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Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 163 records · Page 9Linked to original sources
PubMed1996

Extramedullary nasal plasmacytoma--an unusual clinical entity.

A case of extramedullary plasmacytoma with its unusual appearance is reported. This is the second reported case in world literature affecting the paranasal sinuses with intracranial extension. The role of surgery is to obtain tissue for diagnosis and to excise residual disease. Radiotherapy is the treatment of choice and long-term follow-up is necessary for monitoring disease recurrence. The overall 10-year survival is about 50%. The case is discussed with a general review of the management of this pathology.

Humans↗
PubMed1995

Expression of multidrug resistance-associated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution.

Multidrug resistance is a major obstacle to cancer treatment. Using an expression cDNA library transfer approach to elucidating the molecular basis of non-P-glycoprotein-mediated multidrug resistance, we previously established that expression of multidrug resistance protein (MRP), an ATP-binding cassette superfamily transporter, confers multidrug resistance (G. D. Kruh et al., Cancer Res., 54: 1649-1652, 1994). In the present study, we generated NIH/3T3 MRP transfectants without using chemotherapeutic drugs to facilitate the pharmacological analysis of the MRP phenotype. MRP transfectants displayed increased resistance to several lipophilic drugs, including doxorubicin, daunorubicin, etoposide, actinomycin D, vincristine, and vinblastine. However, increased resistance was not observed for Taxol, a drug for which transfection of MDR1 confers high levels of resistance. Verapamil increased the sensitivity of MRP transfectants relative to control transfectants, but reversal was incomplete for doxorubicin and etoposide, the drugs for which MRP conferred the highest resistance levels. For the latter two drugs, MRP transfectants, which were approximately 8- and approximately 10-fold more sensitive than control cells in the absence of verapamil, exhibited 3.8- and 3.3-fold relative sensitization with 10 microM verapamil, respectively, but remained approximately 2 and approximately 3-fold more resistant than control cells. Analysis of drug kinetics using radiolabeled daunorubicin revealed decreased accumulation and increased efflux in MRP transfectants. Confocal microscopic analysis of intracellular daunorubicin in MRP transfectants was consistent with reduced intracellular drug concentrations, and also revealed an altered pattern of intracellular drug distribution characterized by the initial accumulation of drug in a perinuclear location, followed by the development of a punctate pattern of drug scattered throughout the cytoplasm. This pattern was suggestive of a process of drug sequestration, possibly followed by vesicle transport. Both increased drug efflux and perinuclear drug accumulation are consistent with the reported localization of MRP in plasma and cytosolic membranes (N. Krishnamachary and M. S. Center, Cancer Res., 53: 3658-3663, 1993; M. J. Flens et al., Cancer Res., 54: 4557-4563, 1994). These results thus indicate that the drug specificity of MRP is quite similar to that of MDR1, but also suggest potential differences in Taxol specificity and the level of verapamil sensitivity. In addition, these results indicate that MRP functions to extrude drug from the cell, but additionally suggest the intriguing possibility that drug sequestration contributes to drug resistance by protecting cellular targets and/or contributing to drug efflux.

3T3 Cells↗
PubMed1995

Germ cell tumors express a specific alpha-fetoprotein variant detectable by isoelectric focusing.

BACKGROUND: Many nonseminomatous germ cell tumors (NSGCTs) express elevated levels of serum alpha-fetoprotein (AFP), which is widely used for diagnosis and monitoring therapy. Alpha-fetoprotein is also expressed in patients with hepatocellular carcinoma (HCC). In these sera, several variants, some highly specific, recently have been detected by isoelectric focusing. METHODS: Sera were collected from nine patients with NSGCTs, five pregnant women, and five patients with HCC. After isoelectric focusing, the proteins were transferred to nitrocellulose membrane by blotting and incubated with polyclonal rabbit antihuman AFP conjugated with horseradish peroxidase. The enhanced chemiluminescence detection system and Hyperfilm-ECL were used to render the protein bands visible and each was quantified as a percentage of the total AFP using a densitometer. RESULTS: Isoelectric focusing of serum alpha-fetoprotein from the patients with NSGCTs (four testicular, five mediastinal) revealed a consistent pattern characterized by a specific band (band +III). A second band (band +II) that is also seen in sera from patients with hepatocellular carcinoma was present in all patients. The overall pattern was distinct from that of AFP from HCC and that produced during late pregnancy. The two characteristic bands (AFP +II and +III) were responsible for the great majority of total AFP in these patients; estimation of serial sera in patients undergoing treatment showed that total and "malignant" AFP changed in parallel. Banding patterns, apart from one patient, were identical in patients with testicular and mediastinal NSGCTs. CONCLUSION: NSGCTs tumors express a highly consistent and specific pattern of AFP variants. More detailed analysis of AFP patterns in larger numbers of patients may provide further insight into the cellular heterogeneity of germ cell tumors.

