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Biomedical subjects

M Ng

Publications and source records attributed to M Ng.

At least 91 records · Page 5Linked to original sources
PubMed1994

Decreased bone mineral density in premenopausal asthma patients receiving long-term inhaled steroids.

Inhaled corticosteroids have become a key element in the maintenance treatment of bronchial asthma. It is well-known that long-term systemic steroid use causes osteoporosis, whereas its inhaled counterpart has been believed to be devoid of such a side-effect. However, recent studies showed that administration of inhaled corticosteroids was associated with biochemical evidence of derangement in bone turnover. We therefore studied bone mineral density (BMD) by dual energy x-ray absorptiometry in 30 patients (18 females, 12 males) with bronchial asthma treated with steroids, essentially by the inhaled route only (both nasal and tracheobronchial), and compared them with healthy subjects individually matched for age, sex, menopausal status, and body mass index (BMI). There was a significant decrease in BMD in the patient group at the hip (neck of femur, p = 0.007; trochanter of femur, p = 0.034; Ward's triangle, p = 0.016) and the lumbar area of the spine (L2-4, p = 0.041). Further analysis showed that this difference from control subjects was mainly seen in the female patients and not in the male patients (neck of femur, p = 0.049; Ward's triangle, p = 0.025; lumbar spine, p = 0.039). In the female patients, there was significant negative correlation of BMD of the lumbar area of the spine and the trochanter of femur with daily inhaled steroid dose and positive correlation of BMD of the trochanter with BMI.

Absorptiometry, Photon↗
PubMed1994

Vitamin D receptor gene expression in mammalian kidney.

The vitamin D-receptor protein and its mRNA were localized in microscope sections of paraffin-embedded mammalian kidneys by means of immunocytochemistry and in situ hybridization, respectively. A monoclonal antibody against chicken intestinal vitamin D receptor immunostained the nucleus and cytoplasm of cells within the distal convoluted tubule, connecting segment, and initial cortical collecting duct of both rats and pigs. Although fainter, immunostaining also was present over proximal tubular cells. (35S)UTP-labeled cRNA probes were detected over both the proximal and distal portions of the mouse nephron, but silver grain densities were 5.8-fold greater over the latter. In conclusion, localization of both the vitamin D-receptor protein and its mRNA in both the proximal and distal nephron of adult mammals suggests that the gene for this protein is expressed in cells at both of these sites. The intensity of immunostaining and the density of cRNA-associated silver grains suggest that vitamin D-receptor gene expression is greatest in the distal nephron.

Animals↗
PubMed1994

p53 gene mutation spectrum in hepatocellular carcinomas in Hong Kong Chinese.

To examine the significance of mutation of the p53 tumour suppressor gene in the development of human hepatocellular carcinoma in a high-prevalence area for hepatitis B viral infection but a low-exposure area for aflatoxin B1, the spectrum of p53 gene mutations was examined in 21 tumour samples from Hong Kong Chinese patients, all of whom were HBsAg positive. DNA sequencing covering exons 5 to 9 of the p53 gene and Hae III restriction enzyme digestion for preliminary assessment of mutation at codon 249 were performed. Immunohistochemical staining with anti-p53 monoclonal antibodies was done on both tumour and nontumour liver tissues. Six tumours (28.6%) showed a p53 mutation and all were point mutations. Of the six point mutations, two (9.5%) were at codon 249 and both were G to T transversions (AGG-->ATG and AGG-->AGT transversions). The remaining point mutations were transversions scattered at codon 172 (exon 5), 214 (exon 6), 273 (exon 8) and 330 (exon 9). Mutated p53 protein was detected in five of these six cases with demonstrable point mutations by DNA sequencing, in contrast to none detected in all of the 15 cases without demonstrable point mutations. The presence of p53 mutations, including those at codon 249, did not show a significant association with tumour size, sex, age, tumour invasiveness in terms of liver invasion, microsatellites and venous permeation, cirrhosis and encapsulation, but tumours with low cellular differentiation tended to have a higher incidence (71%) of point mutations than those with high cellular differentiation (8%). In conclusion, both the overall p53 mutation rate and that a codon 249 in HCC in Hong Kong Chinese are lower than those reported in tumours from China and sub-Saharan Africa. The low mutation rate at codon 249 is compatible with a low aflatoxin exposure. A special type of p53 mutation has not been found to be associated with hepatitis B viral infection. Mutations of p53 gene tends to occur in tumours with low cellular differentiation, suggesting a late occurrence in the event of tumour progression.

