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Biomedical subjects

Y Noda

Publications and source records attributed to Y Noda.

At least 199 records · Page 11Linked to original sources
PubMed1997

KIFC2 is a novel neuron-specific C-terminal type kinesin superfamily motor for dendritic transport of multivesicular body-like organelles.

We have cloned two novel C-terminal motor domain-type kinesin superfamily motor proteins (KIFCs) from mouse brain by utilizing a KIFC-specific consensus sequence. The first protein was the murine homologue of CHO2 antigen, a member of the kar3-type mitotic motor subfamily, and we designated this protein KIFC1. The other protein, KIFC2 (792 amino acids), is novel, with no significant similarity to known kinesin superfamily proteins (KIFs). KIFC2 was specifically expressed in adult neurons, and was immunofluorescently localized to punctate structures in cell bodies and dendrites, but was not detected in axons. Electron microscopic analysis of the immunoisolated KIFC2-bound organelles revealed that KIFC2 associates with multivesicular body (mvb)-like organelles, suggesting that KIFC2 functions as the motor for the transport of mvb-like organelles in dendrites.

Amino Acid Sequence↗
PubMed1997

Effects of VA-045 on learning and memory deficits in traumatic brain injury (TBI)-induced retrograde and anterograde amnesic mice.

1. No specific regimen has been developed to treat post-traumatic amnesia in man. In the present study, we examined the effects of (+)-eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a novel derivative of apovincaminic acid, on learning and memory deficits associated with a mild traumatic brain injury (TBI) in mice. 2. Two kinds of amnesia, TBI-induced retrograde amnesia (TRA) and anterograde amnesia (TAA), were produced by means of post- and pre-acquisition head injury, respectively, by a simple weight-drop device. A novel procedure of water-finding task was used to assess learning and memory functions. 3. Both TRA and TAA mice were dramatically impaired in the task performance, with prolonged latencies for finding and drinking in either retention test or retest, indicating that retention was impaired in TRA mice while learning and retention were impaired in TAA mice. 4. VA-045 administered 30 min post-trauma in TRA mice dramatically shortened the prolonged latencies for finding and drinking in both retention test and retest, indicating that VA-045 significantly improved the retention deficit observed in TRA mice. 5. VA-045 administered 30 min post-trauma in TAA mice dramatically attenuated the prolonged latencies for finding and drinking in both retention test and retest, indicating that VA-045 significantly improved the learning and retention deficits observed in TAA mice. 6. Administration of VA-045 30 min pre-trauma in normal mice markedly attenuated the delay of latencies for finding and drinking after trauma in both retention test and retest, which shows that VA-045 significantly prevented learning and retention deficits after TBI. 7. Motor activities were not significantly affected by either the TBI or the chemical treatment at the time of task examination in either experimental model. 8. It is concluded that VA-045 may have potential effects on learning and memory deficits observed in either TBI-induced retrograde or anterograde amnesia.

Amnesia↗
PubMed1997

Hydroxyl and superoxide anion radical scavenging activities of natural source antioxidants using the computerized JES-FR30 ESR spectrometer system.

Free radical scavenging activities of water-soluble extracts from some natural sources, health foods, and antioxidant substances were measured using the JES-FR30 JEOL spectrometer. The objective was to develop a standardized method whereby comparison could be made between the radical scavenging activities of complex mixtures. Scavenging of hydroxyl radical was determined using DMPO. Activity was calibrated using a standard material, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1), an analog of vitamin C and vitamin E which is water soluble and stable at room temperature. The order of greatest hydroxyl radical scavenging activity was green tea extract, pine bark extract (Pycnogenol), Ginkgo Biloba extract (EGb 761), a flavonoid blend of several fruit and vegetable extracts (GNLD), and Bio-Normalizer (Sun-O Corp). Activity was determined after treatment of samples with ascorbic acid oxidase. This treatment revealed the presence of ascorbate in some natural extracts and commercial preparations. The pine bark extract was the most heat resistant and had ascorbate-like activity in the preparations. Scavenging of superoxide anion was determined using the spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and analyzed by comparison with a standard curve made with superoxide dismutase. Comparison of the water solubilized components of natural source antioxidants showed that filtrates fractionated using centrifuge type Millipore filter tubes (M.W. < 100,000; M.W. < 10,000) also had almost the same SOD-like activity. Samples were also treated with ascorbate oxidase or by heating (100 degrees C for 10 min). The order of activity, from greatest to least, was Ginkgo biloba extract EGb 761, pycnogenol, beta-catechin, tea and BioNormalizer.

