Function and structure of pressurized and perfused porcine carotid arteries: effects of in vitro balloon angioplasty

In this report we describe the application of an in vitro pressure-perfusion system for study of functional/structural changes after in vitro balloon dilation injury. Pig carotid arteries were perfused at P = 100 mm Hg and Q = 100 ml/min, balloon angioplastied (BA), and cultured under these hemodynamic conditions for 4 or 8 days (n = 5 BA and 6 controls for each time point). To assess endothelial function, outer diameter changes in response to bradykinin (BK) were measured daily. Remodeling was determined from the shift in pressure-passive diameter relation, as obtained after papaverine addition. Arterial samples were processed for histology. Control arteries showed spontaneous tone, BK-induced relaxation, and inward remodeling that was more pronounced at day 8 (ratio end-to-start passive diameter at P = 100 mm Hg, 0.69 +/- 0.04; P < 0.001) than at day 4 (0.85 +/- 0.03, P = 0.03). Intimal hyperplasia was detectable in these control vessels at day 8 with accumulation of alpha-smooth muscle actin-positive cells around the lumen. Angioplasty caused ruptures and dissections and abolished tone that returned after 5 days of perfusion along with BK-dependent relaxation. No significant inward remodeling or intimal hyperplasia was observed at day 8 after angioplasty. Thus, BA inhibits remodeling, which occurs after in vitro perfusion of conductance arteries.     

Cost-effective analysis of candidate genes using htSNPs: a staged approach

We have previously shown that the selection of haplotype tag single nucleotide polymorphisms (htSNPs) and their statistical analysis in a multi-locus transmission/disequilibrium test (TDT) results in a more cost-effective genotyping strategy in disease association studies of genes by minimising redundancy due to linkage disequilibrium between SNPs. Further savings can be achieved by the use of a two-stage genotyping strategy. This approach is illustrated here in conjunction with the multi-locus TDT in determining whether common alleles of the immune regulatory genes RANK and its ligand TRANCE (RANKL) are associated with type 1 diabetes (T1D). A saving of approximately 75% of potential genotyping reactions could be made with minimal loss of power. There was little evidence from our analysis for association between the TRANCE and RANK genes and T1D in the populations tested.     

Jumping translocations in multiple myeloma

Jumping translocations (JT) have been defined as nonreciprocal translocations involving a same donor chromosome arm or chromosome segment onto two or more recipient chromosomes in different cell lines in the same patient, leading to a mosaic karyotype. This definition has been expanded to also include extra copies of a same donor segment on different recipient chromosomes in a single clone. Six patients with multiple myeloma and JT involving chromosome arm 1q were identified among 37 patients presenting with chromosome 1 abnormalities. All six patients had an advanced disease and a short survival. The literature review allowed us to identify 24 additional patients with JT. Chromosomes 16 and 19 were the recipients in 11 (45.8%) and 6 (25%) of these 24 patients, respectively. Breakpoints on the recipient chromosomes were pericentromeric in 46.2% and telomeric in 40.4% of the breakpoints recorded. Since telomeres are made of (TTAGGG)n tandem DNA repeats that are also found in the pericentromeric heterochromatic regions (interstital telomeric sequences), it is presumed that jumping translocations arise through illegimate recombination between telomere repeat sequences and interstitial telomeric sequences.     

Study of genotypes and virB4 secretion gene of Bartonella henselae strains from patients with clinically defined cat scratch disease

Bartonella henselae is the causative agent of cat scratch disease (CSD), which usually presents as a self-limiting lymphadenopathy. Occasionally, the bacteria will spread and be responsible for tissue and visceral involvement. Two B. henselae genotypes (genotypes I and II) have been described to be responsible for uncomplicated CSD on the basis of 16S rRNA sequence analysis. A type IV secretion system (T4SS) similar to the virulence-associated VirB system of Agrobacterium tumefaciens was recently identified in the B. henselae Houston-1 genotype I strain. We studied the correlations of the B. henselae genotypes with the clinical presentations and with the presence of T4SS. Isolates originated from CSD patients whose lymph nodes were prospectively analyzed. B. henselae genotype I was identified in 13 of 42 patients (30%). Among these, two teenage twins presented with hepatosplenic CSD and one immunocompetent adult presented with osteomyelitis. Genotype II was detected in 28 of 42 patients (67%), all of whom presented with uncomplicated CSD. The last patient was infected with both genotypes. T4SS was studied by PCR amplification of the virB4 gene. Amplification of virB4 codons 146 to 256, 273 to 357, and 480 to 537 enabled us to detect 66, 90, and 100% of the B. henselae isolates, respectively. Sequence analysis revealed sequence variations that correlated with genotype distribution. Our studies suggest that B. henselae genotype I strains harbor virB4 genes that are different from those harbored by genotype II strains and that genotype I strains might be more pathogenic.     

