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Biomedical subjects

Y Endo

Publications and source records attributed to Y Endo.

At least 235 records · Page 13Linked to original sources

Immunohistochemical localization of a urokinase-type plasminogen activator system in squamous cell carcinoma of the oral cavity: association with mode of invasion and lymph node metastasis.

The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) has been implicated in cancer invasion and metastasis. This activity is known to be regulated by several inhibitors such as plasminogen activator inhibitors (PAIs). To elucidate the participation of the uPA system in the malignant behaviour of squamous cell carcinoma (SCC) in the oral cavity, uPA, uPAR, PAI-1 and -2 expression and localisation in 34 primary oral cancers were examined immunohistochemically. The results were then compared with clinicopathological findings. The positive rates of uPA, uPAR, PAI-1 and -2 expression were 23.5, 29.4, 29.4 and 11.8%, respectively. uPA expression correlated with mode of cancer invasion according to Yamamoto-Kohama's criteria (p < 0.01) and with secondary regional lymph node metastasis. uPAR expression also correlated with mode of invasion. In particular, the tumours of both uPA- and uPAR-positive [uPA(+)/uPAR(+)] cases were highly invasive. In the present study, neither PAI-1 nor PAI-2 expression correlated with clinicopathological parameters. However, PAI-2 negative cases of uPA(+)/uPAR(+) were significantly more invasive (p < 0.0001). Such uPA(+)/uPAR(+)/PAI-2(-) cases almost always showed secondary lymph node metastasis (p < 0.01). These results indicate that the uPA system plays a significant role in the invasive and metastatic processes of oral SCC, and that this system may be a powerful aid in evaluating the clinical course or prognosis of patients with oral cancer.

Adult↗

The use of two immunosuppressive drugs, cyclosporin A and tacrolimus, to inhibit virus replication and apoptosis in cells infected with feline immunodeficiency virus.

An in vitro model of acute and chronic infections with feline immunodeficiency virus (FIV) was used to examine the effect of two immunosuppressive agents, cyclosporin A (CsA) and tacrolimus (also known as FK506), on the inhibition of the replication of the virus and of apoptosis. Both drugs significantly suppressed virus production in a dose-dependent manner in acutely and chronically infected cells. The ability of FK506 to inhibit virus replication was much lower than that of CsA, and was accompanied by marked antiproliferative activity. Treatment of infected cells with either CsA or FK506 did not affect the rise of free intracellular Ca2+ but did protect the cells against apoptosis. Thus, the antiviral activity of CsA and FK506 makes these compounds promising candidates for the development of drugs suitable for the treatment of AIDS.

Animals↗

Significance of plasminogen activator inhibitor 2 as a prognostic marker in primary lung cancer: association of decreased plasminogen activator inhibitor 2 with lymph node metastasis.

The expression of urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR) and plasminogen activator inhibitor (PAI) 1 and 2 was examined in 105 cases of primary lung cancer tissue using immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. The expression of u-PA, u-PAR and PAI-1 was detected in approximately 80% of primary lung cancers, whereas detectable PAI-2 expression was observed only in half of the overall cases. We assessed the relationships between the expression pattern and clinicopathological findings and found that a diminished expression level of PAI-2 was significantly correlated with lymph node metastasis and a poor prognosis. These results indicate that PAI-2 may play a critical role in the regulation of extracellular matrix degradation during tumour cell invasion and metastasis, and the expression of PAI-2 may be useful as a marker for evaluating the prognosis of lung cancer.

Adenocarcinoma↗

Induction by interleukin-1, tumor necrosis factor and lipopolysaccharides of histidine decarboxylase in the stomach and prolonged accumulation of gastric acid.

