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Biomedical subjects

Joseph W Burnett

Publications and source records attributed to Joseph W Burnett.

17 recordsLinked to original sources

Aberrant DNA methylation silences the novel heat shock protein H11 in melanoma but not benign melanocytic lesions.

BACKGROUND: The heat shock protein H11 is silenced in melanoma cell lines, where its forced expression by demethylation with Aza-C triggers apoptosis. OBJECTIVE: To examine whether H11 is silenced by aberrant DNA methylation in melanoma as compared to nevi and normal skin tissues. METHODS: Cell suspensions from benign intradermal nevi, atypical nevi and malignant melanoma tissues were used in reverse-transcriptase PCR and methylation-specific PCR. Paraffin-embedded tissues were stained with H11 antibody. RESULTS: H11 is methylated in 60-75% of melanoma and atypical nevi, but not in normal skin or most benign nevi. Methylation is inversely correlated with H11 expression. CONCLUSION: The heat shock protein H11 is silenced by aberrant DNA methylation in melanoma, but not benign melanocytic lesions or normal skin melanocytes. The data suggest that H11 is a promising target for the molecular therapy of melanoma.

Apoptosis↗

Prolonged urinary incontinence and biliary dyskinesia following abdominal contact with jellyfish tentacles.

A 16-year-old girl was seriously stung on her abdomen by a jellyfish as she jumped on her small surfboard. She and her mother identified the animal from photographs as Chrysaora fuscescens. Within several minutes the girl developed a massive abdominal cutaneous eruption composed of hundreds of punctuate erythematous papules and macules, which persisted for 5 to 7 days. Persistent urinary incontinence and biliary dyskinesia appeared over the following night. It is theorized that a systemic uptake of venom occurred percutaneously after contact of the jellyfish tentacles with her abdominal skin. The result was an injury to the urinary and biliary bladders. This is the first case report of such sequellae after topical contact with a marine animal. The causal relationship of these abnormalities with the sting is suggested by their temporal association. The gallbladder disorder required surgical intervention, but spontaneous resolution of the urinary bladder dysfunction occurred within 20 months.

Adolescent↗

Toxicity and mAChRs binding activity of Cassiopea xamachana venom from Puerto Rican coasts.

A separation of toxic components from the upside down jellyfish Cassiopea xamachana (Cx) was carried out to study their cytotoxic effects and examine whether these effects are combined with a binding activity to cell membrane receptors. Nematocysts containing toxins were isolated from the autolysed tentacles, ruptured by sonication, and the crude venom (CxTX) was separated from the pellets by ultracentrifugation. For identifying its bioactive components, CxTX was fractionated by gel filtration chromatography into six fractions (named fraction I-VI). The toxicity of CxTX and fractions was tested on mice; however, the hemolytic activity was tested on saline washed human erythrocytes. The LD50 of CxTX was 0.75 microg/g of mouse body and for fraction III, IV and VI were 0.28, 0.25 and 0.12 microg/g, respectively. Fractions I, II and V were not lethal at doses equivalent to LD50 1 microg/g. The hemolytic and phospholipase A2 (PLA2) activities of most fractions were well correlated with their mice toxicity. However, fraction VI, which contains the low molecular mass protein components (< or =10 kDa), has shown no PLA2 activity but highest toxicity to mice, highest hemolytic activity, and bound significantly to the acetylcholine muscarinic receptors (mAChRs) isolated from rat brain. The results suggested that fraction VI contains proteinaceous components contributing to most of cytolysis as well as membrane binding events. Meanwhile, fraction IV has shown high PLA2 that may contribute to the venom lethality and paralytic effects.

Animals↗

CD34+ cells in the peripheral blood transport herpes simplex virus DNA fragments to the skin of patients with erythema multiforme (HAEM).

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) is a recurrent disease characterized by the presence and expression of HSV DNA fragments in lesional skin. Our studies examined the mechanism of viral DNA transport to the skin of HAEM patients. CD34+ cells were isolated from the blood of normal subjects and HSV and HAEM patients during acute lesions and at quiescence. They were cultured with cytokines that favor their differentiation into Langerhans cells (LC) precursors (CD1a+/CD14-) and examined for HSV replication, HSV-induced cellular alterations, viral DNA fragmentation, and clearance. CD34+ cells from all study groups were non-permissive for HSV replication but infection favored their differentiation into CD1a+/CD14- LC precursors and upregulated E-cadherin expression, thereby assisting LC targeting to the skin. Only HAEM patients had CD34+ cells that retained viral DNA fragments, notably polymerase DNA, for at least 7 d of in vitro culture. The percentages of circulating CD34+ (and CD34+/CLA+) cells were significantly higher in HAEM patients at the time of acute lesions. A similar increase was not seen for HSV patients. The data are the first report implicating CD34+ cells in HAEM pathogenesis, likely by transporting HSV DNA fragments to lesional skin.

