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Biomedical subjects

D Han

Publications and source records attributed to D Han.

At least 37 records · Page 2Linked to original sources
PubMed1998

The CVC removal distress syndrome: an unappreciated complication of central venous catheter removal.

The removal of a central venous catheter (CVC) can be complicated by rare but potentially life-threatening neurocardiopulmonary distress. The clinical courses of eight patients who had CVC removal complications are reviewed. Seven patients had catheter removal from the right internal jugular vein, and one from the right subclavian vein. The complications occurred after complete removal of the catheter (four patients), after guidewire replacement for catheter change (three patients), and after detachment of the hemostasis side port of the Swan introducer during sheath removal (one patient). Each of them had more than one complication. The major complications were: neurologic paresis or coma (four patients), respiratory failure (four patients), and shock (two patients). One patient died of pulmonary sepsis. The overall mortality rate was 12.5 per cent. Guidelines for safe removal of central venous catheters are proposed. Possible mechanisms of the complications are discussed. We refer to the observed complications as the CVC removal distress syndrome.

Adult↗
PubMed1997

Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization.

Lipoic acid (thiotic acid) is being used as a dietary supplement, and as a therapeutic agent, and is reported to have beneficial effects in disorders associated with oxidative stress, but its mechanism of action remains unclear. We present evidence that lipoic acid induces a substantial increase in cellular reduced glutathione in cultured human Jurkat T cells human erythrocytes, C6 glial cells, NB41A3 neuroblastoma cells, and peripheral blood lymphocytes. The effect depends on metabolic reduction of lipoic acid to dihydrolipoic acid. Dihydrolipoic acid is released into the culture medium where it reduces cystine. Cysteine thus formed is readily taken up by the neutral amino acid transport system and utilized for glutathione synthesis. By this mechanism lipoic acid enables cystine to bypass the xc- transport system, which is weakly expressed in lymphocytes and inhibited by glutamate. Thereby lipoic acid enables the key enzyme of glutathione synthesis, gamma-glutamylcysteine synthetase, which is regulated by uptake-limited cysteine supply, to work at optimum conditions. Flow cytometric analysis of freshly prepared human peripheral blood lymphocytes, using monobromobimane labeling of cellular thiols, reveals that lipoic acid acts mainly to normalize a subpopulation of cells severely compromised in thiol status rather than to increase thiol content beyond physiological levels. Hence lipoic acid may have clinical relevance in restoration of severely glutathione deficient cells.

Animals↗
PubMed1997

Ventilation inhomogeneities and mixed venous blood N2 in multibreath N2 washout.

The single path model of airway gas transport, with and without a distributed blood source term, was used to simulate multiple-breath N2 washout by breathing pure O2 in two lung models: a single-region lung model (SRLM) which produces series inhomogeneity, and a seven-region lung model (7RLM) incorporating both series and parallel inhomogeneities. Normalized phase III slopes (Sn) from N2 expirograms were computed for each breath and compared with published human experimental data obtained under similar conditions. The 7RLM predicts well the trend of experimental Sn N2 changes and is superior to the SRLM in the first part (the unsteady state), implying that this part of the curve is mostly due to convective mixing of the seven parallel flow streams. In the quasi-steady state, the 7RLM is not obviously superior to the SRLM. Functional residual capacity and pulmonary perfusion are shown to strongly affect the number of breaths required to reach the quasi-steady state. The anatomical dimensions that appear to be critical in SRLM are not as important in the 7RLM.

Computer Simulation↗
PubMed1997

Cytosolic and mitochondrial systems for NADH- and NADPH-dependent reduction of alpha-lipoic acid.

In cellular, tissue, and organismal systems, exogenously supplied alpha-lipoic acid (thioctic acid) has a variety of significant effects, including direct radical scavenging, redox modulation of cell metabolism, and potential to inhibit oxidatively-induced injury. Because reduction of lipoate to dihydrolipoate is a crucial step in many of these processes, we investigated mechanisms of its reduction. The mitochondrial NADH-dependent dihydrolipoamide dehydrogenase exhibits a marked preference for R(+)-lipoate, whereas NADPH-dependent glutathione reductase shows slightly greater activity toward the S(-)-lipoate stereoisomer. Rat liver mitochondria also reduced exogenous lipoic acid. The rate of reduction was stimulated by substrates which increased the NADH content of the mitochondria, and was inhibited by methoxyindole-2-carboxylic acid, a dihydrolipoamide dehydrogenase inhibitor. In rat liver cytosol, NADPH-dependent reduction was greater than NADH, and lipoate reduction was inhibited by glutathione disulfide. In rat heart, kidney, and brain whole cell-soluble fractions, NADH contributed more to reduction (70-90%) than NADPH, whereas with liver, NADH and NADPH were about equally active. An intact organ, the isolated perfused rat heart, reduced R-lipoate six to eight times more rapidly than S-lipoate, consistent with high mitochondrial dihydrolipoamide dehydrogenase activity and results with isolated cardiac mitochondria. On the other hand, erythrocytes, which lack mitochondria, somewhat more actively reduced S- than R-lipoate. These results demonstrate differing stereospecific reduction by intact cells and tissues. Thus, mechanisms of reduction of alpha-lipoate are highly tissue-specific and effects of exogenously supplied alpha-lipoate are determined by tissue glutathione reductase and dihydrolipoamide dehydrogenase activity.