Antioxidants↗
PubMed1997

A concussive-like brain injury model in mice (I): impairment in learning and memory.

The modeling of human concussive brain injury (CBI) in the laboratory has been challenging. In the present study, we developed an experimental CBI model in mice using a novel weight-drop device. Various injury levels were examined by adjusting the height of the falling weight (diameter 10 mm, length 20 cm, weight 21 g). At a height of 50 cm, the impact resulted in a mortality rate of 46.7% with a skull fracture rate of 28.6%. At a height of 25 cm, however, the impact produced a concussive-like brain injury (CLBI) to the mice without skull fracture. A series of pathophysiological and neurobehavioral responses was evaluated at this injury level. The CLBI mice lost muscle tone and righting reflex response immediately following the trauma and recovered from the latter within a short duration of 1.6 +/- 0.32 min (mean +/- SE). Brain edema formation started at 12 h, reached a maximum at 24 h and recovered 48 h. Typically edema was found in the neocortex, hippocampus, and cerebellum, but not in the brain stem. Deficits in the feeding behaviors lasted for 2 days, accompanied by lower body weight persisting for 5 days. The body weight growth rate for 24 h returned to the control levels by the third day postinjury. Learning and memory were evaluated at the end of 1-3 weeks after the trauma using a water-finding task. At 1 week, exploratory behaviors were slightly inhibited while learning and memory were profoundly impaired. Interestingly, the learning and memory deficits lasted for 2 weeks while recovering to the control levels by 3 weeks. No motor disability was found in the CLBI mice during the 3-week evaluations. These results indicate that the weight-drop impact produced graded injury to the brain, and at the injury level of 25 cm it produced a CLBI in the mice in which the characteristics of transient loss of neurobehavioral responses, short duration of brain edema, and long-lasting learning and memory deficits are similar to those of human CBI.

Animals↗
PubMed1997

A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus.

A novel concussive-like brain injury (CLBI) model characterized by transient neurobehavioral depression, short duration of brain edema, and long-lasting memory deficits has been reported in our companion paper. This was achieved by dropping a 21-g weight from a height of 25 cm onto the head of a mouse. In the present study, we examined the histopathological changes in this model. Male ddY mice were subjected to either the trauma or sham injury. Gross pathological examination of the brain 1 h posttrauma did not demonstrate subdural, subarachnoid, intraventricular, periventricular, and intraparenchymatous hemorrhage, focal lesions or contusions. Microscopic examination 24 h posttrauma with Nissl staining (cresyl violet), however, revealed a selective bilateral neuronal cell loss in the cerebral cortex and hippocampus but not in the regions of the thalamus, cerebellum, and brain stem. The characteristics of neuronal cell loss in the cortex suggested that this pathology was related in part, to the head impact dynamics, since the cell loss was noted in the central portion of the supraventricular cerebral cortex (p < 0.001), the site of the weight impact, gradually decreasing peripheral to this site, and disappearing in the areas remote from this locus. In contrast, neuronal cell loss seen in the hippocampus did not suggest that this pathology was directly associated with the impact site. Neuronal cell loss was concentrated in the pyramidal cell layer of CA2 (p < 0.01) and CA3 (p < 0.01), and a lesser degree was noted in the subfields of CA3c (p < 0.05) and the hilar region (p < 0.05) but not in the subfields of CA1 and the dentate gyrus layers. The present study characterized the histopathological change seen in the CLBI model, demonstrating the selective neuronal cell loss following weight-drop concussion in mice.

Animals↗
PubMed1997

NGFI-B, c-fos, and c-jun mRNA expression in mouse brain after acute carbon monoxide intoxication.

