Alkali-metal adsorption on dissimilar alkali-metal monolayers preadsorbed on Cu(001): Li on Na and Na on Li.
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Journal Article↗
Biomedical subjects
S Mizuno
Publications and source records attributed to S Mizuno.
Transmission and reflection times of phonon packets propagating through superlattices.
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Journal Article↗
Conversion of epidermal growth factor (EGF) into a stimulatory ligand for A431-cell growth by herbimycin A by decreasing the level of expression of EGF receptor.
We examined effect of the tyrosine kinase inhibitor herbimycin A on A431 human epidermoid carcinoma cells which over-express epidermal growth factor (EGF) receptor. Herbimycin A inhibited the autophosphorylation of EGF-stimulated receptors in intact cells both time- and dose-dependently. The inhibition was found to be due to a decrease in the level of expression of the receptor amount, because herbimycin A equally decreased the receptor quantity and EGF-stimulated receptor kinase activity in intact cells, but did not exhibit a direct inhibitory effect on EGF receptor kinase activity in vitro. The decrease of the level of EGF receptor was also confirmed by 125I-EGF binding to herbimycin A-treated cells, and Scatchard analysis showed that the decrease in the receptor number occurred in the major population of the low-affinity binding ones, whereas the number with high-affinity binding was unaffected. Interestingly, although the proliferation of A431 cells was inhibited by EGF, herbimycin A converted EGF into a stimulatory ligand for cell growth, as determined by both cell number and DNA synthesis. These findings indicated that herbimycin A decreased the level of expression of EGF receptor by a mechanism other than inactivation of the receptor kinase and reversed the transformed phenotype of A431 cells to a normal one in the proliferative response to EGF.
Benzoquinones↗
Accelerated degradation of 160 kDa epidermal growth factor (EGF) receptor precursor by the tyrosine kinase inhibitor herbimycin A in the endoplasmic reticulum of A431 human epidermoid carcinoma cells.
The effect of herbimycin A on the biosynthesis of epidermal growth factor (EGF) receptor was examined in human epidermoid carcinoma A431 cells. Cells were pulse-labelled with [35S]methionine, and EGF receptor biosynthesis was quantified by immunoprecipitation using a monoclonal anti-(EGF receptor) antibody. In the presence of herbimycin A, an immature 160 kDa EGF receptor precursor accumulated in 1 h and disappeared completely in 4 h. Pulse-labelled 160 kDa receptor precursor in the absence of herbimycin A, however, was converted normally into a 170 kDa one by chase with herbimycin A. Herbimycin A affected neither the synthesis of the secreted form of EGF receptor devoid of cytoplasmic domain, nor that of the transferrin receptor in A431 cells. The herbimycin A-induced degradation of 160 kDa EGF receptor precursor was not inhibited by an inhibitor of lysosomal enzymes, NH4Cl. Endoglycosidase H digestion of the 160 kDa precursor converted it into the deglycosylated 130 kDa precursor peptide. These results suggested that herbimycin A selectively acted on the EGF receptor precursor during the synthesis of the 160 kDa form, probably on the cytoplasmic domain, to form an aberrant molecule which was subjected to rapid degradation in the endoplasmic reticulum.
Benzoquinones↗
Labeling of v-Src and BCR-ABL tyrosine kinases with [14C]herbimycin A and its use in the elucidation of the kinase inactivation mechanism.
The ansamycin antibiotic, herbimycin A, selectively inactivates cytoplasmic tyrosine kinases, most likely by binding irreversibly to the reactive SH group(s) of kinases. To further investigate the mechanism of herbimycin A action, we attempted to label tyrosine kinases with [14C]herbimycin A. p60v-src and p210BCR-ABL in immune complexes were labeled with [14C]herbimycin A, demonstrating that the antibiotic binds directly to tyrosine kinases. Digestion of [14C]herbimycin A-labeled p60v-src with Staphylococcus aureus V8 protease revealed that the herbimycin A binding site is within the C-terminal 26-kDa fragment of p60v-src, which contains the tyrosine kinase domain. Herbimycin A treatment inhibited labeling of p60v-src by [14C]fluorosulfonylbenzoyl adenosine, an affinity labeling reagent of nucleotide binding sites, indicating that herbimycin A-modified p60v-src cannot interact with ATP. The results suggest that herbimycin A inactivates tyrosine kinases by binding directly to the kinase domain, thereby inhibiting access to ATP.
