Biomedical subjects

L Wong

Publications and source records attributed to L Wong.

At least 19 recordsLinked to original sources

PubMed2002

Outcome of hypospadias fistula repair.

Objectives To examine the long-term results of hypospadias fistula repair, the factors involved in recurrence and the outcome in cases where this has occurred. Patients and methods The study comprised 113 children undergoing urethrocutaneous fistula repair between 1984 and 1996. Most of the fistulae were closed in two to three layers, with or without a transpositional skin flap. Tunica vaginalis or a scrotal dartos flap was used in patients with inadequate vascularized tissue adjacent to the fistula. Success rates were calculated for each attempt at fistula repair until the patient was cured. Results The median (range) age at primary fistula repair was 40 (18-169) months and the median follow-up after the most recent repair 7.5 (2.3-17) years. The overall success rate of primary fistula repair was 71%. Fistulae which were >2 mm (11 of 21, 52%) were more likely to recur than were those < or = 2 mm (22 of 92, 24%). Recurrence did not relate to the initial form of hypospadias repair, to the means of skin closure nor, with the exception of multiple lesions, to the location of the fistula. The success rates of subsequent repairs were 70% at the second and 50% at the third, fourth and fifth repairs. One child was cured at the sixth attempt. The use of tunica vaginalis or scrotal dartos as a 'waterproofing' layer was limited to the third or subsequent repairs and was successful in five of six cases. Conclusion A simple layered closure with or with no transpositional skin flap is effective in 71% of repairs. For recurrent fistulae, tissues from an unscarred area (tunica vaginalis or scrotal dartos layer) should be used to cover the fistula.

Adolescent↗

PubMed2001

A crucial role of macrophages in the immune responses to oral DNA vaccination against hepatitis B virus in a murine model.

In the previous study, we had shown that live oral vaccination with Salmonella typhimurium delivering plasmid DNA-HBsAg (oral DNA vaccine) evoked a vigorous T cell response and a weak antibody response with predominant subclass IgG2a in mice, suggesting a significant involvement by professional antigen presenting cells (APC). In the present study, this possibility was further studied by infecting peritoneal macrophages (MPhi) with the oral DNA vaccine. Although, the infected cells could only express low level of the viral antigen, they nevertheless stimulated a vigorous lymphocyte proliferation of splenocytes from immune mice, induced these cells to elaborate interferon-gamma and stimulated development of HBV-specific cytotoxicity against target cells expressing the viral antigen. Infusion of the infected MPhi evoked a vigorous Th 1 and cytotoxic T lymphocyte (CTL) response and a weak IgG2a antibody response in mice, which was essentially the same as response to the oral DNA vaccine. In contrast, recombinant protein vaccine evoked a vigorous IgG1 antibody response and a weak T cell response. While, given intramuscularly, the same plasmid DNA vaccine as that contained in the oral DNA vaccine evoked a vigorous IgG1 antibody response and a moderate T cell response in these animals. It was concluded that professional APC may orchestrate the immune response to live oral DNA vaccine and it was of interest to note that different vaccine formulation and routes of administration evoke distinct immune response to HBV.

Administration, Oral↗

PubMed2001

Folic acid supplements during pregnancy and risk of miscarriage.

BACKGROUND: Although taking supplements that contain 400 microg of folic acid before and during early pregnancy reduces a woman's risk for having a baby with a neural-tube defect (NTD), the effects of such supplements on other pregnancy outcomes remain unclear. We examined whether the use of such supplements affects the occurrence of miscarriage. METHODS: Participants were women in China who had taken part in a recent folic acid campaign to prevent NTDs and who had registered in this campaign before they became pregnant for the first time. We examined the risk for miscarriage among women who had confirmed pregnancies and who had or had not taken pills containing only 400 microg of folic acid before and during early pregnancy. RESULTS: The overall rate of miscarriage was 9.1% (2155/23806). The rates of miscarriage among women who had and had not taken folic acid pills before and during the first trimester were 9.0% and 9.3%, respectively (risk ratio 0.97 [95% CI 0.84-1.12]). The distributions of gestational age at pregnancy diagnosis and at miscarriage were similar for both groups of women. INTERPRETATION: In this population-based study of a cohort of women whose use of folic acid supplements while pregnant had been previously documented and who had been pregnant for the first time, we found no evidence that daily consumption of 400 microg of folic acid before and during early pregnancy influenced their risk for miscarriage.

