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Biomedical subjects

A Leung

Publications and source records attributed to A Leung.

At least 73 records · Page 4Linked to original sources
PubMed1991

Comparison of measurements of human sperm motility characteristics by the automated CellSoft system and time-exposure photomicrography.

Human sperm motility characteristics in 28 semen samples with sperm concentrations less than 40 x 10(6) ml-1, as determined by the World Health Organization manual analysis (WHO, 1987), were measured by the automated CellSoft semen analyser (Cryo Resources Ltd, New York, NY, USA) using different system parameter settings (Mortimer & Mortimer, 1988a). The results were compared with those obtained by time-exposure photomicrographic (TEP) analysis. It was found that the settings of the minimum video frame rate and the threshold velocity used to distinguish motile from immotile sperm by the automated CellSoft system had a significant influence on measurements of percentage motility but not on linear velocity. At the five different parameter settings used in the present study, the automated CellSoft system gave significantly lower mean values for percentage motility in comparison with the WHO manual and TEP analyses. Measurements for linear velocity between the automated CellSoft system and TEP analyses were found not to be significantly different in these defined semen samples.

Humans↗
PubMed1991

Clinical and biochemical parameters of androgen action in normal healthy Caucasian versus Chinese subjects.

Stimulation of androgen-sensitive hair follicles is mediated by dihydrotestosterone (DHT), which is formed in these tissues by 5 alpha-reduction of testosterone. A possible mechanism for increased body hair in some human populations might, therefore, be an increase in 5 alpha-reductase activity, resulting in elevated tissue levels of DHT. If present, this finding could have other important clinical implications, since the 5 alpha-reductase enzyme is pivotal in the pathophysiology of prostatic disease. To explore differences in clinical and biochemical parameters of androgen action, we conducted a study of 184 caucasian and Chinese subjects in whom we evaluated chest hair density and serum levels of androgen precursors and 5 alpha-reduced androgen metabolites. Differences in chest hair density were most notable in the men, in whom comparative mean chest hair scores (using a scale of 0-4) were 3.0 vs. 0.8 (P less than 0.0001), caucasian vs. Chinese. Levels of 5 alpha-reduced androgen products were also strikingly higher in the caucasian vs. Chinese subjects. Serum 3 alpha-androstanediol glucuronide levels (nanomoles per L) were 34.7 +/- 2.4 vs. 19.7 +/- 0.9 (P less than 0.001) for the men and 21.5 +/- 3.2 vs. 9.4 +/- 0.6 (P less than 0.001) for the women, and serum levels of androsterone glucuronide (nanomoles per L) were 179 +/- 26 vs. 107 +/- 7 (P less than 0.01) for the caucasian vs. Chinese men and 173 +/- 23 vs. 81 +/- 9 (P less than 0.001) for the women. Serum levels of total and bioavailable testosterone did not differ between the racial groups, but serum levels of the precursor androgens, dehydroepiandrosterone sulfate and androstenedione, were significantly higher in the caucasian vs. Chinese men, but not in the women. We conclude that increased serum levels of 5 alpha-reduced androgen metabolites in caucasians vs. Chinese subjects provide circumstantial evidence for a racial difference in 5 alpha-reductase activity and suggest a mechanism for the increased body hair observed in the caucasian men. Increased levels of precursor androgens may also play a role.

Adolescent↗
PubMed1991

Computer-assisted assessment of human sperm morphology: comparison with visual assessment.

