Biomedical subjects
Publications and source records attributed to K W Chan.
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Lysine 195 in the K195 MSKS sequence of E. coli tryptophanyl-tRNA synthetase (TrpRS) was replaced with alanine. The resulting K195A mutant TrpRS had essentially unchanged Km values for ATP and Trp, but a 1500-fold decreased kcat in a pyrophosphate-ATP exchange reaction. This large decrease in kcat reduces the rate of aminoacyladenylate formation (step 1) to a rate comparable to the rate of aminoacylation of tRNA(Trp) (step 2) by the K195A mutant enzyme. Both the TIGN and KMSKS sequences are important for step 1 of class I aminoacyl-tRNA synthetase reactions.
A neonate with extensive stage III mesoblastic nephroma was confirmed at operation to have a tumor that was too infiltrative and too advanced for primary excision. The abdomen was closed after multiple biopsies. Vincristine (1.1 mg/m2) was given intravenously once a week for a total of eight doses. Repeat CT scan confirmed shrinkage of the tumor and a nephrectomy could be performed safely and the tumor removed at the second laparotomy. CT scan repeated 1 year later showed no recurrence. This case illustrates the effective use of a single drug pre-excision chemotherapy which allowed a nephrectomy for extensive stage III mesoblastic nephroma to be carried out safely.
We studied p53 over-expression in a series of 42 primary penile carcinomas (seven verrucous carcinomas, 14 well-differentiated, 15 moderately-differentiated and six poorly-differentiated squamous cell carcinomas) from Chinese patients using the p53 protein specific mouse monoclonal antibody DO-7 on paraffin sections. p53 protein was detected in 40% (17 cases) of the tumours. The p53 staining was not observed in the penile warts (n = 6) and verrucous carcinomas (n = 7). Positive p53 staining was identified only in the less differentiated tumour cells in the periphery of the tumour cell nests in all the cases. The non-invasive dysplastic epithelium next to the tumours could also be positive for p53 protein (three out of 10 cases in which the dysplastic epithelium adjacent to the tumour was adequately sampled). Furthermore, 100% of the human papillomavirus (HPV)-positive cases showed positive p53 staining. It is concluded that p53 over-expression is present in penile squamous cell carcinomas and adjacent non-invasive tumour cells. An inverse correlation between HPV and p53 gene mutation is not observed in penile cancers.
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The so-called sclerosing haemangioma of the lung is an uncommon tumour with predilection for Chinese women. Twenty-five cases showed a predominantly solid/cellular pattern in three, a haemorrhagic/angiomatoid pattern in three, a papillary pattern in one, a sclerotic pattern in one, and in seventeen, a mixed pattern was observed. Immunostaining revealed the expression of epithelial membrane antigen, vimentin (V9), and CD68 (KP1) in all tumours, cytokeratin in 23 (Cam 5.2 and MNF116), S-100 protein in 22 and alpha-smooth muscle actin in 23 tumours. All tumours were negative for surfactant, factor VIII-related antigen, CD34 and MAC387. There was strong labelling for progesterone receptor protein in 20 tumours, and oestrogen receptor protein was weakly stainable in 13 tumours. The histogenesis of sclerosing haemangioma of the lung is controversial and origin from pneumocyte, histiocyte, mesothelial, endothelial and Clara cell has been suggested. Our immunohistochemical findings, in the largest series studied to date, indicated a cytokeratin+, vimentin+, epithelial membrane antigen+, alpha-smooth muscle actin+, CD68+, oestrogen+, progesterone+ phenotype, confirming an epithelial lineage but which does not clearly correspond to any recognized cell in the respiratory system. The distinct expression of progesterone and oestrogen receptor proteins correlates with the predilection of this tumour for women.
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A retrospective single-center cohort study was conducted on 35 patients with diffuse proliferative (WHO type IV) and/or membranous (type V) lupus nephritis (22 with type IV, 6 with type V, and 7 with type IV plus V) who had been treated with a sequential regimen comprising prednisolone and cyclophosphamide during active disease, followed by low-dose prednisolone and azathioprine maintenance. The follow-up period was 33.2 +/- 4.5 months. At presentation, 32 (91.4%) patients were nephrotic, and an abnormal serum creatinine level was noted in 14 (48.3%) patients with type IV changes. Cyclophosphamide was given for 26.8 +/- 2.8 weeks. 33 (94.3%) patients achieved complete or partial renal remissions: 77.3 and 22.7% of the type IV patients, 16.7 and 66.6% of the type V patients, and 14.3 and 71.4% of the type IV plus V patients, respectively (p < 0.0001 for type IV versus type V and for type IV versus type IV plus V). The duration of therapy before renal remissions and normalization of C3 were attained was similar among the three groups of patients. Disease relapse occurred in 4 (18.2%) of 22 IV patients and in 1 of the 5 type V patients in remission. Mortality was not observed, and none of the patients had an increase in serum creatinine level to double the baseline value. Adverse effects related to therapy included: hair loss (42.9%), transient amenorrhea (53.6%), leukopenia (11.4%), febrile episodes (14.3%), and herpes zoster(28.6%). We conclude that sequential use of prednisolone and cyclophosphamide followed by low-dose prednisolone and azathioprine can achieve favorable therapeutic results in the majority of patients with diffuse proliferative and/or membranous lupus nephritis, without excessive toxicities.