Abortion, Spontaneous↗

PubMed2001

Effects of retinoic acid and sodium butyrate on gene expression, histone acetylation and inhibition of proliferation of melanoma cells.

Retinoic acid (RA) induces growth-arrest of many tumor cell lines but it is an ineffective therapeutic against melanoma. We investigated whether the histone deacetylase (HDAC)-inhibitor sodium butyrate (BUT) can restore or potentiate the RA-response of RA-resistant human A375, and RA-responsive S91 murine melanoma cells. BUT induced expression of RARbeta and p21(waf1/cip1) mRNA in A375 cells but in S91 cells only p21(waf1/cip1) was induced. RA and BUT synergistically activated transcription of an RA-dependent reporter gene in S91, but not A375 cells. BUT increased histone H4-acetylation in both cell types. RA potentiated BUT-mediated inhibition of S91 cell proliferation, whereas A375 cells remained largely resistant to both compounds. HDAC-inhibitors may enhance the activity of RA on RA-responsive melanoma cells.

Animals↗

PubMed2001

Epidermal growth factor (EGF) receptor kinase-independent signaling by EGF.

The ErbB family of receptors, which includes the epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4, mediate signaling by EGF-like polypeptides. To better understand the role of the EGFR tyrosine kinase, we analyzed signaling by a kinase-inactive EGFR (K721M) in ErbB-devoid 32D cells. K721M alone exhibited no detectable signaling capacity, whereas coexpression of K721M with ErbB2, but not ErbB3 or ErbB4, resulted in EGF-dependent mitogen-activated protein kinase (MAPK) activation. The kinase activity, but not tyrosine phosphorylation, of ErbB2 was required for EGF-induced MAPK activation. The presence of tyrosine phosphorylation sites in K721M was not a requisite for signaling, indicating that transphosphorylation of K721M by ErbB2 was not an essential mechanism of receptor activation. Conversely, the mutated kinase domain of K721M (residues 648-973) and tyrosine phosphorylation of at least one of the receptors were necessary. EGF was found to activate the pro-survival protein kinase Akt in stable cell lines expressing K721M and ErbB2 but, unlike cells expressing wild-type EGFR, was incapable of activating signal transducers and activators of transcription (STAT) or driving cell proliferation. These results demonstrate that EGFR-ErbB2 oligomers are potent activators of MAPK and Akt, and this signaling does not require EGFR kinase activity.

Cell Line↗

PubMed2001

The combined effect of isolation and Fasciola hepatica infection on the life history traits of Fossaria cubensis.

Life history traits of Fossaria cubensis were compared between isolated and paired snails after infection with three miracidia of Fasciola hepatica. Four experimental groups were tested: isolated-unexposed, paired-unexposed, isolated-infected, and paired-infected. A repeated-measures ANOVA showed statistically significant interactions among isolation, infection, and age effects for shell size, number of egg masses per snail, number of eggs per snail, and number of viable eggs per snail. Isolated-unexposed snails exhibited the higher values of these variables and those of survival and finite and intrinsic rates of natural increase. Infection stimulated shell growth during the prepatent period, but differences were present only in paired snails since isolation causes a similar effect. Reproduction, in terms of the number of egg masses per snail and the number of eggs per mass per snail, decreases in the presence of parasitic infection, whereas isolation stimulates it. These effects were observed from early stages of infection.

Animals↗

PubMed2001

Pharmacodynamics induced by direct electric current for the treatment of 5-fluorouracil resistant tumor: an animal experiment.

The repeated use of chemotherapy to treat patients with colorectal carcinoma may be limited by the fact it creates resistance cells. However, we have observed a remarkable decrease in certain types of drug resistance in patients treated with direct electric current. Experimental studies were therefore performed in animals to determine the differences in pharmacodynamics between chemotherapy with and that without electric treatment. Tumors were created in BALB/c mice by intradermal injection of 0.25 ml 4 x 10(6) Colon 26 cells/ml in the abdomen. Seven days later the mice were divided into two groups: controls and those that underwent electric treatment. Direct electric current (1,000 V, 0.2-0.8 microA) was passed between a platinum electrode inserted intradermally and the earth during and for 1 h after a single intravenous injection of 5-fluorouracil (5-FU; 12.5 mg ml(-1) kg(-1)). Peripheral blood samples were collected before and 5, 10, 20, 30, 45, and 60 min after the injection of 5-FU. Concentrations of 5-FU in the sera and tissues were measured by HPLC. The intratumoral concentrations of 5-FU in the electric treatment group were higher than those in the controls (P<0.05, two-factor analysis of variance), but the serum concentrations were not statistically different between the two groups. Pharmacodynamic changes were thus observed as a result of electrostatic treatment during chemotherapy. This elevated 5-FU concentration in the tumor tissue is considered one of the reasons for the effective inhibition of 5-FU resistance in clinical cases.

