Safety and Feasibility of Trans Radial Percutaneous Coronary Intervention Approach in Elderly Patients with Acute Coronary Syndrome.

Coronary catheterization is usually performed using the transfemoral approach but trans-radial has been increasingly used as an alternative to transfemoral approach due to less vascular complications, earlier ambulation time and improved patient comfort. The aim of the study was to compare the safety and feasibility of trans-radial and transfemoral PCI in the elderly ACS patients. This prospective observational study was conducted in the NICVD, Dhaka from October 2017 to September 2018. Total 80 patients were categorized into two groups according to the approach of PCI. Group I consists 40 patients who underwent trans-radial PCI and Group II consists 40 patients who underwent transfemoral PCI. Patients with abnormal Allen's test, history of CABG, CKD were excluded. Patient's demographics were same in both groups. The mean procedural time in min (37.44±5.13 vs. 34.42±4.42, p=0.004) and fluoroscopy time in min (21.6±4.11 vs. 17.55±2.78, p=0.02) were more in Group I but the mean hemostasis time in min (7.58±1.11 vs. 15.59±3.33, p=0.005) and the ambulation time in hour (0.00±0.00 vs. 15.59±3.33, p=0.001) were more in Group II. Significant arterial spasm following puncture (10.0% vs. 0.0%, p=0.01) were more in Group I. Post procedural major bleeding (0.0% vs. 10.0%, p=0.004), minor bleeding (10.0% vs. 20.0%, p=0.004) were significant in Group II but vessel occlusion (5.0% vs. 0.0%, p=0.02) were significant in Group I. Transradial PCI is safe in respect of procedural and post procedural vascular complications. Transradial procedure leads to improved quality of life after the procedure and thus gives much comfort to the patient. It also shortened mean duration of hospital stay. So transradial approach is an attractive alternative to conventional transfemoral approach in the elderly.

Impact of Myocardial Blush Grade on In-Hospital Outcome after Primary Percutaneous Coronary Intervention.

Primary percutaneous coronary intervention (PPCI) is the optimal reperfusion strategy in patients with ST elevation Myocardial Infarction (STEMI). However, despite achieving TIMI 3 flow after PPCI, some patients have less optimal perfusion at the myocardial tissue level, as assessed by Myocardial Blush Grade (MBG) and consequently show adverse outcome. This prospective observational study was performed in the National Institute of Cardiovascular Diseases (NICVD), Dhaka, Bangladesh from March 2016 to February 2017. Total 74 patients with STEMI who underwent primary PCI and achieved TIMI 3 flow were included among them 37 patients were taken with low MBG (grade 0 or 1) in Group I and other 37 patients with high MBG (grade II or III) were taken in Group II. Mean age of Group I and Group II were 53.70±9.17 and 51.49±9.41 years respectively (p=0.536). Male to female ratio was 5.7:1. Smoking (59.5% versus 35.1%, p=0.036) and diabetes mellitus (43.2% versus 18.9%, p=0.024) were significantly higher in low MBG group than high MBG group. Multi vessel involvement (24.3% versus 5.4%, p=0.022) and anterior MI (72.9% versus 51.4%, p=0.047) were significantly higher in low MBG group. LVEF was significantly lower in low MBG group than high MBG group (49.92?6.60% versus 58.84?4.55%, p=0.003). Among the complications acute heart failure was found significantly higher in low MBG group than high MBG group (8.1% versus 0.0%, p=0.048) along with total adverse in hospital outcome (24.3% versus 5.4%, p=0.041). In study population total mortality was 2.7% and all were in low MBG group (5.4%). Multivariate logistic regression analysis showed MBG was an independent predictor of adverse in hospital outcome after PPCI (OR 6.553, 95% CI 1.984-21.643, p=0.002). Low MBG is associated with more adverse in hospital outcome after PPCI. So, along with TIMI 3 flow following PPCI we have to assess MBG for evaluation of complete reperfusion and further outcome.

