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PubMed2001

Overexpression of a heterologous sam gene encoding S-adenosylmethionine synthetase in flax (Linum usitatissimum) cells: Consequences on methylation of lignin precursors and pectins.

The Arabidopsis thaliana sam1 gene encoding S-adenosylmethionine synthetase (EC 2.5.1.6) was transferred to flax (Linum usitatissimum) cells via Agrobacterium tumefaciens. This enzyme catalyses the conversion of methionine to S-adenosylmethionine (SAM), the major methyl group donor in living cells. The aim of this work was to study the consequences of an increased SAM-synthetase (SAM-S) activity in transgenic cell lines on both the production of mono- and dimethoxylated lignin monomers and the degree of methylesterification of pectins. Hypocotyls were cocultivated with Agrobacterium tumefaciens strain GV3101 (pGV2260) harbouring the pO35SSAM binary vector carrying the sam1 gene under the control of the 35S promoter and the nptII gene for selection of putative transformed cells. Most of the transgenic cell lines exhibited a significant (up to 3.2-fold) increase in SAM-S activity compared to the controls. The results showed that for the cell lines analysed this transformation had no effect on caffeic acid O-methyltransferase (COMT, EC 2.1.1.68) in vitro activity, degree of methoxylation of lignin precursors or lignin deposition, pectin methyltransferase (PMT, EC 2.1.1) in vitro activity, but led to an increase of pectin methylesterification in friable and fast-growing transgenic cell lines.

Journal Article↗
PubMed2005

Unusual aggregates from the oxidation of alkene self-assembled monolayers: a previously unrecognized mechanism for SAM ozonolysis?

Self-assembled monolayers (SAMs) of vinyl-terminated 3- and 8-carbon compounds were generated on Si substrates and reacted at room temperature with approximately 1 ppm gaseous O(3). A combination of atomic force microscopy (AFM), scanning electron microscopy (SEM), Auger electron spectroscopy (AES) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used to study the surface composition and morphology after oxidation. A distribution of large ( approximately 0.1-10 microm) organic aggregates was formed, while the surrounding substrate became depleted of carbon compared to the unreacted SAM. This highly unusual result establishes that the mechanism of ozonolysis of alkene SAMs must have a channel that is unique compared to that in the gas phase or in solution, and may involve polymerization induced by the Criegee intermediate (CI). Oxidation at 60% RH led to the formation of a number of smaller aggregates, suggesting water intercepted the CI in competition with aggregate formation. The uptake of water, measured using transmission FTIR, was not increased upon oxidation of these films. In conjunction with literature reports of polymer formation from VOC-NO(x) photooxidations, these results suggest that formation of aggregates and polymers in the atmosphere is much more widespread than previously thought. The implications for the ozonolysis of alkenes on surfaces, for the transformation of organics in the atmosphere, and for the reactions and stability of unsaturated SAMs, are discussed.

Alkenes↗
PubMed2002

Studies of methionine cycle intermediates (SAM, SAH), DNA methylation and the impact of folate deficiency on tumor numbers in Min mice.

Several epidemiological studies have suggested a modulatory effect of dietary folate intake on the risk of colorectal cancer. The molecular basis for this inverse association is not clearly understood, but may involve alterations in DNA methylation. In this study, we examined the levels of methylation intermediates [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)] and of global DNA methylation in the pre-neoplastic small intestine of Min (multiple intestinal neoplasia) mice. We also studied the effect of folate/choline deficiency on these parameters and on tumor multiplicity in this animal model. In folate-adequate Min mice, we identified positive linear correlations between SAM or SAH and tumor numbers (R(2) = 0.38, P < 0.005; R(2) = 0.26, P = 0.025, respectively). A positive correlation between global DNA hypomethylation and tumor multiplicity was also observed (R(2) = 0.29, P = 0.014). These three biochemical determinants (SAM, SAH and DNA hypomethylation) may, therefore, serve as early markers of cell transformation. Folate/choline deficiency, however, did not produce a consistent effect on tumor numbers in three separate experiments. As an increase in tumor numbers was observed only in folate- and choline-deficient mice with low levels of SAM and DNA hypomethylation, the modulatory role of folate may be dependent on the transformation state of the cell.

Animals↗
PubMed1996

The SAM framework: modeling the effects of management factors on human behavior in risk analysis.

