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PubMed2001

Computed tomography of diffuse lung disease: functional correlates.

An appreciation of functional and morphological characteristics is fundamental to the understanding of diffuse lung disease. The detailed information available from high-resolution computed tomography (HRCT) and the facility to subjectively or objectively quantify disease has elucidated the sometimes complex pulmonary function profiles of several diffuse lung diseases. The many reasons why correlations between the extent of HRCT abnormalities and physiological measures of disease may be less strong than expected and are considered in this review.

Diagnosis, Differential↗
PubMed1991

Influence of anabolic steroids on body composition, blood pressure, lipid profile and liver functions in body builders.

The effects of anabolic steroids on body composition, blood pressure, lipid profile and liver functions were studied in male body builders who received a weekly i.m. injection of nandrolone-decanoate (100 mg) or placebo for 8 weeks in a double blind way. In addition, 5 body builders received the same dosage of nandrolone-decanoate or placebo, in a double blind cross-over design during two 8-week periods, interspersed by 12 weeks. Anabolic steroids induced a 25-27% decrease in HDL-cholesterol, which was virtually reversed 6 weeks after cessation of drug use. In the SAD group an increase in diastolic blood pressure was observed, which returned to pre-anabolic values approximately 6 weeks after cessation of drug administration. No deleterious effects of anabolic drugs on plasma activity of liver enzymes were found. Increases in lean body mass were found in all groups, though the increase in the subjects who received anabolic steroids was superior to that in the placebo-treated subjects. The increase in lean body mass suggests increases in muscle mass.

Adult↗
PubMed2004

History of multiple suicide attempts as a behavioral marker of severe psychopathology.

OBJECTIVE: Individuals with a differing number of past suicide attempts are generally considered a homogeneous group, despite emerging evidence to the contrary. The current study aimed to test the hypothesis that multiple suicide attempters would exhibit a more severe clinical profile than single suicide attempters. METHOD: A series of self-report batteries and clinical interviews was administered to 39 single attempters and 114 multiple attempters who came to an urban hospital emergency room after a suicide attempt. The participants were predominantly poor and nonwhite. RESULTS: Multiple suicide attempters versus single attempters exhibited a greater degree of deleterious background characteristics (e.g., a history of childhood emotional abuse, a history of family suicide), increased psychopathology (e.g., depression, substance abuse), higher levels of suicidality (e.g., ideation), and poorer interpersonal functioning. Profile differences existed even after control for borderline personality disorder. CONCLUSIONS: Results indicate that multiple attempters display more severe psychopathology, suicidality, and interpersonal difficulties and are more likely to have histories of deleterious background characteristics than single attempters. Moreover, these differences cannot be explained by the diagnosis of borderline personality disorder. Results suggest that the identification of attempt status is a simple, yet powerful, means of gauging levels of risk and psychopathology.

Adolescent↗
PubMed2001

Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory.

Emerging evidence indicates that CD8+ and CD4+ T-cell immunity is differentially regulated. Here we have delineated differences and commonalities among antiviral T-cell responses by enumeration and functional profiling of eight specific CD8+ and CD4+ T-cell populations during primary, memory and recall responses. A high degree of coordinate regulation among all specific T-cell populations stood out against an approximately 20-fold lower peak expansion and prolonged contraction phase of specific CD4+ T-cell populations. Surprisingly, although CD8+ T-cell memory was stably maintained for life, levels of specific CD4+ memory T cells gradually declined. However, this decay, which seemed to result from less efficient rescue from apoptosis, did not affect functionality of surviving virus-specific CD4+ T cells. Our results indicate that CD4+ T-cell memory might become limiting under physiological conditions and that conditions precipitating CD4+ T-cell loss might compromise protective immunity even in the presence of unimpaired CD8+ T-cell responses.

Amino Acid Sequence↗
PubMed1994

Temporal profile of hepatitis C virus antibody and genome in infants born to mothers infected with hepatitis C virus but without human immunodeficiency virus coinfection.

