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Biomedical subjects

W J Wu

Publications and source records attributed to W J Wu.

At least 19 recordsLinked to original sources

Consumption of flea faeces and eggs by larvae of the cat flea, Ctenocephalides felis.

The effects of the consumption of flea faeces and non-viable eggs on larval development in the cat flea Ctenocephalides felis (Bouché) (Siphonaptera: Pulicidae) were investigated. Only 13.3% of larvae developed into adults when fed a diet of male or female flea faeces alone; however, 90% of larvae developed into adults when fed on flea faeces supplemented with non-viable flea eggs. When fed with non-viable eggs alone, larvae did not develop into adults. Nevertheless, non-viable eggs may provide critical supplemental nutrients, lacking in flea faeces and required for larval development. None of the larvae fed on flea faeces or non-viable eggs alone formed a cocoon. A diet of flea faeces alone significantly extended the second as well as third larval stadia compared to larvae fed on diets containing non-viable eggs. It is suggested that the cannibalism of fertile eggs may limit population growth in the cat flea.

Animals↗

Targeted deletion of the A3 adenosine receptor confers resistance to myocardial ischemic injury and does not prevent early preconditioning.

We used mice with genetic disruption of the A3 adenosine receptor (AR) gene (A3AR(-/-)mice) to assess the in vivo role of the A3AR in modulating myocardial ischemia/reperfusion injury and preconditioning (PC). Surprisingly, infarct size induced by 30 min of coronary artery occlusion and 24 h of reperfusion was 35% smaller in A3AR(-/-)compared to wild-type mice (A3AR(+/+)). The reduction in infarct size was not the result of differences in heart rate, body temperature or increased cardiac expression of A1ARs. However, neutrophil infiltration within infarcted regions was less in A3AR(-/-)mice. Furthermore, ischemic PC induced by either a single episode (one 5 min occlusion) or multiple episodes (six 4 min occlusions) of ischemia produced equivalent reductions in infarct size in A3AR(-/-)and A3AR(+/+)mice. These results indicate that, in the mouse, (i) A3ARs play an injurious role during acute myocardial ischemia/reperfusion injury, possibly by exacerbating the inflammatory response, and (ii) A3ARs are not necessary for the development of the early phase of ischemic PC.

Animals↗

Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat.

The availability of genetic information, transgenic and knock-out animals make the mouse a primary model in biomedical research. Aminoglycoside ototoxicity, however, has rarely been studied in mature mice because they are considered highly resistant to the drugs. This study presents models for kanamycin ototoxicity in adult CBA/J, C57BL/6 and BALB/c mouse strains and a comparison to Sprague-Dawley rats. Five-week-old mice were injected subcutaneously twice daily with 400-900 mg kanamycin base/kg body weight for 15 days. Kanamycin induced dose-dependent auditory threshold shifts of up to 70 dB at 24 kHz as measured by auditory brain stem-evoked responses. Vestibular function was also affected in all strains. The functional deficits were accompanied by hair cell loss in both cochlear and vestibular neurosensory epithelia. Concomitant administration of the antioxidant 2,3-dihydroxybenzoate significantly attenuated the kanamycin-induced threshold shifts. In adult male Sprague-Dawley rats, doses of 1 x 500 mg or 2 x 300 mg kanamycin base/kg body weight/day x 14 days induced threshold shifts of approximately 50 dB at 20 kHz. These were accompanied by loss of outer hair cells. The order of susceptibility, BALB>CBA>C57, was not due to differences in the pharmacokinetics of kanamycin. It also did not correlate with the presence of Ahl/Ahl2 genes which predispose C57 and BALB strains, respectively, to accelerated age-related hearing loss. Pigmentation, however, paralleled this rank order suggesting an influence of melanin on cochlear antioxidant status.

Aminoglycosides↗

Off-host observations of mating and postmating behaviors in the cat flea (Siphonaptera: Pulicidae).

A blood meal was necessary for a male cat flea, Ctenocephalides felis (Bouché), to display the mating attempts to an unfed or fed female. More mating pairs resulted when both sexes were fed. Copulation occurred when fed fleas were placed on surfaces with temperatures from 34 to 42 degrees C. This article not only describes the mating and postmating behaviors of cat fleas, but also compares them with those of other fleas. The sequence of mating behavior began when a male approached a female ventrally, and the male's antennae and claspers became erect to attach to the abdomen of the female. Clasper attachment lasted until copulation ended, whereas the male retrieved his antennae immediately after genitalia linkage. The male generally grasped the female's tarsi with his claws during mating. The length of the mating interval terminated by the male ranged from 25 to 110 min and was significantly longer than that terminated by the female (averaging 12.11 min). After the mating pair separated, the male displayed a series of postmating behaviors discussed herein. This article documents grasping and postmating behaviors of the male cat flea.

