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Biomedical subjects

C C Lu

Publications and source records attributed to C C Lu.

At least 19 recordsLinked to original sources

A frequent Y chromosome b2/b3 subdeletion shows strong association with male infertility in Han-Chinese population.

BACKGROUND: Azoospermia factor c (AZFc) subdeletions were reported to be significant risk factors for spermatogenesis. In this study, we assessed the occurrence of classical AZF deletions and AZFc subdeletions and their impact on male infertility in a Han-Chinese population. METHODS: This study analysed a population of 699 subjects, including 451 idiopathic infertile patients with a range of fertility disorders and 248 fertile controls, using a retrospective design. Deletions were identified by multiplex PCR. RESULTS: The prevalence and phenotypes of the classical AZF deletions were similar to previous studies. Subdeletions of the AZFc region in patients showed similar overall frequencies in all sperm concentration categories of gr/gr (7.0%) and b2/b3 (8.9%). For controls, these subdeletions were also found with a prevalence of gr/gr (7.7%) and b2/b3 (3.2%). b1/b3 deletions were not found either in the patients or in the controls. CONCLUSION: Our data showed a higher frequency of deletion events in this Han-Chinese population than in populations elsewhere in the world. The classical AZF deletions were the primary genetic factors for spermatogenic failure, while no significant association was found for AZFc subdeletions with sperm concentration. However, the b2/b3 subdeletion was significantly associated with idiopathic male infertility (odds ratio, 2.93; 95% confidence interval 1.34-6.39) (P = 0.005), indicating a potential impairment of male fertility.

Adult↗

Automating identification of adverse events related to abnormal lab results using standard vocabularies.

Laboratory data need to be imported automatically into central Clinical Study Data Management Systems (CSDMSs), and abnormal laboratory data need to be linked to clinically related adverse events. This import of laboratory data can be automated through mapping to standard vocabularies with HL7/LOINC mapping to the metadata within a CSDMS. We have designed a system that uses the UMLS metathesaurus as a common source to map or link abnormal laboratory values to adverse event CTCAE coded terms and grades in the metadata of TrialDB, a generic CSDMS.

Clinical Laboratory Information Systems↗

The mouse frizzled 8 receptor is expressed in anterior organizer tissues.

Wnt signaling has been shown to be important for axis formation in vertebrates. However, no Wnt ligand or receptor has been shown to be specifically expressed in all the organizer tissues in the mouse embryo. Here we report that the mouse frizzled 8 (mfz8) gene, a Wnt receptor, is expressed in the anterior visceral endoderm (AVE) and the anterior primitive streak, which have been shown to possess organizer activity. mFz8 is also expressed in the descendents of the anterior streak that comprise the anterior mesendoderm (AME) at midgastrulation, with subsequent expression in the anterior neurectoderm, which is specified and patterned by the AVE and AME. Thus, mfz8 is specifically expressed in the organizer tissues that establish the anterior-posterior axis in the mouse embryo.

Animals↗

Pharmacokinetics of desflurane uptake into the brain and body.

The aim of this study was to investigate the pharmacokinetics of desflurane uptake into the brain and body by comparing desflurane concentrations in internal jugular-bulb blood (Jdes), arterial blood (Ades) and pulmonary arterial blood (PAdes) at a fixed inspired desflurane concentration. Thirteen patients (aged 42-72 years) undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 5% inspired desflurane concentration (CIdes) during the first hour of anaesthesia. Under constant volume-controlled ventilation, CIdes and end-tidal desflurane (CEdes) were measured with an infrared analyser. The desflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. It took 24 min for the Jdes to equilibrate with Ades. Both CIdes-CEdes and Ades-PAdes gradients persisted during the study period. There was no further uptake of desflurane into the brain after 24 min but there was near-constant uptake into the body.

Adult↗

Pharmacokinetics of sevoflurane uptake into the brain and body.

