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Biomedical subjects

S Baker

Publications and source records attributed to S Baker.

At least 73 records · Page 4Linked to original sources

Heparinase III limits rat arterial smooth muscle cell proliferation in vitro and in vivo.

Heparinase III degrades heparan sulfate proteoglycans, which are co-receptors for growth factors that stimulate arterial proliferation. We assessed the ability of locally-delivered heparinase III to limit medial vascular smooth muscle cell proliferation induced by balloon catheter injury in rat carotid arteries. Whereas vehicle-treated arteries showed 12% of smooth muscle cells proliferating after 2 days, heparinase III (0.022-5.7 mg/kg) treated arteries showed 0.8-4%. Chemically-inactivated heparinase III did not limit proliferation. In isolated rat A10 vascular smooth muscle cells, heparinase III (1 IU/ml) inhibited both PDGF-BB and bFGF mediated increases in proliferation and migration. These results suggest that heparinase III can limit proliferation by affecting heparan sulfate proteoglycan binding growth factors following arterial injury.

Animals↗

The signal averaged P wave in atrioventricular block--evidence for abnormal atrial conduction?

The incidence of atrial fibrillation in patients with atrioventricular block (AVB) appears increased over that for the unpaced population even if atrioventricular synchrony is maintained by dual chamber pacing. To assess whether atrial fibrillation in these patients might be due to concurrent abnormality in atrial activation we performed signal averaged P wave (SAPW) recordings in 15 patients with dual chamber pacemakers implanted for AVB and compared the results to those from 21 unpaced controls. The median (range) age was 69 (53-89) years for patients and 60 (51-78) years for controls. Eleven patients and 12 controls were male. All patients were pacing in VDD mode at the time of study. SAPW recordings were obtained using our previously reported selective P wave averaging system. We measured P wave duration after high pass filtering at 40 Hz, the rate of change of P wave voltage over time (spatial velocity) and low and high frequency spectral energy after Fourier transformation of the P wave signal. We found increased P wave duration, mean spatial velocity and lower frequency energy in patients with AVB compared to controls [duration, 144 (5) vs. 134 (2) ms, p<0.05; mean spatial velocity, 5.6 (0.4) vs. 4.6 (0.1) mV/s, p<0.05; energy 20-150 Hz, 57.4 (8.2) vs. 36.3 (2.8) muV2.s, p<0.01. All values mean (SEM)]. These results suggest that the increased incidence of atrial fibrillation in patients paced for AVB may be related to intrinsic abnormalities of atrial activation and not solely to the pacing mode. Ensuring sequential atrioventricular pacing in these patients may not completely abolish the increased incidence of atrial fibrillation.

Aged↗

Effects of human lymphocyte-conditioned medium on MG-63 human osteosarcoma cell function.

Lymphocytes are implicated in the pathogenesis of bone disease in chronic inflammation, osteoporosis, transplantation and osteopetrosis. The effects of lymphocytes and lymphocyte-conditioned medium on bone-resorbing activity and osteoclast function have been well studied, but there are few studies of the effects of LCM on bone formation and osteoblast function. The effects of LCM on the function of the MG-63 human osteosarcoma cell line were studied, which, when stimulated with 1,25-(OH)2D3, demonstrates many of the properties of the mature human osteoblast. Lymphocytes contain oestrogen receptors and the model was also used to test the hypothesis that the effects of oestrogen on bone cells may be mediated indirectly via lymphokines. Lymphokines were measured by ELISA in human lymphocyte conditioned medium (LCM) collected following incubation of mixed lymphocytes with or without stimulation for 72 h. Unstimulated LCM increased proliferation of MG-63 cells and this increase was not affected by neutralization of interleukin 1 (IL-1), IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF), lymphotoxin alpha, or interferon gamma (IFN-gamma). Phytohaemagglutinin-stimulated LCM decreased proliferation of MG-63 cells, as well as induced expression of IL-6 mRNA, increased alkaline phosphatase production, and inhibited osteocalcin production. The decrease in proliferation was abolished by neutralization of IFN-gamma but was unaffected by neutralization of IL-1, IL-2, IL-3, IL-4, IL-6, GM-CSF, TNF, or lymphotoxin alpha. Neutralization of IFN-gamma in stimulated LCM also partially inhibited the increase in alkaline phosphatase production but had no effects on the decrease in osteocalcin production. Although oestrogen inhibited lymphocyte proliferation, the effects of LCM collected from lymphocytes in the presence of oestrogen on MG-63 cell proliferation and function was no different than the effects of LCM collected in the absence of oestrogen. LCM has multiple effects on MG-63 cell function and gene expression. Lymphocyte stimulation during the preparation of LCM further modulates these effects. Although partially mediated by IFN-gamma, the effects of LCM on these cells cannot be completely explained by individual component lymphokines. This may have implications for understanding the pathophysiology of bone loss in inflammatory disorders as well as possible feedback loops of locally generated cytokines in bone.

