Generation of full-length cDNA library from single human prostate cancer cells.
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Actins↗
Biomedical subjects
S L Lin
Publications and source records attributed to S L Lin.
Optimal control of blood pressure can reverse left ventricular hypertrophy in uremic hypertensive hemodialysis patients.
We investigated the effects of antihypertensive treatment on left ventricular hypertrophy (LVH) of long-term hemodialysis patients. In uremic patients, it is still controversial in antihypertensive effect to the regression of LVH. The left ventricular size and function of 39 uremic hypertensive long-term hemodialysis patients (27 men, 12 women, mean age 58.3) was evaluated with M-mode, 2-dimensional and Doppler echocardiography before, and 12 months after, the start of combined antihypertensive therapy. This therapy included angiotensin II converting enzyme inhibitors, beta-blockers and calcium antagonists. Patients were classified as responders or nonresponders, depending upon whether their systolic blood pressure (SBP) decreased by more than 10 mmHg after antihypertensive treatment for 12 months. Before treatment, 36 (92%) patients had LVH and diastolic dysfunction and three (8%) had systolic dysfunction. At the end of 12 months, only 25 (64%) patients had LVH, 30 (77%) had diastolic dysfunction and 2 (5%) had systolic dysfunction. Left ventricular mass index (LVMI) also decreased from 203.63 +/- 70.47 g/m2 to 178.57 +/- 67.31 g/m2. LVMI correlated with systolic blood pressure (SBP) but did not correlate with diastolic blood pressure (DBP). There were 26 responders and 13 non-responders. Among responders, both the SBP (153.91 +/- 13.24 mmHg vs 134.43 +/- 14.21 mmHg, p < 0.01) and DBP (90.39 +/- 7.89 mmHg vs 79.98 +/- 7.35 mmHg, p < 0.01) decreased significantly after antihypertensive therapy. Responders also exhibited progressive regression of LVH (LVMI decreased significantly from 208.52 +/- 72.03 g/m2 to 168.52 +/- 55.53 g/m2, p < 0.05). However, LVH regression was not found in nonresponders (LVMI showed 194.84 +/- 64.36 g/m2 vs 193.66 +/- 77.67 g/m2). We conclude that good control of blood pressure can reverse LVH in hypertensive hemodialysis patients.
Adult↗
Circadian and weekly variations in pain onset of acute myocardial infarction.
BACKGROUND: A seasonal variation with more myocardial infarctions in the winter months due to cold weather has been reported. Other reports have described excess numbers of acute myocardial infarction (AMI) in the summer in Southern USA due to hot temperatures. To determine whether circadian and seasonal variations affect the incidence of AMI in the subtropical area of Taiwan, 480 consecutive patients with AMI admitted to our coronary care units were analyzed. METHODS: Six-hourly intervals over 24 hours (4 periods), daily intervals in a week (7 days) and monthly intervals in a year (12 months) were respectively studied. The distributions of the numbers of AMI occurring in the six-hour intervals were tested for differences among the four periods using the chi-squared test for goodness of fit. RESULTS: We found that there was a circadian variation in the onset of AMI with a morning peak (6 am to noon) (35%, chi 2 = 28.52, df = 3, p < 0.01) but no secondary late evening peak. The incidence of AMI was significantly lower on Sundays (9%) than on the other weekdays (chi 2 = 16.37, df = 6, p = 0.012). However, no seasonal variation (no winter or summer peaks) occurred in the incidence of AMI in this study (chi 2 = 0.77, df = 3, p = 0.99). CONCLUSION: Our results showed that there was a predominant morning peak in the onset of AMI. The low incidence of AMI cases on Sunday compared with other weekdays suggested that relief from tension or workload on Sundays might have an important role in this low percentage of AMI. Differing from other reports, there was no seasonal variation in the occurrence of AMI in our study, suggesting that the warm climate of a subtropical region does not provide an environment that is likely to increase the frequency of AMI.
Adult↗
Congenital hepatic arterioportal fistula complicated with gastrointestinal bleeding treated with transcatheter embolization: case report.
