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Biomedical subjects

C M Farber

Publications and source records attributed to C M Farber.

At least 37 records · Page 2Linked to original sources
PubMed1996

Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene.

HIV-1 and related viruses require co-receptors, in addition to CD4, to infect target cells. The chemokine receptor CCR-5 (ref.1) was recently demonstrated to be a co-receptor for macrophage-tropic (M-tropic) HIV-1 strains, and the orphan receptor LESTR (also called fusin) allows infection by strains adapted for growth in transformed T-cell lines (T-tropic strains). Here we show that a mutant allele of CCR-5 is present at a high frequency in caucasian populations (allele frequency, 0.092), but is absent in black populations from Western and Central Africa and Japanese populations. A 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains. In a cohort of HIV-1 infected caucasian subjects, no individual homozygous for the mutation was found, and the frequency of heterozygotes was 35% lower than in the general population. White blood cells from an individual homozygous for the null allele were found to be highly resistant to infection by M-tropic HIV-1 viruses, confirming that CCR-5 is the major co-receptor for primary HIV-1 strains. The lower frequency of heterozygotes in seropositive patients may indicate partial resistance.

Alleles↗
PubMed1996

Decreased skin reactivity to codeine in patients with the acquired immunodeficiency syndrome.

To evaluate the skin reactivity and the mast cell releasibility in the acquired immunodeficiency syndrome (AIDS), 24 patients with AIDS were skin tested with histamine (1 mg/ml) and codeine phosphate (0.9, 0.09, and 0.009 mg/ml), a mast cell degranulating agent. They were compared to 12 HIV-negative healthy volunteers and 16 urticaria-prone subjects. Reactivity to codeine phosphate was lower in patients with AIDS than in HIV-negative subjects. This difference in skin reactivity was the more significant when the AIDS group was compared to the urticaria-prone group. There was no correlation between the reactivity to codeine and the IgE levels. Possible explanations to the decreased skin reacting to codeine in patients with AIDS include a decrease of local mast cell density or releasibility. This suggests that a mechanism related to urticaria and involving mast cells is quite unlikely to be at the origin of the hypersensitivity reactions observed in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Contribution of the polymerase chain reaction to the diagnosis of tuberculous infections in children.

UNLABELLED: The purpose of the study was to evaluate the contribution of polymerase chain reaction (PCR) to the diagnosis of tuberculous infection in children. Two different PCR techniques were compared to the standard bacteriological methods for the detection of Mycobacterium tuberculosis in 157 specimens obtained from the respiratory system of 51 children. Patients were classified in three groups: 12 patients with active disease (57 specimens), 12 patients with silent tuberculous infection (23 specimens) and 27 patients without tuberculosis (77 specimens). One PCR method (PCR/Ag85) used amplification of a fragment of the genes coding for the mycobacterial antigen 85 followed by hybridization of a probe specific for M. tuberculosis on the Southern blot of amplified DNA. The other PCR technique was a nested PCR (NPCR) using double amplification of a fragment of the insertion element IS6110 only present in the M. tuberculosis genome. The sensitivities of the different techniques, compared to the clinical diagnosis, were 7.0% for acid fast staining, 22.8% for culture, 24.6% for PCR/Ag85 and 44.9% for NPCR in active disease, 4.3% for culture, 8.7% for PCR/Ag85 and 28.6% for NPCR in silent tuberculous infection. The specificities were 100% for culture, 94.8% for PCR/Ag85 and 87.9% for NPCR. Among the 12 children clinically considered as having active tuberculosis, 1 had smear positive samples, 4 had at least one positive culture, 7 at least one positive PCR/Ag85 and 9 at least one NPCR positive sample. Among the 12 children having silent tuberculous infection, none had positive smears, 1 had one positive culture, 2 had at least one positive PCR/Ag85 and 5 at least one NPCR positive sample. CONCLUSION: Our study suggests that both PCR techniques, and especially NPCR, are able to detect M. tuberculosis DNA in specimens containing few micro-organisms. PCR methods are more sensitive than culture and the results are available more quickly. Testing multiple samples from the same individual increased the sensitivity. In view of occasional false-positive results, cultures remain the gold standard to establish definitive diagnosis of primary tuberculous infection in children.

Adolescent↗
PubMed1995

T helper type 1/T helper type 2 cytokines and T cell death: preventive effect of interleukin 12 on activation-induced and CD95 (FAS/APO-1)-mediated apoptosis of CD4+ T cells from human immunodeficiency virus-infected persons.

