Biomedical subjects

F Lee

Publications and source records attributed to F Lee.

At least 55 records · Page 3Linked to original sources

PubMed2001

Laparoscopic repair of incisional hernia.

A 75-year-old man developed an incisional hernia over the upper abdomen following a wedge resection of a gastric stromal tumour in 1996. This is the first published report of a successful repair of an incisional hernia via a laparoscopic intraperitoneal on-lay technique using GORE-TEX DualMesh material in Hong Kong. Compared with conventional open repair of incisional hernia, long incisions and wound tension are avoided using the laparoscopic approach. This translates into a reduced risk of wound-related complications and facilitates recovery. In selected cases, minimally invasive surgery is a safe technique for the repair of incisional hernias.

Aged↗

PubMed2000

Constitutive expression of functional 4-1BB (CD137) ligand on carcinoma cells.

Members of the TNF superfamily, including Fas, Fas ligand, and CD40, have been shown to be expressed on tumor cells. In the studies described in this work, we report that another family member, the ligand for 4-1BB (CD137), is expressed on various human carcinoma cell lines, on cells of solid tumors derived from these cell lines, and cells obtained from human tumors. Expression of 4-1BB ligand (4-1BBL) mRNA was detected by both RT-PCR and Northern blot analysis, and expression of 4-1BBL protein was detected by Western blot analysis of whole cell lysates and by FACS analysis of tumor cells and cell lines. Incubation of tumor cells with a 4-1BB-Ig fusion protein led to the production of IL-8 by the cells, demonstrating that the 4-1BBL is functionally active and signals back into the tumor cells. Furthermore, 4-1BBL expressed on the carcinoma cells functioned as a costimulatory molecule for the production of cytokines (most notably IFN-gamma) in cocultures of T cells and tumor cells. These findings suggest that 4-1BBL expressed on carcinoma cells may significantly influence the outcome of a T cell-tumor cell interaction.

4-1BB Ligand↗

PubMed2000

Signal transduction mechanisms linking increased extracellular calcium to proliferation in ovarian surface epithelial cells.

Although ovarian surface epithelial (OSE) cells are the cell type responsible for malignant ovarian carcinoma, relatively little is known about either the extracellular stimuli or the intracellular signaling mechanisms responsible for regulating proliferation in these cells. We have demonstrated that OSE cells proliferate in response to elevation of extracellular calcium and that OSE cells express functional calcium-sensing receptors (CaR). Here we show that agonists of the CaR increase the kinase activity of Src and ERKs (extracellular signal-regulated kinases) in rat OSE cells and promote association between tyrosine-phosphorylated Shc and p120rasGAP. Expression of an interfering mutant CaR inhibited the proliferative response to elevated extracellular calcium, as well as CaR agonist-induced tyrosine phosphorylation and ERK activation. Transfection with dominant negative mutants of Ras, Raf, and MKK1 also inhibited the increase in ERK activity in response to calcium, as did treatment with herbimycin, a selective inhibitor for Src family kinases. These results indicate that the ability of OSE cells to proliferate in response to increases in extracellular calcium involves cross-talk between the G-protein-coupled CaR and the activation of a tyrosine kinase-dependent Ras-Raf-ERK signaling pathway.

Amino Acid Substitution↗

PubMed2000

TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation.

We and others recently reported tumor necrosis factor (TNF) and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-1) as a novel member of the TNF ligand family that is functionally involved in B cell proliferation. Transgenic mice overexpressing TALL-1 have severe B cell hyperplasia and lupus-like autoimmune disease. Here, we describe expression cloning of a cell surface receptor for TALL-1 from a human Burkitt's lymphoma RAJI cell library. The cloned receptor is identical to the previously reported TNF receptor (TNFR) homologue transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). Murine TACI was subsequently isolated from the mouse B lymphoma A20 cells. Human and murine TACI share 54% identity overall. Human TACI exhibits high binding affinities to both human and murine TALL-1. Soluble TACI extracellular domain protein specifically blocks TALL-1-mediated B cell proliferation without affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro. In addition, when injected into mice, soluble TACI inhibits antibody production to both T cell-dependent and -independent antigens. By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6. Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation. The identification and characterization of the receptor for TALL-1 provides useful information for the development of a treatment for B cell-mediated autoimmune diseases such as systemic lupus erythematosus.

