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Biomedical subjects

R C Smith

Publications and source records attributed to R C Smith.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of MRI in classifying proximal focal femoral deficiency.

OBJECTIVE: To evaluate the efficacy of MRI in classifying PFFD and to compare MRI to radiographic classification of PFFD. DESIGN: Radiographic and MRI classification of the cases was performed utilizing the Amstutz classification system. PATIENTS: Retrospective evaluation of radiographs and MRI exams in nine hips of eight patients with proximal focal femoral deficiency was performed by two radiologists. RESULTS: The cases were classified by radiographs as Amstutz 1: n=3, Amstutz 3: n=3, Amstutz 4: n=1 and Amstutz 5: n=2. The classifications based on MRI were Amstutz 1: n=6, Amstutz 2: n=1, Amstutz 3: n=0, Amstutz 4: n=2 and Amstutz 5: n=0. Three hips demonstrated complete agreement. There were six discordant hips. In two of the discordant cases, follow-up radiographs of 6 months or greater intervals were available and helped to confirm MRI findings. Errors in radiographic evaluation consisted of overestimating the degree of deficiency. CONCLUSION: MRI is more accurate than radiographic evaluation for the classification of PFFD, particularly early on, prior to the ossification of cartilaginous components in the femurs. Since radiographic evaluation tends to overestimate the degree of deficiency, MRI is a more definitive modality for evaluation of PFFD.

Bone Diseases, Developmental↗
PubMed2006

Microbial community development in a laboratory-scale nitrifying activated sludge system with input from a side-stream bioreactor treating digester supernatant.

Three laboratory-scale activated sludge treatment trains were operated to investigate the effect on biodiversity in plug flow (PFR) main-stream sewage treatment from input of biomass from side-stream reactors treating anaerobic digester supernatant. One train had a completely mixed (CSTR) side-stream reactor, one a PFR side-stream reactor, and the third train was a control that did not receive input from a side-stream reactor. Restriction endonucleases were used to digest polymerase chain reaction-amplified ammonia monooxygenase subunit A (amoA) genes in monthly samples from each reactor. Restriction fragment banding patterns from polyacrylimide gel electrophoresis indicated that the structure of the ammonia oxidizing bacteria (AOB) populations in all five reactors stabilized by the fourth month of operation and then did not vary subsequently. Furthermore, a dendrogram generated using the Jaccard distance showed that the AOB in each side-stream reactor was most similar to the main-stream reactor in the same train indicating that the AOB population in the side-stream reactor exerts a strong influence on the population in the main-stream reactor. Sequencing results indicated that Nitrosomonas europea, an r-strategist, was the dominant AOB in the PFR side-stream reactor, while Nitrosomonas europea and Nitrosomonas marina, a marine bacterium, were strongly represented in the CSTR side-stream reactor.

Base Sequence↗
PubMed2005

Stress proteins in Alzheimer's disease.

Environmental and genetic conditions can cause proteins to misfold or to accumulate abnormally due to impaired clearance. The chaperones which include heat shock proteins, aid survival by preventing protein mis-folding and the formation of cytotoxic protein aggregates. An increasing number of studies point to important roles for molecular chaperones in the biology of neurodegenerative diseases. Heat shock proteins can suppress neurotoxicity in animal models of Parkinson's and polyglutamine diseases, suggesting potential new therapeutic approaches in neurodegenerative disorders associated with abnormal protein folding and toxicity. Recent findings suggest that heat shock proteins can also be neuroprotective in Alzheimer's disease, but this area of research remains largely unexplored. This paper will review the literature related to the role of heat shock proteins in Alzheimer's disease.

Alzheimer Disease↗
PubMed2005

Characterization of a serodiagnostic complement fixation antigen of Coccidioides posadasii expressed in the nonpathogenic Fungus Uncinocarpus reesii.

