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Biomedical subjects

K Yasuda

Publications and source records attributed to K Yasuda.

At least 199 records · Page 11Linked to original sources

Serine 6 of Lck tyrosine kinase: a critical site for Lck myristoylation, membrane localization, and function in T lymphocytes.

Lck is a member of the Src family kinases expressed predominantly in T cells, and plays a pivotal role in TCR-mediated signal transduction. Myristoylation of glysine 2 in the N-terminal Src homology 4 (SH4) domain of Lck is essential for membrane localization and function. In this study, we examined a site within the SH4 domain of Lck regulating myristoylation, membrane localization, and function of Lck. A Lck mutant in which serine 6 (Ser6) was substituted by an alanine was almost completely cytosolic in COS-7 cells, and this change of localization was associated with a drastic inhibition of myristoylation in this mutant. To assess the role of Ser6 of Lck in T cell function, we established stable transfectants expressing various Lck mutants using Lck-negative JCaM1 cells. The Lck mutant of Ser6 to alanine, most of which did not target to the plasma membrane, was not able to reconstitute TCR-mediated signaling events in JCaM1 cells, as analyzed by tyrosine phosphorylation of intracellular proteins and CD69 expression. These results demonstrate that Ser6 is a critical factor for Lck myristoylation, membrane localization, and function in T cells, presumably because the residue is important for N-myristoyl transferase recognition.

Alanine↗

Surgical experience of the thoracic aortic aneurysm due to Takayasu's arteritis.

We have treated 10 patients with thoracic aortic aneurysms due to Takayasu's arteritis during the last 15 years and presented surgical results. In the surgical treatment of thoracic aortic aneurysm due to Takayasu's arteritis, therapeutic strategy is different from that for atherosclerotic aneurysm and should be determined by the location and the extent of aneurysmal lesions and the degree of inflammation. Palliative procedure, which was taken to reduce surgical risk, has failed to prevent the recurrence of aneurysmal formation or to minimize surgical risk in the later period. Radical surgical treatment for thoracic aortic aneurysms is highly recommended if technically possible. Penoperative steroid therapy to control the degree of inflammation, appropriate strategy for multiple or extensive lesions and progress in the organ protection method that enabled radical treatment, all these will contribute to the improvement of surgical results.

Adult↗

Current status of thromboangiitis obliterans (Buerger's disease) in Japan.

We analysed clinical features and outcome in 850 patients with thromboangiitis obliterans (TAO), based on the 1993 Nationwide Survey of Vasculitis database collected from 3722 clinical sites in Japan. The survey was designed to assess clinical manifestation categorized by Fontaine's classification, distribution of lesions (arterial involvement and migratory superficial phlebitis), response to medical and surgical treatment, and outcome. There were 771 males (90.7%) and 79 females (9.3%), with a mean age of 50.8+/-0.4 (range: 17-81) years. Clinical manifestations at the first consultation were Fontaine I in 8.0%, Fontaine II in 29.6%, Fontaine III in 23.9%, and Fontaine IV in 38.1%. These symptoms had been significantly improved by the time of survey. Ulcer formation in the past history had occurred in 45.2%, which was the most common in toes (85.9%). Failure of smoking cessation significantly affected the risk of ulcer formation (odds ratio=1.71, 95% CI=1.19-2.47; P=0.004) and amputation (odds ratio=2.73, 95% CI=1.86-4.01; P<0.0001). Clinical features in female patients with TAO were equal to those in male patients, except for the fact that non-smokers were more common in female patients. Abstinence from tobacco significantly reduces the risk of ulcer formation and amputation, and thus improves the quality of life in patients with TAO.

Adult↗

Early and late recurrence after gastrectomy for gastric carcinoma. Univariate and multivariate analyses.

BACKGROUND: To the authors' knowledge, there are few studies regarding the predictors of early and late recurrence after gastrectomy for gastric carcinoma, and it is unknown whether prognostic factors can be applied to the timing of recurrence. The current study analyzed patients who died of recurrent gastric carcinoma and clarified histopathologic indicators associated with early and late recurrence. METHODS: The study included 138 patients who died of recurrent gastric carcinoma after gastrectomy that was performed in the Department of Surgery I, Oita Medical University, between 1982-1995. Clinicopathologic findings were compared between 104 patients who died within 2 years after gastrectomy (early recurrence group) and 34 patients who died > 2 years after gastrectomy (late recurrence group). Multivariate analysis was performed to determine the independent factors correlated with the timing of recurrence. RESULTS: When compared with the late recurrence group, the early recurrence group was characterized by a tumor size >/= 5 cm (92% in the early recurrence group vs. 74% in the late recurrence group), positive lymphatic invasion (64% vs. 38%), extended lymph node metastasis (73% vs. 35%), Stage III or IV disease (87% vs. 62%), and limited lymph node dissection (32% vs. 3%). The mean survival time was influenced by the lymphatic invasion (P < 0.01), vascular invasion (P < 0.05), level of lymph node metastasis (P < 0.01), stage of disease (P < 0.01), and extent of lymph node dissection (P < 0.01). On multivariate analysis, survival time was found to be associated independently with the stage of disease (Stage I, II vs. Stage III, IV) or the level of lymph node metastasis (N0, N1 vs. N2, N3). CONCLUSIONS: The stage of disease and level of lymph node metastasis were found to be the most significant factors independently associated with the survival time after gastrectomy for gastric carcinoma. Patients with more advanced stage of disease (Stage III, IV) or those with extended lymph node metastasis (N2, N3) frequently died of recurrence within 2 years after gastrectomy.

