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P Hanson

Publications and source records attributed to P Hanson.

At least 37 records · Page 2Linked to original sources

Orientation and immersion depth of a helical lipopeptaibol in membranes using TOAC as an ESR probe.

Trichogin GA IV is a lipopeptaibol antibiotic characterized by the sequence nOct-Aib1-Gly-Leu-Aib4-Gly-Gly-Leu-Aib8-Gly-Ile- Lol (nOct: n-octanoyl; Aib: alpha-aminoisobutyric acid; Lol, leucinol), which exhibits membrane-modifying properties. We synthesized step-by-step by solution methods three trichogin analogues, each with a single Aib --> 2,2,6,6-tetramethylpiperidin-1-oxyl-4-amino-4-carboxylic acid (TOAC) substitution. The similarity in the conformational propensities of the Calpha-tetrasubstituted alpha-amino acids Aib and TOAC allowed us to exploit these analogues to investigate the orientation and therefore the mechanism of action of trichogin in the membranes by the electron spin resonance (ESR) technique. A conformational analysis by Fourier transform ir absorption and CD in different organic solvents and in a membrane-mimetic environment indicated that the conformation of the natural lipopeptaibol remains almost unchanged in the three analogues. Moreover, for all of the analogues permeability measurements revealed membrane-modifying properties comparable to those of trichogin. Our ESR investigation demonstrated that, in liposomes based on phosphatidylcholine, trichogin lays parallel to the membrane surface with its hydrophobic face oriented toward the membrane interior. These results suggest that trichogin might modify membrane permeability via a carpet-like mechanism, at least in liposomes and in the absence of a transmembrane potential.

Anti-Bacterial Agents↗

Axillary schwannoma masquerading as cervical radiculopathy.

A 58-year-old woman, suffering from radicular-like pain in the left arm for 3 years, presented an entirely negative cervical imaging. Careful clinical examination disclosed Tinel's sign in the axilla. This clinical finding led to further investigation of this region. Computed tomography and magnetic resonance imaging disclosed a small tumour highly suggestive of a schwannoma. Surgical exploration and microscopic examination confirmed a diagnosis of schwannoma located on the radial trunk of the left brachial plexus. After tumour excision, the patient had immediate relief of pain without sensitive or motor sequelae. No recurrence has been observed after 3 years.

Axilla↗

Determining the occurrence of a 3(10)-helix and an alpha-helix in two different segments of a lipopeptaibol antibiotic using TOAC, a nitroxide spin-labeled C(alpha)-tetrasubstituted alpha-aminoacid.

Trichogin GA IV is a 11-residue lipopeptaibol antibiotic exhibiting membrane modifying properties. We synthesized step-by-step by solution methods three trichogin analogues, each with a double Aib (alpha-aminoisobutyric acid)-->TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) replacement. The strict similarity in the conformational propensities of Aib and TOAC allowed us to exploit these analogues in a detailed investigation of the conformation of this lipopeptaibol in different organic solvents and in a membrane-mimetic environment using in particular the double spin labeling ESR technique. We conclude that the secondary structure in solution remains essentially unchanged if compared to that previously found in the crystal state for trichogin. More specifically, the N-terminal region of the peptide folds in a 3(10)-helix, while the central and C-terminal regions are mainly alpha-helical. An additional, significant proof for the modest plasticity of the trichogin structure was obtained by an X-ray diffraction analysis of the nOct-[TOAC4,8, Leu-OMe11] analogue. For the three analogues permeability measurements revealed membrane-modifying properties comparable to those of natural trichogin.

Aminoisobutyric Acids↗

Identification and characterization of a novel high affinity metal-binding site in the hammerhead ribozyme.

