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Biomedical subjects

S S Lin

Publications and source records attributed to S S Lin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Ellagic [correction of ellagica] acid inhibits arylamine N-acetyltransferase activity and DNA adduct formation in human bladder tumor cell lines (T24 and TSGH 8301).

The fact that vitamin C (ascorbic acid) exhibits a protective effect in certain types of cancer is well documented. Our previous studies demonstrated that human bladder tumor cell line (T24) has N-acetyltransferase (NAT) activity in cytosols and intact cells. The present studies examined the inhibition of arylamine NAT activity and carcinogen (2-aminofluorene)-DNA adduct formation by ellagic acid (EA) in human bladder tumor cell lines (T24 and TSGH 8301). Two assay systems were performed, one with cellular cytosols (9,000 g supernatant), the other with intact bladder tumor cell suspensions. NAT activity and 2-aminofluorene-DNA adduct formation in T24 and TSGH 8301 cells was inhibited by EA in a dose-dependent manner in both systems, i.e.. the greater the concentration of EA in the reaction the greater the inhibition of NAT activity (dose- and time-course dependent effects). The data also indicated that EA decreased the apparent Km and Vmax of NAT enzymes from T24 and TSGH 8301 cells in cytosols. NAT activity and 2-aminofluorene-DNA adducts in T24 is higher than in TSGH 8301. This report is the first to demonstrate that EA affects human bladder tumor cell NAT activity.

2-Acetylaminofluorene↗
PubMed2000

The role of anti-Galalpha1-3Gal antibodies in acute vascular rejection and accommodation of xenografts.

BACKGROUND: A major impediment to the transplanting of porcine organs into humans is the susceptibility of porcine organs to acute vascular rejection, which can destroy a vascularized xenograft over a period of hours to days. Acute vascular rejection of porcine-to-primate xenografts is thought to be triggered by binding of xenoreactive antibodies to the graft. We tested whether antibodies, binding to Galalpha1-3Gal epitopes in porcine tissue, initiate this phenomenon. METHODS AND RESULTS: Specific depletion of anti-Galalpha1-3Gal antibodies from the blood of baboons, using extracorporeal perfusion of separated plasma through columns of Sepharose beads covalently linked to the antigenic trisaccharide, Galalpha1-3Galbeta1-4GlcAc, averted the development of acute vascular rejection in porcine organs transgenic for human decay-accelerating factor and CD59. More importantly, after immunodepletion was stopped and Gala1-3Gal antibodies were allowed to return, these same organs continued to function and remained pathologically normal and thus seemed to achieve a state of accommodation. CONCLUSION: These results demonstrate that anti-Galalpha1-3Gal antibodies cause acute vascular rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.

Acute Disease↗
PubMed2000

Prediction of thrombus-related mechanical prosthetic valve dysfunction using transesophageal echocardiography.

Identification of thrombus-related mechanical prosthetic valve dysfunction (MPVD) has important therapeutic implications. We sought to develop an algorithm, combining clinical and echocardiographic parameters, for prediction of thrombus-related MPVD in a series of 53 patients (24 men, age 52 +/- 16 years) who had intraoperative diagnosis of thrombus or pannus from 1992 to 1997. Clinical and echocardiographic parameters were analyzed to identify predictors of thrombus and pannus. Prevalence of thrombus and diagnostic yields relative to the number of predictors were determined. There were 22 patients with thrombus, 19 patients with pannus, and 12 patients with both. Forty-two of 53 masses were visualized using transesophageal echocardiography (TEE), including 29 of 34 thrombi or both thrombi and panni and 13 of 19 isolated panni. Predictors of thrombus or mixed presentation include mobile mass (p = 0.009), attachment to occluder (p = 0.02), elevated gradients (p = 0.04), and an international normalized ratio of < or = 2.5 (p = 0.03). All 34 patients with thrombus or mixed presentation had > or = 1 predictor. The prevalence of thrombus in the presence of < or = 1, 2, and > or = 3 predictors is 14%, 69%, and 91%, respectively. Thus, TEE is sensitive in the identification of abnormal mass in the setting of MPVD. An algorithm based on clinical and transesophageal echocardiographic predictors may be useful to estimate the likelihood of thrombus in the setting of MPVD. In the presence of > or = 3 predictors, the probability of thrombus is high.

