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Biomedical subjects

K C Wong

Publications and source records attributed to K C Wong.

At least 55 records · Page 3Linked to original sources
PubMed1998

Rng2p, a protein required for cytokinesis in fission yeast, is a component of the actomyosin ring and the spindle pole body.

BACKGROUND: An actomyosin-based contractile ring plays a pivotal role in cytokinesis. Despite the identification of many components of the ring, the steps involved in its assembly are unknown. The fission yeast Schizosaccharomyces pombe is an attractive organism in which to study cytokinesis because its cell cycle has been well characterized; it divides by medial fission using an actomyosin ring; and a number of S. pombe mutants defective in actomyosin ring assembly have been isolated. Here, we have characterized one such mutant, rng2. RESULTS: Temperature-sensitive rng2 mutants accumulated F-actin cables in the medial region of the cell but failed to organize the cables into a ring. In rng2-null mutants, only a spot-like structure containing F-actin was detected. The rng2+ gene encodes a protein related to human IQGAP1, a protein that binds actin and calmodulin and is a potential effector for the Rho family of GTPases. Rng2p localized to the actomyosin ring and to the spindle pole body (SPB) of interphase and mitotic cells. Localization of Rng2p to the actomyosin ring but not the SPB required F-actin. Rng2p interacted with calmodulin, a component of the SPB and the actomyosin ring. The rng2 gene showed genetic interactions with three other actomyosin ring assembly mutants, cdc4, cdc12, and rng5. CONCLUSIONS: The S. pombe IQGAP-related protein Rng2p is a component of the actomyosin ring and the SPB and is required for actomyosin ring construction following assembly of F-actin at the division site.

Actomyosin↗
PubMed1998

Cloning and characterization of two isoforms of the zebrafish thyrotroph embryonic factor (tef alpha and tefbeta).

We have cloned and sequenced two cDNAs representing two isoforms of the zebrafish thyrotroph embryonic factor (TEF) gene products (tef alpha and beta), a member of the PAR subfamily of bZIP transcription factors. The two isoforms encode two potential proteins of 300 and 293 amino acids respectively. Sequence comparison analysis indicate that the zebrafish tefs show high homology to PAR family of transcription factors of other species in the PAR domain, DNA binding domain and leucine zipper domain. Expression analysis by Northern blot and RT-PCR indicates that tef alpha and tefbeta are expressed in adult fish and throughout the zebrafish embryonic development. In addition, the two tefs are expressed in some adult tissues, but not others.

Amino Acid Sequence↗
PubMed1998

Isolation and characterization of new fission yeast cytokinesis mutants.

Schizosaccharomyces pombe is an excellent organism in which to study cytokinesis as it divides by medial fission using an F-actin contractile ring. To enhance our understanding of the cell division process, a large genetic screen was carried out in which 17 genetic loci essential for cytokinesis were identified, 5 of which are novel. Mutants identifying three genes, rng3(+), rng4(+), and rng5(+), were defective in organizing an actin contractile ring. Four mutants defective in septum deposition, septum initiation defective (sid)1, sid2, sid3, and sid4, were also identified and characterized. Genetic analyses revealed that the sid mutants display strong negative interactions with the previously described septation mutants cdc7-24, cdc11-123, and cdc14-118. The rng5(+), sid2(+), and sid3(+) genes were cloned and shown to encode Myo2p (a myosin heavy chain), a protein kinase related to budding yeast Dbf2p, and Spg1p, a GTP binding protein that is a member of the ras superfamily of GTPases, respectively. The ability of Spg1p to promote septum formation from any point in the cell cycle depends on the activity of Sid4p. In addition, we have characterized a phenotype that has not been described previously in cytokinesis mutants, namely the failure to reorganize actin patches to the medial region of the cell in preparation for septum formation.

Actins↗
PubMed1998

Long-term treatment of lupus nephritis with cyclosporin A.

