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Biomedical subjects

S S Lin

Publications and source records attributed to S S Lin.

At least 19 recordsLinked to original sources
PubMed1999

Bone healing of tibial lengthening is delayed by cigarette smoking: study of bone mineral density and torsional strength on rabbits.

OBJECTIVE: We investigated the effect of intermittent cigarette smoke inhalation on the bone healing of tibial lengthening in rabbits. METHODS: Twelve male rabbits were divided into two groups of six animals each. The first group underwent intermittent cigarette smoke inhalation, and the second group did not undergo intermittent cigarette smoke inhalation. Each animal's right tibia was lengthened 5 mm by using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all of the animals 1 day before operation and 3, 4, 5, and 6 weeks after operation. All of the animals were killed 6 weeks postoperatively for biomechanical testing. RESULTS: By using the preoperative BMD as an internal control, we found that the BMD of the smoke-inhalation group was decreased significantly compared with the non-smoke-inhalation group. The mean %BMD at 3, 4, 5, and 6 weeks were 49.9%, 61.2%, 65.9%, and 71.0%, respectively, in the smoke-inhalation group, whereas the mean %BMD were 54.9%, 71.8%, 76.4%, and 82.0%, respectively, in the non-smoke-inhalation group (two-tailed t test, p > 0.05, p < 0.01, p < 0.01 and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). By using the contralateral nonoperated tibia as internal control, we found that torsional strength of the smoke-inhalation group was decreased significantly compared with the non-smoke-inhalation group. The mean percentage of maximal torque was 63.8% in the smoke-inhalation group, whereas the mean percentage of maximal torque was 77.1% in the non-smoke-inhalation group (two tailed t test, p < 0.01). CONCLUSION: This study suggests that cigarette smoking delays the mineralization during the bone healing process of distraction osteogenesis and, thus, decreases the mechanical strength of the regenerating bone.

Absorptiometry, Photon↗
PubMed1998

The future promises of xenotransplantation.

The use of animals as a source of organs and tissues for humans has been an enduring goal of transplantation. Xenotransplantation, as such, would overcome a shortage of human donors and allow for biochemical or genetic approaches to modification of transplants. The use of animal organs and tissue, however, is hindered by an intense immune response of the recipient against the graft. The molecular basis for this immune response has recently been elucidated, at least in part, and specific approaches to therapy, including the genetic engineering of source animals, have been developed. Other hurdles, including the physiologic limitations of the transplant and the possibility of transferring infectious agents from the transplant into the host, may also be important. The development of specific therapies and the application of genetic engineering to overcome these problems can now be envisioned. As the immunologic, physiologic, and infectious hurdles to xenotransplantation are addressed, new efforts will focus on the use of the transplant to impart novel functions to answer the therapeutic needs of the transplant recipient.

Animals↗
PubMed1998

Risk stratification of patients with medically treated unstable angina using exercise echocardiography.

Functional testing is recommended for risk stratification of medically treated patients with unstable angina. Exercise echocardiography is used in this situation, but its safety and prognostic value are not well defined. The objective of this study was to assess the incremental prognostic value of exercise echocardiography in 226 consecutive patients (128 men, age 59+/-13 years) with medically treated unstable angina, who underwent exercise echocardiography from 1991 to 1996. Clinical risk was designated as low in 108 patients, intermediate in 116, and high in 2 patients according to the unstable angina practice guidelines. There were no major complications from the stress tests. The exercise electrocardiogram was nondiagnostic in 57 patients (25%). Ischemia was identified by exercise electrocardiography in 33 patients and exercise echocardiography in 55 patients. Patients were followed for 29+/-18 months. After exclusion of 38 patients who underwent early revascularization, 28 patients had cardiac death, nonfatal infarction, and late (>3 months) revascularization. Ischemia at exercise echocardiography was associated with a 24-month event-free survival of 81%, compared to 95% with negative exercise echocardiography (p=0.02). A positive exercise electrocardiogram was associated with a 24-month event-free survival of 84%, compared to 93% with negative exercise electrocardiograms (p=0.08). In a Cox regression model, event-free survival was predicted by ischemia at exercise echocardiography (relative risk 2.8, confidence interval: 1.3 to 6.3, p=0.05), but not at exercise electrocardiography (relative risk 2.1, confidence interval 0.7 to 5.8, p=0.16).

Aged↗
PubMed1998

Enhancement of serum-response factor-dependent transcription and DNA binding by the architectural transcription factor HMG-I(Y).

