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Biomedical subjects

Y Katayama

Publications and source records attributed to Y Katayama.

At least 163 records · Page 9Linked to original sources

Mutations in sixth transmembrane domain of AQP2 inhibit its translocation induced by vasopression.

Vasopression-induced phosphorylation of serine 256 of the aquaporin-2 (AQP2) water channel triggers translocation of the protein from cystolic reservoir vesicles to the apical membrane of collecting duct principal cells. Dileucine motifs are located in the sixth transmembrane domain (6TM) of AQP2 and are known as the signal sequence for internalization, sorting from the trans-Golgi network to endosomes/lysosomes, and basolateral sorting. In this study, involvement of 6TM in vasopressin-induced translocation of the protein was investigated. A series of mutations in 6TM of AQP2 was introduced to rat cDNA and expressed in LLC-PK(1) cells. Immunofluorescence microscopy indicated that the mutant AQP2 proteins were retained in the cytoplasm after vasopressin stimulation, which actually promoted the plasma membrane expression of wild-type protein. Immunoelectron microscopy showed that the mutant AQP2 proteins reached the endosomes but did not reach the plasma membrane. These results demonstrate that 6TM has essential domains for vasopressin-induced translocation from endosomes to the plasma membrane.

Animals↗

Thalamotomy caused by cardioversion in a patient treated with deep brain stimulation.

Deep brain stimulation (DBS) has been applied mainly for the treatment of intractable pain and involuntary movement disorders. Based on the rising numbers of patients undergoing DBS therapy, the possibility of emergent application of cardioversion for the treatment of occasional severe arrhythmia in DBS patients has also increased. However, there has been insufficient discussion about cardioversion in DBS patients. We employed a radiofrequency receiver that transmits to the brain impulses provided by an external generator through an antenna applied to the skin in front of the receiver. We experienced a patient who displayed almost complete cessation of his action tremor with thalamic stimulation. He also developed central dysesthetic pain and showed complete disappearance of his action tremor, even without stimulation, following successful application of cardioversion. It is considered that slight changes in the high-voltage electrical current or high-voltage electrical current spread induced central dysesthetic pain and almost identical effects to thalamotomy. We report for the first time a case of thalamotomy induced by cardioversion in a DBS patient. Clearly, we need to bear in mind that cardioversion has the capability to cause brain lesions in DBS patients with a radiofrequency receiver implanted subcutaneously at the anterior chest wall.

Atrial Fibrillation↗

Effects of anterodorsal pallidal stimulation on gait freezing (Kinesia paradoxa) in Parkinson's disease.

The results of a double-blind evaluation of the effects of internal globus pallidus (GPi) stimulation in 7 patients with advanced Parkinson's disease are summarized. The evaluation was performed 6-8 months after surgery while the patients were on medication with an optimal dose and schedule. The stimulation was turned off for at least 12 h. It was turned on in the morning (or maintained turned off), and the best and worst scores during their daytime activity were recorded as the on-period and off-period scores, respectively. A significant reduction in the total score on part III of the Unified Parkinson's Disease Rating Scale was induced by GPi stimulation at the off-period (-57%) as well as the on-period (-36%). Clinically important improvement was also achieved in severe gait freezing (kinesia paradoxa) in 2 patients when stimulation was applied to the anterodorsal portion of the GPi. Such an effect was observed during unilateral stimulation of the right side alone.

Aged↗

The characteristics and applications of recombinant cholesterol dehydrogenase.