Aged↗
PubMed2000

Sip2p and its partner snf1p kinase affect aging in S. cerevisiae.

For a number of organisms, the ability to withstand periods of nutrient deprivation correlates directly with lifespan. However, the underlying molecular mechanisms are poorly understood. We show that deletion of the N-myristoylprotein, Sip2p, reduces resistance to nutrient deprivation and shortens lifespan in Saccharomyces cerevisiae. This reduced lifespan is due to accelerated aging, as defined by loss of silencing from telomeres and mating loci, nucleolar fragmentation, and accumulation of extrachromosomal rDNA. Genetic studies indicate that sip2Delta produces its effect on aging by increasing the activity of Snf1p, a serine/threonine kinase involved in regulating global cellular responses to glucose starvation. Biochemical analyses reveal that as yeast age, hexokinase activity increases as does cellular ATP and NAD(+) content. The change in glucose metabolism represents a new correlate of aging in yeast and occurs to a greater degree, and at earlier generational ages in sip2Delta cells. Sip2p and Snf1p provide new molecular links between the regulation of cellular energy utilization and aging.

Carbon↗
PubMed2000

Specific interaction between the hepatitis delta virus RNA and glyceraldehyde 3-phosphate dehydrogenase: an enhancement on ribozyme catalysis.

Replication of hepatitis delta virus (HDV) RNA occurs in the nuclei of infected cells. The replication is mediated by cellular factors containing an RNA polymerase II-like enzyme activity through a double rolling-circle mechanism and is regulated by delta antigens. In this study, UV cross-linking experiments were carried out to examine interactions between HDV RNA and proteins present in HeLa nuclear extract. Cellular proteins with molecular mass of 23 (p23), 36 (p36), 38 (p38), and 58 (p58) kDa bound to full-length HDV RNA of both genomic and antigenomic strands. Deletion analysis on the antigenomic strand mapped the interacting domain within a 79-nucleotide fragment but not at the ends of the rod-shaped viral RNA structure. The specificity of the RNA-protein interactions was demonstrated by competition experiments and the specific HDV RNA-binding proteins were purified through column chromatography. Electrophoresis mobility shift assay with the purified fractions demonstrated that the interaction between p36 and HDV RNA was relatively stable even in the presence of 0.5 M NaCl. Biochemical analysis including protein microsequencing identified the p36 as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). RNase footprinting indicated that the UC-rich domain between nucleotides 379 and 414 of the HDV antigenomic RNA was involved in the GAPDH binding. Functional studies further demonstrated an enhancing effect of GAPDH on the ribozyme activity of HDV antigenomic RNA. In addition, in the presence of HDV RNA cellular GAPDH relocalized from the cytoplasm to the nucleus where HDV replication occurs. These results suggest that GAPDH is involved in the replication of HDV.

Amino Acid Sequence↗
PubMed2000

Alternative therapies used by women with breast cancer in four ethnic populations.

BACKGROUND: Interest in alternative therapies is growing rapidly in the United States. We studied the types and prevalence of conventional and alternative therapies used by women in four ethnic groups (Latino, white, black, and Chinese) diagnosed with breast cancer from 1990 through 1992 in San Francisco, CA, and explored factors influencing the choices of their therapies. METHODS: Subjects (n = 379) completed a 30-minute telephone interview in their preferred language. Logistic regression models assessed factors associated with the use of alternative therapies after a diagnosis of breast cancer. RESULTS: About one half of the women used at least one type of alternative therapy, and about one third used two types; most therapies were used for a duration of less than 6 months. Both the alternative therapies used and factors influencing the choice of therapy varied by ethnicity. Blacks most often used spiritual healing (36%), Chinese most often used herbal remedies (22%), and Latino women most often used dietary therapies (30%) and spiritual healing (26%). Among whites, 35% used dietary methods and 21% used physical methods, such as massage and acupuncture. In general, women who had a higher educational level or income, were of younger age, had private insurance, and exercised or attended support groups were more likely to use alternative therapies. About half of the women using alternative therapies reported discussing this use with their physicians. More than 90% of the subjects found the therapies helpful and would recommend them to their friends. CONCLUSIONS: Given the high prevalence of alternative therapies used in San Francisco by the four ethnic groups and the relatively poor communication between patients and doctors, physicians who treat patients with breast cancer should initiate dialogues on this topic to better understand patients' choices with regard to treatment options.