Animals↗

Cystitis glandularis mimics bladder cancer--three case reports and literature review.

Cystitis glandularis is an uncommon proliferative disorder of the mucus-producing glands within the mucosa and submucosa of urinary bladder epithelium. We report three cases with gross hematuria on first presentation. Both sonography and computer tomography revealing bladder tumor and transurethral resection was performed in all three cases. Cystitis glandularis was confirmed by pathology. Short-term follow-up of sonography and cystoscopy showed good results.

Adult↗

Adrenal cyst--a case report.

Adrenal cysts are rare and mostly silent clinically. Herein we report a case of adrenal cyst. A 55-year-old female was incidentally found to have a left suprarenal cystic lesion with a calcified wall by abdominal sonography during a work-up for her epigastralgia and left flank pain. Then, computed tomography (CT) revealed a left adrenal cystic mass with wall calcification, magnetic resonance imaging (MRI) showed left retroperitoneal cystic mass with fluid content, and angiography demonstrated an avascular lesion. Surgical exploration was performed via a flank incision and a calcified cystic adrenal mass was excised. The pathologic diagnosis was adrenal pseudocyst with calcified wall. We discuss the diagnosis and management of adrenal cyst and briefly review the literature.

Adrenal Gland Diseases↗

Telomerase activity in human bladder tumors and bladder washing specimens.

Telomerase appears to be an important factor for the control of cellular proliferation and tumorigenesis. Enzyme activity dramatically increases in almost all human tumors. The purpose of our study was to evaluate the role of telomerase activity as a marker for bladder cancer diagnosis and follow-up. By using the PCR-ELISA based on the TRAP (telomerase repeat amplification protocol) method, telomerase activity of bladder tumors (n = 77), normal-appearing adjacent tissues (n = 21) and bladder washings (n = 37) were analyzed. Telomerase activity was detected in 87% (67/77) of cancer tissues and in 38% (8/21) of normal-appearing adjacent tissues. However, the levels of enzyme activity were significantly higher in cancer tissues than in normal-appearing adjacent tissues (p < 0.05). Telomerase activity in bladder cancer tissues was not correlated to the tumor stage or grade. During a 26 months follow-up period, disease progression occurred in 66.7% of patients with invasive tumors where telomerase activity of the normal-appearing adjacent tissue was detectable, as compared to only 14.3% for patients who showed undetectable telomerase activity in adjacent, normal-appearing tissues (p = 0.094). When telomerase activity of bladder washing fluid was compared with its corresponding tumors, sensitivity of detection was 81% and specificity was 75%. In contrast, urine cytology only yielded a sensitivity of 31% in the detection of cancer. The detection ability between telomerase activity measurement in washing fluid and cytological examination had a trend toward the telomerase measurement identifying more cancer cases than the cytologic examination (p = 0.07). In conclusion, telomerase activity is present in early-stage bladder cancer and is a potential molecular marker for bladder tumors diagnosis. The expression of telomerase activity in normal-appearing mucosa adjacent to bladder tumor is probably an indicator of disease progression. Using the telomerase activity to detect exfoliated cells in bladder washing fluids could be a useful method in adjunct to urine cytology and cystoscopy in establishing the diagnosis and follow-up of bladder cancer.

Humans↗

Retroperitoneal laparoscopic nephrectomy in the treatment of incontinence from ectopic ureter with renal hypoplasia in the child--a case report.

Unilateral single vaginal ectopic ureteral opening with ipsilateral hypoplastic kidney is a rare disease. It is classically presented with continuous urinary incontinence, but a normal voiding pattern after successful toilet training. The kidneys associated with this condition are usually nonfunctional and nephrectomy is the treatment of choice to cure the incontinence. We present a 7-year old girl with such a problem successfully treated by retroperitoneal laparoscopy. The patient resumed her normal unrestricted activity level on postoperative day 3. She was free of symptoms related to the operation during a 6-year follow-up period. It is suggested from this case that despite the reduced working space in children, retroperitoneal laparoscopic nephrectomy in the treatment of small kidney with complications is a feasible procedure.

Child↗

[Innervation of medial olivocochlear efferents in the cochlea of gerbils].