Coccidioides spp. (immitis and posadasii) are the causative agents of human coccidioidomycosis. In this study, we developed a novel system to overexpress coccidioidal proteins in a nonpathogenic fungus, Uncinocarpus reesii, which is closely related to Coccidioides. A promoter derived from the heat shock protein gene (HSP60) of Coccidioides posadasii was used to control the transcription of the inserted gene in the constructed coccidioidal protein expression vector (pCE). The chitinase gene (CTS1) of C. posadasii, which encodes the complement fixation antigen, was expressed using this system. The recombinant Cts1 protein (rCts1(Ur)) was induced in pCE-CTS1-transformed U. reesii by elevating the cultivation temperature. The isolated rCts1(Ur) showed chitinolytic activity that was identical to that of the native protein and had serodiagnostic efficacy comparable to those of the commercially available antigens in immunodiffusion-complement fixation tests. Using the purified rCts1(Ur), 74 out of the 77 coccidioidomycosis patients examined (96.1%) were positively identified by enzyme-linked immunosorbent assay. The rCts1(Ur) protein showed higher chitinolytic activity and slightly greater seroreactivity than the bacterially expressed recombinant Cts1. These data suggest that this novel expression system is a useful tool to produce coccidioidal antigens for use as diagnostic antigens.

Antigens, Fungal↗
PubMed2005

Adult intussusception: case reports and review of literature.

Adult intussusception occurs infrequently and differs from childhood intussusception in its presentation, aetiology, and treatment. Diagnosis can be delayed because of its longstanding, intermittent, and non-specific symptoms and most cases are diagnosed at emergency laparotomy. With more frequent use of computed tomography in the evaluation of patients with abdominal pain, the condition can be diagnosed more reliably. Treatment entails simple bowel resection in most cases. Reduction of the intussusception before resection is controversial, but there is a shift against this, especially in colonic cases. Surgical treatment can be difficult in gastroduodenal and coloanal intussusceptions, sometimes requiring innovative techniques. This paper presents the diagnosis and management of four cases of adult intussusception, followed by review of the literature.

Abdominal Pain↗
PubMed2004

Comparative analysis of the in vivo angiogenic properties of stable prostacyclin analogs: a possible role for peroxisome proliferator-activated receptors.

OBJECTIVE: Until recently, prostacyclin (PGI2) biological activities were thought to be exclusively mediated by cell surface receptors named IP. Recent studies have instead identified a novel pathway of PGI2 signaling, occurring through activation of peroxisome proliferator-activated receptors (PPARs) located in the nucleus. The availability of stable PGI2 analogs with different affinity for IP receptors and PPARs provides the possibility to test the importance and function of this dual pathway in vitro and in vivo. In this study, the in vivo angiogenic properties of different PGI2 analogs and the potential relationship between PPAR-mediated pathways, vascular endothelial growth factor (VEGF), and angiogenesis were investigated. METHODS AND RESULTS: By using the murine corneal model of angiogenesis, we found that PGI2 analogs able to act on nuclear PPARs, such as iloprost and carbaprostacyclin (cPGI), induce angiogenesis in vivo. In contrast, cicaprost, a PGI2 analog that only acts on IP receptors, has no in vivo angiogenic activity. Interestingly, angiogenesis induced by iloprost and cPGI does not differ in extent and morphology from that induced by VEGF and is associated with local increment of VEGF mRNA expression and protein levels. Finally, iloprost-induced angiogenesis is significantly decreased by systemic inhibition of VEGF activity, obtained by gene transfer of a soluble form of the VEGF receptor Flt-1. CONCLUSIONS: These data demonstrate that stable PGI2 analogs may have angiogenic properties in vivo, depending on their ability to act on PPARs. The resulting angiogenic process appears to be mediated by VEGF. These findings indicate that important physiological activities in the cardiovascular system, such as angiogenesis and VEGF induction, may be modulated by PGI2 through specific activation of the PPAR signaling pathway in vivo, with potentially important fundamental and clinical implications.

Animals↗
PubMed2003

Transgene delivery of plasmid DNA to smooth muscle cells and macrophages from a biostable polymer-coated stent.

Metallic stents coated with a polyurethane emulsion containing plasmid DNA were implanted in rabbit iliac arteries to evaluate transgene delivery and expression in the vessel wall. The expression of the plasmid-encoded marker genes, beta-galactosidase, luciferase and green fluorescence protein (GFP), were evaluated at 7 days after implantation. In all cases, plasmid transfer was confined to the vessel wall at the site of stent implantation, plasmid DNA was not observed in vessel segments immediately proximal or distal to the stent and dissemination of plasmid DNA to lung, liver or spleen was not observed. Expression of transgenes occurred only in vessel segments in contact with the stent and analysis of the GFP expression pattern revealed a high frequency of marker protein-positive cells occurring at or near the luminal surface. The extent of transgene expression was dependent upon the quantity of DNA loaded onto the stent and no signal was detected in vessel segments that received polymer-coated stents lacking plasmid DNA. Of significance, colocalization studies identified transgene expression not only in vascular smooth muscle cells but also in macrophages. Hence, polymer-coated stents provide a new capability for transgene delivery to immune cells that are believed to contribute to the development of in-stent restenosis.

