Biomedical subjects

K Sugita

Publications and source records attributed to K Sugita.

At least 19 recordsLinked to original sources

PubMed1992

CD27, a member of the nerve growth factor receptor family, is preferentially expressed on CD45RA+ CD4 T cell clones and involved in distinct immunoregulatory functions.

CD27 is a disulfide-linked 120-kDa homodimer expressed on the majority of peripheral T cells at variable density that belongs to the recently defined nerve growth factor receptor family. mAb reactive with CD27 can either enhance or inhibit T cell activation, suggesting a crucial role in the process of T cell activation. We now show that CD27 is preferentially expressed on the CD45RA+CD45RO-CD29low subset of CD4 cells. CD27 expression on this subset is maintained for a prolonged period in culture after PHA activation. In contrast, CD45RA-CD45RO(+)-CD29high subset of CD4 cells express very low level of CD27, and its expression is lost within 2 wk after PHA activation. To further analyze the differential expression of CD27 on these reciprocal subsets of CD4 cells, we developed T cell clones by stimulating isolated CD4+CD45RA+ and CD4+CD45RO+ populations with PHA. T cell clones derived from cells originally CD45RA+ retained both CD45RA and CD27 expression, whereas T cell clones derived from cells originally CD45RO+ were CD45RA- and CD27-. In functional assays, IL-4 production could only be induced in CD45RA-CD27- CD4 clones by stimulation with PMA and ionomycin. Four of six CD45RA+ CD4 clones had suppressor activity in PWM-driven IgG synthesis, whereas five of six CD45RA- CD4 clones had helper activity. Of interest, the suppressor activity of CD45RA+CD27+ clones was partially blocked by pretreatment with anti-CD27 mAb (1A4). Anti-1A4 pretreatment of these T cell clones resulted in elevation of intracellular cAMP levels. Thus, CD27 appears to play a role in the function of CD45RA+CD27+ CD4 cells, and may be involved in suppressor activity of these cells at least in part via its effects on cAMP production.

Antigens, CD↗

PubMed1992

Possible prophylactic potential of HA1077, a Ca2+ channel antagonist and vasodilator, on chronic cerebral vasospasm.

We examined the possible prophylactic potential of HA1077, a calcium antagonist and vasodilator, on chronic cerebral vasospasm induced in a two-hemorrhage canine model, and also its effects on cerebral hemodynamics. The intravenous infusion of HA1077 3 mg/kg over 30 min twice daily (day 1-day 7) after the first intracisternal injection of 5 ml autologous blood significantly prevented the occurrence of chronic cerebral vasospasm. The mean diameter of the basilar arteries on day 7 was 66.1 +/- 1.6% (n = 7) of the baseline before the intracisternal injection of blood, compared to 54.2 +/- 1.6% (n = 9) of the baseline in the untreated group (P less than 0.01). Bolus intravenous administration of HA1077 (0.1 and 0.3 mg/kg) dose dependently increased local cerebral blood flow. Since HA1077 prevents the development of chronic cerebral vasospasm after subarachnoid hemorrhage and improves hemodynamic functions, as manifested by increases in local cerebral blood flow, further study is warranted regarding the possible clinical use of this drug.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1992

Different utilization of Ca2+ in the contractile action of endothelin-1 on cerebral, coronary and mesenteric arteries of the dog.

Vasoconstrictor responses to endothelin-1 (ET) were compared between endothelium-denuded strips of cerebral, coronary and mesenteric arteries of the dog. Contractile responses to lower concentrations (below 3 x 10(-10) M) of ET were significantly greater in the cerebral and coronary arteries than in the mesenteric artery. The cerebral and coronary arteries, but not the mesenteric artery, relaxed significantly from the resting level when placed in a 0-Ca solution. Readdition of Ca2+ to the cerebral and coronary arteries placed in the 0-Ca solution caused a biphasic contraction which was susceptible to inhibition by nifedipine. When ET below 10(-10) M was introduced before the Ca2+ contraction, this peptide produced no detectable contraction, but augmented the Ca2+ contraction. The augmented Ca2+ contractions were abolished by 10(-7) M nifedipine. These effects of ET were not observed in the mesenteric artery. The contractile responses of the mesenteric artery to ET determined in the presence of elevated extracellular K+ concentrations were comparable to the responses of the cerebral artery to this peptide determined in the presence of normal K+ concentrations. These results indicate that the enhanced responses to ET in the cerebral and coronary arteries were dependent on the Ca2+ influx through voltage-dependent Ca2+ channels and suggest that these channels are in an activated state when these arteries are in a resting state.

