[Autopsy case of Osler-Rendu-Weber disease with peculiar nodular lesions in the liver].
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Aged↗
Biomedical subjects
S Tomioka
Publications and source records attributed to S Tomioka.
Calpain dissociates into subunits in the presence of calcium ions.
Calpain is a calcium dependent cysteine protease consisting of a catalytic 80K subunit and a regulatory 30K subunit. It has therefore been believed that calpain functions as a dimer. Here we have found that calpain dissociates into subunits in the presence of the Ca2+ required for the expression of activity and that the dissociated 80K subunit is enzymatically fully active. Moreover, the 80K subunit shows a calcium sensitivity identical to the activated form of calpain but not to the original control calpain. The results suggest that the activation of calpain corresponds to the dissociation into subunits in the presence of Ca2+ and that calpain functions as a monomer of the 80K subunit in vivo.
Amino Acid Sequence↗
A catalytic subunit of calpain possesses full proteolytic activity.
Previous studies on the refolding of calpain, a heterodimer comprising a catalytic 80 kDa subunit and a regulatory 30 kDa subunit, indicate that both subunits are required for the expression of full protease activity. We reexamined the conditions for refolding of calpain and found that under optimized conditions the renatured 80 kDa subunit has full enzyme activity even in the absence of the 30 kDa subunit. The 30 kDa subunit stabilizes the 80 kDa subunit rather than enhancing its activity. The theory that calpain functions as a dimer requires reexamination.
Bacterial Proteins↗
Discordant findings between krypton-81m gas and Tc-99m labeled ultrafine aerosol lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis.
Technegas, a newly developed ultra-fine dry dispersion of Tc-99m labeled carbon with a particle size of approximately 5 nm to 20 nm, possesses the properties for lung ventilation imaging using SPECT. The authors observed a discrepancy between krypton-81m gas and technegas lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis who demonstrated heterogeneously decreased distribution of technegas without regions of high count density (focal hot spots) of tracer in their lungs in spite of the almost homogenous distribution of krypton-81m gas. This finding could be explained by the duration of radioactive gas inhalation. Technegas lung ventilation SPECT images reflected lung ventilation with tidal breathing. Conversely, Kr-81m gas lung ventilation SPECT images reflected not only lung ventilation, but also lung volumes. These two radioactive agents for lung ventilation SPECT show different findings.
Administration, Inhalation↗
[A case of polymyositis presenting histological picture of bronchiolitis obliterans organizing pneumonia with transbronchial lung biopsy specimens].
A 69-year-old woman was admitted to our hospital because of slight fever, general fatigue, joint pain and proximal muscle weakness. Severe elevation of serum enzyme levels of CPK, transaminase and aldolase was noted. The chest roentgengram showed diffuse reticular and nodular infiltrates. Histological examination of the transbronchial lung biopsy specimens revealed alveolitis and organizing pneumonia. Daily administration of 80 mg predonisolone was effective for both lung findings and myositis.
Aged↗
Reduction of aluminium concentration in albumin products.
The aluminium concentration in albumin products has been reduced to < or = 100 ppb by an anion exchanger treatment. Furthermore, we have found that this low aluminium concentration in a albumin products has been maintained for extensive periods of time, when they are stored in de-alkalized soft glass containers.
Aluminum↗
[Clinico-statistical observation of patients referred from our hospital at the Department of Oral Surgery].
The patients referred from our hospital at the Department of Oral Surgery, University of Tokyo, during the two years from January 1990 to December 1991 were analyzed statistically. The results were as follows: 1. Our subjects were 1,152 patients (24.2% of first-time patients), 540 males and 612 females. 2. Concerning age distribution, the majority was in their forties, fifties and sixties. 3. More patients were from internal medicine, ENT clinic, plastic surgery and cardiothoracic surgery. 4. On the number of patients categorized by disease at other departments, the largest number was cardiovascular disease. 5. On the number of patients categorized by disease at our department, the majority were dental diseases (dental caries, marginal periodontitis and missing teeth).
