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S Lin

Publications and source records attributed to S Lin.

At least 109 records · Page 6Linked to original sources
PubMed2001

Genetic crossover interference in the human genome.

Positive crossover interference refers to the phenomenon that the occurrence of a crossover reduces the probability of another crossover in its vicinity. There have been studies reporting the presence of positive interference in humans. Some studies have also found evidence suggesting within and between chromosomal interference heterogeneity on some of the chromosomes. However, there has been no systematic study of interference and interference heterogeneity in the whole human genome, using pedigree data without first inferring crossovers. In this paper, we studied the Chi-square interference model and other models extensively to compare the relative performance of each of these models for accounting for interference and measuring strength of interference. Our results showed that the Chi-square model consistently fitted the data well and provided easily interpretable estimates of interference strength. The Chi-square model was then used to study interference and interference heterogeneity within and between chromosomes. We found strong evidence of positive interference in the whole human genome. Our results also indicated that the level of interference was fairly constant in most parts of the genome, but there was some evidence suggesting that the levels of interference for two of the chromosomes were different from the rest. We also found evidence of within chromosomal interference heterogeneity for several of the chromosomes.

Chromosomes↗
PubMed2001

Identification of up-regulated Ras-like GTPase, Rap1b, by suppression subtractive hybridization.

BACKGROUND: Diabetic nephropathy accounts for over 30% of the end-stage renal disease (ESRD). A number of defined mechanisms and molecules that are involved in its pathogenesis are known, while others remain to be identified. METHODS: Suppression subtraction hybridization (SSH)-polymerase chain reaction (PCR) was employed to search for new genes that may be relevant to the pathogenesis of diabetic nephropathy during embryonic development, the time when the kidney is most susceptible to various forms of stress. A diabetic state was induced in pregnant mice at day-13 of gestation by administration of streptozotocin. The kidneys of newborn mice with blood glucose level> 200 mg/dL were harvested, mRNA isolated and subjected to SSH-PCR. Several differentially expressed cDNA fragments with up-regulated expression were isolated. One of the cDNA fragments had homology with human Ras-like guanine 5'-triphosphate (GTPase), Rap1b gene. By utilizing the lambdaZAP II mouse cDNA library and SMART RACE amplification, a full-length Rap1b cDNA was isolated. A recombinant protein was generated in pET15b bacterial expression system. An anti-Rap1b antibody was raised in rabbits by immunizing them with the fusion protein, and its specificity was confirmed by Western blot analysis. RESULTS: Rap1b cDNA had an open reading frame of 552 bp with a predicted putative protein size of approximately 21 kD. In vitro translation verified the authentication of the Rap1b cDNA clone. Northern blot analyses revealed a single approximately 2.3 kb Rap1b mRNA transcript. Its expression was up-regulated in several tissues, including the kidney of newborn diabetic mice. The degree of up-regulation of Rap1b mRNA expression was proportional to the blood glucose levels. Western blot analyses confirmed the hyperglycemia-induced up-regulation of the Rap1b expression. In situ hybridization and immunofluorescence studies revealed that Rap1b was expressed in the inner medullary collecting tubules. During hyperglycemia, its expression was accentuated and extended into the outer medullary and cortical collecting tubules. Similar up-regulation of Rap1b was observed when embryonic kidneys, harvested at day-13 of gestation, were exposed to high glucose ambience. CONCLUSION: The data suggest that Rap1b, a GTP-binding protein that plays a critical role in various signaling intracellular events, is another molecule that may be relevant to the pathobiology of diabetic nephropathy.

Amino Acid Sequence↗
PubMed2001

Use of high-frequency ultrasound imaging to improve delineation of anterior uveal melanoma for proton irradiation.