Animals↗

PubMed1992

Participation of the CD27 antigen in the regulation of IL-2-activated human natural killer cells.

The CD27 Ag is expressed by the majority of resting T lymphocytes and appears to play a crucial role in T cell activation. We found that some resting peripheral blood NK cells also express CD27. Furthermore, CD27 expression was up-regulated on NK cells stimulated by IL-2. The cytolytic activity of IL-2-activated, but not resting, NK cells was inhibited by an anti-CD27 mAb (anti-1A4). However, anti-1A4 did not affect conjugate formation between IL-2-activated NK cells and tumor cell targets. In contrast, anti-1A4 inhibited CD2-mediated calcium mobilization and the serine esterase activity of NK cell granules. These inhibitory effects could be mediated in part by increase in intracellular cAMP levels induced by anti-1A4. Our results suggest that the CD27 Ag plays an important role in the regulation of activated NK cells.

Antigens, CD↗

PubMed1992

Ultrastructural and ultracytochemical differences between megakaryoblastic leukemia in children and adults. Analysis of 49 patients.

BACKGROUND: Acute megakaryoblastic leukemia (AMKL) has two peaks in distribution of incidence (in adults and children 1 to 2 years of age) and is frequently seen in children with Down syndrome. The current study was undertaken to disclose whether there were any differences between these groups. METHODS: Electron microscopic and ultrastructural cytochemical features of 49 children and adults with a AMKL or chronic myelogenous leukemia (CML) in megakaryoblastic crisis were compared. RESULTS: Blast cells from children with AMKL, including those with and without Down syndrome, had immature features lacking typical alpha granules and a demarcation membrane system (DMS). However, blast cells from patients with AMKL with Down syndrome had more theta, electron-lucent, and basophil-like granules, suggesting that the blast cells had more potential to differentiate into other cell lines than megakaryocytes. The AMKL blast cells of adult patients showed a higher percentage of platelet peroxidase (PPO) positivity than other subgroups, and they occasionally contained typical alpha granules and DMS. This indicated that the blast cells of adults with AMKL were more mature than those of children and CML in megakaryoblastic crisis. CONCLUSIONS: By electron microscopic analysis, leukemic megakaryoblasts differed between children with AMKL with and without Down syndrome, adults with AMKL, and patients with CML in megakaryoblastic crisis.

Acid Phosphatase↗

PubMed1992

Ligation of VLA-4 on T cells stimulates tyrosine phosphorylation of a 105-kD protein.

The VLA/integrins are a family of heterodimeric adhesion receptors shown to be involved in cell-to-cell and cell-to-extracellular matrix (ECM) interactions. Given recent evidence that VLA molecules can synergize with the CD3/T cell receptor (TCR) pathway to activate T cells, it is important to identify biochemical event(s) generated by these molecules. Here, we report that the engagement of VLA-4 on T cells with specific antibodies or its ligand activates protein-tyrosine kinase (PTK) activity as detected by antiphosphotyrosine immunoblotting. The crosslinking of VLA-beta 1 (CD29) with a specific monoclonal antibody (mAb) (anti-4B4) plus anti-mouse immunoglobulin resulted in the rapid tyrosine phosphorylation of a 105-kD protein (pp105) in the human T cell line H9, as well as in peripheral resting T cells. The increase in tyrosine phosphorylation of pp105 was specifically mediated by VLA-4, since mAbs against alpha 4, but not against other VLA alpha chains, could induce this phosphorylation. In addition, the binding of T cells with the CS1 alternatively spliced segment of fibronectin (the binding site recognized by VLA-4) induced pp105 tyrosine phosphorylation. Crosslinking the CD3 complex or VLA-4 molecules with mAbs demonstrated that each of these molecules stimulated the tyrosine phosphorylation of unique sets of proteins with different kinetics, suggesting that these two receptor systems are coupled to distinct PTKs. Since tyrosine phosphorylation of cellular proteins has been shown to be a crucial biochemical event in cell growth, our findings suggest that the induction of pp105 tyrosine phosphorylation via VLA-4 may play a role in the transduction of activation signals through this molecule.

