No abstract available.
Angiogenesis Inducing Agents*

The effect of Roentgen rays on carcinoma of the cervix has long been of great interest to both radiologists and gynecologists. Since most cervical carcinomas are treated by irradiation, any additional knowledge either concerning the radiosensitivity of cervical tumors or their ultimate prognosis would be of value. The vaginal smear is considered to be one of convenient and rapid methods to study the effects of radiation on cervical malignancy. We observed morphologic changes in 297 cytologic preparations obtained from 60 patients who had underwent irradiation for cancer of the cervix. With the morphologic parameters such as cytoplasmic vacuolization, cytoplasmic basophilia, multinucleated giant cell formation, polymorphonuclear leucocytes (PMNL) sticking and postradiation dysplasia, we analyzed the findings in relation to the follow up time interval. The most common effect was the cytoplasmic vacuolization with basophilia of basaloid cells, which were noted in more than 90% of followed patients. The multinucleated giant cell formation and PMNL stickering were noted in 38 cases(63%) and 48 cases(80% ) respectively. The differential diagnosis of postradiation dysplasia from recurrent or persistent carcinoma, reparative atypical cells, and regressing tumor cells was difficult and further study seems to be needed to clarify the more accurate morphologic features and biologic behavior.
Cervix Uteri ; Cytoplasm ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Giant Cells ; Humans ; Pancreas ; Prognosis ; Radiation Tolerance ; Regeneration* ; Uterine Cervical Neoplasms ; Vaginal Smears

The purpose of the present study was to define the normal range of plasma concentration of angiotensin I-converting enzyme(ACE), N-acetyl-b-D-glucosaminidase(NAG), inactive and active renin, and atrial natriuretic peptide(ANP) in normal Korean adult male in terms of aging. Both plasma ACE activity and NAG concentration were measured by spectrofluorometry, and the plasma renin activity and ANP concentration were measured using radioimmunoassay. The ACE was 67.7+-3.6 nM His-Leu/min/ml and did not change in terms of age. The plasma NAG activity tended to decrease. Both plasma active and inactive renin activities were 2.1+-0.2 and 3.0+-0.3 ngAI/ml/h and tended to decrease in terms of aging. The percentage of inactive renin to total renin was 57.2+-2.9% at age 21-30 and also tended to decrease in terms of aging. Plasma ANP concentration at age 22 was 59.6+-2.9 pg/ml.
Adult ; Aging ; Angiotensins ; Atrial Natriuretic Factor ; Humans ; Male ; Plasma ; Radioimmunoassay ; Reference Values ; Renin ; Spectrometry, Fluorescence

To evaluate the association between ACE gene I/D polymorphism and ecNOS gene a/b polymorphism in IgA nephropathy, 158 IgA nephropathy patients and 121 control subjects were examined. In genotype distribution of the ACE gene I/D polymorphism, there was no significant difference in genotype distribution between controls and IgA nephropathy patients. We also examined the association between ACE genotype and clinical characteristics in the patients with IgA nephropathy. The incidence of hypertension in patients with DD genotype was higher than that of other genotypes. There were no significant association between I/D polymorphism distribution and chronic renal failure, nephrotic range proteinuria, and glomerular sclerosis in IgA nephropathy. In genotype distribution of ecNOS gene a/b polymorphism, there was no significant difference between IgA nephropathy patients and controls. There was no significant difference in frequency of chronic renal failure, hypertension, nephrotic range proteinuria and glomerular sclerosis among ecNOS genotypes. In addition, we failed to detect any significant association between the ACE and ecNOS gene-polymorphis ms and the decline of renal function in IgA nephropathy. A further study with larger number of patient population would be necessary.
Angiotensins* ; Genotype ; Glomerulonephritis, IGA* ; Humans ; Hypertension ; Immunoglobulin A* ; Incidence ; Kidney Failure, Chronic ; Nitric Oxide Synthase Type III* ; Peptidyl-Dipeptidase A* ; Proteinuria ; Sclerosis