The aim of this study was to investigate the pharmacokinetics of sevoflurane uptake into the brain and body by comparing sevoflurane concentrations in internal jugular-bulb blood (Jsev), arterial blood (Asev) and pulmonary arterial blood (PAsev) over a fixed inspired sevoflurane concentration. Ten patients (aged 51-73 years), undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 3.5% inspired sevoflurane concentration (CIsev) during the first hour of anaesthesia. During constant volume-controlled ventilation, we measured CIsev and end-tidal sevoflurane (CEsev) using infrared analysis. The sevoflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. We found that it took 40 min for the brain concentration to equilibrate with arterial blood (Asev). Both CIsev-CEsev and Asev-PAsev gradients persisted during the study period. There was no further uptake of sevoflurane into the brain after 40 min; however, there was near-constant uptake into the body.

Aged↗

Nodal signalling in the epiblast patterns the early mouse embryo.

Shortly after implantation the mouse embryo comprises three tissue layers. The founder tissue of the embryo proper, the epiblast, forms a radially symmetric cup of epithelial cells that grows in close apposition to the extra-embryonic ectoderm and the visceral endoderm. This simple cylindrical structure exhibits a distinct molecular pattern along its proximal-distal axis. The anterior-posterior axis of the embryo is positioned later by coordinated cell movements that rotate the pre-existing proximal-distal axis. The transforming growth factor-beta family member Nodal is known to be required for formation of the anterior-posterior axis. Here we show that signals from the epiblast are responsible for the initiation of proximal-distal polarity. Nodal acts to promote posterior cell fates in the epiblast and to maintain molecular pattern in the adjacent extra-embryonic ectoderm. Both of these functions are independent of Smad2. Moreover, Nodal signals from the epiblast also pattern the visceral endoderm by activating the Smad2-dependent pathway required for specification of anterior identity in overlying epiblast cells. Our experiments show that proximal-distal and subsequent anterior-posterior polarity of the pregastrulation embryo result from reciprocal cell-cell interactions between the epiblast and the two extra-embryonic tissues.

Animals↗

From fertilization to gastrulation: axis formation in the mouse embryo.

Although much remains unknown about how the embryonic axis is laid down in the mouse, it is now clear that reciprocal interactions between the extraembryonic and embryonic lineages establish and reinforce patterning of the embryo. At early post-implantation stages, the extraembryonic ectoderm appears to impart proximal-posterior identity to the adjacent proximal epiblast, whereas the distal visceral endoderm signals to the underlying epiblast to restrict posterior identity as it moves anteriorward. At gastrulation, the visceral endoderm is necessary for specifying anterior primitive streak derivatives, which, in turn, pattern the anterior epiblast. Polarity of these extraembryonic tissues can be traced back to the blastocyst stage, where asymmetry has been linked to the point of sperm entry at fertilization.

Animals↗

Prevalence and significance of hepatitis B virus (HBV) pre-S mutants in serum and liver at different replicative stages of chronic HBV infection.

Several types of naturally occurring pre-S mutants in sera or liver tissues in patients with chronic hepatitis B virus (HBV) infection have been identified. To clarify the prevalence and significance of emergence of pre-S mutants, 140 sera and 18 resected livers from patients with HBV were studied. Replicative status was designated as high, intermediate, and low based on the HBV-DNA levels in serum or the expression of HBV antigens in liver. In vitro transfection and Western blot analysis were performed to characterize expression and secretion of HBsAg by the mutant constructs. Five major types (I to V) of pre-S deletion mutants in serum and liver and 2 types (VI and VII) in liver were identified. Pre-S mutant was 6.4% at high replicative phase, 13% at intermediate, and 37.5% at low or nonreplicative phases in serum. In livers, the same tendency existed: pre-S2 deletion mutants emerged and prevailed at a low replicative phase in hepatocytes that expressed a novel marginal pattern of HBsAg and usually clustered in groups. The deletion sequence of pre-S2 region coincides with human leukocyte antigen-restricted T- and B-cell epitopes. In vitro HBsAg was retained in the hepatocytes and synthesis and secretion of major surface antigen decreased for most of the pre-S mutants. Pre-S mutants prevailed with evolution of chronic HBV, probably under immune pressure. Emergence of pre-S mutants may account for the life-long persistence and discrepancy of HBsAg in serum and liver in HBV and may confer growth advantage in view of the clustering proliferation of hepatocytes harboring pre-S2 mutant.

Blotting, Western↗

Syntactic priming of nouns and verbs in Chinese.

