Balancing the rates of cell proliferation and cell death is important in maintaining normal tissue homeostasis. The relationship among apoptosis, cell proliferation and factors influencing apoptosis according to the histologic types in chemically induced mammary tumorigenesis appears important in understanding the pathogenesis of breast carcinoma. In this study, we investigated alterations in the kinetics of cell proliferation and apoptosis during rat mammary tumorigenesis induced by 7, 12-dimethylbenzanthracene (DMBA) and we related these changes to the expressions of bcl-2, p53, and TGF-beta. Seven-week-old female Sprague-Dawley rats were divided into an experimental group (20 mg/ml DMBA by oral intubation) and a control group. The results were as follows. 1. In the experimental group, breast tumors occurred in twenty two of fifty nine rats(37.3%, 22/59), and the total number of tumors was 100 (4.5 2.0/rat). The histological classification was infiltrating ductal carcinomas (n=5), ductal carcinomas with focal invasion (n=10), intraductal carcinomas (n=36), adenomas accompanied with intraductal proliferation (n=35), intraductal proliferation (n=9), and adenomas (n=5); 2. The differentiation of terminal end bud into alveolar bud (AB) in the experimental group was significantly lower than that of the control group (p<0.05); 3. BrdU labeled tumor cells were mainly located at the peripheral portion of tumor cell nests. BrdU labeling indices were highest in ductal carcinomas, less pronounced in intraductal proliferation, and lowest in adenomas, whereas apoptosis levels were highest in adenomas, less pronounced in intraductal proliferation, and lowest in ductal carcinomas (p<0.05); 4. p53 protein was not expressed in any breast tumors. Although the expression of bcl-2 protein was highest in infiltrating and focal infiltrative ductal carcinomas (58.3%), compared with adenomas, intraductal proliferation, and intraductal carcinomas (p<0.05), the extent of its expression was less than 1% of all tumor cells; 5. TGF-beta was mainly expressed in the central portion of tumor cell nests rather than in peripheral portion, and TGF-beta immunoreactive tumor cells displayed good differentiation and did not reveal BrdU immunoreactivity. TGF-beta labeling index of infiltrating and focal infiltrative ductal carcinomas was significantly higher than that of intraductal carcinomas, intraductal proliferation, and adenomas (p<0.05). Based on these results, it is thought that high cell proliferation and the suppression of apoptosis are closely associated with DMBA-induced rat mammary carcinogenesis. However, the suppression of apoptosis is not related to p53 mutation, bcl-2, and TGF-beta. TGF-beta seems to be reversely related to tumor cell proliferation but closely associated with the progression of the tumor, especially an invasion of breast carcinomas.
9,10-Dimethyl-1,2-benzanthracene ; Adenoma ; Animals ; Apoptosis* ; Breast Neoplasms ; Bromodeoxyuridine ; Carcinogenesis* ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Cell Death ; Cell Proliferation* ; Classification ; Female ; Homeostasis ; Humans ; Kinetics ; Rats* ; Rats, Sprague-Dawley ; Transforming Growth Factor beta

