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Biomedical subjects

S M Jung

Publications and source records attributed to S M Jung.

At least 19 recordsLinked to original sources

Characterization of a patient with glycoprotein (GP) VI deficiency possessing neither anti-GPVI autoantibody nor genetic aberration.

BACKGROUND: There have been only seven reported cases of glycoprotein (GP) VI deficiency. However, the pathogenesis of this disorder has not been well-elucidated. OBJECTIVES: We characterized a novel patient with GPVI deficiency and used these platelets to investigate the role of GPVI in normal hemostasis. PATIENT: A 31-year-old female with immune thrombocytopenic purpura who had been suffering from mild bleeding diathesis even after recovery from thrombocytopenia. RESULTS AND CONCLUSION: The patient's platelets did not aggregate in response to either convulxin or collagen-related peptide. Immunoblotting revealed complete absence of the GPVI molecule, whereas a significantly reduced but substantial amount of Fc receptor (FcR) gamma-chain was expressed. Platelet stimulation with convulxin did not induce tyrosine-phosphorylation of FcR gamma-chain, indicating a defect in GPVI-mediated signaling. Concerning the underlying pathogenesis, we found normal level of GPVI-mRNA expression, no aberration of the sequence of the entire coding region of GPVI, and presence of degraded GPVI in her plasma. However, no anti-GPVI autoantibody was detected either by the binding assay to GPVI-Fc2 fusion protein or by immunoblotting/immunoprecipitation using the patient's immunoglobulin. We thus consider that either a short-time exposure to anti-GPVI autoantibody or a continuous exposure to low titers of the autoantibody has resulted in persistent GPVI deficiency. Under high shear flow, the patient's platelets could not form large aggregates, although initial platelet attachment was obviously observed. These results suggest that GPVI deficiency in this patient resulted in defective platelet thrombi development, manifesting as bleeding diathesis. Furthermore, our observations indicate that coordination of GPVI with integrin alpha2beta1 is essential for physiological platelet thrombus formation.

Adult↗

Change in right ventricular function during off-pump coronary artery bypass graft surgery.

OBJECTIVES: Hemodynamic derangement during displacement of beating heart in off-pump coronary artery bypass graft (OPCAB) surgery might be related with right ventricular (RV) dysfunction. We evaluated RV function and hemodynamic alterations using a thermodilution pulmonary artery catheter. METHODS: The study included 30 patients undergoing OPCAB, using single pericardial suture and tissue stabilizer. A thermodilution pulmonary artery catheter for continuous monitoring of the cardiac output (CO), right ventricular ejection fraction (RVEF) and RV volume was inserted before anesthesia. The hemodynamic variables were measured after the induction of anesthesia, 5 min after the heart was positioned for each coronary anastomosis and after the sternum was closed. RESULTS: There was no significant change in the RVEF and cardiac index during anastomosis of the left anterior descending artery and right coronary artery. However, the significantly reduced RVEF accompanied by an increase in RV afterload and decrease in the CO was observed during anastomosis of the obtuse marginal (OM) artery. RV volumes did not significantly change during anastomoses, though the right atrial pressure increased during anastomoses of all coronary arteries. CONCLUSIONS: The displacement of beating heart for positioning during anastomosis of the graft to OM artery caused significant derangement of RV function and decrease in CO. A thermodilution catheter continuously measuring the CO and RVEF was useful to monitor the change in RV function and volume during OPCAB.

Aged↗

Primary intracranial myxopapillary ependymomas: report of two cases and review of the literature.

Myxopapillary ependymoma is a variant of ependymoma occurring almost exclusively in the conus medullaris or filum terminale. Myxopapillary ependymoma found primarily in the brain is extremely rare. Two such cases appearing at the 4th ventricle and cerebral falx are reported. The imaging features of such tumors are a primary cystic mass with strong enhancement at its solid part. Myxopapillary ependymoma should be a possible differential diagnosis when an intracranial cystic tumor is found.

Adult↗

Mucin gene expression in cardiac myxoma.

Myxoma is the most common benign neoplasm of the heart. This work is the first to present an unusual left atrium and mitral valve cardiac myxoma which cannot be completely resected. This cardiac myxoma was also associated with abundant mucopolysaccharidic matrix, including mucin. Mucin gene expression is cell- and tissue-specific, with variations during cell differentiation and inflammation, and is altered during carcinogenesis. The expression of mucin genes in cardiac myxoma has never been elucidated previously. Detailed immunohistochemical analysis of MUC1, MUC2 and MUC5AC has been performed in this left atrium and mitral valve myxoma. Notably, the expressions of mucins in cardiac myxoma must be further evaluated.

