Neuropathology of the Central Nervous System in Acquired Immune Deficiency Syndrome (AIDS) in Japan

The neuropathologiesl features of the central nervous system in IS autopsy cases of Japanese male with AIDS were reported. Nine patients had various histological changes including a variety of opportunistic infections in six patients (40%), primary malignant lymphoma of the brain in two (13%), AIDS encephalopathy in four (27%) and vacuolar myelopathy in one (7%). Usually, these pathological changes were present concomitantly. AIDS encephalopathy was characterized by infiltration of mono and multinucleated cells and myelin pallor with astrogliosis located predominantly in the cerebral white matter and subcortical gray matter. Furthermore, unevenly distributed neuronal loss of the cerebral cortex was apparent in one case. Diffuse astrocytosis of the gray matter out of proportion to neuronal loss was also an outstanding finding in another case. The present study suggested that not only the white matter changes but also gray matter alterations might be the morphological substrates of AIDS encephalopathy.     

Neutrophil Functions in Immunodeficiency Due to DOCK8 Deficiency

Neutrophil chemotactic defects have been reported previously in patients with hyper-IgE syndrome. Bi-allelic mutations in dedicator of cytokinesis 8 (DOCK8) gene usually cause an autosomal recessive hyper-IgE syndrome phenotype. Data are lacking about expression of DOCK8 protein in neutrophils or the possible role of DOCK8 in neutrophil function. We sought to determine if DOCK8 protein is expressed in neutrophils and if DOCK8 plays a role in neutrophil function. The expression of DOCK8 protein was assessed in neutrophils from healthy volunteers with and without activators. Neutrophil chemotaxis, phagocytosis and superoxide generation were studied in neutrophils from DOCK8-deficient patients compared to neutrophils from healthy controls before and after stimulation with activators: phorbol 12-myristate 13-acetate (PMA) or N-Formylmethionyl-leucyl-phenylalanine (fMLP). DOCK8 protein is expressed in resting neutrophils from healthy controls, with a significant increase in DOCK8 expression after stimulation. Neutrophil functions were assessed in 6 DOCK8-deficient patients. All patients had the same non-sense mutation (c.C5134A, p.S1711X). Normal chemotaxis was recorded in 4/6 patients while a mild to moderate chemotaxis defect was recorded in 2/6. Superoxide generation was mainly normal in neutrophils from all six patients and phagocytosis was normal in five patients tested. We conclude that DOCK8 protein is expressed in resting human neutrophils and DOCK8 expression is increased after stimulation with either PMA or fMLP. Most patients with a disease-causing mutation in DOCK8 have normal neutrophil functions, while a minority showed a mild to moderate chemotactic defect.     

Acute Idiopathic Hemorrhagic Pericarditis with Cardiac Tamponade as the Initial Presentation of Acquired Immune Deficiency Syndrome

This paper presents a case of cardiac tamponade with idiopathic hemorrhagic pericarditis as the initial symptom of human immunodeficiency virus (HIV) infection. A 29-year-old male came to the emergency room with a sudden onset of dizziness. Upon arrival, he was hypotensive although not tachycardic, and his jugular venous pressure was not elevated. His chest X-rays revealed a mild cardiomegaly. Transthoracic echocardiography revealed a large amount of pericardial effusion with a diastolic collapse of the right ventricle, a dilated inferior vena cava with little change in respiration, and exaggerated respiratory variation of mitral inflow velocities, representing echocardiographic evidence of cardiac tamponade. After pericardiocentesis, his blood pressure improved to 110/70 mmHg without inotropics support. Serial 12-lead electrocardiograms during hospitalization revealed upwardly concave diffuse ST-segment elevation followed by a T-wave inversion suggestive of acute pericarditis. Pericardial fluid cytology and cultures for bacteria, mycobacteria, adenovirus, and fungus were all negative. HIV enzyme-linked immunosorbent assay (ELISA) was positive and confirmed by Western blot. The CD4 cell count was 168/mm³. Finally, the diagnosis of cardiac tamponade due to HIV-associated hemorrhagic pericarditis was made. It was concluded that HIV infection should be considered in the diagnosis of unexplained pericardial effusion or cardiac tamponade in Korea.     