We evaluated the efficacy and safety of long-term treatment with cyclosporin A (CSA) in type IV lupus nephritis. Seventeen patients with biopsy-proven WHO type IV lupus nephritis were enrolled in a prospective, open study. Twelve of the 17 completed 48 months of treatment with CSA and prednisolone. Three patients required the addition of azathioprine, at 12, 38 and 47 months, respectively, for cutaneous disease flare with refractory rashes. One patient was lost to follow-up at 40 months. The mean +/- SD duration of treatment was 43.2 +/- 10.1 months (range 15.7-48 months). A significant reduction of proteinuria and a significant rise in serum albumin were noted 1 month after initiation of treatment. Improvement was maintained throughout the study except for three patients who relapsed with recurrence of nephrotic syndrome. There were no significant changes in serum creatinine level or creatinine clearances throughout the study. Repeat renal biopsy at 12 months following treatment with CSA showed histological improvement, with WHO type II changes in all 17 patients accompanying significant reduction in activity indices. Patients with baseline haemoglobin (Hgb) levels < 12 g/dl showed significant improvement. Serum C3 and C4 levels were not changed significantly. Corticosteroid-sparing effects were noted. Side-effects included hypertension, gum hypertrophy and mild hirsuitism, but were not serious. Combination therapy using CSA and prednisone is effective and safe for long-term treatment in lupus patients with WHO type IV nephritis.

Adult↗
PubMed1998

Primary cutaneous B cell lymphoma: outcomes and treatment.

This retrospective study documents six patients with primary cutaneous follicular centre cell lymphoma (FCCL) of the head and trunk. The back was the most common site of presentation of the primary. Despite a good response to initial therapy, cutaneous relapses were common and one patient developed lymph node metastases. Intralesional steroids may be effective in controlling localized skin relapses of this B cell lymphoma. All patients are currently alive with two surviving over 5 years.

Adult↗
PubMed1998

Clinical management and treatment outcomes of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC), first described in 1972, is an uncommon, highly malignant tumour of skin. Its aetiology is unknown although the tumour occurs most frequently in sun-exposed sites. This skin cancer is characterized by a high incidence of metastases, local and regional recurrence and has a high mortality. Few survival data beyond 3 years are available. Treatment strategies include wide local excision of the primary and lymph node dissection, as indicated together with adjuvant radiotherapy. The tumour has also been shown to be chemosensitive. Definitive treatment is inconclusive due to the relative rarity of this malignancy. METHODS: A retrospective study was undertaken between the years 1985 and 1996 of 33 patients with MCC at Concord Repatriation General Hospital (CRGH). Demographic details were noted, together with the site and appearance of the primary lesion and the sites and date of metastases. The response and outcome to various modalities of treatment were documented. RESULTS: There were 27 men and six women with an average age of 80 years (range: 60-86 years). The primary lesion in the present series most often resembled a basal cell carcinoma (BCC), with 53% occurring in the head and neck region. Twenty-seven patients (82%) developed metastatic disease, with an average interval of 13.4 months between diagnosis of the primary lesion and the development of metastases. The incidence of locoregional recurrence in the present series was 42%. Radiation combined with surgery achieved locoregional control in 15 of 19 patients with primary, regional or recurrent locoregional disease. Fourteen patients died of MCC and five others from unrelated causes. The 14 survivors have a mean survival of 54 months with six patients surviving more than 5 years. CONCLUSIONS: Local excision together with regional lymph node clearance as indicated, combined with adjuvant radiation treatment was associated with an improved survival. The role of chemotherapy remains unclear.

Aged↗
PubMed1998

Effects of dobutamine, norepinephrine and epinephrine on intramucosal pH and hemodynamics of dogs during endotoxic shock.

