Search

Proton magnetic resonance spectroscopy (1H‐MRS) studies have demonstrated abnormal levels of a variety of neurometabolites in inpatients/outpatients with alcohol use disorder (AUD) following acute alcohol withdrawal relative to healthy controls. In contrast, few studies have compared neurometabolite levels between less severe, treatment‐naïve AUDindividuals and light drinkers (LD) or related them to recent alcohol consumption. The present study compared neurometabolite levels between treatment‐naïve AUDand LDindividuals. Twenty treatment‐naïve individuals with AUDand 20 demographically matched LDcompleted an 1H‐MRSscan, approximately 2.5 days following their last reported drink. 1H‐MRSdata were acquired in dorsal anterior cingulate (dACC) using a 2‐dimensional J‐resolved point‐resolved spectroscopy sequence. dACCneurometabolite levels, with a focus on glutamate, glutamine, and GABA, were compared between AUDand LDparticipants. The associations between metabolite levels and recent drinking were explored. AUDparticipants had significantly lower concentrations of GABA(Cohen's d= 0.79, p =0.017) and glutamine (Cohen's d= 1.12, p =0.005), but not glutamate (Cohen's d= 0.05, p =0.893), relative to LD. As previously reported, AUDparticipants’ glutamate and N‐acetylaspartate concentrations were inversely associated with their number of heavy drinking days. In contrast, neither number of drinking (mean p =0.56) nor heavy drinking (mean p =0.47) days were associated with metabolite concentrations in LD. The present study demonstrated significantly lower levels of prefrontal γ‐aminobutyric acidand glutamine in treatment‐naïve individuals with AUDrelative to LD. Whether these findings reflect the neurotoxic consequence and/or neuroadaptive response of alcohol consumption versus a predrinking trait, and therefore a more durable neurochemical disturbance, awaits elucidation from longitudinal studies. Treatment‐naïve individuals with Alcohol Use Disorder (n = 20, M[SD] Age = 26.8[6.2]) had significantly lower levels of dorsal Anterior Cingulate Cortex GABA(Cohen's‐D= 0.79) and Glutamine (Cohen's‐D= 1.12) relative to demographically‐matched light‐drinkers via Proton Magnetic Resonance Spectroscopy. These results are important because they demonstrate AUD‐associated neurochemical disturbances in a younger/less severe sample than has previously been studied with 1H‐MRS. If replicated, these findings may lead to enhanced knowledge of how the GABAand glutamate systems change with drinking and also to novel pharmacological interventional/preventative strategies.

Background and purposeCurrently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD.Materials and methodsA patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Inter-phantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR).ResultsQuantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5–6.2, showing reproducible phantom durability.ConclusionsA plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization.

Proton magnetic resonance spectroscopy (1H‐MRS) studies have consistently found abnormal brain concentrations of N‐acetylaspartate (NAA) and glutamate in individuals with alcohol use disorders (AUD) relative to light drinkers. However, most such studies have focused on individuals in treatment for severe alcohol dependence (AD), and few studies have investigated associations between neurochemical concentrations and recent alcohol consumption. This study focused on associations between recent drinking and prefrontal neurometabolite concentrations in nonsevere, non‐treatment‐seeking individuals with AUD. Nineteen treatment‐naïve alcohol‐dependent individuals aged 21 to 40 completed a 1H‐MRSscan. Single‐voxel 1H‐MRSspectra were acquired in dorsal anterior cingulate cortex (dACC) using a 2‐dimensional J‐resolved point resolved spectroscopy sequence. Associations between recent heavy drinking, assessed using the Timeline FollowBack, and dACCmetabolite concentrations were estimated via regression controlling for within‐voxel tissue composition. Participants provided a negative breathalyzer reading and reported between 1 and 5 days (M= 2.45, SD= 1.23) since their last drink. Number of heavy drinking days in the 14 days preceding the scan (M= 4.84, SD= 3.32) was significantly inversely associated with both glutamate/water (β = −0.63, t(17) = −3.37, p= 0.004) and NAA/water concentrations (β = −0.59, t(17) = −2.98, p= 0.008). This study extends the literature by demonstrating inverse associations between recent heavy drinking and dACCglutamate and NAAconcentrations in a sample of nonsevere, non‐treatment‐seeking individuals with AD. These findings may support the hypothesis that amount of recent alcohol consumption may account for differences in neuronal metabolism, even in nonsevere, non‐treatment‐seeking alcoholics. Proton magnetic resonance spectroscopy (1H‐MRS) studies have historically focused on severe, treatment‐seeking alcoholics, and few studies have investigated associations between neurochemistry and alcohol consumption. In this study, 19 treatment‐naïve alcoholics completed a 2D J‐resolved 1H‐MRSscan. For the past 2 weeks, the number of heavy drinking days was significantly inversely associated with dorsal anterior cingulate glutamate/water (left) and NAA/water (right) concentrations. These findings may suggest that amount of recent alcohol consumption may account for differences in neuronal metabolism, even in nonsevere, non‐treatment‐seeking alcoholics.

