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Biomedical subjects

A Yoshida

Publications and source records attributed to A Yoshida.

At least 253 records · Page 14Linked to original sources
PubMed1999

Suppression of retinal neovascularization by the NF-kappaB inhibitor pyrrolidine dithiocarbamate in mice.

PURPOSE: To evaluate the effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), on retinal neovascularization in a murine model of ischemic retinopathy. METHODS: One-week-old C57BL/6N mice were exposed to 75%+/-2% oxygen for 5 days and then were returned to room air to induce retinal neovascularization. After the return to room air, the left and right eyes were injected intravitreally with PDTC or a vehicle, respectively. Retinal neovascularization was examined by injecting fluorescein dextran and angiography after 5 days in room air and was quantitated histologically with a masked protocol. The effects of PDTC on NF-kappaB activation were evaluated by immunohistochemistry. To examine the toxicity of PDTC, the histologic change in the retina was examined by light and electron microscopy. RESULTS: Retinal neovascularization in the eye injected with PDTC by intravitreal methods was reduced in 100% of animals compared with that apparent in the vehicle-treated eye. The inhibitory effect was dose-dependent, with a maximal inhibition of 39% (P < 0.01) at a dose of 1 nmole. The immunostaining intensity for NF-KB in the retina was reduced by PDTC injections. No side effects by PDTC in the retina were observed by light and electron microscopy. CONCLUSIONS: NF-kappaB activation appears to be required for retinal angiogenesis, given that the administration of PDTC suppressed retinal neovascularization. PDTC may prove beneficial in the treatment of ischemic neovascular diseases such as diabetic retinopathy and retinal vein occlusion.

Animals↗
PubMed1999

Recent progress in P-glycoprotein research.

P-glycoprotein can extrude a variety of structurally diverse, toxic xenobiotic compounds from cells. It is believed to be one of key molecules which can cause multidrug resistance in cancer. This paper deals with recent progress in P-glycoprotein research, especially in its structure, mechanisms for substrate recognition and transport. The review also discusses specific modulators of multidrug resistance in cancer and gene therapy using the MDR1 gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Successful treatment of cytomegalovirus retinitis in a patient with malignant lymphoma: a case report and review of the literature.

A 52-year-old Japanese woman was diagnosed as having angioimmunoblastic T-cell lymphoma (stage IV-B). She received 6 courses of chemotherapy including cyclophosphamide, doxorubicin, vincristine, and prednisolone every two weeks (biweekly CHOP), and was considered to be in partial remission. She complained of loss of visual acuity in her right eye during her last cycle of chemotherapy. Cytomegalovirus (CMV) retinitis was suspected from the characteristic ophthalmoscopic appearance. This diagnosis was further supported by the detection of CMV DNA in blood and antigens in polymorphonuclear leukocytes, a sign of CMV reactivation. Although DNAemia and antigenemia became negative, retinitis remained slightly active despite a 4-week systemic treatment of ganciclovir. Intraocular injection of ganciclovir was started and continued until the retinitis became inactive ophthalmoscopically. The patient received high-dose chemotherapy with peripheral blood stem cell transplantation and achieved complete remission. During the after this therapy no recurrence of CMV infections was observed. This case shows that 1) a quick and accurate diagnosis of CMV retinitis was possible by applying DNAemia and antigenemia and 2) intensive treatment for the CMV infection enabled the accomplishment of cure-oriented chemotherapy of the lymphoma without the recurrence of CMV retinitis.

Cytomegalovirus Retinitis↗
PubMed1999

[Effect of topical levobunolol on retinal, optic nerve head, and choroidal circulation in normal volunteers].

PURPOSE: Using three different techniques of ocular blood flow measurement, we evaluated the effects of topical levobunolol on retinal, optic nerve head, and choroidal circulation. METHODS: Twenty normal volunteers received one drop of levobunolol in one eye and one drop of placebo in the fellow eye. Retinal venous blood flow was measured using multiple scattering laser velocimetry. Retinal capillary blood flow and optic nerve head blood flow were measured by Heidelberg Retina Flowmeter. Pulsatile ocular blood flow was measured by ocular blood flow tonography. Changes in blood pressure, heart rate, retinal venous blood flow, retinal capillary blood flow, optic nerve head blood flow, intraocular pressure and pulsatile ocular blood flow were detected from measurements taken at baseline and at 90 to 120 minutes following the instillation. RESULTS: Intraocular pressure decreased significantly in both eyes. Retinal capillary blood flow increased significantly in both eyes. Optic nerve head blood flow increased significantly in treated eyes but remained unchanged in placebo eyes. There were no significant changes in retinal venous blood flow or pulsatile ocular blood flow in either eyes. CONCLUSION: Our results suggest that one administration of levobunolol may increase the retinal and optic nerve circulation but does not decrease the choroidal circulation.

