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Biomedical subjects

D T Chiu

Publications and source records attributed to D T Chiu.

At least 55 records · Page 3Linked to original sources
PubMed1996

Enhanced vesiculation exacerbates complement-dependent hemolysis in glucose-6-phosphate dehydrogenase deficient red blood cells.

Glucose-6-phosphate dehydrogenase (G6PD) deficient red blood cells (RBCs) are known to be more susceptible to oxidant-induced hemolysis. Erythrocytes from G6PD-deficient individuals are significantly more susceptible to Ca(2+)-induced vesiculation than normal control cells. The enhanced susceptibility of G6PD-deficient RBCs to Ca(2+)-induced vesiculation is not due to ATP depletion. The remnant G6PD-deficient RBCs following vesiculation are more sensitive to complement-mediated hemolysis than control normal RBCs. A strong positive correlation exists between the level of Ca(2+)-induced vesiculation and the extent of complement mediated hemolysis.

Calcium↗
PubMed1996

Purification and characterization of endogenous digoxin-like immunoreactive factors in chicken blood.

Studies have been performed to determine whether an endogenous material capable of binding to digoxin antibodies is present in the chicken plasma. In the blood of 12 chickens without feed control, endogenous digoxin-like immunoreactive factors (DLIF) binding of digoxin antibodies in enzyme immunoassays amounted to 866 / 302 pg digoxin equivalents/mL of plasma (mean +/- SEM). Immunoreactivity of DLIF increased to 1848***331 pg/mL with a double value of control after boiling and acid pretreating the plasma. The major purification steps employed in this report were gel filtration column chromatography, high performance liquid chromatography (HPLC) and isoelectric focusing (IEF). Using HPLC for the separation, at least 10 chicken DLIFs with different molecular weight (MW) have been found. The MW of the smallest is 300 daltons (Da) while the largest is 100 kDa. The value of the isoelectric point of the most abundant type of DLIF from untreated chicken plasma is 6.3 as determined by IEF. The partially purified DLIF inhibits Na+, K(+)-ATPase from a porcine cerebral cortex as well as three human red blood cell membrane preparations in a dose-response fashion.

Animals↗
PubMed1996

Correlation of membrane lipid peroxidation with oxidation of hemoglobin variants: possibly related to the rates of hemin release.

Experiments were performed to delineate the biochemical mechanism of hemoglobin (Hb)-catalyzed lipid peroxidation in human red blood cells (RBCs). Using a modified Langmuir trough lipid monolayer technique, we found that oxidized Hb induced an increase in lipid monolayer surface pressure, suggesting that oxidized Hb readily releases its heme moiety into the lipid monolayer. To confirm our interpretation that oxidized Hb readily releases its heme moiety, we monitored the fluorescence of Hb tryptophan upon oxidation of Hb. We found an increase in Hb fluorescence in the aqueous phase of our monolayer system after the addition of H2O2. The increase in fluorescence should reflect the departure of heme from globin due to a decrease in fluorescent quenching effect by the heme moiety. The rate of increase in lipid monolayer surface pressure upon Hb oxidation differed from Hb to Hb with an order of Hb E > F > S > A. The ability of various Hbs to affect lipid peroxidation in the RBC membrane, as monitored by the parinaric acid oxidation technique, followed this same order. In addition, hemin was shown to be a more potent catalyst of lipid peroxidation in RBC membrane than nonheme irons.

Adult↗
PubMed1995

The toxicity of azidothymidine (AZT) on human and animal cells in culture at concentrations used for antiviral therapy.