To investigate mother-to-infant transmission of hepatitis C virus, serial follow-up of anti-HCV and hepatitis C virus RNA was undertaken in 11 infants born to hepatitis C virus-infected mothers who had been screened from 11,688 pregnant women. None of the hepatitis C virus-infected mothers was infected by human immunodeficiency virus. Anti-HCV was checked by the second-generation enzyme immunoassay kit, and hepatitis C virus RNA was examined by reverse transcriptase-nested polymerase chain reaction. Hepatitis C virus RNA was found in more than two serum samples in two of these 11 infants; those two infants were regarded as hepatitis C virus-infected. One of the two had hepatitis C virus RNA at the age of 1, 3, and 6 months, but not later. The course of hepatitis C virus RNA and anti-HCV in this baby may reflect fluctuating viral replication in chronic infectious disease or viral clearance in acute infection. The other infant had hepatitis C virus RNA detectable at the age of 3 months and at 15, 18 and 24 months. In the other nine non-hepatitis C virus-infected infants, maternally acquired anti-HCV gradually disappeared by the age of 6 months. The liver function profile fell to the normal range in all the infants, including the two hepatitis C virus-infected infants. This may indicate the subclinical nature of hepatitis C virus infection in infancy. Seven fathers and four siblings of these 11 infants were checked for anti-HCV and liver function tests; none had evidence of hepatitis C virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed2006

Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas.

The classification of peripheral T-cell lymphomas (PTCL) is still a matter of debate. To establish a molecular classification of PTCL, we analysed 59 primary nodal T-cell lymphomas using cDNA microarrays, including 56 PTCL and three T-lymphoblastic lymphoma (T-LBL). The expression profiles could discriminate angioimmunoblastic lymphoma, anaplastic large-cell lymphoma and T-LBL. In contrast, cases belonging to the broad category of 'PTCL, unspecified' (PTCL-U) did not share a single molecular profile. Using a multiclass predictor, we could separate PTCL-U into three molecular subgroups called U1, U2 and U3. The U1 gene expression signature included genes known to be associated with poor outcome in other tumors, such as CCND2. The U2 subgroup was associated with overexpression of genes involved in T-cell activation and apoptosis, including NFKB1 and BCL-2. The U3 subgroup was mainly defined by overexpression of genes involved in the IFN/JAK/STAT pathway. It comprised a majority of histiocyte-rich PTCL samples. Gene Ontology annotations revealed different functional profile for each subgroup. These results suggest the existence of distinct subtypes of PTCL-U with specific molecular profiles, and thus provide a basis to improve their classification and to develop new therapeutic targets.

Gene Expression Profiling↗
PubMed1998

Generation of intestinal mucosal lymphocytes in SCID mice reconstituted with mature, thymus-derived T cells.

Transfer of peripheral lymph node lymphocytes to SCID mice leads to the long term establishment of mucosal T lymphocytes within the epithelium and lamina propria of the small and large intestines. Analysis of engrafted intraepithelial lymphocytes (IEL) showed that they had acquired a surface phenotype that in several respects is typical of IEL. In addition, the functional profile of engrafted IEL derived from lymph node T cells was similar to that of normal IEL; as the donor-derived T cells exhibited a strong cytolytic activity, a poor proliferative response to mitogenic stimuli, and a tendency to home and expand specifically in the intestine upon transfer to secondary SCID recipients. Optimal engraftment of intestinal T cells required bacterial flora, as the number of lymphocytes was greatly reduced in SCID recipients with a reduced flora. These results demonstrate that mature, thymus-derived T cells can migrate to the intestine and become functionally specialized to the intestinal milieu. The acquisition of phenotypic markers characteristic of the intestinal microenvironment by engrafted cells suggests that T cell migration of lymphocytes to the SCID intestine is not aberrant, but it may reflect processes that are ongoing in immunocompetent mice. Furthermore, these data suggest that the homing and/or expansion of typical, thymus-derived T cells in the intestine may be driven by luminal Ags such as those derived from bacterial flora.

