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Biomedical subjects

J Albert

Publications and source records attributed to J Albert.

At least 181 records · Page 10Linked to original sources
PubMed1989

The opsonizing ligand on Salmonella typhimurium influences incorporation of specific, but not azurophil, granule constituents into neutrophil phagosomes.

Phagosomes were purified from human neutrophils ingesting Salmonella typhimurium opsonized with adsorbed normal human serum or with rabbit IgG. Constituents within the phagosome were endogenously labeled by supplying the cells with 125INa during phagocytosis. Lactoferrin and vitamin B12 binding protein (TC1 and TC3), markers for specific granules, were present in the phagosomes from neutrophils ingesting S. typhimurium opsonized with IgG but were 3.5- to 5-fold less prominent in phagosomes from cells phagocytosing Salmonella bearing C3 fragments only. In contrast, iodinated azurophilic granule components, most prominently defensins, were the major constituents in phagosomes prepared under both opsonization conditions. Furthermore, labeled complement (CR1 and CR3) and immunoglobulin (Fc gamma RIII) receptors were incorporated in the phagosome regardless of the ligand mediating phagocytosis. These results suggest that the ligand-receptor interactions mediating phagocytosis influence incorporation of neutrophil-specific granule contents into phagosomes.

Animals↗
PubMed1989

HIV-1-specific antibodies in cerebrospinal fluid mediate cellular cytotoxicity and neutralization.

Antibodies mediating HIV-1-specific cellular cytotoxicity (ADCC) and virus neutralizing activity were detected in the cerebrospinal fluid (CSF) and, as previously reported, in sera of subjects with varying severity of HIV-1 infection, including patients with or without neurologic or psychiatric symptoms. ADCC-mediating antibodies against target cells infected with the HTLV-IIIB strain of HIV-1 were less frequently present in CSF than in sera, 32 and 60%, respectively. The frequency of ADCC-positive CSF was comparable for the different clinical stages of the disease and was apparently not influenced by the presence or absence of neurologic/psychiatric symptoms. Virus-neutralizing activity was tested against HTLV-IIIB and one CSF-derived viral isolate. Serum antibodies neutralized HTLV-IIIB more frequently than the CSF isolate, 53 and 35%, respectively. In contrast, only three (7%) of the CSF specimens contained neutralizing activity to the CSF-derived isolate and none to HTLV-IIIB. Despite an intact blood-brain barrier in many subjects, the serum/CSF ratios of ADCC or neutralizing antibodies were lower than normally expected. This indicates that both ADCC-mediating and virus neutralizing antibodies may be intrathecally synthesized. Whether these antibodies are protective against or contribute to the histopathologic changes in the brain is not known at present.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Replicative capacity, cytopathic effect and cell tropism of HIV.

Naturally occurring HIV variants show distinct biologic features that correspond to the severity of HIV infection. Virus from asymptomatic HIV carriers or individuals with mild disease replicates slowly and inefficiently in the patients' peripheral blood mononuclear cell cultures. Attempts to passage these viruses in CD4-positive cell lines usually fail or result in transient replication only. In contrast, viruses from patients with severe immunodeficiency replicate rapidly and efficiently in peripheral blood mononuclear cell cultures as well as cell lines: hence the designation slow/low and rapid/high, respectively. These two groups of viruses can also be distinguished by the type of cytopathogenicity exerted in peripheral blood mononuclear cells. Rapid/high viruses are characterized by extensive syncytia formation, whereas syncytia are rarely seen with slow/low viruses. Instead cultures infected with slow/low viruses show signs of cell death or no cytopathic changes at all. It has also been observed that shift from the slow/low type of virus to rapid/high may occur in the same individual over time. Whether this change signals the emergence of HIV variants with increased virulence or reflects the damage to the immune system that can no longer control virus replication remains to be seen. Rapid/high and slow/low viruses can also be distinguished by cell tropism when tested in a model system on indicator cell lines of T-lymphoid or monocytoid origin. Infection by rapid/high viruses activates chloramphenicol acetyl transferase in both T-lymphoid and monocytoid indicator cells, whereas slow/low viruses activate chloramphenicol acetyl transferase only in monocytoid cell lines. A difference between slow/low and rapid/high viruses cannot be demonstrated in fresh normal macrophage cultures, since most isolates can be successfully passaged in macrophages. Whether the viruses that infect macrophages are truly macrophage-tropic or dual-tropic, and infect macrophages and lymphocytes with equal efficiency, remains to be studied.

Cytopathogenic Effect, Viral↗
PubMed1989

Neopterin concentrations in cerebrospinal fluid and serum of individuals infected with HIV-1.

