Biomedical subjects

D Tom

Publications and source records attributed to D Tom.

8 recordsLinked to original sources

PubMed1998

The HHQK domain of beta-amyloid provides a structural basis for the immunopathology of Alzheimer's disease.

The beta-amyloid peptide 1-42 (Abeta1-42), a major component of neuritic and core plaques found in Alzheimer's disease, activates microglia to kill neurons. Selective modifications of amino acids near the N terminus of Abeta showed that residues 13-16, the HHQK domain, bind to microglial cells. This same cluster of basic amino acids is also known as a domain with high binding affinity for heparan sulfate. Both Abeta binding to microglia and Abeta induction of microglial killing of neurons were sensitive to heparitinase cleavage and to competition with heparan sulfate, suggesting membrane-associated heparan sulfate mediated plaque-microglia interactions through the HHQK domain. Importantly, small peptides containing HHQK inhibited Abeta1-42 cell binding as well as plaque induction of neurotoxicity in human microglia. In vivo experiments confirmed that the HHQK peptide reduces rat brain inflammation elicited after infusion of Abeta peptides or implantation of native plaque fragments. Strategies which exploit HHQK-like agents may offer a specific therapy to block plaque-induced microgliosis and, in this way, slow the neuronal loss and dementia of Alzheimer's disease.

Alzheimer Disease↗

PubMed1996

Specific domains of beta-amyloid from Alzheimer plaque elicit neuron killing in human microglia.

Alzheimer's disease (AD) is found to have striking brain inflammation characterized by clusters of reactive microglia that surround senile plaques. A recent study has shown that microglia placed in contact with isolated plaque fragments release neurotoxins. To explore further this process of immunoactivation in AD, we fractionated plaque proteins and tested for the ability to stimulate microglia. Three plaque-derived fractions, each containing full-length native A beta 1-40 or A beta 1-42 peptides, elicited neurotoxin release from microglia. Screening of various synthetic peptides (A beta 1-16, A beta 1-28, A beta 12-28, A beta 25-35, A beta 17-43, A beta 1-40, and A beta 1-42) confirmed that microglia killed neurons only after exposure to nanomolar concentrations of human A beta 1-40 or human A beta 1-42, whereas the rodent A beta 1-40 (5Arg-->Gly, 10Tyr-->Phe 13His-->Arg) was not active. These findings suggested that specific portions of human A beta were necessary for microglia-plaque interactions. When coupled to microspheres, N-terminal portions of human A beta (A beta 1-16, A beta 1-28, A beta 12-28) provided anchoring sites for microglial adherence whereas C-terminal regions did not. Although itself not toxic, the 10-16 domain of human A beta was necessary for both microglial binding and activation. Peptide blockade of microglia-plaque interactions that occur in AD might prevent the immune-driven injury to neurons.

Alzheimer Disease↗

PubMed1996

Study of receptor-mediated neurotoxins released by HIV-1-infected mononuclear phagocytes found in human brain.

Although there is growing evidence that neurotoxic molecules produced by HIV-1-infected mononuclear phagocytes damage neurons, the precise mechanisms of neuronal attack remain uncertain. One class of cytotoxin involves neuronal injury mediated via the NMDA receptor. We examined blood monocytes and brain mononuclear cells isolated at autopsy from HIV-1-infected individuals for the ability to release NMDA-like neuron-killing factors. We found that a neurotoxic amine, NTox, was produced by blood monocytes and by brain mononuclear phagocytes infected with retrovirus. In vivo injections of minute quantities of NTox produced selective damage to hippocampal pyramidal neurons. NTox can be extracted directly from brain tissues infected with HIV-1 and showed structural features similar to wasp and spider venoms. In contrast to NTox, HIV-1 infection did not increase the release of the NMDA excitotoxin quinolinic acid (QUIN) from mononuclear cells. Although we found modest elevations of QUIN in the CSF of HIV-1-infected individuals, the increases were likely attributable to entry through damaged blood-brain barrier. Taken together, our data pinpoint NTox, rather than QUIN, as a major NMDA receptor-directed toxin associated with neuro-AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Senile plaques stimulate microglia to release a neurotoxin found in Alzheimer brain.