Animals↗

PubMed2001

Children with persistent conduct problems who dropout of treatment.

Dropout of treatment is one of the key issues in outcome in a child and adolescent mental health service. We report two studies focusing on the treatment process and the dropout rate of children with persistent conduct problems presenting to a community mental health service, using a prospective design. The first study included 32 children and used a randomised controlled treatment design comparing a CBT approach with conjoint family therapy and an eclectic approach. The overall dropout rate was 36%. Dropout occurred significantly less frequently in the CBT group. The dropout group was associated with mothers who were younger and less educated, a poorer rating by the clinicians at the last meeting, parental dissatisfaction with the treatment service and perception that the treatment was less organised and having less behavioural tasks. In the second study we used a naturalistic follow-up design. Forty-six children were included. The overall dropout rate was 48%. Again, the children who defaulted were rated by clinicians as less likely to have improved and dropout was also significantly associated with parental perception of a less organised treatment. In both studies dropout usually occurred after assessment and at the early phase of treatment.

Adolescent↗

PubMed2001

A comparison of human dental plaque microcosm biofilms grown in an undefined medium and a chemically defined artificial saliva.

The growth and pathogenic properties of dental plaque result from interactions between the microbiota and the oral environment and have been studied in laboratory experimental systems ranging from single or a few species (such as in chemostats) to dental plaque microcosms. Microcosm plaque is an in vitro version of natural plaque and has been explored as a microflora model because it is sited a more manipulable and controllable environment. It is obtained as microcosm biofilms in an 'artificial mouth' plaque culture system by culturing the bacteria in natural plaque-enriched saliva (i.e. salivary bacteria where a whole-saliva donor has abstained from oral hygiene for 24 h to increase the plaque bacteria in the saliva). The aim here was to examine whether a new, chemically defined analogue of saliva (defined medium mucin, DMM) could substitute for a previously used, chemically undefined medium (basal medium mucin, BMM) as an analogue of saliva for large-scale biofilm culturing. DMM contains various ions, mucin, amino acids, vitamins and growth factors at concentrations generally similar to those in saliva, whereas BMM contains yeast extract, peptones and mucin. To model the nutrient functions of salivary proteins, amino acids equivalent to 5 g/l casein were also included in DMM. In earlier studies, BMM-grown plaques were similar to natural plaques in structure, composition, growth rate and pH response to substrates. Their doubling-time patterns over a 20-day period were similar, except that the DMM-grown plaques showed biphasic growth patterns that were more pronounced than with BMM. Variation in enzyme profiles between BMM- and DMM-grown plaque, measured using the API-ZYM technique, provided evidence of nutritional effects on plaque composition. It was concluded that realistic growth rates and patterns are generated in microcosm plaque biofilms by supplying both DMM and BMM. However, the use of DMM enables specific modifications to be made to nutrient conditions during large-scale culture in our 'artificial mouth' biofilm system.

Amino Acids↗

PubMed2001

Intraoperative positioning for circumferential extremity burns.

A technique for intra-operative patient positioning is described which allows circumferential access to burned extremities for prepping and surgery. This technique avoids the need for turning the patient during the operative procedure. In our 13 yr experience, there have been no complications attributed to this technique.

Burns↗

PubMed2001

Retinoic acid receptor-independent mechanism of apoptosis of melanoma cells by the retinoid CD437 (AHPN).

Retinoic acid (RA) induces differentiation of S91 melanoma cells through activation of RA receptor (RAR)gamma without affecting cell viability. The novel RARgamma-agonist CD437 (AHPN), however, also induces concomitant apoptosis through an unknown mechanism which was investigated here. By utilizing DNA microarray analysis, five apoptosis-associated, CD437-induced transcripts (CITs) were identified. Interestingly, all CITs are also regulated by p53 in a DNA damage response, and consistent with this interpretation, CD437 was found to cause DNA adduct-formation. However, p53 is not required for CD437-dependent regulation of CITs. Among this set of genes, induction of p21(WAF1/CIP1) is likely to be responsible for early S-phase growth-arrest of CD437-treated cells, whereas ei24 is a critical mediator of CD437-induced apoptosis in S91 cells. These data suggest an RAR-independent mechanism in which CD437 causes DNA adduct-formation, resulting in induction of a p53-independent DNA damage response, and subsequent growth-arrest and apoptosis. CD437-mediated DNA adduct-formation may also explain its apoptotic effects in other cell types.

