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Biomedical subjects

G Lee

Publications and source records attributed to G Lee.

At least 217 records · Page 12Linked to original sources
PubMed1994

Orbital venous approach to the cavernous sinus: an analysis of the facial and orbital venous system.

Carotid-cavernous fistulas are abnormal communications between the internal carotid artery and the cavernous sinus produced by a rupture of the wall of the carotid artery or one of its branches into the sinus. Extradural branches of the internal or external carotid arteries may communicate with the cavernous sinus, producing proptosis, progressive glaucoma, and ocular vascular engorgement. Various approaches to obliterate these fistulas have evolved, many of which carry high morbidity or are precluded by anatomical considerations. Analysis of the venous anatomy of the orbit and face, including human cadaver dissections, reveals a new and safe approach to the cavernous sinus, requiring microsurgical isolation and cannulation of the superior ophthalmic vein through an anterior orbital approach. Selective embolization of a carotid-cavernous fistula can be performed successfully through this route. We present pertinent anatomy and technical considerations and the successful clinical application of these principles. Surgeons familiar with craniofacial anatomy and microvascular techniques can apply these principles and play an active role in the treatment of these complex problems.

Aged↗
PubMed1994

Dual modes of control of c-fos mRNA induction by intracellular calcium in T cells.

Cytoplasmic calcium is a nearly universal second messenger in eukaryotes. In many cell types, elevated intracellular calcium interacts synergistically with inducers of protein kinase C to elicit activation of complete biological programs normally induced by extracellular signals. In T cells, elevated cytoplasmic calcium is a critical mediator of activation in response to stimulation of the antigen receptor, and in some T-cell lines, treatment with a combination of calcium ionophore and protein kinase C activator mimics authentic antigen treatment. The synergistic interaction of calcium and protein kinase C in T cells is also observed at the level of gene expression. Here we examine the molecular mechanisms through which these agents exert synergistic control over the expression of the c-fos proto-oncogene in a T-cell hybridoma. We find that the principal effect of calcium is on the elongation of c-fos transcripts. This step constitutes the major control of c-fos mRNA accumulation in these cells. In addition, calcium regulates the initiation of c-fos transcription. This effect requires the serum response element of the c-fos gene and an additional sequence immediately 3' to this element. Thus, calcium regulates c-fos expression through at least two distinct molecular pathways.

Animals↗
PubMed1994

Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes "variant acute intermittent porphyria" with normal expression of the erythroid-specific enzyme.

Acute intermittent porphyria (AIP), an autosomal dominant inborn error, results from the half-normal activity of the heme biosynthetic enzyme, hydroxymethylbilane synthase (EC 4.3.1.8). Diagnosis of AIP heterozygotes is essential to prevent acute, life-threatening neurologic attacks by avoiding various precipitating factors. Since biochemical diagnosis is problematic, the identification of hydroxymethylbilane synthase mutations has facilitated the detection of AIP heterozygotes. Molecular analyses of unrelated AIP patients revealed six exonic mutations: an initiating methionine to isoleucine substitution (M1I) in a patient with variant AIP, which precluded translation of the housekeeping, but not the erythroid-specific isozyme; four missense mutations in classical AIP patients, V93F, R116W, R201W, C247F; and a nonsense mutation W283X in a classical AIP patient, which truncated the housekeeping and erythroid-specific isozymes. Each mutation was confirmed in genomic DNA from family members. The W283X lesion was found in another unrelated AIP family. Expression of each mutation in Escherichia coli revealed that R201W, C247F, and W283X had residual activity. In vitro transcription/translation studies indicated that the M1I allele produced only the erythroid-specific enzyme, while the other mutant alleles encoded both isozymes. These mutations provide insight into the molecular pathology of classic and variant AIP and facilitate molecular diagnosis in AIP families.

Base Sequence↗
PubMed1994

Identification of tau protein regions required for process formation in PC12 cells.