To explore the distributions of the medial olivocochlear (MOC) fibers and terminals in the cochlea of Mongolian gerbils and their physiological significance, a quantitative study on the distribution of MOC efferent fibers and terminals in whole cochlea of gerbils was performed using histochemical staining of acetylcholinesterase in the surface preparations. The relation between the density and size of MOC fibers and terminals in the cochlea and cochlear place-frequency map was analysed. The results were that the MOC fibers and terminals unevenly spreaded in the cochlea; the densest and the thickest MOC fibers and terminals were found in the distal part of the base turn and the second turn. These results demonstrate that the distribution of MOC fibers and terminals in the cochlea of gerbils is closely related to the function of frequency analysis of the cochlea.

Animals↗

Cdc42 stimulates RNA splicing via the S6 kinase and a novel S6 kinase target, the nuclear cap-binding complex.

Cdc42 is a low molecular weight GTP-binding protein that plays a key regulatory role in a variety of cellular activities. The importance of the coordination of different cell functions by Cdc42 is underscored by the fact that a constitutively active Cdc42 mutant induces cellular transformation. In this study, we describe a novel function for Cdc42: its ability to stimulate pre-messenger RNA splicing. This activity is dependent on cysteine 37 in the effector loop of Cdc42 but is not dependent on cell growth. A likely candidate protein for mediating the Cdc42 effects on pre-mRNA splicing is the nuclear RNA cap-binding complex (CBC), which plays a key role in an early step of cap-dependent RNA splicing. Activation of the CBC by Cdc42 can be inhibited by rapamycin. Additionally, phosphatidylinositol 3-kinase and the Cdc42 effector, pp70 S6 kinase, stimulate the RNA cap-binding activity of the CBC. S6 kinase may directly target the CBC in vivo as it can phosphorylate the 80-kDa subunit of the CBC, CBP80, at residues that are subject to a growth factor-dependent and rapamycin-sensitive phosphorylation in vivo. Together these data suggest the involvement of a Cdc42-S6 kinase pathway in the regulation of RNA splicing, mediated by an increase in capped RNA binding by the CBC, as well as raise the possibility that the effects of Cdc42 on cell growth may be due in part to its regulation of RNA processing.

3T3 Cells↗

The gamma-subunit of the coatomer complex binds Cdc42 to mediate transformation.

The Ras-related GTP-binding protein Cdc42 is implicated in a variety of biological activities including the establishment of cell polarity in yeast, the regulation of cell morphology, motility and cell-cycle progression in mammalian cells and the induction of malignant transformation. We identified a Cdc42 mutant (Cdc42F28L) which binds GTP in the absence of a guanine nucleotide exchange factor, but still hydrolyses GTP with a turnover number identical to that for wild-type Cdc42. Expression of this mutant in NIH 3T3 fibroblasts causes cellular transformation, mimicking many of the characteristics of cells transformed by the Dbl oncoprotein, a known guanine nucleotide exchange factor for Cdc42. Here we searched for new Cdc42 targets in an effort to understand how Cdc42 mediates cellular transformation. We identified the gamma-subunit of the coatomer complex (gammaCOP) as a specific binding partner for activated Cdc42. The binding of Cdc42 to gammaCOP is essential for a transforming signal distinct from those elicited by Ras.

3T3 Cells↗

Activation of phospholipase D1 by Cdc42 requires the Rho insert region.

Members of the Rho subfamily of GTP-binding proteins are implicated in the regulation of phospholipase D (PLD). In the present study, we demonstrate a physical association between a Rho family member, Cdc42, and PLD1. Binding of Cdc42 to PLD1 and subsequent activation are GTP-dependent. Although binding of Cdc42 to PLD1 does not require geranylgeranylation, activation of PLD1 is dependent on this lipid modification of Cdc42. Specific point mutations in the switch I region of Cdc42 abolish binding to and, therefore, activation of PLD1 by Cdc42. Deletion of the Rho insert region, which consists of residues 120-139, from Cdc42 does not interfere with binding to PLD1 but inhibits Cdc42 stimulated PLD1 activity. Interestingly, deletion of the insert region from Cdc42 also inhibits activation of PLD1 by Arf and protein kinase C. With the lack of specific inhibitors of PLD activity, the insert deletion mutant of Cdc42 (designated (DeltaL8)Cdc42) is a novel reagent for in vitro studies of PLD1 regulation, as well as for in vivo studies of Cdc42-mediated signaling pathways leading to PLD1 activation. Because the insert region is required for the transforming activity of Cdc42, regulation of PLD1 by this region on Cdc42 is of major interest.

