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PubMed2006

Hepatitis, cholangitis, pulmonary hypertension, digital gangrene, and conjunctivitis sicca in a woman with anticentromere antibodies.

A 46-year-old woman presented with chronic fluctuated liver function impairment, Raynaud's phenomenon, digital gangrene, pulmonary hypertension, and intense pruritus within a period of 2 years. Laboratory investigations revealed antinuclear antibodies, anticentromere antibodies (ACA), hypergammaglobulinemia, lymphocytic infiltration of the liver parenchyma, and mild cholangitis. The associated symptoms included thyroiditis, conjunctivitis sicca, xerostomia, and polyarthralgia. There was no conspicuous sclerodactyly, calcinosis, or dysphagia. The symptoms were relieved with intravenous, as well as oral, methylprednisolone. This constellation of presentations, including chronic autoimmune hepatitis with mild cholangitis and pulmonary hypertension, suggested that the presence of serum ACA might indicate relentless visceral organ damage.

Journal Article↗
PubMed2005

Introduction of MMF in conjunction with stepwise reduction of calcineurin inhibitor in stable liver transplant patients with renal dysfunction.

Mycophenolat mofetil (MMF) is a new imunosuppressant without nephrotoxic adverse effects. The aim of this study was to evaluate feasibility and effect of MMF introduction in conjunction with stepwise reduction of calcineurin inhibitors (CNI) in stable liver transplant patients with chronic CNI-induced renal dysfunction (RDF). In the MMF-group (n=27) but not in the controls (n=16), mean serum level of creatinine fell from a baseline of 227.4+/-67.9 micromol/l to 159.2+/-48.2 micromol/l (P<0,001), while mean urea level declined significantly from a baseline of 18.5+/-8.7 mmol/l to 11.4+/-4.2 mmol/l 6 months after initiation of MMF. Additionally, systolic and diastolic blood pressure values improved. In 52% of patients, dose reduction (n=11) or withdrawal (n=3) of MMF was necessary due to gastrointestinal or hematologic adverse effects. But also in patients on low dose MMF, there was a significant improvement of renal function without increased immunological risk.

Adult↗
PubMed2004

Foldable versus rigid intraocular lenses in conjunction with pars plana vitrectomy and other vitreoretinal procedures.

PURPOSE: To compare the results of foldable acrylic intraocular lens (IOL) implantation through a clear corneal incision with those of rigid IOL implantation in eyes having pars plana vitrectomy (PPV). SETTING: Tertiary referral-based university institute. METHODS: A consecutive retrospective comparative chart review was performed in all eyes that had PPV and foldable IOL implantation between May 15, 1999, and November 1, 2000 (n = 30), and all eyes that had PPV and rigid IOL implantation between April 1, 1996, and May 14, 1999 (n = 30). Preoperative baseline data and postoperative outcome data were recorded. Pars plana vitrectomy and associated vitreoretinal procedures were performed as indicated according to individual circumstances. A minimum of 1 week of follow-up information was available for all eyes. RESULTS: Baseline characteristics in both groups of patients, including age, sex, eye involved, and phakic state, were similar. The preoperative visual acuities were also similar, ranging from 20/30 to hand motions; the mean visual acuity was 20/200. The IOL was implanted in all eyes uneventfully and did not restrict fundoscopy. The mean follow-up was significantly longer in the rigid IOL group (20 months) than in the foldable IOL group (7 months) (P<.001), probably because of the earlier case acquisition. The mean postoperative best corrected visual acuity was 20/200 in the foldable IOL group and 20/100 in the rigid IOL group. There was no difference between the 2 groups in the rate of postoperative retinal detachment, recurrent macular hole, or repeat PPV. Elevated intraocular pressure (IOP) on the first postoperative day was more common in the rigid IOL group than in the foldable IOL group (P =.078) because more patients in the rigid IOL group had surgery for diabetic ocular complications and these patients had a greater IOP rise. CONCLUSION: Acrylic IOLs can be safely implanted in conjunction with PPV in selected cases.

Acrylic Resins↗
PubMed2004

Selective search for conjunctively defined targets by children and young adults.

