The molecular mechanisms of probiotic strains in improving ageing bone and muscle of d-galactose-induced ageing rats.

AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system. METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P < 0·05). Strain L. fermentum DR9 demonstrated improved expression of SOD in bone and muscle compared to the aged rats (P < 0·05). In the evaluation of myogenesis-related genes, L. paracasei OFS 0291 and L. fermentum DR9 increased the mRNA expression of IGF-1; L. helveticus OFS 1515 and L. fermentum DR9 reduced the expression of MyoD, in contrast to the aged controls (P < 0·05). Protective effects of L. fermentum DR9 on ageing muscle were believed to be contributed by increased AMPK-α2 expression. Among the osteoclastogenesis genes studied, TNF-α expression was highly elevated in tibia of aged rats, while all three probiotics strains ameliorated the expression. Lactobacillus fermentum DR9 also reduced the expression of IL-6 and TRAP in tibia when compared to the aged rats (P < 0·05). All probiotics treatment resulted in declined proinflammatory cytokines IL-1ß in muscle and bone. CONCLUSIONS: Lactobacillus fermentum DR9 appeared to be the strongest strain in modulation of musculoskeletal health during ageing. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated the protective effects of the bacteria on muscle and bone through antioxidative and anti-inflammatory actions. Therefore, L. fermentum DR9 may serve as a promising targeted anti-ageing therapy.

What is the publication rate for presentations given at the British Academic Conference in Otolaryngology (BACO)?

OBJECTIVES: The publication rate of some large academic meetings such as the American Academy of Otolaryngology-Head and Neck Surgery has been reported as 32%. We aimed to compare the rate of publication at the British Academic Conference in Otolaryngology (BACO) to allow surveillance of research activity in the United Kingdom (UK). DESIGN AND SETTING: The abstract records of both BACO 2009 and 2012 were examined. The MEDLINE database was searched using PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and an iterative approach. We recorded time to publication as well as the authors' region and journal. MAIN OUTCOME MEASURES: publication rate by conference, region and journal. RESULTS: Twice the number of presentations were made at BACO 2012 (n = 814) compared to BACO 2009 (n = 387). Absolute numbers of publications were 158 in 2012 and 92 in 2009. Overall, the publication rate dropped from 24% overall in 2009 to 19% in 2012. This difference in proportions was not significant (P = 0.08). The number of abstracts accepted for BACO 2012 doubled from BACO 2009 in nearly every subspecialty category, except the general/training category, which trebled. For both conferences, head and neck was the largest subspecialty abstract category, as well as the largest subspecialty publication category. CONCLUSIONS: This study showed that the majority of abstracts presented at BACO 2009 and 2012 did not progress to publication. The rate of publication was similar to that seen in other general ENT meetings but do not compare favourably to the 69% rate seen for presentations made at the Otorhinolaryngological Research Society (ORS). The large increase in accepted abstracts at BACO 2012 may reflect growing competition for entry to specialist training.

A re-appraisal of publication rates of scientific papers presented at the Otorhinolaryngology Research Society meetings.

OBJECTIVES: To review the rate of publication of papers in peer-reviewed journals after oral presentations at the Otorhinolaryngology Research Society meetings between 1996 and 2013 and to compare trends with the previous review (1979-1995). DESIGN: Literature review. SETTING: Merseyside ENT Research Collaborative. PARTICIPANTS: The abstracts of presentations at Otorhinolaryngology Research Society meetings are published in Clinical Otolaryngology. A structured search of PubMed was undertaken to identify published Otorhinolaryngology Research Society presentations. MAIN OUTCOME MEASURES: Publication rates. RESULTS: A total of 460 abstracts were identified. The interobserver reliability among reviewers was 98%. Of the total, 259 (56.3%) abstracts were published in peer-reviewed journals. The average time from Otorhinolaryngology Research Society presentation to publication was 27.7 months (median 23), which was not significantly different from the previous review. Publication by subspeciality was as follows: head and neck (45.6%), otology (30.5%), rhinology (22%) and others (1.9%). Most published Otorhinolaryngology Research Society presentations were published in Clinical Otolaryngology (22.4%), followed by the Journal of Laryngology and Otology (8.1%) and the Laryngoscope (7.3%). Clinical research was the most common category of abstracts being presented at Otorhinolaryngology Research Society meetings, followed by laboratory-based research. Over half (56.5%) of laboratory research presented were head and neck themed, while otology and rhinology predominated clinical research presentations. Over half (52.1%) of Otorhinolaryngology Research Society abstracts originated from units in the North of England. Bristol presented the most abstracts (30.1%), followed by Newcastle (25.1%). CONCLUSIONS: The publication rate of Otorhinolaryngology Research Society presentations remains high and many are subsequently published in high-impact factor otolaryngology journals. More Otorhinolaryngology Research Society presentations are now published in American and European journals.

