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Biomedical subjects

T Ueyama

Publications and source records attributed to T Ueyama.

At least 109 records · Page 6Linked to original sources

Mutation of the trkB gene encoding the high-affinity receptor for brain-derived neurotrophic factor in stroke-prone spontaneously hypertensive rats.

Brain-derived neurotrophic factor and its receptor, trkB, are thought to play a crucial role for protection against neuronal death induced by brain ischemia, such as in stroke. In the present study we found a missense mutation in the trkB gene from all of the five substrains of stroke-prone spontaneously hypertensive rats (SHRSP) that were examined. This mutation was not found in six out of seven hypertensive but stroke-resistant ancestral strains (SHR) of SHRSP, nor in any of seven strains of normotensive, non-stroke-prone strains. Hippocampal neurons, which are particularly vulnerable to damage in stroke, were shown to be more susceptible to ischemic damage in SHRSP than in either SHR or normotensive, stroke-resistant controls. The association of a mutated trkB gene with the stroke-prone genotype found in this study suggests that the trkB gene merits further study as a promising candidate gene for stroke.

Animals↗

Mutation of low affinity nerve growth factor receptor gene is associated with the hypertensive phenotype in spontaneously hypertensive inbred rat strains.

We previously reported a missense mutation in the low affinity nerve growth factor receptor (LNGFR) gene of spontaneously hypertensive rats (SHR), proposing this gene as a promising candidate in genetic hypertension. In this study we provide further support for implicating this gene in genetic hypertension using two new inbred strains, WKHT and WKHA rats. These strains originated from crossbreeding SHR rats with normotensive Wistar-Kyoto rats (WKY): WKHT rats are hypertensive but not hyperactive, and WKHA rats are hyperactive but not hypertensive. Nucleotide sequence analysis of the LNGFR gene revealed that WKHT has the same mutation as SHR, whereas WKHA has the normal sequence, as seen in WKY. These results support our original hypothesis that the mutated LNGFR gene is linked to hypertension, since the mutation had co-segregated with the hypertensive trait, and not hyperactivity trait of SHR.

Amino Acid Sequence↗

In situ hybridization analysis of substance P receptor in the rat retina.

Substance P receptor is known to provide a principal interface between tachykinin peptides and tachykinin-sensitive cells in retinal circuitry and to produce several physiological functions such as excitation of ganglion cells. We reported results of in situ hybridization analysis of substance P receptor in rat retina using digoxigenin-labeled RNA probes to yield discrete cell labeling. Distinct hybridization signal was present in a great majority of ganglion cells that provide retinal fibers to a central target. It was also present in a subpopulation of amacrine cells. Following optic nerve crush, ganglion cells lost their hybridization signal in a time-dependent manner, while hybridization-positive amacrine cells were persistently seen. From the results, we identified the hybridization message as distinctly localized to two systems, output cells and intrinsic cells in retinal circuitry.

Animals↗

Immobilization stress induces c-fos and c-jun immediate early genes expression in the heart.

Emotional stress is considered to be one of the etiological factors in ischemic heart disease (IHD) and sudden cardiac death (SCD), mechanisms of which are poorly understood. Immediate early genes (IEGs), such as c-fos and c-jun are used as tools for detection of cellular activation. Male Wistar rats were exposed to acute immobilization (IMO). IMO stress for 30 min induced c-fos and c-jun mRNAs expression in the myocardium and the smooth muscle layer of the coronary arteries. IMO stress for 2 h also induced Fos and Jun like-immunoreactivities in the same regions. Distribution of IEG mRNAs and their protein products in the myocardium was not uniform but rather localized. These data provided histological evidence for an early cellular event in the stress response whose consequences could result in activation of tissues in the myocardium and coronary arterial smooth muscle cells which play a role in the pathophysiological changes in IHD and SCD.

Animals↗

Nitric oxide synthase-containing magnocellular neurons of the rat hypothalamus synthesize oxytocin and vasopressin and express Fos following stress stimuli.

We investigated the chemical and anatomical features of nitric oxide synthase (NOS)-containing neurons in the paraventricular and supraoptic nuclei in the rat hypothalamus using combinations of enzyme histochemistry, in situ hybridization and immuno-histochemistry. Neurons expressing NOS mRNA completely overlapped with NADPH-diaphorase-positive neurons. Topographical distribution of NOS was segregated from that of CRF-containing parvicellular neurons in the posterior paraventricular nucleus but overlapped with that of magnocellular neurons. In the paraventricular nucleus, 70% of oxytocin neurons contained NOS, which corresponded to one half of NOS neurons. About one third of vasopressin-immunoreactive neurons were NADPH-diaphorase-positive and the same proportion of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. In the supraoptic nucleus, 50% of oxytocin neurons were NADPH-diaphorase-positive, which corresponded to 40% of NOS neurons. About 25% of vasopressin neurons were NADPH-diaphorase-positive, and 30% of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. When NADPH-diaphorase histochemistry was performed first, subsequent immunostaining was markedly perturbed. Using fluoro-gold as a retrograde tracer, 4% of NADPH-diaphorase-positive neurons were shown to contribute to the descending projection to the spinal cord. About 40%-50% of NADPH-diaphorase-positive neurons exhibited Fos immunoreactivity after injection of lipopolysaccharide or hypertonic saline, while only 10%-15% of these neurons expressed Fos in response to immobilization or pain. Endogenous NO may be involved in the regulation of magnocellular functions, especially when the internal environment is disturbed.

