Oral and dermatologic manifestations of HIV infection.

Because an estimated 1 million persons in the United States are infected with HIV, all physicians, especially those in primary care, need to be able to recognize the protean manifestations of the disease and make a diagnosis as early as possible. In this article, Drs Jewell and Sweet review the mucocutaneous conditions that occur in patients with HIV infection and discuss diagnostic clues and treatment.

Asymptomatic HIV infection. A primary care disease.

Asymptomatic human immunodeficiency virus infection is a disease entering the primary care arena more and more frequently. Patients may be monitored in this setting until complications and clinical deterioration develop (typically after several years). As the disease progresses, referral to consultants who specialize in AIDS may be appropriate. However, many patients do not live near a major healthcare center and do not have the financial, physical, or emotional capability to travel to one as they become sicker. In these cases, primary care physicians, with the aid of a personally chosen network of specialized consultants, should offer care as the disease progresses to its terminal stage.

FK-506 and cyclosporin A: selective inhibition of calcium ionophore-induced polymorphonuclear leukocyte degranulation.

This paper investigates the abilities of FK-506 and cyclosporin A (CsA) to inhibit human polymorphonuclear leukocyte (PMNL) degranulation. PMNLs, purified from human blood, were stimulated in vitro with A23187, ionomycin, the complement derived peptide C5a, formylmethionylleucinylphenylalanine (FMLP) or phorbol myristate acetate (PMA). Degranulation was assessed by measuring the release of either lactoferrin or N-acetyl-beta-D-glucosaminidase (NAG). Both FK-506 and CsA produced a concentration-related inhibition of degranulation induced by either A23187 or ionomycin but did not affect C5a-, FMLP- or PMA-induced degranulation. The IC50 values for inhibition of degranulation (approximately 0.7 nM for FK-506 and 33.7 nM for CsA) are very close to the published values for inhibition of human T-cell proliferation. Removal of calcium from the incubation medium with ethyleneglycolbis(aminoethylether)tetra-acetate (EGTA) totally inhibited calcium ionophore-induced degranulation but had no effect against C5a-, FMLP- or PMA-induced degranulation. Preincubation of PMNLs with actinomycin D or cycloheximide did not affect either A23187- or PMA-induced degranulation. Non-immunosuppressive analogs of CsA were ineffective at inhibiting degranulation. Rapamycin, a macrolide structurally related to FK-506, did not inhibit degranulation but it did antagonize the inhibition produced by FK-506. Given the similar profiles of activity of FK-506 and CsA in neutrophils and T cells, we conclude that similar activation or signal transduction pathways may be present in both T cells and neutrophils. Because A23187-induced PMNL degranulation was not sensitive to either actinomycin D or cycloheximide, it is apparent that the signal transduction pathways ultimately control different cellular functions.

How to assess the risk of HIV exposure.

The physician must screen patients for risk of exposure to the human immunodeficiency virus (HIV). This requires direct and specific questioning about blood product exposure, sexual practices and use of intravenous drugs. If risk factors are uncovered, patients must then be counseled on how to minimize their risk. The screening process is potentially uncomfortable for both the physician and the patient. However, intensive educational efforts, including behavioral changes, are necessary to reduce the number of HIV-infected individuals.

Activation of murine natural killer cells and macrophages by 8-bromoguanosine.

It has been shown that 8-bromoguanosine (8-BrGuo) activates T and B cells, but the underlying mechanism of this effect is not clear. We found that it also activates NK cells and macrophages by induction of IFN production. Culturing spleen cells with 8-BrGuo for 16 to 18 h induced cytotoxic activity to YAC cells. The cytotoxic cells expressed Qa-5, asialo-Gm-1, and NK-1.1 Ag. Similarly, preincubation of peptone-elicited peritoneal macrophages with 8-BrGuo induced macrophage cytolytic activity to P815 cells in an 18-h assay. Anti-IFN antibodies to IFN-alpha -beta and -gamma abolished these inductive events. Furthermore, elimination of asialo-Gm-1+ cells reduced the responses of NK and macrophages to 8-BrGuo, indicating that these cells possibly produce the IFN. We conclude from these observations that one biologic effect of 8-BrGuo is due to IFN production.

Breast feeding.

Breast feeding is becoming more popular among all socioeconomic classes. By providing instruction and care of the mother and infant, the physician can greatly enhance the chances for success. Although breast feeding is a natural function, the proper technique needs to be learned. There are relatively few contraindications. The infant requires vitamin K at the first opportunity and supplementation with vitamin D and fluoride as necessary. Recommended daily dietary allowances are increased for nursing mothers. The physician must understand the effects of different contraceptive methods on lactation.

Pig bronchial mucous membrane: a model system for assessing respiratory mucus release in vitro.

A convenient organ culture system is described in which fragments of mucous membrane isolated from bronchi of the pig were maintained in either screw-cap tubes or multiwell tissue culture plates. The mucous membrane of the pig bronchus, like that of the human, is rich in mucus-secreting submucosal glands and can respond to cholinergic stimulation in vitro by releasing either L-[3H]fucose- or L-[3H]serine-labeled acid-precipitable macromolecules. Reproducible cholinergic-mediated release of labeled macromolecules was attained by first washing the mucous membrane fragments in serum-free modified Earles medium (Dulbecco's) for 120 min at 4 degrees C. Maximum stimulation was obtained when the incubation medium was supplemented with 0.5-2.0% horse serum. Approximately 50% of L-[3H]fucose-labeled macromolecules were eluted in the void volume from a column of Sepharose CL-6B in 6 M urea. Cochromatography of L-[3H]- and L-[14C]fucose-labeled glycoproteins released by mucous membranes of control and methacholine-treated tissue fragments failed to reveal any significant difference in any specific population of fucose-labeled glycoproteins. It is concluded that, as a whole, many different labeled molecules are released in response to cholinergic stimulation. Taken together, these results suggest that the mucous membrane of the porcine bronchus is a useful in vitro model for studying respiratory mucus secretion.