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Scott Roberts

Publications and source records attributed to Scott Roberts.

14 recordsLinked to original sources
PubMed2007

Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization.

UNLABELLED: PHOSPHO1 is a phosphatase highly expressed in bone. We studied its functional involvement in mineralization through the use of novel small molecule inhibitors. PHOSPHO1 expression was present within matrix vesicles, and inhibition of enzyme action caused a decrease in the ability of matrix vesicles to calcify. INTRODUCTION: The novel phosphatase, PHOSPHO1, belongs to the haloacid dehalogenase superfamily of hydrolases and is capable of cleaving phosphoethanolamine (PEA) and phosphocholine to generate inorganic phosphate. Our aims in this study were to examine the expression of PHOSPHO1 in murine mineralizing cells and matrix vesicles (MV) and to screen a series of small-molecule PHOSPHO1-specific inhibitors for their ability to pharmacologically inhibit the first step of MV-mediated mineralization. MATERIALS AND METHODS: q-PCR and immunohistochemistry were used to study the expression and localization profiles of PHOSPHO1. Inhibitors of PHOSPHO1's PEA hydrolase activity were discovered using high-throughput screening of commercially available chemical libraries. To asses the efficacy of these inhibitors to inhibit MV mineralization, MVs were isolated from TNAP-deficient (Akp2(-/-)) osteoblasts and induced to calcify in their presence. RESULTS: q-PCR revealed a 120-fold higher level of PHOSPHO1 expression in bone compared with a range of soft tissues. The enzyme was immunolocalized to the early hypertrophic chondrocytes of the growth plate and to osteoblasts of trabecular surfaces and infilling primary osteons of cortical bone. Isolated MVs also contained PHOSPHO1. PEA hydrolase activity was observed in sonicated MVs from Akp2(-/-) osteoblasts but not intact MVs. Inhibitors to PHOSPHO1 were identified and characterized. Lansoprazole and SCH202676 inhibited the mineralization of MVs from Akp2(-/-) osteoblasts by 56.8% and 70.7%, respectively. CONCLUSIONS: The results show that PHOSPHO1 localization is restricted to mineralizing regions of bone and growth plate and that the enzyme present within MVs is in an active state, inhibition of which decreases the capacity of MVs to mineralize. These data further support our hypothesis that PHOSPHO1 plays a role in the initiation of matrix mineralization.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Areas of intervention for genetic counselling of dementia: cross-cultural comparison between Italians and Americans.

OBJECTIVE: Purposes of this study are: (1) to evaluate attitudes, beliefs and experiences towards dementia among relatives of Italian familial cases; (2) to perform a cross-cultural comparison between Italian and American samples; (3) to identify predictors of intentions to undergo hypothetical genetic testing. METHODS: Participants were 134 relatives of patients affected by familial forms of dementia. We administered tests measuring health psychological styles, social variables, illness perceptions, intentions regarding genetic testing, and perceptions of the pros and cons of genetic testing. RESULTS: Respondents had a poor Alzheimer's disease knowledge and a low perceived dementia threat. When compared to Americans, Italians reported greater willingness to undergo genetic testing and perceived a different subset of benefits and risks. The strongest predictors of test intention were decisional balance, homemaker status and two beliefs concerning dementia causes. CONCLUSIONS: Italians had a poor knowledge of the disease and a low awareness of personal risk of developing dementia. As compared to Americans, they expressed higher intentions to undergo genetic testing and they have a different perception of benefits and risks. PRACTICE IMPLICATIONS: Understanding of cultural differences in knowledge, attitudes and perception of the disease is important to design optimal health services and education programs for dementia.

Adult↗
PubMed2006

Cost-effectiveness of universal influenza vaccination in a pregnant population.

OBJECTIVE: The purpose of this study was to estimate whether universal influenza vaccination of pregnant women was cost-effective in the management of influenza-like illness during influenza season. METHODS: A decision analysis model was developed to investigate the cost-effectiveness of providing inactivated trivalent influenza vaccine to all pregnant women. This scenario was compared with providing supportive care only on a case-by-case basis to the unvaccinated pregnant population. RESULTS: Vaccination of 100% of pregnant women would save approximately 50 dollars per woman, resulting in a net gain of approximately 45 quality-adjusted hours relative to providing supportive care only. CONCLUSION: Universal vaccination with inactivated trivalent influenza vaccine is cost-saving relative to providing supportive care alone in the pregnant population. LEVEL OF EVIDENCE: III.

