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Biomedical subjects

D Y Wang

Publications and source records attributed to D Y Wang.

At least 73 records · Page 4Linked to original sources

Arthroscopic ankle arthrodesis: a preliminary report.

BACKGROUND: Over the past decade, arthroscopy has become a well-accepted technique for treating complex ankle problems. Recently, technical refinement with improvements in instrumentation has allowed more extensive arthroscopic debridement. With these improvements, arthroscopy can be used to perform successful arthrodesis of the ankle. METHODS: Five arthroscopic ankle arthrodesis procedures were performed. Three patients had post-traumatic osteoarthritis, one had rheumatoid arthritis and one had gouty arthritis combined with pyogenic arthritis. Following arthroscopic resection of the synovial membrane, cartilage and subchondral bone from the tibial, fibular and talar articular surfaces, an autogenous iliac bone graft was performed using arthroscopic guidance. Two percutaneous screws were used for internal fixation in three cases. Postoperatively, patients wore a short leg walking cast for eight weeks. The average follow-up was 18.8 months (range, 12-24 months). RESULTS: Clinical ankylosis was achieved in all cases and there was radiologic evidence of bone fusion in four cases. In one case, delayed union occurred, but it was achieved at the 12th postoperative month of follow-up. CONCLUSIONS: Arthroscopic ankle arthrodesis is less invasive than open techniques and less painful after surgery; it also allows for a better cosmetic effect. There is a learning curve associated with arthroscopic ankle fusion, and it is time-consuming. Severe deformity is a contraindication for this method and such cases should only be treated using the open method.

Aged↗

Expression of high-mobility group-1 mRNA in human gastrointestinal adenocarcinoma and corresponding non-cancerous mucosa.

An 1194-nucleotide complementary DNA clone, FM1, encoding a human high-mobility group-1 protein (HMG-1) was isolated from a well-differentiated human gastric-carcinoma cell line complementary DNA library by a differential screening method. FM1 is similar to the published human HMG-1 in mature protein, with only 3 different codons at positions 11, 149, and 190. We analyzed 33 gastric and colorectal adenocarcinomas for expression of the FM1 gene. Northern-blot analysis revealed that all of the cancers expressed FM1 at a higher level than in corresponding non-cancerous mucosa, with 2 transcripts of approximately 1.4 and 2.4 kilobases. The FM1 expression level in the non-cancerous tissues increased with the depth of accompanying cancer invasion. Only 18.2% of well-differentiated cancers showed a higher expression level in corresponding non-cancerous tissues, whereas the expression in corresponding non-cancerous tissues was significantly higher in moderately (60%) and poorly differentiated (83.3%) cancers. In situ hybridization demonstrated the location of FM1 mRNA in well- and poorly differentiated gastric-cancer cells as well as in non-cancerous tissue adjacent to poorly differentiated gastric cancer, but no hybridization was detected in normal epithelial cells adjacent to well-differentiated gastric cancer. These findings may provide new information on HMG-1 mRNA expression in human gastrointestinal cancer and suggest a correlation between FM1 mRNA expression to the differentiation and the stage of human gastrointestinal adenocarcinomas.

Aged↗

Oxidized LDL inhibits vascular endothelial cell morphogenesis in culture.

Human umbilical cord vein endothelial cells can be induced to undergo morphogenesis (tube formation) by phorbol ester (TPA) when cultured on or in three-dimensional collagen gels. Induction of morphogenesis by TPA is accompanied by increased activity of the collagenase gene transcription factors, ETS1 and API, and the elaboration of collagenase by the endothelial cells. In the present study, we used endothelial cell elongation as a measure of morphogenesis and showed that oxidized low density lipoprotein (oxLDL) inhibited endothelial cell migration in monolayer cultures and TPA-induced morphogenesis in collagen gels in a dose-dependent manner. Moreover, the inhibition was positively correlated with the extent of LDL oxidation. In contrast, native LDL stimulated cell migration and TPA-induced morphogenesis under the same culture conditions. However, in the absence of TPA, LDL showed no effect on EC morphogenesis. Further studies showed that inhibition of TPA-induced endothelial cell morphogenesis by oxLDL is correlated with suppression of the protein kinase C (PKC) and ETS1/AP1 activities. The results indicated that the inhibition of endothelial cell morphogenesis by oxLDL is probably mediated through inhibition of the TPA-activated PKC pathway and its subsequent suppression of the ETS1/AP1 activity. The results also indicated that EC migration can be mediated through PKC-dependent and independent pathways and only the former pathway can induce EC morphogenesis as well.

