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Biomedical subjects

W Yu

Publications and source records attributed to W Yu.

At least 253 records · Page 14Linked to original sources
PubMed1997

[In vitro expansion of human umbilical cord blood hematopiotic cells and its subpopulation].

OBJECTIVE: To study the effect of expansion of cord blood stem cells in vitro. METHODS: The mononuclear cells of human umbilical cord blood was cultured in vitro and the cell cycle and CD34+ subset analysis was performed on these cell preparations using flow cytometry. RESULTS: After 35 days, the number of nucleated cells showed over a comulative 252 fold expansion. CD34+ cells increased 50-fold in 7-21 days. CD33+ cells increased 280-fold during 7-28 days. CD19+ and CD34+ cells disappared after 14 days. The cells remained in G0/G1 phase and increased in the S phase. CONCLUSION: Single umbilical cord blood would be enough to transplant to adults if suitable time and a novel expansion strategies are set.

Antigens, CD↗
PubMed1997

[The relation between expression of PML-RAR alpha gene and effects of ATRA on proliferation and differentiation of NB4 cells].

OBJECTIVE: To study the relation between the PML-RAR alpha gene and the effects of ATRA on proliferation and differentiation in acute promyelocytic leukemia cell line NB4 cells. METHODS: ASODN-mediated inactivation of the PML-RAR alpha mRNA was measured by RT-PCR. The proliferation and differentiation of NB4 cells were determined by proliferation curve, morphology, CD antigen of membrane and NBT test. NB4 Cell cycle was analyzed by FACS. RESULTS: The inactivation of PML-RAR alpha mRNA by ASODN could egnhance the maturation effects and growth suppression of ATRA on NB4 cells. The percentage of S phase cell was decreased from 52% to 29%, and NBT rate increased. All suggest that the sensitivity of NB4 cell to ATRA was improved. CONCLUSION: The PML-RAR alpha gene, as a molecular marker of APL, is responsible for pathogenesis of APL, and it also decreases the sensitivity of ATRA to APL cells.

Antineoplastic Agents↗
PubMed1997

[The relationship between concentration of growth hormone in serum and microangiopathy in patients with diabetes mellitus].

OBJECTIVE: To study the relationship between growth hormone (GH) and microangiopathy in patients with diabetes mellitus in order to elucidate pathogenesis on microangiopathy in diabetics. METHODS: GH and insulin (INS) were detected by rdioimmunoassay, and blood sugar (BS) was detected by oxydase method. RESULTS: 138 NIDDM diabetics were examined. The concentration of serum GH in diabetics without microangiopathy (2.3 +/- 1.2 micrograms/L) was higher than in normal people (1.0 +/- 1.2 micrograms/L) and GH in diabetics with microangiopathy (5.74 +/- 1.94 micrograms/L) was higher than in diabetics without microangiopathy. The differences were significant (P < 0.01). As the history of diabetes went on, the level of GH in serum increased, and the incidence of microangiopathy increased too. The correlation of GH in serum with BS was parallel. The correlation of GH in serum with INS was not apparent. 27 ID-DM diabetics were examined, their level of GH in serum (6.8 +/- 3.4 micrograms/L) was higher than that of NIDDM diabetics (4.6 +/- 1.8 micrograms/L). They were all patients with microangiopathy. CONCLUSION: The rise of GH in serum may be an important pathogeny that causes microangiopathy in diabetics.

Adult↗
PubMed1996

Repair of abdominal aortic aneurysms by the endoluminal method: outcome in the first 100 patients.

