Biomedical subjects

J Wong

Publications and source records attributed to J Wong.

At least 307 records · Page 17Linked to original sources

PubMed1998

Characteristics and prognosis of KI-1 positive anaplastic large cell lymphoma in Asians.

BACKGROUND: Ki-1 positive anaplastic large cell lymphoma is a rare type of non-Hodgkin's lymphoma (NHL), and has not been extensively described in Asian patients. AIM: To evaluate the clinical characteristics, prognostic factors and treatment outcome of Ki-1 positive lymphoma in an Asian community. METHODS: A retrospective analysis of all patients with CD30 antigen positive anaplastic large cell lymphoma from 1987 to 1996 in a single institution. RESULTS: Of 218 patients with NHL, ten (5%) were identified with Ki-1 positive anaplastic large cell lymphoma. Eight were Chinese, two Indians. The male:female ratio was 1.5:1, and the median age was 32 years. Seven patients presented with B-symptoms, and five had stage III/IV disease. The majority (seven of ten) was low- or low-intermediate risk according to the International Prognostic Index (IPI). Four out of five cases immunophenotyped showed a T-cell origin. Five out of eight patients who received first-line combination chemotherapy achieved a complete remission. Two relapsed, with one being re-induced into a durable second remission. One patient with recurrent cutaneous lymphoma received solely radiotherapy and was disease-free at 20+ years from diagnosis. At analysis, two patients had died, five were disease-free at four, 27, 78, 89 months and 20 years respectively, and three were alive with disease. The IPI appears to have prognostic significance. CONCLUSION: Incidence and clinical characteristics in our Asian patients were similar to those described in Western populations. The IPI appears to have prognostic relevance. In approximately one-third of patients, long term survival can be achieved with standard treatment.

Adolescent↗

PubMed1998

A prospective randomized trial comparing the use of omeprazole-based dual and triple therapy for eradication of Helicobacter pylori.

BACKGROUND: Controversy surrounds the optimal composition, dosage, and duration of therapies for eradication of Helicobacter pylori. We prospectively compared omeprazole-based dual and triple therapies in the eradication of H. pylori in a randomized manner. METHODS: Between June 1995 and March 1997, 1000 consecutive patients with acid-peptic disease associated with H. pylori infection (duodenal ulcer, 388 patients, gastric ulcer, 179 patients; duodenitis, 173 patients; gastritis, 260 patients) were prospectively recruited. They were randomized to either a 2-wk (OA) course of omeprazole 20 mg and amoxicillin 1 g, both given twice daily, or treatment for 1 wk (OCM) with omeprazole 20 mg once daily, clarithromycin 500 mg twice daily, and metronidazole 400 mg twice daily. RESULTS: The age of these 1000 patients ranged from 16 to 90 yr, with a mean of 54.9 yr. Side effects occurred in 29.6% (95% confidence interval [CI] 25.6-33.8%) and 10.6% (95% CI 8.0-13.6%) of patients taking OCM and OA, respectively (p < 0.0001). Apart from taste disturbance, however, there were no significant differences in the incidences of side effects between the two groups. One patient in the OA group and four patients of the OCM group could not tolerate the medications, and therefore did not complete treatment (p = 0.37). Seven and 13 patients in the OA and OCM groups, respectively, refused a second endoscopy (p = 0.25). The remaining 975 patients underwent a second endoscopy. Positive endoscopic findings were significantly more common in the OA group (51/492; 10.4%; 95% CI 7.8-13.4%) than in the OCM group (25/483; 5.2%; 95% CI 3.4-7.5%) in the per-protocol (PP) analysis (p = 0.004). On intent-to-treat (ITT) analysis, the overall eradication rates in the OA and OCM groups were 73.6% (95% CI 69.5-77.4%) and 92% (95% CI 89.3-94.2%), respectively (p < 0.0001). On PP analysis, the corresponding rates were 74.8% (95% CI 70.7-78.6%) and 95.2% (95% CI 92.9-97.0%), respectively (p < 0.0001). CONCLUSIONS: A course of omeprazole, clarithromycin, and metronidazole for 1 wk is a safe, well-tolerated, efficacious, and cost-effective treatment for H. pylori infection.

