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Biomedical subjects

B Kim

Publications and source records attributed to B Kim.

At least 109 records · Page 6Linked to original sources

Anatomical communications of the perirenal space.

There are controversies over the anatomical communications between the perirenal space and the adjacent extraperitoneal spaces. Clinical studies, mainly based on CT, show fluid collections extending into the adjacent space; into the bare area of the liver on the right, into the superior extraperitoneal space on the left, towards the midline from each perirenal space, and into the lower retroperitoneal space of the abdomen and pelvis. There are certain constant anatomical barriers limiting free extension of fluid or pathology. The pattern of fluid collection in the perirenal space and extension into the adjacent extraperitoneal space is relatively consistent although it varies with the amount and nature of the pathological fluid collection. This pictorial review illustrates anatomical barriers and CT findings of perirenal fluid collections and their extension into adjacent extraperitoneal spaces.

Adult↗

The life history and host specificity of Hepatozoon clamatae (Apicomplexa: Adeleorina) and ITS-1 nucleotide sequence variation of Hepatozoon species of frogs and mosquitoes from Ontario.

The life cycle of an intraerythrocytic hemogregarine, Hepatozoon clamatae, was studied in green frogs (Rana clamitans melanota), bullfrogs (Rana catesbeiana), northern leopard frogs (Rana pipiens), and in the mosquito, Culex territans. Gametogenesis, fertilization, and sporogony occurred within cells of the Malpighian tubules of laboratory-reared Cx. territans that had fed on naturally infected frogs. Mature oocysts containing hundreds of sporocysts were observed in mosquitoes 30 days postfeeding. Each sporocyst enclosed 4 sporozoites. Merozoites appeared in the peripheral circulation of laboratory-reared bullfrogs, green frogs and leopard frogs that had been fed sporocysts 35-70 days previously. Attempts to infect American toads (Bufo americanus) and blue-spotted salamanders (Ambystoma laterale) were not successful. Gamonts of this parasite induced nuclear fragmentation or segmentation in host erythrocytes. The life cycle, morphological, and morphometric features of H. clamatae are compared with H. catesbianae, a similar species that also infects ranids. Nucleotide sequence analysis of the internal transcribed spacer region (ITS-1) of these sympatric species revealed that only 6 nucleotide sites of the 129 base pairs of this region were variable among 4 isolates of H. clamatae and 2 isolates of H. catesbianae. A redescription of H. clamatae is presented based on data from this study and from the original description by Stebbins in 1905.

Animals↗

Nocardia, nocardiosis and mycetoma.

The recent emergence of invasive infections due to Nocardia spp., including nosocomial outbreak, is now evident. Newer molecular diagnostic and typing methods are developed. Although sulfonamide-based therapy is generally effective, optimal treatment may be guided by antimicrobial susceptibility testing of isolates. The improved classification of nocardiae and other related genera such as actinomadurae, using the 16S ribosomal RNA sequencing, provide a sound basis for improved diagnostic methods for the identification of members of clinically significant species. The commonest cause of eumycetoma in Sudan is Madurella mycetomatis, and Streptomyces somaliensis and Actinomadura madurae for actinomycetoma. The humoral immunity response in actinomycetoma patients and in experimental mice was measured and significant titre of anti-P24 antibody was demonstrated.

Actinomycetales↗

Insulin-like growth factor-I-mediated neurite outgrowth in vitro requires mitogen-activated protein kinase activation.

