Selective display of histamine receptors on lymphocytes.

Histamine, acting on histamine type 2 receptors, increases intracellular cyclic adenosine monophosphate (AMP) and thus modulates the immunologic functions of lymphocytes. Lymphocyte cyclic AMP levels were used to follow the development of histamine receptors. The B lymphocytes have no functional histamine receptors. As T lymphocytes "mature" in immunologic function--from thymocytes to cortisone-resistant thymocytes to splenic T lymphocytes--their response to histamine increases. The response of these subpopulations of lymphocytes to isoproterenol is the inverse of the histamine response. It is suggested that the changing display of histamine receptors plays an important part in the control of immunologic responses.

Purified staphylococcal alpha toxin: effect on epithelial ion transport.

Purified staphylococcal alpha toxin, when added to the serosal bathing medium of the isolated toad bladder, causes a rapid fall in short-circuit current and transepithelial potential difference. It has no effect when added to the mucosal bathing medium. Oxygen consumption by suspensions of minced bladder tissue is stimulated by the toxin. These effects are neutralized by staphylococcal antitoxin.

Effect of purified staphylococal alpha toxin on active sodium transport and aerobic respiration in the isolated toad bladder.

Purified staphylococcal alpha toxin was found to inhibit the active transport of sodium across the isolated toad bladder when applied to the serosal but not to mucosal surface. Heating or the addition of specific antitoxin abolished this effect. Low temperatures reduced this activity significantly. Application of vasopressin to the bladder serosa shortly after toxin resulted in only weak and transient stimulation of sodium transport; once maximal toxin activity had been established, exposure to the hormone was without effect. Transport in bladders previously stimulated by vasopressin was rapidly inhibited by alpha toxin. Concentrations that suppressed active sodium transport completely within 30-45 min produced a significant increase in oxygen consumption by minced bladder tissue within the same period; antitoxin neutralized this activity. 2,4-dinitrophenol also inhibited sodium transport and stimulated oxygen consumption by the toad bladder. The addition of 2,4 dinitrophenol to bladder tissue in which respiration was maximally stimulated by alpha toxin resulted in a further increase in respiratory rate. The addition of toxin to bladder tissue after its exposure to a concentration of 2,4 dinitrophenol known to uncouple oxidative phosphorylation produced a significant stabilization but no increment in respiratory rate. The data are consistent with the previously suggested action of staphylococcal alpha toxin on cell membranes and suggest that energy-dependent transport processes are inhibited. The stimulation of oxygen consumption may be due to an additional effect on oxidative phosphorylation.

Properties of a subpopulation of T cells bearing histamine receptors.

C57BL/6 mice immunized i.p. with alloantigen (P815 mastocytoma cells) develop cytolytically active thymus-derived (T) splenic lymphocytes. The definition of specific histamine receptor sites on effector T cells has been studied by measuring the in vitro effects of the hormone on cytolytic activity. Histamine was found to inhibit cytolysis reversibly and to increase lymphoid cell cyclic AMP levels. Both of these histamine activities were reversed by burimamide and metiamide; neither activity was affected by diphenhydramine or pyrilamine. These findings indicate that modulation of effector T cell activity by histamine is mediated only by one of the subtypes of tissue histamine receptors, designated a histamine-type 2 receptor. This receptor appears to be present on cytolytically active cells; there is no evidence for activation by histamine of auxiliary or "suppressor" cells. The estimated dissociation constant (KB) for the burimamide-receptor complex (9 times 10-minus 6 tm) and for the metiamide-receptor complex (8 times 10-minus 7 M) indicated that the histamine receptor on T cells is quite similar to histamine-type 2 receptors in other tissues. Cells bearing such receptors could not be isolated by passage through a column of histamine-coated tsepharose beads. The cytolytic activity of spleen cells taken from mice early (days 7-9) after immunization is virtually unaffected by histamine in vitro. In contrast, the activity of spleen cells taken from mice later in the immune response is progressively more susceptible to inhibition by histamine. After reaching a maximum at day 11, the spleen cell cytolytic activity falls in a pattern that parallels the increase in susceptibility to histamine. The susceptibility of effector T cells to histamine appears also to reflect their site of origin, for peritoneal exudate effector cells were found to be significantly less sensitive than spleen cells to inhibition by histamine. The progressive increase in inhibition by histamine apparently reflects the appearance of greater numbers of specific histamine-type 2 receptors, and is probably a general phenomenon, for spleen cells from A/J or C3H mice immunized with either P815 mastocytoma (H-2d) or EL-4 (H-2b) cells showed the same effect. However, the appearance of histamine receptors could be altered by prior immunization with an unrelated alloantigen: thus, when A/J mice are preimmunized with EL-4, a subsequent immunization with mastocytoma cells results in peak spleen anti-H-2d activity at day 9 instead of days 11-13, and the appearance of significant (greater than 40 percent) inhibition by histamine as early as day 8 instead of day 16. The physiological role of the histamine receptors is as yet undefined, though their unexpected rate of appearance on effector T cells, coincident with a decline in the number of lytically active cells in vivo, may be a significant hint that hormone receptors play a role in the control of T-cell proliferation.

