Solid-phase peptide synthesis and circular dichroism study of chiral beta-peptoid homooligomers.

N-alkyl-beta-alanine oligomers (beta-peptoids) with alpha-chiral side chains [(R)- or (S)-1-(phenylethyl)amino groups] were synthesized and analyzed by CD spectroscopy. These chiral beta-peptoid homomers exhibited chain-length-dependent and solvent-dependent ellipticity, strongly indicating the presence of a secondary structure in solution. The CD behaviour was only slightly temperature-dependent upon heating, as also previously observed for stable alpha-peptoid helices containing the same type of side chains. Thus, the data presented here comprise the first evidence for a chain length-dependent secondary folding of compounds with this novel peptidomimetic backbone design. In addition, applicability of a novel hyphenated technique, HPLC-SPE-NMR/MS, for analysis of crude SPPS reaction products was demonstrated.

Influence of pre-operative bone mineral content of the proximal tibia on revision rate after uncemented knee arthroplasty.

Between 1986 and 1991, 106 patients (127 knees) underwent uncemented knee arthroplasty for osteoarthritis. There were 106 total knee arthroplasties and 21 medial unicompartmental knee arthroplasties. The arthroplasties were evaluated for aseptic loosening during the year 2000. For total arthroplasty we used 77 porous-coated anatomic prostheses and 29 press-fit condylar prostheses. The mean bone mineral content of the proximal tibia, measured the day before surgery using dual-photon absorptiometry was 5.48 g/cm for the porous-coated anatomic prostheses which were revised for aseptic loosening (n = 9). This was significantly higher (p = 0.02) than the mean of 4.33 g/cm for those which were not revised. Values for the two revised press-fit condylar knees (4.78 and 4.93 g/cm) were above the mean value (4.23 g/cm) for those which were not revised. We found no statistically significant (p = 0.38) difference between the bone mineral content of the 12 revised and nine unrevised unicompartmental arthroplasties. Low trabecular bone quality, measured as the pre-operative bone mineral content of the proximal tibia, was not a predictor for later revision surgery following uncemented total knee or unicompartmental knee arthroplasty.

Selenium regulates expression in rat liver of genes for proteins involved in iron metabolism.

Suppression subtractive hybridization analysis in our laboratory recently revealed that transferrin mRNA may be elevated in Sedeficient rat liver. In this work, we compared expression in rat liver of genes for transferrin, transferrin receptor, ferritin light and heavy chains, and iron-regulatory proteins 1 and 2 in Se adequacy and deficiency. Weanling male Sprague-Dawley rats were fed Torula yeast diets supplemented with 0 or 0.15 microg Se/kg diet as sodium selenite for 15 wk. Activity of cellular glutathione peroxidase was virtually abolished in Se-deficient rat liver, whereas activity of glutathione S-transferase was 43% higher than in Se-adequate liver. There were no differences in hematocrit, hemoglobin, or liver iron content. To examine differential gene expression, we used a multiplex relative reverse transcriptase-polymerase chain reaction method. Three of the six genes examined showed modest but consistent upregulation in Se deficiency. Transferrin mRNA was 30% more abundant in Se-deficient than in Se-adequate liver. For the transferrin receptor, the difference was 32%, and for iron regulatory protein 1, it was 63%. No consistent differences were observed for iron regulatory protein 2 or for ferritin light or heavy chain. These findings suggest a possible role for dietary Se in moderating iron metabolism.

Susceptibility of S49 lymphoma cell membranes to hydrolysis by secretory phospholipase A(2) during early phase of apoptosis.

During cell death, plasma membranes of cells become vulnerable to attack by extracellular secretory phospholipase A(2). The purpose of this study was to identify the timing of this phenomenon relative to other events that occur during the process of cell death. Death was induced in S49 murine lymphoma cells by treatment with dexamethasone, dibutyryl cAMP, ionomycin, thapsigargin, or heat shock (1 h at 43 degrees C). The appearance of membrane susceptibility to secretory phospholipase A(2) was compared to the following apoptotic events: loss of mitochondrial membrane potential, phosphatidylserine exposure in the outer leaflet of the cell membrane, early DNA damage assessed by the comet assay, and changes in cell size and internal complexity assessed by flow cytometry. Each inducer of death was distinct in the time course of events produced. Although dead cells were susceptible to the action of phospholipase A(2), live cells (impermeable to propidium iodide) also became vulnerable to the enzyme during characteristic time courses after exposure to each inducer. In fact, susceptibility to sPLA(2) was observed in each case prior to or concurrent with the earliest of the markers of apoptosis. These results demonstrate that the onset of susceptibility to sPLA(2) is an early event in apoptosis suggesting that changes in membrane structure may be relevant to initial aspects of the apoptotic process.

Influence of cuff size on blood pressure among schoolchildren.