Animals↗
PubMed1997

Regulation of cellular thiols in human lymphocytes by alpha-lipoic acid: a flow cytometric analysis.

Modulation of cellular thiols is an effective therapeutic strategy, particularly in the treatment of AIDS. Lipoic acid, a metabolic antioxidant, functions as a redox modulator and has proven clinically beneficial effects. It is also used as a dietary supplement. We utilized the specific capabilities of N-ethylmaleimide to block total cellular thiols, phenylarsine oxide to block vicinal dithiols, and buthionine sulfoximine to deplete cellular GSH to flow cytometrically investigate how these thiol pools are influenced by exogenous lipoate treatment. Low concentrations of lipoate and its analogue lipoamide increased Jurkat cell GSH in a dose-dependent manner between 10 (25 microM for lipoamide) to 100 microM. This was also observed in mitogenically stimulated peripheral blood lymphocytes (PBL). Studies with Jurkat cells and its Wurzburg subclone showed that lipoate dependent increase in cellular GSH was similar in CD4+ and - cells. Chronic (16 week) exposure of cells to lipoate resulted in further increase of total cellular thiols, vicinal dithiols, and GSH. High concentration (2 and 5 mM) of lipoate exhibited cell shrinkage, thiol depletion, and DNA fragmentation effects. Based on similar effects of octanoic acid, the cytotoxic effects of lipoate at high concentration could be attributed to its fatty acid structure. In certain diseases such as AIDS and cancer, elevated plasma glutamate lowers cellular GSH by inhibiting cystine uptake. Low concentrations of lipoate and lipoamide were able to bypass the adverse effect of elevated extracellular glutamate. A heterogeneity in the thiol status of PBL was observed. Lipoate, lipoamide, or N-acetylcysteine corrected the deficient thiol status of cell subpopulations. Hence, the favorable effects of low concentrations of lipoate treatment appears clinically relevant.

Acetylcysteine↗
PubMed1997

Zatebradine slows ectopic ventricular rhythms in canine heart 24 hours after coronary artery ligation.

Arrhythmias occur 24 h after occlusion of the left anterior descending (LAD) coronary artery in the canine heart and have been attributed to the abnormal spontaneous activity in subendocardial Purkinje fibers, which are markedly depolarized. The major current underlying normal automaticity in these fibers is i(f). Although the i(f) activation range is generally considered to be more negative than the diastolic membrane potential in these depolarized fibers in infarcts, this activation range has been shown to shift in a positive direction in response to hormonal influences. Thus i(f) could still mediate automaticity in these fibers in infarcts. Furthermore, recent reports indicate that a depolarizing diastolic current, probably i(f), also can be measured in ventricular muscle during abnormal experimental conditions, which may occur during ischemia. To test whether there is a role of i(f) currents in sustaining ventricular ectopy, we administered the selective i(f) channel blocker, zatebradine, 24 h after LAD ligation in canine hearts. We report that intravenous injections of zatebradine (0.25 or 1.0 mg/kg) significantly slow ventricular rhythms (with average reductions of 19 or 26%, respectively). Moreover, because zatebradine also slows sinus nodal rate, it can lead to an increased incidence of ectopic beats. However, during right atrial pacing, when sinus slowing has no effect on ventricular rhythms, capture of ventricular rhythms occurs at lower rates in the presence of zatebradine. The reduction of capture threshold is comparable to the reduction in the rate of the ectopic rhythm. Thus zatebradine eliminated the arrhythmia when the right atrium was paced at the original sinus rate.

Animals↗
PubMed1997

Neurotransmitter modulation of gap junctional communication in the rat hippocampus.

