired with a slow irregular pattern at an average rate of 1.1 +/- 0.1 spikes/s (mean +/- S.E.M.). 2. Arginine vasopressin (AVP) was applied by perfusion in 196 of the 297 cells. Most of the neurones (190/196, 97%) were excited by 10(-6) M AVP with an increase in firing rate from the basal level of 1.1 +/- 0.1 to a maximum of 2.5 +/- 0.2 spikes/s. There was a dose-dependent relation between the concentration of AVP and the increased firing rate in all DMV neurones tested (n = 38). The threshold concentration of the peptide to produce changes in firing rate was assumed to be about 10(-10) M. The remaining six neurones were not affected by application of AVP. 3. Application of oxytocin (OXT, 10(-6) M) increased the firing rate of all thirty-eight neurones tested. The effects of AVP and OXT on all neurones examined (n = 20 and 4, respectively) still persisted after blocking the synaptic transmission in a low-Ca2+ or Ca(2+)-free-high-Mg2+ solution, indicating the direct action of both AVP and OXT on the postsynaptic membranes. 4. The AVP-induced excitatory responses were completely but reversibly blocked by the V1-type receptor antagonists, [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid), 2-(O-methyl)tyrosine]-arginine vasopressin (d(CH2)5Tyr(Me)AVP) (n = 5) and Phaa-D-Tyr(Et)Phe-Gln-Asn-Lys-Pro-Arg-NH2 (n = 6), whereas a selective and reversible OXT receptor antagonist, desGly-NH2d(CH2)5[Tyr-(Me)2Thr4]ornithine vasotocin, which suppressed the OXT-induced excitation, did not block the responses to AVP (n = 11). 5. Application of angiotensin II (AII, 10(-6) M) to 153 neurones increased the firing rates of 60 (39%) neurones. The firing rate was increased from the basal level of 1.0 +/- 0.1 to a maximum of 1.8 +/- 0.2 spikes/s (n = 60). The effect of AII was completely abolished by an AII receptor antagonist, [Sar1,Ile8]angiotensin II (n = 6). There was a dose dependence of the excitatory response on AII concentration in all of eleven neurones tested. The threshold concentration was assumed to be about 10(-9) M. The activity of 5 (3%) of 153 neurones was decreased, and the remaining 88 (58%) neurones were not affected by AII.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Effects of temperature and neuroactive substances on hypothalamic neurones in vitro: possible implications for the induction of fever.

This paper reviews some of our findings which have shown the usefulness of in vitro methods in the study of hypothalamic neurones. (1) Membrane current analyses of dispersed neurones of the rat preoptic and anterior hypothalamus (POA) during thermal stimulation have revealed that warm-sensitive neurones are endowed with a non-inactivating Na+ channel having a high Q10 in the hyperthermic range (35-41 degrees C). (2) A brain slice study has shown that neurones in the organum vasculosum lamina terminalis (OVLT) region have much higher sensitivity to PGE2 than POA neurones. This provides further evidence of a critical role of the OVLT in translation of blood-borne cytokine signals into brain signals for fever induction. (3) Local application of IL-1 beta and IFN alpha altered the activity of thermosensitive (TS) neurones and glucose responsive (GR) neurones in vitro in an appropriate way to produce fever and anorexia. While the responses to IL-1 beta required the local release of prostaglandins, the responses to IFN alpha were found to be mediated by opioid receptor mechanisms. (4) The responses of POA TS neurones and VMH GR neurones to IL-1 beta but not those to IFN alpha, were reversibly blocked by alpha MSH, an endogenous antipyretic peptide. Thus, immune cytokines and their related neuroactive substances may affect hypothalamic TS and GR neurones thereby producing elaborately regulated changes in homeostatic functions such as thermoregulation (fever) and feeding (anorexia), which are considered as host defence responses.

Animals↗
PubMed1992

[Diagnostic accuracy of coronary artery lesion by 99mTc-MIBI exercise myocardial scintigraphy--containing the utility of simultaneous assessment of left ventricular function].

To determine whether technetium-99m hexakis-2-methoxy isobutyl isonitrile (99mTc-MIBI) myocardial scintigraphy is a superior method in the detection of coronary artery disease, exercise and rest 99mTc-MIBI planar and SPECT scintigraphy were performed on 27 patients with coronary artery disease. When 99mTc-MIBI (555 MBq (15 mCi)) was injected, first-pass radionuclide angiography (FPRNA) was simultaneously performed by a new mobile multicrystal gamma camera (SIM-400), and LV function (LVEF) was evaluated quantitatively. Visual semiquantitative detection of coronary lesions using 99mTc-MIBI images showed superior accuracy to that obtained using 201TlCl images. 99mTc-MIBI SPECT images were particularly useful in diagnosing LCX and RCA lesions. Moreover, the simultaneous assessment of perfusion and left ventricular function by 99mTc-MIBI FPRNA proved to be useful in the diagnosis of multi-vessel disease. In summary, 99mTc-MIBI SPECT scintigraphy with simultaneous assessment of left ventricular function showed better diagnostic accuracy than 201TlCl myocardial scintigraphy.

Aged↗
PubMed1992

Application of artificial neural network to computer-aided diagnosis of coronary artery disease in myocardial SPECT bull's-eye images.

We have developed a computerized system that can aid in the radiologist's diagnosis in the detection and classification of coronary artery diseases. The technique employs a neural network to analyze 201Tl myocardial SPECT bull's-eye images. This multi-layer feed-forward neural network with a backpropagation algorithm has 256 input units (pattern: compressed 16 x 16-matrix images), 5-140 units in a single hidden layer, and eight output units (diagnosis: one normal and seven different types of abnormalities). The neural network was taught using pairs of training (learning) input data (bull's-eye "EXTENT" image) and desired output data ("correct" diagnosis). The effects of the numbers of hidden units and learning iterations in the network on the recognition performance were examined. In our initial stage, the results show that the recognition performance of the neural network is better than that of the radiology resident but worse than that of the experienced radiologist. Our study also demonstrates that the result produced in the neural network depends on the variety of the training examples used. The preliminary study suggests that the neural network approach is useful for the computer-aided diagnosis of coronary artery diseases in myocardial SPECT bull's-eye images.

Coronary Disease↗
PubMed1991

Central administration of interferon-alpha enhances rat sympathetic nerve activity to the spleen.

Intracerebroventricular injection of recombinant human interferon-alpha (IFN-alpha) in a dose of 1 x 10(4) U, but not 3 x 10(3) U, produced a long-lasting (at least for 60 min) increase (2.5-5 times the preinjection level) in the electrical activity of splenic sympathetic nerve filaments in urethane-alpha chloralose-anesthetized rats. Intravenous injection of IFN-alpha (3 x 10(4) U) also produced a similar excitation of splenic sympathetic nerves. There were no changes in arterial blood pressure and body temperature. The result, together with the previous findings, provides further evidence that the central IFN-alpha-induced suppression of cytotoxic activity of splenic natural killer cells may be mediated by the sympathetic innervation.

Animals↗