Search PubMed⌕ Search

Biomedical subjects

T Komatsu

Publications and source records attributed to T Komatsu.

At least 91 records · Page 5Linked to original sources

Cytoplasmic elongation and rupture in megakaryoblastic leukemia cells via activation of adhesion and motility by staurosporine on fibronectin-bound substratum.

Human megakaryoblastic leukemia Meg-01 cells were attached to fibronectin (FN)-coated substratum, on which remarkable spreading and cytoplasmic elongation was induced by treatment with a protein kinase inhibitor, staurosporine (stp). This effect was inhibited by RGDS and was also not seen on FN-lacking substratum. The extended cytoplasm had swollen terminals and nodes, which contained GpIIb and beta-thromboglobulin, occasionally included alpha granules, and tended to form particles (2-5 microm) after rupture of the narrowed cytoplasm. Among other protein kinase modulators tested, only K252a promoted the elongation, while calphostin, herbimycin, TPA, and calyculin suppressed it. The cells began to migrate soon after addition of stp, with attachment to the substratum held at some sites during the migration. This tethered movement seemed to cause the cytoplasmic elongation and the rupture into particles. The elongation was retarded by pretreating the cells with cytochalasin A and Clostridium C3 toxin but not with demecolcine. Actin microfilaments in the stp-treated Meg-01 cells accumulated in the filopodia and periphery of the extended cytoplasm, in which vinculin was colocalized as adhesion plaques. The microtubules were longitudinally oriented through the cytoplasmic extension and showed no ring profile in the nodes and particles. Thus, stp in the presence of FN appears to stimulate reorganization of actin-based cytoskeleton and formation of focal contacts in Meg-01 cells. This leads to the activation of cell adhesion and motility, and then cytoplasmic elongation and rupture into particles.

Animals↗

Regulation of the BBB during viral encephalitis: roles of IL-12 and NOS.

Intranasal infection of mice by Vesicular Stomatitis Virus (VSV) often leads to breakdown of the blood-brain barrier (BBB). The role of Interleukin 12 (IL-12) and nitric oxide synthase (NOS) was examined here. Wild-type (WT), NOS-1 knockout (KO), and NOS-3 KO mice were infected with VSV and treated with either IL-12 or medium. IL-12 treatment of uninfected hosts did not result in pathology. In contrast with WT and NOS-1 KO mice, where extensive gross and ultrastructural correlation of BBB breakdown were evident following infection, in NOS-3 KO mice, integrity of the BBB was observed. Thus NOS-3 activity in astrocytes, endothelial cells, or ependymal cells may play an essential role in regulating the BBB.

Animals↗

Transfer function analysis of the circulation in patients undergoing sevoflurane anesthesia.

PURPOSE: The effects of sevoflurane anesthesia on the interactions between heart rate, blood pressure and respiration were assessed using transfer function analysis. METHODS: Nine ASA 1 or 2 patients undergoing elective surgery were involved. They were paralysed and their lungs were mechanically ventilated during sevoflurane anesthesia. Instantaneous heart rate (IHR) from electrocardiogram, instantaneous lung volume (ILV) by respiratory inductive plethysmography and mean blood pressure (MBP) by arterial tonometry were obtained during conscious state, and 1MAC and 2MAC of sevoflurane anesthesia. Transfer function analysis for the relationships between ILV and IHR, ILV and MBP, MBP and IHR were made for five minute periods during which the respiratory rate was varied in a standardized fashion. RESULTS: In awake patients transfer magnitudes for the relationships between ILV and IHR and between MBP and IHR in the 0.04-0.5Hz frequency band were 8.9 +/- 7.7 bpm x l(-1) and 0.95 +/- 0.44 bpm x mmHg(-1) respectively. Sevoflurane 2MAC decreased these values to 1.2 +/- 0.7 (P = 0.014) and 0.26 +/- 0.14 (P < 0.01) respectively, but phases were not affected. Neither transfer magnitudes nor phases between ILV and MBP were affected during sevoflurane anesthesia. Coherence for the relationships between ILV and IHR and between MBP and IHR were decreased during 1MAC sevoflurane anesthesia but not affected during 2MAC sevoflurane anesthesia. CONCLUSIONS: The interactions between heart rate, blood pressure and respiration were altered by sevoflurane anesthesia. These findings could be explained by the attenuation of autonomic nervous system activity.

Adult↗

Heart rate and blood pressure power spectral analysis during calcium channel blocker induced hypotension.