Interferon dysregulation and virus-induced cell death in avian influenza H5N1 virus infections.

1. Hyper-induction of cytokines and chemokines was found in human blood macrophages infected with the avian influenza H5N1 and H9N2/G1 viruses, as compared to those infected with human influenza H1N1 virus. 2. IRF3 played a significant role in the hyperinduction of cytokines including IFN-ß, IFN-λ1,IFN-α subtypes, MCP-1, and TNF-α, and also played a part in subsequent cytokine-induced cell signalling cascades. 3. Compared with H1N1 viruses, avian influenza viruses including H5N1/97 and its precursors triggered a caspase-mediated but delayed apoptotic response in human macrophages. 4. Therapies that can minimise immunopathology-associated dysregulation of innate immunity without impairing effective host defence may be valuable adjuncts to antiviral therapy.

Epistaxis and atorvastatin: is there an association and are clinicians aware? A retrospective audit of 100 patients.

OBJECTIVE: Epistaxis is a common ENT presentation. The British National Formulary lists epistaxis as a common side effect of atorvastatin. This study aimed to better understand the relationship between epistaxis and atorvastatin use, and determine whether ENT doctors are aware of its side effect profile. METHODS: A retrospective analysis over 10 months identified 100 individuals who presented to hospital with epistaxis. A questionnaire of 24 ENT registrars was undertaken. RESULTS: Of the 100 patients admitted with epistaxis, 27 were receiving atorvastatin and 21 simvastatin. None of the 24 ENT registrars were aware that epistaxis was a listed common side effect of atorvastatin. CONCLUSION: There was no apparent difference in the proportion of patients admitted with epistaxis taking atorvastatin versus simvastatin. Epistaxis is an unknown side effect of atorvastatin; doctors have an obligation to be aware of the pharmaceutical literature and to consider alternatives, particularly in re-admissions cases.

A multi-centre analysis of a decade of endoscopic pharyngeal pouch surgery in Cheshire and Merseyside.

BACKGROUND: There are sparse data on the outcomes of endoscopic stapling of pharyngeal pouches. The Mersey ENT Trainee Collaborative compared regional practice against published benchmarks. METHODS: A 10-year retrospective analysis of endoscopic pharyngeal pouch surgery was conducted and practice was assessed against eight standards. Comparisons were made between results from the tertiary centre and other sites. RESULTS: A total of 225 procedures were performed (range of 1.2-9.2 cases per centre per year). All centres achieved 90 per cent resumption of oral intake within 2 days. All centres achieved less than 2-day hospital stays. Primary success (84 per cent (i.e. abandonment of endoscopic stapling in 16 per cent)), symptom resolution (83 per cent) and recurrence rates (13 per cent) failed to meet the standard across the non-tertiary centres. CONCLUSION: Endoscopic pharyngeal pouch stapling is a procedure with a low mortality and brief in-patient stay. There was significant variance in outcomes across the region. This raises the question of whether this service should become centralised and the preserve of either tertiary centres or sub-specialist practitioners.

Therapist Reports of EBP Client Engagement Challenges in Sessions with Diverse Youth and Families in Community Mental Health Settings.

