Production of Monoclonal Antibodies Against Human Colon Cancer Cell Line(SNU-C1) and Study of the Antigen.

To study human colon cancer antigens, monoclonal antibodies were produced by immunizing balb/c mice with colon cancer cells(SNlJ-CI, originated from a Korean colon cancer patient). Among these monoclonal antibodies, one of IgM type antibody 7E02 was selected for further study. The 7E02 was proved to be effective for immunohistological staining of colorectal cancer tissues. After purification by ammonium sulfate fractionation and Sephacryl S-3OO gel filtration, 7E02 was labeled by 1-125. Using the radiolabeled 7E02, its dissociation constants (Kd) against SNlJ-Cl and SNlJ-C4 were measured by Scatchard plotting, and found to be 10.7 nM and 7.1 nM, respectively. When SNlJ-CI was treated with 10 mM sodium periodate, 7E02 was not bound to the cell surface. However, SNlJ-CI preserved the activity to bind to 7E02 after N-acetyl neuraminidase treatment. With these results, we could conclude that the 7E02 binds to carbohydrate antigen that exists on the surface of colon cancer cell and excreted mucin. The antigen was proved not to contain terminal sialic acid

Acanthopanax koreanum Fruit Waste Inhibits Lipopolysaccharide-Induced Production of Nitric Oxide and Prostaglandin E2 in RAW 264.7 Macrophages

The Acanthopanax koreanum fruit is a popular fruit in Jeju Island, but the byproducts of the alcoholic beverage prepared using this fruit are major agricultural wastes. The fermentability of this waste causes many economic and environmental problems. Therefore, we investigated the suitability of using A. koreanum fruit waste (AFW) as a source of antiinflammatory agents. AFWs were extracted with 80% EtOH. The ethanolic extract was then successively partitioned with hexane, CH2Cl2, EtOAc, BuOH, and water. The results indicate that the CH2Cl2 fraction (100 μg/mL) of AFW inhibited the LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 cells by 79.6% and 39.7%, respectively. These inhibitory effects of the CH2Cl2 fraction of AFWs were accompanied by decreases in the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and iNOS and COX-2 mRNA in a dose-dependent pattern. The CH2Cl2 fraction of AFWs also prevented degradation of IκB-α in a dose-dependent manner. Ursolic acid was identified as major compound present in AFW, and CH2Cl2 extracts by high performance liquid chromatography (HPLC). Furthermore using pure ursolic acid as standard and by HPLC, AFW and CH2Cl2 extracts was found to contain 1.58 mg/g and 1.75 mg/g, respectively. Moreover, we tested the potential application of AFW extracts as a cosmetic material by performing human skin primary irritation tests. In these tests, AFW extracts did not induce any adverse reactions. Based on these results, we suggest that AFW extracts be considered possible anti-inflammatory candidates for topical application

In Antimyosin Monoclonal Antibody in the Detection of Doxorubicin Cardiotoxicity: a Comparison with Histology and 99mTc Pyrophosphate

Recently, lllIn-antimyosin monoclonal antibidies (IllIn-AMAb) have been introduced for the diagnosis of myocardial infarction. The purpose of this study was to investigate the feasibility of using this agent for the early detection of cardiac damage induced by doxorubicin. The degree of drug induced change in the myocardium was evaluated histologically. 99mTc pyrophosphate (99mTc-PYP), known to preferentially accumulate in Adriamycin caused lesions, was used as a control radiopharmaceutical. Myocardial uptake of 111In-AMAb and 99mTc-PYP was measured in 12 controls and 10 Adriamycin treated rabbits. The results indicated the following: 1) 111In-AMAb uptake in the heart correlated well with the degree of pathology (r=O.95); 2) 99mTc-PYP uptake was also correlated with cardiac damage (r=O.77); 3) The uptake ratio (expressed as percent injected dose per gram myocardial tissue) of Adriamycin treated animals vs. controls was 2.7: 1 for 111In-AMAb and 9.2 for 99mTc-PYP nt 24 and 2 hours after intravenous injection, respectively; 4) considerable non-specific 99mTc_PYP accumulation was measured in the lungs and kidneys and was significantly higher in drug treated animals compared to controls. 111In-AMAb accumulation remained unchanged in these organs. We conclude that 111In-AMAb accurately detects cardiac toxicity induced by Adriamycin but that 99mTc_PYP still remains an acceptable agent in part because, of its availability and higher tracer concentration in the cardiac lesions

