Effect of Prior ChAdOx1 COVID-19 Immunisation on T-Cell Responses to ChAdOx1-HBV.

There are varying data concerning the effect of prior anti-vector immunity on the T-cell response induced by immunisation with an identical vectored vaccine containing a heterologous antigen insert. To determine whether prior exposure to ChAdOx1-SARS-CoV2 immunisation (Vaxzevria) impacts magnitudes of antigen-specific T-cell responses elicited by subsequent administration of the same viral vector (encoding HBV antigens, ChAdOx1-HBV), healthy volunteers that had received Vaxzevria (n = 15) or the Pfizer or Moderna mRNA COVID-19 vaccine (n = 11) between 10 and 18 weeks prior were recruited to receive a single intramuscular injection of ChAdOx1-HBV. Anti-ChAdOx1-neutralising antibody titers were determined, and vector or insert-specific T-cell responses were measured by a gamma-interferon ELISpot and intracellular cytokine staining (ICS) assay using multiparameter flow cytometry.

A comprehensive human leukocyte antigen analysis of 36 782 cord blood units stored in the Australian Public Cord Blood Banking Network.

Background And Aims: The network of public cord blood banks (CBBs) in Australia, known as AusCord, comprises CBBs located in Brisbane, Sydney and Melbourne. A novel comprehensive analysis has been performed to determine whether the cryopreserved, searchable cord blood unit (CBU) inventory of approximately 36 000 units share similar tissue types or haplotypes.

Methods: Human leukocyte antigen (HLA) data was analysed using Microsoft Excel following standardisation of typing data.

New science and treatment paradigms for atopic dermatitis.

Purpose Of The Review: The prevalence of atopic dermatitis is increasing in industrialized countries for unclear reasons. One theory centers on reduced exposure to microbes during infancy and childhood. Alterations in the epidermal permeability barrier, place certain patients at risk for the immunological dysfunction seen in atopic dermatitis.

Haematopoietic stem cell transplantation for primary immunodeficiency syndromes: A 5-year single-centre experience.

Aim: Haematopoietic stem cell transplantation (HSCT) is a central therapy in the treatment of primary immunodeficiency diseases (PIDs). Over the past 5 years, outcomes have been greatly improved due to earlier diagnosis, improved donor availability, advancements in graft manipulation and the use of less toxic preparative regimens. We present a 5-year audit of HSCT for PID at a single Australian tertiary hospital.

Optimization of microbial screening for cord blood.

Background: Collection and processing of cord blood (CB) is associated with significant risk of contamination; hence standards mandate microbial screening of the final product. The sensitivity of current methods to evaluate the microbial content of CB is unknown, given the small volume tested and reduced sensitivity of pediatric bottles. Hence, this study was undertaken to evaluate an optimal microbial screening method.

Effects of cryopreservation on microbial-contaminated cord blood.

Background: Cord blood units (CBUs) are associated with significant risk of exposure to microbial contamination during collection and processing; however, the survival of bacteria within a CBU is poorly understood. This study aimed to determine whether contaminating organisms in CBU survive the cryopreservation, frozen storage, and subsequent thawing conditions before infusion.

Study Design And Methods: A total of 134 CBUs rejected from banking due to known contamination were thawed and rescreened using blood culture bottles (BacT/ALERT, bioMérieux).

The use of adjusted ideal body weight for overweight patients undergoing HPC mobilisation for autologous transplantation.

Generally, patients' actual body weight (ABW) is used to calculate the number of CD34⁺ cells to be harvested for autologous haematopoietic progenitor cell (HPC) transplantation. In our institution, 'overweight' patients weighing at least 25% more than their ideal body weight (IBW) have their adjusted ideal body weight (AdjIBW) used for determination of blood volume to be processed to achieve a minimum target of CD34⁺ cells per kilogram, as well as CD34⁺ cell dosage calculation at transplant. AdjIBW is calculated as follows: AdjIBW = IBW + 0.

Factors affecting microbial contamination rate of cord blood collected for transplantation.

