Epstein-Barr virus latent membrane protein 1 genetic variability in peripheral blood B cells and oropharyngeal fluids.

Unlabelled: We report the diversity of latent membrane protein 1 (LMP1) gene founder sequences and the level of Epstein-Barr virus (EBV) genome variability over time and across anatomic compartments by using virus genomes amplified directly from oropharyngeal wash specimens and peripheral blood B cells during acute infection and convalescence. The intrahost nucleotide variability of the founder virus was 0.02% across the region sequences, and diversity increased significantly over time in the oropharyngeal compartment (P = 0.

Exacerbation of signs and symptoms of allergic conjunctivitis by a controlled adverse environment challenge in subjects with a history of dry eye and ocular allergy.

Background: The goal of this study was to assess the effect of a controlled adverse environment (CAE) challenge on subjects with both allergic conjunctivitis and dry eye.

Methods: Thirty-three subjects were screened and 17 completed this institutional review board-approved study. Subjects underwent baseline ocular assessments and conjunctival allergen challenge (CAC) on days 0 and 3.

The radiobiological principles of boron neutron capture therapy: a critical review.

The radiobiology of the dose components in a BNCT exposure is examined. The effect of exposure time in determining the biological effectiveness of γ-rays, due to the repair of sublethal damage, has been largely overlooked in the application of BNCT. Recoil protons from fast neutrons vary in their relative biological effectiveness (RBE) as a function of energy and tissue endpoint.

LET-dependent bystander effects caused by irradiation of human prostate carcinoma cells with X rays or alpha particles.

Radiation-induced bystander effects have been demonstrated in both normal and tumor cells using a variety of different radiation qualities. Literature reports are contradictory, however, on whether there is an LET dependence of the bystander effect. This study investigated the ability of DU-145 human prostate carcinoma cells irradiated with either alpha particles or 250 kVp X rays to cause medium-mediated bystander effects in unirradiated populations of DU-145 cells or in AG01522 human fibroblasts.

Functional and histological changes in rat lung after boron neutron capture therapy.

The motivation for this work was an unexpected occurrence of lung side effects in two human subjects undergoing cranial boron neutron capture therapy (BNCT). The objectives were to determine experimentally the biological weighting factors in rat lung for the high-LET dose components for a retrospective assessment of the dose to human lung during cranial BNCT. Lung damage after whole-thorax irradiation was assessed by serial measurement of breathing rate and evaluation of terminal lung histology.

No significant endothelial apoptosis in the radiation-induced gastrointestinal syndrome.

Purpose: This report addresses the incidence of vascular endothelial cell apoptosis in the mouse small intestine in relation to the radiation-induced gastrointestinal (GI) syndrome.

Methods And Materials: Nonanesthetized mice received whole-body irradiation at doses above and below the threshold for death from the GI syndrome with 250 kVp X-rays, (137)Cs gamma rays, epithermal neutrons alone, or a unique approach for selective vascular irradiation using epithermal neutrons in combination with boronated liposomes that are restricted to the blood. Both terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining for apoptosis and dual-fluorescence staining for apoptosis and endothelial cells were carried out in jejunal cross-sections at 4 h postirradiation.

Boronated DNA-binding compounds as potential agents for boron neutron capture therapy.

Boron Neutron Capture Therapy (BNCT) is a binary cancer treatment that exploits the short range particles released from a nuclear fission reaction involving the non-radioactive 10B nucleus and low-energy (thermal) neutrons for the destruction of tumour cells. If boronated agents are targeted towards chromosomal DNA, the efficiency of BNCT is greatly enhanced. This article presents a concise review of DNA-binding compounds that have been functionalised with boron.

Late effects of radiation on the central nervous system: role of vascular endothelial damage and glial stem cell survival.

Selective irradiation of the vasculature of the rat spinal cord was used in this study, which was designed specifically to address the question as to whether it is the endothelial cell or the glial progenitor cell that is the target responsible for late white matter necrosis in the CNS. Selective irradiation of the vascular endothelium was achieved by the intraperitoneal (ip) administration of a boron compound known as BSH (Na(2)B(12)H(11)SH), followed by local irradiation with thermal neutrons. The blood-brain barrier is known to exclude BSH from the CNS parenchyma.

