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Biomedical subjects

David Wang

Publications and source records attributed to David Wang.

At least 19 recordsLinked to original sources
PubMed2025

Blockade of interleukin-6 (IL-6) signaling in dedifferentiated liposarcoma (DDLPS) decreases mouse double minute 2 (MDM2) oncogenicity via alternative splicing.

Effective therapies for retroperitoneal (RP) dedifferentiated liposarcoma (DDLPS) remain unavailable. Loco-regional recurrence occurs in >80% of cases; 5-year disease-specific survival is only 20%. DDLPS is especially prevalent in the retroperitoneum and abdomen; evaluation of the DDLPS microenvironment in these high-fat compartments appears pertinent. Adipose is a main supplier of interleukin-6 (IL6); excessive activation of IL6 signal transducer glycoprotein 130 (GP130) underlies the development of some diseases. The role of GP130 pathway activation remains unstudied in DDLPS, so we examined the role of microenvironment fat cell activation of the IL6/GP130 signaling cascade in DDLPS. All DDLPS tumors and cell lines studied expressed elevated levels of the GP130-encoding gene IL6ST and GP130 protein compared to normal tissue and cell line controls. IL6 increased DDLPS cell growth and migration, possibly through increased signal transducer and activator of transcription 1 (STAT1) and 3 (STAT3) activation, and upregulated mouse double minute 2 (MDM2). GP130 loss conveyed opposite effects; pharmacological blockade of GP130 by SC144 produced the MDM2 splice variant MDM2-ALT1, known to inhibit full length MDM2 (MDM2-FL). Although genomic MDM2 amplification is pathognomonic for DDLPS, mechanisms driving MDM2 expression, regulation, and function beyond the MDM2:p53 negative feedback loop are poorly understood. Our findings suggest a novel preadipocyte DDLPS-promoting role due to IL6 release, via upregulation of DDLPS MDM2 expression. Pharmacological GP130 blockade reduced the IL6-induced increase in DDLPS MDM2 mRNA and protein levels, possibly through enhanced expression of MDM2-ALT1, a possibly targetable pathway with potential as future DDLPS patient therapy.

Proto-Oncogene Proteins c-mdm2↗
PubMed2007

Association between ventilatory response to hypercapnia and obstructive sleep apnea-hypopnea index in asymptomatic subjects.

The majority of awake ventilatory control studies have shown normal or decreased ventilatory response to hypercapnia (HCVR) in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. These findings are contrary to experimental studies suggesting increased loop gain and greater breathing instability in OSAHS patients. We have investigated the relationship between central chemoreflex sensitivity tested by HCVR and obstructive sleep apnea/hypopnea index (OSAHI) in asymptomatic subjects. Twenty normal volunteers (10 men and 10 women) from the general population without physical complaints including sleep-related symptoms were included. The subjects were studied for awake ventilatory responses to hypoxia (HVR) and hypercapnia. Overnight polysomnography (PSG) was performed in two consecutive nights with the first night used as acclimatization. The subjects have an average body mass index (BMI) of 27 +/- 5 SD kg/m(2), ages of 35 +/- 9 SD years and Epworth sleepiness scale of 2.1 +/- 1.8 SD. A positive linear relationship was found between HCVR and logarithmically transformed OSAHI (r = 0.67, p = 0.001). BMI and age were not significantly correlated to HCVR or Log OSAHI. No relationship was found between HVR and Log OSAHI (r = 0.25, p = 0.29). Percentage oxygen saturation nadir during sleep was found to significantly correlate to both daytime HCVR (r = -0.60, p = 0.005) and Log OSAHI (r = -0.65, p = 0.002) and tended to correlate to HVR (r = -0.41, p = 0.07). Arousal index during sleep was not associated with either HCVR (p = 0.93) or HVR (p = 0.26). In conclusion, heightened central chemosensitivity was positively related to OSAHI in asymptomatic volunteers. We believe these findings are in keeping with the evolving theory of loop gain being a significant factor for respiratory control instability and obstructive apnea genesis. The mechanism can be applied to asymptomatic subjects with even minimal sleep-disordered breathing.

Adult↗
PubMed2006

Opioids, sleep architecture and sleep-disordered breathing.

