Biomedical subjects

Patrick Ryan

Publications and source records attributed to Patrick Ryan.

11 recordsLinked to original sources

PubMed2006

High prevalence of aeroallergen sensitization among infants of atopic parents.

OBJECTIVE: To present methodology to identify atopic parents and determine the prevalence of sensitization to 15 aeroallergens in their infant offspring. STUDY DESIGN: A birth cohort of infants was identified from birth records; an infant was enrolled if 1 of the parents reported allergy respiratory symptoms and had a positive skin prick test (SPT) to a common aeroallergen. At age 1 year, these infants were tested to the same aeroallergens. RESULTS: Of the 680 enrolled infants, 28.4% were SPT+ to 1 or more aeroallergens and/or food, and 18.0% were positive to 1 or more aeroallergens. By category of allergens, 9.7% were sensitized to pollens, 7.5% to molds, 4.3% to house dust mite and/or cockroach, and 3.4% to dog and/or cat. Of the infants who were positive to an aeroallergen, 65.7% remained positive at age 2 years. CONCLUSIONS: Infants born to atopic parents with percutaneous sensitization to aeroallergens are at increased risk for aeroallergen sensitization during infancy, which persists to age 2 years. These findings suggest that current clinical practices, which generally avoid skin testing before age 2 years, be reassessed in this population of high-risk children.

Allergens↗

PubMed2006

Mold damage in homes and wheezing in infants.

BACKGROUND: In most studies that investigate the association of mold or water damage and respiratory disorders in infants, the analysis is not adjusted for exposure to house dust mite (HDM), which is also a known cause of respiratory illnesses. OBJECTIVE: To investigate the relationship between visually observable mold or water damage and HDM (Der f 1) levels and the prevalence of lower respiratory tract symptoms and allergen sensitization in infants of atopic parents as part of a prospective birth cohort study. METHODS: On-site home visits (at the infants' age of 8 months) were performed to evaluate observable mold or water damage and HDM exposure. At a clinic visit near the infant's first birthday, medical histories, including parent-reported wheezing episodes, and a skin prick test to food and 15 common aeroallergens were conducted in 640 infants. RESULTS: More than half of the homes were found to have mold or water damage, and 5% had major mold or water damage with visible mold at 0.2 m2 or more. Only 16% of homes had a HDM allergen (Der f 1) concentration of more than 2 microg/g. Major mold or water damage increased the risk of recurrent wheezing nearly 2 times in infants, 5 times in food or aeroallergen-sensitized infants, and 6 times in aeroallergen-sensitized infants. Neither visible mold or water damage nor HDM exposure was associated with sensitization to either mold or aeroallergens. CONCLUSIONS: Visible mold was shown to be a significant risk factor for recurrent wheezing in infants at high risk of developing atopic disorders, whereas HDM exposure did not significantly increase the risk.

Allergens↗

PubMed2006

Buttock spots.

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Arthritis↗

PubMed2004

Expression of genes in the TGF-beta signaling pathway is significantly deregulated in smooth muscle cells from aorta of aryl hydrocarbon receptor knockout mice.

The molecular basis for the adverse biological effects of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD), a pervasive environmental toxin, is largely unknown. TCDD is a ligand for the cytosolic aromatic hydrocarbon receptor (AHR) which mediates the transcriptional induction of the xenobiotic metabolizing genes in the CYP1 family of cytochromes P450. Previous studies have suggested that the AHR may carry out important functions in the cell in addition to metabolizing toxins. We present gene expression profiles of smooth muscle cells from wild type and Ahr(-/-) mice that show significant changes in the RNA levels of the transforming growth factor-beta3 (Tgfb3) gene and genes involved in the modulation and processing of TGF-beta. The RNA expression profiles support a hypothesis that in the wild type, the AHR represses Tgfb gene expression and affects the gene expression of several TGF-beta-modulating and processing genes. We also observed that RNA levels increased for TGF-beta2, CYP1b1, and TGF-beta-related genes in Ahr(-/-) smooth muscle cells exposed to TCDD. These data are consistent with a hypothesis that TCDD stimulates the TGF-beta2 signaling pathway in the absence of the AHR to activate the Cyp1b1 gene. The above results provide a possible explanation for some of the multiple biological effects of TCDD and the physiological role played by the AHR in the absence of environmental agents.

Animals↗

PubMed2004

Different global gene expression profiles in benzo[a]pyrene- and dioxin-treated vascular smooth muscle cells of AHR-knockout and wild-type mice.