Neopterin, a biochemical marker for the activation of cell-mediated immune reactions, was determined in serum and cerebrospinal fluid (CSF) from patients infected with HIV-1. A significant correlation was found between serum and CSF neopterin concentrations, although concentrations of neopterin in serum were more closely correlated with the clinical severity of HIV-1 infection than those in CSF. However, higher CSF levels were observed in patients with neurologic/psychiatric symptoms than in unaffected patients. Also, quotients of CSF neopterin versus serum neopterin concentrations were increased, indicating intrathecal production of neopterin. Positive HIV-1 isolation from peripheral blood mononuclear cells (PBMC) was associated with higher neopterin concentrations in serum, when compared with negative HIV-1 isolation. Neopterin in CSF appears to be a suitable biochemical marker in patients with HIV-1 infection for detecting overt neurologic/psychiatric disturbances. The data suggest that in HIV-1 infected patients, cell-mediated immune reactions might be activated intrathecally and might contribute to neuropsychiatric disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Analysis of a subclass-restricted HIV-1 gp41 epitope by omission peptides.

To define the amino acids involved in IgG subclass reactivity to two overlapping HIV-1 gp41 (E34/32; amino acid positions 582-613) peptides, sera from 18 HIV-infected individuals were studied. Peptides mimicking E34 but with single amino acid deletions or glycine substitutions were used to define the amino acid residues necessary for antibody binding. Two dominating immunogenic epitopes, containing highly hydrophilic amino acids, were found on the original peptide. Further analysis was undertaken with two corresponding omission sets of dodecapeptides representing halves of the complete E34 plus a terminal cystein peptide. The subclass reactivities usually differed between the patients with regard to the epitopes with which the different IgG subclasses reacted and also to the importance of different amino acids in antibody binding. The 600 glycine and the 601 lysine were involved in the binding of all IgG1, 2 and 4 and most IgG3. The development of E34/32-reactive IgM and IgG subclasses showed different patterns in four patients with primary HIV infections, contradicting the existence of a general pattern for the development of IgG subclasses to this peptide. The findings suggest that different progenitor clones are selected for synthesis of the different subclasses.

Amino Acid Sequence↗
PubMed1989

Experimental infection of cynomolgus monkeys (Macaca fascicularis) with HIV-2.

Ten healthy adult cynomolgus monkeys (Macaca fascicularis) were inoculated with two different isolates of human immunodeficiency virus type 2 (HIV-2), SBL-6669 and SBL-K135, to establish an animal model for HIV infection. HIV-2SBL-6669 had been propagated for a long time in continuous human cell lines whereas HIV-2SBL-K135 had been grown only in fresh human and monkey lymphocyte cultures or previously for a short time in a continuous cell line. Virus was isolated from three or four animals inoculated with HIV-2SBL-K135 but in none of six monkeys inoculated with HIV-2SBL-6669. All animals seroconverted although the antibody response was higher in SBL-K135 virus-infected monkeys. Varying degrees of lymphadenopathy were observed but there were no significant changes in the numbers of CD4+ and CD8+ T cells. The infection was transferred to two monkeys inoculated with blood from a previously SBL-K135 virus-infected monkey. Four animals inoculated with HIV-2SBL-K135, which had never been propagated in continuous human cell lines, showed strong antibody responses against both gag- and env- encoded proteins of HIV-2. None of the SBL-6669 infected monkeys showed antibodies to core proteins. HIV-2 infection of cynomolgus monkeys represents a useful experimental model for HIV vaccine trials and antiviral testing.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Experimental infection of cynomolgus monkeys (Macaca fascicularis) with simian immunodeficiency virus (SIVsm).

Five healthy cynomolgus monkeys were inoculated intravenously with simian immunodeficiency virus (SIVsm) propagated in human lymphocytes. All five animals became infected. Virus was recovered from blood mononuclear cells and viral antigen was detected in serum 12 days postinoculation (PI) in all inoculated animals. Virus was also isolated in all five animals tested 74 to 226 days PI. Antibodies to different structural proteins of SIV and HIV-2 were demonstrated by ELISA, Western blot, and radioimmunoprecipitation assay from day 31 PI concomitantly with a reduction of viral proteins in the serum. Reappearance of antigen accompanied by a fall in antibody to gag products (p26) was observed in two monkeys 69 days PI. All SIV-infected monkeys showed a pronounced decrease in CD4+ lymphocytes demonstrable already 12 days PI. They also developed persistent lymphadenopathy. Thus, infection of cynomolgus monkeys with SIVsm mimics events in human immunodeficiency virus infection in humans but the course of evolution of pathogenic events in the monkey is markedly compressed. This experimental model will be useful for evaluation of HIV vaccines and antiviral testing.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Thermodynamic-geometric correlations for the morphology of self-assembled structures of glycosphingolipids and their mixtures with dipalmitoylphosphatidylcholine.

The morphology of aqueous dispersions of five neutral glycosphingolipids (GalCer, GlcCer, LacCer, asialo-GM2, asialo-GM1), sulfatide, and five gangliosides (GM3, GM2, GM1, GD1a and GT1b) and their mixtures with dipalmitoylphosphatidylcholine was studied by negative staining electron microscopy. The morphological features are interpreted on the basis of thermodynamic and geometric constraints previously studied in these systems (Maggio, B (1985) Biochim. Biophys. Acta 815, 245-258). The correlation between the theoretical predictions and the experimental findings are in reasonable agreement. Small changes in the molecular parameters of the individual glycosphingolipids or in their proportion in mixtures with dipalmitoylphosphatidylcholine bring about remarkable variations on the type of structure formed, its radius of curvature and thermodynamic stability.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

Application of bromodeoxyuridine incorporation measurements to the determination of cell distribution within the S phase of the cell cycle.

