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Biomedical subjects

J L Martin

Publications and source records attributed to J L Martin.

At least 181 records · Page 10Linked to original sources

Cretan Mediterranean diet for prevention of coronary heart disease.

As a result of the Seven Countries Study, the Mediterranean diet has been popularized as a healthy diet. Nevertheless, it has not replaced the prudent diet commonly prescribed to coronary patients. Recently, we completed a secondary, randomized, prospective prevention trial in 605 patients recovering from myocardial infarction in which we compared an adaptation of the Cretan Mediterranean diet with the usual prescribed diet. After a mean follow-up period of 27 mo, recurrent myocardial infarction, all cardiovascular events, and cardiac and total death were significantly decreased by > 70% in the group consuming the Mediterranean diet. These protective effects were not related to serum concentrations of total, low-density-lipoprotein (LDL), or high-density-lipoprotein (HDL) cholesterol. In contrast, protective effects were related to changes observed in plasma fatty acids: an increase in n-3 fatty acids and oleic acid and a decrease in linoleic acid that resulted from higher intakes of linolenic and oleic acids, but lower intakes of saturated fatty acids and linoleic acid. In addition, higher plasma concentrations of antioxidant vitamins C and E were observed. We conclude that a Cretan Mediterranean diet adapted to a Western population protected against coronary heart disease much more efficiently than did the prudent diet. Thus, it appears that the favorable life expectancy of the Cretans could be largely due to their diet.

Adult↗

Use of the polymerase chain reaction for the detection of Chlamydia trachomatis in clinical specimens and its comparison to commercially available tests.

A polymerase chain reaction (PCR) was developed to detect Chlamydia trachomatis in genital tract specimens. Two sets of primers for the PCR were used; one set amplifies a region of the plasmid present in all C trachomatis strains and the other amplifies a conserved region of the genome coding for the major outer membrane protein. The sensitivity of these PCRs were compared with each other, and with the sensitivities of antigen ELISA, Clearview and culture. Southern blotting and probing was used to increase sensitivity of detection.

Bacteriological Techniques↗

Sexual abuse in childhood and deliberate self-harm.

OBJECTIVE: The authors investigated the association between sexual abuse in childhood and subsequent incidents of deliberate self-harm in women. METHOD: A random community sample of women (N = 252) that reported having been sexually abused as children was interviewed and compared to a similarly sized group (N = 225) that did not report abuse. The subgroup of women sexually abused as children who reported subsequent incidents of deliberate self-harm was then contrasted with abused women who did not report self-harm. RESULTS: There was a clear statistical association between sexual abuse in childhood and self-harm that was most marked in those subjected to more intrusive and more frequent abuse. Self-harm was also associated with major interpersonal problems in the subject's family of origin and with becoming involved in further abusive relationships as an adult. CONCLUSIONS: Sexual abuse in childhood is associated with later incidents of deliberate self-harm and may well be an etiologic factor in its development.

Adolescent↗

Insulin-like growth factor-binding protein-3 production by MCF-7 breast cancer cells: stimulation by retinoic acid and cyclic adenosine monophosphate and differential effects of estradiol.

The insulin-like growth factors (IGFs) stimulate the proliferation of human breast cancer cells, including the estrogen-dependent cell line MCF-7. These cells secrete regulatory IGF-binding proteins (IGFBPs) which may enhance or attenuate IGF-stimulated cell proliferation. In this study, we have used RIA to quantify the production and regulation of IGFBP-3 and IGFBP-6 by MCF-7 cells in vitro. Under basal (serum- and phenol red-free) conditions, IGFBP-3 and IGFBP-6 accumulated in 72 h-conditioned MCF-7 medium to concentrations of approximately 0.18 nM and 0.02 nM, respectively. Treatment with retinoic acid (RA, 100 nM) increased medium concentrations of IGFBP-3 to 175 +/- 8% (mean +/- SE, n = 4), and IGFBP-6 to 217 +/- 20% of control values. Forskolin (0.5 microM) or dibutyryl cAMP (db-cAMP, 1 mM) increased both proteins 2- to 3-fold. In the presence of 100 nM RA, the stimulation elicited by these agents was enhanced, with IGFBP-3 levels increasing to 6-fold above that seen with RA alone. IGFBP-6 increased 12-fold with RA + forskolin and 20-fold with RA + dbcAMP. Estrogen (10 nM estradiol) reduced basal IGFBP-3 levels by 25% but increased IGFBP-6 1.5- to 2-fold. The stimulatory effect of RA + forskolin on IGFBP-3 was partially reversed by estrogen, whereas RA + forskolin-stimulated IGFBP-6 levels were further increased by estrogen. Increased IGFBP-3 and -6 production in response to RA + forskolin was accompanied by a decrease in IGF-stimulated thymidine incorporation into DNA; by contrast, the bioactivity of an IGF analog that does not bind with IGFBPs, [Gln3, Ala4, Tyr15, Leu16]IGF-I, was unchanged under these conditions. These data demonstrate that modulating the production of IGFBPs can lead to changes in the sensitivity of breast cancer cells to IGFs, and as a result change the cell proliferative effects of these growth factors. Further, IGFBP-3 and IGFBP-6 are differentially regulated by estrogen. Dissecting the roles of the individual IGFBPs is essential to understanding how such differential regulation will ultimately affect IGF-stimulated cell proliferation in breast cancer.