Congenital hepatic arterioportal fistula (HAVF) is extremely rare in children. We present a patient with congenital hepaticoportal arteriovenous fistula complicated with gastrointestinal bleeding treated using transcatheter arterial embolization. Our patient was the youngest (2 days old) case ever reported with congenital HAVF and the first one to receive arterial embolization for HAVF during childhood. The 3-year-old girl was suggested of having congenital HAVF using Doppler ultrasonography. However, her family refused further investigation, and she was lost to follow-up. Three years later, she was sent to our hospital due to melaena. Repeated ultrasonography revealed dilated intrahepatic portal vein with arterial flow demonstrated using Doppler imaging. No esophageal varices or gastric or duodenal ulcer was seen during endoscopy. Angiography showed a HAVF and transcatheter embolization was done simultaneously. Follow-up at one and two weeks post-embolization revealed no more shunt flow within the portal vein, though cystic like dilatation of the portal vein persisted, and no thrombosis was observed. This case emphasizes that transcatheter arterial embolization can be easily and successfully used for treating childhood congenital HAVF. Abnormal dilatation of the portal vein in children needs doppler evaluation and possibly angiography.
Arteriovenous Fistula↗
Intussusception in a child infected with enterovirus: case report.
Most intussusceptions in childhood are idiopathic. The association of viral infection has been suspected for decades. We report a case of ileocolonic intussusception in a child during a course of enterovirus infection. A 20-month-old girl with vomiting and irritable crying of 4 days' duration was found to have intussusception by sonography. She had suffered from herpangina one week earlier. Due to her peritoneal signs, she underwent surgical manual reduction. A cluster of enlarged lymph nodes in the intussuscipiens was noted preoperatively by high resolution ultrasound. Two swollen lymph nodes were removed for pathologic evaluation and examined for a viral genome by polymerase chain reaction (PCR) amplification. Panenterovirus base pairs were confirmed on the electrophoresis print. During postoperative sonographic follow-up, significant shrinkage of previous mesenteric lymphoid hyperplasia was observed. In this article, we present the first case of childhood intussusception in associated with enterovirus infection, in which the panenterovirus genome was identified in the patient's mesenteric lymph nodes. This was also the first evaluation of the role of mesenteric lymph nodes in intussusception by high resolution sonography.
Enterovirus Infections↗
Multiplane transesophageal echocardiography for assessing cardiac abnormalities: comparison to biplane imaging.
BACKGROUND: Transesophageal echocardiography (TEE) is useful for visualizing the spatial relationships of the cardiac anatomy. The purpose of this study was to compare the diagnostic yield of multiplane TEE with that of biplane TEE in assessing cardiac abnormalities. METHODS: A total of 102 consecutive patients underwent an initial comprehensive diagnostic assessment using transverse (0 degree) and longitudinal (90 degrees +/- 2 degrees) planes in the biplane imaging technique. "Off-axis" tomographic sections through the full 0 degree to 180 degrees angle were obtained later by means of the gradual electrical rotation of the transducer. The echoscope can be manipulated to improve the quality of images. All data were recorded on high fidelity videotapes. Subsequently, one observer reviewed only biplane TEE images, while another reviewed only multiplane TEE images; both were blinded to the other's TEE data. The echocardiographic results obtained by these two observers were compared to determine whether multiplane TEE provides any additional information. RESULTS: Multiplane TEE detected more cardiac lesions (275) compared to biplane TEE (235). Significantly more (70 cases) information affecting patient management was obtained using multiplane TEE. Among these patients, biplane TEE detected cardiac lesions in 48 (68.6%) patients. Additional diagnoses provided by multiplane TEE were found in 22 (31.4%) patients. These findings included ventricular septal defect in two patients, prosthetic valve dysfunction in three, cardiac tumor or clot in four, endocarditis in two, aortic dissection in one, valvular abnormality in nine and coronary arteriovenous fistula in one. CONCLUSIONS: Multiplane TEE provides precise visualization of cardiac structures without undue probe manipulation, resulting in greater diagnostic assurance than does biplane TEE.
Adolescent↗
Identification of free deaminated sialic acid (2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) in human red blood cells and its elevated expression in fetal cord red blood cells and ovarian cancer cells.
Chemical studies have shown the occurrence of the deaminated sialic acid 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) in paired samples of blood obtained from mothers and newborns of healthy human individuals. Most of the KDN was found in red blood cells, although low levels were detected in mononuclear cells. No N-glycolylneuraminic acid was detected. Unexpectedly, nearly all of the KDN in fetal cord and matched maternal red blood cells was present as the free sugar and comparatively little occurred conjugated or as cytidine 5'-KDN phosphate. The amount of free KDN in fetal newborn red blood cells was 2.4-fold higher than in red blood cells from the mothers or from healthy nonpregnant women. Free KDN was also identified in normal human ovaries, in ovarian tumors, and in ascites cells obtained from ovarian cancer patients. Importantly, as in fetal cord red blood cells, a distinguishing feature of KDN expression in ovarian tumor cells was an elevated level of free KDN compared with normal controls. A positive correlation was found between an increase in the ratio of free KDN/N-acetylneuraminic acid in ovarian adenocarcinomas and the stage of malignancy. This was particularly evident in tumor cells isolated from the ascites fluid. The central importance of these new findings is 2-fold. First, they show that free KDN is a minor but ubiquitous sialic acid in human red blood cells and that its elevated expression in red blood cells from fetal cord blood compared with maternal red blood cells may be developmentally related to blood cell formation during embryogenesis. Second, the enhanced expression of KDN in ovarian cancer cells suggests that this sialic acid, like the alpha2,8-linked polysialic acid glycotope, may be an oncofetal antigen in these tumors and thus could be an "early warning" signal for onset of disease and/or a marker for detection of recurrence of disease. These new findings highlight the importance of elucidating the role that KDN and KDN-containing glycoconjugates may play in normal development and malignancy.