AZT, a chain terminator of DNA synthesis originally developed for chemotherapy, is now prescribed as an anti-human immunodeficiency virus (HIV) drug at 500 to 1500 mg/person/day, which corresponds to 20 to 60 microM AZT. The human dosage is based on a study by the manufacturer of the drug and their collaborators, which reported in 1986 that the inhibitory dose for HIV replication was 0.05 to 0.5 microM AZT and that for human T-cells was 2000 to 20,000 times higher, i.e. 1000 microM AZT. This suggested that HIV could be safely inhibited in humans at 20 to 60 microM AZT. However, after the licensing of AZT as an anti-HIV drug, several independent studies reported 20- to 1000-fold lower inhibitory doses of AZT for human and animal cells than did the manufacturer's study, ranging from 1 to 50 microM. In accord with this, life threatening toxic effects were reported in humans treated with AZT at 20 to 60 microM. Therefore, we have re-examined the growth inhibitory doses of AZT for the human CEM T-cell line and several other human and animal cells. It was found that at 10 microM and 25 microM AZT, all cells are inhibited at least 50% after 6 to 12 days, and between 20 and 100% after 38 to 48 days. Unexpectedly, variants of all cell types emerged over time that were partially resistant to AZT. It is concluded that AZT, at the dosage prescribed as an anti-HIV drug, is highly toxic to human cells.

Animals↗
PubMed1995

Heterotopic transplantation of a reattached digit.

A patient who had suffered amputations at different levels of his nondominant left hand, and who had initially been treated with reattachment of his index and long fingers, presented with a minimally functional left hand. He was then managed by transplantation of his reattached index finger stump to the shortened ring finger. This significantly improved hand function and contour and alleviated a painful neuroma at the former ring finger amputation site. However, compared with the long finger, which was reattached once, the twice-reattached finger had less sensibility recovery, more pronounced cold intolerance, decreased basal skin temperature, and a slower digital rewarming time. Thus, even though it is technically feasible to transfer a previously reattached digit, other possible physiologic limitations must be considered before doing so.

Adult↗
PubMed1995

Carpal tunnel release using limited direct vision.

A novel method to release the carpal tunnel is presented. It combines the advantages of endoscopic and open techniques while utilizing standard instruments. A lighted Killian nasal speculum is introduced between the palmar fascia and the transverse carpal ligament. The ligament is incised under direct vision. The procedure was performed in 28 cadaver hands and followed by inspection utilizing the open method through an interthenar incision. The transverse carpal ligament was completely divided in all hands without nerve or tendon injury. The superficial palmar arch was injured in one hand (3.6 percent). The advantages, disadvantages, pitfalls, and results are discussed. The technique is simple and effective, employs inexpensive instruments, and has a low complication rate.

Cadaver↗
PubMed1995

The posterior intermuscular approach to the vessels of the leg.

The posterior intermuscular approach emphasizes preservation of the soleus muscle by an intermuscular surgical approach to the vessels of the leg. The dissection proceeds from a normal zone proximally toward the zone of injury and facilitates selection of the site of microanastomosis. The neurovascular supply of the soleus is guarded, and its numerous venous channels are avoided. The indications and surgical planning are discussed. Two illustrative cases are presented.

Adult↗
PubMed1994

Detection of a novel lactate dehydrogenase isozyme and an apparent differentiation-associated shift in isozyme profile in hepatoma cell lines.

A hitherto unreported lactate dehydrogenase (LD) isoenzyme, which migrates electrophoretically to the relative position between LD2 and LD3 has been identified in the electropheratogram in 7 of 7 (100%) cultured hepatoma cell lines with various degrees of differentiation and is thus given the name LD2-3. LD2-3 seems to be specific for hepatoma cells because this atypical isoenzyme can not be detected in other tumor cell lines. In addition, the hepatoma cell lines also show a distinct pattern of LD isoenzyme and the isoenzyme pattern varies with the degree of differentiation. Hence, the expression pattern of LD isoenzyme phenotypes may provide a good marker for the investigation of human hepatoma cell differentiation.

Carcinoma, Hepatocellular↗
PubMed1994

Probing individual molecules with confocal fluorescence microscopy.