Antigens, CD↗

PubMed1992

A novel compound, depudecin, induces production of transformation to the flat phenotype of NIH3T3 cells transformed by ras-oncogene.

A novel compound, depudecin, induced production of the flat phenotype of Ki-ras-transformed NIH3T3 cells at the low concentration of 1 microgram/ml. This effect was reversible. Actin stress fiber was detected in these cells after depudecin treatment. Almost complete reversion to the flat phenotype was observed at 6 h after depudecin addition. The synthesis of ras-mRNA did not decrease enough with depudecin treatment at the concentration of 10 micrograms/ml to reverse the transformed morphology.

3T3 Cells↗

PubMed1992

Morphological reversion of sis-transformed NIH3T3 cells by trichostatin A.

Trichostatin A (TSA) induced the normal and flat phenotype of sis-transformed NIH3T3 cells at quite a low concentration of 1 ng/ml. Although morphological changes were found in other oncogene-transformed cells, they were not the same as those seen for the sis-transformed cells. Almost complete reversion into the flat phenotype was seen at 6 h after administration of the compound, suggesting that the morphological change was caused not merely by selection of TSA-resistant cells of the flat phenotype. The effect of TSA was reversible when the cell culture was incubated after its removal. Synthesis of sis-mRNA did not decrease with the treatment of TSA at a concentration sufficient to reverse the transformed morphology. Cycloheximide abolished the activity of TSA, showing that TSA required new protein synthesis to express its activity.

3T3 Cells↗

PubMed1992

Primary chronic intrasellar haematoma: a case report.

This report describes a rare case of primary intrasellar haematoma in a 66 year-old man with hypopituitarism. Computerized tomography (CT) and magnetic resonance imaging (MRI) showed an intrasellar cystic lesion with small suprasellar extension. Transsphenoidal surgery revealed that the lesion was a chronic haematoma, without evidence of a tumour or vascular anomaly. Pathological diagnosis confirmed this. This is the first report of a chronic intrasellar haematoma, which is probably primary.

Aged↗

PubMed1992

Serum factors responsible for unusual induction of plasminogen activator activity in tuberous sclerosis.

Peripheral blood lymphocytes derived from tuberous sclerosis (TS) patients showed unusually high levels of plasminogen activator (PA) activity after treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Serum obtained from peripheral blood of TS patients also enhanced the PA activity level when normal control lymphocytes were incubated with the serum prior to MNNG treatment. Factors exhibiting the enhancing activity were eluted with a solution of about 0.70 M KCl on dye-ligand chromatography, which were inhibited on incubation with an anti-human interferon (HuIFN)-beta antibody, but not with anti-HuIFN-alpha or anti-HuIFN-gamma antibodies. Unlike in the case of HuIFN-beta, the eluted samples did not possess antiviral or anticellular activity. Thus, it seems likely that serum from TS patients contains factors which are responsible for the unusual PA induction and which have a similar epitope to HuIFN-beta.

Adolescent↗

PubMed1992

Pelizaeus-Merzbacher disease: cellular hypersensitivity to ultraviolet light.

We report two connatal cases of Pelizaeus-Merzbacher disease (PMD) with cellular ultraviolet (UV)-hypersensitivity. We studied the UV-sensitivity of cultured fibroblast cells derived from these PMD cases, as compared with UV-sensitive Cockayne syndrome (CS) and xeroderma pigmentosum (XP) cells as positive controls. The ability of the PMD cells to form colonies after UV irradiation was intermediate between those of CS cells and normal controls. There were no differences in both colony-forming ability after x-ray irradiation and unscheduled DNA synthesis (UDS) activity after UV irradiation between the PMD cells and the control cells. These cytological results suggest the possibility that a DNA defect might be involved in PMD.

Cells, Cultured↗

PubMed1992

A neuropathological study of early onset Cockayne syndrome with chromosomal anomaly 47XXX.

