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Biomedical subjects

C S Chen

Publications and source records attributed to C S Chen.

At least 145 records · Page 8Linked to original sources

Renal malacoplakia with secondary hepato-duodenal involvement.

Renal parenchymal malacoplakia is uncommon, and coexistence of extensive invasion into the liver and duodenum is extremely rare. Typically, there is an associated long-term urinary tract infection. We report on a 53-year-old woman with a history of diabetes and recurring pyelonephritis, who presented with a renal tumor and upper gastrointestinal bleeding. Surgical intervention included radical nephrectomy, lymphadenectomy, segmental hepatectomy, cholecystostomy, duodenorrhaphy, jejunostomy and appendectomy. There was no surgical morbidity. A pathologist confirmed the diagnosis of malacoplakia. All of the diagnostic criteria, including hematoxylin and eosin stain, iron stain, calcium stain and electron microscopy of Michaelis-Gutmann bodies, were classic. The literature is reviewed.

Duodenal Diseases↗

Deoxyribonucleic acid flow cytometric study in pheochromocytomas and its correlation with clinical parameters.

OBJECTIVES: To study deoxyribonucleic acid flow cytometry (DNA-FC) in pheochromocytomas and its correlation with clinical parameters. METHODS: Fifty cases of pheochromocytomas of a total of 58 cases were studied for DNA-FC from archival paraffin-embedded tissue blocks and were correlated with clinical parameters (ie, size of tumor, benign or malignant pathologic type, vanillymandelic acid [VMA] level in 24 hour urine, age, sex, duration of symptoms, symptom scores). RESULTS: A total of 19 cases were diploid while 31 cases (62%) showed DNA aneuploidy with 21 cases tetraploid. Four cases were malignant. All of them were tetraploid. However, among the 46 benign cases, 10 were aneuploid and 17 were tetraploid. All 19 cases with DNA diploidy were benign. The DNA-FC did not correlate with other clinical parameters in our study. CONCLUSIONS: We confirmed a high incidence of DNA aneuploidy in pheochromocytomas. All malignant pheochromocytomas were tetraploid and all cases with DNA diploidy were benign. Long-term follow-up of all cases, especially those with DNA aneuploidy (including tetraploidy), is mandatory.

Adrenal Gland Neoplasms↗

D-myo-inositol 1,4,5-trisphosphate analogues as useful tools in biochemical studies of intracellular calcium mobilization.

Two types of structural variants of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] were prepared by a chemoenzymatic route. These 6-O-substituted analogues retained the biological activity of Ins(1,4,5)P3, and were able to elicit Ca2+ release from porcine brain microsomes. Moreover, these derivatives allowed the preparation of Ins(1,4,5)P3-based immunogens and affinity matrix which were successfully applied to the preparation and purification of antibodies against Ins(1,4,5)P3. These antibodies displayed discriminative affinity towards Ins(1,4,5)P3, and provide a useful tool to study intracellular Ca2+ mobilization.

Animals↗

A drug dissolution monitor employing multiple fiber optic probes and a UV/visible diode array spectrophotometer.

A traditional dissolution pumping system was recently replaced with a fiber optic interface between the spectrometer and the samples. However, the system was limited to a single sample vessel. In this study, a dissolution testing system with six vessels connected to a diode array spectrometer via six optical fibers was investigated. A bifurcated fiber optic bundle was used to transfer the light from the source to the dissolution vessels and was networked so that spectra of each sample can be measured periodically. A full spectrum calibration method based on Principal Component Regression (PCR) was used to determine the concentrations of active ingredients and to account for interferences due to excipients in tablet formulations. Results on this new fiber optic interface system are compared with those obtained previously with the traditional pumping system. Standard errors of prediction are between 1.5 and 3.2% using cross-validation and between 1.1 and 1.7% for the direct validation of two active ingredients in two different drug formulations.

Calibration↗

Hidden Markov model approach to skill learning and its application to telerobotics.

In this paper, we discuss the problem of how human skill can be represented as a parametric model using a hidden Markov model (HMM), and how an HMM-based skill model can be used to learn human skill. HMM is feasible to characterize a doubly stochastic process--measurable action and immeasurable mental states--that is involved in the skill learning. We formulated the learning problem as a multidimensional HMM and developed a testbed for a variety of skill learning applications. Based on "the most likely performance" criterion, the best action sequence can be selected from all previously measured action data by modeling the skill as an HMM. The proposed method has been implemented in the teleoperation control of space station robot system, and some important implementation issues have been discussed. The method allows a robot to learn human skill in certain tasks and to improve motion performance.

Algorithms↗

Molecular rearrangements of the MLL gene are present in most cases of infant acute myeloid leukemia and are strongly correlated with monocytic or myelomonocytic phenotypes.