3T3 Cells↗
Molecular genetics for clinical management of colorectal carcinoma. 17p, 18q, and 22q loss of heterozygosity and decreased DCC expression are correlated with the metastatic potential.
BACKGROUND: The molecular genetic changes associated with colorectal carcinoma are among the best understood of any common human cancer. The genetic changes during the late stages of colorectal carcinomas may be useful in clinical management for determining the metastatic potential of the carcinoma. METHODS: Tumor tissues were evaluated by restriction fragment length polymorphism (RFLP) analysis of chromosomes 5q, 17p, 18q, and 22q (n = 98), by reverse transcription-polymerase chain reaction (RT-PCR) analysis of messenger RNA expression of the DCC gene (deleted in colorectal carcinoma) (n = 27) and by immunohistochemical analysis of p53 protein expression (n = 44). RESULTS: Loss of heterozygosity (LOH) on chromosomes 17p, 18q, and 22q, but not on 5q, was much more frequently detected in advanced carcinomas than in intramucosal carcinomas (P < 0.01). 17p LOH was significantly correlated with vascular invasion (P < 0.001), whereas 18q LOH was correlated with lymphatic invasion and hepatic metastasis (P < 0.01), and 22q LOH was correlated with lymph node metastasis (P < 0.05). LOH on 5q did not show a significant correlation with any factors of tumor invasion or metastasis. DCC expression was not observed in any of five hepatic metastasis or in five of seven advanced carcinomas that were accompanied by hepatic metastasis (10 of 12). However, a similar lack of expression was observed in only 5 of 15 carcinomas without hepatic metastasis (P < 0.05). p53 Expression was found to vary in both primary and metastatic carcinomas by immunohistochemistry. CONCLUSIONS: The clinical application of molecular genetics (i.e., RFLP analysis of chromosome 17p, 18q, and 22q and RT-PCR analysis of DCC expression into messenger RNA) can be used to determine the metastatic potential of colorectal carcinomas.
Adult↗
Observations of coverage- and temperature-dependent surface structures formed upon Li deposition on Cu(110).
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Journal Article↗
Hepatic resection for metastatic tumours from gastric cancer: analysis of prognostic factors.
Determinants of prognosis after hepatic resection for metastasis from gastric cancer were studied in a retrospective series of 21 patients, including four who survived more than 5 years after surgery. All patients underwent apparently curative resection. Synchronous or metachronous resection, age, sex, histological type, depth of invasion, lymphatic and venous invasion, lymph node involvement and number of hepatic metastases were analysed as prognostic factors for survival. Serosal invasion was the only significant determinant at synchronous resection. Both lymphatic and venous invasion were significant prognostic factors available after histological examination. Combined analysis of these two histological variables revealed that patients positive for both were at a significantly higher risk for both overall and disease-free survival. It is suggested that hepatic resection should be attempted in patients with synchronous or metachronous metastases if there is no serosal invasion by the primary gastric tumour, and if the primary tumour has neither venous nor lymphatic invasion in the case of metachronous metastases.
Adult↗
The effects of using a leukocyte removal filter during cold blood cardioplegia.
