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Biomedical subjects

D Y Wang

Publications and source records attributed to D Y Wang.

At least 91 records · Page 5Linked to original sources

Serum prolactin levels and their relationship to survival in women with operable breast cancer.

The prognostic value of serum prolactin levels was assessed in a sequential series of 739 patients who were initially treated at Guy's Hospital, London, between 1975 and 1980. Prolactin was measured in 472 patients 1 day before (Hpr1) and in 457 patients 10 days after (Hpr2) mastectomy. Follow-up of the patients was up to August 1992 giving 6139 women-years with a median follow-up time of 11.5 years (13.7 for patients still living and 5.1 for those dead). The association between the three prolactin variables and reproductive and clinical factors was examined before assessing the prognostic value of prolactin levels in terms of overall, disease-specific and disease-free survival. Multivariate survival models were used in order to adjust for the effect of other prognostic variables. These were found to be: tumour size, degree of nodal involvement, tumour grade and age at diagnosis. The results showed that high Hpr2 or high postoperative increase in prolactin (i.e. Hpr2-Hpr1) were significantly related to shorter disease-specific survival (p = 0.04 and 0.01, respectively) in postmenopausal women. In addition there was some indication, which did not attain formal significance, for this association to occur for disease-free survival. Thus the rise in blood prolactin levels after surgery may be a weak indicator of poor prognosis of breast cancer in postmenopausal women.

Adult↗

Prostaglandin D2 measurement in nasal secretions is not a reliable marker for mast cell activation in atopic patients.

BACKGROUND: Prostaglandin D2 (PGD2) is a very important mast cell product during the early-phase nasal allergic reaction. However, the quantification of PGD2 in nasal secretions has not yet been well established. OBJECTIVE: Quantitative determination of PGD2 in nasal secretions of atopic patients (n = 17) after nasal allergen challenge (NAC) and in non-allergic healthy volunteers (n = 10). METHODS: The nasal microsuction sampling technique was used to obtain the nasal secretions with an exactly known and minimally diluted volume. A sensitive and specific enzyme immunoassay was chosen to measure the more stable 11-methoxime derivative of PGD2, which was obtained after extraction in acetone/ethanol and conversion using methoxamine-HCl. The concentrations of PGD2 in nasal secretions obtained from 10 non-allergic healthy volunteers were used as reference values. RESULTS: There was no significant difference in the concentrations of PGD2 between men (median: 569 pg/mL) and women (median: 407 pg/mL), nor between the baseline concentrations from atopic patients (median: 410 pg/mL) and non-allergic controls (median: 477 pg/mL). In the atopic patient group, PGD2 did not significantly increase during the entire sampling period after NAC. The absence of PGD2 response contrasted with the nasal symptoms manifested by sneezing, increased nasal airway resistance, and the significant increases of the concentrations of histamine, tryptase, and leukotriene C4 (LTC4) 5 min after NAC. CONCLUSION: This observation suggests that the measurement of PGD2 alone in the nasal secretions does not give reliable information on mast cell activation during a nasal allergic reaction.

Adolescent↗

Efficient and specific induction of esophageal tumors in rats by precursors of N-nitrososarcosine ethyl ester.

Cancers and precancerous lesions of the esophagus were efficiently induced in rats by the simulation of a clinico-epidemiological setting; that is, the administration of precursors of nitrosamine. Six week old non-inbred male Wistar rats were given 2g/kg bodyweight of sarcosine ethyl ester hydrochloride (SEEH) and concurrently 0.3g/kg bodyweight of sodium nitrite (NaNO2), precursors of N-nitrososarcosine ethyl ester (NSEE), in 2% sucrose as drinking water. Group 1 received the precursors twice a week for 6 weeks followed by 8 weeks observation, and group 2, once every 3 days for 7 weeks followed by 26 weeks observation. At the end of treatment, no tumor had developed in the esophagus of rats in group 1, but the [3H]-thymidine labeling indices in both basal and superficial layer cells were higher than in the control group. On subsequent observation, papillomas appeared in group 1 (33.3%), and carcinomas in group 2 (33.3%), within 4 weeks. The tumors induced in group 1 were mostly papillomas and rarely carcinomas. When the observation was prolonged in group 2, 100% of the animals had cancer in week 20. The pathological changes of the lesions paralleled the sequential development of human squamous cell carcinoma of the esophagus. Our system has the advantages in that papillomas and cancers can be induced in rats in a short time and the agents used are less toxic than preformed nitrosamines administered previously by gastric intubation. It would serve as a useful experimental tool to study premalignant lesions and cancers of the esophagus.