Culture Media, Conditioned↗

The use of neuromuscular blocking agents in the emergency department to facilitate tracheal intubation in the trauma patient: help or hindrance?

PURPOSE: The purpose of this study is to examine the relationship between the occurrence of a difficult intubation and (1) the use of neuromuscular blocking agents (NMB) and (2) the presence of airway injuries. It is a retrospective analysis of data from a trauma registry. MATERIALS AND METHODS: Registry records of patients (n = 160) who required emergent endotracheal intubation or establishment of a surgical airway over a 3.5-year period in the emergency department were reviewed. Risk factors for difficult intubations were identified and analyzed using multivariate logistic regression analysis. RESULTS: NMB were used in 75% of patients requiring intubation. Fifteen percent of the intubations were considered difficult. No association was found between the presence of airway injuries and difficult intubations; however, the use of succinylcholine was associated with a lower risk of difficult intubations compared with intubations where a nondepolarizing NMB was used. CONCLUSIONS: The use of succinylcholine may result in fewer difficult intubations in the trauma patient than when a nondepolarizing NMB is used. The presence of airway injuries did not appear to predispose to difficult intubations.

Adult↗

Isolation and characterization of two proteins from Moraxella catarrhalis that bear a common epitope.

The UspA1 and UspA2 proteins of Moraxella catarrhalis are potential vaccine candidates for preventing disease caused by this organism. We have characterized both proteins and evaluated their vaccine potential using both in vitro and in vivo assays. Both proteins were purified from the O35E isolate by Triton X-100 extraction, followed by ion-exchange and hydroxyapatite chromatography. Analysis of the sequences of internal peptides, prepared by enzymatic and chemical cleavage of the proteins, revealed that UspA1 and UspA2 exhibited distinct structural differences but shared a common sequence including an epitope recognized by the monoclonal antibody 17C7. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), purified UspA1 exhibited a molecular weight of approximately 350, 000 when unheated and a molecular weight of 100,000 after being heated for 10 min at 100 degreesC. In contrast, purified UspA2 exhibited an apparent molecular weight of 240,000 by SDS-PAGE that did not change with the length of time of heating. Their sizes as determined by gel filtration were 1,150,000 and 830,000 for UspA1 and UspA2, respectively. Preliminary results indicate the proteins have separate functions in bacterial pathogenesis. Purified UspA1 was found to bind HEp-2 cells, and sera against UspA1, but not against UspA2, blocked binding of the O35E isolate to the HEp-2 cells. UspA1 also bound fibronectin and appears to have a role in bacterial attachment. Purified UspA2, however, did not bind fibronectin but had an affinity for vitronectin. Both proteins elicited bactericidal antibodies in mice to homologous and heterologous disease isolates. Finally, mice immunized with each of the proteins, followed by pulmonary challenge with either the homologous or a heterologous isolate, cleared the bacteria more rapidly than mock-immunized mice. These results suggest that UspA1 and UspA2 serve different virulence functions and that both are promising vaccine candidates.