Administration, Topical↗
PubMed1999

[Prediction of postoperative refraction using intraoperative retinoscopy].

PURPOSE: Postoperative refraction was calculated using aphakic refraction measured with intraoperative retinoscopy, and its clinical usefulness was investigated statistically. OBJECTS AND METHODS: We studied 115 eyes of 89 patients, 28 males and 61 females aged 35 to 90 years, who had received intracapsular insertion of an intraocular lens. To decrease the error in measuring, retinoscopy was performed after the attachment of a hard contact lens of +15 D to the patient's cornea, with the exclusion of high myopia. We modified the Haigis calculation and used it to predict the postoperative refraction. RESULTS: The refraction could be measured in 112 eyes. The mean error between the actual and the predicted (actual minus predicted) in 112 eyes was 0.40 +/- 1.05 (mean +/- standard deviation) D. The mean error calculated using the SRK-II method, the Binkhorst method, and the Holladay method was -0.09 +/- 1.13 D, -0.58 +/- 1.00 D, and -0.44 +/- 1.00 D, respectively. The mean error of the average of these three formulas and our method was 0.15 +/- 0.82 D, -0.09 +/- 0.83 D, and -0.02 +/- 0.82 D, respectively. CONCLUSION: Our method seemed to have the same accuracy as other calculation formulas. By using our method together with other formulas, the postoperative refraction could be predicted more accurately.

Adult↗
PubMed1999

Dispersion of the monophasic action potential duration in patients with polymorphic ventricular tachycardia.

The mechanism of polymorphic ventricular tachycardia (PMVT) remains unclear. To investigate the electrophysiologic mechanism of PMVT, monophasic action potentials (MAPs) were recorded with a contact electrode technique from right ventricular sites during sinus rhythm and right ventricular pacing. MAPs were obtained from 6 patients with PMVT (PMVT group) and 11 patients without PMVT (control group). The duration from the onset of the upstroke to 90% repolarization of the MAP (MAPD90) during right ventricular pacing at both pacing cycle lengths of 600 and 400 ms was significantly longer in the PMVT group than in the control group (332+/-60 ms vs 279+/-33 ms [P < .005] and 276+/-32 ms vs 229+/-23 ms [P < .0001], respectively). Dispersion of the MAPD90 in sinus rhythm was significantly larger in the PMVT group than in the control group (52.5+/-34.6 ms vs 26.1+/-12.0 ms [P < .005]), and dispersion of the MAPD90 during right ventricular pacing at both pacing cycle lengths of 600 and 400 ms was also significantly larger in the PMVT group than in the control group (86.0+/-44.2 ms vs 37.4+/-28.6 ms [P < .005], and 48.8+/-19.3 ms vs 27.1+/-7.1 ms [P < .05], respectively). Dispersion of repolarization time (activation time plus MAPD90) at a pacing cycle length of 600 ms was longer in the PMVT group than in the control group (104.3+/-38.9 ms vs 49.4+/-31.2 ms [P < .05]). These results suggest that the patients with PMVT have a greater regional dispersion of ventricular repolarization time and that the heterogeneity of ventricular repolarization may play an important role in the genesis of PMVT.

Action Potentials↗
PubMed1999

[Telemedicine and telescience in the field of ophthalmology at Asahikawa Medical College].

Department of Ophthalmology at Asahikawa Medical University has established a video conferencing telemedicine network system between the department and each branch hospital in Japan to transmit full-motion (30 frames/second) color ophthalmological images since October 1994. Nowadays, the department has 15 branches to communicate with our system including one hospital in Fukushima Prefecture; Department of Ophthalmology, Harvard Medical School in USA; Nanjing Medical University in China with the use of INS net 1500 or INS net 64 (3 lines). This system is aimed for telemedicine, telescience as well as supports for ophthalmological surgeries. In this article, we described the present status and future prospective of our telemedicine project for the purpose of the elimination of areas without enough medical facilities and promotion of international scientific collaboration. We also described our "Telemedicine Center" at Asahikawa Medical University which is now under construction. We believe that this technology literally opens up the world to scientific and medical collaboration.

