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Biomedical subjects

K Sugita

Publications and source records attributed to K Sugita.

At least 19 recordsLinked to original sources

Purification and characterization of a novel protein activator of Ca2+/calmodulin-dependent protein kinase I.

A protein activator of Ca2+/calmodulin (CaM)-dependent protein kinase I was purified from rat brain. The activator was retained on a CaM-Sepharose column in the presence of Ca2+ and kinase assay of renatured gel revealed the 64 kDa molecule in the purified activator fraction to be autophosphorylated and to phosphorylate recombinant CaM kinase I in the presence of Ca2+/calmodulin. These results suggest that this activator of CaM kinase I is also a CaM-dependent protein kinase. Phosphorylation of CaM kinase I by the activator resulted in drastic potentiation of its CaM-dependent activity. Furthermore, kinetic analyses demonstrated that the activation decreases the Km values of CaM kinase I for both ATP and syntide-2 without a change in Vmax values. Considering the quite low enzymatic activity of recombinant CaM kinase I without activation, the 64 kDa species might be essential for CaM kinase I function in vivo.

Adenosine Triphosphate

Direct cellular communications between CD45R0 and CD45RA T cell subsets via CD27/CD70.

The engagement of CD27 with its ligand CD70 is considered to play an important role in T cell costimulation. In the present study, we investigated both the kinetics of CD70 expression and the contribution of its interaction with CD27 in T cell immune responses. CD70 was found to be expressed almost equally on both activated CD4 and CD8 T cells. On subsets of CD4 T cells, however, CD70 expression was induced preferentially on the CD45R0 T cell population after activation, whereas its expression was not noted on CD45RA T cells for almost 2 wk following activation. In long-term culture with media containing T cell growth factor (TCGF) and rIL-2, the expression of CD70 was increased markedly on CD45R0 T cells and minimally expressed on CD45RA T cells. In addition, strong surface expression of CD70 was observed on T cell clones originally derived from CD45R0+ CD4 T cells, whereas T cell clones originally derived from CD45RA+ CD4 T cells showed lower levels of expression. The addition of irradiated, activated CD45R0 T cells to CD45RA T cells caused a down-regulation of CD27 expression and an up-regulation of CD25 expression. These changes were blocked by addition of the anti-CD70 mAb, suggesting that direct contact between CD45R0 T cells and CD45RA T cells via CD27/CD70 occurred, leading to the activation of CD45RA T cells as measured by CD25 expression. These observations strongly support the notion that the engagement of CD27 plays an important regulatory role in the communication of subsets of CD45R0 and CD45RA T cells.

Antigens, CD

The bipotential glial progenitor cell line can develop into both oligodendrocytes and astrocytes in the mouse forebrain.

Oligodendrocyte-type 2 astrocyte (O2A) progenitor cells in vivo might differentiate into oligodendrocytes. To examine the influence of the brain micro-environment on the differentiation, a bipotential glial cell line from the mouse cerebrum, designated OS3 cells, was implanted into the telencephalon of infant and adult mice. About a half of the OS3 cells injected into 1-week postnatal brain expressed galactocerebroside (GalC), and even myelin basic protein, which were not observed to be expressed in vitro. By contrast, in the brain over 6 months postnatally, many OS3 cells expressed glial fibrillary acidic protein, and did not express much GalC. These findings suggest that the differentiation of glial cells is controlled by stage specific factors in the brain.

Animals

The effects of pituitary adenylate cyclase-activating polypeptide on cerebral arteries and vertebral artery blood flow in anesthetized dogs.

