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Biomedical subjects

A Leung

Publications and source records attributed to A Leung.

At least 19 recordsLinked to original sources
PubMed1999

Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy.

Atomic force microscopy (AFM) has been used to measure the strength of bonds between biological receptor molecules and their ligands. But for weak noncovalent bonds, a dynamic spectrum of bond strengths is predicted as the loading rate is altered, with the measured strength being governed by the prominent barriers traversed in the energy landscape along the force-driven bond-dissociation pathway. In other words, the pioneering early AFM measurements represent only a single point in a continuous spectrum of bond strengths, because theory predicts that these will depend on the rate at which the load is applied. Here we report the strength spectra for the bonds between streptavidin (or avidin) and biotins-the prototype of receptor-ligand interactions used in earlier AFM studies, and which have been modelled by molecular dynamics. We have probed bond formation over six orders of magnitude in loading rate, and find that the bond survival time diminished from about 1 min to 0.001 s with increasing loading rate over this range. The bond strength, meanwhile, increased from about 5 pN to 170 pN. Thus, although they are among the strongest noncovalent linkages in biology (affinity of 10(13) to 10(15) M(-1)), these bonds in fact appear strong or weak depending on how fast they are loaded. We are also able to relate the activation barriers derived from our strength spectra to the shape of the energy landscape derived from simulations of the biotin-avidin complex.

Biotin↗
PubMed1999

Variations in regional cerebral blood volume in neonates associated with nursery care events.

This pilot study investigated the frequency of events that cause cerebral oxygenation disturbances in ventilator-dependant neonates in the neonatal intensive care unit. Continuous, noninvasive, near infrared spectrophotometry measurements (changes in oxy and deoxy hemoglobin concentration, and cytochrome C oxidase redox status) were made at half-second intervals on 10 ventilator-dependent neonates (30.5 weeks average corrected gestation age, 1051 g average weight) and annotated to nursery events at the bedside. Examples of disturbances affecting cerebral oxygenation were opening incubator doors, handling, heel stabs, conversation, blanket tucking, and steno-paging. These events produced 7-40% changes in blood volume for durations of 5-60 sec, and occurred at a rate of up to 45 events within a 2 hr period. Spectrometry detected 63% more events than were observed and documented clinically. Noninvasive monitoring of cerebral oxygenation status could give new insight into managing the high-risk infant environment.

British Columbia↗
PubMed1999

Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity.

Short term exposure of the testis to heat causes degeneration of germ cells. However, the mechanisms underlying this process are poorly understood. The major objectives of this study were to determine whether the heat-induced loss of germ cells in the adult rat occurs via apoptosis, to document its stage-specific and cell-specific distribution, and to examine whether intratesticular testosterone (T) plays any role in the stage specificity of heat-induced germ cell death. Testes of adult male Sprague-Dawley rats were exposed to 22 C (control) or 43 C for 15 min. Animals were killed on days 1, 2, 9, and 56 after heat exposure. Germ cell apoptosis was characterized by DNA gel electrophoresis and in situ terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling assay. The incidence of germ cell apoptosis [apoptotic index (AI)] was quite low in control rats (AI = 0.04-0.1). Mild hyperthermia within 1 or 2 days resulted in a marked activation (AI = 4.7-5.6) of germ cell apoptosis predominantly at early (I-IV) and late (XII-XIV) stages. Stages V-VI and VII-VIII were relatively protected from heat-induced apoptosis. Spermatocytes, including pachytenes at stages I-IV and IX-XII, diplotene and dividing spermatocytes at stages XIII-XIV, and early (steps 1-4) spermatids, were most susceptible to heat. On day 9, the majority of the tubules were severely damaged and displayed only a few remaining apoptotic germ cells. By day 56, spermatogenesis was completely recovered, and the incidence of germ cell apoptosis was compatible with the control levels. To determine whether intratesticular T plays a role in protecting germ cells at stages VII-VIII against heat-induced cell death, adult rats were exposed to local testicular heating on day 2 or were given a daily sc injection of GnRH antagonist (GnRH-A) for 4 days with and without a single exposure of testes to heat applied on day 2. By day 4, the incidence of increased germ cell apoptosis at stages other than VII-VIII were not different between heat-treated and GnRH-A- plus heat-treated groups, whereas the control group and the group treated with GnRH-A alone showed minimal apoptosis. GnRH-A addition to heat resulted in a further increase in apoptosis (by 3.2-fold) at stages VII-VIII over the values measured in the heat-treated group, and it became comparable to that at all other stages. Collectively, these results provide evidence that 1) heat induces germ cell apoptosis in a stage-specific and cell-specific fashion; and 2) intratesticular T plays a pivotal role in protecting germ cells at stages VII-VIII against heat-induced cell death. However, the possible involvement of various other factors, including growth factors, thermoprotectants, cytokines, and various death-related proteins, in protecting germ cells against heat-induced apoptosis cannot be ruled out.