We present the clinical and neuropathological findings in a female patient with early onset Cockayne syndrome and a chromosomal anomaly (47XXX). The girl was the only child of healthy, unrelated parents. She was born with a birth weight of 1,930 gm. She had progeroid facial features with bilateral cataracts. A diagnosis of 47XXX was made on the basis of a chromosomal study. Physical shortness became increasingly prominent while her weight remained stationary. Psychomotor retardation was noted, and she could never sit alone. A brain CT scan showed cerebral atrophy and calcification of the basal ganglia. Cultured skin fibroblast exhibited significant sensitivity to the ultraviolet light. She died from a chest infection at the age of 7 years and 4 months. Microscopically, the renal glomeruli showed diffuse sclerotic changes with thick capillary basement membranes. A neuropathological examination revealed a very small brain (295 gm), extensive myelin deficiency, gliosis in the white matter, and calcifications in the basal ganglia, and cerebral and cerebellar cortices. The loss of both Purkinje and granular cells was noticed in the cerebellar cortex. This is the first report of a case with the Cockayne syndrome and 47XXX, and the 47XXX in this patient seems to be coincidental.

Brain↗

PubMed1992

Introduction of high definition television system to neurosurgical documentation.

The high definition television (HDTV) system is introduced to microneurosurgery. Five cases with intracranial lesions: three cerebral aneurysms (giant aneurysms of the anterior communicating artery and internal carotid artery, aneurysm of the basilar artery), one acoustic neurinoma and one skull base meningioma, were operated on under the microscope using the HDTV system. The surgical procedures of each case were relayed and recorded by the system. In two of the five cases, we used two sets of HDTV system to produce stereoscopic projection. The HDTV system provided us with images of superior quality with a distinctly greater resolution than ordinary video systems.

Adult↗

PubMed1992

Strong immunoreactivity of cathepsin L at the site of rimmed vacuoles in diseased muscles.

Skeletal muscle samples from four patients with myopathies showing autophagic vacuole formation were examined by immunohistochemical, biochemical and immunoblot analyses. Immunochemical studies demonstrated strongly positive reactions of cathepsins B and L in and around the rimmed vacuoles and weak reactions in intramyofibral portions of degenerating muscle fibres. Faint staining of cathepsin H was also seen at the sites of rimmed vacuoles. Biochemical analyses showed increased activity of cathepsin B and L in muscle specimens from the patients with rimmed vacuole formation. However, there was no remarkable cathepsin H activity in the muscle specimens from these patients. Cathepsin L immunoblot analysis of muscle extracts showed three bands with molecular masses of 30 kDa, 36 kDa and 39 kDa. The immunostaining of cathepsin L from patients with rimmed vacuole formation was stronger than that of normal controls. Cathepsin B immunoblot analysis showed only faint bands in samples from patients with rimmed vacuole formation and normal controls. This study demonstrated, for the first time, strong immunoreactivity of cathepsin L at the sites of rimmed vacuoles. Possible mechanisms of rimmed vacuole formation are discussed.

Adult↗

PubMed1992

Comparison of vasoconstrictor actions of endothelin-1 in cerebral, coronary, and mesenteric arteries of the dog.

Vasoconstrictor actions of endothelin-1 (ET) were compared between endothelium-removed strips of cerebral (basilar, posterior cerebral, and middle cerebral) and peripheral (coronary and mesenteric) arteries of the dog. ET produced a concentration-dependent contraction in these arteries. A threshold concentration and EC50 value for ET were significantly lower in the basilar, posterior cerebral, middle cerebral, and coronary arteries than in the mesenteric artery. In the basilar artery, nifedipine caused a rightward displacement of the concentration-response curve for ET with a significant reduction in the maximum response to ET. On the other hand, nifedipine showed a typical noncompetitive antagonism against ET in the mesenteric artery. Contractile responses of the mesenteric artery to ET determined under an elevation of extracellular K+ concentration were comparable to the responses of the basilar artery to this peptide determined under normal K+ concentrations. The cerebral and coronary arteries, but not the mesenteric artery, relaxed significantly from the resting level when placed in a Ca(2+)-free solution containing 0.1 mM EGTA (0-Ca solution). The readdition of Ca2+ to the cerebral and coronary arteries soaked in the 0-Ca solution caused a biphasic contraction that was susceptible to inhibition by nifedipine. When ET in concentrations below 10(-9) M was introduced before the Ca(2+)-induced contraction, this peptide produced no detectable contraction, but potentiated the Ca(2+)-induced contraction. The extent of potentiation induced by ET was much greater in the cerebral and coronary arteries than in the mesenteric artery. Even in the 0-Ca solution, higher concentrations of ET (1 x 10(-8) and 3 x 10(-8) M) produced a contraction that was weaker in the basilar artery than in the mesenteric artery. These results indicate that the cerebral and coronary arteries exhibited more potent contractions in response to lower concentrations (below 10(-9) M) of ET than the mesenteric artery. A likely possibility for these enhanced responses to ET in the cerebral and coronary arteries appears to be that the voltage-dependent Ca2+ channels in these arteries are more activated in the resting state than those in the mesenteric artery.