Amino Acid Sequence↗

Caregiver characteristics and types of assistance provided by caregivers to minority women living with HIV/AIDS.

The incidence of HIV/AIDS has escalated among African American and Hispanic women in the United States and particularly in urban centers such as New York City. As a chronic illness, it is important to understand to whom minority women living with HIV/AIDS turn to for assistance and support. The purpose of this exploratory qualitative study was to identify the characteristics of informal caregivers and the types of assistance that they provide to minority women living with the HIV virus. Thirty one caregivers were interviewed using semi-structured and opened ended questions. Data analyses included the constant comparative method consistent with the grounded theory approach. A topology of two caregiver groups were identified, male companions and relative/girlfriend caregivers. Caregiving activities are described within each group in the areas of emotional support, child care, personal advisement, social welfare and financial assistance. Implications for practice and recommendations for further study are discussed.

Acquired Immunodeficiency Syndrome↗

Gossypol modification of Ala-1 of secreted phospholipase A2: a probe for the kinetic effects of sulfate glycoconjugates.

Gossypol is shown to covalently modify secreted phospholipase A2 (PLA2) in the aqueous phase, but not at the interface. A rapid initial noncovalent binding of gossypol is followed by a slow covalent modification of the alpha-amino group of Ala-1 by stoichiometric amounts of gossypol. The rate of modification increases in the presence of calcium, but occupancy of the substrate binding site does not alter the rate. Pancreatic PLA2 is modified at the alpha-amino group of the N terminus to form a Schiff base, which can be stabilized by reduction with borohydride. Residual activity of the gossypol-modified PLA2 from several different sources is about 10%, indicative of impaired catalytic turnover. The half-time for the inactivation is about 10 min, and it is more than 100-fold longer for PLA2 at the interface. Gossypol promotes binding of PLA2 to the interface, and the binding of PLA2 to the interface promotes only the noncovalent binding of gossypol, but not the covalent modification. Gossypol, in conjunction with spectroscopic and kinetic protocols, is used to characterize the kinetic effects of sulfated glycoconjugates, heparin and artery wall proteoglycans, with human inflammatory and pancreatic PLA2.1 The conjugates do not interfere with the binding of PLA2 to the interface or with the catalytic cycle at the interface. The conjugates do not influence the kinetics of modification of PLA2 by gossypol in the aqueous phase, and the enzyme at the interface is not modified in the presence of the conjugates. The conjugates bind to PLA2 at the interface with only a modest effect on the interfacial catalytic turnover without dislodging the bound enzyme. Complex kinetic effects induced by the conjugates are shown to be due to sequestration of PLA2 in the aqueous phase as a high-molecular mass complex, which dissociates with added NaCl.

Alanine↗

Role of substance P in several models of bladder inflammation.

Substance P (SP) is a peptide found in the sensory nervous system which has multiple biologic effects including stimulation of muscle contraction, pain nociception, immune cell functions, plasma extravasation and a constellation of inflammatory effects. Here we investigate the role of SP in several animals models of bladder inflammation. Using the female Lewis rat, inflammation was induced using either xylene, lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (polyIC). Inflammation occurred rapidly (4 h) and was maintained in each model for at least 7 days. Each of these protocols decreased the bladder content of immunoreactive SP by approximately 50%, suggesting enhanced release. There was no change in the urinary frequency of these animals over 3 weeks, suggesting that urinary frequency changes are not mediated by acute inflammation. We also found that the SP receptor (NK1) antagonist, (-)CP96345, was unable to block the inflammation produced by polyIC, suggesting that SP is not an obligatory mediator of immune cell stimulation in this model.

Animals↗

Inflammatory markers in chronic hepatitis C.

