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Biomedical subjects

M Tanabe

Publications and source records attributed to M Tanabe.

At least 19 recordsLinked to original sources

Spatiotemporal dynamics of inositol 1,4,5-trisphosphate that underlies complex Ca2+ mobilization patterns.

Inositol 1,4,5-trisphosphate (IP3) is a second messenger that elicits complex spatiotemporal patterns of calcium ion (Ca2+) mobilization and has essential roles in the regulation of many cellular functions. In Madin-Darby canine kidney epithelial cells, green fluorescent protein-tagged pleckstrin homology domain translocated from the plasma membrane to the cytoplasm in response to increased concentration of IP3. The detection of translocation enabled monitoring of IP3 concentration changes within single cells and revealed spatiotemporal dynamics in the concentration of IP3 synchronous with Ca2+ oscillations and intracellular and intercellular IP3 waves that accompanied Ca2+ waves. Such changes in IP3 concentration may be fundamental to Ca2+ signaling.

Adenosine Triphosphate

The diagnostic and prognostic value of eardrum mobility in otitis media with effusion.

Diagnostic and prognostic values of eardrum mobility were determined by pneumatic otoscopy in 37 patients (56 ears) having otitis media with effusion (OME). Eardrum mobility was impaired or lost in less than half of the ears (46.4%), while a tympanogram detected 77.8% of OME. In 27 of the 37 patients (42 of the 56 ears), aeration of the middle ear space was examined by CT and demonstrated that the presence or absence of aeration was significantly correlated with the presence or absence of eardrum mobility. In another 38 children (62 ears with OME), effect of antibiotics was correlated with eardrum mobility before treatment, and the improvement rate was found to be significantly higher in ears with positive mobility of eardrum (34.3%) than in ears without eardrum mobility (10.0%). These results indicate that eardrum mobility is a good prognostic indicator of OME rather than its diagnostic indicator alone.

Acoustic Impedance Tests

Factors affecting recovery of mastoid aeration after ear surgery.

Fifty-six patients after tympanomastoid surgery were examined to determine recovery of mastoid aeration and various pre- and intraoperative factors such as eustachian tube (ET) function, how the mastoid mucosa had been treated during surgery and whether or not a large silastic sheet had been placed in the middle ear or a ventilation tube used. Mastoid aeration recovery was confirmed by computed tomography in 27 of the 57 cases (47%) within 12 months of surgery. Among the factors examined, preservation of the epitympanic mucosa was found to be most important in mastoid aeration recovery. Use of a large silastic sheet to cover the area from the bony ET and tympanic cavity to epitympanum, aditus ad antrum or antrum was found to be of some help in recovery mastoid aeration after complete resection of the mucosa and mastoid air cells. Preoperative ET function, anterior tympanotomy and use of a ventilation tube did not influence recovery.

Adolescent

Core temperature and sweating onset in humans acclimated to heat given at a fixed daily time.

The thermoregulatory functions of rats acclimated to heat given daily at a fixed time are altered, especially during the period in which they were previously exposed to heat. In this study, we investigated the existence of similar phenomena in humans. Volunteers were exposed to an ambient temperature (Ta) of 46 degrees C and a relative humidity of 20% for 4 h (1400-1800) for 9-10 consecutive days. In the first experiment, the rectal temperatures (Tre) of six subjects were measured over 24 h at a Ta of 27 degrees C with and without heat acclimation. Heat acclimation significantly lowered Tre only between 1400 and 1800. In the second experiment, six subjects rested in a chair at a Ta of 28 degrees C and a relative humidity of 40% with both legs immersed in warm water (42 degrees C) for 30 min. The Tre and sweating rates at the forearm and chest were measured. Measurements were made in the morning (0900-1100) and afternoon (1500-1700) on the same day before and after heat acclimation. Heat acclimation shortened the sweating latency and decreased the threshold Tre for sweating. However, these changes were significant only in the afternoon. The results suggest that repeated heat exposure in humans, limited to a fixed time daily, alters the core temperature level and thermoregulatory function, especially during the period in which the subjects had previously been exposed to heat.

Acclimatization

Soft-wall reconstruction of posterior canal wall for surgery of noninflamed ears: a preliminary report.

OBJECTIVE: To test whether the posterior external auditory canal (EAC) wall reconstructed only by soft tissues retracts after surgery in the noninflamed ear. STUDY DESIGN: The condition of the posterior EAC wall was observed for more than 1 year after surgery in 20 noninflamed ears in which only the posterior EAC wall skin was preserved or in which the wall was reconstructed only by soft tissue during surgery. PATIENTS: Eighteen patients (20 ears) underwent ear surgery for conditions other than otitis media, including ossiculoplasty in 12 ears, cochlear implant in 3, resection of congenital cholesteatoma in 4, and resection of glomus tympanicum tumor in 1. RESULTS: Retraction of the soft posterior EAC wall was observed in only 1 of the 20 ears. In this ear, the posterior EAC wall showed only a slight retraction without any serious problems. Computed tomography revealed that mastoid aeration recovered in all 20 ears. CONCLUSIONS: In noninflamed ears, surgeons can remove the bony posterior EAC wall if necessary, and may not need to reinforce or reconstruct the wall with hard tissue. This enables surgeons to spare time and energy and obtain the same advantages as in the intact-canal-wall technique or canal wall reconstruction by a hard material.

