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Biomedical subjects

J Wong

Publications and source records attributed to J Wong.

At least 199 records · Page 11Linked to original sources

The significance of serum levels of insulin-like growth factor-1 in patients with prostate cancer.

OBJECTIVES: To compare the serum levels of insulin-like growth factor-1 (IGF-1) in patients with prostate cancer and in control patients with no malignancy, and to evaluate any possible influence of testicular androgen withdrawal on the level of IGF-1 in patients with prostate cancer. PATIENTS AND METHODS: IGF-1 was measured in serum samples from 238 patients using both a chemiluminescence method and a radio-immunoassay. From a subgroup of 19 patients presenting with newly diagnosed carcinoma of the prostate, IGF-1 and testosterone values were measured before and during the course of testicular androgen withdrawal, achieved by the administration of luteinizing hormone-releasing hormone (LHRH) analogues combined with anti-androgens. RESULTS: There were no significant differences in the mean serum levels of IGF-1 patients with and without prostate cancer (158.6 and 159.1 ng/mL, respectively). There were no significant differences in mean IGF-1 levels before and after antiandrogen therapy; the mean (median, SD, range) levels of testosterone (microg/L) and IGF-1 (ng/mL) before androgen withdrawal were 4.81 (4.84, 1.26, 3.11-6.93) and 157.1 (152.5, 26.7, 122.8-195. 1). After androgen withdrawal the corresponding values were 0.303 (0. 218, 0.24, 0.13-0.81) and 169.7 (31.7, 168.6, 124.9-227.6). A linear regression analysis (P = 0.76) and Spearman rank order correlation test (correlation coefficient -0.0613, P = 0.64) showed no association between levels of testosterone and IGF-1. Freeze and thaw cycles applied to the samples had no effect on the IGF-1 values measured. CONCLUSIONS: There was no significant association between IGF-1 serum levels and prostate cancer. Short-term androgen withdrawal using LHRH analogues combined with anti-androgens had no effect on the levels of IGF-1.

Aged↗

The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives.

The purpose of this study was to determine the prevalence of BRCA1 mutations in Chinese breast cancer patients in Singapore. BRCA1 analysis was conducted in consecutive patients with breast cancer before the age of 40 years (76 women), or whose relatives had breast or ovarian cancer (16 women). Ten patients had both early onset breast cancer and affected relatives. Genomic DNA from peripheral mononuclear blood cells was studied by using the protein transcription-translation assay (exon 11) and single-strand conformational polymorphism, with subsequent DNA sequencing. All six disease-causing mutations occurred in women under 40 years (8.6%) with three occurring in patients under 35 years (three out of 22 patients, 13.6%). Mis-sense mutations of unknown significance were found in three patients. Two of the ten women with affected relatives under 40 years had BRCA1 mutations. The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer is similar to that observed in Caucasian women. Most Chinese patients with affected relatives were not carriers of BRCA1 mutations.

Adult↗

Adjunctive donepezil in attention deficit hyperactivity disorder youth: case series.

Despite well-documented improvement in attention deficit hyperactivity disorder (ADHD) in youths with the available single and combined pharmacologic agents, a number of youths remain with residual symptomatology causing impairment in multiple domains. Recent work has suggested a potential cognitive-enhancing role of cholinergic agents in ADHD. We describe five cases of ADHD youths aged 8-17 years being treated for ADHD with the acetylcholinesterase inhibitor donepezil (Aricept), all of whom demonstrated improvement.

Adolescent↗

A B220(-), CD19(-) population of B cells in the peripheral blood of quasimonoclonal mice.

We describe a new population of non-naive B cells in the peripheral blood of quasimonoclonal (QM) mice. Surface Ig of switched isotypes is expressed, but not B220 nor CD19. These cells are larger and denser than naive B cells but smaller than blasts or plasma cells; they do not stain with syndecan, a marker for plasma cells. Telomerase, which is usually expressed in B cell blasts, was not present in this population. We sorted the switched, idiotype-positive, B220(-) B cells from the peripheral blood of QM mice and sequenced Ig H chain and lambda L chain cDNA. There were many point mutations but no V gene replacements, gene conversions or other type of diversifications. As they express switched isotypes and have mutated their Ig genes, cells in the B220(-), CD19(-) population must have been in an immune response and we suggest that it includes the memory B cell subset.

