High temporal and spatial quality petawatt-class Ti:sapphire chirped-pulse amplification laser system.

Optical parametric chirped-pulse amplification (OPCPA) operation with low gain by seeding with high-energy, clean pulses is shown to significantly improve the contrast to better than 10(-10) to 10(-11) in a high-intensity Ti:sapphire laser system that is based on chirped-pulse amplification. In addition to the high-contrast broadband, high-energy output from the final amplifier is achieved with a flat-topped spatial profile of filling factor near 77%. This is the result of pump beam spatial profile homogenization with diffractive optical elements. Final pulse energies exceed 30 J, indicating capability for reaching peak powers in excess of 500 TW.

Cerebral activation related to the control of mastication during changes in food hardness.

To investigate the neural network involved in the control of mastication during changes in food hardness, we employed functional magnetic resonance imaging while 15 healthy subjects chewed gum whose hardness was changed by chewing. By comparing the areas activated when the hardness of the bolus varied widely with those seen when the hardness of the bolus had stabilized, we identified selective activations of the supplementary motor area, the dorsolateral prefrontal cortex, the superior temporal gyrus of the left hemisphere, and the premotor area and inferior parietal lobule of the right hemisphere. These findings indicate that these areas are probably related to processes linking sensory input and motor output involved in the change of hardness food during mastication.

Visualization and detectability of elements rarely contained in soft tissue by X-ray scanning analytical microscopy and electron-probe micro analysis.

The detectability of elements rarely contained in soft tissue was compared using X-ray scanning analytical microscope (XSAM) and electron-probe micro analysis (EPMA). Mapping images of Ca, S and P in normal soft tissue of the rat and dissolved Ni in Ni implanted soft tissue could be obtained by XSAM and EPMA. EPMA was more sensitive in detection of P, while XSAM was superior for Ca, S and Ni mapping. The high detectability for heavier elements by XSAM was explained by the large volume of characteristic X-ray generation in XSAM and low attenuation of the characteristic X-rays from heavier elements. XSAM could provide clearer mapping images for heavier elements whose concentration was low without radiation damage to specimens.

Effects of dietary arginine supplementation on protein turnover and tissue protein synthesis in scald-burn rats.

We assessed the effects of dietary arginine supplementation on protein turnover and organ protein synthesis in burned rats. Male Wistar rats weighing about 200 g underwent catheter jejunostomy and received scald burns covering 30% of the whole-body surface area. Animals were divided into a control group (n = 9) and an arginine group (n = 9) and continuously received total enteral nutrition for 7 d (250 kcal.kg-1.d-1, 1.72 gN.kg-1.d-1). Changes in body weight, plasma total protein, plasma albumin, urinary excretion of polyamines, nitrogen balance, whole-body protein kinetics, and tissue protein synthesis rates were determined. Whole-body protein kinetics and tissue fractional protein synthetic rates (Ks, percent/d) were estimated using a 24-h constant enteral infusion of 15N glycine on the last day. The changes in body weight were not different between the control and arginine groups. The urinary excretion of polyamines was higher in the arginine group than in the control group (P < 0.01). Burned rats enterally fed arginine-supplemented diet yielded significantly greater cumulative and daily nitrogen balance on days 3 and 5 than those fed a control diet (cumulative, P < 0.05; day 3, P < 0.01; day 5, P < 0.01). Whole-body protein turnover rate was significantly elevated in the arginine group as compared to that in the control group (P < 0.05). The Ks of rectus abdominis muscles were significantly increased in the arginine group in comparison to the control group (P < 0.01). We have shown that dietary arginine supplementation improved protein anabolism and attenuated muscle protein catabolism after thermal injury.

Induction of differentiation of myelogenous leukemia cells by humulone, a bitter in the hop.

The active form of vitamin D, 1alpha,25-dihydroxyvitamin D3 (VD3), inhibits proliferation and induces differentiation of myelomonocytic leukemia cells, but its clinical use is limited by the adverse effect of hypercalcemia. VD3 mobilizes calcium stores from bone by inducing the dissolution of bone mineral and matrix. We have recently found that humulone, a bitter in the hop extract for beer brewing, effectively inhibits bone resorption. In this study we examined the effect of humulone on the differentiation of human myelogenous leukemia cells. Humulone alone inhibited the growth of monoblastic leukemia U937 cells while only slightly increasing differentiation markers such as nitroblue tetrazolium (NBT)-reducing and lysozyme activities. Humulone effectively enhanced the differentiation-inducing action of VD3. Other myelomonocytic leukemia cells were induced to differentiate by VD3 and this was also enhanced by humulone. Since humulone is a less-toxic inhibitor of bone resorption, the combination of humulone and VD3 may be useful in differentiation therapy of myelomonocytic leukemia.

Assessment of radiochemical design of antibodies using an ester bond as the metabolizable linkage: evaluation of maleimidoethyl 3-(tri-n-butylstannyl)hippurate as a radioiodination reagent of antibodies for diagnostic and therapeutic applications.

