Biomedical subjects
Publications and source records attributed to C L Wu.
Two minor diterpenoids, 15(16)-peroxy-3, 13-clerodadien-18-oic acid (4) and totarol (7), were isolated from the liverwort Schistochila acuminata. The former is a further oxidized cyclic peroxide from the major component. The latter is a rearranged abietane alcohol which skeleton was found in liverworts for the first time.
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BACKGROUND AND PURPOSE: Invasive pulmonary aspergillosis (IPA) is usually an acute life-threatening infection in cancer patients receiving chemotherapy and in organ transplant recipients receiving immunosuppressive therapy. In some immunocompetent patients, IPA has a chronic and indolent clinical course. We compared the clinical patterns among IPA patients who had received recent intensive immunosuppressive therapy (RIIT) and those who had not (N-RIIT). METHODS: We reviewed the medical records of patients with a diagnosis of IPA made between 1992 and 1999. RIIT was defined as chemotherapy or high-dose corticosteroid therapy (at least 500 mg/d methylprednisolone, or equivalent, for at least 3 d) within 2 weeks before the onset of symptoms. RIIT patients were divided into those with and without malignancy. We compared clinical characteristics including age, sex, chest image patterns, diagnostic methods, culture results, treatment conditions, mortality, and recurrence rate in IPA patients: RIIT versus N-RIIT, and RIIT with and without malignancy. RESULTS: A total of 24 patients with IPA, 17 patients who had received RIIT and seven patients who had not (N-RIIT), were included. In the RIIT group, 11 patients had malignancy and six did not. No significant differences in gender, chest image patterns, diagnostic methods, and culture results were found between the RIIT and N-RIIT groups. The N-RIIT group was older and was treated significantly later after the onset of symptoms than the RIIT group (mean +/- standard deviation, SD, 89.43 +/- 129.47 vs 9.70 +/- 9.33 d, p = 0.018). Only one of the seven N-RIIT patients died, while nine of the 17 RIIT patients died (p = 0.08). Among the RIIT patients, five of the six without malignancy died, while four of the 11 patients with malignancy died. IPA recurred in seven of the eight RIIT patients, all of whom had malignancy, but in none of the six N-RIIT patients during a similar follow-up period (mean +/- SD, 16.3 +/- 18.9 vs 27.0 +/- 54.5 mo, p = 0.505). CONCLUSIONS: No differences were noted in image and culture studies between RIIT and N-RIIT IPA patients. RIIT IPA patients had acute and fulminant clinical courses, especially patients without malignancy, even though they received treatment with a mean duration of about 10 days starting from the onset of symptoms. All patients with malignancy undergoing further chemotherapy had recurrence of IPA. N-RIIT IPA patients had chronic clinical courses, a trend of lower mortality rate even with delayed diagnosis, and no recurrence.
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To know the clinical characteristics of male patients with systemic lupus erythema(SLE), the clinical and laboratory indications of 46 male SLE patients were analysed and compared with those of 269 females. The results showed that: 1. There was family history in 21.28% of male patients. 2. As compared with female SLE patients, pleurisy, pericarditis, lupus nephritis(LN), proteinuria, renal failure, the incidence of types, V-LN and the positive rate of Sm antibody were more common in males while facial erythema, Raynaud's phenomenon and photoallergy were less in male. There were statistical differences between the male and female. 3. The confirmed diagnosis for the male SLE was delayed. The recovery rate was lower and the mortality was higher in males. These findings suggest that evident genetic predisposition, atypical clinical manifestations, serious renal injury and the worse prognosis are the characteristics of male SLE.
This paper describes a new in vitro experimental model that records temperature changes over a culture plate, which then can be used to assess the biological effects of cryosurgery. A cryoprobe and 16 thermocouples set up by a computer control system were used to monitor the temperature changes during freezing and thawing in a culture plate, and the data were used to create a temperature profile of the entire plate. Location of the thermocouples was confirmed by a digital camera viewing from under the plate, and temperature changes at any point in the interpolated areas were estimated using a curve fitting method. The estimated temperature was checked by sampling with four additional randomly placed thermocouples. Linear regression analysis showed that the estimated temperature and measured temperature were very close (correlation coefficients 0.98-0.99). MBT-2 tumor cells were cultured and then subjected to simulated cryosurgery. The surviving cells were stained with crystal violet and the cell death boundary was detected by image processing. Temperature history at the cell death boundary was retrieved and analyzed. With this system it is possible to recreate the temperature changes that result in a certain biological effect (such as cell death) during the process of simulated cryosurgery.
The cytotoxicity of the dominant lignans and sesquiterpenoids from Taiwania (Taiwania cryptomerioides Hayata) was investigated. Three human tumor cells including A-549 lung carcinoma. MCF-7 breast adenocarcinoma and HT-29 colon adenocarcinoma were selected to illustrate the structure-cytotoxicity relationships of Taiwania's dominant compounds. Taiwanin A, taiwanin E and dimethylmatairesinol exhibited significant cytotoxicity against three human tumor cells. Among them, taiwanin A possesses the strongest cytotoxic activity. In addition, the morphology-based evaluation, flow cytometric analysis, and DNA fragmentation assays demonstrated that the tumor cell death induced by taiwanin A was due to apoptosis.