Background: Collection and processing of cord blood (CB) is associated with significant risk of microbial contamination and hence relevant standards mandate microbial screening of the final product. This study aimed to determine the contamination rate and associated risk factors during 14 years of banking at the Sydney Cord Blood Bank.

Study Design And Methods: CB was collected and processed using a closed system and tested for contamination using blood culture bottles (BacT/ALERT, bioMérieux) incubated for a minimum of 5 days.

Regulation of cellular therapy in Australia.

Use of cellular products for therapeutic purposes has predominantly been unregulated in Australia until recently. Transplant of haemopoietic progenitor cells (HPC) for bone marrow regeneration is now a routine treatment for many disorders with an established mechanism of facility accreditation. However, other cellular therapies do not have any form of accreditation, are not well evaluated and may be associated with significant risks.

Ethnicity, equity and public benefit: a critical evaluation of public umbilical cord blood banking in Australia.

Over the past decade umbilical cord blood (UCB) has been increasingly used as a source of haematopoietic stem cells (HSCs) for patients who require a HSC transplant but do not have an HLA-matched donor. It was anticipated that using UCB as an alternative source of HSCs would increase the chance of finding a donor, particularly for the otherwise underrepresented ethnic minority groups. To evaluate the effectiveness of the Australian public UCB banks to increase the ethnic diversity of available HSC donations, this paper analyses the ethnic diversity of the Sydney Cord Blood Bank (SCBB), comparing this diversity to that of the Australian Bone Marrow Donor Registry (ABMDR).

The expansion of megakaryocyte progenitors from CD34+-enriched mobilized peripheral blood stem cells is inhibited by Flt3-L.

This study aimed to determine the optimal growth factor combination for expansion of megakaryocyte (Mk) progenitors with clonogenic potential from CD34+-enriched mobilized peripheral blood stem cells (PBSC). Mobilized PBSC were monocyte depleted and CD34+ enriched, then cultured with various combinations of interleukin-3 (IL-3), IL-6, IL-11, Flt3 ligand (Flt3-L), stem cell factor (SCF), granulocyte-macrophage colonystimulating factor (GM-CSF), and erythropoietin (EPO), using a 2(7-3) IV fractional factorial design. Expansion of Mk committed progenitors (CD41+) and primitive precursors (CD61+ CD34+) was determined using FACS and colony-forming assays.

Overexpression of antioxidant enzyme peroxiredoxin 5 protects human tendon cells against apoptosis and loss of cellular function during oxidative stress.

Oxidative stress and apoptosis are implicated in tendon degeneration. Peroxiredoxin 5 (PRDX5) is a novel thioredoxin peroxidase recently identified in mammals, participating directly in eliminating hydrogen peroxide (H(2)O(2)) and neutralizing other reactive oxygen species (ROS). We have previously reported that PRDX5 is upregulated in degenerative human tendon.

Involvement of cytochrome c release and caspase-3 activation in the oxidative stress-induced apoptosis in human tendon fibroblasts.

Our previous studies have demonstrated that oxidative stress and apoptosis are involved in human tendon degeneration. The objectives of our current study were to investigate the effect of oxidative stress on human tendon cell apoptosis, and to explore pathways by which tendon cell apoptosis was induced. In vitro oxidative stress was created by exposure of cultured human rotator cuff tendon cells to H(2)O(2).

Successful peripheral blood stem cell mobilisation with filgrastim in patients with chronic myeloid leukaemia achieving complete cytogenetic response with imatinib, without increasing disease burden as measured by quantitative real-time PCR.

Imatinib mesylate (Glivec) is a selective inhibitor of bcr-abl tyrosine kinase, the product of the Philadelphia chromosome, which is the hallmark of chronic myeloid leukaemia (CML). With imatinib, complete cytogenetic response (CCR) can be achieved in over 70% of newly diagnosed patients with CML. However, the optimal long-term management of patients who achieve CCR after imatinib is unknown.

T cell stimulation and expansion using anti-CD3/CD28 beads.

Following appropriate stimulation, T lymphocytes will proliferate extensively in vitro. Traditionally, mitogenic lectins such as phytohemagglutinin (PHA) and concanavalin A (Con A) have been used for polyclonal T cell stimulation. A more physiologically relevant approach uses beads coated with anti-CD3 and anti-CD28 to stimulate T cells in a manner that partially mimics stimulation by antigen-presenting cells.