Carcinoma, Hepatocellular↗
PubMed1993

Surgical lateral clearance in resected rectal carcinomas. A multivariate analysis of clinicopathologic features.

BACKGROUND: Incomplete removal of the tumor is the main cause of local recurrence in rectal carcinomas; this often occurs at the lateral aspects devoid of the peritoneum. The authors examined prospectively 80 resected rectal carcinoma specimens in an attempt to discover a reliable method to detect lateral resection margin (LRM) involvement by these tumors and to identify pathologic factors that would be prognostically important. METHODS: In each of the 80 resected specimens, the whole tumor was embedded, and whole-mount sections of the entire tumor and the surrounding mesorectum were examined after serial transverse slicing. The distance from the outermost part of the tumor to the LRM (surgical clearance) was measured. RESULTS: Six (7.5%) of the 80 specimens showed LRM involvement (defined as surgical clearance < or = 1 mm) in the single slice seen macroscopically to have the deepest tumor invasion, whereas 16 specimens (20%) were found to have LRM involved after examining all slices microscopically. Surgically clearance had a strong inverse relationship with Dukes staging (P < 0.001) and depth of tumor invasion (P = 0.001). The overall local recurrence rate was 28%; it was much higher (53%) in the patients who had LRM involved by tumor. As a whole, local recurrence was related significantly to LRM involvement (P = 0.006). Survival rates were correlated with macroscopic (n = 3) and microscopic (n = 13) features of the resected specimens using Cox multivariate regression analysis. Three of the nine pathologic parameters isolated (i.e., surgical clearance, cellular differentiation, and number of involved pericolic lymph nodes) were identified as favorable independent prognostic factors. CONCLUSIONS: Local recurrence is related closely to LRM involvement. Embedding and examining the entire tumor and mesorectum is the only reliable and satisfactory means of assessing LRM. Detailed pathologic study on the resected tumor is important when assessing the prognosis.

Adenocarcinoma↗
PubMed1993

p53 protein detected by immunohistochemical staining is not always mutant.

The expression of the tumour suppressor gene p53 was analyzed in a variety of human solid tumours by immunohistochemistry and direct DNA sequencing. Positive nuclear staining using a panel of anti-p53 antibodies was used to select tumours for further genetic analysis. Using PCR amplification followed by immobilization onto magnetic beads and direct sequencing, we sequenced exons 5-9 of the p53 gene from 9 melanomas, 8 nasopharyngeal carcinomas, 16 sporadic breast carcinomas and 11 patients from familial breast cancer families. No sequence alterations of the p53 gene were detected in either the melanoma or nasopharyngeal tumours and only 19% of the primary breast carcinomas showed a variant band indicative of a mutation. Our results indicate firstly that p53 mutations are not generally involved in the tumour types studied and secondly the data emphasize the disparity encountered when attempting to correlate p53 immunohistochemical positivity with mutations within the p53 gene.

Breast Neoplasms↗
PubMed1993

Autorotation test of the horizontal vestibulo-ocular reflex in Menière's disease.

Sixty-four patients with the diagnosis of Menière's disease were tested at the House Ear Clinic with an active head-rotation test system, the Vestibular Autorotation Test (VAT). The VAT is a portable, computerized test that measures the horizontal vestibulo-ocular reflex (VOR) with the use of high-frequency (2 to 6 Hz) active head movements to obtain gain and phase. The purpose of this study was to characterize the horizontal VOR at high frequencies in patients with Menière's disease. At frequencies from 5 to 6 Hz, all patients demonstrated horizontal phase greater than 180 degrees and 85% showed abnormal VAT results. The most common patterns were decreased gain or increased phase values, or both, relative to normative data. No significant differences in the degree of abnormality in gain and phase were noted among groups of patients when the patients were clinically staged. We conclude that, in our test population of patients with Menière's disease, the VAT shows common gain and phase patterns and abnormalities of the horizontal VOR. This may contribute to high retinal image velocities, which render the patient unable to stabilize retinal images during locomotion (visual field image slip), in as many as 85% of the patients tested, regardless of clinical stage. Such high-frequency testing can reveal abnormalities of the horizontal VOR not apparent from conventional vestibular testing. Thus VAT provides additional information about the functioning VOR when combined with the present vestibular test battery.