Amino Acid Sequence↗

Follicular development and atresia in the B6.Y(TIR) sex-reversed mouse ovary.

The B6.Y(TIR) mouse fails to develop normal testes despite transcription of Sry, the primary testis-determining gene on the Y chromosome. Consequently, B6.Y(TIR) fetuses with bilateral ovaries develop into apparently normal but infertile females. This infertility can be mainly attributed to oocyte incompatibility for postfertilization development. In addition, abnormality in preovulatory follicles and rapid loss of oocytes have been observed in XY ovaries. This study examined the effect of gonadotropins on follicular development and atresia in B6.Y(TIR) prepubertal females. The results show that untreated XY females had fewer late preantral follicles and their frequency of atresia was lower. No other difference was found when they were compared with XX females. After treatment with gonadotropins for 24 h, frequency of atresia decreased in both XX and XY ovaries. After 48 h, most preovulatory follicles in XY ovaries were nonatretic, but the oocytes often were denuded. Immunocytochemical staining for connexin 43 detected punctate foci along the oocyte plasma membrane. The density of these foci changed during follicular development, which was similar in XX and XY ovaries. In conclusion, follicular development and atresia under the control of gonadotropins is not influenced by defective oocytes until the preovulatory phase.

Animals↗

Significance of resection margin in hepatectomy for hepatocellular carcinoma: A critical reappraisal.

OBJECTIVE: To evaluate the influence of the width and histologic involvement of the resection margin on postoperative recurrence after resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The significance of the resection margin in hepatectomy for HCC remains controversial. A precise evaluation of the effects of the width and histologic involvement of the resection margin on postoperative recurrence is required to clarify the issue. METHODS: Two hundred eighty-eight patients with macroscopically complete resection of HCC were divided into groups with narrow (<1 cm) or wide (>/=1 cm) resection margins. The two groups were compared for postoperative recurrence rate and pattern of recurrence. A further analysis was performed to investigate the effects of histologic involvement of the resection margin on postoperative recurrence. RESULTS: Recurrence rates were similar between 150 patients with a narrow margin and 138 patients with a wide margin; the groups were comparable in other clinicopathologic variables. Most recurrent tumors occurred in the liver remnant at a segment distant from the resection margin or at multiple segments. Thirty-four patients had margin involved histologically by microscopic invasion from the main tumor (n = 13), venous tumor thrombi (n = 13), or microsatellites separate from the main tumor (n = 8). These patients had significantly higher recurrence rates than those with a histologically clear margin. However, a positive histologic margin was not a significant risk factor for recurrence by multivariate analysis. Tumor stage and perioperative transfusion were the only independent risk factors. CONCLUSIONS: The width of the resection margin did not influence the postoperative recurrence rates after hepatectomy for HCC. A positive histologic margin was associated with a higher incidence of postoperative recurrence, but in most patients this was related to the underlying venous invasion or microsatellites. Most intrahepatic recurrences were considered to arise from intrahepatic metastasis by means of venous dissemination, which a wide resection margin could not prevent.

Aged↗

Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma.

