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Biomedical subjects

B J Chen

Publications and source records attributed to B J Chen.

At least 19 recordsLinked to original sources
PubMed1996

Circulating clonal lymphocytes in myeloma constitute a minor subpopulation of B cells.

The mononuclear cells in the blood of myeloma patients have been reported to contain a high proportion of phenotypically abnormal myeloma B lymphocytes. These cells have been proposed to constitute the drug-resistant proliferative myeloma cell compartment. To determine the extent of B lymphocyte involvement, the proportion of clonotypic cells among the CD19-expressing cells from myeloma patients was estimated by quantitative polymerase chain reaction analysis of the third complementarity determining region (CDR3). The results indicate that the B lymphocytes constitute, on average, 6% of blood mononuclear cells, and that only a minor fraction of these are clonally related to the myeloma cells. While the small number of circulating clonal cells is not incompatible with their proposed role as a reservoir of proliferating myeloma progenitors, the majority of the B cells appear not to be clonally related to the myeloma cells.

Antigens, CD19↗
PubMed1996

A noninvasive method in the differential diagnosis of vecuronium-induced and magnesium-induced protracted neuromuscular block in a severely preeclamptic patient.

The occurrence of neuromuscular blockade and the resulting potentiation of muscle relaxants during magnesium sulfate (MgSO4) administration is well known. However, a method to differentiate the neuromuscular block induced by magnesium from that induced by curariform nondepolarizing muscle relaxant in the clinical setting has never been reported. We report a case in which the duration of action of 1 mg of vecuronium lasted 4 hours in a patient with severe preeclampsia whose serum magnesium level was in the therapeutic range. We believe this is a remarkable potentiation on record in the literature. We also describe a new, noninvasive method to assess magnesium-induced neuromuscular block when curariform muscle relaxant was given simultaneously.

Adult↗
PubMed1995

Suppression of Escherichia coli alkB mutants by Saccharomyces cerevisiae genes.

The alkB gene is one of a group of alkylation-inducible genes in Escherichia coli, and its product protects cells from SN2-type alkylating agents such as methyl methanesulfonate (MMS). However, the precise biochemical function of the AlkB protein remains unknown. Here, we describe the cloning, sequencing, and characterization of three Saccharomyces cerevisiae genes (YFW1, YFW12, and YFW16) that functionally complement E. coli alkB mutant cells. DNA sequence analysis showed that none of the three gene products have any amino acid sequence homology with the AlkB protein. The YFW1 and YFW12 proteins are highly serine and threonine rich, and YFW1 contains a stretch of 28 hydrophobic residues, indicating that it may be a membrane protein. The YFW16 gene turned out to be allelic with the S. cerevisiae STE11 gene. STE11 is a protein kinase known to be involved in pheromone signal transduction in S. cerevisiae; however, the kinase activity is not required for MMS resistance because mutant STE11 proteins lacking kinase activity could still complement E. coli alkB mutants. Despite the fact that YFW1, YFW12, and YFW16/STE11 each confer substantial MMS resistance upon E. coli alkB cells, S. cerevisiae null mutants for each gene were not MMS sensitive. Whether these three genes provide alkylation resistance in E. coli via an alkB-like mechanism remains to be determined, but protection appears to be specific for AlkB-deficient E. coli because none of the genes protect other alkylation-sensitive E. coli strains from killing by MMS.

Alkylation↗
PubMed1994

The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity.

Escherichia coli can ameliorate the toxic effects of alkylating agents either by preventing DNA alkylation or by repairing DNA alkylation damage. The alkylation-sensitive phenotype of E. coli alkB mutants marks the alkB pathway as an extremely effective defense mechanism against the cytotoxic effects of the SN2, but not the SN1, alkylating agents. Although it is clear that AlkB helps cells to better handle alkylated DNA, no DNA alkylation repair function could be assigned to the purified AlkB protein, suggesting that AlkB either acts as part of a complex or acts to regulate the expression of other genes whose products are directly responsible for alkylation resistance. However, here we present evidence that the provision of alkylation resistance is an intrinsic function of the AlkB protein per se. We expressed the E. coli AlkB protein in two human cell lines and found that it confers the same characteristic alkylation-resistant phenotype in this foreign environment as it does in E. coli. AlkB expression rendered human cells extremely resistant to cell killing by the SN2 but not the SN1 alkylating agents but did not affect the ability of dimethyl sulfate (an SN2 agent) to alkylate the genome. We infer that SN2 agents produce a class of DNA damage that is not efficiently produced by SN1 agents and that AlkB somehow prevents this damage from killing the cell.

