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Functional magnetic resonance imaging (fMRI) has been widely used for investigating the brain representation associated with dental pain evoked by pulpal electrical stimulation. However, because of the heterogeneity of experimental designs and the small sample size of individual studies, the common brain representation regarding dental pain has remained elusive. We used imaging meta-analysis to investigate six dental pain-related fMRI studies (n = 87) and tested 3 hypotheses: (1) Dental pain is associated with the ‘core’ pain-related network; (2) pain-related brain activation is somatotopically organized in the somatosensory cortex; and (3) dental pain is associated with the cognitive-affective network related to pain. Qualitative and quantitative meta-analyses revealed: (1) common activation of the core pain-related network, including the somatosensory cortex, the insula, and the cingulate cortex; (2) inconsistency in somatotopically organized activation of the primary somatosensory cortex; and (3) common activation in the dorsolateral prefrontal cortex, suggesting a role of re-appraisal and coping in the experience of dental pain. In conclusion, fMRI combined with pulpal stimulation can effectively evoke activity in the pain-related network. The dental pain-related brain representation disclosed the mechanisms of how sensory and cognitive-affective factors shape dental pain, which will help in the development of more effective customized methods for central pain control. [ABSTRACT FROM PUBLISHER]

Pain is associated with anxiety in a dental setting. It has remained unclear how cognitive-affective factors modulate pain and anxiety in a stressful context, such as receiving dental procedures. We hypothesized that both the situational factor (unpredictability about painful stimuli) and the trait factor (pain catastrophizing, i.e., the tendency to interpret pain in negative orientation) account for dental pain. Fifteen healthy participants were recruited to perform an associative learning task. They were asked to learn the pairing between visual cues and the intensity of incoming painful stimuli delivered at the right upper central incisor. Brain activation associated with pain was recorded by functional magnetic resonance imaging (fMRI). The participants reported increased anxiety and pain in the stressful context, where stimuli intensity was not predicted by the preceding cue. The score of the Pain Catastrophizing Scale was positively correlated with the increased pain modulated by unpredictability. Brain activation at the right posterior hippocampus, a region critically related to associative learning of aversive stimuli and context, was correlated with the individual catastrophizing level. Our findings suggest that both the situational factor (unpredictability) and the trait factor (catastrophizing) influence dental pain, highlighting the role of cognitive-affective factors in pain control of dental patients. [ABSTRACT FROM PUBLISHER]

This study anatomized algorithm effects of specific contributing area (SCA) on soil wetness estimation, consequently landslide prediction, in SHALSTAB. A subtropical mountainous catchment during three typhoon invasions is targeted. The peak 2-day rainfall intensity of the three typhoons: Haitang, Mindulle and Herb are 144, 248 and 327 mm/day, respectively. We use modified success rate (MSR) to retrieve the most satisfying mean condition for model parameters in SHALSTAB at three rainfall intensities and respective pre-typhoon NDVI themes. Simulation indicates that algorithm affects the prediction of landslide susceptibility (i.e. FS, Factor of Safety) significantly. Based on fixed NDVI and the mean condition, we simulate by using full scale rainfall intensity from 0 to 1200 mm/day. Simulations show that predicted unstable area coverage increases non-linearly as rainfall intensity increases for all algorithms yet with different increasing trends. Compared to Dinf, D8 always gives lower coverage of predicted unstable area during three typhoons. By contrast, FD8 gives higher coverage areas. The absolute difference (compared to Dinf) in predicted unstable area ranges from ~-3% to +4% (percent watershed area). The relative difference (compared to Dinf) ranges from -15% to as high as +40%. The maximum absolute and relative differences in unstable area prediction occur around the condition of 100--300 mm/day, which is common in subtropical mountainous region. Theoretical relationship among slope, rainfall intensity, SCA and FS value was derived in which FS values are very sensitive to algorithms in the field of slope from 37 to 52degree. Results imply any comparison among SCA-related landslide models or engineering application of rainfall return period analysis must base on the same algorithm to obtain comparable results. This study clarifies the SCA algorithm effect on FS prediction and deepens our understanding on landslide modeling. [ABSTRACT FROM AUTHOR]

This paper intends to investigate the connection between HIV transmission knowledge and prejudicial attitudes towards people with HIV/AIDS (PWAs), with an emphasis on exploring the pattern of cognitive profile in response to knowledge questions. Data for the present study were derived from the 'Health Attitudes and Health Seeking Behavior Study', a telephone survey of a nationally representative sample, aged 20 to 70, from April to May 1997 in Taiwan. A total of 2,471 respondents who had heard of AIDS and knew that it was infectious were included in the analysis. Based on answers to four transmission-route items (blood transfusion, mother-foetus, sexual contacts, needle sharing) and two casual-contact items (shaking hands and sharing utensil), a variable 'pattern of knowledge performance' was constructed, by which the respondents were clustered into five knowledge groups. Bivariate and multivariate analyses illustrated the greater explanatory power of pattern of knowledge performance rather than additive scoring of knowledge items to PWAs' prejudice. Moreover, it was the responses to casual-contact rather than transmission-route questions that made a greater contribution to PWAs' prejudice. Special attention is given to the possible perceptual undertaking inherent in the five types of knowledge group. To implement effective AIDS prevention campaigns and interventions, the design for increasing the risk perception of the correct HIV transmission routes should differ from that of reducing the risk perception of the casually transmitted routes. [ABSTRACT FROM AUTHOR]