Cell Division↗

Measurement of oestrone sulphatase activity in white blood cells to monitor in vivo inhibition of steroid sulphatase activity by oestrone-3-O-sulphamate.

Formation of oestrone via the sulphatase pathway is considered to be a major source of the oestrogen present in breast tumours. Several inhibitors of steroid sulphatase have now been developed for use in the treatment of postmenopausal women with breast cancer. In order to be able to monitor the extent and duration of the inhibition of oestrone sulphatase (E1-STS) readily, we have developed a method to measure the activity of this enzyme in white blood cells (WBCs). Hydrolysis of oestrone sulphate by E1-STS in WBCs was linear with respect to time and the volume of WBCs used. To examine whether the extent of inhibition of E1-STS activity in WBCs, by the inhibitor oestrone-3-O-sulphamate (EMATE), reflected inhibition in other body tissues, activity in WBCs was compared with that in liver and spleen tissue samples from rats. Two hours after an oral dose of EMATE the extent of inhibition of E1-STS detected in WBCs was the same as in the liver. The duration of the inhibition of E1-STS by EMATE, examined over a 1-28 day period in rats, was similar whether monitored in WBCs, liver or spleen. Measurements of E1-STS activity in WBCs were also used to examine the effectiveness of EMATE (0.5 mg/kg) in two male volunteers. E1-STS activity was rapidly inhibited and had only recovered by 27% after 1 month. A marked decrease in the ratio of plasma dehydroepiandrosterone:dehydroepiandrosterone-sulphate (DHA:DHA-S) concentrations was also detected, confirming that EMATE also inhibits DHA-STS activity. The ability to monitor the extent and duration of steroid sulphatase inhibition in WBCs will facilitate the evaluation of this new form of endocrine therapy in women with breast cancer.

Animals↗

Breast cancer risk is positively associated with height.

Inter- and intra-national epidemiological studies point to an association between socio-economic status and breast cancer risk. Although there is no direct evidence, the most favoured reason for this relationship is nutritional. An enhanced dietary status, especially during childhood, would be reflected in adult body build. It is, therefore, surprising that there is uncertainty in the literature concerning the association between height and breast cancer risk. In reviewing the publications on this topic it became apparent that case-control studies which found no association between height and risk tended to use self-reported height. In contrast reports claiming a significant, and positive, correlation tended to use heights which were measured by the investigators. In a prospective study we found in a cohort of 2731 ostensibly normal women that, although there was a highly significant linear correlation between self-reported and measured height, the shortest women over-estimated their height whilst the tallest volunteers under-estimated theirs. The significance of crude relative risk and height in this cohort was markedly attenuated when self-reported height was used compared to measured height. Such a systematic error could have a profound effect on the conclusions of studies in this field which relied on self-reporting and could explain the conflicting reports in the literature.

Adult↗

A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey.

The associations between serum concentrations of oestradiol, progesterone, testosterone and sex hormone-binding globulin (SHBG) and risk of breast cancer in premenopausal women were investigated in a prospective study of breast cancer on the island of Guernsey. Sixty-two women diagnosed with breast cancer an average of 8 years subsequent to blood collection were matched for day of menstrual cycle, age and year of blood collection with 182 control subjects. Cases had a 12% higher mean oestradiol concentration over the whole menstrual cycle (P = 0.17) with a large difference at mid-cycle (75% higher, P = 0.04). Differences between cases and control subjects in progesterone (luteal phase), testosterone and SHBG were small and not statistically significant: luteal phase progesterone 9% lower in cases, P = 0.64; testosterone 4% higher, P = 0.57; SHBG 8% higher, P = 0.24. The small difference in oestradiol concentration could be aetiologically important, but larger prospective studies are needed.

Breast Neoplasms↗

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey.