Aged↗

Ventilatory response to exercise in patients with major aortopulmonary collateral arteries after definitive surgery.

Patients with pulmonary atresia and major aortopulmonary collateral arteries (MAPCAs) may be at risk for both ventilatory impairment and abnormal pulmonary circulation after definitive surgery. We measured the ventilatory response to exercise in 16 patients with MAPCAs after definitive surgery (group A) and compared the results with those in 16 patients with tetralogy of Fallot with pulmonary atresia and without MAPCAs after definitive operation (group B), with 24 patients with tetralogy of Fallot after one-stage repair without previous palliation (group C), and with 48 healthy subjects (group D). Pulmonary function and treadmill exercise tests were performed. Arterial blood gases were also analyzed and the dead space to tidal volume ratio calculated. In group A, the vital capacity, diffusion capacity, and peak oxygen uptake were lowest (p <0.001), whereas the ventilatory equivalent for carbon dioxide was highest and its value at peak exercise correlated with age at time of surgery (r = 0.73, p <0.002). The arterial oxygen tension decreased progressively in group A and its value at peak exercise inversely correlated with the mean pulmonary artery pressure in all patients (r = -0.75, p <0.001). The arterial carbon dioxide tension decreased significantly at peak exercise in controls but showed no change in group A. The dead space to tidal volume ratio decreased during exercise in patients without MAPCAs and in controls but increased in group A, and the dead space to tidal volume ratio at peak exercise was inversely correlated with vital capacity in all patients (r = -0.77, p <0.001). Diffusion capacity independently predicted arterial carbon dioxide tension and dead space ventilation during exercise. Marked restrictive ventilatory impairment with low diffusion capacity along with a pulmonary obstructive change contributed to the abnormal pulmonary gas exchange during exercise in group A. Earlier repair of MAPCAs may prevent the progression of the impaired ventilatory response to exercise in these patients.

Adolescent↗

The Pro12Ala polymorphism in PPAR gamma2 may confer resistance to type 2 diabetes.

Peroxisome proliferator-activated receptor gamma (PPARgamma) has been implicated in adipocyte differentiation. Recently it was reported that heterozygous deficiency of PPARgamma led to the protection from high-fat diet-induced insulin resistance in an animal model. A Pro12Ala polymorphism has been detected in the human PPARgamma2 gene. Since this amino acid substitution may cause a reduction in the transcriptional activity of PPARgamma, this polymorphism may be associated with decreased insulin resistance and decreased risk of type 2 diabetes. To investigate this hypothesis, we performed a case-control study of the Pro12Ala PPARgamma2 polymorphism in Japanese diabetic and non-diabetic subjects. The frequency of Ala12 was significantly lower in the diabetic group. In an overweight or obese group, subjects with Ala12 were more insulin sensitive than those without. These results suggest that the PPARgamma is a thrifty gene and that the Pro12Ala PPARgamma2 polymorphism protects against type 2 diabetes in the Japanese.

Aged↗

Wortmannin, a PI3-kinase inhibitor: promoting effect on insulin secretion from pancreatic beta cells through a cAMP-dependent pathway.

