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Biomedical subjects

D Chin

Publications and source records attributed to D Chin.

At least 55 records · Page 3Linked to original sources

Continuous versus intermittent bladder irrigation of amphotericin B for the treatment of candiduria.

PURPOSE: The efficacy of continuous versus intermittent bladder irrigation with amphotericin B in the treatment of candiduria was compared. MATERIALS AND METHODS: A prospective, randomized and comparative pilot study was done on 20 patients. Continuous bladder irrigation with 50 mg./l. amphotericin B infused during 24 hours for 2 days was compared to 3 intermittent bladder irrigations of 10 mg./100 ml. amphotericin B in 1 day. Urine cultures were obtained 72 hours after treatment. RESULTS: The organism was eradicated in 8 patients (80%) who received continuous irrigation and 3 (30%) who received intermittent irrigation (p = 0.035). CONCLUSIONS: Continuous amphotericin B bladder irrigation was superior in terms of efficacy, ease of administration and patient comfort.

Aged↗

Neu differentiation factor (heregulin) induces expression of intercellular adhesion molecule 1: implications for mammary tumors.

Neu differentiation factor (NDF, also called heregulin) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation of the Neu/HER-2 receptor and induces phenotypic differentiation of certain mammary cancer cell lines to growth-arrested and milk-producing cells. To determine which molecules participate in the concomitant morphological alterations, we analyzed the expression of several cytoskeletal and surface molecules and found that NDF elevated the expression of the intercellular adhesion molecule 1 (ICAM-1) in cultured AU-565 human adenocarcinoma cells. The levels of both the protein and the mRNA of ICAM-1 were elevated after 3-5 days of treatment with NDF. Elevated expression of ICAM-1 was induced also by gamma-interferon and by the tumor-promoting phorbol ester (PMA), albeit with different kinetics. Down-regulation of protein kinase C or its inhibition by calphostin C partially inhibited the effect of NDF, implying that the induction of ICAM-1 may be mediated by protein kinase C. NDF transcripts were detectable in 3 of 9 human mammary tumors, suggesting that the in vitro effect of the factor may be relevant to breast cancer. By selecting Neu-positive human mammary tumors (n = 39), we found a significant correlation (P < 0.001) between the expression of ICAM-1 and histological features of invasive ductal carcinoma with a prominent carcinoma in situ component. When cultured in vitro the cells of these tumors grew in clusters and formed domelike structures reminiscent of comedo-type carcinoma in situ. In addition, the majority of patients with tumors that coexpressed ICAM-1 and Neu had no lymph node involvement, unlike most Neu-positive but ICAM-1-negative tumors, which metastasized to the lymphatic system. Taken together, our observations suggest that the induction of ICAM-1 by NDF may affect the morphology, differentiation state, and metastasis of Neu-expressing mammary tumor cells.

Adenocarcinoma↗

Botulinum toxin: preferred treatment for hemifacial spasm.

This paper retrospectively analyses the clinical data of 65 consecutive cases of hemifacial spasm. A benign etiology was clinically evident in the majority of cases. Neuroradiologic investigation ruled out serious intracranial pathology in atypical cases. Trials of oral medication in 26 patients were consistently unsuccessful. Fifty-one patients had repeated lid and facial muscle injections of botulinum toxin during a period of 8 years. The mean duration of effective relief from spasm following an initial treatment was 18.9 weeks. This effect did not diminish with repeated injections.

Adult↗

Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells.