Leukocyte Ig-like receptor (LIR)-1 is a member of the Ig superfamily which has been shown to bind the human cytomegalovirus MHC class I homologue UL-18 protein. In this study, we have analyzed the expression and function of LIR-1 in human NK cells. We show that LIR-1 is expressed by a subset of NK cells variable in size among different donors. When compared to the known HLA class I-specific NK receptors, the expression of LIR-1 was found to be partially overlapped with that of CD94-NKG2A or with that of killer inhibitory receptors (KIR) belonging to the Ig superfamily. The use of the soluble form of UL-18 molecule revealed, in double fluorescence analysis, a selective binding to LIR-1+ cells while no correlation was observed between expression of either KIR or CD94-NKG2A molecules and ability to bind UL18. We further determined whether LIR-1 could also function as receptor for HLA class I molecules. To this end, we assessed the capability of LIR-1+ NK cell clones of lysing HLA class I- target cells transfected with different class I alleles, including HLA-A, -B, -C and -G alleles. Data revealed that LIR-1 functions as a broad HLA class I-specific inhibitory receptor recognizing different alleles coded for by different HLA loci. [ABSTRACT FROM PUBLISHER]

Cytomegalovirus causes pneumonia, hepatitis, thrombocytopenia, and hemolytic anemia. Cytomegalovirus adrenalitis in premature infants, however, is rare. This report described a premature newborn who had progressively worsening hyperbilirubinemia, pancytopenia, and hepatosplenomegaly at the age of 4 days. The baby's mother had prolonged rupture of amniotic membrane for about 8 weeks. The infant received exchange blood transfusion, empiric antibiotics treatment, and mechanical ventilation. Pneumonia and sepsis developed at the age of 18 days. Serum anticytomegalovirus immunoglobulin M and urine virus culture were positive for cytomegalovirus. The baby died at the age of 22 days. Autopsy showed cytomegalovirus infection complicated with interstitial pneumonitis and pulmonary edema, subacute bronchopulmonary dysplasia with interstitial fibrosis, and adrenalitis. We concluded that the functional status of the adrenal glands in cytomegalovirus-infected premature newborns who have unexplained electrolytes imbalance, fever, diarrhea, weight loss, or hypotension should be closely followed because of the possible involvement of adrenal glands.

Caffeic acid phenethyl ester (CAPE) is an active component isolated from propolis. The aim of this study was to investigate the mechanism of CAPE-induced apoptosis in human leukemic HL-60 cells. It was found that CAPE entered HL-60 cells very quickly and then inhibited their survival in a concentration- and time-dependent manner. CAPE induced characteristic DNA fragmentation and morphological changes typical of apoptosis in these cells. Estimation of the apoptotic percentage showed a time-dependent increase after CAPE (6 microg/mL) treatment (up to 66.7 +/- 2.0% at 72 h). Treatment with CAPE caused rapid activation of caspase-3 after 4 h, down-regulation of Bcl-2 expression after 6 h, and up-regulation of Bax expression after 16 h. These results suggest that CAPE is a potent apoptosis-inducing agent; its action is accompanied by activation of caspase-3, down-regulation of Bcl-2, and up-regulation of Bax in human leukemic HL-60 cells.

A total of 50 human umbilical cord blood (UCB) samples were studied. The hematopoietic stem/progenitor (CD34+) populations were isolated from UCB mononuclear cells (MNC) by means of immunomagnetic separation. Double immunofluorescent staining of UCB CD34+ cells revealed that there was a high proportion (82.33 +/- 4.47%) of CD34+ cells co-expressing CD13, while the percentage of CD34+ CD33+ cells was much lower (22.17 +/- 3.35%). In contrast, for co-expressing lymphoid differentiation antigens, the proportion of CD34+CD38+ cells (38.34 +/- 6.09%) was relatively higher than that of CD34+CD10+ cells (11.52 +/- 1.24%) or CD34+CD2+ cells (9.84 +/- 2.30%). For stimulating the ex vivo expansion of UCB progenitor cells, no single hematopoietic growth factor (HGF) was efficacious when used alone, while combination of 4 HGFs, such as GM-CSF, G-CSF, IL-3, and SCF could induce a 55-fold increase in the myeloid progenitor cells, day-14 CFU-GM, in a short term of 7 days' liquid culture. Cryopreservation of UCB as MNC preparations at -196 degrees C could satisfactorily retain the number and activity of CD34+ cells. After thawing, a high recovery rate of about 80% CD34+ cells was obtained. When suspended in liquid cultures containing a combination of 4 HGFs, as shown above, the frozen cord blood progenitor cells could be well expanded, reaching a >50-fold increase in day-14 CFU-GM, which was very similar to that of the fresh UCB samples. In addition, a similar result was also seen in CFU-GEMM, indicating that after cryopreservation the recovered UCB progenitor cells retain an intact clonogeneic ability capable of efficiently responding to hematopoietic growth factors for ex vivo expansion., (Copyright 2001 S. Karger AG, Basel)

