Biomedical subjects

K Seki

Publications and source records attributed to K Seki.

At least 163 records · Page 9Linked to original sources

PubMed1996

Binding of myristoylated alanine-rich protein kinase C substrate to phosphoinositides attenuates the phosphorylation by protein kinase C.

The myristoylated aline-rich protein kinase C substrate (MARCKS) is a peripheral membrane protein that undergoes phosphorylation-dependent translocation between membrane and cytosol. MARCKS binds to acidic phospholipids with high affinity (Kd less than 0.5 microM) but binds poorly to neutral phospholipids. Although interaction of MARCKS with acidic phospholipids lacks specificity when determined by binding assay, these phospholipids exert distinctive effects on the phosphorylation of this protein by protein kinase C (PKC). Preincubation of MARCKS with phosphatidylserine (PS) or phosphatidylglycerol enhanced the phosphorylation; whereas with phosphatidic acid, phosphatidylinositol (PI), phosphatidylinositol-4-phosphate, or phosphatidylinositol-4,5-biphosphate inhibited the phosphorylation of this substrate by PKC. Phosphoinositide inhibition of MARCKS phosphorylation was apparently directed at the substrate rather than at the kinase as the phosphorylation of two other phospholipid-binding PKC substrates, neuromodulin and neurogranin, exhibited different responses from those of MARCKS. Furthermore, the inhibition of phosphoinositides on MARCKS phosphorylation was seen with PKC isozymes alpha, beta, gamma, and delta and with the catalytic fragment of PKC, protein kinase M. A 25-amino-acid synthetic peptide corresponding to the phosphorylation site domain (PSD) of MARCKS, but not to the myristoylated N-terminal peptide, competed equally effectively with MARCKS in binding to either PS- or PI-containing vesicles, suggesting that both phospholipids bind to the PSD of MARCKS. Binding of PI to MARCKS inhibited PKC phosphorylation of all three phosphorylation sites. These results suggest that phosphoinositides and PS bind at different residues within the MARCKS PSD, so that the resulting phospholipid/MARCKS complexes are differentially phosphorylated by PKC.

Amino Acid Sequence↗

PubMed1996

Lack of association of very low density lipoprotein receptor gene polymorphism with Caucasian Alzheimer's disease.

To determine whether the association of the very low density lipoprotein receptor (VLDL-R) gene with Alzheimer's disease (AD), which has recently been identified in Japanese AD patients, is commonly observed in AD patients of other ethnic backgrounds, we have investigated the allele frequency of the polymorphic CGG repeat in the 5'-UTR of the VLDL-R gene using a data set of 84 Caucasian AD patients with 104 Caucasian controls. Although the allele frequency of the 8-repeat allele was slightly lower, and that of 9-repeat allele was slightly higher, in the Caucasian AD patients than in Caucasian controls, the differences were not statistically significant. Multiple logistic regression analysis using apolipoprotein E4 (APOE4) allele, 5, 8-, or 9-repeat allele of the VLDL-R gene, sex, and age at onset as the predictors revealed that only the APOE4 allele was significantly associated with AD in the data set of the Caucasian AD patients and controls.

Aged↗

PubMed1996

Cardiovascular and respiratory responses to passive leg cycle exercise in people with spinal cord injuries.

The purpose of this study was to determine the effect of passive leg cycle exercise (PLE) on cardiovascular and respiratory responses in people with spinal cord injuries (PSCI). Eight PSCI with lesions from T8 to L1 and five control subjects (CS) performed PLE at pedalling frequencies of 20 or 40 rpm for 7 min at room temperature of about 25 degrees C. We measured, at rest and during PLE, the pulmonary ventilation (VE), oxygen uptake (VO2), cardiac output (Q), stroke volume (SV), heart rate (HR) and arterial blood pressure, as well as the skin blood flow (SBF) in the lower limb after PLE. An increase in pedalling frequency promoted an increase in VE and VO2 in both groups. Compared with the CS, the PSCI showed significantly smaller increases in VO2 (P < 0.05). The Qc was significantly elevated during PLE at 20 and 40 rpm in CS, and at 40 rpm in PSCI (P < 0.05). In CS, it resulted from increases in both SV and HR, whereas in PSCI, it was contributed to by a greater increase in SV without a rise in HR. In CS, the increase in pedalling frequency promoted the increases in SV and HR and consequently in Qc. In PSCI, however, the values remained constant irrespective of pedalling frequency. The arterial blood pressure and SBF in the lower limbs were unchanged by PLE in both groups. These results would suggest that passive leg exercise promotes venous return from the paralyzed lower limbs in PSCI.

