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Biomedical subjects

J Albert

Publications and source records attributed to J Albert.

At least 127 records · Page 7Linked to original sources

Analysis of a rape case by direct sequencing of the human immunodeficiency virus type 1 pol and gag genes.

Transmission of human immunodeficiency virus type 1 (HIV-1) from a male accused of rape and deliberate transmission of HIV-1 was investigated by sequencing of the HIV-1 pol and gag genes from virus obtained from the male and from the female victim. Parts of the reverse transcriptase and p17gag genes were amplified and directly sequenced from uncultured peripheral blood mononuclear cells. The sequences were compared with sequences from 21 unrelated HIV-1-infected controls from the same geographic area (Stockholm, Sweden). Bootstrap analysis of phylogenetic trees demonstrated that the sequences from the female were significantly more closely related to the sequences from the male than to sequences from the controls. Furthermore, we found that the male and female shared two distinct genetic variants of HIV-1. In p17gag the major variant had an unusual, out-of-frame deletion of 3 nucleotides which the minor variant lacked. These results indicated that the male had transmitted more than one infectious unit to the female. From this study we concluded that it was highly likely that the HIV-1 strains carried by the male and female were closely epidemiologically linked.

Base Sequence↗

Immunological and virological interactions in patients receiving passive immunotherapy with HIV-1 neutralizing monoclonal antibodies.

Mouse monoclonal antibodies with high human immunodeficiency virus type 1 (HIV-1) neutralizing titers were used for passive immunotherapy of eleven late-state HIV-infected patients. In five patients the serum level of the core protein p24 decreased, while in five cases it remained unchanged. The level of viral RNA in plasma as measured by quantitative polymerase chain reaction (PCR) decreased in four cases, was stable in another four, and increased in three cases. An anti-mouse (HAMA) response developed in eight patients and anti-idiotypic antibodies appeared in six. Immune complexes that formed in patient sera during the treatment were shown to contain mostly envelope glycoprotein gp120 which decreased in nine of the eleven treated patients toward the end of treatment. Antibodies inhibiting gp120 binding to CD4 became detectable or increased in six patients during immunotherapy. Serology of the HIV-1 V3 region was studied for both the HIV-1 IIIB and MN strains with no or very small changes in titer or avidity after treatment. No change in neutralizing titers to strain HTLVIIIB was observed in serum samples collected before and after treatment was terminated. In nine of the eleven patients stimulation of the T lymphocytes to proliferate in vitro when activated by phytohemagglutinin (PHA) was shown to be increased compared to before treatment. Increased T-cell proliferation was also noted with several antigens such as HIV-1 recombinant antigens, cytomegalovirus (CMV), tetanus toxoid (TT), and purified protein derivate of mycobacterium tuberculosis (PPD). These findings indicate a decreased total gp120 content in serum, permitting better T-cell activation.

Adult↗

Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers.

We have compared the variable region 3 sequences from 10 human immunodeficiency virus type 1 (HIV-1)-infected infants to virus sequences from the corresponding mothers. The sequences were derived from DNA of uncultured peripheral blood mononuclear cells (PBMC), DNA of cultured PBMC, and RNA from serum collected at or shortly after delivery. The infected infants, in contrast to the mothers, harbored homogeneous virus populations. Comparison of sequences from the children and clones derived from DNA of the corresponding mothers showed that the transmitted virus represented either a minor or a major virus population of the mother. In contrast to an earlier study, we found no evidence of selection of minor virus variants during transmission. Furthermore, the transmitted virus variant did not show any characteristic molecular features. In some cases the transmitted virus was more related to the virus RNA population of the mother and in other cases it was more related to the virus DNA population. This suggests that either cell-free or cell-associated virus may be transmitted. These data will help AIDS researchers to understand the mechanism of transmission and to plan strategies for prevention of transmission.

Amino Acid Sequence↗

Human immunodeficiency virus type 1 and cytomegalovirus in saliva.