Insulin-like growth factor-I (IGF-I) induces neuronal differentiation in vitro. In the present study, we examined the signaling pathway underlying IGF-I-mediated neurite outgrowth. In SH-SY5Y human neuroblastoma cells, treatment with IGF-I induced concentration- and time-dependent tyrosine phosphorylation of the type I IGF receptor (IGF-IR) and extracellular signal-regulated protein kinases (ERK) 1 and 2. These effects of IGF-I were blocked by a neutralizing antibody against IGF-IR. Whereas IGF-IR phosphorylation was observed within 1 min, maximal phosphorylation of ERKs was not reached for 30 min. Both IGF-IR and ERK phosphorylation were maintained for at least 24 h. Also, the concentration dependence of IGF-I-stimulated IGF-IR and ERK tyrosine phosphorylation paralleled that of IGF-I-mediated neurite outgrowth. We further examined the role of mitogen-activated protein kinase activation in IGF-I-stimulated neuronal differentiation using the mitogen-activated protein kinase/ERK kinase inhibitor PD98059. Whereas PD98059 had no effect on IGF-IR phosphorylation, PD98059 reduced IGF-I-mediated ERK tyrosine phosphorylation and ERK phosphorylation of the substrate Elk-1. PD98059 also produced a parallel reduction of IGF-I-stimulated neurite outgrowth. Finally, consistent with its ability to block neuronal differentiation, PD98059 inhibited IGF-I-dependent changes of GAP-43 and c-myc gene expression. Together these results suggest that activation of ERKs is essential for IGF-I-stimulated neuronal differentiation.

Calcium-Calmodulin-Dependent Protein Kinases↗

Tyrosine phosphorylation of paxillin and focal adhesion kinase during insulin-like growth factor-I-stimulated lamellipodial advance.

In the current studies, we examined whether focal adhesion kinase (FAK) and paxillin play a role in insulin-like growth factor-I (IGF-I)-stimulated morphological changes in neuronal cells. In SH-SY5Y human neuroblastoma cells, 10 nM IGF-I enhanced the extension of lamellipodia within 30 min. Scanning electron microscopy and staining with rhodamine-phalloidin showed that these lamellipodia displayed ruffles, filopodia, and a distinct meshwork of actin filaments. Immunofluorescent staining identified focal concentrations of FAK, paxillin, and phosphotyrosine within the lamellipodia. Immunoprecipitation experiments revealed that FAK and paxillin are tyrosine-phosphorylated during IGF-I-stimulated lamellipodial extension. Maximal phosphorylation of FAK and paxillin was observed 15-30 min after the addition of 10 nM IGF-I, whereas maximal IGF-I receptor phosphorylation occurred within 5 min. FAK, paxillin, and IGF-I receptor tyrosine phosphorylation had similar concentration-response curves and were inhibited by the receptor blocking antibody alphaIR-3. These results indicate that FAK and paxillin are tyrosine-phosphorylated during IGF-I-stimulated lamellipodial advance and suggest that the tyrosine phosphorylation of these two proteins helps mediate IGF-I-stimulated cell and growth cone motility. These responses contrast directly with recent reports showing insulin-stimulated dephosphorylation of FAK and paxillin.

Cell Adhesion Molecules↗

Suramin disrupts insulin-like growth factor-II (IGF-II) mediated autocrine growth in human SH-SY5Y neuroblastoma cells.

Suramin, traditionally used in the treatment of trypanosomiasis, is under investigation in the treatment of cancer. One side effect that limits its use is the onset of a sensorimotor polyneuropathy. In order to investigate the mechanism by which suramin induces polyneuropathy, we examined its effects on SH-SY5Y human neuroblastoma cells, an in vitro model of neuronal growth and differentiation. Addition of 50-400 micrograms/ml suramin to SH-SY5Y cells grown in 0.6% CS inhibited [3H]thymidine ([3H]TdR) incorporation and cell growth. Upon removal of suramin, [3H]TdR incorporation increased, demonstrating that levels of suramin used were cytostatic and not cytotoxic. Analysis of suramin-treated SH-SY5Y cells by flow cytometry revealed growth arrest in the G1/G0 phase of the cell cycle. IGF-II-induced SH-SY5Y growth is mediated by the type I IGF receptor (IGF-IR). Therefore, we examined its effect on IGF-IR tyrosine phosphorylation. Suramin prevented IGF-II-stimulated IGF-IR tyrosine phosphorylation. These results indicate that in SH-SY5Y cells, suramin acts as a cytostatic agent and can block IGF-II-dependent cell growth by preventing IGF-IR activation. Thus, suramin toxicity in the peripheral nervous system may be due, in part, to preventing IGF and other growth factors from activating their receptors.