Breast Neoplasms↗

Coherent nuclear dynamics at room temperature in bacterial reaction centers.

A room-temperature study is reported of the femtosecond spectral evolution of the stimulated emission band of the primary electron-transfer precursor P* in bacterial photosynthesis. The study was performed with membranes of the antenna-deficient RCO1 mutant of Rhodobacter sphaeroides. A time-dependent red shift, reflecting nuclear motion out of the Franck-Condon region of the excited state, is resolved. Analysis of oscillatory features persisting for > 1 ps in the kinetics revealed main frequencies of the activated motions at 30, 84, 145, and 192 cm-1. The oscillations occur on the time scale of primary electron transfer. Our results set a lower limit for the vibrational dephasing time in P* that is not compatible with the usual assumption in theoretical treatments of complete vibrational relaxation prior to electron transfer, even at room temperature.

Bacteriochlorophylls↗

Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.

In a prospective, randomised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infarct prudent diet. After a first myocardial infarction, patients were randomly assigned to the experimental (n = 302) or control group (n = 303). Patients were seen again 8 weeks after randomisation, and each year for 5 years. The experimental group consumed significantly less lipids, saturated fat, cholesterol, and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma. Serum lipids, blood pressure, and body mass index remained similar in the 2 groups. In the experimental group, plasma levels of albumin, vitamin E, and vitamin C were increased, and granulocyte count decreased. After a mean follow up of 27 months, there were 16 cardiac deaths in the control and 3 in the experimental group; 17 non-fatal myocardial infarction in the control and 5 in the experimental groups: a risk ratio for these two main endpoints combined of 0.27 (95% CI 0.12-0.59, p = 0.001) after adjustment for prognostic variables. Overall mortality was 20 in the control, 8 in the experimental group, an adjusted risk ratio of 0.30 (95% CI 0.11-0.82, p = 0.02). An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death.

Coronary Disease↗

Coherent dynamics during the primary electron-transfer reaction in membrane-bound reaction centers of Rhodobacter sphaeroides.

The temporal evolution of the near-infrared stimulated emission band of the special pair excited state (P*) in the reaction center of Rhodobacter sphaeroides has been studied in intracytoplasmic membranes of the antenna-deficient RCO1 mutant at 10 K with a resolution of 30 fs. On the 100-fs time scale the emission band gradually shifts to longer wavelengths. After 150 fs the band shifts back to shorter wavelengths and continues to develop on the picosecond time scale in a damped oscillatory manner (most prominent fundamental frequencies around 15 cm-1 and at 92, 122, and 153 cm-1). These phenomena are shown to be due to low-frequency vibrational motions in the P* excited state that conserve their phase on the time scale of electron transfer. These results imply that the vibrational manifold of P* is not thermalized during the electron-transfer reaction in functional reaction centers. The initial Stokes shift dynamics are largely determined by the modes in the 90-160-cm-1 frequency range, which probably involve motions of several chromophores, including the bacteriopheophytin electron acceptor HL.

Electron Transport↗

Ultrafast measurements of geminate recombination of NO with site-specific mutants of human myoglobin.

Flash photolysis studies of NO recombination to heme proteins offer a direct probe of protein structural changes on the tens of picoseconds timescale where they can be compared with molecular dynamics simulations. The geminate recombination of NO to site-specific mutants of human myoglobin (Mb) was studied following photodissociation of the MbNO form. Single amino acid changes were introduced at positions Val68, His64, Lys45 and Asp60 because motions of residues at these positions are generally regarded as important for the mechanism of ligand binding. In sharp contrast to the properties of simple porphyrin-NO complexes, the rebinding kinetics are found to be non-exponential for all mutants, even in aqueous solution at 298 K. The Val68 and His64 mutants substantially affect the NO rebinding rates but, surprisingly, so do changes on the protein surface that are further away from the iron. These changes in kinetics occur on a tens of picoseconds timescale, and therefore there is either a fast communication between protein residues over quite long distances or there are subtle differences in protein structure that exert great control over the reaction dynamics. Various models for the rebinding kinetics are evaluated. A model-free approach to data analysis using the maximum entropy method is found to be most useful. This analysis shows that the rate distributions are very different for the mutants, but are generally bimodal.

Asparagine↗

Regulation of immunoreactive insulin-like growth factor binding protein-6 in normal and transformed human fibroblasts.