Benzo[a]pyrene (B[a]P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are potent ligands for the aryl hydrocarbon receptor (AHR). High-density oligonucleotide microarrays were used to generate global gene expression profiles of wild-type and Ahr(-/-) vascular smooth muscle cells (SMCs) from mouse aorta. To determine whether there are signaling pathways other than the AHR involved in B[a]P metabolism, wild-type and AHR knockout (Ahr(-/-) SMCs were exposed to B[a]P. Two signaling pathways, represented by TGF-beta2 and IGF-1, were identified as potential candidates of an AHR alternate pathway for cells to respond to B[a]P. The wild-type SMCs responded similarly to B[a]P and TCDD in the regulation of a small set of common genes known to respond to the activated AHR (e.g., glutamine S-transferase). However, wild-type SMCs responded in a way that involves many additional genes, suggesting that a very divergent cellular response may be involved when SMCs are exposed to the two classic inducers of the AHR. In contrast, many more genes in the Ahr(-/-) cells responded similarly to B[a]P and TCDD, including Cyp1b1, than responded differently, which indicates that eliminating the AHR is effective for investigating potential alternate cellular mechanisms that respond to B[a]P and TCDD.

Animals↗

PubMed2004

Retrograde autologous prime with shortened bypass circuits decreases blood transfusion in high-risk coronary artery surgery patients.

Previous studies have shown that minimizing the amount of hemodilution during open-heart surgery reduces the need for a blood transfusion. Transfusion increases a patient's medical risks and leads to increased costs. We used a shortened bypass circuit, primed with autologous blood in a retrograde fashion, to decrease red cell transfusion in high-risk patients. One hundred twenty-three patients having first-time, nonemergent coronary artery surgery were chosen for this trial, based on their low prebypass hematocrit and weight. In seventy-two cases, we used a shortened bypass circuit and retrograde autologous prime. A historical control group of fifty-one patients received a standard bypass circuit and prime method. The prebypass hematocrit was 35 +/- 2.62% and 34 +/- 2.99% in the control and study groups, respectively. Red blood cell transfusion was necessary in 70% of the control group during their hospital stay, whereas only 51.4% of the study group required transfusion (p = .006). Patients receiving no blood products were significantly higher in the study group, 48.6% vs. 30.0% (p = .005). The postbypass hematocrit was similar at 26.5 +/- 1.82% vs. 25.5 +/- 2.38%, and the discharge hematocrit was 30.8 +/- 3.33% and 31.2 +/- 3.04% in the control and study groups. respectively. Minimizing hemodilution by shortening the bypass circuit and performing retrograde autologous prime conserves the use of blood during routine coronary artery bypass surgery. These methods can be used for patients who are at greater risk for transfusion.

Aged↗

PubMed2003

A prospective, randomized, controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the ATLANTIS anterior cervical plate.

STUDY DESIGN: A prospective, randomized, pilot clinical trial compared recombinant human bone morphogenetic protein-2 (rhBMP-2) with iliac crest autograft bone for the treatment of human cervical disc disease. OBJECTIVE: To examine the safety and effectiveness of using INFUSE Bone Graft (rhBMP-2 applied to an absorbable collagen sponge), as compared with an autogenous iliac crest bone graft placed inside the CORNERSTONE-SR fibular allograft, in anterior cervical discectomy and interbody fusion. SUMMARY OF BACKGROUND DATA: Recombinant human bone morphogenetic protein-2 is an osteoinductive protein that induces a reliable fusion in the lumbar spine, but it has not been studied in patients with degenerative cervical disc disease. METHODS: For this study, 33 patients with degenerative cervical disc disease were randomly assigned to investigational or control groups. The investigational group received a fibular allograft (CORNERSTONE-SR Allograft Ring) with an rhBMP-2-laden collagen carrier inside the graft along with an ATLANTIS anterior cervical plate. The control group received a fibular allograft with cancellous iliac crest autograft placed inside it, along with an ATLANTIS anterior cervical plate. The patients underwent plain radiographs at 6 weeks, then at 3, 6, 12, and 24 months, and CT scans at 3 and 6 months after surgery. They also completed general health profiles and self-evaluation scales. Adverse events were evaluated for severity, duration, association with the implant, and the need for a second surgical procedure. RESULTS: All the patients evaluated had solid fusions 6, 12, and 24 months after surgery. There were no device-related adverse events. At 24 months, the investigational group had mean improvement superior to that of the control group in neck disability and arm pain scores (P < 0.03 each). CONCLUSIONS: This pilot study demonstrates the feasibility of using rhBMP-2 safely and effectively in the cervical spine.

Bone Morphogenetic Protein 2↗

PubMed2003

A role for glycoprotein C in pseudorabies virus entry that is independent of virus attachment to heparan sulfate and which involves the actin cytoskeleton.

