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Biomedical subjects

S Lin

Publications and source records attributed to S Lin.

At least 469 records · Page 26Linked to original sources
PubMed1995

[Endoscopic mucosectomy for resection of early gastric cancer and precancerous lesions].

The authors collected 14 cases of early gastric cancer located in the mucosa and precancerous lesions which were resected with endoscopic mucosectomy. These lesions were as follows: 6 cases were early cancer (IIc type: 4 cases; IIa type: 2 cases); 3 cases were severe dysplasia; 5 cases were adenoma, Yamada I type. The size of all the lesions was less than 20mm. Four cases of early gastric cancer were resected completely. Two cases were resected incompletely, but radical gastrectomy was performed one month after endoscopic mucosectomy. All the three cases of severe dysplasia had complete resection. But two of them received resection twice. Five cases of adenoma were also resected completely. The criteria of complete endoscopic resection were those reported in the Japanese literature. All cases have been followed up for 4-41 months; endoscopic and histological studies showed that there were no residual and recurrent cancer cells. The complete resection rate was 85.7% (12/14). The results suggest that endoscopic mucosectomy can be applied to the patients with early gastric cancer located in the mucosa and precancerous lesions less than 20mm in size, which can be resected completely. This method is safe, entails less complications and is especially suitable for the old and weak patients.

Adenoma↗
PubMed1995

[The olfactory neurotoxicity of cisplatin and effects of two drugs].

32 guinea pigs were used as animal models for the study of cisplatin induced olfactory neurotoxicity and the effects of sodium thiosulfate (STS) and cystine on the toxicity by light and electron microscopy. The results revealed that the olfactory epithelium, olfactory nerve and the olfactory bulb were all damaged by the application of cisplatin and manifested as the lysis of the myelinated nerve fibers of olfactory epithelium, edema and degeneration of the axons, atrophy of the olfactory epithelium and the compensatory proliferation of Bowman's glands. STS and cystine did not show significant effects on the neurotoxicity of cisplatin. The data suggested that cisplatin is an important toxic drug for olfactory system.

Animals↗
PubMed1994

Spinal disorders at the cervicothoracic junction.

STUDY DESIGN: This study reviewed 36 retrospective patients who underwent surgeries for rare cervico-thoracic junctional problems. OBJECTIVES: The authors review cervico-thoracic junctional disorders and study diagnostic methods, surgical approaches, surgical outcomes, and associated complications. SUMMARY OF BACKGROUND DATA: The literature is sparse on cervico-thoracic junctional problems. This paper is the largest series to date on this subject. METHODS: Thirty-six patients who underwent surgeries for spinal problems at the cervico-thoracic region (C7-T3) were reviewed. These included 18 patients with trauma, 15 patients with tumors, 2 patients with herniated discs, and one patient with postlaminectomy instability. There were 20 males and 16 females. The age ranged from 17 to 83 years with a mean of 43.5 years. Surgically, 21 patients had only posterior procedures, that included 12 wiring, 5 Luque rodding, 1 plate-screw fixation for postlaminectomy instability, 1 transpedicular biopsy, 1 foraminotomy for herniated C7-T1 disc, and 1 costotransversectomy for T2-T3 herniated disc. Neurologically, the majority of traumatic patients presented with neurologic deficits (10 complete and 4 incomplete, and 1 root injuries), and nontraumatic disorders were associated with 10 incomplete cord syndromes and 5 root dysfunctions. RESULTS: Follow-up average was 38 months based on 33 of 36 patients. There were three postoperative deaths (two sternotomies, one anterior C7 corpectomy). Neurologically, patients with complete cord injuries remained complete, whereas patients with incomplete or root deficits improved significantly. Complications included C6-C7 subluxation after C7-T2 fusion, pseudomeningocele, vocal cord paralysis, dysphagia, and Horner's syndrome. Other complications included wound infections, urinary tract infections, decubiti, deep vein thrombosis, pneumonia, and tumor recurrence. CONCLUSIONS: In treating patients with cervico-thoracic problems, one should do careful clinical and radiologic survey to avoid missed or delayed diagnoses, and the surgeon must be thoroughly familiar with anterior and posterior landmarks and associated vital structures and remember that the cervico-thoracic junction is an area of potential instability particularly after trauma or laminectomy. Complications of surgery at the cervico-thoracic junction are frequent, and meticulous surgical techniques and postoperative care are important in the prevention of these complications.

