Biomedical subjects

C Y Lin

Publications and source records attributed to C Y Lin.

At least 73 records · Page 4Linked to original sources

PubMed2001

Effect of smoking on the treatment of vertigo.

OBJECTIVE: To study the effect of smoking on patients with vertigo. SETTING: University hospital. PATIENTS: Thirty patients with vertigo who smoke and 30 patients with vertigo who don't smoke were age-, sex-, and diagnosis-matched and given the same medication consecutively for 3 months. Then treatment efficacy was compared between two groups to investigate the relationship between smoking and vertigo. RESULTS: The efficacy of treatment of vertigo in the smoking group (30%) was lower than the nonsmoking group (74%). Intractable vertigo is related to smoking behavior but unrelated to either smoking year or tobacco year (exposure to smoking). CONCLUSIONS: For patients with vertigo who smoke during the course of treatment, the treatment may be ineffective. Therefore, neurotologists should inquire about the smoking history in vertigo patients and advise them to abstain from smoking.

Adult↗

PubMed2001

Intracranial relapse of nasopharyngeal carcinoma manifested as sudden deafness.

OBJECTIVE: To differentiate tumor relapse from postirradiation sudden deafness (PISD) in patients with nasopharyngeal carcinoma (NPC). STUDY DESIGN: A retrospective study from December 1991 to November 1999. SETTING: University hospital. PATIENTS: Twenty-five irradiated NPC patients with sudden deafness were investigated. All patients received local examination of ears, nose, nasopharynx, and throat fields, as well as a battery of audiologic and neurotologic tests. RESULTS: Three patients with sudden deafness within 3 years after irradiation received a diagnosis of tumor relapse. Magnetic resonance imaging revealed cerebellopontine angle metastasis in one and intracranial invasion in two. Comparison of the remaining 22 NPC patients who had PISD showed that the mean interval between the completion of irradiation to the onset of sudden deafness was 10+/-5 years. CONCLUSION: Magnetic resonance imaging should be performed to exclude intracranial relapse if sudden deafness develops in a patient with NPC within 5 years after irradiation.

Adult↗

PubMed2001

Cellular mechanisms that cause suppressed gamma interferon secretion in endotoxin-tolerant mice.

Endotoxin (lipopolysaccharide [LPS]) tolerance is a state of altered immunity characterized, in part, by suppression of LPS-induced gamma interferon (IFN-gamma) expression. However, the cellular mediators regulating LPS-induced production of IFN-gamma in normal mice and the effect of LPS tolerance on these mediators has not been well characterized. Our studies show that macrophage dysfunction is the primary factor causing suppressed IFN-gamma expression in LPS-tolerant mice. Specifically, LPS-tolerant macrophages have a markedly impaired ability to induce IFN-gamma secretion by T cells and NK cells obtained from either control or LPS-tolerant mice. However, T cells and NK cells isolated from LPS-tolerant mice produce normal levels of IFN-gamma when cocultured with control macrophages or exogenous IFN-gamma-inducing factors. Assessment of important IFN-gamma-regulating factors showed that interleukin-12 (IL-12) and costimulatory signals provided by IL-15, IL-18, and CD86 are largely responsible for LPS-induced IFN-gamma expression in control mice. IL-10 is an inhibitor of IFN-gamma production in both the control and LPS-tolerant groups. Expression of IL-12 and the IL-12 receptor beta1 (IL-12Rbeta1) and IL-12Rbeta2 subunits are suppressed in the spleens of LPS-tolerant mice. LPS-tolerant splenocytes also exhibit decreased production of IL-15 and IL-15Ralpha. However, expression of IL-18 and the B7 proteins CD80 and CD86 are unchanged or increased compared to controls after induction of LPS tolerance. CD28, a major receptor for B7 proteins, is also increased in the spleens of LPS-tolerant mice. Expression of the inhibitory cytokine IL-10 and the IL-10R are sustained after induction of LPS tolerance. These data show that suppression of IFN-gamma production in LPS-tolerant mice is largely due to macrophage dysfunction and provide insight into the cellular alterations that occur in LPS tolerance. This study also better defines the factors that mediate LPS-induced IFN-gamma production in normal mice.

Animals↗

PubMed2001

Sterol efflux mediated by endogenous macrophage ApoE expression is independent of ABCA1.