Adenocarcinoma↗
Up-regulation of CIR1/CROC1 expression upon cell immortalization and in tumor-derived human cell lines.
Acquisition of the immortal phenotype by tumor cells represents an essential and potentially rate-limiting step in tumorigenesis. To identify changes in gene expression that are associated with the early stages of cell immortalization, we compared genetically matched pairs of pre-immortal and immortal human cell clones by mRNA differential display. Two transcripts, denoted CIR1 and CIR2, were identified which were up-regulated in immortal cells. Sequence analysis revealed CIR1 to be identical to the recently cloned CROC1/UEV-1 gene, whereas CIR2 corresponds to an as yet uncharacterized 1.2 kb mRNA. A 5-6-fold elevation in CIR1/CROC1 expression and a 2-3-fold elevation in CIR2 expression were observed in SV40-transformed human embryonic kidney cells immediately following proliferative crisis, suggesting a potential role for these genes in immortalization. Expression of CIR1/CROC1 was found to be elevated also in a variety of immortal human tumor-derived cell lines, as compared to their normal tissue counterparts. These results are compatible with induction of CIR1/CROC1 being an early event in the acquisition of immortality and with a role for this gene in the immortal phenotype of tumor cells.
Base Sequence↗
The products of the yeast MMS2 and two human homologs (hMMS2 and CROC-1) define a structurally and functionally conserved Ubc-like protein family.
Eukaryotic genes encoding ubiquitin-congugating enzyme (Ubc)-like proteins have been isolated from both human and yeast cells. The CROC-1 gene was isolated by its ability to transactivate c- fos expression in cell culture through a tandem repeat enhancer sequence. The yeast MMS2 gene was cloned by its ability to complement the methyl methanesulfonate sensitivity of the mms2-1 mutant and was later shown to be involved in DNA post-replication repair. We report here the identification of a human MMS2 ( hMMS2 ) cDNA encoding a novel human Ubc-like protein. hMMS2 and CROC-1 share >90% amino acid sequence identity, but their DNA probes hybridize to distinct transcripts. hMMS2 and CROC-1 also share approximately 50% identity and 75% similarity with the entire length of yeast Mms2. Unlike CROC-1 , whose transcript appears to be elevated in all tumor cell lines examined, the hMMS2 transcript is only elevated in some tumor cell lines. Collectively, these results indicate that eukaryotic cells may contain a highly conserved family of Ubc-like proteins that play roles in diverse cellular processes, ranging from DNA repair to signal transduction and cell differentiation. The hMMS2 and CROC-1 genes are able to functionally complement the yeast mms2 defects with regard to sensitivity to DNA damaging agents and spontaneous mutagenesis. Conversely, both MMS2 and hMMS2 were able to transactivate a c- fos - CAT reporter gene in Rat-1 cells in a transient co-transfection assay. We propose that either these proteins function in a common cellular process, such as DNA repair, or they exert their diverse biological roles through a similar biochemical interaction relative to ubiquitination.
Amino Acid Sequence↗
High-performance capillary electrophoretic characterization of different types of oligo- and polysialic acid chains.
We have carried out comparative structural analysis of novel oligo- and polysialic acid chains from diverse sources. Controlled acid hydrolysates of (a) colominic acid, alpha2-->8-linked homopolymer of N-acetylneuraminic acid (Neu5Ac), (b) alpha2-->8-linked oligo/polyNeu5Gc chains present in rainbow trout egg polysialoglycoprotein, and (c) alpha2-->8-linked oligomers of deaminoneuraminic acid (KDN) residues of KDN-rich glycoprotein derived from rainbow trout vitelline envelope were analyzed by high-performance capillary electrophoresis (HPCE). The results showed that three different types of alpha2-->8-linked oligosialic acids having same degree of polymerization can be separated by HPCE. A partial hydrolysate of colominic acid with mild acid was shown by CE to form intramolecular esters during the controlled hydrolysis and the subsequent workup procedure. In contrast, lactonization of (-->5-Oglycolyl-Neu5Gcalpha2-->)n, alpha2-->5-Oglycolyl-linked homopolymer of N-glycolylneuraminic acid (Neu5Gc) present in the egg jelly coat of sea urchin, did not take place as readily as in (-->8Neu5Acalpha2-->)n.