1. Injection of interleukin-1 (IL-1) into pylorus-ligated rats has been shown strongly to inhibit gastric secretion. However, in the present study, we found that an intraperitoneal injection of IL-1 into intact (non-pylorus-ligated) fasted mice rapidly (within 30 min) induced an accumulation of gastric acid ('early response'). When the dose of IL-1 was larger, the accumulation lasted for a longer period. 2. Injection of IL-1 also caused a later elevation of the activity of histidine decarboxylase (HDC), the histamine-forming enzyme, in the stomach ('later response'). 3. Cimetidine, an antagonist of histamine H2-receptors, suppressed the accumulation of gastric acid in both the early and later periods. An irreversible inhibitor of HDC, alpha-fluoromethylhistidine, partially inhibited the accumulation in the later period. 4. IL-1, when injected 1 h after feeding in mice fasted overnight, markedly retarded gastric emptying. 5. Tumour necrosis factor (TNF) and lipopolysaccharide (LPS) or endotoxin from E. coli both had IL-1-like effects on the stomach, and their effects are presumably mediated by IL-1. 6. These results support the idea that an inhibition of gastric emptying and an elevation of HDC activity in the stomach may explain the findings that a long-lasting accumulation of gastric acid is induced by IL-1 despite its potent inhibition of gastric acid secretion. 7. On the basis of these results, and in the light of the known actions of histamine, the possible roles of IL-1 in gastric inflammation and ulceration are discussed.

Animals↗

Contrasting effects of an aminobisphosphonate, a potent inhibitor of bone resorption, on lipopolysaccharide-induced production of interleukin-1 and tumour necrosis factor alpha in mice.

1. Aminobisphosphonates (aminoBPs), potent inhibitors of bone resorption, have been reported to induce inflammatory reactions such as fever and an increase in acute phase proteins in human patients, and to induce the histamine-forming enzyme, histidine decarboxylase, in mice. In the present study, we examined the effect of aminoBP, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (AHBuBP), on the production of the pro-inflammatory cytokines, IL-1 and TNFalpha, in mice. 2. Intraperitoneal injection of AHBuBP did not itself produce detectable levels of IL-1 (alpha and beta) and TNFalpha in the serum. However, the elevation of serum IL-1 induced by lipopolysaccharide (LPS) was greatly augmented in mice injected with AHBuBP 3 days before the LPS injection, whereas the LPS-induced elevation of serum TNFalpha was almost completely abolished. 3. Spleen and bone marrow cells taken from mice injected with AHBuBP produced IL-1beta in vitro spontaneously, and the production was augmented following the addition of LPS. Cells that accumulated in the peritoneal cavity in response to AHBuBP produced a particularly large amount of IL-1beta. However, AHBuBP treatment of mice did not lead to an impairment of the in vitro production of TNFalpha by these three types of cells. 4. Liposomes encapsulating dichloromethylene bisphosphonate (a non-amino BP) selectively deplete phagocytic macrophages. When an intraperitoneal injection of these liposomes was given 2 days after an injection of AHBuBP, there was a marked decrease in the LPS-induced elevation of serum IL-1 (alpha and beta) (LPS being injected 3 days after the injection of AHBuBP). 5. These results indicate that AHBuBP has contrasting effects on the in vivo LPS-induced production of IL-1 and TNFalpha in mice, enhancing the production of IL-1 by phagocytic macrophages and suppressing the production of TNFalpha, although underling mechanisms remain to be clarified.

Alendronate↗

Perianal hidradenitis suppurativa: early surgical treatment gives good results in chronic or recurrent cases.

Hidradenitis suppurativa (HS) represents a chronic, recurrent, deep-seated folliculitis resulting in abscesses followed by the formation of sinus tracts and scarring. It is an uncommon disorder frequently involving the perianal region. We review the clinical and pathological features of 12 patients (10 men and two women) with perianal HS (PHS). The mean age at presentation was 43 years (range 24-65), and the mean duration of illness was 14 years (range 2-30). Two patients exhibited multiple areas of involvement, including the axilla and the nape of the neck, in addition to the perianal region. Histological examinations showed epidermis-lined sinuses surrounded by dense plasma cell infiltration in four of nine specimens. The complications related with PHS included anal fistula (seven patients), diabetes mellitus (four), malignant tumour (two) and sepsis (one). Three patients died of the complications. Eight patients underwent wide local excision. The defects were managed with a meshed split-thickness skin graft in five patients, and open treatment in the remainder. New lesions developed in untreated skin of two patients. However, no patient relapsed in the surgically treated sites. PHS is frequently complicated with anal fistula and is occasionally life-threatening as a result of the occurrence of malignant tumours or sepsis. Early surgical excision followed by meshed split-thickness skin graft can successfully cure the lesion without functional disturbance.

