muramidase and HIV-Infections

Human immunodeficiency virus (HIV) and many other viruses can be isolated in blood and body fluids, including saliva, and can be transmitted by genital-genital and especially anal-genital sexual activity. The risk of transmission of HIV via oral sexual practices is very low. Unlike other mucosal areas of the body, the oral cavity appears to be an extremely uncommon transmission route for HIV. We present a review of available evidence on the oral-genital transmission of HIV and analyse the factors that act to protect oral tissues from infection, thereby reducing the risk of HIV transmission by oral sex. Among these factors we highlight the levels of HIV RNA in saliva, presence of fewer CD4+ target cells, presence of IgA antibodies in saliva, presence of other infections in the oral cavity and the endogenous salivary antiviral factors lysozyme, defensins, thrombospondin and secretory leucocyte protease inhibitor (SLPI).

Topics: CD4-Positive T-Lymphocytes; Defensins; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunoglobulin A, Secretory; Lactoferrin; Lactoperoxidase; Muramidase; Proteinase Inhibitory Proteins, Secretory; Proteins; RNA, Viral; Saliva; Salivary Proteins and Peptides; Secretory Leukocyte Peptidase Inhibitor; Sexual Behavior; Thrombospondins

Oral microbiome is the second largest microbial community in humans after gut. Human immunodeficiency virus (HIV) infection triggers an impairment of the immune system which could favour the growth and the colonization of pathogens in the oral cavity, and this dysbiosis has been associated with oral manifestations that worsen the quality of life of these patients. Antiretroviral therapy (ART) could also drive changes in specific oral bacterial taxa associated with such periodontal diseases. Integrase strand transfer inhibitors (INSTIs), therapy of choice in the treatment of naive HIV-patients, are able to reverse the impact of HIV infection on systemic inflammation, gut permeability, and gut bacterial diversity/richness. The objective of this study was to analyse the effects of HIV infection per se and INSTIs on salivary bacteriome composition, taking into consideration other factors such as smoking, that could also have a significant impact on oral microbiome. To accomplish this objective, 26 non-HIV-infected volunteers and 30 HIV-infected patients (15 naive and 15 under INSTIs-regimen) were recruited. Salivary samples were collected to measure lysozyme levels. Oral bacteriome composition was analysed using 16S rRNA gene sequencing. Naive HIV-infected patients showed statistically higher levels of lysozyme compared to controls (p < 0.001) and INSTIs-treated patients (p < 0.05). Our study was unable to detect differences in α nor β-diversity among the three groups analysed, although significant differences in the abundance of some bacterial taxonomical orders were detected (higher abundance in the phylum Pseudomonadota, in the order Acholeplasmatales, and in the genera Ezakiella and Acholeplasma in the naive group compared to controls; and higher abundance in the phylum Mycoplasmatota, in the order Acholeplasmatales, and in the genera Acholeplasma and uncultured Eubacteriaceae bacterium in the INTIs-treated HIV-infected patients compared to controls). These differences seem to be partially independent of smoking habit. HIV infection and INSTIs effects on oral microbiota seem not to be very potent, probably due to the modulation of other factors such as smoking and the greatest outward exposure of the oral cavity.

Topics: Anti-HIV Agents; HIV Infections; Humans; Integrase Inhibitors; Muramidase; Quality of Life; RNA, Ribosomal, 16S

Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis.. Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared.. Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits.. Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.

Topics: Adult; Anti-Infective Agents; beta-Defensins; Coinfection; Dysbiosis; Female; Genitalia, Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; Humans; Immunity, Mucosal; Interferon-gamma; Lactobacillus; Microbiota; Middle Aged; Muramidase; Secretory Leukocyte Peptidase Inhibitor; Tumor Necrosis Factor-alpha; Vagina; Virus Shedding