Animals↗
Electrostatics, allostery, and activity of the yeast chorismate mutase.
The predicted active site of chorismate mutase of baker's yeast Saccharomyces cerevisiae has been studied by continuum electrostatics, molecular surface/volume calculations, and molecular modeling. Our study shows that despite being subject to an allosteric transition, the enzyme's active-site pocket neither decreased in volume nor deformed significantly in shape between the active R state and the inactive T state. We find that the polar atmosphere in the pocket is responsible for the enzyme's affinity. A single amino acid, Glu23, can adequately account for the atmospheric variation. This residue swings into the active-site pocket from the R state to the T state. In the R state, Glu23 on helix H2 doubly pairs with Arg204 and Lys208 of H11, which is packed against H2. In the T state, a slide occurs between H11 and H2 such that Glu23 can no longer interact with Lys208 and competes with Asp24 for interacting with Arg204. Consequently, Glu23 is found in the T state to couple with Arg157, an active-site residue critical to substrate binding. The tandem sliding of H11 in both monomers profoundly changes the interactions in the dimer interface. The loop between H11 and H12 demonstrates the largest conformational change. Hence, we establish a connection between the allosteric transition and the activity of the enzyme. The conformational change in the transition is suggested to propagate into the active-site pocket via a series of polar interactions that result in polarity reversal in the active-site pocket, which regulates the enzyme's activity.
Allosteric Regulation↗
Primary intracranial leiomyoma: case report.
We present a case of intracranial parenchymal leiomyoma in a 20-year-old woman with a chief complaint of numbness and a painful sensation over the right limbs for several years. CT and MRI revealed an intensely enhancing calcified mass. The patient was well, without recurrence, 2 years after surgery.
Adult↗
Churg-Strauss syndrome presenting with pulmonary capillaritis and diffuse alveolar hemorrhage.
Churg-Strauss syndrome (CSS) is a rare disorder characterized by the histopathological triad of systemic necrotizing vasculitis, extravascular granuloma, and eosinophilic infiltrate, occurring in individuals with asthma or a history of allergy. We report a case of CSS with rare presentation of diffuse pulmonary hemorrhage. A transbronchial lung biopsy showed necrotizing vasculitis, pulmonary capillaritis, and prominent eosinophilic infiltrate. At autopsy, necrotizing granuloma and diffuse alveolar hemorrhage were found in the lungs. Laboratory data showed hypereosinophilia, disseminated intravascular coagulopathy, and positive anti-proteinase 3 antineutrophil cytoplasmic antibody (ANCA). This case emphasize that CSS should be considered in the differential diagnosis of ANCA-positive vasculitis with diffuse alveolar hemorrhage.
Adult↗
Molecular shape comparisons in searches for active sites and functional similarity.
Here we examine the reliability of surface comparisons in searches for active sites in proteins. Detection of a patch of surface on one protein which is similar to an active site in another, may suggest similarities in enzymatic mechanisms, in enzyme functions and implicate a potential target for ligand/inhibitor design. Specifically, we compare the efficacy of molecular surface comparisons with comparisons of surface atoms and of C(alpha) backbone atoms. We further investigate comparisons of specific atoms, belonging to a predefined pattern of catalytic residues versus comparisons of molecular surfaces and, separately, of surface atoms. This aspect is particularly relevant, as catalytic residues may be (partially) buried. We also explore active site comparisons versus comparisons in which the entire molecular surfaces are scanned. While here we focus on the geometrical aspect of the problem, we also investigate the effect of adding residue labels in these comparisons. Our extensive studies cover the serine proteases, containing the highly conserved triad motif, and the chorismate mutases. Since such active site comparisons entail comparisons between unconnected points in 3D space, an order-independent comparison technique is necessary. The geometric hashing algorithm is ideally suited to handling such a task. It can perform both global shape matching for the whole surfaces of large protein molecules and searching for local shape similarities for small surface motifs. Our results show that molecular surface comparisons work best when the similarity is high. As the similarity deteriorates, the number of potential solutions increases rapidly, making their ranking difficult, particularly when scanning entire molecular surfaces. Utilizing atomic coordinates directly appears more adequate under such circumstances.
Binding Sites↗
Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells.