This study assessed the effects of dobutamine (DOB), epinephrine (EPI) and norepinephrine (NE) on gastric tissue oxygenation indicated by gastric intramucosal pH (pHi) and hemodynamics in dogs subjected to endotoxic shock. Twenty-four dogs were assigned to four groups of 6 dogs each: endotoxin without catecholamine and endotoxin with DOB, or EPI or NE. Endotoxic shock was induced by intravenous injection of 3 mg/kg of E. coli over 1 min, with an additional 3 mg/kg over the next 2 hrs. Dogs were resuscitated with normal saline to maintain pulmonary capillary wedge pressure (PCWP) near baseline levels. Catecholamines were infused at 0.1, 0.4 and 1.6 micrograms/kg/min (EPI and NE) and 2.5, 5.0 and 10.0 micrograms/kg/min (DOB) for 30 min at each rate. After 2 hrs of endotoxemia, mean arterial pressure (MAP) and cardiac index (CI) and oxygenation delivery index (DO2I) for all dogs decreased by 46.5%, 43.9% and 15.1% respectively, while pHi decreased from 7.47 to 7.10. Endotoxemia increased blood lactate by 142%. Following fluid resuscitation, EPI (1.6 micrograms/kg/min) further increased lactate by 178% (1.22 to 3.4 mmol/L). No correlation was found between tonometry pHi and lactate (R2 = 0.003), pHi and pHa (R2 = 0.231), pHi and DO2I (R2 = 0.056) nor between intramucosal PCO2 and PaCO2 (R2 = 0.005). pHi did not reflect the improvements in cardiovascular hemodynamics observed following administration of catecholamines. NE improved MAP, CI and DO2I whereas DOB produced similar effects as NE but further reduced SVR. EPI produced similar effects as NE. DOB, NE and EPI further decreased pHi. EPI significantly (P < 0.05) increased blood lactate levels more than DOB and NE.

Animals↗
PubMed1997

Anti-Helicobacter pylori treatment in bleeding ulcers: randomized controlled trial comparing 2-day versus 7-day bismuth quadruple therapy.

BACKGROUND: One-week bismuth triple therapy has been established to be highly effective in curing H. pylori infection, but patient compliance has been the major factor of success in therapy. For patients hospitalized for ulcer bleeding, an effective regimen that can completed before discharge will ensure full compliance. AIM: To compare 2-day versus 1-wk bismuth triple therapy plus omeprazole in curing H. pylori infection and bleeding peptic ulcers. METHODS: 100 patients with non-actively bleeding duodenal (DU) or gastric ulcers (GU) and confirmed H. pylori infection were randomized to receive either bismuth subcitrate 120 mg, tetracycline 500 mg, and metronidazole 400 mg four times daily for 1 wk (OBTM-7) or bismuth subcitrate 240 mg, tetracycline 500 mg, and metronidazole 400 mg four times daily for 2 days (OBTM-2). Both groups of patients also received omeprazole 20 mg twice daily for the first week. In the OBTM-2 group, the anti-Helicobacter therapy was finished during hospitalization. Endoscopy was repeated 5 wk after randomization to monitor ulcer healing and determine H. pylori status. Side effects related to the anti-Helicobacter therapy was graded as follows: A, mild discomfort, which did not affect daily activity; B, moderate discomfort affecting daily activity; and C, severe discomfort and patients discontinued therapy. RESULTS: Forty-six patients in the OBTM-2 group and 50 in the OBTM-7 group returned for follow-up endoscopy. With an intention-to-treat analysis, ulcer healing was achieved in 44 of 46 patients (95.7%) in the OBTM-2 group versus 49 of 50 (98%) in the OBTM-7 group, p = 0.61. H. pylori eradication was successful in 35 of 46 patients (76.1%) in the OBTM-2 and in all 50 patients (100%) in the OBTM-7 group, p = 0.00024. There was no difference in the severity of side effects experienced by the patients in the OBTM-2 group than in the OBTM-7 group (19 vs 32%, p = 0.16). None of the patients had rebled during the period of follow-up. CONCLUSION: Despite similar efficacy in ulcer healing, the 2-day quadruple therapy is less effective than the 1-wk regimen in curing H. pylori infection.

Activities of Daily Living↗
PubMed1997

Effects of dobutamine, epinephrine and norepinephrine on the hemodynamics of dogs during hemorrhagic shock.