The aim of this study was to evaluate high-frequency ultrasound imaging (HFUI) as an aid in localizing anterior margins of tumours of the eye for proton therapy. Proton irradiation of ocular melanoma requires an accurate assessment of all tumour margins. The tumour is marked surgically by suturing to the sclera four or five tantalum rings on the borders of the tumour defined by transillumination. In order to evaluate the clinical usefulness of high-frequency ultrasound imaging, four and five rings were surgically placed in a patient with an iris/ciliary body melanoma and in a patient with ciliochoroidal melanoma using transillumination to localize the tumour margins. Subsequently margins were verified by HFUI. In the first patient, the distances between the rings and the limbus were measured using calipers during surgery and were compared with HFUI measurements and measurements from planning software. The distances were comparable within 0.5 mm. In the second patient the treatment was planned in two different ways using EYEPLAN software. In the first scenario the shape of the tumour and its relation to the rings were obtained from the surgeon's mapping, the fundus drawing using a transilluminating point light source, and the HFUI. In the second scenario, the shape of the tumour was deduced from the ring positions only. It was observed that the maximum difference between the tumour edge as seen on high-frequency ultrasound images and the rings was 2.6 mm. The tumour volume was underestimated by 39% when tumour shape was obtained from ring positions only. During the past year we have utilized HFUI in 18 patients having tumours involving the anterior segment of the eye, among which four were treated with proton therapy. In conclusion, we believe that high-frequency ultrasound imaging provides additional information with respect to the location of tumour margins in ciliary body and anterior uveal melanoma. Occult extension of the tumour within the ciliary body or posterior iris may not be appreciated by transillumination alone.

Adult↗
PubMed2001

Roles of acyl-coenzyme A:cholesterol acyltransferase-1 and -2.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzyme that produces cholesteryl esters in various tissues. In mammals, two ACAT genes (ACAT1 and ACAT2) have been identified. Together, these two enzymes are involved in storing cholesteryl esters as lipid droplets, in macrophage foam-cell formation, in absorbing dietary cholesterol, and in supplying cholesteryl esters as part of the core lipid for lipoprotein synthesis and assembly. The key difference in tissue distribution of ACAT1 and ACAT2 between humans, mice and monkeys is that, in adult human liver (including hepatocytes and bile duct cells), the major enzyme is ACAT1, rather than ACAT2. There is compelling evidence implicating a role for ACAT1 in macrophage foam-cell formation, and for ACAT2 in intestinal cholesterol absorption. However, further studies at the biochemical and cell biological levels are needed in order to clarify the functional roles of ACAT1 and ACAT2 in the VLDL or chylomicron synthesis/assembly process.

Animals↗
PubMed2001

Epidemiology of thoracolumbar spine injury in blunt trauma.

OBJECTIVE: To evaluate the prevalence, distribution, and demographics of thoracolumbar (TL) spine injuries following blunt trauma. METHODS: Prospective, cross-sectional study of a consecutive sample of all blunt trauma patients presenting initially to the emergency department (ED) of a Level 1 trauma center and undergoing thoracic and/or lumbar spine radiography from August 1997 to November 1998. The age, sex, and mechanism of injury of each patient as well as location and type of spine injury were recorded for those patients with vertebral fractures, dislocations, or subluxations. RESULTS: Two thousand four hundred four blunt trauma patients were enrolled. Vertebral injuries were identified in 152 individuals (6.3%, 95% CI = 5.4% to 7.4%). Two hundred sixty distinct anatomic levels of injury were identified in these 152 individuals. Of these 260 injuries, 42 (16.2%) occurred at L1, 38 (14.6%) at L2, 29 (11.1%) at L3, and 27 (10.4%) at T12, making these the most commonly injured vertebrae. Injuries were most common (34 patients) in those aged 30-39 years and were least common (12 patients) in those under 18 years. Compression fractures (52%) were the most common injury in the thoracic spine, while transverse process fractures (48%) were the most common injuries in the lumbar spine. CONCLUSIONS: The prevalence of TL injuries in ED blunt trauma patients undergoing TL radiographs is 6.3%. The most commonly injured area of the TL spine is the thoracolumbar junction.

Adolescent↗
PubMed2001

Intensity modulated proton therapy: a clinical example.