Adult↗
PubMed2000

Bioelectronic detection of point mutations using discrimination of the H63D polymorphism of the Hfe gene as a model.

BACKGROUND: A bioelectronic detection platform has recently been developed that facilitates the detection and characterization of nucleic acids. The DNA chip platform is compatible with homogeneous assays because separate labeling and wash steps are not required. A one-step, bioelectronic detection assay was developed to genotype patient samples with respect to the H63D polymorphism of the Hfe gene, associated with hereditary hemochromatosis. METHODS AND RESULTS: Electrode arrays were modified with DNA capture probes that were perfectly matched to the wild-type or mutant allele of H63D. Amplicons containing the polymorphic site were hybridized with the capture probes on the electrode arrays in the presence of electronically labeled reporter (signaling) probes. Voltammetric analysis of the electrode arrays was conducted first at ambient temperature and then at elevated temperature. The electronic signal was preferentially diminished at elevated temperature from electrodes that hybridized with mismatched target amplicons. CONCLUSION: An assay for bioelectronic genotyping of the H63D polymorphism was developed and used with six patient specimens to show the feasibility of this system as a model for point mutation detection.

Amino Acid Substitution↗
PubMed2000

Effects of ellagic acid by oral administration on N-acetylation and metabolism of 2-aminofluorene in rat brain tissues.

Numerous studies have demonstrated that the Acetyl Coenzyme A-dependent arylamine NAT enzyme exist in many tissues of experimental animals including humans, and that NAT has been shown to be exist in mouse brain tissue. Increased NAT activity levels are associated with increased sensitivity to the mutagenic effects of arylamine carcinogens. Attenuation of liver NAT activity is related to breast and bladder cancer processes. Therefore, the effects of ellagic acid (EA) on the in vitro and in vivo N-acetylation of 2-aminofluorene (AF) were investigated in cerebrum, cerebellum and pineal gland tissues from male Sprague-Dawley rats. For in vitro examination, cytosols with or without EA (0.5-500 microM) co-treatment decreased 7-72%, 15-63% and 10-78% of AF acetylation for cerebrum, cerebellum and pineal gland tissues, respectively. For in vivo examination, EA and AF at the same time treated groups with all 3 examined tissues did show significant differences (the changes of total amounts of AF and AF metabolites based on the Anova analysis) when compared to the ones without EA cotreatment rats. The pretreatment of male rats with EA (10 mg/kg) 24 hr prior to the administration of AF (50 mg/kg) (one day of EA administration suffice to induce large changes in phase II enzyme activity) resulted in a 76% decrease in total AF and metabolites in pineal gland but did not show significant differences in cerebrum and cerebellum tissues. This is the first demonstration to show that EA decreases the N-acetylation of carcinogens in rat brain tissues.

Acetylation↗
PubMed2000

Transesophageal echocardiography assessment of severe ostial left main coronary stenosis.

Doppler echocardiography is commonly used in the assessment of stenotic valvular orifices. We describe the application of transesophageal echocardiography for the detection of a critical ostial left main coronary stenosis. Because preoperative coronary angiography often is not routinely performed in young patients undergoing valve surgery, application of Doppler echocardiography can potentially prevent catastrophic complications, particularly in atypical cases.

Adult↗
PubMed2000

The role of antibodies in dysfunction of pig-to-baboon pulmonary transplants.

OBJECTIVE: Pulmonary transplantation has become the preferred treatment for end-stage lung disease, but application of the procedure is limited because of a paucity of donors. One way to solve donor limitations is to use animal organs as a donor source or xenotransplantation. The current barrier to pulmonary xenotransplantation is the rapid failure of the pulmonary xenograft. Although antibodies are known to play a role in heart and kidney xenograft rejection, their involvement in lung dysfunction is less defined. This project was designed to define the role of antibodies in pulmonary graft rejection in a pig-to-baboon model. METHODS: Orthotopic transgenic swine left lung transplants were performed in baboons depleted of antibodies by one of three techniques before transplantation: (1) ex vivo swine kidney perfusion, (2) total immunoglobulin-depleting column perfusion, and (3) ex vivo swine lung perfusion. Results were compared with those of transgenic swine lung transplants in unmodified baboons. RESULTS: All three techniques of antibody removal resulted in depletion of xenoreactive antibodies. Only pretransplantation lung perfusion improved pulmonary xenograft function compared with lung transplantation in unmodified baboons. CONCLUSIONS: The pathogenesis of pulmonary injury in a swine-to-primate transplant model is different from that in renal and cardiac xenografts. Depletion of antibodies alone does not have a beneficial effect and may actually be detrimental.

