The current status of histidine-rich proteins in malaria parasites with regard to their genomic organization, protein structure and function is discussed, one of such protein present in an avian malaria parasite Plasmodium lophurae contains about 73% histidine and called as HRP (histidine-rich protein). Among human malaria parasites, in Plasmodium falciparum, only three such proteins have been described, namely knob protein also known as knob associated histidine-rich protein (KP or KAHRP), soluble histidine-alanine rich protein (soluble HARP or PfHRP II) and small histidine-alanine rich protein (SHARP) containing 8, 35 and 30% histidine contents respectively. With rapid emergence of powerful tools in molecular biology the genes of all these histidine-rich proteins have been cloned and sequenced within a short period of time. The genomic organizations of all these proteins are very much similar to each other, in each case the gene contains a signal peptide coding sequence (exon 1) followed by an intron. This intron is followed by the main coding region (exon 2) which has no further intervening sequences. In the main coding region of each gene, the histidine-rich sequences start after 25-30 amino acids from N-terminal end (75-90 nucleotides from 5' in exon 2). All the three histidine-rich proteins of P. falciparum share some homology with the HRP of P. lophurae; they all cross react with anti HRP and incorporate higher amount of exogenous histidine. The relationship between KP and HRP resides in the repeated polyhistidine sequences, (His) 6-9, from the core of the multiple tandem repeats of HRP, whereas, the peptide Ala-His-His is commonly shared by HRP and two other proteins of P. falciparum (soluble HARP and SHARP).(ABSTRACT TRUNCATED AT 250 WORDS)

We show that infants' long-term memory representations for melodies are not just reduced to the structural features of relative pitches and durations, but contain surface or performance tempo- and timbre-specific information. Using a head turn preference procedure, we found that after a one week exposure to an old English folk song, infants preferred to listen to a novel folk song, indicating that they remembered the familiarized melody. However, if the tempo (25% faster or slower) or instrument timbre (harp vs. piano) of the familiarized melody was changed at test, infants showed no preference, indicating that they remembered the specific tempo and timbre of the melodies. The results are consistent with an exemplar-based model of memory in infancy rather than one in which structural features are extracted and performance features forgotten.

BACKGROUND

Pixel-based multimodality tissue tracking (MTT) is a new noninvasive method for the quantification of cardiac deformation from cine image of MRI. The aim of this study is to validate bi-ventricular strain measurement by MTT compared to strain-encoding (SENC) MRI and harmonic phase (HARP) MRI in pulmonary hypertension (PH) patients.

METHODS

In 45 subjects (30 PH patients and 15 normal subjects), RV and LV peak global longitudinal strains (Ell) were measured from long axis 4 chamber view using MTT. LV peak global circumferential strains (Ecc) by MTT were measured from short axis. For validation, RV and LV Ell by MTT were compared to measures by SENC-MRI from short axis, and LV Ecc by MTT was compared to measures by short axis tagged MRI analysis (HARP). Reproducibility of MTT was also determined.

RESULTS

MTT quantified RV Ell correlated closely to those of SENC (r=0.72, p<0.001), with good limits of agreement. LV Ell quantified by MTT showed moderate correlation with SENC (r=0.57, p=0.001), and LV Ecc by MTT also showed moderate correlation with HARP (-16.9±4.1 vs -14.3±3.5, p<0.001 for all, r=0.60, p<0.001). RV Ell negatively correlated with RVEF (r=-0.53, p=0.001) and also positively correlated with mean PAP in PH patients (r=0.60, p=0.001). Strain measurement by MTT showed high reproducibility.

CONCLUSIONS

We demonstrate that MTT is a reproducible tool for quantification of cardiac deformation using cine images in PH patients. Hence, it could serve as a new rapid and comprehensive technique for clinical assessment of regional cardiac function.

MR tagging allows noninvasive examination of regional myocardial function with high accuracy and reproducibility. The current tagging method is limited by low tagging resolution for accurate transmural strain quantification. Previously, a spatial modulation of magnetization (SPAMM)-based method was proposed to increase the tagging resolution by combining two or more tagged images with different tagging grid positions. However, there has been limited application due to the challenge in image processing of multiple data sets. In the current study, we propose a harmonic phase (HARP)-based method for automated and fast analysis of high tagging resolution images. First-order harmonic peaks from low tagging resolution images were combined to generate the composite second-order harmonic peak for strain computation. The combined images reached a tagging resolution of 0.3 mm. The proposed method was applied to the quantification of transmural myocardial wall strain in seven normal C57BL/6 mice. Principal strains, as well as radial and circumferential strains, were quantified using the current method.