The diagnostic value of magnetic resonance imaging in subacromial impingement syndrome

The aim of this study was to assess the diagnostic ability of magnetic resonance imaging (MRI) in subacromial impingement syndrome (SIS), using a physiological standard of reference. MRI of the rotator cuff (RC) and subacromial injection test (SIT), a reference standard for SIS diagnosis, were performed in 125 painful shoulders. MRI diagnostic accuracies were determined using a 2 x 2 table and the percentage values of SIS diagnosis in patients with the three Zlatkin MRI stages were determined. Shoulder function was evaluated using the Constant Scale, and results were compared for stages. The sensitivity, specificity, accuracy, positive and negative predictive values of MRI for SIS diagnosis were 98.85%, 36.84%, 80%, 78.18% and 93.33% respectively. Of the 32 patients with Zlatkin stage 1 changes in MRI, 20 (62%) had SIT approved SIS diagnosis, while 47 (79%) of the 59 patients with Zlatkin 2 and all of the 19 (100%) patients with Zlatkin 3 changes were diagnosed with SIS by SIT. Mean Constant scores were 78.04 +/- 18.3, 65.0 +/- 19.9 and 54.52 +/- 20.7 in patients with Zlatkin stages 1, 2 and 3, respectively (p < 0.05). The MRI of RC did not prove to be an excellent tool for SIT based SIS diagnosis, with its low specificity. However, the technique can give important clues, as its sensitivity and negative predictive values are high.     

Blood velocity in human arteries measured by a bidirectional ultrasonic doppler flowmeter.

Blood velocities in 12 arteries were recorded by an ultrasonic doppler flowmeter in 11 young adults. Two major types of velocity patterns existed at rest. In certain arteries (the common carotid, the external carotid, the superficial temporal and the proper palmar digital arteries) flow was towards the periphery throughout the entire pulse cycle. Other arteries (the common femoral, the popliteal, the posterior tibial and the pedal artery) exhibited retrograde flow in part of the pulse cycle. In each individual a spontaneous variation between these two velocity patterns was observed in the subclavian, the axillary, the brachial and the radial artery. The velocity pattern of each artery is described, and absolute blood velocities at recognizable instances during the pulse cycle are given. The influence of peripheral resistance on the velocity pattern was investigated by reactive hyperaemia of the femoral artery. We find that not only is there an upward displacement of the resting femoral curve relative to the line of zero, but the shape of the velocity pattern is also changed. Our conclusion is that peripheral resistance is of major importance not only for the mean velocity, but also for the shape of the velocity pattern in the artery.     

Myocardial oxygen extraction and oxygen-hemoglobin equilibrium curve during moderate exercise

Summary Conditions of oxygen extraction by the myocardium have been studied in 12 subjects (44±9 years old) with pure mitral stenosis without clinical, metabolic or electrical sign of coronary insufficiency.Oxygen-hemoglobin equilibrium curves (OHEC) have been determined on arterial, mixed venous and coronary sinus blood, at rest and during a moderate (60 W, 10 min) exercise performed on a bicycle ergometer in supine position. Physiological values, at rest and during exercise, of the following functional parameters of the OHEC were determined in the in-vivo conditions of pH and P_CO2P₅₀, n_Hill, DS max = maximal value of OHEC slope (DS=S_O2/P_O2), P_{DS max}, S_{DS max}. The concentration of plasma electrolytes capable to modify one of these parameters was controlled in each blood sample.In coronary sinus blood, P₅₀ rises from 27.5±1.7 to 28.9±1.6 Torr during exercise (p<0.01). At rest, Hill's n in myocardial venous blood (2.67±0.09) is significantly higher than in arterial blood (2.61±0.08, p<0.01). A decrease in DS max (2.67±0.20 to 2.53±0.12%. Torr^–1; p<0.01) and an increase in P_{DS max} (20.9±1.9 to 22.6±2.1 Torr, p<0.01) are observed. At rest, the myocardial venous point (PcsO₂, ScsO₂) is not significantly distinct from the maximal slope point (P_{DS max}, S_{DS max}). After 1 min of exercise, a small gap appears which becomes significant at the end of the exercise (P_{DS max}-PcsO₂=0.2 Torr at rest, 2.7 Torr after exercise; S_{DS max}-ScsO₂=4.1% at rest, 7.9% after exercise). DS value at the myocardial venous point is only 2% at rest and 6% after exercise, lower than its maximal value.The gap between venous point and DS max point could constitute an error signal in the regulation loop of the coronary circulation. The existence of a physiological receptor, sensitive to instant variations in myocardial tissue P_O2 and able to maintain venous point near DS max point could be considered.     