Adolescent↗

PubMed1998

p130 is dispensable in peripheral T lymphocytes: evidence for functional compensation by p107 and pRB.

The proteins encoded by the retinoblastoma gene family, pRB, p107, and p130, have been implicated in the regulation of cellular proliferation, differentiation, and transformation. Because interactions between p130 and E2F transcription factors have been proposed to play a role in the establishment and/or maintenance of quiescence in human peripheral T lymphocytes, we examined lymphoid differentiation and proliferation in p130-deficient mice. We show that p130-/- T cells proliferate normally in culture and exhibit normal cell-mediated immune function in vivo. However, p130-/- T lymphocytes expressed elevated levels of p107, and the characteristic p130-E2F DNA binding complex was replaced by a p107-E2F complex. Adoptive transfer of fetal liver lymphoid progenitors allowed us to circumvent the neonatal lethality associated with loss of p130 and p107 and to analyze the phenotype of p130-/-;p107-/- peripheral T lymphocytes. These cells achieved a quiescent state, exhibited derepression of a subset of E2F target genes, and were hypersensitive to concanavalin A stimulation. Interestingly, a significant portion of the E2F-4 in p130-/-;p107-/- T cells was detected in a complex with pRB and an as-yet-unidentified protein. These findings provide a biochemical basis for functional compensation between pRB family proteins.

Animals↗

PubMed1998

Genetic evidence of a role for Lck in T-cell receptor function independent or downstream of ZAP-70/Syk protein tyrosine kinases.

T-cell antigen receptor (TCR) engagement results in sequential activation of the Src protein tyrosine kinases (PTKs) Lck and Fyn and the Syk PTKs, ZAP-70 and Syk. While the Src PTKs mediate the phosphorylation of TCR-associated signaling subunits and the phosphorylation and activation of the Syk PTKs, the lack of a constitutively active Syk PTK has prohibited the analysis of Lck function downstream of these initiating signaling events. We describe here the generation of an activated Syk family PTK by substituting the kinase domain of Syk for the homologous region in ZAP-70 (designated as KS for kinase swap). Expression of the KS chimera resulted in its autophosphorylation, the phosphorylation of cellular proteins, the upregulation of T-cell activation markers, and the induction of interleukin-2 gene synthesis in a TCR-independent fashion. The KS chimera and downstream ZAP-70 or Syk substrates, such as SLP-76, were still phosphorylated when expressed in Lck-deficient JCaM1.6 T cells. However, expression of the KS chimera in JCaM1.6 cells failed to rescue downstream signaling events, demonstrating a functional role for Lck beyond the activation of the ZAP-70 and Syk PTKs. These results indicate that downstream TCR signaling pathways may be differentially regulated by ZAP-70 and Lck PTKs and provide a mechanism by which effector functions may be selectively activated in response to TCR stimulation.

Enzyme Activation↗

PubMed1998

Preferential binding of lysozyme to elastic fibres in pulmonary emphysema.

BACKGROUND: Lysozyme is increased in inflammatory reactions and is a component of the extracellular matrix, but its possible role in lung diseases such as emphysema and interstitial fibrosis has not been investigated. METHODS: To characterise differences in lysozyme content among normal, emphysematous, and fibrotic human lungs, tissue sections obtained from necropsy specimens were immunostained with rabbit polyclonal anti-human lysozyme antibody using the labelled streptavidin-biotin peroxidase method. The immunostained sections were evaluated semi-quantitatively (grading the degree of immunostaining on a scale of 0-4). To determine if degradation of the extracellular matrix affects lysozyme binding, hyaluronidase-treated normal lung tissues were incubated with egg white lysozyme, immunostained with the lysozyme antibody, which crossreacts with egg white lysozyme, and evaluated for degree of staining. RESULTS: Lysozyme immunostaining was significantly increased in lungs with pulmonary emphysema compared with normal or fibrotic tissues (3.4 versus 1.6 and 1.9, respectively; p < 0.05) and was preferentially associated with interstitial elastic fibres. Hyaluronidase-treated lung tissues incubated with lysozyme showed increased immunostaining for this protein compared with untreated controls (1.9 versus 1.2; p < 0.05). CONCLUSIONS: The results suggest that damage to elastic fibres and/or the surrounding extracellular matrix increases lysozyme binding. It is hypothesised that attachment of lysozyme to elastic fibres may interfere with their repair and possibly enhance the progression of pulmonary emphysema.