PURPOSE: To observe heart rate (HRV) and blood pressure variability (BPV) as indices of neurocirculatory responses to induced hypotension with diltiazem and/or nicardipine for hip surgery. METHODS: Thirty-six ASA I-II patients received diltiazem (group D, n = 12), nicardipine (group N, n = 12) or combination of diltiazem/nicardipine (group DN, n = 12). The intensity of HRV and BPV, was determined by spectral analysis of HRV and BPV before anesthesia (T0), just before induced hypotension (T1), and at 10 and 30 min after the start of induced hypotension (T2 and T3, respectively). The logarithmic HRV and BPV were integrated: sympathetic and parasympathetic mediated low frequency area (0.06-0.1 Hz, LF), parasympathetic related high frequency area (0.15-0.4 Hz, HF) and total frequency area (0.01-0.4 Hz). Blood loss was assessed by weighing gauzes and measuring suction. RESULTS: Group DN had less blood loss (466 +/- 46 ml, mean +/- SEM) than group D (733 +/- 100 ml, P < 0.05). Diltiazem (11.4 +/- 0.9 microg x kg(-1) x min(-1)), and combination of diltiazem (0.25 +/- 0.01 mg x kg(-1)) and nicardipine (5.9 +/- 0.9 microg x kg(-1) x min(-1)) decreased LF-HRV at T2 and T3 (P < 0.05 vs T0 and T1), while nicardipine (8.1 +/- 0.8 microg x kg(-1) x min(-1)) showed increase in LF-HRV at T2 (P < 0.05 vs T1). HF-HRV unchanged through hypotension except for a decrease in group N at T3 (P < 0.05 vs T1). There were no increases in HF-BPV, and LF-BPV, except for a diltiazem induced decrease in LF-BPV at T3 (P < 0.05 vs T0 and T1). CONCLUSION: Group D and group DN can be used for deliberate hypotension without an increase in sympathetically mediated LF-HRV.

Adult↗

Esophageal carcinoma with high serum parathyroid hormone-related protein (PTHrP) level.

We report two patients with esophageal carcinoma with high levels of serum parathyroid hormone-related protein (PTHrP). Patient 1 was a 66-year-old man in whom the serum calcium level was also high, and patient 2 was an 81-year-old woman. The serum PTHrP level was 411 pM (normal range, 13.8-55.3pM) in patient 1 and 94.5 pM in patient 2 (in whom the serum granulocyte colony-stimulating factor level was also high). We demonstrated PTHrP immunohistologically in esophageal carcinoma cells in both patients. After admission, patient 1 died of pneumonia on the 17th day of hospitalization (the 48th day after he had had an episode of frequent hiccuping) and patient 2 died of acute circulatory failure on the 12th day of hospitalization (the 25th day after she had vomited after a meal). Neither of these patients died of cancer. Pneumonia in patient 1 was believed to be due to weakened body defenses, while the acute circulatory failure in patient 2 was due to emaciation. Since esophageal carcinoma with humoral hypercalcemia of malignancy and leukocytosis is characterized by rapid progression and metastasis, early diagnosis and treatment are mandatory.

Aged↗

Epidural block during general anesthesia attenuates urinary trypsin inhibitor excretion in lower abdominal surgery.

PURPOSE: The aim of this study was to elucidate whether urinary trypsin inhibitor excretion differs between general anesthesia (GA) and epidural block during general anesthesia (EPI) in lower abdominal surgery. METHODS: Sixteen women undergoing abdominal total hysterectomy were assigned to the GA and EPI groups. The GA group received propofol induction and maintenance with isoflurane, nitrous oxide, and vecuronium. The EPI group received epidural block, followed by propofol induction and maintenance with isoflurane and nitrous oxide. The levels of adrenocorticotropic hormone and cortisol during anesthesia and on postoperative days 1, 2, and 3, and the levels of urinary trypsin inhibitor in 12-h urine from the day of surgery to postoperative day 3, were measured. RESULTS: As compared with the EPI group, the GA group had a higher level of adrenocorticotropic hormone at the completion of anesthesia, higher levels of cortisol at the completion of anesthesia and postoperative day 2, and higher excretion of urinary trypsin inhibitor on the day of surgery and postoperative days 1 and 2. CONCLUSION: The present results suggest that excretion of urinary trypsin inhibitor into the urine under epidural block during general anesthesia is lower than that under general anesthesia alone in lower abdominal surgery. This is probably due to the difference in endocrine response to surgery between the two types of anesthesia.

Journal Article↗

Replication-incompetent Sendai virus can suppress the antiviral action of type I interferon.

