Bright light of learning snuffed out in Breslau.
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Comment↗
Biomedical subjects
M L Wong
Publications and source records attributed to M L Wong.
Research and treatment approaches to depression.
Depression is a major cause of disability worldwide, but we know little about the underlying fundamental biology. Research is hindered by the difficulties of modelling a disorder of higher cognitive functions in animals. Depression can be understood as the interaction of genetic susceptibility and environmental factors; however, current classifications are purely descriptive. The complexity of this field is best approached by rigorous explorations of known candidate systems in conjunction with the use of genomic tools to discover new targets for antidepressants and to predict therapeutic outcomes.
Animals↗
PEG adsorption of autoantibodies and detection of alloantibodies in warm autoimmune hemolytic anemia.
BACKGROUND: The purpose of this study was to evaluate the effectiveness of PEG in the adsorption of autoantibodies and the detection of alloantibodies in patients with warm autoimmune hemolytic anemia (WAIHA). STUDY DESIGN AND METHODS: The study was divided into three parts. First, the effectiveness of antibody removal by a conventional adsorption procedure and that by the PEG adsorption method were compared by using commercial antisera adsorbed with antigen-positive RBCs. Second, patients' sera with known weak alloanti-E were used to test against screening cells after allogeneic adsorption to show nonspecific coating of antibodies and the dilution effect on the PEG adsorption procedure. Third, conventional and PEG one-cell sample allogeneic adsorptions of WAIHA patients' sera with and without alloantibodies were performed and compared. RESULTS: In the first part, seven of the eight polyclonal antisera gave a lower titer and score when tested against antigen-positive RBCs in the indirect antiglobulin test; this indicated that PEG is more efficient in removing antibodies. In the second part, similar reaction patterns were observed in antibody screening tests on unadsorbed sera and on sera after the first, second, and third adsorptions, which indicated that there was no alloantibody loss, nonspecific antibody coating, or dilution effect when PEG was added in the allogeneic adsorption procedures. In the third part, a 40-percent increase in efficiency in reducing the number of adsorptions and an 85-percent decrease in completion time of the adsorption procedures were obtained when PEG was used for adsorbing sera from 16 patients with WAIHA. Both conventional and PEG procedures were capable of removing autoantibodies to identify the specificities of alloantibodies. CONCLUSION: The PEG adsorption method is an effective, sensitive, and efficient method of enhancing auto- antibody adsorption and alloantibody detection. It can reduce the processing time and minimize the delay of urgent transfusions to patients with WAIHA and can indirectly enhance cost-effectiveness and decrease the labor-intensive testing required by these cases.
Anemia, Hemolytic↗
Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans.
Leptin signals the status of energy reserves to the brain. Leptin stimulates biosynthesis of TRH in vitro and influences the activity of the hypothalamic-pituitary-thyroid axis in vivo in rodents. Because blood levels of both leptin and TSH display diurnal variation with a distinct nocturnal rise, we sought to determine whether a relationship exists between fluctuations in circulating leptin and TSH. We measured serum leptin and TSH levels every 7 min for 24 h in five healthy men and found that both leptin and TSH levels are highly organized and pulsatile. A similar pattern of leptin and TSH rhythms was observed, with TSH and leptin levels reaching a nadir in late morning and a peak in the early morning hours. Importantly, cosinor analysis on the absolute leptin and TSH levels revealed a statistically significant fit for a 24-h period and the two hormones showed similar probabilities of rhythm and superimposable peak values. Furthermore, this study shows a strong positive Pearson correlation between the 24-h patterns of variability of leptin and TSH in healthy subjects. Finally, the ultradian fluctuations in leptin levels showed pattern synchrony with those of TSH as determined by cross-correlation analysis, by cross-approximate enthropy and Bayessian analysis applied independently. To further explore whether these associations could reflect an underlying regulation of TSH secretion by leptin, we also studied frequently sampled leptin and TSH levels in four brothers, members of a family with leptin deficiency (one normal homozygote, two heterozygotes, and one leptin-deficient homozygote). Leptin levels of the homozygous leptin-deficient subject are detectable but bioinactive, and the rhythm of his TSH is disorganized. 24-h pattern of leptin and TSH variability in the heterozygous subjects, although significantly correlated, showed a weaker correlation compared with the strong correlation in the normal subjects. These data are consistent with the possibility that leptin may regulate TSH pulsatility and circadian rhythmicity, but interventional studies are needed to definitively prove whether leptin regulates the minute-to-minute oscillations and ultradian rhythm of TSH levels.