Molecular targeting and treatment of EGFRvIII-positive gliomas using boronated monoclonal antibody L8A4.

Purpose: The purpose of the present study was to evaluate a boronated EGFRvIII-specific monoclonal antibody, L8A4, for boron neutron capture therapy (BNCT) of the receptor-positive rat glioma, F98(npEGFRvIII).

Experimental Design: A heavily boronated polyamido amine (PAMAM) dendrimer (BD) was chemically linked to L8A4 by two heterobifunctional reagents, N-succinimidyl 3-(2-pyridyldithio)propionate and N-(k-maleimidoundecanoic acid)hydrazide. For in vivo studies, F98 wild-type receptor-negative or EGFRvIII human gene-transfected receptor-positive F98(npEGFRvIII) glioma cells were implanted i.

Depletion of neural precursor cells after local brain irradiation is due to radiation dose to the parenchyma, not the vasculature.

The underlying mechanisms associated with radiation-induced cognitive impairments remain elusive but may involve changes in hippocampal neural precursor cells. Proliferating neural precursor cells have been shown to be extremely sensitive to X rays, either from damage to the cells themselves and/or through microenvironmental factors, including the anatomical relationship with the microvasculature, which is altered by radiation. The neutron capture reaction in boron was used to determine whether the sensitivity of neural precursor cells was dominated by direct radiation effects or was mediated through changes in the microvasculature.

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells.

The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received whole-body epithermal neutron irradiation at a dose rate of 0.57 +/- 0.

A bystander effect in alpha-particle irradiations of human prostate tumor cells.

Alpha-particle exposures were used to determine whether cells of the human prostate carcinoma cell line DU-145 can produce and respond to a bystander effect signal. An apparatus for alpha-particle irradiation of cells growing as a monolayer on a 1.4-microm-thick Mylar membrane directly above an 241Am alpha-particle source was constructed and calibrated.

Pneumonitis and multi-organ system disease in common marmosets (Callithrix jacchus) infected with the severe acute respiratory syndrome-associated coronavirus.

Severe acute respiratory syndrome (SARS) is a significant emerging infectious disease. Humans infected with the etiological agent, SARS-associated coronavirus (SARS-CoV), primarily present with pneumonitis but may also develop hepatic, gastrointestinal, and renal pathology. We inoculated common marmosets (Callithrix jacchus) with the objective of developing a small nonhuman primate model of SARS.

The MIT user center for neutron capture therapy research.

Neutron capture therapy (NCT) research encompasses a wide range of preclinical and clinical studies needed to develop this promising but complex cancer treatment. Many specialized facilities and capabilities including thermal and epithermal neutron irradiation facilities, boron analysis, specialized mixed-field dosimetry, animal care facilities and protocols, cell culture laboratories, and, for human clinical studies, licenses and review board approvals are required for NCT research. Such infrastructure is essential, but much of it is not readily available within the community.

Boron neutron capture therapy of cancer: current status and future prospects.

Background: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina.

Differential oxidation of deoxyribose in DNA by gamma and alpha-particle radiation.

Emerging evidence points to the importance of deoxyribose oxidation in the toxicity of oxidative DNA damage, including the formation of protein-DNA crosslinks and base adducts. With the goal of understanding the differences in deoxyribose oxidation chemistry known to occur with different oxidants, we have compared the formation of one product of 3'-oxidation of deoxyribose in DNA, 3'-phosphoglycolaldehyde (PGA) residues, in isolated DNA and cells exposed to ionizing radiations. A recently developed gas chromatography/negative chemical ionization mass spectrometry method was used to quantify PGA residues in purified DNA and in human TK6 lymphoblastoid cells exposed to gamma radiation (60Co) and alpha particles (241Am).

Reduced tumor growth with combined radiofrequency ablation and radiation therapy in a rat breast tumor model.