Sterol efflux importantly contributes to preservation of cellular cholesterol homeostasis, and multiple pathways may be involved for mediating such efflux. Recently, an important role has been ascribed to ABCA1 in facilitating lipid efflux from cells, including macrophages, to extracellular lipid-free apolipoproteins. Macrophages are relatively unique among cells because they express apoprotein E (apoE) as a major protein product, and this endogenous expression of apoE increases sterol and phospholipid efflux from macrophages. The studies in this article were designed to test whether the sterol efflux mediated by the endogenous expression of apoE in macrophages was dependent on ABCA1 expression. These studies were facilitated by comparing apoE-expressing J774 cells (J774E(+)) with nonexpressing parental cells (J774E(-)). Sterol efflux was higher from J774E(+) cells compared with J774E(-) cells, but the increment in efflux between these cell types was not increased by induction of ABCA1 expression with cAMP. Induction of ABCA1 with cAMP, however, did increase sterol efflux to exogenously added apoA1 from both cell types. Inhibitors of ABCA1 activity significantly reduced (by 40% to 50%) sterol efflux from both J774E(+) and J774E(-) cells treated with cAMP and apoA1. This inhibitor did not, however, reduce the increment in sterol efflux due to the expression of endogenous apoE. The results of these studies indicate that the increment in sterol efflux mediated by the endogenous expression of apoE in macrophages does not depend on ABCA1 expression or activity.

ATP Binding Cassette Transporter 1↗

PubMed2001

Evaluation of the Seventh Malaysian Health Plan: a new approach.

Since the First Malaysia Plan (1966-1970) many reviews have been done on the five-year health plans of the Ministry of Health (MOH). These included the Mid-Term Reviews and the review done at the end of the respective five-year plan period. There was no structured evaluation method carried out until the Seventh Malaysia Plan (7MP) period (1996-2000), among others because of the complexity of the MOH health plans. The evaluation of the 7MP was the first one conducted using a better-structured process. The findings and recommendations of the evaluation were used and incorporated in the subsequent 5-year health plan, under the Eighth Malaysia Plan (2001-2005).

Health Planning↗

PubMed2001

Natural history of neonatal herpes simplex virus infections in the acyclovir era.

OBJECTIVE: During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made. DESIGN/METHODS: Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported. RESULTS: Comparisons between patients treated in the periods between 1981-1988 and 1989-1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of >/=10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy. CONCLUSION: Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981-1988 vs 1989-1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within.

Acyclovir↗

PubMed2001

Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections.

OBJECTIVE: The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. PARTICIPANTS: Infants who were </=28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses. METHODS: The study was an open-label evaluation of intravenous acyclovir at dosages higher than the 30 mg/kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) acyclovir (45 mg/kg/d), and the next 72 patients received HD acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) acyclovir for 10 days and in which identical methods (with the exception of acyclovir dosage and duration of therapy) were used. RESULTS: Six (21%) of 29 HD acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count <500/mm(3), and 5 patients had an absolute neutrophil count (ANC) between 500/mm(3) and 1000/mm(3). In all 6 cases, the ANC recovered during continuation of acyclovir at the same dosage or after completion of acyclovir therapy, and there were no apparent adverse sequelae of the transient neutropenia. No other drug-related adverse events were reported among ID or HD recipients, and no other laboratory aberrations could be correlated specifically with antiviral therapy. The survival rate for the patients with disseminated HSV disease treated with HD acyclovir was significantly higher than for those in the previous study treated with SD acyclovir, with an odds ratio (OR) of 3.3 (95% confidence interval [CI]: 1.4-7.9). For patients with CNS disease, however, survival rates were similar for the HD and SD groups. To assess the effect of HD acyclovir on survival for the entire population with neonatal HSV disease, the Cox proportional hazards regression analysis was performed with stratification for disease category (CNS versus disseminated). In performing this analysis, differences in mortality for each disease category were weighted to allow statistical comparison of the treatment dosage groups (HD, ID, and SD). This analysis indicated that the survival rate for patients treated with HD acyclovir was statistically significantly higher than for patients treated with SD acyclovir (OR: 3.3; 95% CI: 1.5-7.3). Recipients of HD acyclovir had a borderline significant decrease in morbidity compared with SD recipients, after stratification for the extent of disease (SEM vs CNS vs disseminated) and controlling for the potential confounding factors of HSV type (HSV-1 vs. HSV-2), prematurity, and disease severity (seizures). Patients treated with HD acyclovir were 6.6 times (adjusted OR; 95% CI: 0.8-113.6) as likely to be developmentally normal at 12 months of age as patients treated with SD therapy. CONCLUSION: These data support the use of a 21-day course of HD (60 mg/kg/d) intravenous acyclovir to treat neonatal CNS and disseminated HSV disease. Throughout the course of HD acyclovir therapy, serial ANC determination should be made at least twice weekly. Decreasing the acyclovir dosage or administering granulocyte colony-stimulating factor should be considered if the ANC remains below 500/mm(3) for a prolonged period.

