Lymphomas with cytotoxic activity.
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Biomedical subjects
Publications and source records attributed to T W Chang.
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A unilateral vesiculobullous eruption associated with fever was seen on the neck, shoulder, and upper part of the chest of a 7-year-old boy. Although three dermatomes in all were involved, the lesions resembled herpes zoster. The patient had had varicella in infancy. Culture of fluid from several bullae yielded echovirus 6; however, and serum neutralizing antibody to this virus rose in titer from 1:32 to 1:640. It is suggested that echovirus 6 and other enteroviruses may cause a number of vesicular eruptions that resemble herpes zoster and similar infections. Viral culture, while often difficult to obtain, is the only way to identify the cause of eruptions like this one.
Some lymphocytes become highly motile upon immunological stimulation in vivo or in vitro. When introduced into a culture of 3T3 or L cells and followed by live-cell microscopy, some of these lymphocytes were observed to crawl on top of, along the edges of, and preferentially beneath the attached fibroblasts. The crawling could be as rapid as 20 mum/min, easily detectable without a time-lapse device. The striking ability of crawling lymphocytes to penetrate beneath attached 3T3 cells provided a quantitative means to compare the crawling activity of different lymphocyte populations under various conditions. Crawling was diminished by inhibitors of energy metabolism, by agents that disrupt the cytoskeleton, and by absence of Mg(2+) and Ca(2+), but not of Ca(2+) alone. Crawling lymphocytes were virtually absent in normal thymus and spleen cells. They increased greatly in 5-day mixed lymphocyte cultures and in peritoneal exudate lymphocytes taken after mice had been immunized with allogeneic tumor cells. T cells accounted for most of the crawlers. Of two T-cell leukemias tested, R1(+) cells were crawlers whereas EL-4 cells were not. The H-2 haplotype of the 3T3 fibroblasts (i.e., whether syngeneic or allogeneic) had no apparent effect on lymphocyte crawling activity. The crawling may relate to the exploration of cell surface antigens by lymphocytes (immune surveillance), to the mode of action of cytotoxic T cells, to the migration of lymphocytes across blood vessel walls, or to the penetration of lymphocytes into "solid" masses of normal tissue or tumor cells.
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Seven patients treated with oral cholestyramine for antibiotic-associated pseudomembranous colitis are reported. Response was variable with only one patient having a totally satisfactory clinical outcome. Five of seven patients had continued systemic signs with fever and leukocytosis throughout the course of cholestyramine. Two observations were relatively consistent. First, six of the seven patient had a decrease in the number of daily stools during therapy. Second, all patients showed persistence of the cytopathic toxin in stools obtained after three to seven days of cholestyramine therapy. Six patients who were subsequently treated with oral vancomycin had a prompt clinical improvement and clearance of the cytopathic toxin in the stool.
The ultrastructure of the surface of primary human amnion monolayer cells undergoing cytopathology induced by Clostridium difficile toxin was examined by scanning electron microscopy. Our observations indicated that the type and distribution of cell surface projections were altered dramatically by this toxin. The patterns of such surface changes were specific for the two different types of cells found in this cell culture. Cells with demarcated borders showed rearrangement of microvilli into globular chains or ridges which lined up with the branching membrane. Cells without demarcated borders exhibited studlike microvilli, all arranged into ridges or globular chains. These changes were noted after 1 h of toxin exposure and persisted without further progression, in spite of continued toxin exposure, up to 48 h. These data indicate that C. difficile produces a cytolytic toxin and that scanning electron microscopy may be useful in determining toxin-cell interactions.
The development of antiviral agents has been hindered by a variety of problems. There are fundamental biological differences between viruses and other infectious agents. Viruses are strictly dependent on cellular metabolic processes and possess very limited intrinsic enzyme systems and building blocks which may serve as targets for drugs. Antiviral drugs must also possess the ability to enter the host cell. Viral replication consists of a series of events, each of which can be interfered with, leading to interruption of the viral replication cycle. Currently, the major antiviral agents in therapeutic use are amantadine, idoxuridine and vidarabine. Methisazone and isoprinosine are also used in some areas. Immunoglobulins have some antiviral activity. Immune serum globulin and high titred hepatitis B immune globulin have both been used in prophylaxis of viral hepatitis. However, studies in this area have not been well controlled and results in some areas are conflicting. Interferon appears to be the most exciting antiviral agent yet discovered. However, its potential is limited by its availability, which remains dependent on biological method. Significant progress has been made recently, though, which may lead to the chemical synthesis of interferon and thus to an antiviral agent active against many viruses.
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Syrian hamsters are exquisitely sensitive to clindamycin; as little as 1 mg/kg of clindamycin given systemically causes a fatal colitis. Clindamycin and erythromycin were applied topically daily to the shaved backs of Syrian hamsters in a hydroalcoholic vehicle. A daily dose of 0.1 mg of clindamycin was lethal to more than half the hamsters and 1 mg to all the animals. The antibiotic-associated toxin from Clostridium difficile was present in their cecal material. Based on body surface areas and estimated usual volumes applied, the lethal dose in hamsters is not dissimilar to that given humans for acne. Oral tetracycline therapy protected the animals from clindamycin toxicity, but the animals died three days after stopping tetracycline if topical clindamycin applications were continued.
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A simple relationship has been derived that may be useful in determining the energy production in the tricarboxylic acid cycle in most tissues or whole organisms during fasting or exercise. The ratio of the rate of acetyl group oxidation to the rate of O2 consumption is nearly constant (0.34), irrespective of the proportion of glucose and fatty acids oxidized in a tissue or an organism. This relationship is derived by multiplying the respiratory quotient by the ratio of acetyl group oxidation to total CO2 production.
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A substance producing cytotoxicity in tissue culture was detected in stool specimens from all of four patients with pseudomembranous colitis due to antibiotics and in one of 54 with antibiotic-associated diarrhea. These stools also caused enterocolitis when injected intracecally into hamsters. On each occasion, cytotoxicity in tissue culture and enterocolitis in hamsters were neutralized by pretreatment with gas-gangrene antitoxin. The toxicity in both tissue cultures and hamsters could be reproduced with broth cultures of clostridia strains isolated from four of the five stools. These results suggest that toxin-producing clostridia are responsible for antibiotic-associated pseudomembranous colitis.