OBJECTIVE: Sperm morphology classification was analyzed by the computer-assisted semen analysis equipped with the Morphologizer II (Cryo Resources Ltd., New York, NY) was compared with the traditional manual method. DESIGN, SETTING, PATIENTS: Fifty stained semen smears from men attending the infertility clinic of a tertiary referral institution were studied. MAIN OUTCOME MEASURES: Sperm head morphology was classified by the two methods into the following forms: normal, small oval, big oval, taper, and amorphous. RESULTS: Overall, the classifications of mean percent normal, small, and amorphous head forms were similar in the two methods. However, the differences between paired values obtained by the two methods were highly variable (range from -20% to +20%). The large differences between the methods were related to the large coefficients of variations present when classifying abnormal sperm morphology even by the same experienced technician. Only the percent normal spermatozoa could be classified by both methods with acceptable precision. In contrast, the variations in the morphometric analyses between the different semen smears were very small. CONCLUSIONS: There was no advantage of the morphologizer over the manual method in sperm morphology classification. The clinical value of morphometric parameters of spermatozoa has to be defined.

Humans↗
PubMed1990

Oxidation-induced changes in microrheologic properties of the red blood cell membrane.

It has been hypothesized that some of the irreversible microrheologic abnormalities of sickle red blood cell (RBC) membranes could result from autoxidative perturbation. To model this possibility, we used micromechanical manipulation to examine the static extensional rigidity and inelastic or plastic behavior of normal RBCs exposed to phenazine methosulfate (PMS), an agent that generates superoxide from within the cell. In response to this stress, RBC membranes became stiff as evidenced by increasing extensional rigidity. At 50 mumol/L PMS they were as stiff as the membranes of most dense, dehydrated sickle RBCs; and at 25 mumols/L PMS the membranes were similar to somewhat less dense sickle RBCs. When examined for inelastic behavior, RBCs exposed to PMS even at 10 mumols/L showed hysteresis in loading and unloading phases of the curve relating aspiration length to suction pressure, and they developed membrane bumps that persisted after RBC release from the pipette. Examination of single cells in both isotonic and hypotonic buffers showed that the effect of PMS on RBC microheology is not mediated by cellular dehydration. Independent confirmation of the membrane stiffening effect of PMS was obtained by ektacytometric analysis of resealed RBC ghosts, with sickle-like increases in membrane rigidity observed between 50 and 100 mumol/L PMS. The rigidity of these ghosts was partially ameliorated by exposure to a thiol reductant. In terms of biochemical abnormalities, treated RBCs became significantly different from control RBCs at 25 mumol/L PMS, at which point they just began to enter the sickle range for amounts of membrane thiol oxidation and membrane-associated heme. The sickle average was achieved at 50 mumol/L PMS (for thiol oxidation) to 100 mumol/L PMS (for membrane heme). Thus, micromolar concentrations of PMS induce abnormalities of membrane microrheology that closely mimic those of unmanipulated sickle RBCs while reproducing similar degrees of oxidative biochemical change. We conclude that membrane protein oxidation could explain existence of an irreversible component to the abnormal rheology of the sickle membrane.

Dithiothreitol↗
PubMed1990

The effect of cefuroxime axetil on the faecal flora of healthy volunteers.

The effect on the faecal flora of cefuroxime axetil, an oral ester of cefuroxime, was examined in ten healthy volunteers following a dose of 250 mg twice a day for 41/2 days. The mean blood concentration 2 h after the ninth dose was 3.6 mg/l and the urinary excretion was approximately 40% in 6 h and 50% in 24 h. Two volunteers developed mild diarrhoea and one candida vaginitis. Although there was variation between volunteers in the changes found in the faecal flora, the major effects were a reduction in the total anaerobic bacterial count, particularly where high levels of cefuroxime were present in the faeces and a significant decrease or elimination of strains of Enterobacteriaceae plus an increase in the streptococcal count. Six volunteers showed an increase in the candida count. Clostridium difficile was not isolated from any volunteer and toxin was not present in the two volunteers who developed diarrhoea. Four volunteers showed high levels of cefuroxime in the faeces on the fourth or fifth days of treatment.

Bacteria, Aerobic↗
PubMed1990

Macrosomic babies.