Adult↗
Transcranial Doppler identification of changing autoregulatory thresholds after autoregulatory impairment.
OBJECTIVE: Transcranial Doppler (TCD) flow velocity (FV) assessment may provide a useful index of autoregulatory impairment after severe head injury. It may define a therapeutic end point against which cerebral perfusion pressure (CPP) can be titrated. This study examines the relationship between cerebral blood flow (CBF) and TCD FV indices in a laboratory model before and after autoregulatory impairment. METHODS: CPP, CBF, and middle cerebral artery TCD FV were measured continuously in nine anesthetized and ventilated sheep. CPP was decreased by hemorrhagic hypotension. The process was repeated after impairment of autoregulation by cisternal infusion, which maintained CPP at 0 mm Hg for 15 minutes. Points of significant change (i.e., breakpoints) from baseline values for each of the measured flow parameters were identified by using a ratio of variance technique. RESULTS: Before any significant change in CBF or systolic TCD, diastolic TCD FV decreased (mean breakpoint, 69 mm Hg; range, 56-78 mm Hg) as CPP was reduced. This divergence of diastolic and systolic TCD FV, which occurred before autoregulatory failure, was associated with an increasing TCD pulsatility index (mean breakpoint, 63 mm Hg; range, 53-70 mm Hg). At diastolic TCD FV congruent with 10 cm/s, systolic TCD FV (mean breakpoint, 48 mm Hg; range, 46-53 mm Hg) and CBF (mean breakpoint, 49 mm Hg; range, 47-51 mm Hg) decreased rapidly, indicating autoregulatory failure. After autoregulatory impairment, the breakpoints for all four indices shifted to higher CPP values (mean, 16 mm Hg). CONCLUSION: TCD FV assessment identified two CPP thresholds of autoregulatory loss. Before autoregulatory failure, an earlier phase of autoregulatory disturbance may be detected by divergent systolic and diastolic TCD FVs. It is important to note that this phase may be detected before CBF decreases. These TCD FV breakpoints depend on the state of autoregulatory impairment and may provide potential targets for CPP-directed therapy.
Animals↗
A case series of six children with primary pulmonary hypertension.
INTRODUCTION: Primary pulmonary hypertension is an uncommon but serious disease in children. Management is difficult despite recent advances in pharmacotherapy. CLINICAL PICTURE: We reviewed patients with this condition with respect to their presenting symptoms, investigations, treatment and outcome. TREATMENT: These children were treated with individualised combinations of oxygen, diuretics and calcium antagonists. OUTCOME: In our follow-up of 5 children, 4 had died. CONCLUSION: This condition is irreversible and progressive with a high mortality rate. A better understanding of, and research into, the pathogenesis would hopefully lead to the formulation of improved therapeutic strategies for this condition.
Adolescent↗
Persistent alterations in dendrites, spines, and dynorphinergic synapses in the nucleus accumbens shell of rats with neuroleptic-induced dyskinesias.
Chronic treatment of humans or experimental animals with classical neuroleptic drugs can lead to abnormal, tardive movements that persist long after the drugs are withdrawn. A role in these neuroleptic-induced dyskinesias may be played by a structural change in the shell of the nucleus accumbens where the opioid peptide dynorphin is upregulated in treated rats that show vacuous chewing movements (VCMs). The shell of the nucleus accumbens normally contains a dense plexus of dynorphinergic fibers especially in its caudomedial part. After 27 weeks of haloperidol administration and 18 weeks of withdrawal, the immunoreactive labeling of this plexus is intensified when compared with that after vehicle treatment. In addition, medium spiny neurons here show a significant increase in spine density, dendritic branching, and numbers of terminal segments. In the VCM-positive animals, the dendritic surface area is reduced, and dynorphin-positive terminals contact more spines and form more asymmetrical specializations than do those in animals without the syndrome (VCM-negative and vehicle-treated groups). Persistent, neuroleptic-induced oral dyskinesias could therefore be caused by incontrovertible alterations, involving terminal remodeling or sprouting, to the synaptic connectivity of the accumbal shell.
