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Biomedical subjects

J Yu

Publications and source records attributed to J Yu.

At least 181 records · Page 10Linked to original sources
PubMed2001

Alcohol use in high school: predicting students' alcohol use and alcohol problems in four-year colleges.

This research examined the effect of students' drinking behaviors in high school on their alcohol use and alcohol problems in college. Five colleges in New York State were randomly selected for the study. The telephone interview method was employed to survey college students during the spring semester of 1998. Within each participating college, students were randomly selected through the use of complete student telephone directories provided by the college administration. A total of 813 students were interviewed. Alcohol problems were measured with items from DSM-IV. Results indicate that both frequency and quantity of alcohol use in high school significantly affect students' alcohol consumption in college. Furthermore, the impact of alcohol use in high school on alcohol problems in college tends to be composed of a moderate direct effect and a relatively strong indirect effect via its impact on current alcohol consumption in college. Prevention efforts for drinking in college may need to start in high school to reduce or delay alcohol use by high school students. Additional assessment services and more readily available treatment services may be required to address potential alcohol problems among college students. Future research should examine the effect and longevity of students' alcohol problem symptoms after they graduate from college.

Adolescent↗
PubMed2001

An in vitro pulmonary permeation system with simulation of respiratory dynamics.

To study the effect of respiration on transpulmonary permeation kinetics of drugs, an in vitro pulmonary permeation system, which consists of a setup for the simulation of respiratory dynamics, was developed. The system is composed offour major components: a pair of horizontal-type half-cells, a model air-blood barrier, an instrument for the application and regulation of respiratory pressure, and a pressure monitoring system. Calibration studies were performed and results showed that the primary respiration parameters (the peak inspiration pressure, respiratory frequency, and the percent inspiration time) can be controlled at a reproducible manner. This system appears to simulate very well the respiratory dynamics observed normally under physiologic conditions. After calibration, the system was utilized to characterize and quantitate the effect of respiration on the transpulmonary permeation of drugs using progesterone as the model drug. The results showed that progesterone permeability is increased as much as 1.8-5.6 folds by application of a respiratory pressure, depending on the combination of respiration parameters. Further studies demonstrated that the enhancement in pulmonary permeation triggered by respiratory pressure is resulted from the stretching of the lung tissue, not by the pressure gradient itself. The observations lead to the conclusion that the system developed in this investigation is a useful in vitro tool for studying the kinetics of pulmonary drug permeation under a physiologically simulating respiratory dynamics. The studies have provided scientific evidence for demonstrating that respiration is an important factor in determining the kinetics of transpulmonary drug permeation through possible alteration in the properties of the air-blood barrier.

Animals↗
PubMed2001

Angiostatin effects on endothelial cells mediated by ceramide and RhoA.

Angiostatin is a cleavage product of plasminogen that has anti-angiogenic properties. We investigated whether the effects of angiostatin on endothelial cells are mediated by ceramide, a lipid implicated in endothelial cell signaling. Our results demonstrate that angiostatin produces a transient increase in ceramide that correlates with actin stress fiber reorganization, detachment and death. DNA array expression analysis performed on ceramide-treated human endothelial cells demonstrated induction of certain genes involved in cytoskeleton organization. Specifically, we report that treatment with angiostatin or ceramide results in the activation of RhoA, an important effector of cytoskeletal structure. We also show that treatment of endothelial cells with the antioxidant N-acetylcysteine abrogates morphological changes and cytotoxic effects of treatment with angiostatin or ceramide. These findings support a model in which angiostatin induces a transient rise in ceramide, RhoA activation and free radical production.

Angiostatins↗
PubMed2001

Expression of MSY2 in mouse oocytes and preimplantation embryos.

Translational control plays a central role during oocyte maturation and early embryogenesis, as these processes occur in the absence of transcription. MSY2, a member of a multifunctional Y-box protein family, is implicated in repressing the translation of paternal mRNAs. Here, we characterize MSY2 expression in mouse oocytes and preimplantation embryos. Northern blot analysis indicates that MSY2 expression is highly restricted and essentially confined to the oocyte in the female mouse. MSY2 transcript and protein, as assessed by reverse transcription-polymerase chain reaction and immunoblotting, respectively, are expressed in growing oocytes, metaphase II-arrested eggs, and 1-cell embryos, but then are degraded by the late 2-cell stage; no expression is detectable in the blastocysts. During oocyte maturation, MSY2 is phosphorylated and following fertilization it is dephosphorylated. Quantification of the mass amount of MSY2 reveals that it represents 2% of the total protein in the fully grown oocyte, i.e., it is a very abundant protein. Both endogenous MSY2 and MSY2-enhanced green fluorescent protein (EGFP), which is synthesized following microinjection of an mRNA encoding MSY2-EGFP, are primarily localized in the cytoplasm, and about 75% of the MSY2 remains associated with oocyte cytoskeletal preparations. Results of these studies are consistent with the proposal that MSY2 functions by stabilizing and/or repressing the translation of maternal mRNAs.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Inositol hexakisphosphate increases L-type Ca2+ channel activity by stimulation of adenylyl cyclase.