The ether extract of the Chilean liverwort Lepicolea ochroleuca yielded three sesquiterpenoids, ent-4 beta-Hydroxy-10 alpha-methoxyaromadendrane, ent-3 beta-Hydroxyspathulenol, and 1,10-Dioxotayloriane, as minor components. The major components were ledol and 13-epi-neoverrucosan-5 beta-ol, four other minor fusicoccanoids were identified.
OBJECTIVES: To report the results of a pilot study on the prognostic value of a newly identified actin-binding protein, thymosin beta-15 (Tbeta15), in predicting prostate-specific antigen (PSA) and bone failure in patients with Gleason 6/10 clinically localized prostate cancer. METHODS: Thirty-two patients (median age 70 years) with clinically localized, moderately differentiated (Gleason 6/10) prostate cancer treated by external beam radiotherapy alone (68.4 Gy) with available paraffin blocks at the Massachusetts General Hospital were evaluated for this pilot study. All patients had clinical Stage M0 disease at initial presentation, which was documented by bone scan (T1c-4,NX). Their corresponding biopsy specimens were stained immunohistochemically for Tbeta15, which was then correlated with the clinical outcome in a blinded manner. The median follow-up was 6 years (range 1 to 19) for all of the patients. RESULTS: The outcomes of the 32 patients can be grouped into three categories: patients with no evidence of disease (n = 11), patients with PSA failure without documented bone failure (n = 11), and patients with PSA failure and documented bone failure (n = 10). Tbeta15 staining intensity strongly correlated with clinical outcome. Of those patients whose specimens stained 3+ (strongest staining), 62% developed bone failure compared with 13% of those patients whose specimens stained 1+ (weakest staining) (P = 0.01). The 5-year freedom from PSA failure was only 25% for those patients with 3+ staining compared with 83% for those with 1+ staining (P = 0.02). CONCLUSIONS: The results of this pilot study have demonstrated that Tbeta15 staining intensity may be a potentially important marker to identify high-risk patients with moderately differentiated, clinically localized prostate cancer.
Although the development of outcomes research in perioperative medicine and anesthesiology has focused on traditional clinical outcomes, there seems to be a transition toward more global assessments of patient-related outcomes. Present trends in outcomes research and EBM may promise an improvement in individual patient and overall quality of care. New roles and opportunities in perioperative medicine and anesthesiology provide additional venues for outcomes research in this millennium.
Cyclin-dependent kinase 5 (Cdk5) is a small serine/threonine kinase that plays a pivotal role during development of the CNS. Cables, a novel protein, interacts with Cdk5 in brain lysates. Cables also binds to and is a substrate of the c-Abl tyrosine kinase. Active c-Abl kinase leads to Cdk5 tyrosine phosphorylation, and this phosphorylation is enhanced by Cables. Phosphorylation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity. Expression of antisense Cables in primary cortical neurons inhibited neurite outgrowth. Furthermore, expression of active Abl resulted in lengthening of neurites. The data provide evidence for a Cables-mediated interplay between the Cdk5 and c-Abl signaling pathways in the developing nervous system.
A patient with an epidural catheter for postoperative analgesia developed a stroke in association with a hypotensive episode resulting from a bolus of local anesthetic. After undergoing resection for femoral chondrosarcoma under epidural anesthesia, the patient received a continuous infusion of epidural morphine for postoperative analgesia. Lidocaine 1% (10 mL in divided doses) was administered through the catheter for breakthrough pain. The patient experienced a hypotensive episode and was noted to have a motor and cortical sensory deficit of the left arm and leg 8 hours after the hypotensive episode. Clinical presentation and subsequent workup were consistent with a watershed infarction. The patient recovered full neurologic function before discharge. Postoperative hypotension from epidural analgesia may be associated with stroke; however, a cause-and-effect relationship usually cannot be established with certainty.
UNLABELLED: Molecular cloning and sequence comparison indicates a high degree of structural homology between muscle nicotinic acetylcholine (nACh) and serotonin-type 3 (5-HT(3A)) receptors, both members of the direct ligand-gated family of ion channels. Because of the structural similarities and common evolutionary origin of these receptors, neuromuscular blockers (competitive nACh antagonists) may demonstrate pharmacologic cross talk and exhibit attributes of 5-HT(3A) receptor antagonists. We examined six clinically-used neuromuscular blockers for their ability to antagonize currents flowing through the 5-HT(3A) receptors in voltage clamped Xenopus oocytes. The neuromuscular blockers reversibly inhibited the 5-HT(3A) receptor-gated current in the rank order potency of (IC50 mean +/- SEM): d-tubocurarine (0.046 +/- 0.003 microM), atracurium (0.40 +/- 0.03 microM), mivacurium (15.1 +/- 2.93 microM), vecuronium (16.3 +/- 2.24 microM), and rocuronium (19.5 +/- 2.31 microM). Gallamine was essentially inactive as a 5-HT(3A) receptor antagonist with an extrapolated IC50 of 1170 microM. We demonstrate that drugs classically known as competitive nACh receptor antagonists also block 5-HT(3A) receptors. It is likely that certain neuromuscular blockers share pharmacological properties with 5-HT(3A) receptor antagonists, such as a reduction in postoperative nausea and vomiting. With careful drug selection, pharmacological cross talk could potentially be used to minimize polypharmacy and optimize patient management. IMPLICATIONS: Muscle nicotinic acetylcholine and serotonin-type 3A (5-HT(3A)) receptors are similar. Therefore neuromuscular relaxants may block 5-HT(3A) receptors. Our pharmacological study demonstrates that neuromuscular relaxants, as with ondansetron, are 5-HT(3A) receptor antagonists. It is likely that certain neuromuscular relaxants exhibit ondansetron-like clinical properties, such as reduction in postoperative nausea and vomiting.
