Echocardiography and Doppler sonography in the evaluation of cardiac structure and function

Physical activity increases the work load of the heart. The adjustments of the heart depend on the quality and quantity of the work performed. These adjustments concern the function and the morphology of the cardiovascular system. It is important to underline that these adjustments are not permanent and can disappear when physical activity is stopped. In young subjects the risks are very few while the benefits may be shown on a better and more armonic body structure. In the elderly the benefits can be achieved with a lesser cost for submaximal activities, but the risks are of course more frequent due the possible onset of cardiovascular disease. It is important to correctly recognize the limits whitin which the physical activity can be allowed because beneficial. Echocardiography has given an important contribution to evaluate the morpho-functional adaptions of the athlete's heart. Similarly, it has proven useful in the detection of pathological cardiovascular modifications, asymptomatic or pausymptomatic, that do not allow certification to practise sport at agonistic levels.     

Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis

T lymphocytes from patients with multiple sclerosis (MS) recognize multiple myelin basic protein (MBP) epitopes. This situation complicates the design of specific immunotherapies. We investigated to which extent the T cell response to MBP is heterogeneous in single subjects in terms of preferentially recognized regions of the molecule, major histocompatibility complex (MHC) restriction, and stability over time. From each of nine patients with MS, a minimum of six MBP-specific T lymphocyte lines (TLL) were assayed for the proliferative response to a panel of overlapping peptides, encompassing the whole MBP. Predominant Tcell recognitions of distinct MBP regions were present in three patients, all HLA-DR2⁺, independently of the clinical features of their disease. Tcell reactivity was preferentially directed to residues 16-38 in one patient. In this case the response was also stable over time, during different phases of the disease. Predominant reactivity to residues 86-99 was detected in the two other DR2⁺ patients. In each of the patients with other HLA-DR haplotypes (DR2^?), as well as in three DR2⁺ non-MS donors, the Tcell response to MBP appeared to be considerably more heterogeneous. The HLA restriction element varied among TLL recognizing the same MBP region, even when raised from the same individual. The genomic HLA typing, performed on the DRB1 and DRB5 genes in the DR2⁺ subjects, showed no obvious correspondence between preferential responses to regions of MBP and HLA-DR2 subtypes. In this context, a simple, new method for the genomic typing of the HLA-DRB1 gene in individuals with the HLA-DR2 serological specificity is also described. We conclude that predominant and stable T cell responses to a single MBP region can be detected in some patients with MS. In these individuals, the MHC restriction of the T cell recognition of predominant regions appears to be variable. Polymorphisms of the HLA-DR2 gene products alone do not account for the selection of the dominant MBP Tcell epitope.     

AgNOR distribution in serous tumours of the ovary.

The present paper investigated the distribution of AgNOR in serous tumours of the ovary, with a particular attention to borderline lesion and carcinomas. AgNOR are classified as large AgNOR (LN) and small AgNOR (SN) and are counted separately in 100 nuclei for each tumor. Total number of AgNOR was also recorded (TN). The study shows that the mean values of LN, SN and TN increase from adenomas to borderline lesions and carcinomas, with highly significant differences (p less than 0.001). LN show the most impressive differences between borderline lesion and carcinomas, without overlap of values. The follow up of the patients is not long enough for any correlation between AgNOR counts and prognosis, but preliminary data suggest that high AgNOR counts in borderline tumors should be interpreted very cautiously, because they do not seem to have any correlation with a more aggressive behaviour.     

Presence of Rickettsia conorii subsp. israelensis, the causative agent of Israeli spotted fever, in Sicily, Italy, ascertained in a retrospective study

A retrospective analysis by molecular-sequence-based techniques was performed to correctly identify the etiological agent of 24 Mediterranean spotted fever cases occurring in Western Sicily, Italy, from 1987 to 2001. Restriction analysis of a 632-bp PCR-amplified portion of the ompA gene allowed presumptive identification of five clinical isolates as belonging to Rickettsia conorii subsp. israelensis, the etiological agent of Israeli spotted fever (ISF). The remaining 19 rickettsial isolates were Rickettsia conorii subsp. conorii, the only pathogenic rickettsia of the spotted fever group reported in Italy until the present. Sequence analysis of the ompA gene confirmed the identification of all the R. conorii subsp. israelensis isolates and demonstrated that rickettsiosis caused by R. conorii subsp. israelensis can be traced back to 1991 in Sicily. The recorded clinical data of the five ISF patients support the idea that these strains could correlate to more-severe forms of human disease. Three of five patients experienced severe disease, and one of them died.     