Inositol hexakisphosphate (InsP6) is a most abundant inositol polyphosphate that changes simultaneously with inositol 1,4,5-trisphosphate in depolarized neurons. However, the role of InsP6 in neuronal signaling is unknown. Mass assay reveals that the basal levels of InsP6 in several brain regions tested are similar. InsP6 mass is significantly elevated in activated brain neurons and lowered by inhibition of neuronal activity. Furthermore, the hippocampus is most sensitive to electrical challenge with regard to percentage accumulation of InsP6. In hippocampal neurons, InsP6 stimulates adenylyl cyclase (AC) without influencing cAMP phosphodiesterases, resulting in activation of protein kinase A (PKA) and thereby selective enhancement of voltage-gated L-type Ca2+ channel activity. This enhancement was abolished by preincubation with PKA and AC inhibitors. These data suggest that InsP6 increases L-type Ca2+ channel activity by facilitating phosphorylation of PKA phosphorylation sites. Thus, in hippocampal neurons, InsP6 serves as an important signal in modulation of voltage-gated L-type Ca2+ channel activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

MRI contrast enhancement of necrosis by MP-2269 and gadophrin-2 in a rat model of liver infarction.

RATIONALE AND OBJECTIVES: The mechanisms of action leading to specific localization of necrosis-avid contrast agents (NACAs) such as gadophrin-2 are not well defined. It has been suggested recently that agents with a high degree of serum albumin binding may also serve as NACAs by virtue of nonspecific hydrophobic interactions. The present MRI-histomorphology correlation study was conducted to verify the likelihood of the proposed albumin-binding mechanism by comparing an albumin-binding blood pool agent, MP-2269, with gadophrin-2 in a rat model of reperfused liver infarction. METHODS: Reperfused infarction in the right liver lobe was surgically induced in six rats. Serial T1-weighted MRI was performed before and after intravenous injection of MP-2269 at 0.05 mmol/kg and repeated in the same rats 24 hours later after intravenous injection of gadophrin-2 at the same dosage (0.05 mmol/kg). The MR images were matched with corresponding histomorphological findings. The signal intensity and contrast ratio of infarcted and normal hepatic lobes were quantified and compared between the two agents during the postcontrast course. RESULTS: Before contrast, the infarcted lobe was indiscernible from normal liver on T1-weighted MRI. Shortly after injection of both MP-2269 and gadophrin-2, a negative contrast occurred between infarcted and normal liver because of a strong liver signal intensity enhancement and an inferior uptake in the necrotic liver. On delayed phase (>60 minutes), a necrosis-specific contrast enhancement (contrast ratio 1.6) developed with gadophrin-2 but not with MP-2269. The MR images matched well with corresponding histomorphological findings. CONCLUSIONS: Although both MP-2269 and gadophrin-2 feature an albumin-binding capacity, only gadophrin-2 displayed a persistent necrosis-specific contrast enhancement in the rat model of reperfused liver infarction. Therefore, the role of albumin binding in the mechanisms of NACAs should be reevaluated.

Animals↗
PubMed2001

Isolation of a CONSTANS ortholog from Pharbitis nil and its role in flowering.

The short-day plant Pharbitis nil is a model plant for the study of photoperiodic control of floral initiation. Flower formation can be induced at the cotyledon stage by a single long night of at least 14 h in duration. Using differential display of mRNA we identified a P. nil ortholog of the Arabidopsis CONSTANS (CO) gene, which will be referred to as PnCO. Expression of PnCO was high after a 14-h night, but low when the dark period was 12 h or less. Our results indicate that the level of the PnCO transcript is photoperiodically regulated. After transfer from continuous light to darkness, PnCO showed a circadian pattern of expression. Expression of the CAB gene, which is a molecular marker for the circadian clock, exhibited a different pattern of expression than did PnCO and was not subject to the same photoperiodic control. A major portion of the PnCO transcripts contained an unspliced intron. Only the intron-free PnCO was able to complement the co mutant of Arabidopsis by shortening the time to flower.

