Lymphokine-activated killer cell regulation of T-cell-mediated immunity to Candida albicans.

Monocytes are important accessory cells in the activation of T cells for specific antigen recognition yet little is known of their regulation. We demonstrated here that interleukin-2 (IL-2)-induced human lymphokine-activated killer (LAK) cells can inhibit monocyte antigen presentation, depending on the state of differentiation of the monocytes. Adherent monocytes cultured for 4 days in medium or granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to equally process and present intact Candida albicans to autologous Percoll gradient-isolated T cells, as measured by [3H]thymidine uptake. However, only the GM-CSF-cultured monocytes were functionally inhibited by autologous 4-day IL-2-induced LAK cells. Even soluble candidal cell wall mannoprotein antigens could not be presented by these monocytes after exposure to LAK cells. Pretreatment of these monocytes with LAK cells for 1 h, followed by subsequent removal of the nonadherent LAK cells, was sufficient to cause significant inhibition, with maximal inhibition observed after 4 h. Northern (RNA) blot analysis indicated that mRNA expression for IL-1 alpha and IL-1 beta in response to C. albicans stimulation was also down-regulated in GM-CSF-cultured monocytes exposed to LAK cells. Interestingly, freshly isolated, Percoll gradient-purified large granular lymphocytes did not suppress antigen presentation in GM-CSF-treated monocytes. Another important finding was the inability of LAK cells to suppress the ability of freshly isolated or gamma interferon-cultured monocytes, which are resistant to LAK cell-mediated lysis, to present antigen to T cells. In contrast, IL-3 was similar to GM-CSF in inducing LAK cell susceptibility in monocytes. Taken together, these results indicated that IL-2 can induce LAK cells to down-regulate antigen presentation function in a select set of monocytes that have been activated by colony-stimulating factor (GM-CSF and IL-3) but not by gamma interferon. LAK cells may therefore play an important role in regulation of monocytes and their function, depending on their differentiation state.     

Managing Q fever during pregnancy: the benefits of long-term cotrimoxazole therapy.

BACKGROUND: Q fever is a zoonosis caused by Coxiella burnetii. During pregnancy, it may result in obstetric complications, such as spontaneous abortion, intrauterine growth retardation, intrauterine fetal death, and premature delivery. Pregnant women are exposed to the risk of chronic Q fever. METHODS: We included 53 pregnant women who received a diagnosis of Q fever. We compared the incidence of obstetric and maternal Q fever complications for women who received long-term cotrimoxazole treatment (n=16) with that for women who did not receive long-term cotrimoxazole treatment (n=37); long-term cotrimoxazole treatment was defined as oral administration of trimethoprim-sulfamethoxazole during at least 5 weeks of pregnancy. RESULTS: Obstetric complications were observed in 81.1% of pregnant women who did not receive long-term cotrimoxazole therapy: 5 (13.5%) women experienced spontaneous abortions, 10 (27%) experienced intrauterine growth retardation, 10 (27%) experienced intrauterine fetal death, and 10 (27%) experienced premature delivery. Oligoamnios was observed in 4 patients (10.8%). Obstetric complications were found to occur significantly more often in patients infected during their first trimester of pregnancy than in those infected later (P=.032). The outcome of the pregnancy was found to depend on placental infection by C. burnetii (P=.013). Long-term cotrimoxazole treatment protected against maternal chronic Q fever (P=.001), placental infection (P=.038), and obstetric complications (P=.009), especially intrauterine fetal death (P=.018), which was found to be related to placental infection (P=.008). CONCLUSIONS: Q fever during pregnancy results in severe obstetric complications, including oligoamnios. Because of its ability to protect against placental infection, intrauterine fetal death, and maternal chronic Q fever, long-term cotrimoxazole treatment should be used to treat pregnant women with Q fever.     

Development of Lhermitte's sign after bone marrow transplantation.

The authors observed Lhermitte's sign in four patients after bone marrow transplantation (BMT) for hematologic malignancies. Three patients had acute myelogenous leukemia (AML), and one had chronic myelogenous leukemia. Before BMT, the patients with AML received daunorubicin, cytosine arabinoside and etoposide, whereas the patient with chronic myelogenous leukemia received hydroxyurea. One patient with AML received MY-9 antibody-depleted autologous BMT. The other patients received human lymphocyte antigen-identical, allogeneic BMT. Preparative therapy for BMT was cytosine arabinoside, cyclophosphamide, and total body exposure to radiation for two patients, and busulfan, cyclophosphamide, and no exposure to radiation in two other patients. Lhermitte's sign appeared 4 to 8 months after BMT and resolved spontaneously after 2 to 5 months. Neurologic sequelae had developed in none of the patients 16 to 34 months after BMT. No unifying etiologic factor could be identified in these patients. The development of Lhermitte's sign after BMT appears to be a benign, self-limited phenomenon that requires no specific treatment.     

Sibship size, sibling sex ratio, birth order, and parental age in homosexual and nonhomosexual gender dysphorics.

