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M Johnson

Publications and source records attributed to M Johnson.

At least 343 records · Page 19Linked to original sources
PubMed1996

Antagonistic properties of centrally truncated analogs of [D-Trp(32)]NPY.

We have previously shown that [D-Trp(32)]NPY can competitively antagonize NPY-induced feeding in rats (Balasubramaniam et al. J. Med. Chem. 1994, 37, 811-815). This peptide, however, did not bind to SK-N-MC cells with Y-1 receptors. Since centrally truncated NPY analogs have been shown to bind Y-1 receptors, we synthesized similar analogs of [D-Trp(32)]NPY and investigated their Y-1 (SK-N-MC) and Y-2 (SK-N-BE2) receptor affinities and their properties in human erythroleukemia (HEL) cells. None of the analogs with D-Trp(32) mobilized intracellular calcium, [Ca2]i, in HEL cells. Although Des-AA(6-24)[Aoc(6)]NPY and the corresponding D-Trp(32) analog exhibited no affinity to Y-1 receptors, Des-AA(7-24)[Aoc(6),D-Trp(32)] NPY(6) exhibited weak binding. Replacing Pro(5) in 6 with D-Ala to stabilize the central chain reversal, and hence the antiparallel alignment of the N- and C-terminal regions known to be important for Y-1 binding, resulted in an analog, Des-AA(7-24)[D-Ala(5),Aoc(6),D-Trp(32)]NPY (7), which exhibited moderate antagonist potency in attenuating NPY effects on cAMP and [Ca2+]i, in SK-N-MC and HEL cells, respectively. This analog also shifted the dose-response curve of NPY on blood pressure in anesthetized rats. Deletion of only the 7-17 and/or the incorporation of N-Me-Ala(5), superior beta-turn stabilizer, in 7 did not improve the Y-1 receptor affinity. Des-AA(7-24)[D-Ala(5), Gly(6),D-Trp(32)]NPY exhibited an affinity similar to that of 7, suggesting that a long spacer arm is not necessary for efficient Y-1 receptor interaction. Locking the antiparallel alignment via a 2/26 or 2/27 lactam bridge did not improve the binding. Finally, replacement of D-Ala(5) in 7 with D-Trp dramatically increased both the binding and the antagonistic potencies. Modeling based on the avian pancreatic polypeptide X-ray structure suggested that analogs which have the N- and C-terminal regions in close proximity might exhibit good binding, and that the D-Trp(32) substitution may induce a beta-turn that could be important for exhibiting antagonism. A systematic investigation has resulted in the development of relatively potent Y-1 receptor antagonists. Further structure-activity studies with these compounds and those previously reported by us and other investigators should result in the development of long-acting and receptor selective antagonists.

Amino Acid Sequence↗
PubMed1996

Beta-amyloidosis in normal aging and transmitter signaling in human temporal lobe.

Interactions between abnormal amyloid precursor protein metabolism and cholinergic dysfunction are increasingly apparent. Both of these major features of Alzheimer's disease occur in restricted loci in normal aging--a potential model for early Alzheimer type pathology. Entorhinal cortex is particularly vulnerable to beta-amyloidosis and compared with other cortical areas is remarkable for the relatively high density of nicotinic (3H-nicotine) but not other cholinergic or glutamate receptor binding. With increasing age, post-maturity, there is a persistent decline in nicotinic receptor binding in entorhinal cortex whereas muscarinic M1 and non-M1, glutamate NMDA and non-NMDA receptors are spared. Normal elderly individuals, distinguished by the absence of beta A4 immunoreactive plaques in this area, are differentiated from those with plaques by higher nicotine binding. Amongst individuals with an established history of smoking tobacco, nicotinic receptor binding and hippocampal choline acetyltransferase were elevated compared with non-smokers and preliminary evidence indicates a reduced density of cortical plaques. These findings are consistent with the hypothesis that down regulation of the nicotinic cholinergic receptor--a ligand gated calcium channel known to control the expression of neurotrophins--plays a role in the evolution of Alzheimer-type pathology.