Acyclovir↗

PubMed2001

Construction of optimum index to maximize overall response across countries in the presence of genotype x environment interaction.

Sire effect is partitioned into two parts: constant effect unaffected by environments and interaction effect specific to each environment and responsible for genotype x environment (GE) interaction. Response to selection for constant effect is the same across environments, thus increasing genetic stability, whereas response to selection for interaction effect would vary depending upon environments. The conventional measure of GE interaction based on genetic correlation (gammaG) considers both constant and interaction components even though the constant component plays no role in GE interaction. In contrast, the proposed measure of GE interaction based on interaction correlation (gammaI) deals only with interaction component responsible for GE interaction and thus indicates the intensity of GE interaction generated by responsible genes. Constant and interaction effects with different economic weights were combined into optimum index to improve both genetic stability and overall response across countries (countries represent environments). Optimum index was more efficient than the unpartitioned index which was more efficient than selection in a single country except when economic weights between constant and interaction effects were equal. Optimum index and unpartitioned index were the same when these economic weights were equal. The advantage of optimum index over the other selection methods increases as the intensity of GE interaction increases. When the relative economic weights are equivalent among countries and between constant and interaction effects, selection in a country with a larger sire variance is more effective than selection in a country with a smaller sire variance.

Animals↗

PubMed2001

Interaction with proteoglycans enhances the sterol efflux produced by endogenous expression of macrophage apoE.

Endogenous expression of apolipoprotein (apo)E in macrophages facilitates cholesterol efflux in the presence and absence of extracellular sterol acceptors. A proteoglycan-associated pool of apoE has also been described. The relationship between a proteoglycan-associated pool of apoE and enhanced cholesterol efflux was investigated in these studies. Inhibition of proteoglycan expression reduced cholesterol efflux from apoE-expressing cells ( J774E(+)) in the presence and absence of HDL, but did not do so from nonexpressing cells ( J774E(-)). The effect of proteoglycan depletion on sterol efflux from J774E(+) cells was confirmed by measuring differences in cell sterol mass, secreted sterol mass, and sterol efflux rates. Furthermore, apoE-containing particles secreted from proteoglycan-depleted J774E(+) cells were denser than those secreted from J774E(+) cells with intact proteoglycan expression. Also, in J774E(+) cells with intact proteoglycans, apoE particles isolated from the cell surface proteoglycan layer were denser than secreted particles. The apoE-lipid particles isolated from the cell surface proteoglycan layer had a lower lipid-to-apoE and cholesterol-to-apoE ratio compared with secreted particles. In distinction, proteoglycan depletion of J774E(-) cells did not reduce sterol efflux produced by the exogenous addition of apoE. These observations indicate that one mechanism by which endogenous expression of apoE facilitates effective cholesterol efflux from macrophages is related to its retention at the cell surface in a proteoglycan-associated pool. Further, our data suggest that apoE arrives at the cell surface in a relatively lipid-poor state, and that a proximate source of lipid available to the proteoglycan-bound apoE at the cell surface resides in the plasma membrane.