The aim of the present study was to compare the lysozyme concentration and candidal count in saliva between HIV-seropositive and HIV-negative individuals, and to correlate the relationship between lysozyme concentrations, candidal count, and CD4 count in HIV patients.. A study was conducted in 90 HIV-seropositive patients (subgroups: 1 [CD4 ≥ 500 cells/μL], 2 [CD4 200-499 cells/μL], and 3 [CD4 ≤ 200 cells/μL] and 30 HIV-negative individuals. A total of 6 mL unstimulated saliva was collected and stored at -80°C. Samples were centrifuged and divided into two portions of 600 μL each. One portion was used for the candidal assay and the other for the lysozyme assay using ready-made kits. Student's independent t-test and Karl Pearson correlation coefficient were used for the statistical analysis.. There was a significant increase (P < 0.001) in lysozyme levels and the candidal count in the saliva of HIV-positive individuals compared with the HIV-negative individuals. A significant increase (P < 0.004) in the salivary candidal count was observed in the HIV subgroups 1-3. There was a significant negative correlation (P < 0.01) between the CD4 and candidal counts in subgroup 1 (P < 0.02) and between the lysozyme concentration and CD4 count in subgroup 3. There was no correlation between the lysozyme concentration and oral candidal carriage.. An association exists between the lysozyme concentration and specific immunity. Yeast colonization serves as a marker of immunodeficiency in HIV disease progression.

Topics: Candida; Case-Control Studies; CD4 Lymphocyte Count; HIV Infections; Humans; Muramidase; Saliva

Insertion of T4 lysozyme (T4L) into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed.. We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects.. Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1) infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5.. Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.

Topics: 3T3 Cells; Animals; Antiviral Agents; Bacteriophage T4; Cell Line; Cell Membrane; Cell Movement; Chemokine CCL5; Chemotactic Factors; Down-Regulation; Escherichia coli; GTP-Binding Proteins; HIV Infections; HIV-1; Humans; Macrophages; Mice; Monocytes; Muramidase; Protein Binding; Receptors, CCR5; Recombinant Fusion Proteins; Solubility; Tissue Donors; Viral Tropism; Virus Replication

The World Health Organization recommends human immunodeficiency virus (HIV)-positive mothers in resource-poor regions heat-treat expressed breastmilk during periods of increased maternal-to-child transmission risk. Flash-heat, a "low tech" pasteurization method, inactivates HIV, but effects on milk protein bioactivity are unknown. The objectives were to measure flash-heat's effect on antimicrobial properties of lactoferrin, lysozyme, and whole milk and on the digestive resistance of lactoferrin and lysozyme.. Flash-heated and unheated breastmilk aliquots from HIV-positive mothers in South Africa were "spiked" with Staphylococcus aureus and Escherichia coli and then cultured for 0, 3, and 6 hours. Lysozyme and lactoferrin activities were determined by lysis of Micrococcus luteus cells and inhibition of enteropathogenic E. coli, respectively, measured spectrophotometrically. Percentages of proteins surviving in vitro digestion, lactoferrin and lysozyme activity, and bacteriostatic activity of whole milk in heated versus unheated samples were compared.. There was no difference in rate of growth of E. coli or S. aureus in flash-heated versus unheated whole milk (p = 0.61 and p = 0.96, respectively). Mean (95% confidence interval) antibacterial activity of lactoferrin was diminished 11.1% (7.8%, 14.3%) and that of lysozyme by up to 56.6% (47.1%, 64.5%) by flash-heat. Digestion of lysozyme was unaffected (p = 0.12), but 25.4% less lactoferrin survived digestion (p < 0.0001).. In summary, flash-heat resulted in minimally decreased lactoferrin and moderately decreased lysozyme bioactivity, but bacteriostatic activity of whole milk against representative bacteria was unaffected. This suggests flash-heated breastmilk likely has a similar profile of resistance to bacterial contamination as that of unheated milk. Clinical significance of the decreased bioactivity should be tested in clinical trials.

Topics: Anti-Infective Agents; Breast Feeding; Developing Countries; HIV Infections; HIV-1; Hot Temperature; Humans; Infectious Disease Transmission, Vertical; Lactoferrin; Microbial Sensitivity Tests; Milk, Human; Muramidase; Risk Factors; Sterilization

Human immunodeficiency virus type 1 (HIV-1) utilizes the macromolecular machinery of the infected host cell to produce progeny virus. The discovery of cellular factors that participate in HIV-1 replication pathways has provided further insight into the molecular basis of virus-host cell interactions. Here, we report that the suppressor of cytokine signaling 1 (SOCS1) is an inducible host factor during HIV-1 infection and regulates the late stages of the HIV-1 replication pathway. SOCS1 can directly bind to the matrix and nucleocapsid regions of the HIV-1 p55 Gag polyprotein and enhance its stability and trafficking, resulting in the efficient production of HIV-1 particles via an IFN signaling-independent mechanism. The depletion of SOCS1 by siRNA reduces both the targeted trafficking and assembly of HIV-1 Gag, resulting in its accumulation as perinuclear solid aggregates that are eventually subjected to lysosomal degradation. These results together indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.

