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Biomedical subjects

M S Shin

Publications and source records attributed to M S Shin.

At least 55 records · Page 3Linked to original sources
PubMed1999

Immunoregulatory potential of urothelium: characterization of NF-kappaB signal transduction.

PURPOSE: To characterize the basal and activated form of nuclear factor-kappaB (NF-kappaB) complex in normal urothelial cell cultures after stimulation with tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and double-stranded ribonucleic acid (dsRNA). MATERIALS AND METHODS: Human urothelial cells cultured from normal bladder specimens underwent immunohistochemical staining and cellular extracts were prepared for Electrophoretic Mobility Shift Assays (EMSA), Western blot analyses, RNA isolation and Northern Blot analyses before and after stimulation with TNF-alpha, LPS, and dsRNA. RESULTS: In normal human urothelial cells, activation of the NF-kappaB complex in response to stimulation with TNF-alpha, LPS, and dsRNA was detected by immunohistochemical methods and EMSA. Depending on the stimulus, a specific NF-kappaB complex was activated as seen by supershift experiments in EMSA. By Western blot, the inhibitor of NF-kappaB complex, IkappaB-alpha, degraded in response to stimulation. Northern blot analysis from total RNA revealed subsequent inducible interleukin-8 (IL-8) mRNA expression of normal urothelial cells when treated with TNF-alpha, LPS, and dsRNA. CONCLUSIONS: Normal human urothelial cells contain basal NF-kappaB complexes in an inactivated state. When these cells are challenged by different agents such as TNF-alpha, LPS, and dsRNA, the cells respond by activation of the NF-kappaB signal transduction pathway, degradation of its inhibitor, IkappaB-alpha, and translocation of this primary factor into the nucleus to induce specific genetic responses such as IL-8 expression.

Cells, Cultured↗
PubMed1999

Immunohistochemical analysis of Fas ligand expression in normal human tissues.

Cross-linking of Fas and Fas ligand (FasL) induces apoptosis in Fas-bearing cells and regulates apoptosis. Fas is widely expressed in normal human tissues, but FasL expression has been considered to be restricted to lymphoid tissues. Recent studies have demonstrated that FasL is also expressed in some nonlymphoid tissues. To screen the in situ expression of FasL in normal human tissues, immunohistochemistry was performed using paraffin-embedded human tissues. FasL immunostaining was easily detected in testis, neurons, trophoblasts, tonsil, lymph node, Paneth cells, hepatocytes, renal tubular epithelium and bronchial epithelium, consistent with previous reports. Surprisingly, FasL was also expressed in many other cell types, including thymic medulla, skeletal muscle, cardiac muscle, pituitary gland, parathyroid gland, prostate glands, oocytes, epithelium of fallopian tube, endometrial glands, and gastric parietal cells. These findings demonstrate that FasL is widely expressed in human tissues and suggest that wide but cell-type specific expression of FasL may not only be implicated in the regulation of immune homeostasis but also in the regulation of cell death and life in many cell types in vivo.

Apoptosis↗
PubMed1999

Immunohistochemical localization of FAP-1, an inhibitor of Fas-mediated apoptosis, in normal and neoplastic human tissues.

Fas, a death receptor, is widely expressed in human tissue, but its expression, although a prerequisite for the induction of apoptosis, does not predict its biological function. To understand the mechanisms of Fas resistance in human tissues in vivo, we performed immunohistochemistry using an antibody against Fas-associated phosphatase-1 (FAP-1), which interacts with the cytosolic domain of Fas and inhibits Fas-mediated apoptosis. In normal human tissues, FAP-1 immunostaining was easily detected, for example, in renal tubules, skeletal muscle, myocardiocytes, pituitary gland, parathyroid gland, pancreatic islets, hepatocytes, testicular germ cells, prostatic glands, neurons, epithelium of fallopian tube, endometrial glands, trophoblasts, bronchial epithelial cells, and some types of gastrointestinal epithelial cells. In 123 (78%) of 158 cancers of various origins, including breast carcinomas, stomach carcinomas, colon carcinomas, lung carcinomas and several types of sarcomas, variable intensities of FAP-1 expression were evident. Taken together, these findings demonstrated that FAP-1 is widely expressed in normal human tissues and partly overlapped with Fas expression described in earlier reports, suggesting that FAP-1 may have an important role in the regulation of apoptosis in vivo. In addition, FAP-1 expression in cancers suggests that many cancers may be resistant to Fas-mediated apoptosis through the action of FAP-1 in vivo.

