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Biomedical subjects

H S Lawrence

Publications and source records attributed to H S Lawrence.

At least 19 recordsLinked to original sources

A controlled trial of bovine dialyzable leukocyte extract for cryptosporidiosis in patients with AIDS.

Cryptosporidial infection causes severe diarrheal disease in patients with AIDS. Fourteen patients with AIDS and symptomatic cryptosporidiosis were treated with a specific bovine dialyzable leukocyte extract (immune DLE) prepared from lymph node lymphocytes of calves immunized with cryptosporidia or a nonspecific (nonimmune) DLE prepared from nonimmunized calves. Six of 7 patients given immune DLE gained weight and had a decrease in bowel movement frequency, with eradication of oocysts from stool in 5 patients. Six of 7 patients given nonimmune DLE showed no decrease in bowel movement and 4, no clearing of oocytes from stool; 5 continued to lose weight. Subsequently, 5 of these 7 were treated with immune DLE; 4 had a decrease in bowel movement frequency and significant weight gain, with eradication of oocytes from stool in 2 patients. Immune DLE produces sustained symptomatic improvement in patients with AIDS and active cryptosporidiosis, but lack of an appropriate cryptosporidial antigen allows only postulation that an augmentation of cellular immunity to Cryptosporidium parvum induced by immune DLE resulted in the microbiologic and clinical improvement observed.

Acquired Immunodeficiency Syndrome

Fatal nonpowder firearm wounds: case report and review of the literature.

A previously unreported fatality due to a head wound from a CO2-powered BB pistol is described. In a review of the English language medical literature (primarily forensic), ten previous reports of fatality due to nonpowder firearms were found. A common mechanism is identified in the head wounds leading to fatality. Modern day technology has elevated the BB gun from toy to weapon. Often appearing trivial, BB and pellet gun injuries must be considered in the same class as those from small-caliber low-velocity powder firearms. A patient with a nonpowder firearm injury must be evaluated with a high index of suspicion for injuries that are not apparent during a general physical examination.

Carbon Dioxide

Treatment of cryptosporidiosis with oral bovine transfer factor.

Cryptosporidia are intestinal protozoans long known to cause diarrhea in humans, especially those with acquired immune deficiency syndrome (AIDS). When transfer factor prepared from calves which possessed delayed-type hypersensitivity to Eimeria bovis was given to nonimmune calves and mice it conferred protection against clinical infection (coccidiosis). Recent studies with oral bovine transfer factor have shown that it can confer cell-mediated immunity to humans. Based on these findings we decided to treat eight AIDS patients suffering from Cryptosporidium-associated diarrhea with transfer factor prepared from calves immune to Cryptosporidium. Prior to treatment with transfer factor, three patients had been treated with spiramycin, one patient with alpha-difluoromethylornithine (DFMO), and one patient with furazolidone for greater than 1 month without clinical or laboratory improvement. Following administration of transfer factor, five or eight patients exhibited a decrease in the number of bowel movements and the development of formed stools. Cryptosporidium was eradicated from the stools of four patients but two of these patients subsequently relapsed and one patient continued to have diarrhea despite the absence of Cryptosporidium in the stool. One patient has been free of diarrhea and Cryptosporidium for 2 years after discontinuation of transfer factor therapy.

Acquired Immunodeficiency Syndrome

Emergency department management of the intoxicated adolescent.

It is widely recognized that many young people will have experiences with alcohol and with psychoactive recreational drugs before emerging from the adolescent years. It is estimated that before leaving ninth grade, one half of the total student population will have had experience with alcohol, and approximately one third with marijuana. Cocaine also is more available to adolescents. For these reasons, the emergency physician is more likely to see teenage patients for drug-related problems.

Adolescent

Antigen-specific activity of murine leukocyte dialysates containing transfer factor on human leukocytes in the leukocyte migration inhibition (LMI) assay.