BACKGROUND New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear. OBJECTIVE To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study. DESIGN A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York. SETTING The Washington Heights/Inwood Columbia Aging Project. PARTICIPANTS Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements. MAIN OUTCOME MEASURE Incident AD. RESULTS White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03). Relative hippocampal volume did not predict incident dementia when considered alone (HR = 0.419; P = .77) or with the WMH measures included in the model (HR = 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR = 1.197; P = .049). CONCLUSIONS The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology.

BACKGROUND The importance of subclinical cerebrovascular disease in the elderly is increasingly recognized, but its determinants have not been fully explicated. Elevated blood pressure (BP) and fluctuation in BP may lead to cerebrovascular disease through ischemic changes and compromised cerebral autoregulation. OBJECTIVE To determine the association of BP and long-term fluctuation in BP with cerebrovascular disease. DESIGN A community-based epidemiological study of older adults from northern Manhattan. SETTING The Washington Heights–Inwood Columbia Aging Project. PARTICIPANTS A total of 686 nondemented older adults who had BP measurements during 3 study visits at 24-month intervals and underwent structural magnetic resonance imaging (corresponding temporally with the third assessment). We derived the mean (SD) of the mean BP for each participant during the 3 intervals and divided the participants into 4 groups defined as below or above the group median (≤96.48 or >96.48 mm Hg) and further subdivided them as below or above the median SD (≤7.21 or >7.21 mm Hg). This scheme yielded 4 groups representing the full range of BPs and fluctuations in BP. MAIN OUTCOME MEASURES Differences in white matter hyperintensity (WMH) volume and presence of brain infarctions across groups. RESULTS White matter hyperintensity volume increased across the 4 groups in a linear manner, with the lowest WMH volume in the lowest mean/lowest SD group and the highest WMH volume in the highest mean/highest SD group (F3,610 = 3.52, P = .02). Frequency of infarction also increased monotonically across groups (from 22% to 41%, P for trend = .004). CONCLUSIONS Compared with individuals with low BP and low fluctuations in BP, the risk of cerebrovascular disease increased with higher BP and BP fluctuations. Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating BP and elevated BP.Arch Neurol. 2010;67(5):564-569--