Among the enzymes which are responsible for basement membrane breakdown, matrix metalloproteinases (MMP) form a family of neutral proteases that are regulated at the levels of gene transcription, proenzyme activation by the cleavage of protein, and the inhibition of the active enzyme by tissue inhibitors of matrix metalloproteinases (TIMP). Recent reports have demonstrated that the expression of these proteolytic enzymes are elevated in several solid tumors and that it can be associated with invasiveness and poor prognosis. We examined the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemistry in 160 cases of infiltrating ductal carcinoma. And we compared these data with the established prognostic parameters - tumor size, nodal status, clinical stage, hormonal receptor status, microvessel density, and TGF-beta1 expression in order to evaluate how MMP and TIMP expression are associated with breast cancer progression and prognosis. Microvessel density in invasive breast carcinoma was significantly correlated with tumor size and recurrence (p<0.05). The immunohistochemical expression of TGF-beta1 was significantly associated with tumor size, lymph node metastasis, and clinical stage (p<0.05). The microvessel density was significantly correlated with TGF-beta1 expression in more than 50% of tumor cells. The immunohistochemical expression of MMP-2 and MMP-9 were significantly correlated with nodal metastasis and absence of immunoreactivity for estrogen and progesterone receptors. The immunohistochemical expression of TIMP-1 was inversely correlated with clinical stage and microvessel density while that of TIMP-2 was inversely correlated with clinical stage (p<0.05). Small size of tumor, presence of progesterone receptor, highly differentiated histologic grade, and absence of immunoreactivity for MMP-9 were significantly associated with higher survival rate, but in multivariate analysis only tumor size and MMP-9 expression appeared to affect survival independently.
Basement Membrane ; Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Estrogens ; Humans ; Immunohistochemistry ; Lymph Nodes ; Matrix Metalloproteinases ; Microvessels ; Multivariate Analysis ; Neoplasm Metastasis ; Peptide Hydrolases ; Prognosis ; Receptors, Progesterone ; Recurrence ; Survival Rate ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2 ; Transforming Growth Factor beta1

Both spindle cell variant of squamous cell carcinoma and atypical fibroxanthoma are most commonly presented as a solitary, often ulcerated nodule, occurring on sun-exposed skin of the elderly. These lesions also share the histologic features of diffuse or indistinct fascicular arrangement of polygonal or pulmp spindle cells. Therefore it is not easy to differentiate immunohistochemistry is done. A case of 73 year old woman with squamous cell carcinoma of the skin resembling atypical fibroxanthoma is presented.
Female ; Humans

No abstract available.
Islets of Langerhans* ; Lymph Nodes* ; Neoplasm Metastasis*

No abstract available.
Biopsy, Fine-Needle* ; Fasciitis*

Polyarteritis nodosa is systemic necrotizing vasculitis of medium and small-sized arteries and results in variable manifestations due to ischemia of the involving organs. Diagnosis can either be made pathologically by demonstrating necrotizing vasculitis of arteries or angiographycally by demonstrating small arterial aneurysm. We experienced a case of PAN with dilated cardiomyopathy, confirmed by clinical feature, renal biopsy, angiography and echocardiography.
Aneurysm ; Angiography ; Arteries ; Biopsy ; Cardiomyopathy, Dilated* ; Diagnosis ; Echocardiography ; Ischemia ; Polyarteritis Nodosa* ; Vasculitis

The Her-2/neu protooncogene encodes a transmembrane tyrosine kinase that is structurally homologous to the receptor for epidermal growth factor. Its amplification and overexpression are associated with poor prognosis in breast cancer patients. Neu differentiation factor is a ligand for Her-2/neu protooncogene and was detected in ras-transformed rat fibroblasts. Heregulin (human homologue of neu differentiation factor) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation and induces growth arrest or stimulation and differentiation in human breast cancer cell lines. In this study we examined the expression of heregulin mRNA by nested reverse transcription (RT) PCR with fresh tissue, Her-2/neu protein, ICAM-1 and steroid receptors by immunohistochemistry, and DNA ploidy pattern by flow cytometry with paraffin-embedded tissue in invasive breast carcinoma. We compared the data with nodal status, lymphovascular invasion, steroid receptor status and DNA ploidy pattern. For RT-PCR to heregulin mRNA, 38 cases of fresh breast cancer tissue were obtained. Total 68 cases of invasive breast carcinoma tissue were fixed in formalin, which were used for routine histology, immunohistochemistry and flow cytometry. The results are as follows; 1) Heregulin mRNA was expressed in 86.1% of patients with invasive breast carcinoma and 100% of patients with benign breast lesion using nested RT-PCR analysis. 2) Her-2/neu protein was overexpressed in 50.0% of tumors using immunohistochemistry. The expression of Her-2/neu protein was significantly correlated with high counts of lymph nodes with metastasis (p<0.05), and high nuclear grade (p<0.05). 3) Her-2/neu protein overexpression was significantly correlated with a high DNA index(p<0.05). All of the tumors showing Her-2/neu protein overexpression and no heregulin mRNA expression revealed near tetraploid DNA content. However, both Her-2/neu overexpression and heregulin mRNA expressing tumors revealed near tetraploidy in 38.9% and diploidy in 50.0%. Based on these results, heregulin mRNA expression rate was 86.1% in human invasive breast carcinoma. Her-2/neu protein overexpression is associated with high positive lymph node number and DNA index. Statistically significant reverse correlation with lymph node metastasis is not present.
Animals ; Breast Neoplasms* ; Breast* ; Cell Line ; Diploidy ; DNA* ; Epidermal Growth Factor ; Fibroblasts ; Flow Cytometry ; Formaldehyde ; Glycoproteins ; Humans* ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; Lymph Nodes ; Neoplasm Metastasis* ; Neuregulin-1* ; Phosphorylation ; Ploidies* ; Polymerase Chain Reaction ; Prognosis ; Protein-Tyrosine Kinases ; Rats ; Receptors, Steroid ; Reverse Transcription ; RNA, Messenger* ; Tetraploidy ; Tyrosine