BACKGROUND AND PURPOSE: We investigated the influence of alcohol consumption and cigarette smoking on all types of stroke and cerebral infarction, in particular among a representative sample of elderly residents in Taiwan. METHODS: This study was a component of a nationwide survey of health and living status of residents aged 65 years or older in Taiwan in which subjects received detailed physical, neurological, and laboratory examinations. Inquiries were made about medical history, and information on the amount and duration of drinking and smoking was obtained. Diagnoses of stroke were made according to the results of brain computed tomography at the onset of disease or were based on criteria established by the World Health Organization. RESULTS: Of the 2600 subjects, there were 155 elderly persons with stroke (prevalence, 6%). Excessive drinking of more than 367.6 g/wk of alcohol was associated with a high prevalence of cerebral infarction. Consumption of < or = 367.5 g/wk of alcohol did not have an influence on stroke prevalence. The relationship between duration of alcohol drinking and stroke was equivocal. More than 30 pack-years of cigarette smoking was a significant risk factor for all types of stroke and cerebral infarction in particular. Using multiple logistic regression to control for possible confounders, it was found that smoking was an independent risk factors for all stroke and was of borderline significance for cerebral infarction. Although excessive drinking was a significant risk factor for cerebral infarction in univariate analysis, this effect was lost after adjustment for other confounders. CONCLUSIONS: Cigarette smoking was a more important risk factor for stroke and cerebral infarction than excessive drinking of alcohol.
We report a rare case of rectosigmoid stricture associated with colitis cystica profunda that occurred 21 years after local therapeutic irradiation given for carcinoma of the bladder. We reviewed the literature and compared the clinical features, etiology, and macroscopic findings. The pathogenesis of the lesion may be related to repeated ulceration and regeneration, while chronic colonic ischemia may also play a role. The recognition of this rare entity is important because of its low-power "penetrating" architecture, which may be mistaken histologically as well-differentiated adenocarcinoma.
Despite the use of conventional chemoprophylaxis regimens, patients receiving unrelated-donor BMT are at high risk of developing severe acute GVHD. We evaluated a prophylactic regimen combining CsA, MTX and anti-CD5-ricin A chain immunotoxin (H65-RTA) in 31 patients; pentoxifylline was also given to reduce the anticipated nephrotoxicity of CsA. In most cases, planned doses of CsA, MTX and H65-RTA were given (i.e. to 77%, 77% and 93% of patients, respectively). Although fluid retention requiring diuretic therapy was frequent, only 1 patient had a > 10% unexplained increase in body weight during the first 21 days post-BMT. Also, while significant increase of the baseline serum creatinine was noted in 7 patients, none required dialysis. One patient suffered a reversible allergic reaction to the immunotoxin; no other side effects attributable to this regimen were observed. All but 2 patients engrafted (1 died of fungemia on d + 19 and the other had persistent leukemia) and no late graft failures were observed. Seventeen patients developed acute GVHD grade > or = II (probability, 58% [95% CI 41-76%]); 7 had grade > or = III (probability, 24% [95% CI 12-43%]). In the 27 patients who achieved stable engraftment and have survived beyond d + 100, the 3-year probability of developing chronic GVHD was 66% (95% CI 48-84%). As of the last follow-up prior to 01 May 1994, 13 patients are alive in CR and one in relapse; 9 of these patients are off all immunosuppressives and well. Four other patients relapsed and died, and 13 died of other transplant-related causes.(ABSTRACT TRUNCATED AT 250 WORDS)
We report our first local case of pulmonary alveolar proteinosis that required symptomatic therapy with whole lung lavage. This is a rare condition associated with the accumulation of phospholipid material in the alveoli. The presentation is usually insidious and the symptomatology varies from vague complaints to severe crippling dyspnoea. The diagnosis is often delayed and usually made after the exclusion of other conditions. While there is no definitive treatment apart from lung transplant, whole-lung lavage is a safe, repeatable procedure which offers the best prospect for symptomatic, physiological and radiological improvement in severe cases.