BACKGROUND Hippocampal atrophy and reductions in basal cerebral blood volume (CBV), a hemodynamic correlate of brain function, occur with cognitive impairment in Alzheimer disease, but whether these are early or late changes remains unclear. Magnetic resonance imaging is used to assess structure and function in the hippocampal formation. OBJECTIVE To estimate differences in the associations of hippocampal and entorhinal cortex volumes and CBV with memory function in the early and late stages of cognitive impairment by relating these measures to memory function in persons with and without dementia who underwent detailed brain imaging and neuropsychological assessment. DESIGN Multivariate regression analyses were used to relate entorhinal cortex volume, entorhinal cortex CBV, hippocampal volume, and hippocampal CBV to measurements of memory performance. The same measures were related to language function as a reference cognitive domain. SETTING Community-based cohort. PARTICIPANTS Two hundred thirty-one elderly Medicare recipients (aged ≥65 years) residing in northern Manhattan, New York. MAIN OUTCOME MEASURES Values for entorhinal cortex volume, hippocampal volume, entorhinal cortex CBV, and hippocampal CBV and their relation to memory performance. RESULTS No association was noted between entorhinal cortex volume or hippocampal CBV and memory. Decreased hippocampal volume was strongly associated with worse performance in total recall, and lower entorhinal cortex CBV was associated with lower performance in delayed recall. Excluding persons with Alzheimer disease, the association of entorhinal cortex CBV with memory measures was stronger, whereas the association between hippocampal volume and total recall became nonsignificant. CONCLUSIONS In the early stages of Alzheimer disease or in persons without dementia with worse memory ability, functional and metabolic hippocampal hypofunction contributes to memory impairment, whereas in the later stages, functional and structural changes play a role.Arch Neurol. 2009;66(11):1385-1392--

Inflammatory biomarkers, including lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) are associated with ischemic stroke risk. White matter hyperintensities (WMH) seen on brain MRI scans are associated with vascular risk factors and an increased risk of incident stroke, but their relation to inflammatory biomarkers is unclear.

BACKGROUND Mild parkinsonian signs (MPS) are a marker of incident dementia. They have been linked with cerebrovascular disease, which can be evaluated using magnetic resonance imaging (MRI). Also, if MPS are a marker for developing Alzheimer-type changes, hippocampal volume on MRI might be diminished in individuals with MPS. OBJECTIVE To examine white matter hyperintensity (WMH) volume and total hippocampal volume in elderly individuals with and without MPS. METHODS Community-dwelling elderly persons in northern Manhattan (New York), New York, underwent neurologic examination and brain MRI. The WMH volume (derived from fluid-attenuated inversion recovery–weighted MRIs using a semiautomated thresholding approach) and total hippocampal volume (derived manually) were expressed relative to total cranial volume. RESULTS Mild parkinsonian signs were present in 111 of 666 participants (16.7%). Mean (SD) relative WMH volume was larger in participants with MPS vs those without MPS (1.70 [1.28] vs 1.17 [1.18]; P < .001). In a multivariate logistic regression analysis adjusting for age, sex, race/ethnicity, years of educational achievement, and depression, relative WMH volume was associated with MPS (odds ratio, 1.26; 95% confidence interval, 1.08-1.47; P = .004). In both unadjusted and adjusted analyses, total relative hippocampal volume was similar in participants with MPS vs those without MPS regardless of cognitive status. CONCLUSIONS In this MRI study of community-dwelling elderly persons, WMH volume was associated with MPS and total relative hippocampal volume was not. These data raise the possibility that vascular disease could have a role in the development of MPS.Arch Neurol. 2008;65(12):1649-1654--

BACKGROUND Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease. OBJECTIVE To examine the effects of age, sex, race/ethnicity, and vascular disease history on measures of brain morphology, including relative brain volume, ventricular volume, hippocampus and entorhinal cortex volumes, and white matter hyperintensity (WMH) burden, in a large community-based cohort of racially/ethnically diverse older adults without dementia. DESIGN The associations of age, sex, race/ethnicity, and self-reported vascular disease history with brain morphology were examined in a cross-sectional study using multiple linear regression analyses. Sex × race/ethnicity interactions were also considered. SETTING The Washington Heights–Inwood Columbia Aging Project, a community-based epidemiological study of older adults from 3 racial/ethnic groups (white, Hispanic, and African American) from northern Manhattan. PARTICIPANTS Beginning in 2003, high-resolution quantitative magnetic resonance (MR) images were acquired in 769 participants without dementia. MAIN OUTCOME MEASURES Relative brain volume (total brain volume/intracranial volume), ventricular volume, and hippocampus and entorhinal cortex volumes were derived manually on high-resolution MR images. White matter hyperintensities were quantified semiautomatically on fluid-attenuated inversion recovery–T2-weighted MR images. RESULTS Older age was associated with decreased relative brain volume and with increased ventricular and WMH volumes. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than white participants, but the associations of these variables with age were similar across racial/ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and with higher WMH burden, particularly among African Americans. CONCLUSIONS Older age and vascular disease, particularly among African Americans, are associated with increased brain atrophy and WMH burden. African American and Hispanic subjects have larger relative brain volumes and more WMH than white subjects. Racial/ethnic group differences in WMH severity seem to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.Arch Neurol. 2008;65(8):1053-1061--

