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Biomedical subjects

A Katoh

Publications and source records attributed to A Katoh.

At least 19 recordsLinked to original sources
PubMed1992

Systemic administration of a cholecystokinin analogue, ceruletide, protects against ischemia-induced neurodegeneration in gerbils.

The neuroprotective action of a cholecystokinin octapeptide analogue, ceruletide, was evaluated in models of cerebral ischemia using Mongolian gerbils. Ceruletide significantly suppressed the hyperactivity and amnesia induced by ischemia when injected s.c. 30 min before 5-min occlusion of the bilateral common carotid arteries at room temperature or immediately after their reperfusion. Ceruletide also reduced behavioral changes in ischemic gerbils whose body temperature was maintained at 37 degrees C during the 3-min occlusion. In these groups, delayed neuronal cell death in the hippocampal CA1 area following ischemia was markedly attenuated by s.c. administration of ceruletide. On the other hand, ceruletide could not inhibit the behavioral changes or the neurodegeneration induced in the hippocampal CA1 area by 5-min occlusion at 37 degrees C. These findings indicate that peripheral injection of ceruletide produces a neuroprotective action against moderate cerebral ischemia, which is the first evidence suggesting the efficacy of ceruletide in neurodegenerative diseases.

Amnesia↗
PubMed1992

Substrate specificity of Saccharomyces cerevisiae myristoyl-CoA: protein N-myristoyltransferase. Analysis of fatty acid analogs containing carbonyl groups, nitrogen heteroatoms, and nitrogen heterocycles in an in vitro enzyme assay and subsequent identification of inhibitors of human immunodeficiency virus I replication.

Covalent attachment of myristic acid (C14:0) to the amino-terminal glycine residue of a variety of eukaryotic cellular and viral proteins can have a profound influence on their biological properties. The enzyme that catalyzes this modification, myristoyl-CoA-protein N-myristoyltransferase (NMT), has been identified as a potential target for antiviral and antifungal therapy. Its reaction mechanism is ordered Bi Bi with myristoyl-CoA binding occurring before binding of peptide and CoA release preceding release of myristoylpeptide. Perturbations in the binding of its acyl-CoA substrate would therefore be expected to have an important influence on catalysis. We have synthesized 56 analogs of myristic acid (C14:0) to further characterize the acyl-CoA binding site of Saccharomyces cerevisiae NMT. The activity of fatty acid analogs was assessed using a coupled in vitro assay system that employed the reportedly nonspecific Pseudomonas acyl-CoA synthetase, purified S. cerevisiae NMT, and octapeptide substrates derived from residues 2-9 of the catalytic subunit of cyclic AMP-dependent protein kinase and the Pr55gag polyprotein precursor of human immunodeficiency virus I (HIV-I). Analysis of ketocarbonyl-, ester-, and amide-containing myristic acid analogs (the latter in two isomeric arrangements, the acylamino acid (-CO-NH-) and the amide (-NH-CO)) indicated that the enzyme's binding site is able to accommodate a dipolar protrusion from C4 through C13. This includes the region of the acyl chain occurring near C5-C6 (numbered from carboxyl) that appears to be bound in a bent conformation of 140-150 degrees. The activities of NMT's acyl-CoA substrates decrease with increasing polarity. This relationship was particularly apparent from an analysis of a series of analogs in which the hydrocarbon chain was terminated by (i) an azido group or (ii) one of three nitrogen heterocycles (imidazole, triazole, and tetrazole) alkylated at either nitrogen or carbon. This inverse relationship between polarity and activity was confirmed after comparison of the activities of the closely related ester- or amide-containing tetradecanoyl-CoA derivatives. Members from all of the analog series were surveyed to determine whether they could inhibit replication of human immunodeficiency virus I (HIV-I), a retrovirus that depends upon N-myristoylation of its Pr55gag for propagation. 12-Azidododecanoic acid was the most active analog tested, producing a 60-90% inhibition of viral production in both acutely and chronically infected T-lymphocyte cell lines at a concentration of 10-50 microM without associated cellular toxicity.

Acyltransferases↗
PubMed1992

Ischemia-induced irreversible deficit of memory function in gerbils.

