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.

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.

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.

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.

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.

Spontaneous and plasma factor-mediated transfer of pyrenyl cerebrosides between model and native lipoproteins.

A series of pyrenyl glucocerebrosides was synthesized by reacylation of psychosine with pyrene-labeled fatty acids having 3-11 methylene units. When incorporated into model high-density lipoproteins consisting of dimyristoylphosphatidylcholine-apolipoprotein A-II complexes and incubated with unlabeled complexes, these lipids exhibited spontaneous transfer. Half times of transfer varied from 1.5 min to 365 min at 37 degrees C. The logarithm of the rate of transfer was linearly related to the number of fatty acyl methylene units and HPLC retention time. Transfer occurred by passage of lipid monomers through the aqueous phase. Spontaneous transfer of the glycolipids also occurred when they were incorporated into native high-density lipoproteins. Rates of transfer between native high-density lipoprotein particles were higher than those observed between model high-density lipoprotein particles. A partially purified lipid exchange protein from plasma, as well as unfractionated lipoprotein-deficient serum, stimulated the transfer of fluorescent glycolipid between model high-density lipoprotein or native high-density lipoprotein and low-density lipoprotein 2-24 fold. The protein also stimulated the transfer of tritiated ganglioside GM3 between native low-density lipoprotein and high-density lipoprotein. This protein may play a role in glycolipid exchange in vivo.

Laser balloon angioplasty: potential for reduction of the thrombogenicity of the injured arterial wall and for local application of bioprotective materials.

Mitigation of adverse biologic reactivity after balloon angioplasty is necessary before the incidence of restenosis can be appreciably reduced. A brief review of experimental evidence supports the hypothesis that the thrombogenicity of the injured arterial wall can be reduced by a suitable level of thermal denaturation or cross-linking of thrombogenic proteins. In addition, the concept of local pharmacologic therapy, which can be provided with laser balloon angioplasty at the site of arterial injury, is introduced. Preliminary in vitro and in vivo data suggest that guide catheter-injected albumin-heparin conjugates fabricated as water-insoluble microspheres remain adherent to the injured luminal surface and deeper arterial layers after physical trapping by the inflated balloon and subsequent laser/thermal exposure. The combination of initially adequate luminal morphology, reduction of the thrombogenicity of the injured arterial wall and application of local pharmacologic therapy with laser balloon angioplasty may eventually prove helpful in reducing the incidence of restenosis.

Equivalent recognition of HIV proteins, Env, Gag and Pol, by CD4+ and CD8+ cytotoxic T-lymphocytes.

OBJECTIVES: Cytotoxic T-lymphocytes (CTL) appear to be an important defense mechanism against HIV infection. This study proposes to examine the major histocompatibility complex (MHC)-restricted HIV-1 Env-, Gag- and Pol-specific CTL activities in HIV-infected asymptomatic patients. DESIGN: CD4+ and CD8+ CTL were examined to establish whether the same HIV-1 protein (Env, Gag or Pol) was recognized by both CD4+ and CD8+ CTL with MHC antigen restriction. METHODS: Peripheral blood mononuclear cells, CD4+ and CD8+ T-cells from 17 HIV-infected asymptomatic patients and 10 HIV-seronegative individuals were examined for HIV-1 Env-, Gag- and Pol-specific MHC-restricted cytotoxicity using autologous and heterologous B-lymphoblastoid cell lines infected with vaccinia recombinant expressing HIV-1 Env, Gag and Pol proteins as targets. RESULTS: CD4+ and CD8+ CTL specific for the HIV-1 Env, Gag and Pol were demonstrated in the peripheral blood. DR4 and DQw2 were possible sites of MHC class II restriction of CD4+ CTL. Possible MHC class I restriction sites of CD8+ CTL included A2 and B8 for Env, A1 and A2 for Gag, and A2 and B8 for Pol antigen. CONCLUSIONS: These observations should help to define more precisely the nature and elements of protective immunity and to evaluate AIDS vaccine strategies.

Muscle glycolipids in inherited muscular dystrophy of chickens.

