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Biomedical subjects

Y Katayama

Publications and source records attributed to Y Katayama.

At least 109 records · Page 6Linked to original sources

Electrochemical sensing for the determination of activated cyclic AMP-dependent protein kinase.

A novel electrochemical system has been developed for monitoring the cyclic AMP-dependent protein kinase (PKA) activity. In this method, PKA activity was monitored as the change in the redox current of a ferrocene-pendant PKA substrate peptide (Fe-LRRASLG) on a gold electrode, which had been modified with thioctic acid, using cyclic voltammetry. The phosphrylation of the ferrocene-pendant substrate with PKA changed the net charge from +1 to -1. This caused a decrease in the redox current of the ferrocene unit due to an electrostatic repulsion between the substrate and the anionic surface of the electrode. We expect that this method is potentially useful for monitoring the enzyme activity in medical or pharmacological fields.

Biosensing Techniques↗

Novel biosensor for the rapid measurement of estrogen based on a ligand-receptor interaction.

A bioaffinity sensor was developed aiming at the detection of estrogen. This biosensor system is based on the specific binding of estrogen to its receptor immobilized on a gold disk electrode. The recombinant DNA encoding human estrogen receptor ligand-binding domain was expressed in bacteria using the histidine-tag fusion system. The expression of the fusion protein was under control of a bacteriophage T7 promoter, and the protein was purified under native conditions by affinity chromatography, which is based on a specific interaction between a histidine-tag, located in the N-terminus of the protein, and the Ni(II) chelate adsorbent. The protein was immobilized on an Au-electrode with Ni(II)-mediated chemisorption using a histidine tag and thiol-modified iminodiacetic acid. Cyclic voltammetric measurements showed that the reversible electrochemical reaction of a ferrocyanide/ferricyanide redox couple was suppressed by the presence of estrogen in a concentration-dependent manner. It seems reasonable to suppose that the electrostatic property of the protein layer on the electrode surface was altered by complexation with estrogen. These data suggest that this biosensor is applicable to the evaluation binding activities of the chemicals toward the human estrogen receptor.

Biosensing Techniques↗

Hemolytic uremic syndrome with intracranial hemorrhage following mitomycin C administration.

A 50-year-old woman treated for breast cancer with mitomycin C developed severe hypertension, followed by deep coma 3 days later. Computed tomography of the brain showed frontoparietal intracranial hemorrhage accompanied by subarachnoid hemorrhage. The patient was diagnosed additionally with hemolytic uremic syndrome (HUS) based on hemolytic anemia with schistocytosis, thrombocytopenia, and acute renal failure. The patient underwent hemodialysis and plasmapheresis with no improvement. We present the pathologic findings of the general vessels, which has been reported rarely. This case represents the first reported intracranial hemorrhage in HUS following mitomycin C administration. We emphasize the need to control blood pressure in patients with HUS.

Alkylating Agents↗

Subthalamic nucleus stimulation for Parkinson disease: benefits observed in levodopa-intolerant patients.