This study investigated whether demographic variables previously reported to differentiate ordinary homosexuals from heterosexuals also differentiate gender-dysphoric homosexuals from gender-dysphoric persons with other sexual orientations. Subjects were outpatients aged 16 and older who were referred by physicians to a specialty clinic for the assessment of gender identity disorders. The subjects were divided into three groups: 204 homosexual women, 193 homosexual men, and 273 nonhomosexual men; the last category included men sexually attracted to females, to both sexes, and to neither sex. Demographic data on patients' families of origin were extracted from their clinical charts and from structured interview protocols. A multiple-range test at the .05 level showed that the homosexual men had significantly more siblings than the homosexual women, who, in turn, had significantly more siblings than the nonhomosexual men. The sibling sex ratio of the homosexual men, 131 brothers per 100 sisters, was significantly higher than the sex ratio of live births for the population as a whole (106 men per 100 women; p = .01); the sibling sex ratios of the other groups did not differ from the expected value. The homosexual men had a significantly later birth order than the nonhomosexual men (p = .004); the homosexual women, who fell in between, did not differ significantly from either male group. There were no between-groups differences in paternal or maternal age at the time of the subject's birth. The results concerning sibling sex ratio and birth order are consistent with previous findings for homosexual men.     

Mycobacteria and AIDS.

Mycobacteria are acid-fast, slow-growing microorganisms which have gained attention due to increasing prevalence in AIDS patients. Until the advent of AIDS, the only true pathogens of this group were Mycobacterium tuberculosis and M. leprae and the remaining mycobacteria were considered to be saprophytes or opportunistic pathogens. Infection with the MOTT (mycobacteria other than tuberculosis) bacilli was only seen in elderly or immunocompromised patients and was generally limited to caseating pulmonary granulomas, with rare extrapulmonary involvement. In AIDS patients, however, the incidence of mycobacterial infections ranges from 10 to 60% of HIV-positive persons, depending on location, method of identification, and patient population. Furthermore the pathogenesis of these mycobacterioses is distinct from that seen in non-AIDS patients because disseminated disease is the rule rather than the exception. Finally treatment of mycobacterial infections is increasingly difficult due to multiple drug resistances as well as the length of antimicrobial therapy required to cure the disease. Because of the prevalence and importance of these microorganisms, much research has been performed with the mycobacteria to develop new therapies and to understand their modes of pathogenesis.     

Cytomegalovirus (CMV) prophylaxis by acyclovir in pre-transplant CMV-positive renal transplant recipients

Abstract Cytomegalovirus (CMV) infections, either primoinfection or reactivation, remain an important problem in organ transplantation. We therefore designed a prospective study in which pre-transplant CMV-positive renal transplant (RT) patients were randomized to receive for 3 months starting immediately after transplantation either acyclovir or nothing. Between April 1992 and January 1993, 53 cadaveric renal transplantations were performed in our institution. The immunosuppressive regimen included anti-thymo-globulins (ATG), azathioprine, steroids and cyclosporine A. Patients randomized in the acyclovir arm received the drug from day 1 to day 90 (D 90) intravenously as long as the creatinine clearance was not above 10 ml/min and per os afterwards (3200 mg/day if the creatinine clearance was above 50 ml/min). CMV viraemia tests were systematically performed every 2 weeks until day 90 or when febrile episodes occurred. The patients were 53 adults who received a RT during the study period; 37 were included in the study of which 19 received acyclovir prophylaxis (group A) and 18, no prophylaxis (group B). The two groups did not significantly differ according to sex ratio, recipient's age, number of CMV-negative donors and number of days on ATG (10.76 ± 6.16 vs. 8.28 ± 4.21 days). There were significantly fewer viraemia episodes in group A ( n = 6) than in group B ( n = 13, P < 0.05); nevertheless, the percentage of symptomatic CMV viraemia was the same in both groups (35% vs. 38.5%). The onset of CMV viraemia occurred in the same period in both groups (39 ± 13.8 days vs. 34.3 ± 15 days; P = NS). The number of rejection episodes in the study period was the same in both groups (8 in each). We conclude from this prospective study that post-RT acyclovir prophyfaxis reduces significantly the number of CMV viraemia episodes but does not delay their onset. Furthermore, it has no effect upon the percentage of symptomatic viraemias.     

Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis in portacaval shunted rats

Hepatocarcinogenesis was initiated in rats with diethylnitrosamine(DEN) followed by a selection with 2-acetylaminofluorene (2-AAF).Portacaval shunt was then performed in order to promote tumordevelopment. Control rats were not submitted to the initiation-selectionprotocol and were sham-operated. In control rats, adenylatecyclase activity from crude liver membranes was stimulated 7-to 8-fold by maximal doses of glucagon (10^–6 M) or guanyl-5'-yl-imidophosphate[Gpp(NH)p] (10^–3 M), and 17-fold by a maximal (10^–5M) dose of forskolin. Guanosine-5'-O-(2-thiodiphosphate) inhibitedthe response to forskolin (–38%) and to low doses of glucagon(–50%). The initiation-selection protocol increased theactivity in basal conditions and in response to various stimuli.The portacaval shunt did not modify the activity of the enzymewith respect to basal activity or the response to glucagon.It significantly decreased the response to Gpp(NH)p (–45%)and to forskolin (–27%). The initiation-selection protocolincreased the basal activity of the enzyme (+150%) and its responseto Gpp(NH)p (+300%). When tumors developed, the activity ofthe cyclase further increased (+200%) and an inhibitory effectof GTP on the hormone-stimulated enzyme appeared (–40%).From these results, it is concluded that the promotion of hepatocarcinogenesisby portacaval shunt is coupled with modifications in the activityof adenylate cyclase in response to glucagon and guanylnucleotides.