BACKGROUND AND OBJECTIVES: Transforming growth factor-beta1 (TGF-beta1) plays an important role on cardiac muscle differentiation, cardiac septa and valve formation during heart development. However, the role of TGF-beta1 in cardiac valves of adult animals is largely unknown. Cardiac valves are target portion from repetitive, periodic and continuous physical loading in the body. Therefore, we examined the mRNA, protein levels, and protein distribution of TGF-beta1 in cardiac valves of adult animals to clarify the biological importance of TGF-beta1. MATERIALS AND METHODS: Adult mice, rats and pigs were used. Cardiac valves of pig were frozen and were pulverized with liquid nitrogen. To measure the mRNA levels of TGF-beta1 in cardiac valves, total RNA was extracted using Tri-reagent and performed Northern blot analysis. To measure the protein levels of TGF-beta1 in cardiac valves, total protein was extracted and performed Western blot analysis. To examine the TGF-beta1 distribution, immuno-histochemistry with anti-CC-1-30 antibody was performed. RESULTS: The mRNA level of TGF-beta1 in pulmonary valve was higher than those in the other valves. However, the protein levels of TGF-beta1 were similar among valves. The mRNA and protein levels of TGF-beta1 in cardiac valves were higher than those in atria or ventricles. The TGF-beta1 protein was located mainly in cellular interstitium in cardiac valves. The distribution of TGF-beta1 protein in surface area was higher than in the mid-portion of valves. CONCLUSION: These results suggest that synthesis and distribution of TGF-beta1 in cardiac interstitum is essential for maintaining of normal structure and function on various physical loading.
Adult ; Animals ; Blotting, Northern ; Blotting, Western ; Heart ; Heart Valves* ; Humans ; Mice ; Myocardium ; Nitrogen ; Pulmonary Valve ; Rats ; RNA ; RNA, Messenger ; Swine ; Transforming Growth Factor beta1*

BACKGROUND AND OBJECTIVES: In our previous study, we found that the gene transfer of a potent derivative of cartilage oligomeric matrix protein Angiopoietin-1 (COMP-Ang-1) substantially prevented hypertension, microvascular rarefaction, and target organ damage in spontaneously hypertensive rats (SHRs). The purpose of the present study was to examine the role of nitric oxide (NO) in the therapeutic effects observed after COMP-Ang-1 gene transfer. MATERIALS AND METHODS: To exclude the NO-mediated effects in COMP-Ang-1 gene therapy, the SHRs were treated with an NO synthase (NOS) inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) before the electrophoretic gene transfer. RESULTS: The pretreatment with L-NAME induced a severe and sustained increase in systolic blood pressure (BP) in a LacZ plasmid transferred control SHR. However, the electrophoretic transfer of a COMP-Ang-1 plasmid instead of LacZ plasmid in L-NAME-pretreated SHRs substantially blocked the development of hypertension without any significant difference in comparison with L-NAME-untreated COMP-Ang-1 plasmid transferred groups. In addition, the COMP-Ang-1 plasmid transfer substantially attenuated microvascular rarefaction and arteriole remodeling in the heart and kidney, which might account for the mild histological alterations observed in the COMP-Ang-1 plasmid transferred group, in contrast to the severe fibrosis and necrosis seen in the LacZ plasmid controls. CONCLUSION: These therapeutic outcomes of COMP-Ang-1 gene transfer even in NOS inhibited SHRs suggested that the antihypertensive effect of COMP-Ang-1 was not merely secondary to NO-mediated vasorelaxation, but it may be associated with its ability to protect the vascular endothelium probably via an NO-independent mechanism which serves to attenuate microvascular rarefaction and target organ damage, and also to prevent hypertension by reducing peripheral vascular resistance.
Angiopoietin-1 ; Arterioles ; Blood Pressure ; Cartilage ; Endothelium ; Endothelium, Vascular ; Extracellular Matrix Proteins ; Fibrosis ; Genetic Therapy ; Glycoproteins ; Heart ; Hypertension ; Kidney ; Necrosis ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Plasmids ; Rats, Inbred SHR ; Vascular Resistance ; Vasodilation