Mass production of an r-CDH derived from Nocardia species was made possible by gene technology. (Horinouchi et al., Applied and Environmental Microbiology, 57, 1386-1393 (1991)). However, the characteristics of the r-CDH have not been studied in detail and have not been improved enough for industrial use. We accordingly characterized both the native-CDH and the r-CDH prepared from Streptomyces lividans. Both CDHs were monomers with molecular masses of 37 kDa. The Km of r-CDH was 2.50 x 10(-3) M for cholesterol and 2.33 x 10(-4) M for NAD. The activators of CDHs were TritonX-100 and cholate. TritonX-405, Ag+, and Zn2+ inhibited both enzymes. The residual activity of native CDH after heat treatment was 32% (37 degrees C, 60 min), while the r-CDH showed a residual activity of 87% (37 degrees C, 60 min). The r-CDH is an enzyme with high substrate specificity for cholesterol as well as native CDH and higher thermal stability than native CDH. We have developed a novel serum cholesterol assay using the r-CDH, which permits the direct measurement of cholesterol by measuring NADH reaction products. We conclude that this r-CDH enzyme is useful and can be used to measure cholesterol in a clinical chemistry setting.

Cholesterol↗

Molecular cloning of equine chromogranin A and its expression in endocrine and exocrine tissues.

Chromogranin A (CGA) is a member of a family of highly acidic proteins co-stored and co-released with catecholamines in the adrenal medullary cells as well as in other neurons and paraneurons. The nucleotide sequence encoding equine CGA was determined using RT-PCR and rapid amplification of complementary DNA (cDNA) ends (RACE) techniques. A total 1,828 bp of the nucleotide sequence reveals that equine CGA is a 448-residue protein preceded by an 18-residue signal peptide. Comparison of the amino acid sequence of equine CGA with those of human, porcine, bovine, mouse, rat and frog CGA showed high conservation at the NH2-terminal 1-77 amino acids regions (94.8%, 93.5%, 92.2%, 81.8%, 83.1% and 66.2%, respectively) and COOH-terminal 314-430 amino acids regions (90.6%, 81.4%, 90.6%, 80.5%, 83.3% and 39.0%, respectively), as well as a potential dibasic cleavage site, whereas the middle portion showed marked sequence variation (52.5%, 49.1%, 38.9%, 26.6%, 27.9% and 6.2%, respectively). Northern blot analysis and RT-PCR elucidated the tissue distribution of equine CGA mRNA. Its expression was confirmed not only in the adrenal medullary cells but also in other organs (cerebrum, cerebellum, pituitary gland, spinal cord, liver, thyroid gland, striated muscle, lung, spleen, kidney, parotid gland and sublingual gland). Further, in adrenal chromaffin cells and pituitary cells of the anterior-intermediate lobe, the expression was confirmed by in situ hybridization with anti-sense CGA cRNA probe.

Amino Acid Sequence↗

Sjögren's syndrome complicated with autoimmune hepatitis and antiphospholipid antibody syndrome.

A 56-year-old Japanese female simultaneously developed thrombocytopenia, sicca symptoms, and an elevation of transaminase. Antiphospholipid antibodies were detected in her serum. The presence of anti-SS-A antibodies in the serum and sialectasis, disclosed by sialography, suggested the presence of primary Sjogren's syndrome (SjS). The laboratory data and the biopsy of the liver showed compatible findings with autoimmune hepatitis (AIH). Thrombocytopenia and liver dysfunction satisfactorily responded to corticosteroid. To our knowledge, this is the first reported case of SjS with AIH and antiphospholipid antibody syndrome (APAS). Analysis of serum cytokine levels showed a predominance of Th0-Th1 response, which is not compatible with AIH, in this complicated autoimmune state.

Antibodies, Antiphospholipid↗

Disproportion of helper T cell subsets in peripheral blood of patients with primary Sjögren's syndrome.