We investigated and compared the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) on cerebral circulation in anesthetized dogs. The intracisternal administration of PACAP-27, PACAP-38, and VIP dilated canine cerebral arteries in a dose-dependent manner. A 10 nmol dose of PACAP-27, PACAP-38, and VIP dilated the basilar artery by 23 +/- 3, 27 +/- 3 and 30 +/- 3%, respectively. Rostrally located arteries tended to be more responsive to PACAP-27. Pretreatment with NG-monomethyl-L-arginine did not affect PACAP-27-induced vasodilation. Vertebral artery blood flow was also affected by intra-arterial injection of these peptides in a dose-dependent manner. A 100 pmol dose of PACAP-27, PACAP-38, and VIP increased the vertebral artery blood flow by 42 +/- 10, 29 +/- 4, and 62 +/- 11%, respectively. The VIP receptor antagonist, [Lys1,Pro2,5,Arg3,4,Tyr6]VIP, inhibited both the VIP- and PACAP-38-induced increase in vertebral artery blood flow. These findings suggest that PACAP plays a role in the regulation of cerebral circulation.

Anesthesia

CD27/CD70 interaction directly drives B cell IgG and IgM synthesis.

CD27 is a T cell activation antigen expressed on a majority of peripheral blood T cells. CD27 is also expressed on a subpopulation of human B cells, and it is reported that CD27+ B cells secrete both IgG and IgM. CD70, a ligand for CD27, is expressed on activated T and B cells, suggesting an interaction between T and B cells via CD27/CD70 ligation. Here, we analyze B cell immunoglobulin synthesis using a CD70 transfectant and present functional data showing that B cells secrete large amounts of IgG and IgM as a result of the CD27/CD70 interaction. A flow cytometric analysis showed that CD27 expression was increased and CD70 was expressed on tonsillar and peripheral blood B cells after activation with Staphylococcus aureus Cowan strain (SAC) plus interleukin (IL-2). In addition, the proliferation of B cells was enhanced mildly by the addition of CD70 transfectant, and its proliferation was blocked by anti-CD70 mAb. More importantly, the CD70 transfectant enhanced IgG and IgM production by purified B cells greatly in the presence of SAC plus IL-2. The enhancement was completely blocked by the addition of either anti-CD70 mAb or anti-CD27 mAb. Strongly suggesting that the interaction of CD27 with its ligand, CD70, on B cells plays an important role in B cell growth and differentiation to produce IgG and IgM.

Adult

Staging, scoring and grading of medulloblastoma. A postoperative prognosis predicting system based on the cases of a single institute.

Although recently survival of some medulloblastoma patients increased remarkably, it remains a serious diagnosis in others. In order to predict the postoperative prognosis in patients treated for medulloblastoma, a new staging, scoring and grading system was developed. Sixty-six patients operated on microsurgically between 1975 and 1990 at a single neurosurgical center were fully followed-up. No patient was excluded due to a poor postoperative course. Completion of commonly used radiotherapy protocols was attempted in all patients. Survival of patients was evaluated by the Kaplan-Meier method. The following 5 parameters were selected to define subgroups: patients' age, tumour location and histology, degree of resection and presence or absence of metastases. Patients older than 10 years had a better prognosis than individuals aged 10 or less (p < 0.01), patients with lateral tumours had a better prognosis than patients with midline tumours with brain stem infiltration (p < 0.05), patients with complete tumour resection had a more favourable prognosis than individuals with subtotal (p < 0.01) or partial resection (p < 0.001), patients without metastases at the time of diagnosis had a better prognosis than individuals without such evidence (p < 0.001), patients with the desmoplastic tumour variant had a better prognosis than patients with classical tumour histology (p < 0.01). According to the prognosis of a distinct subgroup, scoring points were distributed which correlated with the degree of inter-subgroup significances. The sum of a single patient's scoring points was called the total score. Based on this score, three groups of prognosis were distinguished.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Changes in the cerebrocortical capillary network following venous sinus occlusion in cats.

