Carcinoembryonic Antigen and Cystic Fibrosis Protein in Blood from Cystic Fibrosis Homozygotes and Heterozygote Carriers

Carcinoembryonic antigen (CEA) activity was measured by radioimmunoassay in blood from cystic fibrosis (CF) homozygotes, heterozygote carriers of CF, normal healthy controls, and other patient controls with carcinomas involving gastrointestinal organs. All samples were also screened by electrofocusing for cystic fibrosis protein (CFP), a metabolic marker previously shown to be associated with the CF gene. Significantly increased levels of CEA activity were found in all CFP-positive groups; however, with one exception all patient controls with marked increases in CEA activity were CFP-negative. Immunodiffusion of perchloric acid extracts of CEA-like material from heterozygote carrier blood indicated that the CEA-like material, which was elevated in homozygotes and heterozygotes for CF, showed only partial identity with two separate CEA preparations obtained from colon carcinomas and was not identical to either A, B, or O (H) blood group substances. This glycoprotein material did, however, react with three different anti-CRA antisera. Our finding of an abnormally increased glycoprotein in cystic fibrosis, taken together with previous reports demonstrating abnormalities in the carbohydrate portion of glycoproteins found in various exocrine secretions in CF, further suggests that the primary defect in this disease is manifested partly as a defect in glycoprotein metabolism. This defect may result from an abnormality in one or more of the glycosyltransferases, possibly caused by a more primary defect in polyamine metabolism.     

HMB-45抗原在毛囊黑素细胞中的表达

用单克隆抗体ＨＭＢ－４５，以ＡＰＡＡＰ法对２０份头皮活检标本的９８个毛囊组织进行染色。其中２０个毛囊为生长早期，６３个为成熟生长期，７个为退行期和８个是休止期。结果，５２个成熟生长期及２０个生长早期毛囊的黑素细胞与单克隆抗体ＨＭＢ－４５显著结合。所有退行期、休止期及工１１个成熟生长期毛囊未被染色。结果提示；ＨＭＢ－４５在毛囊中的表达随毛发生过周期而变化，且与黑素细胞功能活性状态有关。     

Greater hypertrophy in right than left ventricles is associated with pulmonary vasculopathy in sinoaortic-denervated Wistar-Kyoto rats

1. Biventricular hypertrophy has been described in a high blood pressure variability (BPV) model of sinoaortic-denervated (SAD) rats without systemic hypertension. To explore the possible involvement of the lung in SAD-induced right ventricular hypertrophy (RVH), we examined lung morphology, in addition to systemic haemodynamics and ventricle morphology, in Wistar-Kyoto rats 32 weeks after SAD. 2. In Wistar-Kyoto rats 32 weeks after SAD, there existed a substantial elevation in BPV, with no change in the average level of arterial pressure. Biventricular hypertrophy following SAD was characterized by a greater hypertrophy in right than left ventricles; both absolute and normalized right ventricular weights were significantly increased by 22 and 27％, respectively, and only normalized left ventricular weight was significantly increased by 12％. No infarcts were found in any ventricles examined. 3. In the lung, the most prominent change following SAD was pulmonary vasculopathy, including wall thickening, perivascular fibrosis and cell infiltration. In pulmonary arteries with an internal diameter of 70-130 microm, the external diameter, wall thickness and wall thickness to internal diameter ratio were increased in SAD compared with control rats. 4. There was no correlation between right and left ventricular weights. In contrast with BPV-correlated left ventricular weight, right ventricular weight was correlated with the wall thickness of the pulmonary artery, but not with BPV. 5. These findings suggest that greater RVH following SAD is associated with pulmonary vasculopathy, but is not secondary to the left ventricular problems or high BPV.     

Polyclonal Activation of Human Peripheral Blood B Lymphocytes by Formaldehyde-Fixed Salmonella paratyphi B

B-cell 'activation' in cultures stimulated with pokeweed mitogen (PWM), Staphylococcus aureus strain Cowan I, or formaldehyde-fixed Salmonella paratyphi B (SPB) was evaluated by enumeration of cells secreting immunoglobulin (Ig) and by quantitation of Ig released into culture supernatants. A dissociation between these two values was found after day 6 in cultures activated with PWM or SPB, suggesting that Ig-secreting cells (ISC) are heterogeneous in terms of Ig secretion rate. Generation of ISC in cultures activated with PWM or SPB was partially inhibited by hydroxyurea, but [g levels in culture supernatants were not affected. These results indicate that there are at least two subpopulations of ISC in stimulated peripheral blood lymphocyte cultures, one sensitive to, and the other resistant to, hydroxyurea. The hydroxyurea-resistant subpopulation appeared to be more mature and to release almost all of the Ig detected in culture supernatants. Furthermore, time-course studies of ISC numbers and Ig levels showed that each ISC in SPB-stimulted cultures (but not in PWM-stimulated cultures) was more active in Ig synthesis and secretion after day 8 than before day 6, indicating that after day 8 most of the ISC in cultures activated with SPB were hydroxyurea-resistant. These studies suggest that SPB is another useful polyclonal B-cell 'activator' for studies of human B-cell differentiation and function, and that SPB defines two distinct subsets of B cells.     

Thrombomodulin, an endothelial anticoagulant protein, is absent from the human brain

Protein C activation by thrombin is significantly accelerated by the endothelial cell cofactor, thrombomodulin. In this study, we have developed a radioimmunoassay for thrombomodulin and have measured the cofactor content in several human tissues. The assay method detects as little as 2 ng of thrombomodulin. The highest thrombomodulin content was found in lung and placenta, but the antigen was also detected in spleen, pancreas, liver, kidney, skin, heart, and aorta. Unexpectedly, thrombomodulin was absent from brain. Extracts from cerebral cortex, cerebellum, centrum semiovale, midbrain, basal ganglia, pons, and medulla were devoid of thrombomodulin. In contrast, thrombomodulin antigen is present in extracerebral intracranial vessels, including basilar and internal carotid arteries and choroid plexus, as well as in endothelium of the pia-arachnoid.     

Colorectal carcinoma: detection with indium-111 anticarcinoembryonic- antigen monoclonal antibody ZCE-025

A phase I and II clinical trial with indium-111-labeled anticarcinoembryonic-antigen monoclonal antibody ZCE-025 (In-111 ZCE-025) was initiated. Fifteen patients with colorectal tumors underwent external scintigraphy following the administration of 5.5 mCi (203.5 MBq) In-111 ZCE-025 at doses of 2.5-80.0 mg. Eighteen of 20 documented tumor sites, excluding those in the liver, were detected with In-111 ZCE-025. Lesions less than 1.5 cm could not be detected. Twenty-five percent of liver metastases exhibited positive accumulation of In-111 ZCE-025 at doses of 40-80 mg. No side effects were encountered. Because of the high detection rate of lymph node metastases from colorectal carcinoma with In-111 ZCE-025, this technique may be helpful in preoperative staging of patients with colorectal tumors, as well as in distinguishing recurrent tumors from postoperative or postradiation changes seen on computed tomography scans or other radiologic images.