Biomedical subjects

M S Hasan

Publications and source records attributed to M S Hasan.

7 recordsLinked to original sources

PubMed2001

Hepatitis B immunization of healthy elderly adults: relationship between naïve CD4+ T cells and primary immune response and evaluation of GM-CSF as an adjuvant.

The efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance the primary immune response to hepatitis B vaccine was studied in healthy elderly with young volunteers included as controls in this double-blind, placebo-controlled trial of GM-CSF as an immune adjuvant. Naïve T-helper cells (CD4+CD45RA+) were determined at baseline. Forty-five healthy elderly (average age, 74 years) and 37 healthy young controls (average age, 28 years) were randomized. Hepatitis B vaccine was administered at 0, 1, and 6 months. GM-CSF as a single injection of either 80 microg or 250 microg with the first and second doses of hepatitis B vaccine. In this trial GM-CSF did not enhance antibody responses. However, the antibody responses were dramatically different between these two groups: 35/35 young developed a protective titer versus 19/45 elderly (P < 0.0001). In addition, the mean logarithm of anti-hepatitis B antibody level in the 35 young who completed the study was 3.17 (log mIU/ml) but only 2.21 in the 19 elderly responders (P < 0.0001). Naïve T-helper cells differed significantly between the two groups: the mean percentage of CD4+CD45RA+ T cells was 47.9% versus 35.0% (P < 0.0001) in the young and elderly volunteers respectively. Naïve T cells also differed significantly between elderly who did or did not respond to HBV (39.9% vs. 31.7%, P = 0.039). Using linear regression, age, and percent naive, CD4 T cells were determined to significantly influence the anti-hepatitis B antibody response, but sex and dose of GM-CSF did not. For a two-parameter model: logarithm of antibody titer = (-0.038 x age in years) + (0.031 x % naïve CD4T cells) + 2.68; adjusted r2 = 0.605 and P < 0.0001. However, age had a larger effect than naive CD4 T cells, i.e., in comparing young and elderly groups the log antibody titer decreased by 1.73 due to the increase in age but only 0.40 due to the decrease in naive CD4 T cells. Thus, there was a large effect of age that could not be explained by the quantitative change in the naïve T-helper cells.

Adjuvants, Immunologic↗

PubMed2000

Effects of interleukin-15 on in vitro human T cell proliferation and activation.

Interleukin-15 (IL-15) has been reported to have many activities on T cell populations, including a potential role in improving antigen-specific proliferation in HIV-1 disease. We tested this response in healthy adults by studying the response of T cell populations after stimulation with medium, tetanus, cytomegalovirus (CMV) antigens in cultures from 21 volunteers. IL-15 caused a dose-dependent increase in medium and antigen-induced proliferation. The expansion was due to CD8>natural killer (NK)>CD4 lymphocytes and memory > naive cells. The IL-15-stimulated CD8 cells had increased levels of the activation markers CD69 and DR. The published CMV-induced expression of CD57 on CD8+ cells was increased in CMV seronegative and seropositive subjects by IL-15. IL-15 appears to be a stimulator of T cell populations in healthy adults and may be useful in settings to enhance nonspecific NK activity or antigen-specific CD8 activity.

Adult↗

PubMed1999

Primary isolate neutralization by HIV type 1-infected patient sera in the era of highly active antiretroviral therapy.

Sera from highly selected HIV-1-positive patients are known to have the ability to neutralize a diverse array of primary isolates of HIV-1. The human osteosarcoma cell line that expresses CD4 and chemokine receptors (GHOST cells) was adapted to study HIV-1 neutralization in 37 HIV-1-infected individuals who were selected because of slow disease progression or nonprogression. Many of these individuals were receiving combination drug therapy. Molecularly cloned HIV-1 JR-FL and NL4-3 viruses were used as prototypes to define assay conditions. Sera were then tested at a 1:40 dilution against six additional primary isolates, three of which utilized CCR5 and three of which used both CCR5 and CXCR4. The assay was highly reproducible and independent of viral input titer, with a readout at 48 hr equivalent to that at later time points. As previously reported, neutralization sensitivity was entirely independent of coreceptor usage. Only a few sera from slow progressors were able to neutralize a broad array of primary isolates at a 1:40 dilution, and the best clinical predictor of broadly neutralizing antibody for primary isolates was the present use of antiretroviral agents. In further studies it was found that purified antibody accounted for the majority of the measured neutralization. However, experiments with exogenous addition of antiviral agents showed that the use of nucleosides also greatly contributed to the measured neutralization in some patients. Measurement of neutralization of HIV-1 primary isolates by sera from patients receiving antiretroviral therapy must be carried out with some caution.

Anti-HIV Agents↗

PubMed1999

Development of a fluorescent light technique for evaluating microdamage in bone subjected to fatigue loading.