The spatio-temporal nature of focused ultrasound-induced blood-brain barrier (BBB) opening as a brain drug delivery method was investigated in Alzheimer's disease model mice. The left hippocampus of transgenic (APP/PS1, n= 3) and nontransgenic (n= 3) mice was sonicated (frequency: 1.525 MHz, peak-negative pressure: 600 kPa, pulse length: 20 ms, duty cycle: 20%, duration: 1 min) in vivo, through their intact skin and skull, after intravenous injection of microbubbles (SonoVue®5; 25 μl). Sequential, high-field MR images (9.4 Tesla) were acquired before and after injection of gadolinium (Omniscan™ 0.75 ml, molecular weight: 573.7 Da) on two separate days for each mouse. Gadolinium deposits through the ultrasound-induced BBB opening in the left hippocampus revealed significant contrast-enhancement in the MRI. On the following day, MRI revealed significant BBB closure within the same region. However, the BBB opening extent and BBB closing timeline varied in different regions within the same sonicated location. This indicates that opening and closing were dependent on the brain region targeted. No significant difference in BBB opening or closing behaviors was observed between the APP/PS1 and the nontransgenic mice. In conclusion, a BBB-impermeable molecule was noninvasively, transiently and reproducibly delivered to the hippocampus of Alzheimer's APP/PS1 mice.

We examined white matter hyperintensity volume (WMHV) and subclinical infarction (no history of clinical stroke; SI) in relation to performance on tests of sequencing, cognitive flexibility, and sensorimotor ability.

BACKGROUND Neurotoxicity related to the Aβ peptide is thought to be a primary mechanism of dysfunction in Alzheimer disease (AD). Although numerous imaging studies have observed brain dysfunction in AD, whether these imaged defects reflect Aβ-related neurotoxicity remains unknown. OBJECTIVE To study Aβ-related neurotoxicity by means of functional imaging maps of the hippocampal formation in human patients and mouse models. DESIGN Cross-sectional study comparing humans with AD and control subjects, cross-sectional study of J20 mice, a transgenic mouse model of AD, and a longitudinal study of flurbiprofen administration to transgenic mice. SETTING Alzheimer disease research center. SUBJECTS Eleven subjects with probable Alzheimer disease and 11 age-matched controls, plus J20 mice and wild-type littermates. INTERVENTIONS In the first study, human subjects and controls underwent magnetic resonance imaging. In the second study, mice underwent imaging at 3, 6, 12, 15, and 21 months of age, for a total of 57 imaging experiments. In the third study, 12 J20 mice underwent imaging repeatedly over time; 6 received flurbiprofen to ameliorate Aβ-related neurotoxicity and 6 received vehicle control. MAIN OUTCOME MEASURES Comparison of hippocampal functional maps. RESULTS Among all hippocampal subregions, the entorhinal cortex was the dominant site of dysfunction observed in both human patients and J20 mice. Long-term administration of flurbiprofen rescued entorhinal cortex dysfunction in transgenic mice. CONCLUSION Our results establish that the neurotoxicity related to the Aβ peptide can be captured in vivo by functional imaging and suggest hippocampal subregions most vulnerable to its toxic effects.Arch Neurol. 2007;64:(10)938-944--

Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases.

SUMMARYLeprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium lepraeremains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. lepraeand the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases.