AlkB Homolog 1, Histone H2a Dioxygenase↗
PubMed1993

A clinical assessment of desflurane anaesthesia and comparison with isoflurane.

In 48 randomly assigned ASA I adult patients undergoing elective orthopaedic procedures, we compared the pharmacodynamics of desflurane (DF) and isoflurane (IF), and their pharmacokinetics during rapid induction of deep anaesthesia (via face mask, to 1.5-2 MAC, after thiopentone), maintenance of anaesthesia at 1.25 MAC, and emergence therefrom. During induction, laryngeal reactions ranging from mild crowing to laryngospasm occurred more frequently with DF than with IF (15/24 DF, 5/24 IF; P < 0.05) and was more severe (9/24 DF, 1/24 IF, excluding the mildest form, P < 0.05). As a result, induction of anaesthesia was not accomplished faster with DF, in spite of a faster equilibration between exhaled and inhaled concentrations. Emergence from DF was more rapid and less complicated by delirium. Pharmacokinetically, the exhaled concentration of DF reached 90% of the inhaled concentration within five minutes of induction, whereas that of IF lagged behind and remained 25% below the inhaled concentration (1 vs 1.34 +/- 0.05) even one hour after induction. Premature ventricular contractions did not occur in any patient even during periods of difficulty with the airway and oxygen desaturation. It is concluded that DF is a safe anaesthetic, pharmacokinetically superior to IF but clinically inferior for induction of anaesthesia via a face mask. Because of the fast equilibration, the exhaled concentration of DF can be controlled more precisely by the dial setting of the vaporiser.

Adolescent↗
PubMed1993

Cloning and characterization of a mouse 3-methyladenine/7-methyl-guanine/3-methylguanine DNA glycosylase cDNA whose gene maps to chromosome 11.

In Escherichia coli, the repair of 3-methyladenine (3MeA) DNA lesions by DNA glycosylases prevents alkylation induced cell death. We described previously the isolation of a human 3MeA DNA glycosylase (AAG) cDNA that maps to chromosome 16 and hybridizes to specific genomic DNA fragments from a number of mammals, including mouse. As a first step in the generation of a 3MeA DNA glycosylase deficient mouse by homologous replacement in embryonic stem cells, we have cloned the mouse 3MeA DNA glycosylase cDNA. The cloned 1095 base pair cDNA contains a complete 333 amino acid open reading frame that predicts a 36.5 kDa protein and hybridizes to a 1.5 kb mRNA transcript. Mouse 3MeA DNA glycosylase (Aag) transcript levels vary by up to 21 fold among tissues, being highest in the testes and lowest in the heart. The Aag cDNA encodes a glycosylase able to release 3MeA, 7-methylguanine (7MeG) and 3-methylguanine (3MeG) from alkylated DNA. The expression of Aag in E. coli provides substantial resistance against killing by methylating agents, but, unlike its E. coli counterparts, the Aag glycosylase fails to protect against killing by ethylating and propylating agents. A 232 amino acid stretch of the predicted mouse protein shares extensive amino acid identity with rat (93%) and human (83%) 3MeA DNA glycosylases and we observe that all three mammalian glycosylases have a bipartite nuclear localization signal. The Aag gene maps to mouse chromosome 11, suggesting a segment of conserved synteny between mouse chromosome 11 and human chromosome 16, which bears the human 3MeA DNA glycosylase gene. Cloning the mouse 3MeA DNA glycosylase cDNA is a step toward understanding the role of this DNA repair enzyme in mammals.

Adenine↗
PubMed1993

[A study of left ventricular function in normal persons and patients with old myocardial infarction with three dimensional echocardiography (3-DE)].