Subglottic hemangioma (SGH) is a benign neoplasm that may cause severe and life-threatening respiratory obstruction in infants. However, patients usually present with inspiratory stridor in the first few months of life and may be mistakenly diagnosed as recurrent or persistent croup. Definitive diagnosis is made by image studies, endoscopic examination and biopsy or all. We report a 2-month-old female infant of SGH with initial clinical manifestations of dyspnea and inspiratory stridor co-existing with cutaneous and cerebellar hemangiomas. Clinicians must be alert the possibility of SGH when associated with cutaneous hemangioma. This patient has received oral steroid treatment for more than two months with improvement of the airway obstruction. Although purplish patch lesions over left side of face, eyelid, cheek, and peri-oral regions regressed, the size of the SGH on the followed MRI was slightly enlarged. The diagnosis and various treatments of SGH are discussed and reviewed in this paper.

Neonates with cerebral infarction do not present with specific symptoms and the condition is usually insidious, so many atypical cases are not diagnosed properly during the neonatal stage. Normal neurological examination results may be found in newborns who have actually had a cerebral infarction insidiously. We present two newborns with cerebral infarction. One had clinical symptoms of seizures. Brain computed tomography showed a low-attenuated area and magnetic resonance angiography showed a decreased caliber and number of cerebral artery branches. The other had normal neurological examination results. He was referred to our hospital due to cyanosis. Brain sonography revealed a focal hyperechoic area and T2 weighted magnetic resonance image showed an increased signal intensity area. The incidence, etiologies, clinical and radiographic findings are also reviewed.

Pyogenic liver abscess (PLA), a very uncommon liver disease in the normal pediatric group is often associated with immunocompromised conditions. Pseudomonas aeruginosa has long been regarded as a relatively rare pathogen of PLA, especially in patients without underlying problems. A previously healthy one-year-and-seven-month-old boy who had symptoms of fever, vomiting and diarrhea got a liver abscess at right hepatic lobe which was confirmed by abdominal ultrasound and computed tomography (CT) diagnoses. Ultrasound-guided percutaneous aspiration of liver abscess was done soon after the confirmation. The culture result of aspirate grew P. aeruginosa. The patient received a 4-week course of adequate antibiotics treatment after the aforementioned aspiration procedure. In addition, a series of ultrasounds were performed to follow the resolution of abscess during the treatment period. The immune function tests of the patient were within normal ranges. Finally, the lesion resolved completely without leaving any complication.

The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship between endogenous cytokine levels and circulating platelet counts, we measured the serum levels of both thrombopoietic and inflammatory cytokines in the peripheral blood and bone marrow samples from 70 patients with clonal thrombocytosis (CT) caused by myeloproliferative disorders, 28 patients with reactive thrombocytosis (RT), and 35 normal control subjects. The levels of thrombopoietin (TPO), interleukin-6 (IL-6), soluble IL-6 (sIL-6) receptor, IL-11, stem cell factor (SCF), IL-3, and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). Platelet counts were significantly higher in both CT and patients with RT (699+/-399x10(9)/L, P<.001; 642+/-200 x 10(9)/L, P<.001; respectively) as compared with the normal control subjects (240+/-47x10(9)/L). The concentrations of cytokines in the bone marrow correlated well with those in the peripheral blood. The endogenous levels of TPO, IL-6, and sIL-6 receptor were significantly higher in both CT and patients with RT than those in normal control subjects. The median level of IL-6 was significantly higher in patients with RT than in patients with CT (40 pg/mL vs. 5 pg/mL; P<.001); however, there was no detectable difference in TPO and sIL-6 receptor levels between the two groups. Significantly higher levels of SCF and IL-8 were also found in patients with CT as compared with those found in normal control subjects (median 2460 pg/mL vs 1995 pg/mL, P<.05; 20 ng/mL vs. 5 ng/mL, P = .001; respectively). Finally, IL-11 and IL-3 levels were undetectable in most patients with thrombocytosis. Our results reveal that the endogenous levels of TPO, IL-6, sIL-6 receptor, IL-8, and SCF are elevated in patients with CT or RT. These cytokines appear to be active mediators involved in the regulation of thrombopoiesis during clonal and reactive thrombocytosis.