Two experiments were conducted to investigate age-related differences in visual search for targets defined by the conjunction of two features. In the experiments, 7- and 10-year-old children and young adults searched visual displays for a black circle among distractors consisting of gray circles and black squares. In Experiment 1 (N = 60), we compared performance in the standard search task (where an equal number of each type of distractor appeared across all display sizes) with performance in a modified search task (where the number of black squares was fixed at two and the number of gray circles increased as the display size increased). In Experiment 2 (N = 60), the ratio of black stimuli to gray stimuli was varied systematically as the display size increased. Results of both experiments indicated that all participants were able to restrict search to an appropriate subset of the display rather than conduct an exhaustive search. However, the young adults were more efficient in their ability to do so than were either the 7- or 10-year-old participants. The 10-year-olds were as efficient as the young adults when the number of black stimuli in the display was relatively small. However, these children became relatively less able to restrict search effectively as the number of black stimuli increased. Discussion focused on possible preattentive and attentive processes that may change systematically with age.

Adolescent↗
PubMed2005

Strategies for characterization of drug metabolites using liquid chromatography-tandem mass spectrometry in conjunction with chemical derivatization and on-line H/D exchange approaches.

Strategies using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in conjunction with techniques such as chemical derivatization and on-line hydrogen/deuterium (H/D) exchange for structural elucidation of drug metabolites in crude samples are reviewed. Useful mass spectrometric scan techniques discussed include product ion scan, constant neutral-loss scan, precursor ion scan, multistage MS(n), and accurate mass measurements. In biological systems, xenobiotics are transformed into metabolites, which usually involves introduction of one or more polar functional groups or removal or blockage of such structural moieties. Therefore, chemical derivatization strategies for determination of functional groups and on-line H/D exchange approaches for probing number of exchangeable hydrogens are powerful tools for structural elucidation of drug metabolites in drug metabolism studies. More importantly, these experiments can be carried out on crude samples in microscale, providing sufficient material for LC-MS/MS analysis. Therefore, labor intensive and technically challenging purification of low levels of drug metabolites from complex biological matrices can be avoided. It is the authors' conclusion that strategies such as chemical derivatization and on-line H/D exchange should be used more routinely in drug metabolism studies in order to facilitate metabolite identification.

Chromatography, Liquid↗
PubMed2004

Insights into Vitamin D metabolism using cyp24 over-expression and knockout systems in conjunction with liquid chromatography/mass spectrometry (LC/MS).

The development of novel gene expression systems for cytochrome P450s (CYPs) together with a revolution in analytical mass spectrometry with the emergence of liquid chromatography/mass spectrometry (LC/MS) has opened the door to answering some long-standing questions in Vitamin D metabolism. Our studies focused on: (1) elucidating the role of CYP24 in 25-OH-D3 and 1alpha,25-(OH)2D3 metabolism; (2) exploring how DBP influences this process; (3) measuring 25-OH-D3 metabolism in CYP24-knockout (CYP24-XO) cells and; (4) comparing 1alpha-OH-D2 metabolism in the CYP24-XO mouse in vivo and in vitro. Methodology employed CYP24 over-expression and knockout systems in conjunction with state-of-the-art analytical LC/MS, diode array, and radioisotopic detection methods. We found that CYP24 metabolizes 25-OH-D3 and 1alpha,25-(OH)2D3 at similar rates in vitro, but that for 25-OH-D3 but not 1alpha,25-(OH)2D3, this rate is strongly influenced by the concentration of DBP. Unlike their wild type littermates, the administration of 25-OH-D3 to CYP24-XO mice results in no measurable 24,25-(OH)2D3 production. When neonatal murine keratinocytes are prepared from wild type and CYP24-XO mice there was no measurable production of 24,25-(OH)2D3 or 1alpha,24,25-(OH)2D3 in CYP24-XO mice. Similar experiments using the same wild type and CYP24-XO animals and cells and [3H] 1alpha-OH-D2 resulted in the apparent paradox that the Vitamin D prodrug was 25-hydroxylated in vivo but 24-hydroxylated in vitro.

Animals↗
PubMed2005

Shared networks for auditory and motor processing in professional pianists: evidence from fMRI conjunction.