A novel metal-binding site has been identified in the hammerhead ribozyme by 31P NMR. The metal-binding site is associated with the A13 phosphate in the catalytic core of the hammerhead ribozyme and is distinct from any previously identified metal-binding sites. 31P NMR spectroscopy was used to measure the metal-binding affinity for this site and leads to an apparent dissociation constant of 250-570 microM at 25 degrees C for binding of a single Mg2+ ion. The NMR data also show evidence of a structural change at this site upon metal binding and these results are compared with previous data on metal-induced structural changes in the core of the hammerhead ribozyme. These NMR data were combined with the X-ray structure of the hammerhead ribozyme (Pley HW, Flaherty KM, McKay DB. 1994. Nature 372:68-74) to model RNA ligands involved in binding the metal at this A13 site. In this model, the A13 metal-binding site is structurally similar to the previously identified A(g) metal-binding site and illustrates the symmetrical nature of the tandem G x A base pairs in domain 2 of the hammerhead ribozyme. These results demonstrate that 31P NMR represents an important method for both identification and characterization of metal-binding sites in nucleic acids.

Base Sequence↗

Cervical spinal cord injury in sapho syndrome.

Cervical spinal fracture and pseudarthrosis are previously described causes of spinal cord injury (SCI) in patients with spondylarthropathy. SAPHO (Synovitis Acne Pustulosis Hyperostosis Osteitis) syndrome is a recently recognized rheumatic condition characterized by hyperostosis and arthro-osteitis of the upper anterior chest wall, spinal involvement similar to spondylarthropathies and skin manifestations including palmoplantar pustulosis and pustular psoriasis. We report the first case of SAPHO syndrome disclosed by SCI related to cervical spine ankylosis.

Acquired Hyperostosis Syndrome↗

Anatomical differences in the psoas muscles in young black and white men.

The anatomy of the psoas major muscle (PMA) in young black and white men was studied during routine autopsies. The forensic autopsies included 44 fresh male cadavers (21 black, 23 white) with an age span of 14 to 25 y. The range for weight was 66-76 kg and for height 169-182 cm. The PMA was initially measured in its entire length before measuring the diameter and circumference at each segmental level (L1-S1). At each segmental level, the calculated anatomical cross-sectional area (ACSA) was more than 3 times greater in the black group compared with the white (P < 0.001). The psoas minor muscle (PMI) was absent in 91% of the black subjects, but only in 13% of the white subjects. These data show that the PMA is markedly larger in black than white subjects. The marked race specific difference in the size of the PMA may have implications for hip flexor strength, spine function and race specific incidence in low back pathology, and warrants further investigation.

Adolescent↗

The influence of skin temperature on latency and amplitude of the sympathetic skin response in normal subjects.

The influence of skin temperature on latency and amplitude of the sympathetic skin response (SSR) was studied in 10 normal subjects. SSRs were elicited in all four limbs of each subject by electrical stimulation after cooling of the right arm and after cooling of the right hand only. At low skin temperature, the latency was prolonged and the amplitude decreased. Latency and amplitude were linearly correlated with skin temperature of the right arm. There were no changes in the left arm and the legs, which basically excludes involvement of central pathways in these response parameters. With regard to the skin temperature of the arm, a temperature correction factor of 0.088 s/degrees C was calculated for latency. With regard to the skin temperature of the hand, latency prolongation was significantly greater after cooling of the whole arm. This suggests that not only the neuroglandular junction, but also the postganglionic sympathetic C fibers were responsible for latency modifications. In contrast, amplitude was reduced similarly after cooling of the whole arm and the hand only, suggesting that mainly the neuroglandular junction is responsible for amplitude modifications. We conclude that skin temperature is a mandatory measurement in the study of the SSR.

Adult↗

An NMR investigation of the conformational effect of nitroxide spin labels on Ala-rich helical peptides.

Nitroxide spin labels, in conjunction with electron spin resonance (ESR) experiments, are extensively employed to probe the structure and dynamics of biomolecules. One of the most ubiquitous spin labeling reagents is the methanethiosulfonate spin label which attaches a spin label selectively to Cys residues via a disulfide bond (Cys-SL). However, the actual effect of the nitroxide spin label upon the conformation of the peptide or protein cannot be unambiguously determined by ESR. In this study, a series of 16-residue Ala-rich helical peptides was characterized by nuclear magnetic resonance techniques. The C alpha H chemical shift analysis, NOEs, and 3JNH alpha coupling constants for peptides with no Cys, free Cys, and Cys-SL (with the N-O group reduced) were compared. These results indicate that while replacement of an Ala with a Cys residue causes a loss of overall helical structure, the Cys-SL residue is helix supporting, as would be expected for a non-beta-branched aliphatic amino acid. Thus, the Cys-SL residue does not perturb helical structure and, instead, exhibits helix-stabilizing characteristics similar to that found for Ala, Met, and Leu.