In this paper, we report on the clinical application of fully automated three-dimensional intensity modulated proton therapy, as applied to a 34-year-old patient presenting with a thoracic chordoma. Due to the anatomically challenging position of the lesion, a three-field technique was adopted in which fields incident through the lungs and heart, as well as beams directed directly at the spinal cord, could be avoided. A homogeneous target dose and sparing of the spinal cord was achieved through field patching and computer optimization of the 3D fluence of each field. Sensitivity of the resultant plan to delivery and calculational errors was determined through both the assessment of the potential effects of range and patient setup errors, and by the application of Monte Carlo dose calculation methods. Ionization chamber profile measurements and 2D dosimetry using a scintillator/CCD camera arrangement were performed to verify the calculated fields in water. Modeling of a 10% overshoot of proton range showed that the maximum dose to the spinal cord remained unchanged, but setup error analysis showed that dose homogeneity in the target volume could be sensitive to offsets in the AP direction. No significant difference between the MC and analytic dose calculations was found and the measured dosimetry for all fields was accurate to 3% for all measured points. Over the course of the treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated that organ motion in the region of the target volume was negligible. We conclude that 3D IMPT plans can be applied clinically and safely without modification to our existing delivery system. However, analysis of the calculated intensity matrices should be performed to assess the practicality, or otherwise, of the plan.

Adult↗
PubMed2001

Influence of permeating ions on Kv1.5 channel block by nifedipine.

Nifedipine can block K(+) currents through Kv1.5 channels in an open-channel manner (32). Replacement of internal and external K(+) with equimolar Rb(+) or Cs(+) reduced the potency of nifedipine block of Kv1.5 from an IC(50) of 7.3 microM (K(+)) to 16.0 microM (Rb(+)) and 26.9 microM (Cs(+)). The voltage dependence of block was unaffected, and a single binding site block model was used to describe block for all three ions. By varying ion species at the intra- and extracellular mouth of the channel and by using a nonconducting W472F-Kv1.5 mutant, we demonstrated that block was conditioned by the ion permeating the pore and, to a lesser extent, by the extracellular ion species alone. In Kv1.5, the outer pore mutations R487V and R487Y reduced nifedipine potency close to that of Kv4.2 and other Kv channels with an equivalent valine. Although changing this residue can affect C-type inactivation of Kv channels, the normalized reduction and time course of currents blocked by nifedipine in 5, 135, and 300 mM extracellular K(+) concentration was the same. Similarly, a mean recovery time constant from nifedipine block of 316 ms was unchanged (332 ms) after 5-s prepulses to allow C-type inactivation. This is consistent with the conclusion that nifedipine block and C-type inactivation in the Kv1.5 channel can coexist but are mediated by distinct mechanisms coordinated by outer pore conformation.

Calcium Channel Blockers↗
PubMed2001

Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac disease.

BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) correlate with increased airway inflammation and measurement of exhaled NO is a noninvasive method for the management of bronchial asthma. In various cardiac diseases, bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there have been few studies on the relationship between exhaled NO and bronchial responsiveness in cardiac diseases. OBJECTIVE: The aim of this study was to clarify the association between exhaled NO and bronchial hyperresponsiveness in patients with cardiac disease. METHODS: We measured expired NO and bronchial responsiveness to inhaled methacholine in 19 patients with cardiac diseases and 17 with bronchial asthma. We divided the cardiac disease patients into two groups according to their bronchial responsiveness to inhaled methacholine: BHR(+) group consisted of 12 patients with bronchial hyperresponsiveness and BHR(-) group consisted of 7 patients without bronchial hyperresponsiveness. RESULTS: The concentration of exhaled NO in the asthmatic patients was significantly higher than that in the BHR(+) and BHR(-) groups (142.0 +/- 17.0, 33.6 +/- 6.4 and 42.3 +/- 10.3 ppb, respectively, p < 0.01). There was no significant difference in exhaled NO between BHR(+) and BHR(-) groups. There were also no significant differences in the parameters of bronchial hyperresponsiveness between the cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial hyperresponsiveness in patients with cardiac diseases is not a consequence of eosinophilic inflammation or of exhaled NO. CONCLUSION: We conclude that bronchial hyperresponsiveness in patients with cardiac diseases can occur independently of NO production.