Adult↗
PubMed1993

On chronic illness: immigrant women in Canada's work force--a feminist perspective.

Data from a comparative ethnographic study were examined to define factors that influence the management of illness among Euro-Canadian and first-generation Chinese women in the Canadian labour force. Compared with Euro-Canadians, Chinese women had a lower level of education, and more of them held blue collar jobs. Many of them had reservations about disclosing their chronic health problem (diabetes) to coworkers and employers, some fearing job loss if this information was revealed. Life circumstances prevented some of these individuals from properly managing their illness. In many cases they had difficulty gaining access to health facilities, learned little from health professionals, and had few resources to help them understand their condition. These complex issues that add to the burden of living with a chronic illness are not always recognized by health professionals, whose interactions with immigrant women are not structured to reveal the social context of the patient's illness.

Adaptation, Psychological↗
PubMed1992

Analysis of free intracellular nucleotides using high-performance capillary electrophoresis.

High-performance capillary electrophoresis (HPCE) with UV absorbance detection (254 nm) has been applied for analyzing intracellular free ribonucleotides. The nucleotide profiles obtained from peripheral blood lymphocytes differ from those obtained from Molt4 human leukemic cells. With a 140 mM borate buffer, pH 9.4, a nearly complete profile can be obtained in 25 min. HPCE has comparable resolution to that of high-performance liquid chromatography (HPLC) but is faster in terms of time per sample run (25 min vs 45 min) and requires much less sample (nanoliter range for HPCE vs microliter range for HPLC).

Chromatography, High Pressure Liquid↗
PubMed1992

Mycophenolic acid inhibits the degranulation of rat peritoneal mast cells.

The effect of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase, on the degranulation of rat peritoneal mast cells (RMC) was studied. RMC were pretreated for 48 hr with 0.1-10 microM MPA before the cells were sensitized with IgE and triggered with specific Ag. The net amount of [3H]5-HT released from granules was decreased by 44 and 32% with 1 and 10 microM MPA treatment, respectively. MPA inhibition of degranulation was completely reversed by the addition of 30 microM guanosine to the incubation medium. There was no difference in the apparent number or affinity of IgE binding sites between control and MPA-treated RMC. MPA pretreatment also had no effect on the IgE receptor-mediated production of PGD2 in RMC. These results suggest that depletion of intracellular GTP pools by MPA can disrupt the signaling between the IgE receptor and the secretory granules and that, under these same conditions, the release and metabolism of arachidonic acid are unaffected.

Animals↗
PubMed1992

Long-term effects of Silastic sheeting in the middle ear.

Silastic sheeting is used to restore a mucosally lined middle ear space and to prevent mucosal adhesions between the medial surface of the tympanic membrane and the promontory after surgical procedures involving the removal of middle ear mucosa. To determine the long-term (1.2 to 21.2 years) effects of Silastic sheeting in the middle ear, six temporal bones from patients with permanent Silastic sheeting in the middle ear cavity after single-stage tympanoplasty were examined. In all six bones, no histologic evidence of foreign body reaction, rejection, or chronic inflammation in the middle ear surrounding the silicone sheeting was observed. Furthermore, the middle ear space was lined by normal-appearing, continuous middle ear mucosa. In four temporal bones, there was no evidence of significant submucosal fibrosis. In two bones, significant submucosal fibrosis was attributable to concurrent middle ear disease rather than to the presence of the silicone. It is concluded that Silastic sheeting in the middle ear after single-stage procedures may prevent adhesions between mucosal surfaces. Given eustachian tube function, Silastic promotes a mucosally lined, aerated middle ear cavity without apparent foreign body reaction, rejection, or chronic inflammatory response.

Ear, Middle↗
PubMed1992

Periductal vessels of the endolymphatic duct.

Light microscope was used to examine the rich vascular plexus surrounding the human endolymphatic duct, both in the periductal loose connective tissue and in the bony channels surrounding the bony vestibular aqueduct. We also performed computer-aided three-dimensional reconstruction on one serially sectioned region of the endolymphatic duct. We found an anastomotic and looping network of vessels residing in the loose connective tissue close to the epithelium of the endolymphatic duct. This network often received a vascular contribution from the vessels in the periaqueductal bony channels. These findings were verified by light microscopic examination of 50 temporal bone specimens. Concurrent with this finding, histologic examination also showed different characteristic features of the vascular system of the endolymphatic duct-proximal sac areas and of the more distal parts of the endolymphatic sac. These features include the arrangement, quantity, and contents of the periaqueductal bony channels, as well as the organization of the bone containing these periductal bony channels. Findings from this study help the understanding of the anatomy of the human endolymphatic duct. In addition, they support and supplement earlier observations of the structure of the endolymphatic duct. We suggest the possible existence of a periductal vasculature system, similar in pattern to that in the endolymphatic sac, but specialized to work with the duct to aid its function.

