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Biomedical subjects

W Yu

Publications and source records attributed to W Yu.

At least 307 records · Page 17Linked to original sources

Male sterility and double heterozygosity for chromosomal inversion.

A meiotic analysis has been carried out on male mice heterozygous for one of two inversions in Chromosome 2, In(2)5Rk and In(2)2H, as well as on double heterozygotes for these two overlapping inversions. Electron microscopic observation of synaptonemal complexes revealed that heterosynapsis had occurred in a large number of spermatocytes, producing a small number of cells with an inversion loop. Heterozygous carriers of a single inversion loop reproduced quite normally, whereas doubly heterozygous carriers of a double loop showed a reduction in spermatogenesis. These data shed new light on the role of inversions in speciation.

Animals↗

Cellular infiltration and eicosanoid synthesis in brown Norway rat lungs after allergen challenge.

Allergen challenge of sensitized Brown-Norway (BN) rats results in increased excretion of cysteinyl-leukotrienes (cLTs) in bile. It is unclear whether this reflects an increased capacity of lung cells to synthesize 5-lipoxygenase products, and, if so, which cells are of primary importance. We have examined the effects of allergen challenge on the capacity of a mixture of isolated lung cells from ovalbumin (OA)-sensitized BN rats to synthesize LTs and other eicosanoids. Cells were isolated by enzymatic digestion of lung tissue before and either 6 or 24 h after challenge of sensitized rats with either OA or saline. A23187-induced synthesis of eicosanoids by these cells was measured using high-pressure liquid chromatography. OA challenge resulted in a significant influx of neutrophils into the lungs and a significant increase in the synthesis of 5-lipoxygenase products, in particular LTB4, by lung cells after 6 h. There was a positive correlation between the percentage of neutrophils in unfractionated lung cells and the amounts of LTB4 produced by these cells. OA challenge had little or no effect on the production of cLTs and the cyclooxygenase product 12-hydroxy-5,8,10-heptadecatrienoic acid. There was a significant increase in the infiltration of eosinophils into the lungs 24 h after OA challenge but no increase in the production of cLTs by lung cells at this time, suggesting that eosinophils from BN rats are unlikely to be the major site for the production of these substances. This was confirmed in experiments with partially purified eosinophils obtained from Sephadex-treated rats. In contrast, cLTs were major products of arachidonic acid metabolism by alveolar macrophages from BN rats. We conclude that allergen challenge results in an increased capacity of lung cells to synthesize 5-lipoxygenase products, in particular LTB4. Macrophages, rather than eosinophils, may be an important site for the synthesis of cLTs in BN rat lungs.

Allergens↗

Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase.

We have identified recessive overproliferation mutations by screening and examining clones of mutant cells in genetic mosaics of the fruitfly Drosophila melanogaster. This type of screen provides a powerful approach for identifying and studying potential tumor suppressors. One of the identified genes, lats, has been cloned and encodes a putative protein kinase that shares high levels of sequence similarity with three proteins in budding yeast and Neurospora that are involved in regulation of the cell cycle and growth. Mutations in lats cause dramatic overproliferation phenotypes and various developmental defects in both mosaic animals and homozygous mutants.

Amino Acid Sequence↗

Early experience with the Sydney and EVT prostheses for endoluminal treatment of abdominal aortic aneurysms.

PURPOSE: The aim of this study was to report early experiences with the Sydney and Endovascular Technologies (EVT) prostheses for the treatment of abdominal aortic aneurysms (AAA) deemed suitable for endoluminal tube graft repair. METHODS: Consecutive endoluminal tube graft repairs were analyzed over the first 12 months in which the Sydney and EVT prostheses were used. Patients eligible for the EVT prosthesis had type I AAAs: a proximal neck length > or = 2 cm, a distal cuff length > or = 1.5 cm, and nontortuous iliac arteries > or = 8 mm. Selection criteria for the Sydney device were more liberal and included AAAs that had distal cuffs < 1.5 cm. During the study period, 28 of 91 patients evaluated for AAA repair were thus selected for endoluminal grafting: 18 patients received the Sydney endograft and 10 the EVT device. Medical comorbidities were present in slightly less than one third of patients in both groups. Contrast-enhanced computerized tomography (CT) was performed preoperatively, within 10 days of operation, and at 6 and 12 months postprocedure. RESULTS: All endografts were successfully deployed in both groups. Postprocedural CT scans revealed incomplete aneurysm exclusion in four patients with the Sydney endograft. Subsequent deployment of a second endograft sealed these "leaks" in two cases; the other two were converted to open repair (89% clinical success). No leaks were seen with the EVT device. Local/vascular complications occurred in 33% of the Sydney group compared with 20% for the EVT device (p = 0.001); systemic sequelae were more common in the EVT group (30% versus 17% in the Sydney cohort, p = 0.002). There were no deaths within 30 days; three late deaths were not procedure related. CONCLUSION: AAAs that are suitable for endoluminal tube graft repair may be treated with a high rate of initial success with either the Sydney or EVT prostheses. More liberal selection criteria may increase the likelihood of local/vascular complications.