OBJECTIVE: To report the outcome in our first 100 patients with abdominal aortic aneurysms repaired by the endoluminal method. DESIGN: Analysis of concurrently collected data of patients undergoing repair of an aortic aneurysm. The technique involves the delivery of an endograft into the abdominal aorta by means of a sheath inserted through the femoral or iliac artery. Clinical examination and contrast-enhanced computed tomography (CT) were performed within 10 days, at six months and then annually after operation. SETTING: Royal Prince Alfred Hospital, Sydney, a tertiary referral teaching hospital. PATIENTS: 100 patients, seven women and 93 men, with a mean age of 70 years (range, 46-87), treated between May 1992 and December 1995. Because of comorbidities, 43 of the patients had been considered unsuitable for conventional open repair at other medical centres. Our criteria for inclusion were the presence of a 1.5-cm or greater segment of thrombus-free aorta between the lowermost renal artery and the commencement of the aneurysm, and iliac arteries allowing access to the aorta from the groin. OUTCOME MEASURES: (i) Need to convert to open repair; (ii) damage to the arteries from sheath insertion; (iii) communication between the aneurysmal sac and the circulation; (iv) death within 30 days; (v) effect on aneurysmal diameter. RESULTS: Endografts were successfully deployed in 88 patients. In the remaining 12 patients endoluminal repair was converted to open repair. There were five deaths within 30 days of the operation, including three in the failed group. Damage to the femoral or iliac arteries from sheath insertion occurred in five patients. These were repaired without the need to convert to open repair. No patients were lost to follow-up (62 patients have been followed up for at least six months). Contrast-enhanced computed tomography shows progressive diminution in maximal transverse diameter of the aneurysms with time, after successful exclusion of the aneurysmal sac from the general circulation. CONCLUSION: Endoluminal repair of abdominal aortic aneurysms is feasible and this method of repair is durable in mid-term follow-up.

Aged↗
PubMed1996

Effects of intrathecal vs. systemic clonidine in treating chronic allodynia-like response in spinally injured rats.

A chronic pain-like response to innocuous mechanical stimuli (allodynia) was observed in rats after severe spinal cord ischemia, which resembled some painful conditions observed in spinally injured patients. The present studies examined the effects of clonidine, an alpha 2-adrenoceptor agonist, on this allodynia-like response. Intrathecal (i.t.) clonidine dose-dependently relieved allodynia and doses up to 10 micrograms did not induce motor deficits or sedation, but slightly increased systemic blood pressure. The anti-allodynic effect of i.t. clonidine was reversed by the selective alpha 2-adrenoceptor antagonist atipamezole. In contrast, 50 and 100 micrograms/kg intraperitoneal (i.p.) clonidine did not relieve the chronic allodynia, although the higher dose induced some motor deficits and sedation. Allodynic behavior was abolished after 200 micrograms/kg, i.p. clonidine, which, however, caused strong sedative and motor impairment. The present data suggested that spinal, but not systemic, alpha 2-adrenoceptor agonists may have therapeutic value in treating mechanical allodynia in patients with neuropathic pain of spinal origin.

Animals↗
PubMed1996

Microtubule assembly in growing dendrites.

Dendritic microtubules (MTs) are nonuniform with respect to polarity orientation, with roughly equal proportions having a plus-end-distal or minus-end-distal orientation. In the present studies, we have microinjected biotin-labeled tubulin (Bt-tub) into cultured sympathetic neurons extending dendrites to explore the contribution of MT assembly to the elaboration and maintenance of the dendritic MT array. Within minutes of injecting Bt-tub, an enormous number of MTs were seen emanating from a point source in the cell body. Over time, this pattern changed such that by 120 min after injection, biotinylated MTs no longer emanated from a discrete site, but were distributed over a broad region that extended from the cell body into the dendrites. The observation that biotinylated MTs emanate from a point source in the soma at relatively short times after injection, but not at longer times, suggests that they undergo a redistribution subsequent to their initial nucleation rather than a simple radial expansion from the somal nucleation site. Bt-tub assembly also occurred in dendrites but, unlike in the cell body, assembly was dispersed throughout the dendrite rather than emanating from a discrete site. Immunoelectron microscopic analyses revealed that assembly in dendrites reflected the addition of Bt-tub onto the ends of both plus-end-distal and minus-end-distal MTs that existed in the cell at the time of injection. The time course of Bt-tub appearance in dendritic MTs suggested an average half-life of approximately 76 min for these MTs. We discuss these observations in the context of a model for generating the MT array of dendrites that combines both MT transport and MT assembly.