Syntactic priming of Chinese nouns and verbs was investigated in word recognition (cued shadowing of auditory targets) and production (picture naming). Disyllabic compound words were presented after syntactically congruent, incongruent, or neutral auditory contexts, with a zero delay between offset of the context and onset of the target. Significant priming was observed in both tasks, including facilitation as well as inhibition. Post hoc analyses showed that reaction times were also affected by sublexical variables that are especially relevant for Chinese, including syllable density (number of word types and tokens in the language with the same first or second syllable) and semantic transparency (whether the meaning of the whole word is predictable from the separate meanings of the two syllables within the compound). These patterns suggest competitive effects at the sublexical level. Implications for interactive models of lexical access are discussed.

Cues↗

Prognostic factors of hyperglycemic hyperosmolar nonketotic state.

BACKGROUND: To delineate the prognostic factors of patients suffering from hyperglycemic hyperosmolar nonketotic state (HHNK) in Taiwan. METHODS: We reviewed the charts of patients who had been admitted to the Division of Endocrinology and Metabolism of Kaohsiung Veterans General Hospital from 1992 to 1998 due to HHNK. General and clinical data were collected. The influential factors for prognosis were determined. RESULTS: One hundred and nineteen patients fulfilling the criteria of HHNK were included in our study. The mean age was 67.8 +/- 11.7 years with male predominance. Twenty-nine patients died which produced a fatality rate of 24.4%. Eighty-six (72.3%) cases occurred in patients with known diabetic history, while another thirty-three (27.7%) occurred in patients with no diabetic history. Most patients received oral antidiabetic drugs before HHNK episodes. The patients who died had shorter length of inpatient stay than did survivors. The leading precipitating factor was infection (57.1%), followed by poor compliance of medication (21.0%) and undiagnosed diabetes (10.9%). Fifty patients (42%) had a history of stroke. The risk factors for death included precipitation of HHNK by infection and low Glasgow coma scale (GCS) on admission. Old age itself did not contribute to death. Severity of hyperglycemia or hyperosmolarity was also not an important prognostic factor. Multiple logistic regression revealed that low GCS on admission was the most influential factor of leading to death. Most of the patients who died did so due to underlying precipitating factors. CONCLUSIONS: Neither age nor osmolarity, but underlying precipitating factors and state of consciousness were the most influential factors affecting the prognosis of HHNK.

Adult↗

Resection of triple synchronous tumors--gastric adenocarcinoma, gallbladder adenocarcinoma and stromal tumor of the stomach.

We herein report a rare case of triple synchronous tumors: gastric adenocarcinoma, gallbladder adenocarcinoma and stromal cell tumor of stomach, which were resected in the same operation. A 72-year-old male patient suffered from poor appetite and epigastric pain that radiated to his back for one month. Upper gastrointestinal endoscopy showed a gastric ulcer measuring 1.5 cm at the prepyloric area, which was proven to be adenocarcinoma by biopsy. A second tumor was found in the gallbladder, measuring 3 cm, by ultrasonography. On computed tomography, a third tumor about 2.5 cm in size was recognized posterior to the gastric high body and anterior to the pancreas. Given the presence of three tumors, he underwent a radical subtotal gastrectomy with Billroth-II gastrojejunostomy and simultaneous cholecystectomy. Pathological findings revealed gastric adenocarcinoma, gallbladder adenocarcinoma and stromal cell tumor of the stomach. The postoperative course was smooth.

Adenocarcinoma↗

A progressive growing inflammatory pseudotumor of the liver.

Inflammatory pseudotumors of the liver are very rare, and their etiology and pathogenesis remain unclear. The diagnosis is often difficult to make because these masses often mimic other lesions such as primary neoplasms, metastases or liver abscesses. Herein, we report a rare case of progressive growing hepatic pseudotumor in a 47-year-old man. The patient presented with body weight loss and general malaise. A series of radiological examinations showed the progressive growth of the hepatic tumor from 3.5 cm to 10.0 cm in diameter within 8 months. He underwent a right lobectomy of the liver, and the final diagnosis was proven by pathology. There were no complications in the post-operative course.

Granuloma, Plasma Cell↗

An on-line quantitative immunoassay system based on a quartz crystal microbalance.