Aged↗

A prospective study of changes in morphology and dimensions of abdominal aortic aneurysms following endoluminal repair: a preliminary report.

PURPOSE: The aim of this prospective study was to analyze early changes in morphology and dimensions of abdominal aortic aneurysms (AAA) following endoluminal repair. METHODS: Forty-two of 62 patients undergoing endoluminal repair of AAAs between May 1992 and November 1994 were potentially available for follow-up at 6 months or longer after operation. After excluding patients with failed endoluminal repairs, patients who died within 6 months of operation, and patients with anastomotic aneurysms, a study group of 30 patients remained. Contrast-enhanced computed tomography (CE-CT) was performed preoperatively, within 10 days of operation, and at 6 and 12 months postprocedure. Based on the postoperative CE-CT findings, patients were divided into two groups: those with no extravasation of contrast into the aneurysmal sac (group I; n = 26), and those in which there was contrast extravasation ("leak") into the aneurysmal sac (group II; n = 4). RESULTS: The mean maximum diameters of AAAs in group I diminished progressively at 6 and 12 months, while those in group II increased. Twenty-three (88%) patients in group I had decreased diameter of AAA, while all patients in group II had progressive increase in AAA diameter. Patients who had an increase in AAA diameter had a significantly higher incidence of leak compared with those who had a decrease in diameter (p = 0.001). CONCLUSIONS: The majority of AAAs in which the sac has been excluded from the general circulation diminish in size following successful endoluminal repair. An increase in size occurs in those AAAs in which a communication exists between the aortic lumen and the sac. These results suggest that successfully excluded AAAs that continue to increase in size should be suspected of having an undetected leak.

Aortic Aneurysm, Abdominal↗

Results of autopsy 7 months after successful endoluminal treatment of an infrarenal abdominal aortic aneurysm.

PURPOSE: To report the results of a postmortem examination in a patient who died of unrelated causes 7 months following endoluminal treatment of an infrarenal abdominal aortic aneurysm (AAA). METHODS: As part of an FDA Phase I pilot study, a 73-year-old man underwent successful endoluminal exclusion of an infrarenal AAA using a 9-cm-long endograft (Endovascular Grafting System). Seven months later, he succumbed to complications of a spontaneous esophageal rupture. At autopsy, the aorta was dissected in situ by a vascular surgeon and pathologist before being explanted in order to examine the wound healing characteristics at the aorta-endograft interface. Particular attention was also directed to the hooks composing the attachment system at each end of the endograft. RESULTS: Macroscopic and microscopic examination revealed that the graft had completely excluded the aneurysm sac from the circulation and was incorporated into the aortic wall at the proximal neck and distal cuff. A smooth pannus of endothelial cells covered the proximal end of the endograft at the areas of contact with the aorta, while microscopic examination of the distal end of the graft revealed poorly formed, fibrinous pannus. The neointima deep to the endothelium consisted of a collagenous matrix containing myofibroblasts and histiocytes, providing evidence of healing between the endograft and aorta. Both renal arteries were clear of the proximal end of the endograft, but a previously unrecognized right lower pole renal artery with an extremely caudal origin was excluded from the aortic lumen. Each hook of the attachment system was seen protruding through the adventitia of the aorta. There was no evidence of trauma to the aortic wall or the surrounding tissues caused by these hooks. CONCLUSION: There appears to be evidence that an endoluminally placed aortic graft may be incorporated by the host aortic tissue.

Aged↗

The growth of the axon is not dependent upon net microtubule assembly at its distal tip.

Although there is agreement that the net addition of new microtubule polymer to the axon is required for its growth, controversy exists concerning the principal site in the neuron where this occurs. Some models hold that microtubule polymer is assembled within the cell body and translocated down the axon, while others hold that the net addition of polymer occurs at the distal tip of the axon. The foundation for the latter idea was a study in which anti-microtubule drugs were applied topically for 30 min to discrete regions of cultured sensory neurons (Bamburg et al., 1986). The axon continued to grow when the drugs were applied to the cell body, but stopped growing when the drugs were applied to the distal tip of the axon. Assuming that the sole action of the drug was to inhibit microtubule assembly, many workers have interpreted these findings as indicating that the growth of the axon requires net microtubule assembly at its distal tip. We repeated these experiments using a broader range of drug treatments, and evaluated using electron microscopy the effects of these treatments on microtubule levels. Our results indicate that the previous drug treatments went beyond inhibiting microtubule assembly, and also caused substantial microtubule disassembly. When the drug regime was altered so as to induce lower levels of microtubule disassembly in the distal region of the axon, the axon continued to grow. These results indicate that the growth of the axon is not dependent upon net microtubule assembly at its distal tip.

Animals↗

Pre-exposure of mice to low dose or low dose rate ionizing radiation reduces chromosome aberrations induced by subsequent exposure to high dose of radiation or mitomycin C.