Adult↗

Two new actions of sea nettle (Chrysaora quinquecirrha) nematocyst venom: studies on the mechanism of actions on complement activation and on the central nervous system.

Chrysaora quinquecirrha (sea nettle) nematocyst venom is lethal to rainbow killifish (Adina xenica) when injected intraperitoneally or topically applied to the exposed brain or denuded epithelium. The lethal activity is thermostable requiring 100 degrees C heat for inactivation. This paper reports here for the first time that the venom also activates the complement system with the subsequent formation of the C5b-9 terminal complement complex. The events are associated with both a strong chemoattractant release and the tissue damage. These are also, at least in part, responsible for the pathogenesis of some clinical signs and symptoms associated to the jellyfish stings.

Administration, Cutaneous↗

Irukandji-like syndrome in South Florida divers.

Irukandji syndrome is a constellation of delayed severe local and systemic symptoms occurring after a Carukia barnesi box jellyfish sting involving any exposed skin. These cases are limited to Australia, the habitat of that animal. Numerous other cases of an Irukandji-like syndrome after other small Carybdeid genus envenomations have been reported elsewhere in the world. There have yet been no reports of Irukandji-like syndrome occurring in continental US coastal waters. We describe 3 cases of marine envenomation causing such a symptom complex in US military combat divers off Key West, FL. It is unclear what species caused the injuries, but a member of the Carybdeid genus seems most likely.

Adult↗

Some toxicological characteristics of three venomous soft corals from the Red Sea.

Three common Red Sea soft corals (Cnidaria: Anthozoa), Nephthea sp, Dendronephthya sp and Heteroxenia fuscescens sting humans. Nematocyst venoms of each animal are lethal to mice and hemolytic to human erythrocytes. However, these hemolysins are partially inhibited by known anti-hemolytic agents. Venoms and their gel chromatography-separated fractions have different dermonecrosis and vasopermeability potency in mouse skin. The venom of Heteroxenia fuscescens (Hf) was more lethal (LD50: 0.7 mg/kg), with one prominent 97-kDa protein fraction (LD50: 0.55 mg/kg). Hf venom was more hemolytic, more dermonecrotic, and had more vasopermeable factors than that of the two other species. SDS polyacrylamide gel electrophoresis of soft coral whole venoms and fractions showed different protein molecular masses ranging from 200 to less than 6 kDa. High IgG titers were assayed from venom-sensitized mice blood sera. Enzyme-linked immunosorbent assays (ELISA) marked significant immunological cross-reaction between the studied soft coral venoms and their bioactive fractions.

Animals↗

Aquatic antagonists: Catalaphyllia jardinei sting.

Catalaphyllia jardinei is a blue-green soft coral whose red-violet tipped tentacles have made it a very colorful, popular animal prized by amateur aquarists (Figure 1). Its normal habitat is the Indo-Pacific area from Seychelles through Vanuatu and from Northern Australia to Southern Japan. It is regarded as mildly venomous. However, to our knowledge, no reports exist on its sting's effects on man.

Anthozoa↗

A double-blind study of the efficacy and safety of the ICP10deltaPK vaccine against recurrent genital HSV-2 infections.

A randomized double-blind trial to evaluate the safety of a novel recombinant virus, ICP10deltaPK, for reduction or prevention of recurrent herpes simplex virus type 2 (HSV-2) infection was carried out in public hospitals in Mexico City. Persons having a minimum of 5 documented herpetic recurrences in the previous year were randomized for vaccination. Patients were examined within 72 hours of lesion occurrence. If accepted into the study, the patient was inoculated subcutaneously in the upper deltoid muscle area at days 7, 17, and 28 after initiation of lesion occurrence. Recurrences were recorded by patient diary and physician examination. During the observation period (extending from 10 to 180 days after the last booster dose), recurrences in the vaccine (V) group were prevented completely in 37.5% of the patients, whereas in the placebo (P) group, 100% of the patients had at least one recurrence (P = .068). Vaccinated patients had fewer recurrences (V, 1.58; P, 3.13 [P = .028]). The mean number of illness days was 10 for the vaccine group and 18 for the placebo group (P = .028). Further studies to evaluate this vaccine and its dosimetry for the treatment of genital herpes infections appear warranted.

Adolescent↗