Aged↗

Apoptosis in primary cardiac tumours.

Apoptosis, or programmed cell death, is now recognised as an important cellular event during both normal development and specific disease progression. Apoptosis has been suggested to play a critical role in several cardiovascular diseases, but has not yet been identified as a major influence in primary cardiac tumours. A retrospective review of the achieved material at Chang Gung Memorial Hospital revealed seven patients with cardiac myxoma and one with a tumour originating from the crista terminalis, from January 2002 to December 2002. The medical chart, surgical pathology reports and microscopic slides were available in all cases. All patients, including eight cardiac myxomas and one tumour from crista terminalis, were assessed for apoptosis by terminal deoxynucleotidyl transferase nick-end labelling assay. In this study, apoptosis is well documented in all seven myxoma and has even been reported in tumour from the crista terminalis. Interestingly, apoptosis appears related to the nature of the cell properties rather than the incidence of embolism. In conclusion, apoptosis is important in the progression of the primary cardiac tumours, but the mechanism of cardiac tumour regression still remains uncertain.

Adult↗

Performance of a web-based, realtime, tele-ultrasound consultation system over high-speed commercial telecommunication lines.

A Web-based, realtime, tele-ultrasound consultation system was designed. The system employed ActiveX control, MPEG-4 coding of full-resolution ultrasound video (640 x 480 pixels at 30 frames/s) and H.320 videoconferencing. It could be used via a Web browser. The system was evaluated over three types of commercial line: a cable connection, ADSL and VDSL. Three radiologists assessed the quality of compressed and uncompressed ultrasound video-sequences from 16 cases (10 abnormal livers, four abnormal kidneys and two abnormal gallbladders). The radiologists' scores showed that, at a given frame rate, increasing the bit rate was associated with increasing quality; however, at a certain threshold bit rate the quality did not increase significantly. The peak signal to noise ratio (PSNR) was also measured between the compressed and uncompressed images. In most cases, the PSNR increased as the bit rate increased, and increased as the number of dropped frames increased. There was a threshold bit rate, at a given frame rate, at which the PSNR did not improve significantly. Taking into account both sets of threshold values, a bit rate of more than 0.6 Mbit/s, at 30 frames/s, is suggested as the threshold for the maintenance of diagnostic image quality.

Data Compression↗

Successful salvage treatment of recurrent endometrial cancer with bulky central tumor and extensive lymph node metastasis. A case report.

Recurrent endometrial cancer with both local and distant metastasis is very difficult to treat. A 55-year-old endometrial adenocarcinoma patient with bulky central recurrences and pelvic and inguinal lymph node metastases underwent laparotomy and paraaortic, pelvic and inguinal lymphadenectomy followed by concurrent chemoradiation (with cisplatin) to the paraaortic and inguinal lymph nodes as well as the whole pelvis. Neck and mediastinal lymph node metastasis emerged during treatment. Neck-node radiation and epirubicin was added followed by paclitaxel and carboplatin. Complete remission was achieved. Ten months later, isolated central re-recurrence happened and total pelvic exenteration was performed. The patient has survived without further recurrence for more than five years after the exenteration. Therefore, a multimodality approach with a combination of radical resection (even pelvic exenteration), radiotherapy and chemotherapy could be offered to well-selected patients with recurrent endometrial cancer despite out-of-field progression during therapy and in-field local failure to initial salvage treatment.

Adenocarcinoma↗

Real-time analysis of the interaction of platelets with immobilized thrombospondin under flow conditions.