Adolescent↗
PubMed1995

Constitutional translocation t(1;17)(p36.31-p36.13;q11.2-q12.1) in a neuroblastoma patient. Establishment of somatic cell hybrids and identification of PND/A12M2 on chromosome 1 and NF1/SCYA7 on chromosome 17 as breakpoint flanking single copy markers.

Cytogenetic and molecular studies in neuroblastoma suggest the presence of a tumor suppressor gene at the distal band p36 of human chromosome 1. We described a constitutional translocation t(1;17)(p36;q12-q21), involving the critical region 1p36, in a patient with neuroblastoma, and hypothesized that the translocation predisposed the patient to tumor development. Here we report the molecular delineation of the translocation breakpoints. Somatic cell hybrids were generated by fusion of the patient's fibroblasts with the thymidine kinase deficient hamster cell line, a3. In hybrid cell lines which retained the human derivative chromosomes, the position of chromosome 1p and 17q DNA probes respective to the translocation breakpoints was determined by fluorescence in situ hybridization and Southern blot analysis. The chromosome 1p breakpoint was localized within a repetitive region encoding t-RNA genes, with 12A-2 (PND) as most distal and pHE2.6 (A12M2) as most proximal single-copy breakpoint flanking markers. For the chromosome 17 breakpoint, the proximal and distal flanking markers were identified as 7G4 (NF1) and cMCP-3 (SCYA7), respectively. In this study, cMCP-3 (SCYA7), encoding the human monocyte chemotactic protein-3, was mapped between NF1 and ERBB2. As a pivotal step towards breakpoint cloning, at present these flanking markers optimally delineate the breakpoint regions of both chromosomes 1 and 17 at the molecular level.

Animals↗
PubMed1995

Deletion mapping in neuroblastoma cell lines suggests two distinct tumor suppressor genes in the 1p35-36 region, only one of which is associated with N-myc amplification.

Neuroblastoma is characterized by deletions of the short arm of chromosome 1 (1p) and amplification of the N-myc oncogene. We have made somatic cell hybrids of two human neuroblastoma cell lines, one with and one without N-myc expression and amplification. The expression of the amplified N-myc gene is completely switched off in the hybrids. This suggests that N-myc expression results from loss of a repressor function. As N-myc amplification is associated with loss of heterozygosity (LOH) of 1p36, we analysed 1p deletions in 16 neuroblastoma cell lines. The seven cell lines without N-myc amplification have no deletions or relatively small deletions, with an SRO on 1p36.23-33. This suggests that a tumor suppressor gene maps in this region. All nine cell lines with N-myc amplification have larger deletions, with an SRO from 1p35-36.1 to the telomere. This suggests that a second tumor suppressor gene which is associated with N-myc amplification maps more proximally. Fine mapping of 1p36 deletions in the two cell lines of the fusion experiment suggests that the distal locus is not a repressor of N-myc expression, but the more proximal locus could be a candidate for this function.

Blotting, Northern↗
PubMed1995

Balanced translocation in a neuroblastoma patient disrupts a cluster of small nuclear RNA U1 and tRNA genes in chromosomal band 1p36.

Chromosomal band 1p36 probably harbours several neuroblastoma suppressor genes. A neuroblastoma patient has been described with a constitutional balanced translocation, t(1;17)(p36;q12-21). Cytogenetically, no loss of chromosomal material was visible. The 1p36 translocation breakpoint could therefore have inactivated one allele of a tumour suppressor gene, thus predisposing the patient to develop neuroblastoma. We localized this breakpoint by pulsed field gel electrophoresis, analysis of yeast artificial chromosomes, and fluorescence in situ hybridization. Here we report that the breakpoint is within a large cluster of small nuclear RNA U1 (RNU1) and some tRNA genes (TRE, TRN) on chromosomal band 1p36. The size of this cluster is over two megabases and it contains many other locally repeated sequences. Polyadenylated transcripts were identified for some of these sequences. In addition, the cluster is the target for integration of an adenovirus 5/SV40 hybrid virus. The translocation breakpoint maps distal of this viral integration site and proximal of marker PND.

Animals↗
PubMed1995

A comparison of amitriptyline, vasopressin and amitriptyline with vasopressin in nocturnal enuresis.

