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Biomedical subjects

S Lin

Publications and source records attributed to S Lin.

At least 487 records · Page 27Linked to original sources

Redox effects on the bacteriochlorophyll a-containing Fenna-Matthews-Olson protein from Chlorobium tepidum.

The BChl a-containing Fenna-Matthews-Olson (FMO) protein from the green sulfur bacterium Chlorobium tepidum was purified and characterized. Fluorescence spectra indicate that efficient excited state quenching occurs at neutral or oxidizing redox potentials. The major fluorescence lifetime at room temperature is approximately 60 ps in samples that are in neutral or oxidizing conditions, and approximately 2 ns in samples where the strong reductant sodium dithionite has been added. A similar change is observed in pump-probe picosecond absorbance difference experiments, where the long life time component increases after dithionite addition. A 16 Gauss wide EPR signal with g factor = 2.005 is observed in samples without dithionite. This signal largely disappears upon addition of dithionite. Dithionite induces large reversible changes in the 77 K absorbance spectra of the purified FMO protein and in whole cells. These results indicate that the FMO protein contains redox active groups, which may be involved in the regulation of energy transfer. Room temperature circular dichroism and low temperature absorption spectra show that dithionite also induces conformational or structural changes of the FMO protein complex.

Bacterial Proteins↗

Spectral heterogeneity and time-resolved spectroscopy of excitation energy transfer in membranes of Heliobacillus mobilis at low temperatures.

Transient absorption difference spectra in the Qy absorption band from membranes of Heliobacillus mobilis were recorded at 140 and 20 K upon 200 fs laser pulse excitation at 590 nm. Excitation transfer from short wavelength absorbing forms of bacteriochlorophyll g to long wavelength bacteriochlorophyll g occurred within 1-2 ps at both long wavelength bacteriochlorophyll g occurred within 1-2 ps at both temperatures. In addition, a slower energy transfer process with a time constant of 15 ps was observed at 20 K within the pool of long wavelength-absorbing bacteriochlorophyll g. Energy transfer from long wavelength antenna pigments to the primary electron donor P798 was observed, yielding the primary charge-separated state P798+A0-. The time constant for this process was 30 ps at 140 K and about 70 ps at 20 K. A decay component with smaller amplitude and a lifetime of up to hundreds of picoseconds was observed that was centered around 814 nm at 20 K. Kinetic simulations using simple lattice models reproduce the observed decay kinetics at 295 and 140 K, but not at 20 K. The kinetics of energy redistribution within the spectrally heterogeneous antenna system at low temperature argue against a simple "funnel" model for the organization of the antenna of Heliobacillus mobilis and favor a more random spatial distribution of spectral forms. However, the relatively high rate of energy transfer from long wavelength antenna bacteriochlorophyll g to the primary electron donor P798 at low temperature is difficult to explain with either of these models.

Bacteria↗

Time-resolved spectroscopy of energy and electron transfer processes in the photosynthetic bacterium Heliobacillus mobilis.

The kinetics of excitation energy transfer and electron transfer processes within the membrane of Heliobacillus mobilis were investigated using femtosecond transient absorption difference spectroscopy at room temperature. The kinetics in the 725- to 865-nm region, upon excitation at 590 and 670 nm, were fit using global analysis. The fits returned three kinetic components with lifetimes of 1-2 ps and 27-30 ps, and a component that does not decay within several nanoseconds. The 1- to 2-ps component is attributed to excitation equilibration to form a thermally relaxed excited state. The 27- to 30-ps phase corresponds to the decay of the relaxed excited state to form a charge-separated state. The intrinsic energy and electron transfer rates were estimated using the experimental results and theoretical models for excitation migration and trapping dynamics. Taking into account the number of antenna pigments and their spectral distribution, an upper limit of 1.2 ps for the intrinsic time constant for charge separation in the reaction center is calculated. This upper limit corresponds with the trapping-limited case for excitation migration and trapping. Reduction of the primary electron acceptor A0 was observed in the 640 to 700 nm region using excitation at 780 nm. An instantaneous absorbance increase followed by a decay of about 30 ps was observed over a broad wavelength region due to the excited state absorption and decay of BChl g molecules in the antenna. In addition, a narrow bleaching band centered at 670 nm grows in with an apparent time constant of about 1.0 ps, superimposed on the 30-ps absorbance increase due to excited state absorption. Measurements on a longer time scale showed that besides the 670 nm pigment a BChl g molecule absorbing near 785 nm may be involved in the primary charge separation, and that this pigment may be in equilibrium with the 670 nm pigment. The bleaching bands at 670 nm and 785nm recovered with a time constant of about 600 ps, due to forward electron transport to a secondary electron acceptor. Energy and electron transfer properties of H. mobilis membranes are compared with Photosystem 1, to which the heliobacteria bear an evolutionary relationship.