Animals↗
PubMed1987

Clonal and frequency analyses of tumor-infiltrating T lymphocytes from human solid tumors.

A limiting dilution analysis (LDA) was used to assess the functional profiles of tumor-infiltrating lymphocytes (TIL) recovered from 15 human solid tumors. The microculture system applied in this study has been shown to allow virtually all normal peripheral blood T lymphocytes (PBL-T) to undergo clonal proliferation and was applied to obtain estimates of the frequency of both proliferating and cytolytic cells among the TIL population. A total of 624 microcultures proliferating in the presence of irradiated allogeneic spleen cells and interleukin 2 (IL 2) were expanded for clonal analysis. These TIL microcultures were assessed for surface antigen phenotype, IL 2 production (helper function) and for their cytolytic capabilities against the human erythroleukemic line K562 (natural killer (NK)-like activity) and P815, a mouse mastocytoma line, in the presence of phytohemagglutinin (PHA), i.e., lectin-dependent cell cytotoxicity (LDCC) which allows the detection of cytolytic activity irrespective of the antigenic specificity of the effector cells. Whenever feasible, cytolytic activity against autologous and allogeneic tumor cells was tested. LDA first demonstrated that the proliferative potential was decreased in T lymphocytes infiltrating human solid tumors (approximately 1 in 50 to 1 in 2 proliferating T lymphocyte precursors (PTL-P) in this series) as compared to normal PBL-T (1 in 2 to 1 in 1 PTL-P). The growth pattern in the titration cultures showed a remarkable agreement with the single-hit Poisson model implying that third party cells are unlikely to be involved in the reduced proliferative potential. Quantitative estimates of functional precursors showed that, in spite of reduced proliferative potential, cytolytic T lymphocyte precursors (CTL-P) against unknown antigens (LDCC-reactive) accounted for a considerable part of the microcultures in many cases. The precursor frequency of T lymphocytes with NK-like activity was usually low in situ (with the exception of glioma), whereas it was in the normal range in the patient's autologous PBL-T. In four evaluable cases, quantitative assessment showed that 1 in 200 to 1 in 1000 T lymphocytes from TIL was cytolytic against allogeneic tumor cells, which is in the range of alloreactive cytolytic T lymphocytes (CTL) generated in the mixed lymphocyte culture from normal PBL. Cytolytic activity against autologous target cells could not be quantitatively estimated but out of 88 clones from 4 patients, 3 clones originating from 2 glioma patients showed high lytic values against autologous tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Differentiation, T-Lymphocyte↗
PubMed2002

Functional annotation of a full-length Arabidopsis cDNA collection.

Full-length complementary DNAs (cDNAs) are essential for the correct annotation of genomic sequences and for the functional analysis of genes and their products. We isolated 155,144 RIKEN Arabidopsis full-length (RAFL) cDNA clones. The 3'-end expressed sequence tags (ESTs) of 155,144 RAFL cDNAs were clustered into 14,668 nonredundant cDNA groups, about 60% of predicted genes. We also obtained 5' ESTs from 14,034 nonredundant cDNA groups and constructed a promoter database. The sequence database of the RAFL cDNAs is useful for promoter analysis and correct annotation of predicted transcription units and gene products. Furthermore, the full-length cDNAs are useful resources for analyses of the expression profiles, functions, and structures of plant proteins.

Arabidopsis↗
PubMed2001

Cellular specificity for the activation of fibroblast growth factor-2 by heparan sulfate proteoglycan.