We studied the proportions of Th1 and Th2 cells in peripheral blood of 15 patients with primary Sjögren's syndrome (p-SS), by using a procedure to enumerate the cells synthesizing cytokines such as INF-gamma or IL-4 in cytoplasm of CD4+ lymphocytes. The frequency of Th1 (INF-gamma containing) cells in p-SS patients was significantly reduced as compared to normal control (20.57+/-7.48% vs 28.78+/-11.56%, p < 0.05), while that of Th2 (IL-4 containing) cells was not different from normal control (3.33+/-0.98% vs 2.85+/-1.88%). The ratio of Th1 to Th2 cells in p-SS patients was significantly decreased as compared to normal control (6.60+/-3.15 vs 11.55+/-6.72, p < 0.05). There was no difference in frequency of Th1 or of Th2 cells between 8 patients given small amounts of prednisolone (PSL) and 7 patients not given PSL (21.44+/-9.39% vs 19.57+/-5.05%, 3.12+/-0.80% vs 3.56+/-1.17%). The percentage of Th1 cells was not different between 7 patients with glandular symptoms (G) and 8 patients with extraglandular symptoms (EG) (18.61+/-9.63% vs 22.27+/-5.02%). Although the frequency of Th2 cells was higher in EG-patients than that in G-patients (3.84+/-0.78% vs 2.74+/-0.86%) with tendency of elevated IgG level in sera, the ratio of Th1 to Th2 cells was not different among them (6.26+/-2.84 vs 6.99+/-3.64). These results suggest that the reduced ratio of Th1 to Th2 cells is essential and is related to the dysfunction of cellular immunity in p-SS.

Female↗

Intracerebral steal phenomenon associated with global hyperemia in moyamoya disease during revascularization surgery.

OBJECT: The collateral vessels in moyamoya disease appear to retain their ability to constrict during hypocapnia but not to dilate during hypercapnia. It has been claimed that hypercapnia, as well as hypocapnia, decreases the blood flow in regions perfused by collateral vessels, presumably because of intracerebral steal. If this holds true, the decrease in blood flow may be proportional to the global hyperemia in the brain. To establish appropriate hemodynamic control during revascularization surgery, the authors monitored the jugular bulb oxygen saturation (SjO2) intraoperatively, a method that could sensitively detect global hyperemia. METHODS: A total of 17 patients, most of whom presented with transient ischemic attacks or fluctuating neurological deficits, underwent intraoperative monitoring of their SjO2 and end-tidal carbon dioxide (ETCO2) after a state of anesthesia had been induced with isoflurane (Group 1) or propofol (Group 2). In eight of these patients, the regional cerebral blood flow (rCBF) of the collateral vessel territory was also monitored by laser Doppler flowmetry during the period of cortical exposure, and a total of 113 data sets (averaged values during 2.5-minute intervals) was collected. There was fluctuation in the ETCO2 levels ranging from 36 to 44 mm Hg. The mean SjO2 level was clearly greater (p < 0.01) in Group 1 (71.8 +/- 2.2%) than in Group 2 (63.3 +/- 2.1%). An episodic fall in rCBF was observed in association with a transient increase in SjO2. Such an event was not uncommon in Group 1 and there was a greater risk of rCBF decreasing when SjO2 exceeded a cutoff level of 76% (p < 0.01). This level could sometimes be reached at a broad range of ETCO2 readings (37-44 mm Hg). In Group 2, similar events sometimes occurred when SjO2 increased beyond 70%. However, this level could be reached only with a higher ETCO2 (42-44 mm Hg). The rCBF level was negatively correlated to SjO2 (p < 0.01), but not always to ETCO2, indicating that the episodic fall in rCBF was closely related to global hyperemia rather than the absolute level of hypercapnia. CONCLUSIONS: The observed association between a fall in rCBF and global hyperemia supports the intracerebral steal hypothesis and indicates that it is prudent to avoid excessive global hyperemia. The optimal range of CO2 for isoflurane is more restricted than that for propofol, presumably because isoflurane induces hyperemia by itself. Monitoring of SjO2 appears to represent the most practical technique for detecting global hyperemia as well as global ischemia, both of which may cause ischemic complications in moyamoya disease.

Adolescent↗

MCC-134, a novel vascular relaxing agent, is an inverse agonist for the pancreatic-type ATP-sensitive K(+) channel.