Adolescent

Proteasome inhibition leads to the activation of all members of the heat-shock-factor family.

Heat-shock proteins and molecular chaperones are involved in various cellular metabolic processes including protein synthesis and degradation. These expressions are elevated at the level of transcription by the accumulation of abnormal proteins when these metabolic processes are disturbed. Recent works suggest the induction of heat-shock proteins by the inhibiton of proteasome. To elucidate the mechanism of this induction, we examined the activation of heat-shock transcription factors by proteasome inhibitors in avian cells. Activation of the two heat-shock-inducible factors, HSF1 and HSF3, was produced by the treatment of cells with proteasome inhibitors. This activation was not produced by treatment with various other protease inhibitors. The HSF activation by proteasome inhibitors was completely blocked in the presence of the protein synthesis inhibitor cycloheximide. Unexpectedly, the development-related factor HSF2 was also activated by proteasome inhibitors, with an increase in its protein level. These results suggest that the ubiqutin-proteasome pathway may regulate all of the three HSFs by controlling the level of some regulatory factor for HSF or HSF itself, as well as controlling abnormal proteins.

Animals

Neuronal src and trk a protooncogene expression in neuroblastomas and patient prognosis.

Neuroblastomas present a wide variety of clinical and biological behaviors, which are reflected by the heterogeneous expressions of protooncogenes related to the neuronal differentiation and amplification of the N-myc gene. High expression of trk A and Ha-ras in neuroblastomas has been shown to be associated with an excellent patient outcome. We have previously reported that neuron-specific src mRNA was increased in chemically differentiated neuroblastoma cell lines and in clinically observed neuroblastomas without N-myc amplification. In the present study, to clarify both the value of neuronal c-srcN2 expression as a prognostic indicator and the significance of the coexpression of these protooncogenes, we examined the expression of 3 alternatively spliced src, trk A and Ha-ras in neuroblastoma tissues from 60 patients by competitive RNA-polymerase chain reaction (PCR). The results indicate that protooncogene expression in neuroblastomas correlated with a favorable outcome for c-srcN2 and trk A. N-myc gene was amplified exclusively in tumors with low levels of trk A. Low expression of c-srcN2 and trk A might thus characterize different aggressive phenotypes due to different signal transduction pathways of neural differentiation in neuroblastoma. The combined analyses for c-srcN2 and trk A expression by RNA-PCR should provide information about the biological phenotype of a neuroblastoma within a short period of time after obtaining tumor material.

Genes, myc

Glial cell line-derived neurotrophic factor/neurturin-induced differentiation and its enhancement by retinoic acid in primary human neuroblastomas expressing c-Ret, GFR alpha-1, and GFR alpha-2.

Neuroblastomas often undergo spontaneous differentiation and/or regression in vivo, which is at least partly regulated by the signals through neurotrophins and their receptors. Recently, glial cell line-derived neurotrophic factor (GDNF) and a second family member, neurturin (NTN), have been found to mediate their signals by binding to a heterotetrameric complex of c-Ret tyrosine kinase receptors and glycosylphosphatidylinositol-linked proteins, GFR alpha-1 (GDNFR-alpha) or GFR alpha-2 (TrnR2/GDNFR-beta/NTNR-alpha/RETL2). Here, we studied the effect of GDNF and NTN on human neuroblastomas in the short-term primary culture system, as well as the expression of c-Ret, GFR alpha-1, GFR alpha-2, GDNF, and NTN. GDNF (1-100 ng/ml) induced morphological differentiation in 34 of 38 primary neuroblastomas and an accompanying increase in c-Fos induction. These effects were markedly enhanced by treatment with 5 microM all-trans-retinoic acid. Although GDNF alone induced a rather weak differentiation independent of the disease stages, the enhancement of neurite outgrowth induced by treatment with both GDNF and all-trans-retinoic acid was significantly correlated with younger age (less than 1 year; P = 0.0039), non-stage 4 diseases (P = 0.0023), a single copy of N-myc (P = 0.027), and high levels of TRK-A expression (P = 0.0062). To examine the expression levels of GFR alpha-1, we cloned a short form of the human GFR alpha-1 gene with a 15-bp deletion by screening a human adult substantia nigra cDNA library. Many primary neuroblastomas expressed c-Ret, GFR alpha-1, and GFR alpha-2 as well as their ligands, GDNF and NTN, suggesting the presence of a paracrine or autocrine signaling system within the tumor tissue. The effect of NTN on primary culture cells of neuroblastoma was similar to that of GDNF. These imply that the GDNF(NTN)/c-Ret/GFR alpha-1(GFR alpha-2) signaling may have an important role in regulating the growth, differentiation, and cell death of neuroblastomas.

