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Biomedical subjects

M McCarty

Publications and source records attributed to M McCarty.

At least 19 recordsLinked to original sources
PubMed2007

Loss of AP-2alpha results in deregulation of E-cadherin and MMP-9 and an increase in tumorigenicity of colon cancer cells in vivo.

Activator protein-2 (AP-2) is a transcription factor that regulates proliferation and differentiation in mammalian cells and has been implicated in the acquisition of the metastatic phenotype in several types of cancer. Herein, we examine the role of AP-2alpha in colon cancer progression. We provide evidence for the lack of AP-2alpha expression in the late stages of colon cancer cells. Re-expression of the AP-2alpha gene in the AP-2alpha-negative SW480 colon cancer cells suppressed their tumorigenicity following orthotopic injection into the cecal wall of nude mice. The inhibition of tumor growth could be attributed to the increased expression of E-cadherin and decreased expression and activity of matrix-metalloproteinase-9 (MMP-9) in the transfected cells, as well as a substantial loss of their in vitro invasive properties. Conversely, targeting constitutive expression of AP-2alpha in AP-2-positive KM12C colon cancer cells with small interfering RNA resulted in an increase in their invasive potential, downregulation of E-cadherin and increased expression of MMP-9. In SW480 cells, re-expression of AP-2alpha resulted in a fourfold increase in the activity of E-cadherin promoter, and a 5-14-fold decrease in the activity of MMP-9 promoter, indicating transcriptional regulation of these genes by AP-2alpha. Chromatin immunoprecipitation assay showed that re-expressed AP-2alpha directly binds to the promoter of E-cadherin, where it has been previously reported to act as a transcriptional activator. Furthermore, chromatin immunoprecipitation assay revealed AP-2alpha binding to the MMP-9 promoter, which ensued by decreased binding of transcription factor Sp-1 and changes in the recruitment of transcription factors to a distal AP-1 element, thus, contributing to the overall downregulation of MMP-9 promoter activity. Collectively, our data provide evidence that AP-2alpha acts as a tumor suppressor gene in colon cancer..

Animals↗
PubMed2001

Paediatric pelvic imaging: optimisation of dose and technique using digital grid-controlled pulsed fluoroscopy.

BACKGROUND: An audit of paediatric pelvic radiographs identified deficiencies in gonad shield placement and radiographic technique. OBJECTIVE: A technique using grid-controlled fluoroscopy (GCF), with hard copy images in frame grab and digital spot image (DSI) format was evaluated to optimise gonad shield placement and reduce the dose given to children with Perthes disease and Developmental Hip Dysplasia (DDH) attending for pelvic radiography. MATERIALS AND METHODS: Phantom and patient dose surveys of conventional and fluoroscopic techniques were carried out. Image quality and radiation dose were compared for the frame grab and DSI techniques. Retrospective evaluation was undertaken to compare their clinical acceptability. RESULTS: Both fluoroscopic techniques gave considerably less radiation than conventional non-grid radiography (67-83%, P < 0.05). The frame grab technique gave less radiation than DSI (P < 0.05). There was no significant difference in the clinical acceptability scores of the DSI and frame grab images. CONCLUSION: Fluoroscopy acquired images are now used since the fluoroscopic techniques give much less dose than conventional radiography and provide images of sufficient quality for clinical assessment. Indeed, as there was no significant difference in clinical usefulness between the frame grab and DSI techniques, it is planned to use frame grab alone, thus gaining additional dose saving.

Adolescent↗
PubMed2001

Paediatric pelvic imaging: improvement in gonad shield placement by multidisciplinary audit.