To investigate cortical auditory and motor coupling in professional musicians, we compared the functional magnetic resonance imaging (fMRI) activity of seven pianists to seven non-musicians utilizing a passive task paradigm established in a previous learning study. The tasks involved either passively listening to short piano melodies or pressing keys on a mute MRI-compliant piano keyboard. Both groups were matched with respect to age and gender, and did not exhibit any overt performance differences in the keypressing task. The professional pianists showed increased activity compared to the non-musicians in a distributed cortical network during both the acoustic and the mute motion-related task. A conjunction analysis revealed a distinct musicianship-specific network being co-activated during either task type, indicating areas involved in auditory-sensorimotor integration. This network is comprised of dorsolateral and inferior frontal cortex (including Broca's area), the superior temporal gyrus (Wernicke's area), the supramarginal gyrus, and supplementary motor and premotor areas.

Adult↗
PubMed2006

Illusory conjunctions in simultanagnosia: coarse coding of visual feature location?

Simultanagnosia is a disorder characterized by an inability to see more than one object at a time. We report a simultanagnosic patient (ED) with bilateral posterior infarctions who produced frequent illusory conjunctions on tasks involving form and surface features (e.g., a red T) and form alone. ED also produced "blend" errors in which features of one familiar perceptual unit appeared to migrate to another familiar perceptual unit (e.g., "RO" read as "PQ"). ED often misread scrambled letter strings as a familiar word (e.g., "hmoe" read as "home"). Finally, ED's success in reporting two letters in an array was inversely related to the distance between the letters. These findings are consistent with the hypothesis that ED's illusory reflect coarse coding of visual feature location that is ameliorated in part by top-down information from object and word recognition systems; the findings are also consistent, however, with Treisman's Feature Integration Theory. Finally, the data provide additional support for the claim that the dorsal parieto-occipital cortex is implicated in the binding of visual feature information.

Aged↗
PubMed2004

Histologic evaluation of a 12-year-old threaded hydroxyapatite-coated implant placed in conjunction with subantral augmentation procedure: a clinical report.

This clinical report presents a histologic evaluation of a threaded hydroxyapatite-coated root-form implant retrieved from the posterior maxillary area of a patient after being in function for 12 years. The implant had been placed in conjunction with subantral augmentation. Histologically, the portion of the implant that was examined under light microscopy appeared to be integrated with the surrounding bone; 74.3% of the surface of the implant had close bone apposition at the interface. The residual graft particles were present and in close proximity to the implant surface. These observations suggest that subantral augmentation procedure performed simultaneously with the placement of a hydroxyapatite-coated implant by using hydroxyapatite as a graft material may result in osseointegration between the implant and the surrounding bone that can be maintained under long-term function.

Aged↗
PubMed2005

Donor MHC class I peptides in conjunction with self-epitopes induce donor-specific tolerance in a dose-dependent manner but unable to abrogate chronic rejection.

Understanding specific tolerance mechanisms is a primary goal of transplantation science. We have previously shown that hosts treated with MHC class I protein have donor sequences in the alpha1-helix of the alpha1 domain on a background of self-epitopes, resulting in the development of donor-specific tolerance. However, the nature of class I alloantigenic determinants that regulate the alloimmune response remains unclear. The alpha1-helical sequence of RT1.A,1 which shares RT1.A(u) sequences, was substituted in the RT1.A(a) molecule to produce the composite [alpha1h(l/u)]-RT1.A(a) MHC class I allochimeric molecule. Immunodominant epitopes were identified within the hypervariable region of the alpha1 domain of RT1.A(a) (ACI), RT1.Al (Lewis, LEW), and RT1.A(u) (Wistar Furth [WF]). To clarify the mechanisms of tolerance development through presentation of donor-type immunogenic epitopes and cryptic self-epitopes we used synthetic peptides corresponding to donor immunogenic determinants with peptides derived from recipient self-sequences (RT1.A(a)--aa 10 to 49 P1 and 91 to 120 P3; and P2 RT1.A(l/u) 50 to 90). ACI recipients of LEW and WF cardiac allografts were injected through the portal vein (PV) at day 0 with four doses (2, 0.5, 0.25, and 0.125 mg/rat) of three peptide mixtures in conjunction with subtherapeutic CsA (10 mg/kg for 3 days). Allograft survival was strongly dose-dependent. Only low-dose regimens were consistent in tolerance induction, but such therapy did not abrogate development of chronic rejection (CR), unlike allochimeric therapy with soluble MHC class I protein. Different effects of protein or synthetic peptide therapies on development of CR suggest that development of specific tolerance is an active immunologic process and it depends on the form of allogeneic epitopes presented.