Ischemia for 5 min temporarily increased locomotor activity in gerbils after 1 and 3 days. Temporary increases were also noted within 7 and 5 days after 20-min ischemia and repeated ischemia (three 2-min ischemia at 1-h intervals), respectively. In a passive avoidance task, gerbils were trained 2 or 14 days before the occlusion and then tested 1 day after it. Shortened step-through latency was observed in the retention test 3 days after 5-min ischemia, but not after 15 days (reversible deficit). In contrast, following 20-min ischemia, the step-through latency was significantly lower after 3 days and also after 15 days (irreversible deficit). Working memory was also tested with gerbils trained for an 8-arm radial maze task. A significantly higher working error was observed 1 day after 5-min ischemia but not after 5 days (reversible deficit). However, ischemia for 20-min and repeated ischemia led to markedly increase working error 1 day after the occlusion, with significant increases even after 14 and 28 days (irreversible deficit). In addition, while 5-min ischemia occurred the neuronal death in the hippocampal CA1 subfield, 20-min ischemia produced it not only in the CA1 subfield but also in the CA2-4 subfield and dorsal striatum. These results indicated that 5-min ischemia led to a reversible memory deficit, while 20-min and repeated ischemia produced an irreversible deficit.

Amnesia↗
PubMed1992

Stress-induced changes in brain Met-enkephalin, Leu-enkephalin and dynorphin concentrations.

Methionine-enkephalin (Met-enkephalin), leucine-enkephalin (Leu-enkephalin) and dynorphin A (1-17) (dynorphin A) concentrations in discrete brain areas were determined in the mice showing behavioral changes induced by stress using radioimmunoassay (RIA). In the present experiment, we used environment-induced conditioned suppression of motility and forced swimming-induced immobility. In the environment-induced conditioned suppression of motility, Met-enkephalin concentration in the striatum and hypothalamus significantly decreased. Leu-enkephalin concentration in the hypothalamus also decreased. Dynorphin A concentration in the striatum decreased, but significantly increased in the hypothalamus and pituitary. In the forced swimming-induced immobility, Met-enkephalin concentration in the striatum significantly decreased. Leu-enkephalin concentration in the hypothalamus and pituitary significantly decreased. Dynorphin A concentration in the pituitary decreased, but significantly increased in the hypothalamus. Our results indicated that the concentrations of Met-enkephalin, Leu-enkephalin and dynorphin A in the discrete brain areas changed in two different stressful situations. These findings suggested that these peptides might modulate the behavioral changes induced by stressors.

Animals↗
PubMed1992

Experimental studies on the pathogenesis of the gastric mucosal lesions induced by whole-body vibration.

In order to determine the pathogenesis of gastric mucosal lesions induced by whole-body vibration (WBV), the effects of WBV (3.0 G, 10 Hz, 90 min) on gastric mucosal blood flow (GMBF), plasma corticosterone (COR) and catecholamines (CA), and gastric ulcer formation were investigated in relation to the effects of forced water-immersion stress (FWI) upon the same parameters. While WBV increased GMBF during the exposure, FWI decreased it both during and after the stress. No difference in the severity of ulcer formation between the WBV and the FWI groups was seen. Both WBV and FWI increased plasma COR and CA, although the degree of the increase in COR that accompanied WBV was less than that associated with FWI. Truncal vagotomy attenuated the reduction of GMBF and the extent of ulcer formation that occurred with FWI, but promoted a reduction of GMBF with WBV. These findings indicate that ulceration induced by WBV may be caused primarily by its direct and specific mechanical actions and not by indirect, central nervous system effects known to be important in the pathogenesis of ulcerations produced by mental stress.

Animals↗
PubMed1992

Interferon modulation of 5-fluorouracil: use in neoadjuvant therapy inhibits experimental liver metastases in nude mice.

Experimental liver metastasis was studied in 4-5 week old athymic nude mice that were injected intrasplenically with a human colorectal tumor cell line (LoVo). A treatment schedule combining 5-fluorouracil and interferon (IFN) was previously shown to inhibit liver metastases. When this treatment was delayed until after splenectomy at 1, 2 and 3 weeks after tumor cell injections, liver metastases were not inhibited. However, when IFN was given during the interval between tumor cell injections and splenectomy (as neoadjuvant therapy), liver metastases were inhibited in the 2 and 3 week groups, but not in the 1 week group.

Animals↗
PubMed1992

Effects of N-methyl-D-aspartate receptor antagonists on carbon monoxide-induced brain damage in mice.