The aim of this study was to evaluate whether HIV-1 or cytomegalovirus (CMV) may contribute to oral lesions frequently found in patients with the acquired immunodeficiency syndrome (AIDS). Saliva samples from 63 HIV-1 positive patients and 21 healthy controls were tested for the presence of HIV-1 and CMV using the polymerase chain reaction (PCR) and virus isolation. CMV IgG titres in serum were also compared in the different groups. HIV-1 RNA, but not DNA, was detected in saliva from 15% (9 out of 59) of the HIV-infected patients. There was no correlation between the presence of HIV-1 RNA and oral symptoms in the patients. CMV DNA was detected significantly more frequently in samples from HIV-1 seropositive than from seronegative patients. CMV was detected in saliva from AIDS patients more often than in saliva from patients with mild or no symptoms. CMV IgG titres were also significantly higher in symptomatic than in asymptomatic patients. There was a significant correlation between the presence of CMV DNA and necrotizing gingivitis, and oral Kaposi's sarcoma in the patients, and also between these lesions and the stage of disease. This does not prove that CMV causes these oral lesions, but a direct or indirect role for CMV cannot be excluded.

Acquired Immunodeficiency Syndrome↗

Autologous neutralizing antibodies prevail in HIV-2 but not in HIV-1 infection.

Human immunodeficiency virus type 2 (HIV-2) has been reported to be less pathogenic than HIV-1. We have investigated the capacity of sera from nine HIV-2-infected individuals to neutralize their own autologous virus. All nine HIV-2-infected individuals neutralized autologous virus with titers ranging between 20 and 320. In contrast, we have previously reported that most HIV-1-infected individuals lack such antibodies. The difference between HIV-1 and HIV-2 infection was statistically significant (P < 0.0002, Pearson test) and the difference in neutralizing antibody prevalence may explain the faster disease progression in HIV-1-infected individuals than in HIV-2-infected individuals.

HIV Antibodies↗

Autologous neutralizing antibodies to SIVsm in cynomolgus monkeys correlate to prognosis.

Sequential virus isolates from eight cynomolgus monkeys experimentally infected with SIVsm were studied for susceptibility to neutralization by autologous antibodies. The biological and antigenic characteristics of sequential reisolates differed both from the inoculum virus and from each other. Five monkeys developed neutralizing antibodies to the inoculum virus and the 12-day reisolate at 4 months postinfection, while the remaining three monkeys produced very little, if any, neutralizing antibodies. Strikingly, the two long survivor monkeys developed neutralizing antibody response to a second or third autologous reisolate and to 12 reisolates obtained from other monkeys. Thus the neutralizing antibody response of the long survivor monkeys showed a relatively broad specificity, whereas the neutralizing antibody response of the monkeys with early disease, if at all present, was specific for the infecting strain only and lost over time. Our results show that the pattern of virus neutralization in SIVsm-infected monkeys is similar to human immunodeficiency virus type 1-infected humans. In both cases, variant viruses resistant to neutralization by autologous sera emerge during the entire course of infection. In addition, the ability to produce autologous neutralizing antibodies to sequential virus reisolates appeared to correlate with the degree of immunodeficiency in the host.

Animals↗

Transmission of human immunodeficiency virus type 1 (HIV-1) from mother to child correlates with viral phenotype.

The aim of this study was to investigate if the risk of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) is influenced by the biological phenotype of the mother's virus. Virus isolates from 30 HIV-1 infected mothers and 12 infected children born to these mothers were analyzed for replication on several cell lines (Jurkat-tat, Jurkat, CEM, U937 clone 2, and MT-2). We show that mothers who harbor virus able to replicate in cell lines (rapid/high virus) have a significantly higher risk to infect their children than mothers with slow/low virus (P = 0.017). Children born to mothers with rapid/high viruses can be infected by slow/low as well as rapid/high viruses, while mothers with slow/low virus appear to transmit slow/low virus in every case. Our study shows that the biological phenotype of the mother's virus may serve as a complementary marker to CD4+ lymphocyte counts and p24 antigenemia in predicting the risk of transmission of HIV-1 to the child.