Reduction of radioactivity levels in nontarget tissues such as the liver and kidney constitutes a problem to be resolved in diagnostic and therapeutic applications of radiolabeled monoclonal antibodies (mAbs). A new radioiodination reagent with an ester bond to liberate m-iodohippuric acid from covalently conjugated proteins, maleimidoethyl 3-(tri-n-butylstannyl)hippurate (MIH), was recently developed. MIH liberated m-iodohippuric acid from galactosylneoglycoalbumin in murine liver, and the radiometabolite was rapidly eliminated from the liver into urine as an intact structure. In this study, intact IgG and Fab fragment of a mAb against osteogenic sarcoma were radioiodinated with MIH to further assess the applicability of MIH to radioimmunoimaging and therapy. For comparison, a mAb radioiodinated with N-succinimidyl iodobenzoate (SIB) and indium-111 (111In)-labeled mAbs with diethylenetriaminepentaacetic dianhydride (cDTPA) or 1-[4-[(5-maleimidopentyl)amino]benzyl]-ethylenediaminetetraacetic acid (EMCS-Bz-EDTA) were used. Size-exclusion HPLC analysis and cell binding assays indicated the preservation of both structure and antigen binding affinity of radioiodinated MIH-OST7 (IgG). In biodistribution studies in mice, [125I]MIH-OST7 (IgG) showed faster systemic clearance of radioactivity after 24 h postinjection than did [131I]SIB- and [111In]EMCS-Bz-EDTA-OST7 (IgG). [125I]MIH-OST7 (IgG) also exhibited much lower radioactivity levels in nontarget tissues such as the liver and kidney, with higher radioactivity levels in the blood up to 72 h postinjection when compared with [111In]cDTPA-OST7 (IgG). Radioactivity excreted from the mice was found in the urine as m-iodohippuric acid, following administration of [125I]MIH-OST7 (IgG). In athymic mice bearing osteogenic sarcoma, [131I]MIH-OST7 (IgG) indicated higher tumor-to-nontarget ratios of radioactivity at both 24 and 48 h postinjection than [125I]SIB-OST7 (IgG). Although both radioiodinated OST7s showed similar radioactivity levels in the target at 24 h postinjection, a small but significant decrease in the target radioactivity level was observed with [131I]MIH-OST7 (IgG) at 48 h postinjection. In addition, [131I]MIH-OST7 (Fab) showed very rapid cleavage of the ester bond both in vivo and in vitro. These findings indicated that while MIH may be a useful reagent for radioimmunoimaging using IgG, mAb, its application to smaller molecular weight mAbs and radioimmunotherapy would be hindered due to the labile characteristics of the ester bond in plasma. Thus, while the present study reinforced the usefulness of metabolizable linkages for reducing nontarget radioactivity levels, a development of plasma-stable metabolizable linkages is also warranted for radioimmunotherapy and for smaller molecular weight polypeptides.

Ginseng pretreatment protects against transient global cerebral ischemia in the rat: measurement of local cerebral glucose utilization by [14C]deoxyglucose autoradiography.

The effect of ginseng on brain glucose metabolism has been determined in normal and transient cerebral ischemic rat using the autoradiographic [14C]2-deoxyglucose method. Ginseng had no effect on local cerebral glucose utilization (LCGU) in normal rat. By contrast, in rats subjected to 30 min of four vessel occlusion, a significant reduction of LCGU was shown in parts of the cortex and striatum in comparison to the control group. One-week administration of ginseng at 200 mg/kg/d before the occlusion produced an improvement of LCGU compared with the untreated group. These findings indicate that ginseng has some protective effects against brain damage in transient global cerebral ischemia.

Initial clinical experiences with dopamine D2 receptor imaging by means of 2'-iodospiperone and single-photon emission computed tomography.

Dopamine D2 receptor imaging was performed with 123I labeled 2'-iodospiperone (2'-ISP) and single-photon emission computed tomography (SPECT) in 9 patients: 4 with idiopathic Parkinson's disease, 2 with parkinsonism, 1 with Wilson's disease and 2 with pituitary tumor, and the results were compared with the data for 9 normal subjects. Following an intravenous injection of 123I-2'-ISP, early (within 30 min) and late (between 2 and 4 hr) SPECT images were obtained by means of a multi-detector SPECT scanner or a rotating gamma camera. In normal subjects, early SPECT images demonstrated uniform distribution of radioactivity in the cerebral gray matter and cerebellum reflecting regional cerebral blood flow, whereas late SPECT images showed high radioactivity only in the basal ganglia. All the patients with Parkinson's disease also demonstrated symmetrical basal ganglia uptake in the late SPECT images, but it was diminished in parkinsonism and Wilson's disease. One patient with a growth hormone-producing pituitary tumor had a positive uptake in the tumor. These preliminary clinical data demonstrated that 2'-ISP can be used for SPECT imaging of D2 dopamine receptors and may be of clinical value for the diagnosis and planning of the treatment of neurological diseases.

Effects of progesterone on concentrations of monoamines in hypothalamic areas and plasma prolactin levels in rats.

The role of progesterone to increase prolactin (PRL) secretion on the first estrous day in pubertal rats was compared with its role in adult cyclic rats. The first estrus was induced by the administration of pregnant mare serum gonadotrophin (5 IU) at 28 days of age. A subcutaneous administration of 2.5 or 7.5 mg of progesterone/100 g body wt significantly increased the concentration of plasma PRL in pubertal rats within 4 hr. The PRL level obtained after progesterone administration was greater than that in similarly treated adult rats. The concentration of dopamine in the arcuate nucleus-median eminence (ARC-ME) in pubertal rats significantly decreased after a lower dosage of progesterone was administered, but no change was found in the preoptic area concentration. In adult estrous rats, the concentration of dopamine in the ARC-ME showed a tendency to decrease after the administration of a larger dose of progesterone (7.5 mg/100 g body wt). No change was observed in the concentrations of indoleamines in the preoptic area and ARC-ME after the administration of progesterone in both pubertal and adult rats. The concentrations of dopamine in the preoptic area and ARC-ME were lower in pubertal rats than in adults. The concentration of 5-hydroxyindole acetic acid and the ratio of 5-hydroxyindole acetic acid to 5-hydroxytryptamine in the ARC-ME were higher in pubertal rats than in adults. These results indicate that progesterone causes a greater increase in tonic PRL secretion in pubertal rats than in adult rats and that a lower hypothalamic dopamine activity and a higher serotonin activity in pubertal rats may account for these differences.