Brain Neoplasms↗

Endotoxin-induced macrophage gene expression depends on platelet-activating factor.

BACKGROUND: The development of multiple organ failure in septic patients is due to a systemic inflammation orchestrated by macrophages (Mphi). Elucidation and control of the mechanism involved in Mphi activation in sepsis is crucial to improving survival. An early event of Mphi activation involves the hydrolysis of membrane phospholipid by phospholipase A2 (PLA2) and subsequent generation of platelet-activating factor (PAF). OBJECTIVE: We designed this study to test the hypothesis that Mphi gene expression depends on PAF. DESIGN: Rabbit alveolar Mphi were obtained by bronchoalveolar lavage and were stimulated with 10 ng/mL of Escherichia coli endotoxin lipopolysaccharide (LPS), PAF (1 micromol/L), LPS+/-CV3988 (10 micromol/L), a PAF receptor antagonist, or LPS+/-PLA2 inhibitors: AACOCF3 (50 micromol/L) or manoalide (10 micromol/L). After 4 hours of incubation, Mphi tumor necrosis factor (TNF) messenger RNA (mRNA) expression was assessed by Northern blot analyses. The TNF production in the Mphi supernatant was measured by L929 bioassays. RESULTS: The LPS-stimulated Mphi expressed increased levels of TNF mRNA and produced an enormous amount of TNF. CV3988, a PAF antagonist, inhibited LPS-induced TNF mRNA. Furthermore, inhibiting PAF production with AACOCF3, or manoalide, also inhibited LPS-induced Mphi TNF mRNA expression. The effect of PAF depends on changes in intracellular calcium concentration. Inhibitors of calcium flux attenuated the PAF effects on LPS-stimulated Mphi. CONCLUSIONS: Our data suggest that LPS-induced Mphi gene expression is mediated by PAF. It is likely that modulation of PAF production or activity may be beneficial in down-regulating the overactivity of Mphi in sepsis.

Animals↗

Macrophage TNF mRNA expression is modulated by protease inhibitors.

BACKGROUND: Nuclear factor kappa B (NF kappa B) is an important transcriptional activator protein and is a crucial component of the host's response to infection. The activation of NF kappa B is correlated with the phosphorylation of inhibitory kappa B (I kappa B) and its subsequent degradation. We hypothesized that protease inhibitors which prevented I kappa B degradation could inhibit the macrophage gene activation and reduce the production of inflammatory cytokines. METHODS: Rabbit alveolar macrophages (M phi) were obtained by bronchoalveolar lavage. M phi were exposed to Escherichia coli lipopolysaccharide (LPS) (10 ng/ml) in the presence of various concentrations of protease inhibitors, either N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) or N-benzoyl-L-tyrosine ethyl ester (BTEE). Total RNA was extracted for Northern blot assay of tumor necrosis factor (TNF) mRNA expression using a rabbit genomic DNA probe. Total nuclear extracts were also obtained for the measurement of the NF kappa B activity with the electrophoretic mobility shift assay. The TNF production in the M phi supernatant was measured by L929 bio-assays. RESULTS: NF kappa B activity induced by LPS was inhibited by either BTEE or TPCK. Inhibition of NF kappa B activity by these agents also prevented TNF mRNA expression and TNF production induced by LPS. The cellular mechanism leading to NF kappa B activation was further studied. TNF mRNA expression and NF kappa B activation were inhibited by D609, a phospholipase C (PLC) inhibitor, as well as by protein kinase C (PKC) inhibitors. In addition, direct stimulation of PKC led to NF kappa B activation and TNF mRNA expression. CONCLUSIONS: These data suggest that TNF mRNA expression of LPS-stimulated M phi is mediated through NF kappa B, NF kappa B activation is intimately regulated by the PLC signaling pathway.

Animals↗

Genetic selection in Escherichia coli for active human immunodeficiency virus reverse transcriptase mutants.