Amino Acid Sequence↗
PubMed2001

Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease.

OBJECTIVE: Both bacterial virulence factors and the pattern of Helicobacter pylori (H. pylori) gastritis may contribute to the development of clinically relevant gastroduodenal disease. The aim of our study was to investigate the frequency of H. pylori vacA alleles, iceA, and cagA, and the pattern of gastritis in patients with gastric cancer (GC), gastric lymphoma (MALT), duodenal ulcer (DU), and functional dyspepsia (FD). METHODS: H. pylori was cultured from 141 patients (34 GC, 26 MALT, 49 DU, 32 FD). Allelic variants of vacA and iceA, and cagA were identified by polymerase chain reaction. Antrum and corpus biopsies were obtained for assessment of gastritis according to the updated Sydney System. RESULTS: The vacA sl,ml genotype was more frequently detected in H. pylori from GC patients (70.6%) than from MALT, DU, and FD patients (p < 0.05). The frequency of iceA1 and cagA did not differ among the groups. The proportion of patients with severe gastritis in the corpus was significantly higher in patients with GC and MALT compared with patients with DU (p < 0.001). CONCLUSIONS: In a German patient population, only the vacA s1,m1 genotype of H. pylori is associated with GC, and therefore may be useful to identify infected patients being at an increased risk for GC.

Aged↗
PubMed2001

Visualizing pneumococcal infections in the lungs of live mice using bioluminescent Streptococcus pneumoniae transformed with a novel gram-positive lux transposon.

Animal studies with Streptococcus pneumoniae have provided valuable models for drug development. In order to monitor long-term pneumococcal infections noninvasively in living mice, a novel gram-positive lux transposon cassette, Tn4001 luxABCDE Km(r), that allows random integration of lux genes onto the bacterial chromosome was constructed. The cassette was designed so that the luxABCDE and kanamycin resistance genes were linked to form a single promoterless operon. Bioluminescence and kanamycin resistance only occur in a bacterial cell if this operon has transposed downstream of a promoter on the bacterium's chromosome. S. pneumoniae D39 was transformed with plasmid pAUL-A Tn4001 luxABCDE Km(r), and a number of highly bioluminescent colonies were recovered. Genomic DNA from the brightest D39 strain was used to transform a number of clinical S. pneumoniae isolates, and several of these strains were tested in animal models, including a pneumococcal lung infection model. Strong bioluminescent signals were seen in the lungs of the animals containing these pneumococci, allowing the course and antibiotic treatment of the infections to be readily monitored in real time in the living animals. Recovery of the bacteria from the animals showed that the bioluminescent signal corresponded to the number of CFU and that the lux construct was highly stable even after several days in vivo. We believe that this lux transposon will greatly expand the ability to evaluate drug efficacy against gram-positive bacteria in living animals using bioluminescence.

Amoxicillin↗
PubMed2001

Structural and functional analysis of an mRNP complex that mediates the high stability of human beta-globin mRNA.

Human globins are encoded by mRNAs exhibiting high stabilities in transcriptionally silenced erythrocyte progenitors. Unlike alpha-globin mRNA, whose stability is enhanced by assembly of a specific messenger RNP (mRNP) alpha complex on its 3' untranslated region (UTR), neither the structure(s) nor the mechanism(s) that effects the high-level stability of human beta-globin mRNA has been identified. The present work describes an mRNP complex assembling on the 3' UTR of the beta-globin mRNA that exhibits many of the properties of the stability-enhancing alpha complex. The beta-globin mRNP complex is shown to contain one or more factors homologous to alphaCP, a 39-kDa RNA-binding protein that is integral to alpha-complex assembly. Sequence analysis implicates a specific 14-nucleotide pyrimidine-rich track within its 3' UTR as the site of beta-globin mRNP assembly. The importance of this track to mRNA stability is subsequently verified in vivo using mice expressing human beta-globin transgenes that contain informative mutations in this region. In combination, the in vitro and in vivo analyses indicate that the high stabilities of the alpha- and beta-globin mRNAs are maintained through related mRNP complexes that may share a common regulatory pathway.

3' Untranslated Regions↗
PubMed2001

Synergistic regulation of immunoreceptor signaling by SLP-76-related adaptor Clnk and serine/threonine protein kinase HPK-1.