Cell Line↗

Effect of resistance on combination chemotherapy for human immunodeficiency virus infection.

The effect of 3 drug combinations (AZT/FLT, AZT/ddI and FLT/ddI) upon the replication of AZT-sensitive and -resistant human immunodeficiency virus (HIV) was studied. The 3 combinations synergistically inhibited drug sensitive virus. However, AZT resistant virus showed an altered response to the combinations containing AZT: synergy was replaced by addition or antagonism. Thus, the susceptibility to a drug may affect the synergistic effect of combinations containing that drug. Other drug combinations may not be affected, since the AZT resistant virus retained a synergistic response to the combination of FLT/ddI. The synergistic effect could be regained upon reversion of resistance; a viral isolate taken after cessation of therapy, which had reverted to sensitivity to AZT, regained the synergistic response to drug combinations containing AZT. These results have implications for the use of combination chemotherapy to treat infection with HIV. Drug combinations will be most useful if the virus is sensitive to all components in the combination. It might be preferable to avoid the inclusion in combinations of drugs to which there is resistance, since we saw an antagonistic effect for combinations containing AZT in AZT resistant virus. Other combinations not containing the drug to which resistance has arisen may maintain their synergistic effect and remain good choices. Thus, a strategy of monitoring drug sensitivity and altering the combination therapy accordingly would appear to offer promise for the treatment of HIV infection.

Antiviral Agents↗

Radiographic analysis of femoral interference screw placement during ACL reconstruction: endoscopic versus open technique.

Fifty patients with anterior cruciate ligament reconstruction using a bone-patellar tendon-bone autograft performed by two techniques were evaluated roentgenographically to compare the position of the femoral interference screws. Group I consisted of 25 patients in whom the screw was placed using a distal lateral femoral incision (the two-incision technique). Group II patients underwent arthroscopically assisted intraarticular placement of the screw. These patients were then evaluated with anterior-posterior (AP) and lateral roentgenograms. We observed that the AP and lateral screw angles were significantly different with the two techniques. In addition, the endoscopic placement of the femoral screw had an associated divergence of the screw relative to the bone plug in nine of 25 patients compared with zero of 25 in the open group. In conclusion, radiographic differences do exist between femoral interference screws placed for fixation of an ACL graft using the open approach and those placed endoscopically. Although the clinical significance of these differences is not known, we raise the question of greater divergence in femoral interference screw placement with the newer intraarticular femoral interference screw placement techniques.

Anterior Cruciate Ligament↗

Mother-to-child transmission of human immunodeficiency virus type 1: correlation with neutralizing antibodies against primary isolates.

The aim of this study was to investigate the influence of neutralizing antibodies in mother's serum on the risk of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). Sera from 20 HIV-1 infected mothers were analyzed for their ability to neutralize their own virus (autologous neutralization) and virus obtained from other mothers (heterologous neutralization). A statistically significant correlation was found between the capacity to neutralize 1 selected primary isolate and protection of the child from infection. Also, neutralizing antibodies against autologous virus were more frequently present in nontransmitting mothers than in transmitting mothers (5 and 2, respectively, of 10 mothers). The mothers with autologous neutralizing antibodies also neutralized at least 2 heterologous primary isolates. Thus, mothers with neutralizing antibodies to primary HIV-1 isolates have a reduced risk of infecting their children.

Adult↗

Neutralizing antibodies and viral characteristics in mother-to-child transmission of HIV-1.