Animals↗

Ovarian mucinous cystadenocarcinoma with sarcoma-like mural nodules.

We present a rare case of a 31-year-old woman with a mucinous ovarian tumor with sarcoma-like mural nodules. The epithelial elements consisted of a mixture of benign, borderline-malignant, and mucinous adenocarcinoma; the sarcoma-like mural nodules consisted of pleomorphic and epulis-like cells. The lesion was resected for an ovarian tumor. In an immunohistochemical study, these cells stained for lysozyme and vimentin. The patient received 2 courses of cisplatin (100 mg/m2). There was no evidence of disease at a second-look laparotomy after 1 year, and none upon examination 6 years after the initial operation. The mural nodules might be of non-epithelial origin. The prognosis of patients with this rare lesion appears favorable, according to this and previous reports.

Adult↗

Synthesis, characterization, and immunologic properties of detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins.

Nontypeable Haemophilus influenzae (NTHi) is an important cause of otitis media in children and of pneumonitis in adults with depressed resistance. Lipooligosaccharide (LOS) is a major surface antigen of NTHi and elicits bactericidal and opsonic antibodies. We prepared detoxified LOS (dLOS) protein conjugates from NTHi for use as experimental vaccines. LOS from NTHi 9274 was treated with anhydrous hydrazine and had its toxicity reduced to clinically acceptable levels. dLOS was bound to tetanus toxoid (TT) or high- molecular-weight proteins (HMPs) from NTHi through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratio of the dLOS to protein carriers ranged from 26:1 to 50:1. The antigenicity of the conjugates was similar to that of the LOS alone as determined by double immunodiffusion. Subcutaneous or intramuscular injection of the conjugates elicited a 28- to 486-fold rise in the level of immunoglobulin G antibodies in mice to the homologous LOS after two or three injections and a 169- to 243-fold rise in the level of immunoglobulin G antibodies in rabbits after two injections. The immunogenicity of the conjugates in mice and rabbits was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced LOS antibodies induced complement-mediated bactericidal activity against the homologous strain 9274 and prototype strain 3189. These results indicate that a detoxified LOS-protein conjugate is a candidate vaccine for otitis media and pneumonitis caused by NTHi.

Animals↗

A case of hypertrophic obstructive cardiomyopathy associated with autonomic nervous dysfunction.

Autonomic nervous dysfunction has recently been considered to be an etiological factor in syncope and sudden death in cases of hypertrophic cardiomyopathy. However, the precise mechanism is still unknown. A 73-year-old woman with obstructive hypertrophic cardiomyopathy was hospitalized with complaints of impaired consciousness; faintness 3 to 4 h after meals, lightheadedness while walking, and syncope during and after defecation and micturition. Faintness was induced by alimentary hypoglycemia related to gastrectomy performed 5 years previously. Lightheadedness and syncope were accounted for by autonomic nervous failure combined with an impairment of alpha 1-adrenoceptor in vasoconstriction and the carotid sinus hypersensitivity which accompanied preceding events such as abdominal pain, defecation and micturition, which could enhance the vagally-mediated baroreceptor reflex.

Aged↗

Effects of fatty acids on accumulation and secretion of histamine in RBL-2H3 cells and leukotriene release from peritoneal exudate cells isolated from Wistar rats.

Effects of fatty acids on accumulation and secretion of histamine in rat basophilic leukemia RBL-2H3 cells and leukotriene release from peritoneal exudate cells isolated from Wistar rats were examined in relation to the manifestation of type I allergic reactions. When RBL-2H3 cells were cultured for 24 h in the presence of 1 mM short chain fatty acids, a marked increase in histamine accumulation was observed, especially with butyric acid. In addition, Ca-ionophore A23187-stimulated histamine release was enhanced in the cells treated with 0.1 mM mono to hexa unsaturated fatty acids with 18 to 22 carbon-chains. On the other hand, LTB4 release from rat peritoneal exudate cells was inhibited in the presence of polyunsaturated fatty acids, both n-6 and n-3, having more than 3 double bonds. Inhibitory activity was enhanced by an increase in the number of double bonds, and docosahexaenoic acid (DHA) exerted the highest activity with complete inhibition at 0.1 mM and 35.5% inhibition even at 10 microM. A hydrophobic radical scavenger (9,10-diphenylanthracene) and two antioxidants (butyrated hydroxytoluene and alpha-tocopherol) inhibited the production of LTB4, but hydrophilic counterparts (mannitol and ascorbic acid) did not. These results suggest that lipophilic anti-oxidative agents, as well as PUFA, inhibit the production of LTB4.