The expression of immediate early genes (IEG) has been documented in the brain after various kinds of insults such as ischemia and hypoxia. To determine whether acute carbon monoxide intoxication (ACOI) might trigger IEG expression, adult ddY mice were subjected to carbon monoxide exposure at a rate of 30 mL/min for 35 seconds. The levels of NGFI-B, c-fos, and c-jun mRNA were determined by Northern blot analysis. A time-course study in the cerebral cortex indicated that the induction of NGFI-B, c-fos, and c-jun mRNA started as early as 15 minutes, reached a peak at 30 minutes, and returned to the basal level at 1 hour after the ACOI. In addition, the temporal feature of the induction of these IEG mRNA in the hippocampus was very similar to that in the cerebral cortex. Examination of brain regions at 30 minutes after the ACOI revealed a significant induction of NGFI-B mRNA in the cerebellum, thalamus-hypothalamus, brainstem. as well as in the cortex and hippocampus, but not in the striatum or olfactory bulb. Furthermore, the neuroanatomical distribution of c-fos mRNA at 30 minutes after the ACOI was very similar to that of the NGFI-B mRNA. The widespread distribution of these IEG in the brain, especially in the cerebellum and brainstem, indicates that the major cause for the triggering of IEG expression in the brain by the ACOI might be a diffuse hypoxia. These findings show for the first time the temporal and spatial expression of IEG in the brain after ACOI.

Acute Disease↗
PubMed1997

Mixed osteoclastic/pleomorphic-type giant cell tumor of the pancreas with ductal adenocarcinoma: histochemical and immunohistochemical study with review of the literature.

We described a rare form of giant cell tumor of the pancreas composed of mixed osteoclastic/pleomorphic-type giant cell tumor with ductal adenocarcinoma. Immunohistochemical study showed positive staining of cytokeratin and epithelial membrane antigen for pleomorphic-type giant cells and ductal adenocarcinoma but negative for osteoclastic-type giant cells. Vimentin stained positive in both types of giant cells but negative in adenocarcinoma. Osteoclastic-type giant cells were strongly positive for CD68 and tartarate-resistant acid phosphatase was present in these cells, suggesting the osteoclast-like character. CD68 was negative for both pleomorphic-type giant cells and ductal adenocarcinoma. From these findings, we consider that this tumor might be a carcinosarcoma-like neoplasm consisting of both an epithelial and a histiocytic-mesenchymal component.

Aged↗
PubMed1997

Hemidiaphragmatic paralysis following subclavian vein catheterization.

The right subclavian artery was inadvertently punctured during attempted preoperative insertion of a right subclavian venous catheter in a 59-yr-old woman undergoing radical hysterectomy. Large supraclavicular swelling became apparent soon after the arterial puncture. The postoperative chest X-ray obtained approximately 24 h after the catheterization revealed significant elevation of the right hemidiaphragm, which was further augmented on the 2nd to 4th postoperative days; oxygenation was concurrently impaired during these days. It was clinically judged that the hemidiaphragmatic paralysis was responsible for the elevated diaphragm. Both chest roentogenogram and arterial blood gas analyses started to improve on the 5th day, finally returning to normal on the 6th day. It is unlikely that the surgical procedure caused the paralysis, because it dealt only with the lower abdomen. Rather, the attempts at the subclavian venous catheterization probably caused the phrenic nerve paralysis, because the phrenic nerve travels very close to the subclavian vessels. Both the large haematoma formation following the arterial puncture and the time course of the paralysis suggest that compression of the right phrenic nerve by the haematoma, rather than needle trauma, was responsible for the paralysis.

Catheterization, Central Venous↗
PubMed1997

Involvement of activation of dopaminergic neuronal system in learning and memory deficits associated with experimental mild traumatic brain injury.