BACKGROUND: Although the important protective effect of venous collateral pathways in sinus occlusion on parenchymal injury has been demonstrated in previous works, the vascular response in the capillary microcirculation itself after cerebral venous occlusion has not been fully elucidated. We examined the morphology of the capillary network after venous occlusion by relating stereologic morphometric parameters to changes in local cerebral blood flow and the development of brain edema. METHODS: Experimental venous sinus occlusion was induced by injection of 0.5 mL of cyanoacrylate into the superior sagittal sinus and by immediate ligation of both external jugular veins in chloralose-urethane anesthetized cats (n = 24). Capillaries in the adjacent cortex (marginal and suprasylvian cortex) and remote cortex (piriform cortex) were injected with Evans blue dye 2 minutes before sacrifice at 15-minute and 120-minute postsinus occlusion. The stereologic morphometric parameters including volume density, minimum intercapillary distance, capillary diameter, and number of perfused capillaries were computed on a fluorescence microscopic photograph using an image analysis system. Cerebral blood flow (CBF) was measured by hydrogen clearance method, and brain tissue water content was measured using the dry-wet method. RESULTS: In the cortex adjacent to the superior sagittal sinus, the volume density and the number of perfused capillaries were increased significantly (p < 0.02, and p < 0.05, respectively) and the minimum intercapillary distance was decreased significantly (p < 0.02) at 15 minutes after venous occlusion (n = 10). Cerebral blood flow (CBF) was also decreased to 53% of that in the control group (p < 0.01). Although the morphologic parameters returned to the control level by 120 minutes after venous occlusion, the CBF remained decreased after venous occlusion. No change was observed in the water content of the adjacent gray matter at 15 minutes after venous occlusion; however, it was increased (p < 0.05) at 120 minutes. CONCLUSION: These results indicate that the recruitment of reserve capillaries occurs during the early phase of venous occlusion. While CBF decreased to half of the control after venous occlusion, capillary perfusion remained above or near the control level until 120 minutes postocclusion, suggesting that venous recruitment would be potentially beneficial in clinical patients in the early stage of venous occlusion.

Animals

Optic neuritis with silent cerebral lesions: availability of FLAIR sequences.

A 10-year-old male suffering from acute optic neuritis is reported with multiple silent cerebral lesions, which remained visible only with fluid-attenuated inversion recovery sequences at 3-week intervals. Conventional sequences with magnetic resonance imaging did not visualize the lesions. Fluid-attenuated inversion recovery sequences are highly sensitive for the detection of silent lesions in acute optic neuritis.

Brain

Effects of adrenomedullin, calcitonin gene-related peptide, and amylin on cerebral circulation in dogs.

The effect of human adrenomedullin on cerebral circulation was investigated in dogs in vivo and in vitro. Bolus administration of adrenomedullin or its homologous peptides, calcitonin gene-related peptide (CGRP) and amylin, into the vertebral artery induced a dose-dependent increase in vertebral blood flow. The potencies of adrenomedullin and CGRP were similar and approximately 100 times more than that of amylin. The effects of adrenomedullin and CGRP were inhibited by CGRP8-37, an antagonist of CGRP. In contrast to substance P, adrenomedullin did not induce an increase in blood flow after prior administration of CGRP. Pretreatment with either NG-nitro-L-arginine methyl ester or indomethacin did not affect the adrenomedullin-induced increase in blood flow. Intracisternal administration of adrenomedullin induced dilation of the basilar and other major cerebral arteries in a dose-dependent manner, accompanied by an increase in the concentration of cyclic AMP in the cerebrospinal fluid. Adrenomedullin also induced relaxation of isolated basilar and middle cerebral arterial rings. These data suggest that adrenomedullin induces vasodilation of cerebral arteries and an increase in vertebral blood by acting at CGRP receptors positively coupled to adenylate cyclase, and that these effects are not dependent on nitric oxide or prostaglandin formation.

Adrenomedullin

Reinforced cytotoxicity of lymphokine-activated killer cells toward glioma cells by transfection of the killer cells with the gamma-interferon gene.

Lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 were transfected with the human gamma-interferon (HuIFN-gamma) gene by means of liposomes having a positive charge on their surface. The cells secreted significant amounts of HuIFN-gamma (reaching more than 5 U/ml) into the culture medium. The HuIFN-gamma produced by the cells induced intercellular adhesion molecule-1 (ICAM-1) and enhanced the expression of Fas antigen on the surface of human glioma cells. Also, LAK cells transfected with HuIFN-gamma gene exhibited reinforcement of cytotoxicity toward human glioma cell lines (U251-MG and SK-MG-1). Furthermore, the reinforcement was significantly quenched by anti-ICAM-1 and/or anti-TNF-alpha monoclonal antibody.