Amino Acid Sequence↗

PubMed2000

Patient satisfaction after ambulatory inguinal hernia repair in Hong Kong.

Ambulatory surgery was introduced to Asia in the 1990s. Acceptance of ambulatory surgery by oriental patients remains largely unknown. A telephone survey was conducted to evaluate the level of patient satisfaction following ambulatory inguinal hernia repair. A total of 157 patients (61%) completed the telephone survey. More than 90% of the respondents expressed satisfaction with regard to the pre-operative, operative and post-operative service. The majority of the respondents (>80%) preferred to undergo day surgery again in case of hernia recurrence. Our findings prove that ambulatory surgery has a high level of acceptance in Chinese patients and supports the expansion of a day surgery service in Hong Kong.

Journal Article↗

PubMed2000

Synthesis, structure proof, and biological activity of epothilone cyclopropanes.

[structure--see text] A semisynthetic route to epothilone cyclopropanes from epothilones A and B is described. Of significance, the deoxygenation of the 12, 13-epoxide to give the corresponding olefin was achieved with high efficiency. The title compounds (8, 9) were active in both tubulin polymerization and cytotoxicity assays, which is in direct contrast to a previously published report. These results provide further evidence that the role of the 12,13-epoxide of epothilones is largely conformational and argue against some of the current pharmacophore models.

Antineoplastic Agents↗

PubMed2000

Detection of novel NF2 mutations by an RNA mismatch cleavage method.

Mutations in the neurofibromatosis type 2 gene (NF2) cause benign nervous system tumors. Common methods for detecting NF2 mutations (such as single stranded conformational polymorphism analysis and denaturing gradient gel electrophoresis) are laborious and time-consuming. We adapted and improved a commercial assay, the Non-Isotopic RNase Cleavage Assay (NIRCAtrade mark, Ambion, Austin, TX) for rapid, non-isotopic, high-sensitivity screening for NF2 mutations in tumors. We improved the assay by: 1) extending the typical NIRCAtrade mark template size of < 500 bp to 1.3 kb without decreasing detection efficiency; 2) modifying the transcription step of the original protocol so that transcription of PCR products was increased by up to 50%; 3) optimizing the combination of cleavage enzymes and reaction time. With these modifications, mutations were found in 15 of 20 patients (75%) using NIRCAtrade mark. Seven of the point mutations detected (two nonsense, two missense, and three splice-site) are novel. All mutations were confirmed by direct sequencing and no mutations were found using direct sequencing in patients that were negative by NIRCAtrade mark. The 75% NF2 mutation detection rate using this design is similar to detection rates in tumors using other mutation detection methods.

Amino Acid Substitution↗

PubMed2000

MR imaging of simple bone cysts in children: not so simple.

OBJECTIVE: The unicameral bone cyst (UBC) is a common cystic bone lesion seen in children. We review and summarize its MR findings, focusing on their appearance following contrast enhancement, and correlating them to known histologic features of UBC. SUBJECTS AND METHODS: A retrospective review of 20 cases (13 boys, 7 girls; age range, 1-17 years; mean age, 8.9) diagnosed as UBC was conducted. Clinical histories, radiographic and MR features, follow-up data, and available pathologic findings were noted. RESULTS: At initial presentation 18 (90 %) of the patients with UBC had a history of acute or remote pathologic fracture. Cysts with history of fracture displayed heterogeneous fluid signals on T1-(n = 9, 50%), and T2-weighted (n = 15, 83 %) MR images. Gadolinium-enhanced images were obtained in 15 of the 18 UBC cases with history of previous fracture. All showed enhancement with focal, thick peripheral, heterogeneous, or subcortical patterns. Focal nodules of homogeneous enhancement (diameter > 1 cm) within the UBC (n = 5) correlated with areas of ground-glass opacification on plain film. Other interesting MR features were fluid-fluid levels (n = 11), "fallen-leaf" sign (n = 1), soft-tissue changes (n = 2), and detection of septations not seen on plain film (n = 2). CONCLUSION: UBCs frequently appear complicated on MR imaging, with heterogeneous fluid signals and regions of nodular and thick peripheral enhancement related to previous pathologic fracture and early healing.

Adolescent↗

PubMed2000

CD4(+) T cells kill HLA-class-II-antigen-positive melanoma cells presenting peptide in vitro.