The associations between serum concentrations of oestradiol, testosterone and sex hormone-binding globulin (SHBG) and risk of breast cancer in post-menopausal women were investigated in a prospective study on the island of Guernsey. Sixty-one women who developed breast cancer an average of 7.8 years after blood collection were matched for age, year of blood collection and number of years post-menopausal with 179 control subjects. Women using exogenous hormones at the time of blood collection were excluded from the study. Women who subsequently developed breast cancer had a 29% higher geometric mean oestradiol concentration than control women (P = 0.004). The odds ratio for breast cancer in the top third compared with the lowest third of the oestradiol concentration distribution was 5.03 (95% confidence interval 2.02-12.49, P for trend < 0.001). Adjusting for testosterone and SHBG concentrations did not substantially alter the odds ratio for oestradiol. Although testosterone and SHBG concentrations were associated with breast cancer risk, the concentrations of these hormones were correlated with those of oestradiol; the associations were not statistically significant after adjusting for oestradiol concentration. These data provide evidence that serum oestradiol concentrations in post-menopausal women may have a substantial effect on breast cancer risk.

Adult↗

Assessment of adenoid size in children by fibreoptic examination.

In order to investigate the relationship between the size of the adenoid and upper respiratory symptoms in children, fibreoptic examination of the nasal cavity and nasopharynx was performed in 817 children. The size of the adenoid was classified into three categories according to the distance between the vomer and the adenoid tissue. There was a significant relation between the size of the adenoid and the complaints of nasal obstruction (P < 0.001) and of snoring (P < 0.001), but not with the presence of purulent sinusitis. In the whole population, the size of the adenoid correlated well with the results of tympanometry (P < 0.001), but this does not hold in all age groups. This study has confirmed adenoid hypertrophy as a common aetiological factor in children with the complaints of nasal obstruction and snoring. The enlargement of the adenoid only partially explains the occurrence of otitis media with effusion. The introduction of the flexible fibrescope in the examination of the nasal cavity and nasopharynx in children is of great clinical value, especially in the selection of children for adenoidectomy. It is a minor invasive examination well tolerated by most children, giving more information than a lateral skull radiograph and avoiding unnecessary radiation.

Acoustic Impedance Tests↗

A novel aspect of photodynamic action: induction of recurrent spikes in cytosolic calcium concentration.

Effects of photodynamic action of gadolinium porphyrin-like macrocycle B (PLMGdB) on cytosolic Ca2+ concentration, [Ca2+]c, was investigated in isolated rat pancreatic acini. The PLMGdB alone or light alone (2 min) had no effect on [Ca2+]c. Cell-bound PLMGdB upon brief (0.5-2.0 min) light activation triggered recurrent spikes in [Ca2+]c. At lower PLMGdB concentration (100 nM) the spikes continued during the whole period of monitoring [Ca2+]c. At a higher concentration of 500 nM, the spikes continued for the first 40 min, followed by a gradual increase in basal [Ca2+]c upon which smaller spikes were superimposed. At 1 microM, the spikes continued for the first 20 min, after that spiking gradually degenerated into a plateau phase. In many aspects, photodynamically triggered spikes resembled spikes generated by physiological concentrations of cholecystokinin. The spikes triggered by photodynamic action were likely to be the result of the ignition of a physiological "chain reaction", because functional inositol-1,4,5-trisphosphate (IP3) receptors were required for spiking to occur. Two-aminoethoxydiphenylborate, an inhibitory modulator of IP3-triggered Ca2+ release from intracellular stores, effectively inhibited photodynamically generated spikes. Therefore photodynamic action appears to be able to permanently transfix a physiological process, leading to long-lasting pharmacological or therapeutic effects.

Animals↗

Agrobacterium radiobacter bacteremia in a patient with chronic obstructive pulmonary disease.

