Chemokines in depression in health and in inflammatory illness: a systematic review and meta-analysis.

Inflammatory illness is associated with depression. Preclinical work has shown that chemokines are linked with peripheral-central crosstalk and may be important in mediating depressive behaviours. We sought to establish what evidence exists that differences in blood or cerebrospinal fluid chemokine concentration discriminate between individuals with depression and those without. Following PRISMA guidelines, we systematically searched Embase, PsycINFO and Medline databases. We included participants with physical illness for subgroup analysis, and excluded participants with comorbid psychiatric diagnoses. Seventy-three studies met the inclusion criteria for the meta-analysis. Individuals with depression had higher levels of blood CXCL4 and CXCL7 and lower levels of blood CCL4. Sensitivity analysis of studies with only physically healthy participants identified higher blood levels of CCL2, CCL3, CCL11, CXCL7 and CXCL8 and lower blood levels of CCL4. All other chemokines examined did not reveal significant differences (blood CCL5, CCL7, CXCL9, CXCL10 and cerebrospinal fluid CXCL8 and CXCL10). Analysis of the clinical utility of the effect size of plasma CXCL8 in healthy individuals found a negative predictive value 93.5%, given the population prevalence of depression of 10%. Overall, our meta-analysis finds evidence linking abnormalities of blood chemokines with depression in humans. Furthermore, we have demonstrated the possibility of classifying individuals with depression based on their inflammatory biomarker profile. Future research should explore putative mechanisms underlying this association, attempt to replicate existing findings in larger populations and aim to develop new diagnostic and therapeutic strategies.

Antisense phosphorothioate oligodeoxynucleotides alter HIV type 1 replication in cultured human macrophages and peripheral blood mononuclear cells.

The use of antisense oligodeoxynucleotides as antiviral drugs to combat HIV-1 infection may offer an alternative to traditional pharmacological therapies. We compared the effects of two 28-mer antisense phosphorothioate oligodeoxynucleotides [PS-oligo(dN)] with non-sequence-specific controls on HIV-1 replication in long-term human monocyte/macrophage and PBMC cultures. The anti-rev PS-oligo(dN) was complementary to the messenger RNA (mRNA) sequences derived from the overlapping region of the HIV-1 regulatory genes tat and rev, while anti-gag targeted the translational initiation site of the gag mRNA. In vitro cytotoxicity of the PS-oligo(dN) was evaluated at concentrations ranging from 0.1 to 10.0 microM for a period of 20 days. Cell survival was 100% at 0.1 microM, but decreased to 5% at 10.0 microM in relation to the untreated control cultures. Our data demonstrate that replication of both the T cell-tropic and macrophage-tropic HIV-1 strains in primary cells can be inhibited by PS-oligo(dN) in a sequence-specific and dose-dependent manner at concentrations achievable in vivo. However, the sequence-dependent antiviral activity of the utilized PS-oligo(dN) was limited to a window of specificity at concentrations between 0.25 and 1.0 microM.

Human retroviruses: their role in neoplasia and immunodeficiency.

Human retroviruses (HTLVs and HIVs) infect the cells of the immune system and cause mild-to-severe immune dysfunction. They are directly or indirectly responsible for associated neoplasia and central nervous system disorders. The study of these viruses is of great importance, not only because they cause grave illnesses like AIDS, neoplasias, and CNS disease, but also because they have the ability to exert such fine levels of gene regulatory control in their replication and expression. These studies will ultimately shed light on fundamental mechanisms of genetic control in human cells in their normal state and the alterations of these controls in neoplastic or immunologically aberrant states.

Frequency of asymptomatic genital herpes in pregnant women at term.

A group of 579 asymptomatic women from Jackson Memorial Hospital, Miami, Florida, and 207 from Kaiser Foundation Hospital in Honolulu, Hawaii, admitted in labor at 37 to 40 weeks of gestation had vaginal cultures for herpes simplex virus (HSV). No cultures were positive and no neonates developed HSV infection. Seven patients gave a history of previous HSV infection in the group from Florida and three from the group in Hawaii. Herpes appears to be a low incidence risk factor in both the populations studied.

Human retroviruses: cancer and AIDS.