By means of differential RNA display, we have isolated a cDNA corresponding to transcripts that are down-regulated upon differentiation of the goblet cell-like HT-29-M6 human colon carcinoma cell line. These transcripts encode proteins originally identified as CROC-1 on the basis of their capacity to activate transcription of c-fos. We show that these proteins are similar in sequence, and in predicted secondary and tertiary structure, to the ubiquitin-conjugating enzymes, also known as E2. Despite the similarities, these proteins lack a critical cysteine residue essential for the catalytic activity of E2 enzymes and, in vitro, they do not conjugate or transfer ubiquitin to protein substrates. These proteins constitute a distinct subfamily within the E2 protein family and are highly conserved in phylogeny from yeasts to mammals. Therefore, we have designated them UEV (ubiquitin-conjugating E2 enzyme variant) proteins, defined as proteins similar in sequence and structure to the E2 ubiquitin-conjugating enzymes but lacking their enzymatic activity (HW/GDB-approved gene symbol, UBE2V). At least two human genes code for UEV proteins, and one of them, located on chromosome 20q13.2, is expressed as at least four isoforms, generated by alternative splicing. All human cell types analyzed expressed at least one of these isoforms. Constitutive expression of exogenous human UEV in HT-29-M6 cells inhibited their capacity to differentiate upon confluence and caused both the entry of a larger proportion of cells in the division cycle and an accumulation in G2-M. This was accompanied with a profound inhibition of the mitotic kinase, cdk1. These results suggest that UEV proteins are involved in the control of differentiation and could exert their effects by altering cell cycle distribution.
Amino Acid Sequence↗
Absence of a seasonal variation in myocardial infarction onset in a region without temperature extremes.
To evaluate whether the incidence of acute myocardial infarction (AMI) attack would have circadian, weekly and monthly variations in a subtropical area, 540 consecutive patients with AMI who were admitted to our coronary care units were analyzed. Six-hour intervals over 24 h, daily intervals in a week (7 days) and monthly intervals in a year (12 months) were studied, respectively. Results showed that there was a circadian variation in the onset of AMI with a morning (6 a.m. to noon) peak (34%, p < 0.01) but no secondary late evening (18-24 p.m.) peak. The incidence of AMI was significantly lower on Sundays (9%) than on the other weekdays (Monday through Saturday; p < 0.05). However, no monthly and seasonal variations in the incidence of AMI (no winter or summer peaks) were observed in this series. This study demonstrated a circadian variation in the onset of AMI attack with a predominant morning peak. The fewer AMI cases on Sundays compared to the other weekdays suggested that freedom from 'stress' or 'work-load' on Sundays might have an important impact on this low incidence of AMI. Unlike the large ranges in cold or hot weather found in temperate regions, the warm climate of a subtropical region does not affect the frequency of AMI.
Adult↗
Effects of age and diabetes on blood flow rate and primary outcome of newly created hemodialysis arteriovenous fistulas.
To study the feasibility of creating a radiocephalic hemodialysis fistula in elderly and diabetic patients, we prospectively studied 176 patients undergoing the first permanent vascular access creation and followed the outcome of fistula until primary failure or success was assessed. Color duplex ultrasonography was used to measure the blood flow rate. Fistula blood flow rate was significantly smaller in elderly patients, however, it was > 400 ml/min in over 78% of the elderly patients with successful fistulas. There was no difference in fistula blood flow rate between nondiabetics and diabetics. Dialysis adequacy (Kt/V) via fistula was the same between age groups and between diabetes mellitus status. Old age or diabetes per se did not significantly predispose a new fistula to primary failure, but concurrent old age and diabetes markedly increase the risk. In conclusion, a good primary outcome of newly created radiocephalic fistula and adequate dialysis via fistula were demonstrated for elderly and diabetic patients. However, the longevity of fistula in elderly and diabetic patients needs further study.
Adult↗
Spindle cell carcinoma of the lung: a clinicopathologic presentation of three cases.
Three patients with spindle cell carcinoma located in the lower respiratory tract are presented, including cases of two monophasic and one biphasic tumor. On light microscopic examination, the spindle cell components of the tumors were histologically characterized by sheets of fusiform spindle cells that closely resembled a sarcoma. Keratin expression in the spindle cell components of these tumors, as shown by anti-cytokeratin antibody staining, demonstrated their epithelial nature. It is supposed that the spindle cell component displays a spectrum of phenotypes originating from epithelial cells with varying degrees of mesenchymal transformation. It is difficult to establish a diagnosis of this rare primary pulmonary malignancy prior to surgical intervention. A review of the literature allowed for a summary of the clinicopathologic characteristics of this tumor.
Aged↗