Confocal fluorescence microscopy coupled with a diffraction-limited laser beam and a high-efficiency detection system has been used to study the diffusive movement and emission process of individual fluorescent molecules in the liquid phase at room temperature. The high detection sensitivity achieved at fast data acquisition speeds (greater than 1 kilohertz) allows real-time observation of single-molecule fluorescence without statistical analysis. The results show fluorescence-cycle saturation at the single-molecule level and multiple recrossings of a single molecule into and out of the probe volume as well as the triplet state.

Fluorescein↗
PubMed1994

Enhanced susceptibility of erythrocytes deficient in glucose-6-phosphate dehydrogenase to alloxan/glutathione-induced decrease in red cell deformability.

It has been hypothesized that enhanced oxidant sensitivity of glucose-6-phosphate dehydrogenase (G6PD) deficient red cells(RBCs) is the underlying mechanism for drug- or chemical-induced hemolytic crises in G6PD-deficiency. To further test this hypothesis, we used an alloxan-glutathione system to mimic oxidative stress and see how oxidative damage might affect RBC deformability. RBC deformability, a major determinant of RBC survival in vivo, was monitored by a laser viscodiffractometer. Under our experimental conditions, GSH alone had very little effect on the deformability of either normal or G6PD-deficient RBCs. In contrast, alloxan alone induced a small but significant decrease in the deformability of either normal or G6PD-deficient RBCs. Interestingly, alloxan and GSH together induced a further decrease in the deformability of either normal or G6PD-deficient RBCs. The decrease in deformability in G6PD-deficient RBCs was much more profound than in normal RBCs. In addition, an alloxan-vitamin C system produced a similar deleterious effect on RBC deformability as that produced by the alloxan-GSH system. Appreciable amount of hydroxyl radicals was generated by both alloxan-GSH and alloxan-vitamin C systems as evidenced by the production of hydroxylated products of salicylate which was used as a radical trap. Moreover, salicylate could ameliorate the deleterious effect of the alloxan system on the deformability of RBCs. Taken together, our results demonstrated that G6PD-deficient RBCs were particularly susceptible to oxidant-induced damage leading to a dramatic decrease in their deformability and thus provided strong support for the hypothesis that enhanced oxidant sensitivity of G6PD-deficient RBCs is the underlying mechanism for accelerated destruction of these RBCs in vivo.

Alloxan↗
PubMed1994

Effects of H2O2 on protein tyrosine phosphatase activity in HER14 cells.

Oxidative stress has been implicated in protein phosphorylation and dephosphorylation in cells. In our current studies, H2O2 was shown to reversibly inhibit protein tyrosine phosphatase (PTPase) activity in HER14 cells. H2O2 (150 mM) resulted in 40% inhibition of PTPase activity by 15 min and recovery from inhibition was nearly complete by 60 min. H2O2-induced inhibition or recovery of PTPase activity was not affected by cycloheximide, a protein synthesis inhibitor. L-Buthionine-[S,R]-sulfoximine (BSO), an inhibitor of glutathione synthesis, had no effect on H2O2-induced inhibition of PTPase activity but retarded the recovery of activity. Epidermal growth factor (EGF) and EGTA, a Ca2+ chelator, did not influence H2O2-induced inhibition or recovery of PTPase activity. These results suggest that at least 40% of fibroblast PTPase activity can be regulated by cellular redox activity.

3T3 Cells↗
PubMed1994

An intramuscular ganglion presenting as a thenar mass.

Soft-tissue masses in the hand are frequently due to ganglion cysts. We report a ganglion originating from a common location, the volar wrist, but presenting in a unique fashion as a thenar mass. This case helps demonstrate why ganglion cysts should be considered in the differential diagnosis of any soft-tissue hand mass.

Child↗
PubMed1993

Decreased catalase activity is the underlying mechanism of oxidant susceptibility in glucose-6-phosphate dehydrogenase-deficient erythrocytes.