Bacteria↗

Government size, demographic changes, and economic growth.

"This paper examines the effect of government size on the growth rate of per capita output by incorporating demographic variables. Evidence from more than 86 countries suggests that the demographic variables not only affect economic growth, but also determine the size of government. Both the young and the old age dependency ratios were positively related to the size of government, while population density and population size were negatively related to the size of government. Moreover, when the demographic variables are included in the growth equations, the effect of government size on the growth rate of per capita output became insignificant rather than, as prior studies showed, significantly negative."

Demography↗

Stability of cataplexy over several months--information for the design of therapeutic trials.

Twenty-seven narcoleptic patients severely affected with cataplexy completed four symptom diaries over a 4-month period in order to clarify some of the controversies surrounding assessment of anticataplectic medications. The home diary method was found to be a viable model for the assessment of anticataplectic activity. Assessment of reliability in 1-, 2-, 3-, 4-, 5- and 10-day intervals indicated that reliability increases with the number of days included. A 10-day design was found to be optimal. Reliability decreased, however, with each successive diary over the 4-month period. Power analysis indicates that two groups of 30-40 subjects in a parallel design, or one group of 30-40 subjects in a crossover design, would be sufficient to demonstrate a significant therapeutic anticataplectic effect in most cases. A "first diary effect" was observed, suggesting that a training period prior to the actual trial might improve reliability. Whether the patient was treated or untreated with stimulant medications did not affect severity or fluctuation of cataplexy, suggesting that both groups of patients could be included in therapeutic trials. No time-of-day fluctuation was observed in the daily distribution of cataplexy attacks. Sudden increases in cataplexy were often, although not always, caused by unusual emotional events or sleepiness. The finding of a long-lasting "precataplectic" feeling or "aura" pointed to the need to carefully clarify the symptom prior to beginning a therapeutic trial.

Catalepsy↗

Propofol causes a dose-dependent decrease in the thermoregulatory threshold for vasoconstriction but has little effect on sweating.

BACKGROUND: Volatile anesthetics increase the core temperature required to trigger sweating and decrease the core temperature required to trigger vasoconstriction. However, little is known about the effects of intravenous anesthetics on thermoregulation. We therefore tested the hypothesis that propofol increases the sweating threshold and decreases the vasoconstriction threshold, thereby increasing the inter-threshold range (core temperatures not triggering autonomic thermoregulatory responses). The study was conducted using a new model in which thermal manipulations were restricted to insensate skin, and sensate skin temperature was controlled. METHODS: Six healthy, male volunteers were studied on 3 randomly ordered days: no propofol, target propofol blood concentration 2 micrograms/ml, and target blood propofol concentration 4 micrograms/ml. Each day, epidural anesthesia (approximately T11 level) was induced, using 2% 2-chloroprocaine (one volunteer received bupivacaine). Thermal manipulations were confined to the legs, and we attempted to maintain upper-body (sensate) skin temperature constant. Propofol was infused by a computer-controlled infusion pump. Volunteers were heated until sweating was observed, then cooled until fingertip vasoconstriction was observed. The sweating threshold was defined as the tympanic membrane temperature triggering sustained evaporative heat loss > 40 g.m-2.h-1. Similarly, the vasoconstriction threshold was defined as the tympanic membrane temperature triggering a sustained reduction in fingertip blood flow to < 0.25 ml/min. Central venous blood was assayed for propofol blood concentration. RESULTS: Increasing propofol concentration produced a linear decrease the vasoconstriction threshold (slope = -0.53 +/- 0.34 degrees C.microgram-1.ml-1; R2 = 0.98 +/- 0.04 [mean +/- SD]), but had little effect on the sweating threshold. The inter-threshold range was 0.51 +/- 0.46 degrees C during epidural anesthesia alone, and increased significantly, by 0.49 +/- 0.31 degrees C.microgram-1.ml-1 during propofol administration. CONCLUSIONS: Like volatile anesthetics, propofol reduces the vasoconstriction threshold and increases the inter-threshold range. However, propofol differs in leaving the sweating threshold unchanged.

