Analysis of the association of a heat shock protein70-1 gene promoter polymorphism with myocardial infarction and coronary risk traits

In 12 depressed inpatients referred for bilateral electroconvulsive therapy (ECT), each patient was titrated at the first treatment session by using an ascending method-of-limits procedure with a step-wise increase in pulse frequency (frequency titration) or train duration (duration titration). At the second treatment session, seizure threshold was redetermined by using the method (frequency or duration titration) not used at the first treatment. Frequency or duration was maintained at the lowest level when the other parameter was titrated. Seizure threshold was significantly lower with duration titration (mean, 90 mC; SD, 27.3) than frequency titration (mean, 114 mC; SD, 35.6; p = 0.03). On average, patients in the duration-titration group required 1.2 (SD, 0.6) subconvulsive stimulations before a seizure was elicited, and patients in the frequency-titration group required 1.7 (SD, 0.9) subconvulsive stimulations before a seizure was elicited, a nonsignificant difference. These findings suggest that to elicit a seizure during ECT, increasing train duration may be slightly more efficient than increasing frequency. Basic and other clinical research findings indicate that increasing pulse width may be an inefficient way to elicit a seizure. Therefore the following sequence in the determination of seizure threshold is worth considering when using dose-titration or related techniques: the train duration should be increased first before increasing pulse frequency, and the decision to increase pulse width should be reserved for patients who do not seize at the maximal duration and frequency settings. Further empiric research is needed to establish the utility of this approach.     

Electrical impedance tomography with compensation for electrode positioning variations

Ideally electrical impedance tomography (EIT) should not be oversensitive to electrode positions, but this conflicts with efforts to produce high-resolution images. Two procedures are presented that balance reducing the sensitivity to electrode position errors with generating practicable EIT images. The first provides a criterion based on electrode sensitivity for regularizing the reconstruction through spectral expansion. The main consequences of this are that smoother images are produced and the number of artefacts and their magnitude are generally reduced. The second modification uses the recorded data to compensate for electrode movements that have occurred after the reference data were measured. Image smoothness is used as the criterion for the readjustment. Computer simulation tests have shown that this modification produces improved image fidelity.     

Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination

Development of CD8 alphabeta CTL epitope-based vaccines requires an effective strategy capable of co-delivering large numbers of CTL epitopes. Here we describe a DNA plasmid encoding a polyepitope or "polytope" protein, which contained multiple contiguous minimal murine CTL epitopes. Mice vaccinated with this plasmid made MHC-restricted CTL responses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge models. CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-macrophage CSF, and appeared to be induced in the absence of CD4 T cell-mediated help. The ability to deliver large numbers of CTL epitopes using relatively small polytope constructs and DNA vaccination technology should find application in the design of human epitope-based CTL vaccines, in particular in vaccines against EBV, HIV, and certain cancers.     

Sugar-induced molten-globule model

Proteins denature at low pH because of intramolecular electrostatic repulsions. The addition of salt partially overcomes this repulsion for some proteins, yielding a collapsed conformation called the A-state. A-states have characteristics expected for the molten globule, a notional kinetic protein folding intermediate. Here we show that the addition of neutral sugars to solutions of acid-denatured equine ferricytochrome c induces formation of the A-state in the absence of added salt. We characterized the structure and stability of the sugar-induced A-state with circular dichroism spectropolarimetry (CD) and NMR-monitored hydrogen-deuterium exchange experiments. We also examined the stability of the sugar-induced A-state as a function of sugar size and concentration. The results are interpreted using several models and we conclude that the stabilizing effect is consistent with increased steric repulsion between the protein and the sugar solutions.     

Inefficiency of lactation in primiparous rats: the costs of first reproduction

To investigate the energetic costs of lactation in a female mammal in relation to previous reproductive history, we compared the performance of adult female Long-Evans rats that had previously bred (multiparous) with young females that had not previously given birth (primiparous). All litters were standardized to 10 +/- 1 young. We compared maternal production (growth of pups), body mass, and energy intake (food consumption) of mothers, as well as their energy expenditure (resting oxygen consumption). The mass of litters at birth and the growth of pups during lactation did not differ according to reproductive history of the mothers. The body mass of primiparous mothers was less than that of multiparous mothers, and primiparous mothers showed an increase in mass during early lactation. To accomplish the essentially identical production of offspring under these circumstances, the primiparous mothers consumed and expended more energy than the multiparous mothers. This remarkable performance of first-time mothers results in an overall efficiency of energy allocation to reproduction amounting to only 25%, compared with 38% in multiparous mothers. The energetic inefficiency of primiparous female lactation results largely from the excessive expenditures associated with physiological and behavioral performances of first-time reproduction, together with a small component of additional expenditure due to further growth by the primiparous mothers. We suggest that this inefficiency probably contributes to the observed low reproductive success of novice breeders; furthermore, active restraint of fecundity may be an evolutionary response to the constraints of the energetic inefficiency of primiparous breeding by female mammals.     