BACKGROUND: In 1996, there were local reports of poor gonad protection for paediatric pelvic radiographs. OBJECTIVES: To investigate the nature of the problem and make necessary improvements. MATERIALS AND METHODS: A retrospective audit of 218 paediatric pelvic radiographs was undertaken in 1997. Each radiograph was assessed for the presence of a gonad shield, appropriateness of the device and its position. A multidisciplinary team was formed with representation from radiology, radiography, orthopaedics and medical physics to investigate ways of improving technique and reducing patient dose. These included radiographer training and the introduction of digital fluoroscopy as an alternative imaging technique in follow-up patients. There were further rounds of data collection in 1998 and 1999. RESULTS: In round 1, a gonad shield was present in 77.9 % of boys' films and 76 % of girls' films where one should have been, increasing to 85.2 % and 85.4 % respectively by round 3 of the audit (P < 0.05). Only 31.6 % of boys' devices and 21.9 % of girls' devices were correctly positioned in round 1, increasing to 78.3 % and 94.3 %, respectively, by round 3 of the audit (P < 0.05). After round 1, no inappropriate devices were used. CONCLUSION: Audit was an effective tool in gaining the resources needed to improve technique and reduce radiation exposure in children. The multidisciplinary approach was vital in the success of this project.

Child, Preschool↗
PubMed2001

Growth and characterization of N-methyl-N-nitrosourea-induced mammary tumors in intact and ovariectomized rats.

It is well established that 85-90% of chemically induced mammary tumors in rats will disappear or diminish significantly in size after the ovaries are removed from the animal. However, it is less well established whether a high percentage of these mammary tumors will grow back with prolonged time after ovariectomy. It is also not known what changes in gene expression take place in the tumors as they develop an independence from hormones for growth. This study was carried out to investigate this. Virgin, 50-day-old female Sprague-Dawley rats were injected with N-methyl-N-nitrosourea (MNU) at the dose of 50 mg MNU/kg body wt. When at least one mammary tumor had grown to 1.0-1.5 cm in one dimension, the animal was bilaterally ovariectomized and reduction and then re-growth of the tumors monitored. Control animals were treated identically except they were not ovariectomized when tumors appeared. Re-growths and new tumors and tumors that developed in the control rats were removed when they reached 1.0-1.5 cm in diameter and all animals were killed 25 weeks after the MNU injection. All the animals in the study (100%) developed mammary tumors after MNU injection with an average latency of 56.5 days. After ovariectomy, 93% of the tumors showed 50% or more reduction in size and 76% of the tumors could not be detected by palpation. However, in 96% of the animals where tumor reduction or disappearance occurred, a re-growth or new mammary tumor development took place with an average latency period of 52.8 days from the day of ovariectomy. Of these post-ovariectomy tumors, 36% occurred at a location where tumors had developed prior to ovariectomy, but 64% appeared at new locations. The circulating levels of 17beta-estradiol (E2) was undetectable in the ovariectomized (OVX) rats and significant reduction was seen in the serum concentrations of progesterone (P4), prolactin (PRL), growth hormone (GH) and insulin-like growth factor-I (IGF-I). The tumors from the OVX rats showed indications of progression as evident from loss of differentiation and invasive characteristics. Comparison between tumors from OVX and intact rats revealed a significantly increased expression of P450 aromatase and elevated activation of extracellular signal-regulated kinase 1 and 2, but reduced levels of the progesterone receptor and cyclin D1 in OVX rats. However, the estrogen receptor (ER) content remained similar in tumors from both groups, at least at the protein level, and so did the expression of IGF-I, IGF-II, insulin receptor substrate-1 (IRS1), IRS-2 and epidermal growth factor receptor. IGF-I receptor (IGF-IR) and ErbB-2 were expressed, respectively, in 50 and 70% of the tumors from the OVX animals, whereas these genes were expressed in 100% of the tumors from the intact rats. It is concluded that chemically induced rat mammary tumors may still depend on the ER and local syntheses of E2 and growth factors for growth initially after ovariectomy. However, as these tumors progress, they develop a more aggressive phenotype and lose their dependency on the ER and possibly growth factors.

Animals↗
PubMed2000

Mekk3 is essential for early embryonic cardiovascular development.