Human retroviruses are associated with a wide spectrum of clinical entities including cancers, immune deficiency and neurological disorders. They have become the focal point of all retrovirology by virtue of their extreme clinical relevance, their novel and complex biologic and genetic properties, as well as their regulation strategies. The study of these viruses is of great importance as understanding of their interactions with the host will ultimately shed light on fundamental mechanisms of genetic controls in human cells in their normal state and the alterations in these controls in neoplastic or immunologically aberrant states.

Proliferation of alveolar macrophages in hyperoxia.

The effect of oxygen on the proliferative response of alveolar macrophages (AMs) was investigated. Alveolar macrophages cultured in hyperoxic atmosphere (95% O2 + 5% CO2) for 18 hours showed increased incorporation of [3H]-thymidine and proliferation in contrast to those cultured in a control atmosphere (95% air + 5% CO2). The proliferating cell was shown to be a macrophage by morphology, esterase staining, and phagocytic ability. The results suggest an oxygen-induced proliferation of AMs that may play a critical role in AM influx into the alveoli particularly at times of hyperoxia, eg, the neonatal period.

Measurement of plasma histamine in patients with suspected food hypersensitivity.

Plasma histamine determinations were performed on 15 subjects with suspected food hypersensitivity following subcutaneous food provocation with milk, egg or wheat antigens. Significant rises in plasma histamine were observed in four of the 15 subjects tested; in these four subjects positive responses were seen with a total of five food test challenges. No changes were observed in total blood counts, differential eosinophil counts in six subjects and no correlation was observed with allergen-specific IgE responses. The results of these preliminary studies lend further support to the heterogeneity of causes of food allergy and suggest that the measurement of plasma histamine may provide an additional predictive marker for the diagnosis of food allergy. This technique permits the measurement of the ultimate mediator system(s) suspected to play a pathogenetic role in many food hypersensitivities.

Chemotactic and candidacidal responses of rabbit alveolar macrophages during postnatal development and the modulating roles of surfactant in these responses.

Chemotactic responses of alveolar macrophages from 1-, 7-, and 28-day-old rabbits to various concentrations of endotoxin-activated serum and n-formyl-methionyl-phenylalanine were tested utilizing both blind well and agarose plate assay systems. A dramatic increase in both the chemotactic response and responsiveness to various concentrations of chemoattractant was observed during postnatal maturation. The pattern of result was similar with both methods of assay. An age-related increase was also found to occur in the candidacidal activity of alveolar macrophages in contrast to their phagocytic uptake, which showed no age-related increases. Furthermore, the decreased function of macrophages from newborn animals correlated with a morphologically and biochemically less mature cell population which contained large amounts of phagocytosed surfactant-related material. Moreover, pretreatment of macrophages from 7- and 28-day-old animals with vesicles of surfactant-related material resulted in decreases in both chemotactic and candidacidal activity, with a paradoxical increase in their phagocytic activity. The resulting activities were similar to those of macrophages from 1-day-old animals treated with buffer alone. These data suggest that there is an age-related increase in the chemotactic and candidacidal activity of alveolar macrophages during maturation and that the decreased activity of macrophages from newborn animals is related in part to the large amount of surfactant-related material present at that time.

Comparison of standard tissue culture, tissue culture plus staining, and direct staining for detection of genital herpes simplex virus infection.

Genital herpes simplex virus infection in women was studied by using conventional tissue culture (TC) virus isolation compared with short-term (24-h) TC on Lab-Tek chamber slides followed by fluorescent-antibody (FA) staining. Three different staining techniques were used after TC: (i) staining with biotin-avidin (TC-BA/FA), (ii) direct FA (TC-FA), and (iii) indirect FA. The TC-BA/FA method showed complete correlation with the TC method. The TC-FA method showed no false-positive results but 31.5% false-negative results compared with the TC method. In contrast, the TC-indirect FA method showed 11.9% false-positive results and 11.7% false-negative results. The direct staining of specimens by the biotin-avidin technique (direct BA/FA) without prior tissue culture showed 37.7% false-positive results and 11.1% false-negative results. The TC-BA/FA technique thus was as sensitive as, but more rapid than, the TC method. The quality of fluorescence was far superior in TC-BA/FA staining as compared with TC-FA or TC-indirect FA procedures. The TC-BA/FA appears to be a valuable technique in laboratory diagnosis of genital herpes infections, especially in clinical situations requiring rapid detection of the virus.

Maturation of the rabbit alveolar macrophage during animal development. III. Phagocytic and bactericidal functions.