Computer Communication Networks↗
PubMed1999

Dose-related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord.

We previously reported that the intraplantar (i.pl.) application of nociceptin/orphanin FQ (N/OFQ) at extremely low doses elicited a nociception through a substance P (SP) release from nociceptor endings. In the present study, the nociception induced by SP (and N/OFQ) was abolished by intrathecal (i.t.) injection of neurokinin(1) (SP receptor) antagonist, suggesting the involvement of the stimulation of nociceptive primary SP neuron and SP release into spinal synapses. On the other hand, similar low doses of N/OFQ (i.t.) exerted nociceptive responses, characterized by scratching, biting, and licking, and these responses were blocked by an neurokinin(1) antagonist (i.t.) or capsaicin pretreatment or in tachykinin 1 gene knockout mice (tac1(-/-) mice), suggesting that N/OFQ receptor (NOR) also exists on the spinal terminals of SP neurons. When wide ranges of N/OFQ doses were used, a typical bell-shaped dose-response relationship was observed in both peripheral and central nociception tests. Furthermore, N/OFQ (1 nmol) administered i.pl. blocked SP (i.pl.)-induced flexor responses, which were abolished by pertussis toxin pretreatment or in NOR gene knockout (NOR(-/-)) mice. On the other hand, N/OFQ administered i.t. blocked SP (i.t.)-induced scratching, biting, and licking in capsaicin-pretreated and tac1(-/-) mice, and this antinociception was abolished in NOR(-/-) mice. All these findings suggest that N/OFQ has biphasic actions depending on doses in the nociceptors and spinal synapses and has postsynaptic antinociceptive actions in spinal cord by modulating SP signaling.

Analgesics↗
PubMed1999

[Sigma (sigma) receptor and neurosteroids].

Studies on the sigma receptor and related compounds are becoming more attractive since they were found to be closely related to higher brain functions such as memory, learning, depression, anxiety, schizophrenia and neuroprotection. Along with these pharmacological findings, the single transmembrane-type, non-metabotropic sigma binding protein has been cloned, while the presence of metabotropic sigma receptor has been also claimed. Thus, various pharmacological findings are now ready to be characterized on the molecular basis of receptor mechanisms. On the other hand, neurosteroids have higher brain functions such as non-genomic fast actions, which are similar to the actions of sigma compounds. Indeed some neurosteroids were revealed to behave as sigma agonists while others behave like antagonists of metabotropic sigma receptors. Pharmacological studies to determine if sigma compounds can be used to cure various central symptoms related to neurosteroids or steroid hormones can be expected.

Animals↗
PubMed1999

Organophosphate metabolic changes in the rat lens during the development of galactose-induced cataract.

Using phosphorous-31 nuclear magnetic resonance (31P-NMR) spectroscopy, we observed the metabolic kinetics of organophosphate compounds in the rat lens during cataract development induced by different doses of galactose (5%, 15%, 25%, and 40%) added to rat chow. The metabolic and histologic changes in the lenses were compared among the rats fed with different doses of galactose. alpha-Glycerophosphate significantly increased in response to the galactose doses, followed by a decrease to steady values of approximately 120% of the base line value, except in the 40% galactose group, which had a marked decrease to 68% of the base line value. Choline phosphate decreased rapidly during dosing in all but the 5% group, but no changes in those levels were observed after 2 weeks of galactose dosing. ATP decreased significantly when the histologic destruction progressed in the entire lens. Although inorganic phosphate increased significantly in a dose-dependent manner, it did not exceed the peak level. The histologic changes were closely related to the dynamic changes in the phosphorous compounds in the rat lens during formation of the galactose-induced cataract. Our results indicated that the development of a galactose-induced cataract was associated with the metabolic changes of the phosphate compounds.

Adenosine Triphosphate↗
PubMed1999

Case study of paired cadaver renal allografts from the same donor: influence of local DIC kidney and concomitant acute rejection on early graft outcome.

