Upregulation of CYP17A1 by Sp1-mediated DNA demethylation confers temozolomide resistance through DHEA-mediated protection in glioma.

Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroepiandrosterone (DHEA) in endocrine organs and the brain, is required for prostate cancer progression and acquired chemotherapeutic resistance. However, whether CYP17A1-mediated DHEA synthesis is involved in brain tumor malignancy, especially in glioma, the most prevalent brain tumor, is unknown. To investigate the role of CYP17A1 in glioma, we determined that CYP17A1 expression is significantly increased in gliomas, which secrete more DHEA than normal astrocytes. We found that as gliomas became more malignant, both CYP17A1 and DHEA were significantly upregulated in temozolomide (TMZ)-resistant cells and highly invasive cells. In particular, the increase of CYP17A1 was caused by Sp1-mediated DNA demethylation, whereby Sp1 competed with DNMT3a for binding to the CYP17A1 promoter in TMZ-resistant glioma cells. CYP17A1 was required for the development of glioma cell invasiveness and resistance to TMZ-induced cytotoxicity. In addition, DHEA markedly attenuated TMZ-induced DNA damage and apoptosis. Together, our results suggest that components of the Sp1-CYP17A1-DHEA axis, which promotes the development of TMZ resistance, may serve as potential biomarkers and therapeutic targets in recurrent glioma.

Ruptured splenic artery aneurysm detected by emergency ultrasound-a case report.

Splenic artery aneurysm is a rare but a potentially fatal condition. It is usually asymptomatic until it ruptures. Here, we present a case of ruptured splenic artery aneurysm in a 59-year-old gentleman presenting with epigastric pain and hypovolemic shock. The diagnosis was made by emergency ultrasound and CT scan, and he was managed by laparotomy and excision of the splenic artery aneurysm. Priorities in patient management lie in rapid resuscitation, diagnostic imaging, surgical consultation, and subsequent laparotomy. Pitfalls should be borne in mind to differentiate splenic artery aneurysm from abdominal aortic aneurysm when using the emergency ultrasound.

Oral carcinoma with perineural invasion has higher nerve growth factor expression and worse prognosis.

BACKGROUND: This study elucidated the association between histopathological factors and the prognosis of oral carcinoma. As the histopathological factors were determined from the surgical specimen and this can only be used for the choices of postoperative regimens, this study also investigated the linkage between prognostic factors and the expression of key molecules to examine the feasibility of markers as predictors. METHODS: Clinicopathological factors of 101 oral carcinomas were cross-analyzed with disease-free survival. The expression of nerve growth factor (NGF) and its receptor, tyrosine kinase A receptor, was assayed with immunohistochemistry. RESULTS: Nodal metastasis was the most crucial clinical predictor for disease-free survival. Perineural invasion (PNI) was an independent histopathological predictor for both nodal metastasis (P = 0.004) and disease-free survival (P = 0.019). Patients with advanced tumor and PNI exhibited the high hazard for tumor progression and poor disease-free survival. NGF immunoreactivity in tumors was correlated with PNI (P = 0.005) and neck lymph node metastasis (P = 0.036). CONCLUSION: Perineural invasion is the indicator of worst prognosis. As NGF immunoreactivity was found to be associated with PNI and nodal metastasis, the NGF immunoreactivity of oral carcinoma revealed by diagnostic biopsy suggests that alternative therapeutic approaches might be appropriate.

Histopathological factors affecting nodal metastasis in tongue cancer: analysis of 94 patients in Taiwan.

The overall prognosis for tongue cancer patients in Taiwan is unpredictable, even when patients are treated following the guidelines according to TNM stages. In order to determine the optimal treatment modality for tongue cancer in Taiwan the authors aimed to correlate histopathological parameters with neck nodal metastasis. A retrospective analysis of 94 patients with different stages of tongue cancer treated in the Taipei Veterans General Hospital was performed. All 94 patients were clinically diagnosed with stage I-IV tongue cancer before surgery and received primary tumor-wide excision and neck dissection. There were 42 (45%) patients with nodal metastasis. Univariate analysis revealed that cases of tongue cancer with moderate or poor differentiation, an invasion depth more than 3mm and positive perineural invasion or lymphovascular permeation at the time of presentation may be subject to a higher incidence of neck nodal metastasis. An elective neck dissection or neck treatment should be considered if these histopathological risk factors are present. Cases of tongue cancer with these risk factors also warrant close follow-up after surgery.