Elastic Tissue↗

PubMed1998

Retinoid receptor-induced alteration of the chromatin assembled on a ligand-responsive promoter in Xenopus oocytes.

Retinoic acid (RA) stimulates transcription from the retinoic acid receptor beta2 (RARbeta2) promoter in mammalian embryonal cells. Evidence by in vivo deoxyribonuclease I (DNase I) hypersensitivity assay indicates that RA treatment of these cells results in an alteration of chromatin structure in and near the promoter. To study the role of chromatin in RA-activated transcription, we assembled the RARbeta2 promoter into chromatin in Xenopus oocytes. Ectopic expression of RAR and retinoid X receptor (RXR) enhanced transcription without ligand, irrespective of whether chromatin was assembled in a replication-dependent or -independent manner, although ligand addition led to a further, marked increase in transcription. Moreover, expression of RAR and RXR, without ligand addition, induced DNase I-hypersensitive sites in the chromatin-assembled promoter. Furthermore, expression of RAR and RXR in oocytes led to local disruption of chromatin assembled over the promoter without ligand. Similar ligand-independent, but RXR/RAR-dependent nucleosomal disruption was observed in an in vitro chromatin reconstitution system using Drosophila embryonic extracts. Thus, unliganded receptors expressed in oocytes are capable of accessing to the chromatin-assembled promoter and activating transcription without ligand, indicating that chromatin assembly per se is not sufficient to reproduce ligand-dependent chromatin changes and promoter activation seen in mammalian cells. The oocyte system may serve as a model to study mechanisms of RA-dependent alterations of chromatin structure.

Animals↗

PubMed1998

Recent advances in assisted reproductive technologies.

Assisted reproductive technologies (ART) have received considerable attention, both clinically and empirically. Drs. Steptoe and Edwards removed one oocyte surgically from a woman with infertility related to tubal disease. They fertilized this oocyte in vitro and transferred the formed embryo to the woman's uterus and achieved pregnancy and delivery. The technique of in vitro fertilization (IVF) and embryo transfer (ET) quickly became widely utilized for other causes of infertility as well as for tubal disease. In the last 5 years there has been a number of new developments that are reviewed in this article. The most important and now widely practiced technology has been direct intracytoplasmic injection (ICSI) of the husband's sperm into the wife's oocyte. This was developed for treatment of infertility related to low sperm count. Subsequently it was shown that sperm can be aspirated from epididymis or found in testicular biopsy in obstructive azoospermia. Another promising development is in vitro maturation (IVM) of immature oocytes. This has the potential of avoiding ovarian hyperstimulation, which can be uncomfortable and occasionally dangerous. Some oocytes are unable to fertilize and/or develop into normal embryos. It may be possible that the problem is with the machinery of cytoplasm of the oocyte. Therefore cytoplasmic transfer from a normal oocyte to an abnormal oocyte may overcome the problem. Infertile couples may be faced with many psychological problems that become even more complex with various treatments. Whereas donation of oocytes or embryos can be technically quite simple, there are many psychological issues involved. As can be gathered from aforementioned discussions, the treatments developed for infertility appear to be somewhat illogical and in the style of "shot gun therapy." In the field of infertility, as in other areas of medicine, it is of paramount importance to know the details of disease mechanisms. This in turn will allow specific and logical treatments to be developed.

Animals↗

PubMed1998

Anorectic drugs and valvular heart disease: a biological and clinical perspective.

The epidemiologic and pathologic evidence that fenfluramine and related drugs cause valvular heart disease is still speculative. However, at present, there is no alternative explanation for the cases of valvular disease found in patients taking these drugs, and there is evidence that similar substances can cause similar lesions. The manufacturer of fenfluramine and dexfenfluramine has prudently removed them from sale pending further studies.