Adult↗

PubMed1996

Relationship between core temperature and skin blood flux in lower limbs during prolonged arm exercise in persons with spinal cord injury.

The purposes of the present study were to examine the response of the skin blood flux (SBF) in the paralyzed lower limbs of persons with spinal cord injury (PSCI) and to clarify the relationship between the SBF and core temperature during prolonged arm exercise. Eight male PSCI with lesions from T6 to L5 and six male control subjects (CS) participated in this study. The subjects rested for 60 min and then performed arm-cranking exercise at 20 W for 30 min at 25 degrees C. The tympanic membrane temperature (Tty) and SBF in the anterior thigh (SBFT) and in the posterior calf (SBFC) were continuously measured throughout the experiment. The SBFC did not change in either PSCI or CS during the experiment. The SBFT in four PSCI with high lesions (T6 to T12), remained unchanged during exercise. The SBFT in the other four PSCI with low lesions (T12 to L5, delta SBFT+) began to elevate markedly when the Tty exceeded a threshold temperature of 36.69 degrees C. The pattern of increase of SBFT in delta SBFT+ was similar to that in CS, although onset of the increase in SBFT was delayed and the peak of SBFT during exercise was significantly lower in comparison with the CS. We consider that these differences between the delta SBFT+ and CS were largely attributable to the lower Tty in the former group, which took a prolonged time to reach the threshold of 36.69 degrees C.

Adult↗

PubMed1996

Ineffective leftward search in line bisection and mechanisms of left unilateral spatial neglect.

We examined the eye-fixation pattern of a patient with severe left unilateral spatial neglect who showed leftward searches of various extent in more than half of line bisection trials. Because of complete left homonymous hemianopia, he perceived only the segment of the line between its right endpoint and the point of the leftmost fixation. In the trials with leftward searches, he frequently placed the subjective midpoint on the right part of the perceived segment. In the trials without leftward searches, he placed it near the left extreme point of the perceived segment. For all these bisections, the subjective midpoint was constantly placed far to the right of the true midpoint of the line irrespective of the length perceived. We consider that in severe left unilateral spatial neglect, rightward attentional bias is the predominant factor that determines where to place the subjective midpoint. Transient attentional shift to the left may produce leftward searches, but it does not induce effective processing of line bisection.

Aged↗

PubMed1996

Diverse patterns of performance in copying and severity of unilateral spatial neglect.

We analysed the performances of 69 patients with left unilateral spatial neglect in copying a multi-object figure, as well as their performance of the line cancellation and line bisection tests. Three patterns of copying were mainly observed. The first pattern was almost satisfactory performance in copying the central figure with occasional omission of the elements located more laterally to the left. The second pattern was omission of the left half of the whole figure, which was the pattern expected of patients with typical left unilateral spatial neglect. The third pattern was left unilateral spatial neglect when copying the central figure, with favourable copying of left lateral objects; this may be regarded as "object-centered" neglect. Performance of the line cancellation test, which requires exploratory ability, was significantly better for the patients with the third pattern than for those with the second pattern. A significant difference was also observed between the two groups of patients in performance of the line bisection test, in which exploratory ability plays a more minor role. No significant difference was found in performance of the line cancellation and line bisection tests between the patients with the third and first patterns, in spite of remarkable differences in their copying performances. No distinctive characteristics were found for any group of patients as regards lesion, age, duration after onset, education, and WAIS scores. Therefore we concluded that in most of our patients with neglect, these diverse patterns of copying deficits resulted from different levels of neglect severity but not from different types of unilateral spatial neglect.

Adult↗

PubMed1996

Effect of maximal arm exercise on skin blood flux in the paralyzed lower limbs in persons with spinal cord injury.

