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Biomedical subjects

J L Hsu

Publications and source records attributed to J L Hsu.

12 recordsLinked to original sources

Stereoselective synthesis of delta-lactones from 5-oxoalkanals via one-pot sequential acetalization, Tishchenko reaction, and lactonization by cooperative catalysis of samarium Ion and mercaptan.

By the synergistic catalysis of samarium ion and mercaptan, a series of 5-oxoalkanals was converted to (substituted) delta-lactones in efficient and stereoselective manners. This one-pot procedure comprises a sequence of acetalization, Tishchenko reaction and lactonization. The deliberative use of mercaptan, by comparison with alcohol, is advantageous to facilitate the catalytic cycle. The reaction mechanism and stereochemistry are proposed and supported by some experimental evidence. Such samarium ion/mercaptan cocatalyzed reactions show the feature of remote control, which is applicable to the asymmetric synthesis of optically active delta-lactones. This study also demonstrates the synthesis of two insect pheromones, (2S,5R)-2-methylhexanolide and (R)-hexadecanolide, as examples of a new protocol for asymmetric reduction of long-chain aliphatic ketones.

Acetylation↗

Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications.

Epstein-Barr virus (EBV), a ubiquitous B-lymphotrophic herpesvirus, has been found in the tumor cells of a heterogeneous group of malignancies (Burkitt's lymphoma, lymphomas associated with immunosuppression, other non-Hodgkin's lymphomas, Hodgkin's disease, nasopharyngeal carcinoma, gastric adenocarcinoma, lymphoepithelioma-like carcinomas, and immunodeficiency-related leiomyosarcoma). As the epidemiologic characteristics of these cancers have not been considered together, this review seeks to relate their incidence patterns and risk factors to EBV biology and virus-host interaction in an attempt to help elucidate factors involved in EBV-related carcinogenesis. We include a brief review of EBV virology and primary infection to provide a biologic context for considering the epidemiology, summarize the most salient epidemiologic features of each malignancy, synthesize epidemiologic data by risk factor to uncover commonalities and informative contrasts across the diseases, and propose hypotheses regarding etiologic mechanisms, based on the possible effect of the risk factors at various stages in the viral life cycle.

Animals↗

In vivo architecture of the manganese superoxide dismutase promoter.

Mitochondrial manganese superoxide dismutase (Mn-SOD) is the primary cellular defense against damaging superoxide radicals generated by aerobic metabolism and as a consequence of inflammatory disease. Elevated expression of Mn-SOD therefore provides a potent cytoprotective advantage during acute inflammation. Mn-SOD contains a GC-rich and TATA/CAAT-less promoter characteristic of a housekeeping gene. In contrast, however, Mn-SOD expression is dramatically regulated in a variety of cells by numerous proinflammatory mediators, including lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-1. To understand the underlying regulatory mechanisms controlling Mn-SOD expression, we utilized DNase I-hypersensitive (HS) site analysis, which revealed seven hypersensitive sites throughout the gene. Following high resolution DNase I HS site analysis, the promoter was found to contain five HS subsites, including a subsite that only appears following stimulus treatment. Dimethyl sulfate in vivo footprinting identified 10 putative constitutive protein-DNA binding sites in the proximal Mn-SOD promoter as well as two stimulus-specific enhanced guanine residues possibly due to alterations in chromatin structure. In vitro footprinting data implied that five of the binding sites may be occupied by a combination of Sp1 and gut-enriched Kr uppel-like factor. These studies have revealed the complex promoter architecture of a highly regulated cytoprotective gene.

Animals↗

Absence of Epstein-Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers.

Epstein-Barr virus (EBV), a ubiquitous herpesvirus associated with certain lymphomas and carcinomas, has been identified within the malignant cells of a small proportion of breast tumors. As breast cancer is a very common malignancy in women, a pathogenetic role of EBV for even a subgroup of patients could have important implications for etiology and prevention. Therefore, we attempted to confirm the EBV-breast cancer association by exploring it in a representative case series stratified by characteristics that modify breast cancer risk. We studied a sample of 97 female and 28 male patients identified from a US population-based cancer registry. Patients were selected randomly within age, sex, ethnicity and tumor estrogen-receptor status groups. With their archived tumor tissues, we examined EBV presence using in situ hybridization for the EBER-1 transcript. In the 107 technically adequate specimens, we did not detect this viral transcript in any tumors, including one from a woman who also had an EBER-positive nasopharyngeal carcinoma. Our uniformly negative findings are extremely unlikely to have occurred by chance and cannot be attributed to selective sampling, as our study group included persons at diverse risk for breast cancer. We conclude that the EBV EBER-1 transcript is not commonly expressed in breast cancer, based on a broadly representative case series, though we cannot exclude an association of EBV within a particular population subgroup.

