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Biomedical subjects

E Cho

Publications and source records attributed to E Cho.

107 records · Page 6Linked to original sources

Effect of bilateral nephrectomy on plasma fibronectin levels: its influence on acute fibronectin response to trauma and RE blockade.

Plasma fibronectin is important to reticuloendothelial (RE) function and resistance to experimental shock. However, the factors that regulate its level have remained undefined. The present study evaluated the concept that the kidneys may play a role in the modulation of plasma fibronectin levels. Immunoreactive and opsonically active fibronectin in blood over a 28-hour period following bilateral nephrectomy was assessed in male rats (250-350 gm) by electroimmunoassay, peritoneal macrophage monolayer assay, and liver slice bioassay. Controls consisted of sham-operated rats. An acute 25%-30% fibronectin deficiency was detected within the initial 1-2 hours posttrauma in both experimental and control rats. Thereafter, a significant (P less than 0.05) increase in immunoreactive fibronectin developed by 24 hours which was much greater after bilateral nephrectomy as compared to controls (P less than 0.05). With the peritoneal macrophage assay or with the liver slice assay, the plasma or serum from bilateral nephrectomized rats has greater opsonic activity as compared to controls. This corresponded to increased hepatic RE phagocytic function in vivo after nephrectomy. In the 24-hour postnephrectomized rats, fibronectin decreased acutely after RE blockade or traumatic shock (NCD) indicating it was biologically active. These data suggest that the kidneys may participate in regulating the blood level of this protein, which has a role in reticuloendothelial system function and shock resistance.

Animals↗

Neurotoxicology of vincristine in the cat. Electrophysiological studies.

Cats were given vincristine sulfate (50 micrograms/kg i.v. every 4 days) and studied after 7-29 injections when neurological deficits became evident. The conduction velocity spectrum of individual afferent nerves from soleus muscles was shifted toward slower velocities. Relatively few functional muscle spindles or other proprioceptors which responded to muscle stretch were encountered. Those primary endings of soleus muscle spindles which did respond were significantly reduced in dynamic but not length sensitivity. Length sensitivity of secondary endings was unchanged. Thresholds of secondary but not primary endings were elevated. The average conduction velocity of soleus motor axons was reduced 30% but no deficit was detected in motor nerve terminal function. Indirectly-elicited contractile tension of the soleus muscles of the neuropathic cats was not significantly lower than that in untreated animals. Amplitudes of spinal monosynaptic reflexes were unaffected. These data indicate, that in the cat, neurological impairment results partly from dysfunction in muscle spindles and peripheral nerves.

Afferent Pathways↗

Evaluation of a rapid immunoturbidimetric assay for opsonic fibronectin in surgical and trauma patients.

A rapid and sensitive method for determination of plasma or serum opsonic fibronectin was developed and evaluated. This is a kinetic immunoturbidimetric assay based on the measurement of an antigen-antibody reaction. Comparison with electroimmunoassay was conducted in septic surgical and trauma patients with opsonic fibronectin deficiency before and after infusion of fibronectin-rich plasma cryoprecipitate. In contrast to the 24 to 48 hr needed for obtaining quantitative determinations by electroimmunoassay, the immunoturbidimetric assay can be accomplished within 10 min and requires only 5 microliters of serum or plasma. The concentration of opsonic fibronectin in plasma is greater than in serum. Plasma anticoagulated with EDTA and supplemented with aprotinin (Trasylol) to inhibit proteolytic activity is the procedure of choice for preparation of samples prior to analysis. The rapid immunoturbidimetric assay has clinical value as a rapid, sensitive, noninvasive means of assessing opsonic fibronectin and indirectly evaluating RES function. Its diagnostic as well as prognostic value with respect to various diseases remains to be carefully studied.

Adult↗

Humoral regulation of plasma opsonic fibronectin levels: its role in reticuloendothelial recovery after RE blockade.

The present study in rats evaluated the concept that a humoral factor regulates opsonic fibronectin levels. Intravenous administration of gelatin-coated particles depletes immunoreactive opsonic fibronectin by 95% within 30 minutes. Partial restoration of opsonic protein was observed by 3 hours with complete recovery 6-24 hours. Post-blockade serum was then evaluated with respect to this humoral factor. Controls were given either normal serum or serum rendered fibronectin-deficient by affinity chromatography. Affinity-adsorbed fibronectin-deficient serum did not increase immunoreactive opsonic fibronectin. Injection of normal serum resulted in the expected elevation in fibronectin due to its fibronectin content. In contrast, injection of fibronectin-deficient serum obtained during RE blockade dramatically elevated (P less than 0.02) immunoreactive opsonic fibronectin to 160.6 +/- 14% of control levels by 3 hours. Thereafter, fibronectin levels returned to control over the 6-24 hour period. Our temporal studies suggest that a circulating transferable factor, which may be a hormone, may influence the synthesis and/or release of opsonic fibronectin.

