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Biomedical subjects

R McCoy

Publications and source records attributed to R McCoy.

At least 19 recordsLinked to original sources
PubMed2001

Morphological and physiological characteristics of urethral circular and longitudinal smooth muscle.

The urethral wall contains circular and longitudinal smooth muscle. Both layers can develop spontaneous tone, and contract further or relax in response to excitatory or inhibitory stimuli. In the pig the cells do not generate action potentials, and the membranes possess L-type calcium channels and a variety of potassium channels which may modulate the membrane potential and tone. The importance of these layers in generating the urethral pressure is not well understood in the human, but it seems likely that the circular smooth muscle is involved in generating urethral pressure in the pig.

Animals↗
PubMed2000

Studies of the pathophysiology of idiopathic detrusor instability: the physiological properties of the detrusor smooth muscle and its pattern of innervation.

PURPOSE: Idiopathic detrusor instability (IDI) is a common cause of lower urinary tract storage symptoms, such as urgency, frequency and urge incontinence. We have investigated the in vitro properties and pattern of innervation of the detrusor from patients with this condition. MATERIALS AND METHODS: Full thickness bladder specimens were obtained perioperatively from 14 patients with IDI and from 14 cadaveric controls undergoing transplant organ retrieval. Isolated detrusor smooth muscle strips were mounted in organ baths for isometric tension recording. Frequency-response curves to electrical field stimulation (EFS) (1 Hz to 50 Hz) and concentration response curves for carbachol (10(-7) M to 5 x 10(-4) M) and potassium (12 mM to 120 mM) were constructed. Acetylcholinesterase histochemistry and immunohistochemistry for both phosphorylated and non-phosphorylated neurofilaments was carried out on frozen sections of control and IDI bladders. RESULTS: IDI strips developed greater spontaneous tone (0.25 gm./mg. versus 0.12 gm./mg.; p <0.0001) and more spontaneous fused tetanic contractions (16.8% versus 6.8%; p <0.005) during an initial 90 minutes equilibration period. The IDI strips were less responsive than controls to nerve stimulation (max. response to EFS 0.79 gm./mg. versus 1.23 gm./mg.; p <0.0001) and were supersensitive to potassium (EC50 39.7 mM versus 45.7 mM; p = 0.003) but not to carbachol (EC50 7.3 x 10(-6) M versus 6.6 x 10(-6) M; p = 0.48). Morphometric studies revealed reduced staining of presumed cholinergic nerves, with 34.7% of IDI smooth muscle bundles appearing denervated compared with 1.5% of controls (p <0.0001). CONCLUSIONS: Our study supports the notion that there is a fundamental abnormality in IDI at the level of the bladder wall, with evidence of altered spontaneous contractile activity consistent with an increased electrical coupling of cells, a patchy denervation of the detrusor and a potassium supersensitivity.

Adult↗
PubMed2000

Structural and functional denervation of human detrusor after spinal cord injury.

The bladder receives an extensive nerve supply that is predominantly cholinergic, but several putative transmitters are present, some of which are colocalized. Previous studies have shown increased levels of sensory nerves, reduced inhibitory transmitters, and structural and functional changes in the excitatory input in unstable bladder conditions. The present study compared the end-organ nerve supply to the bladder in spinal cord injury (SCI) with uninjured controls. Acetylcholinesterase histochemistry and double-label immunofluorescence were used to investigate neurotransmitter content, with confocal laser scanning microscopy to assess colocalization. Organ bath studies provided functional correlates for the structural changes in the excitatory innervation. Control samples had dense innervation of the detrusor containing a diverse range of transmitters. Hyperreflexic SCI samples showed patchy denervation, and areflexic SCI samples were diffusely denervated. Vasoactive intestinal polypeptide-, neuropeptide Y-, neuronal nitric oxide synthase-, and galanin-immunoreactive nerve fibers were reduced from frequent or moderately frequent to infrequent or very infrequent in SCI. Calcitonin gene-related peptide-immunoreactive fibers were infrequent in controls and SCI samples. Patterns of colocalization were unchanged, but significantly fewer fibers expressed more than one transmitter. The subepithelial plexus was markedly reduced and several of the smaller coarse nerve trunks showed no immunoreactivity to the transmitters assessed. There was no reduction in sensitivity to electrical field stimulation of intrinsic nerves in SCI, but the maximum force generated by each milligram of bladder tissue and the peak force as a proportion of the maximum carbachol contraction were significantly reduced and the responses were protracted. There was no significant functional atropine-resistant neuromuscular transmission in controls or SCI. The reported findings have clinical implications in the management of chronic SCI and development of new treatments.