Tagged Magnetic Resonance Imaging (MRI) is a noninvasive technique for examining myocardial function and deformation. Tagged MRI can also be used in quasi-static MR elastography to acquire strain maps of other biological soft tissues. Harmonic phase (HARP) provides automatic and rapid analysis of tagged MR images for the quantification and visualization of myocardial strain. We propose a new artifact reduction method in strain maps. Image intensity of the DC component is estimated and subtracted from spatial modulation of magnetization (SPAMM) tagged MR images. DC peak interference in harmonic phase extraction is greatly reduced after DC component subtraction. The proposed method is validated using both simulated and MR acquired tagged images. Strain maps are obtained with better accuracy and smoothness after DC component subtraction.

Using a virus neutralization technique, we found phocine distemper virus (PDV) antibody in 130 (83% of 157) harp seals (Phoca groenlandica) from the western North Atlantic sampled between 1988 and 1993 inclusive. In contrast, only 44 (24% of 185) hooded seals (Cystophora cristata) had antibodies against PDV even though they were sympatric with harp seals and were sampled over a similar period, from 1989 to 1994 inclusive. Antibodies occurred in 106 (41%) of 259 ringed seals (Phoca hispida); this prevalence was higher than expected given the solitary behavior and territoriality characteristic of this species. Seropositive ringed seals were found at each of seven locations across Arctic Canada from Baffin Bay to Amundsen Gulf at which samples were collected between 1992 and 1994. However, the prevalence of infection was highest where ringed seals are sympatric with harp seals in the eastern Canadian Arctic.

Mutations in the triple PDZ domain-containing protein harmonin have been identified as the cause of Usher deafness syndrome type 1C. Independently, we identified harmonin in a screen for genes expressed in pancreatic beta cells. Using a yeast two-hybrid assay, we show that the first PDZ domain of harmonin interacts with a novel protein, designated harp for harmonin-interacting, ankyrin repeat-containing protein. This interaction was confirmed in an over-expression system and in mammalian cells, and shown to be mediated by the three C-terminal amino acids of harp. Harp is expressed in many of the same epithelia as harmonin and co-localization of native harp and harmonin was demonstrated by confocal microscopy in pancreatic duct epithelium and in a pancreatic beta-cell line. Harp, predicted molecular mass 48 kDa, has a domain structure which includes three ankyrin repeats and a sterile alpha motif. Human harp maps to chromosome 16, and its mouse homologue to chromosome 7. Sequences with similarity to harp include the sans gene, mutations of which are responsible for deafness in the Jackson shaker 2 (js) mutant mouse and in human Usher syndrome type 1G. The functional domain structures of harp and harmonin, their interaction under native conditions and their co-localization suggest they constitute a scaffolding complex to facilitate signal transduction in epithelia.

Excised lungs from eight marine mammal species [harp seal (Pagophilus groenlandicus), harbor seal (Phoca vitulina), gray seal (Halichoerus grypush), Atlantic white-sided dolphin (Lagenorhynchus acutus), common dolphin (Delphinus delphis), Risso's dolphin (Grampus griseus), long-finned pilot whale (Globicephala melas) and harbor porpoise (Phocoena phocoena)] were used to determine the minimum air volume of the relaxed lung (MAV, N=15), the elastic properties (pressure-volume curves, N=24) of the respiratory system and the total lung capacity (TLC). Our data indicate that mass-specific TLC (sTLC, l kg(-1)) does not differ between species or groups (odontocete vs phocid) and agree with that estimated (TLC(est)) from body mass (M(b)) by applying the equation: TLC(est)=0.135 M(b)(0.92). Measured MAV was on average 7% of TLC, with a range from 0 to 16%. The pressure-volume curves were similar among species on inflation but diverged during deflation in phocids in comparison with odontocetes. These differences provide a structural basis for observed species differences in the depth at which lungs collapse and gas exchange ceases.

