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Biomedical subjects

M K Chan

Publications and source records attributed to M K Chan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cardiac malformations associated with the congenital nephrotic syndrome.

The association of cardiac malformation with the congenital nephrotic syndrome (CNS) has been previously reported in only one family. We report four patients with CNS: three with pulmonary valve stenosis (one requiring valvuloplasty) and one with discrete subaortic stenosis requiring surgical resection. We conclude that the cardiac status of all patients with CNS should be reviewed regularly by a paediatrician, with a low threshold for referral to a cardiologist, as flow murmurs due to chronic anaemia may obscure cardiac pathology. It is important to diagnose any associated cardiac lesions as these may require intervention, and may also predispose to the development of bacterial endocarditis if surgical or dental procedures are undertaken without appropriate antibiotic prophylaxis.

Aortic Valve Stenosis↗
PubMed2000

A randomized clinical trial comparing autologous blood clot and gelfoam in transarterial chemoembolization for inoperable hepatocellular carcinoma.

BACKGROUND/AIM: Inoperable hepatocellular carcinoma is common in Asia and is usually treated with repeated transarterial chemoembolization. Gunji et al. showed better survival and fewer complications with autologous blood clot as compared with gelfoam used for embolization. Our aim was to compare the effect of blood clot versus gelfoam. METHODS: We conducted a prospective randomized trial in 100 patients with inoperable hepatocellular carcinoma, and compared the side effects and cumulative survival in the two groups. Cox's proportional hazard model was used to study the prognostic factors. RESULTS: The diameter of the main tumor was 7.9+/-4.6 cm. Our study did not show additional beneficial effects of blood clot. The proportion of side effects was similar and the common ones included fever, pain and vomiting. Though the hepatic artery remained patent for a longer period with blood clot (p=0.061), there was no difference in survival (p=0.129 for Okuda I disease and p=0.388 for Okuda II disease). Subgroup analysis showed longer survival in patients with vascular occlusion (p=0.034 for Okuda I and p=0.029 for Okuda II disease). The independent factors of survival were sex, Child's class, Okuda stage, tumor type and presence of metastases. CONCLUSION: This study showed no additional benefits of blood clot in patients with inoperable hepatocellular carcinoma, in Okuda I and II disease. The longer survival in patients with vascular occlusion suggested that the damage to normal liver tissue by planned periodic transarterial chemoembolization may outweigh its benefit in later sessions of repeated TACE in certain patients.

Aged↗
PubMed1999

Structural basis for the design of antibiotics targeting peptide deformylase.

While protein synthesis in bacteria begins with a formylated methionine, the formyl group of the nascent polypeptide is removed by peptide deformylase. Since eukaryotic protein synthesis does not involve formylation and deformylation at the N-terminus, there has been increasing interest in peptide deformylase as a potential target for antibacterial chemotherapy. Toward this end and to aid in the design of effective antibiotics targeting peptide deformylase, the structures of the protein-inhibitor complexes of both the cobalt and the zinc containing Escherichia coli peptide deformylase bound to the transition-state analogue, (S)-2-O-(H-phosphonoxy)-L-caproyl-L-leucyl-p-nitroanilide (PCLNA), have been determined. The proteins for both deformylase-inhibitor complexes show basically the same fold as for the native enzyme. The PCLNA inhibitor adopts an extended conformation and fits nicely into a hydrophobic cavity located near the metal site. On the basis of these structures, guidelines for the design of high-affinity deformylase inhibitors are suggested. As our results show that the protein residues which interact with the PCLNA inhibitor are conserved over a wide variety of species, we suggest that antibiotics targeting deformylase could have wide applicability.

Amidohydrolases↗
PubMed1998

Structure of a biological oxygen sensor: a new mechanism for heme-driven signal transduction.

The FixL proteins are biological oxygen sensors that restrict the expression of specific genes to hypoxic conditions. FixL's oxygen-detecting domain is a heme binding region that controls the activity of an attached histidine kinase. The FixL switch is regulated by binding of oxygen and other strong-field ligands. In the absence of bound ligand, the heme domain permits kinase activity. In the presence of bound ligand, this domain turns off kinase activity. Comparison of the structures of two forms of the Bradyrhizobium japonicum FixL heme domain, one in the "on" state without bound ligand and one in the "off" state with bound cyanide, reveals a mechanism of regulation by a heme that is distinct from the classical hemoglobin models. The close structural resemblance of the FixL heme domain to the photoactive yellow protein confirms the existence of a PAS structural motif but reveals the presence of an alternative regulatory gateway.

Amino Acid Sequence↗
PubMed1998

Expression of p16INK4 and retinoblastoma protein Rb in vulvar lesions of Chinese women.