Expression and regulation of peroxiredoxin 5 in human osteoarthritis.

Reactive oxygen species (ROS) are implicated in the pathogenesis of osteoarthritis (OA). However, little is known about the antioxidant defence system in articular cartilage. We investigated the expression and regulation of peroxiredoxin 5 (PRDX5), a newly discovered thioredoxin peroxidase, in human normal and osteoarthritic cartilage.

Platelet activation in the hypertensive disorders of pregnancy.

Objective: The purpose of this study was to determine whether platelet activation occurs only in preeclampsia or also in normal pregnancy.

Study Design: Thirty women with preeclampsia, 30 women with gestational hypertension, 20 women with essential hypertension, 30 pregnant women with normotension, and 30 nonpregnant women were recruited at St George Hospital, Sydney, Australia. Platelet activation was determined by flow cytometry on whole blood samples.

Flexible low-intensity combination chemotherapy for elderly patients with acute myeloid leukemia.

Twenty-five patients aged 57 to 88 years (median, 70 years) with acute myeloid leukemia were treated with a flexible low-intensity treatment regimen comprising mitozantrone (mitoxantrone) 6 mg/m2 administered by intravenous infusion x3 days, cytarabine 10 mg/m2 subcutaneously every 12 hours x7 to 14 days, and etoposide 100 mg orally x7 to 14 days. Seventeen of these patients had a preexisting myelodysplastic syndrome. The clinical response was correlated to the results of cytogenetic studies (23 patients) and of viability studies of leukemic blasts (7 patients).

Accurate calculation of blood volume to be processed by apheresis to achieve target CD34+ cell numbers for PBPC transplantation.

Background: In recent years there have been clear improvements in the procurement of peripheral blood progenitor cells (PBPC) for autologous transplantation, such as the description of more effective mobilization regimens and the use of CD34 monitoring to determine the appropriate time to start collection. However, currently there is no accurate method of predicting the volume of blood required to be processed by apheresis to yield the target number of CD34(+) progenitor cells.

Methods: This study was performed to determine whether there is a correlation between the harvested number of CD34(+) cells per kilogram body weight and the 'CD34 prediction score' calculated from the concentration of CD34(+) cells in the blood prior to harvest, the blood volume processed, and the patient's weight.

Ex vivo expansion of functional T lymphocytes from HIV-infected individuals.

This study was designed to define the conditions for expansion of functional T lymphocytes from human immunodeficiency virus (HIV)-infected subjects, with the ultimate goal of using these cells for immunotherapy. The most appropriate culture conditions for good T cell proliferation included stimulation with anti-CD3 and anti-CD28 coated microspheres, and propagation in Aim V serum-free media with 20 U/ml interleukin-2 (IL-2), supplemented with decreasing concentrations of serum for the initial 8 days. Under these conditions, a 14-day culture period yielded approximately a 10,000-fold expansion of T lymphocytes from HIV-infected donors.

A preliminary study to determine the effect of an infusion of cryopreserved autologous lymphocytes on immunocompetence and viral load in HIV-infected patients.

Therapeutic measures aimed at boosting the immunity of HIV-infected patients are a critical component of strategies for effective therapy of HIV and AIDS. To improve immunocompetence in patients with progressive disease, autologous lymphocytes that were collected and cryopreserved earlier in the course of HIV-infection were reinfused. None of the 12 patients receiving cell infusions experienced any adverse effects.

Suppression of HIV replication in vitro by CD8+ T-cells from HIV-infected and HIV-seronegative individuals.

The inhibitory effect of CD8+ T-cells from HIV-infected or HIV-seronegative individuals on HIV replication in the naturally-infected CD4+ T-cells in vitro was examined. Not only autologous CD8+ T-cells from HIV-infected individuals but also allogeneic CD8+ T-cells from HIV-seronegative individuals prevented or delayed HIV replication, even in transwell cocultures using a semi-permeable 0.45 micron filter.