Adult↗
PubMed1994

Vaccinia protein kinase 2: a second essential serine/threonine protein kinase encoded by vaccinia virus.

The major protein kinase activity from vaccinia virus core particles was purified to near homogeneity. The protein kinase is a 50-kDa polypeptide that is shown here to phosphorylate primarily seryl residues in alpha-casein, a casein kinase I-specific peptide substrate, and itself through autophosphorylation. The sequence of four peptides derived from the protein kinase demonstrated that it is encoded by the vaccinia virus F10L gene. Expression of the F10L gene product in bacteria as a fusion with glutathione S-transferase confirmed that the vaccinia F10L gene encodes the protein kinase. We have termed this enzyme vaccinia protein kinase 2 (VPK2) to distinguish it from the protein kinase encoded by the vaccinia B1R gene. Targeted disruption of the VPK2 gene with a positive selectable marker demonstrated that all viruses with a disrupted gene also possessed a wild-type gene, suggesting that VPK2 is essential for viability. The discovery of a second essential protein kinase encoded by vaccinia virus, in addition to a protein phosphatase, underscores the importance of protein phosphorylation in poxvirus biogenesis.

Amino Acid Sequence↗
PubMed1994

Integration and germ-line transmission of a pseudotyped retroviral vector in zebrafish.

The zebrafish is rapidly becoming a popular model system for the study of vertebrate development because it is ideal for both embryological studies and genetic analysis. To determine if a retroviral vector pseudotyped with the envelope glycoprotein of the vesicular stomatitis virus could infect zebrafish embryos, and in particular, the cells destined to become the germ line, a pseudotyped virus was injected into blastula-stage zebrafish embryos. Fifty-one embryos were allowed to develop and eight transmitted proviral DNA to their progeny. Founders were mosaic, but as expected, transgenic F1's transmitted proviral DNA in a Mendelian fashion to the F2 progeny. Transgenic F1 fish inherited a single integrated provirus, and a single founder could transmit more than one viral integration to its progeny. These results demonstrate that this pantropic pseudotyped vector, originally developed for human gene therapy, will make the use of retroviral vectors in zebrafish possible.

Animals↗
PubMed1994

Femtosecond pump-probe analysis of energy and electron transfer in photosynthetic membranes of Rhodobacter capsulatus.

Low-intensity, 295 K, femtosecond pump-probe transient absorption measurements are described that have been performed to investigate energy and electron transfer in photosynthetic membranes from a Rhodobacter capsulatus strain lacking functional light harvesting antenna complex II. Spectral and kinetic similarities between the absorption changes of isolated reaction centers and those of reaction centers in membranes upon 800-nm excitation suggest that the charge separation process in both cases is very similar. An ultrafast energy relaxation process observed near 872 nm when 800-nm excitation is used is interpreted as interexcitonic relaxation within the antenna, though other interpretations, such as vibrational relaxation, are possible. On the basis of global exponential fitting analysis of the time-dependent spectral changes using 800- and 880-nm excitation wavelengths to selectively excite the reaction center and the LHI antenna, respectively, it is found that excitation energy transfer and trapping in Rb. capsulatus is limited by the overall rate of energy transfer between the antenna and the reaction center. This conclusion is supported by the observation that excitation at 800 nm, but not 880 nm, results in absorbance changes indicative of charge separation with a lifetime (3.1 ps) very close to that reported for charge separation in isolated reaction centers (3.5 ps). Thus, most reaction centers that are directly excited undergo charge separation and not backward energy transfer to the LHI antenna complexes. Both a kinetic model analysis and a direct comparison between time-resolved spectra obtained using different excitation wavelengths resulted in an energy-detrapping efficiency of about 15 +/- 10%.