The effects of a novel vasorelaxant agent, MCC-134 (1-[4-(1H-imidazol-1-yl)benzoyl]-N-methyl-cyclobutanecarbothioamide++ +), were examined on reconstituted ATP-sensitive K(+) (K(ATP)) channels, which are composed of an inwardly rectifying K(+) channel, Kir6.2, and three types of sulfonylurea receptors (SUR): SUR1, SUR2A, and SUR2B. Each type of K(ATP) channel was heterologously expressed in human embryonic kidney 293T cells. The expressed K(ATP) channel currents were measured with the whole-cell configuration of the patch-clamp method. MCC-134 activated the SUR2B/Kir6.2 channel, was a weak activator of the SUR2A/Kir6.2 channel, but did not activate the SUR1/Kir6.2 channel. MCC-134 suppressed SUR1/Kir6.2 channel currents that had been fully activated by either diazoxide or NaCN, whereas it did not affect the fully activated SUR2A/Kir6.2 or SUR2B/Kir6.2 channel currents. Thus, MCC-134, which is a relatively effective opener of the vascular smooth muscle type (SUR2B) of K(ATP) channel, is an antagonist of the pancreatic type (SUR1) of K(ATP) channel. Therefore, depending on the subtype of SUR, a pharmacological agent can cause either activation or inhibition of K(ATP) channel activity.

ATP-Binding Cassette Transporters↗

[Evaluation of in vitro human blood transparentized using near-infrared light].

We developed a new technique for the in vitro imaging of transparent human blood and examined the resolution of a test chart in transparent blood. We utilized mainly three devices: a laser diode (wavelength 833 nm) that served as the light source, a near-infrared camera, and a fiberscope adapted for the camera. Blood was collected from a human femoral artery. We observed the images of transparent blood and the fiberscope image of a target in the blood using the light. These results indicate that further improvements in this system can be expected and real-time viewing by angioscope may be realized in vivo.

Blood↗

Changes in cerebral blood oxygenation induced by deep brain stimulation: study by near-infrared spectroscopy (NIRS).

Previous studies have demonstrated that neural activation causes changes in cerebral blood oxygenation (CBO), i.e. increases in tissue levels of oxy-Hb and total-Hb with a decrease in deoxy-Hb concentration. It is unclear, however, whether neural activation always induces the same pattern of CBO changes or not. In the present study, employing a near-infrared spectroscopy (NIRS), we investigated the CBO changes in the frontal lobe induced by direct stimulation of the thalamus (Vim) or globus pallidus (GPi) in patients with Parkinson's disease or essential tremor. The results indicated that under conditions of neural activation in the frontal lobe, oxy-Hb and total-Hb increased in all 6 cases. Deoxy-Hb decreased in 2 cases during GPi stimulation, and increased in 4 cases during low frequency stimulation of the Vim. The above findings suggest that neural activation induces various patterns of CBO change, especially in deoxy-Hb. This implies that functional MRI based on the BOLD contrast may not consistently detect the area of neural activation.

Cerebrovascular Circulation↗

Semi-automatic ROI placement system for analysis of brain PET images based on elastic model: application to diagnosis of Alzheimer's disease.

UNLABELLED: PET with 18F-fluorodeoxyglucose (FDG) is a useful technique to image cerebral glucose metabolism and to detect patients with Alzheimer's disease in the early stage, in which characteristic temporoparietal hypometabolism is visualized. We have developed a new system, in which the standard brain ROI atlas made of networks of segments is elastically transformed to match the subject brain images, so that standard ROIs defined on the segments are placed on the individual brain images and are used to measure radioactivity over each brain region. We applied this methods to Alzheimer's disease. METHODS: This method was applied to the images of 10 normal subjects (ages 55 +/- 12) and 21 patient clinically diagnosed as Alzheimer's disease (age 61 +/- 10). The FDG uptake reflecting glucose metabolism was evaluated with SUV, i.e. decay corrected radioactivity divided by injected dose per body weight in (Bq/ml)/(Bq/g). RESULTS: The system worked all right in every subject including those with extensive hypometabolism. Alzheimer patients showed markedly lower in the parietal cortex (4.0-4.1). When the threshold value of FDG uptake in the parietal lobe was set as 5(Bq/ml)/(Bq/g), we could discriminate the patients with Alzheimer's disease from the normal subjects. The sensitivity was 86% and the specificity was 90%. CONCLUSIONS: This system can assist diagnosis of FDG images and may be useful for treating data of a large number of subjects; e.g. when PET is applied to health screening.