Apoptosis↗
PubMed1999

Pulmonary malacoplakia associated with Rhodococcus equi infection in a patient with AIDS.

An AIDS patient with a cavitary lung lesion was found to have pulmonary malacoplakia associated with Rhodococcus equi infection. The diagnosis was based on the typical histologic features of transbronchial biopsy and a positive bacterial culture. All 13 reported cases of AIDS patients with pulmonary malacoplakia were associated with R equi. The recognition of this unique entity is important because of its responsiveness to therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Ultrastructural changes of the external elastic lamina in experimental hypercholesterolemic porcine coronary arteries.

The external elastic lamina (EEL) serves as a barrier for cells and macromolecules between the media and adventitia in the vascular wall. We evaluated the morphological changes and quantitative assessments of the EEL architecture in the coronary circulation of pigs fed with a high cholesterol diet. Confocal microscopy analysis of the EEL from hypercholesterolemic coronary arteries revealed an altered pattern characterized by fragmentation and disorganization of the EEL associated with an increase in the thickness. Computerized digital analysis of the images obtained by confocal scanning microscopy demonstrated that compared to normal coronary arteries, the EEL of hypercholesterolemic coronary arteries decreased in the percentage of their elastin content (30.80 +/- 1.64% vs. 47.85 +/- 1.82%, p = 0.001). The percentage of elastin content was negatively correlated with the vessel wall area (r = -0.82, p = 0.001). The immunoreactivity for matrix metalloproteinase-3 (MMP-3) increased in cholesterol-fed coronary arteries, predominantly in the neointima and adventitia. This study demonstrates that experimental hypercholesterolemia induced ultrastructural changes of the EEL in coronary circulation. The EEL may also be an atherosclerosis-prone area compared with the intima. The EEL may play an important role in the development of structural changes which characterizes the early phase of coronary atherosclerosis and vascular remodeling.

Animals↗
PubMed1998

Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer.

We analyzed somatic mutation and loss of heterozygosity (LOH) in the serine/threonine kinase 11 (STK11)/Peutz-Jeghers syndrome gene in 49 colorectal tumors in three different stages of a dysplasia-carcinoma sequence. We detected LOH in 10 of 19 (52.6%) informative colorectal cancers at loci D19S886 and/or D19S883, but no LOH was observed in 25 informative adenomas. We detected a total of 9 somatic mutations [7 of 13 (53.8%) left-sided colon cancers and 2 of 7 (28.6%) left-sided adenomas with high-grade dysplasia], but no mutations were detected in right-sided colon tumors. Of the nine mutations, one was a frameshift mutation (the same mutation detected in Peutz-Jeghers syndrome family previously), and the other eight were missense mutations. This results indicate that STK11 is a tumor suppressor gene and that genetic changes of STK11 play an important role in left-sided colon cancer carcinogenesis.

AMP-Activated Protein Kinase Kinases↗
PubMed1998

A distinct region of chromosome 19p13.3 associated with the sporadic form of adenoma malignum of the uterine cervix.