Topics: Acquired Immunodeficiency Syndrome; Cell Line; Cell Membrane; Gene Products, gag; HIV Infections; HIV-1; Humans; Jurkat Cells; Microscopy, Electron; Microscopy, Electron, Transmission; Muramidase; Plasmids; RNA Processing, Post-Transcriptional; RNA, Small Interfering; Signal Transduction; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins; Virus Replication

The aim of the study was the comparison of lysozyme concentration and peroxidase activity in mixed, non-stimulated saliva of HIV-positive patients and healthy subjects.. The study was carried out in the group of 37 patients infected with HIV. The control group comprised of non-infected individuals, counterpart of the examined group. Mixed non-stimulated saliva, collected using expectoration method in the amount of 3-5 ml 2 hours after meal, was used for the study. Saliva samples were centrifuged, divided into portions 200 microl each, and stored at -80 degrees C. Peroxidase activity was determined using the method by Mansson-Rahemtull et al. Lysozyme concentrations were determined with the use of radial immunodiffusion method, ready-made kits (Human NL Nanorid plate--The Binding Site Ltd., UK).. Higher concentrations of lysozyme as well as peroxidase activity were observed in the group of patients with HIV as compared to the control group, and they were 35.08 microg/ml, 46.74 IU/1, 21.3 microg/ml, 37.73 IU/l, respectively. The difference was statistically significant only in case of peroxidase activity.. 1. HIV infection triggers immune mechanisms, that are manifested by the increase in salivary enzymes responsible for local non-specific resistance. 2. The immunological resistance decrease, manifested by the drop of the absolute number of CD4 lymphocytes T, is compensated by the increase in lysozyme concentration and peroxidase activity in non-stimulated saliva of HIV-positive patients.

Topics: Adult; Aged; Female; HIV Infections; Humans; Male; Middle Aged; Muramidase; Peroxidase; Saliva

The aim of this study was the evaluation of connection between parodontium determined by using GI and PBI indexes and specific immunity status and non-specific in HIV infected group and in control group.. The study was carried out in the group of 37 patients infected with HIV. Mixed non-stimulated saliva was used for the study. Peroxidase activity was determined using the method by Mansson-Rahemtull. Lysozyme and A, G, M antibodies concentrations were determined with the use of radial immunodiffusion method. The concentration of lactoferrin was determined by using ELISA method. The clinical state of parodontium estimated by means of GI and PBI evaluating quality changes in the gum.. Deterioration of the immunological status of subjects was accompanied by the increase of the values of GI and PBI. The strong negative correlation between GI and PBI and the concentration of lactoferrin and positive activity of the peroxidase in the whole examined population was determined. In the infected group the correlation between the status of gingiva expressed by GI and concentration or activity of examined enzymes and immunoglobulins was not ascertained.. 1. HIV infection is connected to worsening of paradontium status expressed by values of GI and PBI indexes. 2. Paradontium status correlated positively with immunological status of HIV positive subjects. 3. In HIV infected group, no connection between number of IgA, IgG, IgM, concentration of lysozyme, lactoferrin, activity of peroxidase and paradontium status was observed.

Topics: Adult; Aged; Female; HIV Infections; Humans; Immunoglobulins; Lactoferrin; Male; Middle Aged; Muramidase; Periodontal Diseases; Periodontium; Peroxidase; Saliva