A new method using fluorescent light microscopy has been developed to visualize and evaluate bone microdamage. We report the findings of two different experiments with a common aim of comparing the fluorescent light technique to the brightfield method for quantifying microdamage in bone. In Experiment 1, 36 canine femurs were tested in four-point cyclic bending until they had lost between 5 and 43% of their stiffness. The loaded portion of the bone was stained en bloc with basic fuchsin for the presence of damage. Standard point counting techniques were used to calculate fractional damaged area (Dm.Ar = Cr.Ar/B.Ar, mm2/mm2) under brightfield and fluorescent microscopy. In Experiment 2, bone microdamage adjacent to endosseous implants, subjected to fatigue loading (150,000 cycles, 2 Hz and 37 degrees C) ex vivo was examined. The bone around the implant was either allowed to heal (adapted specimen) for 12 weeks after placement in dog mid-femoral diaphyses prior to testing or was loaded immediately to simulate non-healed bone surrounding endosseous implants (non-adapted). Crack numerical density (Cr.Dn = Cr.N/B.Ar, #/mm2), crack surface density (Cr.S.Dn = Tt.Cr.Le/B.Ar, mm/mm2) and fractional damaged area were calculated separately by both techniques in the adapted and non-adapted specimens. In both Experiments 1 and 2, significantly more microdamage was detected by the fluorescent technique than by the brightfield method. Also, there was a trend towards higher intraobserver repeatability when using the fluorescent method. These results suggest that the brightfield technique underestimates microdamage accumulation and that the fluorescent technique better represents the actual amounts of microdamage present. The results demonstrate that the fluorescent method provides an accurate and precise approach for bone microdamage evaluation, and that it improves the prediction of stiffness loss from damage accumulation.

Animals↗

PubMed1999

Granulocyte macrophage colony-stimulating factor as an adjuvant for hepatitis B vaccination of healthy adults.

Granulocyte macrophage colony-stimulating factor (GM-CSF) has shown promise as an adjuvant to improve the kinetics and magnitude of the immune response after vaccination. It was hypothesized that GM-CSF given intramuscularly (IM) with hepatitis B vaccine would result in increased seroconversion rates and antibody titers. In total, 108 healthy volunteers (18-45 years old) received recombinant hepatitis B vaccine IM at 0, 1, and 6 months and were randomized to receive either concurrent GM-CSF (80 or 250 microgram) or placebo IM with the first two vaccinations. The percentages of subjects achieving a protective level of antibody at day 56 were 58.3%, 58.8%, and 58.3% in the placebo and 80- and 250-microgram GM-CSF arms, respectively. The geometric mean titers of antibody measured on days 28, 56, and 189 were not statistically different between arms. GM-CSF given immediately before recombinant hepatitis B vaccination was safe and well tolerated but did not appear to provide significant adjuvant activity at this dose.

Adjuvants, Immunologic↗

PubMed1998

Does microdamage accumulation affect the mechanical properties of bone?

It has never been demonstrated that microcrack accumulation in bone leads to impaired mechanical properties. We hypothesized that microdamage accumulation is positively and linearly correlated with a reduction in bone's elastic modulus. We also tested the hypothesis that damage accumulates more rapidly in tensile cortices, but crack growth is greater in compressive cortices. Canine femurs (n = 26) were tested in four-point cyclic bending under load control until they had lost between 5 and 43% of their stiffness. Ten femurs were used as nonloaded controls. The loaded portion of the bone was stained en bloc with basic fuchsin to detect the presence of microdamage. The number of stained microcracks, their lengths and the area of damaged bone were measured under the microscope. Crack numerical density, surface density, mean crack length, and the percentage of damaged area were calculated. Significant microdamage accumulation was not detected until the bone had lost 15% of its elastic modulus. The relationship between crack density and stiffness loss was approximately quadratic, but the relationship between damaged area and stiffness loss was linear. There were significantly more microcracks in tensile cortices, but on average cracks were significantly longer in compressive cortices. We conclude that microcrack accumulation impairs the mechanical properties of bone by reducing its elastic modulus. We also conclude that damage accumulates more rapidly in tensile cortices, but crack growth is greater in compressive cortices.

Animals↗

PubMed1997

Application of artificial neural network for micro-crack and damage evaluation of bone.

This paper presents the reasoning and adaptive learning method of artificial neural network (ANN) for micro-crack assessment and damage accumulation due to stiffness loss of dog bone. The importance of using the alternative approach of ANN is that it avoids the complexity of modeling problems, overrides the consideration of simplified assumptions and can be developed directly from experimental data using adaptive learning mechanisms. The proposed artificial neural network model provides a relationship between microdamage accumulation, stiffness loss and number of fatigue cycles (Nf) to failure from an experimental study where stiffness loss and crack area (Cr.Ar., mm2/mm2) are evaluated. This preliminary study using ANN for microdamage evaluation shows that ANN accurately predicts the amount of damage accumulation from stiffness loss.

Animals↗