Alanine↗

The difference in anatomy of the lumbar anterior longitudinal ligament in young African-Americans and Scandinavians.

OBJECTIVE: To examine possible structural differences in the lumbar anterior longitudinal ligament between young African-American and Scandinavian people. DESIGN: The lumbar anterior longitudinal ligament was examined in 48 African-American and Scandinavian young men and women (17 to 30 years old). Apart from the selection of gender, age, height, and weight, all subjects were recruited consecutively during routine forensic autopsies. Sections of the ligament were obtained from the L1 and the L5 vertebra for thickness and width measurements and histologic preparations. The measurements were performed with a digital vernier caliper with an accuracy of 0.1 mm. RESULTS: The width of the L1 part of the lumbar anterior longitudinal ligament in the African-American group (27.5+/-1.8mm) was greater than that in the Scandinavian group (17.7+/-1.5mm) (p < .001), and the thickness of the L1 part in the African-American group (3.8+/-0.4mm) was greater than that in the Scandinavian group (3.3+/-0.3mm) (p < .001). The width of the L5 part in the African-American group (34.1+/-2.0mm) was greater than that in the Scandinavian group (25.0+/-1.5mm) (p < .001), and the thickness of the L5 part in the African-American group (3.3+/-0.3mm) was greater than that in the Scandinavian group (2.2+/-0.3mm) (p < .001). The cross-sectional area was greater in the African-American group in both sections (L1, African-American 106.4+/-13.7mm2 vs Scandinavian 52.8+/-7.9mm2; L5, African-American 112.2+/-14.6mm2 vs Scandinavian 55.6+/-6.7mm2) (p < .001). No histologic differences between the two groups were observed. CONCLUSIONS: The lumbar anterior longitudinal ligament was considerably wider and thicker, which yielded a markedly greater cross-sectional area, in African-American than in Scandinavian subjects. In contrast, the ligament appears to be histologically similar in the two groups. These are previously unrecognized differences in anatomy between young African-American and Scandinavian people.

Adolescent↗

Effects of respiratory muscle work on cardiac output and its distribution during maximal exercise.

We have recently demonstrated that changes in the work of breathing during maximal exercise affect leg blood flow and leg vascular conductance (C. A. Harms, M. A. Babcock, S. R. McClaran, D. F. Pegelow, G. A. Nickele, W. B. Nelson, and J. A. Dempsey. J. Appl. Physiol. 82: 1573-1583, 1997). Our present study examined the effects of changes in the work of breathing on cardiac output (CO) during maximal exercise. Eight male cyclists [maximal O2 consumption (VO2 max): 62 +/- 5 ml . kg-1 . min-1] performed repeated 2.5-min bouts of cycle exercise at VO2 max. Inspiratory muscle work was either 1) at control levels [inspiratory esophageal pressure (Pes): -27.8 +/- 0.6 cmH2O], 2) reduced via a proportional-assist ventilator (Pes: -16.3 +/- 0.5 cmH2O), or 3) increased via resistive loads (Pes: -35.6 +/- 0.8 cmH2O). O2 contents measured in arterial and mixed venous blood were used to calculate CO via the direct Fick method. Stroke volume, CO, and pulmonary O2 consumption (VO2) were not different (P > 0.05) between control and loaded trials at VO2 max but were lower (-8, -9, and -7%, respectively) than control with inspiratory muscle unloading at VO2 max. The arterial-mixed venous O2 difference was unchanged with unloading or loading. We combined these findings with our recent study to show that the respiratory muscle work normally expended during maximal exercise has two significant effects on the cardiovascular system: 1) up to 14-16% of the CO is directed to the respiratory muscles; and 2) local reflex vasoconstriction significantly compromises blood flow to leg locomotor muscles.

Adult↗

Differences in sacral angulation and lumbosacral curvature in black and white young men and women.