Opioid use whether acute or chronic, illicit or therapeutic is prevalent in Western societies. Opioid receptors are located in the same nuclei that are active in sleep regulation and opioid peptides are suggested to be involved in the induction and maintenance of the sleep state. mu-Opioids are the most commonly used opioids and are recognized respiratory depressants that cause abnormal awake ventilatory responses to hypercapnia and hypoxia. Abnormal sleep architecture has been reported during the process of opioids induction, maintenance and withdrawal. During induction and maintenance of opioid use there is reduction of rapid eye movement (REM) sleep and slow wave sleep. More recently, central sleep apnoea (CSA) has been reported with chronic opioid use and 30% of stable methadone maintenance treatment patients have CSA. Given these facts, it is sobering to note the paucity of human data available regarding the effects of short and long-term opioid use on sleep architecture and respiration during sleep. In this manuscript, we review the current knowledge regarding the effects of mu-opioids on sleep and respiration during sleep and suggest research pathways to advance our knowledge and to explore the possible responsible mechanisms related to these effects.

Analgesics, Opioid↗
PubMed2006

Intravenous recombinant tissue plasminogen activator in a pregnant woman with cardioembolic stroke.

BACKGROUND AND PURPOSE: Historically, the use of tissue plasminogen activator (tPA) thrombolysis in pregnancy has been regarded as relatively contraindicated. Underlying this stance has been the concern over the risk of bleeding complications in both mother and child. SUMMARY OF CASE: We report the successful use of intravenous recombinant tPA (rtPA) thrombolysis in a pregnant woman with acute cardioembolic stroke. CONCLUSIONS: The patient improved clinically, did not develop complications after receiving rtPA, and at 37 weeks' gestation, delivered a healthy infant, demonstrating that rtPA thrombolysis may be used safely in pregnant women.

Adult↗
PubMed2006

Positioned to inhibit: netrin-1 and netrin receptor expression after spinal cord injury.

Netrin-1 regulates axon extension during embryonic development and is expressed by neurons and myelinating oligodendrocytes in the adult CNS. To investigate the potential role of netrin-1 after spinal cord injury, we examined the expression of netrin-1 and netrin receptors after sagittal myelotomy in adult rats. This lesion targets spinal commissural projections, which respond to netrin-1 during development. Netrin-1 mRNA and protein levels were dramatically reduced at the site of injury and reduced expression persisted for at least 7 months. Neither netrin-1 protein nor mRNA was associated with the glial scar, but netrin-1 was expressed by neurons and oligodendrocytes immediately adjacent to the lesion. The post-injury distribution detected is similar to that reported for myelin-associated inhibitors of axon regeneration, such as Nogo, and is distinct from the distribution of inhibitors associated with a glial scar. DCC and UNC-5 homologue (UNC5H) expression also was reduced after injury. Although UNC5H levels recovered, DCC expression at the site of injury remained approximately 50% of pre-injury values at 7 months. Increased UNC5H immunoreactivity was associated with fibers in the superficial layers of the dorsal horn and in fibers located in white matter adjacent to the lesion. The dominant expression of UNC5H on axons and neurons in the spinal cord after injury and the persistent expression of netrin-1 by oligodendrocytes surrounding the lesion are consistent with the hypothesis that netrin-1 is a myelin-associated inhibitor of axonal regeneration after spinal cord injury.

Animals↗
PubMed2006

Tickborne arbovirus surveillance in market livestock, Nairobi, Kenya.

To identify tickborne viruses circulating in Kenya and the surrounding region, we conducted surveillance at abattoirs in Nairobi, Kenya. Species of ticks collected included Rhipicephalus pulchellus (56%), Amblyomma gemma (14%), R. appendiculatus (8%), A. variegatum (6%), and others. A total of 56 virus isolates were obtained, 26 from A. gemma, 17 from R. pulchellus, 6 from A. variegatum, and 7 from other species. Virus isolates included Dugbe virus (DUGV), an unknown virus related to DUGV, Thogoto, Bhanja, Kadam, Dhori, Barur, and foot-and-mouth disease (FMDV) viruses. This is the first report of Dhori virus isolation in East Africa and the first known isolation of FMDV associated with tick collection. Our results demonstrate the potential for tickborne dissemination of endemic and emergent viruses and the relevance of A. gemma in the maintenance of tickborne viruses in this region.

Abattoirs↗
PubMed2005

E-Predict: a computational strategy for species identification based on observed DNA microarray hybridization patterns.

DNA microarrays may be used to identify microbial species present in environmental and clinical samples. However, automated tools for reliable species identification based on observed microarray hybridization patterns are lacking. We present an algorithm, E-Predict, for microarray-based species identification. E-Predict compares observed hybridization patterns with theoretical energy profiles representing different species. We demonstrate the application of the algorithm to viral detection in a set of clinical samples and discuss its relevance to other metagenomic applications.