The platelet granule protein (TS) is extracellularly secreted upon platelet activation and then binds to the platelet surface where it can interact with various adhesive proteins. Here, we have analyzed platelet interactions with a TS-coated surface under flow conditions, a model for platelet adhesion onto surface-bound TS under physiological conditions. Platelets exhibited temporary, very short-time adhesion on the TS surface, but no firm adhesion. This adhesion was inhibited by NNKY5-5 (anti-glycoprotein (GP) Ib antibody) and AJvW-2 (anti-von Willebrand factor (vWF)), indicating that both platelet GP Ib and plasma vWF contribute to this interaction. Antibodies against platelet collagen receptor integrin alpha(2)beta(1) had no significant effect. These results suggested that binding of vWF to TS is the first step in platelet interaction with the TS surface. By surface plasmon resonance spectroscopy, a dissociation constant (K(d)) of 3.97x10(-7) M was obtained for the binding reaction between immobilized TS and vWF. These results suggest the following model for platelet interaction with the TS surface under flow: plasma vWF first binds to the immobilized TS and then platelets interact with the TS-bound vWF. A low density of bound vWF would account for the observed weak interaction between TS and platelets under flow.

Blood Flow Velocity↗

Platelet collagen receptor integrin alpha2beta1 activation involves differential participation of ADP-receptor subtypes P2Y1 and P2Y12 but not intracellular calcium change.

In agonist-induced platelet activation, the collagen platelet receptor integrin alpha2beta1 is activated to high-affinity states through ADP involvement [Jung, S.M. & Moroi, M. (2000) J. Biol. Chem. 275, 8016-8026]. Here we determined the ADP-receptor subtypes involved and their relative contributions to alpha2beta1 activation (assessed by soluble-collagen binding) using the P2Y12 antagonist AR-C69931MX and P2Y1 antagonists adenosine 3',5'-diphosphate (Ado(3,5)PP) and adenosine 3'-phosphate 5'-phosphosulfate (AdoPPS). All three inhibited alpha2beta1 activation induced by low or high ADP, low thrombin, or low collagen-related peptide (CRP) concentrations; however, AR-C69931MX was markedly more inhibitory than the P2Y1 antagonists, suggesting the greater contribution of P2Y12. Inhibition patterns by various combinations of AR-C69931MX, AdoPPS, and wortmannin suggested that P2Y1 and P2Y12 mediate alpha2beta1 activation through different pathways, with possible involvement of phosphoinositide 3-kinase in both. Low concentrations of the acetoxy-methyl derivative of 1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid (calcium chelator) markedly decreased alpha2beta1 activation by low thrombin or CRP, but did not affect that by low or high ADP. Measurements of intracellular Ca2+ level (fluorimetric method) and alpha2beta1 activation (soluble-collagen binding) in the same platelet preparation indicated that alpha2beta1 activation via ADP receptors was independent of intracellular Ca2+ release. Our data indicate that integrin alpha2beta1 activation by ADP occurs through an inside-out signaling mechanism involving differential contributions by P2Y1 and P2Y12 wherein each contributes to some portion of the activation, with the stronger contribution of P2Y12. Furthermore, intracellular Ca2+ increase is not directly related to integrin alpha2beta1 activation, meaning that it is separate from the calcium mobilization pathways that these two ADP receptors are involved in.

Adenosine Diphosphate↗

High prevalence of high grade squamous intraepithelial lesions and microinvasive carcinoma in women with a cytologic diagnosis of low grade squamous intraepithelial lesions.

OBJECTIVE: To evaluate the histologic nature of low grade intraepithelial lesion (LSIL) in a region with a high prevalence of invasive cervical carcinoma and to propose a management protocol. STUDY DESIGN: Comparing the follow-up of 877 women with LSIL during a 43-month period, taking into consideration the histologic nature determined by colposcopic biopsy, endocervical curettage, conization or hysterectomy as the final pathologic diagnosis. RESULTS: During the study period, from July 1994 to February 1998, a total of 128,925 Pap smears were performed at our institute, with 877 (0.68%) diagnosed as LSIL. Among these, 722 women with CIN1-SIL and 32 with human papillomavirus-related changes (HPV-SIL) were enrolled in the study. Of the 543 women with CIN 1/squamous intraepithelial lesion, 145 (27%) cases of high grade squamous intraepithelial lesion were disclosed histologically, as were 16 (3%) cases of microinvasion. Among those followed at an interval of three months with a Pap smear alone, the persistence rate was 46.8%, while the regression rate was 40%. Thirty-two women with HPV/SIL underwent histologic evaluation, revealing 18% CIN 2/3 with no microinvasion. CONCLUSION: A high percentage of CIN 2/3 as well as microinvasive lesions will go unnoticed in the absence of colposcopic evaluation.

Colposcopy↗

Cloning and expression of the platelet-specific collagen receptor glycoprotein VI.