Adolescent↗
PubMed1996

D2 gastrectomy: lessons from a prospective audit of the learning curve.

A 3-year prospective study of the learning curve for D2 gastrectomy was carried out by one surgeon beginning to perform the operation independently after intensive specialist training. Some 38 patients were treated; there were four postoperative deaths and 22 patients had complications. Postoperative morbidity decreased significantly with time (rS = -0.38, P = 0.02, 95 per cent confidence interval -0.62 to -0.07). The physiological component of POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) was significantly lower in the third year (median value 15, 16 and 14 for years 1, 2 and 3, n = 31, chi 2 = 7.5, 2 d.f., P = 0.02, Kruskal-Wallis test), but the operative POSSUM scores and the number of lymph nodes found were not decreased (median operative POSSUM score 19, 18 and 21, n = 31, chi 2 = 0.2, 2 d.f., P = 0.91, Kruskal-Wallis test). The results suggest a learning curve lasting about 18-24 months or 15 to 25 procedures before a plateau is reached. Improved results were associated with changes in case selection and operative tactics but not with reduced extent of lymphadenectomy. D2 gastrectomy should be restricted to specialist centres where adequate training and supervision can be provided during the learning curve.

Female↗
PubMed1996

The effect of bacterial toxins on levels of intracellular adenosine nucleotides and human ciliary beat frequency.

Toxins that slow ciliary beat are virulence determinants of bacteria that infect or invade ciliated epithelial surfaces. We have previously shown that the effect of the Pseudomonas aeruginosa toxin pyocyanin on ciliary beat is associated with a fall in intracellular cAMP and ATP. We have now investigated whether reduction in intracellular adenosine nucleotides might be a common mechanism of action of other bacterial toxins which slow ciliary beat. Two other P. aeruginosa toxins, 1-hydroxyphenazine (1-HP) and rhamnolipid, and two Haemophilus influenzae fractions produced by gel filtration of broth cultures were tested. The effect on human nasal epithelium ciliary beat frequency (CBF), and intracellular cAMP and ATP were measured, and the effect of two pharmacological agents, dibutyryl cAMP and salmeterol, on these changes was assessed. 1-HP, rhamnolipid and the two H. influenzae fractions slowed CBF before there was significant release of lactate dehydrogenase from the cells. The toxins also caused a fall in intracellular cAMP and ATP. Dibutyryl cAMP and salmeterol at the concentrations used do not increase baseline CBF, but diminished the fall in CBF and intracellular adenosine nucleotides. The cAMP and ATP levels in these studies were combined with those previously obtained with pyocyanin. there was a good correlation between cAMP and ATP levels and CBF. Bacterial toxins which slow CBF may act by causing a fall in intracellular adenosine nucleotides, and agents which stimulate cAMP may prevent toxin-induced slowing of ciliary beat.

Adenine Nucleotides↗
PubMed1996

Mechanisms for tolerance to methamphetamine effects.

Pretreatment with incremental increases in methamphetamine causes tolerance to serotonergic effects caused by challenging with multiple high doses of methamphetamine (11.5 mg/kg/dose). The brain concentration of methamphetamine following this challenge was reduced in tolerant rats, yet the plasma concentration was elevated. The tolerance was selective for methamphetamine and did not occur when cocaine was used in the pretreatment. The possibility that tolerance affects the distribution of methamphetamine in or out of the brain through an active transport system was examined by combining the transport-blocking drug, probenecid, with a low dose of methamphetamine. The presence of probenecid enhanced methamphetamine-induced serotonergic changes in the hippocampus. The brain concentration of methamphetamine increased in the presence of probenecid; however, a similar increase in the plasma methamphetamine concentration suggests that the effects of probenecid on methamphetamine distribution are not related to the redistribution of methamphetamine that occurs in tolerant animals.