Serum Albumin Level and In-Hospital Outcome of Patients with First Attack Acute Myocardial Infarction.

Acute myocardial infarction (AMI) patients constitute a large proportion of admissions in coronary care unit and their management and risk stratification is of immense importance. A decrease in serum albumin concentration might be associated with an increased risk in the incident of both cardiovascular diseases and worse hospital outcome. We assessed whether serum albumin levels at admission was associated with in-hospital adverse outcome in patients with first attack of acute myocardial infarction (AMI). The aim of the study was to evaluate association of serum albumin level with in-hospital outcome in patients with first attack of acute myocardial infarction. This cross-sectional analytical study was conducted in the department of cardiology in Mymensingh Medical College Hospital, Mymensingh, Bangladesh from March 2017 to February 2018. Total 374 patients of first attack of acute myocardial infarction included considering inclusion and exclusion criteria. The sample population was divided into two groups: Group I (Patients with acute myocardial infarction with serum albumin <3.5gm/dl) and. Group II (Patients with acute myocardial infarction with serum albumin ≥3.5gm/dl). Serum albumin level was measured within 24 hours of admission and the incidence of in-hospital major cardiac outcomes was observed. In this study mean±SD serum albumin level of Group I, Group II were 3.02±0.12gm/dl, 4.48±0.50gm/dl respectively. In Group I patient, 52(59.80%), 7(8.00%), 10(11.50%), developed heart failure, cardiogenic shock, arrhythmias respectively and 8(9.20%) died and in Group II patient 20(7.90%), 7(2.80%), 8(3.20%) developed heart failure, cardiogenic shock, arrhythmias respectively and 4(1.60%) died out of them and all of these outcome were statistically significant. Mean±SD duration of hospital stay of the study population according serum albumin level, in Group I, 5.76±1.83 days, in Group II, 4.40±1.22 days which was statistically significant (p<0.05). In conclusion, patient with first attack of acute myocardial infarction serum albumin level below 3.50gm/dl increased the risk of worse in-hospital outcome.

Combination of Sonodynamic and Photodynamic Therapy against Cancer Would Be Effective through Using a Regulated Size of Nanoparticles.

Nanoparticles have been used for many functional materials in nano-sciences and photo-catalyzing surface chemistry. The titanium oxide nanoparticles will be useful for the treatment of tumor by laser and/or ultrasound as the sensitizers in nano-medicine. We have studied the combination therapy of photo- and sono-dynamic therapies in an animal tumor model. Oral-administration of two sensitizers titanium oxide, 0.2%-TiO2 nanoparticles for sono-dynamic and 1 mM 5-aminolevulinic acid for photodynamic therapies have resulted in the best combination therapeutic effects for the cancer treatment. Our light microscopic and Raman spectroscopic studies revealed that the titanium nanoparticles were distributed inside the blood vessel of the cancer tissue (1-3 µm sizes). Among these nanoparticles with a broad size distribution, only particular-sized particles could penetrate through the blood vessel of the cancer tissue, while other particles may only exhibit the side effects in the model mouse. Therefore, it may be necessary to separate the optimum size particles. For this purpose we have separated TiO2 nanoparticles by countercurrent chromatography with a flat coiled column (1.6 mm ID) immersed in an ultrasonic bath (42 KHz). Separation was performed with a two-phase solvent system composed of 1-butanol-acetic acid-water at a volume ratio of 4:1:5 at a flow rate of 0.1 ml/min. Countercurrent chromatographic separation yielded fractions containing particle aggregates at 31 and 4400 nm in diameter.

Relaxation dynamics of liposomes in an aqueous solution.