BACKGROUND: The implementation of evidence-based practices (EBPs) in community settings appears to result in reduced benefit relative to controlled trials. This difference in outcomes may be attributable in part to engagement challenges therapists encounter when delivering EBPs to low-income ethnic minority youth and families. OBJECTIVE: The current study sought to identify therapist, client, and session characteristics associated with therapist-reported engagement challenges in therapy sessions, as well the associations between two types of client engagement challenges and therapists' self-reported ability to deliver the EBP in sessions within a system-driven implementation in public children's mental health services. METHOD: One hundred and three therapists reported on two types of engagement challenges-Limited Client Engagement and Expressed Client Concerns-in 702 sessions with 274 clients. RESULTS: Results indicated that therapists reported a higher frequency of Limited Client Engagement in sessions with male clients and in sessions where the youth was present, and by therapists with smaller caseloads. No variables significantly predicted Expressed Client Concerns. Both types of engagement challenges were negatively associated with therapists' report of their ability to carry out intended activities in the same session. CONCLUSIONS: Findings suggest that therapists may benefit from learning strategies to address these two distinct types of engagement challenges encountered in implementation of EBPs with diverse families in community settings.

Lactobacilli modulated AMPK activity and prevented telomere shortening in ageing rats.

This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5'adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 (P<0.05). Plasma lipid peroxidation was lower (P<0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control (P<0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.

Bifidobacterium longum BB536 alleviated upper respiratory illnesses and modulated gut microbiota profiles in Malaysian pre-school children.

This 10-months randomised, double-blind, parallel and placebo-controlled study evaluated the effects of Bifidobacterium longum BB536 on diarrhoea and/or upper respiratory illnesses in 520 healthy Malaysian pre-school children aged 2-6 years old. The subjects randomly received a one-gram sachet containing either BB536 (5×109 cfu) or placebo daily. Data analysis was performed on 219 subjects who fully complied over 10-months (placebo n=110, BB536 n=109). While BB536 did not exert significant effects against diarrhoea in children, Poisson regression with generalised estimating equations model indicated significant intergroup difference in the mean number of times of respiratory illnesses over 10 months. The duration of sore throat was reduced by 46% (P=0.018), with marginal reduction for duration of fever (reduced by 27%, P=0.084), runny nose (reduced by 15%, P=0.087) and cough (reduced by 16%, P=0.087) as compared to the placebo. Principal coordinate analysis at genus level of the gut microbiota revealed significant differences between 0 and 10 months in the BB536 group (P<0.01) but not in placebo group (P>0.05). The abundance of the genus Faecalibacterium which is associated with anti-inflammatory and immuno-modulatory properties was significantly higher in the BB536 group (P<0.05) compared to the placebo group. Altogether, our present study illustrated the potential protective effects of BB536 against upper respiratory illnesses in pre-school Malaysian children, with gut microbiota modulating properties.

Endotoxin induction of tumor necrosis factor is enhanced by acid-labile interferon-alpha in acquired immunodeficiency syndrome.

High levels of an acid-labile IFN-alpha have been demonstrated in the sera of patients with symptomatic HIV infection. IFNs have been shown to enhance the cytotoxic and antiproliferative actions of tumor necrosis factor (TNF), which is a potent mediator of inflammation and sepsis. We show that the acid-labile IFN-alpha present in AIDS sera can induce TNF synthesis and sensitize blood monocytes (BM) to endotoxin stimulation resulting in further synthesis of TNF in vitro. TNF production by BM from patients with HIV infections and normal controls was measured by a cytotoxicity assay on L929 cells using human TNF alpha as a standard. BM from AIDS patients spontaneously produce high levels of TNF and are hypersensitive to endotoxin stimulation, resulting in enhanced synthesis of TNF. In determining the mechanism involved, we demonstrated that treatment of normal BM with AIDS sera results in induction of TNF. Neutralization of the acid-labile IFN-alpha in AIDS sera with polyclonal anti-IFN-alpha antibodies results in diminution of TNF induction. In addition, pretreatment of normal BM with AIDS sera, IFN-alpha, or IFN-gamma renders the cells hypersensitive to endotoxin. Consequently, activation of the TNF system by the acid-labile IFN-alpha contributes to some of the physiological disturbances, such as the wasting syndrome, and to the pathophysiology of sepsis in AIDS patients.