To identify which proteins are differentially secreted from monocyte/macrophages (M/M phi) of HIV-1 seropositive patients with HIV-1-associated dementia (HAD).. To compare profiles of secreted M/M phi proteins from individuals with HAD, HIV-1 infection or controls using surface-enhanced laser desorption/ionization (SELDI)-time of flight (TOF) ProteinChip technology.. M/M phi were isolated by Percoll gradient centrifugation and cultured from whole blood of 11 patients with HAD, 13 HIV-1 seropositive subjects with no dementia (HIV-1 group) and nine HIV-1 seronegative subjects (controls). M/M phi supernatants were removed after 7 days in culture and analyzed by SELDI-TOF. A 14.6 kDa-secreted protein in control M/M phi supernatants was significantly decreased in patients with HAD. The protein was purified from HIV-1 seronegative controls and identified by peptide mapping. Protein concentration in the supernatants was quantified by enzyme-linked immunosorbent assay.. A 14.6 kDa protein was identified as lysozyme. Secreted lysozyme concentrations from M/M phi of patients with HAD (81 +/- 35 ng/ml) were significantly lower than that of the HIV-1 group (326 +/- 303 ng/ml) and controls (764 +/- 211 ng/ml). Intracellular lysozyme was similar in all three groups. All patients with HAD were on highly active antiretroviral therapy (HAART). There was no correlation between lysozyme, viral load, CD4 cell count or use of HAART.. A comparison of protein profiles from M/M phi supernatants of patients with HIV-1 infection indicated a specific protein consistently decreased in HAD. The protein was identified as lysozyme, a major macrophage defense protein. This further demonstrates macrophage dysfunction as a significant consequence of HAD.

Topics: AIDS Dementia Complex; Antiretroviral Therapy, Highly Active; Biomarkers; CD4 Lymphocyte Count; HIV Infections; HIV-1; Humans; Macrophages; Muramidase; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Viral Load

The aim of this study was to explore lysozyme and lactoferrin concentrations in human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis (OPC). These proteins were measured by time-resolved immunofluorometric assay, validated in Part I of this study, in paired serum and salivary secretions of 30 patients. Eleven HIV-positive patients without OPC, eight HIV-positive patients with OPC and eleven HIV-negative healthy subjects were included in the study. The relative coefficient of excretion of salivary albumin was used to establish protein origin. In serum, the low lactoferrin concentrations in HIV-infected patients with and without OPC (0.610 mg/l (p < 0.05) and 0.896 mg/l (p < 0.01) vs. 1.439 mg/l in healthy subjects) were probably due to a decrease in nonspecific immunity, particularly the polymorphonuclear cells. In HIV-infected patients with OPC, the high salivary lysozyme and lactoferrin concentrations (170.94 mg/l and 66.48 mg/l vs. 23.35 mg/l and 10.20 mg/l in healthy subjects, respectively) and their mean relative coefficient of excretion of above 1 indicated a high local production of lysozyme and lactoferrin in saliva. The development of OPC in HIV-infected patients could be a consequence of inefficient lysozyme and lactoferrin concentrations and of decreased cooperation between innate and adaptative immune systems.

Topics: Candidiasis, Oral; Female; Fluoroimmunoassay; HIV Infections; Humans; Lactoferrin; Male; Mucous Membrane; Muramidase; Reference Standards; Saliva; Sensitivity and Specificity; Time Factors

To evaluate the salivary lysozyme concentration, flow rate and pH of a predominantly Chinese, HIV-infected group in Hong Kong, and to compare with an equal number of age and gender-matched HIV-free individuals.. A prospective longitudinal study over a 12-month period of 32 predominantly Chinese, male, HIV-infected group in a hospital setting in Hong Kong. Whole saliva collection by expectoration, lysozyme evaluation by 'lysoplate method'; pH and flow rate evaluation using standard methods and correlation with other clinical parameters using regression analysis.. The flow rate and the pH of saliva were lower compared with HIV-free, healthy individuals (both P < 0.0001) and salivary lysozyme concentration of the HIV-infected group was 23% higher compared with the HIV-free group (P < 0.001), though there was no significant difference between the lysozyme output (P > 0.05) expressed as microg min-1. On multiple regression analysis, intravenous drug users had a higher salivary lysozyme concentration compared with the homosexual group (P = 0.0015) though other variables investigated were not significantly related to the salivary lysozyme concentrations.. The significant changes in the flow rate, pH value and lysozyme concentration of whole saliva of the HIV-infected individuals as compared with the HIV-free, healthy individuals, may be due to the disease itself or a combination of factors including the medications used in the disease management.