OBJECTIVE: To evaluate the current knowledge on the risk factors for recurrence, efficacy of adjuvant therapy in preventing recurrence, and the optimal management of recurrence after resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The long-term prognosis after resection of HCC remains unsatisfactory as a result of a high incidence of recurrence. Prevention and effective management of recurrence are the most important strategies to improve the long-term survival results. METHODS: A review of relevant English articles was undertaken based on a Medline search from January 1980 to July 1999. RESULTS: Pathologic factors indicative of tumor invasiveness such as venous invasion, presence of satellite nodules, large tumor size, and advanced pTNM stage, are the best-established risk factors for recurrence. Active hepatitis activity in the nontumorous liver and perioperative transfusion also appear to enhance recurrence. Recent molecular research has identified tumor biologic factors such as the proliferative and angiogenic activities of the tumor as new risk factors for recurrence. There is a lack of convincing evidence for the efficacy of neoadjuvant or adjuvant therapy in preventing recurrence. Retrospective studies suggested that postoperative hepatic arterial chemotherapy might improve disease-free survival, but results were conflicting. For the management of postoperative recurrence, studies have consistently indicated that surgical resection should be the treatment of choice for localized recurrence, be it in the liver remnant or extrahepatic organs. Transarterial chemoembolization and percutaneous ethanol injection are widely used to prolong survival in patients with unresectable intrahepatic recurrence, and combined therapy with these two modalities may offer additional benefit. CONCLUSIONS: Knowledge of the risk factors for postoperative recurrence provides a basis for logical approaches to prevention. Minimal surgical manipulation of tumors to prevent tumor cell dissemination, avoidance of perioperative blood transfusion, and suppression of chronic hepatitis activity in the liver remnant are strategies that may be useful in preventing recurrence. The efficacy of postoperative adjuvant regional chemotherapy deserves further evaluation. New concepts on the influence of tumor biologic factors such as angiogenic activity on recurrence of HCC suggest a potential role of novel approaches such as antiangiogenesis for adjuvant therapy in the future. Currently, the most realistic approach in prolonging survival after resection of HCC is early detection and aggressive management of recurrence. Randomized trials are needed to define the roles of various treatment modalities for recurrence and the benefit of multimodality therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Anterior approach for major right hepatic resection for large hepatocellular carcinoma.

OBJECTIVE: To report the surgical and long-term outcomes of major right hepatic resection for large hepatocellular carcinoma (HCC) using the anterior approach compared with the conventional approach. SUMMARY BACKGROUND DATA: Great difficulty can be encountered during major right hepatic resection for large HCC using the conventional approach. Forceful retraction during mobilization of the tumor might result in serious complications, including dissemination of cancer cells, iatrogenic tumor rupture, and excessive bleeding, leading to unfavorable surgical and long-term outcomes. METHODS: In patients who had large HCC at the right lobe of liver and underwent major hepatic resection, the technique of anterior approach was used. After hilar control of the inflow blood vessels and without prior mobilization of the right lobe of liver and the tumor, parenchymal transection was performed using an ultrasonic dissector from the anterior surface of the liver until the anterior surface of the inferior vena cava was exposed. All venous tributaries, including the right hepatic vein, were controlled before the right lobe of liver was mobilized. Surgical and long-term outcomes were analyzed retrospectively and compared with patients who underwent surgery using the conventional approach. RESULTS: From 1989 to 1997, the anterior approach was used for major right hepatic resection in 54 patients with HCC of 5 cm or more in diameter. When compared with the 106 patients with similar clinical parameters who underwent hepatic resection using the conventional approach during the same period, the patients in the anterior approach group had significantly less intraoperative blood loss and blood transfusion, a lower hospital death rate, a lower incidence of pulmonary metastases, and a better median disease-free survival and median overall cumulative survival. CONCLUSION: The anterior approach is the preferred technique for major right hepatic resection for large HCC because it resulted in improved surgical and survival outcomes compared with the conventional approach.

Adolescent↗

Esophageal cancer.

Papers published in the English literature on esophageal cancer in 1999 were retrieved by a MEDLINE search. Selective publications were reviewed in light of current knowledge. Many studies were performed to refine staging methods of esophageal cancer, especially in the use of endoscopic ultrasound. Although better designs have overcome the problem of nontraversable tumors, its use in staging after neoadjuvant therapies remains suboptimal. Important studies on various surgical techniques were reported, including randomized trials on different routes of reconstruction after esophageal extirpation, and the updated results of transhiatal resections. In contrast to the minimalist approach of transhiatal resection, investigators from both East and West have also described the pathologic basis of lymphatic spread of esophageal cancer and its implications, favoring more radical lymphadenectomy. Another avenue that was explored is the use of neoadjuvant therapies to improve outcome. Different regimens were studied, and many papers focused on the molecular prediction of favorable response to such therapies. Overenthusiastic adoption of multimodality treatments is cautioned, however, in that they have not been validated. Further work is much needed in this area of research.