Adenoma malignum (AM) is known to be one of the malignant tumors that is commonly associated with Peutz-Jeghers syndrome. Recently, the genetic locus of Peutz-Jeghers syndrome was mapped to the telomeric region of chromosome 19p. We analyzed nine sporadic cases of AM with high-density loss of heterozygosity to study the region of chromosome 19p13.2-13.3 using eight microsatellite markers. Our deletion mapping data revealed a distinct region with 100% loss of heterozygosity frequency at marker D19S216. This result indicates that a putative tumor suppressor gene for AM is located at D19S216 on chromosomal band 19p13.3 and plays an important role in AM tumorigenesis.

Adenocarcinoma↗
PubMed1998

Fas ligand is expressed in normal skin and in some cutaneous malignancies.

Fas, a cell surface receptor and member of the tumour necrosis factor receptor superfamily, induces apoptosis upon oligomerization by its ligand (Fas ligand: FasL). Detailed studies have revealed that Fas is broadly expressed in normal human tissues, but relatively little is known about the range of cell types capable of expressing FasL. The aim of this study was to determine the in vivo patterns of expression of Fas and FasL in human skin tissues. Immunohistochemistry was performed using paraffin-embedded samples of normal and neoplastic skin tissues. In normal skin, FasL was expressed in the epidermis, sebaceous glands, sweat glands and outer root sheath of the hair. In squamous cell carcinomas (SCC), all cases analysed expressed FasL at high levels, whereas 60% of basal cell carcinomas (BCC) were positive for FasL. Expression of Fas in normal skin was observed in the basal and spinous layers of the epidermis, the outer root sheath of the hair, and the sebaceous glands. Expression of Fas was observed in all the SCC tested and none of the BCC tested. Expression of FasL by normal cells and tumour cells in skin tissue, demonstrated for the first time in the present study, may provide an important clue to understanding skin physiology, and immune evasion of skin tumours.

Adult↗
PubMed1998

Detection of soluble Fas mRNA using in situ reverse transcription-polymerase chain reaction.

Fas protein (Fas) is known to induce cell death by apoptosis in susceptible cells. Alternative splicing of the Fas gene produces soluble Fas protein (sFas), which is considered to block the function of Fas. The serum level of sFas is elevated in patients with various malignancies in a manner reflective of disease stage and tumor burden, but the precise cellular origin of sFas in vivo has not yet been clarified. To identify the cells that synthesize sFas mRNA on histologic specimens, we applied in situ reverse transcription-polymerase chain reaction (in situ RT-PCR) in 11 cases of gastric adenocarcinoma/metastatic lymph node. Furthermore, we studied the distribution of Fas using immunohistochemistry and Fas mRNA using in situ RT-PCR. In all primary tumors and 10 of 11 metastatic tumors, tumor cells expressed both Fas- and sFas mRNA. Lymphocytes infiltrated in the tumor tissues and the lymph nodes also revealed both mRNA signals. A clear correlation between the tissue distribution for Fas and its mRNA was also observed. These observations demonstrated that solid tumors in vivo can synthesize sFas mRNA and suggest that tumor cells are responsible in part for elevated sFas in human malignancies. However, the additional expression of sFas mRNA in tissue lymphocytes indicates the complex regulatory mechanisms of Fas-mediated apoptosis pathway in tumor pathogenesis and host defense. We also demonstrated that in situ RT-PCR can be a suitable method for in situ detection of alternatively spliced mRNA.

Alternative Splicing↗
PubMed1997

Genetic alterations of p16INK4a and p53 genes in sporadic dysplastic nevus.