Topics: Adult; Candida albicans; Case-Control Studies; HIV Infections; Hong Kong; Humans; Hydrogen-Ion Concentration; Longitudinal Studies; Male; Middle Aged; Muramidase; Regression Analysis; Saliva; Secretory Rate

Human milk contains important immunological factors that protect the breast from infection and are thought to protect infants from infection, including human immunodeficiency virus (HIV) infection. Human milk immunological factors have not been well characterized in HIV-infected lactating women. Lysozyme, secretory leukocyte protease inhibitor (SLPI), sodium (an indicator of mastitis), and HIV were measured in breast milk of 334 HIV-infected women at 6 weeks postpartum. Women with mastitis, as indicated by elevated breast milk sodium concentrations, had higher median levels lysozyme (290 vs 221 mg/L, p < 0.04), SLPI (38 vs 19 mg/L, p < 0.0001) and HIV (920 copies/mL vs undetectable, p < 0.0001) compared with women without mastitis. Lower total plasma carotenoid levels (p < 0.02) and higher maternal HIV load (p < 0.006) by quartile were risk factors for mastitis. Mastitis, as indicated by elevated breast milk sodium levels, is associated with high concentrations of immunological factors and higher HIV load in breast milk.

Topics: Adult; Carotenoids; Female; HIV Infections; Humans; Longitudinal Studies; Malawi; Mastitis; Milk, Human; Muramidase; Pregnancy; Proteinase Inhibitory Proteins, Secretory; Proteins; Puerperal Disorders; Risk Factors; Secretory Leukocyte Peptidase Inhibitor; Sodium; Viral Load

The mechanisms accounting for T cell depletion in AIDS patients are not yet fully understood, nor are the roles of host factors in HIV pathogenesis. We show here that an ongoing humoral immune response to HIV gp120 can sensitize non-infected cells towards apoptosis. Thus, i.v. injection of 1 microg recombinant(r) gp120 into gp120-immunized human CD4-transgenic mice (huCD4 Tg), which express huCD4 on both T and B cells, results in T and B cell depletion in peripheral blood and lymphoid tissues. On day 6 after a bolus injection of gp120, the numbers of peripheral T cells and B cells in gp120-immunized huCD4 Tg decreased sevenfold and two- to threefold, respectively. Annexin V staining revealed a higher percentage of early apoptotic cells on day 1 of gp120 i.v. injection from gp120-primed huCD4 Tg spleens compared to gp120-primed controls. Boosting the primed huCD4 Tg mice with soluble gp120 and hen egg-white lysozyme led to lower secondary titers to both antigens than found in controls. Furthermore, splenocytes from gp120-pretreated immunized huCD4 Tg had a lower level of stimulation in response to anti-CD3 treatment. These in vivo results are consistent with in vitro data demonstrating that cross-linking CD4 on splenocytes of huCD4 Tg by rgp120SF2 and anti-gp120 not only sensitizes T cells for apoptosis, but also induces apoptosis per se, and suggest that anti-gp120 responsiveness can contribute to T cell depletion in AIDS.

Topics: Animals; Apoptosis; B-Lymphocytes; CD3 Complex; CD4 Antigens; CD4 Lymphocyte Count; Female; HIV Antibodies; HIV Envelope Protein gp120; HIV Infections; Humans; Immunization; In Vitro Techniques; Injections, Intravenous; Lymphoid Tissue; Lymphopenia; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Muramidase; Recombinant Proteins; T-Lymphocytes

It has been demonstrated that morphine stimulates the replication of human immunodeficiency virus in peripheral blood mononuclear cells as well as in Kupffer cells. Since the mechanism of action of this drug is still unknown, we have studied its effects on different properties of isolated human blood monocytes. In the presence of morphine, cultured monocytes showed an increase in the fluidity of their membranes as well as an inhibition in their capacity to differentiate into macrophages. Furthermore, the response of the cells to interferon-gamma was significantly decreased and the release of superoxide anions was altered. Finally the production of interferon-alpha and of prostaglandin E2 induced by stimulation of the cells with endotoxin (LPS) was diminished. We conclude that morphine decreases the functions of monocytes that are essential for their antiviral defence and inhibits their response to activating stimuli, which may explain the increased multiplication of HIV in morphine treated monocytes.