Glycoprotein C (gC) of pseudorabies virus, a swine herpesvirus, initiates virus attachment by binding to heparan sulfate (HS) linked to proteoglycans (HSPGs) on the cell surface. This interaction facilitates a required step in virus entry, the binding to a non-HS coreceptor, likely by another viral glycoprotein, gD. We demonstrate that gC has an even more direct role in virus entry than simply promoting adhesion strengthening. A porcine cell line expressing gC trans-complemented the penetration, but not attachment, defect of gC null mutants. In addition, gC promoted the colocalization of cell surface HSPGs and the actin cytoskeleton, suggesting a role for filamentous actin in virus entry. This was supported by results showing that both the engagement of a non-HS coreceptor and entry events subsequent to coreceptor binding were impaired if cells were first treated with an actin depolymerizing agent, cytochalasin D. Our results suggest a model in which gC-HS interactions promote not only virus attachment but also virus entry by usurping the normal properties of HSPGs.

Actins↗

PubMed2003

Localization of preganglionic neurons that innervate choroidal neurons of pterygopalatine ganglion.

PURPOSE: The pterygopalatine ganglion (PPG) receives preganglionic input from the superior salivatory nucleus (SSN) of the facial motor complex and is the main source of parasympathetic input to the choroid in mammals. The present study was undertaken to determine in rats the location and neurotransmitters of SSN neurons innervating those PPG neurons that target the choroid and to determine the location and neurotransmitters of the PPG choroidal neurons themselves. METHODS: Retrograde labeling from rat choroid using a fluorescent tracer, in combination with immunofluorescence labeling for nitric oxide synthase (NOS), vasoactive intestinal polypeptide (VIP), and choline acetyltransferase (ChAT), was used to characterize the location and neurotransmitters of choroidal PPG neurons. To identify SSN neurons that innervate the choroidal PPG neurons, the Bartha strain of the retrograde transneuronal tracer pseudorabies virus (PRV-Ba) was injected into rat choroid, and immunolabeling for NOS or ChAT was used to characterize their neurochemistry. RESULTS: Fluorescent retrograde labeling showed that PPG neurons projecting to the choroid contained NOS, VIP, and ChAT and were widely distributed in PPG and its preganglionic root, the greater petrosal nerve. SSN neurons were ChAT(+), and a subset of them was found to contain NOS. PRV-Ba transneuronal retrograde labeling revealed that choroidal preganglionic neurons were localized to the rostral medioventral part of the ipsilateral SSN. The choroidal SSN neurons were ChAT(+) and appeared largely to correspond to the NOS(+) neurons of the SSN. CONCLUSIONS: These results show that preganglionic neurons in rats that are presumed to regulate choroidal blood flow through the PPG reside within the rostral medioventral SSN, and that NOS is a marker for these SSN neurons.

Animals↗

PubMed2002

Characterization of pseudorabies virus glycoprotein C attachment to heparan sulfate proteoglycans.

Pseudorabies virus first attaches to cells through an interaction between the envelope glycoprotein C (gC) and the cell surface heparan sulfate (HS) that is linked to proteoglycans (HSPGs). The HS-binding domain of gC is composed of three discrete heparin-binding domains (HBDs), designated HBD1, -2 and -3 for their proximity to the amino terminus of gC. Each HBD can independently mediate virus attachment to HS, yet each also exhibits a distinct binding preference for differentially sulfated derivatives of heparin. To demonstrate this, affinity columns composed of wild-type gC or mutant gC retaining a single HBD to capture several HSPGs from cultured pig and bovine kidney cells were used. The wild-type gC column bound all of the HSPGs well and, overall, bound more than 90% of the total sample applied to the column. Columns composed of either HBD2 or -3 bound intermediate amounts (40%) of the total sample applied, while the HBD1 column bound low amounts of HSPGs. HBD2 and -3 columns did not uniformly bind all of the HSPGs from bovine kidney cells, but the same HSPGs were bound with equal efficiency on each column. Thus, despite their different preferences for sulfation patterns on HS side-chains, HBD2 and -3 appear to bind the same proteoglycan cores. These results established a hierarchy of HBD2=HBD3>HBD1 in importance for HSPG binding. These in vitro-binding results correlated with the attachment phenotype of virus strains expressing gC with a single HBD in their envelopes.

Animals↗

PubMed2002

Human exposure following Mycobacterium tuberculosis infection of multiple animal species in a Metropolitan Zoo.

From 1997 to 2000, Mycobacterium tuberculosis was diagnosed in two Asian elephants (Elephas maximus), three Rocky Mountain goats (Oreamnos americanus), and one black rhinoceros (Diceros bicornis) in the Los Angeles Zoo. DNA fingerprint patterns suggested recent transmission. An investigation found no active cases of tuberculosis in humans; however, tuberculin skin-test conversions in humans were associated with training elephants and attending an elephant necropsy.

Animal Husbandry↗