Cytogenetic studies have previously identified abnormalities of chromosome band 11q23 in many cases of infant acute leukemia. Recent studies by ourselves and others have demonstrated breakpoint clustering in acute leukemias bearing translocations involving 11q23, and a Drosophila trithorax gene homologue (called MLL, HRX, or ALL-1) has been shown to span the 11q23 breakpoints of these translocations. To determine if this gene is affected in infant acute myeloid leukemia (AML), we have analyzed 26 infant AML cases for molecular alterations of this 11q23 gene. 15 out of 26 cases studied (58%) showed rearrangement of the MLL gene at the molecular level, and these rearrangements were clustered within an approximately 11-kb region containing nine exons of this gene. Moreover, 14 of the 15 cases with 11q23 rearrangements (93%) had myelomonocytic or monocytic phenotypes (M4 or M5 FAB subtypes, respectively), both of which are associated with a poor prognosis in childhood AML. In contrast, only 1 of 11 nonrearranged cases had an M4 or M5 phenotype (P = 0.00002). Rearrangement also correlated significantly with hyperleukocytosis (P = 0.02), another clinical parameter associated with poor outcome in this disease. Our results demonstrate that molecular rearrangements of MLL are common in M4 or M5 infant AML, and suggest that alteration of this gene may result in abnormal control of proliferation and differentiation in monocytic progenitor cells.

Acute Disease↗

[Detection of serum anti-histone antibodies in patients with ankylosing spondylitis and its clinical significance].

Serum anti-total and subtypical histone antibodies were detected with ELISA and Western-Blotting in 78 ankylosing spondylitis (AS) and 38 gouty arthritis (GA) patients as well as in 45 normal subjects. The results showed that the positive rate of anti-histone antibodies (AHA) was about 5% in normal subjects or GA patients and 24.4% in AS patients. The mean level of AHAs was much higher in AS group than those in the controls. IgG- and IgM-AHA levels in AS patients during active stage were higher than in those during inactive stage. AHA levels were much more elevated in AS patients with present illness or past history of uveitis than in those without. The high levels of AHAs (especially anti-H3 antibody) were associated with uveitis in AS patients. The results suggested that the high level of AHAs might be a monitoring parameter for disease activity and occurrence of uveitis in patients with AS.

Adolescent↗

The effect of single bolus dose of esmolol for controlling the tachycardia and hypertension during laryngoscopy and tracheal intubation.

Tachycardia and hypertension usually accompany laryngoscopy and tracheal intubation. This response is undesirable, especially in patients with cardiovascular or intracranial diseases. Esmolol is a cardioselective, ultrashort-acting beta adrenergic blocking agent with a very short half-life. The efficacy of bolus dose of esmolol in blunting hemodynamic responses during laryngoscopy and tracheal intubation was evaluated. 45 patients (15 in each group) of ASA physical status I and II scheduled for elective non-cardiac surgery were included in this randomized, placebo-controlled study. At time zero, the study preparation (placebo, 100 or 200 mg of esmolol) was administered intravenously, followed by thiopentone 5 mg/kg and succinylcholine 1.5 mg/kg for induction. Tracheal intubation was performed 2 minutes after time zero. Anesthesia was maintained with 50% nitrous oxide and 1.0 MAC halothane in oxygen, and vecuronium 0.08 mg/kg. Heart rate (HR) and systolic blood pressure (SBP) were recorded every minute for 10 minutes. To compare with the placebo group, there was a significant decrease in either HR or SBP in 200 mg group in the 8 minutes course after intubation (p < 0.05). There was a significant decrease in HR in the 100 mg group at the 3rd, 4th, and 5th minutes when compared with the placebo group (p < 0.05). The differences in SBP between the 100 mg group and placebo group were significant at the 3rd and 4th minutes (p < 0.05). Both bolus dosages of esmolol could effectively attenuate the tachycardia and hypertension produced by laryngoscopy and tracheal intubation. Furthermore, esmolol 200 mg presented a better hemodynamic stability than esmolol 100 mg during induction of anesthesia.

Adrenergic beta-Antagonists↗

Assessment of ibuprofen-associated nephrotoxicity in renal dysfunction.

Ibuprofen-incurred nephrotoxicity in renal insufficiency was assessed by examining renal functional and pathological changes in rabbits with pre-existing renal failure after receiving consecutive doses of ibuprofen. The pharmacokinetic behavior of ibuprofen enantiomers in rabbits with renal dysfunction appeared to qualitatively parallel that of their human counterparts. Modifications of the pharmacokinetic profile occurred in a stereoselective fashion: (R)-ibuprofen disposition was independent of renal conditions, whereas (S)-ibuprofen clearance was significantly hampered. Pathological damage associated with ibuprofen use in renal dysfunction was evident from the renal necropsy specimens, which was characterized by tubular necrosis and interstitial nephritis. This animal model study indicates clearly that renal insufficiency is a causative factor for ibuprofen-induced interstitial nephritis. Moreover, based on the evidence of interstitial lymphocytic infiltration, this nephrotoxic syndrome is assumed to be a manifestation of a disordered cellular immunity.

Acute Kidney Injury↗

Stereoselective disposition of ibuprofen in patients with renal dysfunction.

