HIV infection and tuberculosis.
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Biomedical subjects
Publications and source records attributed to R Zangerle.
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In the course of the infection with the human immunodeficiency virus (HIV), we frequently observe disorders of the mucous membranes and, occasionally, they present the first manifestation of HIV-induced immunodeficiency. Like in other organs, opportunistic infections and malignant tumors prevail as a result of the impaired immune system. Opportunistic infections are characterized by frequency (candidiasis), aggressive expansion, persistence, frequent recurrences, and resistance to therapy (gingivitis, parodontitis, herpes simplex, warts). Oral hairy leucoplakia is considered a specific lesion of HIV infection. Malignant tumors, such as Kaposi's sarcoma, non-Hodgkin's lymphoma, and squamous cell carcinoma, may cause marked morbidity in AIDS patients; occasionally, the clinical picture of Kaposi's sarcoma and non-Hodgkin's lymphoma is rather uncharacteristic. Other manifestations on the mucous membranes may arise in association with systemic reactions, such as drug eruptions, thrombocytopenic purpura, or acute HIV infection. The etiology of still other lesions of the mucous membranes (e.g. chronic recurrent ulcers, xerostomia, disorders of pigmentation) is incompletely understood. The awareness of these disorders of the mucous membranes in HIV infection is of diagnostic, therapeutic and epidemiological importance.
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Skin and mucous membranes including the oral mucosa are among the preferential locations of opportunistic infections and secondary neoplasms in patients infected with the human immunodeficiency virus (HIV). Infections of the oral mucosa such as thrush occur in a high percentage of AIDS patients, patients with AIDS-related complex or HIV-seropositive individuals. The clinical appearance of the infections (herpes virus infection, periodontitis) is often marked by aggressive expansion, frequent recurrences or resistance to therapy. Oral "hairy" leukoplakia is considered to be a characteristic lesion in HIV-infected individuals. Tumors like Kaposi's sarcoma, squamous cell carcinoma and non-Hodgkin lymphoma of the oral mucosa may cause marked morbidity in AIDS patients. Such oral lesions are frequently the first indication of an HIV-infection. Dentists should be aware of the oral manifestations of HIV-infection and initiate diagnostic and therapeutic measures in the interest of the patients and for epidemiologic reasons.
To evaluate the performance of a serological test for human immunodeficiency virus type 1 (HIV-1) infections based on the use of a recombinant envelope gene-derived protein as the antigen, we caused expression of a 1.4-kilobase fragment of HIV.DNA that codes for the complete gp41 transmembrane protein in an Escherichia coli expression vector and used Western blots (WB; immunoblots) prepared with recombinant material (pEX-41) to detect antibodies to HIV-1. This test detected all 339 sera which were positive by a combination of conventional serodiagnostic assays and produced no false-positive results with 311 negative samples. Also no false-positive results were obtained with 20 sera from systemic lupus erythematosus patients which had high titers of cross-reactive autoantibodies. In six cases, the pEX-41 WB proved to be more sensitive than individual assays applied on their own, and in five cases it was even more sensitive than a combination of conventional assays. We tested 221 sera in both our pEX-41 WB and a commercially available recombinant enzyme immunoassay (EIA [Abbott]). The results were identical in 188 cases. A total of 27 sera containing antibodies to gp41 as demonstrated in the pEX-41 WB, as well as the Abbott recombinant EIA, had no antibodies to the recombinant core antigen as measured in the Abbott EIA. However, 25 of these sera did stain the 24-kilodalton band on a WB with purified virus. Six sera that were positive in all of the conventional confirmatory assays and reacted strongly with the pEX-41 WB did not recognize the surface antigen used in the Abbott recombinant EIA. We conclude that the use of WB prepared with recombinant-derived p41 offers a very sensitive and specific method to detect antibodies to HIV.
