7 research outputs found

    Early Onset of Ventilatory and Airway Response to Hypercapnia is Mediated by Medullary 5-HT1A Receptors in Infant Rats

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    Medullary 5-hydroxytryptamine (5-HT) neurons are involved in ventilatory responses to hypercapnia. Underdeveloped medullary 5-HT neurons and reduced 5-HT1A receptor binding activity in the dorsomedial medulla oblongata (DMM) have been found in infants with sudden infant death syndrome (SIDS). The DMM includes the solitary tract nucleus, which receives primary afferent inputs from the lung, and the hypoglossal nucleus, which affects genioglossal muscle tone. We hypothesized that hypercapnia would elicit 5-HT release in the DMM and that local 5-HT1A receptors would affect ventilatory and airway responses to hypercapnia. This hypothesis was investigated in unanesthetized infant Wistar rats by microdialysis of the DMM coupled with double-chamber plethysmography. After microdialysis probe placement, the rats were acclimatized to the chamber for over 5h, and artificial cerebrospinal fluid (aCSF) or a 5-HT1A receptor antagonist, WAY-100635, was then perfused into the DMM, and extracellular fluid was collected. Respiratory flow curves were recorded while the rats inhaled five concentrations of CO2 in O2 for 10 min each (0% [100% O2], 5%, 7%, 9%, and 0% again). 5-HT concentration was measured using high-performance liquid chromatography with electrochemical detection. 5-HT release in the DMM and hypercapnic ventilatory and airway responses increased dose dependently with CO2 concentration during both aCSF and WAY-100635 perfusion, with no difference between groups. However, early-onset ventilatory and airway responses to hypercapnia were significantly delayed or reduced by WAY-100635 perfusion in the DMM. These results suggest that 5-HT release in the DMM is dependent on hypercapnia, while early ventilatory and airway responses to hypercapnia are mediated by 5-HT1A receptors in the DMM. Blunted early onset of hypercapnic ventilatory and airway responses may be one cause of SIDS

    RAISING is a high-performance method for identifying random transgene integration sites

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    Both natural viral infections and therapeutic interventions using viral vectors pose significant risks of malignant transformation. Monitoring for clonal expansion of infected cells is important for detecting cancer. Here we developed a novel method of tracking clonality via the detection of transgene integration sites. RAISING (Rapid Amplification of Integration Sites without Interference by Genomic DNA contamination) is a sensitive, inexpensive alternative to established methods. Its compatibility with Sanger sequencing combined with our CLOVA (Clonality Value) software is critical for those without access to expensive high throughput sequencing. We analyzed samples from 688 individuals infected with the retrovirus HTLV-1, which causes adult T-cell leukemia/lymphoma (ATL) to model our method. We defined a clonality value identifying ATL patients with 100% sensitivity and 94.8% specificity, and our longitudinal analysis also demonstrates the usefulness of ATL risk assessment. Future studies will confirm the broad applicability of our technology, especially in the emerging gene therapy sector.Communications Biology, 5, art. no. 535; 202
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