Animals↗
PubMed1998

Low-Rate Dynamic Contact Angles on Poly(methyl methacrylate) and the Determination of Solid Surface Tensions.

Low-rate dynamic contact angles of nine liquids on a poly(methyl methacrylate) (PMMA) polymer are measured by an automated axisymmetric drop shape analysis-profile (ADSA-P). It is found that two liquids dissolved the polymer on contact. From the experimental contact angles of the other seven polar and nonpolar liquids, it is found that the liquid-vapor surface tension times cosine of the contact angle changes smoothly with the liquid-vapor surface tension (i.e., gammalnucos theta depends only on gammalnu for a given solid surface). The dependence of gammalnucos theta on gammasnu is explicitly illustrated by replacing the solid surface from the PMMA to other methacrylate polymers: such a procedure shifts the curves in a very regular manner. Thus, because of Young's equation, gammasl depends only on gammalnu and gammasnu. This contact angle pattern is in harmony with those from other inert and noninert (polar and nonpolar) surfaces. The solid-vapor surface tension of PMMA calculated from the equation of state approach for solid-liquid interfacial tensions is found to be 38.5 mJ/m2, with a 95% confidence limit of +/-0.5 mJ/m2 from the experimental contact angles of the seven liquids. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Agonist-dependent phosphorylation of the parathyroid hormone/parathyroid hormone-related peptide receptor.

Native PTH/PTHrP receptors in ROS 17/2.8 cells are downregulated after PTH treatment. Since downregulation may involve receptor phosphorylation, we examined PTH/PTHrP receptor phosphorylation in ROS 17/2.8 cells and we mapped the agonist-induced phosphorylation sites using recombinant PTH/PTHrP receptors expressed in LLCPK-1 and COS-7 cells. The data show that the PTH/PTHrP receptor is rapidly phosphorylated in ROS 17/2.8 cells with a maximum occurring at 20 min. The phosphorylation was dose-dependent; it occurred with PTH concentrations that are known to downregulate the PTH/PTHrP receptor in ROS 17/2.8 cells. The time course and the dose requirement for phosphorylation were similar in ROS 17/2.8 cells, which express native PTH/PTHrP receptors, and in LLCPK-1 cells stably transfected with the PTH/PTHrP receptor cDNA. PTH/PTHrP receptor phosphorylation in ROS 17/2.8, COS-7, and LLCPK-1 cells was also stimulated with forskolin and phorbol myristate acetate (PMA). Additionally, in LLCPK-1 cells, which express native clacitonin receptors, PTH/PTHrP receptor phosphorylation was stimulated by calcitonin. These data suggest involvement of second messenger-stimulated kinases in PTH/PTHrP receptor phosphorylation. However, staurosporine, which fully blocked the effects of PMA, forskolin, and clacitonin, partially decreased the effects of PTH on PTH/PTHrP receptor phosphorylation. These data indicate involvement of other kinase(s) in PTH-induced PTH/PTHrP receptor phosphorylation. CNBr cleavage of recombinant receptors expressed in COS-7 cells combined with site-directed mutagenesis revealed that the phosphorylated residues of the PTH/PTHrP receptor map to two regions of the carboxyl-terminal tail located between residues A480 and M499 and residues M499 and M553. These data indicate that the PTH/PTHrP receptor is phosphorylated after PTH stimulation on two regions of the carboxyl-terminal tail and that agonist-dependent phosphorylation involves both staurosporine-sensitive and -insensitive kinases.

