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Biomedical subjects

H Habu

Publications and source records attributed to H Habu.

At least 19 recordsLinked to original sources

[Mitochondrial benzodiazepine receptors (MBR) in association with neurological disorders].

Ro 5-4864, a specific agonist of the peripheral-type benzodiazepine receptor (PBR), elicited convulsions 2.6 times more potently in EL mice (an animal model of epilepsy) than in DDY mice (control animal). A binding assay revealed a 50% higher density of [3H] Ro 5-4864 binding sites in the mitochondrial fraction (i.e., mitochondrial benzodiazepine receptors; MBR) of the brain tissues in EL mice as compared with DDY mice. On an elevated plus-maze, EL mice showed fear responses similar to those increased in DDY mice after PBR stimulation, suggesting a hyperfunction of MBR underlying the abnormal behaviors of EL mice. In fluorometric studies using NG108-15 cells, Ro 5-4864 depolarized mitochondrial membranes and, possibly as a consequence of this, raised intracellular Ca2+. Finally, we propose that MBR could be a major target of therapy for various neurological disorders, so drugs such as "mitochondrial membrane stabilizers" should be developed.

Animals↗

Age-related increase in nitric oxide synthase activity in senescence accelerated mouse brain and the effect of long-term administration of superoxide radical scavenger.

The levels of nitric oxide (NO) and NO synthase (NOS) activities were compared in the brains of young adult (3 months old), aged (11 months old) and TJ-960 administered (11 months old) senescence accelerated mice (SAM), of which the SAMP8 substrain is inferior in acquisition of learning due to the abnormality of glutamatergic neurotransmission in the cerebral cortex. TJ-960, which is based on the Kampo (Japanese traditional herbal medicine) prescription Sho-saiko-to-go-keishi-ka-shakuyaku-to, acts as a superoxide radical scavenger and attenuates the deterioration of neuronal activity associated with aging. We administered TJ-960 orally for 5 months. In the cerebral cortex of aged SAMP8, NOS activity was increased compared with that of young adult SAMP8. Though TJ-960 did not alter the contents of NO in any brain region compared with those in aged SAMP8, it did prevent the increase in NOS activity in the aged cerebral cortex. Our data suggest that NOS activity may increase to compensate for the reduced sensitivity of the NO reaction system in the aging process, and that TJ-960 may normalize this increased NOS activity in the cerebral cortex, although further work is clearly needed to ascertain maintenance in the acquisition of learning.

Administration, Oral↗

Reduction in nitric oxide synthase activity with development of an epileptogenic focus induced by ferric chloride in the rat brain.

Intracortical injection of iron ion has been shown to induce recurrent seizures and epileptic discharges in electrocorticograms. The importance of the effects of NO on seizure control systems and their regulation is suggested. In this paper, we examined the changes in nitric oxide synthase (NOS) activity in the epileptogenic focus induced by intracortical injection of iron ion at 5 min, 10 min, 1 h, 3 h and 3 days. Iron ion significantly decreased NOS activity in the cortex at the injection site 5 min, 3 h and 3 days after injection. These results suggest that the formation of an epileptic focus induced by iron ion is accompanied by decreased NOS activity.

Animals↗

Seizures induced by alpha-guanidinoglutaric acid, a nitric oxide synthase inhibitor, are controlled by L-arginine.

We evaluated the effect of manipulation of nitric oxide (NO) synthesis on epileptiform discharges recorded from immobilized rats during intracerebroventricular injection of alpha-guanidinoglutaric acid (GGA), an endogenous convulsant and a NO synthase (NOS) inhibitor, alone or in combined with a NOS substrate, l-arginine (ARG). GGA alone, or combined with 50 mM ARG, resulted in prolonged electrographical seizures while co-injection of either 100 or 200 mM of ARG with GGA caused significantly protection. These data show that ARG inhibited epileptiform discharges in a dose-dependent fashion, suggesting that the discharges initiated by inhibition of NOS with the intrinsic convulsant GGA are abated by increasing the concentration of the NOS substrate ARG.

Animals↗

Nitric oxide synthase inhibited by audouine in the rat brain.