It is still unclear whether the sporadic form of dysplastic nevi (SDN) represents a premalignant lesion of malignant melanoma and whether genetic alterations are involved in the development of SDN. To determine whether p16INK4a and p53 genetic abnormalities could be associated with development of SDN, nevus cell nests were procured selectively from H & E-stained slide sections by using a modified microdissection technique and were screened for the presence of mutations and loss of heterozygosity (LOH) of p16INK4a and p53 genes using a polymerase chain reaction-based LOH, single-strand conformation polymorphism, and direct DNA sequencing analyses. Hemizygous deletion was detected in 9 of 12 informative cases (75%) for 9p21-22 (p16INK4a) at one or more loci and 60% (6/10) for 17p13 (p53). As for mutation, we found 3 missense mutations and 1 mutation in the first intron in p16INK4a and 2 missense mutations in p53. Among these mutations in p16INK4a and p53, 5 of 6 mutations were of the C:G to T:A transitional type; this is known to be related to ultraviolet radiation as previously confirmed in other skin cancers. This indicates that p16INK4a and p53 genetic alterations may play an important role in the evolution of SDN and may represent an early event in the development of malignant melanoma. Furthermore, ultraviolet radiation might be the predominant etiologic agent in the development of SDN.

Amino Acid Sequence↗
PubMed1997

Simplified anatomic method of double-eyelid operation: septodermal fixation technique.

Conventionally, it has been argued that the aponeurosis meets the orbital septum below the upper tarsal border in Orientals. However, we have shown that the aponeurosis fused with the orbital septum above the upper tarsal border in 502 patients, which contradicts the classic concept. In 457 patients there were distinct layers of fascia anterior to the orbital septum that originate from the septum and insert onto the pretarsal aponeurotic expansion. In Oriental eyelids, the preaponeurotic fat and orbital septum hang below the fusion line of the septum and aponeurosis. The hanging portion of the septum was dissected from the aponeurosis, plicated, and sutured to the dermis of the pretarsal flap. We performed the septodermal fixation technique in 512 patients over 3 years starting in March of 1992. Complications and changes of the folds were analyzed. The technique produced much less edema and discomfort and created more natural fold lines than any other technique. Patients were very lightly satisfied with the shape of the folds that we were able to design and adjust precisely with this method.

Adolescent↗
PubMed1996

Epidermal growth factor improves intestinal adaptation during somatostatin administration in vivo.

Somatostatin (SMS) is administered to patients with short bowel syndrome and enterocutaneous fistulae. Previous studies have shown detrimental effects of SMS on intestinal adaptation after bowel resection. We examined whether administration of epidermal growth factor (EGF) could reverse the deleterious effects of SMS seen after enterectomy. Sixty-four Sprague-Dawley rats underwent an 80% small bowel resection or transection as control. Rats received either SMS at 50 ng x kg(-1) x h(-1), EGF/Urogastrone at 1.5 microg x kg(1-) x h(-1), or both via subcutaneous miniosmotic pumps. Samples were obtained at 1 day and 1 week after surgery for histologic examination, analysis of apical Na+/glucose cotransporter protein and mRNA expression, and analysis of basolateral Na+/K+ ATPase protein and mRNA expression. Protein expression was analyzed by Western blotting whereas mRNA expression was compared by ribonuclease protection assay. Histologically, villus to crypt length after intestinal resection showed increased adaptation in EGF/SMS vs SMS treated animals in both jejunum and ileum. Analysis of mRNA and protein of epithelial transporters show early increases when EGF is administered with SMS vs SMS only. We conclude that combination therapy using EGF and SMS may be beneficial to intestinal adaptation after small bowel resection. Both histologic and molecular data suggest an enhanced absorptive potential and adaptation of the remaining intestine when EGF is administered.

Analysis of Variance↗
PubMed1996

Extensive pulmonary metastasis of an intracranial meningioma with repeated recurrence: radiographic and pathologic features.

Recurrent intracranial meningioma with multiple pulmonary metastases is rare. In this case, the initial tumor had been diagnosed and removed 10 years earlier, and subsequent locally recurrent tumors were removed three times. Nine pulmonary metastases were discovered and resected recently. The metastatic lesion was confirmed as meningioma or arachnoidocytoma by light and electron microscopy and immunohistochemical studies. The patient survived all the operations.

Adult↗
PubMed1995

Endoscopic-assisted recontouring of the facial skeleton: the forehead.