Adolescent↗
[Lymph node metastasis in bladder cancer].
Forty patients who had transitional cell carcinoma of the bladder with positive pelvic lymph node metastasis, treated at Chiba University Hospital between April 1975 and March 1991 were investigated to evaluate the significance of pelvic lymph node dissection. The frequency of the patients with positive lymph node was 9.1% in all patients with transitional cell carcinoma of the urinary bladder, 4.0% in the clinical T1, 3.4% in T2, 35.7% in T3a, 32.1% in T3b, 46.2% in T4, and none in Tis and Ta. Of the 40 patients, 16 underwent cystectomy pelvic lymph node dissection, 19 had biopsy of suspicious lymph nodes which turned out to be positive for metastasis, and 5 were defined by computed tomography. Pelvic lymph node dissection was performed at the common iliac, presacral, external iliac, internal iliac, and obturator nodes. In the 16 patients who underwent cystectomy with pelvic lymph node dissection, the frequency of metastasis in each nodal group was 38% in common iliac, 31% in external iliac and obturator, and 25% in presacral and internal iliac. Out of the 16 patients, eight had regional lymphatic metastasis, three had only extra regional lymph node metastasis, and five had both regional and extra regional metastasis. Three of nine patients who had single positive node had common iliac or presacral positive node without regional lymph node metastasis.
Adult↗
Enzymatic optical resolution of dibenzoxepins and its application to an optically active antiallergic agent with thromboxane A2 receptor antagonistic activity.
Methyl (+/-)-11-(2-hydroxyethyl)thio-6,11-dihydrodibenz[b,e]oxepin- 2- carboxylate (5) was enantio-selectively acylated with acetic anhydride in an organic medium by Lipase Amano P to give methyl (-)-11-(2-acetoxyethyl)thio-6,11-dihydrodibenz[b,e]oxepin-2- carboxylate (8), and the (+)-enantiomer by Lipase Sigma Type VII. Using Lipase Amano P, (+)- and (-)-(5) could be prepared with high optical purity (84-94% e.e.). These products were respectively converted to (+)- and (-)-KW-4099, which had antiallergic activity with complete retention of the optical purity.
Acylation↗
Synaptic potentials produced in jaw-closer and jaw-opener motoneurons by palatal stimulation.
Excitation and inhibition of temporal and digastric motoneurons (Temp. and Dig. Mns) during transient jaw closing, the so-called jaw-closing reflex, were studied in cats. Application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex and it was found that mechanosensory inputs from the posterior palatal mucosa produce depolarizing potentials on the Temp. Mns responsible for jaw closure during the jaw-closing reflex. We have demonstrated that in one-third of 27 explored Temp. Mns the initial bursts of spikes were elicited before the onset of jaw closure, suggesting that these cells contribute to initiate jaw closure during the jaw-closing reflex. The remaining cells probably contributed to maintain the occlusal phase. Furthermore, it was found that mechanosensory inputs from the posterior palatal mucosa produce a hyperpolarization-depolarization sequence in the Dig. Mns responsible for the jaw-closing reflex. In addition, when pressure stimulation was applied to the anterior palatal mucosa, sustained jaw opening was elicited and an increase of firing frequency of Dig. Mns occurred 40 ms before the onset of jaw opening and continued for 80 ms.
Animals↗
Intrapair differences of physical aging and longevity in identical twins.
The genetic and environmental contributions to physical aging (hair graying, balding, presbyopia) and longevity (age at death) were examined by within-pair comparison in monozygotic (MZ) and dizygotic (DZ) twins in later adulthood. Physical aging was investigated on 135 pairs of adult twins aged over 50. Hair graying and hair loss (baldness) showed significantly higher rates of concordance in the MZ twins than in the DZ twins. The intrapair difference of the degree of hair graying was negligible in 79%, slight in 15% and striking in 5% among the MZ pairs; while negligible in 40%, slight in 50% and striking in 10% among the DZ pairs. The intrapair difference of the degree of hair loss was negligible in 92%, slight in 8% (and striking in none) among the MZ pairs; while negligible in 69%, slight in 25% and striking in 6% among the DZ pairs. The age at onset of presbyopia showed a slightly higher rate of concordance in the MZ than in the DZ pairs. Longevity (age at death) was surveyed on 184 pairs of twins who died at over 40 years of age. The intrapair difference of longevity was 6.65 +/- 5.6 years (maximum 18.0; minimum 0.04) in the MZ pairs, and 8.66 +/- 7.2 years (maximum 18.6; minimum 2.9) in the DZ pairs. The MZ pairs showed a slightly smaller within-pair difference of longevity than the DZ pairs.