Recently, the identification of Clnk, a third member of the SLP-76 family of adaptors expressed exclusively in cytokine-stimulated hemopoietic cells, has been reported by us and by others. Like SLP-76 and Blnk, Clnk was shown to act as a positive regulator of immunoreceptor signaling. Interestingly, however, it did not detectably associate with known binding partners of SLP-76, including Vav, Nck, and GADS. In contrast, it became complexed in activated T cells and myeloid cells with an as yet unknown tyrosine-phosphorylated polypeptide of approximately 92 kDa (p92). In order to understand better the function of Clnk, we sought to identify the Clnk-associated p92. Using a yeast two-hybrid screen and cotransfection experiments with Cos-1 cells, evidence was adduced that p92 is HPK-1, a serine/threonine-specific protein kinase expressed in hemopoietic cells. Further studies showed that Clnk and HPK-1 were also associated in hemopoietic cells and that their interaction was augmented by immunoreceptor stimulation. A much weaker association was detected between HPK-1 and SLP-76. Transient transfections in Jurkat T cells revealed that Clnk and HPK-1 cooperated to increase immunoreceptor-mediated activation of the interleukin 2 (IL-2) promoter. Moreover, the ability of Clnk to stimulate IL-2 promoter activity could be blocked by expression of a kinase-defective version of HPK-1. Lastly we found that in spite of the differential ability of Clnk and SLP-76 to bind cellular proteins, Clnk was apt at rescuing immunoreceptor signaling in a Jurkat T-cell variant lacking SLP-76. Taken together, these results show that Clnk physically and functionally interacts with HPK-1 in hemopoietic cells. Moreover, they suggest that Clnk is capable of functionally substituting for SLP-76 in immunoreceptor signaling, albeit by using a distinct set of intracellular effectors.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Inhibition of glioma cell growth and tumorigenic potential by CCN3 (NOV).

AIMS: To establish whether the ectopic expression of CCN3 (NOV) in glioma cells can interfere with their tumorigenic potential and assess its potential value in molecular medicine. METHODS: Glioma cell lines were used to assess whether differences in the degree of intracellular communication induced by the expression of the gap junction protein connexin 43 (Cx43) is related to the differential expression of CCN3 (NOV). The antiproliferative activity of rat CCN3 (rCCN3; NOV) in glioma cells, has been assessed both in vitro and in vivo with glioma cell lines expressing different amounts of CCN3 (NOV). RESULTS: Upon ectopic expression of Cx43, the growth of C6 glioma cells is decreased. An increase of CCN3 (NOV) expression matches the reduced tumorigenic potential of these transfected cells. The localisation of CCN3 (NOV) is affected by the increased expression of Cx43 in the Cx-13 transfected cells, in which it is detected at areas of cell-cell contact. In a xenograft model, CCN3 (NOV) transfected glioma cells were found to induce tumours to a lesser degree than their parental counterparts, which do not express detectable amounts of CCN3 (NOV). CONCLUSIONS: Previous observations had suggested an inverse relation between CCN3 (NOV) expression in glioma cells and their tumorigenicity. These results establish a direct association between the establishment of functional gap junctional intercellular communication and the expression of rCCN3 (NOV). In addition to a negative effect on murine and human cell growth, CCN3 (NOV) has antiproliferative activity on tumour cells in vivo. Thus, the antiproliferative activity of the CCN3 (NOV) protein might involve reorganisation of cellular contacts that play a crucial role in tumorigenesis. The antiproliferative activity of CCN3 (NOV) established in this work sets the stage for the potential use of CCN proteins in molecular oncology.

Animals↗
PubMed2001

Reverse engineering of metabolic pathways from observed data using genetic programming.

Recent work has demonstrated that genetic programming is capable of automatically creating complex networks (such as analog electrical circuits and controllers) whose behavior is modeled by linear and non-linear continuous-time differential equations and whose behavior matches prespecified output values. The concentrations of substances participating in networks of chemical reactions are also modeled by non-linear continuous-time differential equations. This paper demonstrates that it is possible to automatically create (reverse engineer) a network of chemical reactions from observed time-domain data. Genetic programming starts with observed time-domain concentrations of input substances and automatically creates both the topology of the network of chemical reactions and the rates of each reaction within the network such that the concentration of the final product of the automatically created network matches the observed time-domain data. Specifically, genetic programming automatically created metabolic pathways involved in the phospholipid cycle and the synthesis and degradation of ketone bodies.

Biomedical Engineering↗
PubMed2001

Pathogenesis of the Segond fracture: anatomic and MR imaging evidence of an iliotibial tract or anterior oblique band avulsion.