The mechanisms by which HMG-I proteins regulate cell growth are unknown, and their effects on gene expression have only been partially elucidated. We explored the potential interaction between HMG-I proteins and serum-response factor (SRF), a member of the MADS-box family of transcription factors. In cotransfection experiments, HMG-I(Y) potentiated SRF-dependent activation (by more than 5-fold) of two distinct SRF-responsive promoters, c-fos and the smooth muscle-specific gene SM22alpha. This effect was also observed with a heterologous promoter containing multiple copies of the CC(A/T)6GG (CArG) box. HMG-I proteins bound specifically to the CArG boxes of c-fos and SM22alpha in gel mobility shift analysis and enhanced binding of SRF to these CArG boxes. By chelating peptide-immobilized metal affinity chromatography, we mapped the domain of HMG-I(Y) that interacts with SRF to amino acids 50-81, a region that does not bind specifically to DNA in electrophoretic mobility shift assays even though it includes the third AT-hook DNA-binding domain. Surprisingly, HMG-I(Y) mutants that failed to bind DNA still enhanced SRF binding to DNA and SRF-dependent transcription. In contrast, deletion of the HMG-I(Y) 50-81 domain that bound SRF prevented enhancement of transcription. To our knowledge, this is the first report of an HMG-I protein interacting with a MADS-box transcription factor. Our observations suggest that members of the HMG-I family play an important role in SRF-dependent transcription and that their effect is mediated primarily by a protein-protein interaction.

Animals↗
PubMed1998

The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.

Long-term success in xenotransplantation is currently hampered by acute vascular rejection. The inciting cause of acute vascular rejection is not yet known; however, a variety of observations suggest that the humoral immune response of the recipient against the donor may be involved in the pathogenesis of this process. Using a pig-to-baboon heterotopic cardiac transplant model, we examined the role of antibodies in the development of acute vascular rejection. After transplantation into baboons, hearts from transgenic pigs expressing human decay-accelerating factor and CD59 underwent acute vascular rejection leading to graft failure within 5 d; the histology was characterized by endothelial injury and fibrin thrombi. Hearts from the transgenic pigs transplanted into baboons whose circulating antibodies were depleted using antiimmunoglobulin columns (Therasorb, Unterschleisshein, Germany) did not undergo acute vascular rejection in five of six cases. Biopsies from the xenotransplants in Ig-depleted baboons revealed little or no IgM or IgG, and no histologic evidence of acute vascular rejection in the five cases. Complement activity in the baboons was within the normal range during the period of xenograft survival. In one case, acute vascular rejection of a xenotransplant occurred in a baboon in which the level of antidonor antibody rose after Ig depletion was discontinued. This study provides evidence that antibodies play a significant role in the pathogenesis of acute vascular rejection, and suggests that acute vascular rejection might be prevented or treated by therapies aimed at the humoral immune response to porcine antigens.

Acute Disease↗
PubMed1998

Dobutamine stress Doppler hemodynamics in patients with aortic stenosis: feasibility, safety, and surgical correlations.

OBJECTIVES: This study was designed to describe the experience of our center with the safety and feasibility of dobutamine stress echocardiography (DSE) in aortic stenosis (AS), to characterize the hemodynamic response to dobutamine infusion, and to examine the hemodynamic response in relation to the anatomic evaluation of the valve among patients who underwent valve replacement. BACKGROUND: The diagnosis of the hemodynamic severity of AS can be difficult when the cardiac output is reduced and the gradient is low, but the effective valve area calculates to be small. DSE has been proposed as a means of assessing the severity of AS in this setting. METHODS: We reviewed 27 patients (18 men, 9 women; mean age 71 +/- 12 years) with AS who underwent DSE between 1991 and 1996. RESULTS: Fifteen (55%) patients were New York Heart Association class III or IV, 8 (30%) had angina Canadian class III or IV, and 3 (11%) syncope. Dobutamine peak dose was 27 +/- 11 micrograms/kg/min. Sixteen (59%) patients had mild side effects. DSE resulted in a significant increase in the cardiac output from 4.1 +/- 1.2 L/min at rest to 7.3 +/- 1.9 L/min at peak dose, and in heart rate (76 +/- 16 beats/min to 124 +/- 20 beats/min), systolic blood pressure (128 +/- 26 mm Hg to 137 +/- 26 mm Hg), ejection fraction (38% +/- 20% to 42% +/- 20%), and transvalvular mean gradient (28 +/- 10 mm Hg to 39 +/- 9 mm Hg) (P <.05). There was also a significant increase in the valve area from 0.77 +/- 0.14 cm2 at rest to 0.97 +/- 0.21 cm2 (P <.001). Seven patients underwent surgery; all valves were severely calcified, confirming anatomic disease. In this group, an increase in the mean gradient but also a trend toward an increase in the valve area were noted in response to dobutamine: 33 +/- 10 mm Hg to 47 +/- 6 mm Hg and 0.79 +/- 0.11 cm2 to 0.95 +/- 0.19 cm2, respectively. CONCLUSION: Although more data are needed to fully establish the safety of the test in this indication, this study suggests that patients with AS can safely undergo DSE. Dobutamine results in an increase not only in the mean gradient, but also in the valve area. An increase in valve area with dobutamine was observed in some patients with anatomically confirmed severe AS and thus does not exclude fixed valve disease.