Animals↗
PubMed2002

PDGF-BB enhances expression of, and reduces adhesion to, laminin-5 in vascular smooth muscle cells.

The laminin family of extracellular matrix (ECM) proteins plays crucial roles in regulating cellular growth, migration, and differentiation. We report here that laminin-5 is expressed in the tunica media of the rat aorta and pulmonary arteries. Using indirect immunofluorescence microscopy, Western blots, and RT-PCR analysis, we found that primary cultures of rat arterial smooth muscle cells express laminin-5 and deposit it into their insoluble ECM. These cells also attach strongly to laminin-5 via beta1 integrin receptors in 30 min adhesion assays. Laminin-5 expression in these cells is upregulated by growth factors in vitro and platelet-derived growth factor (PDGF-BB) stimulation reduces adhesion to laminin-5. As laminin-5 promotes enhanced migration of other cell types, the production of and adhesion to laminin-5 by vascular smooth muscle cells may play a role in the pathological growth and migration of these cells associated with restenosis following vascular injury.

Animals↗
PubMed2001

The role of psychosocial factors in the development of breast carcinoma: Part I. The cancer prone personality.

BACKGROUND: The authors conducted the current study to determine whether personality predisposes some individuals to develop cancer. METHODS: The current study examined the role of personality variables in 2224 older women recalled for assessment after routine mammography in a breast screening program. Using a semiprospective design, subjects completed self-report measures of defense style, locus of control, emotional expression and control, self-esteem, trait anxiety, and state anxiety and depression while waiting for medical examination. Multivariate analysis of variance was used to control for known risk factor variables and to examine differences between 3 control groups (normal tissue controls, benign/cystic controls not requiring biopsy, and benign biopsy controls) and 298 breast carcinoma subjects. RESULTS: No differences were detected between breast carcinoma subjects and controls based on measures of mature, immature, and neurotic defense style; locus of control of behavior; emotional expression-in, emotional expression-out, and emotional control; self-esteem; anxiety; or depression. CONCLUSIONS: The results of the current study found no evidence to support an independent association between these personality measures and the development of breast carcinoma. [See accompanying article on pages 686-97, this issue.]

Aged↗
PubMed2001

The role of psychosocial factors in the development of breast carcinoma: Part II. Life event stressors, social support, defense style, and emotional control and their interactions.

BACKGROUND: The evidence supporting an association between life event stress and breast carcinoma development is inconsistent. METHODS: Five hundred fourteen women requiring biopsy after routine mammographic breast screening were interviewed using the Brown and Harris Life Event and Difficulties Schedule. Other psychosocial variables assessed included social support, emotional control, and defense style. Biopsy results identified 239 women with breast carcinoma and 275 women with benign breast disease. Multiple logistic regression analysis was used to distinguish between breast carcinoma subjects and benign breast disease controls based on these psychosocial variables and their interactions. RESULTS: The findings of the current study revealed a significant interaction between highly threatening life stressors and social support. Women experiencing a stressor objectively rated as highly threatening and who were without intimate emotional social support had a ninefold increase in risk of developing breast carcinoma. CONCLUSIONS: Although there was no evidence of an independent association between life event stress and breast carcinoma, the findings of the current study provided strong evidence that social support interacts with highly threatening life stressors to increase the risk of breast carcinoma significantly. [See also accompanying article on pages 679-85, this issue.]

Adaptation, Psychological↗
PubMed2001

The effects of olanzapine on neurocognitive functioning in medication-refractory schizophrenia.