The HER-2/neu protooncogene (also called erbB-2) encodes a tyrosine kinase receptor for a polypeptide growth-regulatory molecule. Amplification and overexpression of the gene have been frequently observed in human adenocarcinomas and correlated with poor prognosis. To explore the potential of antibody therapy directed at the HER-2/Neu receptor, we have raised a panel of murine monoclonal antibodies to the human protein, and tested their effect on the tumorigenic growth of HER-2/neu-transfected fibroblasts in athymic mice. We previously reported that the i.p. injected antibodies either inhibited or accelerated the tumorigenic growth of HER-2/neu transfectants in athymic mice. Here we report that these opposing effects were induced also by i.v. injected antibodies, they lasted over 7 weeks, and were probably mediated by distinct epitopes on the receptor molecule. To understand the cellular mechanisms underlying antibody-induced tumor inhibition, we tested the effect of the monoclonal antibodies on various cultured human breast cancer cells. Our analysis revealed that the tumor-inhibitory antibodies specifically induced phenotypic cellular differentiation that included growth arrest at late S or early G2 phase of the cell cycle, markedly altered cytoplasm and nuclear morphology, synthesis and secretion of milk components (casein and lipids), and translocation of the HER-2/Neu protein to cytoplasmic and perinuclear sites. The extent of cellular differentiation by various antibodies could be correlated with their tumor-inhibitory potential, whereas a tumor-stimulatory monoclonal antibody or control immunoglobulin were completely inactive with respect to cellular differentiation. Taken together, our in vivo and in vitro studies correlate the tumor inhibitory potential of monoclonal antibodies to HER-2/Neu with their capacity to induce cellular differentiation in vitro. This observation may hold promise for immunotherapy of cancers that express the HER-2/neu oncogene.

Animals↗

Specificity of colon specific antigen and colon ovarian tumour antigen.

Sections (5 microns thick) from 101 primary adenocarcinomas (including ovarian, colorectal, gastric, breast, oesophageal, prostatic, pancreatic, endometrial and gall bladder) were incubated wtih anticolon specific antigen (CSA) and anticolon ovarian tumour antigen (COTA) antibodies using the peroxidase antiperoxidase technique with positive and negative controls. Anti-CSA positivity was seen in 19 of 20 colonic adenocarcinomas, but it was also seen in a large number of the other tumours. While anti-COTA staining was positive in 16 of 20 colonic adenocarcinomas and 20 of 30 ovarian adenocarcinomas, it was also positive in a large number of the tumours. Anti-CSA and anti-COTA are not adequately specific in the identification of a colonic or ovarian origin of an adenocarcinoma and cannot reliably be applied to the identification of a metastatic adenocarcinoma of unknown primary site.

Adenocarcinoma↗

Cross-cultural differences in rating hyperactive-disruptive behaviors in children.

OBJECTIVE: To determine the extent to which the reported variations across countries in the prevalence of attention-deficit hyperactivity disorder are due to cultural differences among raters, the authors examined the degree to which mental health professionals in four countries differed in their ratings of hyperactive-disruptive behaviors in children. METHOD: Mental health professionals from China (N = 8), Indonesia (N = 12), Japan (N = 9), and the United States (N = 8) rated the presence and degree of hyperactive-disruptive behaviors in standardized videotape vignettes of four 8-year-old boys participating in individual and group activities. RESULTS: Chinese and Indonesian clinicians gave significantly higher scores for hyperactive-disruptive behaviors than did their Japanese and American colleagues. CONCLUSIONS: These findings suggest that perceptions of hyperactivity vary significantly across countries even if uniform rating criteria are applied. Without correction for these perceptual differences, cross-cultural prevalence rates of hyperactivity may not be comparable.

Attention Deficit Disorder with Hyperactivity↗

A ligand for the erbB-2 oncogene product (gp30) induces differentiation of human breast cancer cells.

The human erbB-2 oncogene encodes a tyrosine kinase receptor. A ligand for the erbB-2 receptor (gp30), with an apparent molecular weight of 30,000, was reported to modulate the growth of cells overexpressing erbB-2. Whereas low concentrations of gp30 induced proliferation of these cells, higher concentrations inhibited their growth. To elucidate the cellular mechanisms underlying cell growth inhibition by gp30, we tested the effect of this ligand on cell growth and differentiation of the human breast cancer cells AU-565 and MDA-MB-453 (which overexpress erbB-2) and MCF-7 cells (which express low levels of this protooncogene). Ligand concentrations that inhibited growth in cells overexpressing erbB-2 induced apparent differentiation of cells with a more mature phenotype, i.e., with characteristics such as inhibited cell growth, altered cytoplasmic and nuclear morphology, and increased synthesis of milk components (casein and lipids). No significant effect of the ligand was observed in the human breast cancer cell line MCF-7. Concomitant with the induction of differentiation in AU-565 and MDA-MB-453 cells, the erbB-2 protein was translocated from membrane to the cytoplasm and perinuclear sites. These findings indicate that ligand-induced growth inhibition in cells overexpressing erbB-2 is associated with an apparent induction of differentiation.