The accuracy of 3-DE in evaluating the volumes of left ventricule (LV) and volume changes in cardiac cycle was discussed. The LV volumes measured with 3-DE in porcine hearts is more closely to the real volumes directly measured (P > 0.05 r = 0.93). The EF value measured with radionuclide has higher correlation with that of 3-DE (r = 0.88) in patients. In a quantitative analysis of LV volume changes in cardiac cycles, we found that the decrease of EF in patients with old myocardial infarction (OMI) occurs mainly at the early stage and lasts to middle stage of systole in anterior myocardial infarction. Dysfunction of filling in OMI took place at the early and middle stages of diostole. Segmental shortening of LV was analysed quantitatively by percentage and pseudocolour mark. The reference values of 3DE in cardiac function were shown.

Adult↗
PubMed1992

Structure of alpha 2-macroglobulin-protease complexes. Methylamine competition shows that proteases bridge two disulfide-bonded half-molecules.

alpha 2-Macroglobulin (alpha 2M) forms several different covalent complexes with proteases. These include unusual forms in which more than one of the four identical subunits of alpha 2M are cross-linked by amide bonds to more than one lysyl amino group of the bound protease. The structure of these complexes and the question of how the identical subunits are arranged to form two protease binding sites are matters of current controversy. The 185-kDa subunits are arranged into two disulfide-bonded half-molecules which are, in turn, noncovalently associated. We have provided evidence that, in the major multivalent cross-linked form, proteases can span the two half-molecules, forming a covalently bonded tetramer [Wang, D., Yuan, A. I., & Feinman, R. D. (1984) Biochemistry 23, 2807-2811]. An alternative theory has recently been proposed in which the major high molecular weight form has two bonds to protease that are within half-molecules--a multivalent cross-linked dimer [Sottrup-Jensen, L., Hansen, H. F., Pedersen, H. S., & Kristensen, L. (1990) J. Biol. Chem. 265, 17727-17737]. To resolve this conflict, experiments were carried out to determine the structure of one of the high molecular weight bands (band 3) seen on SDS-PAGE. Band 3 has anomalous migration, corresponding to markers of apparent molecular mass of 550 kDa (between the tetramer and dimer). In the experiments described here, reactions of thrombin with alpha 2M were run in the presence of methylamine, which competes for one of the two thrombin-alpha 2M covalent bonds.(ABSTRACT TRUNCATED AT 250 WORDS)

Disulfides↗
PubMed1992

Recovery of cognitive functions after anaesthesia with desflurane or isoflurane and nitrous oxide.

We studied recovery in 25 adult patients, ASA I, undergoing elective orthopaedic procedures after anaesthesia with 0.65 MAC desflurane (n = 16) or isoflurane (n = 9) with 60% nitrous oxide in oxygen. Early emergence from anaesthesia was assessed in the operating room by measuring time to spontaneous movement, cough, response to painful pinch, tracheal extubation, opening of the eyes and stating correct age, name and body parts. The return of cognitive functions in the late recovery phase was assessed in the post-anaesthesia care unit (PACU) by post-anaesthesia recovery scores (PARS), the Trieger dot test (TDT), and the digit substitution test (DST). In the early recovery phase, time to tracheal extubation, opening eyes, telling correct name, age and body parts occurred significantly faster in the desflurane group than in the isoflurane group (P < 0.05). The mean "triple orientation" time (to name, age, body parts) was 10.9 (SEM 0.9) min for desflurane, compared with 18.6 (2.5) min for isoflurane (P < 0.01). In the late recovery phase, desflurane patients had significantly greater PARS, more correct responses to the DST and fewer error responses to the TDT. Recovery times were not increased by increased duration of desflurane anaesthesia. The desflurane patients showed no delirium, minimal sedation and less shivering during the entire postoperative course. We conclude that desflurane anaesthesia was superior to isoflurane anaesthesia, not only in emergence, but also in the recovery of cognitive functions.

Adolescent↗
PubMed1992

[Clinical analysis of 30 cases of stiff-man syndrome].