During myocardial ischemia, neutrophils and platelets exert negative effects on the myocardium. In this study, we used a leukocyte removal filter during cardioplegia, and investigated its effect on myocardial damage during reperfusion by measuring the plasma levels of granulocyte components, platelet components, and cardiac enzymes [creatinine phosphokinase (CK) and creatinine phosphokinase myocardial band (CK-MB)] in 24 patients who underwent cardiopulmonary bypass. The patients were divided into two groups of 12 according to whether or not a filter was placed in the cardioplegic route. Blood samples were drawn directly from the coronary sinus before aortic cross clamping, and at 1, 5, and 15 min after declamping. Group F, which had the filter, showed better cardiac enzyme and lipid peroxidation results than group N, which did not. The results of this study suggest that the application of a filter during cold blood cardioplegia may reduce myocardial damage.
6-Ketoprostaglandin F1 alpha↗
Effect of recombinant human erythropoietin administration on peripheral blood neutrophil counts of premature infants.
To clarify whether administration of recombinant human erythropoietin (rHuEpo) may have toxic effects on neutrophil production in premature infants, 10 low birth weight infants who received rHuEpo, 200 U/kg per week, were studied retrospectively. Treated infants were compared with 10 untreated infants. None of the infants studied had infection antenatally or postnatally. In both groups the neutrophil count remained greater than 5000/mm3 for the first 3 weeks and decreased markedly at approximately 4 weeks. Although reticulocyte counts were significantly elevated in the rHuEpo-treated group, the difference in neutrophil counts between the groups was not significant. In addition, administration of rHuEpo did not exert any significant effect on granulocyte-macrophage colony formation of circulating hematopoietic progenitors in neonates. Thus no evidence was found that administration of rHuEpo has toxic effects on granulopoiesis in premature infants.
Erythropoietin↗
Flow cytometric analysis of nuclear DNA content in tongue squamous cell carcinoma: relation to cervical lymph node metastasis.
The relationship between DNA ploidy and the incidence of cervical lymph node metastasis in 36 patients with tongue squamous cell carcinoma (SCC) was investigated. The aneuploidy rate of tongue carcinomas was 15/36 (42%), and the mean DNA index (DI) was 1.23, with a range from 0.87 to 3.54. Histologically identified cervical lymph node metastasis was observed in 11 cases, and the incidence of the cervical lymph node metastasis was significantly (P < 0.02) higher in the aneuploid cases (8/15) than in the diploid cases (3/21). Recurrence of the primary lesions was seen in nine cases 0.3-2.5 years after the initial treatment. No obvious difference in the incidence of the recurrence was noted, however, between the diploid (5/21) and the aneuploid (4/15) cases. These results indicate a significant relationship between aneuploidy and incidence of the regional lymph node metastasis, in contrast to the absence of a positive relationship between aneuploidy and recurrence of tongue SCC.
Aneuploidy↗
Shape memory alloy catheter system for peroral pancreatoscopy using an ultrathin-caliber endoscope.
Two types of a shape memory alloy (SMA) catheter system with a mechanism for tip control and irrigation were evaluated in performing peroral pancreatoscopy (PPS) using an ultrathin-caliber endoscope. The selective cannulation of SMA catheters into the papilla was made possible in 18 of 19 patients with pancreatic diseases. Endoscopic sphincterotomy was necessary in six of seven patients with the two-directional catheter (2.6 mm) but in only one of 12 patients examined with the one-directional type (2.2 mm). In 17 of the 18 patients, the catheters were smoothly advanced to the desired positions in the main pancreatic duct, even to the distal pancreas, due to their controllable tip. PPS with adequate inspection of the ducts and lesions was successful in 16 of these 17 patients. Features of cancer (duct disruption, tumor infiltration) and chronic pancreatitis (smooth ductal surface, fine vascular network) could be distinguished. In this series, there were no obvious complications during or after the procedure. In our experience, the SMA catheter system is effective for PPS in patients with an intact papilla and without dilation of the main pancreatic duct. Further study will show the clinical benefits this technique may have in pancreatic diseases.
Alloys↗
Immunization of mice by injection with a recombinant retrovirus vector containing human factor IX for production of monoclonal antibody against factor IX.
