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The influence of thyroid function on serum lipid profile.

Serum triglycerides, cholesterol, HDL-C and LDL-C levels as well as the LDL/HDL cholesterol ratio were determined in 11 patients suffering from hyperthyroidism and 7 patients suffering from hypothyroidism, and compared with those of 19 sex-and age-matched controls. In hypothyroidism a net increase of all lipid values was observed. In hyperthyroidism cholesterol and LDL-C values were reduced while those of the triglycerides and HDL-C were unchanged as compared with controls. The LDL/HDL cholesterol ratio in either group of patients was lower than in controls, the lowest being observed in thyrotoxicosis.

Aged↗

Profile of multiple lymphocyte functional defects in acquired hypogrammaglobulinemia, derived from in vitro cell recombination analysis.

Immunoregulatory defects in patients can be assigned to B cells, T helper cells, or T suppressor cells by means of a modification of the in vitro PWM-stimulated Ig biosynthesis assay. When lymphocyte subpopulations from patient and normal are recombined, multiple internal comparisons within a single experiment reveal the functional activity of each subpopulation. By this technique we studied nine adult patients with acquired panhypogammaglobulinemia and one with isolated IgG deficiency. Low total Ig production by the B cell fraction was demonstrated in seven of the nine panhypogammaglobulinemic patients. In four of these seven, IgG and IgA secretion was markedly reduced compared with IgM. In the two patients with normal total Ig production, elevated IgM compensated for lower IgA and IgG. The one patient with no surface Ig+ cells had a B cell defect, but no T cell defect. Reduced T help and excessive T suppression characterized two of the four patients with the most severe B cell defects. Three patients were anergic by delayed hypersensitivity skin testing and failed to sensitize to DNCB, but the patient with the most severe T cell defects in vitro was not among them. One of these three patients showed a mild T cell help defect and suppressor excess and the other two had pure B cell defects. Thus, anergy and T regulator function were not correlated. In three instances where hypersuppression was more evident by adding patient unfractionated cells than by adding patient T cells, suppression by the T depleted fraction could be demonstrated. No cases of radiation-resistant T suppression were revealed among the seven patients tested. Subnormal total protein synthesis, noted in six of seven patients with low Ig production, was invariably less marked than the Ig defect and often affected both T and B cells. One additional patient with pure IgG deficiency of 2 yr duration was essentially normal in her in vitro lymphocyte function. The general applicability of this experimental design for analysis of positive or negative immunoregulatory abnormalities is emphasized.

Adult↗

Cytokine profiles and T cell function in acute coronary syndromes.

AIMS: In advanced human atherosclerotic plaques infiltrating T cells congregate at sites of plaque rupture. However, little is known about the systemic activation of circulating T cells in acute coronary syndromes as a prerequisite for recruitment to atherosclerotic lesions. METHODS AND RESULTS: As a measure for specific lymphocyte activation we analyzed IFN-gamma production of T cells after stimulation with a superantigen and expression of CXCR-3 and CCR-3 in patients with acute myocardial infarction (AMI), unstable angina (uAP) or stable angina (sAP). Furthermore, concentrations of the circulating cytokines interleukin (IL)-1, IL-6, IL-1beta, IL-12 p70 and RANTES that modify T cell function were measured. In uAP an increased Th1 and a decreased Th2 response was identified by enhanced interferon-gamma generation of T lymphocytes, increased levels of IL-1beta, IL-12 p70 and RANTES and decreased expression of CCR3. In AMI a systemic inflammatory reaction predominates with enhanced expression of the early activation marker CD69 on T lymphocytes and elevated levels of IL-6 and IL-10 that suppress Th1 activation. CONCLUSION: Interferon-gamma production of activated T cells in acute coronary syndromes may, therefore, be governed by the release of specific pro- and anti-lymphocyte activating cytokines.

Acute Disease↗

Regulation of macrophage phenotype by long-term exposure to IL-10.

Macrophages are chronically exposed to IL-10 in a variety of physiological and pathological settings. Macrophage responses to short-term stimulation with IL-10 have been extensively studied, but the effects of chronic exposure to IL-10 on macrophage function are not known. Herein we used transcriptional profiling and functional studies to characterize the phenotype of macrophages after long-term culture with IL-10. Classical activation of macrophages by LPS and IFNgamma was suppressed by IL-10. In contrast, IL-10 activated expression of genes that suggested acquisition of functions important for cell trafficking, tissue remodeling, recognition of microbial pathogens and responsiveness to the T cell-derived cytokines IL-2 and IL-21. These results demonstrate that IL-10 induces a differentiation program in macrophages and characterize a novel alternatively activated macrophage phenotype.

Enzyme-Linked Immunosorbent Assay↗

Tacrolimus (FK506) versus cyclosporin A microemulsion (Neoral) maintenance immunosuppression: effects on graft survival and function, infection, and metabolic profile following kidney transplantation (KT).