PURPOSE: To demonstrate the normal anatomy of the stabilizing structures of the lateral aspect of the knee and to investigate pathogenesis of the Segond fracture, with emphasis on the iliotibial tract (ITT) and anterior oblique band (AOB) of the fibular collateral ligament. MATERIALS AND METHODS: Dissection of the region of the AOB, ITT, and lateral capsular ligament was performed in three cadaveric knees, with placement of gadopentetate dimeglumine-filled tubes along their course and tibial insertions. These knees, in addition to three nondissected knees, were studied with magnetic resonance (MR) imaging by using standard and specialized oblique planes. Specimen sectioning provided anatomic correlation. Retrospective review of radiographs and MR images in 17 patients with acute Segond fractures was performed, and the relationship between the fragment and the demonstrated lateral supporting structures of the knee was noted. RESULTS: Anatomic dissection and MR imaging of the cadaveric knees demonstrated a broad tibial insertion of the ITT, with fibers extending posterior to the Gerdy tubercle. A firm band of tissue, the AOB, extended from the fibular collateral ligament to the midportion of the lateral tibia, the typical site of a Segond fracture. The lateral capsular ligament proved to be a mere thickening of the capsule, inserting at the lateral tibia. Clinical analysis of acute Segond fractures confirmed the frequent attachment of the ITT and AOB to the avulsed fragment. CONCLUSION: Anatomic and clinical findings suggest that fibers of the ITT and AOB are important factors in the pathogenesis of the Segond fracture.

Adolescent↗
PubMed2001

Tarsal sinus: arthrographic, MR imaging, MR arthrographic, and pathologic findings in cadavers and retrospective study data in patients with sinus tarsi syndrome.

PURPOSE: To evaluate the tarsal sinus by using different imaging techniques and specialized planes. MATERIALS AND METHODS: Magnetic resonance (MR) imaging of the tarsal sinus was performed in 10 cadavers. Conventional arthrography of the anterior and posterior subtalar joints was then performed. Tarsal sinus ligaments were evaluated further on initial and reconstructed MR arthrograms along and perpendicular to their axes. Pathologic correlation was performed in five specimens suspected of having tarsal sinus lesions on the basis of initial imaging findings. In 37 patients with a clinical diagnosis of sinus tarsi syndrome, MR images of the ankle were obtained before and after intravenous gadolinium-based contrast material administration and were reviewed to verify the integrity of the tarsal sinus ligaments. RESULTS: Two complete and three partial cervical ligament (CL) tears and one complete interosseous talocalcaneal ligament (ITCL) tear were diagnosed with MR imaging. Only one complete and one partial CL tear were seen after evaluation of both initial and reconstructed MR arthrograms and confirmed with pathologic correlation. In 18 patients, the diagnosis was confirmed at MR imaging, which depicted ITCL and CL tears in 11 patients, isolated CL tears in three patients, ganglia in three patients, and pigmented villonodular synovitis in one patient. CONCLUSION: Cadaveric study results indicate that initial and reconstructed MR arthrograms along and perpendicular to the ligament axes are potentially useful for further evaluation of individual tarsal sinus structures.

Adult↗
PubMed2001

Excitatory lung reflex may stress inspiratory muscle by suppressing expiratory muscle activity.

Recently, a vagally mediated excitatory lung reflex (ELR) causing neural hyperpnea and tachypnea was identified. Because ventilation is regulated through both inspiratory and expiratory processes, we investigated the effects of the ELR on these two processes simultaneously. In anesthetized, open-chest, and artificially ventilated rabbits, we recorded phrenic nerve activity and abdominal muscle activity to assess the breathing pattern when the ELR was evoked by directly injecting hypertonic saline (8.1%, 0.1 ml) into lung parenchyma. Activation of the ELR stimulated inspiratory activity, which was exhibited by increasing amplitude, burst rate, and duty cycle of the phrenic activity (by 22 +/- 4, 33 +/- 9, and 57 +/- 11%, respectively; n = 13; P < 0.001), but suppressed expiratory muscle activity. The expiratory muscle became silent in most cases. On average, the amplitude of expiratory muscle activity decreased by 88 +/- 5% (P < 0.002). The suppression reached the peak at 6.9 +/- 1 s and lasted for 200 s (median). Injection of H(2)O(2) into the lung parenchyma produced similar responses. By suppressing expiration, the ELR produces a shift in the workload from expiratory muscle to inspiratory muscle. Therefore, we conclude that the ELR may contribute to inspiratory muscle fatigue, not only by directly increasing the inspiratory activity but also by suppressing expiratory activity.

Abdominal Muscles↗