Search PubMed⌕ Search

Biomedical subjects

J D Christensen

Publications and source records attributed to J D Christensen.

At least 37 records · Page 2Linked to original sources

Progression of cerebroventricular enlargement and the subtyping of schizophrenia.

Several anatomic abnormalities in the brains of schizophrenics have frequently been reported. However, it remains unresolved whether such neuropathology is fully expressed and static at the onset of psychosis or whether further deterioration evolves during the course of illness. To address this important question, we obtained serial volumetric magnetic resonance images (MRI) of the cerebral ventricles of 18 patients with schizophrenic symptoms. Repeated blind measurements of total ventricular volume (TVV) revealed < 2% error of the segmentation method. Over a 2-3 year period, the rate of ventricular expansion (RVE) was 2.2 +/- 1.6 cm3/year in the patients and 0.7 +/- 0.6 cm3/year in controls. The RVE in the patients was not normally distributed, but clustered into two groups: a group similar to controls (n = 10; RVE, 0.9 +/- 0.5 cm3/year) and a group with a significantly greater rate of expansion (n = 8; RVE, 3.9 +/- 0.7 cm3/year) (P < 0.001). These results suggest that there are at least two subpopulations within the schizophrenias: one with relatively static ventricles and another with progressively enlarging ventricles. At least two distinct etiologic processes may thus underlie the clinical presentation of schizophrenic symptoms. Factors which might influence ventricular expansion (neuroleptic compliance, alcohol and recreational drug abuse, and some clinical correlates) could not account for differences between groups.

Age Factors↗

Basal ganglia choline levels in depression and response to fluoxetine treatment: an in vivo proton magnetic resonance spectroscopy study.

We have investigated proton magnetic resonance spectra of the basal ganglia in 41 medication-free outpatients with major depression, prior to starting an 8-week standardized trial of open-label fluoxetine, and 22 matched comparison subjects. Upon completing the trial, depressed subjects were classified as treatment responders (n = 18) or nonresponders (n = 23), based on changes in the Hamilton Depression Rating Scale. Depressed subjects had a lower area ratio of the choline resonance to the creatine resonance (Cho/Cr) than comparison subjects. This statistically significant difference between the depressed subjects and comparison subjects was more pronounced in the treatment responders than in the nonresponders. There were no differences in the relative volumes of gray matter or white matter in the voxel used for proton spectroscopy in depressed subjects relative to comparison subjects. These results are consistent with an alteration in the metabolism of cytosolic choline compounds in the basal ganglia of depressed subjects and, in particular, those who are responsive to fluoxetine.

Adult↗

Three-dimensional projection imaging with half the number of projections.

This study demonstrates a sampling scheme for three-dimensional projection imaging with half the number of projections. The angular distribution of projections is designed so that the oversampling of the low spatial frequencies, in tandem with a partial Fourier algorithm, can be used to recreate purposely missing projections. The performance of the sampling scheme and its associated reconstruction algorithm are illustrated with computer-simulated as well as experimental data sets. We find that this technique produces images of comparable quality to the conventional projection imaging scheme. Although a 30% loss of signal-to-noise ratio (SNR) results from its use, the algorithm should prove useful for applications where robustness against motion artifacts and reduced T2* signal loss are desired.

Algorithms↗

Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study.

OBJECTIVE: The purpose of this study was to evaluate whether the concentration of beta-nucleoside triphosphate is lower in the basal ganglia of depressed subjects. METHOD: In vivo 31P magnetic resonance spectra were acquired from a 45-cm3 region surrounding the basal ganglia of 35 unmedicated depressed subjects and 18 comparison subjects. RESULTS: beta-Nucleoside triphosphate, which arises primarily from beta-ATP, was 16% lower in the depressed subjects than in the comparison subjects. CONCLUSIONS: The low level of beta-nucleoside triphosphate is consistent with an abnormality of high-energy phosphate metabolism in the basal ganglia of subjects with major depression.

Adenosine Triphosphate↗

Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients.

This study examined choline augmentation of lithium for rapid-cycling bipolar disorder. Choline bitartrate was given openly to 6 consecutive lithium-treated outpatients with rapid-cycling bipolar disorder. Five patients also underwent brain proton magnetic resonance spectroscopy. Five of 6 rapid-cycling patients had a substantial reduction in manic symptoms, and 4 patients had a marked reduction in all mood symptoms during choline therapy. The patients who responded to choline all exhibited a substantial rise in the basal ganglia concentration of choline-containing compounds. Choline was well tolerated in all cases. Choline, in the presence of lithium, was a safe and effective treatment for 4 of 6 rapid-cycling patients in our series. A hypothesis is suggested to explain both lithium refractoriness in patients with bipolar disorder and the action of choline in mania, which involves the interaction between phosphatidylinositol and phosphatidylcholine second-messenger systems.

Adult↗

Abnormal cerebral metabolism in polydrug abusers during early withdrawal: a 31P MR spectroscopy study.