Acanthopanax koreanum fruit waste inhibits lipopolysaccharide-induced production of nitric oxide and prostaglandin

The Acanthopanax koreanum fruit is a popular fruit in Jeju Island, but the byproducts of the alcoholic beverage prepared using this fruit are major agricultural wastes. The fermentability of this waste causes many economic and environmental problems. Therefore, we investigated the suitability of using A. koreanum fruit waste (AFW) as a source of antiinflammatory agents. AFWs were extracted with 80% EtOH. The ethanolic extract was then successively partitioned with hexane, CH 2 Cl 2 , EtOAc, BuOH, and water. The results indicate that the CH 2 Cl 2 fraction (100 μg/mL) of AFW inhibited the LPS-induced nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) production in RAW 264.7 cells by 79.6% and 39.7%, respectively. These inhibitory effects of the CH 2 Cl 2 fraction of AFWs were accompanied by decreases in the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and iNOS and COX-2 mRNA in a dose-dependent pattern. The CH 2 Cl 2 fraction of AFWs also prevented degradation of IκB-α in a dose-dependent manner. Ursolic acid was identified as major compound present in AFW, and CH 2 Cl 2 extracts by high performance liquid chromatography (HPLC). Furthermore using pure ursolic acid as standard and by HPLC, AFW and CH 2 Cl 2 extracts was found to contain 1.58 mg/g and 1.75 mg/g, respectively. Moreover, we tested the potential application of AFW extracts as a cosmetic material by performing human skin primary irritation tests. In these tests, AFW extracts did not induce any adverse reactions. Based on these results, we suggest that AFW extracts be considered possible anti-inflammatory candidates for topical application

Insulin Level, RBC Na+ Transport and Blood Pressure in Cushing's Syndrome

To test the hypothesis that hyperinsulinemia and / or abnormalities of RBC Na+ transport are concerned in the pathogenesis of hypertension in Cushing's syndrome, we 'investigated the relationship between insulin level, RBC Na + transport and blood pressure in patients with Cushing's syndrome which is frequently associated with hyperinsulinemia, abnormalities of RBC Na + transport and hypertension. Both systolic and diastolic pressure were significantly higher in Cushing's syndrome than in normal subjects. Fasting serum insulin level was higher and both serum glucose and insulin responses after a 75g glucose load were significantly increased in patients with Cushing's syndrome as compared with normal subjects. Both RBC Na+ concentration and passive Na + permeability were significantly lower but Vmax of Na +, K+-pump was significantly higher in patients with Cushing's syndrome than in normal subjects, while Vmaxs of Na+-K+ cotransport and Na+-Li + countertransport were similar in the two groups. In multiple stepwise regression analysis for patients with Cushing's syndrome, fasting serum insulin level was directly correlated with both systolic and diastolic pressures (r=O. 52, p=O. 01; r=O. 51, p=O. 02, respectively). On the other hand,RBC Na + transport parameters showed little correlation with either systolic or diastolic pressures. These results suggest that hyperinsulinemia may contribute to the hypertension in Cushing's syndrome, but that the abnormalities of RBC Na + transport seen in Cushing's syndrome are not causally related to hypertension

Decreased Angiotensin II -Stimulated Aldosterone Production, but Normal Inositol Phosphate Response in Adrenal Glomerulosa Cells from Streptozotocin-Induced Diabetic Rats: Role of lnsulin

