Prevalence of hepatitis B markers in the population of catalonia (Spain). Rationale for universal vaccination of adolescents

The prevalence of hepatitis B markers was determined in a representative sample of the general population of Catalonia (Spain). HBsAg was found in 0.5% of children (less than 15 years of age) and in 1.7% of adults (more than 15 years of age), and anti HBs in 1.6% and 18%, respecitvely. Age-specific prevalence for both markers showed a low risk for hepatitis B before puberty, and a progressive rise since adolescence, suggesting that perinatal transmission and horizontal transmission in children are relatively uncommon in Spain. Prevalence of hepatitis B markers was significantly higher among subjects with low education level, residing in an urban area and born outside Catalonia, but in the stratified analysis, a statistical significant difference was only maintained in the prevalence of HBV markers between those who live in urban and rural areas, and between those who were born outside Catalonia and in Catalonia. These data may be used as a basis for a strategy of hepatitis B prevention in Spain which include universal vaccination of adolescents, passive-active immunization of newborns to HBsAg positive mothers and vaccination of susceptible adults subjects from high-risk groups.Preventive Medicine Unit.Liver Unit.Corresponding author.     

The Essential Oil of Thymus serpylloides ssp. gadorensis

THYMUS SERPYLLOIDES ssp. GADORENSIS is endemic in the Betic region (Spain). Gas chromatography and GC/mass spectrometry studies of its essential oil showed its major components to be carvacrol and its biosynthetic precursors (gamma-terpinene and P-cymene).     

Treatment of systemic sclerosis with recombinant interferon-gamma. A phase I/II clinical trial.

OBJECTIVE. A phase I/II trial to examine the safety and efficacy of interferon-gamma (IFN gamma) therapy for patients with systemic sclerosis (SSc). METHODS. An 18-week open-label study was performed. Eighteen patients with rapidly progressive SSc were enrolled, 14 of whom completed at least 16 weeks of the study. These 14 patients had a mean age of 40 years and had been diagnosed as having SSc an average of 10.1 months prior to study entry. Recombinant IFN gamma was injected intramuscularly 3 times weekly for 18 weeks. Six patients received a 0.1 mg/m2 dose, while 8 patients received a 0.5 mg/m2 dose. Patients who completed the 18-week trial were offered maintenance therapy at a dose of up to 0.5 mg/m2. The effects of IFN gamma on skin involvement were assessed by 2 methods: 1) evaluation of skin thickness, by scoring 15 zones according to a 0 (normal skin) to 3 (hidebound skin) scale; and 2) determination of the total body surface area involved, by using 2-dimensional body diagrams to indicate areas affected, and then having a second, "blinded," assessor calculate the area score with a planimeter. RESULTS. The mean skin thickness score decreased from a baseline of 25.9 to 19.1 (P < 0.03), and the mean area scores declined from 33.1 to 19.6 (P < 0.02) after 18 weeks of IFN gamma treatment. Ten patients had a > 25% decrease in area score. Five patients had a > or = 70% decrease in area score, and 3 of them have not experienced disease recurrence for 6 to 17 months after discontinuation of IFN gamma. Five patients withdrew before the study ended. Three of these patients developed renal crisis, which may reflect the severity of the SSc in the study group, although an adverse effect of IFN gamma in SSc cannot be excluded. CONCLUSION. IFN gamma was associated with a beneficial effect on the skin involvement in most of this series of patients with rapidly progressive SSc. A placebo-controlled study will be necessary to confirm these results.     

Pathological analyses of long-term intracoronary Palmaz-Schatz stenting; Is its efficacy permanent?

BACKGROUND: Angiographic regression of luminal narrowing occurs 6 months to 3 years poststenting. However, after 4 years lesions progressed gradually and late restenosis was observed in 28% of 179 Palmaz-Schatz-stented lesions during the past 10 years. Elucidating its pathogenesis is pivotal to developing preventive strategies. METHODS AND RESULTS: Histopathological and immunohistochemical studies were performed in 19 stented coronary arteries obtained from 19 patients autopsied after noncardiac death 2-7 years poststenting. The quality/severity of chronic inflammatory cells (T lymphocytes, macrophages and multinucleated giant cells) infiltration around the stent struts that is observed even in the absence of restenosis depended on the time elapsed from stenting: a) 2 years postprocedure, in spite of angiographic regression during the first year and pathologically expressed as maturation of the neointimal scar, there was chronic inflammatory response evidence: neovascularization and lymphocyte infiltration, b) > or = 3 years: the neointimal smooth muscle cells were sparse with abundant proliferation of collagen fibers. Presence of slight helper/inducer T lymphocytes and mild macrophage infiltration around the stent struts was evident immunohistochemically, c) > or = 4 years: prominent infiltration by lipid-laden macrophages with strong collagen-degrading matrix metalloproteinase immunoreactivity was observed around the struts. In two of these arteries, the surface contacting the stent was focally disrupted and covered by nonocclusive mural thrombi. CONCLUSIONS: Stainless steel stents evoke a remarkable foreign-body inflammatory reaction to the metal. These persistent peri-strut chronic inflammatory cells may accelerate new indolent atherosclerotic changes and consequent plaque vulnerability.     