Much evidence has indicated that a disturbance in dopamine neurotransmission following mild to moderate traumatic brain injury is involved in the development of post traumatic memory deficits. In the present study we examined the effects of a dopamine receptor agonist and some antagonists on latent learning and memory deficits associated with a concussive traumatic brain injury in mice. Anaesthetized animals were subjected to mild traumatic brain injury by dropping a weight onto the head, and a single-dose injection of apomorphine (0.3-3.0 mg/kg) or haloperidol (0.3-3.0 mg/kg) was made i.p. 15 min after the trauma. One week later, a water-finding task consisting of an acquisition trial, a retention test and a retest was employed to assess learning and memory functions. Mice that had received a traumatic brain injury were impaired in task performance, with prolonged latencies for finding and drinking in the retention test and retest. Administration of haloperidol but not of apomorphine significantly shortened the prolonged latency in both of the tests, indicating that antagonism of dopamine receptors is beneficial for the recovery of post traumatic memory deficits. In order to evaluate which receptor subtype plays the major role in this model, we examined the effects of SCH-23390 (0.03-0.3 mg/kg), a D1 receptor antagonist, and sulpiride (3.0-30 mg/kg), a D2 receptor antagonist, in the same experimental paradigm. The results showed that administration of sulpiride but not of SCH-23390 significantly improved the deficits in task performance, indicating that D2 receptors are the major site of action. However, combined treatment with SCH-23390 (0.03-0.3 mg/kg) and sulpiride (3.0 mg/kg) at doses that had no effect when the antagonists were given alone exerted a significant additive effect in improving these deficits, indicating that interaction between D1 and D2 receptors is involved in these processes. The present results suggest that a dopaminergic mechanism contributes to the memory dysfunction associated with traumatic brain injury.

Animals↗
PubMed1997

[An autopsy case of chronic granulomatous disease diagnosed by biopsy].

This report concerns a male patient aged 25 years, diagnosed at the age of 12 years as suffering from chronic granulomatous disease. This patient had p47-phox deficiency. He was admitted to this hospital because of fever and dyspnea accompanied by right spontaneous pneumothorax. He failed to respond to medical treatment. He died from respiratory failure four months after admission. Autopsy demonstrated pigmented lipid histiocytes characteristic of CGD. These characteristic pigmented cells were distributed in the spleen, liver, lymph nodes and in the small intestine. As for the nature of the pigment, lipofuschin-like compound were identified. Granulomatous component was seen in the mucosa of the stomach obtained by operation. The presence and characteristic distribution of such pigmented macrophages in tissue in young adults may suggest the diagnosis of CGD.

Adult↗
PubMed1997

Cytotoxicity of naphthoquinones toward cultured resting murine leukemia L1210 cells in the presence of glutathione, diethyl maleate, or iodoacetamide.

Sixteen naphthoquinones with various substituents were tested for cytotoxicity toward cultured resting leukemia L1210 cells. The cytotoxicity of all the naphthoquinones examined was not affected at all by the treatment in combination with diethyl maleate, a glutathione-specific SH-blocking agent in the cells. Depending on the characteristics of the response to the treatment in combination with iodoacetamide (IAA) and glutathione (GSH), these naphthoquinones were tentatively classified into three groups. The chemicals of Group I, which include naphthoquinones carrying an electron-donating group(s) other than an OH group on the quinone ring moiety, showed synergistic cytotoxicity with IAA and no reduction in cytotoxicity with GSH. Those of Group II, which include naphthoquinones without an electron-donating group on the quinone ring moiety, showed no synergy with IAA but appreciable reductions in cytotoxicity with GSH. Group III includes 2-hydroxylated naphthoquinones, which showed neither synergy with IAA nor cytotoxicity reduction with GSH. Cytotoxicity was discussed in terms of the electron-deficiency of the quinone ring moiety. It is suggested that the cytotoxicity of Group I quinones comes from the active oxygen generation which follows semiquinone formation, whereas that of the other groups of quinones is not likely caused simply by either SH-blocking of biomolecules or active oxygen-related mechanism.

Alkylating Agents↗
PubMed1997

Enhanced cytotoxicity of some triterpenes toward leukemia L1210 cells cultured in low pH media: possibility of a new mode of cell killing.