Agrobacterium radiobacter is a gram-negative bacillus, which is recognized as an emerging opportunistic human pathogen. To our knowledge, there have been only 25 cases of A. radiobacter bacteremia reported. In most of these, A. radiobacter was associated with long-term indwelling plastic central venous catheters. We describe a 78-year-old man who had a history of chronic obstructive pulmonary disease with long-term use of a corticosteroid. He was admitted to the China Medical College Hospital with pneumonia caused by Serratia marcescens. His general condition gradually improved after initiation of appropriate treatment. Unfortunately, he developed A. radiobacter bacteremia while hospitalized in the medical intensive care unit. With the onset of this infection, the patient had a high fever, leukocytosis, raised C-reactive protein level, and positive blood cultures for A. radiobacter. A central venous catheter-related infection was suspected because of redness and localized tenderness at the catheter site. The patient gradually recovered after removal of the catheter and appropriate antimicrobial treatment with latamoxef 1.5 g intravenously every 8 hours for 10 days.

Aged↗

Microbiology of chronic sinusitis.

Much controversy still exists about the role of viruses, bacteria and fungi in sinusitis. Until recently, it was not really known that the sinuses take part in the infectious process of a common cold (viral rhinitis). Indeed, CT scans show that in the vast majority of otherwise healthy volunteers with a common cold, and without a previous history of recurrent or chronic sinusitis, the sinuses are involved too. A viral rhinitis alone, however, does not seem to be able to elicit a "clinical" acute sinusitis. Bacteria determine the clinical picture and outcome of sinusitis. There is not much controversy about the role of bacteria in acute sinusitis, S. pneumoniae, H. influenzae and M. catarrhalis being the most frequently involved bacteria. Much more conflicting reports are published about the normal flora of the sinuses, the role of anaerobes and the microbiology of chronic sinusitis. In this chapter the defense and pathophysiologic mechanisms of viral, bacterial and fungal infection of the nasal and sinusal mucosa are described. It is postulated that, although bacteria are very important in acute sinusitis, their role in chronic sinusitis is minimal, the bacteria being opportunistic colonisers.

Acute Disease↗

Identification of cytokeratin subspecies altered in rat experimental esophageal tumors by subtractive cloning.

By using the subtractive hybridization method, two complementary DNA clones differently expressed in rat normal esophageal epithelium and squamous cell carcinoma induced by administration of precursors of N-nitrososarcosine ethyl ester were isolated. A rat homologue of the human 50-kDa type I cytokeratin 14 was cloned for the first time and shown to be expressed preferentially in squamous cell papillomas and carcinomas, whereas it was weakly expressed or absent in normal squamous epithelial cells and in hyperplastic lesions. A rat homologue of the mouse 57-kDa type II cytokeratin showed strong expression in both normal and tumor tissues. These results are well consistent with the reported alteration of keratin subspecies in human esophageal cancers, therefore, encouraging us to use this experimental system as a model for human esophageal carcinogenesis.

Animals↗

Expression of structure-specific recognition protein mRNA in fetal kidney and Fe-nitrilotriacetate-induced renal carcinoma in the rat.

Specific expression of the structure-specific recognition protein (SSRP) gene was investigated in rat fetal, adult, and tumor tissues using a 2.0-kb partial sequence of rat SSRP cDNA isolated from a cDNA library of rat renal cell carcinoma. The results revealed that it was rather specifically expressed in rat fetal kidney and renal cell carcinoma induced by Fenitrilotriacetate, but not in adult kidney, when various organs were tested by Northern blot analysis. In situ hybridization further demonstrated that it was located in the neoplastic cells of renal cell carcinoma and in the epithelial cells of fetal kidney but undetectable in any cells of normal adult kidney. These observations seem to imply the involvement of SSRP gene, which is believed to recognize structural alterations of DNA, in kidney development and carcinogenesis of certain types of kidney cancer.

Animals↗

Serum progesterone and prognosis in operable breast cancer.

Several studies have now shown that women with operable breast cancer undergoing tumour excision during the luteal phase of the menstrual cycle have a better prognosis than those having surgery during the follicular phase. As part of a prospective study of prognostic factors in breast cancer, blood was taken at the time of surgery. Between 1975 and 1992 this was available from 289 premenopausal women within 3 days of tumour excision. All were treated by either modified radical mastectomy or breast conservation including axillary clearance and the date of last menstrual period (LMP) was known in 239 (80%) cases. Blood samples were assayed for both oestradiol (E2) and progesterone (P). Because of the wide inter-individual variation in E2 levels there was no clear relationship between E2 and LMP. However, using a running mean smoothing technique the expected cyclical variation could be discerned. There was no significant association between E2 and survival. Smoothing of the P data yielded a pattern similar to the normal hormone profile. Those cases with a progesterone level of 4 ng ml-1 or more had a significantly better survival than those with a level < 4 ng ml-1. This was especially clear in node-positive patients (P < 0.01). The possibility of misclassification of menstrual cycle status, because of misreported LMP, has been minimised by applying an independent hormonal measurement (P) of cycle activity. This parameter will also identify women who may be undergoing anovular cycles. Thus this study has confirmed that a raised level of progesterone at the time of tumour excision is associated with an improvement in prognosis for women with operable breast cancer.