Animals↗

Diagnosis of submucosal lesions of the upper gastrointestinal tract by endoscopic ultrasonography.

The use of endoscopic ultrasonography (EUS) in the diagnosis of submucosal upper gastrointestinal tract lesions was examined in 308 patients. Two-hundred ten submucosal tumors, 89 cases of esophagogastric varices, and 9 cases of non-Hodgkin's lymphoma were found. EUS images were interpreted based upon a five-layer EUS structure of the normal gastrointestinal wall. A characteristic EUS image was seen with leiomyoma, cysts, lipoma, and varices. EUS had an accuracy of 80% in staging nine cases of lymphoma. EUS is a valuable technique for the evaluation and diagnosis of submucosal upper gastrointestinal tract lesions.

Esophageal and Gastric Varices↗

Endoscopic ultrasonography in the diagnosis of colorectal cancer invasion.

Endoscopic ultrasonography was pre-operatively performed in 164 patients with colorectal cancer, and the resected specimens confirmed to be cancerous histologically. Normal colorectal wall was visualized by endoscopic ultrasonography as a five-layered structure. The first, third, and fifth layers were hyperechoic, and the second and fourth layers were hypoechoic. The first and second layers comprised the mucosa, the third layer the submucosa, the fourth layer the muscularis propria, and the fifth layer the subserosa and serosa (adventitia). By this technique, cancer of the colon appeared as a hypoechoic mass with an intermediate echo level between the third hyperechoic and fourth hypoechoic layers. Endoscopic ultrasonographic determination of the depth of tumor invasion was based on abnormal changes of these layered structures and adjacent organs. Overall, the accuracy rate of endoscopic ultrasonography in the diagnosis of the depth of colorectal cancer was 83%. A hypoechoic round mass adjacent to the cancer was interpreted as a metastatic lymph node. The sensitivity and specificity of endoscopic ultrasonography in the diagnosis of lymph node metastasis were 68% and 70%, respectively. The overall accuracy rate of tumor staging by endoscopic ultrasonography according to Dukes' classification was 62%. Endoscopic ultrasonography is a valuable tool in the management of colorectal cancer. It has a high accuracy rate in determining the depth of tumor invasion. The pre-operative information obtained with this tool may influence the choice of therapy.

Colon↗

Point mutations in the c-K-ras 2 gene in multiple colorectal carcinomas.

The c-K-ras 2 gene mutations were examined in colorectal tumours from patients with synchronous or metachronous tumours in order to investigate tumorigenesis. Sixty-seven colorectal carcinomas from patients with a single lesion, 50 from patients with synchronous lesions, and 12 from patients with metachronous lesions were analysed for the presence of point mutations in codons 12 and 13 of c-K-ras proto-oncogene. In the patients with metachronous or synchronous lesions, the finding of the mutation in one tumour was not associated with a greater frequency of the mutation in other carcinomas from the same patient. In the patients with tumours that each contained the mutation, the mutations were not always the same. In tumours from the patients with original and synchronous lesions, the mutation frequency was significantly lower in advanced carcinomas invading through the entire muscularis propria (10.5%) than in early carcinomas confined to the mucosa (47.8%), and the mutation frequency in carcinomas invading through the entire muscularis propria was significantly lower in patients with synchronous lesions (10.5%) than in patients with a single lesion (37.7%). These results suggest that the tumorigenesis of colorectal carcinomas from patients with synchronous lesions is different from that in patients with a single lesion.

Adult↗

Decreased plasma fibronectin during starvation in man.