Several triterpenes were tested for cytotoxicity by our contrived primary screening method using resting or dormant leukemia L1210 cells after 3 d-preculture without medium change. Some triterpenes were found to be more cytotoxic toward the 3 d-precultured resting cells than toward the growing cells in a fresh medium. These triterpenes are distinguished by highly selective cytotoxicity toward the starved resting cells unlike common anticancer agents. The highest selectivity was shown by betulinic acid, the ratio of its IC50 values toward the growing versus resting cells amounting to 175. It is suggested that this selective cytotoxicity is attributable to low pH (< or = 6.8) of the medium. It is noteworthy that betulinic acid is not cytotoxic at all in media of ordinary pH (> or = 7.0) even after a 48-h exposure. Betulinic acid might be promising as an antitumor agent toward solid tumors because the interior pH of tumor tissues is generally lower than in normal tissues.

Animals↗
PubMed1997

[Comparison of echograms by a microscanner and histological findings of the common bile duct, in vitro study].

To confirm the relationship between the layer structure of the common bile duct by a microscanner (MS) and its histological features, we performed a study using the pinning method with needles and catgut. The locations of 67 needles inserted at random depths in 29 slices of the resected common bile duct from 18 patients were confirmed both by a MS and a microscope. The wall of the common bile duct was delineated as a two- (42 points) or three-layer structure (25 points); "low and high" or "high, low, and high echoic layers" from the mucosal side. A fibrotic layer (ss 1) was often (56/67 points, 16/18 patients) seen in the subserosa (ss) containing nerves and vessels larger than 100 mu in diameter. Among the 51 needle echoes demonstrated in the inner hypoechoic layer, 2 were located in the mucosa (m), 12 in the fm, 19 in the af, 17 in the ss 1, and 1 in the fatty layer of the ss (ss 2). Five of the 6 needles in the outer hyperechoic layer were in the ss 2, and 1 was in the pancreatic parenchyma (pa). Four of the 8 needles at the border between the inner hypoechoic layer and the outer hyperechoic layer histologically corresponded to fm, af, ss 1, and pa, respectively, and the other four corresponded to ss 2. From these results, we conclude that the inner hypoechoic layer contains not only m, fm, and af, but also ss 1. Therefore, this should be kept in mind for the preoperative assessment of the depth of bile duct carcinoma by MS.

Bile Duct Neoplasms↗
PubMed1997

[Relationship between the activity of serum adenosine deaminase including its isozymes and lymphocyte subpopulation in patients with pulmonary tuberculosis].

Adenosine deaminase (ADA) is one of the enzymes in the purine metabolism and divided into two isozymes, ADA-1 and ADA-2. It is known that the activity of this enzyme is elevated in the sera of patients with pulmonary tuberculosis, sarcoidosis and other diseases, however there are few reports about the change of the activity of this enzyme under treatment. It is often said that this enzyme may have its origin in T lymphocyte, but it remains to be proved. That goes for each of two isozymes, too. In this study, we investigated the activity of serum total ADA, ADA-1 and ADA-2 in patients with pulmonary tuberculosis on admission and after three months' treatment. We also studied the correlation of lymphocyte subpopulation with these enzymes. The activity of total ADA, ADA-1 and ADA-2 was significantly higher in the sera of patients with pulmonary tuberculosis than in those of healthy persons. ADA-2 activity correlated significantly and negatively with the number of CD3+ lymphocytes and CD4+ lymphocytes. The change rate of ADA-2 activity during three months' treatment correlated significantly and negatively with the change rate of CD4/8. These results may suggest that there is a close correlation between the activity of ADA-2 and lymphocyte subpopulation in the sera of patients with pulmonary tuberculosis. ADA-1 activity did not correlate with lymphocyte subpopulation significantly, but it decreased significantly after three months' treatment. The activity of ADA-1 also may have certain relations with the disease process of pulmonary tuberculosis.

Adenosine Deaminase↗
PubMed1997

Gliclazide scavenges hydroxyl, superoxide and nitric oxide radicals: an ESR study.