Adult↗

Benzodiazepine receptor distribution and cerebral blood flow in early blindness--a PET study.

We studied benzodiazepine receptor (BZR) distribution, which is thought to be affected by neuronal density in the cerebral cortex, and CBF using [11C]flumazenil and [15O]water PET in early blind (EB) and in blindfold sighted control (SC) subjects. PET images were co-registered to the subject's MRI. Using SPM96, MRI images were normalized in the Talairach and Tournoux coordinate system, and accordingly MRI-registered PET images were spatially normalized. Statistical parametric maps were computed on a voxel-by-voxel basis, using the general linear model. CBF for EB was significantly larger in the Brodmann area 17 and 18, especially anterior area, than that for SC, while there was no significant difference in BZR distribution. Our BZR data suggest that the amount of neurons do not change due to early visual deprivation in the visual cortex, in spite of high CBF in visual cortex of EB subjects.

Adult↗

[Deep brain stimulation therapy: control of human brain function by chronically implanted electrodes].

During the last decade, it has become increasingly clear that deep brain stimulation(DBS) is useful for controlling various neurological disorders, including intractable pain and involuntary movements. The development of an implantable and programmable pulse-generator has greatly facilitated the clinical application of DBS therapy. The history and clinical data of DBS therapy currently available from the literature, together with our own cases treated by DBS, are reviewed. DBS therapy has many advantages over conventional neuroablative therapies, including reversibility of the procedure, controllability and relative selectivity of the effects, and possible plastic effects on neural function. Further evolution of the stimulation system, such as through integration with neuromonitoring devices, would open up a new field of restorative neurology and neurosurgery.

Brain↗

[Congenital thrombophilia caused by protein C deficiency].

To clarify the prevalence of protein C deficiency in patients with cardiovascular problems, we identified 54 patients with protein C deficiency by screening approximately 26,800 patients. The observed prevalence of protein C deficiency was 1 in 500. From the results of genetic analysis of 67 Japanese families with protein C deficiency, the recurrent defects of Phe139Val, Arg169Trp, Val297Met, Met364Ile substitutions and a G8857 deletion were accounting 49% of Japanese families with protein C deficiency. The defects including Phe139Val and Met364Ile substitutions and a G8857 deletion were only found in Japanese subjects and seemed to be a founder effect. Protein C deficiency is associated with a predisposition to venous thrombosis. It is not clear whether the deficiency is involved in arterial occlusion. We identified 34 patients with protein C deficiency manifested 45 episodes of arterial occlusive disease. We compared the onset age of arterial occlusive disease between patients with protein C deficiency and a group of patients with normal protein C levels. We found the early onset of acute myocardial infarction and atherothrombotic cerebral infarction in patients with protein C deficiency. Thus, our study suggests that congenital protein C deficiency contributes to earlier onset of arterial occlusive diseases in Japanese subjects.

Arterial Occlusive Diseases↗

[Three-channeled aortic dissection: selection of surgery based on the images].

Three patients with 3-channeled dissection were operated upon. Images of the dissection were enlargement of the false lumens, compression of the true lumen by enlarged false lumens and visceral arteries of false lumen origin. These prevent the use of cardiopulmonary bypass (CPB) and cause malperfusion of the viscera. Three-channeled dissecion is easy to rupture for its peculiar anatomy and total repair of the thoraco-abdominal aorta is mandatory. Fenestration brings functional recovery of malperfused viscera and enables the patients to be placed on CPB for total repair. Two patients underwent infrarenal and descending aorta fenestration followed by the total repair of thoraco-abdominal aorta successfully. A third patient has been placed on the strict CT follow-up following the infrarenal fenestration.

Adult↗