Submicroscopic Profile of Isospora belli Enteritis in a Patient with Acquired Immune Deficiency Syndrome(doubt)

Small bowel mucosal fragments from a human immunodeficiency virus-positive female patient with chronic diarrhea were investigated by transmission electron microscopy, and Isospora belli enteritis was documented. The submicroscopic profile was characterized by a moderate abnormality of mucosal architecture with reduction in height of villi and hypertrophy of crypts. Stages of both asexual (trophozoite, schizont, and merozoite) and sexual (macrogametocyte) phases of the life cycle of the parasite were identified in the epithelium, always enclosed within a parasitophorous vacuole. Moreover, the presence of occasional extracellular merozoites in the intestinal lumen and in the lamina propria near or within lymphatic vessels was documented. These findings expand the current knowledge of this parasite regarding its capacity to survive in an extracellular environment and document a possible mechanism by which extraintestinal infection can take place.     

Submicroscopic Profile of Isospora belli Enteritis in a Patient with Acquired Immune Deficiency Syndrome(doubt)

Small bowel mucosal fragments from a human immunodeficiency virus-positive female patient with chronic diarrhea were investigated by transmission electron microscopy, and Isospora belli enteritis was documented. The submicroscopic profile was characterized by a moderate abnormality of mucosal architecture with reduction in height of villi and hypertrophy of crypts. Stages of both asexual (trophozoite, schizont, and merozoite) and sexual (macrogametocyte) phases of the life cycle of the parasite were identified in the epithelium, always enclosed within a parasitophorous vacuole. Moreover, the presence of occasional extracellular merozoites in the intestinal lumen and in the lamina propria near or within lymphatic vessels was documented. These findings expand the current knowledge of this parasite regarding its capacity to survive in an extracellular environment and document a possible mechanism by which extraintestinal infection can take place.     

Impaired Functions of Peripheral Blood Monocyte Subpopulations in Aged Humans

Aging is associated with increased susceptibility to microbial infections, and monocytes play an important role in microbial defense. In this study, we have identified and compared four subpopulations of monocytes (CD14^++(high)CD16⁻, CD14^+(low)CD16⁻, CD14^++(high)CD16⁺, and CD14^+(low)CD16⁺) in the peripheral blood of young and aged subjects with regard to their numbers, cytokine production, TLR expression, and phosphorylation of ERK1/2 in response to pam3Cys a TLR-1/2 ligand. Proportions and numbers of CD14^++(high)CD16⁺ and CD14^+(low)CD16⁺ monocytes were significantly increased, whereas proportions of CD14^+(low)CD16⁻ monocytes were decreased in aged subjects as compared to young subjects. In aged subjects, IL-6 production by all four subsets of monocytes was significantly decreased, whereas TNF-α production was decreased in monocyte subsets, except the CD14^+(low)CD16⁻ subset. A significantly reduced expression of TLR1 was observed in CD14^++(high)CD16⁺ and CD14^+(low)CD16⁺ monocyte subsets in aged subjects. Furthermore, following pam3Cys stimulation, ERK1/2 phosphorylation was significantly lower in CD14^+(low)CD16⁺, CD14^++(high)CD16⁺, and CD14^+(low)CD16⁻ subsets of monocytes from aged subjects. This is the first study of four subpopulations of monocytes in aging, which demonstrates that their functions are differentially impaired with regard to the production of cytokines, expression of TLR, and signaling via the ERK–MAPK pathway. Finally, changes in the number of monocyte subsets, and impairment of TLR1 expression, TNF-α production, and EK1/2 phosphorylation was more consistent in CD16⁺ monocyte subsets regardless of expression of CD14^high or CD14^+low, therefore highlighting the significance of further subdivision of monocytes into four subpopulations.     

Adult Nephrotic Syndrome and Acquired Coagulopathies: Hageman Factor Deficiency

Analysis of tests of coagulation and fibrinolysis from 20 adult nephrotics prior to the onset of therapy disclosed that 40 percent had low factor XII levels. The mean factor XI was normal. The platelet count and fibrinogen concentration were elevated. The findings of this study on adults are similar to those of Honig and Lindley²¹ in the nephrotic syndrome of childhood. Subjects with minimal change disease constituted a small (15 percent) but readily segregated subpopulation without evidence of fibrinolysis in association with low factor XII activity. Prolongation of the activated partial thromboplastin time corresponded in every instance with factor XII activities of ≤30 percent. Lengthening of the one stage prothrombin time was not directly attributable to factor deficiencies.     