Most catalytically active human immunodeficiency virus (HIV) reverse transcriptase (RT) mutants characterized to date have been isolated from the virus after treatment with HIV RT inhibitors such as nucleoside analogs. However, detailed understanding of structure-function relationships, and of the roles of the several catalytic activities of HIV RT in viral replication, requires characterization of a greater diversity of mutant enzymes than has been obtained from viral variants. Coupling of a bacterial genetic selection system for functional HIV RT with random mutagenesis has yielded a large number of active mutant enzymes, most of which have not been found in viral variants. The genetic selection system, combined with biochemical characterization of active mutant proteins, affords three major benefits. First, we can increase our understanding of the roles of individual amino acids in catalysis. Second, the mutational spectrum observed among active HIV RT variants can identify amino acids that are intolerant, or relatively intolerant, of substitution. Third, this system provides us with HIV RT variants with altered biochemical properties, such as replicational fidelity and processivity. Characterization of HIV harboring these mutant RTs with defined structural and functional alterations will contribute to elucidation of the roles of each catalytic activity of HIV RT in viral replication.

Chromatography, Affinity↗

Insulin-like growth factors regulate neuronal differentiation and survival.

Insulin-like growth factor I (IGF-I) and IGF-II are potent trophic factors for motor and sensory neurons and glial cells. The actions of IGF-I and IGF-II are mediated via the IGF-I receptor (IGF-IR). IGF:IGF-IR binding activates distinct signaling cascades, which in turn mediate the trophic effects of the IGFs. We discuss three main IGF coupled events: growth cone motility, long-term neurite outgrowth, and neuroprotection. Our data suggest that IGF-I enhances growth cone motility by promoting reorganization of actin and activation of focal adhesion proteins via the phosphatidylinositol-3 kinase (Pl-3K) pathway. Long-term treatment with IGF-I activates the mitogen-activated protein (MAP) kinase cascade and promotes neurite outgrowth. A separable, but likely linked, action of the IGFs via Pl-3K is protection of neurons from apoptosis. These pleotrophic effects of IGFs suggest that this family of growth factors may have potential clinical utility in the treatment of neurological disorders.

Animals↗

Mutual information for automated unwarping of rat brain autoradiographs.

An automated multimodal warping based on mutual information metric (MI) as a mapping cost function is demonstrated. Mutual information (I) is calculated from a two-dimensional (2D) gray scale histogram of an image pair, and MI (= -I) provides a matching cost function which can be effective in registration of two- or three-dimensional data sets independent of modality. Most histological image data, though information rich and high resolution, present nonlinear deformations due to the specimen sectioning and need reconstitution into deformation-corrected volumes prior to geometric mapping to an anatomical volume for spatial analyses. Section alignment via automatic 2D registrations employing MI as a global cost function and thin-plate-spline (TPS) warping is applied to deoxy-D-[14C]glucose autoradiographic image slices of a rat brain with video reference images of the uncut block face to reconstitute a cerebral glucose metabolic volume data. Unlike the traditional feature-based TPS warping algorithms, initial control points are defined independently from feature landmarks. Registration quality using automated multimodal image warping is validated by comparing MIs of the image pair registered by automated affine registration and manual warping method. The MI proves to be a robust objective matching cost function effective for automatic multimodality warping for 2D data sets and can be readily applied to volume registrations.

Algorithms↗

Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations.

This paper applies and evaluates an automatic mutual information-based registration algorithm across a broad spectrum of multimodal volume data sets. The algorithm requires little or no pre-processing, minimal user input and easily implements either affine, i.e. linear or thin-plate spline (TPS) warped registrations. We have evaluated the algorithm in phantom studies as well as in selected cases where few other algorithms could perform as well, if at all, to demonstrate the value of this new method. Pairs of multimodal gray-scale volume data sets were registered by iteratively changing registration parameters to maximize mutual information. Quantitative registration errors were assessed in registrations of a thorax phantom using PET/CT and in the National Library of Medicine's Visible Male using MRI T2-/T1-weighted acquisitions. Registrations of diverse clinical data sets were demonstrated including rotate-translate mapping of PET/MRI brain scans with significant missing data, full affine mapping of thoracic PET/CT and rotate-translate mapping of abdominal SPECT/CT. A five-point thin-plate spline (TPS) warped registration of thoracic PET/CT is also demonstrated. The registration algorithm converged in times ranging between 3.5 and 31 min for affine clinical registrations and 57 min for TPS warping. Mean error vector lengths for rotate-translate registrations were measured to be subvoxel in phantoms. More importantly the rotate-translate algorithm performs well even with missing data. The demonstrated clinical fusions are qualitatively excellent at all levels. We conclude that such automatic, rapid, robust algorithms significantly increase the likelihood that multimodality registrations will be routinely used to aid clinical diagnoses and post-therapeutic assessment in the near future.