BACKGROUND: The present study examined how effective epinephrine (EPI), norepinephrine (NOR) and dobutamine (DOB) were for resuscitating dogs subjected to hemorrhagic shock (HS). METHODS: Dogs (n = 42) were randomly assigned to seven test groups: EPI, NOR and DOB infusion with and without HS, and HS dogs with no catecholamine. Following baseline measurements, the dogs were bled to a mean arterial blood pressure of 40 mmHg. After 3 h, the shed blood was reinfused. EPI and NOR (0.1, 0.4 and 1.6 micrograms/kg/min) and DOB (2.5, 5.0 and 10.0 micrograms/kg/min) were given and the dog allowed to stabilize for 30 min. Hemodynamic and blood gas data were obtained at 6 time points (control, shock, resuscitation and after catecholamine infusion). RESULTS: There was no significant difference in myocardial performance (dP/dt) between the respective shocked and unshocked groups after blood resuscitation. In dogs without catecholamine infusion, CO and SvO2 continued to decline whereas SVR increased. DOB (2.5 to 10.0 micrograms/kg/min) with and without shock improved CO, LV dP/dt, SVR and SvO2. EPI did not further improve CO or SvO2 at infusion rates above 0.1 microgram/kg/min (with and without shock). NOR did not improve SvO2 at any infusion rate (with and without shock) and did not improve CO until the infusion rate was at 0.4 microgram/kg/min (without shock). CONCLUSIONS: This study advocates the use of both volume replacement therapy and DOB for resuscitation of HS dogs.

Animals↗
PubMed1996

Common occurrence of an antiidiotypic antibody that recognizes T14+ anti-DNA antibodies in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate whether antibodies to a T14 anti-DNA antibody can be found in patients with systemic lupus erythematosus (SLE). METHODS: Seventy-six serum samples (37 from patients with SLE) were randomly selected from among sera submitted for routine antinuclear antibody testing. Short, overlapping peptides based on the partial VH (variable region of the heavy chain) sequence of the T14 antibody were synthesized on multipins and screened for reactivity with SLE sera. In addition, selected peptides from T14 and related proteins were synthesized in bulk and screened for reactivity with both SLE and control sera. A monoclonal antibody was generated to determine the prevalence of the T14 idiotype (T14+ Id) in the different study populations. RESULTS: Antibodies were detected by a peptide based on the third complementarity-determining region (CDR3) of the T14 protein in 15 (41%) of 37 patients with SLE or 15 (54%) of 28 who had anti-DNA antibodies, in 3 (9%) of 34 patients without anti-DNA antibodies (9 of whom had SLE), and in 6 (10%) of 57 healthy controls. In SLE sera, the antiidiotypic (anti-Id) responses (IgM and IgG) correlated well with the anti-DNA responses (IgG), and both responses correlated well with the T14+ Id activity in SLE sera. Control peptides based on the 18/2 (16/6+ Id) and S107 proteins detected low antibody activities in SLE sera, attributable to cross-reactivity with the T14 peptide. A peptide based on an unrelated human antibody was not reactive with these sera. CONCLUSION: Anti-Id antibodies directed to T14 VHCDR3 were found commonly in the sera of patients with SLE, and they appeared to be induced by the anti-DNA antibodies present in the sera. Based on these findings, these secondary antibodies may be pathogenic in SLE.

Adolescent↗
PubMed1996

Upregulation of adhesion molecule expression on endothelial cells by anti-DNA autoantibodies in systemic lupus erythematosus.