Amino Acid Sequence↗
PubMed1998

The effect of occlusal reduction on pain after endodontic instrumentation.

One hundred seventeen patients with posterior teeth requiring endodontic treatment were studied. Specific clinical findings were recorded, including pulp, vitality, preoperative pain, sensitivity to percussion, and the presence of a periradicular radiolucency. Excluded from the study were teeth with restorations to be maintained, greater than class I mobility, pocket depths > 5 mm, endodontic retreatments, and patients taking pain altering medications. Teeth were randomly assigned to 1 of 3 groups: (i) total occlusal reduction, (ii) simulated occlusal reduction (nonfunctional cusp reduction), or (iii) control (occlusion untouched). After canal instrumentation, a questionnaire was used by patients to record pain responses over a 48-h post-operative period. Responses were tabulated using a chi(2) test (p = < 0.05), and a statistically valid profile of patients most likely to benefit from occlusal reduction was developed. Occlusal reduction should prevent postoperative pain in those patients whose teeth initially exhibit pulp vitality, percussion sensitivity, preoperative pain, and/or the absence of a periradicular radiolucency.

Chi-Square Distribution↗
PubMed1997

Two mechanisms for the recapture of extracellular GM2 activator protein: evidence for a major secretory form of the protein.

The GM2 activator protein is a small monomeric protein containing a single site for Asn-linked glycosylation. Its only proven in vivo function is to act as a substrate specific cofactor for the hydrolysis of GM2 ganglioside by lysosomal beta-hexosaminidase A. However, we and others have shown it can act as a general glycolipid transporter at neutral pH in vitro. Any other possible in vivo functions would require that some of the newly synthesized activator molecules not be targeted to the lysosome. The lysosomal targeting mechanism for the activator has not been conclusively identified. While earlier reports suggested that it is likely through the mannose-6-phosphate receptor, another more recent report demonstrated that deficient human cells could recapture nonglycosylated, bacterially produced activator, suggesting its use of an alternate targeting pathway. Here, we demonstrate that the mannose-6-phosphate pathway is likely the major intracellular, biosynthetic route to the lysosome, as well as a high affinity recapture pathway for the endocytosis of activator protein from extracellular fluids. Additionally, we show that there exists a second lower affinity recapture pathway that requires its native protein structure, is carbohydrate independent, and likely does not involve its ability to bind glycosphingolipids in the plasma membrane. Finally, we document that the pool of newly synthesized precursor activator protein contains a majority of molecules with a complex-type oligosaccharide, which cannot contain a functional mannose-6-phosphate targeting signal. These molecules makeup the secreted forms of the protein in normal human fibroblasts.

Amino Acid Sequence↗
PubMed1997

Oligozoospermia induced by exogenous testosterone is associated with normal functioning residual spermatozoa.