Analysis of the action of euxanthone, a plant-derived compound that stimulates neurite outgrowth.

We have investigated the neurite growth-stimulating properties of euxanthone, a xanthone derivative isolated from the Chinese medicinal plant Polygala caudata. Euxanthone was shown to exert a marked stimulatory action on neurite outgrowth from chick embryo dorsal root ganglia explanted in collagen gels, in the absence of added neurotrophins. It was also shown to promote cell survival in explanted chick embryo ganglia, and to stimulate neurite outgrowth from isolated adult rat primary sensory neurons in vitro. The further finding that euxanthone stimulates neurite outgrowth from explants of chick embryo retina and ventral spinal cord suggests an action on signaling pathways downstream of neuronal receptors for specific neurotrophic factors. Consistent with this, euxanthone did not promote neurite outgrowth from non-transfected PC12 cells, or from PC12 cells transfected with TrkB or TrkC, under conditions in which these cells extended neurites in response to, respectively, the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3. Western blot analysis of euxanthone-stimulated dorsal root ganglion explants showed that expression of phospho-mitogen-activated protein (MAP) kinase was up-regulated after 1 h of euxanthone-treatment. Inhibition of the MAP kinase pathway using PD98059, a specific inhibitor of MAP kinase kinase, blocked all euxanthone-stimulated neurite outgrowth. However, analysis of phospho-Akt expression indicated that the phosphatidylinositol-3 kinase-Akt pathway, another major signaling pathway engaged by neurotrophins, is not significantly activated by euxanthone. These results suggest that euxanthone promotes neurite outgrowth by selectively activating the MAP kinase pathway.

On-line lower-order modeling via neural networks.

This paper presents a novel method to determine the parameters of a first-order plus dead-time model using neural networks. The outputs of the neural networks are the gain, dominant time constant, and apparent time delay. By combining this algorithm with a conventional PI or PID controller, we also present an adaptive controller which requires very little a priori knowledge about the plant under control. The simplicity of the scheme for real-time control provides a new approach for implementing neural network applications for a variety of on-line industrial control problems. Simulation and experimental results demonstrate the feasibility and adaptive property of the proposed scheme.

Role of cell surface components on Cu2+ adsorption by Pseudomonas putida 5-x isolated from electroplating effluent.

A gram-negative bacterium Pseudomonas putida 5-x with high Cu2+ accumulating capability was isolated from electroplating effluent in Kwun Tong, Hong Kong. The pretreated cells without superficial layer-capsule, isolated cell envelopes and the separated peptidoglycan layer materials were obtained from fresh P. putida 5-x cells, their Cu2+ adsorption capacities and properties were compared with that of the fresh cells. Pretreatment by 0.1 mol L(-1) HCl enhanced Cu2+ adsorption capacity due to the degradation of cell superficial layer-capsule of P. putida 5-x cells. Isolated cell envelopes possessed five times more Cu2+ adsorption capacity than that of fresh intact cell. The Cu2+ adsorption of separated peptidoglycan layer materials indicated that the peptidoglycan layer only played 10-15% part of the Cu2+ adsorption capacity, and implied other cell surface components such as outer membrane or inner membrane might play an important role in such high Cu2+ binding of the cell envelopes. The adsorption process of fresh cells, pretreated cells and cell envelopes of P. putida 5-x could be described with Freundlich isotherm, while the adsorption of Cu2+ by separated peptidoglycan layer materials was better described with Langmuir isotherm.

Self-tuning control of systems with unknown time delay via extended polynomial identification.