Purpose: To determine whether use of combined radiofrequency (RF) ablation and external-beam radiation therapy increases end-point survival beyond that with either RF ablation or radiation therapy alone in an animal tumor model.

Materials And Methods: With a protocol approved by the institutional animal care and use committee, R3230 mammary adenocarcinoma (12.5 mm +/- 0.

Porphyrin-mediated boron neutron capture therapy: a preclinical evaluation of the response of the oral mucosa.

Preclinical studies are in progress to determine the potential of boron neutron capture therapy (BNCT) for the treatment of carcinomas of the head and neck. Recently, it has been demonstrated that various boronated porphyrins can target a variety of tumor types. Of the porphyrins evaluated so far, copper tetracarboranylphenyl porphyrin (CuTCPH) is potentially a strong candidate for clinical use.

Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2.

Infection of receptor-bearing cells by coronaviruses is mediated by their spike (S) proteins. The coronavirus (SARS-CoV) that causes severe acute respiratory syndrome (SARS) infects cells expressing the receptor angiotensin-converting enzyme 2 (ACE2). Here we show that codon optimization of the SARS-CoV S-protein gene substantially enhanced S-protein expression.

Tolerance of normal human brain to boron neutron capture therapy.

Data from the Harvard-MIT and the BNL Phase I and Phase I/II clinical trials, conducted between 1994 and 1999, have been analyzed and combined, providing the most complete data set yet available on the tolerance of the normal human brain to BPA-mediated boron neutron capture therapy. Both peak (1cm(3)) dose and average whole-brain dose show a steep dose-response relationship using somnolence syndrome as the clinical endpoint. Probit analysis indicates that the doses associated with a 50% incidence for somnolence (ED(50)+/-SE) were 6.

Boronated epidermal growth factor as a delivery agent for neutron capture therapy of EGF receptor positive gliomas.

The purpose of the present study was to further evaluate a boronated dendrimer (BD)-epidermal growth factor bioconjugate (BD-EGF), administered by means of convection enhanced delivery (CED), as a molecular targeting agent for boron neutron capture therapy (BNCT) of the F98(EGFR) glioma. Twenty-four hours following CED of (125)I-labeled BD-EGF 47.4% of the injected dose (ID) was retained in F98(EGFR) gliomas compared to 12.

Effects of boron neutron capture irradiation on the normal lung of rats.

The whole lung of rats was irradiated with X-rays, thermal neutrons, or thermal neutrons in the presence of p-boronophenylalanine (BPA). A >/= 20% increase in breathing rate, in the period 40-80 days after irradiation, was indicative of radiation-induced pneumonitis. The ED(50) (+/-SE) for a >/= 20% increase in breathing rate, relative to age-matched controls, was 11.

The effect of dexamethasone on the uptake of p-boronophenylalanine in the rat brain and intracranial 9L gliosarcoma.

The steroid dexamethasone sodium phosphate (DEX) is routinely used to treat edema in brain tumor patients. The objective of the present study was to evaluate the effects of DEX on the uptake of boronophenylalanine (BPA) using the rat 9L gliosarcoma tumor model and surrounding brain tissue. Two steroid dosage protocols were used.

Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent.

Cetuximab (IMC-C225) is a monoclonal antibody directed against both the wild-type and mutant vIII isoform of the epidermal growth factor receptor (EGFR). The purpose of the present study was to evaluate the monoclonal antibody (MoAb), cetuximab, as a boron delivery agent for neutron capture therapy (NCT) of brain tumors. Twenty-four hours following intratumoral (i.

Combination of boron neutron capture therapy and external beam radiotherapy for brain tumors.

Purpose: Boron neutron capture therapy (BNCT) has been used clinically as a single modality treatment for high-grade gliomas and melanomas metastatic to the brain. The purpose of the present study was to determine whether its efficacy could be enhanced by an X-ray boost administered after BNCT. Two brain tumor models were used, the F98 glioma as a model for primary brain tumors and the MRA 27 human melanoma as a model for metastatic brain tumors.