Autoradiographic Analysis of Radiolabeled Anti-carcinoembryonic Antigen Monoclonal Antibody CEA102 in Colorectal Cancer Using Computed Radiography

Anti-carcinoembryonic antigen monoclonal antibody (MAb) CEA102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with ¹³¹I-labeled intact CEA102 or its F(ab')₂. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of ¹³¹I-labeled CEA102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of administered radiolabeled MAb in individual tumors, but the density of the tumors was higher than that of the normal tissues. In the quantitative distribution analysis of CEA102, the uptake of the primary tumor (mean 1.10%ID/kg) was ten-fold greater than that of the normal colon mucosa (mean G.10%ID/kg). These results revealed that the application of MAb has great potential in radioimmunodetection as well as in antibody-directed therapy.     

Effects of RA642, a new central pressor agent, on renal sympathetic nerve activity and blood pressure during hemorrhagic shock in rabbits

This experiment was designed to evaluate effects of RA642, a pyrimido-pyrimidine derivative, on renal nerve activity (RNA), mean blood pressure (MBP), central venous pressure (CVP), and heart rate (HR) during hemorrhagic shock in anesthetized rabbits. Hemorrhagic hypotension of 30 mmHg was induced by rapid bleeding and was controlled by a servocontrolled pump. Following the onset of hemorrhagic hypotension, RNA response showed a triphagic pattern: an initial increase in RNA and a secondary increase followed by a profound decline in RNA. In all animals, decreases in RNA occurred within approximately 30 min after bleeding in association with significant decreases in heart rate. When RNA fell to near noise level, the effects of RA642 (0.25 mg/kg, iv, N = 10), physiological saline (N = 7), epinephrine (10 micrograms/kg, iv, N = 6), and dopamine (10 micrograms/kg, iv, N = 5) were then tested. Intravenous injection of saline produced no significant improvements of hypotension nor of reduction in RNA. However, treatment with RA642 produced a significant increase in MBP simultaneously with an increase in RNA. During the hypovolemic hypotensive phase, tachycardia did not occur after the treatment with RA642. Twenty-five minutes after the retransfusion, MBP and RNA in the RA642-treated group were at significantly higher levels than in the saline group. HR did not significantly change with the RA642 treatment after the retransfusion. In another six animals, when RNA fell to near noise level, epinephrine caused a transient increase in MBP and HR. Ventricular arrythmias occurred in 50% of epinephrine-treated animals. However, the level of MBP as improved by epinephrine was significantly lower than that by RA642 at 25 min after the retransfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemobilia: Review of Recent Experience with a Worldwide Problem

Between 1981 and 1985, the reported incidence of hemobilia increased for two major reasons. First, a more sophisticated and better-trained medical community could entertain the diagnosis readily in certain settings and had broader access to diagnostic methods that precisely defined the source of bleeding into the biliary tract. Second, there was wider use of percutaneous techniques of diagnosis and treatment of biliary diseases. Once the diagnosis of hemobilia was made by endoscopic or arteriographic means, physicians and surgeons were quicker to institute proper therapeutic measures. For this reason, the mortality associated with hemobilia decreased compared with that reported earlier. The medical community must be aware that modern treatments are now the most common cause of this problem. Since invasive diagnostic methods are increasingly used by nonsurgeons, it is imperative that these patients are studied in the context of complete consultation with surgeons who can use definitive treatments when required.     

gamma-Aminobutyric acid enhances the tone of human internal anal sphincter.