Downregulation of interferon alpha but not gamma receptor expression in vivo in the acquired immunodeficiency syndrome.

Interferons (IFN) elicit antiviral and antineoplastic activities by binding to specific receptors on the cell surface. In evaluating the role of IFN as therapeutic agents in AIDS, we investigated the expression of IFN alpha and gamma receptors on peripheral blood mononuclear cells (PBM) from patients with AIDS, ARC, and heterosexual control subjects using radioiodinated IFN alpha 2 and IFN gamma. The binding characteristics of the 125I-IFN alpha and gamma to PBM were analyzed to determine receptor numbers and dissociation constants. PBM from controls expressed 498 +/- 247 IFN alpha receptor sites/cell (n = 17). However, eight patients with ARC and seven patients with AIDS had a mean number of IFN alpha receptor/cell of 286 +/- 235 (P less than 0.05) and 92 +/- 88 (P less than 0.001), respectively. This was consistent with elevated levels of serum acid-labile IFN alpha and cellular 2-5A synthetase activity in patients. Treatment of PBM from the AIDS patients with exogenous IFN alpha in vitro resulted in minimal 2-5A synthetase induction in comparison to controls. In contrast, the expression of IFN gamma receptors in ARC (n = 5) and AIDS (n = 4) patients remained normal. Thus the decrease in IFN alpha receptor expression and consequent hyporesponsiveness to IFN alpha raises the question of the usefulness of IFN alpha therapy in end-stage AIDS. The normal expression of IFN gamma receptors in AIDS patients suggests that IFN gamma may prove useful in attempts to provide immune reconstitution.

Regulation of interferon receptor expression in human blood lymphocytes in vitro and during interferon therapy.

Interferons (IFN) elicit antiviral and antineoplastic activities by binding to specific receptors on the cell surface. The binding characteristics of IFN to human lymphocytes were studied using IFN alpha 2 labeled with 125I to high specific activity. The specific binding curves generated were analyzed by the LIGAND program of Munson and Rodbard to determine receptor numbers. The number of receptors in peripheral blood lymphocytes (PBL) and tonsillar B-lymphocytes (TBL) from normal individuals were 505 +/- 293 (n = 10) and 393 +/- 147 (n = 3) respectively. When these cells were preincubated in vitro with unlabeled IFN alpha 2, the receptor number decreased to 82 +/- 45 and 61 +/- 16 respectively. Receptor binding activities recovered gradually over a period of 72 h when the cells were incubated in IFN-free medium. This recovery of receptors could be blocked by the addition of actinomycin D to the incubation medium. A similar decrease in receptor expression was observed in vivo in PBL from patients being treated daily with 5 X 10(6) units/m2 per d of IFN alpha 2 by subcutaneous injection, for acute lymphoblastic leukemia or papilloma virus infections. Receptor numbers in PBL in vivo were further reduced concurrent with the progression of IFN therapy. Thus the reduction in IFN receptor expression observed in vitro can be demonstrated in vivo. These studies indicate that monitoring IFN receptor expression in vivo can provide information regarding the availability of IFN receptors at the cell surface for the mediation of IFN actions during the course of IFN therapy.

Induction of matrix metalloproteinases by Epstein-Barr virus latent membrane protein 1 isolated from nasopharyngeal carcinoma.