The gel-liquid crystal phase transition has been studied by the temperature and frequency dependent dielectric relaxation behavior of liposomes in an aqueous solution (40 g L(-1) DPPC-water mixture). Four relaxation processes were observed in the frequency range from 40 Hz to 30 GHz which were ascribed to different molecular mechanisms, related to the structural units of the system. The gel-liquid crystal phase transition was also described very accurately from the temperature-dependent dielectric relaxation strength, relaxation time and symmetric shape parameter of the relaxation functions obtained from the fitting procedure. Relaxation process 3, obtained from the dielectric fitting procedure, was confirmed by dielectric modulus analysis. A comparison of the lipid membrane with non-biological systems like liquid crystals was performed. It was determined that the lipid membrane has a ferroelectric liquid crystal like behavior. Process 3 is comparable to the soft mode relaxation process observed in ferroelectric liquid crystals which was detected close to the smectic-C*-smectic-A phase transition. Differential scanning calorimetry was also used to confirm the gel-liquid crystal phase transition of this mixture.

Advanced rheological characterization of soft colloidal model systems.

The complex flow behavior of polymer-based soft colloidal model systems was investigated using steady and oscillatory shear to prove new concepts for advanced rheological characterization. In the very dilute regime we investigated high molecular weight polybutadiene star polymers to quantify the internal relaxation time arising from the polymeric nature of these ultra-soft colloids. The observed shear-induced brush deformation is interpreted in terms of the internal Zimm time τ(z). The observed dependence of τ(z) on matrix viscosity can be explained by shrinkage of the star polymer due to an increasing incompatibility with increasing matrix molecular weight. The influence of the polymeric nature on the characteristic structural relaxation time in the concentrated regime was investigated using non-linear rheology following Wyss et al (SRFS) (2007 Phys. Rev. Lett. 98 238303). Here we used star-like block copolymer micelles to systematically tune the 'softness' of the colloids by variation of the block ratio. A master curve with proper scaling parameters could be generated independent of the degree of colloidal 'softness'. However, the obtained strain-rate independent structural relaxation time τ(0) was not observed in the linear regime. In addition, a high frequency discrepancy was clearly found in all our experimental data. Both reflect the shortcomings of the SRFS approach.

Targeted therapy in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) of multi-factorial etiopathogenesis is rising worldwide. Treatment-associated toxicity problems and treatment failure in advanced disease stages with conventional therapies have necessitated a focus on alternative strategies. Molecular targeted therapy, with the potential for increased selectivity and fewer adverse effects, hold promise in the treatment of HNSCC. In an attempt to improve outcomes in HNSCC, targeted therapeutic strategies have been developed. These strategies are focusing on the molecular biology of HNSCC in an attempt to target selected pathways involved in carcinogenesis. Inhibiting tumor growth and metastasis by focusing on specific protein or signal transduction pathways or by targeting the tumor microenvironment or vasculature are some of the new approaches. Targeted agents for HNSCC expected to improve the effectiveness of current therapy include EGFR inhibitors (Cetuximab, Panitumumab, Zalutumumab), EGFR tyrosine kinase inhibitors (Gefitinib, Erloitinib), VEGFR inhibitors (Bevacizumab, Vandetanib), and various inhibitors of, e.g., Src-family kinase, PARP, proteasome, mTOR, COX, and heat shock protein. Moreover, targeted molecular therapy can also act as a complement to other existing cancer therapies. Several studies have demonstrated that the combination of targeting techniques with conventional current treatment protocols may improve the treatment outcome and disease control, without exacerbating the treatment related toxicities. Some of the targeted approaches have been proved as promising therapeutic potentials and are already in use, whereas remainder exhibits mixed result and necessitates further studies. Identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from targeted treatment.

Dielectric relaxation behavior of a liquid crystal showing an unusual type of antiferroelectric-ferroelectric-antiferroelectric phase sequence.