We have established a QCM immunoassay system which allows on-line and quantitative monitoring throughout the entire detection procedure and provides information on the surface coverage and the binding ratio of antibody to antigen. Compared to conventional immunoassay systems the QCM system offers advantages of short response times, obviates the need for additive labeling reagents, and permits direct conversion of a frequency signal into mass accumulation.

Crystallization↗

Do phosphatidylinositides modulate vertebrate phototransduction?

Mammalian rod cyclic nucleotide gated (CNG) channels (i.e., alpha plus beta subunits) are strongly inhibited by phosphatidylinositol 4, 5-bisphosphate (PIP(2)) when they are expressed in Xenopus oocytes and studied in giant membrane patches. Cytoplasmic Mg-ATP inhibits CNG currents similarly, and monoclonal antibodies to PIP(2) reverse the effect and hyperactivate currents. When alpha subunits are expressed alone, PIP(2) inhibition is less strong; olfactory CNG channels are not inhibited. In giant patches from rod outer segments, inhibition by PIP(2) is intermediate. Other anionic lipids (e.g., phosphatidyl serine and phosphatidic acid), a phosphatidylinositol-specific phospholipase C, and full-length diacylglycerol have stimulatory effects. Although ATP also potently inhibits cGMP-activated currents in rod patches, the following findings indicate that ATP is used to transphosphorylate GMP, generated from cGMP, to GTP. First, a phosphodiesterase (PDE) inhibitor, Zaprinast, blocks inhibition by ATP. Second, inhibition can be rapidly reversed by exogenous regulator of G-protein signaling 9, suggesting G-protein activation by ATP. Third, the reversal of ATP effects is greatly slowed when cyclic inosine 5'-monophosphate is used to activate currents, as expected for slow inosine 5' triphosphate hydrolysis by G-proteins. Still, other results remain suggestive of regulatory roles for PIP(2). First, the cGMP concentration producing half-maximal CNG channel activity (K(1/2)) is decreased by PIP(2) antibody in the presence of PDE inhibitors. Second, the activation of PDE activity by several nucleotides, monitored electrophysiologically and biochemically, is reversed by PIP(2) antibody. Third, exogenous PIP(2) can enhance PDE activation by nucleotides.

Adenosine Triphosphate↗

Age-related differences in the secretion of calcitonin in male rats.

The mechanism of hypercalcitoninemia associated with aging was investigated in male rats. To mimic some of the hormonal changes with aging, orchidectomized (Orch) and hyperprolactinemic rats were used to mimic the physiological status of aging. Orch and haloperidol-induced hyperprolactinemic rats aged 3, 8, and 17 months were infused with CaCl2 and then bled from a jugular catheter following the CaCl2 challenge. Rat thyroid gland was incubated with Locke's medium at 37 degrees C for 30 minutes. Compared with 8- and 3-month-old rats, 17-month-old rats exhibited the lowest levels of plasma testosterone and the highest levels of plasma prolactin (PRL) and calcitonin (CT). The release of CT in the thyroid glands in vitro was highest in 17-month-old rats. Orchidectomy decreased rat plasma CT and thyroid CT release in vitro. Hyperprolactinemic rats had higher levels of plasma PRL and CT compared with control animals. The release of thyroid CT in vitro was greater in hyperprolactinemic rats. These results suggest that the hypersecretion of CT in 17-month-old rats may be due in part to hyperprolactinemia.

Aging↗

Identification of a pre-S2 mutant in hepatocytes expressing a novel marginal pattern of surface antigen in advanced diseases of chronic hepatitis B virus infection.