Limb anomalies: Developmental and evolutionary aspects

In this review we describe the developmental mechanisms involved in the making of a limb, by focusing on the nature and types of interactions of the molecules that play a part in the regulation of limb patterning and characterizing clinical conditions that are known to result from the abnormal function of these molecules. The latter subject is divided into sections dealing with syndromal and nonsyndromal deficiencies, polydactylies, and brachydactylies. Conditions caused by mutations in homeobox genes and fibroblast growth factors and their receptor genes are listed separately. Since the process of limb development has been conserved for more than 300 millions years, with all the necessary adaptive modifications occurring throughout evolution, we also take into consideration the evolutionary aspects of limb development in terms of genetic repertoire, molecular pathways, and morphogenetic events.     

Early detection of negative BACTEC MGIT 960 cultures by PCR-reverse cross-blot hybridization assay

We evaluated the efficacy of a PCR-reverse cross-blot hybridization assay, a test which permits identification of mycobacteria by means of species-specific probes and a Mycobacterium-specific probe, for early detection of negative BACTEC MGIT 960 mycobacterial cultures. Aliquots of 549 cultures were collected 7 days after the culture media were inoculated with various clinical specimens and tested with the molecular assay. PCR results were compared to those obtained at the end times with the BACTEC MGIT 960 system. Of the 549 specimens analyzed, 484 were found to be negative and 64 were found positive by both methods; one specimen, found to be positive by the BACTEC MGIT 960 system, was identified as negative by the molecular assay. In view of its high negative predictive value (99.8%), the PCR-reverse cross-blot hybridization assay appears to be a valid tool for early detection of negative BACTEC MGIT 960 cultures.     

Paromomycin and Geneticin Inhibit Intracellular Cryptosporidium parvum without Trafficking through the Host Cell Cytoplasm: Implications for Drug Delivery

Cryptosporidium parvum, which causes intractable diarrhea and lethal wasting in people with AIDS, occupies an unusual intracellular but extracytoplasmic niche. No reliable therapy for cryptosporidiosis exists, though the aminoglycoside paromomycin is somewhat effective. We report that paromomycin and the related compound geneticin manifest their major in vitro anti-C. parvum activity against intracellular parasites via a mechanism that does not require drug trafficking through the host cell cytoplasm. We used both normal and transformed aminoglycoside-resistant Caco-2 or MDBK cells in these studies. Timed-exposure experiments demonstrated that these drugs inhibit intracellular but not extracellular parasites. Apical but not basolateral exposure of infected cells to these drugs led to very significant parasite inhibition, indicating an apical topological restriction of action. We estimated intracytoplasmic concentrations of paromomycin, using an intracellular bacterial killing assay, and found that C. parvum infection did not lead to increased paromomycin concentrations compared to those in uninfected cells. Global [³H]paromomycin uptake by Caco-2 cells was ~200-fold higher than the estimated intracytoplasmic paromomycin concentration, suggestive of host cell vesicular uptake and concentration (as has been reported with other cell lines). However, preinfection exposure of Caco-2 cells to paromomycin did not result in subsequent inhibition of parasite development, indicating that if exogenous paromomycin enters the infected host cell vesicular compartment, it does not effectively communicate with the parasite. Thus, the apical membranes overlying the parasite and parasitophorous vacuole may be the unsuspected major route of entry for paromomycin and may be of importance in the design and discovery of novel drug therapies for the otherwise untreatable C. parvum.     