The purpose of the present study was to examine the effect of maximal arm exercise on the skin blood circulation of the paralyzed lower limbs in persons with spinal cord injury (PSCI). Eight male PSCI with complete lesions located between T3 and L1 performed graded maximal arm-cranking exercise (MACE) to exhaustion. The skin blood flux at the thigh (SBFT) and that at the calf (SBFC) were monitored using laser-Doppler flowmeter at rest and for 15 s immediately after the MACE. The subject's mean peak oxygen uptake and peak heart rate was 1.41 +/- 0.22 l.min-1 and 171.6 +/- 19.2 beats.min-1, respectively. No PSCI showed any increase in either SBFT or SBFC after the MACE, when compared with the values at rest. These results suggest that the blood circulation of the skin in the paralyzed lower limbs in PSCI is unaffected by the MACE.

Adult↗

PubMed1996

Surgical treatment of isolated secundum atrial septal defect in patients more than 50 years old.

BACKGROUND: Arrhythmia-related thromboembolic accidents continue to occur in patients even after closure of secundum atrial septal defect. Older age is usually not a contraindication to the repair of an atrial septal defect. To assess the importance of the type of management in elderly patients with atrial septal defect our clinical experience is reviewed. METHODS: Between 1974 and 1994, 49 patients 50 years of age or older (average, 57.4 years) underwent surgical closure of secundum atrial septal defect. All patients have been followed up for 2 to 21 years (mean, 9.7 years). RESULTS: There were no operative deaths. Functional classes in most of the patients were improved after operation. There were two cerebrovascular thromboembolic accidents with one permanent neurologic dysfunction, hemiparesis, and one septal dehiscence in the early postoperative period. One patient (2%) died of renal failure 6 years after operation, late arrhythmias developed in 3 patients (6%), 3 patients had a late stroke (6%), and 1 patient was not available for follow-up. CONCLUSIONS: Long-term operative results are satisfactory and beneficial to the quality of life in elderly patients. Because there is no safe and effective nonsurgical alternative to surgical closure, atrial septal defect repair in elderly patients without severe pulmonary vascular disease should not be delayed once the diagnosis had been made.

Age Factors↗

PubMed1996

Appearance and disappearance of unilateral spatial neglect for an object: influence of attention-attracting peripheral stimuli.

We reported a dramatic phenomenon of appearance and disappearance of left unilateral spatial neglect for the same single object. In experiment 1, four patients with mild neglect who copied a single flower satisfactorily showed left neglect in copying of the same flower when it was accompanied with some peripheral stimuli. In experiment 2, we included three additional conditions to determine the stimulus component crucial for left neglect of the flower: a flower with a stem and a flower with either right or left peripheral stimuli were also used for copying. Overall results showed that neglect was most evident for the flower with the right peripheral stimuli. On the other hand, the presence of left stimuli provoked less severe neglect of the flower, which was as mild as that in the single flower condition. The results were explained in terms of an attentional mechanism underlying unilateral spatial neglect. When copying the flower with peripheral stimuli on both sides or on the right side, the stimuli on the right side might attract the patient's attention. Consequently, he exhibited left neglect on the central flower. On the other hand, neglect was less evident in the other conditions, since the figures did not include such attention-attracting stimuli on the right side.

Adult↗

PubMed1996

Mechanisms of unilateral spatial neglect in copying a single object.

The present study examined 13 patients with typical left unilateral spatial neglect to explore the mechanisms of neglect in copying a single object. All patients identified the figure of a sunflower as a flower that had petals all around the central circle. Besides, in the free viewing of the flowers prepared by the examiner, 10 of the 13 patients could discriminate between the presence and absence of the left-sided petals. When copying the flower, however, they always left the left side unfinished without noticing the incompleteness. Whether perception in the left visual field was impaired or not was irrelevant to the performances in the copying and the free viewing of the flowers. We consider the mechanism of left unilateral spatial neglect in copying a flower as follows. Small leftward shift of attention may take place during the free observation of the stimulus flower. While copying, however, neglect patients pay attention exclusively to the right-sided petals they are drawing. The strong engagement of attention to the right side results in the lack of discovery of the left-sided omission. The close integration of attentional and premotor mechanisms seems to be crucial for the appearance of unilateral spatial neglect in copying a single object.

Aged↗

PubMed1996

Neuromagnetic evidence of pre- and post-central cortical sources of somatosensory evoked responses.