Animals↗
PubMed1996

Capsaicin-sensitive afferents mediate chronic cold, but not mechanical, allodynia-like behavior in spinally injured rats.

Pain-like responses to cold or innocuous mechanical stimuli were observed chronically in rats after spinal cord ischemia. These resembled the symptoms of mechanical allodynia and cold hyperalgesia that are frequently observed in spinally injured patients. We evaluated the involvement of capsaicin-sensitive afferents in mediating these responses. A single subcutaneous injection of resiniferatoxin (RTX), an ultrapotent capsaicin analogue, produced hypoalgesia to noxious heat stimulus and normalized the enhanced response to cold stimulus. In contrast, the mechanical allodynia-like response was not influenced by RTX. Thus, the enhanced response to cold, but not light touch, is mediated by capsaicin-sensitive afferents. Capsaicin and related compounds may have therapeutic potential in treating neuropathic pain elicited by some, but not all, modalities of stimulation.

Animals↗
PubMed1996

The mechanism by which NBQX enhances NMDA currents in retinal ganglion cells.

When the quinoxaline NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) quinoxaline), a KA/AMPA antagonist, is bath applied to the tiger salamander retina, a paradoxical action is evident in the light-evoked synaptic responses of ganglion cells: NBQX enhances excitatory synaptic currents at light onset observed under whole-cell voltage-clamp conditions in a perfused retinal slice preparation. This observation was surprising because synaptic inputs into ganglion cells that are mediated by KA/AMPA receptors are entirely blocked by NBQX. Thus, the NBQX-enhanced current is entirely mediated by NMDA receptors. The purpose of this study was to determine the mechanism(s) by which blocking KA/AMPA receptors appears to enhance NMDA currents. Using hyperosmotic sucrose stimulation to activate neurotransmitter release from the inner retina, we observed that NBQX augmented the sucrose-evoked response, suggesting that at least a component of this enhancement may reside in the inner retina. NBQX does not enhance NMDA currents activated by bath applied NMDA, demonstrating that the NBQX-induced enhancement does not result from modulation of NMDA receptors. Voltage-clamp studies, carried out at the appropriate holding potential, indicate that NBQX enhances glutamatergic transmission and reduces inhibitory inputs onto ganglion cells. In the presence of strychnine and picrotoxin, the NBQX-induced enhancement of NMDA currents is eliminated, suggesting that NBQX facilitates the expression of NMDA currents by a selective and partial reduction of inhibitory mechanisms. Additional studies suggest that part of the NMDA enhancement by NBQX is evident at the postsynaptic level, but a presynaptic component probably also participates, perhaps at the level of bipolar cell terminals. One way to account for this observation is to assume that a subpopulation of inhibitory amacrine cells requires KA/AMPA receptors exclusively for their synaptic activation: previous studies of sustained amacrine cells support this interpretation. Thus the NBQX-induced enhancement phenomenon may reflect a network-selective distribution of NMDA and KA/AMPA receptors among third-order neurons.

Animals↗
PubMed1996

Loss of plasmid-mediated oligopeptide transport system in lactococci: another reason for slow milk coagulation.

Fast milk-coagulating (Fmc+) strains of lactococci are known to segregate slow milk-coagulating (Fmc-) variants, which has been attributed to loss of proteinase (Prt) activity encoded by plasmid DNA. It was found that the Fmc- phenotype could also be due to loss of a plasmid encoding an oligopeptide permease (Opp) system. In Lactococcus lactis subsp. lactis (L. lactis) C2O, lactose metabolism (Lac) and Prt were linked to pJK550 and the Opp system to pJK430. In Lactococcus lactis subsp. cremoris SK11, known to possess Prt on a 78-kb plasmid, DNA sequence analysis of a 7.4-kb region from the Lac plasmid, pSK11L, revealed that it possessed the Opp system. The Lac plasmid in L. lactis C2 encoded both the Prt and Opp systems. Fmc- derivatives of L. lactis C2 were missing the prt genes and had Opp integrated into the chromosome, possibly due to transposition events. Growth studies showed the Opp systems were functional and, in combination with Prt, produced the Fmc+ phenotype.