Heparan sulfate proteoglycans (HSPGs) promote cellular proliferation through interaction with FGF-2. To examine the role of cellular specificity of HSPG in FGF-2 function, a recombinant soluble isoform of CD44 (rsCD44v3,8-10) was expressed in various cell types; 293 T fibroblasts, the epithelial carcinoma cell lines A431 and HOTZ, the myelomonocytic cell line THP-1, and the Ig-secreting B lymphoblast IM9. The capacity of the recombinant HSPGs expressed in these cell lines to bind and present FGF-2 to the high-affinity receptor FGFR1 was addressed. This novel approach showed a minor difference in the binding and in the FGF-2 stimulating activity of rsCD44v3,8-10 HSPGs from fibroblasts and epithelial cells. However, FGF-2 binding of rsCD44v3,8-10 from IM9 and THP-1 cells was significantly lower, and stimulation of FGF-2 by rsCD44v3,8-10 from these two cell types could not be detected. We tested the possibility that the differences among cell types were related to the functional profile of endogenous HSPGs. The initial survey of a wider panel of cell types revealed high levels of HSPGs synthesis on the surface of 293 T, epithelial and IM9 cells, but low levels on the surface of other cells of hematopoietic origin. Surprisingly, native HSPGs from fibroblasts and epithelial cell lines promoted FGF-2 biological activity to vastly different extents, and cell surface HSPGs from IM9 cells induced an FGF-2 response. Altogether, the results suggested a role for cell-specific HS modification in addition to synthesis as regulatory mechanisms for the cellular specificity of proteoglycan function.

B-Lymphocytes↗
PubMed2000

Single-pinhole confocal imaging of sub-resolution sparse objects using experimental point spread function and image restoration.

Sparse fluorescent pointlike subresolution objects have been imaged using a diffraction limited single-pinhole confocal fluorescence microscope. A Maximum likelihood image restoration algorithm has been used in conjunction with a measure of the experimental point spread function for improving the three-dimensional imaging of subresolution sparse objects. The experimental point-spread-function profiles have been improved by a factor of 1.95 in lateral direction and 3.75 in axial direction resulting in full-width half maximum (FWHM) values of 91 +/- 11 nm and 160 +/- 26 nm. This amounts to 1. 43 and 2.15 in optical units, respectively. The lateral and axial FWHM of the sparse pointlike subresolution objects is about 5 and 3 times smaller than the wavelength. This result points to the attractive possibility of utilising a compact confocal architecture for localising punctuate fluorescent objects having subresolution dimensions. The key resides in the utilisation of the measured point spread function coupled to an appropriate image restoration approach, and, of course, in the stability of the confocal system being used.

Algorithms↗
PubMed2006

Xenopus Zic4: conservation and diversification of expression profiles and protein function among the Xenopus Zic family.

We compared the expression and function of Xenopus Zic4 with those of the other four Xenopus laevis Zic family members (Zic1, Zic2, Zic3, and Zic5). Zic4 expression was detected mainly in the neural plate border, dorsal neural tube, and somites, and was similar to that of Zic1, which is adjacent to Zic4 on the same chromosome. Injection of wild-type or mutant Zic4 RNA caused the induction of neural crest marker gene expression, hyperplastic neural tissue, and ectopic pigment cell formation, indicating that Zic4 can induce neural and neural crest tissue, as can other Xenopus Zic genes. Deletion analysis showed that the zinc-finger domain is critical for many Zic4 functions, but the C-terminal region is differently involved in induction of two neural crest markers, Slug and Sox10. The protein function as determined by the animal cap explant assay was similar to that of Zic5, but different from those of Zic1, Zic2, and Zic3, suggesting that Xenopus Zic genes can be divided into two groups based on function. These results indicate that the five Xenopus Zic genes cooperatively regulate both neural and neural crest development, despite significantly diverged expression profiles and functions.

Amino Acid Sequence↗
PubMed2002

T-cell-mediated lysis of endothelial cells in acute coronary syndromes.