Breast Neoplasms↗

A prospective study of urinary oestrogen excretion and breast cancer risk.

To test the hypothesis that high levels of endogenous oestrogens increase the risk for developing breast cancer, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 1000 women participants in a prospective study of breast cancer on the island of Guernsey. Sixty-nine subjects were diagnosed with breast cancer subsequent to urine collection. Among women who were premenopausal at the time of urine collection, cases excreted less oestrogen than controls; the odds ratios (95% CI) for breast cancer in the middle and upper thirds of the distribution of oestrogen excretion, in comparison with the lower third (reference group, assigned odds ratio = 1.0), were 0.5(0.2-1.2) and 0.4(0.2-1.1) respectively for oestrone, 0.8(0.4-1.8 and 0.4(0.2-1.1) for oestradiol, 0.7(0.3-1.6) and 0.7(0.3-1.6) for oestriol and 0.9(0.4-2.0) and 0.5(0.2-1.3) for total oestrogens. Among women who were post-menopausal at the time of urine collection, the trend was in the opposite direction, with an increase in risk associated with increased oestrogen excretion; the odds ratios were 0.9(0.3-2.2) and 1.1(0.5-2.8) for oestrone, 0.8(0.3-2.3) and 1.9(0.8-4.6) for oestradiol, 1.5(0.6-3.9) and 1.8(0.7-4.6) for oestriol and 0.9(0.4-2.6) and 1.9(0.7-4.7) for total oestrogens. The trends of increasing risk with increasing oestrogen excretion among post-menopausal women were statistically significant for oestradiol (P = 0.022) and for total oestrogens (P = 0.016). We conclude that high levels of endogenous oestrogens in post-menopausal women are associated with increased breast cancer risk, but that the relationship of oestrogens in premenopausal women with risk is unclear.

Adult↗

Cigarette smoking and urinary oestrogen excretion in premenopausal and post-menopausal women.

Cigarette smoking is associated with a reduction in the risk for endometrial cancer in post-menopausal women and it has been suggested that this is because smoking has an anti-oestrogenic effect. To investigate this, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 167 premenopausal women (53 smokers, 114 non-smokers) and 200 post-menopausal women (54 smokers, 146 non-smokers). Among premenopausal women there were no significant differences in oestrogen excretion between smokers and non-smokers. Among post-menopausal women, geometric mean excretion rates for oestrone and oestradiol did not differ significantly between groups, but oestriol excretion was 19% lower (95% confidence interval -34% to -1%) in smokers than in non-smokers. This may partly explain the reduced risk for endometrial cancer among post-menopausal smokers.

Adult↗

Regulation of aromatase and sulphatase in breast tumour cells.

In situ oestrogen synthesis makes an important contribution to the high oestrogen concentration found in breast tumours. Cytokines, including interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha), have been shown to regulate aromatase activity in fibroblasts derived from normal and malignant breast tissues. In the present study, the ability of other cytokines in the IL-6 superfamily (IL-11 and oncostatin M) to stimulate aromatase activity has been confirmed. Formation of oestrone via the oestrone sulphatase pathway may be the major route of tumour oestrogen synthesis and in the present study TNF alpha was found to stimulate sulphatase activity in a dose-dependent manner. Human serum albumin was also found to be a potent stimulator of oestrone sulphatase activity. Its stimulatory effect was blocked by basic fibroblast growth factor, but not by several other growth factors tested. Insight into the regulation of oestrogen synthesis in breast tumours should enable the development of novel compounds to inhibit oestrogen synthesis in women with breast cancer.

Antineoplastic Agents, Hormonal↗