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Y Kohda

Publications and source records attributed to Y Kohda.

At least 19 recordsLinked to original sources
PubMed1999

Postictal blockade of ischemic hippocampal neuronal death in primates using selective cathepsin inhibitors.

This paper is to study the participation of cathepsin in ischemic neuronal death of the monkey hippocampal cornu ammonis (CA) 1 sector and also to clarify whether its selective inhibitor epoxysuccinyl peptides such as CA-074 and E-64c can inhibit the neuronal death or not. In the preceding reports, we demonstrated mu-calpain activation and subsequent rupturing of the lysosomal membrane of postischemic CA1 neurons and also increase of enzyme activity of cathepsins B and L in monkeys undergoing a complete 20-min whole brain ischemia. Here, morphological, immunohistochemical and enzymatical analyses were performed to examine the efficacy of two selective cathepsin inhibitors in the postictal blockade of delayed neuronal death in the monkey hippocampus. Both inhibitors could significantly decrease enzyme activities of cathepsins B and L in all hippocampal sectors. When CA-074 was intravenously administered immediately after the ischemic insult, approximately 67% of CA1 neurons were saved from delayed neuronal death on day 5 after ischemia. In contrast, when E-64c was similarly administered, approximately 84% of CA1 neurons were saved from delayed neuronal death on day 5. The surviving neurons showed mild central chromatolysis and negligible immunoreactivity for cathepsins B and L. These observations indicate that the use of cathepsin inhibitors may become novel strategy for prevention of ischemic delayed neuronal death in the primate hippocampus.

Animals↗
PubMed1999

A toxicokinetic analysis in a patient with acute glufosinate poisoning.

Incidents of poisoning in humans caused by the ingestion of the glufosinate ammonium containing herbicides are gradually increasing in Japan. This poisoning is characterized by various neurological symptoms such as disturbances of consciousness, convulsions and apnea which appear after an asymptomatic interval of several hours. We studied the toxicokinetics of glufosinate in a patient with this poisoning successfully treated without extracorporeal hemopurification. A 65-year-old male ingested BASTA, which contains 20% w/v of glufosinate ammonium, about 300 ml, more than the estimated human toxic dose. Four and a half hours after ingestion, he showed speech ataxia and systemic tremor. He was prophylactically intubated before the occurrence of serious respiratory failure. After 5 days of artificial ventilation he was extubated and discharged without any sequelae. We studied the serial change of serum glufosinate concentration every 3-6 h and assessed the urinary excretion of glufosinate every 24 h. The absorbed amount of glufosinate was estimated from the cumulative excreted in urine. Toxicokinetic analysis was performed using the two-compartment model. The changes in serum glufosinate concentration exhibited T1/2alpha of 1.84 and T1/2beta of 9.59 h. The apparent distribution volume at beta-phase and the total body clearance were 1.44 l/kg and 86.6 ml/min, respectively. Renal clearance was estimated to be 77.9 ml/min. The indication for extracorporeal hemopurification for this poisoning has been discussed.

Aged↗
PubMed1999

Effect of plasma alpha1-acid glycoprotein concentration on the accumulation of lidocaine metabolites during continuous epidural anesthesia in infants and children.

OBJECTIVE: Alpha1-acid glycoprotein (AAG) is an acute-phase protein that is responsible for binding basic drugs such as lidocaine (LDC). The effect of AAG on the duration of LDC during continuous epidural anesthesia in infants and young children was investigated. PATIENTS, MATERIALS AND METHODS: Plasma levels of LDC and its active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were monitored in 20 infants and children, 5 months to 6 years of age, who received continuous epidural infusion of 2.5 mg kg(-1) LDC hourly during abdominal or thoracic surgeries. RESULTS: Plasma LDC concentrations were constant after the first hour of injection. In contrast, the concentrations of MEGX and GX increased continuously during epidural infusion in all patients. The plasma AAG concentration correlated significantly (r = 0.814, p<0.001) with the steady-state LDC level. In addition, significant inverse correlation was observed between the plasma AAG concentration and the accumulation rate of MEGX (r = 0.742, p = 0.002). The plasma AAG concentration and the accumulation rate of GX correlated weakly (r = 0.474, p = 0.035). There was no correlation between the age of the patient and the plasma AAG concentrations (r = 0.295, p = 0.206). CONCLUSION: Our results suggest that the plasma AAG concentration is a valuable index in preventing the toxicity caused by accumulation of MEGX during continuous epidural anesthesia of LDC.

Anesthesia, Epidural↗
PubMed1998

Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on 'calpain-cathepsin hypothesis'.