Journal Article↗

Treatment of advanced hepatocellular carcinoma with tamoxifen and the correlation with expression of hormone receptors: a prospective randomized study.

OBJECTIVES: A prospective randomized study was performed to test the hypothesis that tamoxifen might improve the survival of patients with advanced hepatocellular carcinoma (HCC) and to correlate the response of treatment with the expression of hormone receptors. METHODS: One hundred nineteen patients with advanced and otherwise untreatable HCC were included in a placebo-controlled, single-blind trial. The patients were randomized to tamoxifen group (61 patients) and control group (58 patients) and were prescribed with a daily dose of 30 mg of tamoxifen and placebo, respectively. Immunohistochemical tests for estrogen and progesterone receptors were performed on the tumor tissues obtained from 66 patients. All patients were closely monitored and the survival outcome of the two groups of patients was compared and stratified according to the hormonal receptor status. RESULTS: There was no difference in the 1-month mortality rates (32.8% vs. 43.1%, p = 0.246) and the median survival (44 days vs. 41 days, p = 0.703) between the tamoxifen group and the control group. Furthermore, the expression of hormone receptors in the tumors did not affect the survival outcome of the patients treated with tamoxifen. None of the patients who survived longer than 3 months had tumor that had partial response to tamoxifen treatment on follow-up imaging study. CONCLUSIONS: Tamoxifen has no efficacy in the treatment of patients with advanced HCC and response to treatment was not affected by the expression of hormone receptors.

Adult↗

Estimating the dose variation in a volume of interest with explicit consideration of patient geometric variation.

A method to measure the effects of internal organ motion and deformation and patient setup error on cumulative dose variation in a volume of interest is proposed. The method uses multiple CT scans and electronic portal images of a single patient to numerically simulate dose-volume effects over the entire course of the patient's external beam treatment. The results are expressed in the form of a novel dose-volume histogram, called an expected dose-volume histogram (EDVH).

Humans↗

Activation of p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase by double-stranded RNA and encephalomyocarditis virus: involvement of RNase L, protein kinase R, and alternative pathways.

Double-stranded RNA (dsRNA) accumulates in virus-infected mammalian cells and signals the activation of host defense pathways of the interferon system. We describe here a novel form of dsRNA-triggered signaling that leads to the stimulation of the p38 mitogen-activated protein kinase (p38 MAPK) and the c-Jun NH(2)-terminal kinase (JNK) and of their respective activators MKK3/6 and SEK1/MKK4. The dsRNA-dependent signaling to p38 MAPK was largely intact in cells lacking both RNase L and the dsRNA-activated protein kinase (PKR), i. e., the two best-characterized mediators of dsRNA-triggered antiviral responses. In contrast, activation of both MKK4 and JNK by dsRNA was greatly reduced in cells lacking RNase L (or lacking both RNase L and PKR) but was restored in these cells when introduction of dsRNA was followed by inhibition of ongoing protein synthesis or transcription. These results are consistent with the notion that the role of RNase L and PKR in the activation of MKK4 and JNK is the elimination, via inhibition of protein synthesis, of a labile negative regulator(s) of the signaling to JNK acting upstream of SEK1/MKK4. In the course of these studies, we identified a long-sought site of RNase L-mediated cleavage in the 28S rRNA, which could cause inhibition of translation, thus allowing the activation of JNK by dsRNA. We propose that p38 MAPK is a general participant in dsRNA-triggered cellular responses, whereas the activation of JNK might be restricted to cells with reduced rates of protein synthesis. Our studies demonstrate the existence of alternative (RNase L- and PKR-independent) dsRNA-triggered signaling pathways that lead to the stimulation of stress-activated MAPKs. Activation of p38 MAPK (but not of JNK) was demonstrated in mouse fibroblasts in response to infection with encephalomyocarditis virus (ECMV), a picornavirus that replicates through a dsRNA intermediate. Fibroblasts infected with EMCV (or treated with dsRNA) produced interleukin-6, an inflammatory and pyrogenic cytokine, in a p38 MAPK-dependent fashion. These findings suggest that stress-activated MAPKs participate in mediating inflammatory and febrile responses to viral infections.