Thirty cases of SMS, including 22 cases reported previously in China, were analysed clinically manifested by involvement of neck and facial muscles, slurred speech, dysphagia or dyspnea, exaggerated tendon reflexes, ankle clonus and/or Hoffmann's sign. Half of them had past history of infection. Five out of 18 CSF examined showed elevation of protein content, immunoglobulin and white cell count, suggesting the presence of inflammation or demyelination changes in CNS. The pathology of the syndrome is probably located in the spinal cord or brain stem. The criteria for diagnosis are proposed. For treatment, the dosage and way of administration of diazepam should be judged according to the severeness of the disease; nitrazepam and clonazepam are effective, too.

Adolescent↗
PubMed1992

Neuromuscular blocking effect and placental gradient of pipecuronium bromide in elective caesarean section.

We studied the suitability of pipecuronium for maintenance of neuromuscular block during 20 elective Caesarean sections under light general anaesthesia with a rapid-sequence technique facilitated by i.v. suxamethonium 0.6-0.8 mg kg-1. An initial dose of 0.035 mg kg-1 or 0.05 mg kg-1 of pipecuronium provided satisfactory relaxation of similar speed of onset (3.1 +/- 0.3 vs 3.8 +/- 0.6 min, p = 0.25); however the higher dose had a significantly longer duration of action than the lower dose (from injection to recovery to 20% of baseline 13.1 +/- 1.8 vs 39.3 +/- 6.9 min, p < 0.05). A spontaneous recovery of the T1 twitch of the train-of-four to 25% of baseline (residual block 75%) assured rapid antagonism of the residual block with either edrophonium 0.5 mg kg-1 or neostigmine 0.04 mg kg-1. A residual block greater than 80% depression of T1 markedly prolonged the time taken to achieve a satisfactory reversal. Pipecuronium had negligible cardiovascular effects and placental transfer. It had no observable effect on the newborn. In spite of some advantages, we conclude that pipecuronium is a suitable alternative during Caesarean section only when used judiciously in small doses for maintenance of neuromuscular block and recommend that the initial dose be no greater than 0.035 mg kg-1.

Adolescent↗
PubMed1991

[Clinical evaluation of antepartum vibratory acoustic stimulation test].

A prospective comparative study between antepartum vibratory acoustic stimulation test (VAS-T) and nonstress test (NST) was done in 103 pregnant women. Of the 103 cases, 101 of VAS-Ts were positive and 2 negative, with no false negative result. 76 of NSTs were positive and 27 NSTs were negative, with 26 false negative result. The mean duration of VAS-T was 56 seconds. It showed that VAS-T as an effective antepartum monitoring test was safe and much less time consuming. As compared with NST, the false negative rate of VAS-T was reduced, thus the predictive value of negative VAS-T increased. A positive VAS-T predicts with high precision that the fetal well-being is satisfactory, while a negative VAS-T prognostic that the fetal outcome is poor.

Acoustic Stimulation↗
PubMed1990

Effect of methylamine on the reaction of alpha 2-macroglobulin with enzymes.

The kinetics of reaction of alpha 2-macroglobulin (alpha 2M) with thrombin and with trypsin were studied in the presence and absence of methylamine. The rate of enzyme-induced thiol release was found to be the same whether or not amine was present. The result suggests that covalent bond formation and enzyme-catalyzed amine incorporation proceed via a common (enzyme-dependent) rate-determining step. The reaction of lysyl-modified enzymes (which show poor covalent binding with alpha 2M) was similarly unaffected by amine, indicating that enzyme-catalyzed steps were also rate determining for hydrolysis of the thiol ester. The products of the reactions were analyzed by native and denaturing gel electrophoresis. Methylamine did not affect the total binding of enzyme to alpha 2M but did cause a substantial decrease in covalent binding. Surprisingly, not all covalent complexes were affected by the presence of amine: complexes in which enzyme was covalently bound to one half-molecule increased compared to the reaction with no amine; complexes in which two half-molecules are cross-linked by two bonds to a single enzyme were substantially reduced, however. The results are consistent with a mechanism of reaction in which an enzyme-dependent step is rate determining. This step is accompanied by activation of two thiol esters. One of these reacts immediately with the bound enzyme (or may be hydrolyzed if the enzyme amine groups are blocked). The other activated center is capable of reaction with external nucleophiles such as methylamine.

Humans↗