Historically, it has been theorized that the enhanced oxidant sensitivity of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes arises as a direct consequence of an inability to maintain cellular glutathione (GSH) levels. This study alternatively hypothesizes that decreased NADPH concentration leads to impaired catalase activity which, in turn, underlies the observed oxidant susceptibility. To investigate this hypothesis, normal and G6PD-deficient erythrocytes and hemolysates were challenged with a H2O2-generating agent. The results of this study demonstrated that catalase activity was severely impaired upon H2O2 challenge in the G6PD-deficient cell while only a transient decrease was observed in normal cells. Supplementation of either normal or G6PD-deficient hemolysates with purified NADPH was found to significantly (P < 0.001) inhibit catalase inactivation upon oxidant challenge while addition of NADP+ had no effect. Analysis of these results demonstrated direct correlation between NADPH concentration and catalase activity (r = 0.881) and an inverse correlation between catalase activity and erythrocyte oxidant sensitivity (r = 0.906). In contrast, no correlation was found to exist between glutathione concentration (r = 0.170) and oxidant sensitivity. Analysis of NADPH/NADPt ratio in acatalasemic mouse erythrocytes demonstrated that NADPH maintenance alone was not sufficient to explain oxidant resistance, and that catalase activity was required. This study supports the hypothesis that impaired catalase activity underlies the enhanced oxidant sensitivity of G6PD-deficient erythrocytes and elucidates the importance of NADPH in the maintenance of normal catalase activity.

Animals↗
PubMed1993

Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in patients of Chinese descent and identification of new base substitutions in the human G6PD gene.

The underlying DNA changes associated with glucose-6-phosphate dehydrogenase (G6PD)-deficient Asians have not been extensively investigated. To fill this gap, we sequenced the G6PD gene of 43 G6PD-deficient Chinese whose G6PD was well characterized biochemically. DNA samples were obtained from peripheral blood of these individuals for sequencing using a direct polymerase chain reaction (PCR) sequencing procedure. From these 43 samples, we have identified five different types of nucleotide substitutions in the G6PD gene: at cDNA 1388 from G to A (Arg to His); at cDNA 1376 from G to T (Arg to Leu); at cDNA 1024 from C to T (Leu to Phe); at cDNA 392 from G to T (Gly to Val); at cDNA 95 from A to G (His to Arg). These five nucleotide substitutions account for over 83% of our 43 G6PD-deficient samples and these substitutions have not been reported in non-Asians. The substitutions found at cDNA 392 and cDNA 1024 are new findings. The substitutions at cDNA 1376 and 1388 account for over 50% of the 43 samples examined indicating a high prevalence of these two alleles among G6PD-deficient Chinese. Our findings add support to the notion that diverse point mutations may account largely for much of the phenotypic heterogeneity of G6PD deficiency.

Asian↗
PubMed1993

Rat ear transplantation: a feasibility study.

The feasibility of rat ear replantation and its inherent advantages as an experimental model have previously been demonstrated. The purpose of this study was to validate the technical feasibility of rat ear transplantation. To eliminate immunologic rejection as a complicating factor, highly inbred Lewis rats (strain LEW/CRIBR) were utilized. The external, internal, or common carotid artery served as the arterial pedicle, and the posterior facial vein as the venous pedicle; tubal cartilage was anastomosed for structural support. Four of five transplanted ears were viable at 10 to 14 weeks postoperatively. The other ear appeared entirely viable, when its host animal died of respiratory complications on postoperative day 2. Rat ears therefore seem to provide a feasible model for transplantation of non-vital organs.

Anastomosis, Surgical↗
PubMed1993

"Karate kid" finger.

The ulnar dorsal digital nerve of the little finger overlies the prominence of the ulnar hemicondyle of the middle phalanx at the proximal interphalangeal joint level and is vulnerable to contusion injury when the hand is used to perform karate chops. Localized perineural and interfascicular fibrosis may ensue. Neurolysis is curative.

Child↗