Much of the work reported on self-tuning control addresses the class of systems with known time delay. In this paper, the continuous time self-tuning control algorithm is extended to systems with unknown or varying time delay. The original polynomial identification is further modified in this paper to estimate both poles, zeros, and unknown time delay. An explicit self-tuner is then designed based on the estimated parameters. Experimental studies are used to evaluate the performance of this algorithm.

Aspergillosis of the temporomandibular joint following irradiation of the parotid region: a case report.

We report a case of aspergillosis in the right temporomandibular joint (TMJ) with a history of parotid carcinoma and post-irradiation otitis. Previous treatment attempts with surgery and antibiotics were unsuccessful. Radical debridement of the glenoid fossae, supplemented with amphotericin B and adjunct hyperbaric oxygen (HBO) therapy, was provided to resolve the symptoms. This case report highlights the need to be aware of the possibility of invasive mycosis in immunocompromised patients.

Different enzyme activities of sialyltransferases in gynecological cancer cell lines.

PURPOSE: Due to rarity of a relationship between sialyltransferase enzyme activities and gynecological cancers, we arranged the study to evaluate sialyltransferase enzyme activity in the various kinds of gynecological cancer cell lines. METHODS: Ten cell lines from various kinds of gynecological cancers and two cell lines from normal tissue were enrolled in this study. The activities of each subtype of sialyltransferases were detected using Gal beta1,3GalNAc-acetyl-lactosamine)-Obz1 (acceptor for ST2,3Gal I), Gal beta1,3GlcNAc beta1,3Gal beta1,4GlcNAc (acceptor for ST2,3Gal III), Gal beta1,4GlcNAc (acceptor for ST2,3Gal IV), asialo-bovine submaxillary mucin (acceptor for ST2,6GalNAc I), asialo-fetuin (acceptor for STalpha2,6GalNAc II), and fetuin (acceptor for ST2,6GalNAc III), respectively. The amounts of sialic acids were measured using fluorescein-conjugated Sambucus nigra agglutinin (SNA) specific for alpha2,6-sialic acids and fluorescein-conjugated Maackia Amurensis agglutinin (MAA) specific for alpha2,3-sialic acids. RESULTS: The activities of two sialyltransferase subtypes, ST3Gal I & ST6GalNAc II, were significantly higher in nearly all cell lines. More specifically, cervical cancer cell line-ME 180, ovarian cancer cell line-ES-2, and choriocarcinoma cell line-BeWo showed high levels of ST3Gal I enzyme activity; all gynecological cancer cell lines except endometrial cancer cell line-RL95-2 had high levels of ST6GalNAc II enzyme activity when compared with a normal control cell line--fibroblast cell line (CCD-966Sk). Cell lines tested in this study have diverse levels of surface alpha2,6-sialic acid sugar chains (enhanced SNA binding) when compared with alpha2,3-sialic acid sugar chains (enhanced MAA binding) but we found that some cell lines such as Ca Ski (cervical cancer cell line), CC7T (cervical cancer cell line), PA-I (ovarian cancer cell line), and BeWo showed significantly altered cell surface alpha2,6-sialic acid sugar chains. CONCLUSION: Increasing enzyme activity of ST3Gal I and ST6GalNAc II might be important in various kinds of gynecological cancers. More specifically, enhanced activity of sialyltransferases involving alpha2,6-sialic acid sugar chains might be more important in cancer development. Future studies will investigate whether the enzyme activity of these sialyltransferases can be helpful for clinical practice.

Universal antenatal human immunodeficiency virus testing in Hong Kong: consensus statement.