Bacterial Proteins↗
PubMed1994

Relationship between thermodynamics and mechanism during photoinduced charge separation in reaction centers from Rhodobacter sphaeroides.

Detailed fast transient absorption measurements have been performed at low temperature on reaction centers from Rhodobacter sphaeroides strain R-26 and on a double mutant, [LH(L131) + LH-(M160)], in which the P/P+ oxidation potential is roughly 140 mV (1100 cm-1) above that of wild-type reaction centers. In both samples, the decay of the excited singlet state of the initial electron donor is not well described by a single-exponential decay term. This is particularly true for reaction centers from the double mutant where at least three exponential kinetic components are required to describe the decay, with time constants ranging from a few picoseconds to hundreds of picoseconds. However, singular value decomposition analysis of the time-dependent absorption change spectra indicates the presence of only two spectrally distinct states in reaction centers from both R-26 and the double mutant. Thus, the complex decay of P* at low temperature does not appear to be due to formation of either the state P+BA- as a distinct intermediate in electron transfer or P+BB- as an equilibrated side product of electron transfer. Instead, the decay kinetics are modeled by assuming dynamic solvation of the charge-separated state, as was done for the long-lived fluorescence decay in the accompanying paper [Peloquin, J. M., Williams, J. C., Lin, X., Alden, R. G., Taguchi, A. K. W., Allen, J.P., & Woodbury, N. W. (1994) Biochemistry 33, 8089-8100]. The results of assuming a static distribution of electron-transfer rates at early times followed by dynamic solvation of the charge-separated states on longer time scales are also presented. Regardless of which model is used to describe the early time kinetics of excited-state decay, the time-dependent excited-state population on the 100-ps or longer time scale is best described in terms of thermal repopulation of P* from the charge-separated state, even at 20 K. This results in a time- and temperature-dependent driving force estimated for initial electron transfer of less than 200 cm-1 on all time scales from picoseconds to nanoseconds. Assuming a nonzero internal reorganization energy associated with charge separation, the small driving force does not appear to be consistent with the lack of temperature dependence of electron transfer and the fact that a mutant with a P/P+ oxidation potential 140 mV (1100 cm-1) higher than wild type is still able to undergo electron transfer, even at low temperature.(ABSTRACT TRUNCATED AT 400 WORDS)

Electron Transport↗
PubMed1994

Relationship of phospholipid distribution to shape change in Ca(2+)-crenated and recovered human erythrocytes.

Echinocytosis induced by elevation of intracellular Ca2+ in human erythrocytes can be reversed by removal of the cation. Using back-extraction of radiolabeled dilauroyl phospholipid analogs which had been incorporated into the cell membrane, we examined the relationship between this reversible shape transformation and phospholipid distribution. Upon Ca2+ crenation of cells, surface exposure of phosphatidylserine and phosphatidylethanolamine was observed simultaneously with inward diffusion of phosphatidylcholine. Removal of Ca2+ allowed resequestration of exposed phosphatidylserine to the membrane inner monolayer, but randomized phosphatidylethanolamine and phosphatidylcholine were not redistributed to their original states. Both shape reversion and retranslocation of phosphatidylserine were reversibly inhibited vanadate. On the other hand, the cell shape recovery was found to be independent of membrane skeleton and phosphoinositide metabolism and was supported by ATP resynthesis only under conditions where the aminophospholipid translocator is active. Other Ca(2+)-mediated biochemical changes, such as generation of diacylglycerol and fatty acids, were found to have no effect on Ca2+ crenation or its reversal, or upon transbilayer distribution of any phospholipid. These findings suggest that Ca2+ induces phospholipid redistribution, possibly by direct interaction with the lipid bilayer and, further, that metabolic recovery from Ca2+ crenation reflects selective retransport of phosphatidylserine to the membrane inner monolayer.

