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Biomedical subjects

D Lee

Publications and source records attributed to D Lee.

At least 397 records · Page 22Linked to original sources
PubMed1993

Targeted modification of the apolipoprotein B gene results in hypobetalipoproteinemia and developmental abnormalities in mice.

Familial hypobetalipoproteinemia is an autosomal codominant disorder resulting in a dramatic reduction in plasma concentrations of apolipoprotein (apo) B, cholesterol, and beta-migrating lipoproteins. A benefit of hypobetalipoproteinemia is that mildly affected individuals may be protected from coronary vascular disease. We have used gene targeting to generate mice with a modified Apob allele. Mice containing this allele display all of the hallmarks of human hypobetalipoproteinemia: they produce a truncated apoB protein, apoB70, and have markedly decreased plasma concentrations of apoB, beta-lipoproteins, and total cholesterol. In addition, the mice manifest several characteristics that are occasionally observed in human hypobetalipoproteinemia, including reduced plasma triglyceride concentrations, fasting chylomicronemia, and reduced high density lipoprotein cholesterol. An unexpected finding is that the modified Apob allele is strongly associated with exencephalus and hydrocephalus. These mice should help increase our understanding of hypobetalipoproteinemia, atherogenesis, and the etiology of exencephalus and hydrocephalus.

Alleles↗
PubMed1993

Molecular and cellular heterogeneity of Wilms' tumor.

We developed a Wilms' tumor-cell culture system to investigate the molecular basis of nephrogenesis and oncogenesis. Several distinct fractions of cells were isolated and characterized from the same tumor specimen. The cells exhibited striking differences in morphology, immunocytochemical staining profiles and cytogenetics. One fraction contained cells with features of epithelium; other cell fractions resembled partially differentiated mesenchyme (blastema or stroma). While the Wilms' tumor-suppressor gene WT1 was not altered, loss of heterozygosity (LOH) and an insertion in intron I of the p53 tumor-suppressor gene occurred in the tumor and the cultured cell types. LOH for RB was detected only in the cultured cells. These findings are consistent with a model of tumor initiation in a pluripotent cell that is able to undergo subsequent differentiation along multiple different lines and which mimics normal nephrogenesis.

Cell Separation↗
PubMed1993

Pathologic correlates of increased signals of the centrum ovale on magnetic resonance imaging.

The pathologic correlates of increased signal in the white matter of the centrum ovale in postmortem magnetic resonance imaging were investigated in an unselected series of 15 autopsies. Two types of magnetic resonance imaging hyperintensities could be separated on the basis of size (10-mm cutoff): extensive and punctate. The pathologic basis of extensive hyperintensities was large areas of pallor with ill-defined margins, located in the central white matter and sparing the subcortical U fibers on both myelin and axonal stains. Microscopically, these areas showed diffuse vacuolation and significant reduction in the areal densities of glial cells. This change was never seen in areas that did not show extensive white matter hyperdensities on magnetic resonance imaging. The correlates of punctate magnetic resonance imaging hyperintensities were less well defined; dilated Virchow-Robin spaces probably represent a common cause of this phenomenon.

Aged↗
PubMed1993

Gadolinium enhancement in acute and chronic-progressive experimental allergic encephalomyelitis in the guinea pig.

Magnetic resonance imaging detects blood-brain barrier disruption after gadolinium-DTPA enhancement of central nervous system lesions of multiple sclerosis. Experimental allergic encephalomyelitis has many clinical and pathological features in common with multiple sclerosis including alterations in the integrity of the blood-brain barrier. We have compared T2-weighted cranial MR images with Gd-DTPA dimeglumine-enhanced T1-weighted images of myelin basic protein-induced acute (Days 8-42 postimmunization) and central nervous system-induced chronic-progressive (Days 70-95 postimmunization) forms of experimental allergic encephalomyelitis in the guinea pig. Although animals from both groups had abnormal T2-weighted images, only the myelin basic protein-acute-EAE animals (Days 14-24 postimmunization) showed enhancement on postcontrast MR studies. The different responses of the acute and chronic diseases may result from different immunogens, severity of disease, or different permeability of the blood-brain barrier. Therefore, gadolinium-DTPA-enhanced, T1-weighted MR images distinguish acutely active and chronic inflammatory lesions in experimental allergic encephalomyelitis.

Animals↗
PubMed1993

Genetic aspects of the organization of legumin genes in pea.

We have compared physical and genetic maps of the region around the legJ gene in pea. In this vicinity there are four B-type legumin genes, arranged as two close pairs. The detection of a recombination event within this gene cluster allows the orientation of this group of genes within the surrounding linkage group to be determined. The relationship between physical and genetic distances in this region is discussed, as are the implications of this for relating physical and genetic maps elsewhere in the pea genome.