Adult↗
PubMed2001

Sample size requirement for detecting interference under the chi-square model.

The chi-square model (CHS) of recombination has been studied extensively, in recent years, for its ability of capturing the process and estimating the level of crossover interference. Exploration thus far shows that this model yields much better fits to human genetic data than Haldane's no-interference model, and the explicit level of interference can be easily estimated as well. This paper provides calculations of sample sizes required to detect interference under CHS for a variety of settings. Two data types, fully informative meioses and phase-unknown backcross families, are studied. Under each setting, we calculate the number of meioses/families needed to ensure that the expected log-likelihood difference between the chi(2) interference model and Haldane's no-interference model exceeds a prespecified threshold. It is found that joint consideration of multiple (more than three) markers dramatically reduces the number of meioses/families needed when compared to an analysis based on three-point data, a traditional setting for detecting interference using three-point tests. The results indicate that the numbers of meioses needed to detect interference under CHS are well within the reach of most genetic mapping studies.

Chi-Square Distribution↗
PubMed2001

Antitumor effect of VNP20009, an attenuated Salmonella, in murine tumor models.

VNP20009, a genetically modified strain of Salmonella typhimurium with deletions in the msbB and purI loci, exhibited antitumor activities when given systemically to tumor-bearing mice. VNP20009 inhibited the growth of subcutaneously implanted B16F10 murine melanoma, and the human tumor xenografts Lox, DLD-1, A549, WiDr, HTB177, and MDA-MB-231. A single intravenous injection of VNP20009, at doses ranging from 1 x 10(4) to 3 x 10(6) cfu/mouse, produced tumor growth inhibitions of 57-95%. Tumor volume doubling time, another indicator for tumor growth inhibition, also significantly increased in mice treated with VNP20009. Using mice with immune system deficiencies, we also demonstrated that the antitumor effects of VNP20009 did not depend on the presence of T and B cells. In addition, VNP20009, given intravenously, inhibited the growth of lung metastases in mice. Only live bacteria showed the antitumor effect.

Animals↗
PubMed2001

Cytokeratin 20 as an immunocytochemical marker for detection of urothelial carcinoma in atypical cytology: preliminary retrospective study on archived urine slides.

Previous studies have shown that expression of cytokeratin 20 (CK20), a constituent of intermediate filaments, is increased in malignant versus benign urine samples. To evaluate whether immunocytochemical staining of CK20 on archived urine slides could be used as a potential adjunct marker for triage of atypical urine cytology, we analyzed a total of 77 archived urine slides obtained from a spectrum of patients with various risks of developing urothelial carcinoma. These patients were divided into four groups on the basis of initial urine cytologic results and subsequent follow-up biopsy findings; group 1 had negative results in both evaluations, whereas the results in group 4 were positive for both cytology and biopsy. Groups 2 and 3 had a diagnosis of atypical urine cytology; however, patients in group 3 had a positive follow-up biopsy, and patients in group 2 did not. The Papanicolaou-stained archived urine slides were destained and then restained immunocytochemically with monoclonal antibody against CK20. With 5% positively stained nonumbrella cells as a threshold, CK20 was positive in 94.4% of group 3 or 4 patients. In contrast, CK20 was positive in 27.3% of group 2 patients and in 10.5% of group 1 patients. The overall sensitivity and specificity for CK20 for the detection of urothelial carcinoma in this population of patients were 94.4% and 80.5%, respectively. This study demonstrated that immunocytochemical analysis of CK20 on archived urine slides could be used to triage atypical urine cytology into low- and high-risk categories and that CK20 might be a simple and useful early detection marker for urothelial carcinoma.

Adult↗
PubMed2001

[Study of susceptibility loci located within Xp11 in attention deficit hyperactivity disorder].