Streptozotocin(SlZ)-induced diabetic rats develop hyporeninemic hypoaldosteronism during the progression of diabetes mellitus. However,the nature and mechanism of aldosterone deficiency in diabetic rats still remain unclear and acute effects of insulin on aldosterone production in-vitro are not known. We evaluated the responses of aldosterone production to angiotensin 11 (AlI), potassium (K+), AClH and insulin in adrenal glomerulosa cells prepared from SlZ-induced diabetic rats with and without insulin treatment 2 weeks after diabetes induction. We also measured inositol phosphate<IP) levels in All-stimulated glomerulosa cells labeled with [3HI myoinositol using standardized anion exchange chromatography. Plasma renin activity and aldosterone level were not different among control rats,untreated and insulin-treated diabetic rats. Basal aldosterone production was similar in cells from the three groups. Cells from untreated diabetic rats showed a significant decrease in the maximal All (to-8M)-stimuiated aldosterone production and a tendency to be low in the maximal K+(8.7 mM)-stimulated aldosterone production, compared with control rats (3.2±2.2 \IS 7.7±2.4, P (0.05 and 4.8±1.8 \IS 8.0±3.2 ng/105 cells/hr, 0.05 (P (0.1, respectively). In contrast, there were no differences in All- and K+-stimulated aldosterone production between control and insulin-treated diabetic rats. AClH (to-8M), however, caused a similar effect on aldosterone production and insulin (I mU /ml for 1 hour) did not alter either basal or agonists-stimulated aldosterone production in cells from the three groups. All (to-8M)-induced IP formation among the three groups was similar and did not change with the addition of insulin u mU / ml), These results indicate that reduced response to All in the early phase of SlZ-induced diabetes in rats may be due to the zona glomerulosa dysfunction secondary to chronic lack of insulin and the main defect responsible for altered All effects may be located at some step(s) mediating All action downstream from IP formation

Crossed Cerebellar Diaschisis in Cerebral Infarction: Correlation of SPECT and Clinical Features

Patients with supratentorial cerebral infarction frequently show depressed metabolic activity in the contralateral cerebellar hemisphere which is known as crossed cerebellar diaschtsisfCt.D). In order to investigate the relationship between this phenomenon and the characteristics of the supratentorial lesion, we retrospectively evaluated the findings of 99mTc-HMPAO single photon emission computed tomography(SPECT) in 26 patients with a single supratentorial infarction lesion. A cerebellar asymmetry index (AIcbll), percent difference between both cerebellar hemispherestzx'Scbll],SPECT volume deficit (SVD), and magnetic resonance volume deficit (MVD) were quantitated. A CCD, defined as AIcbll >12%, was observed in 12 of the 26 patients (46.2%). No correlation was found between the ~%cbll and duration of disease, SVD, or MVD. SVD and MVD values showed no significant difference between CCD positive and negative groups (71+47ml \IS. 70+68ml and 90+84ml \IS. 67+77ml, respectively). Patients with frontoparietal lobe or deep middle cerebral artery territory infarctions showed a significantly higher incidence of CCD and lower ~%cbll values. Patients with severe hemiparesis had a higher incidence of CCD and lower ~%cbll values than those with milder or no hemiparesis (incidence, 5/5 \IS. 6/18, p=0.008; ~ %cbll,-21. 4+3.8% \IS -8. 3±11. 1%, p=O. 014). None of the 12 patients with CCD showed clinical signs of cerebellar dysfunction. In conclusion, the location rather than the extent of the lesion appears to be the major determinant for the occurrence and magnitude of CCD in stroke patients

Comparison of Clinical Efficacy of Newfactan® versus Surfacten® for the Treatment of Respiratory Distress Syndrome in the Newborn Infants

Newfactan® is a domestically developed, bovine lung-derived, semi-synthetic surfactant. The aim of this study was to compare the clinical efficacy of Newfactan® with that of Surfacten® in the treatment of respiratory distress syndrome (RDS). Newfactan® or Surfacten® was randomly allocated to 492 newborn infants who were diagnosed as RDS and required surfactant instillation in four participating hospitals. The comparisons were made individually in two subsets of infants by birth weight (<1,500 g group [n=253] and ≥1,500 g group [n=239]). Short-term responses to surfactant and acute complications, such as the total doses of surfactant instilled, response type, extubation rate, ventilator settings, changes in respiratory parameters, air leak, patent ductus arteriosus, pulmonary hemorrhage, and intraventricular hemorrhage, and mortality during the 96 hr after surfactant instillation were measured. Long-term outcome and complications, such as total duration of intubation, bronchopulmonary dysplasia and periventricular leukomalacia, and ultimate mortality were measured. There were no significant differences in demographic and perinatal variables, short-term responses to surfactant and acute complications, and long-term outcome and complications between Newfactan® and Surfacten® in both birth weight groups. We concluded that Newfactan® was comparable to Surfacten® in the clinical efficacy in the treatment of RDS in both birth weight groups