Tau is a neuronal microtubule-associated protein that is required for the development and maintenance of neuronal cell polarity. It promotes microtubule assembly in vitro and we have recently reported that a specific tau region, which spans amino acid residues 154-172 of human fetal tau, is not required for growth of existing microtubules, but is required for nucleation of new microtubules. These residues also confer stronger microtubule binding activity in 3T3 cells. The aim of this study was to investigate the functional organization of tau in relation to its role in promoting process formation in a neuronal model system. We transfected undifferentiated PC12 cells with vectors expressing tau fragments and treated the expressing cells with cytochalasin B to allow process extension. We found that deletion of amino acid residues 154-172 greatly reduced the percentage of transfected cells bearing processes compared to that of cells transfected with full-length tau or with an amino-terminally deleted tau fragment containing residues 154-172. These differences do not appear to result from a quantitative difference in protein expression, as shown by immunoblot analysis of transfected cells. We also observed that while the presence of tau fragments increases acetylation of microtubules, the pattern of acetylation in cells transfected with the fragment missing residues 154-172 is less extensive, suggesting that it does not result in the same level of stabilization as the longer tau fragments. Taxol promoted process outgrowth in cells treated with cytochalasin and restored process outgrowth to cells transfected with the tau fragment lacking this activity. Therefore, process formation involves primarily the stabilization and nucleation of microtubules. We conclude that the residues necessary for conferring microtubule nucleation activity of tau in vitro are important for process formation in vivo. It is likely that these residues influence the binding affinity and therefore the stabilization activity of tau.

Amino Acid Sequence↗
PubMed1994

The preparation and planning of artwork for book publication: the artist's viewpoint.

When becoming involved in the production of artwork for book publications the medical artist must interact and work with publishers through whom authors' instructions are conveyed. Procedures and job titles vary from one publisher to the other and misunderstandings can lead to costly mistakes. From a typical publishing situation a common approach to medical artwork preparation for book publication is described that will prepare the medical artist to work in close cooperation with the publishing team.

Book Industry↗
PubMed1994

A pilot study of anti-CD5 ricin A chain immunoconjugate in systemic lupus erythematosus.

OBJECTIVE: To determine the safety and clinical and biological effects of a murine monoclonal anti-CD5 ricin A chain immunoconjugate (CD5 Plus) in patients with systemic lupus erythematosus (SLE). METHODS: An open label phase I study of CD5 Plus. A dose of 0.1 mg/kg was administered intravenously on 5 consecutive days. A second course of immunoconjugate was given to patients who failed to show any clinical response one to 2 months later. RESULTS: Six patients (4 with glomerulonephritis and 2 with thrombocytopenia) were studied. Improvement was documented in 2 patients with nephritis; no effect on thrombocytopenia was observed. Adverse effects were mild and transient. Relative to pretreatment lymphocyte counts, the mean reduction in CD3+ T cell count was 69% at 2 weeks, 32% at one month, and 34% at 6 months following initial treatment. A comparable decrease in all subpopulations of mature T cells was noted, using a variety of surface markers, including CD4 and CD8. The mean percentage of T cells expressing the activation markers HLA-DR and interleukin 2R (IL-2R) was high before treatment, and remained so. There was a transient decrease in CD5+ B cells, but no persistent depletion of total B cell numbers. There was no consistent change in natural killer cell populations. CONCLUSION: Anti-CD5 ricin A chain immunoconjugate is well tolerated in patients with SLE, causes modest T cell depletion which may persist for months, and may have some clinical efficacy in lupus nephritis.

Antibodies, Monoclonal↗
PubMed1994

Death in the workplace.

Death in the workplace can have devastating effects on an organization, its employees, and the family of the deceased worker. Recognition of the industries in which deaths are more common will assist in initiating an analysis of risk factors. Planning a response to the potential occurrence of an occupational death can reduce later problems. Complying with legal and regulatory requirements includes preservation of the death site, completion of designated reports, investigations, and resolution of issues that may have contributed to the death. The long term effects of a fatality must be kept in mind in the planning process to ensure an organization's appropriate response and successful coping during the grieving process. Through involvement of the planning process, the occupational health nurse plays an integral part in the successful coping of the organization.

Accidents, Occupational↗
PubMed1994

Angiography, scintigraphy, intraosseous pressure, and histologic findings in high-risk osteonecrotic femoral heads with negative magnetic resonance images.

One hundred twenty-six hips of 68 patients who were suspected of having osteonecrosis or being at risk for osteonecrosis were studied with magnetic resonance (MR) imaging. Abnormal patterns on MR imaging characteristic of osteonecrosis were observed in 98 hips. The remaining 28 hips (22 patients) with negative MR images underwent superselective angiography of the medial femoral circumflex artery. Angiography showed interruption of the superior retinacular arteries in 13 hips (12 patients), including 6 of 7 symptomatic hips. Bone scans were performed on 8 of 13 hips angiographically positive for osteonecrosis. Decrease of radionuclide uptake (cold lesions) was observed in all 8 of these femoral heads. Thirteen femoral heads with interruption of superior retinacular arteries underwent intraosseous pressure measurement and core biopsy. Intraosseous pressure was elevated in 11 hips. The results of histologic study showed evidence of early necrosis in 10 femoral heads. This study indicates that there are a considerable number of femoral heads at high risk, even when they have negative MR images. They do, however, show positive findings on angiography, scintigraphy (cold lesions), intraosseous pressure measurement, and histologic study.