We reviewed two groups of kidney transplant patients receiving neoral (Group I, 27 patients) or FK506 (Group II, 25 patients) as maintenance immunosuppression between December 1998 and May 2002. The recipient and donor demographics and induction therapy were comparable in both groups except for more highly sensitized patients in Group II. Acute rejection (AR) rate and timing were similar in both groups except for more steroid resistant AR in Group II (P=0.04). Infections rate was similar in both groups (25.9% in Group I and 36% in Group II; P=N.S.), but there were less viral infections in Group I (0%) than Group II (29%; 4 CMV). CMV infections were related to the presence in Group II of more CMV-negative recipients getting kidneys from CMV-positive donors. The metabolic profile was comparable between the two groups, except for a better HDL in Group II (48.2+/-7.6) versus Group I (45+/-2.2; P=0.021). Mean serum creatinine levels upon discharge, at 1, 3 and 6 months were: 1.62+/-0.32, 1.4+/-0.17, 1.39+/-0.14 and 1.4+/-0.14 in Group I and 2.15+/-0.5, 1.48+/-0.23, 1.41+/-0.21 and 1.23+/-0.11 in Group II, respectively. The 6 months actuarial patient and graft survival were identical in both groups (100 and 100%). Both calcineurin inhibitors are effective and safe in KT. The higher rate of AR in Group II was related to more highly sensitized patients and the higher CMV infections was due to the presence of more CMV-negative recipients receiving kidneys from CMV-positive donors. The same study will be continued to evaluate the long term effects of both drugs.

Acute Disease↗

Glaucoma visual field analysis by computed profile of nerve fiber function in optic disc sectors.

Automated perimetry has decreased the subjective aspects of data collection, but analysis has remained largely subjective. A microcomputer permits more objective analysis by regrouping and averaging data points in the threshold static visual field according to their retinotopic projection onto the optic disc rather than according to their eccentricity from the point of fixation. The applications of the technique include (1) following glaucomatous visual field loss, (2) differentiating glaucomatous from other forms of visual loss, and (3) studying the effects of aging on the visual field. Six formulas for data analysis are described, and their relative usefulness discussed. Percent loss or gain seemed to convey the most diagnostic information to the clinician. Percent of expected sensitivity was less than the decimal visual acuity when the diagnosis was glaucoma but greater when the diagnosis was cataract. In some cases this analytic method should provide information that could favorably affect patient management.

Adolescent↗

Who uses over-the-counter psychotropics? Characteristics, functioning, and (mental) health profile.

As part of a population study on the prevalence of psychopathology, users of "Over-The-Counter" Psychotropics (OTC-Ps) were studied. First, their mental health profile was examined by a number of subjective and objective assessments. Second, the medical consumption of the users was studied with special attention to the psychotropic drugs prescribed. The prevalence of psychological problems and symptoms of psychological distress was higher among OTC-P users than among non-users. Somatic problems and symptoms were comparable in the two groups; social support was better in the OTC-P users. Half of the users were known to have mental health problems by their Primary Care Physician (PCP). The DSM IV Axis I disorders were mostly mood and anxiety disorders. A benzodiazepine had been prescribed to one-third of the OTC-P users. No other psychotropic drugs had been prescribed, and the medical consumption was comparable in the two groups. PCPs should be aware of concomitant OTC-Ps use.

Adolescent↗

Cytokine profile associated to effector functions of human T cell clones specific for Schistosoma mansoni antigens.

T cell lines and clones specific for Schistosoma mansoni antigens were established to study cellular immunity in human schistosomiasis. Flow cytometric analysis of the clones demonstrated that all of them were of the helper inducer T cell subset (CD3+, CD4+, CD8-), and expressed the alphabeta T cell receptor, besides the IL-2 low affinity receptor CD25. Lymphokine analysis revealed that clones presented Th1, Th2, or either Th0 patterns of secretion. More interestingly, the capability of clones to induce in vitro granuloma reactions seems to be related to the presence of TNF-alpha and the absence of IL-10. In counterpart, IL-10 producer clones did not help in vitro granuloma formation, even in the presence of TNF-alpha.

Animals↗

Streptococcus pyogenes collagen type I-binding Cpa surface protein. Expression profile, binding characteristics, biological functions, and potential clinical impact.

The Streptococcus pyogenes collagen type I-binding protein Cpa (collagen-binding protein of group A streptococci) expressed by 28 serotypes of group A streptococci has been extensively characterized at the gene and protein levels. Evidence for three distinct families of cpa genes was found, all of which shared a common sequence encoding a 60-amino acid domain that accounted for selective binding to type I collagen. Surface plasmon resonance-based affinity measurements and functional studies indicated that the expression of Cpa was consistent with an attachment role for bacteria to tissue containing collagen type I. A cpa mutant displayed a significantly decreased internalization rate when incubated with HEp-2 cells but had no effect on the host cell viability. By utilizing serum from patients with a positive titer for streptolysin/DNase antibody, an increased anti-Cpa antibody titer was noted for patients with a clinical history of arthritis or osteomyelitis. Taken together, these results suggest Cpa may be a relevant matrix adhesin contributing to the pathogenesis of S. pyogenes infection of bones and joints.

Amino Acid Sequence↗

nth-Nearest-neighbor distribution functions of an interacting fluid from the pair correlation function: a hierarchical approach.

The paper presents a general formalism for the nth-nearest-neighbor distribution (NND) of identical interacting particles in a fluid confined in a nu-dimensional space. The nth-NND functions, W(n,r) (for n=1,2,3, em leader) in a fluid are obtained hierarchically in terms of the pair correlation function and W(n-1,r) alone. The radial distribution function (RDF) profiles obtained from the molecular dynamics (MD) simulation of Lennard-Jones (LJ) fluid is used to illustrate the results. It is demonstrated that the collective structural information contained in the maxima and minima of the RDF profiles being resolved in terms of individual NND functions may provide more insights about the microscopic neighborhood structure around a reference particle in a fluid. Representative comparison between the results obtained from the formalism and the MD simulation data shows good agreement. Apart from the quantities such as nth-NND functions and nth-nearest-neighbor distances, the average neighbor population number is defined. These quantities are evaluated for the LJ model system and interesting density dependence of the microscopic neighborhood shell structures are discussed in terms of them. The relevance of the NND functions in various phenomena is also pointed out.

Journal Article↗