Phagocytic and bactericidal function of rabbit alveolar macrophages (AMs) lavaged from animals during the course of postnatal maturation was studied. Staphylococcus aureus and a temperature-sensitive mutant of Escherichia coli, which could not replicate at 37 degrees during the functional assays, were employed as test bacteria. Assays of the phagocytic capacity of AMs from rabbits of various age groups revealed no significant differences either in the percentage of AMs which took up bacteria (79-90%) or in the number of bacteria taken up per AM (Table 1). In contrast, bactericidal activity of AMs was found to increase with increasing animal age. No bactericidal activity was detected in AMs from newborn animals (Figs. 1 and 2), whereas AMs from 7-day-old animals exhibited at least a bacteristatic activity against S. aureus (Fig. 1) and AMs from 28-day-old rabbits showed marked bactericidal activity, essentially the same as that of AMs from adult rabbits. Adult AMs killed 75% of the S. aureus and 60% of the E. coli within 120 min (Figs. 1 and 2).

Chronic granulomatous disease in an adult.

We have described a 49-year-old man with chronic granulomatous disease. The diagnosis was established by a deficiency of NBT dye reduction by neutrophils, in addition to impairment in 14C-1-glucose utilization, 125I-iodination of zymosan, chemiluminescence, superoxide radical generation, and bactericidal activity toward S aureus. This adult patient exhibits many characteristics of chronic granulomatous disease of childhood but of less severity, which may explain his unusually long survival. It is thus important to consider the diagnosis of chronic granulomatous disease not only in children but also in adult patients having the characteristic pattern of recurrent infections.

Survival of herpes simplex virus in water specimens collected from hot tubs in spa facilities and on plastic surfaces.

Several health spas were closed temporarily because of possible nonvenereal spread of herpes simplex virus (HSV) in spa water at these facilities. We collected water specimens from two health spas and studied them for (1) the presence of HSV; (2) bromine (Br2), chlorine (Cl2), and pH levels; and (3) the ability of HSV to survive in water. No HSV could be isolated from the spa water specimens. Spa water had high levels of Cl2 and Br2, tap water specimens had low levels of Cl2, and distilled water had no detectable Cl2 or Br2. The addition of spa water to laboratory stock virus immediately inactivated the virus. The HSV survived four hours in the tap water and 24 hours in distilled water. The survival of HSV appeared to be related to the free halogen content of water. To approximate the conditions of survival of HSV on plastic-coated benches and seats in spa facilities, HSV was placed on plastic surfaces in a humid atmosphere at 37 to 40 degrees C. The virus was found to survive up to 4.5 hours under these conditions. The survival of HSV from human lesions may be different due to the presence of tissue secretions and proteins. Furthermore, transmission may require other factors, such as rubbing of skin or penetration through abrasions. However, survival of significant amounts of virus for 4.5 hours on plastic surfaces suggests that fomites such as these may be nonvenereal routes of HSV transmission.

Maturation of the rabbit alveolar macrophage during animal development. I. Perinatal influx into alveoli and ultrastructural differentiation.

Rabbit alveolar macrophages (AM's) were collected by tracheobronchial lavege at sequential times during animal development. The total number of cells recovered by this technique was found to increase markedly shortly before birth (Fig. 4). This apparent influx of macrophages into the alveoli continued during the first postnatal week, and, at a reduced rate, throughout the first postnatal month of life (Fig. 3). Ultrastructurally, AM's of the prenatal period resembled their monocyte precursors, and contained modest numbers of lysosomes and mitochondria, scant lamellae of ribosome-studded endoplasmic reticulum (RER), and a small Golgi apparatus (Fig. 12). A considerable amount of phagocytosed material was observed in these AM's, and consisted largely of cellular debris and two forms of surfactant-related phospholipids, termed tubular and lamellar myelin (Figs. 12-15). The quantity of these ingested phospholipids increased dramatically shortly after birth, in correlation with the known release of similar material from type II pneumocytes at this time. (Figs. 16 and 19). During the first postnatal week AM's showed a considerable increase in number of mitochondria and in the development of the RER and Golgi apparatus (Fig. 22). Increased accumulations of lipid droplets were also noted during this period. Ingested material continued to consist largely of surfactant-related phospholipids, but was less abundant at this time. By 28 days after birth, AM's were nearly morphologically mature (Fig. 25). They showed large numbers of lysosomes and mitochondria, and well developed RER and Golgi apparatuses. Ingested phospholipid material was still visualized, and the incomplete degradation of this material appeared to give rise to the dense intraphagolysosomal whorls characteristic of the mature AM.