Nitric oxide synthase (NOS) synthesizes nitric oxide (NO) from L-arginine (Arg) which has a guanidino group in its molecule. Audouine, a derivative of Arg, is the diguanidino compound. In this study, the effects of audouine on rat brain NOS activity were investigated by measuring nitrite and nitrate formation. Audouine inhibited NOS activity in a competitive (Ki = 2.10 microM) and partially uncompetitive (Ki = 49.7 microM) manner. Audouine is not substituted at the guanidino nitrogen, in contrast to most previously reported NOS inhibitors which were synthesized by substituting the guanidino nitrogen of Arg. Audouine is a novel inhibitor of NOS and should be useful for investigating the chemical nature of NOS and the roles of NO in the central nervous system.

Amino Acid Oxidoreductases↗

Inhibitory effect of arcaine on nitric oxide synthase in the rat brain.

Nitric oxide is synthesized by nitric oxide synthase (NOS) from L-Arg, which contains a guanidino group. Arcaine is the diguanidino compound and a derivative of Arg. This study was conducted to investigate the effects of arcaine on rat brain NOS activity, using nitrite and nitrate as indicators. Arcaine inhibited NOS activity in a linear mixed manner (K1 = 18.68 microM). Almost all previously reported NOS inhibitors were synthesized by substituting the guanidino nitrogen of Arg, but the guanidino nitrogens of arcaine were not substituted. Arcaine was also reported to be a competitive antagonist of the polyamine site on the N-methyl-D-aspartic acid (NMDA) receptor. Arcaine appears to be an excellent drug to investigate not only the chemical nature of NOS but also the functional and structural relationship between NOS and NMDA receptors.

Amino Acid Oxidoreductases↗

What is the most appropriate variable for estimation of mean pulmonary capillary wedge pressure by transesophageal pulsed Doppler echocardiography?

UNLABELLED: Although left ventricular (LV) inflow and pulmonary venous (PV) flow variables estimated by transesophageal Doppler echocardiography (TEE) reflect pulmonary capillary wedge pressure (PCWP), they are also affected by changes in cardiac function. The purpose of the present study was to detect the most appropriate variable for the estimation of PCWP by TEE in patients (pts) with ischemic heart disease. Several variables of LV inflow and left upper PV flow were compared with PCWP in 36 pts (six with angina pectoris and 30 with old myocardial infarction). Early diastolic flow (E) and atrial contraction flow (A) were used as LV inflow, while systolic forward flow (X), diastolic forward flow (Y) and atrial contractile reversal flow (z) were used as PV flow. The peak velocity of each flow wave (Ep, Ap, Xp, Yp, and Zp) and the time-velocity integral (Ei, Ai, Xi, Yi, and Zi) were measured. The ratio of Ep to Ap (Ep/Ap), Ei to Ai (Ei/Ai), Xp to Yp (Xp/Yp), Xi to Yi (Xi/Yi), Zp to Ap (Zp/Ap), Zi to Ai (Zi/Ai) and the systolic fraction of PV forward flow were calculated. Among these variables, the Zi/Ai ratio was most strongly correlated with PCWP (R = 0.80). The Zi/Ai ratio may not be influenced by atrial function because the augmentation of atrial pump function increases Zi as well as Ai, and this may be one reason why the ratio correlated well with PCWP. CONCLUSION: The Zi/Ai ratio is a new useful variable for estimating PCWP by TEE.

Aged↗

Application of automated flow injection analysis to determine nitrite and nitrate in mouse brain.

Nitric oxide level in the mouse brain was estimated by determination of nitrite and nitrate using an automated flow injection analyser for NOx. Different experimental conditions were examined to determine which produced reproducible results. After pretreatment of tissue specimens by the ZnSO4-NaOH method for deproteinization, reproducible and constant values were obtained. The values were more accurate immediately after sectioning without freezing than after 24 h with freezing. Two sacrifice methods, decapitation and microwave irradiation of the head, were investigated, but there was no significant difference between the two. No substances in the mouse brain exerted a positive or negative influence on the results. These results show that our method is indeed applicable to the brain tissue.

Animals↗

Structure-activity relationships of arginine analogues on nitric oxide synthase activity in the rat brain.