Differentiation therapy with all-trans retinoic acid (ATRA) represents a landmark approach in the treatment of acute promyelocytic leukemia (APL). However, a potentially fatal complication of retinoic acid (RA) syndrome occurs in about a quarter of patients and its pathophysiology is still unclear. In order to investigate whether or not the treatment with ATRA leads to increased elaboration of inflammatory cytokines and adhesion molecules by the APL cells, the expression of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-8, L-selectin and intercellular adhesion molecule-1 (ICAM-1) was examined in the APL cells after induction of differentiation with ATRA in the presence or absence of granulocyte-colony stimulating factor (G-CSF) or IL-3 in the present study. Cytokine elaboration by the treated cells was detected using both Northern blotting and enzyme-linked immunosorbent assay. Our results have shown that ATRA induces an increased expression of IL-8, IL-1beta, TNF-alpha and ICAM-1 in APL cells, which can be amplified by the addition of G-CSF. These data imply that the induction of inflammatory cytokines in APL cells may play an important role in the pathogenesis of RA syndrome. Furthermore, G-CSF, through its potent differentiating activity, may increase the risk of such complications during ATRA treatment.

A 45 kDa glycoprotein was purified from the culture media of human cytomegalovirus (HCMV)-infected fibroblasts. N-terminal sequencing revealed that the protein, R27080, is the translation product of the R27080 open reading frame of HCMV. R27080 is highly glycosylated and contains no cysteine or methionine residues. Proteolytic cleavage of R27080 by a furin-like enzyme was analysed in transfected COS-7 cells. R27080 is the first identified viral protein secreted from HCMV-infected cells.

Leukocyte Ig-like receptor (LIR)-1 is a member of the Ig superfamily which has been shown to bind the human cytomegalovirus MHC class I homologue UL-18 protein. In this study, we have analyzed the expression and function of LIR-1 in human NK cells. We show that LIR-1 is expressed by a subset of NK cells variable in size among different donors. When compared to the known HLA class I-specific NK receptors, the expression of LIR-1 was found to be partially overlapped with that of CD94-NKG2A or with that of killer inhibitory receptors (KIR) belonging to the Ig superfamily. The use of the soluble form of UL-18 molecule revealed, in double fluorescence analysis, a selective binding to LIR-1 + cells while no correlation was observed between expression of either KIR or CD94-NKG2A molecules and ability to bind UL18. We further determined whether LIR-1 could also function as receptor for HLA class I molecules. To this end, we assessed the capability of LIR-1 + NK cell clones of lysing HLA class I- target cells transfected with different class I alleles, including HLA-A, -B, -C and -G alleles. Data revealed that LIR-1 functions as a broad HLA class I-specific inhibitory receptor recognizing different alleles coded for by different HLA loci.

Human T lymphocytes isolated from peripheral blood were cryopreserved at -196 degreesC for different periods of 3, 14, 21, 35, and 50 days. Viability and cytokine-producing activity of T cells were examined before and after cryopreservation. A high recovery (90 +/- 1%) of viable T cells was obtained at each frozen period, indicating that a 10% loss of cells was due to the freezing process rather than the duration of cryopreservation. There was no difference in cell cycle distribution between PHA-treated fresh and frozen lymphocytes. Resting human T cells produced little or no cytokine. After stimulation of fresh T cells with PHA, an apparent increase in cytokine production was noted in IL-2 (35.5 +/- 8.3 pg/ml), IL-6 (1280.4 +/- 64.7 pg/ml), tumor necrosis factor-alpha (874.3 +/- 71.7 pg/ml), interferon-gamma (58.9 +/- 2.2 pg/ml), and granulocyte macrophage-colony-stimulating factor (59.5 +/- 4.4 colonies/5 x 10(4) bone marrow cells). Compared with PHA-activated fresh T cells, all the above cytokines did not diminish in their levels in conditioned medium from PHA-treated frozen T cells thawed at each storage period, suggesting that cryopreservation could well retain the cytokine-producing activity of human T lymphocytes. In addition, our results also revealed that cryopreservation rendered T lymphocytes more responsive to PHA in IL-2 production than fresh T cells., (Copyright 1998 Academic Press.)

Leukocyte Ig-like receptors (LIRs) are a newly discovered family of immunoreceptors expressed on monocytes and B cells and at lower levels on dendritic cells and NK cells. The amino acid sequences in the extracellular regions of eight of these receptors show between 63 and 84% identity to the prototypic LIR-1 sequence. LIRs contain either two or four Ig domains and fall into three classes: those with cytoplasmic domains containing two, three, or four immunoreceptor tyrosine-based inhibitory motif-like motifs; those with a short cytoplasmic domain and no immunoreceptor tyrosine-based inhibitory motif-like motifs; and those with no transmembrane domain represented by a single LIR molecule that is presumably secreted. The LIRs are structurally related to the human Fc(alpha)R and the killer inhibitory receptors and map to the same region of chromosome 19 as these genes. Like killer inhibitory receptors, at least two LIRs bind to MHC class I Ags, but their different cellular distribution suggests a distinct role in immune system modulation.