The mechanism of vasculopathy in systemic lupus erythematosus (SLE) remains unclear and the evidence for a direct pathogenic role of anti-double-stranded DNA antibodies (anti-dsDNA) is not strong. Our study aims to determine whether anti-dsDNA exerts any effect on the expression of adhesion molecules on endothelial cells. IgG was purified from 17 patients with SLE (median anti-dsDNA titer, 404 IU/ml) and from 9 healthy controls (median titer 16 IU/ml). Anti-dsDNA-depleted polyclonal IgG (anti-dsDNA-dep-IgG) (median anti-dsDNA titer 17 IU/ml) was prepared from sera of these patients with SLE by affinity chromatography with DNA cellulose column. Expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin on human umbilical vein endothelial cells (HUVEC) cultured with either control IgG or anti-dsDNA were compared by flow cytometry. The levels of adhesion molecules in the supernatant of cultured HUVEC were assessed by sandwich ELISA. Compared with either control IgG or anti-dsDNA-dep-IgG, HUVEC incubated with anti-dsDNA expressed a significantly higher mean fluorescence intensity of ICAM-1 and in VCAM-1 and a higher supernatant concentration of ICAM-1 and VCAM-1 but not E-selectin. At the same time, ICAM-1 mRNA was also raised with increased neutrophil adherence in HUVEC incubated with anti-dsDNA. Pretreatment of HUVEC with native DNA or histone before incubation with anti-dsDNA did not increase the expression of adhesion molecules. Our study provides in vitro evidence that anti-dsDNA could play an important pathogenic role in inducing inflammatory injury of vascular endothelium in SLE.

Adult↗
PubMed1996

The prevalence of and risk factors for neck pain in Hong Kong Chinese.

BACKGROUND: Neck pain has been found to be a prevalent musculoskeletal complaint among Caucasians living in Europe and North America. The prevalence of and risk factors for this condition have not been studied among Chinese living in urbanised cities. The objective of this study was to describe the prevalence of and risk factors for neck pain in Hong Kong Chinese. METHODS: A household survey was conducted in two housing blocks, one being government-subvented housing and the other being private housing. Eight hundred men and women who were 30 years and older were interviewed on the occurrence and characteristics of neck pain, occupations and recreational activities. The life-time and one-year prevalence of neck pain were calculated, and the odds ratio (OR) and 95 per cent confidence intervals (95 per cent CI) for various risk factors were derived by logistic regression. RESULTS: The one-year prevalence of neck pain was 15 per cent and 17 per cent in men and women, respectively. The OR was 1.6 (95 per cent CI = 1.2-2.4) for living in private housing and 2.1 (95 per cent CI = 1.1-4.0) for working as managers and professionals. Subjects with neck pain spent more time reading and a history of trauma to the neck was a significant risk factor for subsequent pain (OR = 5.6, 95 per cent CI = 3.3-9.4). CONCLUSION: Neck pain is a prevalent problem in Hong Kong Chinese, particularly among subjects of a high socioeconomic status. There was little association between life-style and neck pain, although subjects with neck pain spent more time in reading.

Adult↗
PubMed1996

Dialyzer reuse: interaction between dialyzer membrane, disinfectant (formalin), and blood during dialyzer reprocessing.

The growing practice of dialyzer reuse in recent years is mainly based on medical and economic considerations. However, adverse reactions such as immunohemolytic anemia due to anti-Nform antibody associated with dialyzer reuse have been reported. In this study, scanning electron microscopy and cytologic staining were used to evaluate the interaction between blood components and the reprocessed synthetic dialyzer membrane (polysulfone) after disinfectant (formaldehyde) treatment. The results showed that various blood components such as fibrin and blood cells still adhered to the dialyzer membrane after reprocessing. The study also demonstrated that the adhered denatured blood components could be detached by sonication and/or simulated hemodialysis and then gain access into the circulation. The re-entry of the denatured blood components to the patients exposed to reused dialyzers may result in an enhanced immunological response which may contribute to antibody formation (such as anti-Nform antibody) with a reused hemodialyzer.

Anemia, Hemolytic↗
PubMed1996

Increased release of von Willebrand factor antigen from endothelial cells by anti-DNA autoantibodies.