Staphylococcal bacteremia in a "Germ-free" unit.

The rate of carriage and infections due to strains of Staphylococcus aureus were evaluated in adults with acute leukemia in isolators characterized by laminar air flow and barrier isolation. Patients were randomly given antimicrobial prophylaxis with oral nonabsorbed antibiotics and a nasal antibiotic ointment. In four years S aureus was isolated from the nostrils or other sites in 36 patients. Persistent isolation was noted in 24 patients. Suppression of gut flora was associated with a higher carriage rate of S aureus. Five episodes of bacteremia due to S aureus occurred at the nadir of leukopenia induced by chemotherapy. Death occurred within five days in the three patients whose peripheral white blood cell count did not rise. Patient isolation and suppression of gut flora helped reduce infections due to Pseudomonas sp and fungi, but S aureus emerged as a life-threatening pathogen.

Wound infections and systemic antibiotic prophylaxis in gynecologic surgery. A review.

The gynecologic literature was reviewed and yielded 11 well-designed and well-conducted studies since 1960 involving the use of systemic prophylactic antibiotics. Five had significant results that support using prophylactic antibiotics in vaginal hysterectomy while three supported prophylaxis in cesarean sections. A cephalosporin agent is effective as a prophylactic agent and should be administered 2 hours before surgery by the intravenous route and discontinued 24-72 hours after surgery. A change in the bacteriologic flora of the cervical cuff occurs after surgery with an increase in E. coli and enterococci and a decrease in coagulose negative staphylococci and steptococci. Future studies should be randomized, prospective, and performed in a double-blind manner with antibiotics begun preoperatively. Special attention should be given to bacteriologic techniques, especially the search for anaerobic pathogens.

Use of systemic antibiotics for prophylaxis in surgery: a critical review.

We reviewed the English-language literature over a 16-year period (1960 through 1976) on the subject of prophylaxis with systemic antibiotics in surgery. Trials in genitourinary and cardiovascular surgery were not reviewed. Our definition of prophylaxis is antibiotic administration of the absence of infection or contamination. Of 131 articles reporting clinical trials using systemic antibiotics for prophylaxis, only 24 met the criterion on an appropriately designed study that generated evaluable data. In these, systemic antibiotics were shown to be of value in reducing wound infections after abdominal and vaginal hysterectomy, cesarean section, biliary surgery, total hip replacement, and microneurosurgical craniotomy. Antibiotic prophylaxis was of no value in laparotomy and groin hernia repair. Patients undergoing any of 21 different operations did not benefit from prophylactic antibiotic administration, though study groups were too small or infection rates too low to allow for firm conclusions. In certain patients at high risk of infection, systemic prophylaxis is warranted. Future clinical studies must be designed as randomized, blinded, prospective trials, with antibiotics administered by a parenteral route beginning preoperatively.

Anatomic variations of the sella turcica.

Structural variations of the sella turcica occur more often than might be supposed. Some of these may assume technical significance in surgery for intracranial aneurysm.