BACKGROUND: CD4 T lymphocytes accumulate in unstable plaque. The direct and indirect involvement of these T cells in tissue injury and plaque instability is not understood. METHODS AND RESULTS: Gene profiling identified perforin, CD161, and members of the killer-cell immunoglobulin-like receptors as being differentially expressed in CD4(+)CD28(null) T cells, a T-cell subset that preferentially infiltrates unstable plaque. Frequencies of CD161(+) and perforin-expressing CD4 T cells in peripheral blood were significantly increased in patients with unstable angina (UA). CD161 appeared on CD4(+)CD28(null) T cells after stimulation, suggesting spontaneous activation of circulating CD4 T cells in UA. Perforin-expressing CD4(+) T-cell clones from patients with UA exhibited cytotoxic activity against human umbilical vein endothelial cells (HUVECs) in redirected cytotoxicity assays after T-cell receptor triggering and also after stimulation of major histocompatibility complex class I-recognizing killer-cell immunoglobulin-like receptors. HUVEC cytolysis was dependent on granule exocytosis, as demonstrated by the paralyzing effect of pretreating CD4(+)CD28(null) T cells with strontium. Incubation of HUVECs with C-reactive protein (CRP) increased HUVEC lysis in a dose-dependent fashion. CONCLUSIONS: In patients with UA, CD4 T cells undergo a change in functional profile and acquire cytotoxic capability. Cytotoxic CD4 T cells effectively kill endothelial cells; CRP sensitizes endothelial cells to the cytotoxic process. We propose that T-cell-mediated endothelial cell injury is a novel pathway of tissue damage that contributes to plaque destabilization. The sensitizing effect of CRP suggests synergy between dysregulated T-cell function and acute phase proteins in acute coronary syndromes.

Acute Disease↗
PubMed2006

MitoK(ATP)-dependent changes in mitochondrial volume and in complex II activity during ischemic and pharmacological preconditioning of Langendorff-perfused rat heart.

It has been proposed that activation of the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) is part of signaling pathways triggering the cardioprotection afforded by ischemic preconditioning of the heart. This work was to analyze the mitochondrial function profile of Langendorff-perfused rat hearts during the different phases of various ischemia-reperfusion protocols. Specifically, skinned fibers of ischemic preconditioned hearts exhibit a decline in the succinate-supported respiration and complex II activity during ischemia, followed by a recovery during reperfusion. Meanwhile, the apparent affinity of respiration for ADP (which reflects the matrix volume expansion) is increased during preconditioning stimulus and, to a larger extent, during prolonged ischemia. This evolution pattern is mimicked by diazoxide and abolished by 5-hydroxydecanoate. It is concluded that opening the mitoK(ATP) channel mediates the preservation of mitochondrial structure-function via a mitochondrial matrix shrinkage and a reversible inactivation of complex II during prolonged ischemic insult.

Adenosine Diphosphate↗
PubMed1997

Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment.

For an understanding of the aberrant biology seen in mouse mutations and identification of more subtle phenotype variation, there is a need for a full clinical and pathological characterization of the animals. Although there has been some use of sophisticated techniques, the majority of behavioral and functional analyses in mice have been qualitative rather than quantitative in nature. There is, however, no comprehensive routine screening and testing protocol designed to identify and characterize phenotype variation or disorders associated with the mouse genome. We have developed the SHIRPA procedure to characterize the phenotype of mice in three stages. The primary screen utilizes standard methods to provide a behavioral and functional profile by observational assessment. The secondary screen involves a comprehensive behavioral assessment battery and pathological analysis. These protocols provide the framework for a general phenotype assessment that is suitable for a wide range of applications, including the characterization of spontaneous and induced mutants, the analysis of transgenic and gene-targeted phenotypes, and the definition of variation between strains. The tertiary screening stage described is tailored to the assessment of existing or potential models of neurological disease, as well as the assessment of phenotypic variability that may be the result of unknown genetic influences. SHIRPA utilizes standardized protocols for behavioral and functional assessment that provide a sensitive measure for quantifying phenotype expression in the mouse. These paradigms can be refined to test the function of specific neural pathways, which will, in turn, contribute to a greater understanding of neurological disorders.

Animals↗
PubMed2006

Significance and fate of septal fibrosis of the liver.