Nitric oxide (NO) is synthesized by nitric oxide synthase (NOS) from L-arginine (Arg) which has a guanidino group in its molecule. We examined the effect of 23 different Arg analogues on NOS activity in the rat brain. Though homoarginine, epsilon-guanidinocaproic acid and canavanine act as substrates of NOS, production of NO from them was lower than that from Arg. alpha-Guanidinoglutaric acid (2-GGA) and arcaine inhibited NOS activity at levels equal to NG-monomethyl-L-arginine (MeArg), a well known NOS inhibitor. Though almost all previously reported NOS inhibitors were synthesized by substituting the guanidino nitrogen of Arg, the guanidino nitrogens of arcaine and 2-GGA were not substituted. Furthermore, 2-GGA is a known endogenous convulsant in mammals, and arcaine, which was isolated from a marine mollusc, is also a convulsive substance. Hence, 2-GGA and arcaine will be excellent drugs to investigate not only the chemical nature of NOS but also the physiologic function of NO.

Amino Acid Oxidoreductases↗

alpha-Guanidinoglutaric acid, an endogenous convulsant, as a novel nitric oxide synthase inhibitor.

The effects of alpha-guanidinoglutaric acid (GGA), the levels of which were increased in the cobalt-induced epileptic focus tissue in the cerebral cortex of cats, on brain nitric oxide synthase (NOS) activity were observed. GGA inhibited NOS activity in a linear mixed manner (Ki = 2.69 microM) and was as effective as NG-monomethyl-L-arginine (MeArg; Ki = 3.51 microM), a well-known NOS inhibitor. Although MeArg was synthesized by substituting the guanidino nitrogen of L-arginine (Arg), GGA was a non-guanidino nitrogen-substituted guanidino compound. On the other hand, Arg, which is an endogenous NOS substrate, elevates the threshold of seizures induced by GGA. There is evidence that GGA is an endogenous, potent, and non-guanidino nitrogen-substituted NOS inhibitor and that suppression of nitric oxide biosynthesis may be involved in GGA-induced convulsions. Therefore, GGA may be a useful tool in elucidating the chemical nature of NOS and the physiological function of nitric oxide.

Amino Acid Oxidoreductases↗

Effect of lentinan on lymphocyte subsets of peripheral blood, lymph nodes, and tumor tissues in patients with gastric cancer.

The effect of lentinan on lymphocyte subsets of peripheral blood, lymph nodes, and tumor tissues in gastric cancer patients was investigated. A 2-mg dose of lentinan was administered to 12 patients intravenously twice, the first at 3-9 days before and the second the day before surgery. The results were then compared with a control group without lentinan administration comprising 12 patients. Regarding peripheral blood and lymph nodes without metastasis, lymphocyte subsets defined with anti-CD3, anti-CD4, anti-CD8, anti-Leu7, and anti-Leu11 were analyzed by flow-cytometry. As for tumor tissues, lymphocyte subsets defined with anti-CD3, anti-CD4, anti-CD8, anti-Leu11, and anti-M3 were analyzed after immunohistochemical staining. There were no significant changes in the lymphocyte subsets of peripheral blood between the two groups. In the lymph nodes, the CD4 cell ratios increased; otherwise in regard to tumor-infiltrating lymphocytes (TILs), the number of CD4, Leu11 and LeuM3 cells showed a prominent increase. Therefore, lentinan was observed to produce different effects in accordance with the subjective organs.

Aged↗

Property variations of stone casts following high-temperature sterilization.

The effects of high-temperature sterilization methods (boiling, dry-heating, autoclaving and chemiclaving) on the properties of four types of stone cast were determined. SEM observations were made of the cast surface before and after sterilization. High-temperature sterilization affected the properties of the stone casts. Boiling, dry-heating and autoclaving were considered to be unacceptable methods for sterilizing stone casts before making prosthetic restorations.

Calcium Sulfate↗

Endoscopic and clinicopathological features of primary gastric lymphoma.

Thirty-three patients with primary gastric lymphoma over a period of 32 years were studied. Endoscopic findings indicated that there were many cases of multiple lymphoma in the stomach, or with extensive tumor-infiltration, and that it was necessary to carefully inspect the entire stomach to determine the scope of resection and improve diagnostic accuracy. It is also particularly important not to damage the tissue during biopsy and to take deep large specimens from the ulcer margin, surrounding wall, and area of erosion. As compared clinicopathologically with gastric carcinoma, primary gastric lymphoma is found more frequently in younger females, with invasion of the entire stomach and extensive lymph node infiltration. By performing adequate resection of lymph nodes, as is done for gastric carcinoma, and administering appropriate combination chemotherapy, postoperative longterm results were similar to, or better than, those obtained with gastric carcinoma.

