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Biomedical subjects

M W Chang

Publications and source records attributed to M W Chang.

At least 19 recordsLinked to original sources

Increased expression of extracellular proteins as a hallmark of human endothelial cell in vitro senescence.

A convenient way to study processes of aging in distinct human tissues consists of a molecular analysis of cells from the tissue in question, that were explanted and grown in vitro until they reach senescence. Using human umbilical vein endothelial cells (HUVEC), we have established an in vitro senescence model for human endothelial cells. A major hallmark of HUVEC in vitro senescence is the increased frequency of apoptotic cell death, which occurs as a determining feature of HUVEC senescence. Senescent endothelial cells are also found in vivo in atherosclerotic lesions, suggesting that the presence of such cells may contribute to the development of vascular pathology. To elucidate mechanisms underlying endothelial cell senescence and age-associated apoptosis, gene expression analyses were carried out. In these experiments, we observed the up-regulation of genes coding for extracellular proteins in senescent HUVEC. In particular, a significant upregulation of interleukin-8, VEGI, and the IGF-binding proteins 3 and 5 was observed. Upregulation of these genes was confirmed by both RT-PCR and Western blot. In the case of interleukin-8, a roughly 50-fold upregulation of the protein was also found in cellular supernatants. The extracellular proteins encoded by these genes are well known for their ability to modulate the apoptotic response of human cells, and in the case of interleukin-8, clear links to the establishment of atherosclerotic lesions have been defined. The results described here support a new model, where changes in the secretome of human endothelial cells contribute to vascular aging and vascular pathology.

Apoptosis↗

Cantharidin revisited: a blistering defense of an ancient medicine.

Cantharidin, a vesicant produced by beetles in the order Coleoptera, has a long history in both folk and traditional medicine. In dermatology, topical cantharidin has long been used to treat warts and molluscum. In 1962, cantharidin lost Food and Drug Administration (FDA) approval owing to the failure of its manufacturers to submit data attesting to cantharidin's efficacy. However, it is expected that the FDA will soon include cantharidin on its "Bulk Substances List," which would permit physicians or pharmacists to compound cantharidin to be used in the office for individual patients. A comprehensive discussion of the origins, folk uses, current FDA status, current dermatologic uses, and effects of cantharidin poisoning has been compiled herein. No cases of systemic intoxication or scarring have been reported with the proper use of cantharidin by a physician. Cantharidin is a safe and valuable medication and should be readded to the dermatologic therapeutic armamentarium.

Animals↗

Trichorhinophalangeal syndrome, type II (Langer-Giedion syndrome).

Trichorhinophalangeal syndrome (TRPS) is characterized by its unique facial features and skeletal abnormalities. A bulbous, pear-shaped nose, elongated philtrum, sparse hair, cone-shaped epiphyses and mild growth retardation are found in both type I (TRPSI) and type II (TRPSII). TRPSII can be distinguished from TRPSI when multiple exostoses or redundant skin are present. While TRPSI is inherited in an autosomal dominant fashion, most cases of TRPSII are sporadic although there are a few cases which are familial. The following is a case report of TRPSII with incomplete penetrance in the index case and exostoses and growth retardation in the patient's two siblings.

Adolescent↗

Topical tretinoin and 5-fluorouracil in the treatment of linear verrucous epidermal nevus.

Treatment of a linear verrucous epidermal nevus using topical 0.1% tretinoin cream and 5% 5-fluorouracil in a young patient is described. In 1994, successful topical therapy using this combination was described in the management of an inflammatory linear verrucous epidermal nevus. We report another case in which treatment of a noninflamed epidermal verrucous nevus with 0.1% tretinoin and 5% 5-fluorouracil resulted in significant improvement. An updated summary of the literature discussing management of epidermal nevi is presented.

Antimetabolites↗

Contour tracking using a knowledge-based snake algorithm to construct three-dimensional pharyngeal bolus movement.