The phenomenon of cytogenetic adaptive and cross-adaptive response induced by low dose irradiation and chemical mutagen in mice is described. We found, firstly, that adaptation can be induced by acute low dose X-irradiation (0-100 mGy). Secondly, a cross-adaptation can occur between X-irradiation and mitomycin C (MMC). And finally, mice pre-exposed to chronic low dose rate 60Co-Gamma irradiation (0-226.0 mGy/day) are less susceptible to chromosome aberration induced by subsequent acute higher X-irradiation. Therefore, our data suggest that radioadaptive response depends on dose, dose rate and time interval. Possible mechanisms are also discussed.

Adaptation, Physiological↗

[Large-scale culture of human keratinocytes].

We propose a modification of the conventional keratinocyte subculture method, showing a significant improvement in the colony growth capacity of subcultured keratinocytes. This method utilized mouse 3T3 fibroblasts and MCDB153 medium, and it has been shown that they could improve the colony growth of human keratinocytes. Compare with the conventional procedure, this culture method was shorter in time, and resulted in a higher colony growth capacity of cells, reaching confluence 3 days earlier. In the treatment of extensively burned patients using cultured epidermal sheets, the time required for their production remains the main problem. Thus, the significantly reduced time to obtain confluent keratinocyte sheets with our method is very important for the treatment of large burn wounds.

3T3 Cells↗

Endoluminal repair of abdominal aortic aneurysms.

OBJECTIVE: To review the outcome of endoluminal repair of abdominal aortic aneurysm. PATIENTS: Twelve patients with abdominal aortic aneurysms (mean diameter, 5 cm; range, 4.4-7.8 cm) were selected according to strict criteria relating to the morphology of the aneurysm and iliac arteries. The aneurysms all had a proximal neck between the renal arteries and the aneurysm and a distal neck between the aneurysm and the bifurcation of the aorta. The iliac arteries were not tortuous and were 8 mm or greater in diameter. INTERVENTION: The aneurysm was repaired with a graft stent device introduced into the aorta via a sheath in the femoral artery. RESULTS: Successful endoluminal repair was achieved in 10 of 12 patients (83%). The two patients in whom the endoluminal repair was abandoned were treated by standard open repair. All patients have since had an aortogram and duplex ultrasound examination to confirm exclusion of the aneurysm from the general circulation (mean period of follow-up, seven months). There have been no deaths. CONCLUSION: Abdominal aortic aneurysms conforming to strict morphological criteria can be treated safely and successfully by this minimally invasive endoluminal method.

Aged↗

Dominance of metallothionein in metal ion buffering in yeast capable of synthesis of (gamma EC)nG isopeptides.

The relationship of yeast metallothionein (MT) and (gamma EC)nG isopeptides (phytochelatins) in metal ion buffering was assessed. The effect of constitutive expression of yeast metallothionein (MT) genes on accumulation of metal-(gamma EC)nG isopeptide (phytochelatin) complexes was analyzed in Candida glabrata and Schizosaccharomyces pombe cultures incubated in the presence of cadmium salts. Constitutive expression of the Saccharomyces cerevisiae MT (CUP1) gene inhibited the accumulation of metal-phytochelatin complexes in both C. glabrata and S. pombe. Intracellular Cd(II) sequestration occurred by formation of CdMT complexes. Phytochelatin (gamma EC)nG complexes appear to function in metal buffering in cells when MT genes are not present or expressed. A third condition in which metal-(gamma EC)nG complexes are observed is when constitutively expressed MT does not accumulate. We observed that C. glabrata lacking the AMT1 gene necessary for copper induction of the MT genes expressed MTII constitutively, but this expression does not lead to CdMTII accumulation. Only Cd-(gamma EC)nG complexes accumulate. Likewise, metal exposed cultures of S. cerevisiae (cup1) transformed with C. glabrata MTII under the constitutive ADH1 promoter resulted in constitutive expression of MTII and accumulation of CuMTII complexes but no CdMTII complexes. The inability of constitutively expressed C. glabrata MTII to buffer Cd(II) ions may arise in part from an inherent kinetic lability of CdMTII complexes. Incubation of ZnMTII with a metallochromic chelator, 4-(2-pyridylazo)resorcinol resulted in greater Zn(II) loss than Zn(II) complexes with CUP1 MT and C. glabrata MTI. C. glabrata MTII appears to be the first MT described which forms an unstable Cd(II) complex.

Binding Sites↗

NBQX suppresses inhibitory glycine currents in retinal ganglion cells.

The quinoxaline NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) quinoxaline) is a potent non-NMDA receptor antagonist, which appears to be relatively free of antagonistic action at the glycine binding site of the NMDA receptor. However, we report here that at 50 microM, NBQX significantly attenuated the inhibitory currents induced by the exogenous application of 100 microM glycine as observed using whole-cell recordings from ganglion cells in a slice preparation of the tiger salamander retina. In contrast, NBQX had no effect on GABA-mediated inhibition. This observation suggests that care should be taken when attributing the action of NBQX solely to its antagonism of non-NMDA glutamate receptors, particularly when higher concentrations are used.

Ambystoma↗