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Biomedical subjects

D Norman

Publications and source records attributed to D Norman.

At least 127 records · Page 7Linked to original sources

NMR and computational characterization of the N-(deoxyguanosin-8-yl)aminofluorene adduct [(AF)G] opposite adenosine in DNA: (AF)G[syn].A[anti] pair formation and its pH dependence.

This paper reports on a combined two-dimensional NMR and energy minimization computational characterization of the conformation of the N-(deoxyguanosyl-8-yl)aminofluorene adduct [(AF)G] positioned across adenosine in a DNA oligomer duplex as a function of pH in aqueous solution. This study was undertaken on the d[C1-C2-A3-T4-C5-(AF)G6-C7-T8-A9-C10-C11].[G12-G13-T14 -A15-G16-A17-G18- A19-T20-G21-G22] complementary undecamer [(AF)G 11-mer duplex]. The modification of the single G6 on the pyrimidine-rich strand was accomplished by reaction of the oligonucleotide with N-acetoxy-2-(acetylamino)fluorene and subsequent deacetylation under alkaline conditions. The HPLC-purified modified strand was annealed with the unmodified purine-rich strand to generate the (AF)G 11-mer duplex. The exchangeable and nonexchangeable protons are well resolved and narrow in the NMR spectra of the (AF)G 11-mer duplex so that the base and the majority of sugar nucleic acid protons, as well as several aminofluorene ring protons, have been assigned following analysis of two-dimensional NOESY and COSY data sets at pH 6.9, 30 degrees C in H2O and D2O solution. The NOE distance constraints establish that the glycosidic torsion angle is syn at (AF)G6 and anti at A17, which results in the aminofluorene ring being positioned in the minor groove. A very large downfield shift is detected at the H2' sugar proton of (AF)G6 associated with the (AF)G6[syn].A17[anti] alignment in the (AF)G 11-mer duplex. The NMR parameters demonstrate formation of Watson-Crick C5.G18 and C7.G16 base pairs on either side of the (AF)G6[syn].A17[anti] modification site with the imino proton of G18 more stable to exchange than the imino proton of G16. Several nonexchangeable aminofluorene protons undergo large downfield shifts as do the imino and H8 protons of G16 on lowering of the pH from neutrality to acidic values for the (AF)G 11-mer duplex. Both the neutral and acidic pH conformations have been defined by assigning the NOE constraints in the [C5-(AF)G6-C7].[G16-A17-G18] segment centered about the modification site and incorporating them in distance constrained minimized potential energy calculations in torsion angle space with the DUPLEX program. A series of NOEs between the aminofluorene protons and the DNA sugar protons in the neutral pH conformation establish that the aminofluorene ring spans the minor groove and is directed toward the G16-A17-G18 sugar-phosphate backbone on the partner strand.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Acetylaminofluorene↗

Lithium carbonate intoxication. A case report and review of the literature.

Lithium carbonate is a widely used and invaluable drug in the treatment and prevention of manic-depressive illness. However, this medication has a low therapeutic index and, therefore, many attendant side effects. Acute lithium carbonate intoxication affects predominantly the central nervous system and the renal system and is potentially lethal. We studied a case of acute lithium carbonate intoxication characterized by a prolonged comatose state, severe nephrogenic diabetes insipidus, and glucose intolerance. Of interest, the patient's symptoms and signs of toxic reaction developed after normalization of the plasma lithium ion levels. We reviewed the multisystemic toxic effects of lithium carbonate as well as its teratogenic potential and guidelines for its use during pregnancy. The management of acute lithium carbonate intoxication should include hydration with normal saline, intensive care monitoring, and dialysis if indicated.

Humans↗

MRS of ischemic/hypoxic brain disease.

Significant increases in magnetic field strengths and improvements in magnetic field homogeneity have made combined high-resolution magnetic resonance imaging (MRI) and multinuclear spectroscopy (MRS) feasible for investigating the relationship between biochemical and structural changes induced by ischemic brain disease. Magnetic resonance spectroscopy is the only noninvasive technique capable of measuring concentrations of high-energy phosphate metabolites, lactate, and other metabolically relevant compounds. Anticipated advances in localization of the volume of tissue from which spectra are obtained will enhance the clinical potential of MRS in the diagnosis of ischemic disease.

Animals↗

Intradural spinal cord lesions: Gd-DTPA-enhanced MR imaging.