The mechanism of neurodegeneration and the possible therapeutic amelioration were investigated in a model induced by successive carbon monoxide (CO) exposures. Successive CO exposures resulted in a consistent pattern of degeneration of hippocampal CA1 pyramidal cells, which was quantified using an image analyzer. Competitive and noncompetitive antagonists of N-methyl-D-aspartate (NMDA) receptors, cyclopentenophenanthrene, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten,5,10-imine maleate and an antagonist of glycine binding sites, 7-chlorokynurenic acid, significantly reduced the CO-induced neurodegeneration. Ifenprodil (a antagonist of polyamine binding sites) and glycine had no effect. From these results, it is clear that NMDA receptor/ion channel complex is involved in the mechanism of CO-induced neurodegeneration, and that glycine binding site antagonist as well as NMDA competitive and noncompetitive antagonists may have neuroprotective properties in neurological disorders associated with overactivation of NMDA receptors.

Animals↗
PubMed1992

[Experimental studies on the development of acute gastric lesions induced by vibration stress in rats and its pathogenetic mechanisms].

To clarify the pathogenetic mechanisms in acute gastric lesions induced by vibration (VIB), the effects of VIB (3.0 G, 10 Hz, 90 min) on changes in gastric mucosal blood flow (GMBF), plasma corticosterone (COR) and catecholamines (CA) as well as ulcer formation were compared with those of forced water immersion stress (FWI). While the VIB increased the GMBF during the exposure, the FWI decreased it during and after the stress. No difference in the severity of ulcer formation between the VIB groups was seen. Although both VIB and FWI increased the COR and CA, the degree of increased in the COR by the VIB tended to be less than that by the FWI. The truncal vagotomy inhibited the reduction of the GMBF and ulcer formation by the FWI, but promoted the reduction of the GMBF by the VIB. These results suggest that ulceration induced by VIB is caused primarily by its direct, mechanical and specific actions and not through the central nerve system.

Animals↗
PubMed1992

Y-27152, a long-acting K+ channel opener with less tachycardia: antihypertensive effects in hypertensive rats and dogs in conscious state.

(+)-(3S,4R)-4-(N-Acetyl-N-benzyloxyamino)-6-cyano-3,4-dihydro-2,2- dimethyl- 2H-1-benzopyran-3-ol (Y-27152) is a new K+ channel opener with a long duration of action and less tachycardia. In this study, Y-27152 was compared with a K+ channel opener lemakalim and a Ca++ channel blocker nifedipine for antihypertensive activity in conscious spontaneously hypertensive rats (SHR) and two-kidney, one-clip renal hypertensive dogs (RHD). In conscious SHR, Y-27152 (0.1-1 mg/kg, p.o.) produced long-lasting dose-related decreases in systolic blood pressure. At 1 mg/kg, the maximum response occurred 5 to 7 hr after dosing, and 24 hr later, the pressure was still significantly reduced. Heart rate was not changed by these doses of Y-27152, whereas equihypotensive doses of lemakalim or nifedipine were strongly tachycardic. The cardiovascular effects of Y-27152 were antagonized by glibenclamide (20 mg/kg, i.v.). In conscious unrestrained RHD, Y-27152 at doses of 0.01, 0.03 and 0.1 mg/kg lowered blood pressure with a slow onset and long duration of action and had only a minimal effect on heart rate, whereas both lemakalim and nifedipine reduced blood pressure and markedly increased heart rate. No tolerance to the antihypertensive effect of Y-27152 (0.1 mg/kg) occurred during an 8-week repeated daily dosing to RHD and plasma renin activity, and aldosterone levels were not elevated during this period. In rat aortic rings contracted with 20 mM KCl, Y-27152 did not modify the tension; however, its desbenzyl form (Y-26763) produced vasorelaxation, and this effect was antagonized competitively by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Effects of successive carbon monoxide exposures on delayed neuronal death in mice under the maintenance of normal body temperature.

The 3 time carbon monoxide (CO) exposures potentiated the delayed neuronal death (DND) in comparison with that induced by single CO exposure. Deterioration of DND induced by CO exposures was observed when normal body temperature was maintained during the exposures, since CO exposure fell the body temperature to about 34 degrees C. Pretreatment with noncompetitive NMDA receptor antagonist, MK-801 (30 nmol/mouse), ameliorated DND induced by successive CO exposures under the maintenance of normal body temperature. These results suggest that the mice exposed successively to CO under the maintenance of normal body temperature is a useful hypoxic model.

Animals↗
PubMed1991

The substrate specificity of Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase. Analysis of myristic acid analogs containing oxygen, sulfur, double bonds, triple bonds, and/or an aromatic residue.