The angle between the base of the sacrum and its pelvic surface (SA), and the lumbosacral curve (LSC) defined as the anteroposterior distance between the L1 vertebra and the sacrum were studied in 105 fresh cadavers aged 15-32 years at death. The sample is comprised of 27 black males, 20 black females, 37 white males and 21 white females. Measurements of the SA were made with an adjustable protractor with an accuracy of +/-1 degrees. A new method using a specially designed instrument was developed for taking LSC measurements. A sliding scale that could be moved in the cranialcaudal direction was fitted with a measurement stick which measured the depth of the lumbar and sacral vertebral bodies (ventral to dorsal). The measuring device was placed on the autopsy table above the supine cadaver to measure these depths from the ventral side. The LSC was calculated as the mean difference between lumbar and sacral depths. The SA is smaller in black than in white men (43.6 +/- 3.4 vs. 61.7 +/- 2.1 degrees, p <0.001). Similarly, black women have a smaller SA than white women (36.0 +/- 2.2 vs. 50. 2 +/- 1.9 degrees, p <0.001). The LSC is also larger in black than white men (9.4 +/- 1.1 vs. 5.1 +/- 0.3 cm, p <0.001), and black women also have significantly larger LSC compared to white women (13. 2 +/- 0.5 vs. 9.2 +/- 0.6 cm, p <0.001). These data are so far the largest empirical evidence of differences in the SA and the LSC in young black and white cadaver specimens.

Adolescent↗

Differences in the iliolumbar ligament and the transverse process of the L5 vertebra in young white and black people.

The anatomy of the iliolumbar ligament (ILL) and the spatial orientation of the transverse process of the L5 vertebra were studied in 62 young black (n = 29) and white (n = 33) men and women during routine autopsy. The aim of the study was to determine possible racial differences in the structure and attachments of the iliolumbar ligament. The present study also investigated the spatial orientation of the transverse process of the L5 vertebra since the ILL has been reported to attach to the transverse process. The measurements of the iliolumbar ligament were carried out with a digital vernier caliper while the transverse process angles were measured with an adjustable protractor. The ligament in black people was made up of a single, markedly longer band compared to white people, where the ligament was made up of two shorter bands. The ILL measured 61.8 +/- 1.3 mm in black and 33.2 +/- 1.5 mm white men, and in black women 61.3 +/- 0.9 mm versus 32.2 +/- 1.2 mm in white women (p <0.01). Further, the ILL was markedly wider in black than white subjects (p <0.01). The horizontal and vertical angle also varied greatly between black and white subjects (p <0.01). These are previously unrecognized observations. Albeit unsubstantiated, these findings may have implications for understanding the etiology of various low back stress problems.

Adolescent↗

Estimating the relative populations of 3(10)-helix and alpha-helix in Ala-rich peptides: a hydrogen exchange and high field NMR study.

Recent experimental and theoretical work suggests that alanine-rich peptides fold as a mixture of 3(10)-helix (i --> i + 3 hydrogen bonding) and alpha-helix (i --> i + 4 hydrogen bonding). In order to assess the relative proportions of the two conformers, NMR studies were performed on the 16 residue sequences: Ac-AAAAKAAAAKAAAAKA-NH2 (3K) and Ac-AMAAKAWAAKAAAARA-NH2 (MW). Hydrogen/deuterium-exchange kinetics measured for the first three amide protons of the 3K peptide indicate that the NH of Ala3 is partially protected from exchange. This result is consistent with the presence of an i --> i + 3 hydrogen bond between the carbonyl group of the acetyl blocking group and the NH group of Ala3. The MW peptide is a modified version of the 3K peptide, designed to increase alphaH signal dispersion. 1H NMR spectra of the MW peptide at 750 MHz reveal a series of intermediate range (NOEs) consistent with a mixture of 3(10)-helix and alpha-helix. The relative intensities of the alphaN(i,i + 3) and alphabeta(i,i + 3) (nuclear Overhauser enhancements) NOEs suggest that 3(10)-helix is present throughout the peptide, but with the greatest contribution at the termini. A model was developed to determine the relative contributions of 3(10)-helix and alpha-helix. Lower bounds for the population of 3(10)-helix are approximately 50% at the termini and 25% in the middle of the peptide. The greatest alpha-helical content is between the middle of the peptide and the N terminus.