Endoscopic techniques have revolutionized current surgical techniques and have now been introduced to plastic surgery. Advantages of endoscopic assistance include direct visualization, hidden scars, and decreased morbidity. We sought to implement endoscopic techniques to recontour the facial skeleton and avoid the disadvantages of open procedures. A standard video system and endoscopic instrumentation including a 4-mm 30-degree endoscope and a power bur were used. Cadaveric dissections were performed before clinical use. Using endoscopic assistance, the frontal bone of a 42-year-old Korean woman with bony deformities was visualized and sculpted using a power bur. An uneventful postoperative course ensued. This case illustrates the feasibility of using endoscopic techniques in forehead recontouring and sets the stage for further work in malar and mandible recontouring.

Adult↗
PubMed1995

Squamous cell carcinoma of the uterine cervix. Patterns of thoracic metastases.

RATIONALE AND OBJECTIVES: Distant metastasis of cervical cancer, once considered rather uncommon, has become more common in recent years because of longer survival of the patients. The purpose of this study is to evaluate the radiographic patterns of its thoracic metastases correlating with the pathways of metastatic tumor spread. METHODS: The conventional radiographs (62 cases), thoracic computed tomography images (20 cases), and medical records of 62 patients with advanced squamous cell carcinoma of the uterine cervix with thoracic metastases who died of extensive disease and its complications during a recent 5-year period were reviewed retrospectively. RESULTS AND CONCLUSIONS: In addition to the most typical pattern of multiple pulmonary nodules (71%), mediastinal and hilar lymphadenopathy (32%) and pleural metastases (27%) were frequently observed. Rare findings included bone metastases (6%), endobronchial obstruction (5%), and lymphangitic carcinomatosis (3%). The mechanisms of metastasis in relation to the above manifestations are proposed.

Adult↗
PubMed1995

Clinical risk factors for pulmonary barotrauma: a multivariate analysis.

Previous investigations have suggested that elevated airway pressures increase the risk of ventilator-induced pneumothorax. However, risk factor analysis using multivariate techniques has not been done. We investigated the hypothesis that airway pressures would not independently correlate with pneumothorax when underlying disease was considered. All ventilated patients over a 1 yr period in the Hohenburg Critical Care Unit at the University of Alabama were followed until death or discharge from the ICU. Ventilator data were collected daily and the presence of pneumomediastinum and pneumothorax determined by review of chest radiographs. Maximal values of airway pressures, minute ventilation, tidal volume, and respiratory rate, as well as age, sex, and underlying disease, were entered into logistic regression analysis. A total of 168 patients was studied, and 20 experienced pneumothorax. Multivariate analysis of the entire ventilated population revealed that only the presence of ARDS independently correlated with pneumothorax. A similar analysis performed on the ARDS population revealed independent correlation only with male sex. Trends toward elevation in airway pressures were seen that did not reach statistical significance. We conclude that development of pneumothorax is most closely correlated with underlying disease, specifically ARDS, and that the associations previously noted between airway pressures and barotrauma largely relate to the occurrence of high airway pressures in ARDS.

Adult↗
PubMed1994

Refinement in aesthetic contouring of the prominent mandibular angle.

Oriental women, in general, greatly desire a more delicate and feminine facial shape. This can be obtained by contouring the prominent mandibular angles that give a strong, masculine image. Western authors regarded masseteric muscular hypertrophy the main cause of a square facial appearance, so they usually corrected it by partially excising the masseter muscle. In the authors' view, a square facial appearance in the Oriental is not due to masseteric hypertrophy but to a posterior projection and lateral flaring of the mandibular angle. However, it is sometimes difficult to make the square face narrow and ovoid by using only the conventional curved-angle osteotomy. We divided patients, whose chief complaint was a square facial appearance, into three groups after clinical, photographic, and radiographic evaluation. We applied different contouring methods to each of the three groups and obtained cosmetically improved facial appearance in both lateral and frontal views.

Adult↗