The role of reactive oxygen species in diabetes and its complications are well known. Two therapeutic agents commonly used in the treatment of diabetes are the sulfonylureas, gliclazide and glibenclamide. These drugs effectively reduce blood sugar in non-insulin dependent diabetes millitus by augmenting insulin release. Gliclazide is known to be a general free radical scavenger as demonstrated by inhibition of o-dianisidine photo-oxidation. In this study, the effects of gliclazide and glibenclamide on free radicals were examined in vitro, using electron spin resonance (ESR) spectroscopy. Superoxide radical (O2.-) generated from hypoxanthine-xanthine oxidase system, or hydroxyl radical (.OH) generated by the Fenton reaction, were analyzed as spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). NO was generated from 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7), and analyzed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (carboxy-PTI) produced from the reaction between 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and NO. Gliclazide scavenged O2.-, .OH and NO in a dose-dependent manner whereas glibenclamide was without effect. These findings suggest that gliclazide is not only effective in reducing blood sugar but also may be beneficial by inhibition of lipid and protein denaturation, which leads to the development of diabetic complications.

Dose-Response Relationship, Drug↗
PubMed1997

Free radical scavenging properties of alacepril metabolites and lisinopril.

Alacepril is an inhibitor of the angiotensin converting enzyme (ACE), and is commonly used as an antihypertensive. In this study, the effects of alacepril, its metabolites, desacetylalacepril and captopril, and also lisinopril, which has no sulfhydryl group in the structure, on free radicals were examined in vitro, using an ESR method. Superoxide and hydroxyl radical scavenging activities of alacepril metabolites, desacetylalacepril and captopril, were observed, whereas lisinopril hardly scavenged the superoxide or the hydroxyl radicals. Alacepril and its metabolites did not scavenge nitric oxide, but lisinopril showed slight scavenging activity. These findings suggest that the biological action of alacepril may be partly due to the antioxidant effect of its metabolites, having a sulfhydryl group.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Non-Hodgkin's lymphoma of Waldeyer's ring as a manifestation of lymphoproliferative diseases associated with human T-cell leukemia virus type 1 in southwestern Japan.

Adult T-cell leukemia/lymphoma (ATL) usually presents with node- and/or cutaneous-based diseases, with a leukemic picture. It is not clear whether ATL initially manifests with lesions in Waldeyer's ring (WR) in an ATL-endemic area. In the present study, we examined distributions of immunophenotypes and the presence of human T-cell leukemia virus type 1 (HTLV-1) and Epstein-Barr virus (EBV) genomes in 62 cases of non-Hodgkin's lymphoma (NHL) of WR (NHL-WR) from two areas of Japan: Osaka, an ATL-nonendemic area (25 cases), and Okinawa, an ATL-endemic area (37 cases). In both areas, age ranged from 10 to 94 years (median, 64 yr), with a male-to-female ratio of 1.81:1. Twelve patients were in Stage I, 34 in Stage II, and 6 in Stage III; stage was unknown in 10. The 25 Osaka cases were B-cell type (16 diffuse immunoblastic type (DIB), 8 diffuse large cell predominantly noncleaved cell (DLNC), 1 cleaved cell (DLC)). Of the 37 Okinawa cases, 20 were B-cell type (3 DIB, 10 DLNC, 2 DLC, 5 other). The remaining 17 cases showed T-cell phenotype (4 DIB, 3 DLC, 3 diffuse large cell not otherwise specified, 7 other). There was a significant difference in the distribution of immunophenotypes between these two areas (P < .001). Combined studies of polymerase chain reaction (PCR) and in situ hybridization revealed the presence of EBV genome in 1 (4%) of 24 Osaka cases, 2 (13%) of 16 B-cell NHLs from Okinawa, and 3 (23%) of 13 T-cell NHLs from Okinawa. HTLV-1 proviral genome was found in 11 (85%) of 13 T-cell lymphomas from Okinawa but could not be detected in B-cell lymphomas from Osaka and Okinawa. Combined clinical, histologic, serologic, and PCR findings suggest that NHL-WR in an ATL-endemic area could be an initial manifestation of ATL.

Adolescent↗