Adult↗
PubMed2000

Oxygen-conserving techniques and devices.

OCDs are available and their use is growing in the home care market because of economic factors associated with LTOT, but this trend has evolved with little clinical research. There is great variability among the oxygen control systems, and physicians need to test patients on each device, at each activity level the patient is capable of in the home, and to write a prescription for each activity level. OCDs should be used because of the patient benefits of improved activity and compliance with a 24-hour prescription, and the economic benefit associated with reduced delivery of oxygen. Clinicians and patients need to be thoroughly familiar with the oxygen system they are using and to understand its capabilities and limitations. More research is required to evaluate the application and effectiveness of and the differences between products and outcomes of OCDs used in home care. Equivalency between CFO and OCDs should not be necessary because of the differences between these delivery methods and the great variability of products.

Ambulatory Care↗
PubMed1999

alpha1-adrenoceptors in urethral function.

The external urethral sphincteric mechanism generates forces which seal the urethra and can be measured as urethral pressure. Resting pressure can be augmented transiently through a reflex pathway during increases in intra-abdominal pressure. The exact role of the various components of the urethral wall that generate this pressure is so far unknown. Urethral contributions to continence come from the mucosal hermetic seal, the submucosa and its vascular filling and the smooth and striated muscle. In humans alpha1-adrenoceptor antagonists can reduce urethral pressure, whereas agonists have little effect. A significant part of urethral resting tone is thought to be mediated through the smooth muscles. In vitro, longitudinal and circular smooth muscle components possess spontaneous tone and are innervated by excitatory and inhibitory nerves. Both types possess alpha1-adrenoceptors and contract on stimulation of intrinsic sympathetic nerves or application of alpha1-adrenoceptor agonists. In human urethra, longitudinal smooth muscle predominates but its functional role is unclear. alpha1 stimulation may also affect the vasculature of the submucosa, the striated muscle of the urethra or transmitter release from neurones in the control pathways. Insufficient knowledge of alpha1-adrenoceptor distribution and function within the urethra and the surrounding tissues currently prevents accurate prediction of the therapeutic potential of alpha1-adrenoceptor ligands.

Animals↗
PubMed1998

Fowl adenovirus recombinant expressing VP2 of infectious bursal disease virus induces protective immunity against bursal disease.

The right hand end Nde I fragment 3 (90.8-100 map units) of the fowl adenovirus serotype 10 (FAV-10) was characterised so as to allow the location of an insertion site for recombinant vector construction. Infectious bursal disease virus (IBDV) VP2 gene from the Australian classical strain 002/73, under the control of the FAV-10 major late promoter/leader sequence (MLP/LS) was inserted into a unique Not I site that was generated at 99.5 map units. This recombinant virus was produced without deletion of any portion of the FAV-10 genome. When administered to specific pathogen free (SPF) chickens intravenously, intraperitoneally, subcutaneously or intramuscularly, it was shown that the FAV-10/VP2 recombinant induced a serum VP2 antibody response and protected chickens against challenge with IBDV V877, an intermediate virulent classical strain. Birds were not protected when the recombinant was delivered via the conjunctival sac.

Animals↗
PubMed1997

Alarm bells. When to worry about your patient with HIV.

General practitioners with little or no clinical experience of HIV infection may not be prepared when they are suddenly required to treat an HIV infected person. However, a thorough history, examination and assessment will quickly reveal if there are any emergencies that require urgent attention and specialist referral.

CD4 Lymphocyte Count↗
PubMed1995

N-formylpeptide and complement C5a receptors are expressed in liver cells and mediate hepatic acute phase gene regulation.