Animals↗
PubMed1996

Facial expression processing after amygdalotomy.

Facial expression processing impairments were studied in D.R., a 51-year-old woman with a partial bilateral amygdalotomy. D.R. was poor at recognising emotional facial expressions, both in static and moving stimuli. In identity matching tasks (same vs different person) and expression matching tasks (same vs different expression), D.R. was impaired at expression matching with simultaneously or successively presented faces; she experienced difficulties whenever the faces' identities were discrepant with their expressions. For identity matching, she also had problems when simultaneously presented images showed the same face with two different expressions; her deficit in interpreting facial expressions could lead her to mistake differences in expression for a difference in identity. In imagery tasks, D.R. was able to answer questions about the appearance of familiar people, yet she was very poor at imaging facial expressions of emotion. We suggest that her problems in processing facial expressions included impaired knowledge of the patterning of facial features in each emotion; without this, remembering or reconstructing what emotional facial expressions look like is as impaired as perceptual recognition. These findings are consistent with the hypothesis of a role for the amygdala in social behaviour.

Adult↗
PubMed1996

The effects of extracellular matrix and osteogenic protein-1 on the morphological differentiation of rat sympathetic neurons.

The growth patterns of axons and dendrites differ with respect to their number, length, branching, and spatial orientation; therefore, it is likely that these processes differ in their growth requirements. To examine this hypothesis, we have been analyzing the responses of cultured rat sympathetic neurons to three types of stimuli: large structural proteins of the extracellular matrix, matrix-associated growth factors, and neurotrophins. Purified structural proteins such as laminin and collagen IV have been found to promote only axonal growth; whereas the matrix associated growth factor, osteogenic protein-1, selectively stimulates dendritic growth. In contrast, nerve growth factor modulates the growth of both types of processes. These data suggest that process-specific interactions with the extracellular environment may be critical determinants of cell shape in neurons. Perinatal rat sympathetic neurons grown in culture in the absence of serum or glial cells extend a single process which is axonal in nature. Exposure to osteogenic protein-1 causes the formation of additional processes which express the morphological, cytoskeletal, and ultrastructural characteristics of dendrites. Consistent with observations on the regulation of dendritic growth in sympathetic neurons in situ, the dendrite-promoting activity of osteogenic protein-1 is independent of synaptic or electrical activity, but is modulated by nerve growth factor. In the presence of optimal concentrations of osteogenic protein-1 and nerve growth factor, the size of the dendritic arbor extended by cultured sympathetic neurons approximates that seen in situ at comparable developmental stages. Osteogenic protein-1 does not promote dendritic growth in cultured neurons obtained from embryonic ciliary, dorsal root, trigeminal or nodose ganglia, suggesting that its morphogenetic effects are cell selective. Since mRNA for osteogenic protein-1 is expressed in mature as well as embryonic target tissues of the sympathetic nervous system, we also examined the effects of osteogenic protein-1 on cultures of sympathetic neurons derived from adult rats. Consistent with results obtained with perinatal neurons, osteogenic protein-1 selectively promoted dendritic growth in adult neurons. These data suggest that this matrix-associated growth factor could play a role not only in the morphogenesis of the developing nervous system, but also in the maintenance and remodeling of dendritic structures in the mature animal.

Animals↗
PubMed1996

Fluid shifts across human dentine in vitro in response to hydrodynamic stimuli.