Complex engineered systems, such as nuclear reactors and chemical plants, have the potential for catastrophic failure with disastrous consequences. In recent years, human and management factors have been recognized as frequent root causes of major failures in such systems. However, classical probabilistic risk analysis (PRA) techniques do not account for the underlying causes of these errors because they focus on the physical system and do not explicitly address the link between components' performance and organizational factors. This paper describes a general approach for addressing the human and management causes of system failure, called the SAM (System-Action-Management) framework. Beginning with a quantitative risk model of the physical system, SAM expands the scope of analysis to incorporate first the decisions and actions of individuals that affect the physical system. SAM then links management factors (incentives, training, policies and procedures, selection criteria, etc.) to those decisions and actions. The focus of this paper is on four quantitative models of action that describe this last relationship. These models address the formation of intentions for action and their execution as a function of the organizational environment. Intention formation is described by three alternative models: a rational model, a bounded rationality model, and a rule-based model. The execution of intentions is then modeled separately. These four models are designed to assess the probabilities of individual actions from the perspective of management, thus reflecting the uncertainties inherent to human behavior. The SAM framework is illustrated for a hypothetical case of hazardous materials transportation. This framework can be used as a tool to increase the safety and reliability of complex technical systems by modifying the organization, rather than, or in addition to, re-designing the physical system.

Accidents, Traffic↗
PubMed2004

S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS.

BACKGROUND: This study reports on clinical data from an 8-week open-label study of 20 HIV-seropositive individuals, diagnosed with Major Depressive Disorder (DSM-IV), who were treated with SAM-e (S-Adenosylmethionine). SAM-e may be a treatment alternative for the management of depression in a population reluctant to add another "pill" or another set of related side effects to an already complex highly active antiretroviral therapy (HAART) regimen. METHODS: The Hamilton Rating Scale for Depression (HAM-D) and the Beck Depression Inventory (BDI) were used to assess depressive symptomatology from 1,2,4,6 and 8 weeks after initiation of treatment with SAM-e. RESULTS: Data show a significant acute reduction in depressive symptomatology, as measured by both the HAM-D and the BDI instruments. CONCLUSIONS: SAM-e has a rapid effect evident as soon as week 1 (p < .001), with progressive decreases in depression symptom rating scores throughout the 8 week study.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Senescence-accelerated mouse (SAM): with special reference to age-associated pathologies and their modulation].

The senescence-accelerated mouse (SAM) has been under development by our research team at Kyoto University since 1970 through selective inbreeding of the AKR/J strain of mice donated by the Jackson Laboratory in 1968, based on the data of the grading score of senescence, life span, and pathologic phenotypes. At present, there are 12 lines of SAM; the 9 senescence-prone inbred strains (SAMP) include SAMP1, SAMP2, SAMP3, SAMP6, SAMP7, SAMP8, SAMP9, SAMP10 and SAMP11, and the 3 senescence-resistant inbred strains (SAMR) SAMR1, SANR4 and SAMR5. Data from survival curves, the Gompertzian function and the grading score of senescence, together with growth patterns of body weight of these SAMP and SAMR mice revealed that the characteristic feature of aging common to all SAMP mice is "accelerated senescence": early onset and irreversible advance of senescence manifested by several signs and gross lesions such as the loss of normal behavior, various skin lesions, increased lordokyphosis, etc., after a period of normal development. Routine postmortem examinations and the pathobiological features revealed by systematically designed studies have shown several pathologic phenotypes, which are often characteristic enough to differentiate among the various SAM strains: senile amyloidosis in SAMP1, -P2, -P7, -P9, -P10 and -P11, secondary amyloidosis in SAMP2 and -P6, contracted kidney in SAMP1, -P2, -P10, -P11, immunoblastic lymphoma in SAMR1 and -R4, histiocytic sarcoma in SAMR1 and -R4, ovarian cysts in SAMR1, impaired immune response in SAMP1, -P2 and -P8, hyperinflation of the lungs in SAMP1, hearing impairment in SAMP1, degenerative temporomandibular joint disease in SAMP3, senile osteoporosis in SAMP6, deficits in learning and memory in SAMP8 and -P10, emotional disorders in SAMP8 and -P10, cataracts in SAMP9, and brain atrophy in SAMP10. These are all age-associated pathologies, the incidence and severity of which increase with advancing age. The SAM model in which these pathobiological features have been carefully monitored will be a valuable tool for the clarification of the pathogenic mechanisms of age-associated pathologies and in research for effective methods to modulate or ameliorate these pathologies.