Increasing experimental evidence indicates that gap junctions can be modulated by neurotransmitters, in particular dopamine. To examine possible modulation of gap junctional communication in the rat hippocampus by neurotransmitters, we studied dye coupling and electrotonic transmission in the CA1 area in the presence of carbachol, a cholinergic agonist, and dopamine agonists. Carbachol markedly reduced dye coupling and the frequency of electrotonic potentials (spikelets). Spikelet amplitudes were decreased in the presence of carbachol. These effects were reversed by the cholinergic antagonist atropine, suggesting a muscarinic action of carbachol on gap junctional function. The non-specific dopamine agonist apomorphine, and the specific D1 receptor agonist SKF 38393, reduced dye coupling between pyramidal cells. Spikelet frequency was also decreased in the presence of dopamine agonists, but less than with carbachol. The specific D1 receptor antagonist, SCH 23390, reversed the effects of both dopamine agonists. These observations indicate that cholinergic and dopaminergic transmission can affect electrical and chemical (dye coupling) communication through gap junctions, and could therefore alter properties of neuronal assemblies, in addition to their effects on intrinsic membrane properties.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

A two year prospective study to compare culture and polymerase chain reaction amplification for the detection and diagnosis of Lyme borreliosis.

AIM: To compare polymerase chain reaction (PCR) amplification of borrelial DNA and culture isolation of spirochaetes for the diagnosis of Lyme borreliosis by direct detection of Borrelia burgdorferi sensu lato in patients with erythema migrans and acrodermatitis chronica atrophicans lesions. METHODS: Skin biopsy specimens from erythema migrans and acrodermatitis chronica atrophicans lesions were subdivided and tested by PCR amplification assay and culture using two artificial growth media, Barbour-Stoenner-Kelly II (BSK II) and modified Kelly-Pettenkofer (MKP). Five classes of lesions were studied: typical erythema migrans, spontaneously resolved erythema migrans, atypical/partially treated erythema migrans, typical acrodermatitis chronica atrophicans, and atypical/partially treated acrodermatitis chronica atrophicans. RESULTS: For both erythema migrans and acrodermatitis chronica atrophicans lesions, the most sensitive detection method was MKP culture. PCR was less sensitive than MKP culture, but more sensitive than BSK II culture. Results for 758 typical erythema migrans specimens showed positivity rates of 36% for MKP, 25% for PCR, and 24% for BSK II. Differences were statistically significant. The overall positivity rate for all three methods combined was 54%, but few specimens (6%) were positive by all three methods. Examination of multiple erythema migrans lesions from the same patient increased the diagnostic yield. These findings, and similar results for acrodermatitis chronica atrophicans lesions, suggest that the distribution of spirochaetes in skin biopsies is not homogeneous. CONCLUSIONS: Although possessing the potential to provide a rapid diagnosis, PCR is not more sensitive than culture for the direct detection of borrelia. Spirochaetes appear to be unevenly distributed throughout biopsy specimens, suggesting that diagnosis of Lyme borreliosis by direct detection of the causative agent in skin lesions in vulnerable to sample bias.

Acrodermatitis↗
PubMed1997

Protection against glutamate-induced cytotoxicity in C6 glial cells by thiol antioxidants.

In many cell lines, glutamate cytotoxicity is known to be medicated by an inhibition of cystine transport. Because glutamate and cystine share the same transporter, elevated levels of extracellular glutamate competitively inhibit cystine transport leading to depletion of intracellular glutathione. A glutathione-depleted state impairs cellular antioxidant defenses resulting in oxidative stress. It was therefore of interest to investigate whether proglutathione agents, e.g., N-acetylcysteine and lipoic acid, are able to protect against glutamate cytotoxicity. Both lipoic acid (100 microM-1 mM) and N-acetylcysteine (100 microM-1 mM) completely protected C6 cells from the glutamate-induced cell death. Both agents facilitate extracellular supply of cysteine, the reduced form of cystine, that is transported into the cell by a glutamate-insensitive transport mechanism. Protection by lipoic acid and N-acetylcysteine corresponded with a sparing effect on cellular glutathione, which is usually depleted after glutamate treatment. In the presence of L-buthionine-(S,R)-sulfoximine, a gamma-glutamylcysteine synthetase inhibitor, low doses (< 100 microM) of lipoic acid and N-acetylcysteine did not protect cells against glutamate-induced cytotoxicity. At higher concentrations (> 500 microM), however, both lipoic acid and N-acetylcysteine provided partial protection against glutamate cytotoxicity even in glutathione synthesis-arrested cells. These results indicate that at low concentrations the primary mechanism of protection by the thiol antioxidants was mediated by their proglutathione property rather than direct scavenging of reactive oxygen. At higher concentrations (> 500 microM), a GSH-independent direct antioxidant effect of lipoic and N-acetylcysteine was observed. Dichlorofluorescin fluorescence, a measure of intracellular peroxides, increased sixfold after glutamate treatment of C6 cells. Lipoic acid and N-acetylcysteine treatment significantly lowered glutamate-induced dichlorofluorescin fluorescence compared with that of controls. Interestingly, alpha-tocopherol (50 microM) also suppressed glutamate-induced dichlorofluorescin fluorescence, indicating the peroxides detected by dichlorofluorescin were likely lipid hydroperoxides. Both thiol antioxidants, particularly lipoic acid, appear to have remarkable therapeutic potential in protecting against neurological injuries involving glutamate and oxidative stress.