Secobarbital in humans discriminating triazolam under two-response and novel-response procedures

The percentage of long-term survivors after intensive chemotherapy and the outcome of MDS patients who achieve partial remission (PR) with intensive chemotherapy (IC) are not known. Between 1981 and 1996 we treated 99 patients with de novo MDS who had high-risk MDS or progression to AML, with IC. 41 (41%) achieved CR, 16 (16%) achieved partial remission (PR), 26 (26%) had failure, and 16 (16%) died in aplasia. Eight of the patients who achieved CR were autografted, three were allografted and the remaining cases received moderate consolidation chemotherapy. After IC, the 16 PR patients fulfilled the criteria for RA in 15 cases and CMML in one case. Median PR duration was 17 months, and three PR were > 3 years (39, 50+, 82+ months). Median actuarial survival of patients who achieved PR and CR was 18 months and 20 months from the onset of IC, respectively (difference not significant). Of the 71 patients treated before 1993, with sufficient follow-up, 10 (14%) had survived > 4 years (long-term survivors). Four of them were alive in first CR after 49+ to 110+ months and probably cured, two were alive in PR after 50+ and 82+ months and four had died after 49-78 months. Long-term survivors were characterized by a significantly higher incidence of RAEB-T at diagnosis, and with normal or favourable cytogenetic findings. In patients with RAEB-T at diagnosis included before 1993, 8/23 (35%) cases who had no unfavourable karyotype had survived > 4 years. Our findings suggest that MDS patients who achieve PR with IC, and not only those who achieve CR, can benefit from this type of treatment. The percentage of long-term survivors remains low, however, and is almost restricted to patients with RAEB-T at diagnosis and no unfavourable karyotype.     

Force and myosin content variation in isolated intact single muscle fibres from Rana temporaria

We studied the relation between force normalized by dry mass per unit length and the myosin fraction of muscle dry mass. The two tibialis anterior muscles were dissected from 12 frogs (Rana temporaria). Then, from one muscle, two single fast-twitch fibres were isolated. Each fibre was mounted isometrically in Ringer's solution, and electrically stimulated using a standardized protocol. Peak force production, normalized by the fibre's dry mass per unit length, varied by a factor of 1.4. Little variation in normalized force was measured between fibres from the same animal, whereas between animals a significant difference was found (P<0.05). The contralateral muscle was used to determine the myosin fraction of the dry mass. The relationship between the fraction myosin of the dry mass and force normalized by dry mass per unit length showed a high correlation (r = 0.81; n = 12). From this we conclude that variation in normalized tetanic force is determined greatly (65%) by variations in myosin content.     

Optically stimulated luminescence (OSL) and laser excited photo luminescence of electron beam treated (EBT) diamonds: Radiation sensitization and potential for tissue equivalent dosimetry

We report the first optically stimulated luminescence (OSL; blue light stimulated luminescence (BLSL) and infrared light stimulated luminescence (IRSL)) results on colored diamonds and present experimental evidence that electron beam treatment (EBT) increases the radiation sensitivity of diamonds to a level that makes them suitable for low level radiation dosimetry. A suite of seven samples was examined. These comprise a white, three brown and three yellow diamond pieces. The FT-IR spectra of these diamonds revealed the nature and concentration of nitrogen impurity. The white diamond was kept as a control. The brown and yellow (with varied saturation) diamonds were irradiated by a 1.7 MeV electron beam. These turned blue/dark green; three of them were then heated in vacuum in the temperature range of 850-900 °C for two hours. Heating turned the irradiated diamonds to lemon yellow, pink, and purple colors. The irradiated and unheated blue samples were designated as 2C and 2D.The control sample, an un-irradiated white type Ia diamond, did not yield any significant IRSL/BLSL with doses up to 100 Gy. The BLSL/IRSL sensitivity of irradiated and heat treated diamonds was very poor, and depended on the heat cycle and hence were not pursued. Sample 2C exhibited significant BLSL and negligible IRSL sensitivity. Sample 2D gave an intense orange red emission under IR excitation as also responded to BLSL. The dose response of the BLSL signal in 2C suggested a minimum detectable dose of ~ 0.1 Gy and its use as a tissue equivalent dosimeter.Based on supporting experiments such as laser excited photoluminescence, we suggest that the BLSL process in 2C is primarily driven by carbon vacancies, which release a mobile hole when excited by GR2 band in the blue region. BLSL intensity exhibited a maximum around 285 °C. Given that TL glow peak also occurs near this temperature and that the nitrogen-interstitial carbon (N-Ci) complex also forms at this temperature (as reported in the literature), and it appears that the e-h recombination at sites with N-Ci complex could be involved in BLSL production. Laser excited photoluminescence (PL) at wavelengths 325, 514 and 785 nm and absorption spectra in UV-Visible range gave insights into the contrasting BLSL/IRSL responses of 2C and 2D. These differences were due to differences in nitrogen impurity complexes and the concentration of carbon vacancies produced by EBT in 2C and 2D. In 2D, the presence of Ni as NE8 center (four nitrogens coordinated to Ni) giving 800 nm emission on 785 nm excitation, appeared to suppress BLSL and sensitize IRSL in the orange window.