OBJECTIVES: The molecular mechanisms that regulate cardiomyocyte cell cycle and terminal differentiation in humans remain largely unknown. To determine which cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) are important for cardiomyocyte proliferation, we have examined protein levels of cyclins, CDKs and CKIs during normal atrial development in humans. METHODS: Atrial tissues were obtained in the fetus from inevitable abortion and in the adult during surgery. Cyclin and CDK proteins were determined by Western blot analysis. CDK activities were determined by phosphorylation amount using specific substrate. RESULTS: Most cyclins and CDKs were high during the fetal period and their levels decreased at different rates during the adult period. While the protein levels of cyclin D1, cyclin D3, CDK4, CDK6 and CDK2 were still detectable in adult atria, the protein levels of cyclin E, cyclin A, cyclin B, cdc2 and PCNA were not detectable. Interestingly, p27KIP1 protein increased markedly in the adult period, while p21CIP1 protein in atria was detectable only in the fetal period. While the activities of CDK6, CDK2 and cdc2 decreased markedly, the activity of CDK4 did not change from the fetal period to the adult period. CONCLUSION: These findings indicate that marked reduction of protein levels and activities of cyclins and CDKs, and marked induction of p27KIP1 in atria, are associated with the withdrawal of cardiac cell cycle in adult humans.
Adult ; Age Factors ; Animal ; Blotting, Western ; Cell Cycle ; Cells, Cultured ; Comparative Study ; Cyclin A/analysis ; Cyclin B/analysis ; Cyclin D1/analysis ; Cyclin E/analysis ; Cyclin-Dependent Kinases/analysis* ; Cyclins/analysis* ; Female ; Fetal Development ; Heart Atrium/growth & development* ; Heart Atrium/embryology ; Heart Atrium/cytology* ; Heart Atrium/chemistry ; Human ; Male ; Middle Age ; Myocardium/chemistry* ; Rats ; Rats, Sprague-Dawley ; Substances: Cyclin D1 ; Substances: Cyclins ; Substances: Cyclin-Dependent Kinases ; Substances: Cyclin E ; Substances: Cyclin B ; Substances: Cyclin A

BACKGROUND: Angiogenesis is crucial for wound healing and exogenous supplements of the angiogenic growth factors have been known to promote cutaneous wound healing. Angiopoietin (Ang) 1 is a recently discovered angiogenic factor and there have been few studies of its effect on cutaneous wound healing. OBJECTIVE: We examined the effect of Ang 1 on cutaneous wound healing. METHODS: Cartilage oligomeric matrix protein (COMP)-Ang 1 (Ade-COMP-Ang 1)- was intravenously injected to rats two days before surgery creating full-thickness wounds. The clinical wound healing rate and the number of vessels in the skin samples were evaluated on days 3, 7 and 14 post operation. RESULTS: At post-operation day 3, 7 and 14, the clinical wound healing rate was 38.3%, 59.4% and 92.1%, respectively, in the Ade-COMP-Ang 1-treated group, compared with 20.5%, 47.5% and 87.3%, respectively, in the Ade-LacZ-treated group. There were significant differences in the results of day 3 and day 7 between two groups (p<0.05). Histopathologically, the number of the vessels of the Ade-COMP-Ang 1-treated group was 73.7, 94.1 and 62.7 at day 3, 7 and 14, compared with that of the Ade-LacZ-treated group, 53.5, 83.9, and 56.9. The differences in the results of the two groups were statistically significant (p<0.05). CONCLUSION: These results indicate that Ade-COMP-Ang 1 therapy significantly accelerats wound healing by promoting angiogenesis. However, further study using Ade-COMP-Ang 1 gene therapy for chronic wounds in which the formation of new blood vessels is impaired is needed in the near future.
Angiogenesis Inducing Agents ; Animals ; Blood Vessels ; Cartilage ; Extracellular Matrix Proteins ; Genetic Therapy ; Glycoproteins ; Intercellular Signaling Peptides and Proteins ; Rats ; Skin ; Wound Healing