OBJECTIVE: To detect the genetic relationship between monoamine oxidase(MAO) A type gene and attention deficit hyperactivity disorder(ADHD) in Chinese. METHODS: The haplotype-based haplotype relative risk(HHRR) and the transmission disequilibrium test(TDT) methods were used to analyze the genetic association and linkage in 60 ADHD children and their parents. RESULTS: In this sample were found significant association (chi(2)=4.90, P<0.05) and linkage (chi(2)=4.84, P<0.05) between the MAOCA 114bp allele and DSM-III-R-diagnosed ADHD in trios composed of father, mother and affected offspring. CONCLUSION: The above results suggested that ADHD was associated and in linkage with MAO A gene, and the susceptibility loci might reside in chromosome Xp11 for ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

GL331 induces down-regulation of cyclin D1 expression via enhanced proteolysis and repressed transcription.

GL331 is a novel podophyllotoxin-derived compound. In this study, GL331 induced human lung adenocarcinoma cell line CL1-5 growth arrest before death during the initial 24-h incubation period. We found that GL331 had no inhibitory effect on the expression of cyclins E, A, B1, CDK 4, and CDK 2; instead, its cell growth-inhibitory effect was partly attributable to an early down-regulation of cyclin D1 expression and in turn the reduction of retinoblastoma protein phosphorylation. GL331 enhanced the proteolysis of cyclin D1, and a proteasome inhibitor was able to block GL331-caused cyclin D1 reduction, suggesting that GL331-stimulated cyclin D1 degradation was through proteasomal processes. Additionally, GL331 reduced cellular cyclin D1 mRNA level down to 45% of control in 4 h and further to around 20% in 12 h. However, GL331 did not accelerate the disappearance of cyclin D1 mRNA under the condition of transcription blockage induced by actinomycin D. It was reported that a certain region in the 3'-untranslated region (UTR) of cyclin D1 mRNA mediated the mRNA degradation upon extracellular stresses. Herein, transient transfection studies demonstrated that the 3'-UTR insertion did not confer the susceptibility of luciferase reporter gene to the GL331 treatment. Together, these data suggested that GL331 did not decrease the stability of cyclin D1 mRNA. On the other hand, we found that GL331 specifically inhibited the cyclin D1 promoter-driven luciferase reporter activity. Western blot analyses showed that GL331 decreased the level of phosphorylated extracellular signal-regulated kinase (Erk), with no effect on p38 or c-Jun NH(2)-terminal kinase. Furthermore, GL331's inhibition of cyclin D1 promoter was attenuated by ectopic Erk-2 overexpression. These data suggested that GL331 inhibited cyclin D1 gene transcription via the Erk signaling pathway. In summary, we report that GL331 induced an early decline of cyclin D1 expression by dual mechanisms: 1) enhancement of protein turnover and 2) repression of Erk-mediated gene transcription.

Antineoplastic Agents, Phytogenic↗
PubMed2001

[Mortality study of major non-communicable diseases in Shanghai, from 1951 to 1998].

OBJECTIVE: To study the transition of major non-communicable diseases (NCDs) in Shanghai. METHODS: Demographic and mortality data since early 1950s in Shanghai was used. Linear regression model was employed to evaluate the mortality trends of diseases. RESULTS: During the past five decades, age-adjusted mortality had been gradually decreasing, with leading cause of deaths shifting from infectious diseases to NCDs. In 1998, the average life expectancy reached 77.03, and the three leading causes of deaths, i.e. tumor, cardio-vascular diseases and respiratory diseases, accounted for 75% of all deaths. The crude mortality of major NCDs increased consistently. However, the age-adjusted mortality trends of major NCDs decreased during the past two decades after a 30-year's increase. Turnover took place in the late 1970s for tumors, for coronary heart in late 1980s diseases and in the early 1990s for strokes. For malignant tumors, the age-adjusted mortality of breast cancer, cancer of colon and rectum did not significantly decrease in the past two decades. CONCLUSION: The increase of crude mortality of major NCDs was mainly due to the trend of aging in Shanghai. It is suggested that the risk factors of major NCDs had decreased to some extent but the behavior and dietary related risk factors remained serious.

China↗
PubMed2001

Catalysis of ACAT may be completed within the plane of the membrane: a working hypothesis.