Animals↗
PubMed1996

Results of endoluminal grafting of abdominal aortic aneurysms are dependent on aneurysm morphology.

The aim of this prospective study was to analyze the outcome of elective endoluminal grafting in patients with various morphologies of abdominal aortic aneurysms (AAA). Between May 1992 and May 1994, endoluminal repair of AAA was undertaken in 40 patients. After detailed imaging by means of CT scanning and arteriography, aneurysms were classified into one of two types according to the following criteria: type I (suitable for transfemoral implantation of a straight tube graft), AAA with a proximal neck (2 cm or longer), a distal neck (1.5 cm or longer), and an iliac artery diameter of 8 mm or greater (N = 19); or type II (requiring tapered aortoiliac or bifurcated grafts or access through an iliac approach), AAA that did not fit the type I criteria (N = 21). Radiographic guidance was used to pass the aortic endografts (38 Dacron and 2 PTFE) via a delivery sheath introduced through the femoral or iliac arteries into the aorta. The configuration of the aortic endografts was tubular in 26 patients, tapered aortoiliac in 11, and bifurcated in three. Successful endoluminal repair was achieved in 17 (89%) of 19 patients with type I AAA and in 15 (71%) of 21 patients with type II AAA. All failed endoluminal repairs proceeded to successful open repair, and there were no deaths during the period of hospitalization for the operation. The mean operative time and mean hospital stay were shorter in patients with type I AAA compared to patients with type II AAA. The incidence of postoperative complications was 37% in type I endoluminal repairs compared to 71% in type II endoluminal repairs. There was one cardiac death (procedure related) within 30 days, and there were three late deaths (one cardiac, one from liver failure in a type II AAA repair, and one from a ruptured esophagus in a type I repair). These preliminary results suggest that there is a better outcome in transfemoral endoluminal tube graft repair of aneurysms conforming to type I criteria compared to endoluminal repair of the more complex type II AAA.

Aged↗
PubMed1996

A composite model for establishing the microtubule arrays of the neuron.

Neurons generate two distinct types of processes, termed axons and dendrites, both of which rely on a highly organized array of microtubules for their growth and maintenance. Axonal microtubules are uniformly oriented with their plus ends distal to the cell body, whereas dendritic microtubules are nonuniformly oriented. In neither case are the microtubules attached to the centrosome or any detectable structure that could establish their distinct patterns of polarity orientation. Studies from our laboratory over the past few years have led us to propose the following model for the establishment of the axonal and dendritic microtubule arrays. Microtubules destined for these processes are nucleated at the centrosome within the cell body of the neuron and rapidly released. The released microtubules are then transported into developing axons and dendrites to support their growth. Early in neuronal development, the microtubules are transported with their plus ends leading into immature processes that are the common progenitors of both axons and dendrites. This sets up a uniformly plus-end distal pattern of polarity orientation, which is preserved in the developing axon. In the case of the dendrite, the plus-end-distal microtubules are joined by another population of microtubules that are transported into these processes with their minus-ends leading. Implicit in this model is that neurons have specialized machinery for regulating the release of microtubules from the centrosome and for transporting them with great specificity.

Animals↗
PubMed1996

Fetal ethanol exposure alters pituitary-adrenal sensitivity to dexamethasone suppression.