Animals↗

[Coronary artery bypass grafting surgery without cardiopulmonary bypass in a patient with calcified aorta].

Coronary artery bypass surgery in a 67-year-old male with severe calcified ascending aorta was performed without cardiopulmonary bypass under beating heart, utilizing the left internal thoracic artery graft. No neurological complication was observed and postoperative angiogram showed good graft patency. We think coronary revascularization without cardiopulmonary bypass can be one of the safe and reliable methods to avoid complications associated with aortic cross clamping and aortic cannulation with severely calcified aorta.

Aged↗

[Traumatic basilar artery dissection presenting with "locked-in" syndrome: report of a case].

We encountered a case of traumatic basilar artery dissection presenting with "locked-in" syndrome. A 46-year-old-man fell approximately 2 meters and landed in an inverted position. He was admitted to our hospital after 4 days. He was in coma on admission, and neurological examination revealed that his pupils were 2 mm in size and reactive, the corneal reflex of both sides was absent, the pharyngeal reflex was absent, and quadriplegia was present. CT and MRI showed infarction at the ventral portion of the pons. 3D-CT and CT using a bone algorithm showed fractures of the upper clivus, the left petrous bone, and the left occipital condyle. Angiography showed a pearl and string sign at the upper basilar artery. It is suggested that the cause of the infarction of the ventral portion of the pons was the occlusion of the perforating arteries due to the basilar artery dissection, and the mechanism of the basilar artery dissection was the hyperextension or hyperflexion of the basilar artery by the movement of the brain stem caused by the traumatic impact. Repeated angiography revealed gradual improvement. Eventually he freed himself from the "locked-in" syndrome.

Basilar Artery↗

[Transsphenoidal surgery for a case of empty sella syndrome associated with GH secreting pituitary adenoma].

A 33-year-old woman was admitted to our hospital with acromegalic face as her chief complaint. Her neurological examination was normal, and endocrinological examination revealed a high level of growth hormone (GH) (12.8 ng/ml). CT cisternography and MRI showed an enlarged empty sella and a pituitary tumor. We performed a transsphenoidal approach operation to remove the tumor and to repair the empty sella. The tumor, which was compressed to the lateral and posterior wall of the sella turcica by the empty sella, was totally removed by meticulous curetting. It was histologically diagnosed to be a pituitary adenoma. The empty sella was elevated by coagulation of intrasellar dura and herniated arachnoid membrane, and then we filled the residual intrasellar cavity with bone fragments and fat. Postoperative hormonal examination showed normal findings, and MRI revealed obliteration of the empty sella. Surgical indication for primary empty sella is not established, but in cases associated with pituitary adenoma, transsphenoidal surgery is necessary. We reported a case of empty sella syndrome associated with GH secreting pituitary adenoma, and in this report, we introduced a new surgical technique for repairing an empty sella.

Adenoma↗

Detection of Haemophilus influenzae in adenoids and nasopharyngeal secretions by polymerase chain reaction.

Haemophilus influenzae in the nasopharynx is thought to be related to the pathogenesis of otitis media with effusion (OME). However, the positive rate measured by the conventional culture method is not high enough for bacterial infection to be considered the chief pathogenic factor. Polymerase chain reaction (PRC) and the conventional culture method were applied to detect H. influenzae in the adenoids and nasopharyngeal secretions of 17 children with OME (2 to 7 years of age). The percentage of P6-positive adenoid samples was 82.4% while 70.6% were culture positive. In nasopharyngeal secretions, 88.2% were P6-positive and 64.7% were culture positive. All samples in which H. influenzae was cultured were positive with PCR. The positive rate was significantly greater with PCR than with the culture method, and it showed a significant concordance between adenoids and nasopharyngeal secretions (p = 0.0027). These findings suggest that the presence of H. influenzae in the nasopharynx is more common in children with OME than previously reported, and that H. influenzae in adenoids might play an important role in OME.

Adenoids↗

Enkephalin-immunoreactive fastigial neurons in the rat cerebellum project to upper cervical cord segments.

By using enkephalin immunohistochemistry combined with retrograde fluorescent labelling, a great majority of neurons in the rat cerebellum sending their axons to the spinal cord were shown to contain enkephalin immunoreactivity. These neurons were numerous and clustered in the fastigial nucleus but far less abundant in other cerebellar nuclei. Enkephalin-immunoreactive fibers present in the ventral horn and the central cervical nucleus of upper cervical cord segments almost completely disappeared contralaterally following kainic acid-induced cell loss in the fastigial nucleus. The results indicate that fastigial and some other cerebellar nucleus neurons provide enkephalin-containing projections toward these spinal sites.