Although the classical chemotactic receptor for complement anaphylatoxin C5a has been associated with polymorphonuclear and mononuclear phagocytes, several recent studies have indicated that this receptor is expressed on nonmyeloid cells including human endothelial cells, vascular smooth muscle cells, bronchial and alveolar epithelial cells, hepatocytes, and in the human hepatoma cell line HepG2. In this study, we examined the possibility that other members of the chemotactic receptor family are expressed in HepG2 cells and human liver, and the possibility that such receptors mediate changes in acute phase gene expression in HepG2 cells. Using polymerase chain reaction (PCR) amplification of HepG2 mRNA with primers based on highly conserved regions of the chemotactic subgroup of the G protein-coupled receptor family, we identified a PCR fragment from the formyl-methionyl-leucyl-phenylalanine (FMLP) receptor, as well as one from the C5a receptor. Immunostaining with antipeptide antisera to FMLPR confirmed the presence of this receptor in HepG2 cells. Receptor binding studies showed specific saturable binding of a radioiodinated FMLP analogue to HepG2 cells (Kd approximately 2.47 nM; R approximately 6 x 10(3) plasma membrane receptors per cell). In situ hybridization analysis showed the presence of FMLPR mRNA in parenchymal cells of the human liver in vivo. Both C5a and FMLP mediated concentration- and time-dependent changes in synthesis of acute phase proteins in HepG2 cells including increases in complement C3, factor B, and alpha 1-antichymotrypsin, as well as concomitant decreases in albumin and transferrin synthesis. The effects of C5a and FMLP on the synthesis of these acute phase proteins was evident at concentrations as low as 1 nM, and they were specifically blocked by antipeptide antisera for the corresponding receptor. In contrast to the effect of other mediators of hepatic acute phase gene regulation, such as interleukin 6, the effects of C5a and FMLP were reversed by increased concentrations well above the saturation point of the respective receptor. These results suggest that acute phase gene regulation by C5a and FMLP is desensitized at high concentrations, a property that is unique among the several known mechanisms for hepatic acute phase gene regulation.

Acute-Phase Proteins↗
PubMed1993

Nontuberculous mycobacterial infections in continuous ambulatory peritoneal dialysis patients.

Nontuberculous mycobacterial infections are a rare but clinically important cause of infections in continuous ambulatory peritoneal dialysis (CAPD) patients. We describe seven cases of catheter-related nontuberculous mycobacterial infections associated with CAPD. Six patients had Mycobacterium fortuitum infections and one had a Mycobacterium kansasii infection. Three patients presented with peritonitis, three presented with exit site infections, and one developed an infection at the exit site after catheter removal. There were no specific clinical findings that differentiated these infections from those caused by common bacterial pathogens. Initial routine peritoneal dialysis fluid and exit site cultures were negative in two patients and grew M fortuitum in four patients and M kansasii in one patient. M fortuitum and M kansasii were sensitive to amikacin, and M fortuitum was sensitive to ciprofloxacin when tested. Sensitivities to other antibiotics were variable. All patients were treated with a combination of antibiotics from 3 weeks to 6 months. Catheter removal was necessary for cure of the infection in all patients with peritonitis and in a majority of patients with exit site infections. The majority of patients changed to hemodialysis after catheter removal. Two patients remained on CAPD, with follow-up ranging from 2 months to 4 years. One patient has received a successful renal transplant. In conclusion, M fortuitum is the most common nontuberculous mycobacterial catheter-related infection in CAPD patients. Nontuberculous mycobacterial infections should be considered in the differential diagnosis of any culture-negative infection associated with CAPD. In patients with infections secondary to M fortuitum, our findings suggest that amikacin and ciprofloxacin are the initial antibiotics of choice until antibiotic sensitivities are available.

Aged↗
PubMed1992

A DNase I-hypersensitive site in the second intron of the murine IL-4 gene defines a mast cell-specific enhancer.