We report on the extension of the direct leukocyte migration inhibition (LMI) test as an assay for antigen-specific activity in human leukocyte dialysates (DLE) containing transfer factor to an evaluation of antigen-specific activity in DLE prepared from inbred mice. Murine DLE was observed to cause antigen-dependent and antigen-specific effects on the inhibition of migration of nonimmune human leukocyte populations. Pulsing of nonimmune human leukocyte with DLE preparations from BALB/c and SJL mice immunized with Candida, diphtheria toxoid, and SK-SD resulted in their inhibition of migration in the presence of the respective antigens. The antigen-specific activity in murine DLE was found to be present in lymph node cell preparations and to be absent from spleen cell preparations of the same donors. The activity of DLE in lymph node cells was found to be present in the theta-cell enriched subpopulation of nonadherent lymphocytes after passage through nylon wool columns. The antigen-specific activity of murine DLE, as we have reported for human DLE, was found to reside in the < 3500 dalton dialysis fraction and not in the < 3500 dalton fraction. We conclude that nonimmune human leukocytes in the LMI test provide a suitable assay for the detection of antigen-specific activity in murine DLE as well as that in human DLE. Additionally, murine DLE is active across species barriers and appears to share properties with human DLE.

Animals

Deletion of antigen-specific activity from leukocyte dialysates containing transfer factor by antigen-coated polystyrene.

We have reported finding antigen-specific activity in human leukocyte dialysates (DLE) containing TF in the leukocyte migration inhibition (LMI) assay. To analyze this activity further, we have used polystyrene bound to antibody or to antigen as immunoadsorbent for DLE before pulsing nonimmune cells in the LMI assay. Candida-(CAN) immune or diphtheria toxoid-(TOX) immune DLE were depleted of all antigen-specific activity after absorption with specific antigen but not affected by absorption with specific antibody, respectively, and depletion of activity with antigen was abrogated by coating bound antigen with specific antibody before absorption of DLE. CAN-immune, TOX-immune DLE was selectively depleted for either CAN activity or TOX activity after absorption with CAN- or TOX-coated polystryrene, respectively, retaining its CAN-activity when absorbed with TOX and conversely retaining its TOX activity when absorbed with CAN; thus the antigen-specific activity binds to related but not unrelated antigen. The polystyrene-bound antigen-specific activity could be recovered by treatment with 8 M urea. We interpret these findings to suggest that such antigen-specific activity may be either a dialysable fragment of a T cell antigen receptor site, or a portion of the V-region, or a unique Ir gene product that assists in antigen presentation to other T cells.

Absorption

Development of antigen-induced proliferative responsiveness by murine lymph node cells. I. Identification of differences in the in vitro proliferative responses during a first and a second period of responsiveness.

The development and course of antigen-induced proliferative responsiveness by murine lymph node cells (LNC) was observed for 16 weeks post-immunization. The initial phase of responsiveness was characterized by antigen-induced proliferative responsiveness in vitro which reached a maximum 3-5 weeks post-immunization and then declined to low levels by 6-8 weeks. Without injection of additional antigen, the initial phase of responsiveness was followed by the development of a second phase of antigen-induced proliferative responsiveness 10-12 weeks post-immunization. These findings suggest that the in vivo development of lymph node lymphocytes capable of a proliferative response to antigen is under some type of modulation which is maximal 6-8 weeks post-immunization. Early in the first phase the proliferative responses to higher concentrations of antigen peaked early in the culture period (days 3-4), whereas responses to the lower concentrations of antigen were optimal after 5-6 days of culture. During the latter half of the first phase, however, peak proliferative responses were made to all the concentrations of antigen on the same day of culture (day 6). In contrast, the responses detected at the beginning and throughout the second phase of responsiveness were characterized by maximum proliferation to all the concentrations of antigen late in the culture period (day 7). These results delineate the temporal requirements for maturation of antigen-induced proliferative responsiveness of murine LNC post-immunization and indicate the time interval when optimal responses may be detected.

Animals

Interaction of subpopulations of murine lymph node lymphocytes in antigen-induced [14C]-thymidine incorporation: T and B cell synergy in the response to antigen.