Aged↗
PubMed1998

Soft and hard tissue changes in Class III patients treated by bimaxillary surgery.

A cephalometric study of 17 non-growing dentate Class III subjects treated by bimaxillary surgery was undertaken to assess the results of treatment and to evaluate the correlation between soft and hard tissue change. It was concluded that: (i) the orthognathic profiles achieved were brought about by a combination of maxillary advancement and mandibular setback; (ii) a strong correlation in the horizontal direction occurred between all the selected landmarks of the lower lip and chin, but only between superior labial sulcus and point A in the upper lip; highest intra-group correlations were seen between corresponding soft and hard tissue points; the ratios of soft tissue to corresponding hard tissue movements in lower lip and chin approached 1:1; (iii) in the vertical direction, a strong correlation occurred in the lower lip and chin; highest intra-group correlations were not necessarily with corresponding landmarks; and (iv) vertical movement of landmarks on the nasal base and upper lip generally showed poor or weak correlation with corresponding soft tissue points. The most reliable hard tissue predictors of horizontal and vertical soft tissue change are tabulated for application in bimaxillary surgery for the Class III patient.

Adult↗
PubMed1998

Differential recognition by proteins of alpha-galactosyl residues on endothelial cell surfaces.

The binding of proteins to cell surface carbohydrates contributes to cell-cell interactions in development, immunity, and various physiologic processes. Such interactions are presumably dictated not only by the chemical structure of the carbohydrate but also reflect the properties of the protein and the microenvironment in which the protein-carbohydrate interaction occurs. To explore the factors influencing the recognition of cell surface carbohydrates by proteins, the extent to which three classes of proteins--anti-Gal alpha 1-3Gal IgM found in higher primates, Griffonia simplicifolia type I lectin, isolectin B4 (GS-IB4), and alpha-galactosidase--interact with Gal alpha 1-3Gal on porcine cell surfaces was tested. Although the Gal alpha 1-3Gal residues expressed on porcine endothelial cells and recognized by anti-Gal alpha 1-3Gal IgM and GS-IB4 were both sensitive to cleavage by alpha-galactosidase, the sites recognized by GS-IB4 were more sensitive to cleavage than sites recognized by anti-Gal alpha 1-3Gal IgM. Cross-blocking studies on porcine cell surfaces revealed that a significant proportion of anti-Gal alpha 1-3Gal IgM bound to sites not recognized by GS-IB4; however, anti-Gal alpha 1-3Gal IgM and GS-IB4 recognized the same sites on solubilized membrane proteins and model compounds. These results suggest that features of the cell surface such as the three-dimensional arrangement of Gal alpha 1-3Gal and characteristics of the protein such as size and valency play critical roles in specific interactions on cell surfaces.

Animals↗
PubMed1998

Bone healing of tibial lengthening is enhanced by hyperbaric oxygen therapy: a study of bone mineral density and torsional strength on rabbits.

We investigated the effect of intermittent hyperbaric oxygen (HBO) therapy on the bone healing of tibial lengthening in rabbits. Twelve male rabbits were divided into two groups of six animals each. The first group went through 2.5 atmospheres absolute of hyperbaric oxygenation for 2 hours daily, and the second group did not go through hyperbaric oxygenation. Each animal's right tibia was lengthened 5 mm using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all of the animals at 1 day before operation and at 3, 4, 5, and 6 weeks after operation. All of the animals were killed at 6 weeks postoperatively for biomechanical testing. Using the preoperative BMD as an internal control, we found that the BMD of the HBO group was increased significantly compared with the non HBO group. The mean %BMD at 3, 4, 5, and 6 weeks were 69.5%, 80.1%, 87.8%, and 96.9%, respectively, in HBO group, whereas the mean %BMD were 51.6%, 67.7%, 70.5%, and 79.2%, respectively, in non-HBO group (two tailed t test, p < 0.01, p < 0.01, p < 0.01, and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). Using the contralateral nonoperated tibia as an internal control, we found that torsional strength of lengthened tibia of the HBO group was increased significantly compared with the non-HBO group. The mean percent of maximal torque was 88.6% in HBO group at 6 weeks, whereas the mean percent of maximal torque was 76.0% in non-HBO group (two-tailed t test, p < 0.01). The results of this study suggest that the bone healing of tibial lengthening is enhanced by intermittent hyperbaric oxygen therapy.

