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Biomedical subjects

M Y Chan

Publications and source records attributed to M Y Chan.

At least 37 records · Page 2Linked to original sources

High prevalence of human papillomavirus type 58 in Chinese women with cervical cancer and precancerous lesions.

The prevalence of human papillomavirus (HPV) among 332 Hong Kong Chinese women with abnormal Papanicolaou smears were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The overall HPV positive rate was 44.3% with 18.6% (16/86) for normal/inflamed cervices, 36.4% (32/88) for condyloma, 64.7% (33/51) for cervical intraepithelial neoplasia grade 1 (CIN 1), 37.9% (11/29) for CIN 2, 68.3 (41/60) for CIN 3, and 77.8% (14/18) for carcinoma. Double HPV infection was detected in 17 of the 147 positive samples, with a significantly higher proportion in patients with normal or inflamed cervices than those with CIN or carcinoma (31.3% vs 10.5%, P =.029). The six most commonly identified genotypes were HPV 16 (33.3%), HPV 58 (23.8%), HPV 11, 18, 31 (8.8% each), and HPV 33 (6.8%). The worldwide uncommon genotype HPV 58 was found to be the second most common genotype detected in patients with cervical carcinoma (6 of 18 patients). HPV 58 infection showed a significant association with CIN/carcinoma (odds ratio [OR] = 3.98; 95% confidence interval [CI] = 1.22-14.35) and a significant trend of increase in prevalence with increasing severity of cervical lesion (chi(2) = 5.84; P =.016). Among Hong Kong Chinese women with abnormal cervical cytology, the detection of HPV 58 carried a positive predictive value of 68.6% for a cervical lesion of CIN 1 or higher severity. The high prevalence of HPV 58 among Chinese women, particularly in patients with carcinoma, has an implication on the design of HPV detection methods and the development of vaccines.

Adolescent↗

Potential prognostic factors of relapse-free survival in childhood optic pathway glioma: a multivariate analysis.

There is still no consensus on the natural history and optimal management of optic pathway gliomas (OPG) in children. In order to tackle optimal management issues, we need to clearly understand the prognostic and confounding factors affecting relapse of OPG. We propose the use of the Cox proportional hazards (PH) model in a retrospective study of childhood OPG of 69 children seen from 1977 to 1994. We have developed a comprehensive model capable of multivariate analyses and handling time-dependencies. Our studies showed that relapse-free survival improves with increasing age, the presence of neurofibromatosis 1 (NF1), and chemotherapy and radiotherapy (p < 0.0005). Sex, tumor position and surgery do not significantly affect survival. Older children with NF1 have extremely good prognosis. We noted behavior that departs from the strictly proportional hazards model, but results were inconclusive.

Adolescent↗

You can tell by the nose--judging sex from an isolated facial feature.

Measurements taken from the nose are among the most important physical variables which discriminate statistically between male and female faces, yet several investigators have claimed that it is difficult to judge sex on the basis of noses presented in isolation. Previous work on the isolated nose has, however, involved the use of frontal views only, which may have obscured important physical differences between the noses of males and females. An investigation of the accuracy of judgments of the sex of isolated noses observed in frontal, profile, and three-quarter views by male and female subjects is reported. Judgment of sex was performed significantly more accurately than chance in all cases except for frontal views of female noses, where judgment was significantly less accurate than chance. Analysis of variance demonstrated a significant interaction of sex of nose and view of nose, such that male noses were identified better in frontal and in profile views, but female noses better in the three-quarter view. It is suggested that one possible reason for the seemingly contradictory role of the nose in previous studies of sex judgment is that all noses look more male in frontal views. For a nose to be perceived as female, its distinctive shape must be made available to the perceiver; this is most likely from the three-quarter view.

Adolescent↗

Prevalence and significance of HER-2/neu amplification in epithelial ovarian cancer.