Flow cytofluorimetric measurement of incorporated bromodeoxyuridine, using a double-stained cell population, allows the determination of the distribution of cells along the cell cycle. We have developed a simple computer program for the direct treatment of 64 x 64 channel histograms. This analysis appears to provide interesting data about the distribution of cells in the various phases of the cell cycle, namely the S phase. Two examples have been chosen to illustrate possible fields for the application of such a program. Comparison of two cell lines such as friend murine erythroleukemia cells (MELC) and fibroblasts FR3T3 cells has shown that this analysis can be used for cell-cycle characterization of a given cell line. The program also allows the differential analysis of cell distribution along the cell cycle as a function of a given parameter. This possibility has been applied to study the variation of cell-cycle parameters as a function of the time of induced differentiation of MELC and reveals changes in the distribution of the cells along the various phases of the cell cycle, namely in the S phase.

Animals↗
PubMed1988

Human immunodeficiency virus infection of the brain. I. Virus isolation and detection of HIV specific antibodies in the cerebrospinal fluid of patients with varying clinical conditions.

Isolation of the human immunodeficiency virus (HIV) has been attempted from the cerebrospinal fluid (CSF) of 29 subjects with varying severity of HIV infection. Virus could be isolated from patients in all stages of disease including patients with primary HIV infection and asymptomatic carriers. In the early stages of infection free virus was infrequently present in the CSF but could be isolated from the cells present in CSF. This suggests that HIV may reach the brain at a very early stage of infection and that initially there is little production of virus from infected cells. In the late stages of HIV infection, associated with increasing severity of immunodeficiency, free virus could readily be isolated from the CSF. With one exception, all of these patients had neurological and/or psychiatric symptoms, as compared to only 2 (of 13) subjects in the early stages of infection. All patients with HIV-specific antibodies in serum had antibodies also in CSF. Examined by a radioimmunoprecipitation assay, CSF was more often found to contain antibodies to the precursor (p55) of viral core proteins than the corresponding serum of the patients. We propose that immune disturbances have an essential pathogenic role in the neurological/psychiatric symptoms associated with HIV infection, possibly through allowing increased viral expression in the central nervous system.

AIDS-Related Complex↗
PubMed1988

Acid hydrolysis of serum samples to increase detection of HIV antigen.

Sera from 32 HIV-infected patients and 20 controls were assayed for HIV antigen (HIV-Ag) and antibodies following acid hydrolysis. Acid hydrolysis, followed by neutralization immediately prior to the assay, was found to be a simple means to solubilize immune complexes and allowed recovery of 40-50% of complexed antigen. Following acid hydrolysis, HIV-Ag levels rose or became detectable in 22/32 patients and HIV IgG1-4 levels rose in 17/20 patients studied. The results show that complexed HIV-Ag may evade detection in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Isolation frequency of human immunodeficiency virus from cerebrospinal fluid and blood of patients with varying severity of HIV infection.

Isolation of the human immunodeficiency virus (HIV) has been attempted from the cerebrospinal fluid (CSF) of 63 subjects at different stages of HIV infection, including asymptomatic carriers and patients with or without neurologic or psychiatric complications. In addition blood was collected from 40 of these subjects for virus isolation. HIV could be isolated from the CSF at all clinical stages with an overall frequency of 40%. In contrast, the frequency of HIV isolation from the blood was lower (32%) at the early stages of infection than in patients with severe disease (77%). HIV isolation from the CSF was more frequently positive in patients with neurologic or psychiatric complications than in patients showing no such disturbances (48 and 32%, respectively).

Acquired Immunodeficiency Syndrome↗
PubMed1988

HIV isolation and antigen detection in infected individuals and their seronegative sexual partners.

We have examined 39 couples, each consisting of one HIV-seropositive index case and one seronegative sexual partner. HIV isolations, HIV antigen (HIV-Ag) tests and HIV antibody tests were performed on samples from these 78 individuals. Results were compared with those of 68 unselected individuals. Neither HIV, nor HIV-Ag was detected in any of the seronegative individuals. HIV-Ag tests, but not HIV isolations showed positive results with a significantly lower frequency in symptomatic index cases than in unselected patients with symptoms. This indicates that the absence of HIV-Ag in the serum may be correlated with a low level of contagiousness.

Adult↗
PubMed1988

Do nonorganic signs help to predict the return to activity of patients with low-back pain?

The value of the nonorganic signs in predicting return to activity following an initial episode of low-back pain was determined. One hundred and twenty patients were assessed within 6 months of the onset of their first episode of disabling low-back pain and again at a mean of 15.3 months following injury. No correlation was found between the presence of nonorganic signs at initial assessment and either return to activity or resolution of the patient's symptoms.

Adolescent↗