Adult↗

[A case of cardiac lipoma of the anterior tricuspid leaflet].

A 42-year-old man with cardiac lipoma of the anterior tricuspid leaflet is reported. He had a chief complaint of epigastric discomfort, and a pansystolic murmur was heard at the left sternal border in the 4th intercostal space. Two-dimensional echocardiography disclosed a mobile high density stalkless mass having several areas of low density. Two-dimensional Doppler echocardiogram revealed a moderate degree of tricuspid regurgitation. These findings were more clearly visualized on transesophageal echocardiogram. MRI revealed a high signal intensity on the T1-weighted image and a high radiodensity surrounding the mass using a contrast medium of Gd-DTPA. A 2.0 x 1.3 x 0.8 cm hemispherical, lobulated and sessile yellow mass was excised by means of open heart surgery, and tricuspid valvuloplasty was performed. The mass was adipose tissue and was surrounded by fibrous tissue just under the lamina fibrosa. These findings were compatible with those of the preoperative examinations, although the preoperative diagnosis was not conclusive. This was our first case of cardiac lipoma in which the tricuspid valve was successfully excised.

Adult↗

Multiple carcinoid tumors of the stomach with hypergastrinemia.

A 42-yr-old woman presented with multiple carcinoid tumors in her stomach and a markedly elevated serum gastrin level. Total gastrectomy was performed, and 22 small carcinoid tumors were found in the gastric fundus and body. A high serum gastrin level was revealed in the gastric drainage veins; still more gastrin was detected in the carcinoid tumors by the immunohistochemical method, and many secretory granules were found in the tumor cells with an electron microscope. The fundic gland showed marked atrophy, and there was some conglobation of endocrine cells (ECL cells). This case suggests a hypothetic sequence of anacidity due to atrophic gastritis----hypergastrinemia----proliferation of ECL cells----multiple carcinoids. A search of the Japanese literature revealed that 26 cases of multiple carcinoid tumors in the stomach have been reported so far, and most of them support this hypothesis.

Adult↗

The use of endoscopic ultrasound in determining the depth of cancer invasion in patients with gastric cancer.

Endoscopic ultrasonography (EUS) was performed in 110 patients with gastric cancer to examine the depth of cancer invasion. The normal gastric wall has a five-layer structure on EUS. In 19 lesions, changes on EUS were limited to the first and/or second layers, suggesting that invasion was limited within the mucosa. In 91 lesions, changes were evident in the third or deeper layers. Alterations in the EUS appearance could be divided into two types: type A, with destruction of the layered structure and type B with thickening of the layers. The amount of interstitial tissue in cancer was classified as medullary or intermediate in 90% of type A, and as scirrhous in 82% of type B tumor. The EUS diagnosis of invasion was 95% accurate for stage M cancers, 75% for SM, 64% for PM, 100% for SS, 79% for SE, and 100% for SI lesions. The overall accuracy was 81%. Accompanying fibrosis and metastatic perigastric nodes were the main reasons for overestimating the extent of disease.

Gastroscopy↗

[Diversity of complement activation by lentinan, an antitumor polysaccharide, in gastric cancer patients].

Lentinan, a pure polysaccharide, augments many immune responses in vivo but not in vitro. Therefore reaction with any factor is thought to be required for triggering of immunopotentiation by lentinan. To clarify the role of complement in this effect, we investigated whether lentinan could activate alternative pathway of complement or not and the relation with the immunopotentiation in 13 gastric cancer patients. C3, C3a, C5 and C5a levels as parameters of complement activation and interleukin-2 producing activity as parameter of immunopotentiation were assayed before and immediately after intravenous injection of lentinan. Among these complement components, remarkable change was observed only in C3a level. C3a level elevated to more than 1000ng/ml from less than 300ng/ml. And according to the degree and continuation of the elevation, these patients were classified into 3 types-(1) every time little elevation, (2) first remarkable and thereafter little elevation and (3) continuous remarkable elevation. Such an elevated C3a level returned to the level before lentinan injection within one day. When C3a level elevated to more than 1000ng/ml, leukocyte counts of peripheral blood decreased significantly and interleukin-2 producing activity increased concomitantly. Thus, there was diversity in response to lentinan and complement activation was suggested to have contribution in immunopotentiation by lentinan.

Adjuvants, Immunologic↗