Detection of genital herpes simplex infections by a tissue culture-fluorescent-antibody technique with biotin-avidin.

Several cell lines were evaluated for their suitability for rapid detection of herpes simplex virus (HSV) from clinical genital specimens. Human foreskin fibroblast (Flow 7000) cells were found to be most suitable in terms of sensitivity and adherence characteristics. HSV in clinical specimens was isolated by a standard tissue culture method by monitoring the cytopathic effect, and the titers of the HSV-positive specimens were determined. More than 65% of the HSV-positive genital specimens showed titers of less than or equal to 10(4) 50% tissue culture infective doses per ml. The standard tissue culture-cytopathic effect method required 3 to 10 days for detection of HSV in clinical specimens of low infectivity. A more rapid technique was developed which involved a short-term tissue culture (24 h) on Lab-Tek chambers followed by staining with biotin-linked HSV antibody and avidin-fluorescein conjugate. Because of the high binding affinity of this system due to multiple binding of biotin to avidin and multiple attachment of biotin to the antibody molecule, the biotin-avidin fluorescent-antibody technique produced a quality of fluorescence far superior to that of the conventional fluorescent-antibody techniques. The tissue culture-biotin-avidin fluorescent-antibody method was as sensitive as the tissue culture-cytopathic effect test. This method provides an improved, more rapid test (26 h) for detecting HSV in clinical specimens.

Comparison of enzyme-linked immunosorbent assay with enzyme-linked fluorescence assay with automated readers for detection of rubella virus antibody and herpes simplex virus.

The enzyme-linked immunosorbent assay (ELISA) was compared with the enzyme-linked fluorescence assay (ELFA) for the detection of rubella antibody and herpes simplex virus antigen. Test parameters, specimens, antigen or antibody, and conjugates for the two types of assays were identical except that p-nitrophenyl phosphate was used as the substrate for the ELISA and 4-methylumbelliferyl phosphate was used as the substrate for ELFA. Automated readers were used for both assays. Antibody titers and sensitivity of antigen detection were quite similar for ELISA and ELFA. ELFA for rubella antibody, however, could be conducted with less antigen or shorter substrate incubation time (5 min for ELFA versus 30 min for ELISA). For herpes simplex virus antigen detection, ELFA could also be read after a shorter substrate incubation time (15 min for ELFA versus 30 min for ELISA). Clear polystyrene microtiter plates routinely used for ELISA could be used for ELFA, but clear polyvinyl chloride plates had high background fluorescence. Black polystyrene and polyvinyl chloride plates gave lower background fluorescence than did clear plates. ELFA is of particular value as a substitute for ELISAs in which long substrate incubations are required or antigens of only low titer are available.

Typing of herpes simplex virus by capture biotin-streptavidin enzyme-linked immunosorbent assay and comparison with restriction endonuclease analysis and immunofluorescence method using monoclonal antibodies.

A sensitive enzyme-linked immunosorbent capture assay using biotin and streptavidin (capture B/SA ELISA) was developed using type-specific monoclonal antibodies for typing of herpes simplex virus. Rabbit anti-herpes simplex virus immunoglobulin G was used as the capturing antibody, and biotin-linked type-1-specific mouse monoclonal antibody or rabbit type-1- or type-2-specific polyclonal antibody served as the detecting antibody. The captured antigen was detected by an ELISA with alkaline phosphatase-conjugated streptavidin, which reacted with biotin molecules on the detector antibody. The capture B/SA ELISA was compared with other methods for efficiency and reliability in typing. Results obtained by restriction endonuclease digestion of the radiolabeled viral genome were used to determine the type (1 or 2) of clinical isolates. These results were then used as a reference for determining the accuracy of the capture B/SA ELISA, as well as that of the immunofluorescence method, both of which are easily adaptable for use in the clinical laboratory. The three methods were in perfect agreement. It was determined that both the capture B/SA ELISA and the immunofluorescence method using monoclonal antibodies provided typing results with 100% specificity and 100% sensitivity and thus were accurate and reliable. However, the ELISA was the method of choice because of its simplicity, rapidity, and use of nonradioisotopic reagents.