The protein products of the two tumor suppressor genes located on 9p and 13p, p16INK4 and Rb, respectively, play an important role in regulation of the cell cycle and are implicated in tumorigenesis. We examined 49 cases of benign vulvar lesions, vulvar intraepithelial neoplasia (VIN), and squamous cell carcinoma with immunohistochemical staining to determine expression of p16INK4 and Rb. All and 86% of benign lesions expressed Rb and p16INK4, respectively; 40% each of VIN I and VIN III expressed p16INK4 and Rb, respectively; and 37 and 68% of squamous cell carcinomas expressed p16INK4 and Rb, respectively. The combination of the lack of p16INK4 and/or Rb expression increased from benign lesions (14.3%), through VIN I (60%) and VIN III (60%), to invasive squamous cell carcinoma (72%), thus supporting the postulation that alterations in p16INK4 or Rb could be significant events in progression of disease. The loss of Rb expression also increased from stage I carcinoma (16.7%) through stage II (26.7%) and III (44.4%), to IV (50%), suggesting that Rb may play an important role in tumor progression. A larger study on VIN lesions and genetic coding is suggested to further investigate the role of p16INK4, Rb, and other factors in tumorigenesis and progression of vulvar cancers.

Carcinoma, Squamous Cell↗
PubMed1998

The health consequences of vertebral deformity in elderly Chinese men and women.

The following health consequences of vertebral deformity in Hong Kong elderly Chinese men and women were studied: the prevalence of back pain, disability due to back pain, and low morale. Lateral X-ray films were taken of the thoracic and lumbar spine of 796 community-dwelling Chinese subjects (396 men, 400 women) (aged 70-79). Subjects with one or more definitely deformed vertebra (reduction in vertebral height 3 SD or more below the mean) were classified as definite cases, those with one or more mildly deformed vertebra (reduction in vertebral height 2-2.99 SD below the mean) as mild cases, and the rest as controls. The prevalence and consequences of back pain were measured by a standardized questionnaire, and morale was measured by the Geriatric Morale Score. The relative risk (RR) and 95% confidence interval (CI) of having back pain and being depressed were calculated by logistic regression. Classifications included 16% of men and 30% of women as definite cases, 37% of men and 35% of women as mild cases, and 47% of men and 35% of women as controls. The relative risk (RR) of back pain was 2.3 (95% CI 1.4-3.9) (P < 0.05) in women with definite deformity and 1.5 (95% CI 0.9-2.5) (P > 0.05) in women with mild deformity, as compared with controls. Sixty-four percent of all men had back pain. This prevalence was much higher than figures obtained in a previous survey on low back pain. The prevalence of back pain did not differ by deformity status, but more men with vertebral deformity were on analgesic. There was no significant association between disability due to back pain and vertebral deformity in women. The RR for having a low morale score (of 5 and below) was 2.3 (95% CI 1.3-4.1) (P < 0. 05) in women with mild deformity; men with vertebral deformity did not have a low morale. It was concluded that vertebral deformity was associated with significant back pain and psychological morbidity in elderly Chinese women. Although men with vertebral deformity did not report more back pain, more were on analgesics than controls.

Aged↗
PubMed1997

Crystal structure of the Escherichia coli peptide deformylase.

Protein synthesis in bacteria involves the formylation and deformylation of the N-terminal methionine. As eukaryotic organisms differ in their protein biosynthetic mechanisms, peptide deformylase, the bacterial enzyme responsible for deformylation, represents a potential target for antibiotic studies. Here we report the crystallization and 2.9 A X-ray structure solution of the zinc containing Escherichia coli peptide deformylase. While the primary sequence, tertiary structure, and use of coordinated cysteine suggest that E. coli deformylase belongs to a new subfamily of metalloproteases, the environment around the metal appears to have strong geometric similarity to the active sites of the thermolysin family. This suggests a possible similarity in their hydrolytic mechanisms. Another important issue is the origin of the enzyme's specificity for N-formylated over N-acetylated substrates. Based on the structure, the specificity appears to result from hydrogen-bonding interactions which orient the substrate for cleavage, and steric factors which physically limit the size of the N-terminal carbonyl group.

Amidohydrolases↗
PubMed1996

Human papillomavirus infection in Hong Kong Chinese women with normal and abnormal cervix--detection by polymerase chain reaction method on cervical scrapes.

Detection of human papillomavirus (HPV) was accomplished by utilizing polymerase chain reaction methods on cervical scrapes from a total of 488 Hong Kong Chinese women attending the colposcopy, general, and antenatal clinics. From colposcopy clinic, 10% of normal cervix, 31% of condyloma, 56, 50, and 57% of CIN I, CIN II, and CIN III, respectively, and 88% of squamous cell carcinoma contain HPV. The overall detection rate is 30%. The most prevalent type is 16. Four percent of scrapes from normal cervix of patients attending general gynecology clinic and none from antenatal clinic show HPV. The detection rate appears to be more related to the types of cervical lesions than to the age of the patients.

Adolescent↗
PubMed1996

Ovarian epithelial tumour in gonadal dysgenesis. A case report and literature review.