Angiotensin converting enzyme gene insertion/ deletion polymorphism has been shown to be associated with cardiovascular disease including cardiomyopathy, myocardial infarction, essential hypertension, progression of IgA nephropathy and diabetic nephropathy. Since glomerulosclerosis has similarities to atherosclerosis, angiotensin converting enzyme gene polymorphism may be associated with glomerulsclerosis. Therefore, we tested whether genotype distribution of the insertion/deletion polymorphism in angiotensin converting enzyme gene is different in patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis. In genotype distribution of the angiotensin converting enzyme gene I/D polymorphism, control subjects were II type 44.3%, ID type 40.9%, DD type 14.8% and patients with minimal change nephrotic syndrome were II type 38.2%, ID type 45.5%, DD type 16.3% and patients with focal segmental glomerulosclerosis were II type 13.3%, ID type 46.7%, DD type 40.0%. This result suggests that DD genotype was more frequent in patients with focal segmental glomerulosclerosis than minimal change nephrotic syndrome and control subjects. We also examined the association between ACE genotype and clinical characteristics in the patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis. There were no significant association between I/D polymorphism distribution and hypertension, chronic renal failure, response to steroid in patients with minimal change nephrotic syndrome. The incidence of chronic renal failure in patients with focal segmental glomerulosclerosis DD genotype was higher than that of other genotypes. The response rate to steroid in patients with focal segmental glomerulosclerosis DD genotype was lower than that of other genotypes.
Angiotensins* ; Atherosclerosis ; Cardiomyopathies ; Cardiovascular Diseases ; Diabetic Nephropathies ; Genotype ; Glomerulonephritis, IGA ; Glomerulosclerosis, Focal Segmental* ; Humans ; Hypertension ; Incidence ; Kidney Failure, Chronic ; Myocardial Infarction ; Nephrosis, Lipoid* ; Nephrotic Syndrome ; Peptidyl-Dipeptidase A*

Until recently, vascular endothelial growth factor (VEGF) was the only growth factor proven to be specific and critical for blood vessel formation. Other long-known factors, such as the fibroblast growth factors (FGFs), platelet-derived growth factor, or transforming growth factor-beta, had profound effects in endothelial cells. But such factors were nonspecific, in that they could act on many other cells, and it seemed unlikely that these growth factors would be effective targets for treatment of endothelial cell diseases. A recently discovered endothelial cell specific growth factor, angiopoietin, has greatly contributed to our understanding of the development, physiology, and pathology of endothelial cells (Davis et al., 1996; Yancopoulos et al., 2000). The recent studies that identified and characterized the physiological and pathological roles of angiopoietin have allowed us to widen and deepen our knowledge about blood vessel formation and vascular endothelial function. Therefore, in this review, we describe the biomedical significance of these endothelial cell growth factors, the angiopoietins, in the vascular system under normal and pathological states.
Alternative Splicing ; Angiogenesis Factor/genetics/*metabolism ; Animal ; Cell Survival ; Endothelial Growth Factors/metabolism ; Endothelium, Vascular/cytology/*physiology ; Hematopoiesis/physiology ; Human ; Intercellular Signaling Peptides and Proteins/metabolism ; Lymphokines/metabolism ; Membrane Glycoproteins/genetics/*metabolism ; Neoplasm Proteins/metabolism ; Neovascularization, Pathologic ; Neovascularization, Physiologic ; Signal Transduction/physiology ; Urogenital System/physiology