Human immunodeficiency virus (HIV) infection leads to a progressive loss of CD4+ T helper (Th) type 1 cell-mediated immunity that is associated with defective in vitro CD4+ T cell proliferation and abnormal T cell death by apoptosis in response to T cell receptor (TCR) stimulation. Quantification of interleukin (IL)-2, interferon gamma, IL-4, IL-5, and IL-10 secretion by immunoassays, and of interferon gamma, IL-4 and IL-10 messenger RNA expression by competitive reverse transcriptase polymerase chain reaction after in vitro stimulation of the TCR revealed a similar Th1 cytokine profile in T cells from HIV-infected persons and from controls. These data indicated that the loss of CD4+ Th1 cell function in HIV-infected persons is not related to a Th1 to Th2 cytokine switch as previously proposed, but to a process of activation-induced death of CD4+ Th1 cells. Despite the absence of elevated levels of Th2 cytokines, apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented in vitro by antibodies to IL-10 or IL-4, two Th2 cytokines that downregulate Th1 cell responses, or by the addition of recombinant IL-12, a cytokine that upregulates Th1 functions. TCR-induced apoptosis of T cell hybridomas and preactivated T cells has been shown to involve the CD95 (Fas/Apo-1) molecule. CD4+ and CD8+ T cells from HIV-infected persons expressed high levels of the CD95 molecule, and, in contrast to T cells from controls, were highly sensitive to antibody-mediated CD95 ligation, which induced apoptosis in a percentage of T cells similar to that induced by TCR stimulation. As TCR-induced apoptosis, CD95-mediated apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented by the addition of recombinant IL-12. Together, these findings suggest that apoptosis of CD4+ T cells from HIV-infected persons involves an abnormal sensitivity to CD95 ligation, and to TCR stimulation in the presence of normal levels of Th2 cytokines. The preventive effect of IL-12 on both mechanisms has potential implications for the design of immunotherapy strategies aimed at the upregulation of CD4+ Th1 cell functions in AIDS.

Apoptosis↗
PubMed1994

Human HL-60 myeloid leukemia cells transport dehydroascorbic acid via the glucose transporters and accumulate reduced ascorbic acid.

The cellular accumulation of vitamin C, a substance critical to human physiology, is mediated by transporters located at the cell membrane, and is regulated in a cell-specific manner. Neoplastic cells may have special needs for vitamin C. Therefore, we investigated the transport of vitamin C in a human myeloid leukemia cell line (HL-60). The HL-60 cells lacked the capacity to transport the reduced form of vitamin C, ascorbic acid, but they showed a remarkable ability to transport the oxidized form of vitamin C, dehydroascorbic acid (DHA). Uptake-accumulation studies indicated that the HL-60 cells accumulated ascorbic acid when provided with DHA. Kinetic analysis showed the presence of two functional activities involved in the uptake of DHA, one with low affinity and one with high affinity. Cytochalasin B and phloretin, which inhibit the passage of glucose through the facilitative glucose transporters, also inhibited the transport of DHA by HL-60 cells. Transport of DHA was completed by D- but not L-hexoses, and was sensitive to D-hexose-dependent counter transport acceleration. These data support the concept that HL-60 myeloid leukemic cells transport DHA through the facilitative hexose transporters (glucose transporters) and accumulate the reduced form of ascorbic acid.

3-O-Methylglucose↗
PubMed1994

Tumor necrosis factor and intravenous gammaglobulins in common variable immunodeficiency.

Common variable immunodeficiency (CVI) patients require regular intravenous immunoglobulin substitution therapy (IVGG). We studied eight patients; four of whom had adverse reactions to IVGG, and found that those coincided with elevated tumor necrosis factor-alpha (TNF-alpha) levels during infusion. Those reactions and TNF production were abolished by switching from one IVGG preparation to another in two patients. Reappearance of adverse reactions after switching preparation was preceded by a progressive rise in peak TNF levels in one patient.

Adolescent↗
PubMed1994

Herpes simplex virus tracheitis in a patient with the acquired immunodeficiency syndrome.

Herpetic tracheobronchitis and pneumonia occur basically in immunodepressed patients, but have rarely been reported in patients with the acquired immunodeficiency syndrome (AIDS). Some large reviews on pulmonary manifestations in AIDS report a small number of herpetic pulmonary infections, without determining any prevalence of this particular viral involvement. Predisposing factors are alteration of cell-mediated immunity and invasive procedures (such as endotracheal tube use) in debilitated patients. The case we report illustrates the occurrence of a herpetic tracheitis in an HIV-infected patient with severe P. carinii pneumonia, needing systemic corticotherapy and mechanical ventilation. It illustrates the risk of dissemination of herpes simplex virus (HSV) from a herpetic stomatitis to the lower respiratory tract, even after the endotracheal cannula has been removed.

AIDS-Related Opportunistic Infections↗