Animals↗
PubMed2000

Biodegradable alginate antibiotic beads.

The authors investigated the poly-L-lysine-coated alginate beads as an antibiotic delivery system for the treatment of various surgical infections. The sodium alginate was mixed with vancomycin, coated with poly-L-lysine, and lyophilized to form five types of the biodegradable antibiotic beads. Type I, 2.5% alginate, nonpoly-L-lysine coated and nonlyophilized; Type II, 2.5% alginate, poly-L-lysine coated but nonlyophilized; Type III, 2.5% alginate, poly-L-lysine coated and lyophilized; Type IV, 5% alginate, poly-L-lysine coated and lyophilized; and Type V, 7.5% alginate, poly-L-lysine coated and lyophilized. Cytotoxicity of the alginate beads to fibroblasts and HeLa cells was evaluated by the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] colorimetric assay. A study of in vitro elution of vancomycin of the alginate antibiotic beads was performed. The results suggested that the alginate antibiotic beads present no obvious toxic risk to their use as a drug delivery system. The concentration of vancomycin in these five types of beads was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for 9,11,12, 14, and 17 days respectively. The release was most marked during the first 3 days. The duration of antibiotic release was prolonged by using techniques of poly-L-lysine coating, lyophilization, and by increasing the content of alginate. This study offers a biodegradable delivery system of antibiotics to treat various surgical infections.

Alginates↗
PubMed2000

Acute traumatic compartment syndrome of the foot in children.

Acute traumatic compartment syndrome of the foot is a sequelae of serious injury to the foot, which, if unrecognized, may result in significant motor and sensory deficits, pain, stiffness, and deformity. It is nearly always associated with fractures, dislocations, and crush injuries to the foot. Vascular injuries and coagulopathic states are also risk factors for the development of an acute foot compartment syndrome. In children, the presentation of an acute foot compartment syndrome may be masked by the pain and edema caused by associated fractures and dislocations. A high index of suspicion is warranted in children presenting with foot injuries that are associated with foot compartment syndrome. Recognition of the signs and symptoms of compartment syndrome in the emergency room are paramount; the diagnosis is best confirmed by multiple compartment pressure readings. The urgency of diagnosis of a compartment syndrome must be underscored, as the complications of a missed foot compartment syndrome includes contractures, claw toe deformity, sensory loss, stiffness, and chronic pain. Prompt orthopaedic consultation is mandatory; urgent compartment fasciotomies are associated with a good clinical outcome.

Acute Disease↗
PubMed2000

Pyomyositis of the leg with early neurologic compromise.

Pyomyositis, although uncommon, is being reported with greater frequency in temperate climates. The presentation is similar to a number of infectious processes, and when associated with a traumatic event, the clinical picture may be confused with that of a musculoskeletal injury. This, coupled with an unfamiliarity of the disease, may result in a delay in diagnosis. Early antibiotic therapy may obviate surgery. Progression to the suppurative stage requires surgical drainage along with antibiotics. CT guided drainage may be accomplished in certain cases. In immunocompromised patients, progression to the septicemic stage is associated with high morbidity and mortality.

Ankle Injuries↗
PubMed2000

The anticonvulsant SGB-017 (ADCI) blocks voltage-gated sodium channels in rat and human neurons: comparison with carbamazepine.