Monoclonal Antibody-Defined β2-Microglobulin-Positive Mononuclear Cells in Acquired Immune Deficiency Syndrome

In healthy heterosexuals, by means of a monoclonal antibody against beta 2-microglobulin (beta 2m) and fluorescence-activated cell sorter analyser (FACS analyser), we observed two populations of beta 2m+ mononuclear cells (MNC); a large population with high-intensity cells and a small population of relatively low-intensity cells. Because elevated beta 2m levels have been shown in the sera of patients with acquired immune deficiency syndrome (AIDS), we examined the proportions of beta 2m+ MNC in AIDS and AIDS-related complex (ARC). The proportions and numbers of high-fluorescence intensity beta 2m+ MNC were significantly (P less than 0.05) decreased in AIDS and ARC when compared with those of asymptomatic homosexuals and healthy heterosexuals. The proportion and number of total beta 2m+ MNC (both high- and low-intensity beta 2m+) in ARC were comparable to those of control groups; however, the numbers of total beta 2m+ MNC were significantly (P less than 0.01) reduced only in the AIDS group. This relative deficiency of high-intensity beta 2m+ MNC appears to be due to a shift from high-intensity beta 2m+ to low-intensity beta 2m+ MNC. A linear correlation was observed between the deficiency of high-intensity beta 2m+ cells and T helper to T suppressor phenotype cell ratios.     

Monocyte Phenotype and Function in Patients with the Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related Disorders

The CD4 molecule, which is known to play an important role in the susceptibility of T lymphocytes to infection by the human immunodeficiency virus (HIV), is also expressed in small amounts on the surface of monocytes. Since monocytes can also be infected by the virus, we investigated peripheral blood monocytes of patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), and HIV seropositive and seronegative haemophiliacs without symptoms for the expression of the CD4 molecule and for other functionally important surface molecules such as CD11 (C3bi receptor), transferrin receptor, Fc receptor, and the three major histocompatibility complex (MHC) class II antigens HLA-DP, HLA-DR, and HLA-DQ. With immunofluorescence staining and flow cytometry no difference was found between patients and controls for the expression of the CD4 molecule and for the other antigens as assessed by the percentage of positive staining and the specific fluorescence intensity in a double marker analysis. The percentage of CD4+ monocytes was found to be 59.2 +/- 14.4% for 16 patients with AIDS and 52.9 +/- 12.8% for 12 healthy controls. Similar to our results on phenotype, we found no significant difference with respect to the production of tumour necrosis factor (TNF), in that monocytes of AIDS and ARC patients showed an increase in TNF secretion after stimulation with LPS comparable to controls.     

The Correlation Between Perceived Social Support and Illness Uncertainty in People with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome in Iran

Background:

Illness uncertainty is a source of a chronic and pervasive psychological stress for people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (PLWH), and largely affects their quality of life and the ability to cope with the disease. Based on the uncertainty in illness theory, the social support is one of the illness uncertainty antecedents, and influences the level of uncertainty perceived by patients.

Aim:

To examine uncertainty in PLWH and its correlation with social support in Iran.

Materials and Methods:

This cross-sectional correlational study was conducted with 80 PLWH presenting to AIDS Research Center, Tehran, Iran in 2013. The data collected using illness uncertainty and social support inventories were analyzed through Pearson''s correlation coefficient, Spearman''s correlation coefficient, and regression analysis.

Results:

The results showed a high level of illness uncertainty in PLWH and a negative significant correlation between perceived social support and illness uncertainty (P = 0.01, r = -0.29).

Conclusion:

Uncertainty is a serious aspect of illness experience in Iranian PLWH. Providing adequate, structured information to patients as well as opportunities to discuss their concerns with other PLWH and receive emotional support from their health care providers may be worthwhile.     

表面增强拉曼光谱无创检测艾滋病的方法初探

目的利用人体唾液拉曼谱无创检测艾滋病。方法利用一种便携式表面增强拉曼检测系统,获取45例艾滋病患者和55例正常人的唾液拉曼谱。结果应用数据挖掘技术对样本进行分类,计算灵敏度为100％,特异度大于96％。结论艾滋病患者和正常人群可以通过其唾液的表面增强拉曼光谱进行有效区分。     