Aging↗
PubMed1996

Neural-network-based classification of Space Acceleration Measurement Systems (SAMS) data via supervised learning.

This paper illustrates the applicability of neural networks in classifying events using Space Acceleration Measurement System (SAMS) data. Computer programs have been written in the MATLAB environment for the following purposes: automatic retrieval of SAMS data from NASA CDROM disks, computation of power spectral densities for SAMS data and construction of input patterns for the training of a multi-layer neural network (MNN). The MNN has been trained using the backpropagation learning algorithm and the SAMS data collected on the STS-50 Space Shuttle mission for three crew exercise events. It is found that the trained MNN is highly successful in classifying events. In addition, the performance of MNN is found to be better than that of the nearest neighbor classifier.

Acceleration↗
PubMed1999

Self-organizing map (SOM) of space acceleration measurement system (SAMS) data.

In this paper, space acceleration measurement system (SAMS) data have been classified using self-organizing map (SOM) networks without any supervision; i.e., no a priori knowledge is assumed regarding input patterns belonging to a certain class. Input patterns are created on the basis of power spectral densities of SAMS data. Results for SAMS data from STS-50 and STS-57 missions are presented. Following issues are discussed in details: impact of number of neurons, global ordering of SOM weight vectors, effectiveness of a SOM in data classification, and effects of shifting time windows in the generation of input patterns. The concept of 'cascade of SOM networks' is also developed and tested. It has been found that a SOM network can successfully classify SAMS data obtained during STS-50 and STS-57 missions.

Acceleration↗
PubMed1989

Immune responses in newly developed short-lived SAM mice. III. Genetic control of defective helper T-cell activity in in vitro primary antibody response.

Immune activities of newly developed, short-lived SAM-P/1 mice declined sharply after a few months of age. As early as 2 months of age, the activity of T-helper (Th) cells ('Th2'-like) in the in vitro primary antibody response was profoundly impaired, in contrast to normal activity of Th cells ('Th1'-like) engaged in cell-mediated immune responses. Thus, young SAM-P/1 mice show a functional heterogeneity of Th cells. To determine how such a 'Th2' abnormality is inherited in SAM-P/1 mice, immune activities of their hybrids and backcrosses between MHC-identical, high responder B10.BR mice were statistically assessed. The distribution of responses did not support the Mendelian single-gene determination for low responsiveness. Moreover, involvement of a single gene which exhibits incomplete dominance was ruled out because of a continuous distribution pattern of antibody response in the F2 generation. Such an analysis strongly suggests that the impaired 'Th2'-like activity of SAM-P/1 mice is under control of two genes, based on the proportion of low responders in F2 hybrids (29 out of 267, 10.8%) and on calculation according to Wright's formula (n = 1.72). Further linkage analyses suggest that one of the genes is closely linked to albino coat-colour (c) locus on chromosome 7. The putative two genes are likely to control 'differentiation' or 'maturation' of Th2-like cells defectively, but the defect is not refractory, because in vivo-primed Th cells function in vitro as do those in ordinary strains of mice. Possible mechanisms and biological significance in relation to loss of immune activity with ageing are discussed.

Aging↗
PubMed1998

Amplification of c-myc, K-sam, and c-met in gastric cancers: detection by fluorescence in situ hybridization.

Gene amplifications of c-myc, K-sam, and c-met were examined in cancer nuclei isolated from 154 primary gastric adenocarcinomas by fluorescence in situ hybridization (FISH) using cosmid probes for 8q24 (c-myc locus) and 7q31 (c-met), as well as a DNA probe for K-sam synthesized by PCR. The results were compared with those of Southern blot analysis. Dual-color FISH using gene locus and chromosome-specific probes detected gene amplifications of c-myc in 24 tumors (15.5%), c-met in 6 tumors (3.9%), and K-sam in 3 tumors (2.9%). The six tumors with c-myc amplification had also been found to have amplified c-erbB-2 in our previous study, and coamplification of c-myc and c-met was found in two other tumors. This technique also differentiated the amplified genes on the homogeneous staining region (HSR) and on double minute chromosomes (DMs) in metaphase spreads and interphase nuclei of cell lines established from poorly differentiated adenocarcinomas, KATO III, SNU 16, and HSC 39. Examination of FISH images of these cell lines suggested that the high-level amplifications of c-myc found in primary tumors occurred mainly on DM in four tumors and on HSR in one, and those of K-sam occured on DM in two tumors and on HSR in one. No high-level amplification of c-met was found. These high-level amplifications were also detected in formalin-fixed, paraffin-embedded tissues from primary gastric tumors and metastatic lymph nodes, in some of which heterogeneity of gene amplification was demonstrated within the same tumor. We conclude that FISH is an important tool for examining the proto-oncogene aberrations in intact cells in solid tumors.