PURPOSE: SGB-017 (ADCI) is a novel anticonvulsant that blocks both voltage-activated sodium channels and N-methyl-D-aspartate (NMDA)-receptor-gated channels. Results by Rogawski et al. suggested that SGB-017 produces its anticonvulsant action primarily by inhibition of NMDA-receptor channels. However, SGB-017 is effective in several animal models of epilepsy that are unresponsive to NMDA antagonists. These results indicate that block of NMDA-receptor channels is not the only mechanism contributing to its anticonvulsant activity. Thus the effects of SGB-017 on neuronal sodium channels were investigated. METHODS: Whole cell voltage-clamp techniques were used to record sodium currents in freshly dissociated rat superior cervical ganglion (SCG) and hippocampal neurons and cultured human NT2 neurons. The effects of SGB-017 on the amplitude of sodium currents, elicited by a depolarizing pulse to 0 mV from different holding potentials, were measured and compared with those of carbamazepine (CBZ). RESULTS: SGB-017 inhibited sodium currents in rat SCG and hippocampal neurons with a similar potency to CBZ. Like CBZ, the inhibition of sodium channels by SGB-017 was voltage dependent. Its median inhibitory concentration (IC50) for inhibition of sodium channels at depolarized holding potentials is similar to that for its inhibition of NMDA receptor channels. In human hNT2 neurons, SGB-017 was more potent than CBZ at inhibiting sodium currents. CONCLUSIONS: SGB-017 produces its anticonvulsant activity by blocking both sodium- and NMDA-receptor channels in a voltage- and use-dependent manner. The combination of these two mechanisms of action makes SGB-017 an effective AED in several different animal models of epilepsy.

Animals↗
PubMed2000

Dietary fat and breast cancer.

One of the most often studied associations in epidemiology is dietary fat and breast cancer risk. That migrants from low-risk countries increase their risk on immigrating to higher-risk countries suggests that some modifiable lifestyle or environmental factor is responsible for the development of breast cancer. Although early international correlational studies and experimental animals studies support dietary fat as a risk factor for breast cancer, more recent data from case-control studies and cohort studies have been equivocal, thus the analytical data do not support a strong positive association. The conflicting results from analytic studies may be due to methodologic issues associated with study design, dietary assessment tools, measurement error, improper statistical analyses, and a lack of heterogeneity in fat intake among the study population. Moreover, current dietary questionnaires may be inadequate in capturing true dietary intakes or capturing the risk with exposure during earlier periods of a woman's life. Although two large clinical trials investigating the fat/breast cancer relationships issue are underway, researchers are generally skeptical at their ability to detect an independent association between fat and breast cancer risk. Further epidemiologic studies using current methodology may not prove to be fruitful in generating definitive answers to shed light on this controversial issue. In addition, rather than concentrating on dietary fat, researchers should focus on diets that are not only low in saturated fat, but also high in fruit and vegetable consumption. Researchers should take advantage of advances in molecular and genetic technology for a different perspective in examining the issue. For example, markers of susceptibility to breast cancer that can detect women at higher risk for breast cancer may be helpful in clarifying the role of dietary fat. More comprehensive and multiple approaches to studying dietary factors and breast cancer are recommended.

Age Factors↗
PubMed2000

Total contact casting and Keller arthoplasty for diabetic great toe ulceration under the interphalangeal joint.

Interphalangeal (IP) ulcerations of the great toe are frequently encountered in neuropathic diabetic feet. While total contact casting is usually effective as a first line treatment, recalcitrant ulcers continue to present substantial management challenges. The authors retrospectively reviewed the results of Keller arthroplasty employed to accelerate ulcer resolution with total contact casting in fourteen patients with neuropathic ulcers under the great toe interphalangeal (IP) joint that were resistant to casting alone. These data were compared to a group of similar patients whose ulcers were successfully treated by non-operative measures. No operative complications were observed, and all ulcers healed within twenty-four days with no recurrence documented at an average follow-up of 26 weeks. In cases of resistant great toe IP plantar ulcers associated with hallux rigidus that have failed casting trials, this treatment method can be effective.

Adult↗
PubMed2000

Limited intertarsal arthrodesis using bone grafting and pin fixation.

Iliac crest bone grafting and K wire fixation was used to fuse the arthritic intertarsal articulations of sixteen patients with post-traumatic or primary degenerative disease. Using pre- and post-operative AOFAS scores, foot function indices (FFI), and a subjective scoring system, functional and subjective outcome was critically evaluated. The AOFAS score improved an average of 41 points, the FFI decreased from 64 to 24, and 81 percent of patients rated their results as good or excellent. Fusion of the 4th and 5th TMT joints was associated with significantly poorer functional scores, and people with worker's compensation claims had poorer subjective scores. The authors demonstrated comparable results to previously published series using other methods of fixation.

Activities of Daily Living↗