Twenty-five patients with suspected spinal cord neoplasms were studied with high-field-strength magnetic resonance (MR) imaging (1.5 T) before and after administration of gadolinium diethylenetriamine-pentaacetic acid (DTPA) (gadopentetate dimeglumine). Five patients had enhancing, nonneoplastic lesions, including spinal dural arteriovenous fistulas (AVFs), cord infarction, and chronic arachnoiditis. Fifteen patients had proved spinal cord neoplasms, 13 intramedullary and two extramedullary. Four of the intramedullary tumors were detected only after Gd-DTPA administration; in five others, contrast material enhancement improved observer confidence. Gd-DTPA also demonstrated one dural AVF not detected on precontrast images. Regions of cord ischemia or infarction related to spinal dural AVF also enhanced in three patients. Advantages of Gd-DTPA include the demonstration of small isointense intramedullary tumors and the ability to permit differentiation of tumor from adjacent cord syrinx and solid tumor from postoperative gliosis and arachnoid scarring. Gd-DTPA enhancement is a useful adjunct to high-resolution MR imaging of the spinal cord.

Adult↗

Intraspinal synovial cysts: MR imaging.

Juxtaarticular intraspinal synovial cysts are unusual lesions of the spine associated with facet arthropathy. These lesions can cause radicular symptoms and may masquerade clinically as other, more common entities. Synovial cysts have been detected at myelography and have been well characterized at computed tomography as posterolateral epidural masses, typically at L4-5. Six synovial cysts of the lumbar spine were demonstrated on magnetic resonance (MR) images. The signal-intensity patterns of these lesions are variable. MR imaging can be used to document the presence of hemorrhage within the cyst, which may relate to the exacerbation of symptoms. Air-filled synovial cysts may be difficult to detect and distinguish from facet arthropathy.

Adult↗

Cranial bone marrow in children: assessment of normal development with MR imaging.

Magnetic resonance images of cranial bone marrow in 238 patients (246 examinations) less than 25 years old were reviewed to establish normal age-related standards. Bone marrow in the clivus and calvaria had uniformly low signal intensity (grade 1) on T1-weighted images in most infants less than 1 year old. The number of patients with grade 1 marrow decreased rapidly in early childhood, while the number of patients with marrow of low and high signal intensity (grade 2) and uniformly high signal intensity (grade 3) gradually increased with age. A grade 1 marrow was no longer observed in either the clivus or calvaria after age 7. Most patients had a grade 3 marrow by age 15. Because bone marrow in certain pathologic conditions has decreased signal on T1-weighted images and therefore resembles grade 1 or 2 appearances of normal marrow in children, these results may be useful for differentiating normal and abnormal bone marrow signal intensities in infants and children.

Adult↗

Septo-optic dysplasia: MR imaging.

Septo-optic dysplasia is the diagnosis when optic nerve hypoplasia is seen in conjunction with dysgenesis of the septum pellucidum. Nearly two-thirds of these patients have hypothalamic-pituitary dysfunction, and half have schizencephaly. The disorder is difficult to classify because of the diversity of clinical and pathologic manifestations. Magnetic resonance images of 11 patients with clinical and radiographic evidence of septo-optic dysplasia were reviewed retrospectively. The "syndrome" appears to include two subsets of patients whose abnormalities have different embryogenesis and neuropathologic findings. The existence of these two subsets helps to explain the diversity of the clinical and radiologic findings.

Adolescent↗

Posterior fossa hemangioblastomas: MR imaging.

The magnetic resonance (MR) imaging findings of 18 surgically proved posterior fossa hemangioblastomas (15 patients) were retrospectively analyzed and correlated with computed tomographic (ten patients) and angiographic (eight patients) findings. Thirteen tumors were located in the cerebellar hemisphere, three in the vermis, and two in the medulla with associated syrinxes. Three patients had von Hippel-Lindau disease, two of whom had multiple cerebellar hemangioblastomas. Seven hemangioblastomas appeared as solid tumors, six as solid masses with central cysts, and five as cysts with mural nodules. Abnormal tumor vessels, with characteristic signal void, were demonstrated in 13 tumors. Associated hemorrhage was present in four tumors. Although angiography is usually required for the diagnosis and preoperative assessment of this tumor, MR imaging demonstration of a posterior fossa mass with abnormal vessels should suggest the diagnosis of hemangioblastoma. Moreover, the combination of a peripheral posterior fossa cyst with a mural nodule supplied by enlarged vessels may be pathognomonic.

Adult↗

Neurofibromatosis types 1 and 2: cranial MR findings.