Adult↗

PubMed1998

Abdominal aortic aneurysm in Hong Kong: audit from a teaching hospital (1975-1995).

OBJECTIVE: To analyse the epidemiology and trends of abdominal aortic aneurysm (AAA) in an ethnic Chinese population over a 21-year period in a representative referral institution in Hong Kong. METHODS: Over a 21-year period from 1975 to 1995, 533 patients with abdominal aortic aneurysms were treated in a single Vascular Surgical Unit at the Department of Surgery, Queen Mary Hospital, Hong Kong. Their characteristics, treatment and mortality were reviewed. RESULTS: There was an increase in the incidence from a mean annual admission of 10 cases per year during 1975-1980, to that of 38 per year during 1991-1995. The increase was largely detected in males, the male to female ratio being 2.5:1 in the 1980s and 3.6:1 in the 1990s. There was no parallel increase in the incidence of ruptured aneurysms which accounted for 12.6% of all aneurysm admissions. CONCLUSION: There is a progressive increase in the incidence of AAA in Chinese patients, in a time frame and pattern similar to that reported in the West.

Adult↗

PubMed1998

Paediatric liver transplantation: Queen Mary Hospital experience.

OBJECTIVE: To assess the results of paediatric liver transplantation in our institution. METHODS: From September 1993 to November 1996, 10 living-related liver transplants (LRLT) and 3 reduced-size liver transplants (RSLT) were performed on 12 children at our hospital. The medical records of the patients were reviewed. All patients suffered from end-stage liver disease resulting from biliary atresia with failed Kasai's operations. Their ages at initial transplantation ranged from 8 months to 11 years. Excluding the 2 older children aged 7.5 and 11 years, the remaining patients were aged 10.5 months on the average and weighed 6 to 9.5 kg (mean: 6.8 kg) at the time of initial transplantation. RESULTS: All living donors were discharged on postoperative day 4 to 8 and resumed their previous normal activities. All recipients were alive with normal liver function and growing after a follow-up period of 3-40 months (mean: 21 months). The patient survival rate was 100%. One patient with RSLT had hepatitis of undetermined aetiology and underwent retransplant with a graft from her mother. The graft survival rate was 92%. Postoperative complications included: postoperative bleeding (n = 3), hepatic vein stenosis (n = I), biliary-enteric anastomotic stenosis (n = 3), intestinal perforation (n = I) and portal vein thrombosis (n = I). They were all treated promptly. In all patients, the hepatic artery (diameter ranged from 1.5 to 2.5 mm) anastomosis was achieved by microvascular technique. There was no hepatic artery thrombosis in our patients. CONCLUSION: With technical refinements, early detection and prompt treatment of complications, and advances in immunotherapy, excellent results can be achieved in paediatric liver transplantation.

Biliary Atresia↗

PubMed1998

The value of neck drain in esophageal surgery: a randomized trial.

The use of surgical drains in certain clean elective operations remains controversial. To evaluate the role of closed-suction drain for an esophageal anastomosis in the neck, we conducted a randomized, controlled study in 40 patients with esophageal carcinoma who underwent esophagectomy with an esophageal anastomosis in the neck, half of whom had a neck drain inserted at the end of operation. The median (range) duration of drainage was 46 hours (36 to 88 hours). The median (range) amount of drainage was 63 ml (15 to 210 ml). There was no incidence of haematoma or seroma formation in both the drained and non-drained groups. Anastomotic leakage did not occur in any patient. The benefits of closed suction neck drain could not be demonstrated. Routine use of neck drain for esophageal anastomosis in the neck is not necessary.

Aged↗

PubMed1998

Regression of left ventricular hypertrophy in hypertension: changing patterns with successive meta-analyses.