Outer membrane protein A renders dendritic cells and macrophages responsive to CCL21 and triggers dendritic cell migration to secondary lymphoid organs

Outer membrane protein A (OmpA) is a class of bacterial cell wall protein that is immunogenic without adjuvant. As specific immune responses are initiated in the lymph nodes (LN, we analyzed the effect of the OmpA from Klebsiella pneumoniae (KpOmpA) onchemokine/ chemokine receptor expression by APC and on cell migration to the LN. Upon contact with KpOmpA, human immature DC and macrophages acquire CCR7 expression and responsiveness to CCL21. In parallel, CCR1 and CCR5 expression is down-regulated and CXCL8, CCL2, CCL3 and CCL5 production is up-regulated. Mice injected subcutaneously with KpOmpA present a transient inflammatory reaction at the site of injection accompanied by an enlargement of the draining LN with a higher proportion of DC and macrophages. Lastly, when exposed to KpOmpA prior injection, DC but not macrophages migrate to the draining LN. In conclusion, KpOmpA confers a migratory phenotype to DC and triggers their migration to the regional LN. This property contributes to explain how innate cells initiate adaptive immune response upon recognition of conserved bacterial components and also why OmpA is immunogenic in the absence of adjuvant.     

IMPAIRED H-2 EXPRESSION IN B 16 MELANOMA VARIANTS

We studied the expression of H-2^b alloantigens in three different B16 melanoma lines cultured in vitro, Cell lines were B16-F1 and two cell cultures (named B16-A and B16-B) newly derived from two different in vivo sublines of B16 melanoma. The assays used were in vivo tumour growth in allogeneic (BALB/c and B10.BR) as compared to syngeneic mice, in vitro cell-mediated cytotoxicity by anti-H-2^b immune lymphocytes and absorption of anti-H-2^b antisera activity. The B16-F1 line was able to efficiently kill allogeneic hosts, could not be lysed by anti-H-2^b cytotoxic effectors and did not express any serologically detectable amount of H-2^b alloantigens. The B16-A line was H-2 positive during the early in vitro passages, then, at the 8th–10th passages, it acquired the capacity to kill allogeneic hosts, lost the sensitivity to anti-H-2^b cytotoxic effectors and the H-2K^b antigens became undetectable. The expression of H-2D^b was reduced, although at a lower degree. Similar data were obtained with B 16-B cells, which after 10 in vitro passages grew and killed allogeneic hosts, showed a decreased sensitivity to cytotoxic anti-H-2^b effectors and a very low expression of the K region antigens. The results indicate that H-2 expression is altered in B 16 melanoma lines and this may influence the different metastatic capacity of such cells.     

X-ray investigation on highly oriented polyacetylene, 3 Crystal structure of the iodine/trans-polyacetylene complex

The crystal structure of iodine/trans-polyacetylene complexes (CHI_y)_x (y = 0,009, 0,035, 0,17 and 0,30) was investigated by X-ray diffraction analysis of highly oriented samples. An iodine-containing phase (PAI) was observed in all cases, accompanied by residual crystallinity due to pristine polyacetylene (PA) for y < 0,17. A structural model is proposed for PAI, consisting of blocks of iodine-saturated PA (PAI_s) and blocks of PA, arranged in a mosaic-like lattice, paracrystalline in character. PAI_s, corresponding to (CHI_0,40)_x, is formed by layers of (CH)_x chains alternating with layers containing polyiodide chains, the latter being characterized by ordered stacking of sequentially disordered (I₃^?-I₅^?-I₃^?) groups. I… C non-bonded interactions are identified in the lattice, which may be responsible for the electron transfer from the polymer to the polyiodide anions. Short-range transverse correlation occurs within the polyiodide layers with a resulting quasi-regular two-dimensional lattice of iodines. The iodine and the polymer lattices are incommensurate along c. The model fits the experimental data from an X-ray fibre diagram. A mathematical expression is derived, which allows to evaluate the intensity scattered by the iodine lattice. An approximate expression of the non-equatorial intensity along the ξ reciprocal direction was obtained, which accounts for the modulation of the streaks observed in the fibre pattern.