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Biomedical subjects

M W Lau

Publications and source records attributed to M W Lau.

7 recordsLinked to original sources

A protein interaction map for cell polarity development.

Many genes required for cell polarity development in budding yeast have been identified and arranged into a functional hierarchy. Core elements of the hierarchy are widely conserved, underlying cell polarity development in diverse eukaryotes. To enumerate more fully the protein-protein interactions that mediate cell polarity development, and to uncover novel mechanisms that coordinate the numerous events involved, we carried out a large-scale two-hybrid experiment. 68 Gal4 DNA binding domain fusions of yeast proteins associated with the actin cytoskeleton, septins, the secretory apparatus, and Rho-type GTPases were used to screen an array of yeast transformants that express approximately 90% of the predicted Saccharomyces cerevisiae open reading frames as Gal4 activation domain fusions. 191 protein-protein interactions were detected, of which 128 had not been described previously. 44 interactions implicated 20 previously uncharacterized proteins in cell polarity development. Further insights into possible roles of 13 of these proteins were revealed by their multiple two-hybrid interactions and by subcellular localization. Included in the interaction network were associations of Cdc42 and Rho1 pathways with proteins involved in exocytosis, septin organization, actin assembly, microtubule organization, autophagy, cytokinesis, and cell wall synthesis. Other interactions suggested direct connections between Rho1- and Cdc42-regulated pathways; the secretory apparatus and regulators of polarity establishment; actin assembly and the morphogenesis checkpoint; and the exocytic and endocytic machinery. In total, a network of interactions that provide an integrated response of signaling proteins, the cytoskeleton, and organelles to the spatial cues that direct polarity development was revealed.

Actins↗

The indications for scrotal ultrasound.

Scrotal ultrasound scanning is now a routine and mandatory investigation of the patient presenting with scrotal symptoms. The need for scrotal ultrasound scanning when the physical examination reveals no significant abnormality has not been previously assessed. We conducted a retrospective study of 160 patients attending for scrotal ultrasound over a period of 1 year. The accuracy of clinical examination was compared with the gold standard of ultrasound for identifying clinically significant lesions. The sensitivity, specificity and positive and negative predictive values were calculated. Four clinically relevant groups were used for analysis purposes: Group I, acutely painful scrotum with or without swelling; Group II, chronic testicular pain without swelling; Group III, chronic scrotal swelling with or without pain; and Group IV, the asymptomatic testis. In Group I, sensitivity was 100%, specificity was 81.3%, the positive predictive value was 92.1% and the negative predictive value was 100%. In Group II, sensitivity was 71.4%, specificity was 90.9%, the positive predictive value was 76.9% and the negative predictive value was 88.2%. In Group III, sensitivity was 88.9%, specificity was 66.7%, the positive predictive value was 92.3% and the negative predictive value was 57.1%. In Group IV, sensitivity was 33.3%, specificity was 100%, the positive predictive value was 100% and the negative predictive value was 93.9%. All clinically significant abnormalities were identified on clinical examination. Clinically insignificant lesions identified by ultrasound alone did not affect the clinical management. It is recommended that scrotal ultrasound is used in the acutely painful scrotum where a confident diagnosis cannot be made or there is failure to respond to treatment, and in the chronic swelling where a confident clinical diagnosis cannot be made.

Acute Disease↗

Development of an enzyme-linked immunosorbent assay with monoclonal antibody for quantification of homovanillic acid [corrected] in human urine samples.

A monoclonal antibody to homovanillic acid (HVA) was prepared by synthesis of a HVA-protein conjugate (HVA-ovalbumin) as an immunogen, immunization of mice, and the subsequent hybridization technique. Monoclonal antibodies were screened on the basis of sensitivity, specificity, and accuracy. An indirect ELISA was developed for quantification of HVA in human urine. The assay was characterized and shown to have high specificity, with cross-reactivities to vanillylmandelic acid and normetanephrine at 0.18% and <0.1%, respectively. The assay coefficients of variation were <10% within the working range of 0.5-40 mg/L. Initial results from testing urine samples of patients with neuroblastoma and other diseases were validated by HPLC, suggesting that this ELISA method is a reliable and convenient system for quantification of HVA in urine and can be used in the mass screening of neuroblastoma in infants.

Adolescent↗

Open versus closed epididymal sperm retrieval in men with secondarily obstructed vasal systems--a preliminary report.

OBJECTIVE: To evaluate and compare sperm quality and suitability for intracytoplasmic sperm injection (ICSI) from open and percutaneous epididymal aspiration in men with obstructive azoospermia, and to determine the relevance of epididymal morphology. PATIENTS AND METHODS: A series of 20 men undergoing vasectomy reversal were evaluated by percutaneous (PESA) and open epididymal sperm aspiration (MESA) before undergoing surgery for reversal. Two samples were taken with PESA, one with the needle in situ (PESA1) and the second while withdrawing the needle (PESA2). Epididymal morphology was graded as normal, distended and grossly distended. Five men undergoing vasectomy served as a control, nonobstructed group for percutaneous aspiration. Analysis of the aspirates was performed immediately after operation with no knowledge of the treatment, and aspiration was considered successful if sperm suitable for ICSI were retrieved. RESULTS: In the obstructed group, 15 of 20 men had successful PESA and 13 of these also had successful MESA. PESA was successful bilaterally eight times compared with MESA on five occasions; two men with successful PESA had no success with MESA. PESA2 was five times more successful than PESA1. Only one PESA in the non-obstructed group was suitable for ICSI. PESA was successful in 21 of 25 distended or grossly distended epididymi compared with only three of 21 non-distended systems. CONCLUSION: PESA is a viable alternative to MESA in patients with obstructive azoospermia, particularly when associated with clinically distended epididymi.

Epididymis↗

Urinary tract obstruction and nephrostomy drainage in pelvic malignant disease.

OBJECTIVE: To determine the survival of patients after percutaneous nephrostomy drainage (PND) for obstructive uropathy secondary to pelvic malignant disease. PATIENTS AND METHODS: The records of 77 patients undergoing PND for obstructive uropathy were reviewed. Patients were classified according to the nature of the obstructing lesion: Group I (primary untreated malignancy, 31 patients); Group II (recurrent malignancy with further treatment, 15 patients); Group III (recurrent malignancy with no further treatment, 12 patients); and Group IV (benign disease as a consequence of previous treatment, 19 patients). Outcome was assessed by survival over a mean follow-up of 20 months (range 2 days-8.3 years). RESULTS: Overall median survival was 26 weeks, with a 5-year survival of 22%. The survival in Groups I and II was not significantly different (median survival 27 and 20 weeks, respectively; 5-year survival, 10% and 20%, respectively). Group III patients had a poor prognosis (median survival 6.5 weeks) with no patient surviving beyond one year, whilst Group IV patients fared best with a 5-year survival of 64%. The commonest primary tumour type was carcinoma of the cervix (42 patients), and these patients were analysed as a subset. Benign post-radiation fibrosis was found in 16 of 27 patients (59%). Survival was related to the diagnostic group. CONCLUSION: The nature and extent of the obstructing lesion and its potential for further treatment are the major determinants of post-nephrostomy survival. Every effort should therefore be made to identify the nature of the obstruction before deciding on PND.

Adult↗