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Biomedical subjects

B McMahon

Publications and source records attributed to B McMahon.

At least 19 recordsLinked to original sources

Lipoxin A4 antagonizes the mitogenic effects of leukotriene D4 in human renal mesangial cells. Differential activation of MAP kinases through distinct receptors.

The lipoxygenase-derived eicosanoids leukotrienes and lipoxins are well defined regulators of hemeodynamics and leukocyte recruitment in inflammatory conditions. Here, we describe a novel bioaction of lipoxin A(4) (LXA(4)), namely inhibition of leukotriene D(4) (LTD(4))-induced human renal mesangial cell proliferation, and investigate the signal transduction mechanisms involved. LXA(4) blocked LTD(4)-stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity in parallel to inhibition of LTD(4)-induced mesangial cell proliferation. Screening of a human mesangial cell cDNA library revealed expression of the recently described cys-leukotriene(1)/LTD(4) receptor. LTD(4)-induced mesangial cell proliferation required both extracellular-related signal regulated kinase (erk) and PI 3-kinase activation and may involve platelet-derived growth factor receptor transactivation. LTD(4)-stimulated the MAP kinases erk and p38 via a pertussis toxin (PTX)-sensitive pathway dependent on PI 3-kinase and protein kinase C activation. On screening a cDNA library, mesangial cells were found to express the previously described LXA(4) receptor. In contrast to LTD(4), LXA(4) showed differential activation of erk and p38. LXA(4) activation of erk was insensitive to PTX and PI 3-kinase inhibition, whereas LXA(4) activation of p38 was sensitive to PTX and could be blocked by the LTD(4) receptor antagonist SKF 104353. These data suggest that LXA(4) stimulation of the MAP kinase superfamily involves two distinct receptors: one shared with LTD(4) and coupled to a PTX-sensitive G protein (G(i)) and a second coupled via an alternative G protein, such as G(q) or G(12), to erk activation. These data expand on the spectrum of LXA(4) bioactions within an inflammatory milieu.

Base Sequence↗

Sodium pentobarbital reduces transmural dispersion of repolarization and prevents torsades de Pointes in models of acquired and congenital long QT syndrome.

INTRODUCTION: Sodium pentobarbital is widely used for anesthesia in experimental studies as well as in clinics, and it is known to prevent the development of torsades de pointes (TdP) in in vivo models of the long QT syndrome (LQTS). METHODS AND RESULTS: This study examines the effects of pentobarbital on transmural dispersion of repolarization (TDR) and induction of TdP in arterially perfused canine left ventricular wedge preparations in which transmembrane action potentials were simultaneously recorded from epicardial, M, and endocardial regions using floating glass microelectrodes together with a transmural ECG. d-Sotalol and ATX-II were used to mimic the LQT2 and LQT3 forms of congenital LQTS. Both d-sotalol (100 micromol/L, n = 6) and ATX-II (20 nmol/L, n = 6) preferentially prolonged the action potential duration (APD90) of the M cell, thus increasing in the QT interval and TDR, and leading to the development of spontaneous and stimulation-induced TdP. In the absence and presence of d-sotalol, pentobarbital (10, 20, and 50 microg/mL) prolonged the APD90 of epicardial and endocardial cells, and, to a lesser extent, that of the M cell, thus prolonging the QT interval but reducing TDR. In the ATX-II model, the effects of pentobarbital on the QT interval and APD90 were biphasic: 10 microg/mL pentobarbital further prolonged APD90 of epicardial and endocardial cells more than that of the M cell; 20 to 50 microg/mL pentobarbital abbreviated the APD90 of epicardial and endocardial cells less than that of the M cell, thus abbreviating the QT interval and markedly reducing TDR. Twenty to 50 microg/mL pentobarbital totally suppressed spontaneous as well as stimulation-induced TdP in both models CONCLUSION: Our data indicate that pentobarbital reduces TDR in control and under conditions of congenital and acquired LQTS, and suggest that this mechanism may contribute to the ability of the anesthetic to prevent the development of spontaneous as well as stimulation-induced TdP under conditions mimicking LQT2, LQT3, and acquired (drug-induced) forms of the LQTS. The data also serve to illustrate that there are circumstances under which QT prolongation may not be arrhythmogenic.

Action Potentials↗

Immune responses of prematurely born infants to hepatitis B vaccination: results through three years of age.