OBJECTIVE: To determine the functional capacity of residual spermatozoa in semen samples from normal men with T enanthate-induced oligozoospermia. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Twelve healthy men were studied while participating in a multicenter T enanthate contraceptive efficacy study. Data were analyzed from only eight subjects, whose sperm concentrations were between 1.3 and 10 x 10(6)/mL at the suppression phase. INTERVENTION(S): Testosterone enanthate (200 mg) was administered IM weekly during the suppression and treatment (efficacy) phases (total 15 months). MAIN OUTCOME MEASURE(S): Sperm function tests (stimulated acrosome reaction, sperm hyperactivation [HA], and zona-free hamster oocyte penetration tests) were performed during the pretreatment, suppression (usually after 6 to 10 weeks of treatment, when sperm concentration was anticipated to decrease to < 10 x 10(6)/mL), and recovery phases. Studies were not done during the contraceptive efficacy phase because only one of the subjects was not azoospermic. RESULT(S): Mean sperm concentration was reduced but sperm motility, motility characteristics, and morphology were not affected by T enanthate treatment. The residual spermatozoa in the ejaculate could acrosome react, exhibited normal HA, and maintained the capacity to penetrate and fuse with the oocyte. CONCLUSION(S): Suppression of spermatogenesis to moderate oligozoospermia (< 10 x 10(6)/mL) with exogenous T enanthate administration was not associated with impaired sperm function of the residual spermatozoa. The study did not exclude the possibility that disorders of sperm function might occur when spermatogenesis is suppressed further to very severe oligozoospermia (< 1 x 10(6)/mL), commonly observed in hormonal male contraceptive clinical trials.

Adult↗
PubMed1997

Effect of increased scrotal temperature on sperm production in normal men.

OBJECTIVE: To determine whether application of polyester-lined athletic supports to bring the testes closer to the abdomen increases scrotal temperature and decreases sperm production. DESIGN: Prospective clinical study. SETTING: University academic medical center. PATIENT(S): Twenty-one healthy male volunteers. INTERVENTION(S): The study consisted of a pretreatment period of 6 weeks, a treatment phase of 52 weeks, and a recovery phase until return to normal sperm production. During the treatment phase, the men wore polyester-lined athletic supports (single layer, double layer, or double layer impregnated with aluminum) throughout the day. MAIN OUTCOME MEASURE(S): Semen parameters and sperm function tests. RESULT(S): In all three groups of subjects, scrotal temperature was consistently increased by 0.8 to 1 degree C while the subjects were wearing the athletic supports. Mean sperm concentration; sperm motility, morphology, and viability; sperm hyperactivation; and ability of spermatozoa to penetrate zone-free hamster oocytes were not affected by the increase in scrotal temperature. CONCLUSION(S): The increase in scrotal temperature induced by polyester-lined athletic supports was insufficient to cause significant suppression of spermatogenesis or alteration of sperm function.

Adult↗
PubMed1997

Significance of apoptosis in the temporal and stage-specific loss of germ cells in the adult rat after gonadotropin deprivation.

The major objectives of the present study were to document the temporal and stage-specific acceleration of germ cell apoptosis in adult rats after selective suppression of pituitary gonadotropins by GnRH antagonist (GnRH-A) treatment, and to examine the possibility that apoptosis is the sole mechanism of germ cell death in response to hormonal deprivation. Groups of adult male rats were given a daily injection of a vehicle for 14 days or GnRH-A (1.25 mg/kg BW) for 2, 5, 7, and 14 days. Analysis of testicular apoptotic DNA fragmentation revealed a detectable increase at Day 5 and a maximal increase at 14 days after treatment. In situ analysis of germ cell apoptosis fully corroborated the observed increase in the degree of DNA fragmentation with time and also revealed a stage-related activation of apoptosis of specific germ cells. A low incidence (0.06-0.09) of germ cell apoptosis (expressed as numbers per Sertoli cell) was detectable at stages I, IX-XI, and XII-XIV in control rats. Mean incidence of apoptotic germ cells specifically at stages VII-VIII increased significantly (0.40 +/- 0.06) by Day 5 and increased another 2.2-fold (over the 5-day treatment values) on Day 7 after GnRH-A treatment as compared to values in controls, where no apoptosis was detected. Significantly increased incidence of apoptosis at stages IX-XI (0.37 +/- 0.05) over control values (0.07 +/- 0.01) was noted by Day 7. Within the study paradigm, the highest number of dying cells occurred by Day 14, at which time a modest but significant (p < 0.05) increase in the incidence of apoptosis was also noted at stages I, II-IV, V-VI, and XII-XIV in comparison with control values. Stages VII-VIII and IX-XI still exhibited the higher number of cells undergoing apoptosis (0.97 +/- 0.22, and 1.03 +/- 0.22, respectively). Comparison between rates of apoptosis and cell degeneration measured at stages VII-VIII demonstrated an intimate association (r = 0.94; p < 0.001) between apoptosis and germ cell loss, strongly supporting the concept that germ cell death (at these stages) after removal of hormonal support in the adult rat occurs almost exclusively via apoptosis.