OBJECTIVE: To determine whether antibodies to double stranded DNA (anti-dsDNA) have a pathogenic role in systemic lupus erythematosus (SLE). METHODS: IgG was purified from 17 patients with SLE (median anti-dsDNA titre 1212 IU/ml) and nine healthy controls (median titre 40 IU/ml). Anti-dsDNA depleted polyclonal IgG (median anti-dsDNA titre 17 IU/ml) was also prepared from sera of the 17 patients by affinity chromatography on a DNA cellulose column. Binding to antiendothelial cell antibodies (AECA) and expression of von Willebrand factor (VWF) antigen by cultured human umbilical vein endothelial cells (HUVECs) were studied by flow cytometry. RESULTS: The percentage of HUVECs binding to AECA or expressing VWF was greater for cells incubated with IgG from patients with SLE than for cells incubated with control IgG, though values did not reach statistical significance; nevertheless, HUVECs incubated with IgG from patients expressed a greater mean fluorescence intensity with AECA (p = 0.0001) and greater VWF expression (p = 0.019). Both the fluorescence intensity and percentage of HUVECs binding to AECA or expressing VWF were significantly greater in HUVEC incubated with IgG containing anti-dsDNA than in those incubated with anti-dsDNA depleted IgG. The concentration of VWF in the supernatant was significantly increased in HUVECs incubated with IgG containing anti-dsDNA compared with control IgG or anti-dsDNA depleted IgG. Pretreatment of HUVECs with native DNA before incubation with IgG from lupus patients did not increase binding to AECA, or expression or release of VWF. CONCLUSIONS: Our study provides in vitro evidence that antibodies to DNA have a pathogenic role in the induction of inflammatory injury of the vascular endothelium in SLE.

Adult↗
PubMed1996

Total body protein status assessed by different estimates of fat-free mass in adult peritoneal dialysis patients.

OBJECTIVE: To assess the usefulness of fat-free mass (FFM) as an index of total body protein (TBPr) status in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: TBPr was measured by in vivo neutron activation analysis (IVNAA) and expressed as a standardised protein index (PI). FFM was estimated by dual energy X-ray absorptiometry (DXA), whole body counting of total body potassium (TBK), and creatinine kinetics (CK), and expressed as a standardised FFM index (FFMI). FFM was also determined by a criterion method based on four compartment model (4CM) which is defined as the sum of total body water determined by D2O dilution, TBPr determined by IVNAA, bone mineral determined by DXA, and glycogen estimated to be 4.4% of TBPr. Each patient was measured within a four hour period by all methods. SETTING: Body Composition Laboratory, Monash Medical Centre. SUBJECTS: Six male and twelve female CAPD patients (33-77 years). RESULTS: FFMI assessed by DXA and by TBK agreed with measurements of PI on identifying the mean TBPr status of the CAPD group as significantly below a comparable normal reference population (mean Z score: PI = -1.01 (P < 0.05); FFMI by DXA = -0.50 (P < 0.05); FFMI by TBK = -1.24 (P < 0.05)). In contrast, FFMI assessed by CK did not reveal a significantly reduced TBPr status (mean Z score: -0.70 (NS)). Furthermore, significant linear correlations were noted between PI and FFMI estimated by DXA and by TBK (r = 0.57 (P < 0.05) vs r = 0.69 (P < 0.05)) however no significant correlation was observed between PI and FFMI estimated by CK (r = 0.36 (NS)). Moderate variation in FFM hydration did not compromise the ability of DXA, TBK or CK to differentiate between protein deleted, normal and enriched patients. Comparison of FFM estimates between the criterion method and either DXA, TBK or CK revealed no significant bias (+ 1.8 kg vs -2.0 kg vs +0.8 kg) and respective SEE values of 3.8 kg (8.3%), 5.9 kg (14.3%) and 9.6 kg (21.7%). CONCLUSION: The findings of this study indicate that FFM estimated by either DXA or the whole body counting of TBK is a useful index of TBPr status in CAPD patients. However, FFM assessed by CK does not appear to be an appropriate index of TBPr status in CAPD patients.

Absorptiometry, Photon↗