To test the hypothesis that inflammation in hepatitis C follows mechanisms common to immune-activated pathways, the distributions of T and B cells, adhesion molecules and transforming growth factor-beta (TGF-beta) were assessed in liver biopsies with chronic inflammation due to hepatitis C (HCV, n = 8) and other causes (non-HCV, n = 10). Frozen sections were immunostained using primary antibodies to CD2, CD20, CD4, CD8, intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM)-1, HLA-DR, lymphocyte function-associated antigen (LFA)-1, and TGF-beta. Inflammatory cells positive for each immunophenotypic marker were counted, and positive staining for adhesion molecules, HLA-DR and TGF beta was graded in triads and lobules and compared in HCV and non-HCV biopsies. In all biopsies, T cells were more frequent than B cells, both in triads and lobules. CD20+, CD4+, CD8+ and LFA-1+ cells were increased in HCV compared to non-HCV biopsies. Portal lymphoid aggregates were present in 6 of 8 HCV biopsies and 3 of 10 non-HCV biopsies. Aggregates consisted of CD20+, CD4+, CD8+ and LFA-1+ cells, and ICAM-1 and VCAM-1 were increased. Sinusoidal lining cells in HCV biopsies and non-HCV biopsies with inflammation expressed HLA-DR, ICAM-1, and CD4. TGF-beta was increased in foci of necrosis. Inflammation in chronic HCV involves common immune-mediated cellular effector pathways and the inflammation in the portal triads represents aggregation of both T and B cells, mediated in part by upregulation of adhesion molecules on portal stromal cells; this is possibly in response to antigens draining from necroinflammatory foci in the lobules. TGF-beta is increased in active necroinflammatory foci, but not in portal lymphoid aggregates.

Adult↗

Frequency and distribution of DNA fragmentation as a marker of cell death in chronic liver diseases.

To study the early stages of cell death in various types of chronic liver injury, liver biopsies from a total of 26 patients, including 7 with chronic hepatitis C(CHC), 4 with chronic hepatitis B(CHB), 7 with alcoholic liver disease (ALD), 4 with autoimmune or drug hepatitis (AI/DH), and 4 with primary biliary cirrhosis(PBC), were examined by an in situ nucleotidyl transferase assay (ISNTA), which detects DNA fragmentation. Positive nuclei in hepatocytes and sinusoidal lining cells were counted in all parenchymal areas, excluding triads and areas of fibrosis, using a computer with Sigmascan software. The number of positive hepatocytes/mm2 was similar in the biopsies of patients with CHC, CHB, ALD and AI/DH, but significantly lower in PBC. The number of positive sinusoidal lining cells/mm2 was significantly greater in biopsies with CHC compared to CHB, ALD, AI/DH and PBC. Double staining revealed that the ISNTA-positive sinusoidal lining cells were also CD68 positive, indicating that they were Kupffer cells. The frequency of ISNTA positivity did not correlate with serum AST or ALT levels, steatosis, cell swelling or cirrhosis. ISNTA-positive hepatocytes were more frequent than acidophilic bodies in every disease category. We conclude that apoptosis may be a common pathway of cell death in different liver diseases, that the high frequency of DNA fragmentation in Kupffer cells in CHC suggests that during chronic hepatitis C infection activated Kupffer cells may be subject to regulatory control by apoptosis and that ISNTA is more sensitive than acidophilic bodies in assessing the degree of cell injury in the liver.

Adult↗

A comparison of duplex scanning and continuous wave Doppler in the assessment of primary and uncomplicated varicose veins.