Animals↗

Aromatase activity and interleukin-6 production by normal and malignant breast tissues.

The aromatase enzyme complex, which regulates the conversion of androstenedione to estrone, may have an important role in regulating estrogen synthesis in breast tissues. In this study the effect of tumor location on aromatase activity in adjacent tissue was examined and related to interleukin-6 (IL-6) production, which has been shown to stimulate aromatase activity in breast cancer cells. Samples of normal and malignant breast tissues were obtained from 11 women undergoing mastectomy. In 7 patients, aromatase activity was highest in the quadrant in which the tumor was located or on which the tumor impinged. Aromatase activity in tumor-bearing quadrants was significantly higher than that in adjacent and opposite quadrants. Aromatase activity and IL-6 production, expressed in terms of tissue weight, were significantly higher for tumor tissue compared with normal breast adipose tissue. A significant correlation was found between aromatase activity and IL-6 production for breast tumor tissue (rs = 0.56; P < 0.05), but not for adipose tissue from the breast quadrants. Aromatase activity and IL-6 production were also measured in tissue obtained from a normal woman undergoing reduction mammoplasty who had previously had breast augmentation by silicone injection, not contained within a capsule. In tissue from this patient there was evidence of chronic inflammation and a marked macrophage response. Aromatase activity in this tissue was considerably higher than that detected in mastectomy adipose tissue samples, and a significant correlation was found between aromatase activity and IL-6 production (rs = 0.77; P < 0.05). A preliminary study to examine the potential role of cells of the immune system in regulating breast tissue aromatase activity revealed that conditioned medium collected from macrophages and lymphocytes could markedly stimulate aromatase activity in tumor-derived fibroblasts. The results of this study confirmed that breast tumor location can influence aromatase activity in adjacent tissues and showed that aromatase activity is increased in tumor-bearing quadrants. The increased production of IL-6 by tumor tissue and its correlation with aromatase activity suggest that tumors may be the major source of IL-6, which is able to influence aromatase activity in adjacent tissues.

Adipose Tissue↗

IL-6sR: release from MCF-7 breast cancer cells and role in regulating peripheral oestrogen synthesis.

The interleukin-6 soluble receptor (IL-6sR) may regulate the ability of IL-6 to stimulate oestrogen synthesis in breast cancer cells and breast tumours. Significant aromatase activity was detectable in IL-6 stimulated fibroblasts derived from subcutaneous adipose tissue, but the combination of IL-6sR plus IL-6 resulted in a marked 21-fold stimulation of aromatase activity. To examine the control of IL-6sR release, the effects of oestradiol, 4-hydroxytamoxifen (4-OHT), dexamethasone, TPA, TNF alpha or IL-6 on this process was examined using MCF-7 breast cancer cells. Oestradiol, TNF alpha and dexamethasone all markedly increased IL-6sR release. While 4-OHT had a small stimulatory effect on IL-6sR release, it blocked the ability of oestradiol to increase IL-6sR release. Significant concentrations of IL-6sR were also detected in conditioned medium collected from lymphocytes and macrophages and in cytosols prepared from normal and malignant breast tissues. These results indicate that IL-6sR may have an important role in potentiating the effect of IL-6 on oestrogen synthesis in breast cancer cells. The abilities of oestradiol or tamoxifen to potentiate or inhibit the IL-6 stimulation of oestrogen synthesis in breast cancer cells may result from their effects on IL-6sR release.

Antigens, CD↗

Chronic nasal obstruction in children. A fiberscopic study.

In this prospective study, fiberscopies were gently performed in 375 paediatric patients. The purpose of the study was to evaluate the nasal and nasopharyngeal anatomy and aetiologies of chronic nasal obstruction using fiberoptic examination in children. The essential advantage of this examination is that it allows a more thorough inspection of these cavities. The authors demonstrated that there exists a significant relationship between the relative size of the adenoid tissue and nasal obstruction complaints in children (p < 0.001). When the presence of adenoid hypertrophy was confirmed endoscopically, surgery proved to be highly efficacious in relieving chronic nasal obstruction.

Adenoidectomy↗

Systemic lupus erythematosus presenting as pleural effusion: report of a case.