Alanine↗

Acute corticosteroid myopathy in intensive care patients.

Several recent studies have attributed the occurrence of acute myopathy in intensive care unit patients to the combination of corticosteroids and neuromuscular junction blocking agents (NMBAs) used for mechanical ventilation. We present 4 patients who developed acute myopathy after administration of high doses of glucocorticoids during sedation with propofol without any NMBAs. All patients had elevated creatine kinase levels. Electrophysiological studies indicated normal motor and sensory nerve conduction velocities but reduced motor nerve response amplitudes. Needle electromyography identified abnormal spontaneous activity; motor unit potentials were polyphasic of low amplitude and short duration, characteristic of a myopathic process. Muscle biopsy demonstrated a prominent acute necrotizing myopathy in all 4 patients with a loss of thick filaments. Our observations support glucocorticoids rather than NMBAs as the main offending drug in acute corticosteroid myopathy. The predisposing factor should be the hypersensitivity of paralyzed muscles to corticosteroids regardless of the drug inducing paralysis: NMBAs or propofol.

Acute Disease↗

Hemodynamic patterns and duration of post-dynamic exercise hypotension in hypertensive humans.

We investigated: 1) the mechanism of the hypotensive effect of a single bout of dynamic exercise in hypertensive subjects by measuring hemodynamic parameters before and for 2 h after treadmill exercise, and 2) the duration of the effect using ambulatory blood pressure (BP) monitoring once the subjects left the test site. Ten minutes after exercise there was a significant decrease from baseline systolic pressure (SP; -14 +/- 3 mm Hg), mean arterial pressure (MAP; -7 +/- 2 mm Hg), total peripheral resistance (TPR; -3.7 +/- 1.2 units), calf vascular resistance (CVR; -25.4 +/- 4.1 units), and an increase in HR (19 +/- 2 bpm). The changes in SP, DP, MAP, and HR were maintained during the 2 h of post-exercise monitoring; CVR remained decreased for 1 h; TPR returned to baseline within 20 min and then tended to be slightly elevated. CO was significantly decreased at 50, 60, and 120 min after exercise. We conclude that the early decline in BP after dynamic exercise in hypertensive subjects follows a biphasic pattern: 1) an initial decrease in total and regional vascular resistance with maintained CO, 2) followed by increasing resistance and decrease CO. Pre-exercise hypertensive BP values returned during subsequent ambulatory monitoring.

Blood Pressure↗

Reverse cholesterol transport in the rat following a short-term intravenous infusion of fat emulsion.

The effect on cholesterol transport of an intravenous infusion of a fat emulsion (10%) Intralipid or 10% Lipovenös) in vivo was investigated in the rat. Intralipid (1.85 ml/hr/kg body weight in rts for 3 hr) caused a reduction (P < 0.05) in free cholesterol in the aorta (by 25%), in plasma high-density lipoproteins (64%) and in erythrocytes (11%) with a concomitant enrichment of liver free cholesterol (16%), suggesting an enhanced reverse cholesterol transport in this species. Lipovenös under the same conditions gave similar results. Our data support our previous in vivo study in man indicating that infusion of a fat emulsion is able even to remove cholesterol from the arterial wall and thereby possibly be considered as an antiatherosclerotic agent.

Animals↗

[Streptococcus milleri subacute spinal cord abscess. Apropos of a case].

Since 1830, more than eighty cases of spinal cord abscesses have been reported. In half of these cases, it was unfortunately a post-mortem diagnosis. Magnetic resonance imaging (MRI) now gives new possibilities in the diagnosis and treatment of this rare pathology. We report here a case of cervical spinal cord abscess due to Streptococcus milleri. The clinical and laboratory findings, the MRI features, the pathogenicity of the offending pathogen and the surgical approach are discussed and compared with the data from the literature. The functional course was unexpectedly favourable in this patient. MRI allows prompt diagnosis and a precise localisation of the suspected abscess. Rapid surgical drainage is a critical prognostic factor for effective management of spinal cord abscess.

Abscess↗