We have explored the acyl-CoA substrate specificity of Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (NMT) by synthesizing 81 fatty acid analogs and surveying their activity in a coupled in vitro assay containing Pseudomonas acyl-CoA synthetase and Escherichia coli-derived yeast NMT. Single oxygen or sulfur substitution for C-3 through C-13 is well tolerated by both enzymes. Detailed kinetic analyses suggest that the acyl-CoA and peptide-binding sites of NMT are relatively insensitive to placement of single group 6B heteroatoms. By contrast, di-oxygen-substituted analogs were very poor substrates, producing dramatic reductions in the affinity of NMTs peptide-binding site for a synthetic octapeptide substrate derived from the NH2-terminal sequence of a known N-myristoylprotein, the gag poly-protein precursor of human immunodeficiency virus 1 (HIV-1). This observation provides an example of binding site cooperativity in NMT. Replacement of one oxygen with sulfur at either the 6, 9, or 12 position of dioxatetradecanoic acids results in a general increase in peptide catalytic efficiency (Vmax/Km). An analysis of five fatty acids from octanoic to dodecanoic having terminal phenyl groups indicated that the best substrate was 10-phenyldecanoic acid even though Corey-Pauling-Koltun molecular models indicate that it has a length equivalent to that of tridecanoic acid. Six analogs having an equivalent length of 13 carbon atoms were subsequently prepared in which the phenyl group was systematically moved one methylene group closer to carboxyl. Movement of the phenyl just one carbon closer to carboxyl (producing 9-(p-methylphenyl) nonanoic acid) decreases peptide catalytic efficiency (Vmax/Km) severalfold compared to 10-phenyldecanoic acid. 10-(4-Tolyl)decanoic acid has the same relative positions of phenyl and carboxyl as 10-phenyldecanoic acid even though a methyl group is present on the phenyl ring. It produces peptide Km and Vmax values that are the same as 10-phenyldecanoic acid. Substitution of either oxygen or sulfur for a methylene group fails to override the effects noted when the phenyl group position is altered in the C-14 equivalent fatty acid series. Several fatty acids of differing chain lengths with cyclohexyl-, 2-furyl, and 2-thienyl groups at their omega termnius had activity profiles that paralleled those of the comparable phenyl-substituted compounds. Myristic acid analogs with triple bonds (beginning at positions 2 through 13), cis-double bonds (positions 3 through 13) and trans-double bond isomers (E5, E6, and E7) were also tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Acyltransferases↗
PubMed1991

Interaction between enkephalinergic and dopaminergic systems in stressful situations.

Mice exhibit a marked suppression of mobility when they are placed in the same cage in which they had previously received an electric shock. This suppression of motility is believed to be a stress-induced response. [D-Ala2,Met5]enkephalinamide (DAMEA, 40 and 80 nmol i.c.v.), a derivative resistant to [Met5]enkephalin-degrading enzyme activity, significantly attenuated the conditioned suppression of motility. The attenuation of conditioned suppression of motility induced by DAMEA was antagonized not only by naloxone (0.1 mg/kg s.c.), but also by 6-hydroxydopamine (6-OHDA, 100 micrograms/mouse, i.c.v.)-induced lesions of dopaminergic (DAergic) neurons. Pimozide (100 micrograms/kg i.p.) and a low dose of apomorphine (50 micrograms/kg s.c.) also inhibited the effect of DAMEA. In addition, DAMEA reversed the decrease in DA turnover in the striatum in the conditioned suppression group. These results suggest that the attenuation of conditioned suppression of motility induced by activation of the [Met5]enkephalinergic system may be related to the striatal DAergic system.

Animals↗
PubMed1991

Cells showing immunoreactivity for calcitonin or calcitonin gene-related peptide (CGRP) in the central nervous system of some invertebrates.

In the central nervous system of some species of several invertebrate phyla, including land planarians (Platyhelminthes), ribbon worms (Nemertina), slugs (Mollusca), polychaetes, earthworms and leeches (Annelida), pill bugs (Arthropoda), and beard worms (Pogonophora), salmon calcitonin-immunoreactive cells and rat calcitonin gene-related peptide (CGRP)-immunoreactive cells were found by immunohistochemistry. These immunoreactive cells were located in the region surrounding the neuropile, although the sizes of the cells varied according to species. Some of them were round or polygonal and regarded as apolar nerve cells because of their lack of cytoplasmic processes, whereas others were spindle-shaped or elongated, being comparable with unipolar nerve cells because of extension of their cytoplasmic processes in the direction of the neuropile. In some cases, it was noted that the cytoplasmic processes had complicated branches or formed loop-like structures at their ends. These observations suggest that a calcitonin-like or CGRP-like substance is extensively present in invertebrates as well as vertebrates.