A novel immunization procedure for eliciting murine monoclonal antibodies (mAb) is described. A murine leukemia virus (MLV)-based retroviral vector, designed as a marker protein for the expression of human factor IX (FIX), was constructed. Direct injections of mice with 0.8-1.3 x 10(4) retroviruses were carried out three times at 4-week intervals. Three out of 4 mice that had the viruses injected subcutaneously produced the antibodies against FIX, and 2 out of 3 mice injected intraperitoneally produced the antibodies. From 1 of the mice with the antibodies, an anti-human FIX murine monoclonal antibody, designated ACTIX (IgMk type), was produced. The immunization of mice by direct injection of viruses facilitated mAb production in many instances in which cDNAs are available.
Animals↗
Conductance catheter measurements of left ventricular volume in the intact dog: parallel conductance is independent of left ventricular size.
OBJECTIVE: It has recently been suggested that conductance catheter parallel conductance (alpha Vc) is a function of left ventricular volume. To confirm this, alpha Vc was measured in this study over a wide range of steady state volumes. In addition, conductance derived volumes were compared to those obtained by radionuclide angiography to determine if the conductance catheter can be used to measure absolute left ventricular volume accurately in the intact dog heart. METHODS: Seven dogs were anaesthetised and instrumented with left ventricular conductance and pressure tip catheters, a flow through rho cuvette to continually measure blood resistance, a thermodilution catheter, and a venous catheter for volume infusion/withdrawal. Conductance and angiographic data were acquired at 8(SD 1) variably loaded states. Parallel conductance was measured twice at each state using a saline dilution technique and a new non-linear algorithm that allows variability in the observations of both maximum and minimum conductance volumes. RESULTS: The mean value of alpha Vc was 89.1(18.0) ml (71.8 to 111.3 ml) with a mean within-animal coefficient of variation of 7.3(3.4)%. Multiple linear regression using dummy variables to account for the large interanimal variability did not reveal any relationship between alpha Vc and either maximum or minimum left ventricular volume. Furthermore, no difference was found when alpha Vc values measured at the lowest and highest loading levels in each dog were compared. Linear regression showed good agreement between conductance and radionuclide derived end diastolic volumes (slope = 0.94, R = 0.9, p < 0.001). CONCLUSIONS: While alpha Vc varies between animals, it remains constant within any given animal over a broad range of left ventricular volumes. Thus the conductance catheter can provide reliable absolute left ventricular volume measurements under steady state conditions.
Animals↗
Surgically curable "early" adenocarcinoma in the periphery of the lung.
To define surgically curable "early" adenocarcinoma in the periphery of the lung, we examined histopathologic prognostic factors in 56 cases of stage I mucinous, nonmucinous, and sclerosing bronchioloalveolar carcinomas less than 2 cm in diameter. The death rate 5 years after surgery was only 1.8%, but the recurrence rate within 5 years after surgery was 8.9%. In addition, there were two cases of recurrence more than 5 years after surgery. Vascular invasion (p < 0.05) and mitotic index (p < 0.01) were the most important determinants of prognosis, and there was no recurrence or death in cases showing grades 1 and 2 collagenization in fibrotic foci. These results indicate surgically curable stage I adenocarcinomas to be less than 2 cm in diameter and without vascular invasion, with a low mitotic index and grade 1 or 2 fibrotic scarring, although the significance of nuclear atypia as a prognostic factor remains to be clarified. It may be possible to improve the cure rate by postoperative adjuvant chemotherapy for "early" adenocarcinoma with vascular invasion, high mitotic index, higher scar grade, and probably a high degree of nuclear atypia.
Adenocarcinoma↗
Involvement of interferon-gamma and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults.