Systemic lupus erythematosus (SLE) presenting as a pleural effusion in a young male is not common. This paper describes a 20-year-old man who was admitted to hospital with a spiking fever, chills and cough. A chest x-ray showed alveolar infiltration and a moderate right-sided pleural effusion. The patient was treated for parapneumonic effusion. Thoracentesis was performed and cytology of the aspirated fluid was initially interpreted as showing only numerous polymorphonuclear (PMN) leukocytes. However, in spite of antibiotic treatment the symptoms persisted. A careful review of the cytology specimen showed classic lupus erythematosus (LE) cells in addition to PMN cells. Subsequent investigation, including antinuclear antibodies titer, confirmed the diagnosis of LE pleurisy. Therapy with antibiotics was discontinued and treatment with prednisolone 20 mg daily was begun. There was a rapid clinical response including resolution of the fever and pleural effusion.

Adult↗

High prevalence of p53 protein overexpression in patients with esophageal cancer in Linxian, China and its relationship to progression and prognosis.

BACKGROUND: Linxian is the highest endemic area of esophageal squamous cell carcinoma (ESCC) in China and one of the highest incidence areas in the world. The relationship of p53 protein accumulation to geographic variation, pathologic findings, and prognosis has not been investigated extensively. METHODS: Formalin fixed, paraffin embedded ESCC tissues from 100 patients who underwent esophagectomy between 1973 and 1983 were immunostained by using monoclonal antibody pAB1801. RESULTS: p53 overexpression was observed in 41 (87.2%) of 47 tumors of patients in Linxian and in 16 (64%) of 25 additional patients outside Linxian. Its prevalence in the noncancerous epithelium (11/72, 15.3%) and carcinoma in situ (1/7, 14.3%) was lower than that in invasive lesions (64/93, 68.8%). Its immunostaining intensity increased with the depth of cancer invasion. Of 30 primary carcinomas with lymph node metastasis, 29 (96.7%) were positive. However, only 36 (51.4%) of 70 primary lesions without metastasis were positive, and a higher intensity was noticed in the metastases. There was a lower expression rate in tumors of patients surviving more than 10 years (25/52, 48.1%) than in those surviving less than 3 years (40/48, 83.3%). Overall and nonadvanced or metastasis-free cumulative survival rates were both significantly different in patients with and without p53 protein overexpression. CONCLUSIONS: There is a higher expression rate of p53 protein in ESCC in tumors of patients from Linxian than in those from the surrounding area. The accumulation of p53 protein is related to the invasiveness and capability for metastases of cancer cells and appears to be a useful prognostic factor for patients with ESCC.

Adult↗

Glycosaminoglycans enhance phorbol ester-induced proteolytic activity and angiogenesis in vitro.

It has been reported that endothelial cells suspended in three-dimensional type I collagen gels can be induced to undergo tube formation by 12-o-tetradecanoyl phorbol 13-acetate (TPA). In this report, we show that TPA-induced endothelial cell tube formation can be further enhanced by the addition of other matrix components in the collagen gels. In the presence of TPA, both high molecular weight hyaluronate and chondroitin sulfate elicit a dose-dependent stimulation of tube formation. The enhanced tube formation appears to be due to an increase in the number of cells undergoing morphogenesis as the average length per tube is not obviously increased. Concomitant with the increased cell morphogenesis, there is an increase in proteolytic activity secreted by the cells. Treatment of cells with cycloheximide suppresses hyaluronate- and chondroitin sulfate-enhanced cell morphogenesis and proteolytic activity suggesting that new protein synthesis, perhaps proteases, is necessary for endothelial cell morphogenesis. The possible role of the production of proteolytic activity in endothelial cell tube formation is discussed.

Cell Differentiation↗

Differential regulation of the 2',3'-cyclic nucleotide 3'-phosphodiesterase gene during oligodendrocyte development.

The two major isoforms of 2',3'-cyclic nucleotide phosphodiesterase (CNP), 48 and 46 kDa, have recently been shown to be produced from a single gene by alternative splicing. In addition, messenger RNA encoding the larger isoform is transcribed from a separate promoter, approximately 1 kb upstream from that encoding the smaller isoform. We have investigated the expression of these two CNP isoforms and have found that they are differentially expressed during the process of oligodendrocyte maturation. In oligodendrocyte precursors, only the mRNA encoding the larger protein is found. At the time of oligodendrocyte differentiation, however, both CNP mRNAs are induced. These patterns of CNP expression are likely due to stage-specific transcriptional regulation of the two CNP promoters during the process of oligodendrocyte differentiation.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Serum progesterone at the time of surgery and survival in women with premenopausal operable breast cancer.

