The Effects of Some Autonomic Drugs on the Elevated Intraocular Tension of the Rabbit were Investigated. 1) Intravenous or local administration of Acetylcholine isoproterenol, a small dose of epinephrine and local large dose of epinephrine shortened the recovery time of the elevated. intraocular tension of normal level. 2) Intravenous or local administration of norepinephrine and intravenous large dose of epinephrine lengthened the recovery time. 3) A small dose of intravenous dimethylphenylpiperazinium shortened the recovery time, while large dose of the former lengthened the latter. 4) Intravenous hexamethonium, Bretylium, regitine, and small dose of atropine lengthened it From the above results, it is suggested that there are cholinergic, adrenergic alpha and beta receptor in the regulatory organs of the intraocular tension and autonomic nervous system plays an important role in regulating the intraocular tension.
Acetylcholine ; Atropine ; Autonomic Agents* ; Autonomic Nervous System ; Dimethylphenylpiperazinium Iodide ; Epinephrine ; Hexamethonium ; Isoproterenol ; Norepinephrine ; Phentolamine

A case of cerebral paragonimiasis associated with right homonymous hemianopsia was reported in view of its rarity and a review of the related literaturs was made. The patient was 14 years old man. He had been suffering from poor visual acuity for 2 months and headache for 7 years. He had hsitory of indigestation of crayfish during measle infection. Skull x-ray revealed calcification on temporo-occipital region. He had been treated with bithionol, daily doses of 20mg/kg of body wt. for 70 days. And the rsult was improvement.
Adolescent ; Astacoidea ; Bithionol ; Headache ; Hemianopsia* ; Humans ; Paragonimiasis* ; Skull ; Visual Acuity

MDR1 promoter has been shown to contain heat shock elements (HSE), and it has been reported that FM3A/M and P388/M MDR cells show a constitutively activated heat shock factor (HSF), suggesting that HSF might be an important target for reversing the multidrug resistance. Therefore, it was examined whether quercetin, which has been shown to interfere with the formation of the complex between HSE and HSF, and to downregulate the level of HSF1, can sensitize MDR cells against anticancer drugs by inhibition of HSF DNA-binding activity. In this study, quercetin appeared to inhibit the constitutive HSF DNA-binding activity and the sodium arsenite-induced HSF DNA-binding activity in the MDR cells. The basal and sodium arsenite-induced MDRCAT activities were remarkably suppressed by the treatment of quercetin. These results were well consistent with the finding that the treatment of quercetin decreased the expression level of P-gp, MDR1 gene product, in dose-dependent manner, and markedly increased the sensitivity of MDR cells to vincristine or vinblastine. These results suggest that quercetin can decrease the expression of P-gp via inhibition of HSF DNA-binding activity, and might be useful as a chemosensitizer in MDR cells.
Animal ; Antineoplastic Agents/pharmacology ; Arsenites/pharmacology ; Carcinoma/drug therapy ; Drug Resistance, Multiple/physiology* ; Drug Resistance, Neoplasm/physiology ; Heat-Shock Proteins/metabolism ; Heat-Shock Proteins/drug effects* ; Heat-Shock Proteins/antagonists & inhibitors ; Leukemia, Experimental/drug therapy ; Mice ; P-Glycoprotein/genetics ; P-Glycoprotein/drug effects ; Quercetin/pharmacology* ; Sodium Compounds/pharmacology ; Tumor Cells, Cultured ; Vinblastine/pharmacology ; Vincristine/pharmacology