PURPOSE: Most melanoma cell lines express HLA class II antigens constitutively or can be induced to do so with interferon gamma (IFNgamma). We have previously demonstrated that peptide-specific CD4(+) T cells proliferate in response to HLA-class-II-antigen-mediated peptide presentation by melanoma cells in vitro and produce interleukin-10 (IL-10) and (IFNgamma). We asked whether the responding T cells kill the tumor cells and, if so, whether direct cell contact was required. METHODS: Two HLA class II(+) melanoma cell lines derived from metastases were co-cultured with a human CD4(+) T cell clone specific for influenza hemagglutinin peptide (HA). T cells, melanoma, and HA were co-cultured for 48 h. Melanoma cells with and without HA and/or T cells served as controls. After 36 h, the medium was removed for cytokine analysis by enzyme-linked immunosorbent assay (ELISA). Twelve hours later non-adherent cells were washed away and the adherent melanoma cells were trypsinized and counted. Dual-chamber culture plates were used to determine whether cell contact and/or exposure to cytokine were required for tumor cell death. RESULTS: Melanoma cell counts were over 80% lower in wells containing T cells than in wells with melanoma and peptide alone (P < 0.05). ELISA of supernatants revealed production of IFNgamma and IL-10 by the responding T cells. Direct T cell contact with tumor cells was not required for tumor cell death, as melanoma cells were killed when they shared medium but had no contact with T cells responding to peptide presentation by HLA-class-II-antigen-positive melanoma cells in a separate chamber. Blocking antibody to IFNgamma but not IL-10 prevented melanoma cell death at levels of cytokine similar to that present in co-culture assays. CONCLUSIONS: Peptide-specific CD4(+) T cells kill melanoma cells in vitro when they recognize peptide presented by the tumor cell in the context of HLA class II antigen. Direct cell contact is not required, suggesting that it is a cytokine-mediated event. Immunotherapy, using primed CD4(+) T cells and peptide, may be beneficial in patients whose tumors express HLA class II antigens or can be induced to do so with IFNgamma.

Amino Acid Sequence↗

PubMed2000

PPARgamma: observations in the hematopoietic system.

Human Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) was originally cloned from a human bone marrow library. What role does this ligand activated transcription factor play in hematopoiesis and the immune system? We note that: a) PPARgamma has potential to interact/interfere or synergize with retinoid biology, b) fatty acids and a prostaglandin have been identified as ligands, and c) lymphocytes, monocytes and neutrophils use fatty acids as a major source of energy production, d) PPARgamma has been shown to oppose TNFalpha and down regulate cytokine production in monocytes. Therefore, we undertook a review of the literature and an expression survey of PPARgamma in a number of major organs and cells involved in the hematopoietic system, for the purpose of building a database towards understanding the role and function of PPARgamma gene regulation in the developing blood and immune systems. PPARgamma is expressed before mesodermal induction in tissue in and around Speymann's organizer in the xenopus blastocyst, in erythroid precursors of blood islands and in the circulation of the day 10.0 murine embryo, in human 19 week fetal liver, in some but not all murine and human bone marrow erythroid, myeloid, and monocytoid progenitors, bone marrow stromal cells and adipocytes, osteoblasts, endothelial cells, some T, and B lymphocytes, monocytes, macrophages, and other monocytic derivatives. It can be found in the cells of Peyer's patches, lymphoid follicles, spleen, and thymus. It is not clear if it is ever or transiently expressed in megakaryocytes, mast cells, or neutrophils. Based on the above data and a review of the literature, PPARgamma seems to play a role during the elicitation of immune responses. We propose PPARgamma may be involved in changes in energy states required during activation and development of many cell types involved, and has additional immunologically relevant effects in erythroid, myeloid, monocytic, T and B lymphocytic, stromal, and endothelial cell function.

Amino Acid Sequence↗

PubMed2000

Metastatic extragonadal seminoma associated with cardiac transplantation.