Animals↗
Acute systemic inflammation up-regulates secretory sphingomyelinase in vivo: a possible link between inflammatory cytokines and atherogenesis.
Inflammation plays a critical role in atherogenesis, yet the mediators linking inflammation to specific atherogenic processes remain to be elucidated. One such mediator may be secretory sphingomyelinase (S-SMase), a product of the acid sphingomyelinase gene. The secretion of S-SMase by cultured endothelial cells is induced by inflammatory cytokines, and in vivo data have implicated S-SMase in subendothelial lipoprotein aggregation, macrophage foam cell formation, and possibly other atherogenic processes. Thus, the goal of this study was to seek evidence for S-SMase regulation in vivo during a physiologically relevant inflammatory response. First, wild-type mice were injected with saline or lipopolysaccharide (LPS) as a model of acute systemic inflammation. Serum S-SMase activity 3 h postinjection was increased 2- to 2.5-fold by LPS (P < 0.01). To determine the role of IL-1 in the LPS response, we used IL-1 converting enzyme knockout mice, which exhibit deficient IL-1 bioactivity. The level of serum S-SMase activity in LPS-injected IL-1 converting enzyme knockout mice was approximately 35% less than that in identically treated wild-type mice (P < 0.01). In LPS-injected IL-1-receptor antagonist knockout mice, which have an enhanced response to IL-1, serum S-SMase activity was increased 1. 8-fold compared with LPS-injected wild-type mice (P < 0.01). Finally, when wild-type mice were injected directly with IL-1beta, tumor necrosis factor alpha, or both, serum S-SMase activity increased 1. 6-, 2.3-, and 2.9-fold, respectively (P < 0.01). These data show regulation of S-SMase activity in vivo and they raise the possibility that local stimulation of S-SMase may contribute to the effects of inflammatory cytokines in atherosclerosis.
Acute Disease↗
Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone.
Both stress-system activation and melancholic depression are characterized by fear, constricted affect, stereotyped thinking, and similar changes in autonomic and neuroendocrine function. Because norepinephrine (NE) and corticotropin-releasing hormone (CRH) can produce these physiological and behavioral changes, we measured the cerebrospinal fluid (CSF) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were obtained every 30 min. Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock. Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls. Despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and CSF CRH. However, plasma ACTH and CSF CRH levels in depressed patients were inappropriately high, considering the degree of their hypercortisolism. In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls, patients with depression showed no statistical relationship between these parameters. These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder. These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism. We postulate that alpha-noradrenergic blockade, CRH antagonists, and treatment with antiglucocorticoids may act at different loci, alone or in combination, in the treatment of major depression with melancholic features.
Adrenocorticotropic Hormone↗
Immunological assays for understanding neuroimmune interactions.
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Animals↗
Hepatitis B e antigen-negative chronic hepatitis B in Hong Kong.
Hepatitis B e antigen-negative chronic hepatitis B (e-CHB) has been reported in Asia but its prevalence and clinical significance have not been determined. The aims of this study were to determine the prevalence of e-CHB in Hong Kong and the frequency of precore and core promoter mutations in these patients. A cross-sectional study was performed in 350 consecutive Chinese patients (230 men and 120 women; mean age +/-SD, 42 +/- 13 years) with chronic hepatitis B virus infection. A total of 243 (69%) patients were hepatitis B e antigen (HBeAg)-negative of whom 15% had clinical cirrhosis. In the remaining 85% of patients, 63% had normal and 22% had elevated transaminases. Serum hepatitis B virus (HBV) DNA was detectable using branched DNA assay in 46% of HBeAg-negative patients with clinical cirrhosis/elevated transaminases. Forty-five percent of the patients with e-CHB had the precore stop codon mutation, and an additional 41% had core promoter changes. There was no correlation between the presence of precore/core promoter mutations and liver disease or HBV-DNA levels. Overall, 17% of HBeAg-negative patients were viremic and had evidence of chronic liver disease (e-CHB) with mean HBV-DNA levels comparable with that in HBeAg-positive patients. In summary, we found that e-CHB may be present in up to 17% of HBeAg-negative patients seen in a tertiary referral center in Hong Kong. e-CHB may be a heterogeneous condition and is not invariably associated with the precore HBV mutant. Population studies are needed to determine the true prevalence of e-CHB in Asia and to assess its natural course and response to treatment.