Adult↗

Catalytic properties of human manganese superoxide dismutase.

The depletion of superoxide catalyzed by human manganese superoxide dismutase (MnSOD) was observed spectrophotometrically by measuring the absorbance of superoxide at 250-280 nm following pulse radiolysis and by stopped-flow spectrophotometry. Catalysis showed an initial burst of activity lasting approximately 1 ms followed by the rapid emergence of a greatly inhibited catalysis of zero-order rate. These catalytic properties of human MnSOD are qualitatively similar to those reported for MnSOD from Thermus thermophilus (Bull, C., Niederhoffer, E. C., Yoshida, T., and Fee, J. A.(1991) J. Am. Chem. Soc. 113, 4069-4076). However, there are significant quantitative differences; the emergence of the inhibited form is approximately 30-fold more rapid for human MnSOD. The turnover number for human MnSOD at pH 9.4 and 20 degrees C was kcat = 4 x 10(4) s-1 and kcat/Km = 8 x 10(8) M-1 s-1, determined by a simulated fit of the model of Bull et al. (1991) to the pulse radiolysis data. We also report that the maximum of the visible absorption spectrum of human MnSOD (epsilon480 = 525 M-1 cm-1) showed a strong dependence on pH that could be described by an ionization of pKa 9.4 +/- 0.1 with a maximum at low pH.

Base Sequence↗

[Pre- and intra-operative administration of epidural morphine provides good postoperative pain relief after laminectomy].

BACKGROUND: To evaluate the postoperative analgesic effect of epidural morphine administered at different timing in lumbar spine surgery. METHODS: Eighty-four patients who were scheduled for elective lumbar spine surgery were randomized in three groups. Seventeen patients in group I who received non-steroid analgesics postoperatively (diclophenac sodium 50 mg, iv, q4h) served as control while thirty-six patients in group II who received single dose epidural morphine 3 mg in combination with 10 ml 2% lidocaine given at the lesion site (L4-5 or L5-S1) just before general anesthesia and thirty-one patients in group III who received 3 mg morphine in combination with 3 ml 2% lidocaine administered to the targeted epidural space by means of slow drippings just before wound closure were studied subjects. RESULTS: During the first 24 h postoperatively, the patients in group II and group III suffered a pain which was significantly less in intensity as compared with those in group I (p < 0.05). We used the 10 cm visual analog pain score (VAS) to scale post-operative pain with "no pain" and "worst pain" respectively anchored at 0 and 10 cm. The incidence of side effects such as pruritus, nausea and vomiting was higher in group II and III than in group I. We did not evaluate the occurrence of urinary retention because routine retention urinary catheterization in all patients hampered us to do so. There were no significant differences in the quality and duration of analgesia between group II and III. Respiratory depression of clinical significance was not observed. Neither decrease in oxygen saturation below 92% registered on pulse oximetry nor decrease in respiratory rate below 12 cycles/min was found in the PACU. CONCLUSIONS: Preoperative or intraoperative administration of epidural morphine could provide satisfactory analgesia in lumbar spine surgery during the first 24 h postoperatively.

Adult↗

[Disseminated intravascular coagulation--a case report].

A 31 year-old T1PoAoL1 female developed the early Disseminated Intravascular Coagulation (DIC) signs after cesarean section. The patient had recovery completely after transabdomen total hysterectomy (TAH) and blood products transfusion. Case presentation, literature review, possible pathogenetic mechanism and treatment of DIC were discussed.

Adult↗

Rat copper/zinc superoxide dismutase gene: isolation, characterization, and species comparison.

A 13 kb rat Cu/ZnSOD genomic clone has been purified from a rat liver genomic library and completely characterized by restriction mapping, detailed sequencing and Southern blot analysis. This gene spans approximately 6 kb and contains five exons and four introns. Comparison of rat, mouse, and human Cu/ZnSOD genes reveals a high conservation in genomic organization and exon-intron junctions, including an unusual 5'GC donor sequence at the first intron. The gene contains a TATA box as well as an inverted CCAAT box, a feature common to both the mouse and human genes. Furthermore, several repeats were identified in the 5' promoter region of this gene, and these regulatory elements are also strikingly conserved in these three species.