OBJECTIVES: To compare the findings of continuous wave Doppler (CWD) with duplex ultrasound in the assessment of primary and uncomplicated varicose veins, and to determine how their relative roles might be best applied. MATERIALS AND METHODS: One hundred consecutive limbs were studied in 73 patients with primary (no previous surgery) and uncomplicated (no significant skin change) varicose veins. CWD was employed by a single observer; followed by duplex scanning performed "blind" and independently. RESULTS: There were 87 limbs with long saphenous incompetence on duplex; all but four of which were correctly identified by CWD, by which technique there were no false positives. (Sensitivity 95%, specificity 100%.) There were 21 limbs with short saphenous incompetence on duplex, all but two of which were recognised on CWD. However, CWD incorrectly diagnosed reflux at the saphenopopliteal junction in five limbs (false positives) with what was, in fact, segmental reflux in the long saphenous trunk on duplex (sensitivity 90%, specificity 93%.) This would have led to inappropriate exploration of the saphenopopliteal junction had surgery proceeded without checking with duplex. CONCLUSIONS: CWD is adequate for long saphenous incompetence. All "reflux" demonstrated on CWD in the popliteal fossa (about 25% of cases) should be checked by duplex. If this policy had been followed, all the patients in this study would have undergone the correct procedure. The only "errors" would have been missing coexistent short saphenous incompetence in two limbs undergoing appropriate long saphenous exploration.

Female↗

Recurrent synovial chondromatosis treated with meniscectomy and synovectomy.

Synovial chondromatosis is a rare benign intraarticular metaplasia of synovium. This process may result in the production of detached particles of highly cellular cartilage in the involved joint spaces. It is most often reported in the larger joints of the body including the knee, hip, elbow, and ankle. Since Axhausen in 1993 reported the first case affecting the temporomandibular joint, several articles have been listed in the literature regarding the presentation, diagnosis, and management of this form of an arthropathy. This is a case of a recurrent synovial chondromatosis that was approached with a meniscectomy and a complete synovectomy.

Arthroscopy↗

Formation and development of the Aromatherapy Organisations Council.

Aromatherapy is increasingly used alongside orthodox medicine in hospitals and via GP referral. However, doctors and other health professionals are concerned about training standards, codes of conduct, and standards of practice. These concerns were the focus of a Working Party established in 1990 to promote a single body for the practice of aromatherapy. Today the range of training courses available may seem confusing and this is compounded by aromatherapy massage courses run by many further education colleges under the health and beauty umbrella, which claim to offer recognized qualifications in aromatherapy. So what is a 'qualified aromatherapist'? What are the recognized training standards for the profession? Which professional associations are recognized? Is there a self-regulating and governing body for aromatherapy and what is its remit? What is happening on the European front? This paper describes the role and remit of the Aromatherapy Organisations Council (AOC) who are committed towards identifying unified training standards and maintaining a register of training establishments.

Aromatherapy↗

Clostridium difficile-associated diarrhea: epidemiology, risk factors, and infection control.

OBJECTIVES: To evaluate the effectiveness of specific infection control measures on the incidence of Clostridium difficile-associated diarrhea (CDAD) and to identify risk factors for its development. SETTING: 370-bed, tertiary-care teaching hospital with approximately 12,000 to 15,000 admissions per year. METHODS: Several infection control measures were implemented in 1991 and 1992, and the attack rates of CDAD were calculated quarterly. Antibiotic use for 1988 through 1993 was analyzed. A case-control study was conducted from January 1992 to December 1992 to identify risk factors for acquisition of CDAD. RESULTS: From 1989 to 1992, the attack rate of CDAD increased from 0.49% to 2.25%. An increase in antibiotic use preceded the rise in the incidence of CDAD in 1991. Despite implementation of various infection control measures, the attack rate decreased to 1.32% in 1993, but did not return to baseline. Ninety-two cases and 78 controls (patients with diarrhea but with negative toxin assay) were studied. By univariate analysis, history of prior respiratory tract infections (odds ratio [OR], 3.6; 95% confidence interval [CI95], 1.2-10.4), the number of antibiotics, and the duration of exposure to second-generation cephalosporins (OR, 3.55; CI95, 1.47-9.41) and to ciprofloxacin (OR, 7.27; CI95, 1.13-166.0) were related significantly to the development of CDAD. By stepwise logistic regression analysis, only exposure to antibiotics and prior respiratory tract infections (P = .0001 and .0203, respectively) were found to be significant. CONCLUSION: Antibiotic pressure might have contributed to failure of infection control measures to reduce the incidence of CDAD to baseline.

Analysis of Variance↗