Antineoplastic Agents

Disruption of the HSF3 gene results in the severe reduction of heat shock gene expression and loss of thermotolerance.

The vertebrate genome encodes a family of heat shock factors (HSFs 1-4) of which the DNA-binding and transcriptional activities of HSF1 and HSF3 are activated upon heat shock. HSF1 has the properties of a classical HSF and exhibits rapid activation of DNA-binding and transcriptional activity upon exposure to conditions of heat shock and other stresses, whereas HSF3 typically is activated at higher temperatures and with distinct delayed kinetics. To address the role of HSF3 in the heat shock response, null cells lacking the HSF3 gene were constructed by disruption of the resident gene by somatic recombination in an avian lymphoid cell line. Null cells lacking HSF3, yet expressing normal levels of HSF1, exhibited a severe reduction in the heat shock response, as measured by inducible expression of heat shock genes, and did not exhibit thermotolerance. At intermediate heat shock temperatures, where HSF1 oligomerizes to an active trimer in wild-type cells, HSF1 remained as an inert monomer in the HSF3 null cell line. HSF3 null cells were restored to a nearly normal heat shock-responsive state by reintroduction of an exogenous HSF3 gene. These results reveal that HSF3 has a dominant role in the regulation of the heat shock response and directly influences HSF1 activity.

Animals

Pathophysiological and therapeutic considerations of otitis media with effusion from viewpoint of middle ear ventilation.

Using nitrous oxide, we examined the gas exchange function through the middle ear mucosa in ears with otitis media with effusion (OME) in children, and found the function to be impaired in 50% of them. The size of the mastoid was significantly smaller in ears with negative gas exchange function than those with positive function, and the presence or absence of the function was even more significantly correlated with the presence or absence of aeration in the middle ear. Furthermore, the presence or absence of aeration in ears with OME was found to be significantly correlated with their prognosis (response of OME to antibiotics treatment) and also with the presence or absence of eardrum mobility examined by a pneumatic otoscope. Finally, after myringotomy and removal of effusion, the gas exchange function recovered in most of the ears with impaired function. These results indicate that the eardrum mobility test may serve as an appropriate indicator for the surgical treatment for OME.

Child

Effective endless-loop bougienage through the oral cavity and esophagus to the gastrostomy in corrosive esophageal strictures in children.

The authors present a safe, conservative method of endless-loop bougienage (ELB) through the oral cavity and esophagus to a gastrostomy without general anesthesia in three children with corrosive esophageal burns treated since 1966. Esophagogastroscopy was performed to evaluate for esophagitis at an early phase after ingestion of the caustic substance. When esophageal stricture formation was recognized after subsequent conservative treatment, a feeding gastrostomy was made. A continuous string loop with plummets of progressively larger size was positioned to pass through the patient's oral cavity and esophagus to the gastrostomy. Strictures were found in the upper esophagus in two patients and in the middle and lower esophagus in one. The gastrostomy was performed 15 months, 20 days, and 2 months after the injury, respectively, and the periods of ELB were 3, 5, and 2(1/2) years, respectively. The patients were able to start eating at 26, 42, and 29 months after injury, respectively. They are now 30, 18, and 17 years old, and slight dysphagia remains in patients 1 and 2. No patient developed esophageal carcinoma at the site of the corrosive stricture. Our method of ELB through the patient's oral cavity and esophagus to the gastrostomy appears to be safe, reliable, and useful. We believe that most caustic esophageal strictures in children can be treated by this conservative measure.

Burns, Chemical

Long-term survival in a patient with congenital laryngeal atresia and multiple malformations.

Laryngeal atresia (LA) is an uncommon congenital anomaly, and only a few cases with long-term survival are reported in the literature. The authors describe a 2-year-old boy with LA and esophageal (EA), intestinal, and urethral atresia (UA). Immediately after birth, severe respiratory distress and mild abdominal distension became evident. Endotracheal intubation was unsuccessful and emergency tracheal puncture was performed, after which a tracheostomy was constructed. Direct laryngoscopy revealed LA at the vocal cord level. A cystostomy and gastrostomy were constructed immediately because of UA and EA. A cystocutaneostomy, ileocolic anastomosis, and resection of a tracheoesophageal fistula (TEF) were simultaneously performed 1 day after birth. The EA was proximal with a distal TEF. The gap between the ends of the upper and lower esophagus was 4 cm in length. It was thought impossible to perform a primary anastomosis, and therefore, a gastrostomy and resection of the TEF using multiple-stage surgery was undertaken. Intestinal resection and anastomosis were performed due to intestinal stenosis from necrotizing enterocolitis at the age of 3 months. Hypoxic encephalopathy developed due to accidental obstruction of the tracheostomy tube at the age of 10 months, and physical therapy was begun. He required a cutaneous nephrostomy due to a right hydromegaureter with vesicoureteric reflux and a left non-functioning kidney at the age of 23 months. He has been hospitalized for partial ventilatory assistance for 2 years at our institution. The course of this patient seems noteworthy in relation to the genesis of the multiple malformations.