Adult↗

Therapeutic apheresis for septic patients with organ dysfunction: hemoperfusion using a polymyxin B immobilized column.

A prospective clinical study was performed to evaluate a new method of treatment of endotoxin shock, a column containing polystyrene fibers with covalently bound immobile polymyxin B. Direct hemoperfusion using the column removes circulating endotoxin by adsorption. All of the patients studied, 37 in the treatment group and 33 in the control group, had endotoxemia and failure of 1 or more organs. The perfusion was performed 1-7 times per patient, 2 h/session. The survival rate was significantly higher in the treatment group (54%) than in the controls (36.4%). The mean plasma endotoxin concentration was significantly lowered by the treatment from 83.7 pg/ml before perfusion to 56.4 pg/ml immediately after and 28.5 pg/ml the day after the treatment, and the posttreatment level was much lower in those who survived (mean, 18.8 pg/ml) compared to those who died (mean, 88 pg/ml). Various parameters of cardiac function also improved after the treatment.

Adolescent↗

Juxtaglomerular cell tumor without hypertension.

Juxtaglomerular cell tumors are rare. This report presents a case of juxtaglomerular cell tumor without hypertension. All previously reported cases showed marked hypertension, whereas this is the first case of juxtaglomerular cell tumor without hypertension. The immunohistochemistry and ultrastructure of this case are discussed.

Adenocarcinoma↗

Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene.

Dihydropyrimidinase (DHP) deficiency (MIM 222748) is characterized by dihydropyrimidinuria and is associated with a variable clinical phenotype. This disease might be associated with a risk of 5-fluorouracil toxicity, although no cases have been reported. We present here both the molecular characterization of the human DHP gene and, for the first time, the mutations causing DHP deficiency. The human DHP gene spans >80 kb and consists of 10 exons. It has been assigned to 8q22, by FISH. We performed mutation analysis of genomic DNA in one symptomatic and five asymptomatic individuals presenting with dihydropyrimidinuria. We identified one frameshift mutation and five missense mutations. Two related Japanese adult subjects were homozygous for the Q334R substitution, whereas two other, unrelated Japanese infant subjects were heterozygous for the same mutation, but this mutation is not common in the Japanese population. A Caucasian pediatric patient exhibiting epileptic attacks, dysmorphic features, and severe developmental delay was homozygous for W360R. Using a eukaryotic expression system, we showed that all mutations reduced enzyme activity significantly, indicating that these are crucial DHP deficiency-causing mutations. There was no significant difference, in residual activity, between mutations observed in the symptomatic and those observed in the asymptomatic individuals.

Adult↗

ATPase associated with ribosomal 30S-5SRNP particles and 40S subunits of rat liver.

The ATPase activity of rat liver 30S-5SRNP particles prepared by EDTA treatment of 80S ribosomes, and that of 40S subunits were investigated in correlation with polypeptide elongation. The ATPase activity of 30S-5SRNP particles was higher than that of 40S subunits. Poly(U) and TMV RNA stimulated the ATPase activity of 30S-5SRNP particles more markedly than that of 40S subunits. These two kinds of particles also showed intrinsic GTPase. Poly(U) enhanced the GTPase activity of 30S-5SRNP particles but not that of 40S subunits. An elongation factor (EF-1alpha, EF-2, or EF-1alphabetagamma) alone or in combination with poly(U) and/or other elongation factors stimulated the ATPase activities of both particles. The extent of stimulation of the ATPase activity by a combination of these components was usually somewhat higher than or similar to the sum of those with the individual components. The extents of stimulation by these components were higher in the case of 30S-5SRNP particles than that of 40S subunits, indicating the importance of the 5SRNP moiety in the former particles. The intactness of 18SrRNA was required for promotion of the ATPase activity of 30S-5SRNP particles by Phe(+), (-)tRNA(Phe). The ATPase activities of the two kinds of particles by themselves or those observed with the combinations of the components mentioned above were inhibited by several kinds of translation inhibitors. The degrees of inhibition were generally higher for 30S-5SRNP particles. The ATPase activity of 40S subunits was enhanced by spermidine, suggesting the importance of the conformational change induced by it. These results imply the participation of the intrinsic ATPase of 30S-5SRNP particles and 40S subunits in polypeptide elongation, and the important role of the 5SRNP moiety of 30S-5SRNP particles in the ATPase activity.