OBJECT: A blinded evaluation of the effects of subthalamic nucleus (STN) stimulation was performed in levodopa-intolerant patients with Parkinson disease (PD). These patients (Group I, seven patients) were moderately or severely disabled (Hoehn and Yahr Stages III-V during the off period), but were receiving only a small dose of medication (levodopa-equivalent dose [LED] 0-400 mg/day) because they suffered unbearable side effects. The results were analyzed in comparison with those obtained in patients with advanced PD (Group II, seven patients) who were severely disabled (Hoehn and Yahr Stages IV and V during the off period), but were treated with a large dose of medication (500-990 mg/day). METHODS: The patients were evaluated twice at 6 to 8 months after surgery. To determine the actual benefits afforded by STN stimulation to their overall daily activities, the patients were maintained on their medication regimen with optimal doses and schedules. Stimulation was turned off overnight for at least 12 hours. It was turned on in the morning (or remained turned off), and each patient's best and worst scores on the Unified Parkinson's Disease Rating Scale during waking daytime activity were recorded as on- and off-period scores, respectively. The order of assessment with respect to whether stimulation was occurring was determined randomly. The STN stimulation markedly improved daily activity and total motor scores in Group I patients. The percentage time of immobility (Hoehn and Yahr Stages IV and V) became 0% in patients who were intermittently immobile while not receiving stimulation. Improvements were demonstrated in tremor, rigidity. akinesia, and gait subscores. The STN stimulation produced less marked but still noticeable improvements in the daily activity and total motor scores in Group II patients. The percentage time of immobility as well as the LED was reduced in patients who displayed intermittent immobility with pronounced motor fluctuations while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, and dyskinesia subscores in these patients. In contrast, STN stimulation did not improve the overall daily activities at all in patients who had become unresponsive to a tolerable dose of levodopa and were continuously immobile, even though these patients' tremor and rigidity subscores were still improved by stimulation. CONCLUSIONS: Consistent with earlier findings, the great benefit of STN stimulation in levodopa-intolerant patients is that STN stimulation can reduce the level of required levodopa medication. This suggests that STN stimulation could be a therapeutic option for patients with less-advanced PD by allowing levodopa medication to be maintained at as low a dose as possible, and to prevent adverse reactions to the continued use of large-dose levodopa.

Adult↗

New method of deep brain stimulation therapy with two electrodes implanted in parallel and side by side.

Reversibility and adaptability are preferred features of long-term therapeutic deep brain stimulation (DBS). In such therapy, a permanent stimulating electrode with four contact points is placed at the stimulation site and, generally speaking, bipolar stimulation is induced by various pairs of adjacent contact points on one electrode. The stimulation sites are thus all located along the trajectory of the implanted electrode. In a patient with unilateral severe essential tremor, the authors implanted two electrodes side by side and parallel to each other in the unilateral thalamic ventralis intermedius nucleus. Using these electrodes, the authors were able to deliver current flow not only along the electrode trajectory, but also between the two electrodes in a direction parallel to the anterior commissure-posterior commissure line. Although individual stimulations, delivered by each of the two electrodes using all parameters and all stimulation points, were unable to stop the patient's tremor completely without adverse effects, the new stimulation method, in which electrical currents passed between the two electrodes, effected complete abolition of the tremor without adverse effects. With the aid of this method, one can use two electrodes, implanted in parallel and side by side, to achieve maximum efficacy and to reduce adverse effects in some instances of DBS therapy.

Aged↗

Telomerase activity in peripheral blood mononuclear cells of systemic connective tissue diseases.

OBJECTIVE: Telomerase activity has been detected in a large number of cancers, as well as human germline tissue, but is absent in most normal somatic tissue. It has been reported that telomerase is also expressed at a low level in normal peripheral blood lymphocytes and that its activity is increased by antigen processing. We investigated if the telomerase activity in peripheral blood mononuclear cells (PBMC) from patients with systemic connective tissue diseases reflects disease activity. METHODS: We examined the enzyme activity of PBMC from patients with systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), primary Sjögren's syndrome (SS), and systemic sclerosis (SSc) using the telomeric repeat amplification protocol. In SLE and SS patients, the telomerase activity level was assessed for correlations with clinical disease activity. RESULTS: Telomerase activity was detected in 64.7% (11/17) of SLE patients, 63.6% (7/11) of MCTD, 54.5% (6/11) of SS, and 44.4% (4/9) of SSc. There was a significant correlation between SLE Disease Activity Index scores and telomerase activity in patients with SLE (p < 0.01). In patients with SS, telomerase activity was detected predominantly in patients with extraglandular manifestations, but was less detectable in patients without extraglandular manifestations (p < 0.05). CONCLUSION: Our data show that telomerase activity of PBMC is an indicator of disease activity, and may play a role in pathogenesis of systemic connective tissue diseases.