Animals↗

PubMed2001

Correlation between anti-Ro/La titers and clinical findings of patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with various clinical and serological manifestations. Previous studies have shown the association of SLE and anti-Ro, anti-La and anti-dsDNA autoantibodies with various clinical manifestations. We investigated the relationship between these autoantibodies and clinical findings of our patients with SLE. METHODS: Eighty patients with SLE at Department of Pediatrics, Taipei Veterans General Hospital, Taiwan from October 1999 to March 2000 were enrolled in the study. Frequencies of various clinical manifestations were calculated. Autoantibodies to Ro, La and dsDNA were measured using ELISA method. RESULTS: The most frequent clinical findings were arthritis (92.3%), photosensitivity (90.9%) and malar rash (86.1%). The most frequent laboratory findings were positive anti-nuclear antibody (ANA) (94.9%), low serum CH50 hemolytic titer (88.6%) and positive anti-dsDNA level (72.5%). Patients with anemia or photosensitivity had higher titers of anti-Ro antibody (Ab) than those without the respective clinical findings (p = 0.001 and 0.002, respectively). However, patients with proteinuria had lower anti-Ro Ab titers (p < 0.05). There was no correlation between clinical findings and anti-La Ab titers. Patients have higher titers of anti-dsDNA Ab if they had clinical findings of Raynauld's phenomenon, photosensitivity, arthritis, hypocomplementemia (p < 0.001), thrombocytopenia, proteinuria, or serositis (p < 0.05). No correlation was found between renal involvement and titers of various autoantibodies. CONCLUSIONS: Neither anti-Ro, anti-La nor anti-dsDNA antibodies was correlated with renal involvement in patients with SLE. However, patients with proteinuria had significantly lower titers of anti-Ro Ab than those without proteinuria.

Adult↗

PubMed2001

Spontaneous subconjunctival orbital fat prolapse: report of three cases.

Spontaneous subconjunctival orbital fat prolapse is an uncommon but benign entity. It is seldom discussed in the literature, and is sometimes confused with other ocular surface tumors, such as dermolipoma. We present 3 cases, two of which are bilateral, the other being unilateral. Two cases underwent surgical excision due to ocular irritation, and the pathology proved mature adipose tissue compatible with the diagnosis. Computed tomography (CT) was available for 1 case and revealed a fat-compatible radiolucent mass continuous with the intraconal fat. Some other reports have presumed that the intraconal fat was prolapsed from a dehiscence of Tenon's capsule. However, according to our surgical findings, we suggest that the possible weak point for intraconal orbital fat prolapse is between the regions where the rectus muscle tendons penetrate into Tenon's capsule. The fat just bulges anteriorly, but not penetrates the Tenon's capsule and the intermuscular septum.

Aged↗

PubMed2001

Evaluation of learning effectiveness in endotracheal intubation by the use of a laryngoscope in combination with a flexible fiberoptic bronchoscope.

BACKGROUND: Accidental esophageal intubation may cause lethal complications when undetected. We developed a laryngoscope, which utilizes a laryngoscope blade incorporating with a flexible fiberoptic bronchoscope for teaching new learners. We compared two teaching methods, i.e. the traditional method and the new method we contemplated, for teaching new interns. METHODS: We selected new interns as our study group. Everyone had six turns, four of which for the traditional method (T) and two of which for the new method (N), to perform the procedure under the guidance of a teaching supervisor. The interns were assigned randomly to one of three groups. Group 1 used the series of TTTTNN; group 2, TTNNTT; and group 3, NNTTTT. We used success or failure of intubation as the result of our evaluation. Statistical analyses were performed by chi-square test. RESULTS: 84 interns performed 504 endotracheal intubation trials during a period of 4 years. There was a 91.7% success rate with the new method and a 78.9% success rate with the traditional technique (P < 0.05). The group to which the new method was initially taught achieved the highest success rate of intubation and the greatest feeling of satisfaction according to a self-evaluation record. Of the failed intubations, 82.4% were due to performing the procedure in more than one minute, 15.3% due to esophageal intubation and the remaining 2.3% due to contact bleeding of teeth or oral trauma. CONCLUSIONS: By using the new teaching method, the supervisor could easily teach and assess the success of the new learners. Besides, esophageal intubation could be reduced to a minimum with subsequent increase of success rate.

Anesthesiology↗

PubMed2001

Glucan phosphate potentiates endotoxin-induced interferon-gamma expression in immunocompetent mice, but attenuates induction of endotoxin tolerance.