The human cytomegalovirus UL18 gene product is a homolog of cellular major histocompatibility (MHC) class I antigens. UL18 has been proposed to protect virus-infected cells against natural killer (NK) cell cytotoxicity by engaging NK cell killer inhibitory receptors (KIR) for MHC class I. UL18 binds to a novel immunoglobulin superfamily glycoprotein, designated Leukocyte Immunoglobulin-like Receptor (LIR-1). This protein is distinct from, but related to, known KIRs and binds cellular MHC class I antigens. The cytoplasmic domain of LIR-1 contains four putative immunoreceptor tyrosine-based inhibitory motifs. Upon tyrosine phosphorylation, LIR-1 associates with the tyrosine phosphatase SHP-1. In contrast to KIRs, LIR-1 is expressed predominantly on monocytic and B lymphoid cell types, suggesting a distinct biological function.

The present study was to ascertain the immunomodulating and anti-tumor effects of Ganoderma (G.) lucidum. Polysaccharides (PS) from fresh fruiting bodies of G. lucidum (PS-G) were isolated and used to potentiate cytokine production by human monocytes-macrophages and T lymphocytes. Our results had shown that the levels of interleukin (IL)-1 beta, tumor necrosis factor (TNF)- alpha, and IL-6 in macrophage cultures treated with PS-G (100 micrograms/ml) were 5.1-, 9.8- and 29-fold higher, respectively, than those of untreated controls. In addition, the release of interferon (IFN)- gamma from T lymphocytes was also greatly promoted in the presence of PS-G (25-100 micrograms/ml). Furthermore, these cytokine-containing mononuclear cell-conditioned media (PSG-MNC-CM) were found to suppress the proliferation and clonogenicity of both the HL-60 and the U937 leukemic cell lines. DNA labeling and gel electrophoresis showed that treatment with PSG-MNC-CM markedly induced leukemic-cell apoptosis. Flow-cytometric analysis revealed that few (2.3 +/- 0.8%) apoptotic cells were seen in the control cultures, while PSG-MNC-CM treatment resulted in a significant increase in the apoptotic population both in the HL-60 (38.3 +/- 4.5%) and in the U937 (44.5 +/- 3.8%) cells. In addition, 40 to 45% of the treated leukemic cells were triggered to differentiate into mature monocytic cells expressing CD14 and CD68 surface antigens. However, PS-G alone had no such effects even at a higher dose of 400 micrograms/ml. Since untreated macrophages and T lymphocytes produced little or no cytokine, and normal MNC-CM did not suppress leukemic cell growth, it was suggestive that the anti-tumor activity of PSG-MNC-CM was derived from the elevated levels of cytokines. Antibody-neutralization studies further revealed that the anti-tumor cytokines in the PSG-MNC-CM were mainly of TNF- alpha and IFN- gamma, and these 2 cytokines acted synergistically on the inhibition of leukemic-cell growth.

Background: NB4, a cell line derived from a patient with t(15;17) acute promyelocytic leukemia (APL) that undergoes granulocytic differentiation when treated with pharmacological doses of all-trans retinoic acid (ATRA), was used as a model for induction of differentiation. In this study, we examined the interaction of colony-stimulating factors (CSF) and ATRA in affecting the proliferation and differentiation of NB4 cells., Methods: Nitroblue tetrazolium (NBT) reduction was used as a functional marker of leukemia cell differentiation. The number of viable cells was counted by trypan blue exclusion test., Results: Proliferation of NB4 cells increased when exposed to 10(-9)M of ATRA, but reduced progressively when exposed to ATRA at the concentrations of 10(-8)M to 10(-6)M. After culture for 5 days, NBT-positive cell was not detectable in the control cultures with medium alone, but its percentage apparently increased to 84% at 10(-7)M ATRA. Granulocyte (G)-CSF per se had no effect on the granulocytic differentiation of NB4 cells, but it could enhance the NBT reduction when used in combination with various concentrations (10(-9)M -10(-6)M) of ATRA. Interleukin (IL)-3 or granulocyte-macrophage-CSF (GM-CSF) alone also had no effect on the NBT reduction in NB4 cells. However, when combined with ATRA, both caused a slight suppression of NBT reduction. No synergistic effect was noted between IL-3 and G-CSF on the ATRA-induced granulocytic differentiation., Conclusions: G-CSF, but not IL-3 or GM-CSF, can enhance the differentiating activity of ATRA. Further investigations are necessary to evaluate its clinical use.