Blotting, Southern↗
PubMed2006

Enantiodiscrimination between an N-acetyl-L-cysteine SAM and proline: an in situ spectroscopic and computational study.

A combination of attenuated total reflection infrared (ATR-IR) and modulation excitation spectroscopy (MES) is used to study the enantiodiscriminating interactions between proline and a chiral, self-assembled monolayer (SAM) of N-acetyl-L-cysteine on gold. The N-acetyl-L-cysteine SAM consists of a mixture of protonated and deprotonated molecules. Whereas both species are influenced by adsorbed proline, only the deprotonated molecules are involved in enantiodiscrimination. Density functional theory (DFT) calculations reveal that electrostatics dominates the interaction between the two molecules. By modulating the absolute configuration of proline over the chiral SAM, and a subsequent phase-sensitive detection of the periodically varying signals in the ATR-IR spectra, the small spectral differences between the diastereomeric complexes are spotted. The resulting difference spectrum is in qualitative agreement with the spectrum predicted by the DFT calculations.

Acetylcysteine↗
PubMed2006

The optimal SAM surface functional group for producing a biomimetic HA coating on Ti.

Commercial interest is growing in biomimetic methods that employ self assembled mono-layers (SAMs) to produce biocompatible HA coatings on Ti-based orthopedic implants. Recently, separate studies have considered HA formation for various SAM surface functional groups. However, these have often neglected to verify crystallinity of the HA coating, which is essential for optimal bioactivity. Furthermore, differing experimental and analytical methods make performance comparisons difficult. This article investigates and evaluates HA formation for four of the most promising surface functional groups: --OH, --SO(3)H, --PO(4)H(2) and --COOH. All of them successfully formed a HA coating at Ca/P ratios between 1.49 and 1.62. However, only the --SO(3)H and --COOH end groups produced a predominantly crystalline HA. Furthermore, the --COOH end group yielded the thickest layer and possessed crystalline characteristics very similar to that of the human bone. The --COOH end group appears to provide the optimal SAM surface interface for nucleation and growth of biomimetic crystalline HA. Intriguingly, this finding may lend support to explanations elsewhere of why human bone sialoprotein is such a potent nucleator of HA and is attributed to the protein's glutamic acid-rich sequences.

Coated Materials, Biocompatible↗
PubMed1997

SAM as a protein interaction domain involved in developmental regulation.

More than 60 previously undetected SAM domain-containing proteins have been identified using profile searching methods. Among these are over 40 EPH-related receptor tyrosine kinases (RPTK), Drosophila bicaudal-C, a p53 from Loligo forbesi, and diacyglycerol-kinase isoform delta. This extended dataset suggests that SAM is an evolutionary conserved protein binding domain that is involved in the regulation of numerous developmental processes among diverse eukaryotes. A conserved tyrosine in the SAM sequences of the EPH related RPTKs is likely to mediate cell-cell initiated signal transduction via the binding of SH2 containing proteins to phosphotyrosine.

Amino Acid Sequence↗
PubMed2002

Existence of a hydrophobic gap at the alkanethiol SAM-water interface: an interfacial capacitance study.

The highly hydrophobic neat alkanethiol-coated SAM on evaporated gold shows an unusually low interfacial capacitance in aqueous media. This result cannot be explained by a simple parallel plate model of the double layer with the alkanethiol monolayer as a sole dielectric separator. Interestingly, a hydrophilic SAM prepared from a neat hydroxy thiol does not show any such capacitance lowering in aqueous media. Our results suggest the existence of a "hydrophobic gap" between the alkanethiol SAM-water interface. Such a model is also very much consistent with the predictions of Lum, Chandler, and Weeks theory of length scale dependent hydrophobicity.

Letter↗
PubMed1984

Cataract and other ophthalmic lesions in senescence accelerated mouse (SAM). Morphology and incidence of senescence associated ophthalmic changes in mice.