Animals↗
PubMed2004

Attentional effects on sensory tuning for single-feature detection and double-feature conjunction.

When humans scan their visual environment, relevant objects are selectively attended for enhanced processing. It is still unclear in what ways processing is modified by attention, and whether attentional selection operates on an individual feature (such as colour, orientation or motion) or on binding together different features. In the experiments reported in this paper, these two stages were characterized using psychophysical reverse correlation. Subjects viewed eight patches, briefly flashed and symmetrically arranged around fixation. Each patch consisted of segments that could vary in both colour and orientation. One of the patches ('target') differed from the remaining 'distractor' patches with respect to either its orientation, colour, or both (in three different experiments). Subjects were asked to detect the target patch. The stimulus was preceded by a cue. On some trials ('cued' trials), the cue informed observers that the target patch could only appear at two of the eight possible locations. On remaining ('uncued') trials, all eight positions were valid. Psychophysical reverse correlation was then applied to derive linear estimates of sensory filters for orientation only, colour only, and their conjunction. In line with the properties of single neurons in cortex, attentional cueing did not affect sensory tuning for detecting individual features. However, it affected the way in which features were subsequently (and very inefficiently) combined in a multiplicative fashion. The results are consistent with a model in which attention recalibrates internal responses to the statistics of the stimulus by having signals from different features mutually control each other through reciprocal inhibition.

Attention↗
PubMed2006

An inter-item similarity model unifying feature and conjunction search.

We propose a model of visual search to address the hitherto unresolved issue of reconciling serial deployment of attention accounts with inter-item similarity effects. Target-distractor and distractor-distractor similarity were systematically varied in 85 (17x5) set type-size conditions over seven experiments, including univariate feature and bivariate conjunction search. The model, a power (square root) function of dimension-specific target-distractor and distractor-distractor similarity in linear combination with set size, accounted for 98% of the variance on type-size means. It suggests that much of efficient and inefficient search can be unified under a single theory involving item similarity.

Adult↗
PubMed2001

Granulomatous kerato-conjunctivitis as a manifestation of Hodgkin lymphoma.

PURPOSE: To report atypical kerato-conjunctivitis as a manifestation of Hodgkin disease. METHODS: Case report. RESULTS: A 19-year old woman presented with conjunctival nodules and corneal infiltrates. Diffuse lymph node enlargement occurred, but not in the preauricular or submandibular areas. Extensive microbiologic examination was negative. Conjunctival biopsy showed noncaseating granulomas. Inguinal lymph node biopsy showed Hodgkin lymphoma, and chemotherapy was instituted. Ocular signs resolved after 6 weeks, but a corneal scar remained. CONCLUSIONS: The appearance of conjunctival granulomas and corneal infiltrates may represent a clinical manifestation of Hodgkin lymphoma.

Adult↗
PubMed2003

p21waf1/cip1 is down-regulated in conjunction with up-regulation of c-Fos in the lymphocytes of rheumatoid arthritis patients.

Features characteristic to rheumatoid arthritis (RA) including synovial overgrowth and joint destruction are experimentally produced by augmenting c-fos gene expression. We show that cyclin dependent kinase inhibitor p21waf1/cip1, that inhibits cell proliferation, is down-regulated in conjunction with up-regulation of c-fos in the lymphocytes of patients with RA. As to the mechanism of down-regulation of p21waf1/cip1 gene expression, transfection studies in U937 cells showed that c-fos down-regulated phosphorylation and dimerization of signal transducers and activators of transcription (STAT) 1, thereby inhibiting interferon -induced transactivation of p21waf1/cip1. Phosphorylation of STAT1 was indeed decreased in the lymphocytes of patients with RA. Thus, under overexpression of c-fos gene, c-Fos inactivates STAT1 to down-regulate p21waf1/cip1 gene expression in the lymphocytes of patients with RA, and in this way may enhance proliferation of lymphocytes.