Altered baby hamster kidney (BHK-R) cells, which were established by serial passage of BHK cells in the presence of Sendai virus (SeV), allowed vesicular stomatitis virus (VSV) to replicate despite treatment with type I interferon (IFN). We have analyzed here mechanisms of the unresponsiveness to IFN. BHK-R cells cultured in the absence of SeV for 10 days under the conditions of no cell division (BHK-R10D) became sensitive to IFN. Studies on induction of unresponsiveness to IFN in BHK-R10D cells revealed that entry of SeV nucleocapsids into a cell was essential. Interestingly, even UV-inactivated SeV but not Newcastle disease virus was found to be able to confer resistance to IFN on HeLa or BHK cells as well as on BHK-R10D cells, suggesting that the IFN-resistance resulted from functions of SeV independent of replication of the viral genome but not from mutations of the cellular genome. Furthermore immunofluorescent experiments demonstrated that UV-inactivated SeV could rescue VSV replication from the antiviral action of IFN without expression of SeV antigens, confirming that the secondary transcription resulting in synthesis of large amounts of viral proteins was dispensable for the IFN-resistance. Thus we have revealed a unique strategy of SeV against the antiviral action of IFN.

Animals↗

Complex translocation (6;21;8), a variant of t(8;21), with trisomy 4 in a patient with acute myelogenous leukemia (M2).

The t(8;21)(q22;q22) is the second-most frequently observed nonrandom karyotypic abnormality associated with acute myelogenous leukemia (AML), especially in FAB M2. Trisomy 4 is also a specific chromosomal abnormality for AML FAB M2 or M4. We experienced a 37-year-old woman with a morphologically AML FAB M2 carrying a rare complex translocation (6;21;8)(p21;q22;q22) resulting in AML1 gene rearrangement. A subclone with an additional chromosomal abnormality, trisomy 4, was also revealed. Similarly to the typical t(8;21), a conventional chemotherapy successfully induced into complete remission associated with a recovery of normal karyotype, 46,XX, although AML1/MTG8 (ETO) chimera mRNA was detected by reverse transcriptase polymerase chain reaction.

Adult↗

Derivative (1;7)(q10;p10) in a patient with de novo acute erythroblastic leukemia (AML-M6).

A rare association of der(1;7)(q10;p10) with de novo acute erythroblastic leukemia (AML-M6) in a 63-year-old male is reported. While this unbalanced 1;7 translocation, der(1;7), has been reported often in therapy-related myelodysplastic syndrome (t-MDS) or therapy-related acute myeloid leukemia (t-AML), its associations with de novo AML-FAB-M6 have rarely been reported. Although der(1;7) has been reported as a cytogenetic factor for poor prognosis in t-MDS/AML, our patient showed a good response to chemotherapy and obtained complete remission, although longer observation is required to evaluate the prognosis.

Aged↗

Time dependency of the ratio of umbilical vein/maternal artery concentrations of vecuronium in caesarean section.

BACKGROUND: The ratio of umbilical vein (UV) and maternal artery (MA) concentrations of vecuronium may more accurately determine the placental transfer ratio during caesarean section. This ratio potentially correlates with the time from induction of anaesthesia to delivery (I-D time). The aim of this study was to determine the UV/MA ratio of vecuronium and its relationship with the I-D time. METHODS: Eighteen pregnant women at full term undergoing caesarean section were studied. The parturient was given intravenously 0.01 mg/kg vecuronium as a priming dose, followed 180 s later by 0.11 mg/kg vecuronium as an intubation dose and 4 mg/kg thiamylal. The time from the injection of the intubation dose to the clamping of the umbilical cord was regarded as the I-D time. At the time of clamping the umbilical cord, blood samples were collected and the UV and MA of vecuronium were measured. RESULTS: The UV/MA ratio and the I-D time, expressed as the mean (SD), were 0.056 (0.016) and 280 (57) s, respectively. The regression equation indicated y = 0.0083 + 0.00017 x (R2 = 0.381, r = 0.617, P = 0.0063, I-D time (s) = x, UV/MA = y). CONCLUSION: The present study demonstrated that the UV/MA ratio of vecuronium as an index of the placental transfer becomes smaller as the delivery time after injection of this drug becomes shorter during caesarean section.

Adult↗

What is the connection between true and false memories? The differential roles of interitem associations in recall and recognition.

Veridical memory for presented list words and false memory for nonpresented but related items were tested using the Deese/Roediger and McDermott paradigm. The strength and density of preexisting connections among the list words, and from the list words to the critical items, were manipulated. The likelihood of producing false memories in free recall varied with the strength of connections from the list words to the critical items but was inversely related to the density of the interconnections among the list words. In contrast, veridical recall of list words was positively related to the density of the interconnections. A final recognition test showed that both false and veridical memories were more likely when the list words were more densely interconnected. The results are discussed in terms of an associative model of memory, Processing Implicit and Explicit Representations (PIER 2) that describes the influence of implicitly activated preexisting information on memory performance.