IL-4 is a potent immunoregulatory cytokine that exhibits extremely diverse effects on a number of target cells. Although IL-4 was originally described as a T cell-derived product, it is evident that cells of the basophil/mast cell lineage are also an important source of this cytokine. Based on their different tissue distribution, mast cell and T cell-derived IL-4 may have distinct effects on local immune responses. The physiologic production of IL-4 appears to be tightly regulated because most T and mast cells require activation to express significant levels of IL-4. In contrast, a majority of murine transformed mast cell lines constitutively express relatively high levels of IL-4. In this study, transformed mast cell lines were used as models to define cis acting sequences that regulate mast cell IL-4 transcription. Chloramphenicol acetyltransferase reporter gene constructs containing 6.3 kb of 5' IL-4 flanking sequence direct relatively low chloramphenicol acetyltransferase expression in these cells. These results indicated that additional sequences may be important in stimulating transcriptional activity of the IL-4 gene. Using DNAse I hypersensitive site analysis to define other potential IL-4 transcriptional regulatory regions, two sites were identified in the murine IL-4 gene that appear to be unique to IL-4 expressing transformed mast cells. One site defines an intronic sequence that exhibits prototypic enhancer activity in several independently derived transformed mast cell lines. This enhancer is also active in stimulated, non-transformed mast cells but not stimulated EL-4 T cells. Taken together, these data indicate that the IL-4 intronic sequence contains a mast cell specific enhancer that plays an essential role in the unregulated expression of IL-4 in transformed mast cells and may also be important in the inducible expression of IL-4 in normal mast cells.

Animals↗
PubMed1992

Consistent transcription of the Epstein-Barr virus LMP2 gene in nasopharyngeal carcinoma.

Two species of the Epstein-Barr virus-encoded latent membrane protein 2, LMP2A and LMP2B, are generated by alternative splicing, each species having a distinct first exon. LMP2 transcription in undifferentiated nasopharyngeal carcinoma (NPC), which is consistently associated with the Epstein-Barr virus, was investigated. Fifteen NPC specimens were analyzed by Northern (RNA) blot and RNA-based polymerase chain reaction; the LMP2A transcript was present in all specimens except one. In some specimens the LMP2B transcript was also detected. Sequence analysis of LMP2 cDNAs obtained from two NPC specimens revealed four mutations in exon 1 of the LMP2A transcript, which were present in both tumors and which resulted in nonconservative amino acid changes. These data suggest that the LMP2 expressed in NPC is distinct from that which is expressed in lymphoid cells.

Amino Acid Sequence↗
PubMed1992

Alterations of the p53 gene in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignancy which is consistently associated with the Epstein-Barr virus (EBV). The structure of the EBV genome in NPC suggests that NPC is a clonal proliferation of epithelial cells which emerges after EBV infection. The disease develops with high incidence in specific populations in discrete geographic locations, implicating possible genetic or environmental cofactors. Mutations of the p53 gene are among the most frequent genetic changes found in a large variety of human tumors. Mutations in p53 have been shown to abrogate the suppressor function of wild-type p53 and thus contribute to the transformed phenotype. To determine if mutation in p53 participates in the development of the malignant clone in NPC, the structure and sequence of p53 in 42 primary, metastatic, and nude mouse-passaged NPC specimens was analyzed. A high frequency (6 of 9) of mutations was detected in the nude mouse-passaged tumors, while only 2 of 15 metastatic and 0 of the 18 primary tumors harbored mutant p53. The p53 mutations included single-point mutations and more extensive changes such as frame shifts, deletion, duplication, or complete loss of coding sequences. These data indicate that alterations of the p53 gene are unlikely to be involved in the initial genetic events leading to the clonal outgrowth in NPC. However, although it is a rare NPC which can be established in nude mice, this growth advantage appears to be conferred on tumors bearing a mutant p53.

Animals↗
PubMed1991

Fuel loads in U.S. cities.

Sources of burnable material within U.S. cities are analyzed. Based on a detailed evaluation of construction practices, storage of burnable contents, building function and layout, and density of buildings in city districts, we derive urban fuel load densities in terms of land use type and geographic location. Residential building fuel loads vary regionally from 123 to 150 kg m-2; nonresidential building classes have loads from 39 to 273 kg m-2. The results indicate that average U.S. urban area fuel loads range from 14 to 21 kg m-2.

Construction Materials↗