Epstein--Barr virus latent infection is associated with human malignancies including Burkitt's lymphoma, gastric carcinoma and the highly invasive nasopharyngeal carcinoma (NPC). Increased expression of EBV latent membrane protein 1, LMP1, is correlated with tumor progression and metastasis in NPC. LMP1 induces cellular proteins including cytokines and matrix metalloproteinases (e.g., MMP1, MMP2 and MMP9). MMPs are endopeptidases involved in the degradation of extracellular matrix proteins; and their upregulation in cancer implicates their potential role in tumor metastasis. In light of the role of LMP1 in cytokine dysregulation and the fact that MMPs are regulated by cytokines, we examined whether LMP1 promotes NPC metastasis via the induction of MMPs. To delineate the oncogenic role of LMP1 in NPC, we first investigated the induction of MMP1, MMP2, MMP3 and MMP9 in LMP1-positive NPC tumor samples (n=15) by quantitative RT-PCR. We showed a significant induction of MMP1 and MMP3 transcripts in the EBV LMP1-positive NPC tissues, compared with biopsies obtained from the adjacent non-tumor tissues. To investigate the role of LMP1 in MMP expression in NPC, we cloned the LMP1 gene from NPC samples and transiently expressed it in MRC5 cells (human lung fibroblasts). Following transfection, a time-dependent elevation of endogenous MMP3 expression was found in the LMP1-transfectants by quantitative RT-PCR and Western analysis. Taken together, we observed that MMP3 is upregulated in LMP1-positive NPC tumors and LMP1-expression in fibroblasts is associated with MMP3 and cytokine expression. Our results suggest that LMP1 may contribute to invasiveness of NPC cells via the expression of MMP3 in fibroblasts.

The BeSMART (Best Supportive Management for Adults Referred with Tonsillopharyngitis) multicentre observational study.

Introduction Tonsillopharyngitis is the most common ear, nose and throat emergency admission, with 80,000 episodes recorded in England in 2015-2016. Despite this, there is a paucity of evidence addressing the supportive management of tonsillopharyngitis in inpatients. The aim of this retrospective multicentre observational study was to consider the Best Supportive Management for Adults Referred with Tonsillopharyngitis (BeSMART) in the inpatient setting, and to establish any associations between practice and outcomes. Methods Seven hospitals in North West England and North East Scotland participated in the study. Overall, 236 adult patients admitted with tonsillopharyngitis were included. The main outcome measures were interval to return to soft diet, length of stay (LOS), pain scores and readmissions. Results Women were more likely to seek professional help before presenting to secondary care (p=0.04). Patients admitted at the weekend were more likely to have a shorter LOS (p=0.03). There was no relationship between day of admission and seniority or specialty of the doctor initially seen. Prescription of corticosteroid, analgesia and a higher initial intravenous fluid infusion rate were not related to a shorter LOS. Conclusions This study is the first to yield valuable insights into the inpatient management of tonsillopharyngitis. This work represents part of an ongoing project to establish the evidence for common medical interventions for sore throat. Patient and professional surveys as well as a prospective interventional study are planned for the future.

Recombinant human interferon alpha-2 and juvenile chronic myelogenous leukemia: cell receptor binding, enzymatic induction, and growth suppression in vitro.

Recombinant human leukocyte interferon (HuIFN alpha 2) was studied to determine its potential as a therapeutic agent for the lethal monocytic malignancy of infancy, juvenile chronic myelogenous leukemia (JCML). In sharp contrast to cell cultures of normal marrow, specimens from two patients with JCML yielded an excessive and rapid proliferation of monocyte-macrophage elements without growth factor in clonogenic assay and in liquid culture. Using IFN alpha 2 labeled with 125I, the characteristics of IFN binding to cultured JCML monocyte-macrophages and their receptor site numbers were determined. IFN binding to cells from both patients disclosed two components: a high-affinity of 120 and 430 sites/cell, and a lower affinity of 1230 and 2500 sites/cell, respectively. In control studies, normal blood mononuclear cells or tonsillar B-lymphocytes displayed only a high-affinity component. Brief exposure of JCML cells to IFN alpha 2 in vitro resulted in a sharp increase in the IFN-induced enzyme 2-5A synthetase, indicating the ability of JCML cells to respond metabolically. Dose-response studies performed in a clonogenic assay showed a dose-dependent growth inhibition of JCML monocyte-macrophage colonies using IFN alpha 2 at concentrations of 10(2)-10(5) U/ml. These studies provide new information on the biological characteristics of JCML malignant cells, and suggest that IFN may be useful for treatment of this disorder.