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Platelet activation is involved in serious pathological situations, including atherosclerosis and restenosis. It is important to find efficient antiplatelet medicines to prevent fatal thrombous formation during the course of these diseases. Marchantinquinone, a natural compound isolated from Reboulia hemisphaerica, inhibited platelet aggregation and ATP release stimulated by thrombin (0.1 units mL(-1)), platelet-activating factor (PAF; 2 ng mL(-1)), collagen (10 microg mL(-1)), arachidonic acid (100 microM), or U46619 (1 microM) in rabbit washed platelets. The IC50 values of marchantinquinone on the inhibition of platelet aggregation induced by these five agonists were 62.0 +/- 9.0, 86.0 +/- 7.8, 13.6 +/- 4.7, 20.9 +/- 3.1 and 13.4 +/- 5.3 microM, respectively. Marchantinquinone inhibited thromboxane B2 (TxB2) formation induced by thrombin, PAF or collagen. However, marchantinquinone did not inhibit TxB2 formation induced by arachidonic acid, indicating that marchantinquinone did not affect the activity of cyclooxygenase and thromboxane synthase. Marchantinquinone did inhibit the rising intracellular Ca2+ concentration stimulated by the five platelet-aggregation inducers. The formation of inositol monophosphate induced by thrombin was inhibited by marchantinquinone. Platelet cAMP and cGMP levels were unchanged by marchantinquinone. The results indicate that marchantinquinone exerts antiplatelet effects by inhibiting phosphoinositide turnover.
Spontaneous esophageal perforation (Boerhaave's syndrome) is a rare clinical entity in which overindulgence in a large meal precedes vomiting and chest pain. Early diagnosis and aggressive management are keys to minimizing the morbidity and mortality. We report an unusual presentation of this already uncommon occurrence in a 33-year-old female. She presented to the Emergency Department with severe chest pain following vomiting with hematemesis after a large meal. The initial chest radiograph showed up nothing in particular. Dyspnea developed two days later, and a right-sided pleural effusion was seen on chest x-ray. Panendoscopy was highly suggestive of Boerhaave's syndrome. She underwent emergency operation. After three months of hospital care, she was discharged in relatively good condition. This case of right-sided pleural effusion extends the reported description of Boerhaave's syndrome.
This study, using the MBT-2 murine bladder tumor model, mainly investigated the role of interleukin-12 (IL-12) in the specific antitumor immune response of a tumor-bearing host when systemically administrated after surgery. Day 17 tumor-bearing mice (D17TBM) along with non-tumor bearing naive mice were treated with daily intraperitoneal (i.p.) injection of IL-12 (0.25 microg/mouse) from day 18 to day 24 for a total of 7 doses. Their splenocytes were obtained on Day 31 for natural killer cells (NK), lymphokine activated killer cells (LAK) and cytotoxic T lymphocyte (CTL) activity assay and lymphocyte subsets phenotypic analysis. The tumor suppression effect of systemic IL-12 administration was evaluated based on the tumor outgrowth of the higher number of tumor cells rechallenged 24 hours after resectioning of the primary tumor. After evaluation on Day 31, the result of in vitro cytotoxicity assay revealed that systemic administration of IL-12 mainly enhanced the splenic LAK and CTL activities in non-tumor-primed naive mice, and the NK activity in tumor-primed D17TBM, respectively. However, in vivo administration of IL-12 with or without IL-2 failed to upgrade the proportions of either CD4+ CD44+ or CD8+ CD44+ T cells subsets in the spleens and regional inguinal lymph nodes (LNs) of both the D17TBM and naive mice. However, the splenic CD8+ CD44+ T-cell subset in the IL-12-treated D17TBM increased prominently after further culturing in the presence of IL-2 400 units/ml plus IL-12 25 ng/ml for 4 days. The fact that systemic administration of IL-12 significantly suppressed the outgrowth of Day-18 challenged tumor cells, especially in D17TBM, clearly indicates that the established specific antitumor immunity in tumor-primed D17TBM was efficiently augmented. From the results of this study, we conclude that, after surgical resection of a primary tumor, systemic administration of IL-12 can be an effective adjuvant therapy because it demonstrates a significant augmentation effect on the tumor-specific immune response in the tumor-primed host.