Gangliosides and neutral glycolipids of muscles from normal and dystrophic chickens were studied. Total glycolipid content of the degenerating muscles was higher than the normal muscles. In addition, the myopathic muscles contained a ganglioside which was absent in the unaffected muscles from normal and dystrophic chickens. Based on the thin-layer chromatographic mobility, treatment with neuraminidases from Vibrio cholerae and Arthrobacter ureafaciens, and reactivity of the asialo-derivative towards anti-ganglio-N-triaosylceramide antibody, the dystrophic-specific ganglioside was tentatively identified as GM2. Data obtained from young and old dystrophic chickens suggested a direct relationship of this ganglioside to muscular dystrophy.

Human immunodeficiency virus envelope glycoproteins.

Given the long-term clinical latency and high level of replication of human immunodeficiency virus (HIV), it is not surprising that HIV has developed a method of persistence involving production of novel variants in its proteins. Therapeutic vaccines attempt to harness enhanced immune mechanisms to control viral replication, and thus prevent disease progression. A major problem in the development of a vaccine is the great variety of viral quasispecies in HIV infection worldwide and within the lifetime of a given individual. Furthermore, the protective immune parameters that correlate with the ability to control disease progression remain undefined. Manufacturers have followed a number of paths to select an immunogen. At present, investigators are monitoring different immune and viral parameters to measure the effects of therapeutic vaccination. This monitoring ranges from HIV-specific cellular and humoral immunity to viral load markers and skin tests to recall antigens. Two possible major limitations to this treatment approach are the declining potency of the immune response and the ability of the virus to produce escape mutants, particularly during disease progression as viral replication increases. The latter escape mechanism could be similar to the specific pol mutations that enable the virus to escape the impact of drug therapy. Although apparent safety has been observed in phase II/III studies using several HIV envelope-based therapeutic vaccines, investigators have documented reproducible immunogenicity only in HIV-seropositive individuals with CD4+ T cells > 400/mm3. A convincing impact of vaccine therapy on viral load or the course of HIV disease has not been demonstrated.

Interleukin-2 induced killer cell activity against Epstein-Barr virus-immortalized human B cells.

Interleukin-2 (IL-2) activated killer (LAK) cells, generated in vitro by treating peripheral blood lymphocytes (PBL) with human IL-2, are able to lyse a wide variety of target cells without restriction by major histocompatibility complex (MHC) molecules. Earlier observations from this and other laboratories indicated that patients with Epstein-Barr virus (EBV) induced infectious mononucleosis, a self-limiting viral disease, have high EBV-non-specific natural killer (NK) cell activity. Since the effect of LAK cells on EBV-immortalized B lymphocytes has not yet been studied, we decided to investigate LAK cell activity against autologous and heterologous B lymphocytes immortalized in vitro by EBV and other EBV genome-positive and -negative targets of malignant origin. LAK activity was determined by 51Chromium release assay. The results obtained show that LAK activity was not specific for EBV and was not MHC-restricted. Results of experiments using NK cell reactive monoclonal antibodies suggest that the cytotoxicity is due predominantly to activated NK cells. Our observations suggest that LAK cells may be very effective for immunotherapy in patients with chronic or progressive EBV infections and EBV-induced lymphoproliferative diseases.

Glycosphingolipid receptors for anti-Gd and anti-p cold agglutinins.

Anti-Gd and anti-p cold agglutinins exhibit similar serological properties: neuraminidase treatment of erythrocytes greatly reduces their agglutinability by these antibodies and protease treatment enhances their agglutination. We reported previously that an anti-p cold agglutinin was inhibited by sialosyllactoneotetraosylceramide, NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc-Cer, the most abundant ganglioside of human erythrocytes. We now report that two less abundant gangliosides are more potent inhibitors of this antibody, and of the anti-Gd antibodies, than sialosyllactoneotetraosylceramide. These two gangliosides have the same carbohydrate chain, NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc(SNH), but they differ in their ceramide moiety. The principal fatty acid of SNH-1 is C16:0, whereas SNH-2 contains a predominance of C22:0, C24:0 and C24:1. No inhibition was produced by the ganglioside, NeuAc(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc-Cer. Another monoclonal cold agglutinin, Sa, which shares some serological properties with anti-Gd cold agglutinins, was not inhibited by any of these gangliosides.

Role of Vicia villosa-adherent CD8+ T cells in the immune response to Epstein-Barr virus.