Topics: Biopterins; Cells, Cultured; Dinoprostone; HIV; HIV Infections; Humans; Interferon-alpha; Monocytes; Morphine; Muramidase; Neopterin; Substance Abuse, Intravenous; Superoxides; Virus Replication

The catalytic concentration of pleural adenosine deaminase (ADA) and the ratio of pleural lysozyme (PL) to serum lysozyme (SL) were measured in consecutive patients (49 tuberculous and 179 nontuberculous) with two automated procedures in a Hitachi 717 analyzer. Using sensitivity and specificity curves, we established cutoff values at 33 U/L for ADA and 1.7 for the PL/SL ratio. The sensitivity of ADA activities for tuberculous effusion was 90%, specificity 85%. Combining ADA with the PL/SL ratio enhanced specificity to 99%. However, high values for ADA and lysozyme ratios are not, alone or in combination, sensitive or specific enough to replace pleural biopsy or culture of pleural fluid for the diagnosis of tuberculous empyema.

Topics: Adenosine Deaminase; Autoanalysis; Clinical Enzyme Tests; Diagnosis, Differential; Empyema, Tuberculous; HIV Infections; Humans; Muramidase; Pleural Effusion; Prospective Studies; Reference Values; Tuberculosis

beta 2-Microglobulin and lysozyme were determined in paired serum and cerebrospinal fluid samples from 137 patients, using immunofluorometry and ELISA, respectively. Of these patients, 54 were infected by human immunodeficiency virus type 1 (HIV1) (including 20 AIDS dementia patients), 73 were HIV1-seronegative with neurological diseases (meningitis (n = 10), multiple sclerosis (n = 29), other neurological diseases (n = 34)) and 10 were controls. Intrathecal synthesis of beta 2-microglobulin occurred in each group. Conversely, lysozyme intrathecal synthesis was found only in meningitis (10/10) and in HIV1-infection (24/54). A pathological increase in beta 2-microglobulin intrathecal synthesis (> or = 2 mg/l) was observed in 45 patients (34 HIV1-infected patients and 11 HIV1-seronegative patients with neurological diseases). Serum concentration and intrathecal synthesis of beta 2-microglobulin were correlated only in the 20 AIDS dementia patients. The cerebrospinal fluid beta 2-microglobulin and lysozyme concentrations were correlated in the 54 HIV1-infected patients only. Blood CD4 + T-cell count was correlated negatively with beta 2-microglobulin intrathecal synthesis but not with lysozyme intrathecal synthesis. These data suggest that in the absence of any central nervous system opportunistic process the increase of beta 2-microglobulin intrathecal synthesis (> or = 2 mg/l) may be a reliable marker of central nervous system involvement in HIV1-infected patients. Intrathecal synthesis of lysozyme was related principally to HIV1-encephalitis and central nervous system opportunistic processes.

Topics: Adult; AIDS Dementia Complex; Albumins; beta 2-Microglobulin; Biomarkers; Central Nervous System Diseases; Complement C4; Female; HIV Infections; HIV-1; Humans; Immunoglobulins; Male; Middle Aged; Muramidase; Predictive Value of Tests; Spinal Cord

Lactoferrin, lysozyme, interferon, and neopterin levels were determined in parotid saliva from 44 individuals with different clinical stages of human immunodeficiency virus (HIV) infection and 19 HIV-seronegative controls. The secretory output of individual components was calculated according to the fluid flow rate. No parotid interferon activity was found in any of the HIV-infected subjects or controls, and no significant differences in parotid lysozyme or neopterin outputs were observed. The lactoferrin output was significantly decreased in HIV-seropositive subjects in parallel with their markedly reduced parotid secretory IgA output. This combined deficiency of parotid lactoferrin and secretory IgA may well contribute to the frequent oral infections seen in subjects with HIV infection.

Topics: Adult; Biopterins; HIV Infections; Humans; Interferons; Lactoferrin; Male; Mouth Diseases; Muramidase; Neopterin; Parotid Gland; Saliva

Parotid flow rate and chemistry of 78 HIV + gay/bisexual men and 27 HIV-gay/bisexual controls were compared on a longitudinal basis at 4-month intervals over a 1 yr period for changes indicative of inflammatory or autoimmune diseases of the salivary glands, or reduced protective capacity toward oral opportunistic infection. Parotid saliva was examined for concentrations of sodium, chloride, phosphate, total protein, lysozyme, lactoferrin, secretory IgA, salivary peroxidase, histatin and albumin. Chloride, lysozyme and peroxidase were significantly higher in HIV + at all 3 examinations and increased in concentration over time. Although mean values for stimulated flow rate were not significantly different in the two groups over the year, there was a significant increase in the number of HIV + with reduced flow over time. In 6% of HIV + there was a marked reduction in flow rate and Sjögren's syndrome-like elevations in parotid chemistry but no enlargement. At all examinations low flow rate was significantly related to oral candidiasis; T4 levels were inversely related to oral candidiasis, but not to concentration of salivary components or flow rate; nor was AZT use. As a group the HIV + patients maintained normal flow rate and secreted normal or elevated concentrations of protective proteins. A subgroup, however, exhibited diminished flow over time and an increasing tendency to oral candidiasis and a diminution in output of histatins.