A patient with gonadal dysgenesis was found to have a mucinous epithelial ovarian tumour on the left side and a streak gonad on the right. The preponderance of mucinous tumours (5 of 8) over other epithelial tumours in these patients is noted but the significance is not fully understood. Two models of pathogenesis (incessant ovulation and hypergonadotrophic hypogonadism) were proposed but neither satisfactorily explains the development of the tumours. Further ultrastructural, chromosomal and molecular biological study of these tumours may help to elucidate the underlying cause and pathogenesis.

Adult↗
PubMed1995

Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase.

The crystal structure of the tungsten-containing aldehyde ferredoxin oxidoreductase (AOR) from Pyrococcus furiosus, a hyperthermophilic archaeon (formerly archaebacterium) that grows optimally at 100 degrees C, has been determined at 2.3 angstrom resolution by means of multiple isomorphous replacement and multiple crystal form averaging. AOR consists of two identical subunits, each containing an Fe4S4 cluster and a molybdopterin-based tungsten cofactor that is analogous to the molybdenum cofactor found in a large class of oxotransferases. Whereas the general features of the tungsten coordination in this cofactor were consistent with a previously proposed structure, each AOR subunit unexpectedly contained two molybdopterin molecules that coordinate a tungsten by a total of four sulfur ligands, and the pterin system was modified by an intramolecular cyclization that generated a three-ringed structure. In comparison to other proteins, the hyperthermophilic enzyme AOR has a relatively small solvent-exposed surface area, and a relatively large number of both ion pairs and buried atoms. These properties may contribute to the extreme thermostability of this enzyme.

Aldehyde Oxidoreductases↗
PubMed1995

Molecular characterization of the genes encoding the tungsten-containing aldehyde ferredoxin oxidoreductase from Pyrococcus furiosus and formaldehyde ferredoxin oxidoreductase from Thermococcus litoralis.

The hyperthermophilic archaea Pyrococcus furiosus and Thermococcus litoralis contain the tungstoenzymes aldehyde ferredoxin oxidoreductase, a homodimer, and formaldehyde ferredoxin oxidoreductase, a homotetramer. herein we report the cloning and sequencing of the P. furiosus gene aor (605 residues; M(r), 66,630) and the T. litoralis gene for (621 residues; M(r), 68,941).

Aldehyde Oxidoreductases↗
PubMed1994

Cytomegalovirus infections in renal transplant patients.

The incidence of cytomegalovirus infection in Chinese patients was reviewed in a retrospective study of 99 renal transplant recipients. CMV infection occurred in 18 patients (18.2%). In 4 the infection was considered primary and in 14 it was thought to be reactivation. Of the infections 88.9% occurred within the first 6 months after transplantation, 44.4% were asymptomatic, while the rest had protean manifestations with the commonest combinations of fever, hepatic dysfunction and haematological abnormalities. One patient succumbed to the infection. Significant difference was seen in the incidence of CMV infections among patients who had received different antirejection therapy, being the highest (37%) among those who had received either Atgam or OKT3. Among the various secretions, urine gave the best yield of virus cultures.

Adolescent↗
PubMed1993

The nitrogenase FeMo-cofactor and P-cluster pair: 2.2 A resolution structures.

Structures recently proposed for the FeMo-cofactor and P-cluster pair of the nitrogenase molybdenum-iron (MoFe)-protein from Azotobacter vinelandii have been crystallographically verified at 2.2 angstrom resolution. Significantly, no hexacoordinate sulfur atoms are observed in either type of metal center. Consequently, the six bridged iron atoms in the FeMo-cofactor are trigonally coordinated by nonprotein ligands, although there may be some iron-iron bonding interactions that could provide a fourth coordination interaction for these sites. Two of the cluster sulfurs in the P-cluster pair are very close together (approximately 2.1 angstroms), indicating that they form a disulfide bond. These findings indicate that a cavity exists in the interior of the FeMo-cofactor that could be involved in substrate binding and suggest that redox reactions at the P-cluster pair may be linked to transitions of two cluster-bound sulfurs between disulfide and sulfide oxidation states.

Azotobacter vinelandii↗
PubMed1993

A blood pressure profile of rural Kadazans and Bajaus in Sabah, east Malaysia.

A survey was conducted to document the blood pressures of two indigenous groups (Kadazans and Bajaus) who reside in rural Sabah in East Malaysia. Their health knowledge status is also recorded. Fifty percent of those surveyed were unable to associate high blood pressure with a risk factor and as high as 38% were unaware of the consequences of high blood pressure. A total of 16.2% had blood pressures > or = 140/or 90mm Hg while 3.9% had blood pressures > or = 160/or 95mm Hg. While these figures are low compared to those of developed countries, lifestyle changes associated with rapid urbanization in Malaysia may be expected to increase hypertension prevalence. The strengthening of health education programs is timely as health knowledge is limited and many hypertensives default treatment.

Adult↗