We report the clinical course of 2 recipients whose renal allografts were obtained from the same cadaver donor after cardiac arrest. The recipients showed different outcomes after transplantation. Graft biopsy after reperfusion revealed disseminated intravascular coagulation (so-called DIC kidney) and severe acute tubular necrosis (ATN) in both recipients. While one graft showed primary nonfunction, the other graft became functional after a post-operative anuric period. Serial graft biopsies performed during the oligo-anuric period revealed recovery of ATN and no intra-glomerular fibrin thrombi, but development of acute rejection was detected in both recipients. The left kidney graft showed more severe local DIC kidney than the right kidney, as well as more severe acute rejection in the oligo-anuric period. Despite aggressive anti-rejection therapy, the left kidney graft showed primary nonfunction. Therefore, severe acute rejection leading to primary nonfunction might have been related to more severe ischemic injury and more extensive local DIC kidney in the left kidney.

Adult↗
PubMed1998

Morphologic characteristics of physiologically defined neurons in the cat trigeminal nucleus principalis.

Although the principalis nucleus (Vp) contains trigeminothalamic and internuclear tract cells, the functional and morphologic differences between the two kinds of neurons have remained unsettled. The present study was aimed to address these problems by using the intracellular horseradish peroxidase injection technique in the cat. Of 20 neurons stained, 7 and 13 were located in the dorsomedial subnucleus (Vpd) and ventrolateral subnucleus (Vpv) of Vp, respectively. The Vpd neurons received input from the intraoral structures only but the Vpv neurons from the intraoral or facial structures. Nineteen neurons could be divided as class I and class II, based on the branching pattern of their stem axons. Class I (eight neurons) had an ascending stem axon without branching. Class II was divided into two subclasses (IIa and IIb). Class IIa (eight neurons) had an ascending stem axon from which branches were given off. Their branches formed a local-circuit restricted to the lower brainstem. Class IIb (three neurons) had a stem axon that formed the local-circuit only. The dendritic morphology was indistinguishable between different classes of neurons and between the subdivisions. Although the dendritic arborization pattern was governed by the location of the somata, it was suggested to be also important elements for determining primary afferent arborizations. In the brainstem nuclei, the jaw-closing motor nucleus received the highest density of projections from class II neurons with the receptive field involving the periodontal ligaments. The present study provides new findings that Vp neurons could be divided into three distinct populations and suggests that each population exerts a distinct function with respect to sensory discrimination, sensorimotor reflexes, or both.

Anatomy, Artistic↗
PubMed1998

Optimization of codon usage of plasmid DNA vaccine is required for the effective MHC class I-restricted T cell responses against an intracellular bacterium.

In an attempt to study codon usage effects of DNA vaccines on the induction of MHC class I-restricted T cell responses against an intracellular bacterium, Listeria monocytogenes, we designed two plasmid DNA vaccines encoding an H-2Kd-restricted epitope of listeriolysin O (LLO) of L. monocytogenes, LLO 91-99. One DNA vaccine, p91wt, carries the wild-type DNA sequence encoding LLO 91-99, and the other one, p91mam, possesses the altered DNA sequence in which the codon usage was optimized for murine system. Our read-through analyses with LLO 91-99/luciferase fusion genes confirmed that the optimized 91mam DNA sequence showed extremely higher translation efficiency than the wild-type sequence in murine cells. Consistent with this, i.m. injections of p91mam, but not of p91wt, into BALB/c mice were capable of inducing specific CTL- and IFN-gamma-producing CD8+ T cells able to confer partial protection against listerial challenge. Taken together, these observations suggest that optimization of codon should be taken into consideration in the construction of DNA vaccines against nonviral pathogens.

Animals↗
PubMed1998

Differences in the electrophysiological response to I- and the inhibitory anions SCN- and ClO-4, studied in FRTL-5 cells.