Videofluorography (VFG) using a barium-mixed bolus is in wide clinical use for assessing patients with swallowing disorders. VFG is usually done with both lateral (LA) and anterior-posterior (AP) views, most commonly in two separate sittings. A real-time, three-dimensional (3-D) representation of the evolution of a pharyngeal bolus and its volumetric information can potentially help clinicians analyze and visualize the kinematics of swallowing, dysphagia, and compensatory therapeutic strategies. Active contour models, also known as "Snakes," have been used to solve various image analysis and computer vision problems. We applied a Snake algorithm to automate in part the contour tracking and reconstruction of VFG images to visualize and quantitatively analyze the 3-D evolution of a pharyngeal bolus. To improve the accuracy of the Snake search, we provided the additional "knowledge" of the pharyngeal image itself, which served as an extra constraint to push the Snake curve toward the desired contour. VFG of pharyngeal bolus transport in a normal subject was recorded by using barium-mixed boluses (viscosity: 185 centipoise, density: 2.84 g/cc) with volumes of 5, 10, and 20 ml. The resulting LA and AP video images were digitally captured and matched frame by frame. The knowledge-based Snake search algorithm was used to generate Snake points to satisfy both internal (i.e., smoothness) and external (i.e., boundary fitting) constraints. Using these Snake points, we traced the 3-D bolus movement at each time instant, assuming elliptic geometry in the cross-section of the pharyngeal bolus. By concentrating the 3-D images for each time instant, we developed a 3-D movie representing pharyngeal bolus movement. The efficiency, reproducibility, and accuracy of this algorithm in tracing pharyngeal bolus boundaries and estimating front/tail velocities were assessed and found satisfactory. We conclude that 3-D pharyngeal bolus movement can be traced both accurately and efficiently by using a knowledge-based Snake search algorithm.

Algorithms↗

Update on juvenile xanthogranuloma: unusual cutaneous and systemic variants.

Juvenile xanthogranuloma (JXG) is a well-recognized benign disorder of infancy and early childhood characterized by yellowish cutaneous nodules that spontaneously regress over months to years. In the vast majority of children, JXG is limited to the skin and requires no treatment. Over the past two decades, unusual cutaneous and systemic forms of JXG have been increasingly reported. JXGs have been discovered, usually unexpectedly, in every organ system of the body. Correct diagnosis is crucial to prevent unnecessary invasive diagnostic and therapeutic procedures. Unusual clinical and histological variants of JXG often require immunohistochemical studies and/or electron microscopy to establish the diagnosis. Nonlipidized, giant, intramuscular, subcutaneous, and clustered JXG are but some of the variants that are discussed in this article. The immunohistochemistry of JXG, current nosology, and hypotheses regarding the origins of JXG are also reviewed.

Diagnosis, Differential↗

Advances in the management of dysphagia caused by stroke.

This article reviews the advancements that have occurred, primarily in the last decade, in the management and treatment of swallowing disorders related to stroke. An overview of swallowing physiology is given, and interventions, both indirect and direct, are explored. Expanding knowledge, applying techniques from other scientific disciplines, and developing new technologies provide hope for stroke patients who experience dysphagia.

Biofeedback, Psychology↗

Mucocutaneous manifestations of the hyper-IgM immunodeficiency syndrome.

BACKGROUND: The recurrent pyogenic infections of patients with hyper-IgM syndrome are controlled by intravenous gamma globulin administration, but patients may suffer from early-onset oral ulcerations and warts. OBJECTIVE: We have characterized the mucocutaneous manifestations associated with this condition to allow physicians to more readily identify it. METHODS: Three male patients with the mucocutaneous manifestations of the hyper-IgM syndrome are described. In one, histopathologic examination of the oral mucosal lesion was performed. RESULTS: Recurrent large, painful oral ulcerations can occur that are not necessarily associated with neutropenia nor do they respond to granulocyte colony-stimulating factor administration. Histopathologic examination of an ulcer showed a heavy infiltrate of mixed inflammatory cells. Warts tend to be widespread and resistant to traditional therapy. CONCLUSION: Physicians should consider this uncommon condition when examining a male patient with severe oral ulcers or recalcitrant widespread warts.

Adult↗

Mathematical modeling of normal pharyngeal bolus transport: a preliminary study.

Dysphagia (difficulty in swallowing) is a common clinical symptom associated with many diseases, such as stroke, multiple sclerosis, neuromuscular diseases, and cancer. Its complications include choking, aspiration, malnutrition, cachexia, and dehydration. The goal in dysphagia management is to provide adequate nutrition and hydration while minimizing the risk of choking and aspiration. It is important to advance the individual toward oral feeding in a timely manner to enhance the recovery of swallowing function and preserve the quality of life. Current clinical assessments of dysphagia are limited in providing adequate guidelines for oral feeding. Mathematical modeling of the fluid dynamics of pharyngeal bolus transport provides a unique opportunity for studying the physiology and pathophysiology of swallowing. Finite element analysis (FEA) is a special case of computational fluid dynamics (CFD). In CFD, the flow of a fluid in a space is modeled by covering the space with a grid and predicting how the fluid moves from grid point to grid point. FEA is capable of solving problems with complex geometries and free surfaces. A preliminary pharyngeal model has been constructed using FEA. This model incorporates literature-reported, normal, anatomical data with time-dependent pharyngeal/upper esophageal sphincter (UES) wall motion obtained from videofluorography (VFG). This time-dependent wall motion can be implemented as a moving boundary condition in the model. Clinical kinematic data can be digitized from VFG studies to construct and test the mathematical model. The preliminary model demonstrates the feasibility of modeling pharyngeal bolus transport, which, to our knowledge, has not been attempted before. This model also addresses the need and the potential for CFD in understanding the physiology and pathophysiology of the pharyngeal phase of swallowing. Improvements of the model are underway. Combining the model with individualized clinical data should potentially improve the management of dysphagia.