Direct injection of oxygen into an in-vivo tumor system was performed using saline lavage through a double-lumen catheter inserted into a Walker 256 carcinoma implanted in the flank of a rat. Ten extremely hypoxic tumors (core pO20 to 1 mm Hg) were examined. The mean pO2in these tumors increased from 66 to 112 mm Hg after S minutes of lavage with oxygenated saline. These results indicate a substantial increase in tumor pO2can be obtained with this system, possibly resulting in improved radioresponsiveness. More general applications of this system may also be feasible.

This paper extends the use of principal-component analysis in spectral quantification to the estimation of frequency and phase shifts in a single resonant peak across a series of spectra. The estimated parameters can be used to correct the spectra accordingly, resulting in more accurate peak-area estimation. Further, the removal of the variations in phase and frequency caused by instrumental and experimental fluctuations makes it possible to determine more accurately the remaining variations, which bear biological significance. The procedure is demonstrated on simulated data, a 3D chemical-shift-imaging dataset acquired from a cylinder of inorganic phosphate (Pi), and a set of 73631P NMRin vivospectra taken from a kinetic study of rat muscle energetics. In all cases, the procedure rapidly and automatically identifies the frequency and phase shifts present in the individual spectra. In the kinetic study, the procedure is used twice, first to adjust the phase and frequency of a reference peak (phosphocreatine) and then to determine the individual frequencies of the Pipeak in each of the spectra which further can be used for estimation of pH changes during the experiment.

An RF network and a dual‐tuned surface coil are described for obtaining proton‐decoupled, NOE enhanced 19F spectra from a whole body clinical imager operating at 1.5 Tesla. The network removes 19F frequency noise from the decoupler transmitter and prevents preamplifier saturation from high‐level decoupling signals. Proton decoupling of 19F spectra was optimized using a sample of urine containing 5‐fluorouracil (5‐FU) and its catabolite fluoro‐β‐alanine (FBAL). Protondecoupled 19F spectroscopy in vivois demonstrated by obtaining both nonlocalized spectra and spectra localized with three‐dimensional chemical shift imaging from the liver of patients undergoing 5‐FU chemotherapy.

The results of an initial study on the feasibility of using the phosphonium analog of choline to follow the metabolism of phosphatidylcholine in tumors in vivousing 31P NMR are reported. C3H/He mice bearing a mammary carcinoma tumor on the foot pad were fed a choline‐free diet supplemented with the phosphonium analog of choline. Metabolites of this compound, including the phosphonium analogs of phosphatidylcholine, phosphocholine, glycerophosphocholine, and betaine were observed noninvasively in vivoin tumors by 31P NMR after 2–3 weeks of feeding. Clearance of these phosphonium‐labeled metabolites from tumors was measured after a change to a choline‐containing diet. Significant decreases were seen in the levels of the analogs of betaine (P< 0.003) and phosphatidylcholine (P< 0.004) by Day 4. A significant increase in the level of authentic phosphocholine (P< 0.003) occurred over the same time period.

3-Deoxyglucosone (3DG), a reactive dicarbonyl, is an important intermediate in the formation of advanced glycation end products (AGEs). The AGEs are particularly important in diabetes since they have been correlated with the development of diabetic complications. Consequently, measurements of 3DG are likely to provide valuable insights into the role of this metabolite in the etiology of diabetic complications. While several methods of 3DG quantitation in human plasma have been previously published, a significant discrepancy (over 30-fold) exists in the reported values. Knechtet al.(Arch. Biochem. Biophys.294, 130–137, 1992) have reported the levels of plasma 3DG in normoglycemics to be 61 nm, using a GC/MS procedure. In contrast to this, Niwaet al.(Biochem. Biophys. Res. Commun.196, 837–843, 1993) reported 3DG levels to be 1800 nmin normoglycemics, using a totally independent GC/MS method. To resolve this disagreement and fill the need for a robust assay for this dicarbonyl, suitable for absolute quantitation, a GC/MS procedure was devised for its measurement. Plasma samples were deproteinized either by ultrafiltration or by addition of ethanol as described by Niwaet al.(Biochem. Biophys. Res. Commun.196, 837–843, 1993). 3DG in the ultrafiltrate or the supernatant was conjugated with 2,3-diaminonaphthalene to produce a stable adduct which was then converted to a silyl ether and analyzed by GC/MS. The analyte was monitored by selected ion monitoring at anm/zof 295 and 306 and quantitated using an internal standard of [U-13C]3DG. Using this approach, 3DG levels in plasma deproteinized by ultrafiltration were found to be significantly elevated from 58.5 ± 14 (SD) nmin normoglycemics to 98.5 ± 34 (SD) nmin type I diabetics. When deproteinization of the plasma was carried out using ethanol, the levels of 3DG from normoglycemic plasma were similar to those reported by Niwaet al.(1710 ± 750 (SD) nm). These results suggest that 3DG levels measured by ultrafiltration may represent the free circulating 3DG and those obtained by ethanol extraction may represent aform of 3DG bound to a macromolecule (presumbaly protein).