The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-alpha.

OBJECTIVE: To investigate the induction of cytokines as a possible mechanism for the neurotoxicity of the HIV-1 envelope protein gp120. DESIGN: The gp120 protein was tested directly on primary human brain cultures to examine its ability to induce cytokines and its neurotoxicity on human neural cells because gp120 is known to be toxic to rodent ganglion cultures, and neural cells such as astrocytes and microglia produce cytokines when stimulated. METHODS: Primary cultures of human brain cell aggregates, astrocytes and macrophages were exposed to HIV-1 recombinant (r) gp120SF2. Induction of cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR); neurotoxicity of rgp120SF2 and interleukin (IL)-6 on human brain cultures was examined by electron microscopy. RESULTS: ELISA and RT-PCR studies revealed that rgp120SF2 induced IL-6 and tumor necrosis factor (TNF)-alpha in brain cultures; IL-6 could also be induced by TNF-alpha added to brain cultures. Both IL-6 and TNF-alpha were upregulated in astrocytes and macrophage cultures on rgp120SF2 treatment. Ultrastructural studies demonstrated that IL-6 treatment for 72 h induced large cytoplasmic vacuoles in neural cells with morphology consistent with neurons; rgp120SF2 treatment for 7 days resulted in chromatin condensation along the inner margins of nuclear envelopes of neural cells. CONCLUSIONS: Our results demonstrated that HIV-1 rgp120SF2 can upregulate at least two known neurotoxic cytokines, IL-6 and TNF-alpha, which may injure neural cells and contribute to the neuropathology observed in AIDS dementia patients.

Inhibition of HIV-1 gp120-induced apoptosis in neuroblastoma SK-N-SH cells by an antisense oligodeoxynucleotide against p53.

OBJECTIVES: This study examines the cytotoxicity potential and the mechanism of toxicity of the HIV-1 gp120 on human neuroblastoma cells. DESIGN: Previous data from our group have suggested that the HIV-1 envelope protein gp120 promotes the secretion of tumor necrosis factor-alpha and other factors by astrocytes and microglial cells present in primary human brain cell cultures, thereby contributing to the injury of neurons in these cultures. This study investigates the cytotoxicity potential and the mechanism of toxicity of gp120 on human neuroblastoma cells. METHODS: SK-N-SH cells were treated with HIV-1 gp120, and was followed by in situ DNA fragmentation staining and small molecular weight DNA extraction studies to ascertain the induction of apoptosis by gp120 in these cells. To evaluate a potential role of the growth suppressor gene p53, gp120-treated SK-N-SH cells were subjected to reverse transcription polymerase chain reaction (RT-PCR) and Western blot analyses for the induction of p53. An antisense oligodeoxynucleotide against p53 was used to investigate the role of p53 in the gp120-induced apoptosis in these cells. RESULTS: Data from T7 DNA polymerase staining and small molecular weight DNA extraction studies demonstrated that gp120-induced DNA breakage in SK-N-SH cells with fragmentation patterns characteristic of apoptosis. RT-PCR and Western blot analyses revealed that the gp120-mediated induction of apoptosis was dependent on a gp120-induced and gp120-sustained upregulation of p53. The induction of p53 by gp120 was specific, since an antibody against gp120 prevented both the induction of p53 and subsequent apoptosis in SK-N-SH cells. The critical role of p53 was further illustrated by the effectiveness of a p53 antisense oligodeoxynucleotide to inhibit the gp120-induced apoptosis. As a control, the apoptosis-inducing potential of gp120 on SK-N-SH cells was not seen in the HIV-1 Gag proteins even when used at up to 5 nM. CONCLUSIONS: These results established that HIV-1 gp120 is potentially cytotoxic to human neuronal cells through the induction of p53, which may eventually lead to induction of apoptosis.