Adolescent↗
PubMed2006

Recurrence of clinical chorioamnionitis in subsequent pregnancies.

OBJECTIVE: To establish the role of clinical chorioamnionitis as an independent risk factor for recurrence in a subsequent pregnancy. METHOD: This was a historical cohort study of pregnant women who had their first and second deliveries at our institution between January 1988 and May 2005. The index pregnancy was restricted to those who delivered vaginally. Data were collected from a continuously updated obstetric database and included demographic and labor characteristics and neonatal outcomes. Chorioamnionitis was diagnosed clinically. RESULTS: The study population consisted of 23,397 women. During the index pregnancy, 10% of women developed chorioamnionitis. This group was significantly different from the rest of the cohort in terms of age, ethnicity, length of labor, epidural analgesia, use of internal monitors, and incidence of prolonged rupture of membranes. In the second pregnancy, 6% of those women again developed chorioamnionitis compared with 2% of women who did not have chorioamnionitis in the first pregnancy (odds ratio 2.93, 95% confidence interval 2.40-3.57). After adjusting for the above confounders, the increased risk of recurrence persisted (odds ratio 1.85, 95% confidence interval 1.49-2.30). CONCLUSION: Women delivering vaginally who were diagnosed with chorioamnionitis during their first pregnancy are at increased risk for chorioamnionitis in a subsequent pregnancy. This supports the concept that there may be a predisposition to chorioamnionitis that should be further investigated. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2005

A real-time PCR assay to detect the Panton Valentine Leukocidin toxin in staphylococci: screening Staphylococcus schleiferi subspecies coagulans strains from companion animals.

Recent reports suggest that methicillin-resistant strains of Staphylococcus schleiferi subspecies coagulans are now commonly isolated from dogs. Given the association of a potentially mobile SCCmec type IV element with lysogenic phage-encoded Panton Valentine Leukocidin (PVL) toxin genes in community-acquired methicillin-resistant Staphylococcus aureus strains we hypothesized that methicillin-resistant S. schleiferi ssp. coagulans strains may also encode PVL toxin genes. Forty S. schleiferi ssp. coagulans strains isolated from companion animals were studied. Susceptibility to oxacillin was determined by broth microdilution and all isolates were screened by PCR for the presence of the mecA gene. SCCmec typing was performed on 14 isolates. A real-time PCR assay was developed for the detection of the PVL genes using a SmartCycler. Pulsed-field gel electrophoresis (PFGE) was performed to determine whether S. schleiferi ssp. coagulans strains were homogeneous. Twenty-eight of the 40 isolates (70%) were resistant to oxacillin and 26/28 possessed the mecA gene by PCR. SCCmec IV was identified in seven strains; the other seven isolates were not typable by this technique. All 40 strains were negative for the PVL toxin gene. PFGE showed a heterogeneous population and 13 different profiles were determined. In conclusion, this study showed that PVL toxin genes were not detected in a heterogeneous population of methicillin-resistant S. schleiferi ssp. coagulans strains isolated from companion animals.

Animals↗
PubMed2005

Panton valentine leukocidin (PVL) toxin positive MRSA strains isolated from companion animals.

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly pathogenic multiple-drug resistant (MDR) microorganism that has recently become more prevalent in the community. It has been found that MRSA strains can also contain genes that encode the panton valentine leukocidin toxin (PVL). The PVL toxin has been shown to be responsible for many of the severe clinical symptoms of infection with MRSA, such as furunculosis, severe necrotizing pneumonia, and necrotic lesions of the skin and soft tissues. The aim of this study was to determine the presence of the S. aureus PVL toxin genes (lukS-PV and lukF-PV) in MRSA strains isolated from companion animals. Eleven MRSA isolates, from a total of 23 tested, were shown to possess the mecA gene and the PVL toxin genes. Pulsed-field gel electrophoresis showed that the 11 PVL toxin positive MRSA strains were highly clonal.