Connective Tissue↗
PubMed1991

Active fixation leads--long-term threshold reduction using a drug-infused ceramic collar.

Previous investigators, including our group, have reported the threshold reduction benefits of steroid-releasing leads. To date, all published literature has been for the passive fixation versions. The application of steroids should also enhance the performance of active fixation leads. We have developed and tested an atrial and a ventricular Accufix lead with a dexamethasone acetate-releasing, porous ceramic collar (DA DEC). A long-term sheep study has shown a significant reduction in thresholds (THR) when compared to standard Accufix leads without the collar (ACC) for atrial (ATR) and ventricular (VENT) versions (bipolar THR [0.5 msec] at 24 weeks: VENT DA DEC = 0.51 +/- 0.07, VENT ACC = 1.49 +/- 1.03; ATR DA DEC = 1.31 +/- 1.14, ATR ACC = 2.99 +/- 1.31). All other parameters tested, including pacing and sensing impedance as well as polarization overpotential, were similar for the two groups. The Accufix DEC leads therefore have excellent potential for low energy stimulation.

Aluminum Oxide↗
PubMed1990

Fluorescent oligopeptide substrates for kinetic characterization of the specificity of Astacus protease.

The design of fluorescent N-dansylated oligopeptides based on the tubulin cleavage pattern by Astacus protease yields substrates that are turned over up to 10(5) times faster than those presently available. On the basis of this study, an optimal substrate for Astacus protease contains seven or more amino acids and minimally requires at least five amino acids. Direct examination of the formation and breakdown of the ES complex shows its formation occurs within milliseconds at 25 degrees C. The best heptapeptide substrate, Dns-Pro-Lys-Arg-Ala-Pro-Trp-Val, is cleaved only between the Arg-Ala (P1-P1') bond with kinetic parameters kcat = 380 s-1 and Km = 3.7 x 10(-4) M. The presence of Lys or Arg in the P1 and P2 positions yields high-turnover substrates. In the P3 position, the enzyme prefers Pro greater than Val greater than Leu greater than Ala greater than Gly, following the same order of preference seen in the tubulin cleavage pattern. Substitution of Leu for Ala in P1' and of Ser for Pro in P2' decreases activity by 10(5)- and 10(2)-fold, respectively. In position P3', substitution of Trp for Leu leaves the activity unaltered. However, introduction of the Trp fluorophore greatly enhances the sensitivity of the assay due to a 10-fold increase in indole fluorescence for cleavage of any peptide bond between the tryptophan and the dansyl group. Such an energy-transfer-based assay should have widespread use for detection of neutral proteases.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

In vivo elution rate of drug eluting ceramic leads with a reduced dose of dexamethasone sodium phosphate.

We have evaluated the in vivo elution rate and the threshold voltage performance of a new lead incorporating a controlled delivery device based on a porous ceramic collar. The drug, dexamethasone sodium phosphate (DSP less than 0.2 mg), was contained within the pores of a ceramic collar that was positioned externally and adjacent to a 4 mm2 Pt/Ir coated electrode. Thirty-three leads comprising a porous ceramic drug eluting collar (DEC) were implanted in the right ventricle of 12 sheep. In vivo elution was determined by analyzing the drug remaining in the collar after 1, 3, 11, and 28 days. Voltage thresholds were measured at implant and then weekly for 28 days on three sheep. Results were compared to leads with identical electrodes but with silicone DEC (DSP less than 0.5 mg). The in vivo elution rate of the ceramic DEC leads was fast with approximately 50% of the drug content on the first day. Although the drug content and elution rates were different for the ceramic and silicone DEC leads, the threshold performance of the leads was similar. For ceramic and silicone DEC leads, threshold voltages at implant and at 4 weeks were 0.29 +/- 0.09 compared to 0.37 +/- 0.08 and 0.42 +/- 0.08 compared to 0.44 +/- 0.13, respectively. The results show that a relatively rapid release of a reduced dose of DSP from a DEC is still effective in reducing threshold peaking.

Animals↗