3T3 Cells↗

PubMed2001

Parathyroidectomy promotes wound healing and prolongs survival in patients with calciphylaxis from secondary hyperparathyroidism.

BACKGROUND: Calciphylaxis is a rare but life-threatening condition occasionally affecting patients with secondary hyperparathyroidism. Parathyroidectomy has been advocated as the only potentially curative intervention. METHODS: Between January 1989 and May 2000, 13 patients with pathologic/clinical criteria of calciphylaxis were treated at our institution. Of these 13 patients, 7 were managed with medical therapy alone, and 6 were referred for parathyroidectomy. The medical records were reviewed, and patients/relatives were interviewed. RESULTS: All patients had cutaneous wounds requiring local debridement predominantly located on the lower extremities or abdominal wall. Six patients underwent subtotal (3.5 gland) parathyroidectomy without morbidity. All 6 had significant reductions in parathyroid hormone levels after surgery (mean decrease, 94% +/- 0%), and all reported resolution of pain and healing of cutaneous wounds. Of the remaining 7 patients who had medical management alone, 5 eventually died of complications related to calciphylaxis. In comparing the 2 groups, patients who underwent parathyroidectomy had a significantly longer median survival than those who did not have surgery (36 vs 3 months, P =.021). CONCLUSIONS: Calciphylaxis frequently causes gangrene, sepsis, and eventual death. Parathyroidectomy can be performed with minimal morbidity and is associated with resolution of pain, wound healing, and a significantly longer median survival. Therefore, patients with secondary hyperparathyroidism and signs/symptoms of calciphylaxis should be referred promptly for consideration of parathyroidectomy.

Adult↗

PubMed2001

Intercostal neuromas: a treatable cause of postoperative breast surgery pain.

Patients presenting with pain after breast surgery were selected to undergo resection of intercostal neuromas. The patients had localized Tinel's signs at one or more intercostal nerves at the lateral chest wall with radiation in the distribution of the pain. Patients also responded to diagnostic injections of local anesthetic. The patients were felt to have pain not related to breast implants and capsular contracture or intercostobrachial nerve injury. Neuromas were found in all patients meeting these requirements. Surgical resection resulted in complete pain relief. Diagnosis of this entity and consideration of surgical treatment may be underrecognized.

Adult↗

PubMed2001

Incidence of Helicobacter pylori in patients with interstitial cystitis.

OBJECTIVE: Chronic gastritis has compelling similarities to interstitial cystitis (IC). It is characterised by chronic pain in a tubular organ. Histologically, epithelial damage, inflammatory response in the lamina propria and epithelial ulcerations are seen. An infective cause was rarely considered until the emergence of Helicobacter pylori over the past 15 years. We have had experience of patients with bladder pain and irritability reporting improvement with antihistamines. It has also been reported that IC symptoms improved dramatically after treatment for H. pylori infection. Previous studies have determined the incidence of H. pylori antibodies in women with IC but we examined bladder material histologically and performed the Campylobacter-like organism (CLO) test on the biopsy specimens. MATERIALS AND METHODS: A prospective controlled study was performed. Patients with urinary symptoms fulfilling the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC underwent GA cystoscopy at which the macroscopic appearance of the bladder was noted and biopsies were taken. The biopsy material underwent histological examination and CLO test. Control patients who were undergoing cystoscopy for reasons other than investigation of IC also had biopsy taken and the CLO test was performed on these specimens. RESULTS: Five of 15 patients with symptoms and signs of IC had a positive CLO test. Three of 15 patients of the control group had a positive CLO test. With the 2-sided chi(2) test there was no statistical difference between the 2 groups. CONCLUSION: Our small prospective control study does not support the hypothesis that H. pylori is an important component in the pathogenesis of interstitial cystitis.

Cystitis, Interstitial↗

PubMed2001

Redox control of retinoic acid receptor activity: a novel mechanism for retinoic acid resistance in melanoma cells.