Animals↗
PubMed1997

Specificity of radioiodinated MIBG for neural crest tumors in childhood.

UNLABELLED: The high sensitivity of metaiodobenzylguanidine (MIBG) scintigraphy for sympathomedullary tumors such as neuroblastoma and pheochromocytoma is well documented. The specificity of MIBG scintigraphy for these tumors is also high but has been incompletely characterized for other neural crest tumors and non-neural crest tumors of childhood. METHODS: The medical records and MIBG scans of all children who had undergone MIBG scintigraphy for known or suspected neuroblastoma or pheochromocytoma were retrospectively reviewed at five major referral centers. Those patients found to have pathologies other than neuroblastoma or pheochromocytoma form the basis of this study. RESULTS: One hundred children with a total of 110 lesions met the inclusion criteria. All had negative MIBG scans except 1 of 2 children with infantile myofibromatosis, 1 of 2 with neuroendocrine carcinomas, 1 of 2 with pancreaticoblastomas and 1 of 10 with primitive neuroectodermal tumors. CONCLUSION: MIBG scintigraphy is highly specific for neuroblastoma and pheochromocytoma. Only 4% (4/100) of nonsympathomedullary tumors (non-pheochromocytoma and non-neuroblastoma) in childhood showed MIBG uptake, of which only 2% (2/100) were of non-neural crest origin.

3-Iodobenzylguanidine↗
PubMed1996

Murine cytomegalovirus DNA in peripheral blood of latently infected mice is detectable only in monocytes and polymorphonuclear leukocytes.

Cytomegalovirus (CMV), as do other herpesviruses, establishes a lifelong latent infection in its natural host. While in immunologically intact hosts most CMV infections are subclinical, clinical disease follows severe immunosuppression and immunodeficiency. In these situations CMV may produce serious life-threatening disease, and virus reactivated from the latent state is often responsible. Essential to understanding this virus and its pathogenesis is the need to define particular tissue and cell types harboring viral DNA. We searched for viral DNA and RNA in subpopulations of blood cells from mice latently infected with murine CMV by using differential centrifugation and fluorescent antibody cell sorting followed by polymerase chain reaction analysis. Following intravenous inoculation, the viral DNA was found to be present in the buffy coat at and after 21 days postinfection, and both granulocytes and peripheral blood mononuclear leukocytes (PBML) were reservoirs. Further analysis of the PBML fraction by separation into Mac-1+ and Mac-1- cells revealed that monocytes harbored the DNA while lymphocytes were not sites of persistence. We conclude that in buffy coat of latently infected mice the viral DNA is present only in cells of the myeloid lineage. The relationship of this DNA to the latent infection is discussed.

Animals↗
PubMed1996

Biomembrane templates for nanoscale conduits and networks.

Long nanotubes of fluid-lipid bilayers can be used to create templates for photochemical polymerization into solid-phase conduits and networks. Each nanotube is pulled from a micropipette-held feeder vesicle by mechanical retraction of the vesicle after molecular bonding to a rigid substrate. The caliber of the tube is controlled precisely in a range from 20 to 200 nanometers merely by setting the suction pressure in the micropipette. Branched conduits can be formed by coalescing separate nanotubes drawn serially from the feeder vesicle surface. Single nanotubes and nanotube junctions can be linked together between bonding sites on a surface to create a functionalized network. After assembly, the templates can be stabilized by photoinitiated radical cross-linking of macromonomers contained in the aqueous solution confined by the lipid bilayer boundary.