A review of 3,241 delivery records was made to study the obstetrics and the neonatal outcomes of 129 macrosomic (greater than or equal to 4,000g) babies. They were found to have a nearly 6-fold increase in the neonatal morbidity rate compared with normosomic babies. The emergency Caesarean section rate for nulliparas and parous women with macrosomic babies was 41.3% and 8.4% respectively. Among macrosomic babies, shoulder dystocia was not associated with maternal stature, induction of labour, use of oxytocin or abnormal labour patterns, but was associated with instrumental delivery. Macrosomic babies with shoulder dystocia after instrumental delivery had a higher neonatal morbidity rate than those delivered spontaneously.

Birth Injuries↗
PubMed1990

Serum bioactive follicle-stimulating hormone levels in girls with precocious sexual development.

We studied the serum immunoreactive (immuno) and bioactive (bio) FSH concentrations in 16 prepubertal children (1.3-9 yr old), 6 girls with premature thelarche (0.8-2 yr old), and 9 girls with central precocious puberty (2.5-9.3 yr old). The serum bio-FSH was measured by the granulosa cell aromatase bioassay. The basal serum bio-FSH levels were not significantly different in patients with central precocious puberty (6.4 +/- 1.5 IU/L), premature thelarche (7.5 +/- 0.5 IU/L), and prepubertal controls (4.4 +/- 0.7 IU/L). However, the peak responses of both serum immuno- and bio-FSH levels to iv GnRH were higher in patients with premature thelarche (immuno-FSH, 29.3 +/- 2.3 IU/L; bio-FSH, 100.7 +/- 12.2 IU/L) than in those with central precocious puberty [immuno-FSH, 17.5 +/- 3.1 IU/L (p less than 0.05); bio-FSH, 42.4 +/- 9.8 IU/L (p less than 0.01)]. This suggests that in children with premature thelarche, there is a predominant immuno- as well as bio-FSH response to GnRH. After 12 months of GnRH agonist therapy, both serum immuno- and bio-FSH levels were suppressed in patients with central precocious puberty. The differences in clinical presentation between central precocious puberty and premature thelarche cannot be explained by the differences in FSH bioactivity.

Biological Availability↗
PubMed1990

Evaluation of the semi-automated Autosperm semen analysis system. II. Comparison with conventional method, time-exposure photomicrography, and automated CellSoft system.

Semen analysis results obtained by a recently developed semi-automated Autosperm system (Amsaten N.V.S.A. Corp., De Pinte, Belgium) were compared with those obtained by the conventional, time-exposure photomicrographic, and automated CellSoft system (Cryo Resources Inc., New York, NY) analyses. The Autosperm system either over- or underestimated the sperm concentration in comparison with the conventional analysis and more often underestimated the sperm concentration in comparison with the automated CellSoft system analysis. Comparison of the results for percent sperm motility by the conventional and Autosperm analyses showed that the latter tended to underestimate the percentage of fast-swimming spermatozoa and overestimate the percentage of slow-swimming spermatozoa. There were considerable variations in the measurement of sperm movement characteristics between the Autosperm and time-exposure photomicrographic and automated CellSoft system analyses, respectively. These findings demonstrate that the performance of the Autosperm system does not agree well with those of the currently available methods employed in the present study. Part of the disagreement in measurements of sperm parameters could be because of the subjective elements inherent in the semi-automated Autosperm analysis.

Humans↗
PubMed1989

Introduction of the alpha subunit mutation associated with the B1 variant of Tay-Sachs disease into the beta subunit produces a beta-hexosaminidase B without catalytic activity.