Adolescent↗
The effect of polishing systems on microleakage of tooth-coloured restoratives. Part 2: composite and polyacid-modified composite resins.
The purpose of this in vitro study was to investigate the effect of polishing systems on the microleakage of composite and polyacid-modified composite resins. Class V cavities were prepared at the cemento-enamel junction of 80 freshly extracted posterior teeth. The prepared teeth were randomly divided into two groups and restored with conventional or polyacid-modified composite resins. The restored teeth were stored in distilled water at 37 degrees C for 1 week after removal of excess restorative with diamond finishing burs. The restored teeth were then divided into four groups of ten and finished/polished using the following systems: Two Striper micron finishing system (MFS), Sof-Lex XT (Sof-Lex), Enhance composite finishing and polishing system (Enhance), and Shofu composite finishing kit (Shofu). The finished restorations were subjected to dye penetration testing. Results showed that the microleakage resistance at both enamel and dentin margins of composite and polyacid-modified composite resins are not significantly affected by the different polishing systems.
Adhesives↗
Factors associated with condom use for oral sex among female brothel-based sex workers in Singapore.
BACKGROUND AND OBJECTIVE: The prevalence of oral sex increased from 27.1% in 1992 to 81.1% in 1997, with a concomitant increase in pharyngeal gonorrhea, among female sex workers in Singapore. The extent of condom use for oral sex among them is unknown. GOAL: To determine the prevalence of and factors associated with consistent condom use during oral sex. STUDY DESIGN: A cross-sectional study of 225 women randomly selected from the surveillance scheme register of female brothel-based sex workers with a history of oral sex documented in their medical records. RESULTS: Slightly more than half (56.9%) consistently used condoms for oral sex compared to 97% for vaginal sex. Condom use was significantly higher among middle than high class sex workers (adjusted rate ratio: 1.52, 95% CI: 1.01-2.29) and those with negotiation skills (adjusted rate ratio: 1.95, 95% CI: 1.32-2.07). CONCLUSION: Sex workers should be taught skills to negotiate condom use for oral sex.
Adult↗
A prospective study on condom slippage and breakage among female brothel-based sex workers in Singapore.
BACKGROUND: Concerns about the effectiveness of condoms in preventing sexually transmitted diseases have been raised. Data are lacking on condom failure and its associated factors among sex workers in Southeast Asia. GOAL: To assess factors associated with condom breakage and slippage. STUDY DESIGN: A prospective study on condom breakage and slippage over a 1-day period was conducted among 219 female brothel-based sex workers in Singapore in 1997. RESULTS: Condom breakage and slippage rates among 1,885 episodes of condom use were 1.2% (95% CI, 0.7-1.8) and 2.1% (95% CI, 1.2-3.0), respectively. After adjusting for intracluster effects and confounders, condom breakage and slippage were significantly associated with duration of sex work and spontaneity of clients to use condoms. CONCLUSION: Condom use among sex workers should be promoted in view of the low failure rates. Strategies to reduce condom breakage and slippage should be directed at sex workers with increased risk of condom failure.
Adult↗
Comparison of three different sensitive assays for hepatitis B virus DNA in monitoring of responses to antiviral therapy.