Arthritis, Rheumatoid↗
PubMed2001

Critical implication of transmembrane Phe310, possibly in conjunction with Trp279, in the rat gonadotropin-releasing hormone receptor activation.

The GnRH-R belongs to the superfamily of heptahelical GPCRs. A three-dimensional model of GnRH binding to its receptor predicted that Trp3 was the most deeply buried residue, potentially allowing it to interact with both Trp279, a highly conserved residue in the TMH 6 of GPCRs, and Phe310, present essentially in TMH 7 of GnRH-Rs. Replacement of Phe310 with Leu, the most common positional residue in GPCRs, induced a slightly decreased Bmax (1.6-fold) and affinity (3.8-fold); in addition, IP production was completely abolished. Similarly, replacement of Trp279 with Ser depressed the Bmax by 5.2-fold, the affinity by 2.3-fold, and totally abrogated IP production. The effect of the double mutation was not additive on binding, since the Bmax was reduced to the level of the Phe310Leu mutant, although the Kd was restored to a value not significantly different from that of the wild-type. The double mutant was also unable to induce IP production. Unexpectedly, no influence of any single or double substitution was noted on receptor internalization. These data provide evidence for the crucial role of Phe310, possibly in conjunction with Trp279, on GnRH transduction and suggest that the conformation for phospholipase C activation may not be required for GnRH-R internalization.

Amino Acid Sequence↗
PubMed2001

Potentiation of cadmium-induced cytotoxicity by sulfur amino acid deprivation through activation of extracellular signal-regulated kinase1/2 (ERK1/2) in conjunction with p38 kinase or c-jun N-terminal kinase (JNK). Complete inhibition of the potentiated toxicity by U0126 an ERK1/2 and p38 kinase inhibitor.

The mechanisms of cadmium-induced toxicity may include oxidative stress, altered redox homeostasis, and injuries to organelles. The current study was designed to study the effect of decreased cellular glutathione (GSH) content by sulfur amino acid deprivation on cadmium toxicity and to identify the signaling pathways responsible for the cytotoxicity. GSH content was increased by cadmium in H4IIE cells prior to cell death, which was prevented by excess GSH or cysteine. Cell viability, however, was not improved by GSH or cysteine complexation of cadmium. Cadmium-induced cytotoxicity was 40-fold potentiated in cells with decreased GSH by sulfur amino acid deprivation. Cadmium in combination with decreased GSH markedly increased apoptotic cell death. Mitogen-activated protein kinases including extracellular signal-regulated kinase 1/2, p38 kinase and c-Jun N-terminal kinase (JNK) were all activated 1-12 hr after sulfur amino acid deprivation. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), which inhibited activation of extracellular signal-regulated kinase1/2 and p38 kinase in cells under sulfur amino acid deprivation, completely prevented potentiation in Cd-induced cytotoxicity and apoptosis. Potentiation of cadmium toxicity by sulfur amino acid deprivation was prevented in part by either PD98059 or SB203580, or in cells stably expressing dominant negative mutant of JNK1, and to greater extents by PD98059 in combination with either SB203580 or JNK1(-) transfection. These results demonstrated that decreased cellular GSH content potentiated cytotoxicity induced by cadmium at the level of human exposure, and that the potentiation of cytotoxicity resulted from activation of extracellular signal-regulated kinase1/2 in conjunction with p38 kinase or JNK.

Amino Acids↗
PubMed1998

Feature conjunctions and auditory sensory memory.

This study sought to obtain additional evidence that transient auditory memory stores information about conjunctions of features on an automatic basis. The mismatch negativity of event-related potentials was employed because its operations are based on information that is stored in transient auditory memory. The mismatch negativity was found to be elicited by a tone that differed from standard tones in a combination of its perceived location and frequency. The result lends further support to the hypothesis that the system upon which the mismatch negativity relies processes stimuli in an holistic manner.

Acoustic Stimulation↗