BACKGROUND: Hepatitis B vaccine is effective in infants. Preterm infants also respond but information on long term immunogenicity is limited. PURPOSE OF STUDY: To compare response of premature and full term infants to hepatitis B vaccine. METHODS: Sixty-nine prematurely born Alaska Native infants received three doses of hepatitis B vaccine beginning at discharge. Thirty-seven infants had paired serum samples drawn at approximately 1 and 3 years of life which were tested for antibody to hepatitis B surface antigen. One hundred eight infants born at full term enrolled in a separate study were used for comparison. RESULTS: Both early and late blood sample antibody to hepatitis B surface antigen titers were lower in preterm than in term infants (23.1 mIU/ml vs. 56.8 mIU/ml, early blood sample; and 0.7 mIU/ml vs. 1.32 mIU/ml, late blood sample); however, these values were not statistically different. The drop in titer over time, however, was significant in both groups as was the decrease in the percent of infants with titers > or = 10 mIU/ml (preterm infants 75.7% early specimen and 8.1% late specimen compared with term infants 87% early specimen and 15% late specimen). Both prematurity and longer interval between third vaccination and blood sample were associated with a decreased antibody titer. No infant had evidence of hepatitis B viral infection by developing antibody to hepatitis B core antigen. CONCLUSIONS: Preterm and term infants have a similar decline in antibody titers during the first 3 years, but preterm infants generally have a lower titer. The immunogenicity of the vaccine beyond 3 years and the need for revaccination in these populations requires further study.

Child, Preschool↗

Immunogenicity of a combined hepatitis B and Haemophilus influenzae type b conjugate vaccine in Alaska Native infants.

UNLABELLED: Hepatitis B and Haemophilus influenzae b (Hib), prevalent diseases in Alaska Native infants, have been reduced 95% following universal vaccination. Therefore, we were interested in studying a new combined Hib and hepatitis B vaccine in this population. METHOD: Healthy Alaska Native infants free from Hib and hepatitis B exposure were randomized into four groups, three with different lots of bivalent Hib and hepatitis B vaccine, and one with Hib and hepatitis B monovalent controls. The Hib component had 7.5 micrograms of polyribosylribitol phosphate polysaccharide (PRP) bound to 125 micrograms of Neisseria meningitidis outer membrane protein complex (OMP); the hepatitis B component was 5 micrograms of recombinant hepatitis B surface antigen. The vaccines were given at 2 months, 4 months, and 12-15 months of age. RESULTS: There were no differences in the responses to the bivalent compared to the monovalent controls except for a lower Hib anti-PRP level at 12-15 months in the bivalent recipients; this did not persist after the booster. CONCLUSION: A combined Hib and hepatitis B vaccine appears immunogenic. The recommended schedule for the Hib component (PRP-OMP) of 2 months, 4 months, and 12-15 months appears to promote an optimal response to the hepatitis B component as well.

Alaska↗

Psychotherapy and the search for meaning.

Since the work of Sigmund Freud, psychotherapy has been used to uncover the unconscious processes that affect the conscious state. As this article describes, psychotherapy sessions can be liberating for clients, but they can also be extremely painful and moving for both client and therapist.

Adult↗

Elect within.

Explore the source record for details and available documents.

Conflict, Psychological↗

Mind games.

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Civil Rights↗

Ligand binding to heme proteins. VI. Interconversion of taxonomic substates in carbonmonoxymyoglobin.

The kinetic properties of the three taxonomic A substates of sperm whale carbonmonoxy myoglobin in 75% glycerol/buffer are studied by flash photolysis with monitoring in the infrared stretch bands of bound CO at nu(A0) approximately 1967 cm-1, nu(A1) approximately 1947 cm-1, and nu(A3) approximately 1929 cm-1 between 60 and 300 K. Below 160 K the photodissociated CO rebinds from the heme pocket, no interconversion among the A substates is observed, and rebinding in each A substate is nonexponential in time and described by a different temperature-independent distribution of enthalpy barriers with a different preexponential. Measurements in the electronic bands, e.g., the Soret, contain contributions of all three A substates and can, therefore, be only approximately modeled with a single enthalpy distribution and a single preexponential. The bond formation step at the heme is fastest for the A0 substate, intermediate for the A1 substate, and slowest for A3. Rebinding between 200 and 300 K displays several processes, including geminate rebinding, rebinding after ligand escape to the solvent, and interconversion among the A substates. Different kinetics are measured in each of the A bands for times shorter than the characteristic time of fluctuations among the A substates. At longer times, fluctuational averaging yields the same kinetics in all three A substates. The interconversion rates between A1 and A3 are determined from the time when the scaled kinetic traces of the two substates merge. Fluctuations between A1 and A3 are much faster than those between A0 and either A1 or A3, so A1 and A3 appear as one kinetic species in the exchange with A0. The maximum-entropy method is used to extract the distribution of rate coefficients for the interconversion process A0 <--> A1 + A3 from the flash photolysis data. The temperature dependencies of the A substate interconversion processes are fitted with a non-Arrhenius expression similar to that used to describe relaxation processes in glasses. At 300 K the interconversion time for A0 <--> A1 + A3 is 10 microseconds, and extrapolation yields approximately 1 ns for A1 <--> A3. The pronounced kinetic differences imply different structural rearrangements. Crystallographic data support this conclusion: They show that formation of the A0 substate involves a major change of the protein structure; the distal histidine rotates about the C(alpha)-C(beta) bond, and its imidazole sidechain swings out of the heme pocket into the solvent, whereas it remains in the heme pocket in the A1 <--> A3 interconversion. The fast A1 <--> A3 exchange is inconsistent with structural models that involve differences in the protonation between A1 and A3.