Adult↗

An algorithm for Monte Carlo estimation of genotype probabilities on complex pedigrees.

Exact probability and likelihood computation on complex pedigrees is often infeasible, since exact methods are too computationally intensive even with today's computing technology. A statistical tool, Markov chain Monte Carlo (MCMC), is increasingly being explored as a technique for estimating probabilities of genotypic configurations on pedigrees conditional on phenotypic data. However, this conditional probability distribution on a complex pedigree is, in general, multimodal, and multimodality is one of the major difficulties in MCMC exploration of a probability surface. In this paper, a new member of the MCMC Metropolis-Hastings class of algorithms is proposed; the heated-Metropolis algorithm. The algorithm achieves passage through low probability states to other local modes of the probability distribution, and so provides much improved estimates of probabilities of interest. The example considered is the estimation of the probabilities of carrier genotype for the founders of a complex pedigree in which a very rare lethal recessive trait is segregating.

Algorithms↗

Potential parental exposure to pesticides and limb reduction defects.

OBJECTIVES: The goal of the study was to examine the effects of the potential pesticide exposure of parents on the risk of limb reduction defects in their offspring. METHODS: A case-referent study was conducted utilizing New York State Congenital Malformation Register data. Persons with limb reduction defects and referents were compared in terms of parental occupations and residence counties. Parental occupations and industries reported on birth certificates were qualitatively rated by industrial hygienists to estimate potential pesticide (list four groups) exposures. Residential exposures were estimated from agricultural census data according to county of residence. RESULTS: Neither parental exposure to pesticides [odds ratio (OR) 0.9, 95% confidence interval (95% CI) 0.6-1.4] nor farming occupation (OR 1.1, 95% CI 0.5-2.7) had an effect on the risk of total limb reduction defects. Those persons with limb reduction defects who had additional defects showed weak but consistent elevated risks in relation to parental occupational pesticide exposure. However, isolated cases of limb reduction defects were negatively related to these exposures. Residence in a farming or high pesticide use county was not associated with any type of limb reduction defect. CONCLUSIONS: Cases of limb reduction defect with additional malformations appear to be associated with parental occupational pesticide exposure. Improving exposure classifications and subdividing the limb reduction defects by types in the analyses are suggested for future research.

Adolescent↗

[Materials of history of TCM in Hainan].

TCM therapy began in the Song Dynasty in Hainan. Medical instructor (Xun dao) was first established in the Ming Dynasty, with a total of thirty physicians. In the early Qing Dynasty, monastery of medical kings, Pujitang were built while Hui Ai Yi Ju and Aiseng Hospital were established in late Qing Dynasty. The development of TCM medical exchanges and planting southern herbs during the 20th century are also discussed.

China↗

[Arterial embolization leading to fatal cerebral infarction (a case report)].

A case of severe epistaxis with hypertension and arteriosclerosis was treated by embolizing the ipsilateral internal maxillary artery after routine methods of hemostasis had failed. Although epistaxis stopped after embolization, cerebral infarction, hemiplegia and deep coma developed, and the patient died on the ninth postoperative day. We conclude that superselective embolization of the branches of external carotid artery for treating severe epistaxis should be used with great caution or not be used in patients with arteriosclerosis.

Aged↗

Chemical modification of Lys-6 in Taiwan cobra phospholipase A2 with 4-chloro-3,5-dinitrobenzoate.