Algorithms↗
PubMed2005

Formal dysphagia screening protocols prevent pneumonia.

BACKGROUND: Pneumonia is an important complication of ischemic stroke and increases mortality 3-fold. Five guidelines recommend a dysphagia screen before oral intake. What constitutes an adequate dysphagia screen and which patients should receive it remain unclear. METHODS: Fifteen acute care institutions prospectively collected data on all admitted patients with acute ischemic stroke. Sites were required to collect data on demographics and 4 quality indicators. Optional data included stroke severity and complications. We measured adherence to a screen for dysphagia, the type of screen, and development of in-hospital pneumonia. RESULTS: Between December 2001 and January 2003, 2532 cases were collected. In-hospital complications were recorded on 2329 (92%) of cases. Stroke severity was captured on 1361 (54%). Adherence to a dysphagia screen was 61%. Six sites had a formal dysphagia screen, and their adherence rate was 78% compared with 57% at sites with no formal screen. The pneumonia rate at sites with a formal dysphagia screen was 2.4% versus 5.4% (P=0.0016) at sites with no formal screen. There was no difference in median stroke severity (5 versus 4; P=0.84) between the sites with and without a formal screen. A formal dysphagia screen prevented pneumonia even after adjusting for stroke severity. CONCLUSIONS: A formal dysphagia screen is associated with a higher adherence rate to dysphagia screens and a significantly decreased risk of pneumonia. A formal screening protocol should be offered to all stroke patients, regardless of stroke severity.

Aged↗
PubMed2005

Evolution of endovascular therapy for aneurysm treatment. Historical overview.

The endovascular treatment of intracranial aneurysms has recently become an established therapeutic option. The foundation of this treatment modality was laid by the work done in ground-breaking cases, combined with technological advances since the first half of the 19th century. In this historical overview the authors describe the steps taken by the early pioneers and the results of their work, which was often done under challenging circumstances. The work of these predecessors established the stepping-stones for constant development and refinement for those who have come after them, eventually evolving into the procedures used today. Endovascular treatment of intracranial aneurysms is only possible because of the work of these innovators.

Balloon Occlusion↗
PubMed2005

Laser needle guide for the sonic flashlight.

We have extended the real-time tomographic reflection display of the Sonic Flashlight to a laser guidance system that aims to improve safety and accuracy of needle insertion, especially for deep procedures. This guidance system is fundamentally different from others currently available. Two low-intensity lasers are mounted on opposite sides of a needle aimed parallel to the needle. The needle is placed against a notch in the Sonic Flashlight mirror such that the laser beams reflect off the mirror to create bright red spots on the flat panel display. Due to diffuse reflection from these spots, the virtual image created by the flat panel display contains the spots, identifying the projected destination of the needle at its actual location in the tissue. We have implemented our design and validated its performance, identifying several areas for potential improvement.

Equipment Design↗
PubMed2005

Successful intra-arterial basilar artery thrombolysis in a patient with bilateral vertebral artery occlusion: technical case report.

OBJECTIVE AND IMPORTANCE: Basilar artery occlusion is a clinical event with an exceedingly high mortality rate. Improved survival is closely associated with successful recanalization of the occluded basilar artery. Bilateral vertebral artery occlusion (BVAO) is a unique disease entity that effectively denies any direct access to the basilar artery for endovascular rescue therapy. We report a case of successful intra-arterial basilar artery thrombolysis in a patient with BVAO. CLINICAL PRESENTATION: A 78-year-old man was transferred to our hospital after intravenous administration of tissue plasminogen activator and with deteriorating neurological status requiring intubation. His clinical presentation was highly suggestive of acute basilar artery thrombosis. The cerebral angiogram showed a BVAO and collateral flow reconstituting both distal extracranial vertebral arteries but with significant contrast stasis. There was no retrograde filling of the basilar artery through the only angiographically visible posterior communicating artery. TECHNIQUE: Selective catheterizations of the left occipital artery and the left ascending cervical branch of the thyrocervical trunk were performed to deliver a total of 12 mg of tissue plasminogen activator. At that point, the patient showed significant neurological improvement. The post-tissue plasminogen activator angiogram showed improved flow through the basilar artery. The patient was independent and well at his 1-year follow-up visit. CONCLUSION: Knowledge of potential collateral pathways is important when direct access to the main intracranial vessels is not available. Basilar artery thrombolysis through collateral vessels is clinically effective when a direct approach to the artery is not feasible.