Breast Neoplasms↗

Comparative long-term prognostic value of quantitative HER-2/neu protein expression, DNA ploidy, and morphometric and clinical features in paraffin-embedded invasive breast cancer.

Data regarding the prognostic value of HER-2/neu protein expression in breast cancer are conflicting, perhaps because of short follow-up and technical difficulties in the determination (the admixture of benign elements with the biochemical method and the subjectivity of the immunohistochemical assessment). Therefore, using digital image processing, we compared the correlation between and the prognostic value of (a) quantitative immunohistochemical HER-2/neu protein expression and (b) clinical, morphometric, and flow-cytometric DNA ploidy features; histologic grade; and biochemically assessed estrogen receptor content. Paraffin-embedded invasive breast Pancers of 82 patients with long-term follow-up were used. None of the patients had received adjuvant systemic therapy. HER-2/neu protein expression was significantly correlated with DNA index, lymph node status, and tumor size and, in the diploid tumors, was weakly correlated with the percentage of S-phase cells. Strong HER-2/neu protein expression was associated with a worse prognosis (although not significantly, p = 0.07). No differences were detected between cancers with or without axillary lymph node metastases. In survival analysis, the Multivariate Prognostic Index and the morphometric features were much stronger prognosticators than HER-2/neu protein overexpression, which, however, had additional prognostic value to that of many of the features analyzed, especially when more than 35% HER-2/neu protein levels (relative to the high expression SKBR3 cell line) were present. Combined diploidy and HER-2/neu protein content greater than 35% occurred in a small group of patients (n = 3), all of whom died. Likewise, in tetraploid cancers a combination of S-phase cells greater than or equal to 7% and HER-2/neu protein content greater than 35% was an ominous sign. In multivariate analysis, strong HER-2/neu protein overexpression was prognostically over-shadowed by the morphometric features. Nevertheless, it is important to further analyze the intriguing possibility of identifying a subgroup of breast cancer patients with a very poor outcome merely using cytometric analysis of paraffin-embedded material of the primary tumor.

Biomarkers, Tumor↗

Quantitation of HER-2/neu oncoprotein overexpression in invasive breast cancer by image analysis: a study comparing fresh and paraffin-embedded material.

HER-2/neu oncoprotein overexpression was compared in fresh frozen and paraffin-embedded formalin-fixed invasive breast cancer material from the same patients. The HER-2/neu protein was detected by an immunohistochemical staining method, and the average amount of protein staining per cell was measured using the CAS-200 image analysis system and expressed relative to the amount of HER-2/neu protein of calibration cells of the SKBR3 cell line which are known to have amplification of the HER-2/neu gene and overexpression of the HER-2/neu protein. There was a significant correlation between degree of HER-2/neu protein overexpression and DNA-hyperdiploidy (P less than 0.01, chi 2 test). No significant correlation could be demonstrated between degree of HER-2/neu overexpression and tumor size, lymph node status, number of positive nodes or morphometric features. There was in general a good concordance (r = 0.83) in HER-2/neu expression values between fresh and paraffin-embedded material. Pairwise comparison of the two series (Wilcoxon signed ranks test) revealed no significant differences, indicating that there were no systematic differences between HER-2/neu assessments in fresh and paraffin material. When analysing the HER-2/neu expression values according to thresholds used earlier for overexpression, comparable results for fresh and paraffin material were obtained for most cases. In the fresh and paraffin material a different staining pattern was observed (more membrane staining in the fresh material in contrast to a more diffuse staining pattern in the paraffin material). It was concluded that both fresh-frozen and paraffin-embedded, formalin-fixed material is suitable for assessment of HER-2/neu protein overexpression by image analysis and provides comparable HER-2/neu expression values in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

The use of magnetic resonance imaging in neurological practice--a local experience.