Although Cornu Ammonis (CA) 1 neurons of the hippocampus are known to be vulnerable to transient ischaemia, the mechanism of ischaemic neuronal death is still unknown, and there are very few strategies to prevent neuronal death at present. In a previous report we demonstrated micro-calpain activation at the disrupted lysosomal membrane of postischaemic CA1 neurons in the monkey undergoing a complete 20 min whole brain ischaemia. Using the same experimental paradigm, we observed that the enzyme activity of the lysosomal protease cathepsin B increased throughout the hippocampus on days 3-5 after the transient ischaemia. Furthermore, by immunocytochemistry cathepsin B showed presence of extralysosomal immunoreactivity with specific localization to the cytoplasm of CA1 neurons and the neuropil of the vulnerable CA1 sector. When a specific inhibitor of cathepsin B, the epoxysuccinyl peptide CA-074 (C18H29N3O6) was intravenously administered immediately after the ischaemic insult, approximately 67% of CA1 neurons were saved from delayed neuronal death on day 5 in eight monkeys undergoing 20 min brain ischaemia: the extent of inhibition was excellent in three of eight and good in five of eight monkeys. The surviving neurons rescued by blockade of lysosomal activity, showed mild central chromatolysis and were associated with the decreased immunoreactivity for cathepsin B. These observations indicate that calpain-induced cathepsin B release is crucial for the development of the ischaemic neuronal death, and that a specific inhibitor of cathepsin B is of potential therapeutic utility in ischaemic injuries to the human CNS.

Animals↗
PubMed1998

Alpha-melanocyte-stimulating hormone inhibits renal injury in the absence of neutrophils.

BACKGROUND: We previously showed that alpha-melanocyte stimulating hormone (alpha-MSH) decreases ischemia/reperfusion injury even when started six hours after ischemia. Alpha-MSH inhibits both neutrophil accumulation and nitric oxide production. To determine the relative importance of alpha-MSH on the neutrophil pathway, we examined the effects of alpha-MSH in injury models where neutrophil effects are minimal or absent. METHODS: We studied the effects of alpha-MSH in (1) intercellular adhesion molecule-1 (ICAM-1) knock-out and background mice that were subjected to 40 minutes of ischemia and 24 hours reperfusion, and (2) isolated kidneys that were subjected to in vivo ischemia for 20 minutes and then perfused ex vivo for one hour without neutrophils. To begin to search for direct tubule effects of alpha-MSH, we studied the effect of alpha-MSH on nitric oxide (NO) in endotoxin/interferon-gamma-treated mouse cortical tubule cells. RESULTS: ICAM-1 knock-out mice had 75% less neutrophil infiltration than background mice after ischemia. Despite the relative lack of neutrophils, alpha-MSH inhibited renal injury in ICAM-1 knock-out mice. Alpha-MSH also significantly preserved GFR and tubular sodium reabsorption in the isolated perfused ischemic kidney model. Alpha-MSH and a nitric oxide inhibitor did not exhibit synergy. Finally, alpha-MSH inhibited nitrite production by 20% in the mouse cortical tubule cells (MCT), similar to parallel observations in a cultured mouse macrophage line (RAW cells). CONCLUSIONS: We conclude that alpha-MSH decreases renal injury when neutrophil effects are minimal or absent, indicating that alpha-MSH inhibits neutrophil-independent pathways of renal injury. The preservation of sodium absorption ex vivo and inhibition of nitrite production in cultured MCT cells suggests that alpha-MSH inhibits tubular injury by direct tubular effects.

Animals↗
PubMed1998

Localization of the ROMK potassium channel to the apical membrane of distal nephron in rat kidney.

BACKGROUND: The apical potassium (K+) channels mediate K+ recycling in thick ascending limb (TAL) and K+ secretion in cortical collecting duct (CCD). Recently, the cDNAs for a family of renal K+ channels, ROMK1, -2 and -3, were identified. Based on the biophysical properties and mRNA distribution, it is believed that these ROMK cDNAs encode the apical K+ channels of TAL and CCD. However, the information for cellular and subcellular localization of the ROMK proteins in these tubules is still not available. METHODS: Paraffin or frozen kidney sections from adult Sprague-Dawley rats were stained by polyclonal antibodies against the N- and C-terminal domain of ROMK. Immunoreactive staining was visualized by color development from horseradish peroxidase reaction. Membrane homogenates from kidney were analyzed by Western blot analysis. RESULTS: The polyclonal antibodies against cytoplasmic epitope of ROMK recognized a approximately 42 kD protein in the membrane homogenates from kidney, but not from liver. Staining by immunocytochemistry revealed that ROMK channels were localized to the apical membranes of the distal nephron in cortex and outer medulla, including thick ascending limb and collecting tubule. ROMK staining was absent in glomerulus, proximal tubule and inner medulla. Double staining of the tissue section with both ROMK-specific and H+-ATPase-specific antibodies revealed labeling of ROMK in the principal cells of the collecting tubules. CONCLUSIONS: These results further strengthen the idea that ROMK channels play important roles in the recycling of K+ in TAL and the secretion of K+ in CCD.