Lysosomal beta-hexosaminidase (beta-N-acetylhexosaminidase, EC 3.2.1.52) occurs in two major isozyme forms, hexosaminidase A (alpha beta) and hexosaminidase B (beta beta). Although dimer formation is required for enzymatic activity, both subunits contain active sites which share many common substrates. However, the alpha subunit alone confers on hexosaminidase A the specificity for negatively charged substrates, e.g. GM2 ganglioside. Recently, a point mutation, producing a single amino acid substitution in the alpha subunit (Arg178-His), has been found to be associated with the B1 variant phenotype of Tay-Sachs disease (Ohno, K., and Suzuki, K. (1988) J. Neurochem. 50, 316-318). This variant is characterized by normal levels of hexosaminidase A as measured by a common artificial substrate, but an absence of activity toward alpha subunit-specific substrates. However, because of the presence of an active beta subunit in the mutant hexosaminidase A, it has not been possible to determine whether the affected alpha subunit has undergone a change in substrate specificity or become totally inactive. In order to define the full effect of the B1 mutation we have taken advantage of the common evolutionary origin of the genes coding for the alpha and beta subunits. Since the B1 mutation occurs in a region of extended identity between the two subunits, we have duplicated the Arg178-His mutation in a cDNA coding for the human beta subunit (Arg211-His). By expression of the mutant construct in monkey COS cells we have been able to examine the effect of this mutation on beta subunits which are capable of forming stable, active homodimers, an experiment that could not readily be accomplished with heterodimeric hexosaminidase A. Our data show that beta homodimers containing the Arg211-His substitution are formed and are transported into the lysosome in a manner identical to that of normal pro-hexosaminidase B. However, the mutant homodimers are processed at a slower rate and are less stable in the lysozyme. Their most striking feature was a total lack of normal hexosaminidase B activity. We conclude that while the effect of the Arg178-His substitution is not strictly limited to the active site, the severe B1 phenotype results from a totally inactive alpha-subunit in hexosaminidase A.

Amino Acid Sequence↗
PubMed1989

Membrane assembly and remodeling during reticulocyte maturation.

Membrane skeletal and cytoskeletal remodeling occurs throughout erythroid maturation. Microtubules and microfilaments have been identified morphologically in the nucleated erythroblast but the functional capability of these cytoskeletal structures during reticulocyte maturation has not been studied. Reticulocytes are formed from orthochromatic normoblasts by the process of nuclear extrusion. Two recognizable stages of reticulocyte maturation follow. The least mature reticulocytes are motile and multilobular, while the more mature reticulocytes are cup-shaped and nonmotile. To study the respective roles of microtubules and microfilaments in nuclear extrusion and cell motility, experiments were performed with agents that perturb these structures. Following the injection into rats of colchicine, a microtubule-disrupting substance, the number of normoblasts arrested at the stage of nuclear extrusion increased linearly over four hours. Similar results were obtained when bone marrow cells were incubated in culture in the presence of colchicine. In contrast, cell motility was dramatically decreased by cytochalasin B, a microfilament-disrupting agent, but not by colchicine. These results imply that microtubules are essential for the nuclear extrusion process, while microfilaments are essential for cell motility. Simultaneous changes in membrane skeletal assembly were assessed by measuring membrane deformability and stability, two properties regulated by the skeletal proteins. In ektacytometric assays, membrane deformability and mechanical stability of immature reticulocytes were markedly decreased to approximately 10% of normal, while that of more mature reticulocytes were nearly normal. Since the skeletal protein organization regulates these membrane properties, our findings imply that substantial membrane skeletal remodeling occurs during reticulocyte maturation. Thus we have identified major remodeling of both skeletal and cytoskeletal components during reticulocyte maturation.

Animals↗
PubMed1989

Magnetic resonance imaging in head and neck cancer.

The scans of 120 patients with proven head and neck cancer who underwent magnetic resonance imaging (MRI) at Mt. Vernon hospital were reviewed and, where possible, compared with their clinical, computed tomography (CT) and histological findings. MRI was generally superior to both clinical examination and CT in the detection of cervical lymphadenopathy and in the assessment of primary tumour extent, particularly in the tongue base, nasopharynx and parotid gland. Small intracranial tumour extensions were more readily detected by MRI than CT. MRI was no better than CT in distinguishing between malignant and inflamed tissues and was generally inferior to CT in spatial resolution, patient acceptance and examination cost.