We tested the sampling methods of a volunteer-based monitoring program designed to detect the non-indigenous spiny water flea, Bythotrephes longimanus, and found that the program could detect the majority of Bythotrephes invasions. Volunteers take two vertical hauls with a 30 cm diameter net at each of three pelagic stations. To determine if the volunteers were using a large enough net at their three stations, we performed a 17-lake comparison of the volunteer's net with a 75 cm diameter, research-grade net. We found no difference in the number of stations at which Bythotrephes was detected (paired t-test, p = 0.155) with the two nets, because Bythotrephes densities were above the detection limits for both nets. To determine if three stations were sufficient to detect the invader with the volunteer's net, we deployed it at 30 stations in two lakes with average (Harp Lake, 4.17 Bythotrephes m(-3)) vs. low Bythotrephes densities (Sugar Lake, 0.92 m(-3)). In Harp Lake, repeated randomized sampling of the 30 sets of data indicated that only three stations were needed for 100% capture success. In Sugar Lake, seven stations were needed for 100% capture success, but three stations, the current program design, failed to detect the invasion only 14% of the time.

Standard hematologic and serum chemistry parameters were determined from 28 harp seals (Phoca groenlandica) and 20 hooded seals (Cystophora cristata) sampled from 6 March 2001 to 13 March 2001 during the breeding season. Whole blood was collected immediately postmortem from harp seal mother-pup pairs and from six hooded seal pups, and from live-captured adult hooded seals and three hooded seal pups; blood was analyzed within 24 hr at a local human hospital. A certified veterinary laboratory validated subsamples of whole blood and analyzed all serum chemistry parameters. Significant interlaboratory differences in mean values of packed cell volume (PCV) and mean cell volume (MCV) were found. Significant differences were found between samples from the five seal groups (adult male hooded seals, lactating female hooded seals, unweaned hooded seal pups; lactating female harp seals, and unweaned harp seal pups) for hematology and most serum chemistry parameters. In general, age-class influenced mean values of PCV, hemoglobin (HB), red blood cell (RBC) counts, MCV, mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), and nucleated red blood cell (NRBC) counts per 100 leucocytes, but most age-related variations were species specific. Harp seal pups had significantly lower mean values of HB, PCV, MCH, and MCHC than did other seal groups, and significantly lower mean RBC counts than did hooded seal pups. Mean NRBC counts per 100 leukocytes were more than three times higher in harp seal pups than in hooded seal pups, but this difference was not statistically significant. Mean MCV were significantly lower in harp and hooded seal pups compared to those of adult harp and hooded seals. Differences in hemograms between pup species were likely because of the precocious development of hooded seal pups, which are weaned within 4 days, compared to 12 days for harp seal pups. Among adult seal groups, male hooded seals had significantly higher mean values of PCV and HB than did female harp and hooded seals, and significantly higher mean RBC counts than did adult female hooded seals. Among adult females, mean values of MCH and MCHC were statistically higher in hooded seals than in harp seals. Adult female harp and hooded seals did not differ significantly in other RBC parameters and mean leukocyte counts. Mean values of glucose, blood urea nitrogen, total bilirubin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein, and albumin showed species-specific variations between adults and pups. Except for ALP, few significant differences in mean enzyme activities of aspartate aminotransferase (AST), ALT, creatine kinase and gamma-glutamyltransferase were found between seal groups. Mean concentrations of electrolytes (calcium, phosphorus, sodium, potassium, chloride, magnesium, and total carbon dioxide) varied with age class, but variations in potassium and magnesium were species specific. Harp seal pups had significantly higher mean phosphorus and potassium levels compared to other seal groups.

Since the recent discovery of Helicobacter cetorum in cetaceans and its role in the development of gastritis, speculation has existed as to whether pinnipeds have Helicobacter spp. associated gastritis and peptic ulcer disease. The gastric mucosa of 4 stranded harp seals Phoca groenlandica from the Massachusetts coastline were assessed for Helicobacter spp. by culture and PCR. We cultured 2 novel Helicobacter spp. from the pyloric antrum of 1 of the 4 harp seals studied, and identified these by PCR in 2 of the 4 seals. Both gram-negative bacterial isolates were catalase- and oxidase-positive. However, a fusiform helicobacter with flexispira morphology was urease-positive, and a spiral-shaped helicobacter was urease-negative. Slender, spiral and fusiform-shaped bacteria were detected in the gastric mucosa by the Warthin-Starry stain. Histopathologic analysis revealed mild diffuse lymphoplasmacytic gastritis within the superficial mucosa of the pyloric antrum of both infected seals. The 2 bacterial isolates were classified by 16S rRNA analysis; they clustered with other enteric helicobacters and represent 2 novel Helicobacter spp. The urease-negative bacterial isolate clustered with H. canis and the urease-positive isolate clustered with an isolate from a sea lion and isolates from sea otters. This cluster of pinniped isolates has 97 % similarity to a number of Helicobacter species, but appears to be most closely related to other helicobacters with flexispira morphology. These findings suggest that the novel Helicobacter spp. may play a role in the etiopathogenesis of gastrointestinal diseases in pinnipeds. To our knowledge, this represents the first isolation and characterization of a novel Helicobacter spp. from pinnipeds.