Effect of Cyclosporin A on Human Neutrophil and Monocyte Function

The effect of various concentrations of cyclosporin A (CyA), ranging from below peak blood levels to 20 times higher than blood levels of human peripheral blood polymorphonuclear and mononuclear leukocytes, was examined. CyA was found to bind to neutrophils with Kd values in the range of 20-50 nM. CyA at clinically obtainable blood level concentrations had no effect on neutrophil and monocyte chemotaxis, neutrophil oxidative burst, monocyte phagocytosis, or neutrophil bactericidal activity. The data on the release of lactoferrin, a secondary granule substance, from activated neutrophils showed that the calcium ionophore A 23187-induced lactoferrin release was inhibited by treatment of cells with 4 microM CyA, whereas release of lactoferrin from zymosan- or phorbol myristate acetate-activated neutrophils was not affected by the same concentration of CyA. This effect could either be due to differences in the degree of cell membrane perturbation by the various activators or to calcium dependence of neutrophil activation. A third possibility may be that CyA acts at some subsequent steps in the release process of neutrophils. It is concluded that CyA does not interfere with important functions of human phagocytes, the cells that play a major role in the defence against invading microorganisms.     

Generation of Heat-Labile Chemotactic Activity in Blood after Inhalation Challenge and its Relationship to Neutrophil and Monocyte/Macrophage Turnover and Activity

The chemotactic activity of serum has been monitored in eight patients with bronchial asthma after inhalation of an allergen. Lactoferrin and lysozyme were measured in serum simultaneously as markers of neutrophil and monocyte/macrophage activity and turnover. The heat-labile chemotactic activity of serum showed a two-phase response with an initial reduction in activity (median = 37.5 min after challenge) ( P < 0.05) followed by an increased activity (median = 60 min after challenge) ( P < 0.01). The consistency of this pattern was highly significant ( P < 0.0005). Heat-stable chemotactic activity was significantly increased ( P < 0.01) 15 min after challenge.
The initial reduction in heat-labile chemotactic activity was observed only in those patients who developed a late asthmatic response and could suggest the involvement of immune complex-mediated reactions since a similar reduction in heat-labile chemotactic activity is produced by in vitro activation of serum with aggregated IgG.
The increased heat-labile chemotactic activity showed a close relationship ( P < 0.01) to the extent of the immediate reduction in PEF-rate. No relationship was discernible between the chemotactic activity and the eventually occurring rise in PMN blood count. In contrast the activity and turnover of PMNs after challenge as reflected by serum-lactoferrin levels were significantly reduced ( P < 0.01). A close correlation ( P < 0.001) was found between the heat-labile chemotactic activity in serum and the serum-levels of lysozyme, suggesting the involvement of macrophages/monocytes in the asthmatic reaction and in the generation of the heat-labile chemotactic activity found in serum after inhalation challenge.     

来氟米特与痹祺胶囊联合治疗类风湿关节炎气虚血瘀型的疗效及抗炎、免疫功能调控作用探讨

目的 探讨来氟米特联合痹祺胶囊治疗类风湿关节炎(RA)气虚血瘀型的疗效,并分析联合治疗方案抗炎、免疫功能的调控作用.方法 选取2019年5月至2021年1月我院收治的104例RA气虚血瘀型患者,采用随机配对法分为对照组、研究组,各52例.对照组给予来氟米特治疗,研究组给予来氟米特联合痹祺胶囊治疗.比较两组疗效、疾病活动...     

河南省某县艾滋病致孤儿童生活质量评价

目的:揭示我国艾滋病致孤儿童生活状况及其生活质量脆弱性特点,为制定相应健康促进策略提供依据.方法:采用性别、年龄1∶ 1配对设计,使用儿少主观生活质量问卷对河南省某艾滋病高发县96对艾滋病孤儿(孤儿组)与普通家庭儿童(对照组)生活状况及主观生活质量进行调查分析.结果:(1)与对照组相比,艾滋病孤儿生活满意度更低(45.16% vs.62.37%,P=0.019),遭受更多欺侮与不公(35.48% vs.12.90%,P<0.001),更需打工挣钱(55.91% vs.23.66%,P<0.001),且医疗服务可及性更低(36.36% vs.78.85%,P<0.001).(2)孤儿组生活质量总分、认知成分总分及家庭生活、学校生活、生活环境与自我认知4个维度得分均低于对照组[如,生活质量总分(145.9±16.0)vs.(154.9±16.1,P<0.001].(3)男性孤儿的生活质量总分、认知成分总分及家庭生活、学校生活、生活环境、自我认知维度得分均低于男性对照组[如,生活质量总分(143.2±16.7) vs.(155.8±17.1),P<0.001].结论:艾滋病孤儿面临更多生活问题并影响其生活质量,主要体现在对自我及环境认知水平下降,对情绪情感与心理健康远期影响亦不容忽视.男性孤儿所受影响更为显著.     