The aim of our study was to compare the performances of two new hepatitis B virus (HBV) DNA assays, a cross-linking assay (NAXCOR) and a hybrid-capture amplification assay (Digene), versus the widely used branched-DNA (bDNA) assay (Chiron) in the monitoring of HBV DNA levels during antiviral treatment. Serial serum samples from 12 chronically HBV infected patients undergoing a phase II trial of an antiviral drug, 2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC), were studied. A total of 96 serum samples were tested for HBV DNA using the cross-linking, hybrid-capture amplification, and bDNA assays. In the comparison of the cross-linking and bDNA assays, concordant results were found in 77 (80.3%) samples, no significant difference was found between the median log(10) HBV DNA levels (6.66 versus 7. 17 meq/ml), and the results of the two assays were closely correlated (r = 0.95). In the comparison of the hybrid-capture amplification and bDNA assays, concordant results were found in 79 (82.3%) samples, no significant difference was found between the median log(10) HBV DNA levels (6.98 versus 6.99 meq/ml), and the results of the two assays were closely correlated (r = 0.99). Six (6. 3%) samples by the cross-linking assay and 10 (10.4%) samples by the bDNA assay required retesting because of unacceptably high within-run coefficients of variance. No sample required retesting in the hybrid-capture amplification assay according to the internal validation. In conclusion, the cross-linking and hybrid-capture amplification assays were as sensitive as the bDNA assay for HBV DNA detection and can be recommended for monitoring of HBV DNA levels during antiviral treatment.
Antiviral Agents↗
Mitotic regulators govern progress through steps in the centrosome duplication cycle.
Centrosome duplication is marked by discrete changes in centriole structure that occur in lockstep with cell cycle transitions. We show that mitotic regulators govern steps in centriole replication in Drosophila embryos. Cdc25(string), the expression of which initiates mitosis, is required for completion of daughter centriole assembly. Cdc20(fizzy), which is required for the metaphase-anaphase transition, is required for timely disengagement of mother and daughter centrioles. Stabilization of mitotic cyclins, which prevents exit from mitosis, blocks assembly of new daughter centrioles. Common regulation of the nuclear and centrosome cycles by mitotic regulators may ensure precise duplication of the centrosome.
Amino Acid Sequence↗
Influence of surgery on aortic valve prolapse and aortic regurgitation in doubly committed subarterial ventricular septal defect.
Doubly committed subarterial ventricular septal defects should be closed surgically once aortic valve deformity is present before the onset of aortic regurgitation.
Adolescent↗
alpha5 subunit in Trypanosoma brucei proteasome can self-assemble to form a cylinder of four stacked heptamer rings.
The proteasomes have a central role in catalysing protein degradation among both prokaryotes and eukaryotes. The 20 S proteasome constitutes their catalytic core. In studying the structure of Trypanosoma brucei 20 S proteasomes, we isolated by two-dimensional (2D) gel electrophoresis a 27 kDa subunit protein with an estimated pI of 4.7 and subjected it to mass spectrometric analysis. A tryptic peptide sequence from the protein was found identical with that of the rat alpha5 subunit. With the use of antiserum against T. brucei 20 S proteasomes to screen a T. b. rhodesiense lambda expression cDNA library, we obtained a cDNA clone encoding a full-length protein of 246 amino acid residues with a calculated molecular mass of 27174 Da and a pI of 4.71. It bears 50. 0% and 46.3% sequence identity with rat and yeast proteasome subunit alpha5 respectively, and matches all the peptide sequences derived from MS of the 2D gel-purified protein. The protein is thus designated the alpha5 subunit of T. brucei 20 S proteasome (TbPSA5). The recombinant protein, expressed in plasmid-transformed Escherichia coli, was found in a 27 kDa monomer form as well as polymerized forms with estimated molecular masses ranging from 190 to 800 kDa. Under the electron microscope, the most highly polymerized forms bear the appearance of cylinders of four-stacked heptamer rings with an estimated outer diameter of 14.5 nm and a length of 18 nm, which were immunoprecipitable by anti-(T. brucei 20 S proteasome) antiserum. In view of the documented self-assembly of the archaeon proteasome alpha subunit into double heptamer rings and the spontaneous assembly of the two alpha subunits from the 20 S proteasome of Rhodococcus erythropolis, the self-assembly of the T. brucei alpha subunit might reflect a common feature of proteasome biogenesis shared by prokaryotes and primitive eukaryotes such as the trypanosomes but apparently lost among the higher forms of eukaryote such as the yeast and the mammals.
Amino Acid Sequence↗