Single photon emission computed tomography (SPECT) studies were performed in AIDS dementia complex using IMP in 12 patients (and HM-PAO in four of these same patients). In all patients, SPECT revealed either multiple or focal uptake defects, the latter corresponding with focal signs or symptoms in all but one case. Computerized tomography showed a diffuse cerebral atrophy in eight of 12 patients, magnetic resonance imaging exhibited changes like atrophy and/or leukoencephalopathy in two of five cases. Our data indicate that both disturbance of cerebral amine metabolism and alteration of local perfusion share in the pathogenesis of AIDS dementia complex. SPECT is an important aid in the diagnosis of AIDS dementia complex and contributes to the understanding of the pathophysiological mechanisms of this disorder.
A glycoprotein (s-GP III) was isolated from the soluble lysate of chromaffin granules by chromatography with immunoaffinity and lectin columns. An identical protein (m-GP III) was shown to be present in the granule membranes. The apparent molecular weight of these glycoproteins as determined by the electrophoresis system of Laemmli (1970) was 43,000 under reducing conditions. In the absence of mercaptoethanol they aggregated to dimers. Antisera were raised against both the soluble and the membrane-bound forms of this glycoprotein. With these antisera GP III was further characterized: Immunoreplicas were obtained after two-dimensional electrophoresis of soluble and membrane-bound proteins of chromaffin granules. GP III was identified as a protein with a rather broad pI (4.6-5.3), indicating microheterogeneity. As shown by subcellular fractionation, m-GP III is specifically confined to chromaffin granules. GP III can therefore be used as a marker for the membranes of these organelles. The soluble form is secreted from adrenal medulla during stimulation with carbamylcholine chloride. An immunologically identical antigen was detected in adeno- and neurohypophysis. The physiological function of GP III is still unknown. It does not demonstrate any of the enzymatic activities so far known to occur in chromaffin granules.
We have compared the amino acid and carbohydrate compositions, partial amino acid sequences, immunological crossreactivity, and physical properties of secretory protein I of the parathyroid gland and chromogranin A of adrenal gland. This comparison indicates that these proteins are similar molecules. Because secretory protein I is present in secretory granules containing parathormone and is cosecreted with the hormone, and because chromogranin A is contained within chromaffin granules and, likewise, is secreted with the catecholamines, the present observations raise the possibility that this class of protein plays a general role in hormone secretion or storage mechanisms.
Chromogranin A and two other proteins (A1 and A2) of the soluble proteins of bovine chromaffin granules were isolated by extraction from polyacrylamide gels after electrophoresis. The carbohydrate content of these proteins was 5%, with galactose, N-acetylgalactosamine, and sialic acid as the main sugars. Membranes of chromaffin granules were solubilized with sodium dodecyl sulphate (SDS) and three glycoproteins were isolated by sequential affinity chromatography on Concanavalin A (Con A) and wheat germ lectin (WGL) Sepharose columns. Two glycoproteins, designated GP II and III, were found to have a high carbohydrate content of about 30%. Mannose, galactose, N-acetylgalactosamine, and sialic acid were the main sugars. In addition membrane-bound dopamine beta-hydroxylase was isolated by this procedure. No significant differences between the carbohydrate composition of the membrane-bound and the soluble enzyme were revealed. It was shown that all four subunits of dopamine beta-hydroxylase possess carbohydrate chains with an affinity for Con A. The isolation methods established in this study will be useful for immunological studies on these glycoproteins.
A total of 38 isolates of Candida albicans were collected from clinical specimens and tested for minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of amphotericin B, flucytosine and fluconazole. For amphotericin B and flucytosine all patients had isolates with MICs < or = 2 micrograms ml-1 and < or = 8 micrograms ml-1 respectively. For fluconazole all but two isolates had MICs < or = 16 micrograms ml-1. In vitro susceptibility testing remains problematic since standardized methods have not been established and the susceptibility and resistance ranges of MIC/MFC values still have to be defined in relation to in vivo data. Nevertheless, these results indicate that topical application of amphotericin B (more than 1 kg of amphotericin B per year at an intensive care unit performing selective digestive tract decontamination on certain trauma patients) had no major impact on the resistance patterns of C. albicans. In contrast, in this study both fluconazole-resistant isolates were from AIDS patients who were known to have received fluconazole therapy. Treatment with fluconazole--quite common in patients with AIDS--may produce resistant fungal isolates.