Adult↗
PubMed1994

(R)-methanandamide: a chiral novel anandamide possessing higher potency and metabolic stability.

Four chiral congeners of arachidonylethanolamide (anandamide) have been synthesized and evaluated for (a) their ability to bind to the cannabinoid receptor in rat forebrain membranes and (b) their pharmacological potency as measured by the compounds' ability to inhibit electrically-evoked contractions of the mouse vas deferens. The lead analog was also tested for its potency in vivo. Of the analogs tested, (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide [(R)-methanandamide] exhibited the highest affinity for the cannabinoid receptor with a Ki of 20 +/- 1.6 nM, 4-fold lower than that of anandamide (Ki = 78 +/- 2 nM). Moreover, determination of the cannabinoid binding affinity in the presence and absence of the protease inhibitor phenylmethanesulfonyl fluoride (PMSF) revealed that (R)-methanandamide possesses a remarkable stability to aminopeptidase hydrolysis. Pharmacological studies on mouse isolated vasa deferentia demonstrated that all four analogs produce concentration-related inhibition of the twitch response and the order of potency is the same as the rank order of the affinities of these agonists for cannabinoid binding sites. Furthermore, experiments with mice have demonstrated that (R)-methanandamide also possesses cannabimimetric properties in vivo, as established by the four tests of hypothermia, hypokinesia, ring immobility, and antinociception.

Aminopeptidases↗
PubMed1994

Structure-activity relationships among monoterpene inhibitors of protein isoprenylation and cell proliferation.

The monoterpene d-limonene inhibits the post-translational isoprenylation of p21ras and other small G proteins, a mechanism that may contribute to its efficacy in the chemoprevention and therapy of chemically induced rodent cancers. In the present study, the relative abilities of 26 limonene-like monoterpenes to inhibit protein isoprenylation and cell proliferation were determined. Many monoterpenes were found to be more potent than limonene as inhibitors of small G protein isoprenylation and cell proliferation. The relative potency of limonene-derived monoterpenes was found to be: monohydroxyl = ester = aldehyde > thiol > acid = diol = epoxide > triol = unsubstituted. All monoterpenes that inhibited protein isoprenylation did so in a selective manner, such that 21-26 kDa proteins were preferentially affected. Perillyl alcohol, one of the most potent terpenes, reduced 21-26 kDa protein isoprenylation to 50% of the control level at a concentration of 1 mM, but had no effect on the isoprenylation of 67, 47 or 17 kDa proteins. In particular, p21ras farnesylation was inhibited 40% by 1 mM perillyl alcohol. At the same concentration, perillyl alcohol completely inhibited the proliferation of human HT-29 colon carcinoma cells. The structure-activity relationships observed among the monoterpene isoprenylation inhibitors support a role for small G proteins in cell proliferation, and suggest that many limonene-derived monoterpenes warrant further investigation as antitumor agents.

3T3 Cells↗
PubMed1994

Time-resolved fluorescence and absorption spectroscopy of photosystem I.

Picosecond fluorescence and femtosecond transient absorption spectroscopy have been used to investigate the primary energy transfer and trapping processes in a photosystem II deletion mutant from the cyanobacterium Synechocystis sp. PCC 6803, which contains active photosystem I reaction centers with approximately 100 chlorophylls per P700. In all experiments, low levels of excitation were used which avoid annihilation processes. Following 590-nm excitation, at room temperature, spectral equilibration is observed in both fluorescence and absorption measurements and is characterized by a time constant of 4-6 ps. The shape of the spectra associated with the equilibration process indicates that long wavelength pigments (pigments with absorption maxima at longer wavelength than that of the primary electron donor, P700) are present and functional at physiological temperatures in this preparation. The overall decay of excitations in the antenna is characterized by a time constant of 24-28 ps, in both fluorescence and absorption measurements. The 24-28-ps process results in the appearance of absorption changes associated with only P700+ formation. Absorption changes associated with the reduction of the primary electron acceptor were not resolved under the experimental conditions used here.