A 37-year-old man who had successfully undergone cardiac transplantation for dilated cardiomyopathy presented with a history of severe pain over his left shoulder, rib cage and thoracic spine. Clinical examination revealed the presence of bony tenderness over these sites, but there was no other clinical evidence of malignancy. Further investigations suggested the presence of multiple bony metastases. Bone biopsy revealed extensive bone marrow infiltration by large undifferentiated cells showing pronounced cytoplasmic vacuolation with a striking granulomatous reaction. Immunocytochemistry revealed these anaplastic cells to be cytokeratin and placenta-like alkaline phosphatase positive but S100, CD30 and lymphoid marker negative. Analyses by in situ hybridisation of these cells revealed no evidence of Epstein-Barr virus infection. Overall the pathology suggested a diagnosis of metastatic seminoma. Confirmation of this diagnosis was obtained by the analysis of serum human chorionic gonadotrophin which was elevated at 90 IU/l. In the absence of testicular or retroperitoneal disease, it is very likely that this unusual case of metastatic seminoma was related to the patient's immunosuppressive therapy, which at diagnosis included cyclosporin and prednisolone. The patient was successfully treated with cisplatin based chemotherapy and decreased immunosuppression and remains in complete remission one year after completion of chemotherapy. Seminoma is an uncommon complication of prolonged immunosuppression with very few cases being described in the literature post-organ transplantation. This case shows that the clinical presentation of this treatable tumour in this patient population can be unusual and difficult to diagnose.

Adult↗

PubMed2000

Measuring treatment outcome in a child and adolescent partial hospitalization program.

Mental health practitioners are increasingly being called upon to evaluate the effectiveness of the treatment they provide. The partial hospitalization component of the mental health industry has also felt this call for outcome research. This article presents the results of assessments of treatment outcome at a child and adolescent partial hospitalization program. The research design was an effectiveness study, a type of clinical outcome evaluation. Subjects were evaluated at admission and discharge, using the Revised Behavior Problem Checklist. The article is intended both to demonstrate the effectiveness of a partial hospitalization program and to provide an example of program evaluation that is easy and inexpensive to administer.

Adolescent↗

PubMed2000

Is the conservative management of ureteric calculi of > 4 mm safe?

OBJECTIVE: To determine the safety of the conservative management of ureteric calculi of > 4 mm in diameter, using mercapto-acetyltriglycine (MAG3) radioisotope renography to monitor renal parenchymal function. PATIENTS AND METHODS: Patients with symptomatic unilateral ureteric calculi were recruited prospectively. After confirming the position of the stone using contrast urography, a MAG3 radioisotope renogram was taken within 48 h of admission and again 1 month after the patients became stone-free. The indications for intervention were ipsilateral loss of function (>/= 5% loss), infection, pain or any combination of these factors. The recovery of function was determined by follow-up renography. RESULTS: In all, 54 patients were recruited; 18 were initially allocated to conservative treatment although four later required intervention for pain. The remainder required early intervention for pain (eight), diminished function only (15) or diminished function with infection (13). Of the 54 patients, 28% had 'silent' loss of renal function at presentation. No calculi of > 7 mm diameter passed without intervention. The mode of initial management was determined according to individual clinical need. The upper tracts of all patients were relieved of obstruction and all patients were rendered stone-free. Intervention for reduced function only (at </= 7 days) gave a significantly better (P = 0.03) recovery of function than those undergoing later intervention. The combination of reduced function and infection were unrelated to outcome after intervention. CONCLUSIONS: The conservative management of stones of 5-7 mm diameter is safe, providing that radioisotope renography is used to identify those renal units requiring intervention. This approach allows timely intervention to maximize the recovery of renal function.

Female↗

PubMed2000

Use of esophagectomy to treat recurrent hyperplastic tissue obstruction caused by multiple metallic stent insertion for corrosive stricture.

We report a case of a 75-year-old woman who received repeated metallic stent insertion for corrosive esophageal injury. She underwent esophagectomy and gastric tube reconstruction about 3 years after injury because both stents were occluded in turn by overgrowth of granulation tissue. The gross and microscopic changes of the esophagus secondary to prolonged stent insertion are described. In the literature, no reports of similar cases have been recorded. Our limited experience revealed that using metallic stents to treat benign esophageal stricture should be handled very cautiously because of the complications which can commonly occur and are difficult to manage. Repeated stent insertion, although effective for temporarily relieving dysphagia, is ineffective in the long run and can create complications. We suggest that the feasibility of esophagectomy should be evaluated after the improvement of the general condition of the patient.

Aged↗

PubMed2000

Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip.