The temperature and frequency dependent dielectric relaxation behavior of a liquid crystalline (S)-(+)-1-methylheptyl 4-[2-(4-alkoxyphenyl) thiophene-5-carbonylthiooxy] benzoate system is reported. Interesting successive antiferroelectric-ferroelectric-antiferroelectric (AF-FE-AF) phase transitions are observed in this system resembling the successive phase transitions observed in crystalline Rochelle salt. The smectic-C* (SmC*) to AF1 phase transition (around 103.0 degrees C) is first order in nature, predicted from the use of Orihara and Ishibashi theory. It is also found that a contribution of the ferroelectric SmC* phase ordering penetrates even in the antiferroelectric AF1 (SmC(*)(A)) and AF2 (SmC(*)(A)) phases very close to the SmC*-AF1 and SmC*-AF2 phase boundaries (critical regions). It is suggested that this type of mixing of AF and FE phases might cause surface induced ferroelectric- or ferroelectric-type ordering near the AF-FE phase transitions. A soft mode with Debye-type dispersion was observed in the SmA phase. The thermal behaviors of dielectric dispersion, absorption, and dielectric strength in different phases are also reported and discussed.

Dielectric investigation of electrically oriented ferroelectric smectic mixture CS-1013.

From dielectric spectroscopic study, a first-order ferroelectric phase transition has been observed in ferroelectric smectic mixture CS-1013 having the phase sequence Cr-SmC*-SmA-N*-Iso. Frequency (100 Hz-10 MHz) and temperature-dependent dielectric measurements have been performed on an electrically aligned sample (thickness 15+/-1 microm) gold coated on glass plates. In the unidirectionally aligned sample, two dielectric relaxation modes (Goldstone mode and soft mode) have been clearly observed in the ferroelectric SmC* phase while only one relaxation mode (soft mode) is visualized in the paraelectric SmA phase. Low-frequency molecular relaxation was also observed in the smectic phases. The experimental results have also been analyzed at different temperatures and biasing voltages for an understanding of the dynamics of dielectric processes in the ferroelectric phase. Finally, we proposed the "pseudospin" model for understanding the ferroelectric-antiferroelectric transition in liquid crystals. We associate the tilt angle straight theta and the pitch of the helix, respectively, with biaxial (b) and uniaxial (u) anisotropy parameters as fluctuating parameters around their stability limit (corresponding to the crystalline values). Here, the director acts as the pseudospin variable. This gives rise to a transverse Ising type (or anisotropic Heisenberg model under the mean-field approximation). It is then shown that such a model with fluctuations of (b) and (u) would explain the ferroelectric and antiferroelectric phase transitions in such liquid crystals. Using Landau theory and the stability conditions, we have also shown, in brief, the feasibility of different types of phase transitions in the ferroelectric liquid crystal system.

In vivo persistence of donor cells following adoptive transfer of allogeneic dendritic cells in HIV-infected patients.

Peripheral blood samples from HIV-seropositive individuals enrolled in a pilot clinical trial investigating the use of allogeneic dendritic cell therapy were evaluated for mixed chimerism. In this study, dendritic cells from HLA-identical, HIV-seronegative siblings were used. Patients received an infusion of dendritic cells pulsed with HIV MN gp160 protein or with peptides from HLA-A2 restricted epitopes of env, gag, and pol proteins every month for 6-9 months. Of the five allogeneic dendritic cell recipients, two showed increases in HIV antigen-specific immune responses. Allele-specific polymorphisms were identified in three sib-pairs that allowed infused donor cells to be detected using sensitive PCR-based molecular methods. Analysis of blood samples from patients showed similar patterns of donor cell persistence after the first infusion, in that cells were detectable for at least 1 week. Also, differences were observed in the kinetics of cell survival between the first and subsequent infusion cycles in all three patients. This suggests variation in HIV-specific immune responses detected among these three patients was not due to differences in persistence of infused donor cells.

Frequency of class I HLA-restricted anti-HIV CD8+ T cells in individuals receiving highly active antiretroviral therapy (HAART).