Adolescent↗
PubMed1993

Diffusivity and structural polymorphism in some model stratum corneum lipid systems.

Mixtures of model stratum corneum lipids were prepared in water from cholesterol, six fatty acids and ceramides. The influence of composition on the polymorphism of these mixtures and also on the diffusivity of a model drug within them, Dlip, was determined. The former was obtained from X-ray diffraction and Fourier transform infrared spectrometry, and the latter from a diffusional release model. An L beta structure was formed for the composition approximating that of the extracellular lipids in intact human abdominal stratum corneum. Dlip was independent of water content in the range 20-40% w/w, with the bilayers showing one dimensional swelling without lateral expansion. Although removal of the ceramides did not result in a significant alteration in Dlip, crystalline cholesterol now appeared. The ceramides were, therefore, necessary for solubilization within the fatty acid bilayers of the large proportion of cholesterol present in the lipid fraction of intact SC. They were also responsible for a thermal L alpha-HII transition observed at approx. 68 degrees. At the concentration in which it exists in intact SC, cholesterol also had only a minimal effect on Dlip, but was necessary to suppress HII phase formation within the fatty acids and ensure an L beta structure. All lipid mixtures that had an L beta structure presented a diffusional barrier approx. 1 order of magnitude greater than that of an unstructured, isotropic lipid mixture. HII structures formed at cholesterol/fatty acid proportions less than approx 8:92 mol% and appeared more permeable than L beta ones. All the results indicate that the diffusional barrier within the model lipid mixtures is guaranteed essentially by the presence of an L beta phase. Although the ceramides and cholesterol exert no intrinsic influence on the magnitude of Dlip, their presence in necessary for the existence of an L beta phase at 33 degrees that is free of both crystalline cholesterol and HII character.

Ceramides↗
PubMed1993

Functional organization of microtubule-associated protein tau. Identification of regions which affect microtubule growth, nucleation, and bundle formation in vitro.

Tau protein is a microtubule-associated protein that is almost exclusively expressed in the brain and is enriched in the axon. Determination of tau's sequence has revealed three to four tandem repeats that have been shown to constitute the microtubule binding site. In order to study the functional organization of tau, we prepared a series of truncated tau fragments using an Escherichia coli expression system. We assayed each fragment's activity in promoting growth of microtubules and in nucleating free microtubules. We found that tau's ability to nucleate microtubules requires the presence of additional sequence amino-terminal to that required for growth. We demonstrate that tau's carboxyl and amino termini differentially affect microtubule growth and nucleation. Finally, we show that in vitro microtubule bundle formation occurs when tubulin is assembled in the presence of an amino- and carboxyl-terminally truncated tau protein, whereas almost no bundling is observed in the presence of full-length tau or tau fragments that contain the amino terminus in addition to the repeat domain. We conclude that although the presence of the repeat domain promotes the growth of microtubules, the structural requirements for nucleation activity are more stringent. The differentiation between the growth promoting and nucleation activities on the structural level makes it possible for the two activities to be differentially regulated in vivo.

Animals↗
PubMed1993

A comparison of techniques for introducing macromolecules into living cells.

Flow cytometry has been used to evaluate several techniques for introducing macromolecules into large numbers of living cells. One technique is cell fusion with red blood cell ghosts loaded with a fluorescent reporter molecule (RBCF). The second technique, termed osmotic lysis of pinosomes (OLP), involves a brief exposure of cells to a hypertonic solution containing the reporter molecule; subsequently, a hypotonic media is added which lyses the pinosomes formed during the hypertonic treatment. A third technique, scrape loading (SL), involves the creation of transient holes in the cell membrane through the application of mechanical forces, which allows for the passage of reporter molecules into cells. A comparison of these techniques is presented here. OLP appears to offer several advantages: It is a simple procedure, virtually all cells are fluorescently labelled, and it is capable of loading larger amounts of material more uniformly into cells while maintaining excellent viability.

Cell Fusion↗
PubMed1993

Short-term memory impairments in Alzheimer-type dementia: evidence for separable impairments of articulatory rehearsal and long-term memory.