The present study investigated the hypothesis that a deficit in feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the hormonal hyperresponsiveness seen in fetal ethanol-exposed rats. Male and female Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF) and ad lib-fed control (C) treatment groups were tested in adulthood. The effects of dexamethasone (DEX) blockade on basal and stress corticosterone (CORT) levels and stress adrenocorticotropin (ACTH) levels were examined over a 36-h period. Stress CORT and ACTH levels after DEX administration at the trough (AM) and peak (PM) of the CORT circadian rhythm were compared. DEX administration significantly suppressed both resting and stress levels of CORT and ACTH in all animals, regardless of prenatal treatment. Importantly, E animals did not differ from PF and C animals in basal CORT. However, E males and females had significantly higher stress levels of CORT and/or ACTH than PF and C animals, and further, showed differential responsiveness following DEX administration depending on the time of day when testing occurred. At the trough of the CORT circadian rhythm. E males did not differ from PF and C males, whereas E females had increased stress levels of CORT compared to PF and C females. In contrast, at the peak of the circadian rhythm, E males showed increased stress levels of CORT but not ACTH, whereas E females showed increased stress levels of both CORT and ACTH compared to males and females in respective control groups. These data support the hypothesis that E animals may exhibit deficits in HPA feedback inhibition compared to controls and suggest a sex-specific difference in sensitivity of the mechanism underlying HPA hyperresponsiveness.

Adrenocorticotropic Hormone↗
PubMed1996

Fluorescence generalized polarization of cell membranes: a two-photon scanning microscopy approach.

We use the lipophilic fluorescence probe Laurdan to study cell membranes. The generalized polarization (GP) of Laurdan-labeled cells contains useful information about membrane fluidity and polarity. A high GP is usually associated with low fluidity, low polarity, or high cholesterol content of the membranes, and a low GP is the opposite. We have combined the GP method and two-photon fluorescence microscopy to provide an alternative approach to study cell membranes. Using two-photon excitation in a conventional microscope offers great advantages for studying biological samples. These advantages include efficient background rejection, low photodamage, and improved depth discrimination. We performed GP measurements on mouse fibroblast cells and observed that both intensity and GP images are not spatially uniform. We tested for possible GP artifacts arising from cellular autofluorescence and lifetime quenching, using a procedure for background fluorescence subtraction and by direct lifetime measurements in the microscope. GP measured in a single cell displays a broad distribution, and the GP of 40 different cells grown on the same cover glass is also statistically distributed. The correlations between intensity and GP images were analyzed, and no monotonic dependence between the two was found. By digitally separating high and low GP values, we found that high GP values often associate with the regions of the plasma membrane and low GP values link with the nuclear membranes. Our results also show local GP variations within the plasma and nuclear membranes.

2-Naphthylamine↗
PubMed1996

Historic control comparison of outcome for matched groups of patients undergoing endoluminal versus open repair of abdominal aortic aneurysms.

PURPOSE: Currently no randomized studies show the relative morbidity and mortality of the open and endoluminal methods of abdominal aortic aneurysm (AAA) repair. The aim of this study was to analyze the outcome of two matched groups of patients with AAA, one undergoing open repair and the other undergoing endoluminal repair. METHODS: Two groups of patients who had undergone repair of AAA by open technique (group 1) or by endoluminal methods (group 2) were compared. A historic control cohort of 27 patients was selected from 56 consecutive patients who underwent open repair of AAA between January 1991 and February 1992. Patients considered unsuitable for the endoluminal method on the basis of computed tomography and aortography were excluded (n=29). Between May 1992 and November 1994 prospective data were recorded for 62 consecutive patients who underwent endoluminal repair by tube or bifurcated endografts. Twenty-eight patients who had been specifically referred for endoluminal AAA repairs because of preexisting severe medical comorbidities were excluded. Six of the endoluminal cases had failure, requiring conversion to open operation, and were excluded for separate analysis, leaving 28 patients in group 2. Patients in both groups were thus fit and suitable for either open or endoluminal repair and were comparable in relation to age, sex, risk factors, dimensions, and form of AAA. RESULTS: The mean values for operation time, blood loss, intensive care stay, and hospital stay for group 1 and group 2 were 2.6 versus 3.1 hours, 1422 versus 873 ml,* 1.8 versus 0.7 days,* and 12.4 versus 11.1 days, respectively (*p<0.05). Local/vascular complications occurred in 15% of patients in group 1 compared with 25% in group 2 (p=0.55), whereas remote/systemic complications occurred in 37% and 29%, respectively (p=0.3). Five of 28 patients in the endoluminal group had complications requiring early operative repair (n=3) or late revision (n=2). When comparison was made on an intention-to-treat basis (with failed procedures included), the incidence of local/vascular complications was significantly greater for endoluminal repair (p=0.047). CONCLUSIONS: The incidence of systemic/remote complications was similar for the two groups in spite of significantly less blood loss and shorter intensive care unit stay with endoluminal repair. The incidence of local/vascular complications had a tendency to be higher for endoluminal compared with standard open method (and was significantly greater if failed procedures were included). In this early experience with prototype devices, patients who were medically suitable for open surgical procedures did not derive benefit from the less invasive endoluminal technique with respect to duration of operation, length of hospital stay, or perioperative morbidity and mortality. On the other hand, because they also did not have worse outcome, a randomized study is now justified in this group.