Amplification of the HER-2/neu oncogene was assessed in 80 cases of epithelial ovarian tumors using differential polymerase chain reaction. HER-2/neu gene was amplified in 22 of 46 invasive cancers (48%) and in 5 of 34 borderline cancers (15%), but none of the 20 specimens of normal ovaries showed amplification. THis difference is statistically significant (p = 0.00004). The incidence of HER-2/neu amplification in late stage (III-IV, 77%) was significantly higher than that in early stage (I-II, 21%) in invasive epithelial carcinoma (p = 0.0004). There was no correlation between HER-2/neu amplification and cell type or grade of tumor. In cases of ovarian tumors of borderline malignant potential, the amplification of HER-2/neu was not correlated with clinicopathologic features. Follow-up with a mean of 22 months (6-50 months) was available for 39 cases of invasive ovarian cancers and all 34 borderline ovarian cancers. The incidence of HER-2/neu amplification in the invasive cancer and borderline cancer patients who were alive with disease was 50 and 50%, and is not statistically different from that in the patients who were alive with no evidence of disease (p = 0.662 and 0.345, respectively). The incidence of amplification in the invasive cancers of patients who died of the disease (86%) was higher than that in the patients who were still alive (44%), but the difference is not statistically significant (p = 0.175). This study supports the association of HER-2/neu amplification with progression of invasive ovarian cancer. It also suggests that HER-2/neu amplification may be an adjunctive prognostic factor of invasive epithelial ovarian cancer, shown to be associated with an unfavorable clinical course. In addition, HER-2/neu amplification occurs relatively infrequently in early invasive and borderline ovarian cancers, making it unlikely that such amplification is a general early event in ovarian carcinogenesis.

Base Sequence↗

Shwachman-Diamond syndrome and matched unrelated donor BMT.

A 5 year old with Shwachman-Diamond syndrome (SDS) developed acute monoblastic leukaemia following a period of myelodysplasia associated with a clonal cytogenetic abnormality involving chromosome 7. Matched unrelated BMT was carried out using standard CY/TBI conditioning and GVHD prophylaxis protocols. The patient experienced no toxicity, had temporary committed progenitor cell engraftment but eventually died from bone marrow failure 1 year post-transplant. This report, to our knowledge, documents the first reported case of matched unrelated donor BMT for SDS/AML and we speculate that standard conditioning regimens are probably safe in this group of patients.

Bone Marrow Diseases↗

Brain cholecystokinin octopeptide (CCK-8) concentrations: effect of tryptophan and other serotonergic agents.

The effects of 1-week drug treatment on the brain contents of neuropeptides were investigated. The cholecystokinin (CCK) concentrations in the hypothalamus were significantly decreased by tryptophan treatment but not by imipramine and cyproheptadine, which changed the serotonergic function. Proglumide, the CCK antagonist, induced in the hypothalamic and hippocampal-striatal areas an increase in CCK concentration, which was not reversed in the presence of tryptophan. Dynorphin and substance P(SP) concentrations were also modified by proglumide treatment.

Animals↗

Obturator hernia--case reports.

Two cases of obturator hernia are presented. Both patients presented with intestinal obstruction and the diagnosis was not made preoperatively. A review of recent articles showed 57 cases of obturator hernia in 53 patients reported in the period 1981 to 1990 which also showed no improvement in the management of these cases with a high mortality rate of 30%. A high index of suspicion must be maintained in order to diagnose this condition and reduce morbidity and mortality.

Aged↗

Intrahernial tumour--a case report.

Intrahernial tumour is an uncommon entity. Up to 1980, there are 23 reported cases of primary intrahernial tumours. Suspicion should arise when a longstanding hernia has recently become incarcerated. This is the first reported case of primary tumour of the transverse colon found within a paraumbilical hernia presenting with obstruction.

Adenocarcinoma↗

Immunodeficiency in methylmalonic acidaemia.

Three Chinese infants with methylmalonic acidaemia were described. They presented in the neonatal period with recurrent episodes of poor feeding, lethargy, apnoea and severe acidosis. The diagnosis was established by increased methylmalonic acid concentration in the plasma and/or urine. Pancytopenia was a prominent feature in all three patients. Only patient three had assessment of lymphocyte subsets and it showed diminished population of B-lymphocytes and a reversed CD4/CD8 ratio. All three patients were unresponsive to vitamin B12. They experienced severe infections including Gram-negative septicaemia, candidiasis and Pneumocystis carinii pneumonia which caused their deaths. Patients with this disease should be regarded as having severe immunodeficiency, and in addition to optimal metabolic control, they should be treated aggressively for any suspected infective episodes.

Amino Acid Metabolism, Inborn Errors↗

Nucleoside and nucleotide transport through a model liquid membrane. Periodic-catastrophic transport of a novel amantadine phosphoramidate conjugate of 5'-AMP.

Adenosine 5'-phosphor(adamantyl)amidate (5), an analog derived by linking the antiviral drug amantadine to 5'-AMP is transported through a model membrane system in a discontinuous periodic-catastrophic fashion. The system was composed of a glass cell containing two aqueous buffer phases separated by a chloroform layer. A more lipophilic, but structurally related derivative, adenosine 5'-phosphor(n-decyl)amidate (3) showed linear transport in the same system. Less lipophilic substances, including 5'-AMP and adenosine 5'-phosphor(morpholidyl)amidate (2), did not show transport. It is hypothesized that the periodic-catastrophic transport is a result of the collective activity of amidate 5 at the interface between the first aqueous interface and the chloroform layer. The time between catastrophic events is thought to be a reflection of the time necessary for molecular organization at the interface. The phenomenon is a new example of molecular organization in a system far from equilibrium leading to a repetitive dynamic process.