Phosphorus magnetic resonance spectroscopy (31P MRS) at 1.5 T was performed on nine polysubstance abusing men. All nine patients met DSM-III-R criteria for concurrent cocaine and heroin dependence, were neurologically normal, were negative for the human immunodeficiency virus, and had normal clinical brain MRI scans. Patients were scanned 2-7 days after admission to a drug treatment unit. Eleven age-matched control subjects also were studied. The ISIS localized phosphorus spectra were obtained from a 5-cm thick axial brain slice and a 100-cc white matter volume. In the brain slice, the phosphorus metabolite signal expressed as a percentage of total phosphorus signal was 15% higher for phosphomonoesters, 10% lower for nucleotide triphosphates (beta-NTP), and 7% lower for total nucleotide phosphates in polydrug abusers compared with those in controls. Phosphodiesters, inorganic phosphate, phosphocreatine, total phosphorus, pH, and free magnesium concentration were unchanged. None of these parameters correlated with the methadone dose or the number of days abstinence. Single photon emission computed tomographic imaging of a subgroup of the patients revealed abnormal cerebral perfusion in 80% of the patients scanned. These data suggest that cerebral high energy phosphate and phospholipid metabolite changes result from long term drug abuse and/or withdrawal and that these changes can be detected and studied by 31P MRS.

Adult↗

Quantitative tissue sodium concentration mapping of normal rat brain.

A quantitative in vivo method for obtaining maps of tissue sodium concentration (TSC) by MRI is compared to the invasive, global 22Na radionuclide dilutional technique in the normal rat brain. The MR method uses a three-dimensional projectional acquisition scheme to minimize signal losses from transverse relaxation. Internal calibration standards are used to convert the signal intensity into TSC after correction for B1 inhomogeneities by using the ratio of 23Na and 1H images obtained with identical B1 distributions and sensitivities at the two frequencies. Over the biological range of concentrations, the TSC, measured as the ratio of MR signals of 23Na and 1H, gives a linear response with concentration. In the normal rat brain, the mean TSC measured using the MRI method (TSC = 45 +/- 4 mM, animals = 5) is not significantly different from the global 22Na radionuclide method (TSC = 49 +/- 6 mM, animals = 7).

Animals↗

A technique for detecting GABA in the human brain with PRESS localization and optimized refocusing spectral editing radiofrequency pulses.

A proton magnetic resonance spectral editing technique is presented that uses PRESS excitation to achieve spatially localized measurements of brain gamma-aminobutyric acid (GABA). The homonuclear difference spectroscopy technique employs a frequency selective inversion pulse to suppress the creatine resonance at 3.0 ppm. The timing of this pulse is optimized to maximize the suppression of creatine by minimizing the effect of the editing pulse on the 3.0 ppm resonances. The PRESS excitation achieves three dimensional spatial localization in a single acquisition making it less sensitive to patient motion than multiple acquisition techniques. The performance and utility of this technique were evaluated by phantom experiments and by in vivo measurements of brain GABA concentration in 10 normal subjects.

Brain↗

Interactions between propofol and lipid mediator receptors: inhibition of lysophosphatidate signaling.

As a highly lipophilic drug, propofol may interact with lipophilic domains in addition to its likely primary site of action on the gamma-aminobutyrateA) (GABA(A)) receptor. Likely candidates for such interaction are the G protein-coupled membrane receptors for lipid intercellular mediators. The phospholipid lysophosphatidate (LP) has attracted attention as such a signaling molecule. It has a variety of biological actions, including vasoconstriction. We therefore studied the interaction between propofol and the LP receptor. Intracellular Ca2+ release in response to LP was assessed by measuring C1- flux through Ca(2+)-activated C1- channels in Xenopus oocytes. The average charge movement in response to LP 10(-7)M was 2.0 +/- 0.2 microCoulombs. Propofol in Intralipid (0.01%) dose-dependently inhibited LP signaling (50% inhibitory concentration [IC50] 5.38 microM). Propofol 28 microM inhibited LP signaling by 81%. Intralipid (0.01%) was without effect. To ascertain that intracellular signaling pathways and the Ca(2+)-activated C1- channel were not affected by propofol, we tested the effects of propofol (5.6 microM) on currents induced by methylcholine (10(-7)M) in oocytes expressing the m1 muscarinic acetylcholine receptor. No inhibition was observed. As both receptors share the same intracellular signaling pathway, we conclude that clinically relevant concentrations of propofol most likely inhibit the LP receptor or its G protein. Inhibition of LP signaling may explain some of propofol's vasodilating actions.

Anesthetics, Intravenous↗

Lipopolysaccharide in concentrations above 40 ng/ml stimulates proliferation of the IL-6-dependent B9 cell line.

The B9 assay is known to be a specific and sensitive assay for the estimation of interleukin-6 activity. This assay was found to be compromised by lipopolysaccharide in concentrations > or = 40 ng lipopolysaccharide per ml. The lipopolysaccharide stimulates proliferation of the B9 cell line in a dose-dependent manner both when measuring the proliferation by thymidine incorporation and when using the MTT assay. However the LPS dose-response curve is different compared to the dose-response curve for IL-6. A sample containing 100 ng LPS/ml but no IL-6 would be estimated erroneously to contain 12 pg IL-6. The interference of lipopolysaccharide is totally abolished by the addition of polymyxin B to the samples but the addition has no effect on the IL-6 induced proliferation.