Acetylcysteine↗
PubMed1997

Effect of glutathione, catechin, and epicatechin on the survival of Drosophila melanogaster under paraquat treatment.

The biological effect of antioxidants which showed high superoxide-scavenging (SOS) activity in an in vitro analysis was examined by using Drosophila melanogaster. When the flies were exposed to paraquat as an endogenous source of the superoxide anion, their survival rapidly decreased. Although the SOS antioxidants did not have a preventive effect against paraquat toxicity, a supplement of each SOS antioxidants as glutathione, (+)-catechin and/or (-)-epicatechin to the diet had a reparative effect on flies damaged by the superoxide anion. The survival ratio of flies fed on a diet enriched with SOS antioxidants ranged from 77% to 87%, while that of the control group was 56%. When flies were exposed to paraquat in the presence of hydrogen peroxide or iron, each combination was more toxic than paraquat alone, since the two compounds could accelerate the generation of reactive oxygen species in vivo. The SOS antioxidants, however, allowed the flies to resist the combined toxicity of paraquat and ferrous iron.

Animals↗
PubMed1997

Flat depressed early colon cancer--a case report.

A flat depressed early colon cancer (FDEC) is characterized by non-polypoid growth pattern, no association of adenomatous tissues and a tendency of even small lesions toward submucosal invasion and lymph node metastasis. It supports de novo carcinogenesis of colorectal cancer, although most colorectal cancers arise in pre-existing adenoma (adenoma-carcinoma sequence). There have been few reports of small depressed cancers because of the difficulty in colonoscopic detection and the rapid development to ulcerating advanced cancers. We report a case of flat depressed early colon cancer confined to mucosa detected by indigo carmine contrast colonoscopy.

Colonic Neoplasms↗
PubMed1997

[Scanning electron microscopic observation of the three-dimensional structure of laryngeal carcinoma using freeze-cracking method].

OBJECTIVE: To investigate the relation between the morphology and the biological characteristics of laryngeal carcinoma. METHODS: The freeze-cracking method was used to examine 126 specimens of the larynx under scanning electron microscope (SEM). The specimens were obtained from 12 patients suffering from laryngeal cancer and 4 patients with normal larynx. RESULTS: (1) In the normal larynx, the squamous-cell epithelium showed marked keratinization and the intracellular bridges were clear and regular. (2) In areas adjacent to cancer, the structure of the squamous-cell epithlium could be identified, but the cells were deranged and paramorphic. (3) There were two types in the marginal area of the carcinoma. Along the areas adjacent to cancer, infiltrating lymphocytes were usually observed and the surface of the lymphocytes had many leading lamella. CONCLUSION: The results indicate that the three-dimensional observation with SEM using the freeze-cracking technique is helpful for studying the relation between morphology and biologic characteristics of laryngeal carcinoma.

Carcinoma, Squamous Cell↗
PubMed1997

[The study of effects of immunologic modifier on proliferation and cytotoxicity against HEP-2 of LAK cells in vitro].

Adoptive immunotherapy as a new approach has been used to treat advanced carcinoma for almost ten years, and gained some good results. However, the application of this method is largely restricted by the side effects along with high dose of IL-2 and lack of sufficient amount of LAK cells. Mycobacterial Polysaccharides (MPS) and anti-CD3 antibodies (CD3Ab) have been demonstrated to be effective immunologic modifiers capable of proliferating lymphocytes and increasing cytotoxity against tumor cells. In this article we discussed the effects of MPS and CD3Ab on proliferation and cytotoxity against HEP-2 cells of LAK cells. Our results showed that: 1. MPS group (incubating IL-2 2 x 10(5)/L plus MPS 0.4 mg/L) or CD3 group (IL-2 1 x 10(6)/L plus CD3Ab 4 mg/L) were more proliferative than LAK group (only incubated with IL-2 1 x 10(6)/L). MPS group is the most proliferative in the three groups, P < 0.05. 2. Cytotoxity against HEP-2 in MPS or CD3 group was also better than in LAK group. CD3 group could maintain good cytotoxity in the longest period. These results could provide guidance for adoptive immunotherapy assisted by MPS or CD3Ab.