The chronic myelogenous leukemic K562 cell line carrying Bcr-Abl tyrosine kinase is considered as pluripotent hematopoietic progenitor cells expressing markers for erythroid, granulocytic, monocytic, and megakaryocytic lineages. Here we investigated the signaling modulations required for induction of erythroid differentiation of K562 cells. When the K562 cells were treated with herbimycin A (an inhibitor of protein tyrosine kinase), ras antisense oligonucleotide, and PD98059 (a specific inhibitor of MEK), inhibition of ERK/MAPK activity and cell growth, and induction of erythroid differentiation were observed. The ras mutant, pZIPRas61leu-transfected cells, K562-Ras61leu, have shown a markedly decreased cell proliferation rate with approximately 2-fold doubling time, compared with the parental K562 cells, and about 60% of these cells have shown the phenotype of erythroid differentiation. In addition, herbimycin A inhibited the growth rate and increased the erythroid differentiation, but did not affect the elevated activity of ERK/MAPK in the K562-Ras61leu cells. On the other hand, effects of PD98059 on the growth and differentiation of K562-Ras61leu cells were biphasic. At low concentration of PD98059, which inhibited the elevated activity of ERK/MAPK to the level of parental cells, the growth rate increased and the erythroid differentiation decreased slightly, and at high concentration of PD98059, which inhibited the elevated activity of ERK/MAPK below that of the parental cells, the growth rate turned down and the erythroid differentiation was restored to the untreated control level. Taken together, these results suggest that an appropriate activity of ERK/MAPK is required to maintain the rapid growth and transformed phenotype of K562 cells.
Androstadienes/pharmacology ; Ca(2+)-Calmodulin Dependent Protein Kinase ; Cell Differentiation/drug effects ; Enzyme Inhibitors/pharmacology ; Erythroid Progenitor Cells/physiology* ; Erythroid Progenitor Cells/cytology ; Erythropoiesis* ; Flavones/pharmacology ; Human ; K562 Cells ; Leukemia, Myeloid/pathology ; Oligonucleotides, Antisense/pharmacology ; Quinones/pharmacology ; ras Proteins/metabolism*

This paper describes a student-centered case study program concerning the tumor pathology course for first year students in medical school under the traditional curricular structure. A traditional, discipline-oriented, lecture-laboratory approach was partly modified by introducing a tutuorial session using a modified case matrix format during the laboratory hours without altering the general scheme of the existing system. Small group tutorial sessions were set with the development of learning objectives emphasizing clinicopathologic reasoning and early exposure to future practical presentation which was followed by the large class session; each tutorial was supplied with a short clinical history, gross kodachrome slides, and microslides. The session for problem identification was replaced by proving a series of instructor-designed questions for both pathology and interdisciplinary correlation during which pedagogical implication was stressed the most. Student's active participation, development of self learning skill and vigorous teaching-learning process among students, and motivation/relevance for forthcoming pathology study were among the benefits conferred by this modification. We conclude that this approach is an interim step to meet the advantages of problem-based learning even in a traditional curricular structure.

Tumor hypoxia contributes to the progression of a malignant phenotype and resistance to ionizing radiation and anticancer drug therapy. Many of these effects in hypoxic tumor cells are mediated by expression of specific set of genes whose relation to therapy resistance is poorly understood. In this study, we revealed that DNA-dependent protein kinase (DNA-PK), which plays a crucial role in DNA double strand break repair, would be involved in regulation of hypoxia inducible factor-1 (HIF-1). HIF-1beta-deficient cells showed constitutively reduced expression and DNA-binding activity of Ku, the regulatory subunit of DNA-PK. Under hypoxic condition, the expression and activity of DNA- PK were markedly induced with a concurrent increase in HIF-1alpha expression. Our result also demonstrated that DNA-PK could directly interact with HIF- and especially DNA-PKcs, the catalytic subunit of DNA-PK, could be involved in phosphorylation of HIF-1alpha, suggesting the possibility that the enhanced expression of DNA- PK under hypoxic condition might attribute to modulate HIF-1alpha stabilization. Thus, the correlated regulation of DNA-PK with HIF-1 could contribute to therapy resistance in hypoxic tumor cells, and it provides new evidence for developing therapeutic strategies enhancing the efficacy of cancer therapy in hypoxic tumor cells.
Antibodies/immunology ; Cell Hypoxia ; Cell Line, Tumor ; DNA Helicases/immunology/metabolism ; DNA-Binding Proteins/genetics/*metabolism/*physiology ; Deferoxamine/pharmacology ; Drug Resistance, Neoplasm/*physiology ; Humans ; Immunoprecipitation ; Neoplasms/enzymology/*metabolism ; Nuclear Proteins/genetics/*metabolism/physiology ; Phosphorylation ; Protein-Serine-Threonine Kinases/metabolism/*physiology ; Research Support, Non-U.S. Gov't ; Transcription Factors/genetics/*metabolism/physiology ; Up-Regulation