Phospholipase A2 (PLA2) from Naja naja atra snake venom was modified with 4-chloro-3,5-dinitrobenzoate, and one major carboxydinitrophenylated (CDNP) PLA2 was separated by high performance liquid chromato-graphy. CDNP-PLA2 contained only one CDNP group on Lys-6 and showed a 93% drop in enzymatic activity. However, carboxydinitrophenylation did not significantly affect the secondary structure of the enzyme molecule as revealed by the CD spectra, and Ca2+ binding and antigenicity of CDNP-PLA2 were unaffected. Conversion of nitro groups to amino groups resulted in a partial restoration of enzymatic activity of CDNP-PLA2 to 35% of that of native enzyme. These results suggested that the positively charged side chain of Lys-6 played a role in the enzymatic mechanism of PLA2. However, the partial restoration in PLA2 activity reflects that a distortion of the active conformation arising from incorporation of a bulky CDNP group should occur.

Amino Acid Sequence↗

Impaired esophageal emptying in reflux disease.

OBJECTIVES: The symptoms and mucosal damage that occur in gastroesophageal reflux disease (GERD) may be a consequence of either an increased frequency of reflux events or of a prolonged process of esophageal acid clearance. Acid clearance is dependent both upon effective esophageal emptying of luminal fluid and on normal salivary function to titrate residual acid to neutrality. This investigation examined the efficacy of esophageal emptying in a large group of GERD patients. METHODS: Barium swallow examinations were done to categorize and quantify esophageal emptying dysfunction in 67 consecutive patients with reflux disease, compared with 85 patient asymptomatic controls. Quantitative fluoroscopic estimates of esophageal residua were compared with scintigraphic quantification in 14 controls and 20 GERD patients. RESULTS: There was progressive impairment of esophageal emptying in the reflux patients without esophagitis compared with the controls, and it was even greater in patients with endoscopically evident esophagitis compared with reflux patients without esophagitis. Good correlation existed between the fluoroscopic and scintigraphic assessment of esophageal emptying. CONCLUSIONS: These findings support the hypothesis that impaired esophageal emptying is an important determinant in the development of esophagitis among reflux patients. The dominant site of impaired emptying in the reflux patients was the phrenic ampulla as opposed to the tubular esophagus, suggesting a pathophysiological contribution of hiatus hernia.

Adult↗

Finding noncommunicating sets for Markov chain Monte Carlo estimations on pedigrees.

Markov chain Monte Carlo (MCMC) has recently gained use as a method of estimating required probability and likelihood functions in pedigree analysis, when exact computation is impractical. However, when a multiallelic locus is involved, irreducibility of the constructed Markov chain, an essential requirement of the MCMC method, may fail. Solutions proposed by several researchers, which do not identify all the noncommunicating sets of genotypic configurations, are inefficient with highly polymorphic loci. This is a particularly serious problem in linkage analysis, because highly polymorphic markers are much more informative and thus are preferred. In the present paper, we describe an algorithm that finds all the noncommunicating classes of genotypic configurations on any pedigree. This leads to a more efficient method of defining an irreducible Markov chain. Examples, including a pedigree from a genetic study of familial Alzheimer disease, are used to illustrate how the algorithm works and how penetrances are modified for specific individuals to ensure irreducibility.

Algorithms↗

Bovine pancreatic deoxyribonuclease F: isoelectric focusing, peptide mapping and primary structure.

DNAase F is a minor isoform of bovine pancreatic DNAase which can be separated from the other isoforms (DNAases A, B, C and D) present in a commercial preparation by a preparative isoelectric-focusing cell (Rotofor; Bio-Rad). The ampholytes and other contaminating proteins present in DNAase F preparations can be removed by chromatography on an affinity column (Cibacron Blue 3GA-agarose) and a hydrophobic-interaction column (phenyl-Sepharose CL-4B). The complete separation of DNAase F from the other isoforms is demonstrated on a thin-layer isoelectric-focusing gel, DNAase F being the most basic (pI 5.68). A procedure is described for tryptic peptide mapping by h.p.l.c. requiring only picomolar amounts of DNAase F protein. The DNAase F map shows two peptide peaks not present in the DNAase A map, and the DNAase F map does not have a peak at the position where a C-terminal peptide of DNAase A is normally eluted. The amino acid compositions and sequences for the two new peptides suggest that Gly240 in DNAase A is changed to Arg240 in DNAase F.