Two ACAT sharing protein sequence homology near their C termini have been identified. Both proteins may span the endoplasmic reticulum (ER) membrane several times. There is good evidence implicating the role of ACAT1 in macrophage foam cell formation, and ACAT2 in intestinal cholesterol absorption. On the other hand, the functional roles of ACAT1 and ACAT2 in the VLDL or chylomicron assembly process are less clear. It is possible that both enzymes are able to form lipid droplets (which are present in the cytoplasm), and participate in lipoprotein assembly (which occurs in the ER lumen). To link the site of ACAT catalysis with its function, we propose that part of the ACAT catalytic site may reside within the lipid bilayer, allowing catalysis to be completed within the plane of the membrane. Cholesteryl esters (CE) produced in situ may burst into cytoplasmic lipid droplets, carrying phospholipid monolayers as their outer coats. In cells engaged in lipoprotein assembly and secretion, CE in the bilayer may be recognized by the specific protein microsomal triacylglycerol transfer protein (MTP), reaching out from the lumenal side of the membrane. MTP then lipidates the growing apolipoprotein B (apoB) chain with CE and TG during the early stages of apoB lipoprotein assembly.

Acetyl Coenzyme A↗
PubMed2001

[Clinicopathologic features and prognosis of lymphoepithelioma-like carcinoma of the lung].

OBJECTIVE: To analyze the clinicopathologic features and prognosis of lymphoepithelioma-like carcinoma (LELC) of the lung. METHODS: 26 cases of pulmonary LELC with available long-term follow-up information were compared with 84 cases of pulmonary non-LELC(33 cases of squamous cell carcinoma, 36 cases of adenocarcinoma, 6 cases of adeno-squamous carcinoma and 9 cases of large cell carcinoma) with available long-term follow-up information using Kaplan-Meier method and the generalized Wilcoxon test. RESULTS: LELC of the lung had a better prognosis than non-LELC (P < 0.05). Further study showed that pulmonary LELC had a significantly better prognosis than adeno-squamous carcinoma and large cell carcinoma. However, there was no significant prognostic differences between pulmonary LELC and squamous cell carcinoma and adenocarcinoma. Tumor recurrence and necrosis (> or = 5% of tumor) were associated with poor prognosis. CONCLUSION: Pulmonary LELC, which is a very rare and unique entity, has a better prognosis after therapy.

Adult↗
PubMed2001

[Observation of preventing of bone loss during early postmenopause by percutaneous estradiol in Chinese postmenopausal women].

OBJECTIVE: To investigate the optimal regimen for application of percutaneous estradiol gel in preventing bone loss in Chinese postmenopausal women. METHODS: A 3-year open randomized clinical study was designed. The percutaneous estradiol gel was used in a cyclic regimen combined with micronized progesterone (MP) or medroxyprogesterone acetate (MPA). Sixty healthy women (naturally menopause for 1 to 5 years) were recruited and divided into four groups according to estrogen dosage and two kinds of progestin. All were given for 25 d/month. The cortical bone mineral density (BMD) of right radius was measured by single photon absorptiometry. The trabecular BMD in lumbar vertebrae was measured by quantitative CT. The spine and hip BMD were also measured by dual energy X-ray absorptiometry at baseline, 6, 12, 18, 24 and 36 months, respectively. The bone metabolic markers, scores of menopausal symptoms were also evaluated. RESULTS: Fifty-nine patients (98%) completed 1 year and 56 patients (93%) 2 years, 51 (85%) 3 years of study. The symptoms were alleviated by 80% after 6 months treatment on average. By the end of 24 month, the mean increases of BMD ranged from 4.3% to 7.5% in trabecular bone, and by the end of 36 month 4.2% to 6.2% in the lumbar (L) 2-4, 1.6% to 3.8% in the femur neck, with significant differences (P < 0.05). Comparing the 4 groups with each other, no significant differences (P > 0.05) were found in improvement of symptoms, bone markers and BMD. CONCLUSIONS: Both daily estrogen containing 0.75 mg and 1.5 mg E2 are effective to prevent the early postmenopausal bone loss and improve the menopausal symptoms. During 3 years treatment, the BMD of lumbar increased continuously and the BMD of hip increased in the first 2 years and then plateau.

Administration, Cutaneous↗