Absorptiometry, Photon↗
PubMed1997

Solid phase synthesis and restriction endonuclease cleavage of oligodeoxynucleotides containing 5-(hydroxymethyl)-cytosine.

Emerging data suggest an important role for cytosine methylation in tumorigenesis. Simultaneously, recent studies indicate a significant contribution of endogenous oxidative DNA damage to the development of human disease. Oxidation of the 5-methyl group of 5-methylcytosine (5mC) residues in DNA results in the formation of 5-(hydroxymethyl)cytosine (hmC). The biological consequences ofhmC residues in vertebrate DNA are as yet unknown; however, conversion of the hydrophobic methyl group to the hydrophilic hydroxymethyl group may substantially alter the interaction of sequence-specific binding proteins with DNA. Central to both biophysical and biochemical studies on the potential consequences of specific DNA damage products such as hmC are efficient methods for the synthesis of oligodeoxynucleotides containing such modified bases at selected positions. In this paper, we describe a method for the placement of hmC residues in oligodeoxynucleotides using established phosphoramidite chemistry. In addition, we have examined the influence of specific hmC residues on enzymatic cleavage of oligodeoxynucleotides by the methylation-sensitive restriction endonucleases MspI and HpaII.

5-Methylcytosine↗
PubMed1997

Humoral responses to pig-to-baboon cardiac transplantation: implications for the pathogenesis and treatment of acute vascular rejection and for accommodation.

Organs transplanted between phylogenetically-disparate species, such as from the pig into the primate, are subject to hyperacute and acute vascular rejection. Hyperacute rejection of a porcine organ by a primate is thought to be initiated by the binding of xenoreactive natural antibodies to Galalpha1-3Gal expressed on the endothelial lining of blood vessels in the xenograft. The factor(s) which initiates acute vascular rejection is uncertain; however, there is some evidence implicating xenoreactive antibodies. The nature of the humoral response which might contribute to acute vascular rejection of a porcine organ was investigated in baboons which received a porcine cardiac xenograft plus immunosuppression with methylprednisolone, azathioprine, and cyclosporine. Following rejection and surgical removal of the xenografts, the serum concentration of xenoreactive antibodies increased in untreated animals but in immunosuppressed animals was similar to the concentration in preimmune serum. The antibodies in the sensitized recipients were specific for Galalpha1-3Gal (70-95%) and other determinants (5-30%). However, cross-blocking studies showed that, following xenotransplantation, the immunosuppressed baboons had no detectable IgM or IgG directed against "new" endothelial antigens. These results indicate that antibodies made by immunosuppressed individuals in response to xenotransplantation are much like xenoreactive natural antibodies and suggest that acute vascular rejection might in some cases be addressed by therapeutic strategies aimed at those antibodies.

Animals↗
PubMed1997

The role of natural anti-Gal alpha 1-3Gal antibodies in hyperacute rejection of pig-to-baboon cardiac xenotransplants.

Xenoreactive natural antibodies in humans and higher primates are directed predominantly at Gal alpha 1-3Gal. These antibodies are thought to initiate hyperacute rejection of porcine organ xenografts. The contribution of anti-Gal alpha 1-3Gal antibodies to the xenoractive natural antibody repertoire and to the initiation of hyperacute rejection was tested in a pig-to-baboon cardiac xenograft model. Anti-Gal alpha 1-3Gal antibodies were depleted from baboons by extracorporeal absorption of anti-Gal alpha 1-3Gal antibodies from plasma using columns with a matrix bearing Gal alpha 1-3Galb1-4GlcNAc. Specific removal of anti-Gal alpha 1-3Gal antibodies was achieved prior to transplantation as demonstrated by immunoassay. Porcine hearts were then transplanted into these baboons and the outcome of the transplants was analysed. Immunofluorescence revealed little deposition of baboon antibodies in the grafts. The porcine hearts did not undergo hyperacute rejection even though complement activity was approximately 90% of baseline at the time of transplantation. These findings demonstrate that anti-Gal alpha 1-3Gal antibodies constitute a major fraction of xenoreactive natural antibodies in primate blood and that these antibodies contribute significantly to the pathogenesis of hyperacute xenograft rejection.

Acute Disease↗
PubMed1997

Effect of intermittent cigarette smoke inhalation on tibial lengthening: experimental study on rabbits.