BACKGROUND AND AIMS: The expression of hepatitis B viral (HBV) antigens in liver tissue reflects the replicative status of chronic HBV infection. We have previously recognized a novel marginal pattern of hepatitis B surface antigen (HBsAg) in hepatocytes, which usually clusters in groups and emerges at the late non-replicative phase. This study was designed to investigate whether the marginal-type HBsAg represented the gene product of a specific HBV-surface mutant. METHODS: Microdissection of cirrhotic nodules homogeneously expressing marginal HBsAg was performed on two of 12 resected livers from HBsAg-seropositive patients with hepatocellular carcinoma. The gene presumably encoding marginal HBsAg was polymerase chain reaction (PCR)-cloned, sequenced and analysed. In vitro transfection and expression of the cloned surface mutant plasmids were performed on the Huh7 cell line to illustrate intrahepatic HBsAg expression. RESULTS: Immunohistochemical staining revealed that the marginal HBsAg was positive for pre-S1 and thus contained large surface proteins. The PCR cloning and sequencing of the genes presumably encoding marginal-type HBsAg in both cases revealed the same deletion at the 5' terminus (nt 2-55) of pre-S2. A point mutation on the small-surface (S) antigen was also found in one case. The pre-S2 deletion sequence and the mutation sites of the S gene coincide with human lymphocyte antigen-restricted T- and/or B-cell epitopes. In vitro transfection of the mutant plasmid revealed a blot-like retention or accumulation of HBsAg in the cytoplasm or at the periphery of hepatocytes, accompanied by a decreased secretion of HBsAg in the culture supernatant, mimicking intrahepatic expression. CONCLUSION: A natural pre-S2 deletion mutant was identified in hepatocytes expressing a novel marginal pattern of HBsAg, which probably contains mutant, large, surface proteins. The biological significance of the pre-S2 deletion mutant should be interesting in view of the clustering proliferation of hepatocytes expressing marginal HBsAg.

Female↗

Secular trends of HBeAg prevalence among HBsAg-positive delivery mothers in a hepatitis B endemic area.

A high prevalence of HBeAg among HBsAg-positive mothers at the time of delivery results in a high prevalence of hepatitis B vertical transmission. From 1990 to 1995, 896 pregnant HBsAg-positive women, including 411 (46 per cent) HBeAg-positive subjects, were enrolled in our study to analyse the secular change in HBeAg prevalence. Their mean age, number of pregnancies and parity were 29.5 +/- 4.1 years, 2.0 +/- 1.2, and 0.6 +/- 0.7, respectively. The prevalence rates of HBeAg were 48, 54, 49, 47, 40, and 40 per cent among the subjects enrolled in 1990, 1991, 1992, 1993, 1994, and 1995, respectively. In univariate analyses, prevalence of HBeAg decreased by the calendar year of pregnancy (p = 0.01), and also by age (p < 0.00001), number of pregnancies (p < 0.0001) and parity (p < 0.0002). After adjusting for age in multiple logistic regression, the calendar year of pregnancy was still the independent variable, while gravida and parity became insignificant. The odd ratios (95 per cent confidence interval) of HBeAg negative-seroconversion in the equations were 1.09 (1.00-1.19) per calendar year and 1.14 (1.10-1.18) per year of age. Our results have shown a secular decrease in HBeAg-prevalence among pregnant HBsAg-positive women in Taiwan.

Adolescent↗

Extracellular mutations of protease-activated receptor-1 result in differential activation by thrombin and thrombin receptor agonist peptide.

The protease-activated thrombin receptor-1 (PAR-1) can be activated by both the tethered ligand exposed by thrombin cleavage and a synthetic peptide having the tethered ligand sequence (thrombin receptor agonist peptide or TRAP). We conducted a mutational analysis of extracellular residues of the receptor potentially involved in interaction with both the tethered ligand and the soluble peptide agonist. Agonist-stimulated calcium efflux in X. laevis oocytes or inositol phosphate accumulation in COS-7 cells was used to assess receptor activation. We have also examined the binding of a radiolabeled TRAP for the wild-type and mutant PAR-1 receptors. Our results indicated that most of the mutations strongly affected TRAP-induced responses without significantly altering thrombin-induced responses or TRAP binding. Several point mutations and deletion of extracellular domains (DeltaEC3, DeltaNH3) drastically altered the ability of mutant receptors to respond to TRAP, but not to thrombin, and did not affect the affinity for the radiolabeled TRAP by these mutant receptors. Only mutations that disrupted the putative disulfide bond or substitution of multiple acidic residues in the second extracellular loop by alanine had a significant effect on both ligand binding and thrombin activation. These results suggest that although both agonists can activate PAR-1, there are profound differences in the ability of thrombin and TRAP to activate PAR-1. In addition, we have found PAR-1 mutants with the ability to dissociate receptor-specific binding from functional activity.

Amino Acid Sequence↗