Amino Acid Sequence↗

Modulation of tensin and vimentin expression in chick embryo developing cartilage and cultured differentiating chondrocytes.

It has been proposed that tensin, in association with several other proteins, mediates the micro-filament-integrin link. Here we describe the isolation of clones spanning about 5 kb from the 3' end of tensin mRNA from cultured chick embryo chondrocyte and embryonic heart cDNA libraries. Tensin expression was investigated in cultured chick embryo cells. It was observed that tensin expression is dependent upon substrate adhesion and it is turned off after 7 days of suspension culture. This process is reversible. Tensin expression is also regulated during cartilage cell differentiation in vivo; at Hamburger and Hamilton stage 39-40, non-hypertrophic tibial chondrocytes express both RNA and protein while hypertrophic chondrocytes do not. In the culture system the expression of vimentin, a major component of intermediate filaments, showed an opposite behaviour since the suspension culture enhances the accumulation of both vimentin and its mRNAs. Therefore in chick embryo cultured chondrocytes and in vivo, during cartilage development, cell shape changes and/or integrin-extracellular matrix protein interactions may be involved in the regulation of these two genes coding for cytoskeletal proteins.

Amino Acid Sequence↗

Phase I trial with pharmacokinetic analyses of high-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in patients with refractory germ cell tumors.

Thirty patients with cisplatin-refractory germ cell tumor were treated with high-dose carboplatin, etoposide, and cyclophosphamide and autologous bone marrow transplantation. The total dose of carboplatin was 1500 mg/m2, etoposide 1200 mg/m2, and cyclophosphamide was increased by increments from 60 to 150 mg/kg. Twenty-five cycles of treatment, given to 17 patients, did not include granulocyte-colony stimulating factor (G-CSF). Nineteen cycles of high-dose chemotherapy, given to 13 patients at the 2 highest dose levels of cyclophosphamide, included G-CSF. The dose of cyclophosphamide was escalated to 150 mg/kg/cycle without prohibitive toxicity. The use of G-CSF resulted in a shorter duration of neutropenia (P = 0.07); the median number of days until the recovery of an absolute granulocyte count > 0.5 was 25 without G-CSF and 14 with G-CSF. The most frequent nonhematological toxicity was hepatic, and there were 2 (7%) treatment-related deaths. Thirteen (43%) patients achieved a complete response, and 8 are alive and free of disease (27%); 7 are in continuous complete response (23%), and 1 after resection of a solitary site of disease following a relapse after high-dose chemotherapy. Five patients had pharmacology studies performed to determine the area under the curve (AUC) of free and total platinum, carboplatin, etoposide, cyclophosphamide, and phosphoramide mustard. There was a decrease in the AUC of cyclophosphamide and an increase in the AUC of phosphoramide mustard, the "active" metabolite, with successive days of treatment. The interpatient variability of the AUC of cyclophosphamide/phosphoramide mustard that was demonstrated was most likely a result of each individual's metabolic capacity. The measured AUC of carboplatin and/or free platinum closely approximated the predicted AUC of carboplatin calculated by renal function in 3 of the 5 patients. In summary, cyclophosphamide administered at a dose of 50 mg/kg x 3 days was achieved with acceptable toxicity, and no further dose escalation is planned. High-dose carboplatin, etoposide, and cyclophosphamide achieved a 23% continuous complete response proportion (27% alive, free of disease) when used as third-line therapy in germ cell tumor patients refractory to cisplatin + ifosfamide-based chemotherapy. Ongoing studies are addressing the role of high-dose carboplatin-containing chemotherapy in previously untreated patients with poor prognostic features or as a part of first-line salvage.

Adolescent↗

Monte Carlo analysis on a large pedigree.

Monte Carlo methods for linkage and segregation analysis are applied to the HGAR1 pedigree. To address these data, the methods are extended in several ways. The results are compared with those provided by PAP.

Adolescent↗