Retinoic acid (RA) slows growth and induces differentiation of tumor cells through activation of RA receptors (RARs). However, melanoma cell lines display highly variable responsiveness to RA, which is a poorly understood phenomenon. By using Northern and Western blot analyses, we show that RA-resistant A375 and RA-responsive S91 melanoma cells express comparable levels of major components of RAR-signaling pathways. However, A375 cells have substantially higher intracellular reactive oxygen species (ROS) levels than S91 cells. Lowering ROS levels in A375 cells through hypoxic culture conditions restores RAR-dependent trans-activity, which could be further enhanced by addition of the antioxidant N-acetyl-cysteine. Hypoxia also enhances RAR activity in the moderately RA-responsive C32 cells, which have intermediate ROS levels. Conversely, increasing oxidative stress in highly RA-responsive S91 and B16 cells, which have low ROS levels, by treatment with H(2)O(2) impairs RAR activity. Consistent with these observations, RA more potently inhibited the proliferation of hypoxic A375 cells than that of normoxic cells. Oxidative states diminish, whereas reducing conditions enhance, DNA binding of retinoid X receptor/RAR heterodimers in vitro, providing a molecular basis for the observed inverse correlation between RAR activity and ROS levels. The redox state of melanoma cells provides a novel, epigenetic control mechanism of RAR activity and RA resistance.

Acetylcysteine↗

PubMed2001

Prolonged, symptomatic hypocalcemia with pamidronate administration and subclinical hypoparathyroidism.

A 62-yr-old woman with thyroid carcinoma metastatic to bone, and a history of subclinical hypoparathyroidism was admitted to the hospital in hypocalcemic crisis 5 wk after receiving iv pamidronate. The patient had tetany and laryngospasm. An electrocardiogram showed junctional rhythm with QT segment prolongation. The patient had previously maintained a low-normal serum calcium on 500-750 mg of calcium carbonate and 600 IU of vitamin D daily. One week after pamidronate administration the patient's calcium and vitamin D supplementation were inadvertently discontinued. She continued to take daily intranasal calcitonin. At the time of her hospitalization for hypocalcemia, the patient's serum calcium was 4.3 mg/dL. The patient received aggressive calcium and vitamin D supplementation. However, her serum calcium remained below 6 mg/dL for a 2-wk period, and took another week to return to the normal range. In this article, we discuss the counterregulatory responses necessary to maintain calcium homeostasis following osteoclast inhibition by bisphosphonates. We also review the risk factors for hypocalcemia following bisphosphonate administration. Pamidronate and other bisphosphonates are becoming an integral part of the management of normocalcemic patients with malignant bone disease. Therefore, awareness of risk factors for hypocalcemia and familiarity with avenues available for protection from potentially catastrophic hypocalcemia are both crucial.

Antineoplastic Agents↗

PubMed2001

PIES, a protein interaction extraction system.

We consider the problem of extracting, manipulating, and managing biological pathways, especially protein-protein interaction pathways. We discuss here the Protein Interaction Extraction System (PIES). PIES is contructed on top of three main technologies: Kleisli, BioNLP, and Graphviz. Kleisli is a broad-scale data integration system that we use for downloading Medline abstracts and for general manipulation and management of pathway/interaction databases. BioNLP is a natural language-based information extraction module that we use for analysing Medline abstracts and to extract precise protein-protein and other interaction information. Graphviz is a graphical layout package developed for directed graphs that we use for visualization of the extracted pathways. PIES can be augmented with various means for extracting protein interaction information from sequence databases, for example, by using Kleisli's power to integrate sequence comparison tools to detect gene fusion events in sequence databases.

Abstracting and Indexing↗

PubMed2001

Emerging patterns and gene expression data.

One important purpose of conducting gene expression experiments is to understand the correlation of gene expression profiles to disease states. Based on the notion of emerging patterns and an entropy-oriented discretization method, we discover groups of genes that are correlated to disease states in a significant way. In each group, every member gene constrained by a specific expression interval, unanimously occurs only in one type of cells with a maximally large frequency, but never unanimously happens in the other types of cells. According to our studies on the colon tumor dataset, such gene groups (also called patterns) can reach a frequency of 90%, providing good insight into the correlation of gene expression profiles to disease states. The patterns can be used to correctly predict whether a new cell is normal or cancerous.

Algorithms↗