Peptide/MHC tetrameric complexes were used to enumerate the frequency of HLA class I-restricted epitope-specific CD8+ T cells in 18 HLA-A*0201 HIV type 1-infected asymptomatic patients. HLA-A*0201 molecules were complexed to HIV Gag p17 (amino acids 77-85) and reverse transcriptase (amino acids 464-472) peptides, biotinylated, and bound to streptavidin-phycoerythrin to form tetramers. We show in this study that 17 of 18 HIV-1-infected asymptomatic patients have circulating frequencies of 1/50-1/1000 CD8+ T cells that recognize both Gag and Pol CTL epitopes or either epitope alone. The functional nature of these cells is open to interpretation, as we show that despite relatively high frequencies of fresh epitope-specific CD8+ T cells, variant epitope sequences in viral plasma progeny were rare. In addition, the majority of tetramer-positive cells did not display discernible fresh CTL activity; only after restimulation with specific peptide in culture was there an expansion of epitope-specific CD8+ cells, correlating with high CTL activity. These data suggest that fresh tetramer-stained cells probably represent memory precursors; we demonstrate, with the application of highly active antiretroviral therapy, that the interruption of chronic antigenic stimulation causes significant reductions in the frequency of these cells in five of six patients. In conclusion, this study provides evidence that persistently replicating viral populations are probably required to maintain high frequencies of HIV-1 epitope-specific CD8+ T cells in asymptomatic chronically infected individuals

Variation in net photosynthesis, stomatal characteristics, leaf area and whole-plant phytomass production among ten provenances of neem (Azadirachta indica).

Variation in net photosynthesis, CO(2) exchange parameters, stomatal characteristics, leaf area and seedling dry weight were investigated among 10 provenances of neem (Azadirachta indica A. Juss.). Significant provenance variation was established for net photosynthesis (8.14 to 15.13 &mgr;mol m(-2) s(-1)), stomatal conductance (0.37 to 0.59 mol m(-2) s(-1)), stomatal density (145 to 204 mm(-2)), and total guard cell length (2681 to 3873 &mgr;m). Net photosynthesis was positively correlated with whole-plant dry weight and leaf area. Stomatal density was positively correlated with net photosynthesis, whole-plant dry weight, and leaf area. Total guard cell length was positively correlated with all of these traits. Information on six traits was used in a cluster analysis to construct a dendrogram to assess phenetic relationships among the provenances. With a few exceptions, the dendrogram revealed three major clusters grouped according to rainfall distribution. The study indicated that whole-plant phytomass production of neem seedlings was associated with photosynthesis and stomatal characteristics during the early stages of growth.

Role of preimmunization virus sequences in cellular immunity in HIV-infected patients during HIV type 1 MN recombinant gp160 immunization.

The effect of patient preimmunization virus sequences on CTL responses during gp160 immunization were studied. Ten HLA-A2+, HIV+ asymptomatic patients with CD4+ T cells >500/mm3 were given two courses of HIV-1 MN rgp160 vaccine over a 2-year period. Envelope epitope-specific CTL responses, using PBMCs, were measured against peptide-coated autologous B lymphoblastoid cell lines. Optimum CTL epitopes were determined by HLA-A2-binding affinity of 9- to 10-mer peptides containing the HLA-A2.1-binding motif. Ten of the high- or intermediate-binding peptides were conserved among >50% of reported clade B HIV strains. These peptide-specific CTL activities and the patient virus sequences in peptide-coding regions were monitored. Six patients showed envelope peptide-specific CTL responses, which correlated with the presence of whole envelope antigen-specific CTL responses. Five of these patients, who showed responses to epitopes in the gp41 region (aa 814-824), had preimmunization virus similar to the vaccine sequence in this region. Three patients who did not show these epitope-specific responses had initially different sequences in the HIV gene encoding that region. The epitope-specific CTL responses appear to reflect recall responses, as only patients infected with virus containing the vaccine sequence developed them and they could be recalled with a second set of vaccine injections. This appears to be reminiscent of the concept of T cell "original antigenic sin." This vaccine was also immunogenic as measured by gp160-specific lymphocyte-proliferative responses. However, increased immune responses did not impact the HIV load or CTL epitope sequences during therapy.

A pilot clinical trial of HIV antigen-pulsed allogeneic and autologous dendritic cell therapy in HIV-infected patients.