Aged↗
Risk factors for cognitive aging in adult twins.
Monozygotic (MZ) and dizygotic (DZ) twins in later adulthood were studied in order to examine genetic and environmental contributions to the decline of cognitive performance. In this study, 118 twin pairs took a comprehensive medical examination at a university hospital. Cognitive function was measured by the Wechsler Adult Intelligence Scale (WAIS). The intraclass correlation coefficients on Digit Span (D) and Digit Symbol (DS) subtests of the WAIS did not show any significant difference between MZ and DZ twins although Block Design (BD) showed a significant difference. The values of the intraclass correlation coefficients were mostly around 0.5 and showed significant within-pair similarity of test scores. The mean score of D, DS and BD declined with advancing age. The intraclass correlation coefficients for D, DS and BD were around 0.2 in the MZ twins reared apart, and around 0.6 in the MZ twins reared together. These results indicated a significant environmental influence on cognitive aging in later adulthood.
Aged↗
Synthesis and optical resolution of an antiallergic agent KW4099 with thromboxane A2 antagonistic activity.
A new antiallergic agent with thromboxane A2 antagonistic activity, KW4099, was synthesized by a simple method. Its optical resolution was accomplished with the use of (+)- or (-)-2,2'-(1,1'-binaphthyl)phosphoric acid as a resolving agent.
Dibenzoxepins↗
Excitation and inhibition of trigeminal motoneurons by palatal stimulation.
Excitation and inhibition of jaw-closing motoneurons (Masseteric and Temporal Motoneurons, Mass. and Temp. Mns) during transient jaw closing, the so-called jaw-closing reflex, and prolonged jaw opening elicited by palatal stimulation were studied. By pressing the anterior palatal surfaces sustained jaw opening was elicited, suggesting that sustained jaw opening results from inhibition of tonic background activity of jaw-closing motoneurons by inhibitory postsynaptic potentials (IPSPs) elicited by mechanical stimulation of the anterior palatal mucosa. Recordings showed that the onset of IPSPs was 80 ms earlier than the onset of jaw opening. Application of diffuse pressure stimulation to the posterior palatal surfaces elicited bursts of spikes triggered on excitatory postsynaptic potentials (EPSPs), suggesting that mechanosensory receptors from the posterior palatal mucosa send excitatory synaptic inputs to jaw-closing motoneurons. Furthermore, it is suggested that mechanosensory inputs from the posterior palatal mucosa may excite neurons in the central pattern generator and provide the motor patterns responsible for jaw closure during the jaw-closing reflex. We have demonstrated that excitation of Mass. Mns innervating the deep masseter muscle mainly contributed to maintaining the occlusal phase of jaw closure during the jaw-closing reflex. However, the onset of EPSPs was 100 to 160 ms (n = 27) earlier than the onset of jaw closure. In studies on spontaneously occurring jaw closure it was demonstrated that there was a proportional increase in the number of spikes of the Temp. Mn and the mechanical response (jaw closure).
Animals↗
Synaptic efficacy of inhibitory synapses in the reinnervating hypoglossal motoneurons.