Refocused insensitive nucleus enhancement by polarization transfer (RINEPT) from protons (1H) to a J‐coupled phosphorus (31P) has been incorporated into three‐dimensional (3D) chemical‐shift‐imaging (CSI) sequence on a clinical imager. The technique is demonstrated on a phantom and in in vivohuman brain. The polarization‐transfer efficiency (∼1.2) is lower than the theoretical maximum of γ1H/γ31P≈ 2.4 resulting from 1H‐1H homonuclear J couplings of similar magnitude competing with the 1H →31P transfer. Nevertheless, compared with direct 31P Ernst‐angle excitation, signal gains of up to × 1.8 were obtained mainly as a result of T1differences between 31P and the 1H. Spectral interpretation is simplified by editing out all non‐proton‐coupled 31P signals. The duration, ∼50 min, and power deposition, ∼1 W · kg−1, make the application suitable for human studies.

Simultaneous acquisition of 1H‐decoupled 31P and 19F 3D CSI is demonstrated in the liver of a patient undergoing 5‐fluorouracil chemotherapy. Both 31P and 19F shared the same voxel size (64 or 27 ml), bi‐level 1H‐decoupling and 0.35 s TR.The measurements were done in a 1.5 Tesla clinical imager with three radio‐frequency (RF) channels and a triple‐tuned surface‐coil. The overall MRI and MRS examination time was under 90 min. Simultaneous acquisition of 31P and 19F permits localized study of the influence of hepatic metabolism on the uptake and catabolism of fluoropyrimidine drugs without extra measurement time or higher SAR.

A method is described for quantifying phosphorus metabolites in tissue using spectra localized with surface coils and chemical shift imaging (CSI) and assuming that metabolites are uniformly distributed within a well‐defined volume. An analytical expression is developed that yields a single numerical correction factor that takes into account the excitation and receiver profiles of the coil, T1saturation, and point spread effects associated with Fourier transformation of CSI data. An external phosphorus standard is used to calibrate instrument gain and the B1profile of the coil. For spherical samples, point spread effects can modulate the signal intensities of three‐dimensional CSI spectra from ‐32% to +54%, depending on the voxel size. Measurements of phantoms of known concentrations showed systematic variations of ± 10% and random errors of ± 5%. We have used this method to measure the concentration of phosphocreatine in the thigh muscle of normal volunteers.

A disorder of Norfolk Island pines, Araucaria heterophylla (Salisb.) Franco, has occurred on certain urbanized parts of the coast of New South Wales. Observation and survey work suggested that the disorder was due to excessive foliar uptake of salt, induced by surfactants derived from sewage discharged into the sea. The work described in this paper was part of a programme of studies designed to test this hypothesis. Glasshouse experiments were carried out to test the effects of distilled water and deep-sea water both with and without added surfactants sprayed onto the foliage of young potted Norfolk Island pines. Whereas the distilled water effects were minimal, some needle and shoot necrosis occurred in all plants sprayed with sea water and this effect was markedly accentuated when surfactant was present. Shoot necrosis was highly significantly correlated with the concentration of sodium and chloride taken up by the foliage, and the foliar salt levels were very similar to those found in deteriorating trees located by the seaside. The results showed that a commonly used surfactant, when sprayed in a sea-water solution onto Norfolk Island pine foliage, caused damage similar to that observed in affected seaside trees.