Left ventricular hypertrophy (LVH) may be an important target for therapy in hypertension, although definitive data in humans are not available. An important question is whether antihypertensive drugs vary in their ability to cause the regression of LVH. Without adequately powered controlled comparisons, meta-analysis provides the best method of assessing the overall results of the numerous smaller published studies. A succession of meta-analyses have indicated a strong relationship between changes in blood pressure and LVH regression. We have reviewed studies conducted for 5 years since the first major meta-analysis. Methodology was found to have improved, and the overall ranking of drug classes according to their effects on LVH regression were: calcium antagonists, angiotensin converting enzyme inhibitors, diuretics, alpha-blockers, beta-blockers, and lifestyle changes. Changes from earlier reports may reflect the use of new preparations within some classes of drugs and large studies are required to define whether this will be reflected in clinical outcomes.

Adult↗

PubMed1998

Fortuitous diagnosis of iliac osteomyelitis: septic arthritis of the hip in the neonate.

The neonate is unable to relate specific complaints of pain and may not exhibit the usual signs of illness or infection. Septic arthritis of the hip is a surgical emergency in the neonate, and it should be considered in any irritable or ill child who has a high index of suspicion. Prompt diagnosis and immediate treatment are necessary. Nearly all babies undergo routine examination of the hip for dysplasia. It is recognized that limitation of abduction of the hip in the neonate may not represent developmental dysplasia of the hip but may represent other etiologies, such as fracture, infection, congenital anomaly, or tumor. The following case report illustrates the importance of careful clinical evaluation of an apparent asymptomatic neonate.

Arthritis, Infectious↗

PubMed1997

VH gene replacement in hyperselected B cells of the quasimonoclonal mouse.

The primary repertoire of the quasimonoclonal mouse is monospecific. However, among peripheral B cells, there is a high frequency of variant cells with V(H) replacements, which are also hypermutated. We show in this work that these hyperselected cells expand in numbers as the animals increase in age, switch their isotypes, and with increasing age become the almost exclusive contributors to the pool of serum Ig. The fraction of such cells is higher in the peritoneum than in peripheral blood, supporting the view that the peritoneum is a site of production of nonspecific serum Ig. We have also isolated and partially sequenced the replacing V(H) gene segments from B220-positive, Id-negative cells, and mu-negative, lambda-positive (i.e., switched) cells, and matched them with their germline counterparts. V(H) families are represented proportional to the number of members in the germline, a finding that is consistent with the idea that environmental Ag pressure maintains the germline repertoire of V gene segment.

Animals↗

PubMed1997

Structural and functional features of a specific nucleosome containing a recognition element for the thyroid hormone receptor.

The Xenopus thyroid hormone receptor betaA (TRbetaA) gene contains an important thyroid hormone response element (TRE) that is assembled into a positioned nucleosome. We determine the translational position of the nucleosome containing the TRE and the rotational positioning of the double helix with respect to the histone surface. Histone H1 is incorporated into the nucleosome leading to an asymmetric protection to micrococcal nuclease cleavage of linker DNA relative to the nucleosome core. Histone H1 association is without significant consequence for the binding of the heterodimer of thyroid hormone receptor and 9-cis retinoic acid receptor (TR/RXR) to nucleosomal DNA in vitro, or for the regulation of TRbetaA gene transcription following microinjection into the oocyte nucleus. Small alterations of 3 and 6 bp in the translational positioning of the TRE in chromatin are also without effect on the transcriptional activity of the TRbetaA gene, whereas a small change in the rotational position of the TRE (3 bp) relative to the histone surface significantly reduces the binding of TR/RXR to the nucleosome and decreases transcriptional activation directed by TR/RXR. Our results indicate that the specific architecture of the nucleosome containing the TRE may have regulatory significance for expression of the TRbetaA gene.

Animals↗

PubMed1997

Outcome after splenic vein thrombosis in the pancreas allograft.