Cognition↗

A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three patients with LPG. We detected a novel point mutation in the apo E gene in a patient with LPG, and we characterized the mutant apo E. METHODS: The propositus was a 32-year-old male patient on maintenance hemodialysis because of LPG. The mutation was detected by sequencing of genomic DNA from the patient and was confirmed by restriction fragment length polymorphism (RFLP) with Aor51HI. Recombinant apo E2 (Arg25Cys) Kyoto and normal apo E3 were expressed from COS-1 cells. Low-density lipoprotein (LDL) receptor-binding activities of the variants were determined in an in vitro competition assay. RESULTS: The propositus had the apo E phenotype E2/E4, as determined by isoelectric focusing, and the genotype epsilon3/epsilon4, as determined by RFLP with HhaI. Sequence analysis of amplified DNA showed a C to T transition, changing the codon for residue 25 from arginine to cysteine. The proband was a heterozygous carrier for apo E2 (Arg25Cys) Kyoto. A family study showed that the mother was a heterozygous carrier of apo E2 Kyoto and had dysbetalipoproteinemia, but no LPG. The pathophysiological effect of this mutation was investigated in vitro by binding studies of recombinant apo E2 Kyoto to LDL receptors on human fibroblasts. The ability of recombinant apo E2 Kyoto to displace LDL was reduced to 10% compared with recombinant apo E3. CONCLUSIONS: Apo E2 (Arg25Cys) Kyoto is a novel mutation of apo E that is etiologically related to LPG. However, our case indicates that the development of LPG may involve other genetic or environmental factors. Furthermore, our data suggest that arginine-25 of apo E plays an important functional role by influencing the receptor-binding ability of apo E.

Adult↗

Delayed administration of interleukin-12 is efficacious in promoting recovery from lethal viral encephalitis.

Vesicular stomatitis virus (VSV) applied intranasally to mice initially infects the olfactory receptor neurons, and then spreads quickly to the rest of the central nervous system (CNS). Previously, we have shown that the cytokine interleukin-12 (IL-12) has a significant survival and recovery promoting effect in mice infected with VSV when administered at the time of infection. The question of whether IL-12 is efficacious under the more clinically relevant condition of post-infection administration was explored. The data show that when IL-12 is administered post-infection, it is as effective as at the time of infection.

Animals↗

Decrease in the prevalence of IL-4-producing CD4+ T cells in patients with advanced stage of primary biliary cirrhosis.

OBJECTIVE: To elucidate the precise immunological features in primary biliary cirrhosis (PBC), we examined the relative prevalence of CD4+ T cells in either symptomatic PBC (sPBC) or asymptomatic PBC patients (aPBC), and furthermore, these results were compared with their histological features. METHODS: Cytokine synthesis of peripheral blood mononuclear cells obtained from 24 PBC patients (9 sPBC and 15 aPBC) were examined by intracellular staining method. The relative prevalence of three distinct CD4+ T cells, gamma-interferon (IFN-gamma)-producing cells (Th1), interleukin-4 (IL-4)-producing cells (Th2), and the cells producing both IL-4 and IFN-gamma (Th0), was analyzed by FACScan and compared with those of closely age-matched healthy and disease controls. RESULTS: The results demonstrated that although a significant difference was not observed in the prevalence of Th1 or Th0, a remarkable difference was observed in the prevalence of Th2 (1.2+/-0.7 in sPBC, 4.1+/-1.3 in healthy subjects, 4.1+/-2.1 in aPBC, 3.4+/-1.3 in chronic hepatitis C, and 3.6+/-2.3 in cirrhosis secondary to CH-C; p < 0.05 for sPBC vs all others). Histological examination of these patients showed that all aPBC patients belonged to relatively early stage (stage I-II) and 7 of 8 sPBC patients belonged to late stage (stage III-IV). Thus, our results suggest that, mainly as a result of the decline of Th2, a predominance of Th1 may exist in advanced stage PBC. CONCLUSIONS: The present results demonstrated that a slight elevation of Th1 prevalence, as well as a significant decline of Th2 prevalence, was observed in peripheral blood of advanced stage PBC.

Adult↗

Cytokine secretion of periodontal ligament fibroblasts derived from human deciduous teeth: effect of mechanical stress on the secretion of transforming growth factor-beta 1 and macrophage colony stimulating factor.