Ibuprofen-induced acute renal failure is thought to occur in clinical conditions where maintenance of renal function is prostaglandin-dependent. In this study we used a pharmacokinetic approach to assess the predisposing factors for this therapeutic pitfall. The pharmacokinetics of ibuprofen enantiomers was examined after a single dose of 800 mg of racemic ibuprofen in three groups of subjects: A) patients with pre-existing renal failure (n = 10); B) patients with underlying disease states other than renal failure (n = 11); and C) age-matched healthy controls (n = 10). Most of the patients with renal insufficiency showed elevated plasma (S)-ibuprofen levels, higher area under plasma concentration vs. time curve for (S)-ibuprofen and increased area under plasma concentration vs. time curves for (S)-/(R)-ibuprofen ratios as compared with their healthy counterparts. It appeared that the extent of metabolic activation of (R)-ibuprofen to the (S)-isomer in renally compromised patients was greater than that in a normal setting. Consequently, in susceptible patients, reduced renal clearance coupled with concomitant metabolic inversion leads to elevated (S)-ibuprofen levels which may exacerbate the ischemic effect as a result of the accentuated blockage of prostaglandin synthesis.

Adult↗

Heterogeneity in MLL/AF-4 fusion messenger RNA detected by the polymerase chain reaction in t(4;11) acute leukemia.

We have designed a single polymerase chain reaction (PCR) primer pair that detects the MLL/AF-4 fusion mRNA encoded by the derivative 11 chromosome from t(4;11)(q21;q23) leukemia cells using the reverse transcriptase PCR technique. PCR amplification was possible in seven of seven cells studied. Sequencing of the amplified products showed three different breakpoints on 11q23 and three on 4q21, resulting in six unique fusion sequences. All fusion sequences maintained an open reading frame. The areas of the MLL and AF-4 genes that are conserved in all derivative 11 fusion RNAs and therefore likely to contribute to the function of the oncogenic fusion protein are centromeric regions of MLL through exon 6 (retaining the AT hook motif) and telomeric regions of AF-4 beginning at codon 491 (containing nuclear localization and GTP-binding motifs). A single primer pair was able to detect the derivative 11 fusion transcript in seven of seven cases of t(4;11) acute leukemia tested. Given the variability shown in specific fusion sequences, studies correlating differential exon usage with clinical parameters will require different fusion-specific oligonucleotides or PCR primer pairs.

Adolescent↗

Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product.

A chromosomal translocation, t(4;11)-(q21;q23), is associated with an aggressive mixed-lineage leukemia. A yeast artificial chromosome was used to clone the chromosomal breakpoint of this translocation in the RS4;11 cell line. The breakpoint sequences revealed an inverted repeat bordered by a consensus site for topoisomerase II binding and cleavage as well as chi-like elements. The der(11) chromosome encodes a fusion RNA and predicted chimeric protein between the 11q23 gene MLL and a 4q21 gene designated AF4. The sequence of the complete open reading frame for this fusion transcript reveals the MLL protein to have homology with DNA methyltransferase, the Drosophila trithorax gene product, and the "AT-hook" motif of high-mobility-group proteins. An alternative splice that deletes the AT-hook region of MLL was identified. AF4 is a serine- and proline-rich putative transcription factor with a glutamine-rich carboxyl terminus. The composition of the complete MLL-AF4 fusion product argues that it may act through either a gain-of-function or a dominant negative mechanism in leukemogenesis.

Amino Acid Sequence↗

The chromosome 4q21 gene (AF-4/FEL) is widely expressed in normal tissues and shows breakpoint diversity in t(4;11)(q21;q23) acute leukemia.

The chromosomal translocation, t(4;11)(q21;q23), is the most common type of 11q23 chromosomal abnormality, being highly prevalent in infant acute leukemias and associated with a poor prognosis. The t(4;11) results in the fusion of an 11q23 gene (MLL, HRX, Htrx-1, or ALL-1) and a 4q21 gene (AF-4 or FEL). To further evaluate the 4q21 gene and its role in t(4;11) acute leukemia, we have cloned a 38-kb genomic region and mapped exons of the AF-4 gene. The 4q21 breakpoints in 19 cases of t(4;11) acute leukemia were analyzed by Southern analysis and pulsed-field gels. Seventeen of the 19 cases had breakpoints on chromosome 4q21 that were scattered in this 38 kb region. Expression of the AF-4 gene was studied in a total of 28 various nonhematopoietic, hematopoietic, and t(4;11) leukemic cell lines. The AF-4 gene was expressed in all cell lines as a major and a minor transcript. In addition to the normal transcripts, two fusion transcripts from the derivative 11 and derivative 4 chromosomes were identified in all t(4;11) cell lines except B1, which had only the der(11) transcript. These findings suggest that the breakpoints on 4q21 cluster over a broader area than do the breakpoints in the 11q23 gene, and that der(11) encodes the fusion RNA found consistently in leukemia cells.

Acute Disease↗