BACKGROUND

Anxiety disorders are known to commonly coexist in individuals, both with other anxiety disorders and with mental disorders from other groupings, such as affective disorders. We questioned how frequently anxiety disorders actually occur in isolation, as "pure cultures."

METHODS

We examined diagnostic patterns among the 711 subjects entered into a large, multicenter study of anxiety disorders, the Harvard/ Brown Anxiety Disorders Research Program (HARP), which focused on panic, agoraphobia, generalized anxiety disorder, and social phobias as "index disorders" required for intake.

RESULTS

We used various definitions for "pure culture." By all definitions, subjects with "pure culture" represented a minority, especially in cases of generalized anxiety disorder and social phobia, where comorbidity was virtually ubiquitous. "Pure culture" status was associated with later onset of illness and less chronicity.

CONCLUSIONS

Future studies of anxiety disorder should aim to document the extensive comorbidity, rather than eliminate it by restrictive diagnostic exclusion criteria, lest they yield atypical or even misrepresented groups of patients. Clinicians should not stop at identifying only the "main" diagnosis but look for other, comorbid diagnoses that are often present.

OBJECTIVE

To compare local sine-wave modeling (SinMod) with harmonic phase analysis (HARP), for assessment of left ventricular (LV) circumferential strain (εcc) from tagged cardiovascular magnetic resonance images.

METHODS

Mid-ventricular spatial modulation of magnetization was performed in 60 participants (15 each with hypertrophic, dilated or ischemic cardiomyopathy and 15 healthy controls) at 1.5 Tesla. Global and segmental peak transmural εcc were measured using HARP and SinMod. Repeated measurements were performed on 25% of examinations to assess observer variability. Effect of contrast was assessed in 10 additional patients.

RESULTS

SinMod showed a high level of agreement with HARP for global εcc (mean difference -0.02, 95% limits of agreement -6.46 to 6.43%). Agreement was much lower for segmental εcc. Both methods showed excellent observer agreement for global εcc (intraclass correlation coefficient >0.75). Observer agreement for segmental εcc was also excellent with SinMod, but was significantly lower with HARP. Analysis time was significantly shorter using SinMod. Pre- and postcontrast εcc measurements were not significantly different using either technique, although postcontrast measurements showed greater variability with HARP.

CONCLUSIONS

SinMod and HARP-based measurements of global εcc have a high level of agreement, but segmental agreement is substantially lower. SinMod has generally lower observer variability, is faster and is less affected by contrast, but requires further validation.

HARP (heparin affin regulatory peptide) is a growth factor displaying high affinity for heparin. In the present work, we studied the ability of human recombinant HARP as well as its two terminal peptides (HARP residues 1-21 and residues 121-139) to promote angiogenesis. HARP stimulates endothelial cell tube formation on matrigel, collagen and fibrin gels, stimulates endothelial cell migration and induces angiogenesis in the in vivo chicken embryo chorioallantoic membrane assay. The two HARP peptides seem to be involved in most of the angiogenic effects of HARP. They both stimulate in vivo angiogenesis and in vitro endothelial cell migration and tube formation on matrigel. We conclude that HARP has an angiogenic activity when applied exogenously in several in vitro and in vivo models of angiogenesis and its NH(2) and COOH termini seem to play an important role.