A pilot study was carried out to assess the safety and antigen-presenting properties of allogeneic or autologous dendritic cells (DCs) in six HLA-A2+, HIV-infected patients. Allogeneic DCs obtained from the peripheral blood of HLA-identical, HIV-seronegative siblings were pulsed with recombinant HIV-1 MN gp160 or synthetic peptides corresponding to HLA-A2-restricted cytotoxic epitopes of envelope, Gag, and Pol proteins. The antigen-pulsed cells were infused intravenously six to nine times at monthly intervals and HIV-specific immune responses were monitored. One allogeneic DC recipient with a CD4+ T cell count of 460/mm3 showed increases in envelope-specific CTL- and lymphocyte-proliferative responses, as well as in IFN-gamma and IL-2 production. Another allogeneic DC recipient with a CD4+ T cell count of 434/mm3 also showed an increase in HIV envelope-specific lymphocyte-proliferative responses. A recipient of autologous DCs with a CD4+ T cell count of 730/mm3 showed an increase in peptide-specific lymphocyte-proliferative responses after three infusions. Three other allogeneic DC recipients with CD4+ T cell counts <410/mm3 did not show increases in their HIV-specific immune responses. No clinically significant adverse effects were noted in this study and CD4+ T cell numbers and plasma HIV-1 RNA detected by RT-PCR of all six patients were stable during the study period. Thus, both allogeneic and autologous DC infusions were well tolerated and in patients with normal or near normal CD4+ T cell counts administration of these antigen-pulsed cells enhanced the immune response to HIV. However, since no effect on viral load was observed there was no evidence that this approach provided clinical benefit.

Generation of primary peptide-specific CD8+ cytotoxic T-lymphocytes in vitro using allogeneic dendritic cells.

Dendritic cells (DC) are potent antigen-presenting cells (APC) capable of inducing strong T-cell-mediated immunity. Infusion of lymphoma-specific antigen-loaded autologous DC has been demonstrated to result in the generation of antigen-specific immunity and reduction in tumor burden in B-cell lymphoma patients. Cellular immunotherapy employing antigen-loaded DC could have a potential therapeutic impact in tumors and viral infections, including HIV infection. However, DC in HIV-infected individuals and breast cancer patients are believed to be functionally defective. Therefore, the potential of using allogeneic DC offers significant implications for DC immunotherapy in AIDS and immunocompromised cancer patients. To explore the potential of allogeneic DC therapy in vivo, we tested the ability of allogeneic DC to generate primary peptide-specific CD8+ cytotoxic T-lymphocyte (CTL) responses in vitro. Our results indicate that DC from HLA class I-matched individuals elicit primary immune responses in vitro using viral peptides as naive antigens. A primary peptide-specific immune response could also be detected even when only one HLA allele (HLA-A*0201) was matched between the allogeneic DC and T-lymphocytes. The ability to generate primary peptide-specific responses in vitro is strongly indicative of the in vivo therapeutic potential of allogeneic DC.

Effect of therapeutic immunization with recombinant gp160 HIV-1 vaccine on HIV-1 proviral DNA and plasma RNA: relationship to cellular immune responses.

Therapeutic vaccination has been proposed as a strategy to augment immune mechanisms to control viral replication and slow clinical progression of HIV infection to disease. Following recombinant gp160 (r-gp160) immunization in three clinical trials, plasma HIV-1 RNA and cellular proviral DNA were assessed by quantitative polymerase chain reaction (PCR) in 76 HIV-seropositive subjects with CD4+ T cell counts > or = 300/mm3. Immunization increased HIV-specific cellular immune responses (e.g., cytotoxic T lymphocyte [CTL] activities, lymphocyte proliferative responses); however, there were no significant effects of immunization or cellular immune responses on measures of plasma RNA or cellular DNA viral load.

Heterogeneity of cytokine functions in HIV infection.