We investigated the effect of intermittent cigarette smoke inhalation on the bone healing of tibial lengthening in rabbits. Thirty-eight male rabbits were divided into two groups of 19 animals each. The first group went through intermittent cigarette smoke inhalation, and the second group did not go through intermittent cigarette smoke inhalation. Each animal's right tibia was lengthened 5 mm using an uniplanar lengthening device. Five animals of each group were killed at 4, 6, and 8 weeks postoperatively for biomechanical testing, and one animal of each group was killed at 2, 4, 6, and 8 weeks postoperatively for histologic study. Using the contralateral nonoperated tibia as an internal control, we found that torsional strength of the lengthened tibia of the smoke inhalation group was decreased significantly compared with the non-smoke inhalation group. The mean percent of maximal torque at 4, 6, and 8 weeks were 22.0, 66.3, and 78.6%, respectively, in the smoke inhalation group, whereas the mean percent of maximal torque were 48.0, 84.1, and 90.8% %, respectively, in non-smoke inhalation group (one-tailed t test, p < 0.01, p < 0.01, and p < 0.05 at 4, 6, and 8 weeks, respectively). Our histologic observations revealed that the granulation tissue resorption, bone formation, and remodeling were delayed in smoke inhalation group. The results of this study suggest that intermittent inhalation of cigarette smoke delays, but does not prevent, the bone healing in tibial lengthening.

Animals↗
PubMed1997

Sterol regulation of acetyl coenzyme A carboxylase promoter requires two interdependent binding sites for sterol regulatory element binding proteins.

The sterol regulatory element binding proteins (SREBPs) are central regulators of lipid homeostasis in mammalian cells. Their activity is controlled by a sterol-regulated two-step proteolytic process that releases the nuclear targeted amino-terminal domain from the membrane anchored carboxyl-terminal remnant. This ensures that transcriptional stimulation of the appropriate genes occurs only when increased intracellular sterol accumulation is required. Gene targets for SREBP encode key proteins of cholesterol metabolism as well as essential proteins of fatty acid biosynthesis, providing a mechanism for coordinate control of these two major lipid pathways when sterols and fatty acids need to accumulate together. However, the regulatory mechanism must provide a way to uncouple these two pathways to allow separate regulation when sterol or fat levels need to increase independently of each other. We compared the similarities and differences for how SREBP activates the promoter for the low density lipoprotein (LDL) receptor, which is the key protein involved in cholesterol uptake, relative to how it activates promoters for acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS), which are both key enzymes of fatty acid biosynthesis. In the current studies we show there are two distinct sites for SREBP binding that control activation of the ACC PII promoter whereas previous work has shown there is only a single SREBP site in the LDL receptor. Additionally, disruption of either ACC site results in a total loss in promoter function and a severe decrease in SREBP binding even to the neighboring unaltered site. Thus, the two sites are equally important and dependent on one another for optimal function. This is in contrast to the FAS promoter where SREBP binds to two adjacent sites independently and the one located closer to the binding site for the Sp1 co-regulator is more critical for sterol regulation and activation by SREBP over-expression.

Acetyl-CoA Carboxylase↗
PubMed1997

Comparison of intravenous retention of fentanyl and lidocaine on local analgesia in propofol injection pain.

BACKGROUND: With a tourniquet on arm for arresting venous blood flow, we evaluated the efficacy of intravenous (i.v.) retention of fentanyl and lidocaine in reducing the pain on i.v. propofol injection during general anesthesia. METHODS: One hundred and twelve patients were studied. Following a venous occlusion by a tourniquet inflated to 70 mmHg, patients in Group A (n = 38) received normal saline (NS) 3 ml, while those in Group B (n = 37) and in Group C (n = 37) respectively received fentanyl 150 micrograms or 3 ml and 2% lidocaine 3 ml (60 mg). The venous retention of drug was maintained for 1 min, followed immediately by tourniquet release and propofol 100 mg i.v. injection over 20 s. RESULTS: Both fentanyl and lidocaine treatments (Groups B and C) were significantly better than placebo (Group A) in reducing pain on propofol injection (p < 0.005). Lidocaine 60 mg was more effective than fentanyl 150 micrograms in reduction of pain associated with i.v. propofol (p < 0.001). Injection of fentanyl itself caused pain in 28% of patients as compared to 2% in the lidocaine group. Mild local skin erythema was noted in 14% of patients with fentanyl venous retention versus 0% of patients with lidocaine venous retention. CONCLUSIONS: Intravenous retention of fentanyl 150 micrograms, although less effective than that of lidocaine (p < 0.001), showed local analgesic effect in reducing the pain on propofol injection. The hypothetic mechanisms of action were speculated.

Adolescent↗