Head and Neck Neoplasms↗
PubMed1989

Computer-assisted image analysis of sperm concentration in human semen before and after swim-up separation: comparison with assessment by haemocytometer.

Evaluation of male fertility is based predominantly on results from semen analysis and determination of the sperm concentration is one of the main parameters of the analysis. The availability of a fully automated videomicrographic digital image analyser would offer both an objective and rapid method for determination of the sperm concentration. In the present study the sperm concentration in 327 semen samples was determined by haemocytometer according to the World Health Organization guidelines, and also by a computer-assisted digital image analyser system. Results were classified according to the routine procedure (haemocytometer) before statistical analyses. The computerized measurements caused a shift to the right in the frequency distribution of sperm concentration. Sperm concentrations were more often overestimated significantly (P less than 0.001) by the computerized measurements in semen samples with concentrations up to 80.0 x 10(6)/ml. This overestimation seemed to be caused by the presence of particles in seminal plasma that were recognized incorrectly as sperm by the computer program. The computerized digital image analyser gave an average sperm concentration of 2.2 +/- 0.6 x 10(6)/ml (mean +/- SEM) in 17 azoospermic semen samples while the routine procedure did not detect the presence of sperm cells. After removing the seminal plasma by washing and centrifugation with culture medium, and using the swim-up procedure to harvest motile sperm, the computerized measurements showed comparable results with the routine procedure for those sperm preparations (n = 44) with sperm concentrations greater than 5.0 x 10(6)/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1989

Glucocorticoids stimulate plasminogen activator production by rat granulosa cells.

We studied the direct effects of glucocorticoids on plasminogen activator (PA) production by rat granulosa cells. PA production was assayed by culturing rat granulosa cells on [125I]fibrin plates and determining the extent of fibrinolysis after addition of the specific substrate plasminogen. In granulosa cells from preantral follicles of immature rats, treatment with FSH caused dose-dependent increases in PA production whereas glucocorticoids by itself was without effect. Increasing concentrations (10(-10) to 10(-6) M) of both natural and synthetic glucocorticoids potentiated the stimulating effect of FSH on PA production by 120 to 170%. The stimulatory potencies of the natural corticosteroids correlated with the glucocorticoid potencies (cortisol/corticosterone greater than aldosterone/11-deoxycorticosterone). In granulosa cells from Graafian follicles of mature rats, glucocorticoids on its own had direct stimulating effect on PA production. The stimulatory action of glucocorticoids on FSH-dependent PA production was completely blocked by simultaneous treatment with antiglucocorticoid RU 486. Antiserum directed against tissue-type PA (tPA) neutralized the increased fibrinolytic actions of glucocorticoids. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fibrin autography techniques, we showed that the increase in fibrinolytic activity in response to glucocorticoids resulted from increased production of tPA rather than urokinase-like PA. The effect of glucocorticoids on the production of PA inhibitors (PAI) was examined by 1) neutralization of urokinase activity by increasing amounts of culture media from granulosa cells treated with glucocorticoids, 2) reverse fibrin autography, and 3) Western blot analysis with a specific PAI antiserum. All these methods failed to detect a stimulatory action of glucocorticoids, with or without FSH, on PAI production by rat granulosa cells in the culture media. Our data showed that glucocorticoids have a direct stimulating effect on tPA production, but unlike its action on other in vitro systems, they have no significant effect on PAI production by rat granulosa cells in vitro.

Animals↗
PubMed1988

Localization of the pro-sequence within the total deduced primary structure of human beta-hexosaminidase B.