Chlorophyll↗
PubMed1994

Observation of the reduction and reoxidation of the primary electron acceptor in photosystem I.

Femtosecond transient absorption spectroscopy has been used to investigate the primary charge separation in a photosystem II deletion mutant from the cyanobacterium Synechocystis sp. PCC 6803. These cells contain only the photosystem I reaction center and have a pigment content of approximately 100 chlorophylls per P700. Utilizing relatively high excitation intensities, the difference spectrum for the reduction of primary electron acceptor [(A0(-)-A0) difference spectrum] was obtained from experiments performed under both reducing and oxidizing conditions. Both approaches yield very similar results with the (A0(-)-A0) difference spectrum displaying a maximum bleaching at 687 nm. The shape of the difference spectrum suggests that the primary electron acceptor in photosystem I may be a chlorophyll a molecule. The observed rate of primary radical pair formation depends on the overall rate of decay of excitations in the antenna; the radical pair state forms as the antenna decays. The decay of the primary radical pair state is characterized by a 21-ps time constant. Under conditions that avoid annihilation effects, the mean lifetime for excitations in the antenna is 28 ps [Hastings, G., Kleinherenbrink, F.A.M., Lin, S., & Blankenship, R.E. (1994) Biochemistry (preceding paper in this issue)]. This indicates that the reduced acceptor decays faster than it forms. Therefore, only a low concentration of the reduced acceptor will accumulate under most conditions.

Chlorophyll↗
PubMed1994

DNA helical instability facilitates initiation at the SV40 replication origin.

Previous analysis of mutations in bacterial and yeast replication origins has identified a genetic component, termed a DNA unwinding element (DUE), whose intrinsic helical instability is essential for origin function. For the SV40 replication origin, we show here that the early palindrome (EP) and A + T-rich (AT) domains both exhibit helical instability, despite their dissimilar A + T compositions. To test the possible contribution of helical instability to SV40 origin function, the relationship between helical stability of mutant origin sequences and their known origin activity in vitro and in vivo was examined. Origin activity correlates inversely with the helical stability of mutations within the EP domain but not the AT domain or the T-antigen binding domain. The quantitative correlation holds for four different measures of origin activity determined in vitro and in vivo. An even better-correlated collection of mutations was found in a specific portion of the EP domain. This specific EP subdomain coincides with the sequence known to be strand-separated after T-antigen binds the origin in vitro and with the origin of bidirectional replication in vivo. Our analysis of origin mutations indicates that the helical instability of the specific EP subdomain is required to facilitate T-antigen-induced melting and the initiation of DNA replication. The sensitivity of the required EP subdomain to mutations that stabilize the DNA helix defines the DUE of the SV40 replication origin.

Adenine↗
PubMed1994

lacZ expression in germline transgenic zebrafish can be detected in living embryos.

Use of transgenic technology in zebrafish has been limited by the inability to efficiently express transgenes in early embryos of F1 and subsequent generations and to rapidly detect transgenic fish. We generated transgenic fish by injecting fertilized eggs with the Escherichia coli lacZ gene under the control of the Xenopus elongation factor 1 alpha transcriptional regulatory element. Four of five lines of transgenic fish we obtained express the lacZ gene in early embryos. The pattern of expression was distinct for each line, with two lines showing extensive expression beginning at approximately the midblastula transition, one showing patchy expression and one showing expression almost exclusively in motor neurons. Expression patterns were stable through the F2 generation in the three lines studied to date. The availability of these lines facilitated the development of a reliable and rapid method for live-staining lacZ-expressing embryos using the substrate fluorescein-di-beta-D-galactopyranoside (FDG). Positive embryos of the two most highly lacZ-expressing lines could be identified after 2-3 min of staining in FDG and then picked out and raised. These observations should prove useful for a variety of studies in zebrafish.

Animals↗