The effect of gamma-aminobutyric acid (GABA) on the human internal anal sphincter was investigated. Cumulative applications of GABA produced concentration-dependent contractions (10(-8)-10(-5) M) of the isolated human sphincter. Pretreatment with bicuculline (GABAA antagonist) turned them to relaxation. Muscimol, a GABAA agonist, induced concentration-dependent contractions (10(-8)-10(-5) M); however, baclofen (GABAB agonist, 10(-8)-10(-5) M) promoted concentration-dependent relaxation of the strips. These results suggested that both excitatory GABAA receptors and inhibitory GABAB receptors exist in the internal anal sphincter. Oral administration of sodium valproate (1600 mg/day), a GABA transaminase inhibitor, enhanced the anal canal resting pressure in 10 normal volunteers. Anal manometry showed a significant elevation in tonus without affecting amplitudes or frequencies. These results indicated that endogenous GABA, which was increased by sodium valproate, produced elevations in the anal canal resting pressure through its specific receptors in the human internal anal sphincter.     

Plasma volume estimation using indocyanine green with biexponential regression analysis of the decay curves

We studied seven analytical methods of estimating the plasma volume from the decay curves of indocyanine green. Fifteen volunteers received 1.0 mgkg⁻¹ of the dye by intravenous injection and the plasma concentration was measured continuously using spectrophotometry. Plasma volumes were calculated using three single-regression methods (1-a, 1-b, 1-c) and four biexponential regression methods (2-a, 2-b, 2-c, 2-d). The means (SD) of 1-a, 1-b and 1-c were 39 (5.0), 44 (5.7) and 54 (11.5) mlkg⁻¹, respectively, and these were significantly different from each other (p < 0.05). The values for methods 2-b, 2-c and 2-d were similar to each other: 39 (4.6), 40 (4.1) and 40 (4.0) mlkg⁻¹, respectively. These required more than 3 min circulation or mixing time. When the time allowed for mixing was less than 3 min (method 2-a) the plasma volume was underestimated. We conclude that plasma volume estimation using indocyanine green and spectrophotometry is most accurate when the mixing time is adequate (3–5 min) and the decay curves are analysed using biexponential regression.     

Cadherin dysfunction in a human cancer cell line: possible involvement of loss of alpha-catenin expression in reduced cell-cell adhesiveness.

A human lung cancer cell line, PC 9, was analyzed to elucidate the molecular mechanisms of dysfunction of cadherin-mediated cell-cell adhesion in cancer. Although PC 9 cells strongly expressed E-cadherin at the cell membrane, which was indistinguishable immunochemically from functional E-cadherin, they did not show tight cell-cell adhesion and had reduced E-cadherin-mediated aggregation activity. Immunoprecipitation with E-cadherin and Western blot analysis revealed that PC 9 cells did not express alpha-catenin, a cadherin-associated protein, suggesting that this was the cause of the cadherin dysfunction in the cell line. In addition, Northern and Southern blot analyses disclosed homozygous deletion of part of the alpha-catenin gene, which might have resulted in the loss of alpha-catenin expression in PC 9 cells.     

Antiepileptic effects of CNK-602A, a novel thyrotropin-releasing hormone analog, on absence-like and tonic seizures of spontaneously epileptic rats.

The effects of CNK-602A (N-[(6-methyl-5-oxo-3-thiomorpholinyl) carbonyl]-L-histidyl-L-prolinamide), a novel thyrotropin-releasing hormone related analog, were investigated on absence-like seizure and tonic convulsion in the spontaneously epileptic rat (SER), which is a genetically defined double-mutant. When CNK-602A of 0.2-1 mg/kg was given intravenously to the animal, there were no changes in the background EEG except for an increase in low-voltage fast waves concomitant with behavioral alertness. However, CNK-602A suppressed absence-like seizure and tonic convulsion in a dose-dependent manner for over 1 h. These antiepileptic effects of CNK-602A on both seizures were antagonized by pretreatment with haloperidol (1 mg/kg, i.p.). It was found, using a brain in vivo microdialysis method, that CNK-602A at a dose of 1 mg/kg, which inhibits the seizures, increased the release of dopamine in the caudate nucleus. These results suggest that CNK-602A inhibits the seizures of SER in a similar manner to thyrotropin-releasing hormone (TRH), probably by increasing the release of dopamine in the central nervous system. In addition, the antiepileptic effects of CNK-602A were more potent and lasted longer than those of TRH.