The early development of blood vessels consists of two phases, vasculogenesis and angiogenesis, which involve distinct and also overlapping molecular regulators, but the intracellular signal transduction pathways involved in these processes have not been well defined. We disrupted Map3k3 (also known as Mekk3), which encodes Mekk3, a member of the Mekk/Ste11 family, in mice. Map3k3-/- embryos died at approximately embryonic day (E) 11, displaying disruption of blood vessel development and the structural integrity of the yolk sac. Angiogenesis was blocked at approximately E9.5 in mutant embryos. Map3k3 disruption did not alter the expression of the genes encoding Vegf-1, angiopoietin or their receptors. The development of embryonic, but not maternal, blood vessels in the placentas of Map3k3-/- embryos was impaired, revealing an intrinsic defect in Map3k3-/- endothelial cells. Moreover, Mekk3 activated myocyte-specific enhancer factor 2C (Mef2c), a transcription factor crucial for early embryonic cardiovascular development through the p38 mitogen-activated protein kinase (Mapk) cascade. We conclude that Mekk3 is necessary for blood vessel development and may be a possible target for drugs that control angiogenesis.

Animals↗
PubMed1999

Oral rehydration solution for acute diarrhea prevents subsequent unscheduled follow-up visits.

BACKGROUND: Oral rehydration solutions (ORS) for the treatment of acute diarrhea remain an underutilized therapy in the United States, despite multiple clinical trials confirming their efficacy and safety. Economic barriers to their use have been identified. OBJECTIVE: To determine whether providing ORS to patients at the time of their office visit for acute diarrhea can increase ORS utilization and reduce unscheduled follow-up visits. DESIGN: Randomized, controlled clinical trial. SETTING: Seven health centers of a large health maintenance organization. PARTICIPANTS: Children (N = 479) 0 to 60 months of age with acute diarrhea (at least three watery or loose stools in the previous 24 hours for </=7 days). INTERVENTION: Prescription for 2 quarts of ORS filled for free at on-site pharmacy plus written instructions versus written instructions alone. PRIMARY OUTCOME MEASURES: Self-reported use of ORS; unscheduled follow-up visits in office, urgent care, and/or emergency department setting. RESULTS: Subjects in the intervention group were significantly more likely to use ORS after the initial office visit (85% vs 71%; RR: 1.19; 95% CI: 1.08-1.32). Of the standard treatment group subjects, 40 (17.3%) sought unscheduled follow-up care for diarrhea versus 27 (10.9%) of the intervention group subjects (RR: 0.63; 95% CI: 0.40-0.99). Subjects seeking unscheduled follow-up care tended to younger (15.7 vs 19.4 months old), have more stools (7.1 vs 6.2 stools), and more vomiting episodes (4.1 vs 3.0) in the 24 hours before initial evaluation than those not seeking unscheduled follow-up care. Multivariate analysis showed that randomization to the intervention group was associated with a 25% reduction in unscheduled follow-up visits for acute diarrhea. CONCLUSIONS: Providing ORS to families at the time of their office visit for acute diarrhea is associated with a significant increase in ORS use and substantially reduces the need for unscheduled follow-up visits. Health maintenance organizations should consider routine provision of ORS to children presenting with acute diarrhea.

Acute Disease↗
PubMed1998

Hyperkalemic ascending paralysis.

Hyperkalemia is a life-threatening electrolyte disturbance. The clinical presentation is most commonly related to its effects on cardiac conductivity and contractility, although weakness and respiratory compromise may occur. We describe what we believe to be the first reported case of life-threatening hyperkalemia presenting as an ascending paralysis which was associated with standard-dose trimethoprim-sulfamethoxazole therapy. The patient had mild, underlying renal disease which predisposed him to develop hyperkalemia. This case underscores the need to use caution in prescribing trimethoprim to such patients.

Adult↗
PubMed1998

Why have group A streptococci remained susceptible to penicillin? Report on a symposium.