Serum progesterone and oestradiol levels have been measured in 210 premenopausal women with operable breast cancer on samples taken within 3 days of tumour excision. There was no relation between oestradiol level and time since last menstrual period, nor any effect of oestradiol value on prognosis. However, serum progesterone levels were related to the phase of the cycle as determined by time since last menstrual period. When divided on a basis of levels > 1.5 ng/ml (luteal phase) and < or = 1.5 ng/ml, it was found that there was no difference in survival between the two groups among 117 axillary node negative cases. However, in the 93 patients with positive axillary nodes, higher progesterone levels were associated with significantly better survival. Thus, serum progesterone levels at the time of surgery may affect the prognosis of premenopausal node positive patients with operable breast cancer.

Breast Neoplasms↗

Bone density of normal women in relation to endogenous and exogenous oestrogens.

To evaluate the relationship between duration of hormone replacement therapy (HRT) and forearm bone density, a population-based study has been conducted of 4638 women comparing bone density of 1079 women who had taken HRT for varying times with those who had never taken it. Forearm bone mineral content (BMC) was measured by single photon absorptiometry. Additionally, free oestradiol and sex hormone binding globulin levels were measured in women with high and low bone mineral content. There were no detectable differences in BMC in those who took HRT for up to 24 months compared with those who did not. Thereafter there were significant positive regression coefficients for duration periods of 2 to 5 yr (beta = 0.77, P = 0.04 and beta = 1.76, P = 0.03) and more than 5 yr (beta = 1.66, P < 0.0005 and beta = 1.87, P = 0.009) in post-menopausal and oophorectomized women. The major determinants of BMC were height, and in post-menopausal or oophorectomized women, age. Weight and parity also had additional explanatory power for pre- and post-menopausal women. Those who were in the highest quintile of BMC but had never taken HRT showed significantly elevated percentage free oestradiol compared with those in the lowest quintile. Thus HRT is osteoprotective if taken after the menopause for more than 24 months.

Adult↗

Carcinoid tumours of the thymus.

BACKGROUND: Carcinoid tumours of the thymus are rare. The clinical manifestations, radiographic findings, and cytological features of eight histopathologically verified thymic carcinoid tumours have been assessed. METHODS: One hundred and sixty two patients of mean age 52 (range 31-68) years with malignant mediastinal tumours were reviewed retrospectively and eight cases of thymic carcinoid were identified. Four of the eight patients were diagnosed by percutaneous ultrasound guided fine needle aspiration biopsy via a parasternal approach. RESULTS: Two patients had Cushing's syndrome at presentation and four had symptoms and signs secondary to mediastinal compression. Two were asymptomatic. Local extension of the tumour to pleura, pericardium, great vessels, phrenic nerve or regional lymph nodes, or both, were found in seven patients. Only one had the tumour confined to the thymus at diagnosis. Distant metastases were found in two patients, one to both lungs and the other in the iliac bone. Local recurrence or distant metastases developed 15-60 months after surgery in four of the five patients who underwent radical resection of the thymic tumour. Three patients died at 17 months, 34 months, and 10 years after diagnosis. The other five patients are alive at 9-51 months. CONCLUSION: Thymic carcinoid is a slow growing tumour with a poor prognosis because of its tendency to local and distant spread. Cytological examination of samples obtained by ultrasound guided fine needle aspiration may provide a useful method for diagnosis in selected patients.

Adult↗

Inositolphosphoglycan second messengers.

The mechanisms by which cellular receptors can elicit different biological responses in a maturation state-dependent manner is one of the central problems in cell differentiation which remains to be resolved. The signals generated are likely to be due to additional (as yet unknown) transmembrane signalling pathways. In addition, the recent observation that a single growth factor receptor can activate a whole family of different putative second messengers and that the combinatorial interactions and stoichiometric ratios between the different messengers determine the resulting biological activities has opened up a whole new area of cell biology. It has been proposed that membrane GPI-anchors may function in signal transduction. We have recently confirmed the presence of a family of inositolphosphoglycan second messengers. Partial structural data suggests that these second messengers are not derived from known GPI membrane anchors and may thus constitute a novel class of non-protein-conjugated GPI.

Animals↗

Axons regulate Schwann cell expression of the POU transcription factor SCIP.