In this study, we have investigated if current cancer therapeutic modalities including hyperthermia and ionizing radiation can increase the expression of NKG2D ligands in human cancer cell lines. The expressions of NKG2D ligands were induced by both heat shock and ionizing radiation in various cell lines including KM12, NCI-H23, HeLa and A375 cells with peaks at 2 h and 9 h after treatment, respectively, although inducibility of each NKG2D ligand was various depending on cell lines. During the induction of NKG2D ligands, heat shock protein 70 was induced by heat shock but not by ionizing radiation. These results were followed by increased susceptibilities to NK cell-mediated cytolysis after treatment with heat shock and ionizing radiation. These results suggest that heat shock and ionizing radiation induce NKG2D ligands and consequently might lead to increased NK cell-mediated cytotoxicity in various cancer cells.
Tumor Cells, Cultured ; Receptors, Immunologic/*metabolism ; Radiation, Ionizing ; Neoplasms/immunology/*radiotherapy/therapy ; *Ligands ; Killer Cells, Natural/*immunology ; Hyperthermia, Induced/methods ; Humans ; Hela Cells ; *Heat-Shock Response/physiology ; Heat ; HSP70 Heat-Shock Proteins/metabolism/radiation effects ; Gene Expression Regulation, Neoplastic/radiation effects ; Cytotoxicity, Immunologic/*physiology/*radiation effects ; Antigens, Surface/metabolism/radiation effects

Here we determined which radiation-responsive genes were altered in radioresistant CEM/IR and FM3A/IR variants, which showed higher resistance to irradiation than parental human leukemia CEM and mouse mammary carcinoma FM3A cells, respectively and studied if radioresistance observed after radiotherapy could be restored by inhibition of protein kinase A. The expressions of DNA-PKcs, Ku70/80, Rad51 and Rad54 genes that related to DNA damage repair, and Bcl-2 and NF-kappaB genes that related to antiapoptosis, were up-regulated, but the expression of proapototic Bax gene was down-regulated in the radioresistant cells as compared to each parental counterpart. We also revealed that the combined treatment of radiation and the inhibitor of protein kinase A (PKA) to these radioresistant cells resulted in synergistic inhibition of DNA-PK, Rad51 and Bcl-2 expressions of the cells, and consequently restored radiosensitivity of the cells. Our results propose that combined treatment with radiotherapy and PKA inhibitor can be a novel therapeutic strategy to radioresistant cancers.
Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Cyclic AMP-Dependent Protein Kinases/*antagonists & inhibitors/metabolism ; DNA Damage/drug effects ; DNA Repair/drug effects ; Gamma Rays ; Gene Expression Regulation, Neoplastic/radiation effects ; Genes, bcl-2 ; Humans ; Mice ; Neoplasm Proteins/genetics/metabolism ; Neoplasms/enzymology/*genetics ; Radiation Tolerance/*genetics ; Research Support, Non-U.S. Gov't

This paper describes a student-centered case study program concerning the tumor pathology course for first year students in medical school under the traditional curricular structure. A traditional, discipline-oriented, lecture-laboratory approach was partly modified by introducing a tutuorial session using a modified case matrix format during the laboratory hours without altering the general scheme of the existing system. Small group tutorial sessions were set with the development of learning objectives emphasizing clinicopathologic reasoning and early exposure to future practical presentation which was followed by the large class session; each tutorial was supplied with a short clinical history, gross kodachrome slides, and microslides. The session for problem identification was replaced by proving a series of instructor-designed questions for both pathology and interdisciplinary correlation during which pedagogical implication was stressed the most. Student's active participation, development of self learning skill and vigorous teaching-learning process among students, and motivation/relevance for forthcoming pathology study were among the benefits conferred by this modification. We conclude that this approach is an interim step to meet the advantages of problem-based learning even in a traditional curricular structure.
Humans ; Learning ; Pathology* ; Problem-Based Learning* ; Schools, Medical