Amino Acid Sequence↗

Multiple mRNA species generated by alternate polyadenylation from the rat manganese superoxide dismutase gene.

The mitochondrial enzyme, manganese superoxide dismutase (MnSOD) is an integral component of the cell's defense against superoxide-mediated cellular damage. We have isolated and characterized four cDNA clones and the structural gene for rat MnSOD. Northern analyses using MnSOD cDNA probes detected at least five mRNAs in all tissues and cell types examined. Southern and Northern analysis using a 3' non-coding sequence probe, common to all the cDNAs, showed hybridization only to genomic restriction fragments that correspond to our genomic clone and the five MnSOD mRNAs. These data demonstrate that all of the rat MnSOD transcripts are derived from a single functional gene. Primer extension data indicate that transcription initiation is clustered within a few bases. Northern analysis using intron probes demonstrates that all five transcripts are fully processed. Northern analysis using cDNA and genomic probes from sequences progressively 3' to the end of the coding sequence indicates that size heterogeneity in the MnSOD transcripts results from variations in the length of the 3' non-coding sequence. From this data and the location of potential polyadenylation signals near the expected sites of transcript termination, we conclude that the existence of multiple MnSOD mRNA species originate as the result of alternate polyadenylation.

Animals↗

[Effects of lidocaine cervical epidural blockade on respiratory function].

Cervical epidural anesthesia with 2% lidocaine has been shown to reduce ventilatory capacity in patients with normal lungs by Dr. Bromage. It is important to evaluate the respiratory effect of this technique which may induce intercostal and phrenic nerve paralysis. After institutional approval and informed content had been obtained, 50 patients undergoing OR & IR of upper limbs, mean age 24 +/- 4 yrs mean weight 65 +/- 6 kg, ASA status I-II without preoperative pulmonary dysfunction were studied. C7-T1 intervertebral space was identified by the hanging-drop technique using a 16G Tuochy needle. A catheter was inserted cranially to a distance of 12 cm. Pulmonary function measurement and arterial blood gas data were obtained before and 20', 50', 105' min after injection of 12 ml 2% plain lidocaine. The anesthesia levels were between C3-T3 and obtained at 13 +/- 2 min. Mean arterial blood gas analysis showed mild respiratory acidosis at 20 min (PaCO2: 46.0 +/- 3.5 mmHg). The measured values of IVC, VC, FVC, FEV1, PEF, when compared with control values were decreased over 15.60% of control values and 20% of predicted data at 20 min. The ratio of FEV1/VC, FEV1/FVC were still within normal limit (greater than 80%). The result was significantly compatible to the criteria of mild type of pulmonary function test. No respiratory distress was complained of and only cause little change of arterial blood gas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hepatitis type B virus DNA in patients receiving hemodialysis: correlation with other HBV serological markers.

Possible presence of hepatitis type B virus (HBV) was assessed in 239 end-stage renal failure patients who were receiving long-term maintenance hemodialysis (average 30.8 months; duration: 1-94 months), and who had not shown any other symptom of HBV infection. Their HBV serological markers, including HBV DNA, were evaluated together with those of normal control individuals. HBV surface antigen (HBsAg) was detected in 42 of the 239 dialysis patients, 15 of whom also positive for HBV DNA (mean +/- SD = 56.2 +/- 23.7 pg/100 microliters of serum). HBV DNA was also found in 22 of the 197 (11.2%) dialysis patients who were negative for HBsAg, with an average of 36.2 +/- 19.0 pg/100 microliters of serum. This rate of detecting HBV DNA in HBV seronegative dialysis individuals was significantly higher than the rate of 1.83% found among healthy HBsAg(-) individuals. Among these 22 dialysis patients who were HBsAg(-) but HBV DNA(+), 15 were found to possess antibodies against HBsAg (anti-HBs) and/or antibody against HBV e antigen (anti-HBe). These data suggested that the absence of serum HBV antigen or the presence of antibodies against HBV markers might not be sufficient to identify possible HBV infection in immunocompromised hosts such as hemodialysis patients.

Adult↗