Animals↗
PubMed1998

alpha-Melanocyte-stimulating hormone and acute renal failure.

alpha-Melanocyte-stimulating hormone (MSH) is an endogenous anti-inflammatory cytokine that inhibits all major forms of inflammation, alpha-MSH level is increased at sites of inflammation in humans, and is produced in the pituitary and in macrophages. The effects of alpha-MSH are mediated by melanocortin receptors found on macrophages, neutrophils, and renal tubules. alpha-MSH inhibited ischemic acute renal failure in mice and rats, even when started 6 h after injury. alpha-MSH acts, in part, by inhibiting the maladaptive activation of genes that cause inflammatory and cytotoxic renal injury. However, alpha-MSH is effective even in the absence of neutrophils, suggesting that alpha-MSH also acts directly on renal tubules.

Acute Kidney Injury↗
PubMed1997

Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats.

Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.

Animals↗
PubMed1996

Dynamic changes of cathepsins B and L expression in the monkey hippocampus after transient ischemia.

Enzymatic activities, expressions, and the immunohistochemical localization of lysosomal cystein proteases, cathepsins B and L, were analyzed in the monkey hippocampus after transient ischemia to clarify the mechanism of delayed cornu Ammonis (CA)-1 neuronal death. By enzymatic assay, the activity of cathepsin B increased in CA-1, 24 h after the ischemic insult, while that of cathepsin L decreased. On Western blotting, the protein contents of both cathepsins B and L increased immediately after ischemia. By immunohistochemistry, cathepsins B and L were stained as coarse granules in the perikarya of control CA-1 neurons, but in postischemic CA-1 neurons they were released from lysosome granules. In contrast, in CA-2 and the remaining sectors, enzymatic activities increased after ischemia, and immunoreactivities of cathepsins B and L increased only within lysosome granules. These results suggest that cathepsins B and L may play an important role in the breakdown of certain cell proteins in the postischemic CA-1 neurons.

Animals↗
PubMed1996

Contrast-enhanced MRI of intrasellar arachnoid cysts: relationship between the pituitary gland and cyst.

We recently encountered two large intrasellar arachnoid cysts extending to the suprasellar region. The intensity of the cyst contents was identical to that of the cerebrospinal fluid on both T1- and T2- weighted MRI. On contrast-enhanced MRI, the pituitary gland was compressed posteroinferiorly and flattened in the sella turcica. In this report of rare intrasellar arachnoid cysts the discussion is focused on dislocation of the pituitary gland.

Arachnoid Cysts↗
PubMed1996

Expression of NF2 gene product merlin in arachnoid villi and meningiomas.

Neurofibromatosis type 2 (NF2) gene encodes a novel 595 amino acid protein named merlin. Recently, Ruttledge et al demonstrated inactivation of NF2 gene in approximately 60% of sporadically occurring meningiomas. Merlin is thought to physiologically exist beneath the cell membrane, and to form a part of modulation in signal transduction, for example, information concerning contact inhibition. In NF2-related tumors, it is supposed that the mutation of merlin results in loss of this signal transduction leading to tumorigenesis. In this paper, we investigated the expression of NF2 gene product merlin in arachnoid villi and meningiomas. The immunohistochemical staining of merlin showed a striking contrast between arachnoid villi and meningiomas. In arachnoid cells, merlin was labeled in the whole cytoplasm, but not within the nuclei. In contrast, in meningiomas, immunoreactivity of merlin was mainly seen in the nuclei. These results suggest that arachnoid cells with normal merlin are capable of normal signal transduction, whereas meningioma cells with mutated merlin show impairment of signal transduction which may lead to tumorigenesis.

Arachnoid↗
PubMed1995

Prolongation of epidural anesthesia in the rabbit with the use of a biodegradable copolymer paste containing lidocaine.