Animals↗
PubMed1991

The effect of tacrine (THA) on cycloheximide- and basal forebrain lesion-induced memory deficit in rats.

The effects of 9-amino-1,2,3,4-tetrahydroacridine (tacrine), an active acetylcholinesterase inhibitor, on cycloheximide- and basal forebrain (BF) lesion-induced memory deficit in the water maze and passive avoidance task were investigated. While cycloheximide (1.5 mg/kg, s.c.) produced amnesia in the passive avoidance task, chronic administration of tacrine (1, 3 and 10 mg/kg, once a day for 1 week) improved the amnesia. BF lesion produced amnesia in both the water maze and passive avoidance tasks. Chronic tacrine (0.1-3 mg/kg, passive avoidance task, or 0.3 mg/kg, water maze task, once a day for 1 week) improved BF lesion-induced amnesia in the passive avoidance and water maze tasks. These results suggest that tacrine may be useful for senile dementia.

Administration, Oral↗
PubMed1991

Carbon monoxide-induced delayed amnesia, delayed neuronal death and change in acetylcholine concentration in mice.

We investigated the interrelationship of delayed amnesia, delayed neuronal death and changes in acetylcholine concentration induced by carbon monoxide (CO)-exposure in mice. In the test for retention of the passive avoidance task, amnesia was observed 5 and 7 days after CO-exposure when the mice were exposed to CO 1 day after training; in the case when the mice were exposed to CO 5 and 7 days before training, amnesia was also observed in a retention test given 1 day after training. The number of pyramidal cells in the hippocampal CA1 subfield was lower than that of the control 3, 5 and 7 days after CO-exposure. But the neurodegeneration in the parietal cortex, area 1, was not observed until 7 days after CO-exposure. The findings indicated that the amnesia and the neuronal death were produced after a delay when the mice were exposed to CO. In addition, the delayed amnesia was closely related to the delayed neuronal death in the hippocampal CA1 subfield. Moreover, [3H]glutamate and [3H]glycine binding sites did not change after CO-exposure but, 7 days after CO-exposure, the concentration of acetylcholine and the binding of [3H]quinuclidinyl benzilate in the frontal cortex and the striatum were found to have significantly changed, but those in the hippocampus did not show significant change. Therefore, we suggest that delayed amnesia induced by CO-exposure may result from delayed neuronal death in the hippocampal CA1 subfield and dysfunction in the acetylcholinergic neurons, in the frontal cortex, the striatum and/or the hippocampus.

Acetylcholine↗
PubMed1990

[Esophageal cancer metastatic to the kidney: report of a case].

On December 12, 1988, 51-years-old man was admitted to our clinic with asymptomatic gross hematuria. He had been undergone total esophagectomy for esophageal cancer in the surgery service of our hospital on June 22, 1987, and histopathological diagnosis was squamous cell carcinoma, Stage III, a2, n(-), m0, pl0, ly(+), V(+). X-ray CT revealed a irregular, obscure bordered tumor image in the left kidney and angiography showed a hypovascular tumor. On December 20, nephrectomy was performed. Histologically, it proved to be squamous cell carcinoma metastasized from esophageal cancer. The present case is the 11th of those cases which have been clinically diagnosed as renal metastasis of esophageal cancer in Japan. An extremely small number of clinically reported cases compared with autopsy cases are thought to be ascribable to scarce detectability while living of such metastasis, but not to its rare occurrence. The coming diagnostic improvement may well make such case more and more increasing.

Carcinoma, Squamous Cell↗
PubMed1990

Inhibition of liver metastases in nude mice by the combined action of 5-fluorouracil and interferon.

Liver metastasis in nude mice was studied using LoVo, a cell line developed from a patient with adenocarcinoma of the colon. LoVo cells injected into the spleen of 4-week-old nude mice showed 100% tumorigenicity in the spleen and metastases to the liver. This system was used to study ways in which to improve the efficacy of 5-FU, which was used in combination with alpha-2a interferon. Our results show that interferon can potentiate the effect of 5-FU in inhibiting liver metastases. Either drug given alone did not show comparable inhibition.

Animals↗