Two experiments are described which investigate the short-term memory deficits found in Alzheimer-type dementia. In the first experiment memory span for words of differing spoken duration is related to speech rate. Memory span was lower in subjects suffering from Alzheimer-type dementia than for normal elderly controls but in both cases a linear function related recall to speech rate for items of differing spoken durations. The function for Alzheimer subjects had an equivalent slope (interpreted as reflecting a contribution from a sub-vocal rehearsal process) but a lower intercept (interpreted as reflecting a contribution from a long-term memory component). The second experiment investigated the effects of repeating supra-span lists of items in a serial recall task. As predicted the control subjects showed substantial increases in recall across trials associated with elevations of the speech rate/recall functions while the Alzheimer subjects showed very little benefit from repetition of the lists. We conclude that the verbal short-term memory deficit found in Alzheimer-type dementia has two components: a deficit in the rate of rehearsal and an impairment in the long-term memory component of short-term recall.

Aged↗
PubMed1993

Non-motor microtubule-associated proteins.

This past year, the structure and function of microtubule-associated proteins (MAPs) have been investigated in studies probing their phosphorylation, patterns of expression, and the function of the microtubule-binding domain. Cellular studies have also contributed new insights into the roles of these proteins in process outgrowth.

Amino Acid Sequence↗
PubMed1993

Strong inhibition of fibrinogen binding to platelet receptor alpha IIb beta 3 by RGD sequences installed into a presentation scaffold.

In order to probe the structural constraints on binding of RGD sequences to the platelet receptor alpha IIb beta 3 we have used recombinant DNA techniques to install the RGD sequence into 'presentation scaffolds', small proteins of known 3-D structure chosen to present guest sequences in constrained orientations. Using Escherichia coli expression systems we made sequence variants in which loop residues of the immunoglobulin VL domain REI and of human interleukin-1 beta were replaced (without changing polypeptide length) by the RGD sequence at positions predicted, based on small molecule studies, to orient the RGD moiety into an active conformation. These variants do not compete for fibrinogen binding to alpha IIb beta 3 up to almost 1 mM concentration. Unfolded or proteolytically fragmented forms of these same proteins do compete, however, showing that the RGD sequences in the mutants must be prohibited from binding by constraints imposed by scaffold structure. To suppress the effects of such structural constraints we constructed two sequence variants in which RGD-containing sequences 42-57 or 44-55 from the snake venom platelet antagonist kistrin were inserted (this increasing the length of the loop) into the third complementarity determining loop of REI. Both of these variants compete strongly for fibrinogen binding with IC50s in the nM range. These results, plus data on kistrin-related peptides also presented here, suggest that the molecular scaffold REI is capable of providing to an installed sequence a structural context and conformation beneficial to binding. The results also suggest that in order to bind well to alpha IIb beta 3, RGD sequences in protein ligands must either project significantly from the surface of the scaffold and/or retain a degree of conformational flexibility within the scaffold. Molecular scaffolds like REI should prove useful in the elucidation of structure-function relationships and the discovery of new active sequences, and may also serve as the basis for novel therapeutic agents.

Amino Acid Sequence↗
PubMed1993

Use of a computerized postural sway measurement system for assessing workers exposed to manganese.

1. Computerized postural sway measurement systems have been used recently in human physiology and pharmacology for determining postural stability, but their applicability for the assessment of the effects of exposure to neurotoxic agents is lacking. 2. We have examined the feasibility of using a computerized postural sway measurement system to assess the postural sway parameters of manganese exposed workers compared with a control group. 3. Sway parameter data were collected using a KISLTER multicomponent measuring platform (Type 9281B) connected to VICON motion analysis system for 13 exposed and 16 control subjects. 4. Significant differences in several of the sway parameters (Px, Py--mean distance (mm), from the centre of the platform along the X-axis [anterior-posterior movement] and Y-axis [lateral movement], respectively) between the exposed and control groups were observed even after adjustment for possible confounders. Computerized postural sway measurement system may be a useful method of assessing workers exposed to neurotoxic agents affecting posture.

Adult↗
PubMed1993

The balance between tau protein's microtubule growth and nucleation activities: implications for the formation of axonal microtubules.

The microtubule-associated protein tau is found primarily in neuronal tissues and is highly enriched in the axon. It promotes microtubule assembly in vitro and stabilizes microtubules in cells. To study how tau protein might be involved in the unique features of axonal microtubules, we have analyzed the effect of E. coli-synthesized tau protein using an in vitro centrosome-mediated microtubule regrowth assay over a wide range of tau/tubulin ratios. We report that microtubule assembly promoted by tau protein exhibits characteristic changes dependent on the tau/tubulin ratio. Above a threshold level, nucleation of new microtubules is favored over growth of existing ones. tau isoform variation does not change this phase transition in microtubule assembly. We discuss how tau might participate in the elaboration of axonal morphology based on our results and present evidence that the phase transition from microtubule growth to nucleation is critical for axonal development.

Axons↗