BACKGROUND: Established risk factors for coronary artery disease include smoking, hypertension, diabetes mellitus and hypercholesterolemia. However, these account for less than 50% of the actual incidence of coronary artery disease and the importance of other risk factors is being increasingly realized. It has been known that insulin resistance associated with hyperinsulinemia is a pivotal link to several risk factors of coronary artery disease, including hypertension, glucose intolerance, dyslipidemia and obesity. Recently both experimental and clinical studies have produced evidence suggesting that high plasma insulin level may promote the development of atherosclerotic vascular diseasa. Several prospective studies showed independently that high plasma insulin is associated with an increased risk of major coronary artery disease. In our study, plasma glucose, insulin and C-peptide level were determined with oral glucose tolerance test to assess the insulin resistance or hyperinsulinemia as a risk factory of coronary artery disease. METHOD: From September 1993 to April 1995, after excluding patients with hypertension, diabetes mellitus, hypercholesterolemia and obesity, 17 patients with significant coronary artery stenosis and 10 control subjects with normal coronary finding were selected among the 226 patients who undertook coronary angiography. In the 17 cases(M:F=15:2) of coronary artery disease group, the mean age was 54+/-10 years, and in the 10 cases(M:F=8:2) of control group, 51+/-9 years. All were matched for age, gender and body mass index. Blood pressure, lipid and lipoprotein were measured and smoking history was assessed. Glucose, insulin and C-peptide responses to oral glucose tolerance test were also determined. RESULT: 1) There was no significant difference in systolic and diastolic and diastolic blood pressure, total-cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, ApoA and smoking history except ApoB between the subjects with coronary artery disease and normal control subjects. 2) In oral glucose tolerance test, the plasma glucose levels were not significantly different in the two groups. plasma insulin and C-peptide levels at 60 and 120 minutes were higher in the patient group than control, but the results lack statistical significance. The area under the insulin curve and C-peptide curve were larger in patient group than control, but the result lack statistical significance also. CONCLUSION: Although our study dose not prove the hypothesis that insulin resistance or hyperinsulinemia is statistically an independent risk factor for coronary artery disease, this study showed the tendency of insulinresistance to be correlated with development of coronary artery disease. As this study has limitations due to small sample size, further study is required to confirm the role of hyperinsulinemia using a larger sample size.
Apolipoproteins A ; Apolipoproteins B ; Blood Glucose ; Blood Pressure ; Body Mass Index ; C-Peptide ; Coronary Angiography ; Coronary Artery Disease* ; Coronary Stenosis ; Coronary Vessels* ; Diabetes Mellitus ; Dyslipidemias ; Glucose ; Glucose Intolerance ; Glucose Tolerance Test ; Humans ; Hypercholesterolemia ; Hyperinsulinism ; Hypertension ; Incidence ; Insulin Resistance* ; Insulin* ; Lipoproteins ; Obesity ; Plasma ; Prospective Studies ; Risk Factors* ; Sample Size ; Smoke ; Smoking ; Triglycerides