Biophysical Phenomena↗
PubMed1996

Outcome studies for burn patients in Hong Kong: patients' satisfaction.

With the recent advances in burns treatment, many more survive the burn to experience pain, scarring, physical deformity, loss of function and psychological trauma. Pressure therapy prescribed by occupational therapists for more than 20 years in Hong Kong has proved its effectiveness in treating the visible scars. However, the inconvenience and impaired appearance that is brought about by these garments during the long phase of therapy bears some weight in worsening patients' social acceptance and happiness in life, also their families especially in children. The objects of the studies were to measure the subjective rating of the effectiveness of pressure therapy through patients' satisfaction towards treatment effectiveness and its effect on daily life. Seventy cases with burn injuries over 1 year previously were selected randomly among the centres for the survey. The scale used was ordinal from 1 to 6. Eleven items concerning treatment effectiveness, life at home, work and leisure aspects were questioned. Results were analysed into two streams-satisfaction towards pressure therapy and change of life satisfaction pre- and post-injury. Non-parametric tests were used for data analysis. Through the Wilcoxon Sign Rank Test and Cluster analysis, major determinants were identified. These factors also showed significant correlation with this demographic data. The conclusions helped to evaluate and improve the existing service in both the garment properties and our scope of therapy for these patients, especially in work rehabilitation and finally (sexual) counselling which should be addressed by a team with interdepartmental support.

Activities of Daily Living↗
PubMed1996

I-131 localization in acute megakaryocytic leukemia.

A case of acute megakaryocytic leukemia in a 13-month-old infant was encountered in whom an abnormal bone scan was associated with abnormal I-131 MIBG uptake in the femoral bone marrow. The normal platelet will take up MIBG and thus, uptake of this radiopharmeceutical by the malignant megakaryocyte, a platelet precursor, may be caused by the same mechanism.

3-Iodobenzylguanidine↗
PubMed1996

Effects of lobar atelectasis on the distribution of pleural effusion and pneumothorax.

Atelectasis is known to change the retractility of the involved part of the lung and the pleural pressure adjacent to it. Consequently, pleural effusions or pneumothoraxes will change their distribution and preferentially migrate toward the site of atelectasis. This alteration will often result in an atypical distribution of pleural liquid or gas. The radiological implications of this phenomenon are discussed herein.

Humans↗
PubMed1996

Downregulation of the PTH/PTHrP receptor by vitamin D3 in the osteoblast-like ROS 17/2.8 cells.

Effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the expression of the parathyroid hormone (PTH)/PTH-related peptide (rP) receptor protein and mRNA in ROS 17/2.8 cells were studied. Treatment of ROS 17/2.8 cells with 1,25(OH)2D3 caused time- and dose-dependent suppression of PTH/PTHrP receptor number and immunoreactivity. The effects required more than 24 h incubation with 1,25(OH)2D3 and were maximal by 72 h. The cells did not recover their PTH/PTHrP receptors even after 4 days of treatment with control medium. Treatment with low concentrations of 1,25(OH)2D3 (0.1 M) dramatically decreased the PTH/PTHrP receptor mRNA levels, which were maximal after 24 h of incubation. The half-life of the PTH/PTHrP receptor transcript, 6-8 h, was similar in control and 1,25(OH)2D3-treated cells, suggesting that 1,25(OH)2D3 acts in controlling transcription of the PTH/PTHrP receptor gene but does not change the degradation rate of the PTH/PTHrP receptor transcripts. These data indicate that 1,25(OH)2D3 has a potent inhibitory effect on the expression of the PTH/PTHrP receptor protein and mRNA in ROS 17/2.8 cells.

Amino Acid Sequence↗