Glucan phosphate has been shown to enhance antimicrobial immunity in a variety of experimental models. However, the mechanisms by which glucans enhance resistance to infection remain largely unknown. Interferon-gamma (IFN-gamma) is a key regulator of both innate and acquired immunity. Suppression of IFN-gamma production is a prominent feature of the altered immune response that follows major trauma or sepsis. The present studies were designed to determine the effect of glucan phosphate on IFN-gamma expression in normal mice and endotoxin [lipopolysaccharide (LPS)]-tolerant mice. The model of LPS tolerance was used because it results in patterns of cytokine expression similar to those commonly observed following severe trauma or sepsis. Glucan treatment potentiated LPS-induced IFN-gamma expression in control mice. The induction of LPS tolerance resulted in marked suppression of LPS-induced IFN-gamma production. However, co-administration of glucan with LPS, during the tolerance induction phase, attenuated the LPS-tolerant response. Interleukin-12 (IL-12) and IL-18 are important mediators of LPS-induced IFN-gamma production. LPS-induced IL-12 p40 mRNA expression was increased in the spleens of glucan-treated mice compared with controls. Induction of LPS tolerance caused marked suppression of IL-12 production, a response that was attenuated by glucan treatment. IL-18 was constitutively expressed in both control and LPS-tolerant mice, and LPS-induced serum levels of IL-18 were increased in mice treated with glucan. T cells isolated from glucan-treated mice exhibited increased IFN-gamma expression in response to IL-12 and IL-18, as well as increased expression of the IL-12 and IL-18 receptors. The ability of glucan to potentiate IFN-gamma expression in control mice provides a potential mechanism by which glucan enhances antimicrobial immunity. The ability of glucan to attenuate suppressed IFN-gamma expression in LPS-tolerant mice denotes its potential benefit for the treatment of trauma and sepsis-induced immunosuppression.

Animals↗

PubMed2000

ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli.

ADP-ribosylation factors (ARFs) are highly conserved approximately 20-kDa guanine nucleotide-binding proteins that participate in both exocytic and endocytic vesicular transport pathways via mechanisms that are only partially understood. Although several ARF-like proteins (ARLs) are known, their biological functions remain unclear. To characterize its molecular properties, we cloned mouse and human ARL4 (mARL4 and hARL4) cDNA. The appearance of mouse ARL4 mRNA during embryonic development coincided temporally with the sequential formation of somites and the establishment of brain compartmentation. Using ARL4-specific antibody for immunofluorescence microscopy, we observed that endogenous mARL4 in cultured Sertoli and neuroblastoma cells was mainly concentrated in nuclei. When expressed in COS7 cells, ARL4-T34N mutant, predicted to exist with GDP bound, was concentrated in nucleoli. Yeast two-hybrid screening and in vitro protein-interaction assays showed that hARL4 interacted with importin-alpha through its C-terminal NLS region and that the interaction was not nucleotide-dependent. Like ARL2 and -3, recombinant hARL4 did not enhance cholera toxin-catalyzed auto-ADP-ribosylation. Its binding of guanosine 5'-O-(thiotriphosphate) was modified by phospholipid and detergent, and the N terminus of hARL4, like that of ARF, was myristoylated. Our findings suggest that ARL4, with its distinctive nuclear/nucleolar localization and pattern of developmental expression, may play a unique role(s) in neurogenesis and somitogenesis during embryonic development and in the early stages of spermatogenesis in adults.

ADP-Ribosylation Factors↗

PubMed2000

Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease.

Matriptase is an epithelial-derived, integral membrane serine protease. The enzyme was initially isolated from human breast cancer cells and has been implicated in breast cancer invasion and metastasis. In the current study, using active matriptase isolated from human milk, we demonstrate that matriptase is able to cleave various synthetic substrates with arginine or lysine as their P1 sites and prefers small side chain amino acids, such as Ala and Gly, at P2 sites. For the most reactive substrates, N-tert-butoxycarbonyl (N-t-Boc)-gamma-benzyl-Glu-Ala-Arg-7-amino-4-methylcoumarin (AMC) and N-t-Boc-Gln-Ala-Arg-AMC, the K(m) values were determined to be 3. 81 and 4.89 microm, respectively. We further demonstrated that matriptase can convert hepatocyte growth factor/scattering factor to its active form, which can induce scatter of Madin-Darby canine kidney epithelial cells and can activate c-Met tyrosine phosphorylation in A549 human lung carcinoma cells. In addition, we noted that matriptase can activate urokinase plasminogen activator but has no affect on plasminogen. These results suggest that matriptase could act as an epithelial, upstream membrane activator to recruit and activate stromal-derived downstream effectors important for extracellular matrix degradation and epithelial migration, two major events of tissue remodeling, cancer invasion, and metastasis.