In 236 schoolchildren aged 7-15 years arm blood pressure was measured using a semiautomatic technique. Three different cuffs were chosen among four cuffs with bladder sizes of either 6 x 20 cm, 9 x 27 cm, 12 x 35 cm or 15 x 43 cm. Ideal cuff size in each pupil was defined as the one in which the width of the bladder was closest to 40% of arm circumference. In all subjects ideal cuffs were tested along with two cuffs bigger or smaller than the ideal one. The study showed that "normal blood pressure" in relation to age depended on the cuff used. Using the ideal one, systolic blood pressure increased from 105 mmHg at 7 years of age to 117-119 mmHg at age 11, with no further increase at higher ages, while diastolic blood pressure was almost unchanged in the different age groups. Normal blood pressure curves constructed using the same cuff in all children showed a steeper increase in both systolic and diastolic blood pressure in relation to age compared to the curve based on the ideal cuff in all children. It is strongly recommended that future studies should take the best-suited cuff problem into consideration when planning studies among children. Some of the differences between previous published studies may be explained by the differences introduced by different cuff sizes.

Definition of the specific roles of lysolecithin and palmitic acid in altering the susceptibility of dipalmitoylphosphatidylcholine bilayers to phospholipase A2.

Bilayers composed of phosphatidylcholine initially resist catalysis by phospholipase A2. However, after a latency period, they become susceptible when sufficient reaction products (lysolecithin and fatty acid) accumulate in the membrane. Temperature near the main bilayer phase transition and calcium concentration modulate the effectiveness of the reaction products. The purpose of this study was to examine the individual contributions of lysolecithin and palmitic acid to the susceptibility of dipalmitoylphosphatidylcholine vesicles and to rationalize the effects of temperature and calcium. Various fluorescent probes (Prodan, Laurdan, pyrene-labeled fatty acid, and dansyl-labeled phospholipid) were used to assess changes in the ability of the reaction products to perturb the bilayer and to affect the interactions with the enzyme. Un-ionized palmitic acid decreased bilayer polarity and perturbed the membrane surface exposing some of the Prodan to bulk water. Lysolecithin increased bilayer polarity and the rate of dipolar relaxation in response to the excited states of Laurdan and Prodan. A combination of the individual contributions of each product was observed when palmitic acid and lysolecithin were present together at low calcium, and the effects of lysolecithin dominated at high calcium. Palmitic acid, but not lysolecithin, promoted the binding of phospholipase A2 to the bilayer surface in the absence of calcium. Lysolecithin reduced the ability of fatty acid to enhance binding apparently by altering the structure of fatty acid domains in the membrane. Furthermore, increased temperature and ionization of the fatty acid tended to cause segregation of bound phospholipase A2 into domains poor in phospholipid content which presumably impeded bilayer hydrolysis. In contrast, un-ionized palmitic acid and lysolecithin promoted hydrolysis by augmenting a step distal to the adsorption of enzyme to the bilayer. This kinetic response to lysolecithin was calcium-dependent. A model accounting for these varied influences of the reaction products is presented.

Blood pressure measurement in childhood and adolescence. International recommendations and normal limits of blood pressure.

BLOOD PRESSURE MEASUREMENTS IN CHILDREN SHOULD BE BASED ON THE FOLLOWING RULES: 1. Resting period prior to readings should be about 5-10 minutes. In children under 5 years of age, lying position should be used. In older children sitting position is most suitable. 2. Either flush method or ultrasound technique should be used in newborn. Auscultatory blood pressure is suitable in other children. 3. Width of cuff should be based on circumference of the arm, and not on arm-length: (width = 120% of diameter = 40% of circumference, i.e., 3, 6, 9, 12, or 15 cm). Length of cuff-bladder = circumference or more. 4. Diastolic blood pressure should be read at muffling of Korotkoff sounds (phase IV). 5. Although some agreement exists between different studies, it is obvious, that definition of "normal blood pressure" in children is dependent on the methodological factors involved in the measurement of blood pressure.

Multiple fractures in a young diabetic patient.

Multiple fractures in a patient with juvenile diabetes mellitus are reported. The fractures could be spontaneous due to osteopenia caused by reduced bone mass found in diabetic patients. Bone and joint changes had a severe progression due to diabetic neuropathy. The importance of clinical and radiological examination is emphasized.

The Neer classification of fractures of the proximal humerus. An assessment of interobserver variation.

The reliability of the Neer classification of proximal fractures of humerus was examined by determining the agreement between pairs of observers using weighted kappa statistics. Anteroposterior and lateral radiographs of 100 surgical neck fractures were grouped independently by four observers. A low degree of agreement was found, especially between the most inexperienced observer and the rest. Considering the therapeutic consequences of a correct classification, these fractures should be assessed by experienced orthopedic surgeons or radiologists.

[Estrogen/gestagen induced hypertension. A follow-up study on treatment and subsequent occurrence of hypertension]. / Ostrogen/gestagen-induceret hypertension. Et opfølgningsstudium med henblik på behandling og senere forekomst af forhøjet blodtryk.

PIP: Between 1976-83, 126 cases of suspected estrogen/progestogen hormone-induced hypertension were reported. Probability was established in 86 of the cases. 84 cases were linked to oral contraceptives (OCs). In 72 patients, blood pressure returned to normal levels after withdrawal of the OCs although temporary antihypertensive treatment was necessary in 23 cases. 14 patients remained hypertensive and 18 women were subsequently re-exposed to hormones with the consequent rise in blood pressure for 4 patients. Of the 72 women whose blood pressure returned to normal levels, follow-up data were available for 55 of them; among them, hypertension was then discovered in 14 (25%). Women with previous increases in blood pressure during OC administration required regular blood pressure control. (author's modified)^ieng