The aim of this study was to measure the level of cytokines produced by peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA) and determine their effect on normal bone marrow (BM) colony growth. Thirty-five patients with AA and 21 normal controls were enrolled in the study. Medium conditioned by PBMNC of AA patients in the presence of phytohemagglutinin (PHA) was found to be suppressive to the clonal growth of normal BM cells. Thus, we further determined the presence in the PBMNC conditioned medium (CM) of inhibitory cytokines (macrophage inflammatory protein-1 alpha [MIP-1 alpha], transforming growth factor-beta 2 [TGF-beta 2], interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and stimulatory cytokines (granulocyte-macrophage colony-stimulatory factor [GM-CSF], interleukin-3 [IL-3], and stem cell factor [SCF]). The results show no significant difference between AA patients and normal controls in the spontaneous production of all cytokines by PBMNC. After PHA stimulation, the production of MIP-1 alpha, IFN-gamma, TNF-alpha, and GM-CSF significantly increased in the cultures of AA patients (p = 0.0009, 0.0002, 0.0022, and 0.0156, respectively). However, both TGF-beta 2 and SCF were undetectable in most of the tested samples. IL-3 was measured in the conditioned medium only after PHA stimulation, but without significant difference between the two groups (p = 0.67). Furthermore, the myelopoietic suppressing effect of AA-PBMNC CM could be significantly blocked by pretreatment with specific antibodies to the corresponding inhibitory cytokines (MIP-1 alpha, IFN-gamma, and TNF-alpha). After antibody neutralization, an apparent change occurred in the clonal growth of normal BM cells incubated with AA-PBMNC CM, resulting in colony enhancement of 205, 131, and 237% by anti-MIP-1 alpha, anti-IFN-gamma, and anti-TNF-alpha, respectively. These results suggest that overproduction of inhibitory cytokines, rather than underproduction of stimulating cytokines, may play a role in the progression of at least some patients with AA.

Human hepatocellular carcinoma (HCC) cell lines, HEP-G2, J5, and SK-HEP-1, which differ in their differentiation status, were compared for their trans-activating activities after treatment with cytokines or 12-O-tetradecanoylphorbol-13-acetate (TPA). These cells were transfected with a long terminal repeat (LTR) which was derived from human immunodeficiency virus type 1 (HIV-1) and ligated to chloramphenicol acetyl transferase (CAT) gene. After treatment with interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), or TPA, they exhibited various degrees of enhancement of transactivation. The well differentiated HEP-G2 cells exhibited the highest degree of enhancement with these agents, while the poorly differentiated SK-HEP-1 cells showed no enhancement with cytokines and slight enhancement with TPA. The J5 cells, which were intermediate in their status of differentiation, showed a moderate degree of enhancement with cytokines and TPA. These results suggest that HCC cells at different stages of differentiation may produce different levels of cellular transacting factors activated by each of these agents. To map the cytokine response elements (CREs) in the HIV-1-LTR, HEP-G2 cells were transfected with nested series of 5' deletion mutants of HIV-1-LTR and treated with each of these cytokines. It was found that not only the degrees but also the patterns of enhancement varied depending upon the presence of positive or negative regulatory sequences in HIV-1-LTR, and that the NF-kappa B sequence played an important role, either by itself or in conjunction with the 5'-proximal response elements (REs) to interact with cellular trans-activating factors elicited by the cascade of transduction responses to cytokines. Despite the presence of promoters including kappa B and IFN-gamma RE as well as IL-6RE sequence in HIV-1-LTR-transfected cells, the poorly differentiated SK-HEP-1 cells showed no enhancement of transactivation by these cytokines, suggesting the lack of receptors or activity of some signal transduction factors which are present in well differentiated HEP-G2 and moderately differentiated J5 cells.

The granulomonopoietic enhancing factor (GM-EF) is a novel myelopoietic regulator produced by human monocyte-derived lipid-containing macrophages (MDLMs). In the present study, we examined the effect of lymphocytes on GM-EF production by preincubation of MDLMs with various preparations of lymphocyte subpopulations in cell-mixed and in double agar layer cultures. Our results showed that a cell concentration-dependent suppression of GM-EF production was noted in cultures with mitogen-activated T cells, and mitogen-activated/resting B cells, while those containing resting T cells had no such effect. Thus, GM-EF production in the presence of 1 x 10(5)/ml activated T cells or activated/resting B cells was greatly reduced to 5% or 20%, respectively. The lymphocyte-induced suppression was evident in both cell-mixed and double layer cultures, implying that the effector cells might exert their influences via mediators. Assay for cytokine activity revealed that a high level (648.2-685.2 pg/ml) of tumor necrosis factor-alpha (TNF-alpha) was found in MDLM cultures with resting/activated B cells, and in those with activated T cells high levels of both TNF-alpha (510.5 pg/ml) and interferon-gamma (IFN-gamma) (321.3 pg/ml) could be detected, whereas in cultures with MDLMs and/or resting T cells, these cytokines were not measurable. Treatment of MDLMs with either recombinant (r) TNF-alpha or rIFN-gamma invariably resulted in a dose-dependent decrease in GM-EF production with intense suppression at doses between 400-800 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatocellular carcinoma is the leading cause of male cancer death in Taiwan. We have found that the level of glucocorticoid receptor in hepatocellular carcinoma is significantly higher than that in the peritumoral tissue. In this study, we used a rat liver glucocorticoid receptor complementary DNA probe to examine the expression of glucocorticoid receptor gene in 15 paired samples of hepatocellular carcinoma and their peritumoral tissues. No differences in genomic DNA patterns of the glucocorticoid receptor gene were found between the tumor and peritumoral tissues. The amount of glucocorticoid receptor was found to be significantly higher in hepatoma samples than in peritumoral liver samples. The levels of glucocorticoid receptor messenger RNAs were increased in most tumors compared with their peritumoral samples. To examine the function of glucocorticoid receptors in hepatoma, we examined the expression of glucocorticoid receptor and its relation to cell-cycle progression in human HepG2 cells. Using specific monoclonal antibodies and flow cytometric study, we found glucocorticoid receptor to be expressed constitutively in all cell-cycle phases. In addition, hydrocortisone treatment of HepG2 cells resulted in increased expression of glucocorticoid receptors and increased secretion of alpha-fetoprotein. RU-486, a glucocorticoid antagonist, blocked the hydrocortisone effect, indicating that glucocorticoid receptors are functional in HepG2 cells. Taken together, our data suggest that glucocorticoids and their receptors play an important role in the growth of hepatoma.