Immunological Studies in the Acquired Immunodeficiency Syndrome

The lymphocyte transformation responses to mitogens (phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM)), allogeneic cells, and the antigen-purified protein derivative (PPD) were studied in six acquired immunodeficiency syndrome (AIDS) patients and in six healthy controls, each of whom was HLA-DR- and mixed lymphocyte culture (MLC)-identical with one of the AIDS patients. No evidence of suppression was observed when irradiated or non-irradiated AIDS peripheral blood mononuclear cells (PBMC) were added to cultures of HLA-DR-identical PMBC from healthy controls stimulated with the strong mitogens PHA and Con A or with allogeneic cells, but suppression may be involved in the decreased responses in cultures stimulated with PWM or PPD. Addition of supernatants from macrocultures of AIDS cells did not suppress responses of control PBMC. Thus, suppression by any lymphocyte subset or soluble factor alone cannot explain the generally severely depressed transformation responses in AIDS. Addition of heavily irradiated HLA-DR-identical PBMC from healthy controls or supernatants from these cultures led to increased responses in cultures of mitogen-stimulated AIDS PBMC and in some cultures of antigen or allogeneic cell-stimulated AIDS PBMC, which were of the same magnitude as seen after the addition of commercially obtained T-cell growth factor (TCGF). This indicates that AIDS cells are deficient in producing TCGF. Heavily irradiated AIDS PBMC were capable of restoring the transformation responses to mitogens and antigens of purified HLA-DR-identical normal T cells, indicating that AIDS cells have a normal antigen-presenting capacity and interleukin (IL-1) production. However, AIDS PBMC had a very poor capacity to stimulate normal PBMC in MLC. Together, our experiments suggest that the immune deficiency in AIDS cells may be partially due to a decreased capability of T lymphocytes to produce TCGF and that a decreased number and/or function of dendritic cells may also be involved.     

T Cells Augment Monocyte and Neutrophil Function in Host Resistance against Oropharyngeal Candidiasis

The purpose of this study was to identify the cell populations involved in recovery from oral infections with Candida albicans. Monoclonal antibodies specific for CD4+ cells, CD8+ cells, and polymorphonuclear leukocytes were used to deplete BALB/c and CBA/CaH mice of the relevant cell populations in systemic circulation. Monocytes were inactivated with the cytotoxic chemical carrageenan. Mice were infected with 10(8) C. albicans yeast cells and monitored for 21 days. Systemic depletion of CD4+ and CD8+ T lymphocytes alone did not increase the severity of oral infection compared to that of controls. Oral colonization persisted in animals treated with head and neck irradiation and depleted of CD4+ T cells, whereas infections in animals that received head and neck irradiation alone or irradiation and anti-CD8 antibody cleared the infection in a comparable fashion. The depletion of polymorphonuclear cells and the cytotoxic inactivation of mononuclear phagocytes significantly increased the severity of oral infection in both BALB/c and CBA/CaH mice. High levels of interleukin 12 (IL-12) and gamma interferon (IFN-gamma) were produced by lymphocytes from the draining lymph nodes of recovering animals, whereas IL-6, tumor necrosis factor alpha, and IFN-gamma were detected in the oral mucosae of both na?ve and infected mice. The results indicate that recovery from oropharyngeal candidiasis in this model is dependent on CD4+-T-cell augmentation of monocyte and neutrophil functions exerted by Th1-type cytokines such as IL-12 and IFN-gamma.     

Iron Deficiency and Immune Responses

Iron deficiency is often associated with the impairment of the immune system, particularly the functioning of T-cell lymphocytes. Studies were therefore carried out in mice to investigate the involvement of iron in T-cell functions. Iron deficiency in mice was induced nutritionally by feeding diets differing in iron content for 4 weeks to produce normal, moderately low and severely low haematological indices. The proliferation of lymphocytes stimulated by Con A from these groups of mice was significantly affected by the degree of iron deficiency. Iron depletion also resulted in decreased production of interleukin 2 (IL-2) in the proliferating cells. The implications of these findings in the manifestation of iron deficiency anaemia are discussed.