Topics: Adult; Bisexuality; Candidiasis, Oral; Chlorides; HIV Infections; HIV Seropositivity; HIV-1; Homosexuality; Humans; Lactoferrin; Longitudinal Studies; Male; Muramidase; Parotid Gland; Peroxidases; Saliva; Secretory Rate; Sodium

Active tuberculosis (TB) and leprosy are difficult to diagnose early because there are few organisms to detect and the specific immune response does not distinguish between active and inactive disease. We developed an immunoassay for lysozyme to see whether serum lysozyme levels could be used to identify individuals with clinical leprosy or TB. The immunoassay for lysozyme proved superior to standard enzyme assays that were less sensitive and reliable. The lysozyme assay was compared with assays for antibodies to Mycobacterium tuberculosis lipoarabinomannan (LAM) and M. leprae phenolic glycolipid-1. The sera tested were from Ethiopian leprosy (paucibacillary and multibacillary) and TB patients and from healthy Ethiopian and U.S. controls. The lysozyme assay was able to detect more of the individuals with TB (sensitivity, 100% for 19 patients) or leprosy (sensitivity, 86% for 36 patients) than either antibody assay. In particular, lysozyme levels were raised in a higher proportion of the paucibacillary leprosy patients (83% of 17), for whom the antibody assays were less sensitive; the LAM IgG and the phenolic glycolipid-1 IgM levels were raised in only 62 and 44% of 16 patients, respectively. The data suggest that lysozyme measurements may be useful in the diagnosis of mycobacterial infections and other chronic infectious granulomatoses.

Topics: Antibodies, Bacterial; Antigens, Bacterial; Glycolipids; HIV Infections; Humans; Immunoassay; Leprosy; Lipopolysaccharides; Muramidase; Tuberculosis

The in vitro maturation of peripheral blood monocytes to macrophages can be followed morphologically, and by measurement of cell surface antigens (CD4, HLA-DR, and FcR III) and lysozyme production. We used these markers to correlate monocyte maturation with susceptibility to human immunodeficiency virus (HIV) infection. Maturation of peripheral blood monocytes is associated with a decrease in membrane CD4, while HLA-DR and FcR III expression increase along with lysozyme secretion. Cells at all stages of maturation were susceptible to HIV infection, even mature macrophages without CD4 detectably by immunofluorescent staining. Maximal replication was observed in 7-day-old cells.

Topics: Antibodies, Monoclonal; Antigens, Surface; CD4 Antigens; Disease Susceptibility; Fluorescent Antibody Technique; HIV Infections; HLA-DR Antigens; Humans; In Vitro Techniques; Macrophages; Monocytes; Muramidase; RNA-Directed DNA Polymerase; Virus Replication

Parotid and submandibular gland function were evaluated in 12 HIV-1 antibody-positive men at two visits separated by a median interval of 14.5 months (range 6-22 months). Unstimulated and stimulated flow rates, and the concentrations of total protein, lysozyme, albumin and lactoferrin in these secretions, were determined. Parotid and submandibular gland secretions changed in a specific fashion with time. Lysozyme levels in both glandular stimulated secretions showed significant changes (approximately 40% and 70% elevated, between visits, in parotid and submandibular saliva, respectively). In addition, the frequency with which albumin was detected in unstimulated parotid secretions increased with time. These findings support earlier results suggesting the presence of alterations in major salivary gland function following HIV-1 infection. Submandibular gland function appears to manifest these alterations earlier, but with time the parotid secretions show similar changes.

Topics: Albumins; HIV Infections; Humans; Lactoferrin; Longitudinal Studies; Male; Muramidase; Saliva; Salivary Glands; Salivary Proteins and Peptides; Secretory Rate