Platelet glycoprotein VI (GP VI) was purified from platelet membranes and its internal amino acid sequences were determined. The cloned cDNA of GP VI indicates an open reading frame coding for 20 amino acid signal sequences and a mature protein of 319 amino acids. Its extracellular region has two Ig-like domains and a mucin-like, Ser/Thr-rich region, suggesting that GP VI is a member of the paired Ig-like receptor family. GP VI-transfected cells contained convulxin-(reactive) and antibody against recombinant GP VI-reactive protein bands that migrated at the same position as platelet GP VI in SDS/PAGE-electroblotting. These data indicate that the protein deduced from the cloned cDNA corresponds to platelet GP VI.

Amino Acid Sequence↗

Signal-transducing mechanisms involved in activation of the platelet collagen receptor integrin alpha(2)beta(1).

Evidence was obtained about the mechanism responsible for platelet integrin alpha(2)beta activation by determining effects of various inhibitors on soluble collagen binding, a parameter to assess integrin alpha(2)beta(1) activation, in stimulated platelets. Agonists that can also activate platelet glycoprotein IIb/IIIa are able to activate integrin alpha(2)beta(1), but those operating via glycoprotein Ib cannot. Activation of alpha(2)beta(1) induced by low thrombin or collagen-related peptide concentrations was almost completely inhibited by apyrase, and the inhibitors wortmannin, 4-amino-5-(chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, bisindolylmaleimide I, and SQ29548 significantly inhibited it. Activation induced by high thrombin or collagen-related peptide concentrations was far less sensitive to these inhibitors. However, only wortmannin markedly inhibited ADP-induced integrin alpha(2)beta(1) activation, and this was not ADP concentration-dependent. These results suggest that at the low agonist concentrations, the released ADP would be a primary inducer of integrin alpha(2)beta(1) activation, while at the high agonist concentrations, there would be several pathways through which integrin alpha(2)beta(1) activation can be induced. Kinetic analyses revealed that ADP-induced platelets had about the same number of binding sites (B(max)) as thrombin-induced platelets, but their affinity (K(d)) for soluble collagen was 3.7-12.7-fold lower, suggesting that activated integrin alpha(2)beta(1) induced by ADP is different from that induced by thrombin. The data are consistent with an activation mechanism involving released ADP and in which there exists two different states of activated integrin alpha(2)beta(1); these activated forms of integrin alpha(2)beta(1) would have different conformations that determine their ligand affinity.

Adenosine Diphosphate↗

Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998.

A large scale outbreak of hand-foot-and-mouth disease (HFMD) occurred in Taiwan in 1998, in which more than 80 children died of shock syndrome with pulmonary edema/hemorrhage. Enterovirus 71 was implicated as the cause of this outbreak. In order to understand the virological basis responsible for mortality on this scale, nucleotide sequences of VP1 that is important for serotypic specificity, and the 5'-non-coding region (5'-NCR) that is important for replication efficiency, were analyzed comparatively. Phylogenetic analysis of both VP1 and 5'-NCR of nine EV71 isolates derived from specimens of fatal patients and seven isolates derived from uncomplicated HFMD patients showed that all but one isolate fell into genotype B. The one distinct isolate from a case of uncomplicated HFMD belonged to genotype C that was clustered along with one isolate from Taiwan in 1986. Complete sequence analysis of two selected isolates, one from the spinal cord of a fatal case and one from the vesicle fluid of a patient with mild HFMD, confirmed a high degree (97-100%) of identity in nucleotide sequence throughout the entire genome, except focal regions of 3C and 3'-NCR where the nucleotide homology was 90-91%. The identity of the deduced amino acid sequence in the 3C region that encodes viral proteinase dropped further to 86%, a result of missense mutations at the first nucleotide position of many codons.

5' Untranslated Regions↗

Activation of the platelet collagen receptor integrin alpha(2)beta(1): its mechanism and participation in the physiological functions of platelets.

When platelets are stimulated by agonists, integrin alpha(2)beta(1) (GP Ia/IIa), one of the platelet collagen receptors, is activated to forms with high affinities for its ligand collagen. Here we describe our studies to characterize the binding kinetics of the activated integrin forms and the activation mechanism. Under low agonist concentrations, integrin alpha(2)beta(1) is activated through a mechanism involving ADP/ADP receptors; and under high agonist concentrations, multiple signaling pathways are involved in its activation. Such differences in mechanism at low and high agonist concentrations are also suggested in the activation of integrin alpha(IIb)beta(3), the platelet fibrinogen receptor. We describe our flow adhesion studies, from which evidence was obtained about the involvement of integrin alpha(2)beta(1) activation in the physiological function of platelets, adhesion and thrombus formation.