In spite of 50 years of extensive use of penicillin, group A streptococci remain exquisitely susceptible to this antibiotic. This observation that continuing susceptibility has occurred despite the development of resistance to other antimicrobial agents prompted a day-long meeting at Rockefeller University (New York) in October 1996. Among the most likely explanations for this remarkable state of continued susceptibility to penicillin are that beta-lactamase may not be expressed or may be toxic to the organism and/or that low-affinity penicillin-binding proteins either are not expressed or render organisms nonviable. Other potential explanations are that circumstances favorable for the development of resistance have not yet occurred and/or that there are inefficient mechanisms for or barriers to genetic transfer. Recommended future actions include (1) additional laboratory investigations of gene transfer, penicillin-binding proteins, virulence factors, and homeologous recombination and mismatch repair; (2) increased surveillance for the development of penicillin resistance; (3) application of bioinformatics to analyze streptococcal genome sequences; and (4) development of vaccines and novel antimicrobial agents. Thus far the susceptibility of group A streptococci to penicillin has not been a major clinical or epidemiological problem. A similar observation, however, could have been made decades ago about Streptococcus pneumoniae. It is therefore vital for the scientific community to closely examine why penicillin has remained uniformly highly active against group A streptococci in order to maintain this desirable state.

Humans↗
PubMed1998

Trends in cigarette smoking: the Minnesota Heart Survey, 1980 through 1992.

OBJECTIVES: The purpose of this study was to describe trends in the prevalence of cigarette smoking between 1980 through 1982 and 1990 through 1992 in Minneapolis and St. Paul, Minn. METHODS: Three population-based surveys were conducted among adults 25 to 74 years of age in 1980 through 1982, 1985 through 1987, and 1990 through 1992. RESULTS: Overall age-adjusted prevalences of cigarette smoking declined significantly between 1980-1982 and 1985-1987 and between 1985-1987 and 1990-1992. Serum thiocyanate, a biochemical marker for tobacco use, also declined significantly over the 3 periods. CONCLUSIONS: Favorable trends in smoking prevalence and cigarette consumption among smokers were observed, but disturbing trends in some smoking behaviors were also noted.

Adult↗
PubMed1997

Acrocephalosyndactyly syndromes: a review.

Over the last quarter century, a revision has taken place in the classification of the acrocephalosyndactyly syndromes. This reflects the advances in molecular biology that have led to improved genetic mapping of these syndromes. In this review we provide an overview of these major acrocephalosyndactyly syndromes, including the current classification system. The craniofacial, neurological, cardiac, pulmonary, visceral, and extremity anomalies are discussed with special emphasis on hand anomalies. Hand reconstruction techniques, including specific surgical procedures, the timing of the surgical reconstruction, and postoperative therapy are discussed. The need for coordinated care of the multidisciplinary disorders of these patients cannot be overemphasized, especially in the perioperative period.

Acrocephalosyndactylia↗
PubMed1997

Randomised trial of volume controlled versus time cycled, pressure limited ventilation in preterm infants with respiratory distress syndrome.

Fifty preterm infants weighing 1200 g or more with clinical and radiographic evidence of respiratory distress syndrome, requiring both mechanical ventilation and exogenous surfactant replacement, were randomly allocated to receive either volume controlled ventilation or time cycled, pressure limited ventilation. Tidal volume delivery in each group was deliberately controlled at 5-8 ml/kg so that the only difference between the two groups was the ventilatory modality, the manner in which tidal volume was delivered. The rest of the ventilatory management and clinical care was done according to protocol. The two modes of ventilation were compared by determining the time required to achieve pre-determined success criteria, based on either the alveolar-arterial oxygen gradient or the mean airway pressure as a standard against which the speed of weaning could be objectively assessed. Infants randomised to volume controlled ventilation met success criteria sooner and had a shorter duration of mechanical ventilation. These babies also had a significantly lower incidence of intraventricular haemorrhages and abnormal periventricular echodensities on ultrasound scans. Volume controlled ventilation seems to be both safe and effective in this group of patients.