Senile plaques found in the brains of patients with Alzheimer's disease (AD) are surrounded by clusters of reactive microglia. Isolated human microglia placed in contact with plaques in vitro are activated to release a factor which is toxic to neurons. This same neurotoxin is found in AD brain tissue and causes damage to pyramidal neurons in vivo when infused into rat hippocampus. Highest concentrations of the neurotoxin are in those brain structures most burdened by reactive microglia, suggesting that plaque-activated cells contribute to the neuronal damage and impaired cognition seen in patients with Alzheimer's dementia.

Alzheimer Disease↗

PubMed1995

A patient dose verification program using diode detectors.

In this work, we present a comprehensive patient dose verification program using a commercial dual diode detector system for external photon beam radiotherapy. To achieve acceptable accuracy, factors potentially affecting diode sensitivity need to be carefully considered in dose determination. Several authors have shown that diode sensitivity depends on temperature, saturation, linearity, radiation damage, and beam incidence angle. In addition, we found that the use of wedge filters, block trays at a close distance to the detectors, variation in radiation field size, as well as measurement SSDs may affect diode sensitivity significantly. In practice, we use a 5% dose deviation of measured dose from expected patient dose to prompt reevaluation of patient dosimetry. This yields a 90% acceptance rate in clinical patient cases.

Calibration↗

PubMed1995

Branch retinal artery occlusion associated with directional coronary atherectomy after percutaneous transluminal coronary angioplasty.

PURPOSE: To report a case of branch retinal artery occlusion after atherectomy. METHODS: A 51-year-old man complained of visual loss in the right eye after directional coronary atherectomy, performed secondary to a complicated percutaneous transluminal coronary angioplasty. He underwent a full ophthalmologic examination, including fluorescein angiography and Doppler ultrasound. RESULTS: Visual Acuity was 20/30 with an inferior scotoma present in the right eye. There were three Hollenhorst plaques present inside the superotemporal vascular arcade. CONCLUSIONS: There is a small but definite risk of retinal microinfarctions after atherectomy.

Angioplasty, Balloon, Coronary↗

PubMed1985

Evaluation of the Quantum II yeast identification system.

We compared three methods for identifying clinical yeast isolates: Abbott Quantum II, API 20C, and a modified BBL Minitek system. The API 20C and modified Minitek systems agreed on the identification of 243 of 245 yeasts (99.2%). The Quantum II system correctly identified 197 (80.4%), incorrectly identified 19 (7.8%), and did not identify 29 (11.8%) of the yeasts. Most of the misidentifications with the Quantum II occurred because assimilation or biochemical results were false-positive. Sixteen different species of yeasts and 16 different Quantum II substrates contributed to the discrepancies. On retesting with the Quantum II, 31% of the discrepant strains were correctly identified, while the remaining 69% were incorrectly identified or were not identified. Erroneous biochemical and assimilation results were also noted with yeasts that were correctly identified by the Quantum II system.

Candida↗

PubMedDate not supplied

Indocyanine green angiography in serpiginous choroidopathy.

BACKGROUND: Manifestations of serpiginous choroidopathy have been well described, but very little is known about its true pathogenesis. By virtue of the enhanced imaging of the choroidal circulation, indocyanine green angiography may offer information on the causative factors of the disorder. METHODS: Indocyanine Green (ICG) videoangiography was carried out in 17 patients with serpiginous choroidopathy. A full ophthalmological examination and intravenous fluorescein angiography were simultaneously done as well. The patients were studied at 3 different stages of the disease as follows: 1) with acute manifestations; 2) with subacute lesions; 3) in the inactive or healed state. RESULTS: Acute Lesions: Indocyanine angiography showed active choroidal involvement in the acute stage beyond the limits delineated by corresponding fluorescein studies. Subacute Lesions: ICG angiography showed resolution of choroidal involvement in advance of clinical and fluorescein angiographic changes in some eyes. Healed Lesions: ICG angiography showed better delineation of the atrophic choroid with clearer definitions than corresponding fluorescein studies. Late staining of fibrovascular tissue within atrophic zones was similar to fluorescein findings. Two patients in the healed state showed multifocal hypofluorescence (one patient) and hyperfluorescent choroidal lesions (one patient) with no clinical or fluorescein counterparts, possibly representing occult lesions. CONCLUSIONS: ICG angiography may be useful in understanding certain clinical features of the entity, such as a clearer documentation of the extent and nature of the choroidal damage and possible sites at risk for future recurrences. However, it adds little to our current management of the disorder.

Acute Disease↗