Following the recommendations of the Advisory Council on AIDS, Hong Kong, the Hospital Authority announced plans to introduce universal antenatal screening for human immunodeficiency virus infection and hence, a consensus conference was held to discuss strategies for implementing such screening in Hong Kong. This paper reports the discussions of the consensus conference. The consensus meeting group consisted of 15 clinicians and scientists from Hong Kong, Macau, and Thailand. Seven commonly asked questions concerning mother-to-child transmission of human immunodeficiency virus were selected for discussion by the participating panellists. Information on the laboratory diagnosis of human immunodeficiency virus infection and the efficacy of preventive measures in reducing mother-to-child transmission of human immunodeficiency virus were reviewed. Data from local studies was also presented and discussed. The timing, potential problems, and cost issues involved in testing all pregnant women in Hong Kong for human immunodeficiency virus were then considered.

The prevention of communicable diseases in Hong Kong.

Some of the recent communicable disease problems in Hong Kong are summarised to illustrate the strengths and weaknesses of how Hong Kong currently controls and prevents communicable diseases. Suggestions on how Hong Kong could improve the control and prevention of communicable diseases are made.

[Neuropsychological assessment in a patient with left hemineglect syndrome--a case report].

We performed a sequential neuropsychological tests before and after neurosurgical intervention on a 69-year-old patient with left hemineglect syndrome caused by metastatic right temporal papillary carcinoma. The tests performed before operation and computer tomography revealed marked impairment in visuospatial reasoning, spatial orientation, visual perception, visuoconstructional praxis, effort emory, as well as block design in Wechsler Adult Intellectual Scale-Revised, all of which suggested right temporo-parietal lesion. Left spatial neglect was obviously demonstrated by the Line Cancellation Test, Watch Test, and clinical observation. After surgical debulking of the tumor, his performances on most of the tests were improved. Our study demonstrated that the conventional neuropsychological test is not only useful for localizing the cerebral lesion but also valid for the assessment of functional recovery after treatment, a role that can never be replaced by any other modern technique.

Cognitive dysfunction in early onset parkinsonism.

Cognitive functions of 24 patients with early onset parkinsonism (age of onset before 40 years) and 24 controls were investigated by a battery of neuropsychological tests. Patients were shown to be impaired in performance IQ (PIQ), conceptual ability and regulation behavior, memory, visuospatial perception, and manual dexterity. Patients were also shown to have a higher Zung Depression score. However, analysis of the testing scores appeared to indicate that only a small portion of poor performance on neuropsychological tests are depression related. The results demonstrated that patients with early onset parkinsonism, in whom the factor of aging is not as important, still show cognitive dysfunction and suggested that Parkinson's disease itself can cause cognitive impairment.

Localized pachydermodactyly in tuberous sclerosis.

Pachydermodactyly refers to a rare form of digital fibromatosis involving the proximal portions of the fingers. There are only nine cases reported in the literature, all idiopathic and occurring in young men. We report a 5-year-old Chinese boy with tuberous sclerosis who presented with localized pachydermodactyly since birth. This congenital form of pachydermodactyly may represent an additional cutaneous sign of tuberous sclerosis.

Tripe palms: a significant cutaneous sign of internal malignancy.

Tripe palms is a paraneoplastic keratotic skin sign of great predictive value. It is characterized clinically by a curious rugose thickening of the palms with an accentuation of the normal dermatoglyphic ridges and sulci. Histological examination reveals an undulant epidermis with hyperkeratosis, acanthosis and papillomatosis. More than 80 cases have been reported in the literature; 90% of them were associated with an internal malignancy, mostly a carcinoma of the lung or stomach. We herein report a 66-year-old Chinese man with adenocarcinoma of the lung who presented typical tripe palms. Recognition of this distinctive pattern should prompt a meticulous search for an underlying malignancy, particularly lung or gastric carcinoma.

Solitary sclerotic fibroma.

A 63-year-old Chinese man with a solitary sclerotic fibroma on the abdomen is described. Skin biopsy showed a well-demarcated dermal nodule composed of hypocellular, eosinophilic collagen bundles separated by prominent clefts. Retrospective electron microscopic study revealed wide collagen bundles containing tightly packed collagen fibrils, only 50 nm in diameter. There were no signs of Cowden's disease. To our knowledge, this is the first report of electron microscopic study of sclerotic fibroma. A brief review of the literature is included.