Alleles↗
PubMed1993

Repeated sequences as genetic markers in pooled tissue samples.

We show, using the PDR1 element of pea, that dispersed repeated sequences of moderate copy number can be used simply and efficiently to generate markers linked to a trait of interest. Inspection of hybridization patterns of repeated sequences to DNA mixtures of pooled genotypes is a sensitive way of detecting such markers. The large number of bands in tracks of digests of these mixtures allows the simultaneous sampling of loci at many places in the genome, and the many unlinked loci serve as internal controls. It is also shown that intensity ratios calculated from these band differences can be used to give a rough estimate of linkage distance.

Chromosome Mapping↗
PubMed1993

Polymorphic 2-hydroxylation of desipramine. A population and family study.

We have studied desipramine hydroxylation capacity, determined as the metabolic ratio of desipramine to 2-hydroxydesipramine in the urine after a single oral dose of 10 mg of desipramine, in 340 Swedish Caucasians, including the members of 45 two-generation families. Desipramine metabolic ratios were bimodally distributed among 237 unrelated subjects and 8% were poor metabolizers. There was a strong correlation between the metabolic ratios for desipramine and debrisoquine in 337 subjects phenotyped with both drugs and there was no dissociation between their capacities to hydroxylate desipramine and debrisoquine. Complex segregation analysis in the 45 families gave evidence for a major locus with incomplete recessivity (d = 0.14) controlling the 2-hydroxylation of desipramine. Similar results were obtained in segregation analysis for debrisoquine. There was evidence for linkage between the CYP2D6 gene and the gene regulating the hydroxylation of desipramine and debrisoquine. This study has provided unequivocal evidence that the capacity to 2-hydroxylate desipramine is polymorphic and under similar genetic control to the hydroxylation of debrisoquine.

Adolescent↗
PubMed1993

Pulmonary lymphangiomyomatosis causing bilateral pneumothorax during pregnancy.

A 32-year-old woman, 12 weeks pregnant, presented with bilateral spontaneous pneumothorax that did not heal with tube thoracostomy. At right and left thoracotomy, lymphangiomyomatosis of the lung was found and treated by pleurodesis. Lymphangiomyomatosis has been infrequently reported in the surgical literature, even though it may befall the thoracic surgeon to establish the diagnosis and aid in treatment.

Adult↗
PubMed1993

Is there life after suicide? The systemic belief approach for "survivors" of suicide.

Following suicide of a loved one the lives of survivors can be plagued with anger, sadness, shame, guilt, health problems, and agonizing questions. This report presents the Systemic Belief approach to assisting survivors. A case example illustrates the influence beliefs have on survivors' lives. Constraining beliefs are challenged and facilitative beliefs are coevolved through the healing impact of family systems nursing interventions such as therapeutic letters, interventive questions, rituals, and reflecting teams.

Adaptation, Psychological↗
PubMed1993

Empyema due to Bacteroides gracilis: case report and in vitro susceptibilities to eight antimicrobial agents.

We describe a patient with empyema due to Bacteroides gracilis and a viridans streptococcus. Therapy with both cefoxitin and imipenem failed, and the patient remained symptomatic even after thoracotomy was performed. Clinical response occurred after initiation of clindamycin therapy. The susceptibilities of the patient's isolate, other clinical strains, and the reference strain were determined by an agar dilution method. The isolates were generally susceptible to all the agents tested; however, some strains were resistant to clindamycin (MIC, 8 micrograms/mL), penicillin G (MIC90, 16 micrograms/mL), and metronidazole (MIC90, 64 micrograms/mL). The B. gracilis isolate from our patient was susceptible to all agents tested, including cefoxitin and imipenem.

Adult↗
PubMed1993

A simple collection method for saliva in children: potential for home monitoring of carbamazepine therapy.

We have developed a method of monitoring plasma concentrations of antiepileptic drugs which uses salivary samples, and is suitable for home monitoring in children. To validate the method, paired plasma and saliva samples from 39 children aged between 2 and 15 years were assayed for carbamazepine and its active metabolite, carbamazepine-10,11-epoxide by h.p.l.c. The method uses a gauze-wrapped cotton ball with attached string, to absorb saliva which is then separated using a syringe and plunger. There was no adsorption of CBZ and CBZ-E and they were stable over 1 month in a domestic freezer. Plasma and salivary free CBZ and CBZ-E concentrations were highly correlated (r2 = 0.99 and 0.98, respectively).

Adolescent↗
PubMed1993

The adenylyl cyclase-cyclic AMP system modulates morphological and functional development of hypothalamic beta-endorphin neurons in culture.