A 16-year-old girl with refractory AML received unmanipulated BMT from an unrelated donor. Leukemia relapse occurred 82 days later. The patient was then treated with IL-2 1.8 x 10(6) U/m2 for 5 days per week and 2.5 MU/m2 IFN-alpha three times per week. Toxicities included fever, skin rash, somnolence and a generalized seizure. Treatment was stopped after 2 weeks. Acute GVHD developed at the end of therapy and the patient's leukemia went into remission. She died of fungal pneumonia 30 days later. We conclude that a combination of cytokines may be useful in treating relapsed leukemia after BMT.
We report a retrospective analysis of the experience of a single centre in treating severe aplastic anemia (SAA) with allogeneic bone marrow transplant (BMT). Between 1982 and 1992, we transplanted 21 patients with SAA (14 males, 7 females); median age at BMT was 15 y (range 2-40 y); median time from diagnosis of SAA to BMT was 29 d (range 6 d-5.5 y). Thirteen patients had received multiple transfusions before BMT. Patients were conditioned with cyclophosphamide 50 mg/kg for 4 d, +/- total body irradiation 300-500 cGy as a single fraction; 1 patient received total nodal irradiation (750 cGy) plus antithymocyte globulin. Sixteen patients received bone marrow from human leucocyte antigen (HLA)-identical siblings, 3 from haplo-identical parents, and 2 from unrelated volunteer donors; graft-versus-host disease (GVHD) prophylaxis was variable. Three patients failed to fully engraft following BMT; 2 achieved successful engraftment following a second BMT. Six of 20 evaluable patients (30%) developed grade II-IV acute GVHD, of whom 3 died; 3 patients developed limited and 5 patients (31%) developed extensive chronic GVHD, of whom 1 died. Fourteen patients (67%) are alive and well following BMT with a median follow-up of 6 y (range 2.1-11 y). Survival was superior in patients receiving sibling-donor BMT (75%) compared with those receiving parent- or unrelated-donor BMT (40%). We conclude that allogeneic BMT remains an important mode of treatment for SAA, but long-term survival remains limited by graft failure and GVHD.
Platelet counts (PC) obtained simultaneously from capillary blood (CB) are generally lower than those from venous blood (VB). We quantified this difference in 17 patients with low platelet counts (LPC) and 18 healthy volunteers with normal platelet counts (NPC). The reproducibility of the counts in these 2 groups of subjects was also evaluated. The mean venous platelet count (VPC) and the mean capillary platelet count (CPC) were 67 +/- 30 x 10(3)/ul (+/- SD) and 61 +/- 23 x 10(3)/ul (p = 0.012) in the LPC, and 264 +/- 44 x 10(3)/ul and 234 +/- 45 x 10(3)/ul (p = 0.00016) in the NPC respectively. The mean difference (d) in the PC between VB and CB were 9.4 +/- 13.1 x 10(3)/ul and 19.4 +/- 17.6 x 10(3)/ul in the LPC and NPC respectively. The coefficients of variation (CV) of double counts for VB and CB were 8.1 +/- 8.3% and 9.8 +/- 8.6% for LPC, and 2.3 +/- 1.6% and 2.5 +/- 2.2% for NPC respectively. In conclusion, VPC was frequently (82.9% or 29/35 cases) higher than CPC. In addition, in patients with LPC, the agreement between VPC and CPC was poor and the counts were less reproducible.
Chronic diseases and motor vehicle-related injuries are currently the major causes of death in Taiwan. Smoking, alcohol use and inappropriate driving behavior are important risk factors. Most health behavior develop during adolescence. Smoking and alcohol use always serve as "gateways" for other adverse health behavior. In this study, 1195 high school students from 27 classes were selected by a random systematic cluster sampling method, and a structured self-administered questionnaire was used to investigate their prevalent health behavior. The prevalence of current smoking was 9.9%, alcohol 18.7% and betel-nut chewing 5.4% among the academic high school students, whereas the prevalence among vocational school students was smoking 20.5%, alcohol 26.6% and betel-nut chewing 13.9%. Seventeen percent of vocational students reported that they often rode motorcycles after alcohol consumption. An aggregation of adverse health behavior, such as smoking, alcohol consumption and chewing betel-nuts was commonly observed. Designing comprehensive intervention programs to prevent and modify high school students adverse health behavior is an important task for school health-officials.