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L Francis

Publications and source records attributed to L Francis.

44 records · Page 3Linked to original sources
PubMed1972

Studies on the mechanism of fever accompanying delayed hypersensitivity. The role of the sensitized lymphocyte.

Experiments have been carried out to investigate the possible role of the sensitized lymphocyte in mediating the fevers of delayed hypersensitivity. Rabbits were made delayed hypersensitive to one of several heterologous proteins (bovine gamma globulin, bovine serum albumin, or human serum albumin) by footpad injection of antigen or antigen conjugated with dinitrophenol and incorporated in complete Freund's adjuvant. At intervals after sensitization, various tissues were removed, and single cell suspensions were incubated overnight with either carrier protein or conjugate in vitro. Release of an endogenous pyrogen (EP) was assayed by intravenous injection of the supernatant fluid into unsensitized rabbits. Of the tissues tested only those containing both lymphocytes and pyrogen-producing cells, blood, spleen, and draining lymph nodes, released detectable amounts of EP when incubated with antigen in vitro. Incubation of normal blood cells with specifically sensitized lymphocytes and antigen also resulted in significant release of pyrogen. Similarly, blood leukocytes released EP in vitro after mixture with supernates derived from incubation of sensitized lymphocytes and antigen. Cells and supernatant fluids from draining lymph nodes were usually effective in activating normal blood leukocytes earlier after sensitization than were those from mesenteric lymph nodes, suggesting that such cells, or antigen, had migrated from the original site of sensitization. The activator was soluble, nonpyrogenic in the dosages tested, and required incubation of viable cells with specific antigen for its production. These properties suggest that it may belong to the class of "lymphokines," biologically active agents released from lymphocytes that have been activated by immunologic or certain nonimmunologic stimuli.

Animals↗
PubMed1971

Plasma prolactin activity in inappropriate lactation.

Using a bioassay dependent on the development of a lactogenic response in rabbit mammary tissue cultured in vitro, prolactin distinct from immunoreactive growth hormone has been found in the plasma of patients of both sexes with inappropriate lactation with and without evidence of pituitary tumours. It has also been found in one patient with primary hypothyroidism and galactorrhoea, and in another during chlorpromazine therapy, but not in nine patients with gynaecomastia without galactorrhoea. Plasma prolactin levels were examined in seven patients during oral glucose tolerance tests: no change occurred in the four patients with pituitary tumours, but the levels were suppressed in the three patients with normal pituitary fossae. Prolactin appears to be a distinct pituitary hormone in man, as in animals, and also to be aetiologically related to states of inappropriate lactation.

Acromegaly↗
PubMed1970

Studies on tuberculin fever. IV. The passive transfer of reactivity with various tissues of sensitized donor rabbits.

Utilizing techniques of passive transfer, we have investigated the factors responsible for production of fever when tuberculin is given intravenously to specifically sensitized rabbits. The ability to develop a febrile response to tuberculin could be passively transferred to normal recipients with viable mononuclear cells from peritoneal exudates, spleen, or lymph nodes of donor rabbits sensitized with BCG. Sensitivity was usually apparent 48 hr after transfer, maximal at 7 to 14 days, and rapidly declined thereafter. Granulocytes and nonviable, sonicated, mononuclear cells from similarly sensitized donors were unable to transfer this form of reactivity. Passive transfer of reactivity was also effected with plasma and serum, suggesting that the reaction of antibody with antigen contained in tuberculin is one of the initial steps by which the host cells are activated to release the endogenous pyrogen (EP) that mediates this form of hypersensitivity fever. An intravenous infusion of granulocytes, as well as of several types of mononuclear cells from sensitized donors, made most recipients responsive to the pyrogenic effect of old tuberculin (OT) given 2 hr later. Some of these passively transferred cells, such as the granulocyte and alveolar macrophage, may be activated in vivo by OT, as they are in vitro. However, in the case of splenic and lymph node cells that cannot be activated by OT to produce EP in vitro, it seems likely that an intravenous injection of OT causes these transferred, sensitized cells to liberate an intermediate substance that either directly, or in association with antigen, activates the host's normal cells to produce EP. In support of previous suggestions that leukocytes of several types, as well as phagocytic cells of the reticuloendothelial system, serve as potential sources of EP in tuberculin-induced fever, evidence was presented that OT also activates both granulocytes and mononuclear cells from sterile exudates of BCG-sensitized donors to produce EP in vitro.