HARP (heparin affin regulatory peptide) is an 18 kDa heparin binding protein, also known as HB-GAM or pleiotrophin (PTN) which has been primarily isolated from brain and uterus, and displays neurite outgrowth, angiogenic and mitogenic activities. Previously, we have expressed the human cDNA encoding human HARP in NIH 3T3 cells. Purified recombinant HARP displayed mitogenic activity for endothelial cells. Its NH2-terminal sequence indicates that the HARP molecule possesses a three amino acid extension from the signal peptide more than the NH2-terminal described. For HB-GAM or PTN, these three amino acids may be essential for the stability and the mitogenic activity of this growth factor. In an attempt to further study the mode of action of this growth factor, we have investigated the mitogenic effect of HARP on various cell types. In contrast to FGF-2, HARP failed to induce stimulation of DNA synthesis on a CCL39 cell line. However, we found that in quiescent bovine epithelial lens (BEL) cells, the stimulation of DNA synthesis induced by HARP is dose-dependent (EC50: 2.5 ng/ml) and maximal stimulation is as potent as that induced by FGF-2 (EC50: 25 pg/ml). Interestingly, when BEL cells were allowed to quiesce in the presence of serum, the stimulation induced by HARP is considerably less potent. In this highly responsive cell system, heparin could potentiate the mitogenic activity of HARP at very low doses (0.1-1 microgram/ml) and inhibit this activity at concentrations of 10 micrograms/ml. In contrast to its protective effect on FGF-1 and -2, heparin was unable to preserve HARP from tryptic and chymotryptic degradations.

BACKGROUND

Combination drug therapy has been shown to decrease cholesterol levels in hyperlipidemic patients. However, its efficacy has not been well studied in patients previously considered to be normolipidemic, many of whom are now candidates for this therapy.

OBJECTIVE

To determine the efficacy and tolerability of multidrug therapy designed to improve low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels in patients with coronary heart disease and average lipid levels.

METHODS

Randomized, placebo-controlled, 2.5-year trial comparing patients receiving usual care with patients receiving stepped-care drug therapy.

METHODS

Stepped-care therapy (pravastatin, nicotinic acid, cholestyramine, and gemfibrozil) to decrease total cholesterol levels to less than 4.1 mmol/L (160 mg/dL) and the ratio of LDL cholesterol to HDL cholesterol to less than 2.0.

METHODS

2 academic, urban, tertiary care hospitals.

METHODS

91 patients (80 men and 11 women) with coronary heart disease, a mean age of 60 years, total cholesterol levels less than 6.4 mmol/L (250 mg/dL) at baseline, and ratios of total cholesterol to HDL cholesterol greater than 4.0 at baseline.

METHODS

Fasting serum lipoprotein profile, fasting apolipoprotein levels, and frequency of adverse effects. Patients were assessed every 6 weeks during drug titration and every 3 months thereafter.

RESULTS

Mean lipid levels at baseline were as follows: total cholesterol, 5.5 mmol/L (214 mg/dL); LDL cholesterol, 3.6 mmol/L (140 mg/dL); HDL cholesterol, 1.1 mmol/L (42 mg/dL); and triglycerides, 1.8 mmol/L (159 mg/dL). With pravastatin, changes in levels from baseline were -22% for total cholesterol, -32% for LDL cholesterol +8% for HDL cholesterol, and -15% for triglycerides (P < 0.001 for all comparisons). With the addition of 1.5 g of nicotinic acid, additional changes were -6% for total cholesterol (P < 0.002). -11% for LDL cholesterol, +8% for HDL cholesterol, and -10% for triglycerides (P < 0.001 for all comparisons). With 2.25 to 3 g of nicotinic acid, these changes were -7% for total cholesterol (P = 0.007), -14% for LDL cholesterol (P < 0.001), +6% for HDL cholesterol (P = 0.02), and -13% for triglycerides (P = 0.03). With cholestyramine, total cholesterol and LDL cholesterol levels were unchanged compared with the previous step; the change in HDL cholesterol level was -8% (P = 0.03); and the change in triglyceride level was +46% (P < 0.001). With gemfibrozil, total cholesterol level was unchanged; the additional change in LDL cholesterol level was +12% (P = 0.09); the change in HDL cholesterol level was +12% (P = 0.03); and the change in triglyceride level was -37% (P < 0.001). Apolipoprotein B levels decreased by 25% overall (P < 0.001); lipoprotein(a) levels did not change significantly. Adverse effects were primarily attributable to nicotinic acid or cholestyramine. In 18 of the 35 patients (50%) whose baseline LDL cholesterol levels were greater than 3.35 mmol/L (130 mg/dL), pravastatin decreased LDL cholesterol levels to 2.6 mmol/L (100 mg/dL) or less by 6 weeks; 70% of patients needed combination therapy to reach this National Cholesterol Education Program goal during the 2.5 years of the study. Adding nicotinic acid to pravastatin produced LDL cholesterol levels of 2.6 mmol/L or less in 15 more of these 35 patients, so that 94% (n = 33) of the patients receiving these two drugs reached this goal.