Neurofibromatosis 1 (NF-1) (von Rekhlinghausen disease) and neurofibromatosis 2 (NF-2) (bilateral acoustic neurofibromatosis) have been recently recognized to be distinct disorders through genetic linkages. The authors compared the cranial magnetic resonance (MR) images of 53 patients with NF-1 and 11 with NF-2. In the NF-1 group, MR imaging revealed 19 patients with optic gliomas and eight with parenchymal gliomas. In 32 patients, foci of prolonged T2, similar to those reported previously as hamartomas, were identified in the cerebellar peduncles, globus pallidus, midbrain, and other locations. The frequency of these foci was related to both age and the presence of optic gliomas. In the NF-2 group, MR imaging revealed eight patients with cranial nerve schwannomas and six with meningiomas (in addition to acoustic schwannomas in all 11). These findings demonstrate that NF-1 and NF-2 are different diseases requiring different imaging protocols. NF-1 seems to be associated with tumors of astrocytes and neurons and NF-2 with tumors of meninges and Schwann cells.

Adolescent↗

Marrow conversion before pneumatization of the sphenoid sinus: assessment with MR imaging.

To evaluate the bone marrow change before pneumatization of the sphenoid sinuses in childhood, the authors retrospectively reviewed short repetition time/echo time midsagittal magnetic resonance images in 56 patients younger than 6 years. The signal intensity of the presphenoid bone marrow (anteromedial part of the sphenoid bone) was as low as that of muscle (grade 1) and remained the same as that of the basisphenoid and basiocicput in all infants (n = 6) younger than 6 months. Between 7 months and 2 years, most patients (24 of 27) exhibited fatty conversion of bone marrow limited to the presphenoid (grade 2). After 3 years of age, most patients demonstrated pneumatization (six of 12 at 3-4 years, eight of 11 at 5-6 years) in addition to the grade 2 findings (grade 3). The presphenoid exhibits signal intensity characteristics of fatty marrow before it is invaginated by the developing sphenoid sinus. Fatty change before pneumatization is a normal developmental process and should not be misinterpreted as a pathologic condition.

Bone Marrow↗

Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T.

Magnetic resonance (MR) images of the brain in 285 patients between the ages of 2 and 25 years were retrospectively studied to determine the appearance of brain iron accumulation. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus were evaluated with long TR/TE (repetition time/echo time) spin-echo sequences and staged. All four regions in most patients were initially hyperintense compared with white matter (stage I) before becoming isointense (stage II) and subsequently hypointense (stage III). The globus pallidus was the first to reach stage III, the red nucleus and substantia nigra were next, and the dentate nucleus was last. In general, decreased signal intensity (stage III) was not seen in these regions in patients less than 10 years old; in most patients it was seen by age 25 years. The dentate nucleus decreased in signal intensity more slowly and inconsistently; only one-third of patients had reached stage III by age 25 years. The temporal sequence of normal iron deposition as detected with MR imaging is helpful not only in the diagnosis of known iron-deposition diseases but also in the detection of iron-related pathologic changes.

Adolescent↗

Sex differences result in increased morbidity from hyponatremia in female rats.

The development of symptomatic hyponatremia in otherwise healthy young women can result in death or permanent brain damage. The reasons for the increased female susceptibility to complications from hyponatremia are, however, unclear. To determine whether mechanisms that normally defend the brain against damage from hyponatremia are less effective in females than males, we studied both sodium transport in the brains of hyponatremic male and female rats and the effects of parenteral arginine vasopressin on brain high-energy phosphate metabolism and intracellular pH. Basal sodium uptake in synaptosomes prepared from whole brain of females (2.20 nmol/mg protein) and males (2.98 nmol/mg protein) was not statistically different. In contrast, veratridine-stimulated sodium uptake in female brain was 8.20 nmol/mg protein, which was 86% greater (P less than 0.001) than the 6.12 nmol/mg protein observed for male brain. Additionally, sodium uptake between 5 and 60 s was significantly (P less than 0.001) greater in females than males. These data suggest that the Na+-K+-adenosinetriphosphatase (ATPase) pump function in female rat brain synaptosomes is less effective than in males. To determine whether arginine vasopressin, a peptide hormone that promotes water retention by the kidney, had any effects on cerebral energy metabolism, we performed phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) studies on the brain of normonatremic young adult male and female rats subjected to high (20 IU) peripheral doses of arginine vasopressin. We found decreased high-energy phosphate generation, elevated inorganic phosphate, and intracellular acidosis after arginine vasopressin administration in females but not males.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Nicardipine reduces ischemic brain injury. Magnetic resonance imaging/spectroscopy study in cats.