The regulation of trans-activating activities of two human hepatocellular carcinoma cell (HCC) lines, HEP-G2 and SK-HEP-1, was investigated. These cells were transfected with the wild-type and a nested series of its 5'-deletion mutants of the long terminal (LTR) repeat derived from HIV-1, which were ligated with the chloramphenicol acetyl transferase gene. These two HCC cell lines exhibited different biological characteristics, reflecting their status of differentiation. Both cell lines showed moderate degrees of constitutive (basal) trans-activating activities. While HEP-G2 cells, which are well differentiated, showed marked degrees of enhancement of trans-activation after treatment with 12-O-tetradecanoylphorbol-13-acetate, SK-HEP-1 cells, which are poorly differentiated, showed only moderate or low degrees of enhancement. These two cell lines up-regulated their trans-activating activities in response to the deletion of some regions of positive and negative regulatory elements, suggesting that they produce trans-acting factors that are quantitatively different from each other, and often employ different sets of positive and negative regulatory elements for trans-activation.

A murine colony-promoting activity (CPA) was found in the supernatants of Dexter long-term bone marrow cultures (LTBMC). This activity itself failed to stimulate in vitro granulocyte-macrophage colony (CFU-GM) formation but could increase the number of colonies induced by colony-stimulating factors (CSFs). CPA was produced by the adherent stromal cells but not by the nonadherent cells. No CPA could be detected in cultures of pure marrow fibroblasts, nor was it secreted by the stromal cells following macrophage depletion. In contrast, a large amount of CPA was found in cultures of isolated macrophages, suggesting that marrow macrophages may be the main cell source of CPA. Although colony formation was augmented by adding CPA in combination with various CSFs, the colony type induced by CPA plus CSF was no different from that of CSF alone. Preincubation of bone marrow (BM) cells with CPA at 37 degrees C for 24 hours before using in clonal culture assay resulted in a marked colony enhancement. Furthermore, colony formation by 5-fluorouracil (5-FU)-treated marrow cells could be induced by granulocyte-macrophage (GM)-CSF plus CPA but not by GM-CSF alone. These results suggest that CPA may act on early developing hematopoietic stem cells to induce them to differentiate into more mature myeloid progenitor cells capable of responding to CSF stimulation. CPA was nondialyzable and stable under heat (56 degrees C for 30 minutes) and freeze/thawing (3 times). Its activity was acid-labile (pH 2.0) but relatively alkaline-resistant (pH 11.0). When treated with enzymes, CPA was sensitive to trypsin and bacterial protease but not to neuraminidase. In addition, the activity of CPA could be abrogated by anti-CPA antiserum but remained unchanged after treatment with antibodies to other murine hematopoietic synergizing/stimulating factors, including interleukin-1 (IL-1), IL-3, IL-4, IL-6, and stem cell factor (SCF).

Cutaneous alternariosis is rare. Most infections occur in immunocompromised hosts. We report the first three cases in Taiwan. The patients were elderly farmers residing in Tainan. They developed indolent, erythematous, ulcerated or crusted papules, plaques or pustules over the extensor aspect of the forearms or hands. Pure colonies of Alternaria sp were isolated from biopsy specimens in each case. The diagnosis was confirmed by detecting pleomorphic fungal elements in the dermis within suppurative, granulomatous infiltrates. All three patients were immunocompromised. They showed a negative reaction to an intradermal test of seven common antigens. Cases 2 and 3 had iatrogenic Cushing's syndrome. Cases 1 and 3 had extensive scabies, which in Case 1 was of the Norwegian type. To the best of our knowledge, scabies associated with alternariosis has not been reported previously. The infection showed spontaneous regression in Case 1; in Case 2, it resolved after seven weeks of intralesional amphotericin B at a dose of 1 mg/mL twice a week.