Septal fibrosis commonly occurs during chronic diseases of the liver. It is experimentally reproduced in a proportion of rats treated with pig-serum, and in 100% of rats infected with Capillaria hepatica. These models have only been used in relatively short-term studies. To contribute to the natural history and significance of hepatic septal fibrosis it is important to disclose its fate after prolonged observation, and following partial or total withdrawal of its inciting cause. Adult Wistar rats were sacrificed 3, 6, 9 and 12 months following inoculation of 800 embryonated eggs of C. hepatica. Besides routine histology, liver sections were submitted to immunohistochemical, immunofluorescence and ultrastructural techniques for the identification of cells and extracellular matrix components present in the fibrous septa. Septal blood vessels were studied after portal vein perfusion with India-ink, while the hepatic functional profile and levels of anti-C. hepatica antibodies were determined in collected sera. Results revealed that all parasites were already dead 2 months from inoculation, and the accumulated eggs in the liver lost their capacity to embryonate around the 4th-6th month, when progressive reduction in the number of cells and in the amount of collagen occurred in the septa. Septal fibrosis persisted throughout the time of experimentation (12 months). This fibrosis was seen as a supporting stroma for septal vessels that conducted portal blood directly to the sinusoids. Thus, persistence of fibrosis was probably related to its morphological and functional association with blood vessels.

Journal Article↗
PubMed1998

Expression and transcriptional regulation of the human alpha3 neuronal nicotinic receptor subunit in T lymphocyte cell lines.

The expression of neurotransmitter receptors on the surface of immunocompetent cells is generally accepted as evidence that the nervous system can influence immune responses, even though many aspects of these interactions remain to be elucidated. In this article, we analyzed the expression of the alpha3 nicotinic receptor subunit in human cell lines of myeloid and lymphoid origin and show that the alpha3 mRNA and the receptor molecules containing this subunit are specifically expressed in T lymphocyte cell lines. We have previously characterized the structural properties of the human alpha3 nicotinic subunit gene promoter and defined its functional profile in neuronal cells; in this study, we analyzed the activity of the alpha3 promoter in T lymphocytes and found that the same minimal promoter located in the 0.16-kb BglII-AccIII fragment is responsible for the expression of the alpha3 mRNA in both neuronal and T lymphocyte cell lines. However, the alpha3 transcription initiation patterns in the two cell types were both qualitatively and quantitatively different, and the minimal promoter was differentially modulated by downstream and upstream regulatory elements. These findings suggest that distinct transcriptional mechanisms allow the same promoter to be regulated in a tissue-specific fashion, according to the different functional needs of the two cell types.

Base Sequence↗
PubMed1993

Effects of fumonisin-contaminated corn screenings on growth and health of feeder calves.

Fumonisins are myocotoxins produced by Fusarium moniliforme and F. proliferatum, common molds of corn in North America. The toxin is at especially high concentrations in corn screenings. Fumonisins are toxic to swine and horses, but effects of these toxins in cattle have not been evaluated. This experiment was conducted to determine the effects in cattle of feeding fumonisins at levels known to be toxic to swine and horses. A total of 18 crossbred feeder calves were fed diets containing fumonisins at 15, 31, or 148 micrograms/g for 31 d. Feed consumption, weight gain, complete blood count, serum clinical chemistries, and an immune function profile were done on d -3, 4, 10, 17 and 31 relative to the start of fumonisin feeding. There was no treatment-related effect on feed intake or weight gain, but feed containing 148 micrograms/g of fumonisins seemed to be less palatable than other feeds. Significant increases in serum aspartate amino transferase, gamma glutamyl transpeptidase, lactate dehydrogenase, bilirubin, and cholesterol occurred from d 10 through 31. Mild microscopic liver lesions were present in two calves fed at the highest fumonisin level. Lymphocyte blastogenesis was significantly impaired at the end of the feeding period in the group given the highest dose. Other measures of immune function were not affected significantly. Fumonisins are capable of causing changes in liver function and in some measures of immune function. However, cattle seem to be relatively less susceptible to fumonisins present naturally in grains than either swine or horses.

Animal Feed↗