Immunological responses, especially cytokines, play important roles in determining the persistence of infectious agents in chronic diseases. Th1 responses enhance cellular immunity to control infection whereas Th2 immune responses down-regulate these effector immune responses. It has been suggested that the Th1 to Th2 switch is involved in human immunodeficiency virus (HIV) disease progression. We studied the regulatory role of interleukin-4 (IL-4; Th2 response) on interferon-gamma (IFN-gamma; Th1 response) in HIV infection and its role in the generation of HIV-specific cytotoxic T lymphocytes (CTL) in an in vitro system. Forty HIV-infected, asymptomatic individuals and 20 HIV-seronegative individuals were included in this study. Peripheral blood mononuclear cells were stimulated with phytohaemagglutinin and tetanus toxoid in the presence or absence of IL-4 to determine the effect of IL-4 on IFN-gamma production and HIV-Env-specific CTL activity. IL-4 showed a dual effect on IFN-gamma production in HIV patients. IL-4 down-regulated IFN-gamma production in HIV-seronegative individuals and in 55% of HIV patients whereas it stimulated IFN-gamma production in 45% of HIV patients. IL-4 increased HIV-Env-specific CTL activity in five of seven patients of the latter group. IL-4 has multiple biological activities, e.g. IL-4 inhibits IFN-gamma production as well as stimulates CTL generation which in turn produces IFN-gamma. Understanding the biological significance of these interactions is of importance for immunotherapeutic approaches against HIV infection.

Allogeneic dendritic cell induction of HIV-specific cytotoxic T lymphocyte responses from T cells of HIV type 1-infected and uninfected individuals.

The potential benefit of T cell-based vaccination for HIV-1 infection remains to be determined. Cytotoxic T lymphocytes (CTLs) appear to clear substantial populations of HIV-1 virus in vivo, although CTL activity may contribute to the decline in CD4+ T cell count observed in the course of the disease. To investigate further the role of specific CTL responses in the control of HIV-1 replication, we raised primary CTL lines against a panel of conserved HIV-1 epitopes using blood-derived dendritic cells as antigen-presenting cells (APCs). Specific primary human CTL responses were induced against HLA-A*0201-restricted peptides with dendritic cells from HIV-1-seronegative donors. This method of immunization elicited cytotoxic activities capable of recognizing endogenously processed antigen. The CTL induction protocol was extended in order to explore the capacity of HLA-matched allogeneic dendritic cells to evoke novel CTL responses in T cells from an HIV-seropositive asymptomatic individual. Allogeneic peptide-pulsed dendritic cells from a healthy sibling were capable of eliciting a CTL response directed against an HIV epitope (env814: SLLNATDIAV) that was initially not detected in the CTL effector population of the HIV-1-infected patient. The possibility of manipulating CTL specificity directed against multiple conserved HIV-1 epitopes represents a significant step in the evaluation of T cell-based vaccination for treatment of disease.

Polyethylene glycol-modified interleukin-2 and thymosin alpha 1 in human immunodeficiency virus type 1 infection.

The safety and antiviral effects of polyethylene glycolated interleukin-2 (PEG-IL-2) and thymosin alpha 1 in addition to zidovudine were studied in 12 human immunodeficiency virus (HIV)-infected subjects with 50-250 CD4 T cells/mm3. PEG-IL-2 was administered by intravenous infusions every 2 weeks at 10(6) IU/m2 for 20 weeks. Thymosin alpha 1 was administered subcutaneously at 400 microgram/m2 after four doses of PEG-IL-2, escalating to 1600 microgram/m2 weekly for an additional 2 months. Significant elevations of CD4 T cell numbers of 30%-40% were seen after PEG-IL-2 infusions, but no additional increase in CD4 cell count was observed with thymosin alpha 1. Virologic monitoring by polymerase chain reaction quantitation of proviral DNA and plasma RNA and p24 antigen assays showed no evidence of increased HIV activation during PEG-IL-2 or thymosin alpha 1 therapy. Patients tolerated both PEG-IL-2 and thymosin alpha 1 without significant toxicities.