In an effort to better understand the cognitive and attitudinal factors underlying public opinion on AIDS-related issues, this article proposes and empirically tests a model of the relationships between (1) knowledge of HIV transmission, specifically the misinformation that AIDS can be transmitted easily through casual contact with HIV-infected persons; (2) attitudes toward homosexuals, the most prominent of the social groups presently affected by the AIDS crisis; and (3) support for restrictive public policies aimed at HIV-infected persons. Data from two nationally representative surveys conducted in December of 1985 (N = 2,308) and in July of 1987 (N = 2,095) provide evidence that misinformation about AIDS transmission and negative attitudes toward homosexuals are strong predictors of support for stringent restrictions of persons with AIDS. The findings also suggest that several background factors, in particular, education and political liberalism, may also play decisive roles in influencing levels of support for restricting those infected with the AIDS virus.

The majority of tinea capitis in southern Taiwan occur in adult women and are caused by Trichophyton violaceum. We report the histopathological findings of a series of 10 cases of tinea capitis caused by T. violaceum, the largest such study to date. Our study provides new information regarding the process of hair infection, mechanism of black dot formation, and chronicity of infection caused by this fungus. The cuticle remains intact. The fungi enter the proximal cortex where the cuticle is immature. They then colonize the proximal keratinized cortex and generate septate hyphae which transform gradually into arthrospores as they are carried upwards by the growing hair. At the infundibular level, the hair cortex is almost completely replaced by spores and swells, impeding further exit of the growing hair and causing the already weakened hair to coil up inside the infundibulum, forming a black dot. In one patient who had infection for more than 20 years, there were changes suggestive of cyclic reinfection of the same follicles which might contribute to the chronicity of the infection.

Langerhans cells (LCs) are considered to be responsible for the immunologic presentation of tumor-associated antigens and play a role in the elimination of neoplastic clones. Ultraviolet light B can cause dysfunction and loss of LCs. Both the number and dendritic morphology of LCs are known to be diminished in squamous cell carcinomas from sun-exposed skin. The effects of arsenics on LCs are unknown. Using an OKT-6 monoclonal antibody to stain intraepithelial LCs, we compared their number and morphology in Bowen's lesions and in the perilesional skin from sun-protected sites in ten patients with chronic arsenicism. There was a significant reduction in the numbers of LCs in the Bowen's lesions as compared to the perilesional skin specimens. Loss of dendrites was observed in all Bowen's lesions and in seven of the perilesional skin specimens. Ultrastructurally, the LCs showed an absence of dendrites, but the Birbeck granules were preserved. Since the specimens were not from sun-exposed skin in our study, the findings may be related to chronic arsenic intoxication. The morphologic alteration of LCs observed in the perilesional skin further suggests an arsenic-related systemic dysfunction of the LCs, which in turn may contribute to the development of skin cancers in these patients.

We have found that mitoxantrone can inhibit the polymerization of brain tubulin in a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosine-triphosphatase (GTPase) activity nor could it compete with vinblastine (VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1-10 microM) is antiproliferative to cold-treated (0 degree C) epithelial cells after only brief exposure (30 min). These results indicated that MXT is a microtubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly.

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) secreted by a hepatoma cell line, HA22T/GVH, was purified and assessed for its effects in vivo on blood leukocytes and bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in ICR mice pretreated with a sublethal dose of cyclophosphamide (cytoxan). The hGM-CSF preparations were natural and had no detectable endotoxin. Five days after the administration of 300 mg/kg cytoxan, severe leukopenia with marked myelopoietic suppression was induced. The cytoxan-treated mice were then injected intraperitoneally with 10,000 units of purified hGM-CSF/mouse daily for three days. Leukopenia was totally abrogated and the leukocyte number greatly increased to a level 2- to 3-fold higher than in GM-CSF-uninjected mice. Differential white cell count showed that the subpopulations of leukocytes responsive to hGM-CSF stimulation were mainly of neutrophils and monocytes, while the lymphocytes remained unaffected. Meanwhile, in the bone marrow, hGM-CSF administration induced an apparent (3-fold) increase in the number of myeloid progenitor cells, CFU-GM. However, the effect in vivo of a single hGM-CSF injection could only maintain for 48 hrs. In addition, the loss in body weight caused by cytoxan was less in the mice with subsequent hGM-CSF than those without CSF. These results suggest that injection of GM-CSF can effectively reconstitute the cytotoxic drug-damaged myelopoiesis without apparent in vivo toxic reaction.

We report the clinicomycologic study of 27 culture-proven cases of tinea capitis from southern Taiwan during the years 1988 to 1990. The series is notable for its predominance of adults (63%), of women (89%), and of Trichophyton violaceum infection (74%). The age distribution was clearly bimodal; the median age was 6 years for children and 56 years for adults (older than 18 years). Whether or not these findings represent a new trend of tinea capitis in southern Taiwan remains to be determined. Clinically, our cases of black-dot ringworm caused by T. violaceum often presented with subtle changes of scaling, hair loss, and black dots. The keys to the correct diagnosis are (1) a high clinical index of suspicion with careful inspection of the scalp for the presence of black dots, and (2) microscopic examination and culturing of the black dots or plucked hairs.