Antibodies, Monoclonal

Expression of granulocyte colony-stimulating factor receptor on CD10-positive human B-cell precursors.

We examined the expression of CD10 and G-CSF receptor (G-CSFR) on the lymphoid population of mononuclear cells obtained from bone marrow (BM) using two-colour analysis. In the BM of children with ALL in remission, the CD10+ population was significantly increased (20.6 +/- 5.1% compared with that of controls (2.5 +/- 0.5%). More than half (61.3 +/- 2.9%) of the CD10+ cells co-expressed G-CSFR, but not CD13. These results indicate G-CSFR+ B-cell precursors are markedly increased in BM of ALL in remission, suggesting the probable involvement of G-CSF in the human early B-cell ontogeny.

Adolescent

Central cardiovascular effects induced by intracisternal PACAP in dogs.

The cardiovascular responses to intracisternally administered pituitary adenylate cyclase-activating polypeptide (PACAP) were investigated and compared with those of vasoactive intestinal peptide (VIP) in anesthetized dogs. Intracisternal administration of 10 nmol of PACAP-27 increased mean arterial blood pressure (MABP) significantly with a simultaneous increase of plasma arginine vasopressin and epinephrine concentrations. Intracisternal administration of VIP increased plasma arginine vasopressin concentration significantly but caused no appreciable change in MABP. Systemic infusion of the nonpeptide vasopressin V1 receptor antagonist OPC-21268 did not inhibit the PACAP-27-induced increase in MABP, whereas phentolamine, an alpha-adrenoceptor blocker, reversed the increase. Intracisternal pretreatment with the vasopressin V1 receptor antagonist [Pmp1, Tyr(Me)2]Arg8-vasopressin also inhibited the increase. These findings suggest that PACAP has a central pressor action by increasing sympathetic outflow, which is probably mediated by the vasopressinergic neural network. PACAP seems to play important roles in hormonal and neural control of systemic circulation.

Adrenergic alpha-Antagonists

Evaluation of influential factors of cognitive impairments in idiopathic Parkinson's disease.

Using multivariate analysis, we investigated the influence on cognitive functions of aging, brain atrophy, incidental cerebral hyperintensities (CHs), medication, and severity, duration and the initial symptoms of the disease in 53 patients with idiopathic Parkinson's disease (PD). We semiquantitatively assessed the degree of brain atrophy and CHs based on previously established methods. Cognitive functions were significantly and diffusely impaired in PD when compared with controls who were matched for age as well as for the degree and location of CHs. Patients with PD, however, had larger ventricles. Prefrontal dysfunctions were associated with a variety of predictors such as CHs, brain atrophy, severity of PD and medication whereas dorsolateral frontal functions were related simply to age and CHs in the periventricular region. Posterior brain functions had association with severity of illness, ventricular dilatation and total CH score. Clinically observed cognitive impairments in PD may consist of cognitive defects intrinsic to the disease which are variously modified by these factors. It is essential to consider all these predictors simultaneously in any discussion of cognitive functions in PD.

Aged

Effect of antimicrobial agents on chemotaxis of polymorphonuclear leukocytes.

The effect of antimicrobial agents on polymorphonuclear (PMN) chemotaxis was investigated. No significant effect was obtained in vitro with penicillins, cephems, macrolides, aminoglycosides or quinolones by the agarose plate method. However, chemotaxis was inhibited at 100 micrograms/ml or less of minocycline and doxycycline. The inhibitory effect on chemotaxis is considered to be due to chelation of Ca-ions by minocycline or doxycycline. The chelation reduced the concentrations of Ca-ions in the PMNs. The chemotactic index of minocycline increased when CaCl2 or A23187 were given in combination. Our findings indicate that a small number of the short lamellipodia were observed in PMNs preincubated with minocycline or doxycycline and these two agents affected the movement of PMNs morphologically.