The electrophysiological properties of the Na+/I- symporter (NIS) were examined in a cloned rat thyroid cell line (FRTL-5) using the whole-cell patch-clamp technique. When the holding potential was between -40 mV and -80 mV, 1 mM NaI and NaSCN induced an immediate inward current which was greater with SCN- than with I-. The reversal potential for I- and SCN- induced membrane currents was +50 mV. This is close to the value of +55 mV calculated by the Nernst equation for Na+. These results are consistent with I- and SCN- translocation via the NIS that is energized by the electrochemical gradient of Na+ and coupled to the transport of two or more Na+. There was no change in the membrane current recording with ClO-4 indicating that ClO-4 was either not transported into the cell, or the translocation was electroneutral. ClO-4 addition, however, did reverse the inward currents induced by I- or SCN-. These effects of I-, SCN- and ClO-4 on membrane currents reflect endogenous NIS activity since the responses duplicated those seen in CHO cells transfected with NIS. There were additional currents elicited by SCN- in FRTL-5 cells under certain conditions. For example at holding potentials of 0 and +30 mV, 1 mM SCN- produced an increasingly greater outward current. This outward current was transient. In addition, when SCN- was washed off the cells a transient inward current was detected. Unlike SCN-, 1-10 mM I- had no observable effect on the membrane current at holding potentials of 0 and +30 mV. The results indicate FRTL-5 cells may have a specific SCN- translocation system in addition to the SCN- translocation by the I- porter. Differences demonstrated in current response may explain some of the complicated influx and efflux properties of I-, SCN- and ClO-4 in thyroid cells.

Animals↗
PubMed1998

Inactivation of tumor suppressor p53 by mot-2, a hsp70 family member.

The mortalin genes, mot-1 and mot-2, are hsp70 family members that were originally cloned from normal and immortal murine cells, respectively. Their proteins differ by only two amino acid residues but exhibit different subcellular localizations, arise from two distinct genes, and have contrasting biological activities. We report here that the two proteins also differ in their interactions with the tumor suppressor protein p53. The pancytosolic mot-1 protein in normal cells did not show colocalization with p53; in contrast, nonpancytosolic mot-2 and p53 overlapped significantly in immortal cells. Transfection of mot-2 but not mot-1 resulted in the repression of p53-mediated transactivation in p53-responsive reporter assays. Inactivation of p53 by mot-2 was supported by the down-regulation of p53-responsive genes p21(WAF-1) and mdm-2 in mot-2-transfected cells only. Furthermore, NIH 3T3 cells transfected with expression plasmid encoding green fluorescent protein-tagged mot-2 but not mot-1 showed an abrogation of nuclear translocation of wild-type p53. These results demonstrate a novel mechanism of p53 inactivation by mot-2 protein.

3T3 Cells↗
PubMed1998

Signaling of lysophosphatidic acid-evoked chloride current: calcium release from inositol trisphosphate-sensitive store.

In Xenopus oocytes, lysophosphatidic acid (LPA) evoked inward currents at the holding potential of -60 mV, which were quickly desensitized upon repeated challenges of the compound at 10 nM or 1 microM. This desensitization was prevented by pretreatment with protein kinase A inhibitor or recovered by its post-treatment, but not by the pretreatment with an inhibitor of protein kinase C or calmodulin kinase II. From pharmacological studies, the LPA-evoked currents were found to be mediated by phospholipase C, calcium-mobilization from thapsigargin-sensitive Ca2+ stores, araguspongine E-sensitive inositol trisphosphate receptor, and calcium-dependent chloride channels.

Animals↗
PubMed1998

Production of human compatible high mannose-type (Man5GlcNAc2) sugar chains in Saccharomyces cerevisiae.

A yeast mutant capable of producing Man5GlcNAc2 human compatible sugar chains on glycoproteins was constructed. An expression vector for alpha-1,2-mannosidase with the "HDEL" endoplasmic reticulum retention/retrieval tag was designed and expressed in Saccharomyces cerevisiae. An in vitro alpha-1,2-mannosidase assay and Western blot analysis showed that it was successfully localized in the endoplasmic reticulum. A triple mutant yeast lacking three glycosyltransferase activities was then transformed with an alpha-1, 2-mannosidase expression vector. The oligosaccharide structures of carboxypeptidase Y as well as cell surface glycoproteins were analyzed, and the recombinant yeast was shown to produce a series of high mannose-type sugar chains including Man5GlcNAc2. This is the first report of a recombinant S. cerevisiae able to produce Man5GlcNAc2-oligosaccharides, the intermediate for hybrid-type and complex-type sugar chains.

Amino Acid Sequence↗