SCIP (suppressed cAMP-inducible POU) is a POU domain transcription factor expressed by Schwann cells. Drugs that elevate intracellular cAMP, such as forskolin, increase the expression of SCIP and partially mimic the inductive effects of axons on Schwann cell gene expression. Thus, SCIP may be involved in a differentiation pathway in Schwann cells that is activated by axons. We have examined this issue by studying SCIP expression in developing, degenerating, and regenerating rat peripheral nerves, and in Schwann cell-neuron cocultures. High levels of SCIP mRNA were detected in developing and regenerating nerves, and axotomy at these times caused the level of SCIP mRNA to plummet. Similarly, there were many SCIP-immunoreactive Schwann cell nuclei in developing and regenerating nerves, and their number fell sharply after axotomy. SCIP-immunoreactive Schwann cells were associated with axons in developing and regenerating nerves, and in Schwann cell-neuron cocultures. These data demonstrate that axons upregulate the expression of SCIP in Schwann cells, and that SCIP is expressed in Schwann cells that ensheathe axons. Thus, SCIP may mediate some of the changes in Schwann cell gene expression that accompany axonal ensheathment.

Animals↗

Cytologic screening for esophageal cancer: results from 12,877 subjects from a high-risk population in China.

Linxian, China, has one of the highest esophageal-cancer mortality rates in the world. In 1983, esophageal balloon-cytology screening was performed to identify subjects eligible for 2 nutrition-intervention trials in Linxian; 12,877 subjects had cytology slides which were satisfactory for diagnosis. Of the 12,649 subjects with squamous-cell diagnoses, 31% were normal by Chinese cytologic criteria; 38% showed hyperplasia; 21% showed dysplasia 1; 6% showed dysplasia 2; 2% showed near-cancer; and 2% showed cancer. Of the 1,471 subjects with columnar-cell diagnoses, 31% were normal; 44% showed hyperplasia; 16% showed dysplasia 1; 4% showed dysplasia 2; 2% showed near-cancer; and 3% showed cancer. Squamous dysplasia and cancer were more common among females than males, while columnar dysplasia and cancer showed male predominance. The prevalence of dysplasia and cancer of both cell types increased with age. The prevalence of squamous dysplasia was significantly higher than in earlier balloon-cytology screenings in Linxian, probably reflecting changes in cytologic classification.

Adult↗

Copper in human mammary carcinogenesis: a case-cohort study.

In 1968-1975, a cohort of 5,100 ostensibly healthy women was established on the island of Guernsey, England, for investigation of the influence of hormonal factors on breast cancer. At the women's entry into the study, blood samples were drawn from each participant, and each woman completed a questionnaire that provided information on established risk indicators in human mammary carcinogenesis. Plasma copper levels were measured in 46 breast cancer cases diagnosed an average of 11 years (standard deviation (SD), 4) after entry into the study cohort and in an age-stratified random sample of 138 women drawn from the total initial cohort at risk. Plasma copper levels were 1.31 mg/liter (SD, 0.37) in the cases and 1.26 mg/liter (SD, 0.36) in the controls; the 95% confidence interval for the overall difference was -0.07 to 0.17. A U-shaped relation between premorbid plasma copper levels and the risk of developing breast cancer was seen. Adjusted odds ratios for breast cancer were 1.8, 1.0, 1.6, and 3.2, respectively, in the four quartiles of the copper distribution. No major changes in the risk estimates were observed when statistical evaluation was restricted to cases diagnosed more than 10 years after collection of blood samples.

Adult↗

TGF alpha and TGF beta expression in mammary carcinoma.

TGF alpha and beta expression was examined using rabbit polyclonal antibodies and immunohistochemistry on a series of 195 breast carcinomas. TGF alpha immunoreactivity was observed in all but nine of the tumours, with over 50 per cent staining strongly. The polyclonal TGF alpha antibody (CIM1), when compared with a commercially available mouse monoclonal TGF alpha antibody used on the same sections, gave a good correlation (r = 0.52, P < 0.001). Both TGF alpha antibodies produced a granular cytoplasmic staining pattern, that with CIM1 being coarser, suggestive of binding to an aggregated protein or organelle. Eighty-one per cent of tumours stained with the TGF beta antibody, 35 per cent strongly. There was significant co-expression of TGF alpha and TGF beta (P < 0.001). However, they were not found to be useful prognostic indicators, lacking any significant correlation with histological classification, tumour size, nodal status, oestrogen receptor status, S-phase fraction, or overall survival over a 9-12 year period. The expression of these growth factors in most breast carcinomas suggests that they have important biological roles, but the exact nature of these roles remains unclear at the moment.

Adult↗