Forty-five children aged 6-14 years with primary nocturnal enuresis were randomised to determine whether desmopressin is more effective than amitriptyline and whether the combination of amitriptyline/desmopressin is more effective than amitriptyline or desmopressin alone. Amitriptyline dosage was 25 mg for children 6-10 years and 50 mg for children aged 10-14 years. Desmopressin (20 micrograms) was given in the same dosage for all age groups. After a run-in period of 2 weeks, children were treated for 16 weeks and then observed for 12 weeks. In the amitriptyline group mean wet nights per week decreased from 5.8 +/- 0.9 to 3.3 +/- 1.9 (P < 0.0005); in the desmopressin group mean wet nights per week decreased from 6.0 +/- 0.9 to 4.7 +/- 1.7 (P < 0.02); in the amitriptyline/desmopressin group mean wet nights per week decreased from 6.3 +/- 0.9 to 3.3 +/- 2.5 (P < 0.0006). When comparing the groups, amitriptyline/desmopressin and amitriptyline were statistically more effective than desmopressin in week 6 (P < 0.009), week 8 (P < 0.03) and week 10 (P < 0.04). No significant side effects occurred. At this dose amitriptyline was more effective than desmopressin and the combination of desmopressin and amitriptyline did not confer any additional benefit.

Adolescent↗
PubMed1995

125I-RIA kit cannot distinguish vitamin D deficiency as well as a more specific assay for 25-hydroxyvitamin D.

OBJECTIVES: To compare a new radioimmunoassay (RIA), measuring vitamin D metabolites, against an established, competitive-protein binding assay (CPBA) that uses rat vitamin D binding protein. METHODS: For the CPBA, we first isolated 25-hydroxyvitamin D (25(OH)D) by eluting sample through silica cartridges. For the RIA, serum was added to acetonitrile and centrifuged, followed by RIA using 125I-25(OH)D3. RESULTS: The within-run CV was 1.5% to 4.1% by RIA, compared to 8.1% to 15.0% by CPBA. For both methods, analytical recovery was not significantly different from 100%, and both methods were appropriately linear with sample dilution. We compared RIA values (y axis) from 90 subjects with 25(OH)D ranging from 11 to 232 nmol/L by CPBA (x axis). The slope was 0.9992 (not significantly different from 1). However, the RIA exhibited a bias of 11.15 nmol/L (p < 0.05 vs 0), and a correlation coefficient of r = 0.923. When the comparison was confined to the 37 samples in the lower half of our reference range, the RIA did not compare well: slope, 0.764 (p < 0.05 vs 1.0); intercept 18.7 nmol/L (p < 0.05 vs 0); r = 0.517. For the samples below 36 nmol/L by CPBA, there was no discrimination by RIA between the 11 values below, and the 11 above the decision level (25 nmol/L by CPBA) for vitamin D deficiency. CONCLUSIONS: We conclude that the RIA is not optimized to detect vitamin D deficiency, and for this purpose it is not a valid substitute for conventional 25(OH)D methods.

Binding, Competitive↗
PubMed1995

Morbidity and mortality for elderly patients with fractured neck of femur treated by hemiarthroplasty.

Patients above the age of 60 with displaced femoral neck fractures are treated by hemiarthroplasty in Singapore because of our low life expectancy. This study evaluates the morbidity and mortality of 110 such patients operated on in our department between January 1990 and December 1992. It has clinical significance because of the rapidly ageing population of Singapore. The mean age was 78 years with a female preponderance of 5:1. They were predominantly Chinese. None of the patients were Malay. This is the first study showing that such fractures are rare among Malays. Most fractures were due to trivial trauma. Fifty-eight per cent had co-existing illness(es). The mean hospitalization stay was 20 days. There were considerable and local complications in 15 patients. Twenty-five patients died. Of the remaining patients, 17 (20 per cent) were unable to regain independent ambulation. The mortality rate at 3, 6 and 12 months was 6.4 per cent, 9.1 per cent and 15 per cent respectively. Males showed a significantly higher mortality rate than females. Also, patients living in government-built high rise flats had a significantly higher mortality rate than those residing in privately owned homes.

Aged↗
PubMed1995

An experimental model to determine the effect of irradiated tissue on neutrophil function.

Complications of irradiated tissue include infections and impaired healing. Although fibrosis and hypovascularity contribute, a cellular mechanism has not been identified. This study examines the effect of radiation (10 to 30 Gy) on neutrophil function in a rabbit wound cylinder model. At 3 to 12 weeks after radiation, subcutaneous wound cylinders were implanted in both irradiated and control fields in 19 rabbits. Wound neutrophils were subsequently assayed for phagocytosis (3H-labeled Staphylococcus aureus assay), superoxide production (cytochrome c reduction assay), and surface Mac-1 expression (flow cytometric assay using MHM 23 monoclonal antibody). Phagocytosis of 3H-labeled S. aureus was significantly lower in neutrophils from irradiated fields compared with controls at 6 and 12 weeks after radiation (6.5 versus 18.9 bacteria per neutrophil at 12 weeks; p = 0.027). Stimulated neutrophils from irradiated tissue could not increase superoxide production or Mac-1 expression as much as controls, with differences increasing as postirradiation time increased. The diminished phagocytosis, superoxide production, and Mac-1 expression provide a cellular mechanism that may account for susceptibility to infection and poor healing in irradiated tissues.