Animals↗

PubMed1992

A novel tetracyclic peptide, trapoxin, induces phenotypic change from transformed to normal in sis-oncogene-transformed NIH3T3 cells.

A novel tetracyclic peptide, trapoxin [cyclo(L-phenylalanyl-L-phenylalanyl-D-pipecolinyl-L-2-amino-8-oxo -9,10-epoxy - decanoyl)], was found to induce the flat phenotype in v-sis-transformed NIH3T3 cells at a quite low concentration of 1 ng/ml. Actin stress fiber could be detected after trapoxin treatment. Almost complete reversion into the flat phenotype was observed at 6 h after the administration of the compound. The effect of trapoxin was reversible, when the cell culture was incubated for more than 24 h after its removal. The intracellular level of sis-mRNA did not decrease with trapoxin treatment at a concentration (50 ng/ml), sufficient to reverse the transformed morphology. Substitution of pipecolinic acid with proline in trapoxin did not change the activity. WF3161, in which leucine was substituted for a phenylalanine of trapoxin, showed only one-sixteenth of the activity of trapoxin. Reduction of the epoxide residue of trapoxin destroyed the activity.

3T3 Cells↗

PubMed1992

Neuroradiological findings in children with congenital myotonic dystrophy.

We studied seven children with congenital myotonic dystrophy, aged 2.1-8.3 years, and the results of computed tomography and magnetic resonance imaging of the brain were analyzed and neurological development was assessed from the neonatal period. We found that ventricular dilatation that had been seen on the first day of life in two of three infants had not progressed in sequential follow-up computed tomography scans taken at intervals of one to six years. Also, in T2-weighted magnetic resonance imagings, areas of periventricular hyperintensity were identified in all children, as well as areas of subcortical hyperintensity in one child. Further, an asphyxial episode had occurred at birth in five patients and the extent of the periventricular hyperintensity was found to correlate significantly with Apgar scores, indicating that the degree of perinatal asphyxia that had occurred was responsible for the abnormalities uncovered by the magnetic resonance imagings. However, there was no correlation between the neurodevelopment outcome and the extent of the periventricular hyperintensity or ventriculomegaly. Therefore, in patients with congenital myotonic dystrophy, a neonatal episode of asphyxia can be responsible for a finding of periventricular hyperintensity, but it is unlikely that an integral part of the mental retardation is attributable to brain damage due to perinatal asphyxia.

Apgar Score↗

PubMed1992

[Mycoplasma pneumoniae respiratory tract infection prevailing among infants at a nursery school].

Mycoplasma pneumoniae (M. pneumoniae) infection in infants had been considered to be very rare, but recently some clinical cases have been reported. We experienced an epidemic of M. pneumoniae infection in a nursery school, and compared M. pneumoniae infection in infants with that in preschool and school children to investigate the features of infantile M. pneumoniae infection. We obtained the following clinical findings in 15 infantile patients with M. pneumoniae infection: The maximum body temperature scarcely increased to 38.5 degrees C or more and the period of high temperature and cough was shorter in infant patients than in preschool and school aged patients. Stridor occurred in 4 patients but skin disorder was not observed. In the laboratory findings, the white blood cell count tended to increase with no changes in neutrophil/lymphocyte ratio and CRP increased slightly. M. pneumoniae antibody was negative in all the patients except 3 and old hemagglutination tests were positive in only 4 patients. The chest X-ray examinations showed a mild increase in the hilar shadow. However, the sequentially located homogeneous shadow which is commonly seen in preschool and school aged patients was not detected. M. pneumoniae antibody scarcely increased in infantile patients but M. pneumoniae was isolated by throat culture from 14 of the 15 patients who were diagnosed as having M. pneumoniae infection.

Child Day Care Centers↗