Epstein-Barr virus (EBV) is a lymphotropic human herpesvirus which is also a polyclonal B-cell activator. We show here that Vicia villosa-adherent CD8+ T (VV-T) cells, which have a contrasuppressive activity, play an important role in the B-cell response to EBV and that T-helper cells are not required for antibody production against EBV particles. We have examined this activity by measuring anti-EBV IgM antibody production by B cells in vitro in the presence and the absence of both T-helper and VV-T cells. The presence or absence of T-helper cells did not affect antibody production. Our results suggest that the antigen-presenting activity of VV-T cells was virus specific, while the contrasuppressive activity was not. Control experiments carried out in parallel using human cytomegalovirus (CMV) produced similar results also for CMV-specific IgM production. Taken together, our data lead us to hypothesize that VV-T cells might also play other roles in EBV infections: on the one hand, by presenting EBV to B cells, VV-T cells could contribute to the spread of viral infection of B lymphocytes, as the latter are the exclusive targets for EBV immortalization within the immune system; on the other hand, by inhibiting the effect of T-suppressor cells on T-helper cells, VV-T cells could indirectly help the latter maintain their lymphokine producing activity, especially interleukin-2 and interferon-gamma production, which in turn could directly or indirectly (i.e., by stimulating natural killer and T cells) contribute to control of the EBV infection.

CD8+ CD11+ suppressor cells in HIV-infected asymptomatic patients: effect on HIV-specific cytotoxicity.

CD3+CD8+CD11+ cells were present in the peripheral blood of patients infected with asymptomatic human immunodeficiency virus (HIV) in higher percentage (10-20%) than in normal individuals (3-5%) in this study. These cells, through the release of soluble factors, significantly suppressed the effector phase of anti-HIV cytotoxic activities, both human leukocyte antigen (HLA)-class I or class II restricted, and nonrestricted. The effectors were CD8+CD11-, CD4+ T cells, and CD16+ cells for HLA-class I, class II restricted, and nonrestricted cytotoxicities, respectively. The soluble factors also inhibited natural killer cell activity. Thus, this effect was neither HLA-restricted nor antigen-specific. These CD3+CD8+CD11+ cells may be an important immunopathogenic factor in HIV disease.

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.

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.

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.

Regional blood flow distribution during extracorporeal membrane oxygenation in rabbits.

To study regional blood distribution during extracorporeal membrane oxygenation, we stabilized three groups of five rabbits each (3 to 5 kg) on venoarterial bypass at a flow rate of 30 ml/kg/min. Albumin aggregates (15 to 30 microns) labeled with technetium 99m were injected into the left ventricle during bypass (ventricle), the perfusion cannula during bypass (cannula), and the left ventricle with no bypass (control). Animals were put to death, organs were removed, and the percent distribution was determined with a gamma camera. The Student Newman-Keuls test was used for statistical comparisons. Distribution to both the heart and brain in the cannula group were decreased from control by 55% and 35%, respectively. Distribution to the brain in the ventricle group was also decreased from control by 39%. Intestinal distribution was elevated above control in the ventricle group by 37%, whereas musculoskeletal distribution was elevated 33% above control in the cannula group. No significant changes were noted for the kidneys, stomach, or liver. These data suggest that overall perfusion of some vital organs may be significantly reduced during low-flow extracorporeal membrane oxygenation, specifically in the case of the heart and brain, which may be deprived of oxygenated blood.

Antibodies to glycosphingolipids in patients with multiple sclerosis.

Antibodies to one or more glycosphingolipids were detected by means of a liposome lysis assay in the sera of 60/81 patients with multiple sclerosis, 24/42 patients with systemic lupus erythematosus and in the majority of patients with cranial trauma or cerebrovascular accidents. Antibodies against ganglioside GM1 and asialo GM1 were found most commonly and they were frequently present in the same sera. Among patients whose sera contained antibodies to glycolipids, anti-GM1 alone occurred more frequently in patients with multiple sclerosis (14/59) than in systemic lupus erythematosus (1/22; p = 0.045) and antiasialo GM1 alone was more common in patients with lupus (9/22) than in patients with multiple sclerosis (8/59, p = 0.007). In 10 sera analyzed, all of the antibodies against these two glycolipids were of the IgM class, and some fluctuation in antibody titers was noted over a three-month period. The role of these antibodies in the initiation or perpetuation of inflammatory diseases of the central nervous system remains to be determined.