The synaptic efficacy of inhibitory synapses in tongue protruder motoneurons reinnervating the tongue retractor muscle was studied in cats. We have demonstrated that the percentage magnitude of a short- and a long-lasting inhibitory postsynaptic potential in the inhibitory postsynaptic potentials produced in the tongue protruder motoneurons, whose axons had been cut but allowed to regenerate to make functional contact with the tongue retractor muscles, by lingual nerve or inferior alveolar nerve stimulation, was rearranged to appear like that exhibited by the tongue retractor motoneurons that normally supply that muscle. In addition, the peak amplitude of the summated afterhyperpolarization in a tongue protruder motoneuron on operated cats at nine months axon-union was in the normal range.
Action Potentials↗
Synaptic efficacy of inhibitory synapses and repetitive firing in the reinnervating trigeminal and hypoglossal motoneurons.
The synaptic efficacy and repetitive firing in masseteric motoneurons after the self-union operation and in tongue protruder motoneurons after their cut axons were reunited to tongue retractor muscles, the styloglossus muscle, were studied in cats. To ensure the correct identification of reinnervating motoneurons, the muscle response produce by an induced spike in a motoneuron by intracellularly injected depolarizing current was recorded. In both masseteric and tongue protruder motoneurons there were no differences on the patterns of postsynaptic potentials produced in reinnervating and non-reinnervating motoneurons by peripheral nerve stimulation, suggesting that the recovery of the synaptic efficacy of inhibitory synapses is time-dependent rather than muscle reinnervation. However, the present study demonstrated that the recovery of processes that control rhythmical firing of motoneurons is probably dependent on muscle reinnervation.
Animals↗
Synthesis and antiarrhythmic activity of 5,11-dihydro[1]benzoxepino[3,4-b]pyridines.
During further modification of the new antiulcer agent 5 (KW-5805), a 5,11-dihydro[1]benzoxepino[3,4-b]pyridine derivative, we found that some new derivatives had antiarrhythmic activity. So we continued synthesis and evaluation of a series of 5-substituted 5,11-dihydro[1]benzoxepino[3,4-b]pyridines for antiarrhythmic activity in chloroform-induced ventricular arrhythmias in mice and in ouabain-induced ventricular arrhythmias in dogs. In chloroform-induced ventricular arrhythmias, the 7-methoxy group played an important role in activity and the type of terminal side chain at position 5 had not obvious effect on potency. On the other hand, in ouabain-induced ventricular arrhythmias, the structure-activity relationship was highly specific and only four compounds, 9, 30, 34, and 35, were effective. Compound 9,5-[[2-(diethylamino)ethyl]amino]-7-methoxy-5,11-dihydro[1] benzoxepino[3,4-b]pyridine 1.5-fumarate, which exhibited low affinity for muscarinic acetylcholine receptors and a high ED100(mydriasis)/ED50(antiarrhythmic activity) ratio, was selected for further development and clinical evaluation as KW-3407. The synthesis and antiarrhythmic activity of optically active 9 is described. The order of potency of antiarrhythmic activity in ouabain-induced ventricular arrhythmias in dogs was (-)-9, (+/-)-9, and (+)-9.
Animals↗
[Immunological diagnosis of multidrug resistant cancer in urological malignancies].
A monoclonal antibody, MRK16, recognizing specifically an epitope of P-glycoprotein (P-GP) was used to determine the degree of expression of P-GP in kidney and urinary bladder cancers. Immunohistochemistry, immunoelectronmicroscopy, and immunoprecipitation were used for this study. Expression of P-GP was found in 6 of 20 kidney cancers treated without anticancer drugs. Also expression of P-GP was found in 17 of 47 urinary bladder cancers. 11 of 31 in primary cases, 0 of 5 in recurrent cases treated without anticancer drugs, and 6 of 11 in recurrent cases treated with anticancer drugs were positively expressed. These results indicate that a certain proportion of kidney and urinary bladder cancers intrinsically acquired multidrug resistance, and also that prior administration of anticancer drugs may induce P-GP in initially negative tumors. We also succeeded to detect MDR1 mRNA by means of in situ hybridization. From our present data, our methods to detect P-GP and MDR1 mRNA appeared to be very useful from the point of clinical application.
ATP Binding Cassette Transporter, Subfamily B, Mem↗