Adult↗

[Early operation for acute type a closing dissection].

From March 1997 to January 2000, we operated eleven cases of Stanford type A acute closing dissection. The patients consisted of 4 men and 7 women with a mean age of 71 +/- 9 years. There were 9 cases (81%) of cardiac tamponade and 5 cases (45%) was in the shock state. There were no malperfusion and end organ ischemia. All cases were operated with deep hypothermia and circulatory arrest. Ascending aortic replacement were performed in 9 cases and 2 cases were performed total arch replacement. 6 cases (63%) were not required blood transfusion. There was one operative death and one hospital death. These result suggest that we had better to perform immediate graft replacement for Stanford type A acute closing dissection as soon as possible, even if there were no serious complications.

Acute Disease↗

[A case of minimal invasive aortic valve replacement for quadricuspid aortic valve with aortic regurgitation].

Congenital quadricuspid aortic valve is rare, which may be a cause of sever aortic regurgitation. We report a case of a 55-year-old man who had severe aortic regurgitation with congenital quadricuspid aortic valve. Preoperative aortography showed severe aortic regurgitation. Preoperative trans-esophageal echocardiography revealed abnormal quadricuspid aortic valve. We performed minimal invasive aortic valve replacement with SJM # 21 mm HP prosthetic valve through the limited upper sternotomy. Skin incision was 9 cm. Aortic cross-clamping time was 92 min, cardiopulmonary bypass time was 108 min. At the operation, a quadricuspid valve with three equal cusps and one small cusp was noted. The postoperative course was excellent and he discharged 8 days after the operation.

Aortic Valve↗

[Pathologists and laboratory medicine: personal experiences].

The author started his career as an anatomical pathologist and now works as an anatomical and clinical pathologist. Most Japanese anatomical pathologists are not well trained for laboratory medicine, but they are required to have a knowledge of laboratory medicine and are expected to become managers of laboratories in general hospitals. The reconstruction of the laboratory is necessary to include an anatomical pathology division and a new post-graduate education system should be established in which both anatomical and clinical pathologists should be cross-taught mutual fields.

Laboratories, Hospital↗

[Postoperative right ventricular function after repair of tetralogy of Fallot with respect to the method of right ventricular outflow tract reconstruction].

We evaluated postoperative right ventricular function in the sixty-four consecutive patients with tetralogy of Fallot underwent total correction. The patients were divided to three groups according to the method of right ventricular outflow tract reconstruction: transannular patching (TA group; n = 31); right ventricular outflow patching with preservation of pulmonary valve ring (RV group; n = 12) and transatrial-transpulmonary approach without right ventriculotomy (no-RV group; n = 21). The early results of postoperative cardiac catheterization and echocardiography were compared among the three groups. Degree of pulmonary regurgitation was significantly low in the RV group and no-RV group compared with TA group (p < 0.005). Right ventricular ejection fraction was the highest in the no-RV group (p < 0.002). The repair without right ventriculotomy for tetralogy of Fallot can provide the best results with respect to postoperative right ventricular function.

Cardiac Surgical Procedures↗

[A case of emergency surgery for acute mitral regurgitation due to complete papillary muscle rupture as a severe form of reperfusion injury: report of a case].

Complete rupture of a papillary muscle following acute myocardial infarction is a severe complication associate with acute left ventricular failure and pulmonary edema. Since the introduction of acute percutaneous transluminal coronary angioplasty (PTCA) in the management of acute myocardial infarction, the frequency of this complication has further decreased. We described a patient who had acute mitral regurgitation due to complete rupture of papillary muscle rupture after successful coronary intervention. Transesophageal echocardiography demonstrated severe mitral regurgitation and the ruptured papillary muscle. At operation, posteriol papillary muscle was found to be totally ruptured. Mitral valve replacement was performed. Postoperative course was uneventful, with 2 days of IABP and 5 days of ventilator support.