In rats, opioidergic beta-endorphin (beta EP1-31) is produced and released from neurons of arcuate nuclei in the hypothalamus. Although the neuropeptide has been implicated in sexual maturation and stress-induced reproductive dysfunction, the intra-hypothalamic regulation of beta EP neurons remains unclear. Employing long-term monolayer cultures of neonatal rat hypothalamic cells, we report here that 4 days of treatment with 10 microM forskolin increased approximately 3-fold (P < 0.01) the proportion of immunoreactive (ir)-beta EP positive neurons bearing neurites. In addition, treatment of forskolin also enhanced ir-beta EP release (634 +/- 59 pg/well; mean +/- SE, n = 4, P < 0.01) by 14-fold and ir-beta EP content (119 +/- 13 pg/well; P < 0.01) by 2-fold above that of vehicle-treated cultures; in both instances, the EC50 and the Emax of forskolin were approximately 10 microM and 100 microM, respectively. The forskolin-stimulated release of ir-beta EP was mimicked by cholera toxin and (Bu)2cAMP treatment in a dose-related manner, but not by pertussis toxin. Although by itself 3-isobutyl-1-methyl-xanthine (100 microM) only doubled ir-beta EP secretion, it markedly potentiated the stimulatory effect of forskolin. This forskolin-induced stimulation was reversible and in cultures re-exposed to the same drug within the first 24 h period, there was a marked increase in the stimulated release of ir-beta EP (P < 0.05); re-challenge of forskolin at later stages, however, induced a smaller but significant secretion of ir-beta EP (P < 0.01) compared to that of vehicle-treated control cultures. Sephadex G-50 gel chromatographic profile of the media prepared from forskolin-treated cultures revealed a major ir-beta EP peak of 3 K M(r). High-performance liquid chromatography analysis showed that ir-beta EP of the 3 K M(r) species was eluted with a retention time similar to that of synthetic rat beta EP1-31. We thus conclude that the adenylyl cyclase-cAMP system plays an important role in the modulation of beta EP1-31 production and release from hypothalamic beta EP neurons in culture. Furthermore, the functional responsiveness and the morphological development of these neurons are affected, at least in part, by the intrinsic activity of the adenylyl cyclase-cAMP system.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Characterization of beta-amyloid peptide from human cerebrospinal fluid.

beta-Amyloid peptide (A beta) is one of the main components of senile plaques in the brain tissue of Alzheimer's disease (AD) patients. A beta is proteolytically cleaved from the amyloid precursor protein (APP), an integral membrane protein possessing a large extracellular N-terminal domain followed by a single membrane-spanning region and a short cytoplasmic C-terminal tail. A beta has been isolated from senile plaques and cerebral vascular tissue of AD brain and characterized as a heterogeneous peptide containing 28-43 amino acids whose sequence begins in the extracellular domain of APP and extends into the putative transmembrane sequence. It has long been speculated that A beta may also be present in body fluids, such as CSF, that contact neuritic plaques. Recently using a specific enzyme-linked immunosorbent assay we were able to quantify one form of A beta in CSF. In this report, using one of these antibodies covalently bound as an affinity matrix, multiple complex forms of A beta have been isolated and characterized from CSF derived from patients with either meningitis or other neurological disorders. Amino acid sequencing reveals A beta species with N-termini of Asp1, Glu3, His6, Glu11, and Val12, although on a molar basis, Asp1 represents the predominant aminoterminus. Laser desorption mass spectrometry confirmed the presence in CSF of A beta species containing 27, 28, 30, 34, 35, 40, 42, and 43 amino acids, all beginning at Asp1; two stable trimers, (Asp1-Met35)3 and (His6-Ala42)3; and one stable dimer containing (Asp1-Val40)2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A Pst+ polymorphism in the HEXA gene with an unusual geographic distribution.

A polymorphic variant in the human HEXA gene is described. This gene encodes the alpha-subunit of hexosaminidase A, the enzyme which is deficient in Tay-Sachs disease (TSD). In individuals carrying the polymorphism there is a T-->C transition at position -6 in intron 13. The substitution creates a site for the restriction endonuclease Pst1. This variant has an unusual ethnogeographic distribution. It occurs on 1.4% of non-TSD carrier chromosomes in Ashkenazi Jews. All individuals ascertained carrying the Pst+ allele have ancestry in Lithuania, Belarus and Ukraine. By contrast, no individuals carrying the Pst+ allele have been detected among non-Jewish Lithuanians, Jews of Sephardic origin or in several other ethnic groups. Two unrelated non-Jewish families have been identified in which the Pst+ variant occurs. In both cases the variant occurs on a chromosome carrying a novel TSD mutation (G772C) association with the B1 phenotype. The Pst+ G772C chromosomes are of Scots-Irish descent.

Alleles↗