This study evaluated the effect of 5 days of starvation followed by 5 days of refeeding on immunoreactive plasma and serum fibronectin and associated opsonic activity as studied by peritoneal macrophage monolayer bioassay in 12 healthy women volunteers. The temporal alteration of fibronectin was compared with the serum albumin, total iron-binding capacity, and retinol-binding protein levels. Fibronectin concentration and opsonic activity were also determined in two cachectic patients who were 61 and 78% of their ideal body weight. Prior to starvation, plasma fibronectin was 292 +/- 20 micrograms/ml and serum fibronectin was 182 +/- 16 in all subjects. After 5 days of starvation, immunoreactive fibronectin decreased (p less than 0.05) by 20-25%. This decrease was not great enough to impair opsonic activity as tested by the in vitro macrophage assay. Starvation caused no decrease in serum albumin or total iron-binding capacity, although retinol-binding protein decreased by 35%. During refeeding, subjects were randomized to a diet with (n = 6) and without (n = 6) carbohydrate. After 5 days of refeeding, fibronectin levels were normalized on the carbohydrate-containing diet, but were still low (82% of normal) on the carbohydrate-free diet. Retinol-binding protein did not fully normalize after 5 days of refeeding. In the two cachectic patients, fibronectin levels prior to total parenteral nutrition were 25 and 75% of normal. Thus, starvation can lower fibronectin levels and this protein is rapidly restored with adequate nutrition.

Adult↗

Maternal genistein exposure mimics the effects of estrogen on mammary gland development in female mouse offspring.

Human and animal data indicate that a high maternal estrogen exposure during pregnancy increases breast cancer risk among daughters. This may reflect an increase in the epithelial structures that are the sites for malignant transformation, i.e., terminal end buds (TEBs), and a reduction in epithelial differentiation in the mammary gland. Some phytoestrogens, such as genistein which is a major component in soy-based foods, and zearalenone, a mycotoxin found in agricultural products, have estrogenic effects on the reproductive system, breast and brain. The present study examined whether in utero exposure to genistein or zearalenone influences mammary gland development. Pregnant mice were injected daily with i) 20 ng estradiol (E2); ii) 20 microg genistein; iii) 2 microg zearalenone; iv) 2 microg tamoxifen (TAM), a partial estrogen receptor agonist; or v) oil-vehicle between days 15 and 20 of gestation. E2, genistein, zearalenone, and tamoxifen all increased the density of TEBs in the mammary glands. Genistein reduced, and zearalenone increased, epithelial differentiation. Zearalenone also increased epithelial density, when compared with the vehicle-controls. None of the treatments had permanent effects on circulating E2 levels. Maternal exposure to E2 accelerated body weight gain, physical maturation (eyelid opening), and puberty onset (vaginal opening) in the female offspring. Genistein and tamoxifen had similar effects on puberty onset than E2. Zearalenone caused persistent cornification of the estrus smears. These findings indicate that maternal exposure to physiological doses of genistein mimics the effects of E2 on the mammary gland and reproductive systems in the offspring. Thus, our results suggest that genistein acts as an estrogen in utero, and may increase the incidence of mammary tumors if given through a pregnant mother. The estrogenic effects of zearalenone on the mammary gland, in contrast, are probably counteracted by the permanent changes in estrus cycling.

Adipose Tissue↗

Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring.

A high estrogenic environment in utero may increase subsequent breast cancer risk. It was therefore determined whether a maternal exposure during pregnancy to the phytoestrogen genistein or zearalenone, both of which exhibit estrogenic activities in vitro and in vivo, alters breast cancer risk among female offspring. Pregnant rat dams were treated daily with subcutaneous injections of 20, 100 or 300 microgram genistein, 20 microgram zearalenone, or vehicle between days 15 and 20 of gestation. The offspring were given 7, 12-dimethylbenz(a)anthracene (DMBA) at the age of 2 months to induce mammary tumors. The results indicate that in utero exposure to genistein, but not to zearalenone, dose-dependently increased the incidence of DMBA-induced mammary tumors, when compared with the controls. Tumor growth characteristics were not altered. Prior to the carcinogen administration, the number of estrogen receptor (ER) binding sites, determined using a ligand binding assay, were significantly elevated in the mammary glands of genistein offspring. In contrast, the mammary protein kinase C (PKC) activity was significantly reduced in the genistein offspring. Our results suggest that a maternal exposure to subcutaneous administration of genistein can increase mammary tumorigenesis in the offspring, mimicking the effects of in utero estrogenic exposures. Further, increased ER protein levels and reduced PKC activity in the mammary gland may be involved in increasing susceptibility to carcinogen-induced mammary tumorigenesis in rats exposed to genistein in utero.

9,10-Dimethyl-1,2-benzanthracene↗