Acute Disease↗

[Detection of monoclonal plasma cells in bone marrow and spleen of primary amyloidosis].

A 53-year-old man was diagnosed as primary amyloidosis by biopsy specimens of the mucosa in rectum, spleen and bone marrow (BM). BM examination showed 5.5% of plasma cells with some dysplasia. Immunoglobulin heavy chain gene rearrangement was detected by polymerase chain reaction using third-complementary-determining region (CDR 3) specific primers in BM mononuclear cells and spleen cells embedded in paraffin. The sequence analysis revealed that monoclonal B cells existed in the both, BM and spleen. Flowcytometric analysis using two-color staining showed the phenotype of plasma cells with the expression of CD19+/-, CD27+/-, CD56+/- and CD138+ and CD38++. This phenotype is similar to those of monoclonal gammopathy of undetermined significance (MGUS). Therefore, primary amyloidosis is considered to have two plasma cell populations including normal plasma cells and monoclonal plasma cells in BM. Given that there are two types of plasma cells in patients with primary amyloidosis, amyloid protein is expected to originate from immunoglobulin light chain produced by monoclonal plasma cells.

Amyloid↗

[Deep brain stimulation therapy for involuntary movements].

During the last decade, it has become clear that deep brain stimulation (DBS) therapy provides a dramatic improvement in the symptoms of movement disorders. We have experienced DBS in 110 patients with various types of involuntary movements, and confirmed the benefits of stimulation of the thalamic nucleus ventralis intermedius (Vim), internal globus pallidus (GPi) and subthalamic nucleus (STN) in these patients. DBS therapy affords the best effect on tremor when the Vim is selected as the stimulation site. DBS therapy is also useful for controlling rigidity when the GPi or STN is stimulated. Improvements of bradykinesia and gait disturbance are often induced by DBS therapy involving the GPi or STN. Dopa-induced dyskinesia can be attenuated effectively by the direct and/or indirect effects of DBS therapy. DBS of the Vim also provides excellent control of post-stroke involuntary movements, including hemiballism and hemichoreoathetosis. Dystonia in young patients is controlled effectively by DBS of GPi. Ablative procedures for control of involuntary movement disorders, such as thalamotomy and pallidotomy, always carry a risk associated with creating additional lesions in an already damaged brain. In contrast, there is not such a risk in DBS therapy. This modality of therapy is an important option in treating involuntary movements.

Dyskinesias↗

C-terminal tails of sulfonylurea receptors control ADP-induced activation and diazoxide modulation of ATP-sensitive K(+) channels.

The ATP-sensitive K(+) (K(ATP)) channels are composed of the pore-forming K(+) channel Kir6.0 and different sulfonylurea receptors (SURs). SUR1, SUR2A, and SUR2B are sulfonylurea receptors that are characteristic for pancreatic, cardiac, and vascular smooth muscle-type K(ATP) channels, respectively. The structural elements of SURs that are responsible for their different characteristics have not been entirely determined. Here we report that the 42 amino acid segment at the C-terminal tail of SURs plays a critical role in the differential activation of different SUR-K(ATP) channels by ADP and diazoxide. In inside-out patches of human embryonic kidney 293T cells coexpressing distinct SURs and Kir6.2, much higher concentrations of ADP were needed to activate channels that contained SUR2A than SUR1 or SUR2B. In all types of K(ATP) channels, diazoxide increased potency but not efficacy of ADP to evoke channel activation. Replacement of the C-terminal segment of SUR1 with that of SUR2A inhibited ADP-mediated channel activation and reduced diazoxide modulation. Point mutations of the second nucleotide-binding domains (NBD2) of SUR1 and SUR2B, which would prevent ADP binding or ATP hydrolysis, showed similar effects. It is therefore suggested that the C-terminal segment of SUR2A possesses an inhibitory effect on NBD2-mediated ADP-induced channel activation, which underlies the differential effects of ADP and diazoxide on K(ATP) channels containing different SURs.