BACKGROUND: Circadian rhythms have been described for acute myocardial infarction, sudden cardiac death, cerebrovascular disease, ischemic heart disease, and ventricular arrhythmia. Most of studies reported that the frequency of ventricular permature contractions(VPC's) shows a peak in day time. We tried to see that the circadian rhythm of VPC's in hypertension and ischemic heart disease(IHD) patients. And we will also studied the relationship between heart rate and frequencey of VPC's. METHOD: Twenty four hour holter monitoring was performed in hypertensive patients (N=23), ischemic heart disease patients(N=25), and normal control group(N=30). We tested the circadian pattern of VPC's and heart rates and the relationships of the frequency of VPC's and heart rates. RESULT: In hypertension group, a peak incidence of heart rate is between 5 and 8 P.M., in ischemic heart disease group, between 3 and 6 P.M.. In control group, the heart rate shows a peak beteen 1 and 3 P.M.. The frequency of VPC's in hypertension group shows the first peak between 4 and 10 P.M., and the second peak beteen 7 and 10 A.M.. In ischemic heart disease group, they show a peak between 2 and 8 P.M..In control group, there was no circadian variation for the frequency of VPC;s. Both in hypertension and IHD patients group, there was significant correlation between the frequency of VPC's and the heart rates. CONCLUSION: It seemed that VPC' were more frequently occurred in relation to the increase of heart rate in the afternoon, in hypertensive and ischemic heart disease patients.
Arrhythmias, Cardiac ; Circadian Rhythm ; Death, Sudden, Cardiac ; Electrocardiography, Ambulatory ; Heart ; Heart Rate ; Humans ; Hypertension* ; Incidence ; Myocardial Infarction ; Myocardial Ischemia* ; Ventricular Premature Complexes*

BACKGROUND: This study was designed to examine the interactions between mivacurium and vecuronium when administered during a standardized technique. METHODS: Eighty patients (ASA physical status I or II) were randomly assigned to one of four groups (n=20). Their neuromuscular function was measured in response to ulnar nerve supramaximal square-wave TOF stimulation at 10-sec intervals. After the attainment of a stable baseline neuromuscular response, the patients were randomly assigned to receive a rapid iv bolus of either: (1) 3M group (n=20): mivacurium 0.21 mg/kg. Alone, or (2) 2M1V group (n=20): mivacurium 0.14 mg/kg plus vecuronium 0.05 mg/kg, or (3) 1M2V group (n=20): mivacurium 0.07 mg/kg plus vecuronium 0.10 mg/kg, or (4) 3V group (n=20): vecuronium 0.15 mg/kg alone. The onset time of the neuromuscular block, time of recovery of T1 to 25% and reblock time (the time from the reinjection of vecuronium at the time of recovery of T1 to 25% to the time of recovery of T1 to 25%: T25-25) were measured. The intubating condition was evaluated clinically with a scoring system. RESULTS: The onset of block in the 3M group was 33% slower than in the 3V group. The time durations until 25% recovery in the 2M1V, 1M2V and 3V groups were longer than in the 3M group, and the durations in the 1M2V and 3V groups were longer than in the 2M1V group. The T25-25 reblock times of the 2M1V, 1M2V and 3V groups were prolonged in comparison to that of the 3M group. There was no difference in intubating conditions between any of the groups. CONCLUSIONS: A combination of mivacurium with vecuronium provides rates of onset and duration of block which are more effective than an equivalent dose of mivacuriun alone as an additive reaction.
Anesthesia, General* ; Humans ; Neuromuscular Blockade* ; Ulnar Nerve ; Vecuronium Bromide*