Animals↗
PubMed1995

Evaluation of the gel test for antibody screening in a tertiary hospital in Hong Kong; insensitivity for some cold antibodies that are reactive at 37 degrees C by conventional indirect antiglobulin tests.

The antiglobulin gel test (DiaMed) was compared with conventional IAT methods in pretransfusion antibody screening in a tertiary hospital in Hong Kong. Antibody titrations showed that the gel system was more sensitive than the tube IAT method in detecting anti-D, anti-S, anti-s, but slightly less sensitive with anti-E. The gel tests detected all clinically significant warm reacting allo-antibodies detected by conventional IAT methods except one case of weak anti-E. It detected a case of anti-C missed in conventional screening. The number of serological investigations due to false positive screens, non-specific antibodies and clinically insignificant cold antibodies (anti-P, and anti-Lewis) were reduced. The gel system was fast and easy to use. It would reduce delays and inconvenience caused to patients due to false positive screens and non-specific antibodies without compromising detection of clinically significant antibodies. However, of concern was the failure to detect several cases of anti-Le(a) and anti-P1 that were reactive at 37 degrees C by conventional IAT and one case of anti-H in a patient with Parabombay A.

Blood Grouping and Crossmatching↗
PubMed1995

Perinatal mortality trends among South Australian aboriginal births 1981-92.

OBJECTIVE: To assess changes in perinatal mortality and risk factors for births to Aboriginal mothers in South Australia in 1981-92. METHODOLOGY: All 4013 singleton Aboriginal births in the South Australian perinatal data collection were included. Trends in proportions with specific maternal and infant characteristics, and perinatal mortality by year of birth, were investigated by logistic regression analysis. RESULTS: Changes found included an increase in the proportion of mothers aged 35 years and over, preterm births and births of very low birthweight (< 1500 g), but a decrease in the proportions of births to women under 20 years of age, and of births with a birth defect. There was no statistically significant change in the crude perinatal mortality rate nor in the risk of perinatal death after adjusting for risk factors. CONCLUSIONS: The perinatal mortality rate among Aboriginal births, which is three times higher than the rate for all South Australian births, is not declining, in contrast to the State rate overall. This highlights the need for a concerted approach to Aboriginal perinatal health.

Adult↗
PubMed1995

The sensitivity of ultrasound and serum alpha-fetoprotein in population-based antenatal screening for neural tube defects. South Australia 1986-1991.

OBJECTIVE: To determine the sensitivity of antenatal screening methods for neural tube defects in population-based screening in South Australia in 1986-1991, and whether ultrasound can replace serum alpha-fetoprotein screening in terms of achieving an equivalent level of sensitivity. DESIGN AND SETTING: Ascertainment of all births and terminations of pregnancy with neural tube defects from multiple sources for 1986-1991 in South Australia. Serum and amniotic fluid alpha-fetoprotein results were obtained from the only laboratory performing the tests as a Statewide antenatal screening programme, and information on ultrasound screening from case notifications, hospital case records and medical practitioners who cared for the women. SUBJECTS: All 243 births and terminations of pregnancy with neural tube defects in South Australia in 1986-1991. MAIN OUTCOME MEASURES: The sensitivity of individual screening methods and of all methods used, particularly for spina bifida. RESULTS: For pregnancies with neural tube defects screened by any method (serum alpha-fetoprotein, ultrasound or amniocentesis), 86% sensitivity was achieved. Ultrasound screening for anencephaly achieved 100% sensitivity even in low risk pregnancies, compared with 92% for serum alpha-fetoprotein. For spina bifida, the sensitivity of ultrasound screening increased with the level of risk in pregnancy: it was 60% in low risk pregnancies, which was equivalent to that of serum alpha-fetoprotein screening (64%); 89% in high risk pregnancies and 100% for women referred for confirmation of a suspected spina bifida by another ultrasonographer (chi 1(2) for trend = 23.49, P < 0.0001). Ultrasound screening in high risk pregnancies for spina bifida achieved higher sensitivity in teaching hospitals compared with other ultrasound services in the State (97% vs 65%), but sensitivity was equivalent for low risk pregnancies. It is estimated that, had the serum screening programme not been in place, the level of sensitivity achieved for spina bifida by ultrasound and amniocentesis would have been 62% compared with the actual situation of 76% with the programme in existence, a difference of nearly 15% (95% CI 2.5 to 26.7) (chi 1(2) = 5.45, P = 0.02). CONCLUSIONS: Antenatal screening for neural tube defects in South Australia achieved a higher level of sensitivity with the maternal serum alpha-fetoprotein programme in place. We conclude that the serum screening programme should continue in South Australia pending a significant improvement in the sensitivity of routine ultrasound screening for spina bifida.

Anencephaly↗