The periodontal ligament may play an important role in tooth eruption, root development and resorption. The tissue physiologically receives mechanical force during mastication. We focused on the effects of intermittent mechanical strain on the cytokine synthesis of periodontal ligament (PDL) fibroblasts in vitro. The cells were derived from human periodontal ligament of deciduous teeth (HPLF-Y) and permanent teeth (HPLF). The two kinds of PDL cells and human gingival fibroblasts (HGF) were cultured in flexible bottomed culture plates. The cells were mechanically stretched at 5% elongation, 3-cycles/min for 24 h on d 7 in culture using a Flexercell strain unit. After the stretching, we measured DNA content and alkaline phosphatase activity in the cell layer, transforming growth factor beta 1 (TGF-beta 1) and macrophage colony stimulating factor (M-CSF) contents in the conditioned medium. The TGF-beta 1 level in the conditioned medium of HPLF was significantly higher than that of HPLF-Y and HGF. It was stimulated by mechanical stretching only on HPLF, whereas no significant effect was observed on HPLF-Y and HGF. M-CSF secretion was inhibited by the stretching on all of HPLF, HPLF-Y and HGF. 1 alpha, 25 dihydroxy vitamin D3 (D3) stimulated M-CSF secretion into the culture medium of both HPLF and HPLF-Y, but the stretching inhibited M-CSF secretion and completely blocked the enhancement by D3. These data suggest that periodontal ligament cells synthesize and secrete the molecules as autocrine or paracrine factors that affect bone remodelling and root resorption and the level of those factors change in response to mechanical stress.

Alkaline Phosphatase↗

Clinical implication of vascular cell adhesion molecule-1 and very late activation antigen-4 interaction, and matrix metalloproteinase-2 production in patients with liver disease.

OBJECTIVES: To clarify the role of adhesion molecule in liver cell injury. PATIENTS AND METHODS: The serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), and the expression of VCAM-1 and its ligand, very late activation antigen-4 (VLA-4), were examined in patients with various liver diseases. In addition, the presence of matrix metalloproteinase-2 (MMP-2) was investigated because the release of MMP-2 is thought to be mediated by VLA-4-positive cells. sVCAM-1 and MMP-2 were measured by ELISA assay, and VCAM-1 and VLA-4 were studied by immuno-histological methods. RESULTS: In acute hepatitis (AH) patients, the serum level of sVCAM-1 was significantly elevated compared with that in other cohorts. VCAM-1 was expressed on sinusoidal lining cells but not on hepatocytes. In patients with chronic liver disease, sVCAM-1 levels rose in concert with the progression of chronic hepatitis (CH), and VCAM-1 was also expressed. VLA-4 was detected in both mononuclear cells and Kupffer cells in AH livers, but mainly in Kupffer cells in patients with CH. In AH patients, MMP-2 levels were similar to those in control subjects, but in CH and liver cirrhosis patients, MMP-2 level was elevated in association with CH progression. CONCLUSIONS: The immune response through the VCAM-1 and VLA-4 pathways is important in hepatocyte injury, especially in AH patients, to attach VLA-4-positive mononuclear cells to VCAM-1-positive sinusoidal lining cells. The distribution of VLA-4-positive cells differs between AH and CH patients. VLA-4-positive Kupffer cells in chronic liver diseases might be involved in the progression of CH, perhaps through the mechanism of upregulation of MMP-2 production.

Acute Disease↗

Effect of retinoic acid on proliferation and polyamine metabolism in cultured bovine retinal pigment epithelial cells.

Reports regarding the effect of all-trans-retinoic acid (RA) on the cell growth of retinal pigment epithelial cells (RPE) have been contradictory. The aims of this study are to clarify the in vitro effect of RA on RPE cells and to examine polyamine metabolism after RA stimulation. A 4-day incubation of fetal-calf-serum (FCS)-stimulated RPE cells with 10 or 25 microM RA significantly increased both cell number and [3H]thymidine incorporation. RPE cells grown over an extended period for 8 days also increased in number and reached full confluency. However, if the incubation was further extended to 12 days, no further increase in cell number was detected. RA treatment of FCS-stimulated RPE cells shifted the peak of ornithine decarboxylase (ODC) activity from 16 to 4 h. S-adenosylmethionine decarboxylase (SAMDC) activity and spermidine/spermine N1-acetyltransferase (SAT) activity of RA-treated RPE cells were significantly greater until 8 and 16 h after incubation, respectively. The putrescine content was significantly increased in RA-treated RPE cells up until 24 h, while spermidine, spermine and N1-acetylspermidine contents were significantly increased until 16 h. Our findings suggest that RA treatment increases the intracellular polyamine concentration of RPE cells via activation of ODC, SAMDC and SAT and that this results in the promotion of RPE cell growth until the cells reach full confluency.

Adenosylmethionine Decarboxylase↗