As part of an investigation into the deterioration of Norfolk Island pine, Araucaria heterophylla (Salisb.) Franco, on the coast of eastern Australia, seedlings were grown in nutrient solutions in which sodium was substituted for potassium over the range 0.1 - 2.1 mM to give six treatments, each with four ratios of sulfate to chloride. Potassium was freely taken up and translocated to the shoots, the levels in the shoots being higher than those in the roots. However, the levels of potassium in both shoots and roots were significantly reduced in solutions in which sulfate predominated over chloride. Uptake and translocation of sodium was restricted, the ratio of sodium (shoots) to sodium (roots) being less than unity. The concentration of chloride in the shoots and roots generally increased with increasing solution chloride concentration but was significantly reduced at the lowest potassium-to-sodium ratio. In a second experiment the ratio of sodium to potassium was kept at 50:1, sodium and chloride in the solutions increasing from 2.5 to 460 mM and potassium from 0.05 to 9.2 mM. At the lower concentrations, uptake and translocation followed similar patterns to those found in the first experiment. However at solution concentrations of 20 mM sodium and above, levels of sodium in the shoots exceeded those of potassium and chloride. At sodium chloride concentrations of 260mM - 460mM, plants showed toxic symptoms with salt encrustations appearing on the stems. Analysis of the saturation extracts of soils taken from beneath affected seaside trees showed that the concentrations of sodium and chloride were not sufficiently high to account for the high levels of these elements found in the shoots of affected trees.

Summary WhenPinus radiata plants are grown in solutions containing adequate phosphorus for maximum growth and varying amounts of aluminium, phosphorus uptake in roots and tops is positively related to aluminium uptake. The amounts of both phosphorus and aluminium taken up by the plants bear a direct relationship to the aluminium content of the solution. The increased uptake of phosphorus is not accompanied by any increase in the rate of growth.

A cytological and cytochemical examination of Saprolegnia terrestrisCookson was undertaken to resolve the conflict of opinion regarding the life cycle of fungi in the Saprolegniaceae, i.e., whether meiosis is zygotic or gametic. Microspectrophotometric analysis reveals that pre‐divisional oogonial and antheridial nuclei are 4C; a subsequent reduction division in the sex organs produces 1C male and female gametes. These division products coexist in the developing oospore and presumably fuse to produce the diploid zygote. Analysis of the somatic hyphal nuclei shows a 2C DNA content, with the characteristic skew and bimodal character indicative of predominantly G1, and some S‐period and G2 types. The evidence is completely consistent with gametic meiosis, i.e., a predominant diploid vegetative phase and short haploid phase, and refutes the notion of zygotic meiosis. Further ramifications of the work are discussed along with preliminary results of related work in progress.

William Howard Taft was a central participant at the birth of American imperialism. He won praises for his work with the Philippine Islands, first as head of the commission created to restore the Islands to a peaceful state, then as the first civil governor. He gave up this office to become Secretary of War under President Theodore Roosevelt in 1905. In his position in the Cabinet Taft had direct or indirect oversight over most of America's scattered empire.By March, 1909, when Taft succeeded Roosevelt in the Presidency, the constitution of the American empire had largely been formulated, even if strictly speaking, it had not been formalized. Civil governments had been set up in Puerto Rico, Hawaii, and the Philippine Islands. The “insular cases” of 1901 had defined the limits of claims of the dependent peoples upon the Constitution of the United States; the new possessions were neither foreign nor domestic, and thus even though the Constitution did not follow the flag, tariffs might. The only armed resistance to American control—in the Philippines—had long since ended. It was then to the surprise and dismay of President Taft that tiny Puerto Rico immediately presented a hostile challenge to his new administration, the constitutional rebellion known as the appropriation crisis of 1909.