Antibodies, Monoclonal↗
PubMed1996

Temporal specificity of muscarinic synaptic modulation of the Ca(2+)-dependent K+ current (ISAHP) in rat hippocampal neurones.

1. We examined synaptic modulation of the Ca(2+)-dependent K+ current (ISAHP), which underlies the slow after-hyperpolarization (sAHP) in hippocampal CA1 neurones of rat brain slices. ISAHP was evoked in whole-cell voltage-clamp mode by depolarizing pulses, and synaptic afferents to CA1 neurones were stimulated electrically with a paired-pulse protocol. 2. Afferent stimulation delivered 200-1500 ms prior to be depolarizing pulse produced a profound reduction of ISAHP by 58%, but not other Ca(2+)-dependent outward currents that preceded ISAHP. Perfusion of slices with atropine significantly attenuated the synaptic reduction of ISAHP, indicating an event mediated largely by muscarinic receptor activation. When delivered < 400 ms after the depolarizing pulse, similar synaptic stimuli produced no substantial reduction in ISAHP, even in neurons where the duration of ISAHP was prolonged to 8-10 s either by lowering the recording temperature or by intracellular application of a calcium chelator. 3. To examine the effect of cholinergic stimulation of the depolarization-activated Ca2+ influx, high-threshold voltage-activated Ca2+ currents were recorded in the conventional or perforated whole-cell mode. Perfusion of slices with 5-10 microM carbachol for 5-10 min caused no substantial decrease in these Ca2+ currents, suggesting that the synaptic reduction of ISAHP is unlikely to be due to a blockade of depolarization-induced Ca2+ influx which triggers the generation of ISAHP. 4. The present data demonstrate that afferent stimulation reduces ISAHP only if it occurs prior to the depolarization-induced Ca2+ influx. We propose that modulation of inactive sAHP channels by muscarinic stimulation may decrease their sensitivity to the influx of Ca2+, whereas sAHP channels activated by Ca2+ may compete with the receptor-coupled modulation thus rendering the sAHP channels unresponsive to cholinergic afferent stimulation.

Animals↗
PubMed1996

Evolution of proneural atonal expression during distinct regulatory phases in the developing Drosophila eye.

BACKGROUND: Receptors of the Notch family affect the determination of many cell types. In the Drosophila eye, Notch antagonises the basic helix-loop-helix (bHLH) protein atonal, which is required for R8 photoreceptor determination. Similar antagonism between Notch and proneural bHLH proteins regulates most neural cell determination, however, it is uncertain whether the mechanisms are similar in all cases. Here, we have analyzed the sensitivity of atonal expression to Notch signalling using a temperature-sensitive Notch allele, by the expression of activated Notch or of the ligand Serrate, and by monitoring expression of the atonal-dependant gene scabrous and of the Notch-dependent Enhancer of split genes. RESULTS: The atonal expression pattern evolves from general "prepattern' expression, through transient "intermediate groups' to R8 precursor-specific expression. Successive phases of atonal expression differ in sensitivity to Notch. Prepattern expression of atonal is not inhibited. Inhibition begins at the intermediate group stage, corresponding to the period when atonal gene function is required for its own expression. At the transition to R8 cell-specific expression, Notch is activated in all intermediate group cells except the R8 cell precursor. R8 cells remain sensitive to inhibition in columns 0 and 1, but become less sensitive thereafter; non-R8 cells do not require Notch activity to keep atonal expression inactive. Thus, Notch signaling is coupled to atonal repression for only part of the atonal expression pattern. Accordingly, the Enhancer-of-split m delta protein is expressed reciprocally to atonal at the intermediate group and early R8 stages, but is expressed in other patterns before and after. CONCLUSIONS: In eye development, inhibition by Notch activity is restricted to specific phases of proneural gene expression, beginning when prepattern decays and is replaced by autoregulation. We suggest that Notch signalling inhibits atonal autoregulation, but not expression by other mechanisms, and that a transition from prepattern to autoregulation is necessary for patterning neural cell determination. Distinct neural tissues might differ in their proneural prepatterns, but use Notch in a similar mechanism.

Animals↗