From April 1990 to September 1990, 170 magnetic resonance imaging (MRI) examinations of the brain were made with the Siemens 1.5 Tesla machine (the "Magnetom") in the Hong Kong Baptist Hospital. The indications for the investigation on the referral forms and the results were analysed. The MRI was particularly useful in making the diagnosis in 2 cases of multiple sclerosis, one case of an Arnold Chiari malformation, 6 cases of cerebro-vascular accidents, and 2 cases of encephalitis. MRI has replaced computerised tomography as the study of choice for the majority of central nervous system disorders.

Brain↗

Differentiation of cultured human breast cancer cells (AU-565 and MCF-7) associated with loss of cell surface HER-2/neu antigen.

The relationship between terminal cell differentiation and changes in the subcellular levels of the HER-2/neu antigen was investigated in cultured human breast cancer cells: AU-565 cells (which overexpress the HER-2/neu gene) and MCF-7 cells (which do not overexpress this gene). Differentiation was achieved by treating the cells with mycophenolic acid (MPA), phorbol 12-myristate 13-acetate (PMA), retinoic acid (RA), or the TA-1 monoclonal antibody to the extracellular domain of the HER-2/neu protein. Ten to twenty percent of the cells in untreated, sparsely growing AU-565 cultures exhibited morphological maturation characterized by large lacy nuclei surrounded by sizable flat cytoplasms. A fraction of these cells harbored milk factors such as casein and large lipid droplets. Treatment of the AU-565 cells for 4 d with 9 microM MPA, 1.6 nM PMA, 2.5 microM RA, or 1 microgram/mL TA-1 antibody resulted in cell growth inhibition and an increase in the percentage of cells (48-97%) that exhibit a mature phenotype. MCF-7 cells were also susceptible to differentiation by MPA and RA, but to a lesser degree than the AU-565 cells. Differentiation in the AU-565 and MCF-7 cells was associated with reduced immunostaining for the HER-2/neu protein at the cell surface membrane and with a transient increased diffuse immunostaining for this protein in the cytoplasm.

Blotting, Southern↗

Cerebrovascular disease in Hong Kong Chinese.

Our prospective study of cerebrovascular disease in Hong Kong confirms a previous clinical impression that stroke in the Chinese has a pattern different from that in Caucasians. We studied 540 patients (aged 20-70 years) with stroke. Computed tomography or autopsy was obtained in 86.1% and showed an increase in the proportion with lacunar infarction, striatocapsular infarction, and parenchymal hemorrhage relative to the frequencies in Caucasians. This increase in the incidence of cerebral hemorrhage occurs not only in semicomatose and comatose patients but also in alert patients (16.9%) and those with a lacunar syndrome (12.5%). Our findings suggest that cerebrovascular disease in the Chinese selectively affects small vessels, causing lacunes and hemorrhages. In future community studies on stroke prevalence, researchers should be cautious about interpreting similar prevalence rates as reflecting similar risk factors or pathologies.

Adult↗

HER-2/neu oncogene expression and proliferation in breast cancers.