Air Pressure↗
PubMed1996

A biomechanical analysis of the stability of titanium bone fixation systems in proximal phalangeal fractures.

Apex bending and torsional loading were utilized to study the effects of different plate design and thickness, and screw size and design on the rigidity and strength of seven different titanium mini- and microplates placed onto osteotomized proximal phalanges. One hundred forty-four fresh frozen human cadaveric proximal phalangeal bones underwent a mid shaft osteotomy followed by application of one of the following plates: (1) Synthes linear 1.5-mm five-hole plates, (2) Leibinger linear 1.2-mm five-hole or (3) 1.7-mm four-hole plates, or (4) Leibinger three-dimensional 1.2-mm four-hole, (5) 1.2-mm eight-hole, (6) 1.7-mm four-hole, or (7) 1.7-mm eight-hole plates. Three-point bending (apex dorsal or apex volar) and torsional loading were utilized for each plating configuration. Analysis of variance models of bone specimen width, depth, cortical thickness, and length revealed that increasing plate thickness was associated with increasing rigidity, but that the three-dimensional design yielded a higher relative rigidity except under apex volar loading.

Biomechanical Phenomena↗
PubMed1995

Lymphocyte G proteins reflect response to treatment in congestive heart failure.

Congestive heart failure is associated with chronotropic and inotropic hyporesponsiveness to adrenergic stimulation. A decrease in Gs alpha or an increase in Gi alpha is associated with a decrease in adenylyl cyclase activity. The current study assessed G proteins in response to treatment with direct-acting vasodilators and correlated changes in lymphocyte beta-adrenergic receptor components with changes in hemodynamic variables. Twenty-three patients with severe chronic congestive heart failure (New York Heart Association functional classes III and IV) were studied. Patients were grouped as responders (n = 10) or nonresponders (n = 13) on the basis of clinical assessment of functional status from questionnaires. Therapy was associated with an increase in cardiac index, a decrease in mean arterial pressure, and a decrease in systemic vascular resistance in all patients. Left ventricular filling pressure significantly decreased in responders (26 +/- 2 mm to 13 +/- 3 mm, p < 0.05) but did not change significantly in nonresponders. Similarly, mean right atrial pressure significantly decreased in responders (11 +/- 2 mm Hg to 4 +/- 1 mm Hg, p < 0.05) but did not change in nonresponders. Plasma norepinephrine increased significantly only in nonresponders (679 +/- 100 pg/ml to 1233 +/- 201 pg/ml, p < 0.05). Whereas lymphocyte beta-adrenergic receptor density and Gs did not significantly change, Gi increased after treatment only in the nonresponder group (23 +/- 5 to 51 +/- 11 fmol/mg, p < 0.05). A poor response to direct-acting vasodilators can be distinguished by reactive increases in plasma norepinephrine and lymphocyte Gi in the absence of a decrease in either left- or right-sided filling pressures.

Aged↗
PubMed1995

Mini and micro plating of phalangeal and metacarpal fractures: a biomechanical study.

Biomechanical testing was performed in a cadaver model to evaluate the effects of plate size and position on fracture stability using Leibinger mini and microplates applied on the proximal phalanx and metacarpal. Fresh frozen cadaveric metacarpal and proximal phalanges were subjected to a midshaft transverse osteotomy followed by application of titanium mini (1.7 mm screw diameter) and micro (1.2 mm screw diameter) plates/screws. For the metacarpal, a dorsal miniplate, a dorsal microplate, and bilateral microplates were used. For the proximal phalanx, similar plate configurations and sizes were used with the addition of a unilateral microplate. A three point bending model with both dorsal and palmar apex loading was used for all configurations. This study confirms that a dorsally applied miniplate provides the greatest rigidity to a dorsal apex load.

Biomechanical Phenomena↗