The antigen-induced [14C]-thymidine incorporation of murine lymph node cells (LNC) that were non-adherent (NAD) or adherent (AD) to nylon wool was studied. In contrast to NAD-LNC, AD-LNC responded like unfractionated LNC, and these responses were T lymphocyte dependent. By co-culturing NAD-LNC with subpopulations of AD-LNC the cellular requirements and interactions necessary for maximal incorporation of [14C]-thymidine were determined. A synergistic effect was observed when NAD-LNC and AD-LNC were co-cultured. Synergism was not dependent on T lymphocytes or macrophages in the AD-LNC population but was associated with the B lymphocyte subpopulation. These results indicate that the number of B lymphocytes present in a population of LNC can significantly influence the magnitude of the response to antigen.

Animals

A microculture system for the measurement of antigen-induced murine lymphocyte proliferation: advantages of 5% horse serum and 5 X 10(-5) M mercaptoethanol.

Short term microculture systems which measure murine lymphocyte proliferative responses to mitogens are well established. We demonstrate here that these microculture methods are not suitable for antigen-induced responses because of the high levels of murine lymphocyte proliferation in control cultures associated with the use of fetal calf serum or human serum. We also show that this problem can be eliminated with the use of a combination of 5% horse serum and 5 X 10(-5) M mercaptoethanol. We describe an antigen-induced murine lymphocyte proliferation microculture system in which good stimulation indices are achieved and the lymphocyte proliferation in control cultures remain at a low level throughout the 7 day culture period.

Animals

Concentrations of levamisole required for enhanced proliferation of human lymphocytes and phagocytosis by macrophages.

We studied the in vitro effects of levamisole on phagocytosis by macrophages and on proliferation of lymphocytes obtained from human peripheral blood. It was observed that levamisole directly stimulated phagocytosis in a lymphocyte-free system. Enhancement was optimal at a concentration that inhibited antigen- or mitogen-induced stimulation of sensitive lymphocytes. Lower concentrations of levamisole enhanced the proliferative lymphocyte response.

Dose-Response Relationship, Drug

In vitro augmentation of lymphocyte sheep cell rosette formation by leukocyte dialysates.

We have studied in vitro the effects of leukocyte dialysates containing transfer factor on the formation of sheep cell rosettes by human lymphocytes. Dialysate had no effect on the toral rosettes, but increased the number of rapidly forming ("active") rosettes. This was due to an increased affinity of the lymphocytes for the sheep red cell. Trypsin-treated lymphocytes regained the ability to form rosettes more rapidly when cultured with leukocyte dialysates than with control media. These experiments suggest that leukocyte dialysate acts to increase the number or arrangement of sheep cell receptors on the lymphocyte surface.

Cell Membrane

Requirement of precommitted cells as targets for the augmentation of lymphocyte proliferation by leukocyte dialysates.

After our initial report tha leukocyte dialysates containing transfer factor augment the thymidine incorporation of antigen-stimulated lymphocytes, we have adapted the system to microleukocyte cultures. This modification permits both (a) the simultaneous assay of a single dialysate on the cells of multiple individuals, and (b) the assay of multiple dialysates on the cells of a single individual. The data thus secured, demonstrate that dialysates from both skin-test-positive and -negative donors produced similar degrees of augmentation whether the data are expressed as an arithmetic difference or as a ratio. When expressed as an arithmetic difference, the amount of augmentation is increased in proportion to the level of thymidine incorporation of the assay cells when they were stimulated by antigen alone. When expressed as a ratio, however, the degree of augmentation is independent of the response of the assay cells. An analysis of the ability of dialysates to engage previously uncommitted lymphocytes and thus to augment thymidine incorporation, revealed that precommitted cells were required. In these experiments, antigen-reactive cells were deleted from populations of peripheral blood lymphocytes by incubation with purified protein derivative of tuberculin, diphtheria toxoid, or streptokinase-streptodornase in the presence of [3H]thymidine of high specific activity. This deletion depressed or abolished the effect of dialysate on the residual population when it was recultured with the same antigen, but the effect on the response of the remaining lymphocytes to other antigens was unaltered. In this study, leukocyte dialysate appeared to augment nonspecifically the thymidine incorporation of an antigen-specific precommitted clone of lymphocytes. The relationship of these adjuvant effects on peripheral blood lymphocytes in vitro to the specific and nonspecific activities of transfer factor in vivo remains to be elucidated.

Adjuvants, Immunologic