Animals↗
PubMed2005

Prevalence of hepatitis B and C in pregnant women who are infected with human immunodeficiency virus.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of hepatitis B and hepatitis C virus co-infection among pregnant women who are infected by human immunodeficiency virus and who attend an obstetric complications prenatal clinic. STUDY DESIGN: A de-identified research obstetric human immunodeficiency virus database was reviewed regarding patient demographic characteristics, risk factors for infection, history of sexually transmitted diseases, and initial CD4 count. RESULTS: Four hundred fifty-five women who are infected with human immunodeficiency virus with 572 pregnancies were delivered over 11 years. The overall prevalence of human immunodeficiency virus and hepatitis B or C virus co-infection in our population was 6.3%. More specifically, 1.5% was co-infected with hepatitis B virus, and 4.9% was co-infected with hepatitis C virus. Patients with hepatitis virus were more likely to use intravenous drugs (52% vs 18%; P < .01) and alcohol (38% vs 5%; P < .01). Co-infected patients were older (28 vs 25.6 years; P=.04), but there were no racial differences. Median baseline CD4 counts in hepatitis B virus co-infected patients were significantly lower (310 cells/mm3) than those in either hepatitis C virus co-infected patients (453 cells/mm3) or patients who were not co-infected with human immunodeficiency virus (414 cells/mm3). CONCLUSION: One of 16 pregnant women who were infected with human immunodeficiency virus was co-infected with hepatitis B or hepatitis C virus. Hepatitis B co-infections appear to be associated with more compromised immune status in our cohort.

Female↗
PubMed2005

Herpes simplex virus in pregnancy: new concepts in prevention and management.

Genital herpes simplex virus (HSV) infection is one of the most common viral sexually transmitted diseases in the United States. It is estimated that 45 million adolescents and adults are infected with genital HSV. Most genital herpes infections in the United States are caused by HSV type 2 (HSV-2), and 25% to 30% of women of reproductive age have HSV-2 antibodies. What is more striking is that genital herpes is frequently under-recognized, and that only 5% to 10% of these women have a history of genital herpes. Because such a small percentage of women are aware of being infected with HSV, the risk of maternal transmission of this virus to the fetus or newborn is a significant health issue.

Antibodies, Viral↗
PubMed2005

Clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus in pregnancy.

OBJECTIVE: The objective of this study was to review the presentation and management of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in pregnant women. METHODS: This was a chart review of pregnant patients who were diagnosed with MRSA between January 1, 2000, and July 30, 2004. Data collected included demographic characteristics, clinical presentation, culture results, and pathogen susceptibilities. Patients' pregnancy outcomes were compared with the general obstetric population during the study period. RESULTS: Fifty-seven charts were available for review. There were 2 cases in 2000, 4 in 2001, 11 in 2002, 23 in 2003, and 17 through July of 2004. Comorbid conditions included human immunodeficiency virus and acquired immunodeficiency syndrome (13%), asthma (11%), and diabetes (9%). Diagnostic culture was most commonly obtained in the second trimester (46%); however 18% of cases occurred in the postpartum period. Skin and soft tissue infections accounted for 96% of cases. The most common site for a lesion was the extremities (44%), followed by the buttocks (25%), and breast (mastitis) (23%). Fifty-eight percent of patients had recurrent episodes. Sixty-three percent of patients required inpatient treatment. All MRSA isolates were sensitive to trimethoprim-sulfamethoxazole, vancomycin, and rifampin. Other antibiotics to which the isolates were susceptible included gentamicin (98%) and levofloxacin (84%). In comparison with the general obstetric population, patients with MRSA were more likely to be multiparous and to have had a cesarean delivery. CONCLUSION: Community-acquired MRSA is an emerging problem in our obstetric population. Most commonly, it presents as a skin or soft tissue infection that involves multiple sites. Recurrent skin abscesses during pregnancy should raise prompt investigation for MRSA. LEVEL OF EVIDENCE: II-3.

Adult↗
PubMed2005

Predictive genetic testing for Alzheimer's disease: impact upon risk perception.