Animals↗

Immunohistochemical evidence for enkephalin and neuropeptide Y in rat inferior colliculus neurons that provide ascending or commissural fibers.

Enkephalin- and neuropeptide Y-expressing neurons which offer commissural axons or axons toward auditory thalamus were identified in the rat inferior colliculus. These neurons exhibited a differential distribution pattern. The results provide evidence for regional specificity and chemical heterogeneity of neurons in the auditory midbrain.

Afferent Pathways↗

Correlation between tumor volume doubling time and histologic findings in gastric smooth muscle tumors: clinical implications of tumor volume doubling time.

To assess the clinical implications of the tumor volume doubling time of gastric smooth muscle tumors based on a comparison with the histologic findings, seven tumors (four leiomyomas and three leiomyosarcomas) were followed up by consecutive upper gastrointestinal studies between March 1985 and December 1993. The patients were four men and three women with an average age of 58 years (range: 50-71 years). The observation period ranged from 6 to 51 months, with an average of 35 months. All tumors were surgically resected and the histologic diagnosis was confirmed. The following microscopic features were evaluated: 1) mitotic rate, 2) nuclear atypia, and 3) cellularity. Each tumor was also evaluated for the presence or absence of necrosis, hemorrhage, and degeneration. The doubling time ranged from 5 to 27 months with a mean of 16 months. There was a strong negative correlation between the mitotic rate and the doubling time (r = -0.935, P = 0.0019). The doubling time was also significantly related to nuclear atypia, but the number of tumors studied was so small that its reliability was questionable. The doubling time was not related to any other histologic findings. This study shows that the doubling time is useful for estimating the malignant potential of gastric smooth muscle tumors, and that tumors with a doubling time of 16 months or less should be considered as malignant.

Aged↗

Natural history of minute sessile colonic adenomas based on radiographic findings. Is endoscopic removal of every colonic adenoma necessary?

PURPOSE: With the development of colonoscopy and double-contrast barium enema, detection of minute sessile colonic adenomas has increased. We evaluated progression of these lesions radiologically and attempted to clarify the natural history. METHODS: A total of 125 minute sessile adenomas (< or = 5 mm in size) with histologic confirmation were examined by double-contrast barium enema at an interval of more than one year. The average follow-up period was 24 (range, 12-36; standard deviation, 9.4) months. To allow for differences in magnification, adenomas increasing in size by 2 mm or more were defined as growing, and the other lesions were defined as unchanged. RESULTS: Eighty-six adenomas showed no interval change in size. Four adenomas decreased 1 mm in size, and 27 adenomas increased 1 mm in size. The remaining eight adenomas (6 percent) increased by 2 or 3 mm in size. None of the adenomas showed any morphologic changes. There was also no difference in degree of histologic atypia between growing and unchanged adenomas. None of the adenomas developed into carcinomas during the follow-up period. CONCLUSIONS: These data show that most minute sessile adenomas remain unchanged in size and morphology over the long term. Accordingly, these adenomas probably should be followed up radiologically or endoscopically to avoid excessive polypectomy.

Adenoma↗

Rabphilin-3A binds to a M(r) 115,000 polypeptide in a phosphatidylserine- and Ca(2+)-dependent manner.

Rabphilin-3A is a putative target protein for Rab3A/Smg 25A, which is a member of the Ras-related small GTP-binding protein and implicated in neurotransmitter release from the synapse. Rabphilin-3A is composed of two functionally different domains: the N-terminal Rab3A-binding and the C-terminal phosphatidylserine- and Ca(2+)-binding domains. The C-terminal domain has two copies of an internal repeat that are homologous to the C2 domains of protein kinase C, synaptotagmin, and phospholipase A2 and C-gamma 1, which are known to bind phosphatidylserine and Ca2+. In this study, we attempted to identify the Rabphilin-3A-interacting molecule in bovine brain by use of an overlay assay technique. The 32P-labeled C-terminal fragment of Rabphilin-3A (281-704 amino acids) bound to a protein molecule with a M(r) of about 115 kDa which was immobilized on a nitrocellulose sheet. This protein was highly purified and characterized. The binding of the 32P-labeled C-terminal fragment to this protein was dependent on both phosphatidylserine and Ca2+, and inhibited by an excess amount of the C-terminal fragment and the C2 domain fragment (396-704 amino acids) but not by the N-terminal fragment (1-280 amino acids). These results indicate that Rabphilin-3A binds to a protein molecule with a M(r) of 115 kDa through the C2 domain in the presence of phosphatidylserine and Ca2+.

Adaptor Proteins, Signal Transducing↗