CONCLUSIONS

To reach current goals for LDL cholesterol levels, most normolipidemic patients with coronary heart disease in this study needed combination therapy. Pravastatin with nicotinic acid and pravastatin with gemfibrozil are well-tolerated combinations that can maintain target LDL cholesterol levels, decrease triglyceride levels, and increase HDL cholesterol levels. Adding resin to these combinations produced no further benefit.

Rapid climate changes are occurring in the Arctic, with substantial repercussions for arctic ecosystems. It is challenging to assess ecosystem changes in remote polar environments, but one successful approach has entailed monitoring the diets of upper trophic level consumers. Quantitative fatty acid signature analysis (QFASA) and fatty acid carbon isotope (δ(13) C-FA) patterns were used to assess diets of East Greenland (EG) polar bears (Ursus maritimus) (n = 310) over the past three decades. QFASA-generated diet estimates indicated that, on average, EG bears mainly consumed arctic ringed seals (47.5 ± 2.1%), migratory subarctic harp (30.6 ± 1.5%) and hooded (16.7 ± 1.3%) seals and rarely, if ever, consumed bearded seals, narwhals or walruses. Ringed seal consumption declined by 14%/decade over 28 years (90.1 ± 2.5% in 1984 to 33.9 ± 11.1% in 2011). Hooded seal consumption increased by 9.5%/decade (0.0 ± 0.0% in 1984 to 25.9 ± 9.1% in 2011). This increase may include harp seal, since hooded and harp seal FA signatures were not as well differentiated relative to other prey species. Declining δ(13) C-FA ratios supported shifts from more nearshore/benthic/ice-associated prey to more offshore/pelagic/open-water-associated prey, consistent with diet estimates. Increased hooded seal and decreased ringed seal consumption occurred during years when the North Atlantic Oscillation (NAO) was lower. Thus, periods with warmer temperatures and less sea ice were associated with more subarctic and less arctic seal species consumption. These changes in the relative abundance, accessibility, or distribution of arctic and subarctic marine mammals may have health consequences for EG polar bears. For example, the diet change resulted in consistently slower temporal declines in adipose levels of legacy persistent organic pollutants, as the subarctic seals have higher contaminant burdens than arctic seals. Overall, considerable changes are occurring in the EG marine ecosystem, with consequences for contaminant dynamics.

Heparin affin regulatory peptide (HARP) is a 18-kDa heparin-binding polypeptide that is highly expressed in developing tissues and in several primary human tumors. It seems to play a key role in cellular growth and differentiation. In vitro, HARP displays mitogenic, angiogenic, and neurite outgrowth activities. It is a secreted protein that is organized in two beta-sheet domains, each domain containing a cluster of basic residues. To assess determinants involved in the biological activities of HARP, C-terminally truncated proteins were produced in Chinese hamster ovary-K1 cells and tested for their mitogenic, tumor formation in nude mice and neurite outgrowth activities. Our data clearly indicate that the residues 111-136 of the lysine-rich C-terminal domain are involved in the mitogenic and tumor formation activities of HARP. Correlatively, no signal transduction was detected using the corresponding mutant, suggesting the absence of HARP binding to its high affinity receptor. However, this C-terminal domain of HARP is not involved in the neurite outgrowth activity. We also demonstrate that HARP signal peptide cleavage could led to two maturated forms that are both but differentially mitogenic.

Seals have adapted to the high heat transfer coefficient in the aquatic environment by effective thermal insulation of the body core. While swimming and diving, excess metabolic heat is supposed to be dissipated mainly over the sparsely insulated body appendages, whereas the location of main heat sinks in hauled-out seals remains unclear. Here, we demonstrate thermal windows on the trunk of harbour seals, harp seals and a grey seal examined under various ambient temperatures using infrared thermography. Thermograms were analysed for location, size and development of thermal windows. Thermal windows were observed in all experimental sessions, shared some common characteristics in all seals and tended to reappear in similar body sites of individual seals. Nevertheless, the observed variations in order and location of appearance, number, size and shape of thermal windows would imply no special anatomical site for this avenue of heat loss. Based on our findings, we suggest that, in hauled-out seals, heat may be transported by blood flow to a small area of the wet body surface where the elevation of temperature facilitates evaporation of water trapped within the seals' pelages due to increased saturation vapour pressure. The comparatively large latent heat necessary for evaporation creates a temporary hot spot for heat dissipation.