Animals↗

p300 requires its histone acetyltransferase activity and SRC-1 interaction domain to facilitate thyroid hormone receptor activation in chromatin.

We have characterized the mechanism by which coactivator p300 facilitates transcriptional activation mediated by the heterodimer of thyroid hormone (T3) receptor and 9-cis retinoid acid receptor (TR-RXR) in the context of chromatin. We demonstrate that, while p300 can enhance the transcriptional activation mediated by both liganded TR-RXR and GAL4-VP16, its histone acetyltransferase activity (HAT) is required for its ability to facilitate liganded TR-RXR- but not GAL4-VP16-mediated transcriptional activation. To understand how p300 is recruited by liganded TR-RXR, we have analyzed the interactions between TR-RXR and p300 as well as SRC-1 family coactivators. We show that, in contrast to a strong hormone-dependent interaction between TR-RXR and SRC-1 family coactivators, p300 displays minimal, if any, T3-dependent interaction with TR-RXR. However, p300 can be recruited by liganded TR-RXR through its interaction with SRC-1 family coactivators. Consistent with the protein-protein interaction profile described above, we demonstrate that the SRC-1 interaction domain of p300 is important for its ability to facilitate transcriptional activation mediated by TR-RXR, whereas its nuclear receptor interaction domain is dispensable. Collectively, these results reveal the functional significance of the HAT activity of p300 and define an indirect mode for the action of p300 in TR-RXR activation.

Acetyltransferases↗

Can traumatic brain injury cause psychiatric disorders?

Traumatic brain injury (TBI) may cause psychiatric illness. This article reviews the evidence on the basis of an established set of causation criteria. The evidence is convincing for a strong association between TBI and mood and anxiety disorders. Substance abuse and schizophrenia are not strongly associated with TBI, and there is little research into the rates of personality disorders after TBI. Evidence for a biologic gradient is lacking, but such a gradient may not be relevant to TBI. Evidence for the correct temporal sequence is present. Preliminary evidence suggests a biologic rationale for TBI causing psychiatric illness. Further and methodologically improved research is supported and required.

Brain↗

Long-term prognosis after resection of hepatocellular carcinoma associated with hepatitis B-related cirrhosis.

PURPOSE: The optimum management of hepatocellular carcinoma (HCC) associated with cirrhosis has not yet been clarified. Very few data are available in the literature regarding the prognosis after resection of HCC associated with hepatitis B virus (HBV)-related cirrhosis. This study evaluated the long-term results and prognostic factors after resection of HCC complicating HBV-related cirrhosis. PATIENTS AND METHODS: One hundred forty-six patients with HBV-related Child's A or B cirrhosis who had undergone resection of HCC over a 10-year period were prospectively studied for long-term results. They were compared with 155 noncirrhotic patients with HBV-related HCC resected in the same period. RESULTS: The overall survival results of cirrhotic patients after resection of HCC were comparable to those of noncirrhotic patients (5-year survival, 44.3% v 45.6%, respectively; P =.216), but the former group had significantly smaller tumors. Stratified according to tumor size, the survival results were similar between cirrhotic and noncirrhotic patients with tumors </= 5 cm (5-year survival, 60.7% v 61.7%, respectively; P =.327) but were worse in cirrhotic compared with noncirrhotic patients with tumors greater than 5 cm (5-year survival, 27.8% v 39.5%, respectively; P =.034). Stage by stage, there were no significant differences in survival results between cirrhotic and noncirrhotic patients. Preoperative serum AST level greater than 100 IU/L (P =.004), perioperative transfusion (P =.015), and venous invasion (P <.001) were independent adverse prognostic factors. CONCLUSION: The prognosis after resection of HCCs less than 5 cm in patients with compensated HBV-related cirrhosis was comparable to that of noncirrhotic patients, which suggests that surgical resection may be considered a first-line treatment for these patients. Patients with underlying active hepatitis as indicated by a high preoperative transaminase level are less favorable candidates for resection. Further studies are needed to define the relative roles of resection and transplantation for HCC associated with hepatitis B cirrhosis.