Insulin-like growth factor-binding proteins (IGFBPs) have been shown to both potentiate and inhibit IGF bioactivity in vitro; thus, changes to the type or amount of IGFBPs present in the cellular environment will ultimately affect insulin-like growth factor action. In this study, we have investigated the production of immunoreactive IGFBP-6 by normal human fibroblasts (NHF) and an SV-40-transformed human fibroblast line (AG2804). When analyzed by SDS-polyacrylamide gel electrophoresis and immunoblotting, IGFBP-6 appeared as a doublet of 32-34-kDa in conditioned medium of both cell lines, with the lower molecular mass band predominating in the NHF cell line. Measured by a specific radioimmunoassay, serum-free NHF, and AG2804 cultures secreted IGFBP-6 at 1.44 +/- 0.09 and 1.23 +/- 0.08 ng/10(4) cells (mean +/- S.E.), respectively. Despite a relatively weak IGFBP-6 signal by ligand blot compared with IGFBP-3, the two proteins were secreted in similar molar concentrations by NHF. Retinoic acid increased IGFBP-6 by 3-fold in NHF and AG2804-conditioned media, maximal at approximately 100 nM retinoic acid. In contrast, IGFBP-6 production was inhibited by transforming growth factor-beta 1 and agents that increase intracellular cAMP concentrations, including dibutyryl cAMP, forskolin, isobutylmethylxanthine, and cholera toxin. This study indicates that IGFBP-6 has a pattern of regulation unique among the IGFBPs, supporting the concept of specific roles for each binding protein in regulating cell growth and metabolism.

1-Methyl-3-isobutylxanthine↗

A novel use of differential equations to fit exponential functions to experimental data.

A procedure for fitting multi-exponential functions to experimental data is described. It is fast, requires no initial parameter estimates and is particularly suited to sums of several closely spaced exponentials. The method comprises the application of three well tried numerical techniques: (i) the signal is smoothed by representing it as an abbreviated Legendre series; (ii) the coefficients of a certain kind of differential equation are determined such that it's solution is the closest fit to the smoothed signal; and (iii) the amplitudes of the exponential components are determined, given the calculated values of the exponential rate constants. The method is computationally efficient, since determination of amplitudes and exponents involves the use of linear techniques, and therefore does not require multiple iterations, and the smoothed signal is contained in a handful of coefficients rather than as a lengthy time series. The severe ill-conditioning that is unavoidable in this problem is contained within the well-understood procedures of inverting a matrix and determining the roots of a polynomial. This method is particularly appropriate for analysis of data that may be modelled by a scheme of linked first-order reactions, describing for example the stochastic behaviour of ion channels, a chemical reaction, or the uptake and distribution of a drug within body compartments.

Data Interpretation, Statistical↗

Contingent negative variation (CNV) and erotic preference in self-declared homosexuals and in child sex offenders.

Contingent negative variation (CNV) was recorded bilaterally from central electrodes using a "match/mismatch" paradigm in (Study 1) samples of heterosexual men (N = 6), gay men (N = 10) and lesbian women (N = 14) and (Study 2) in samples of child sex offenders (N = 34) and heterosexual control men (N = 19). Sexual orientation was assessed using the Multidimensional Scale of Sexuality (MSS) and the Human Sexuality Questionnaire (HSQ). Separate CNV averages were formed for each condition of stimulation: for Study 1, slides of adult male and female nudes; for Study 2, slides of child, pubescent and adult male and female nudes. Penile plethysmographic (PPG) data were also obtained from 15 of the child sex offender sample while they viewed stimuli of the same categories as were used in the CNV recording. On the basis of their PPG responses to children, child sex offenders were classified as either "pedophiles" or "non-pedophiles". In Study 1 significant Group x Sex (of slide) and Group x Electrode interactions indicated that: (i) heterosexual men (but neither homosexual group) showed significantly larger CNVs to female than to male slides; (ii) both homosexual groups showed significantly asymmetrical (R > L) CNVs. In Study 2, controls showed significantly greater CNVs to adult females than to both adult males and female children. Child sex offenders showed no significant differences in CNV to male and female slides for any age. "Non-pedophiles" showed significantly larger CNVs to female adults than to female children, but "pedophiles" did not. It is concluded that CNV has promise as a measure of both deviant and non-deviant sexual preference.

Adolescent↗

Hepatitis C virus genotypes in France: comparison of clinical features of patients infected with HCV type I and type II.

Two major hepatitis C virus genotypes, F1 and F2, corresponding to hepatitis C virus type I and type II respectively, were found in France. To investigate the correlation between infection with these genotypes (F1 and F2) and clinical features of patients, serum samples proven to be hepatitis C virus positive by polymerase chain reaction amplification on 5' non-coding region were further amplified in the NS3 region with nested polymerase chain reaction. The NS3-polymerase chain reaction products were Southern blotted and hybridized with specific probes to identify the genotype of hepatitis C virus. Of 70 samples 64 were NS3-polymerase chain reaction positive. Twenty-eight (40%) samples were hepatitis C virus type I (F1) and 34 (49%) were hepatitis C virus type II (F2), while one sample (HB) hybridized with both probes and another (HN) hybridized with neither. Some samples were sequenced, with results consistent with those of hybridization. The HB sample was related more to hepatitis C virus type II than to type I and the HN sample was divergent from both type I and type II genotypes. Clinical profiles of patients infected with hepatitis C virus type I and type II were compared. Type I infected patients were younger (p < 0.01) and more often male (p < 0.05) than those of the type II group. Nine of 28 patients in the type I infected group had a history of drug abuse, whereas none did in the type II group. Five of 22 (23%) type I infected patients and 19 of 32 (59%) type II infected patients had cirrhosis (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