Most authorities agree that the hydrodynamic theory of dentine sensitivity best explains the stimulus-response relations of most painful stimuli. However, as the usual hydrodynamic stimuli are so different, it has been impossible to compare them. The equivalency of hydrodynamic stimuli can be evaluated from measurements of the fluid movement induced in vitro and relating this to the hydraulic conductance (Lp) of the same dentine specimen. From this determination, a common denominator is obtained which is equivalent to the hydrostatic pressure that would be required to cause the same magnitude of fluid movement. The purpose of this study was to measure the direction and magnitude of fluid shifts across dentine in extracted human crown segments with a flat, dentine occlusal surface in response to the following hydrodynamic stimuli; air blast, 56 degrees C water, 2 degrees C water, tactile and osmotic. In acid-etched superficial dentine, which simulates hypersensitive dentine, the largest to the smallest fluid flows obtained were: hot > cold > air blast > osmotic > tactile. When these were converted to equivalency units, the ranking of stimuli from strongest to weakest was hot > cold > air blast > osmotic > tactile. This new approach to comparing hydrodynamic stimuli should be verified in vivo.

Acid Etching, Dental↗
PubMed1996

Clinical implications of endoscopic ultrasound: the American Endosonography Club Study.

BACKGROUND: Despite increased clinical use of endoscopic ultrasound (EUS), there are little data regarding complications of EUS or its impact on patient management. METHODS: A prospective multicenter study was completed to evaluate clinical outcomes of EUS. Before each EUS examination the endosonographer recorded further theoretical patient management plans as if EUS was unavailable. After the EUS, endosonographers recorded actual management plans based on EUS results. The actual management plan after EUS was compared to the theoretical management before EUS. Complications were assessed in short-term follow-up. RESULTS: Four hundred twenty-eight subjects were enrolled. Of subjects able to be evaluated, EUS changed the treatment plan in 74%. Management changes of major importance occurred in 120 patients (31% of subjects able to be evaluated) and included decisions regarding surgery (62 patients), decisions regarding nonsurgical invasive management (36 patients), and decisions regarding further follow-up (22 patients). When there was a change in management, the change was to less costly, risky, or invasive management in 55%, to more costly/risky/invasive in 37%, and to equally costly/risky/invasive in 8%. Short-term follow-up was completed in 81% of subjects, with six complications identified (1.7%). Three complications were mild, two were moderate, one severe, and none fatal. CONCLUSIONS: (1) Changes in management plan may occur in the majority of patients based on EUS results. (2) The management changes are often of major importance with regard to health care costs and safety, and are more often in the direction of less costly, risky, and invasive management. (3) EUS is safe in experienced hands.

Adolescent↗
PubMed1996

Early postoperative angiographic assessment of radial grafts used for coronary artery bypass grafting.

UNLABELLED: Despite a revival of interest in using the radial artery as an alternative conduit for myocardial revascularization, little angiographic documentation of early postoperative results has been presented, particularly in North America. Accordingly, 60 of 150 patients who underwent coronary artery bypass with radial arteries from November 1993 to July 1995 have had postoperative cardiac catheterization at our institution. The patency rate of the radial artery grafts was 95.7% (90 of 94 grafts patent) with an average internal diameter of 2.51 mm. Four radial artery grafts showed diffuse narrowing. The patency rate of the internal thoracic artery grafts was 100% with an average internal diameter of 2.25 mm. Three of 62 grafts demonstrated diffuse narrowing. Two of 24 (7.7%) saphenous vein grafts were occluded; the average internal diameter was 3.23 mm. The internal thoracic artery, the radial artery, and saphenous vein grafts were, respectively, 7.5%, 19.5%, and 53.3% larger than the anastomosed native coronary arteries. Graft-dependent flow was found in 81.1% of the radial artery grafts. CONCLUSION: The results of this study demonstrate that the short-term patency rate of radial artery grafts is excellent.

Adult↗
PubMed1996

Measuring healing in leg ulcers: practice considerations.