Aged↗
PubMed2005

Ventilatory responses to hypoxia and hypercapnia in stable methadone maintenance treatment patients.

RATIONALE: Methadone is a long-acting mu-opioid and is an effective treatment for heroin addiction. Opioids depress respiration, and patients receiving methadone maintenance treatment (MMT) have higher mortality than the general population. Few studies have investigated ventilatory responses to both hypercapnia and hypoxia in these patients. STUDY OBJECTIVES: We measured hypercapnic ventilatory response (HCVR) and hypoxic ventilatory response (HVR) and investigated possible factors associated with both in clinically stable patients receiving MMT. DESIGN AND SETTING: Patients receiving long-term, stable doses of methadone recruited from a statewide MMT program, and normal, non-opioid-using subjects matched for age, sex, height, and body mass index were studied with HCVR and HVR. RESULTS: Fifty MMT patients and 20 normal subjects were studied, and significantly decreased HCVR and increased HVR were found in MMT patients compared to normal subjects (HCVR [mean +/- SD], l.27 +/- 0.61 L/min/mm Hg vs 1.64 +/- 0.57 L/min/mm Hg [p = 0.01]; HVR, 2.14 +/- 1.58 L/min/% arterial oxygen saturation measured by pulse oximetry [Sp(O2)] vs 1.12 +/- 0.7 L/min/% Sp(O2) [p = 0.008]). Respiratory rate and not tidal volume changes were the major physiologic responses contributing to both HCVR and HVR differences between the groups. Variables associated with HCVR in the MMT patients are as follows: obstructive sleep apnea/hypopnea index (t = 5.1, p = 0.00001), Pa(CO2) (t = - 3.6, p = 0.001), body height (t = 2.6, p = 0.01) and alveolar-arterial oxygen pressure gradient (t = 2.5, p = 0.02). Variables associated with HVR in MMT patients are body height (t = 3.2, p = 0.002) and Pa(CO2) (t = - 2.8, p = 0.008). CONCLUSIONS: Stable long-term MMT patients have blunted central and elevated peripheral chemoreceptor responses. The mechanisms and clinical significance of these findings need further investigation.

Adult↗
PubMed2005

Central sleep apnea in stable methadone maintenance treatment patients.

STUDY OBJECTIVES: Methadone, a long-acting mu-opioid agonist, is an effective treatment for heroin addiction. Our previous data show that 6 of 10 methadone maintenance treatment (MMT) patients had central sleep apnea (CSA). This study aims to confirm these results and to investigate the pathogenesis of the CSA. METHODS: Twenty-five male and 25 female MMT patients and 20 age-, sex-, and body mass index (BMI)-matched normal subjects were tested with polysomnography, blood toxicology, and ventilatory responses to hypoxia and hypercapnia. Resting cardiorespiratory tests were performed in the MMT group RESULTS: MMT patients and normal subjects were 35 +/- 9 years old (mean +/- SD), and BMI values were 27 +/- 6 kg/m2 and 27 +/- 5 kg/m2, respectively. Thirty percent of MMT patients had a central apnea index (CAI) > 5, and 20% had a CAI > 10. All normal subjects had a CAI < 1, and no difference was found in obstructive apnea-hypopnea index between the two groups. Methadone blood concentration was the only significant variable (t = 2.33, p = 0.025) associated with CAI and explains 12% of the variance. Awake Pa(CO2), antidepressant use, reduced ventilatory response to hypercapnia, and widened awake alveolar-arterial oxygen pressure gradient together explain a further 17% of the CAI variance. CONCLUSIONS: Thirty percent of stable MMT patients have CSA, a minority of which can be explained by blood methadone concentration. Other physiologic variables may also play a role in the pathogenesis of CSA in MMT patients, and further research is indicated in this area.

Adult↗
PubMed2005

Split cord malformation with associated type IV spinal cord perimedullary arteriovenous fistula. Case report.

The authors describe the case of a 62-year-old woman with a Type II split cord malformation (SCM). At the initial time of workup, the authors observed an associated Klippel-Feil deformity at the level of the SCM and a low-lying conus medullaris; however, they discovered an associated Type IV perimedullary spinal cord arteriovenous fistula (AVF) only after the patient continued to deteriorate following a spinal cord untethering procedure. Although prominent blood vessels have been reported within the median cleft of SCMs, an angiographically and surgically proven perimedullary AVF has not previously been described. The potential coexistence of SCM and perimedullary AVF has significant clinical implications and its recognition is critically important prior to surgical treatment.

Arteriovenous Fistula↗