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Biomedical subjects

T Miyasaka

Publications and source records attributed to T Miyasaka.

At least 37 records · Page 2Linked to original sources

[Vasculo-Behcet's disease with fatal massive hemoptysis].

A 39-year-old man was admitted to our hospital because of hemoptysis. A chest X-ray film on admission showed a patchy shadow in the left lower lung field. Computed tomography revealed nodular opacities in the left pulmonary artery. The patient had history of oral ulcers, erythema nodosum, pustular lesions, and genital ulcers. Furthermore, the needle reaction was positive. Our diagnosis was an incomplete type of Behcet's disease. A radionuclide-venography and lung-perfusion study disclosed deep-vein thrombosis. Combined therapy with prednisolone, colchicine, and indomethacin farnesil was initiated, but the patient died of massive hemoptysis. Pathological examination revealed a ruptured aneurysm in the bronchus segmentalis apacalis and thrombotic angitis in the inferior vena cava. Behcet's disease is rarely a cause of hemoptysis. However, the prevalence of hemoptysis due to pulmonary vasculitis in patients with Behcet's disease has been reported to be 5 to 10% which is not so rare. Because of the poor prognosis, we want to emphasize Behcet's disease as a cause of hemoptysis.

Adult↗

Subcellular localization and protein-protein interaction regions of Ku proteins.

The Ku protein is a complex of Ku70 and Ku80 subunits and is capable of binding promoters in a sequence-specific manner, although it remains unclear whether Ku is involved in transcriptional regulation. We examined the subcellular localization and determined the interaction regions of Ku. Our results indicate that heterodimers of Ku70 and Ku80 are localized in the nucleus, and that the stretches from amino acid (aa) 378 to 482 of Ku70 and from aa 374 to 502 of Ku80 are necessary for heterodimerization. These interaction regions do not contain any previously recognized protein-protein interaction motifs. To determine whether Ku contains a potential transcriptional activation domain, we examined N- and C-terminal deletion mutants of Ku70 and Ku80 for their ability to activate transcription in the GAL4-based one-hybrid system. We found that the whole Ku protein had no transcriptional activity, although the N-terminal peptide fragment of Ku70 was capable of activating transcription of the HIS3 and lacZ reporter genes in yeast cells.

Antigens, Nuclear↗

Inhibitory projections from pronator teres to biceps brachii motoneurones in human.

Neural projections from the pronator teres (PT) muscle to biceps brachii (BB) motoneurones were studied in three healthy human subjects using a post-stimulus time histogram method. In 25 BB motor units, electrical stimulation to the PT nerve with intramuscular needle electrodes induced inhibition in nine units (36%), whereas facilitation was produced in 18 units (72%) by stimulation to the median nerve trunk with surface electrodes at the distal end of the intermuscular septum of the arm or in the cubital fossa. Six motor units (24%) received both inhibition (PT nerve stimulation) and facilitation (median nerve trunk stimulation). In the six, the latency of the inhibition was, on average, 1.2 ms longer than that of the facilitation. The stimulation site for the inhibition was, on average, 4.8 cm distal to that for the facilitation. The inhibition was evoked with an intensity well below the motor threshold. These findings suggest that BB motoneurones receive oligosynaptic inhibition of group I afferents from PT in human.

Adult↗

[The involvement of cytokines, chemokines and inducible nitric oxide synthase (iNOS) induced by a transient ischemia in neuronal survival/death in rat brain].

Inflammatory/immunological processes underlie the survival/damage of neurons after brain ischemia. In glial cells, cytokines such as IL-1 beta and TNF-alpha are produced following ischemic stresses. On the other hand, it is suggested that NO/iNOS is involved in neuronal apoptosis. We here review the ischemia-induced production of cytokine/iNOS and the neurotrophic/neurotoxic effects. It is not clear whether or not the neuronal death after brain ischemia is apoptosis or necrosis. Under the condition of transient forebrain ischemia, however, we obtained results suggesting apoptosis in the delayed neuronal death of the CA1 pyramidal neurons. The time course and cellular localization of postischemic iNOS expression depend on the properties of the ischemic insult. The iNOS induction is detected primarily in astrocytes after the transient forebrain ischemia when the neuronal apoptosis is observed. We discuss a variety of cytokines with neurotrophic/neurotoxic actions that are produced by ischemia or environmental stresses in glial cells. From the neurotoxicological aspect of the neuro-glial interaction, we also review recent findings on signalling pathways of the iNOS induction in glial cells and the mechanisms of the cytotoxic actions of NO.

Animals↗

Allosteric inhibitors against HIV-1 reverse transcriptase: design and synthesis of MKC-442 analogues having an omega-functionalized acyclic structure.

Based on X-ray crystallographic analysis of MKC-442/human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complex, analogues in which the N1-substituent is replaced with omega-functionalized alkyl groups were designed to improve the affinity for the enzyme. Synthesis of these compounds was carried out starting from MKC-442 by a sequence of reactions (N3-protection, removal of N1-ethoxymethyl group, alkylation, and N3-deprotection). The compounds were evaluated for anti-HIV activity. Structure-activity relationships are discussed in terms of the possible interaction with the enzyme.

Allosteric Site↗

Nontraumatic bilateral first rib fractures.

The authors report the case of a 21-year old woman who presented bilateral spontaneous fractures of the first ribs, in the posterior portion on the right side, in the anterior portion on the left side. The pathogenesis of spontaneous fractures of the first rib is discussed.

Adult↗

[Quantitative evaluation of pulmonary perfusion volume using 99mTc-MAA SPECT: a comparison of COPD patients and healthy volunteers].