UNLABELLED: The aim of this study was to determine the impact on risk perceptions of disclosing genetic test results used to estimate the risk of Alzheimer's disease (AD). Adult children (n = 149) of people with AD were randomized to one of two groups--Intervention group: lifetime risk estimates of AD based on age, gender, family history, and Apolipoprotein E (APOE) genotype; CONTROL GROUP: lifetime risk estimates of AD based on the same risk factors excluding APOE genotype. Perceptions of personal risk (PPR) for AD were assessed six weeks after risk assessments. PPR were correlated with actual lifetime risk estimates (r = 0.501; p < 0.0001). After controlling for lifetime risks communicated to participants, age, and number of affected relatives, PPR scores among those with an epsilon4-positive test result (the test result associated with increased AD susceptibility) (adjusted mean: 3.4 (SD: 0.7)) were not different from the PPR scores in the CONTROL GROUP (adjusted mean: 3.4 (SD: 0.7) (F1,91= 1.98; p = 0.162). Again, controlling for lifetime risk estimates, age, and number of affected relatives, the PPR score of those receiving an epsilon4-negative test result was significantly lower (adjusted mean: 3.1 (SD: 0.8)) than those in the CONTROL GROUP (adjusted mean: 3.4 (SD: 0.7) (F1,95 = 6.23; p = 0.014). Perceptions of risk of developing AD are influenced by genetic test disclosure in those receiving epsilon4-negative, but not those receiving epsilon4-positive test results. Despite the reduced perceptions of risk in the former group, there was no evidence of false reassurance (i.e., perceiving risks as equal to or lower than population risks of AD), although this possibility should be assessed in other testing contexts.

Age Factors↗
PubMed2002

Apc modulates embryonic stem-cell differentiation by controlling the dosage of beta-catenin signaling.

The Wnt signal-transduction pathway induces the nuclear translocation of membrane-bound beta-catenin (Catnb) and has a key role in cell-fate determination. Tight somatic regulation of this signal is essential, as uncontrolled nuclear accumulation of beta-catenin can cause developmental defects and tumorigenesis in the adult organism. The adenomatous polyposis coli gene (APC) is a major controller of the Wnt pathway and is essential to prevent tumorigenesis in a variety of tissues and organs. Here, we have investigated the effect of different mutations in Apc on the differentiation potential of mouse embryonic stem (ES) cells. We provide genetic and molecular evidence that the ability and sensitivity of ES cells to differentiate into the three germ layers is inhibited by increased doses of beta-catenin by specific Apc mutations. These range from a severe differentiation blockade in Apc alleles completely deficient in beta-catenin regulation to more specific neuroectodermal, dorsal mesodermal and endodermal defects in more hypomorphic alleles. Accordingly, a targeted oncogenic mutation in Catnb also affects the differentiation potential of ES cells. Expression profiling of wildtype and Apc-mutated teratomas supports the differentiation defects at the molecular level and pinpoints a large number of downstream structural and regulating genes. Chimeric experiments showed that this effect is cell-autonomous. Our results imply that constitutive activation of the Apc/beta-catenin signaling pathway results in differentiation defects in tissue homeostasis, and possibly underlies tumorigenesis in the colon and other self-renewing tissues.

Adenomatous Polyposis Coli Protein↗
PubMed2002

Multiplexed protein profiling on microarrays by rolling-circle amplification.

Fluorescent-sandwich immunoassays on microarrays hold appeal for proteomics studies, because equipment and antibodies are readily available, and assays are simple, scalable, and reproducible. The achievement of adequate sensitivity and specificity, however, requires a general method of immunoassay amplification. We describe coupling of isothermal rolling-circle amplification (RCA) to universal antibodies for this purpose. A total of 75 cytokines were measured simultaneously on glass arrays with signal amplification by RCA with high specificity, femtomolar sensitivity, 3 log quantitative range, and economy of sample consumption. A 51-feature RCA cytokine glass array was used to measure secretion from human dendritic cells (DCs) induced by lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha). As expected, LPS induced rapid secretion of inflammatory cytokines such as macrophage inflammatory protein (MIP)-1beta, interleukin (IL)-8, and interferon-inducible protein (IP)-10. We found that eotaxin-2 and I-309 were induced by LPS; in addition, macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), soluble interleukin 6 receptor (sIL-6R), and soluble tumor necrosis factor receptor I (sTNF-RI) were induced by TNF-alpha treatment. Because microarrays can accommodate approximately 1,000 sandwich immunoassays of this type, a relatively small number of RCA microarrays seem to offer a tractable approach for proteomic surveys.

Antibodies↗