Adenosine Monophosphate↗

Noscapine-induced polyploidy in vitro.

The conditions under which noscapine causes high levels of polyploidy in vitro in human lymphocytes were investigated to try to determine its mode of action and to assess whether it was likely to be a genotoxic hazard when used as an antitussive agent. Irrespective of duration of treatment or type of medium, there seemed to be a threshold for polyploidy induction between 15.0 and 30.0 micrograms/ml and a maximum between 100.0 and 150.0 micrograms/ml noscapine. High levels (10.0-20.0%) of noscapine-induced polyploidy were never found with 4 h treatments or with RPMI 1640 medium plus 15% (v/v) foetal calf serum; the use of Iscove's modified Dulbecco's medium and 24 h treatments were needed. The reasons for these observations seemed to be the faster cell division and greater sensitivity of cells grown in Iscove's medium. There was conflicting evidence about the mechanism of polyploidy induction by noscapine; either spindle damage or cell fusion remain as possibilities. The need for prolonged exposure and the precise nutritional requirements suggest that a short exposure, albeit at high concentration, in the upper gastro-intestinal tract is unlikely to be a hazard for humans. Furthermore, evidence of a threshold at approximately 20 micrograms/ml plus the virtual elimination of noscapine-induced polyploidy by microsomal metabolism (S9 mix) together with published metabolic data imply that the low-level systemic exposure after absorption may well not be hazardous. We conclude that the use of noscapine in cough mixtures does not pose a significant potential hazard for humans.

Bromodeoxyuridine↗

In-vivo and in-vitro studies on the effects of chronic dexamethasone treatment on cardiovascular responses to sympathetic stimulation.

Rats treated with dexamethasone, 1.5 mg/kg s.c. weekly for 3 weeks exhibited significantly greater increases in mean arterial pressure than their controls, following either sympathetic nerve stimulation or noradrenaline administration. The atria from dexamethasone-treated rats showed greater chronotropic activity in response to noradrenaline but not to field stimulation, whereas the force of contraction was significantly less than that of the controls after either field or noradrenaline stimulation. Isolated rat tail artery preparations from dexamethasone-treated rats were found to be twice more sensitive to noradrenaline than the controls. Prazosin antagonised the noradrenaline-induced pressor response to the same extent in control and dexamethasone-treated rats. Dexamethasone treatment did not significantly increase the sensitivity to KCl or the angiotensin-potentiated pressor response to noradrenaline. This study shows that dexamethasone treatment increases postsynaptic sensitivity of the cardiovascular system to noradrenaline in rats.

Animals↗

Synthesis of acyclic and dehydroaspartic acid analogues of Ac-Asp-Glu-OH and their inhibition of rat brain N-acetylated alpha-linked acidic dipeptidase (NAALA dipeptidase).

The following structural and conformationally constrained analogues of Ac-Asp-Glu-OH (1) were synthesized: Ac-Glu-Glu-OH (2), Ac-D-Asp-Glu-OH (3), Ac-Glu-Asp-OH (4), Ac-Asp-Asp-OH (5), Ac-Asp-3-aminohexanedioic acid (6), Ac-3-amino-3-(carboxymethyl)propanoyl-Glu-OH (7), N-succinyl-Glu-OH (8), N-maleyl-Glu-OH (9), N-fumaryl-Glu-OH (10), and Ac-delta ZAsp-Glu-OH (11). These analogues were evaluated for their ability to inhibit the hydrolysis of Ac-Asp-[3,4-3H]-Glu-OH by N-acetylated alpha-linked acidic dipeptidase (NAALA dipeptidase) in order to gain some insight into the structural requirements for the inhibition of this enzyme. Analogues 4-6 and 9 were very weak inhibitors of NAALA dipeptidase (Ki greater than 40 microM), while 2, 3, and 7 with Ki values ranging from 3.2-8.5 microM showed intermediate inhibitory activity. The most active inhibitors of NAALA dipeptidase were compounds 8, 10, and 11 with Ki values of 0.9, 0.4, and 1.4 microM, respectively. These results suggest that the relative spacing between the side chain carboxyl and the alpha-carboxyl group of the C-terminal residue may be important for binding to the active site of the enzyme. They also indicate that the chi 1 torsional angle for the aspartyl residue is in the vicinity of 0 degrees.

Animals↗