Age Factors↗
PubMed1996

NAB domain is essential for the subunit assembly of both alpha-alpha and alpha-beta complexes of shaker-like potassium channels.

There are at least five subfamilies of Shaker-like K+ channels. The diverse function of K+ channels are thought to be further modulated by hydrophilic beta subunits. Here we report that Kv beta 1 inactivates RCK4 and Shaker B K+ channels of the Kv1 subfamily, but not Shal2 of the Kv4 subfamily. This correlates the subfamily-specific bindings of Kv beta 1 to the cytoplasmic N-terminal domains of Kv1 alpha subunits. We map the Kv beta 1-binding site to a region overlapping NABKv1, a domain that specifies different Kv1 alpha subunits to form heterotetramers. Using chimeric alpha subunits, we demonstrate that NABKv1 is essential for the Kv beta 1-mediated inactivation. These results suggest that Kv beta 1 modulates a subset of K+ channels through the specific assembly of alpha-beta complexes and reveal the dual function of the NAB domain in mediating the assembly of both alpha-alpha and alpha-beta complexes.

Amino Acid Sequence↗
PubMed1996

A prospective study of anatomico-pathological changes in abdominal aortic aneurysms following endoluminal repair: is the aneurysmal process reversed?

AIM: The aim of this prospective study was to analyse early anatomico-pathological changes in abdominal aortic aneurysms (AAA) following endoluminal repair to determine if the natural history of continued expansion of AAA is reversed. MATERIALS AND METHODS: Sixty-seven of 85 patients undergoing endoluminal AAA repair between May 1992 and August 1995 had their operations prior to the end of February 1995 and were potentially available for follow up at 6 months or longer after operation. Excluded were: patients with failed endoluminal repairs (n = 14), patients who died within 6 months of operation (n = 5), patients with anastomotic AAA (n = 1), leaving 47 patients in the study group. Based on contrast enhanced CT performed preoperatively, within 10 days of operation and 6, 12 and 18 months after operation patients were divided into two groups: those in whom the AAA maximum transverse diameter (MTD) decreased Group I (n = 39) and those in which it increased Group II (n = 8). The following parameters were analysed: diameter of the supra coeliac aorta, MTD and the dimensions of the proximal and distal necks of the AAA plus extravasation ("leak") of contrast into the aneurysmal sac. RESULTS: Leak of contrast was seen in 0 of 39 patients in Gp I and 5 of 8 patients in Gp II. Patients in Group I experienced a progressive diminution in AAA mean MTD. The diameters of the proximal and distal necks increased but there was no shortening of the length of the necks in this group. In Group II the AAA MTD was dependent on whether or not the aneurysmal sac was isolated from the circulation. The diameter of the proximal and distal necks increased irrespective of this fact. CONCLUSION: We conclude that in early follow up AAA which diminish in diameter following endoluminal repair remain isolated from the general circulation. Co-incident with this decrease in AAA diameter, the proximal and distal necks increase in diameter but do not undergo any shortening in length. This paradoxical increase in neck diameter, was not progressive in the period of follow-up.

Aged↗