Baculoviridae↗

Quantitative analysis of the neuroendocrine-immune axis: linear modeling of the effects of exogenous corticosterone and restraint stress on lymphocyte subpopulations in the spleen and thymus in female B6C3F1 mice.

The effects of exogenous corticosterone and restraint stress on the number and percentage of lymphocyte subpopulations in the spleen and thymus were evaluated. The data were used to generate linear models that describe the relationship between these parameters and the area under the corticosterone concentration vs time curve (AUC). Comparison of the models revealed that the number of nucleated cells in the spleen was decreased similarly by exogenous corticosterone and restraint (at equivalent corticosterone AUC values). However, exogenous corticosterone caused a greater decrease in cell number in the thymus than it did in the spleen. Corticosterone preferentially depleted CD4+CD8+ cells in the thymus, whereas the same corticosterone exposure produced by restraint stress did not. In the spleen, cell number for all major cell types was decreased by both treatments, but there were minor differences in the change in percentage of some subpopulations induced by exogenous corticosterone as compared to restraint. The models derived here provide quantitative data that indicate the magnitude of corticosterone and stress-induced effects on lymphocyte populations in the spleen and thymus. These results have mechanistic implications, and they may be useful in future efforts to extrapolate from mouse to human by completing a risk assessment parallelogram.

Animals↗

Evidence for an essential role of cyclooxygenase-2 as a mediator of the late phase of ischemic preconditioning in mice.

Recent studies have demonstrated that cyclooxygenase-2 (COX-2) is an essential mediator of the cardioprotective effects of the late phase of ischemic preconditioning (PC) in rabbits. The goal of this study was to determine whether COX-2 also plays an essential role in late PC in the mouse. B6129F2/J mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Administration of the COX-2 selective inhibitor, NS-398, 30 min prior to the 30-min occlusion (5 mg/kg i.p.) had no appreciable effect on infarct size compared with untreated controls (58.8 +/- 2.1%, vs. 58.8 +/- 4.3% of the risk region, respectively). When mice were preconditioned with six cycles of 4-min coronary occlusion/4-min reperfusion 24 h prior to the 30-min occlusion, infarct size was markedly reduced (19.3 +/- 3.4%), indicating a late PC effect. The protective effect of late PC was completely abrogated by administration of NS-398 30 min before the 30-min coronary occlusion (67.7 +/- 3.0%), but not by administration of vehicle alone (23.6 +/- 3.7%). These results indicate that COX-2 mediates the late phase of ischemic PC in the mouse and imply that the role of this enzyme in cardioprotection is not species-specific.

Animals↗

Genetic alterations of the p16 gene in urothelial carcinoma in Taiwanese patients.

OBJECTIVE: To measure changes in the p16 gene (MTS1, a negative regulator of cell-cycle progression at the G1 checkpoint, and a tumour suppressor gene) in urothelial carcinomas (including upper tract urothelial and bladder tumours), and to correlate these measurements with the clinical status of such patients in Taiwan, where renal pelvic tumours comprise 47% of all kidney tumours and are more common than the average worldwide. MATERIALS AND METHODS: Thirty-five upper tract urothelial and 61 bladder tumours were examined for changes in p16. Deletion of the gene was assessed by Southern blot analysis and mutation analysed using polymerase chain reaction-single strand conformation polymorphism, followed by direct sequencing. RESULTS: Of the 61 bladder carcinomas, homozygous deletion of p16 was detected in 12 (20%). However, a homozygous deletion was detected in 11 of 35 (31%) upper tract urothelial carcinomas, a higher frequency than that reported for transitional cell bladder carcinomas. Deletion was detected as frequently in stage I tumours as in late-stage tumours, suggesting that p16 deletion is a relatively early event in urothelial tumorigenesis. No point mutations were noted for p16 in any of the primary urothelial tumours. Most multiple and recurrent tumours and metastatic nodules in individual patients contained identical p16 genetic lesions, confirming that the tumours were probably monoclonal. In addition, there was a high gene dose of p16 in bladder carcinomas from patients with lymph node metastasis. CONCLUSION: Deletion of p16 appears to be a common event in urothelial carcinomas, especially in upper tract urothelial tumours. High levels of p16 were detected in tumours with lymph node metastasis. It seems likely that a high p16 level is associated with carcinomas of advanced stage and grade, and with poor prognosis in patients with such cancers.

Blotting, Southern↗

The clinical implications of telomerase activity in upper tract urothelial cancer and washings.