Neurocognitive deficits are an enduring characteristic of schizophrenia, and remain prominent in patients whose positive symptoms have decreased after treatment with typical neuroleptics. Recent research has reported that olanzapine improves cognitive functioning in relapsing schizophrenia followed in an outpatient setting. Whether olanzapine will have an effect on improving cognitive function in chronic schizophrenics who have been hospitalized for long periods of time, and have shown a poor response to other conventional and atypical neuroleptics, has not been established. This study investigated cognitive function in chronic medication refractory schizophrenics who were treated with olanzapine or haloperidol in a double-blind study for 8 wk, and followed in an open olanzapine study for several additional months. Patients were evaluated with psychopathology rating scales and a battery of neuropsychological tests at baseline, end of double-blind and end of open-label phases of the study. At the end of the double-blind phase there were no significant differences between olanzapine and haloperidol, except for a trend for improvement on the Wisconsin Card Sort Test on olanzapine, which was significant at traditional but not corrected significance levels. After an additional 3 months of treatment with olanzapine doses of 20-40 mg/d, our statistical analysis showed significant improvement on overall neuropsychological test performance and specific cognitive tasks assessing verbal memory. However, these open-label results are difficult to interpret definitively because of the lack of a comparison drug group and the olanzapine dose escalation over time. Neurocognitive changes were not correlated with changes in psychopathology as assessed by PANSS or SANS scores.

Antipsychotic Agents↗
PubMed2001

Tissue-specific expression of an anti-proliferative hybrid transgene from the human smooth muscle alpha-actin promoter suppresses smooth muscle cell proliferation and neointima formation.

The retinoblastoma protein (Rb), a key regulator of cell cycle progression, can bind the transcription factor E2F converting it from a positive transcriptional factor capable of driving cells into S phase into a negative complex which arrests cells in G1. We have created a potent transcriptional repressor of E2F-dependent transcription by fusing the C-terminal fragment of Rb (p56) to the DNA and DP1-binding domains of E2F. Because the expression of E2F/56 fusion protein from a constitutive promoter was incompatible with virus growth, adenovirus constructs were prepared where transgenes were expressed from a fragment of the smooth muscle alpha-actin (SMA) promoter. Immunoblot and beta-galactosidase staining demonstrated smooth muscle-specific expression of this transcriptional element in vitro. The SMA-p56 and SMA-E2F/p56 adenoviral constructs also induced G0/G1 cell cycle arrest specifically in smooth muscle cells. Following administration to rat tissues, the SMA-beta-galactosidase construct exhibited expression in balloon-injured carotid arteries, but not in liver, bladder or skeletal muscle. Local delivery of the SMA-E2F/p56 adenoviral construct to balloon-injured carotid arteries inhibited intimal hyperplasia. Our results demonstrate that local delivery of the SMA-E2F/p56 adenoviral construct can limit intimal hyperplasia in balloon-injured vessels, while avoiding toxicity that could occur from the dissemination and expression of the viral transgene.

Actins↗
PubMed2001

Local gene delivery to the vessel wall.

This review will provide an overview of delivery strategies that are being evaluated for vascular gene therapy. We will limit our discussion to those studies that have been demonstrated, utilizing in vivo model systems, to limit post-interventional restenosis. We also discuss the efficacy of the vectors and methods currently being used to transfer genetic material to the vessel wall. The efficiency of these techniques is a critical issue for the successful application of gene therapy.

Angioplasty, Balloon, Coronary↗
PubMed2001

Human truncated Smad 6 (Smad 6s) inhibits the BMP pathway in Xenopus laevis.

A previously identified truncated form of the human Smad 6 gene containing a unique 12 amino acid motif at its N-terminus was studied. We have named this truncated form of the gene Smad 6s, for 'short-form', to distinguish it from the full-length form (Smad 6fl). Reverse transcription-polymerase chain reaction and immunohistochemistry revealed that Smad 6s has a unique pattern of expression in human coronary tissue and is upregulated in diseased heart tissue. We used the expression of human Smad 6s in Xenopus laevis as a model system to assess Smad 6s function. Injection of Smad 6fl RNA (4-cell embryos, 2 x ventral) produced tadpoles with partial secondary axes. In contrast, Smad 6s RNA injected in a similar manner produced tadpoles with a severe 'head-only' phenotype with no morphological appearance of a secondary axis. Mutant Smad 6s RNA lacking the unique 12 amino acids at the N-terminus of the Smad 6s isoform produced no embryonic phenotype, suggesting that this region is important in conferring biological activity. Ectodermal explant assays show that Smad 6s has activity consistent with being a BMP antagonist and can synergize with and enhance the activities of the activin and fibroblast growth factor pathways, all of which are novel findings in this study.

Animals↗