Anti-Infective Agents

Characteristics of pterional routes to basilar bifurcation aneurysm.

In an attempt to clarify the characteristics of the pterional routes to the basilar bifurcation aneurysm, 65 consecutive surgical cases were retrospectively analyzed concerning the size of the aneurysm, the height of the aneurysm neck, the length of the clip blades, and the direction of clip application. Clipping was performed through the pterional route in 59 cases consisting of 14 opticocarotid and 45 retrocarotid routes. A subtemporal approach was performed for six low-positioned aneurysms. The opticocarotid approach was undertaken because of the following situations: 1) laterally protruded and/or highly sclerotic internal carotid artery (n = 8); 2) long, redundant A1 segment (n = 3); 3) an associated aneurysm of the internal carotid artery obstructing the retrocarotid space (n = 2); and 4) a short and/or large posterior communicating artery obstructing the retrocarotid space (n = 1). The range in height of the aneurysm neck was narrower in the opticocarotid approach (1-10 mm) than in the retrocarotid approach (-7-15 mm). The direction of clip application on the axial plane was more anteriorly deviated in the opticocarotid approach (41.4 +/- 12.8 degrees from the glabella-inion line) than in the retrocarotid approach (58.8 +/- 11.1 degrees; P = 0.01). The retrocarotid route (n = 45) was further subdivided into the medial or lateral retrocarotid routes, depending on the medial or lateral side to the posterior communicating artery, respectively. The medial retrocarotid approach (n = 9) made it possible to reach relatively high-positioned aneurysms (7.0 +/- 3.9 mm) compared with the lateral retrocarotid approach (4.2 +/- 4.7 mm; n = 29).(ABSTRACT TRUNCATED AT 250 WORDS)

Basilar Artery

The transsphenoidal removal of nonfunctioning pituitary adenomas with suprasellar extensions: the open sella method and intentionally staged operation.

The surgical treatment of large pituitary adenomas with suprasellar extensions has been controversial. To elucidate the indications for transsphenoidal surgery of large adenomas and to evaluate the techniques for removing the suprasellar portions of the tumors, surgical procedures on 100 consecutive patients with suprasellar extensions of nonfunctioning pituitary adenomas were retrospectively investigated. Patients were followed up for 1 to 12 years (mean, 4.5 yr). One hundred twenty-five transsphenoidal operations were performed on 100 patients. The removal of each suprasellar tumor was facilitated by the placement of a lumbar subarachnoid catheter and the injection of lactated Ringer's solution or saline. This method was used in 77 operations and was effective on 60 of 72 adenomas with < 30-mm suprasellar extensions (Hardy's Grades A, B, and C) but not on those that were fibrous or dumbbell-shaped. The descent of the remaining suprasellar tumor was facilitated by keeping the sella and sellar floor open with an intrasellar drain, and the subsequent removal was achieved with staged transsphenoidal operations. Of nine fibrous or dumbbell-shaped adenomas with 10- to 30-mm suprasellar extensions, gross total removal in eight was achieved by the open sella technique and two-stage transsphenoidal operation, whereas one required transcranial surgery. Adenomas with > 30-mm suprasellar or lateral extensions (Grade D) could not be removed sufficiently by transsphenoidal operations, except one adenoma for which a subtotal removal was achieved in the third staged operation. The disease-free rate 10 years after operation was 74% for all patients: 91% for Grade A, 74% for Grade B, and 61% for Grade C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma

Early endovascular treatment for ruptured basilar bifurcation aneurysm--case report.

A 69-year-old male presented with sudden onset of headache. Computed tomography of the head demonstrated diffuse subarachnoid hemorrhage. Angiography showed a saccular basilar bifurcation aneurysm. Endovascular coil occlusion of the aneurysm on the same day enabled complete obliteration of the aneurysm. He did not develop vasospasm and returned home 4 months later. Early endovascular occlusion of the aneurysmal sac is an alternative method for the management of ruptured basilar bifurcation aneurysms.

Aged