To determine the role of phosphatidylinositol 3-kinase (PI3-kinase) in the regulation of insulin secretion, we examined the effect of wortmannin, a PI3-kinase inhibitor, on insulin secretion using the isolated perfused rat pancreas and freshly isolated islets. In the perfused pancreas, 10(-8) M wortmannin significantly enhanced the insulin secretion induced by the combination of 8.3 mM glucose and 10(-5) M forskolin. In isolated islets, cyclic AMP (cAMP) content was significantly increased by wortmannin in the presence of 3.3 mM, 8.3 mM, and 16.7 mM glucose with or without forskolin. In the presence of 16.7 mM glucose with or without forskolin, wortmannin promoted insulin secretion significantly. On the other hand, in the presence of 8.3 mM glucose with forskolin, wortmannin augmented insulin secretion significantly; although wortmannin tended to promote insulin secretion in the presence of glucose alone, it was not significant. To determine if wortmannin increases cAMP content by promoting cAMP production or by inhibiting cAMP reduction, we examined the effects of wortmannin on 10(-4) M 3-isobutyl-1-methylxantine (IBMX)-induced insulin secretion and cAMP content. In contrast to the effect on forskolin-induced secretion, wortmannin had no effect on IBMX-induced insulin secretion or cAMP content. Moreover, wortmannin had no effect on nonhydrolyzable cAMP analog-induced insulin secretion in the perfusion study. These data indicate that wortmannin induces insulin secretion by inhibiting phosphodiesterase to increase cAMP content, and suggest that PI3-kinase inhibits insulin secretion by activating phosphodiesterase to reduce cAMP content.

1-Methyl-3-isobutylxanthine↗

Phosphorylation of the 105-kDa heat shock proteins, HSP105alpha and HSP105beta, by casein kinase II.

The 105-kDa heat shock protein alpha (HSP105alpha) and HSP105beta are mammalian heat shock proteins that belong to the HSP105/HSP110 family. Both HSP105alpha and HSP105beta consist of acidic and basic isoforms. Here we report that the acidic isoforms are serine phosphorylated HSP105alpha or HSP105beta. Furthermore, using an in-gel kinase assay with HSP105alpha or HSP105beta as the substrate, the protein kinase that phosphorylates HSP105alpha and HSP105beta was identified as casein kinase II. Since phosphorylated HSP105alpha is especially prominent in the brain compared to other tissues of mice and rats, the phosphorylation of HSP105alpha by casein kinase II may be biologically significant.

Animals↗

The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision.

Although the development of the vertebrate eye is well described, the number of transcription factors known to be key to this process is still limited. The localized expression of the orphan nuclear receptor Tlx in the optic cup and discrete parts of the central nervous system suggested the possible role of Tlx in the formation or function of these structures. Analyses of Tlx targeted mice revealed that, in addition to the central nervous system cortical defects, lack of Tlx function results in progressive retinal and optic nerve degeneration with associated blindness. An extensive screen of Tlx-positive and Tlx-negative P19 neural precursors identified Pax2 as a candidate target gene. This identification is significant, because Pax2 is known to be involved in retinal development in both the human and the mouse eye. We find that Pax2 is a direct target and that the Tlx binding site in its promoter is conserved between mouse and human. These studies show that Tlx is a key component of retinal development and vision and an upstream regulator of the Pax2 signaling cascade.

Animals↗

Estimation of photoparoxysmal response elicited by half-field visual stimulation.

We examined photoparoxysmal responses (PPRs) elicited by half-field visual stimulation with deep-red flicker light to determine the neurophysiological features of photosensitive epilepsy (PSE). EEG revealed two types of PPRs. One had the focal spike in the occipital region and the other in the temporo-occipital region at the contralateral hemisphere. The equivalent current dipoles of these types were located at the occipital cortex and the inferior temporal (IT) cortex, respectively. These cortices comprise one of the main pathways in the visual system, and they play important roles in color discrimination. Thus, we propose that the visual system, especially the occipital cortex and the IT cortex, might be involved in the generator mechanism of PSE.

Adolescent↗

Tbx5 and the retinotectum projection.

Dorsal and ventral aspects of the eye are distinct from the early stages of development. The developing eye cup grows dorsally, and the choroidal fissure is formed on its ventral side. Retinal axons from the dorsal and ventral retina project to the ventral and dorsal tectum, respectively. Misexpression of the Tbx5 gene induced dorsalization of the ventral side of the eye and altered projections of retinal ganglion cell axons. Thus, Tbx5 is involved in eye morphogenesis and is a topographic determinant of the visual projections between retina and tectum.

Animals↗

Urethral obstruction in patients with nighttime wetting: urodynamic evaluation and outcome of surgical incision.