Animals↗
PubMed1967

Release of an endogenous pyrogen in vitro from rabbit mononuclear cells.

The capacity of rabbit mononuclear cells to release an endogenous pyrogen (EP) in vitro has been studied. After incubation with tuberculin, preparations of predominantly monocytic cells, derived from the respiratory passages of the lungs of rabbits sensitized with BCG, were activated to release EP. Pyrogen production occurred more slowly with lung monocytes than with blood leukocytes of similarly sensitized rabbits and 9 to 10 hr incubation in a fully supportive medium was required to produce clear-cut results. As previously reported with blood leukocytes, mononuclear cells from the lungs of normal animals were also activated by tuberculin but to a lesser degree than were those from specifically sensitized rabbits. Under a variety of conditions, mononuclear cells from either spleen or lymph nodes of the same sensitized rabbits failed to release detectable amounts of pyrogen when incubated with tuberculin in vitro but were activated in a majority of instances when phagocytosis of heat-killed staphylococci was used as the stimulus. Release of pyrogen from lung monocytes appears to be an active process that is both temperature-dependent and requires protein synthesis. Neither serum antibody nor complement appears to play a role in this process. Evidence is presented that the granulocyte is the main source of pyrogen evolved by blood leukocytes incubated in vitro with OT or heat-killed staphylococci, whereas the lung macrophage and/or monocyte is responsible for most of the pyrogen released from the lung cell preparations. From these studies, it is concluded that mononuclear cells can be activated in vitro by several microbial stimuli and must be considered an additional cellular source of EP. The clinical implications of these findings for the pathogenesis of fever in granulomatous diseases where the monocyte is the predominant cell are discussed.

Animals↗
PubMedDate not supplied

[Behavior characterization of a model of Huntington's disease in rats, induced by quinolinic acid].

INTRODUCTION: Huntington's disease (HD) is a progressive neurodegenerative disorder, characterized by severe degeneration of basal ganglia neurons. Behavioral symptoms of HD include abnormal, uncontrollable and constant choreiform movements, impaired cognitive function and emotional disturbance. OBJECTIVE: In order to explore the changes of cognitive and motor functions induced by quinolinate lesion we realized this experiment. MATERIALS AND METHODS: We studied the behavior of rats with unilateral quinolinate induced lesions of the medial striatum. Intact 3 months old male rats (n = 23) were trained in the Morris Water Maze during three consecutive days, eight trials/day (acquisition), and before surgery they were randomly assigned either to intact or lesion groups. Fifteen days after the lesion the rats were tested using retention test (one day/four trials, with the escape platform in the same position as in acquisition test), on the next three days the rats were tested in the transfer test (three days/eight trials-day, with the platform in the new position). The Paw reaching test and the asymmetrical rotational behavior test in respond to amphetamine were also tested in these rats. RESULTS: Lesioned animals exhibited deficient retrieval of stored memories of visuospatial skills and impaired transfer of learning. In relation with motor activity the lesioned rats showed a profound impairment in the skill of the left forelimb for reaching food compared with its right forelimb as well as with the forelimb abilities of intact rats. The lesioned animals showed significant rotational behavior induced by amphetamine agonist, ipsilateral to the lesioned striatum. CONCLUSIONS: These results are consistent with the notion that the striatal degeneration could sufficiently account for the cognitive abnormalities associated with HD, and with the key role played by basal ganglia in enabling voluntary and postural adjustment of the movements.

Animals↗