We investigated whether the calcium channel entry blocker nicardipine would reduce ischemic brain damage in barbiturate-anesthetized cats subjected to permanent unilateral occlusion of the middle cerebral artery. The evolution of cerebral injury was assessed in vivo in 24 cats by a combination of proton magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy for 5 hours following occlusion. Immediately thereafter, the volume of histochemically ischemic brain tissue was determined planimetrically in triphenyl tetrazolium chloride-stained serial coronal sections. Nicardipine was initially administered as an intravenous bolus injection of 10 mg/kg/hr 15 minutes before or 15 minutes after occlusion, followed by continuous infusion at 8 mg/kg/hr for the 5 hours of the experiment. Compared with untreated controls, cats that received nicardipine before or after occlusion showed a significant reduction in the extent of edema in the ipsilateral cerebral cortex, internal capsule, and basal ganglia. The results of phosphorus-31 magnetic resonance spectroscopy studies suggest that nicardipine may protect against cerebral ischemic damage by an action on cellular metabolic processes that preserve high-energy phosphates during the ischemic period.

Animals↗

High-resolution MR imaging of pituitary microadenomas at 1.5 T: experience with Cushing disease.

The MR images of 27 patients with clinically and biochemically suspected Cushing disease were evaluated retrospectively in a blinded fashion. The MR interpretation was compared with detailed operative diagrams and operative and pathologic reports. The examinations were performed on a 1.5-T MR system with thin-section sagittal and coronal T1-weighted (short TR/TE) images. Each pituitary half was considered separately (54 "halves"). Twenty-one pituitary halves were considered to have glandular abnormalities on MR. Compared with surgical findings, 17 MR findings were true positives and four were false positives (one pars intermedia cyst, three normal tissue). Of the 33 pituitary halves considered normal on MR, 26 were true negatives and seven were false negatives. MR had an overall sensitivity of 71% and a specificity of 87% for these adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. A focal glandular hypointensity identified on coronal images was the most sensitive predictor of adenoma location. Sagittal images were not useful in either detection or localization. Upward convexity of the gland and deviation of the stalk were less useful indicators. Abnormalities of the sellar floor were the least reliable. In comparison with the capabilities of CT detection of microadenomas described in the current literature, it appears that high-field thin-section MR of the sella is the most sensitive imaging method for preoperative localization of ACTH-secreting adenomas in patients with Cushing disease.

Adenoma↗

Histochemical characterization and functional significance of the hyperintense signal on MR images of the posterior pituitary.

MR imaging of the pituitary fossa characteristically shows a well-circumscribed area of high signal intensity in the posterior lobe on T1-weighted images. We used a combination of high-field MR, electron microscopy, and histologic techniques in experimental animals to determine whether the hyperintensity of the posterior lobe might be functionally related to hormone neurosecretory processes, and to attempt to establish its chemical nature. Histologic sections of a dog's pituitary gland processed with lipid-specific markers showed intense staining in the posterior lobe but not in the anterior lobe, thus documenting the location of fat in the posterior pituitary. Administration of vasoactive drugs known to influence vasopressin secretion to anesthetized cats produced changes in the volume of high-intensity signal in the posterior pituitary. Subsequent electron microscopy showed a significant increase in posterior lobe glial cell lipid droplets and neurosecretory granules in dehydration-stimulated cats. The data suggest that the pituitary hyperintensity represents intracellular lipid signal in the glial cell pituicytes of the posterior lobe or neurosecretory granules containing vasopressin. The volume of the signal may, in turn, reflect the functional state of hormonal release from the neurohypophysis.

Animals↗

Absence of the septum pellucidum: a useful sign in the diagnosis of congenital brain malformations.

In a review of more than 2000 MR images of the brain we identified 35 patients with absence of the septum pellucidum. These patients were divided into seven basic groups as follows: septooptic dysplasia; schizencephaly; holoprosencephaly; agenesis of the corpus callosum; chronic, severe hydrocephalus; basilar encephaloceles; and porencephaly/hydranencephaly. Absence of the septum pellucidum was never seen as an isolated finding. By using data gathered from the review of the MR scans of patients in this study, we devised a diagnostic algorithm to aid in the classification of these patients. Absence of the septum pellucidum can provide a valuable clue to the diagnosis of malformations of the brain.

Abnormalities, Multiple↗