ATP-Binding Cassette Transporters↗

Double blinded evaluation of the effects of pallidal and subthalamic nucleus stimulation on daytime activity in advanced Parkinson's disease.

The results of a double blinded evaluation of the effects of globus pallidus (GPi; n=7) and subthalamic nucleus (STN; n=11) stimulation in patients with advanced Parkinson's disease are summarized. The patients were evaluated at 6-8months after surgery. In order to determine the benefits afforded by the stimulation to the actual daily activities, the patients were maintained on-medication with optimal doses and schedules. The stimulation was turned off overnight for at least 12h. It was turned on in the morning (or maintained turned off), and the best and worst scores during daytime activity were recorded, as on-period and off-period scores, respectively. A reduction in total motor score on the Unified Parkinson's Disease Rating Scale was clearly elicited by GPi and STN stimulation at both the off-period (-57 and -29%, respectively) and the on-period (-36 and -25%, respectively). The difference in effects between GPi and STN stimulation appeared to be due largely to an unintended difference in the patients' preoperative symptoms. The benefits provided by stimulation to the actual daily activities appears to be limited in patients who have become unresponsive to a large dose of levodopa. Two advantages of GPi and STN stimulation were identified. Firstly, the stimulation can supplement a reduced action of levodopa during the off-period. It thus improves the patient's daily activities through attenuation of the motor fluctuations. Secondly, the stimulation can replace part of the action of levodopa during the on-period. It thus attenuates dopa-induced dyskinesia through a reduced dose of medication. More importantly, the stimulation improves the daily activities in dopa-intolerant patients who are being administered a small dose of levodopa because of unbearable side effects. In addition, GPi stimulation has its own inhibitory effect on dopa-induced dyskinesia. Clinically important improvement was observed in severe gait freezing in 2 patients following unilateral anterodorsal GPi stimulation on the right side alone.

Journal Article↗

The design of cyclic AMP--recognizing oligopeptides and evaluation of its capability for cyclic AMP recognition using an electrochemical system.

A novel 17-mer peptide ligand for cyclic AMP was designed using the amino acid sequences of essential subsites in various cyclic AMP-dependent protein kinase (protein kinase A) families. The Au disk electrode, which was modified with the designed 17-mer oligopeptide, responded to cyclic AMP but virtually did not respond to any other cyclic nucleotides using the ion channel sensor mechanism. On the other hand, a scrambled peptide, which had the same amino acid composition as and had an amino acid sequence different from the 17-mer oligopeptide, did not respond to any nucleotides. This indicates that the designed 17-mer peptide actually acted as a selective ligand for cyclic AMP. This ligand-designing strategy using peptide sequences in target-binding proteins may possibly be extended to the design of peptide ligands for other second messengers.

Cyclic AMP↗

Pyruvate dehydrogenase activity and energy metabolite levels following bilateral common carotid artery occlusion in rat brain.

The influence of chronic cerebral hypoperfusion on cerebral energy metabolism was studied. The bilateral common carotid arteries of Wistar rats were occluded for 0, 2, 7, and 28 days. Cerebral energy metabolism was evaluated by assaying adenosine triphosphate (ATP), phosphocreatine (PCr), and lactate levels and measuring pyruvate dehydrogenase (PDH) activity (each time point, n = 6). Pathological changes were assessed light-microscopically by Klüver-Barrera staining and immunohistochemical labeling for astroglia (each time point, n = 3). There were no changes in ATP and PCr levels or PDH activity; there was slight but significant transient lactate accumulation at 2 days. Myelin pallor and increase in immuno-reactive astroglia were only observed at 28 days. These results indicate that chronic cerebral hypoperfusion induces delayed white matter changes in the corpus callosum of rat brain, but does not affect energy production.

Adenosine Triphosphate↗