Somatosensory evoked magnetic fields (SEFs), corresponding with electrical median nerve stimulation, were measured using an MRI-linked, whole-head MEG system. In total 184 hemispheres, SEFs were measured, involving 22 normal volunteers and 70 patients with intracranial lesions. The first SEF peak appeared 20.2 +/- 1.5 msec (mean +/- S.D.) after stimulation. The first peak was followed by a second and third peak, 7.7 +/- 3.2 msec and 14.6 +/- 5.4 msec respectively after the first. Corresponding isofield maps suggested a single current dipole oriented in the anterior direction for the first peak, posterior for the second and either anterior or posterior for the third. Using a spherical model and a single current dipole source, the localization of each peak was estimated and superimposed on individually determined MRI images. On a grand average basis, the first-peak dipole was localized on the posterior surface of the central sulcus, "area 3b." The second-peak dipole was localized 3.7 mm medial (P < 0.001) and 2.0 mm superior (P < 0.001) to the first-peak dipole, on the anterior wall of the central sulcus, "area 4." This study with a large number of subjects was able to statistically distinguish two adjacent cortical sources, located on opposite walls of the central sulcus, and within a few millimeters of each other.

Adult↗

PubMed1996

Composite graft replacement of the aortic root in patients with Marfan's syndrome.

Between October, 1979 and September 1994, 18 consecutive patients with Marfan's syndrome underwent replacement of the ascending aorta and aortic valve with a composite graft. There were 11 men and seven women; the mean age was 38.7 years. All patients had annuloaortic ectasia with significant aortic regurgitation. Ten of the 18 patients had aortic dissection. Concomitant procedures were performed in three patients. The hospital mortality rate was 17%, and two patients with concomitant procedures died early after surgery. There were three late deaths, two of which were related to late aortic complications. The actuarial 8-year survival rates in patients with and without aortic dissection were 58.3% and 77.8%, respectively. Since aortic dilatation and its complications are progressive in patients with Marfan's syndrome, improved surgical results can be obtained early in the course of the disease before cardiac disturbances and aortic dissections emerge.

Actuarial Analysis↗

PubMed1996

Solitary fibrous tumor of the soft tissue. An immunohistochemical and ultrastructural study.

Solitary fibrous tumor is a rare spindle cell neoplasm of adults that usually arises in the pleura, recently reported in other locations. The authors describe three cases of solitary fibrous tumors in adults that occurred as circumscribed masses in the somatic soft tissue, including the arm, back, and abdomen. Histologically, they were characterized by a proliferation of spindle cells separated by thick bands of collagen and prominent vascularity often showing a hemangiopericytoma-like pattern. The spindle cells, having low mitotic figures and little nuclear atypicality, exhibited a variety of growth patterns, including storiform, fascicular and herringbone, and nuclear palisading. Vimentin and CD34 immunoreactivities were observed in many spindle cells of all tumors. They had ultrastructural features of fibroblast and myofibroblast in two cases examined. Solitary fibrous tumors seem to represent distinct mesenchymal neoplasms that require us to identify their unusual location other than the pleura and be familiar with their histologic appearances for arriving at the correct diagnosis.

Aged↗

PubMed1996

Myofibroblastic tumor of soft tissue displaying desmin-positive and actin-negative immunophenotypes.

Myofibroblasts have ultrastructural and functional characteristics intermediate between fibroblasts and smooth muscle cells. Previous studies indicated that most myofibroblasts express actin and vimentin but not desmin immunophenotypes. Two benign intramuscular myofibroblastic tumors which displayed a desmin-positive and actin-negative immunophenotype are reported. The tumors occurred on the back of a 45 year old man who had neurofibromatosis 1 and the thigh of a 37 year old man without neurofibromatosis. Both tumors were encapsulated and composed of short intersecting bundles of spindle cells in a collagenous background. Although the tumors were cellular, nuclear pleomorphism was minimal and mitotic figures were rare. Characteristically, most tumor cells were immunoreactive strongly for desmin and vimentin but gave negative staining for muscle-specific actin, alpha-smooth muscle actin, alpha-sarcomeric actin, myosin, S-100 protein, cytokeratins, and CD34. On electron microscopy, the tumor cells were characterized by short spindle-indented nuclei, abundant cytoplasmic intermediate filaments, prominent plasmalemmal pinocytosis and frequent cell coverage by basal lamina. Aggregation of thin myofilaments with focal condensations was identified occasionally. Although the tumors showed distinct morphological and immunohistochemical features enabling delimitation from other soft tissue lesions, they may overlap histologically with myofibroblastoma of the breast, lymph node and soft tissue, low grade malignant nerve sheath tumor, leiomyosarcoma, cellular schwannoma, inflammatory fibrosarcoma and nodular fasciitis.