We describe the clinical and laboratory studies of an 11-year-old girl with prominent orofacial dyskinesia, dystonia, and progressive dementia. Investigations revealed hypoprebetalipoproteinemia, acanthocytosis, atypical retinitis pigmentosa, and evidence of iron deposition in the pallidal nuclei. Electroneuromyography and skin and sural nerve biopsies were normal. The "eye-of-the-tiger" sign, used to describe the pallidal nuclei in Hallervorden-Spatz syndrome, was present on T2-weighted MRIs (GE Signa, 1.5 T). Phase-contrast microscopy of whole blood showed 80 to 90% acanthocytes whose morphology was confirmed by electron microscopy. High-resolution lipoprotein electrophoresis demonstrated an absence of the pre-beta fraction. This case differs phenotypically from the previous reports of Hallervorden-Spatz disease with acanthocytosis by the presence of prominent orofacial dyskinesia and abnormal serum lipoproteins.

Heparin affin regulatory peptide (HARP) is an heparin-binding growth factor, highly expressed in several primary human tumors and considered as a rate-limiting angiogenic factor in tumor growth, invasion, and metastasis. Implication of this protein in carcinogenesis is linked to its mitogenic, angiogenic, and transforming activities. Recently, we have demonstrated that the C-terminal residues 111-136 of HARP are required for its mitogenic and transforming activities (Bernard-Pierrot, I., Delbe, J., Caruelle, D., Barritault, D., Courty, J., and Milhiet, P. E. (2001) J. Biol. Chem. 276, 12228-12234). In this paper, HARP deleted of its last 26 amino acids was shown to act as a dominant negative effector for its mitogenic, angiogenic, transforming, and tumor-formation activities by heterodimerizing with the wild type protein. Similarly, the synthetic corresponding peptide P111-136 displayed in vitro inhibition of wild type HARP activities, but in this case, the inhibition was mainly explained by the competition of the peptide with HARP for the binding to the extracellular domain of the high affinity ALK receptor.

Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aβ), tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aβ, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).

Samples of blubber, liver, kidney and brain, obtained from 10 male, 6 female neonatal, and 4 lactating female harp seals (Pagophilus groenlandicus), were analysed for DDT, dieldrin, PCB, and total mercury. Methyl mercury levels in blood were also determined. Biocide deposition was not significantly different in female and male ten day old pups. There were no significant differences in biocide levels in the liver of the 14/+ day old males, but in blubber there were significant differences in dieldrin and DDT. There was no clear relationship between biocide levels in the 6-18 year old lactating adults and their pups. Younger adult seals (6 and 7 years) were found to have higher levels of PCB and sigmaDDT levels in their blubber than did older females (10 and 18 years). Wide intraspecific variation was noted in organochlorine and mercury residue levels. Pups taken in 1973 were found to have lower organochlorine residues than pups taken in the same area in 1971. Preliminary investigation indicates that detectable amounts of organochlorine and mercury residues are capable of crossing the placenta in the harp seal.

An epizootic of morbillivirus infection killed thousands of common seals (Phoca vitulina) in European seas in 1988. Most of the affected seals had respiratory signs and the main post mortem finding was acute pneumonia. The histopathological changes were similar to those of canine distemper. Six common porpoises (Phocoena phocoena) found stranded on the coast of Northern Ireland in late 1988 had similar lesions. Morbillivirus infection also killed several thousand Siberian seals (Phoca siberica) in Lake Baikal in 1987 and 1988. A morbillivirus (phocine distemper virus) has been isolated from affected seals in several European countries and studies of the antigenicity of the virus indicate that it has several unique epitopes that distinguish it from the other known morbilliviruses. Biochemical studies of the viral proteins, RNA and nucleotide sequence confirm that it is a new morbillivirus. There is seroepizootiological evidence of morbillivirus infection in Greenland harp seals (Pagophilus groenlandicus), ringed seals (Phoca hispida) and Dutch common seals several years before the 1988 epizootic. Antibodies to a morbillivirus have also been found in bottlenose dolphins (Tursiops truncatus) from the eastern coast of the USA. Further studies are required to determine whether these sea mammal populations have been infected with phocine distemper virus.