OBJECTIVE: To determine viral characteristics and the protective effect of virus neutralizing antibodies in mother-to-child transmission of HIV-1. MOLECULAR STUDIES: Ten HIV-1-infected mother-child pairs were sampled within 4 months of delivery. Variable region 3 of the viral envelope was amplified by nested polymerase chain reaction and sequenced, directly and/or after cloning, by solid-phase DNA sequencing. The amino acid sequence of variable region 3 from all 10 children was homogeneous, whereas the mothers showed varying degrees of heterogeneity. Apparently, selection of an HIV-1 variant occurs either at transmission or during initial virus replication in the infected child. No characteristic molecular features of the transmitted virus were identified. BIOLOGICAL STUDIES: Virus isolates from 13 mother-child pairs were characterized for replicative capacity in a variety of cell lines. Eight mothers from whom a virus with a slow/low replicative pattern was isolated transmitted the slow/low virus to their children, whereas mothers with a rapid/high virus transmitted either a rapid/high or a slow/low virus (two cases each). This indicates that viruses with rapid/high replicative capacity do not have a selective advantage during transmission. VIRUS NEUTRALIZING: Sera from 20 mothers were characterized for the ability to neutralize their own virus (autologous neutralization) and virus from other mothers (heterologous neutralization). The results showed that non-transmitting mothers had neutralizing antibodies against autologous virus more frequently than transmitting mothers. In addition, all mothers with autologous neutralizing antibodies also neutralized at least two heterologous primary isolates. This indicates that a broad neutralizing antibody response may be linked to a lower risk of mother-to-child transmission. CONCLUSION: On the basis of the variable region 3 loop sequence, HIV-1-infected infants harbour homogenous virus populations. Despite this, no molecular or biological markers for selective transmission could be identified. A maternal neutralizing antibody response with broad specificity may protect the child from HIV-1 infection.

Amino Acid Sequence↗

Analysis of heterogeneous viral populations by direct DNA sequencing.

The ability of direct PCR sequencing to detect and quantify sequence polymorphisms was investigated using samples containing mixed populations of HIV-1. A part of the genome encoding the polymorphic variable region 3 of the envelope was directly sequenced to yield a consensus sequence of the virus population. The results were compared with sequences obtained by analysis of multiple clones derived from the same clinical samples. The results of five patients suggested that the direct-sequencing method can be used as a rapid tool to analyze and quantify heterogeneous viral populations. Reconstitution experiments using cloned material demonstrated that it was possible to detect and quantify minor sequence variants present in as little as 10% of the total virus population. The use of the method for molecular diagnosis is discussed.

Acquired Immunodeficiency Syndrome↗

Gonadotropin-releasing hormone agonist in treatment of premenstrual symptoms with and without comorbidity of depression: a pilot study.

BACKGROUND: Gonadotropin-releasing hormone agonist (GnRHa) in depot form for once-a-month rather than daily injection was examined in a small open trial to determine the extent of reduction of premenstrual symptoms, particularly premenstrual "depression." METHOD: Women who met criteria for premenstrual syndrome (PMS) or for PMS with comorbidity of major depression (MD), based on DSM-III-R criteria, were evaluated for the study. Evaluation included Structured Clinical Interview for DSM-III-R, administered in the follicular phase, and Daily Symptom Report (DSR), maintained throughout the study. Seven PMS subjects and two subjects who met the severity and change criteria for PMS but had concurrent MD were administered 3.75 mg of depot leuprolide monthly. Symptom change as reported on the DSR was compared with the untreated baseline scores. RESULTS: Six of seven PMS subjects had cessation of menses and significant decreases in premenstrual symptoms (p < .0001), which were reduced to their follicular phase levels. Physical symptoms of swelling and breast tenderness were among the most improved symptoms. Despite cessation of menses, the two MD subjects showed little improvement in premenstrual symptoms and no improvement in depressive symptoms. The premenstrual depression scores decreased almost completely in the PMS subjects, but increased slightly in the MD subjects. CONCLUSION: This small open trial suggests that GnRH agonist therapy reduces premenstrual symptoms including "depression" in women who meet criteria for PMS but not in women with PMS and MD. Further controlled study of the role of ovarian function in mood disorders is needed.

Adult↗