The aim of this study was to investigate urodynamic findings and the outcome of surgical incision in patients with nighttime wetting due to urethral obstruction. A total of 239 patients with nighttime wetting (157 males and 82 females; mean age, 8.7; range, 4-18 years) was studied. One hundred and ten patients had monosymptomatic enuresis alone and 129 both nighttime wetting and daytime symptoms, that is, the majority was not simple bedwetters, but had signs of bladder overactivity. All patients were first treated with bladder training and fluid intake after dinner was restricted. The non-responders were then treated with tricyclic antidepressants, anticholinergics, or intra-nasal desmopressin and conditioning therapy. Ninety-seven patients who did not respond to these conventional treatments were investigated by voiding cystourethrography, bougie à boule, and urodynamic study. Urethral obstruction was noted in 34 patients (14.2%); posterior urethral valves in three males, ring stricture of the bulbar urethra in 26 males and distal urethral stenosis in five females. Detrusor instability was noted in 30 (94%) of 32 patients. Three patients had <15 mL/s of maximum flow rate and none had post-void residual urine. Pressure at maximum flow (PQ(max)) was 106.5 +/- 26.3 cm H(2)O in pressure/flow study. After surgery, nighttime wetting was cured in 25 patients (73.5%), improved in four (11.8%). Detrusor instability disappeared in six of 16 patients studied (37.5%) and improved in 8 (50%), and PQ(max) decreased significantly after operation (P = 0. 0034). In conclusion, most of the patients with urethral obstruction have detrusor instability and high pressure voiding, and these conditions improved after operation.

Adolescent↗

Comprehension and storage of four serially presented radio news stories by mild aphasic subjects.

The present study investigated aphasic subjects' ability to comprehend and store serially presented discourse. Sixteen mild aphasic subjects, eight age-matched normals, and eight younger normals listened to four serially presented radio news stories and a single radio news story. Half of the aphasic subjects performed as well as age-matched normals in a single-news-story comprehension task. However, they demonstrated a drastic deterioration in performance when asked to listen to a series of four news stories. Age-matched normals, and aphasic subjects, to a lesser extent, showed an impairment in the comprehension and storage of the news story heard last in a series of four news stories. These results were discussed in terms of the comprehension and storage resources of working memory.

Aphasia↗

Profound hypothermia and low flow cardiopulmonary bypass in resectioning a massive facial arteriovenous malformation.

A 44-year-old woman underwent resection of a massive facial arteriovenous malformation under profound hypothermia and low-flow cardiopulmonary bypass. A left ventricular vent through a small left anterior thoracotomy avoided ventricular distention associated with peripheral cannulation. Low-dose aprotinin was used to improve hemostasis. These techniques thus show promise for the safe application of profound hypothermic cardiopulmonary bypass in noncardiovascular operations.

Adult↗

Mitral valve replacement and subsequent composite graft replacement of the aortic root for infantile Marfan syndrome.

The cardiovascular lesions commonly seen in Marfan syndrome can frequently be the primary cause of premature death. Cardiac lesions involving both the mitral valve and the aortic root are commonly observed among patients diagnosed during early infancy, as so-called infantile Marfan syndrome. Since the lesions tend to progress rapidly with the end results of high morbidity and mortality, the majority of patients require surgical intervention at a young age. However, patients who undergo surgical intervention for both lesions during the first decade of life have been rarely reported in literature. In this report, we present a case of a 9-year-old boy who underwent aortic root replacement with a composite graft at 3.5 years after a prior prosthetic valve replacement of the mitral valve. Although the immediate result was satisfactory, the long-term result remains to be seen.

Aorta, Thoracic↗

Successful reoperation for diffuse supravalvular aortic stenosis.

We reoperated for diffuse supravalvular aortic stenosis using a modified technique of patch plasty described by Brom. A 36-year-old woman admitted to our hospital with a peak systolic pressure gradient of 92 mmHg across the ascending aorta had previously undergone Doty's operation at another hospital. Aortography showed an ascending aorta diffusely stenotic from the sinotubular junction to the aortic arch. We transected the ascending aorta just above the stenotic portion and incised the proximal wall to the sinus of Valsalva. Three patches were sewn to each sinus to expand them and the ascending aorta. The pressure gradient decreased postoperatively to 11 mmHg, and we conclude that this technique sufficiently relieves diffuse supravalvular aortic stenosis.

Adult↗

Simultaneous coronary artery bypass grafting and ascending aorta bifemoral bypass in small aorta syndrome.

A 55-year-old man with severe coronary artery disease and aortoiliac occlusive disease with small aorta syndrome was admitted to our department with angina pectoris and bilateral claudication. Intravenous subtraction angiography showed total occlusion of the right common iliac artery and 99% stenosis of the left common iliac artery with a markedly hypoplastic infrarenal aorta only 9 mm in diameter. It also revealed 90% stenosis at the origin of the left subclavian artery. Coronary angiography showed total occlusion of the left anterior descending artery and 90% stenosis of the circumflex artery. Simultaneous coronary artery bypass grafting and an ascending aorta-bifemoral bypass were conducted using an in-situ right internal mammary artery graft, an autologous saphenous vein graft, and a Y-figured expanded polytetrafluoroethylene graft. Postoperative angiography showed grafts to the coronary and bifemoral arteries were patient. This combined procedure is useful for patients with coronary artery disease and aortoiliac occlusive disease, especially in those with small aorta syndrome.

Aorta↗