Morphological features in human cortical brain microvessels after head injury: a three-dimensional and immunocytochemical study

We studied the morphology of cortical microvessels in the brains of 10 patients who had died after receiving a traumatic head injury (THI). Scanning electron microscopy (SEM) of vascular corrosion casts, confocal microscopy of histological sections after immunocytochemistry, and detection of apoptosis by terminal dUTP nick end labeling (TUNEL) were used. Microvascular casts showed an angioarchitectonic distribution that was defined as normal according to results obtained in a previous, nontraumatic series of subjects. However, when we compared them with previous works, the cast surface of some of the microvessels showed three types of morphological alterations: longitudinal folds, sunken surfaces with craters, and a significant flattening with reduction of lumen. The vessels that were primarily affected were the arterioles and capillaries of the middle and deep cortical vascular zones. Immunostaining with the monoclonal antibody MAS-336 against endothelial cells also showed the presence of longitudinal folds with a thinning of the vascular lumen, cytoplasmic round bodies, and a thickening of the endothelial cell membrane. The TUNEL technique revealed a positive staining of some endothelial cells. The structural alterations we observed indicate that microvessels undergo endothelial cell damage after THI. We suggest that this kind of lesion and the secondary functional injury to the blood-brain barrier (BBB) could play an important role in the development of the secondary lesions that these patients show in the subacute phase.     

Co-expression of B7-1 and ICAM-1 on tumors is required for rejection and the establishment of a memory response

Although the transfection of B7-1 cDNA into a few mouse tumor cell lines can induce anti-tumor T cell immunity, its expression alone is ineffective in many other tumor cell lines tested. We were interested to study what factors limit B7-1 co-stimulatory activity, and decided to investigate whether B7-1 requires the cooperation of ICAM-1 to provide the minimal co-stimulatory signal for establishing an efficient anti-tumor immunity. We show that the transfection of B7-1 cDNA into three ICAM-1⁺ (plasmocytoma J558L, T lymphomas EL-4 and RMA), but not into two ICAM-1^? tumor cell lines (adenocarcinoma TS/A and melanoma B16.F1), is sufficient to induce their complete rejection in syngeneic mice. The expression of ICAM-1 is necessary for the rejection of the B7 expressing tumors, since the primary response elicited by B7-1⁺ EL-4 and RMA clones expressing reduced levels of ICAM-1 is severely reduced. Furthermore, super-transfection of ICAM-1 cDNA into B7-1⁺ adenocarcinoma and melanoma clones optimizes their primary rejection. Histologic examination of transfected tumors reveals that B7-1 and ICAM-1 exert a potent pro-inflammatory activity. The intra-tumor infiltration is composed of both eosinophils and lymphomono-cytes, and is already massive 5 days after the tumor challenge. The primary rejection of the B7-1⁺ ICAM-1⁺ tumors depends critically on CD8⁺ T cells, natural killer cells and granulocytes, but is independent of CD4⁺ T cells. Remarkably, in addition to its effects on the early phases of the immune response, the co-expression of ICAM-1 and B7-1 on tumors is also necessary for the efficient induction of a memory response. In fact, only the primary challenge with B7-1⁺, ICAM-1⁺ tumor cells protects the majority of the mice from a second injection of parental tumor cells. Collectively, our findings indicate that B7-1 and ICAM-1 are fundamental components for triggering the primary rejection of tumors and establishing a protective memory response. These findings may help to define new strategies for the rational application of co-stimulation in tumor immunotherapy.     

Interleukin-10 haplotypes in Celiac Disease in the Spanish population

Background  

Celiac disease (CD) is a chronic disorder characterized by a pathological inflammatory response after exposure to gluten in genetically susceptible individuals. The HLA complex accounts for less than half of the genetic component of the disease, and additional genes must be implicated. Interleukin-10 (IL-10) is an important regulator of mucosal immunity, and several reports have described alterations of IL-10 levels in celiac patients. The IL-10 gene is located on chromosome 1, and its promoter carries several single nucleotide polymorphisms (SNPs) and microsatellites which have been associated to production levels. Our aim was to study the role of those polymorphisms in susceptibility to CD in our population.     

Proteomic and postproteomic characterization of keratan sulfate-glycanated isoforms of thyroglobulin and transferrin uniquely elaborated by papillary thyroid carcinomas

Previous studies have suggested that surface components of papillary thyroid carcinoma (PTC) cells may be aberrantly glycanated, but the precise nature of these molecules has not been unveiled nor documented to be of clinical relevance. A monoclonal antibody was raised against a unique keratan sulfate (KS) determinant and used to differentially screen benign and malignant thyroid tissue for the expression of components carrying these moieties. In a total of 349 cases of benign and malignant thyroid lesions, 100% of the 115 PTC cases examined (including various histological subtypes) were found to contain KS-bearing molecules, whereas these were virtually absent from benign tissues and other thyroid tumors, with the exception of 21% of the follicular carcinoma cases analyzed. A composite immunoaffinity chromatography, immunochemistry, and mass spectrometric approach revealed that the PTC-specific KS-bearing macromolecules were unique glycoforms of thyroglobulin and transferrin. Combined, reciprocal immunoprecipitation and Western blotting further indicated that the former glycoform predominated and that most of the transferrin produced by PTC was glycanated with KS moieties. Fluorescent keratanase II-based fingerprinting of the KS moieties bound to these isoforms further demonstrated several PTC-specific peculiarities: 1) that a considerable portion of the moieties was covalently attached via a novel core protein linkage structure; 2) they had an unusual extended average length; 3) an unusual relative ratio of highly sulfated disaccharides terminating with alpha (2-3)-linked N-acetylneuraminic acid capping residues; and 4) a novel unidentified oligosaccharide moiety at the nonreducing terminus. Comparative analysis of the relative distribution of transferrin in benign versus PTC tissues highlighted a marked malignancy-associated abundance of the molecule, with a >75% frequency in expression in PTC. These findings demonstrate that PTC cells synthesize unique post-translationally modified thyroglobulin and transferrin variants in situ that may be directly exploitable for diagnosis, through histological and noninvasive cytological procedures; for devising novel strategies for antibody-guided imaging of this tumor in vivo; and for postsurgery follow-up of PTC patients.