Cell-killing Activity and Kinetic Analysis of a Novel Antitumor Compound NC-190, a Benzo[a]phenazine Derivative

A novel antitumor compound, N-β-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190), was evaluated for antitumor activity in vitro against cultured tumor cell lines, and the kinetics of cell killing was elucidated. NC-190 strongly inhibited the growth of all of 3 murine tumor cell lines, 7 human tumor cell lines and 2 normal cell lines. With continuous exposure, the 50% inhibition concentrations were in the range of 0.005–0.06 μg/ml, except for KATO-III (2.15 μ g/ml). By colony-forming assay, concentrations of NC-190 giving 90% cell kill (IC₉₀) at various exposure times were obtained with HeLa S3 cells. The plot of IC₉₀exposure time on a log-log scale was linear for NC-190 with a slope of -1, which is typical for cell cycle phase-nonspecific agents. A 2 h treatment with NC-190 induced a rapid reduction in cell viability at doses of more than 3 μ g/ml. At the dose where colony formation was completely inhibited, cell viability was persistently reduced to below 20% during the cell culture period. NC-190 cauced a dose- and time-dependent reduction in DNA synthesis. The inhibitions of RNA and protein synthesis were less than that of DNA synthesis. Spectroscopic studies of NC-190 mixed with calf thymus DNA demonstrated that NC-190 was capable of interacting with DNA. However, DNA thermal denaturation studies suggested that intercalation of NC-190 was weak in comparison with those of classical intercalating drugs.     

Notes on the use of low magnification telescopes in low vision care

Several areas related to the use of telescopes in low vision are reviewed. These include: contrast sensitivity function; eccentric viewing through a telescope; field of view; telescope used in reverse; and IOL-spectacle lens telescopic systems. Experimental data are included to support selected clinical observations routinely made by low vision clinicians.     

Cortical Distribution of Eeg Activity for Component Processes During Mental Rotation

Alpha power (8–12 Hz) was monitored over the frontal, temporal, parietal and occipital lobes of the left and right cerebral hemispheres while participants mentally rotated three-dimensional shapes to match a specified target. By comparing the activational patterns generated during three experimental conditions, each designed to systematically isolate the involvement of the various subcomponents comprising this mental rotation task, it was suggested that the right frontal lobe mediates encoding and comparison/decision processes, while the left parietal and the left temporal region appear most involved in the generation of images and their mental rotation. A preliminary model describing the cooperative interaction of these cortical regions during mental rotation tasks is proposed.     

Aggressive behaviour in elderly psychiatric inpatients.

We describe the types of aggressive behaviour and determine their prevalence in a sample of hospitalized elderly psychiatric patients. Data were obtained by nurse ratings of aggressive behaviour using the recently developed Rating Scale for Aggressive Behaviour in the Elderly; 90 patients were rated over a 3-d period. Nearly half the sample were at least mildly aggressive; the frequencies of some specific types of aggressive behaviour were high. In contrast, the frequency of injuries and the use of restraints and medication for aggressive behaviour were low. Some correlates of the aggressive behaviour were also analysed.     

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.     

Preparation and Characterization of a Murine Monoclonal Antibody (MDR3M) Reactive with mdr3 Gene Product

A murine monoclonal antibody (MDR3M) (isotype: IgM) reactive with mdr3 gene product was generated by immunizing mice with mdr3 -specific peptide (H₂N-¹²WRPTSAEGDFELGISSKQKRKKTKTVKMI⁴¹G-COOH) and hybridizing the primed mouse splenic B cells with X63-Ag8,6.5.3 mouse plasmacytoma cells. MDR3M did not cross-react with mdr1 gene product. This monoclonal antibody may be useful for analyzing the role of mdr3 gene product in cells and tissues.     

Carbamazepine Side Effects in Children and Adults

Summary: Most of the side effects associated with carbamazepine (Tegretol^®, USP, Geigy Pharmaceuticals) therapy are mild, transient, and reversible with an adjustment in dosage or rate of dosage increase. Direct reports to Geigy Pharmaceuticals for the period 1975 to 1986 totaled 371 hematologic, 396 dermatologic, and 156 hepatic and pancreatic occurrences out of more than 4 million patients treated. These include 27 cases of aplastic anemia and 10 of agranulocytosis. In a study of the incidence of side effects in 220 children below the age of 16 years who were receiving carbamazepine, drowsiness, loss of coordination, and vertigo were the most commonly observed side effects and were almost always transient and dose related. The findings of this study are comparable with those of other series assessing carbam-azepine-associated adverse reactions in children and adults. Overall, 30 to 50% of children and adults were reportedly free of side effects in these studies. Recommendations for carbamazepine therapy include education of patients and parents in the nature and likelihood of possible serious adverse reactions and routine monitoring to detect laboratory abnormalities.     

The spermatozoal volume as indicative of the plasma membrane integrity (modification of the hypoosmotic swelling test). I. Methods

Summary. The aim of the present study was to establish a more differentiating indicator of plasma membrane integrity of spermatozoa than the classic version of the hypoosmotic swelling test according to Jeyendraan. Spermatozoa were prepared by density gradient centrifugation (90% Percoll) to select 'fertilization competent' spermatozoa only. After a second washing procedure sufficiently pure sperm cell suspensions were obtained. The volume distributions of these sperm cells were measured with a Coulter Counter at 25 °C after adaptation in 300 mosmolar NaCl solution resp. 150 mosmolar NaCl solution for 5 min. These volume distributions showed significantly different patterns for the isotonic and hypotonic stress situation in the simple salt solution. Moreover, the comparison of the response to hypoosmotic stress showed more than four reproducible characteristic patterns, promising well differentiated results for different sperm populations. The new method for the detection of hypoosmotic swelling effect might be a real and valuable functional parameter.     

Teaching sociology of medicine: the group process

As a part of any curriculum reorganization, new instructional methods are also tested. When the University of Turku sociology of medicine course was found to need renovation, its goals and objectives, content and instructional methods were closely examined and modified, in order to strengthen institutional and multiprofessional relations and reinforce sociocultural issues in doctors' competence with the patient. This paper discusses this change, emphasizing teaching and learning methodology.