We investigated the role of monocyte/macrophage-activating cytokines in pathogenesis of haemophagocytic lymphohistiocytosis (HLH) in 21 adult patients. Sera from patients with active HLH contained extremely high levels of macrophage colony-stimulating factor (M-CSF) and of interferon-gamma (IFN-gamma). These levels returned to almost normal during remission. Neither interleukin-4 nor granulocyte/macrophage colony-stimulating factor could be detected. Active HLH sera also contained high concentrations of inflammatory monokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). Serum concentrations of soluble CD8 and soluble interleukin-2 receptor were extremely high during active HLH, and returned to virtually normal levels during remission. Circulating CD2+ T-cells obtained from patients with active HLH spontaneously secreted M-CSF and IFN-gamma in vitro, whereas circulating monocytes did not produce detectable levels of both M-CSF and IFN-gamma, but produced high levels of IL-6 and TNF-alpha. These findings suggest that IFN-gamma and M-CSF at least partly from T-cells, such as CD8+ T-cells, might contribute to activation of monocytes or histiocytes, resulting in the up-regulated monokine production and haemophagocytosis in HLH.
Adolescent↗
Adsorption of anaphylatoxins and platelet-specific proteins by filtration of platelet concentrates with a polyester leukocyte reduction filter.
Anaphylatoxins generated during storage of platelet concentrates (PCs) may potentially have side effects on platelet transfusion. We evaluated the anaphylatoxin-scavenging abilities of white blood cell reduction filters. Among the commercially available filters for PCs, one made with polyester fiber (PL50) dramatically adsorbed C3a and C4a anaphylatoxins to the respective mean level of 1,721-208 ng/ml and 1,240-141 ng/ml in 3-day-old PCs. C3a and C4a were measured as the native and des Arg form of each complement by radioimmunoassay. C3a and C4a anaphylatoxins in the supernatant plasma fraction from 3-day-old PC again decreased from 1,136 to 114 ng/ml and from 1,086 to 65 ng/ml, respectively. The filter also adsorbed 85% of platelet factor 4 (PF4) and 31% of beta-thromboglobulin (beta-TG), which had been released from platelets into the plasma during storage. The plasma levels of adhesive proteins such as fibronectin, fibrinogen, and von Willebrand factor, and plasma lactate dehydrogenase activity did not decrease after filtration. Another polyester filter (PL5A), on the other hand, significantly increased C3a and C4a levels with filtration. In addition, there was no PF4 adsorption ability during the filtration. The filters for red cells (RC50, BPF4, and R500A) had no anaphylatoxin adsorption capabilities. The observed specific adsorption of anaphylatoxins might be attributed to the electrostatic force between the positively charged anaphylatoxins with high pI and the possibly negatively charged filter membranes. Since PF4 and beta-TG have positively charged moieties in the C-terminal position, the same adsorption mechanism might operate.(ABSTRACT TRUNCATED AT 250 WORDS)
Adsorption↗
Rapid degradation of the heavy chain of class I major histocompatibility complex antigens in the endoplasmic reticulum of human cytomegalovirus-infected cells.
Human cytomegalovirus (HCMV) infection results in a marked reduction in the surface expression of class I major histocompatibility complex antigens on the host cells, which is thought to be one of the means for HCMV to evade the host immune system. To clarify the precise mechanism(s) of this phenomenon, we investigated the fate of the heavy chain of class I major histocompatibility complex antigens in HCMV-infected human embryonic lung fibroblasts (HEL) by pulse-chase analysis and immunocytochemical techniques. In HCMV-infected HEL, the heavy chain was synthesized at an increasing rate. However, instead of being transported to the cell surface through the Golgi apparatus, it was retained in the endoplasmic reticulum (ER) without acquisition of a complex-type N-linked oligosaccharide. In addition, it was rapidly degraded, with a half time of 20 min, and the amount of the heavy chain remaining at the end of 3 h of chase was 10% (or less) of that initially synthesized. ER degradation of host glycoproteins in HCMV-infected HEL was selective for the heavy chain, since the posttranslational processing of the transferrin receptor in these cells was not affected. The heavy chain degradation in infected cells was resistant to inhibitors of a lysosomal proteolytic pathway and to metabolic poisons. These observations suggest the presence of an energy-dependent nonlysosomal proteolytic pathway in the ER.
1-Deoxynojirimycin↗