Abdomen↗

Epilepsy management. Issues in medical and surgical treatment.

After a single seizure, about 40% of patients have recurrence. The main features correlating with recurrence are cause, seizure type, EEG findings, family history of seizures and, possibly, the presence of a prior febrile seizure, Todd's paresis, and other abnormal neurologic findings. A number of medications are available for treatment. Withdrawal from medication is successful in 60% to 70% of patients. Several factors favor successful drug taper. These include a seizure-free status for at least 2 years during drug therapy, a single type of seizure (partial or generalized), young age at seizure onset, and an epilepsy syndrome with a tendency to remit. Surgery can be considered in certain patients with surgically remediable syndromes. Candidates typically have seizures that impair consciousness, that cause falling with injury, that have adverse psychosocial or social effects, and that persist after trials of three appropriate medications. A multidisciplinary evaluation should take place at a surgery center with experience and documented success. Favorable results from surgery can be expected in a large proportion of patients.

Anticonvulsants↗

Display of coregistered cross-modality images using time-weighted alternation method.

Cross-modality coregistration of functional and anatomical images has rapidly grown as the aid for the interpretation of functional images. Various methods have been previously investigated so that the coregistered images can be easily interpreted and realistically visualized. We used the time/intensity-weighted alternation method to display the coregistered images simultaneously. Stereotactic registration was done with two methods. We realized the automated method of alignment using the boundary of head scalp extracted from the sinogram of a PET emission scan and surface-matching algorithm in brain, and the semi-automated method using a paired point-matching algorithm in the chest and abdomen. For the simultaneous display of the stereotactically registered images, rapid switching of the screens were applied on which both images were written with independent color scales. Rapid alternate display of two images, that is synchronized using the monitor scanning process, could induce the fusion of images in the human visual perception system. Also, intensification of an interesting image is possible by weighting the displaying time or global intensities of images with the degree of interest. These techniques could be useful for the interpretation and visualization of the coregistered images.

Brain↗

Angiocentric T cell lymphoma of the skin presenting as inflammatory nodules of the leg.

We describe two cases of malignant lymphoma presenting as inflammatory nodules of the leg and mimicking panniculitis clinically. In both cases the skin biopsies showed prominent involvement of the subcutaneous tissue by lymphoma cells. In addition, lymphoma cells invaded blood vessels in the dermis or the subcutaneous tissue. One case was characterized by predominantly extravascular and intravascular location of the lymphoma cells, and the other case by the predominantly extravascular and intramural location of lymphoma cells. These histological findings were compatible with those of angiocentric T-cell lymphoma but with some unusual features. Angiocentric T-cell lymphoma of the skin should be listed in the group of diseases which present as inflammatory nodules of the leg.

Adult↗

Hypothermia-induced changes of afferent sensory transmission to the SI cortex of rats and hamsters.

The effects of acute lowering of body temperature on afferent sensory transmission to the primary somatosensory cortex were determined quantitatively in anaesthetized rats and hamsters. Rats showed no change in afferent sensory transmission until 27 degrees C, but dramatic suppression between 26 degrees C and 22 degrees C, reaching 100% inhibition at 21 degrees C. Hamsters exhibited gradual suppression of sensory transmission from 34 degrees C to 18 degrees C, reaching 95% inhibition at 18 degrees C. Differential effects were also observed during rewarming up to 37 degrees C. Response latencies were also differentially affected during hypothermia in rats and hamsters. These results suggest the presence of inherently different neural mechanisms to process somatosensory information during transient lowering of body temperature between hibernators and non-hibernators.

Animals↗