Blood Platelets↗

Acute encephalomyelitis during an outbreak of enterovirus type 71 infection in Taiwan: report of an autopsy case with pathologic, immunofluorescence, and molecular studies.

We report a fatal case of enterovirus type 71 (EV 71) infection in an 8-year-old girl during a summer outbreak of hand, foot, and mouth disease in 1998 in Taiwan. The clinical course was rapidly progressive, with manifestations of hand, foot, and mouth disease, aseptic meningitis, encephalomyelitis, and pulmonary edema. The patient died 24 hours after admission. Postmortem study revealed extensive inflammation in the meninges and central nervous system and marked pulmonary edema with focal hemorrhage. Brain stem and spinal cord were most severely involved. The inflammatory infiltrates consisted largely of neutrophils involving primarily the gray matter with perivascular lymphocytic cuffing, and neuronophagia. The lungs and heart showed no evidence of inflammation. EV 71 was isolated from the fresh brain tissues and identified by immunofluorescence method with type-specific EV 71 monoclonal antibody. It was also confirmed by neutralization test and reverse-transcriptase polymerase chain reaction with sequence analysis. The present case was the first example in which EV 71 was demonstrated to be the causative agent of fatal encephalomyelitis during its epidemic in Taiwan.

Antigens, Viral↗

Telomerase activity is frequently found in metaplastic and malignant human nasopharyngeal tissues.

Telomerase is a specialized ribonucleoprotein polymerase that directs the synthesis of telomere repeats at chromosome ends. Accumulating evidence has indicated that telomerase is stringently repressed in normal human somatic tissues but reactivated in cancers and immortal cells, suggesting that reactivation of telomerase plays an important role in carcinogenesis. In this study, the status of telomerase activity in diseased human nasopharyngeal lesions was determined by the telomeric repeat amplification protocol (TRAP). Fifty-four patients participated including 17 inflammation or hyperplasia, eight with squamous metaplasia, and 29 with different stages of carcinomas. Telomerase activity was detected in 1 of 17 (5.9%) inflammatory or lymphoid hyperplastic tissues, 3 of 8 (37.5%) squamous metaplastic, and 25 of 29 (86.2%) carcinoma tissues. The differences in telomerase expression in these groups is statistically significant (P < 0.001). Levels of telomerase activity correlated with tumour stage (P = 0.024). These results suggest that telomerase reactivation plays a role in the carcinogenesis of nasopharyngeal cancer. Since telomerase activity is found in the majority of nasopharyngeal cancers and a subset of metaplasia, this enzyme may be served as a reference to monitoring the status of abnormal nasopharyngeal tissues.

Biopsy↗

Pulmonary lymphangitic sarcomatosis from cutaneous angiosarcoma: an unusual presentation of diffuse interstitial lung disease.

Pulmonary lymphangitic sarcomatosis (PLS) is not much recognized clinically although it shows similar pathological patterns and diagnostic features to pulmonary lymphangitic carcinomatosis (PLC). We report a case with hand angiosarcoma whose chest X-ray findings revealed a diffuse interstitial pattern consistent with lymphangitic spreading. The final diagnosis was made by open lung biopsy. The clinical, diagnostic and pathological features of this disease process are reviewed.

Adult↗

Primary Sjögren's syndrome manifested as multiple sclerosis and cutaneous erythematous lesions: a case report.

Sjögren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration of the lacrimal and salivary glands, leading to dryness of eyes (kerato-conjunctivitis sicca) and mouth (xerostomia). The skin lesions in Sjögren's syndrome are usually manifested as xeroderma, but sometimes appear as annular erythema or vasculitis. Central nervous system symptoms may be presented as one of extraglandular manifestations, though rare in incidence, and need differential diagnosis from multiple sclerosis. We report a case of a 45-year-old woman diagnosed as multiple sclerosis at first but later as neurologic manifestation of primary Sjögren's syndrome, showing signs of multiple sclerosis and cutaneous erythematous lesions.

Diagnosis, Differential↗