Actins↗

PubMed1996

The effect of nifedipine on ventriculoarterial coupling in old myocardial infarction.

The effect of nifedipine on ventriculoarterial coupling was examined in 8 patients with old myocardial infarction who showed a depressed ejection fraction (37 +/- 7%). Left ventricular (LV) pressure and LV volume were determined simultaneously by micromanometer and conductance catheter, respectively. We measured the slope (Ees) of the end-systolic pressure-volume relation during transient inferior vena caval occlusion, the slope (Ea) of the end-systolic pressure-stroke volume relation, the ratio of Ea to Ees (Ea/Ees), and the work efficiency (the ratio of external work to the systolic pressure-volume area) at baseline and after the sublingual administration of nifedipine (10 mg). Nifedipine slightly increased the heart rate from 71 +/- 14 to 78 +/- 17 beats/min. Although nifedipine had little effect on Ees (2.54 +/- 0.68 vs 2.47 +/- 0.62 mmHg/ml/m2, ns), it significantly decreased Ea from 3.47 +/- 1.16 to 2.37 +/- 0.54 mmHg/ml/m2. Consequently, Ea/Ees decreased from 1.42 +/- 0.47 to 0.97 +/- 0.31 and work efficiency increased from 48 +/- 12 to 59 +/- 13% after nifedipine administration. These data suggest that nifedipine reduces afterload (Ea) and improves left ventriculoarterial coupling without depressing left ventricular contractility in patients with failing hearts due to old myocardial infarction.

Aged↗

PubMed1996

Production of recombinant human monoclonal antibody using ras-amplified BHK-21 cells in a protein-free medium.

A ras oncogene-amplified recombinant BHK-21 cell line (ras-rBHK-IgG) has been established, and was shown to hyperproduce the recombinant IgG chimeric human monoclonal antibody (hMAb) AE6F4, which recognizes lung cancer cells. We found that the ras-rBHK-IgG cell could be easily cultured in a protein-free ERDF medium supplemented with iron(III) nitrate, hydroxyethyliminodiacetic acid, and non-protein synthetic attachment factor as well as in a serum-free ERDF medium supplemented with insulin, transferrin, ethanolamine, and sodium selenite. The productivity of recombinant hMAb from the cells cultured in dishes at high cell densities was higher in protein-free medium than in serum-containing medium. True high density culture of the ras-rBHK-IgG cells was done in protein-free medium using the Tecnomouse, which is a novel hollow fiber bioreactor system. After culture for 30 days in protein-free culture, a total amount of about 14 mg of the recombinant hMAb AE6F4 was obtained, and was shown to be reactive against lung cancer cells in tissues.

Animals↗

PubMed1996

[An improved phagocytic plaque method using gram-negative bacilli].

The phagocytic plaque method developed for evaluation of the phagocytic function of leukocytes is not only very useful but convenient for both basic and clinical investigations. So far, only Staphylococcus aureus has been demonstrated to give clear phagocytic plaques. In this study, we successfully obtained clear phagocytic plaques with gram-negative bacilli (Pseudomonas aeruginosa and Escherichia coli). The plaques given by E. coli were morphologically nearly the same as those by S. aureus, whereas those of P. aeruginosa were elongated.

Escherichia coli↗

PubMed1996

[Coronary artery bypass grafting in a patient with severe coronary disease due to Kawasaki disease: a case report].

A 14-year-old girl with severe coronary artery disease due to mucocutaneous lymph node syndrome, "Kawasaki disease", admitted to our hospital. Though she had no angina on any effort in her daily life, coronary angiography (CAG) demonstrated 90% stenosis and a large aneurysm of left main trunk. Based on the CAG findings, we determined to do the coronary artery bypass grafting (CABG) to left anterior descending artery (LAD) and 1st diagonal branch (D1) to prevent the occurrance of fatal acute myocardial infarction. We attempted to use bilateral internal thoracic arteries (ITAs) at the beginning of this surgery. While LAD was grafted with left one, D1 was done with saphenous vein (SV) because of difficulty of harvesting right one. The weaning from cardiopulmonary bypass was easy and the postoperative course was of no event. A month later, CAG showed the good patency of both left ITA and SV graft.

Adolescent↗