TGF-β2 and PGE2 in Rabbit Blastocoelic Fluid Can Modulate GM-CSF Production by Human Lymphocytes

PROBLEM: During normal pregnancy, major changes occur in the production of Th2/Th1 cytokines at the feto-maternal interface. Th2 cytokines such as interleukin-4 (IL-4) or interleukin-10 (IL-10) are predominantly produced locally in the uterine and placental tissues, whereas the production of Th1 cytokines such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) are decreased. Because these modulations might be induced by the embryo, the current study was carried out to test the effect of rabbit blastocoelic fluid on the production of Th2/Th1 cytokines by lymphocytes, and to investiate the possible implication of transforming growth factor β₂ (TGF-β₂) prostaglandin E₂ (PGE₂) as modulators of the production of these cytokines. METHOD OF STUDY: Human peripheral blood lymphocytes (PBL) were cultured along with ConcanavalinA (Con A), and rabbit blastocoelic fluid was collected on day 12 of gestation (BF d-12). Concentrations of cytokines in culture media were determined by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: Addition of BF d-12 in the culture medium induced a strong inhibition of IL-2, TNF-α, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) production. However, an initial pretreatment of the lymphocytes with BF d-12, followed by a Con A stimulation, led to a marked increase in GM-CSF production, whereas IL-2, TNF-α, and IL-10 secretions were inhibited. It was also demonstrated, for the first time, that a pretreatment of the lymphocytes with TGF-β₂ and PGE₂ increased GM-CSF production to the same level reached after the addition of BF d-12. Furthermore, removal of TGF-β₂ and PGE₂ from BF d-12 by affinity chromatography reduced the effect of BF d-12 on GM-CSF production. CONCLUSIONS: Taken together, these findings suggest that the embryo, in modulating harmful and beneficial cytokine production locally, plays an active role in its protection against maternal immune cellular assault. These results also emphasize the importance of growth factors for successfully maintaining pregnancy.     

Relation of the radial nerve with the sulcus nervi radialis: a morphometric study

The radial nerve's course from the axillary region, branch patterns and the relation of the nerve to fixed anatomical landmarks in the arm region were studied in 27 embalmed intact cadavers. The radial nerve and its relation with the sulcus nervus radialis (SNR) was analyzed. The direct contact of the nerve with humerus in SNR was observed during the dissections. The following measurements were made: the total length of the humerus (the palpable uppermost point of the tuberculum majus and the lateral epicondyle); proximal safe zone (the tuberculum majus and the proximal beginning of the SNR); distal safe zone (the intercondylar axis and the middle of SNR); lateral safe zone (the lateral epicondyle and the distal end of SNR). In conclusion, it was aimed to correlate the osseus palpable landmarks of humerus with the course of the radial nerve for a safe surgery as the sulcus nervi radialis region is one of the main risky areas for the radial nerve palsies.     

Improved amplification of genital human papillomaviruses

Genital human papillomaviruses (HPVs) are commonly detected from clinical samples by consensus PCR methods. Two commonly used primer systems, the MY09-MY11 (MY09/11) primers and the GP5+-GP6+ (GP5+/6+) primers, amplify a broad spectrum of HPV genotypes, but with various levels of sensitivity among the HPV types. Analysis of the primer-target sequence homology for the MY09/11 primers showed an association between inefficient amplification of HPV types and the number and position of mismatches, despite accommodation of sequence variation by inclusion of degenerate base sites. The MY09/11 primers were redesigned to increase the sensitivity of amplification across the type spectrum by using the same primer binding regions in the L1 open reading frame. Sequence heterogeneity was accommodated by designing multiple primer sequences that were combined into an upstream pool of 5 oligonucleotides (PGMY11) and a downstream pool of 13 oligonucleotides (PGMY09), thereby avoiding use of degenerate bases that yield irreproducible primer syntheses. The performance of the PGMY09-PGMY11 (PGMY09/11) primer system relative to that of the standard MY09/11 system was evaluated with a set of 262 cervicovaginal lavage specimens. There was a 91.5% overall agreement between the two systems (kappa = 0.83; P < 0.001). The PGMY09/11 system appeared to be significantly more sensitive than the MY09/11 system, detecting an additional 20 HPV-positive specimens, for a prevalence of 62.8% versus a prevalence of 55.1% with the MY09/11 system (McNemar's chi(2) = 17.2; P < 0.001). The proportion of multiple infections detected increased with the PGMY09/11 system (40. 0 versus 33.8% of positive infections). HPV types 26, 35, 42, 45, 52, 54, 55, 59, 66, 73, and MM7 were detected at least 25% more often with the PGMY09/11 system. The PGMY09/11 primer system affords an increase in type-specific amplification sensitivity over that of the standard MY09/11 primer system. This new primer system will be useful in assessing the natural history of HPV infections, particularly when the analysis requires HPV typing.