Adenosine Triphosphatases↗

A chick embryo model for metastatic human prostate cancer.

OBJECTIVE: To establish a suitable experimental model of bone and liver micrometastases from human prostate cancer for evaluating antitumor agents. METHODS: PC-3 cells, an androgen-independent prostate cancer cell line, were inoculated into the chorioallantoic membrane vein of 10-day-old chick embryos (10(6) cells/egg). The polymerase chain reaction product for the human beta-globin gene in chick embryo femur and liver was quantified at various time points after inoculation, when immunohistochemical staining was done for Ki-67 antigen and cytokeratin. The antitumor effect of suramin was evaluated using the model, as was regional blood flow after thallium injection. RESULTS: Micrometastases were identified in bone and liver 1 day after inoculation and grew to form established metastatic foci in all embryos. Suramin showed significant antitumor effect for liver metastases, but not for those in bone where blood flow was relatively low. CONCLUSION: The chick embryo system provides a highly reproducible model for bone and liver micrometastases from human prostate cancer, suitable for evaluating antineoplastic agents at an early stage of the metastatic process.

Animals↗

Twist form of teleocidin derivatives is active in in vivo tumor promotion by (-)-benzolactam-V8-310.

Teleocidin derivatives and the core structure, (-)-indolactam-V ((-)-IL-V), adopt two conformations in solution, the "twist" and the "sofa" forms. (-)-Benzolactam-V8-310 ((-)-BL-V8-310), which specifically adopts the twist form in solution, has been reported to have a significant effect on HL-60 cells and protein kinase C affinity. In this paper, we describe the biological activity with regard to tumor promotion on mouse skin and the wide variety of biological activity of (-)-BL-V8-310 and its derivatives. In both twist and sofa forms (-)-BL-V8-310 inhibited specific 3H-12-O-tetradecanoylphorbol-13-acetate (TPA) binding to a particulate fraction of mouse skin more strongly than (-)-IL-V. The doses for 50% inhibition (IC50) of (-)-IL-V, (-)-BL-V8-310, and teleocidin B-4 were 1000, 400 and 12 nM, respectively. As for the induction of tumor necrosis factor-alpha (TNF-alpha) release into the medium from HL-60 cells, the EC200 values, which are the concentrations of the compound required to achieve 200 pg/ml TNF-alpha in the medium, were 1700, 500 and 19 nM for (-)-IL-V, (-)-BL-V8-310 and teleocidin B-4, respectively. The same amounts (5.5 nmol per application) of (-)-BL-V8-310 and teleocidin B-4, induced tumors on mouse skin initiated with 7,12-dimethylbenz(a)anthracene (DMBA) in 13.3% and 86.7% of tumor-bearing mice, respectively, in week 20. These results confirmed that the twist form of teleocidin derivatives is the active form as far as the induction of biological activity is concerned. Also (-)-BL-V8-310 is a new synthetic tumor promoter designed from data obtained using the receptor cavity model of TPA-type tumor promoters.

Animals↗

[A method for the assay of histidine decarboxylase activity].

The histamine-forming enzyme histidine decarboxylase (HDC) is induced in various tissues of mice in response to various physiological or inflammatory stimuli including stress, physical exercise, proinflammatory cytokines and hematopoietic cytokines. The induction of HDC also occurs in mast cell-deficient mice. The newly formed histamine produced through the induction of HDC diffuses away from its site of formation without being stored. Therefore, in addition to the release of histamine from mast cells or basophils, the induction of HDC is an important alternative mechanism for supplying histamine. Studies on the newly formed histamine may clarify new physiological or pathological roles of histamine. Here, we introduce a method that we devised for the simultaneous assay of HDC activity of many samples taken from mice. This method is based on (i) a simple method for the preparation of histamine-free enzyme solutions and (ii) a simple manual method for the separation of histamine formed in reaction mixtures containing HDC.

Animals↗

Effect of interleukin-12 and interleukin-10 on the virus replication and apoptosis in T-cells infected with feline immunodeficiency virus.