The beta subunit of beta-hexosaminidase (beta-N-acetylhexosaminidase, EC 3.2.1.52) is synthesized in the rough endoplasmic reticulum as a prepropolypeptide. After the loss of the signal peptide and formation of an enzymatically active dimer, the pro-enzyme is either secreted from the cell or transported into the lysosome for processing to its mature form. In order to characterize the early posttranslational events we have purified nearly 1 mg of pro-hexosaminidase B from the NH4Cl containing medium of fibroblasts derived from a patient with the infantile form of Tay-Sachs disease. The partial N-terminal sequence was mapped to a position 42 residues C-terminal to the first in-frame ATG (Met residue) and 79 residues N-terminal to the known mature N-terminus. This position corresponds to that predicted for the cleavage of a 17 amino acid signal peptide generated through the use of the third rather than the first in-frame ATG as the initiation site for protein synthesis.

Amino Acid Sequence↗
PubMed1988

Proteolytic processing of pro-alpha and pro-beta precursors from human beta-hexosaminidase. Generation of the mature alpha and beta a beta b subunits.

There are two major isozymes of human lysosomal beta-hexosaminidase (beta-N-acetylhexosaminidase, EC 3.2.1.52), hexosaminidase A, alpha(beta a beta b), and hexosaminidase B, 2(beta a beta b). The alpha subunit contains a single polypeptide chain, while the beta subunit is composed of two nonidentical chains (beta a and beta b) derived from a common pro-beta precursor. The mature subunits, like those of most lysosomal enzymes, are produced through the proteolytic processing of propolypeptides once they enter the lysosome. In order to define the structure of the alpha and beta subunits generated in the lysosome, the alpha, beta a, and beta b polypeptides of hexosaminidase A and B were separated by a combination of molecular sieve and ion exchange high performance liquid chromatography, and amino-terminal sequences were determined. These were localized to the deduced amino acid sequences of previously isolated cDNAs coding for the prepro-alpha and beta polypeptides. From this analysis, the sites of hydrolysis generating the mature alpha, beta a, and beta b chains from hexosaminidase A and B could be determined. First, the signal peptide, required for processing of the pre-propolypeptides through the rough endoplasmic reticulum was predicted from the first in-frame Met residue on the cDNA. Second, amino acid sequencing defined the amino termini of the mature polypeptide chains and identified the pro-sequences removed from both the pro-alpha and pro-beta polypeptides. Third, an internal cleavage resulted in the removal of a tetrapeptide, Arg-Gln-Asn-Lys, and tripeptide, Arg-Gln-Asn, from the pro-beta chain of hexosaminidase A and B, respectively , to generate the beta b and beta a chains. This result localized the beta b and beta a chains to the amino-terminal and carboxyl-terminal halves of the pro-beta sequence, respectively. Finally, we previously reported minimal or no carboxyl-terminal processing of the pro-beta chain in the lysosome. On the other hand, we suggest that there is trimming at the carboxyl terminus of the pro-alpha chain based on comparison of molecular weights of deglycosylated alpha with the isolated beta b and beta a chains comprising the mature beta subunit with those predicted from the cDNA. Thus, in the lysosome the pro forms of hexosaminidase A and B undergo extensive proteolytic processing which, while specific in nature, has the appearance of removing easily accessible, nonessential domains, rather than contributing to biosynthetic maturation of function.

Amino Acid Sequence↗
PubMed1988

Pyrazinamide and rifampicin regimens for patients on maintenance dialysis.

We measured pyrazinamide and rifampicin plasma concentrations in five patients with pulmonary tuberculosis and end stage renal failure treated by haemodialysis or continuous ambulatory peritoneal dialysis. Using conventional daily doses of oral pyrazinamide and rifampicin, we found that the drugs were removed efficiently by both dialysis methods, so that plasma levels were sub-optimal for maximal bactericidal action. These findings suggest that in patients with tuberculosis on maintenance dialysis, treatment should be either with higher doses of these two drugs, or with additional replacement doses given after each dialysis. Further detailed pharmacokinetic studies on larger numbers of patients are indicated.

Adolescent↗
PubMed1987

Myoglobinuria from child abuse.

A child with myoglobinuria following rhabdomyolysis from child abuse is described. The importance of early recognition and treatment of this condition is emphasized.

Adolescent↗