Carcinoma, Hepatocellular↗

Intrathoracic Kaposi's sarcoma in women with AIDS.

STUDY OBJECTIVE: To describe the radiographic features of intrathoracic Kaposi's sarcoma in women with AIDS. SUBJECTS AND METHODS: From 1987 to 1998, we identified seven women with biopsy-proven (n = 4) or autopsy-proven (n = 3) pulmonary Kaposi's sarcoma. Charts were reviewed for HIV risk factors, cutaneous and/or oropharyngeal Kaposi's sarcoma, CD4 cell count, and differential diagnosis of pulmonary disease prior to the diagnosis of pulmonary Kaposi's sarcoma. Chest radiographs (n = 6), chest CT scans (n = 3), and reports of unavailable chest radiograph (n = 1) closest to the time of diagnosis of pulmonary Kaposi's sarcoma were reviewed for the following: nodular and peribronchovascular opacities; thickened interlobular septa; pleural effusions; lymphadenopathy; and radiographic stage. RESULTS: Mean patient age was 33 years (range, 27 to 42 years). HIV risk factors were IV drug use (n = 2), heterosexual contact (n = 3), and both (n = 2). All patients had prior opportunistic infections. The median CD4 cell count was 18 /microL (mean, 63/microL; range, 5 to 210/microL). Cutaneous Kaposi's sarcoma was diagnosed prior to pulmonary Kaposi's sarcoma in four patients, subsequently in two patients, and not identified in one patient. Oropharyngeal Kaposi's sarcoma was diagnosed prior to pulmonary Kaposi's sarcoma in three patients. Only infection was considered in the differential diagnosis of the patients' pulmonary disease in five patients. One patient presented with acute hemoptysis and died, and one patient recently received a diagnosis of pulmonary Karposi's sarcoma at another hospital. Chest radiographic findings were the following: nodular opacities in five of seven patients (71%); peribronchovascular opacities in six of seven patients (86%); thickened interlobular septa in two of seven patients (29%); pleural effusion in three of seven patients (43%); and lymphadenopathy in two of seven patients (29%). Five of seven patients (71%) were determined to be in radiographic stage 3, one patient in stage 1, and one patient in stage 2. CT demonstrated additional lymphadenopathy in three of three patients, thickened interlobular septa in two of three patients, and pleural effusion in one of three patients, but it did not change the staging of disease in any patient. CONCLUSION: Pulmonary Kaposi's sarcoma can cause diffuse lung disease in women with AIDS. The disease is usually mistaken clinically for pulmonary infection.

Acquired Immunodeficiency Syndrome↗

Esophageal small cell carcinomas: clinicopathologic parameters, p53 overexpression, proliferation marker, and their impact on pathogenesis.

OBJECTIVE: To evaluate the clinicopathologic features and the roles of p53 and MIB-1 in esophageal small cell carcinoma. METHOD: Twenty patients (14 men and 6 women) with esophageal small cell carcinoma treated in our hospital from 1982 through 1996 were studied. The clinicopathologic features, treatment received, and survival data of these patients were documented. Representative tissue was collected from each tumor, and immunohistochemical preparations for p53 protein and MIB-1 were made. RESULTS: Small cell carcinoma accounted for 1.3% of all esophageal malignant tumors. The median age of patients at presentation was 60 years. On gross examination, the tumors were large ulcerative lesions (median length, 7.5 cm). In 17 patients in whom p53 immunohistochemical study was performed, p53 protein was detected in 65% (9 of 17). All stage IV tumors were negative for p53 expression. The median tumor cell MIB-1 score was high at 855 (range, 810-964) positive cells per 1000. Overall median survival was 3.4 months. In patients who underwent chemotherapy, there was significant response. CONCLUSIONS: Esophageal small cell carcinoma is an aggressive tumor. Overexpression of p53 is associated with early stages of carcinogenesis. The high proliferative index, as defined by the MIB-1 immunohistochemical method, may be related to aggressive behavior and high sensitivity to chemotherapy and radiotherapy.

Adult↗