The outcome and management of isolated splenic vein thrombosis in the pancreas transplant is unknown. We retrospectively reviewed the records of 76 simultaneous pancreas-kidney transplantations (SPK) and 56 solitary pancreas transplantations (SPT) performed at the University of Maryland from January 1995 to December 1996. A total of 24 patients were identified (9 SPK and 15 SPT recipients). All were systemically anticoagulated for a period of 6-8 weeks after diagnosis. In the SPK thrombosis group, anticoagulation resulted in 1-year graft survival that was equivalent to that of SPK controls (86.1% vs. 95.3%). In contrast, in SPT, thrombosis and subsequent anticoagulation were associated with decreased graft survival compared with SPT controls (26.8% vs. 78.3%; P<0.01). Although the outcome of splenic vein thrombosis in the absence of anticoagulation is unknown, these data suggest that (1) in SPK, anticoagulation for splenic vein thrombosis maintains graft survival, and (2) in SPT, anticoagulation does not alter the ultimate progression of splenic vein thrombosis to complete graft thrombosis.

Adult↗

PubMed1997

Angiotensin-converting enzyme inhibition abolishes medial smooth muscle PDGF-AB biosynthesis and attenuates cell proliferation in injured carotid arteries: relationships to neointima formation.

BACKGROUND: ACE inhibitors can attenuate the development of intimal fibrocellular lesions after balloon catheter vessel injury, but the mechanisms responsible are unknown. METHODS AND RESULTS: To evaluate how basic fibroblast growth factor (FGF-2) and the platelet-derived growth factor (PDGF) isoforms are affected by ACE inhibition in injured rat carotid arteries in relation to smooth muscle cell (SMC) proliferation, we examined the effects of oral perindopril on FGF-2 and PDGF isoform levels in carotid arteries 2 days after balloon catheter injury. [3H]Thymidine incorporation into medial and intimal SMCs was also assessed. Uninjured vessels contained two forms of FGF-2, with molecular weights of 18 and 22 kD, and PDGF-AA. Two days after injury, FGF-2 and PDGF-AA levels were markedly reduced, but high levels of PDGF-AB became apparent when the SMCs were proliferating. Perindopril completely abolished the biosynthesis of PDGF-AB but had little effect on residual FGF-2. This was accompanied by a 25% reduction in medial SMC proliferation. Neointimal cell proliferation 10 days after injury was unaffected by perindopril, although neointima size was reduced by 30%. Commencing perindopril treatment 4 days after the injury confirmed that early events associated with effects on medial SMCs were the major contributors to the attenuated neointimal lesions. CONCLUSIONS: The ability of ACE inhibitors such as perindopril to attenuate neointima formation and growth in balloon catheter-injured rat carotid arteries is dependent on early events in the media, the inhibition of SMC PDGF-AB biosynthesis and attenuation of proliferation. Neointima formation in similarly injured vessels containing SMCs that are either unresponsive to PDGF-AB or exhibit an ACE-independent profile of growth factor biosynthesis responses may account for the ineffectiveness of ACE inhibition in some species.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Determinants of chromatin disruption and transcriptional regulation instigated by the thyroid hormone receptor: hormone-regulated chromatin disruption is not sufficient for transcriptional activation.

Chromatin disruption and transcriptional activation are both thyroid hormone-dependent processes regulated by the heterodimer of thyroid hormone receptor and 9-cis retinoic acid receptor (TR-RXR). In the absence of hormone, TR-RXR binds to nucleosomal DNA, locally disrupts histone-DNA contacts and generates a DNase I-hypersensitive site. Chromatin-bound unliganded TR-RXR silences transcription of the Xenopus TRbetaA gene within a canonical nucleosomal array. On addition of hormone, the receptor directs the extensive further disruption of chromatin structure over several hundred base pairs of DNA and activates transcription. We define a domain of the TR protein necessary for directing this extensive hormone-dependent chromatin disruption. Particular TR-RXR heterodimers containing mutations in this domain are able to bind both hormone and their thyroid hormone receptor recognition element (TRE) within chromatin, yet are unable to direct the extensive hormone-dependent disruption of chromatin or to activate transcription. We distinguish the hormone-dependent disruption of chromatin and transcriptional activation as independently regulated events through the mutagenesis of basal promoter elements and by altering the position and number of TREs within the TRbetaA promoter. Chromatin disruption alone on a minichromosome is shown to be insufficient for transcriptional activation of the TRbetaA gene.

Amino Acid Sequence↗