Amplification of the HER-2/neu proto-oncogene in breast cancer has been reported to correlate with poor patient prognosis. The proliferation, or growth fraction, of cells has also been shown to be of prognostic importance in breast cancer. A study was conducted to evaluate the correlation between HER-2/neu gene expression and proliferation in breast cancer. Quantitative immunohistochemical methods for the detection of the HER-2/neu protein expression and for assessing the proliferation fraction on frozen sections of tumor cells were used. The detection of epidermal growth factor receptor (EGFR) along with quantitative DNA ploidy analysis, also was performed on the same breast cancers. The results indicated two subgroups of invasive ductal carcinoma; 1) HER-2/neu overexpressing cases that were negative for EGFR expression and had low proliferation fraction, and a tetraploid DNA pattern (22 cases), and 2) other combinations of HER-2/neu expression and EGFR expression, with a high proliferation fraction and an aneuploid DNA pattern (38 cases). Eight cases of carcinoma in situ were positive for HER-2/neu overexpression and negative for EGFR expression, and had a high proliferation fraction and a tetraploid DNA pattern. Twenty-six cases of low-grade carcinoma exhibited low proliferation and a diploid DNA pattern.

Breast Neoplasms↗

Effects of modifying individual amino or carboxyl groups on the affinity of calmodulin for calcineurin.

The effects of modifying individual lysyl, aspartyl, or glutamyl residues in calmodulin on its ability to bind to the neural phosphatase calcineurin have been investigated using a competitive binding method termed "label selection." Samples of calmodulin were radiochemically labeled at a low level (0.03-0.6 group/molecule) by acetylation of amino groups or coupling carboxyl groups with ethanolamine to produce preparations containing predominantly single-site modified and unmodified molecules. These preparations were incubated in a 5-10-fold molar excess with bovine calcineurin under conditions appropriate for complex formation. The bound population was isolated, and the level of modification of each reactive residue was compared with the level in the corresponding group in the intial unselected preparation to determine if molecules modified at specific sites had been selected for or against during the competition for complex formation. Significant selection was observed against molecules modified at Lys21, Asp64, Glu67, Lys75, Glu84, Glu114, Asp118, or Lys148, whereas modification of Glu83 increased binding. The modification of other groups, including components of the four Ca2+-binding sites, had no effect on the interaction. Glu67, a Ca2+-liganding residue in Ca2+-binding site II that may regulate the orientation of this site in relation to the central helix, had the strongest influence on complex formation. Most of the residues identified form a nearly linear array in the three-dimensional structure of calmodulin and indicate the location of an extended surface for interaction with calcineurin and other enzymes.

Amino Acid Sequence↗

NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum.

Adult cholinergic interneurons of the neostriatum are not immunoreactive for monoclonal antibody to NGF receptor, whereas the developing neostriatum is immunoreactive for this same antibody. Chronic NGF infusion into the adult neostriatum resulted in reexpression of the NGF receptor such that many cholinergic interneurons became immunoreactive for NGF receptor. NGF infusion dramatically increased the size and choline acetyltransferase immunoreactivity of these same cholinergic neurons. Additionally, in situ hybridization demonstrated an increase in the number of cells expressing NGF receptor mRNA in the NGF-infused striatum. These findings indicate that central cholinergic neurons which lose their NGF receptors during postnatal development will resume their NGF responsiveness when the tissue is damaged. Such a damage-induced mechanism may act to enhance the action of trophic factors, including NGF, released at the site of injury and enhance the responsiveness of damaged CNS neurons to exogenously administered trophic factors.

Aging↗

Increased incidence of thymoma in Chinese myasthenia gravis: possible relationship with Epstein-Barr virus.

Thymectomy was carried out for treatment of myasthenia gravis in 27 unselected Chinese patients and thymoma was found in 13 of them. This 48% incidence of thymomas is two to three times greater than in Japanese and European patients, respectively. The reason for the higher incidence of thymomas observed in Chinese patients may be related to the presence of the Epstein-Barr virus genome in thymoma. Furthermore, all of the thymomas in our patients were lymphoepithelial and histologically resemble nasopharyngeal carcinoma and undifferentiated carcinoma of the salivary gland. Both these tumours are closely linked to the Epstein-Barr virus and in Hong Kong, nasopharyngeal carcinoma is the third commonest cause of death from malignancy. We recommend early thymectomy for patients with myasthenia gravis particularly in geographical areas where there is a high incidence of nasopharyngeal carcinoma and undifferentiated carcinoma of the salivary gland.

Adolescent↗