Deglutition↗

The risk intraocular juvenile xanthogranuloma: survey of current practices and assessment of risk.

BACKGROUND: Juvenile xanthogranuloma (JXG) is an uncommon, usually uncomplicated disease of childhood. Ocular involvement, however, can result in glaucoma and blindness if left untreated. The incidence of ocular complications and how best to screen for their occurrence is unknown. OBJECTIVE: We attempted to ascertain management and referral practices among ophthalmologists and dermatologists and to characterize the risk for ocular complications in children with JXG. METHODS: A total of 431 dermatologists and 438 ophthalmologists were surveyed. In addition, the literature was reviewed. RESULTS: The response rate were 28% (dermatologists) and 44% (ophthalmologists). Most believed screening was important, but referral and surveillance practices varied widely. The survey incidence of ocular complications in patients with cutaneous JXG was approximately 0.3% (7 of 2371). The literature incidence was 0.4% (1 of 260). Children at maximum risk were 2 years of age or younger, had multiple skin lesions, and had newly diagnosed JXG. CONCLUSION: Ophthalmologic screening of patients with JXG should be particularly targeted to patients with risk factors of multiple skin lesions, new diagnosis, and age of 2 years or younger.

Age Factors↗

Sudoriferous acrosyringeal acantholytic disease. A subset of Grover's disease.

Three selected cases of transient acantholytic dermatosis were studied because of their definitive correlation with sweating due to fever and/ or bed-ridden situations. Biopsy specimens were serially sectioned and acantholysis was found in the acrosyringium or traced to connect to the acrosyringium in all biopsy specimens. Carcinoembryonic antigen (CEA) and eccrine gland-specific monoclonal antibody, IKH-4, were positive in acantholytic cells. Electron microscopy revealed electron dense material filling the lumen of intraepidermal eccrine ducts. This material leaked into lateral intercellular spaces of the luminal cells, passing tight junctions. Marked edema and numerous lysosomes were reminiscent of those found when eccrine acrosyringium is formed in the embryo; this suggested that an occluded and damaged eccrine intraepidermal duct was being rebuilt via lysosomal digestion.

Acantholysis↗

Vasomotor responses of newly developed coronary collateral vessels.

Well-developed coronary collateral vessels contain an abundant muscular media and can undergo active vasomotion. However, early after coronary occlusion, coronary collateral vessels are thin walled with little smooth muscle, suggesting that vasomotor capability might be limited. Consequently, this study determined whether newly developed coronary collateral vessels have active vasomotor activity and whether endothelial function in these newly developed vessels is impaired. Retrograde blood flow was measured as an index of coronary collateral blood flow approximately 2 wk after embolic occlusion of the anterior descending coronary artery of dogs. Agonists were administered into the left main coronary artery to reach collaterals originating from the left coronary system. Baseline retrograde blood flow was 25.1 +/- 2.7 ml/min and increased to 36.7 +/- 3.7 ml/min after nitroglycerin (6 micrograms.kg-1.min-1, P < 0.05). Cyclooxygenase blockade with indomethacin (5 mg/kg i.v.) decreased retrograde collateral blood flow to 16.8 +/- 2.3 ml/min (P < 0.05). Subsequent administration of acetylcholine increased retrograde flow to 29.4 +/- 3.7 ml/min (P < 0.05), indicating intact endothelium-mediated vasodilation. Inhibition of nitric oxide synthase with NG-nitro-L-arginine further decreased coronary collateral retrograde flow to 12.0 +/- 2.8 ml/min (P < 0.05) and markedly blunted the response to acetylcholine. These findings demonstrate substantial vasomotor capability even early during coronary collateral development and indicate that both nitric oxide and cyclooxygenase-dependent endothelial mechanisms are intact.

Animals↗