OBJECTIVE: To measure telomerase activity in upper tract urothelial carcinomas (as renal pelvic tumours comprise nearly half of all kidney tumours in Taiwan, a much higher percentage than in other countries) and to determine whether telomerase activity could be used as an additional diagnostic marker in exfoliated cancer cells present in upper tract urothelial washing fluids, thus providing earlier diagnosis and treatment. Materials and methods Telomerase activity was assessed using the telomeric repeat amplification protocol assay in tissue samples from 31 upper tract urothelial carcinomas (from 29 patients). The feasibility of identifying cancer using telomerase activity in exfoliated cancer cells in 17 upper tract urothelial washing samples was also investigated. RESULTS: Telomerase activity was found in 30 (97%) of the 31 upper tract urothelial cancer tissue samples; telomerase activity was detectable in 95% of superficial cancers and in all 11 invasive tumours. The sensitivity of measuring telomerase activity was 100% for grade 1, 93% for grade 2 and 100% for grade 3 tumours. In contrast, telomerase activity was detected in only two (8%) of 26 normal adjacent tissue samples. When the telomerase activity of urothelial washing fluid was compared with that in the corresponding tumours, there was compatible telomerase activity in 15 of the 17 samples. Telomerase activity was more sensitive than voided urine cytology (15%) and washing fluid cytology (53%). In addition, the telomerase activity was high in metastatic lesions. CONCLUSION: Telomerase activity is present in most upper tract urothelial cancer tissues and may be present at an early stage of carcinogenesis. Telomerase activity can be detected in exfoliated cells in urothelial washing fluids in a high proportion of patients with upper tract urothelial cancer. These results suggest that measuring telomerase activity in the exfoliated cancer cells obtained from urothelial washing could be a potentially useful addition to the conventional diagnostic tools used to identify patients with upper tract urothelial carcinoma.

Biomarkers, Tumor↗

Protection from ototoxicity of intraperitoneal gentamicin in guinea pig.

BACKGROUND: Aminoglycoside antibiotics are common to treat peritonitis and exit-site infections in patients on peritoneal dialysis. Ototoxicity (loss of hearing or balance) is a well-documented adverse effect of aminoglycosides, and severe ototoxic reactions have been noted in patients receiving these drugs by intraperitoneal lavage. We have proposed a free-radical hypothesis for the mechanism of aminoglycoside ototoxicity and suggested a therapeutic prevention by the concomitant administration of antioxidants or iron chelators. Here we investigate whether 2, 3-dihydroxybenzoate can prevent the ototoxicity of intraperitoneal gentamicin. METHODS: Two strains of pigmented guinea pigs received daily intraperitoneal injections of gentamicin. Both strains developed ototoxicity, although different dosages were needed to produce similar auditory deficits (120 mg gentamicin base/kg body weight daily for 19 days vs. 135 mg/kg for 14 days). Dihydroxybenzoate was administered intraperitoneally once or twice daily. Auditory thresholds were measured by evoked brain stem response. Pathology was assessed as a loss of sensory cells in surface preparations of the organ of Corti. RESULTS: The auditory threshold shifts and hair cell loss were similar to the pathology observed following subcutaneous injections of gentamicin. Animals sustained almost complete loss of outer hair cells in the basal cochlea and a progressive hearing loss with threshold shifts of 60 dB at 18 kHz. The concomitant administration of dihydroxybenzoate significantly attenuated the threshold shift to less than 30 dB and reduced the loss of hair cells. The treatment with dihydroxybenzoate did not affect serum gentamicin levels. CONCLUSIONS: Antioxidant therapy is a promising approach to prevent aminoglycoside-induced hearing loss following intraperitoneal application.

Animals↗

Effects of multiple mating on female reproductive output in the cat flea (Siphonaptera: Pulicidae).

Multiple mating behavior of female cat fleas, Ctenocephalides felis (Bouché), was confirmed in this study, and its effects on fecundity and fertility were investigated as well. The number of fertile eggs produced by mated females was close to nil within 7 d after removal of males, but it was resumed when females were exposed to males again on day 7. Multiple-mated females displayed significantly higher fecundity (400.3 eggs per female) and fertility (182.8 viable eggs per female) than single-mated females (61.7 and 19.0, respectively) in the 24-d period, suggesting that multiple mating by females is an advantageous strategy for cat fleas. The duration of first mating averaged 63.1 min. The high ratio (55.56%) and short duration (34.0 min) of impotent mating suggested that cryptic female choice may be involved during copulation.

Animals↗