Abnormalities, Multiple

In vivo karyotypic evolution with altered biological characteristics in a case of neuroblastoma.

Molecular and biological analyses of a neuroblastoma case in which the original tumor contained a nodular region are described. No significant difference was observed between the nodular and the surrounding tumor tissue with respect to histopathologic examination, N-myc amplification, and trkA expression. However, flow cytometric analysis demonstrated that the nodular region consisted of a hypertetraploid clone, whereas the surrounding tissue mostly contained a hyperdiploid clone. Chromosome analysis showed that each clone had a similar chromosome acquisition pattern, suggesting that the hypertetraploid cells of the nodular region arose from the hyperdiploid cells of the surrounding tissue. Moreover, primary culture findings of the tumor cells showed that the responses to nerve growth factor or retinoic acid were different between the two. Collectively, this case suggests the possibility that neuroblastoma acquires novel biological characteristics through karyotypic evolution in vivo.

Abdominal Neoplasms

Trichomonas foetus meningoencephalitis after allogeneic peripheral blood stem cell transplantation.

A 34-year-old man with refractory acute myelogenous leukemia underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched sibling. Engraftment was prompt and no acute GVHD developed. However, high fever persisted even after engraftment, and the patient developed headache, diplopia, vertigo and nuchal rigidity on day 20 posttransplant. Cerebrospinal fluid (CSF) showed pleocytosis with no detectable microorganisms. Despite therapy with broad-spectrum antibiotics, antifungal agents and antituberculous drugs, he developed rapid mental deterioration with seizures and died on day 40. Just prior to his death, trichomonads were isolated from both CSF and urine. Scanning electron microscopic examination identified the trichomonad as Trichomonas foetus. At autopsy, trichomonads were detected histopathologically in an area involving meningoencephalitis. To our knowledge, this is the first case of T. foetus meningoencephalitis in a recipient of allogeneic PBSCT and, more importantly, the first human case of T. foetus infection.

Adult

Effects of transient oxygen-glucose deprivation on G-proteins and G-protein-coupled receptors in rat CA3 pyramidal cells in vitro.

The role of guanosine triphosphate-binding proteins (G-proteins) in the generation of the outward current during transient oxygen-glucose deprivation (OGD) was investigated in CA3 pyramidal cells in rat hippocampal organotypic slice cultures using the single-electrode voltage-clamp technique with KMeSO4-filled microelectrodes. To simulate ischaemia, brief chemical OGD (2 mM 2-deoxyglucose and 3 mM NaN3 for 4-9 min) was used, which induced an outward K+ current associated with an increase in input conductance. OGD failed to induce the outward current under conditions where G-protein function was disrupted by loading cells with guanosine 5'-O-(2-thiodiphosphate) [GDPbetaS] or after prolonged injection of guanosine 5'-O(3-thiotdphosphate) [GTPgammaS]. However, in slices treated with pertussis toxin (PTX), OGD still elicited the outward current, indicating that PTX-insensitive G-proteins are involved. Consistent with this insensitivity to PTX, neither adenosine receptors nor GABA(B) (gamma-aminobutyric acid) receptors, which operate via PTX-sensitive G-proteins, mediate the OGD-induced outward current. When adenosine receptors or GABA(B) receptors were blocked with 1,3-dipropyl-8-psulphophenylxanthine (DPSPX, 5 microM) or CGP 52 432 (10 microM), respectively, the OGD-induced response was not modified. The response also persisted following pretreatment of slice cultures with tetanus toxin to prevent vesicular release of neurotransmitters and neuromodulators from presynaptic terminals. Both PTX-sensitive and PTX-insensitive G-protein-mediated responses were suppressed during OGD. The inward current induced by the metabotropic glutamate receptor agonist 1 S, 3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD) and the outward current elicited by adenosine or baclofen were strongly or completely attenuated. In contrast, the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) response was not affected. These findings suggest that during OGD there is a functional uncoupling of receptors from G-proteins, and a direct receptor-independent activation of PTX-insensitive G-proteins leading to an increase in membrane K+ conductance.

Adenosine