In a murine model of accelerated senescence (SAM), grading score and incidence in cataract, periophthalmic lesions, opacity and ulcer of the cornea were determined in mice from 4 to 24 months of age. From 4 to 6 months of age, incidence and grading score of these four categories began to increase in both the accelerated senescence prone (SAM) and resistant series with normal aging, and these increases continued with aging. As compared with the resistant series, there was a higher incidence and grading score of the four categories and a higher rate of increase in the prone series. The prone 3 series in particular showed a much higher incidence and grading score on cataract, the rate being 27.5% and 70.6% at 12 and 16 months, respectively. Histologically, the cataract was classified into two types. In one, degeneration of lens fibers, disintegration of lens cortex, and at an advanced stage, liquefaction of the lens cortex and proliferation of the anterior lens epithelial cells occurred. In the other type, lens fibers lost their distinct shapes and a homogenous mass formed at the anterior and posterior superficial cortex. The anterior lens epithelial cells had shrunk. There was an opacity and ulcer of the cornea with keratitis and the corneal epithelium was lost in case of the latter. Periophthalmic lesions included catarrhal changes of the skin of the eyelids and face and blepharitis. There were no lesions specific to each of the prone and resistant series. Thus, SAM should prove to be a suitable murine model for investigation of age-related ophthalmic lesions, including cataract in humans.

Aging↗
PubMed1994

Age-related decreases in the reconstituting ability of hemopoietic cells and the ability of hemopoietic microenvironment to support hemopoietic reconstitution in senescence accelerated (SAM-P) mice.

The effect of the aging process on the hemopoietic system in senescence-accelerated (SAM-P) mice with respect to the reconstituting ability of hemopoietic cells and the ability of the microenvironment to support hemopoietic reconstitution was investigated by bone marrow transplantation (reconstitution assay). When the bone marrow cells, obtained from young or old mice, were transplanted to lethally irradiated young SAM-P mice no difference in the reconstituting pattern of femoral spleen colony-forming units (CFU-S), splenic CFU-S and splenic granulocyte macrophage colony-forming units (CFU-GM) was observed between the mice transplanted with young and old donor cells. However, the reconstitution of femoral CFU-GM in mice transplanted with old donor cells was delayed compared to that in mice transplanted with young donor cells. Moreover, the recovery of WBC in mice transplanted with old donor cells was noticeably delayed. When the bone marrow cells obtained from young mice were transplanted to young or old recipient mice, no difference in the reconstituting pattern of femoral CFU-S and CFU-GM as well as splenic CFU-S and CPU-GM was observed between young and old recipient mice. However, the recovery of WBC in old recipient mice was noticeably delayed. These data indicate that the functions of both the hemopoietic cells and the hemopoietic microenvironment deteriorated with age in SAM-P mice.

Aging↗
PubMedDate not supplied

A novel murine model of aging, Senescence-Accelerated Mouse (SAM).

Senescence-Accelerated Mouse (SAM) has been under development by our research team at Kyoto University since 1970, based on the AKR/J strain donated by the Jackson Laboratory in 1968. The SAM mouse has an accelerated senescence and age-associated pathologies such as senile amyloidosis, senile osteoporosis, degenerative joint disease, cataract, deficits in learning and memory, brain atrophy, hyperinflation of lungs, hearing impairment and so on. SAM research is advancing world-wide and attempts are being made to clarify fundamental mechanisms involved in primary aging processes, pathogenesis of age-associated pathologies and effective methods to modulate or ameliorate the advance of senescence and disease processes involved in age-associated pathologies.

Journal Article↗
PubMed2005

Self-assembled monolayers (SAMs) of alkoxycyanobiphenyl thiols on gold--a study of electron transfer reaction using cyclic voltammetry and electrochemical impedance spectroscopy.

Self-assembled monolayers (SAMs) of liquid crystalline thiol-terminated alkoxycyanobiphenyl molecules with different alkyl chain lengths on Au surface have been studied for the first time using electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The barrier property of the SAM-modified surfaces was evaluated using two different redox probes, namely potassium ferro/ferri cyanide and hexaammineruthenium(III) chloride. It was found that for short-length alkyl chain thiol (C5) the electron transfer reaction of hexaammineruthenium(III) chloride takes place through tunneling mechanism. In contrast, redox reaction of potassium ferro/ferri cyanide is almost completely blocked by the SAM-modified Au surface. From the impedance data, a surface coverage value of >99.9% was calculated for all the thiol molecules.

Journal Article↗