Prolongation of the drug effect using a drug-delivery system has recently been introduced in local anesthesia. In this study, we investigated the prolonging effect of an epidurally injected biodegradable copolymer paste containing 10% lidocaine (Lid-CoPol). Twenty-nine rabbits were studied. A catheter was placed in the epidural space at the level of L6-7 in each animal. A solution of 10% lidocaine (Group I, n = 12), or a copolymer containing 10% lidocaine (Lid-CoPol), (Group II, n = 12) or copolymer paste only (Group III, n = 5) was injected epidurally at a dose of 0.15 mL/kg. The effect of each drug was assessed by evaluation of response to pain stimulation and of the degree of motor block produced. The plasma lidocaine concentration was also measured consecutively in five animals of both Groups I and II. The duration of sensory and motor block of Lid-CoPol was 800% and 975% longer, respectively, than that of plain lidocaine solution. Plasma lidocaine concentration reached a maximum 5 min after injection (5.5 +/- 0.5 micrograms/mL) in Group I. In Group II, the level reached a maximum 30 min after injection (3.7 +/- 1.5 micrograms/mL). The findings are attributed in part to the slow release of lidocaine from the biodegradable copolymer paste, which is suggested as a new drug-delivery system for local anesthetics.

Anesthesia, Epidural↗
PubMed1995

[Valproic acid].

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Adult↗
PubMed1994

Production of two novel monoclonal antibodies against human renal glomeruli and their application to the immunohistochemical investigation of crescentic glomerulonephritis.

Two monoclonal antibodies (MAbs) against human renal glomeruli, HEP1 and HBM1, were produced using isolated human glomeruli as an antigen. Immunohistochemical and immunoelectron microscopic analyses revealed that the recognition site of HEP1 is the cell surface of the visceral glomerular epithelial cells. HEP1 showed no reaction in the renal interstitium or in other tissues. HBM1 recognized an antigen present in the basal lamina of the renal glomeruli, Bowman's capsule, and partly in the basement membrane of renal tubules, but it was not reactive with the mesangial matrix or renal interstitium. The isotype of both MAbs was IgG1, k. The molecular weights of their corresponding antigens were 127-177 and 220 kD, respectively. Besides human tissues, HEP1 also showed cross-reactions with antigens in the visceral glomerular epithelial cells of various animals other than mice. HBM1 recognized human antigen only. Using both MAbs, eight cases of crescentic glomerulonephritis were examined immunohistochemically. As a result, it was demonstrated that the crescents may not be formed by visceral glomerular epithelial cells. From this study, these two MAbs appear to be useful markers for the evaluation of renal glomerular disorders.

Animals↗
PubMed1994

Determination of 17-hydroxycorticosteroids in dialysate solution as a measure of adrenocortical function in hemodialysis patients.

Dialysate contents of 17-hydroxycorticosteroids (17-OHCS) in hemodialysis patients were studied as a potential measure of adrenocortical function. Dialysate 17-OHCS contents after a 2-day interval of hemodialysis in 15 hemodialysis patients were determined. Dialysate 17-OHCS increased after intravenous injection of cortisol the evening prior to hemodialysis (n = 4). Dialysate 17-OHCS content was suppressed, as was plasma cortisol, after a standard dexamethasone (Dex) suppression test (n = 1). Their plasma cortisol was suppressible or nonsuppressible by an overnight Dex suppression test, as reported previously. However, basal dialysate 17-OHCS contents were not different between them, indicating that the nonsuppressible patients with overnight Dex seem not to have hypercortisolism. We conclude that determination of dialysate 17-OHCS seems a useful noninvasive technique for the evaluation of adrenocortical function in hemodialysis patients.

17-Hydroxycorticosteroids↗
PubMed1994

Crude drugs from aquatic plants. IV. On the constituents of alismatis rhizoma. (2). Stereostructures of bioactive sesquiterpenes, alismol, alismoxide, orientalols A, B, and C, from Chinese alismatis rhizoma.

Following the characterization of the triterpene constituents in Chinese Alismatis Rhizoma, we investigated the chemical structures of orientalols A, B, and C, isolated from the less polar fraction of the crude drug together with two known sesquiterpenes, alismol and alismoxide. On the basis of the chemical and physicochemical evidence, the structures of orientalols A, B, and C have been determined and those of alismol and alismoxide were revised. All five sesquiterpenes were found to show an inhibitory effect on the contraction of isolated bladder smooth muscle induced by carbachol.

Animals↗
PubMed1993

[Transcatheter hepatic segmental chemo-Lipiodol-embolization against hepatocellular carcinoma accompanied by tumor thrombosis in the portal vein].

We performed transcatheter hepatic segmental chemo-Lipiodol-embolization against hepatocellular carcinoma accompanied by tumor thrombosis in the portal vein. CT scan after embolization demonstrated good Lipiodol accumulation in the tumor thrombosis in some cases. In one resected case, remarkable necrosis of tumor thrombosis was proved histologically. In five non-resected cases, 6-month survival rate was 100%. We hope this therapeutic method can be useful for hepatocellular carcinoma with tumor thrombosis in the portal vein.

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