Clinical nursing practice requires reliable and valid methods of measuring healing in patients with leg ulcers. By comparing the reliability and validity of four methods of measuring leg ulcer healing, digital planimetry (computerized area measurement), the Kundin Wound Gauge (volume and area measurement), the Healing Scale (measuring perceptions of healing), and the Johnson Scale (measuring wound characteristics), with the standard technique of stereophotogrammetry, implications for nursing practice and research were identified. Stereophotogrammetry, defined as topographical mapping measuring volume and area, was found to be reliable and suitable for clinical trial evaluations and for monitoring healing in hospitals or clinics. In a sample of hospital and community patients with leg ulcers (n = 82), weekly clinical comparisons using digital planimetry and the Kundin Wound Gauge, both reliable methods, supported the suitability of these measures, for monitoring healing in any setting (r = .99; r = .98, respectively). The Healing and Johnson Scales did not show concurrent validity when compared with stereophotogrammetric methods and had limited reliability. This study provided three reliable and valid methods of measuring healing suitable for practice. Time intervals and endpoints for clinical trials and evaluating practice need to be considered in terms of instrument error rates and delayed healing in older people.

Aged↗
PubMed1996

Centromere-linkage analysis and consolidation of the zebrafish genetic map.

The ease of isolating mutations in zebrafish will contribute to an understanding of a variety of processes common to all vertebrates. To facilitate genetic analysis of such mutations, we have identified DNA polymorphisms closely linked to each of the 25 centromeres of zebrafish, placed centromeres on the linkage map, increased the number of mapped PCR-based markers to 652, and consolidated the number of linkage groups to the number of chromosomes. This work makes possible centromere-linkage analysis, a novel, rapid method to assign mutations to a specific linkage group using half-tetrads.

Animals↗
PubMed1996

Infertility among human immunodeficiency virus-positive women: incidence and treatment dilemmas.

The increasing demand for fertility advice among human immunodeficiency virus (HIV)-positive women under our care led us to review the incidence of infertility and the ethical problems associated with its management. All HIV-positive women who attended the HIV outpatients clinic from October 1990 to the end of January 1996 were studied. The main outcome measures were: the number of women undergoing infertility investigations before and after HIV diagnosis, their demographic and social details, and the outcome of these investigations. Most of the 183 women studied were in their reproductive years (mean age 32.7 +/- 6.7 years). Nine women had undergone infertility investigations, and/or treatment before HIV diagnosis, three of whom were diagnosed with HIV during routine testing prior to IVF treatment. Six declined further infertility treatment after discovering their HIV status. Eight women have undergone infertility investigations after HIV diagnosis but none have achieved pregnancy to date. Management decisions may have been hampered by ethical uncertainties in several cases. In conclusion therefore, as requests for infertility treatment from HIV-infected women occur and may become more common as the prevalence of HIV infection in women continues to rise, the ethical issues associated with the management of this problem demand urgent attention so that clear guidelines are available to aid treatment decisions.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Maternal serum concentrations of pregnancy associated placental protein A and pregnancy specific beta-1-glycoprotein in multifetal pregnancies before and after fetal reduction.

Placental function in multifetal pregnancies before and after embryo reduction was investigated by measuring maternal serum concentrations of pregnancy associated placental protein-A (PAPP-A) and pregnancy specific beta-1-glycoprotein (SP-1). Three groups of pregnant women were studied following assisted reproduction; groups 1 and 2, were 12 singleton and 12 twin pregnancies respectively, and group 3 comprised 12 women with multifetal pregnancies undergoing embryo reduction. PAPP-A and SP-1 were measured serially at 8-21 weeks gestation. In all pregnancies, maternal serum PAPP-A and SP-1 increased with gestation. In twin pregnancies the mean concentrations of SP-1 were significantly higher than in singletons at all gestations, whereas for PAPP-A, concentrations were similar between these groups. In multifetal pregnancies before embryo reduction, the serum concentrations of both proteins were significantly higher than in twin pregnancies. Following reduction, the concentrations of PAPP-A remained significantly higher than for twins throughout, whereas the concentrations of SP-1 gradually converged towards those of twins; by 19 weeks there was no difference between the means of the two groups. These findings suggest that circulating concentrations of SP-1 reflect total placental mass, which is proportional to the number of live fetuses, whereas the pattern of PAPP-A changes suggests that this protein is produced by the placenta, decidua and other tissues.

Female↗