Interleukin-12 (IL-12) is an important cytokine for Th1 response which stimulates the T-cell population to produce cytokines for cellular immunity. Interleukin-10 (IL-10) is a pleiotropic cytokine capable of suppressing cytokine production from macrophages and T-cells and participants in Th2 immune response. The present study was carried out to examine the effect of these cytokines on virus replication and apoptosis in T-cells infected with feline immunodeficiency virus (FIV). Infection of a feline T-lymphoid cell line (Fel-039) resulted in an increase of the reverse transcriptase (RT) activity in the culture supernatant accompanied by cell death from apoptosis. Addition of human recombinant IL-12 significantly inhibited the virus replication and apoptosis in Fel-039 cells in a dose dependent manner. Furthermore, the antiviral activity of IL-12 was associated with the expression of IFN-gamma in the FIV-infected Fel-039 cells. In contrast, human recombinant IL-10 did not show any inhibitory effect on the virus replication and apoptosis in the Fel-039 cells infected with FIV. These results suggest that the inhibitory effect of IL-12 on both virus replication and apoptosis has potential implications for the design of immunotherapy strategies using IL-12 in FIV infection.

Adjuvants, Immunologic↗

A novel cell-free system for peptide synthesis driven by pyridine.

Previously we demonstrated that ribosomes can synthesize polypeptides in the presence of high concentrations (40-60%) of pyridine without any protein factors. Here we analyze additional ribosomal parameters in 60% pyridine using Escherichia coli ribosomes. Ribosomal subunits once exposed to pyridine failed to re-associate to 70S ribosomes in aqueous buffer systems even in the presence of 20 mM Mg2+, whereas they formed 70S complexes in the presence of 60% pyridine. Two-dimensional gel electrophoresis of ribosomal proteins revealed that some proteins located at the protuberances of the large subunit, e. g. L7/L12 and L11 forming the elongation factor-binding domain, were released in the pyridine system. The aminoglycoside neomycin, a strong inhibitor of the ribosomal (factor-independent) translocation reaction, completely blocked poly(Phe) synthesis and translocation activities in the pyridine system, whereas these activities were not affected at all by gypsophilin, a ribotoxin that inhibits factor-dependent translocation. Another inhibitor of the ribosomal translocation, thiostrepton, had no effect concerning the two activities, which is consistent with the fact that this antibiotic requires L11 for its binding to the ribosome. These results suggest that the ribosomes can perform a translocation reaction in the pyridine system, but in a factor-independent (spontaneous) manner.

Cell-Free System↗

Localization of cytoplasmic free calcium ions in PC12 cells with varicose fibers.

Differentiated PC12 cells with varicose fibers were used as a model of sympathetic neurons to demonstrate the intracellular localization of cytoplasmic free calcium ions. Changes in the concentration of cytoplasmic free calcium ions were analyzed at individual varicosities upon stimulation with acetylcholine by laser scanning confocal microscopy. Transient increases in cytoplasmic free calcium ion concentration were localized in the varicosities and recognized in both the absence and presence of extracellular Ca2+. Immunocytochemical analysis of intracellular calcium channels, 1, 4, 5-trisphosphate receptors and ryanodine receptors, by electron microscopy demonstrated that immunoreactive sites were mainly localized in large dense core vesicles in the varicosities and neurites. These results suggest that the exocytosis of large dense core vesicles is regulated by an increase in cytoplasmic free calcium ion concentration from an intracellular Ca2+ store.

Acetylcholine↗

Autopsy findings in a long-term survivor with glioblastoma multiforme--case report.

Autopsy detected no tumor tissues in a patient who died 6.5 years after the diagnosis of glioblastoma multiforme. A 54-year-old male developed left hemiparesis one month prior to admission. Computed tomography demonstrated a cystic lesion in the right frontal region with irregular ring-like enhancement. The tumor was extensively removed together with the surrounding tissue followed by irradiation (whole brain 32.4 Gy, local 28.8 Gy), and intravenous administration of interferon-beta. Histological examination confirmed the diagnosis of glioblastoma multiforme. He died of accidental head trauma 6.5 years after surgery. Autopsy of the brain detected no evidence of glioblastoma multiforme. The only findings were cerebral edema and hematoma caused by head trauma, as well as histological changes due to radiation damage. This case apparently confirms the histological disappearance of tumor tissue in a long-term survivor with glioblastoma multiforme.

Brain Neoplasms↗