Animals↗

Dihydropyridine ligands influence the evoked release of oxytocin and vasopressin dependent on stimulation conditions.

The effects of dihydropyridine ligands on the electrically evoked release of neurohypophysial hormones from isolated, rat neurointermediate lobes were investigated as a function of all combinations of two pulse widths (0.2 and 2 ms) and three stimulation frequencies (6.5, 13 and 30 Hz). The dihydropyridine agonist (S)-(+)-202-791 potentiated concentration dependently the release of both oxytocin and vasopressin at a pulse width of 2 ms and a frequency of 6.5 Hz. This effect of (S)-(+)-202-791 was abolished by the antagonist (-)-nitrendipine and stereospecifically by (R)-(-)-202-791 (only vasopressin). The antagonist (R)-(-)-202-791 alone inhibited the release of oxytocin at 13 Hz and 2 ms. The results presented show that the effects of the dihydropyridine ligands are dependent on the stimulation conditions, and thus demonstrate that the entry of Ca2+ through the dihydropyridine sensitive L-type Ca2+ channel is associated with electrically evoked release of neurohypophysial hormones under certain conditions.

Animals↗

Quantitative in vivo tissue sodium concentration maps: the effects of biexponential relaxation.

The biexponential relaxation behavior of the sodium nucleus affects the accuracy of quantitative measurement of in vivo tissue sodium concentration (TSC). Theoretical analysis and in vivo experimental results are used to demonstrate the extent of the large bias in the measured TSC that arises when the relaxation behavior in vivo differs significantly from that of the calibration standards which is when a significant fraction of the total sodium signal decays with a relaxation time much shorter than the echo time (TE) used for imaging. This bias can be as large as 20% for measurements of TSC in a normal rat brain with TE = 2 ms. Our findings indicate that shortening the echo time (TE < 0.5 ms) by projection imaging is a reliable means of obtaining accurate in vivo estimates for TSC using MR.

Animals↗

Detection of lipopolysaccharide in the picogram range of tissue culture media by a kinetic chromogenic Limulus amebocyte lysate assay.

A kinetic chromogenic Limulus amebocyte lysate assay for detection of lipopolysaccharide in the picogram range is described. The kinetic Limulus assay was used to detect lipopolysaccharide in a tissue culture media containing interfering low-molecular-weight substances. The interfering substances were removed by ultrafiltration. The recovery of lipopolysaccharide from the ultrafiltrated tissue culture media was 61.6 +/- 21.4%. The kinetic Limulus assay was compared with the traditional end-point chromogenic Limulus assay. The results in the two assays showed a good correlation. The detection limit was 1 pg/ml in the chromogenic assay and 0.25 pg/ml in the kinetic assay.

Amino Acid Sequence↗

Rectal palpation and transmission of bovine leukemia virus in dairy cattle.

To determine whether rectal palpation, using common obstetrical sleeves, serves as a mode of transmission of bovine leukemia virus in dairy cattle, field studies were conducted at 2 dairies. At a commercial dairy, significant difference was not observed in rate of seroconversion in heifers and cows in which the same sleeve or new sleeves were used for palpations. At a university dairy, where cattle were used to teach dairy husbandry and veterinary procedures, significantly (P less than 0.02) greater rate of seroconversion was observed in heifers and cows palpated with unwashed common sleeves than that observed in heifers and cows palpated with sleeves washed between use. Although rectal transmission of bovine leukemia virus under field conditions was documented, it was related to frequency of palpation and age of cattle.

Animals↗

Comparison of cultured human mononuclear cells, Limulus amebocyte lysate and rabbits in the detection of pyrogens.

Isolated human mononuclear cells exposed to either lipopolysaccharide or Staphylococcus aureus secreted interleukin-1 like material. The secretion was concentration dependent. The minimal detectable level in the test solution of lipopolysaccharide and Staphylococcus aureus was 200 pg/ml and 10(5) cells/ml respectively. The sensitivity and specificity of the Limulus Amebocyte Lysate test, the rabbit pyrogen test and the monocyte test are compared. The monocyte test is proposed as an alternative in-vitro test to the rabbit pyrogen test.

Animals↗

Kappa-opioid receptor agonists differentially affect the release of neurohypophysial hormones.

The influence of kappa-opioid receptor agonists and antagonists on release of oxytocin and vasopressin was examined in isolated rat neurointermediate lobes. Electrically evoked release of oxytocin and vasopressin was concentration-dependently inhibited by the specific kappa-receptor agonist U69593, whereas bremazocine only inhibited the secretion of oxytocin markedly. Treatment with naloxone enhanced the evoked release of oxytocin significantly without effect on vasopressin secretion. The U69593-mediated inhibition of oxytocin release was abolished by naloxone, whereas that of vasopression was unaffected. Naloxone did not reverse the bremazocine-induced inhibition of hormone release. The data support the theory of an inhibiting endogenous control over oxytocin secretion and show that the release of oxytocin and vasopresin is differentially affected by the two K-receptor agonists.

Animals↗