99mTc-MAA pulmonary perfusion single-photon emission computed tomography was performed on 18 patients with chronic obstructive pulmonary disease (COPD) and 41 healthy male volunteers. We quantified the extent of pulmonary perfusion with the Application Visualization System. We measured the pulmonary perfusion volume (PV) at 8 threshold levels encompassing 10 percentage points each from 21-100%. We also calculated the ratio of perfusion volume to total perfusion volume (TPV) at each threshold. Pulmonary perfusion volume in healthy volunteers remained relatively constant at levels of 31-70% and decreased gradually at levels of 71-100%. There was no significant difference in perfusion volume between smokers and non-smokers. Perfusion volume in COPD patients gradually decreased at levels of 31-60% and markedly decreased at levels greater than 60%. Perfusion volume differed significantly between COPD patients and healthy volunteers at levels of 41-100%. The mean PV/TPV value of COPD patients was significantly higher than that of healthy volunteers at levels of 21-40% and significantly lower than that of healthy volunteers at levels of more than 50%. This finding demonstrates that lung volume at high levels of pulmonary perfusion is decreased in COPD patients. The pulmonary perfusion volume at levels of more than 60% is an efficient means of distinguishing COPD patients from healthy subjects.

Adult↗

Asymmetric synthesis of 4'-alpha-alkylcarbovir derivatives.

Asymmetric synthesis of 4'-alpha-alkylcarbovir derivatives 3 were achieved based on Sakai's asymmetric alkylation of beta-keto esters. The key carbocyclic intermediate 12 was synthesized from 6 via an eleven-step sequence. Coupling of 12 with 2-amino-6-chloropurine followed by desilylation and subsequent hydrolysis gave the target compounds 3 in moderate yields.

Alkylation↗

Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors.

Crystal structures of HIV-1 reverse transcriptase (RT) complexed with a range of chemically diverse non-nucleoside inhibitors (NNIs) have shown a single pocket in which the inhibitors bind and details of the inhibitor-protein interactions. To delineate the structural requirements for an effective inhibitor, we have determined the structures of three closely related NNIs which vary widely in their potencies. Crystal structures of HIV-1 RT complexed with two very potent inhibitors, MKC-442 and TNK-651, at 2.55 angstroms resolution complement our previous analysis of the complex with the less effective inhibitor, HEPT. These structures reveal conformational changes which correlate with changes in potency. We suggest that a major determinant of increased potency in the analogues of HEPT is an improved interaction between residue Tyr181 in the protein and the 6-benzyl ring of the inhibitors which stabilizes the structure of the complex. This arises through a conformational switching of the protein structure triggered by the steric bulk of the 5-substituent of the inhibitor pyrimidine ring.

Antiviral Agents↗

Inhibitory projection from brachioradialis to biceps brachii motoneurones in human.

Neural projection from the brachioradialis to the biceps brachii motoneurones in human was studied using the method of post-stimulus time histogram. Electrical stimulation to the radial branch innervating the brachioradialis produced inhibition in 11 out of 21 biceps motor units. The central delays of the inhibition were 0.7-1.2 ms longer than those of the homonymous facilitation. The inhibition was evoked with the intensity below the motor threshold. Pure cutaneous stimulation provoked no effects on the motor-unit firing. These findings suggest that group I afferents from the brachioradials mediate an oligosynaptic inhibition of the biceps brachii motoneurones.

Adult↗

Inhibition of GABAA receptor chloride channel by quinolones and norfloxacin-biphenylacetic acid hybrid compounds.

Receptor binding studies have shown that the combination of some new quinolone antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen, inhibits GABAA receptors. In order to elucidate further the mechanism of these drug interactions, the effect of quinolone antibacterial agents on muscimol-stimulated 36Cl- uptake in rat cerebral cortical synaptoneurosomes was investigated in the absence or presence of BPAA. In the absence of BPAA, quinolones such as norfloxacin (NFLX) and enoxacin attenuated muscimol-stimulated 36Cl- uptake at 10 microM and above. In combination with 10 microM BPAA, the inhibitory effect of these drugs was potentiated and there was a parallel shift of the inhibition curves to the left for these drugs. BPAA alone (1 and 10 microM) did not affect basal or muscimol-stimulated 36Cl- uptake. Hybrid molecules of NFLX and BPAA were synthesized and their inhibitory potency was also investigated. Inhibition curves of muscimol-stimulated 36Cl- uptake revealed that a hybrid with a -CONH(CH2)3- chain between NFLX and BPAA (flexible structure) (1 nM-20 microM) inhibited muscimol-stimulated 36Cl- uptake more potently than did the combination of NFLX (10 nm-100 microM) and 10 microM BPAA. In contrast, another hybrid linked by -CONH-(stretched structure) exhibited a weak inhibitory effect at 10 microM. These results suggest that quinolones in combination with BPAA bind to GABAA receptors, thus inhibiting Cl- channel activity, and that the inhibitory potency of quinolones may be enhanced by an intermolecular interaction with BPAA.

Animals↗

Effect of shape and size of silanated fillers on mechanical properties of experimental photo cure composite resins.

The binary system of hybrid fillers selected from four irregular fillers (1.7-21.5 microns), five spherical fillers (0.46-31.2 microns), and a microfiller of 0.04 micron, were applied to photo cure composite resin and mechanical properties were measured. The strength for the hybrid of irregular and spherical fillers tended to increase as the size of component fillers decreased. The strength for the hybrid of the same fillers in shape also increased as the size of fillers decreased. The strength for the hybrid containing 30% microfiller showed the same trend, especially, the largest strength was obtained from hybrids containing small spherical fillers.

Analysis of Variance↗