Animals↗

Cross-facial nerve grafting for facial reanimation: effect on normal hemiface motion.

Reinnervation of the paralyzed hemiface with a cross-facial nerve graft (CFNG) required division of facial nerve branches on the normal hemiface to serve as axon donors. There is therefore concern about whether any impairment of normal hemiface motion occurs in the postoperative period. To minimize the likelihood of donor-side impairment, donor branches are chosen from the bucco-zygomatic region which was extensive cross branching, as opposed to be the single temporal or marginal mandibular branches. This study chose to determine quantitatively if this practice does, in fact, adversely affect the normal side hemiface motion governed by these branches, viz., eye closure, pucker, and smile. Since surgical procedures near the facial nerve (such as superficial parotidectomy) may leave the patient with transient facial weakness, even in the absence of nerve transection, the hypothesis was that hemiface motion would be impaired on the donor side during the early postoperative period (first month) secondary to edema and/or neuropraxia. However, based on the clinical observation that donor-side facial motion is not demonstrably impaired late after surgery, a further hypothesis was that any early facial motion is not demonstrably impaired late after surgery, a further hypothesis was that any early facial motion impairment would return to normal by 3 months postoperatively. Seven patients underwent sural CFNG as a primary or secondary component of their facial animation procedure. Their facial motion was quantified preoperatively and in serial postoperative examinations using the Maximal Static Response Assay (MSRA) of facial motion. Careful selection of redundant bucco-zygomatic branches of the facial nerve on the normal side for CFNG did not ultimately ( > or = 3 months postoperative) impair the important motions of eye closure, smile, or pucker. Early postoperative ( < or = 1 month) weakness of the smile was seen on both X and Y axes, indicating that both the risorius and zygomatic muscles were transiently weakened. The ability to elevate the lower eyelid was unaffected at any postoperative time point. Movement of the normal hemiface did not appear to be permanently affected by CFNG when a careful choice of redundant bucco-zygomatic donor branches was made.

Adult↗

The functions of space.

This paper describes a participant observation study carried out on a ward for elderly functionally ill people in a large psychiatric hospital in the Midlands, England. My initial interest was in observing the process of institutionalization, and attempts made to counter this process. As the project developed I became interested in four specific cultural domains: the use of space, particularly the ward office; the relationship between ward staff and 'outsiders' or 'others'; the functions of staff handovers; and the characteristics of the physical setting. In my conclusions I describe the relationship between space and the use of space, and the structure of authority and communication on the ward and between the ward and the 'outside world'. I also discuss the functions of handover in terms of the transfer of responsibility, and the psychological process which, it seems to me, underlines the split between 'good' and 'bad' others. I suggest the possibility that this line of research might be extended, and that a synthesy between sociological insight and group dynamic theory might offer a fruitful way forward.

Authoritarianism↗

Adolescent Milieu Rating Scale: tool for therapeutic management.

The Milieu Rating Scale developed at North Star Hospital allows staff to anticipate behavioral problems and respond decisively and immediately. Since a stable community is necessary for effective treatment to take place, the scale ensures superior patient care. Patient anxiety is reduced under a staff that is confident that they have control and are aware of inappropriate and secretive behavior. Use of the scale allows better staffing patterns, justification for acuity, control of expenses, and the opportunity for staff to identify potential problems. The scale also involves the patient community in determining positive and negative reinforcers.

Adolescent↗

What is psychotherapy?

Nurses are increasingly being called on to employ psychotherapeutic skills with their patients and clients. This major new series will examine these skills, which are invaluable in general, as well as psychiatric, settings.

Humans↗