Animals↗

PubMed2000

Increase of GKLF messenger RNA and protein expression during progression of breast cancer.

Genetic alterations found in carcinomas can alter specific regulatory pathways and provide a selective growth advantage by activation of transforming oncogenes. A subset of these genes, including wild-type alleles of GLI or c-MYC, and activated alleles of RAS or beta-catenin, exhibit transforming activity when expressed in diploid epithelial RK3E cells in vitro. By in vitro transformation of these cells, the zinc finger protein GKLF/KLF-4 was recently identified as a novel oncogene. Although GKLF is normally expressed in superficial, differentiating epithelial cells of the skin, oral mucosa, and gut, expression is consistently up-regulated in dysplastic epithelium and in squamous cell carcinoma of the oral cavity. In the current study, we used in situ hybridization, Northern blot analysis, and immunohistochemistry to detect GKLF at various stages of tumor progression in the breast, prostate, and colon. Overall, expression of GKLF mRNA was detected by in situ hybridization in 21 of 31 cases (68%) of carcinoma of the breast. Low-level expression of GKLF mRNA was observed in morphologically normal (uninvolved) breast epithelium adjacent to tumor cells. Increased expression was observed in neoplastic cells compared with adjacent uninvolved epithelium for 14 of 19 cases examined (74%). Ductal carcinoma in situ exhibited similar expression as invasive carcinoma, suggesting that GKLF is activated prior to invasion through the basement membrane. Expression as determined by Northern blot was increased in most breast tumor cell lines and in immortalized human mammary epithelial cells when these were compared with finite-life span human mammary epithelial cells. Alteration of GKLF expression was confirmed by the use of a novel monoclonal antibody that detected the protein in normal and neoplastic tissues in a distribution consistent with localization of the mRNA. In contrast to most breast tumors, expression of GKLF in tumor cells of colorectal or prostatic carcinomas was reduced or unaltered compared with normal epithelium. The results demonstrate that GKLF expression in epithelial compartments is altered in a tissue-type specific fashion during tumor progression, and suggest that increased expression of GKLF mRNA and protein may contribute to the malignant phenotype of breast tumors.

Animals↗

PubMed2000

Peripheral Golgi protein GRASP65 is a target of mitotic polo-like kinase (Plk) and Cdc2.

Cell division is characterized by orchestrated events of chromosome segregation, distribution of cellular organelles, and the eventual partitioning and separation of the two daughter cells. Mitotic kinases, including polo-like kinases (Plk), influence multiple events in mitosis. In yeast two-hybrid screens using mammalian Plk C-terminal domain baits, we have identified Golgi peripheral protein GRASP65 (Golgi reassembly stacking protein of 65 kDa) as a Plk-binding protein. GRASP65 appears to function in the postmitotic reassembly of Golgi stacks. In this report we demonstrate binding between Plk and GRASP65 and provide in vitro and in vivo evidence that Plk is a GRASP65 kinase. Moreover, we show that Cdc2 can also phosphorylate GRASP65. In addition, we present data which support the observation that the conserved C terminus of Plk is important for its function. Deletion or frameshift mutations in the conserved C-terminal domain of Plk greatly diminish its ability to phosphorylate GRASP65. These and previous findings suggest that phosphorylation of Golgi components by mitotic kinases may regulate mechanisms of Golgi inheritance during cell division.

Animals↗

PubMed2000

Inversion symmetry and exact critical exponents of dissipating waves in the sandpile model.

By an inversion symmetry, we show that in the Abelian sandpile model the probability distribution of dissipating waves of topplings that touch the boundary of the system shows a power-law relationship with critical exponent 5/8 and the probability distribution of those dissipating waves that are also last in an avalanche has an exponent of 1. Our extensive numerical simulations not only support these predictions, but also show that inversion symmetry is useful for the analysis of the two-wave probability distributions.

Journal Article↗