We tested the hypothesis that a reduction in sympathetic tone to exercising forearm muscle would increase blood flow, reduce muscle acidosis, and attenuate reflex responses. Subjects performed a progressive, four-stage rhythmic handgrip protocol before and after forearm bier block with bretylium as forearm blood flow (Doppler) and metabolic (venous effluent metabolite concentration and (31)P-NMR indexes) and autonomic reflex responses (heart rate, blood pressure, and sympathetic nerve traffic) were measured. Bretylium inhibits the release of norepinephrine at the neurovascular junction. Bier block increased blood flow as well as oxygen consumption in the exercising forearm (P < 0.03 and P < 0.02, respectively). However, despite this increase in flow, venous K(+) release and H(+) release were both increased during exercise (P < 0.002 for both indexes). Additionally, minimal muscle pH measured during the first minute of recovery with NMR was lower after bier block (6.41 +/- 0.08 vs. 6.20 +/- 0.06; P < 0.036, simple effects). Meanwhile, reflex effects were unaffected by the bretylium bier block. The results support the conclusion that sympathetic stimulation to muscle during exercise not only limits muscle blood flow but also appears to limit anaerobiosis and H(+) release, presumably through a preferential recruitment of oxidative fibers.

Adult↗

PubMed2000

An audit of the early outcomes of ambulatory inguinal hernia repair at a surgical day-care centre.

Ambulatory surgery has been recently gaining popularity owing to the increasing constraints on public-sector health care resources. Inguinal hernia repair is one of the most common day-case operations. This study was conducted to audit the early outcomes of 271 consecutive day-case inguinal hernia repairs performed at the Day Surgery Centre of the Tung Wah Hospital from 1 December 1995 through 31 December 1998. No patients died on the day of their surgery; in 265 (97.8%) cases, patients were discharged home on the day of their operation. Two patients required readmission because of fever and urinary retention, and the postoperative morbidity rate was approximately 5% (14/271 cases). Wound complication was the most common morbidity encountered and pain was the most common discomfort experienced by patients at home. These results suggest that ambulatory hernia repair can be performed safely in a day centre and yields excellent early outcomes.

Adolescent↗

PubMed2000

Laparoscopic totally extraperitoneal inguinal hernioplasty: an audit of the early postoperative results of 100 consecutive repairs.

INTRODUCTION: With the establishment of a hernia specialist service at our medical centre in 1999, laparoscopic inguinal hernia repair was offered to all patients who presented with inguinal hernias. This is a report of our early experience of 100 consecutive laparoscopic totally extraperitoneal inguinal hernioplasties. MATERIALS AND METHODS: Between June 1999 and January 2000, a total of 82 patients with 100 inguinal hernias underwent laparoscopic totally extraperitoneal hernioplasties. The mean age of the study population was 64 +/- 16 (SD) years with a male to female ratio of 79:3. A prospective evaluation and analysis of perioperative outcomes were performed. RESULTS: A total of 97 laparoscopic extraperitoneal inguinal hernioplasties were successfully performed. Three patients required conversion to transabdominal preperitoneal repair because of adhesion (n = 1), large peritoneal defect (n = 1) and the presence of bowel within hernial sac (n = 1). There were no other intraoperative complications. Postoperative morbidity included retention of urine (n = 4), asymptomatic groin collection (n = 4) and wound bruising (n = 2). All complications resolved uneventfully. The visual analogue pain score at rest was 2, 1 and 1 on postoperative days 0, 1 and 2, respectively. The mean length of hospital stay was 2 +/- 1 (SD) days. Forty-seven patients (57%) returned to normal activities within one week. CONCLUSIONS: The early outcomes of laparoscopic extraperitoneal inguinal hernioplasties were encouraging. It confirmed the early success of laparoscopic repairs of inguinal hernias at our centre. Laparoscopic approach is a safe technique for repair of inguinal hernia in specialised centres.

Adult↗

PubMed2000

Cryosurgical ablation therapy for prostate cancer.

Adenocarcinoma of the prostate in the most common malignancy in men and still the leading cause of death from cancer in American men. Current data and published reports indicate that cryotherapy for clinically localized prostate cancer can be an effective treatment method in selective patients. Since 1993, 643 cryosurgical procedures have been performed, including 68 patients who failed radiation therapy, and 20 patients who failed initial cryotherapy. Recently developed targeted cryotherapy techniques, using 6-8 probes, shows promising initial results. The complication rates are also compared favorably to the established therapies for prostate cancer. It is a minimally invasive procedure with a high patient's acceptance rate. It is a highly operator-dependant procedure with a steep learning curve coupled with constantly evolving technology.

Adenocarcinoma↗