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Biomedical subjects

C W Chen

Publications and source records attributed to C W Chen.

At least 73 records · Page 4Linked to original sources

A novel volumetric feature extraction technique with applications to MR images.

A semiautomated feature extraction algorithm is presented for the extraction and measurement of the hippocampus from volumetric magnetic resonance imaging (MRI) head scans. This algorithm makes use of elements of both deformable model and region growing techniques and allows incorporation of a priori operator knowledge of hippocampal location and shape. Experimental results indicate that the algorithm is able to estimate hippocampal volume and asymmetry with an accuracy which approaches that of laborious manual outlining techniques.

Algorithms↗

Role of KATP channels on modulating diaphragmatic microvascular flow during hemorrhagic hypotension.

The effects of glibenclamide (GLB), a specific blocker of ATP-sensitive potassium (KATP) channels, and tetraethylammonium (TEA) on modulating the regulation of diaphragmatic microcirculation were assessed in anesthetized mechanically ventilated rats. With bicarbonate-buffered Ringer solution continuously suffusing the left hemidiaphragm, microcirculatory blood flow was recorded by laser-Doppler flowmetry (QLDF). Hemorrhagic hypotension (HH) was induced via bleeding into a pressure reservoir. Five sets of experiments were performed. In set 1 (n = 6), the vasodilator effect of diazoxide (3 x 10(-4) M) was abolished after a 30-min suffusion with GLB, whereas the vasodilator effect of sodium nitroprusside (3 x 10(-6) M) remained the same. In set 2 (vehicle + HH; n = 23), a stepwise reduction in systemic arterial blood pressure (ABP) induced two distinct patterns of microvascular responses. Regulation of QLDF could be observed in pattern A animals in a range of ABP from 113 to 52 mmHg, whereas QLDF in pattern B animals rose progressively with declining ABP. In set 3 (GLB + HH; n = 17), baseline values of QLDF were not significantly affected after a 30-min suffusion of GLB (10(-5) M). During HH, two microvascular patterns similar to those in set 2 were observed. GLB significantly potentiated the reduction in QLDF in pattern A animals. In contrast, GLB had no effect on QLDF in pattern B animals. In set 4 (TEA + HH; n = 17), similar microvascular responses, compared with the vehicle group, were observed during HH after a 30-min suffusion of TEA (2 x 10(-3) M). In set 5 (n = 5), baseline values of QLDF were not significantly altered during sham hypotension. We conclude that 1) KATP channels are functional but not active in the resting diaphragmatic microcirculation and 2) KATP channels can modulate regulation of the microcirculation in the resting diaphragm during HH.

Adenosine Triphosphate↗

Fatal acute pulmonary oedema after inhalation of fumes from polytetrafluoroethylene (PTFE).

The cases of three patients with acute pulmonary oedema caused by inhalation of fumes from heated polytetrafluoroethylene (PTFE) in a plastic factory are described. One patient died from profound hypoxaemia and shock shortly after admission, and the other two patients survived after medical treatment. This is the first report of fatal pulmonary oedema in a worker exposed to PTFE heated in a plastic extruding operation. From this observation, it appears that inhalation exposure to pyrolytic products from polytetrafluoroethylene can cause fatal respiratory complications. Special precautions are warranted in this kind of operation to prevent workers from being exposed to these substances.

Acute Disease↗

Response of medial medullary reticular neurons to otolith stimulation during bidirectional off-vertical axis rotation of the cat.

In decerebrate cats, the extracellular activities of neurons in the medial medullary reticular formation were studied during constant velocity off-vertical axis rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions (at 10 degrees tilt). Spontaneously active neurons demonstrated sinusoidal position-dependent discharge modulations to OVAR which selectively stimulates the otoliths. Two features of neuronal responses to bidirectional OVAR were identified. Within the velocity spectrum tested (1.75-15 degrees/s), some neurons showed symmetric bidirectional response sensitivity (delta value) to CW and CCW rotations. The spread of the delta values of each of these neurons with velocity was small. This group of reticular neurons were described as exhibiting symmetric and velocity-stable bidirectional response sensitivity. The mathematically derived gain tuning ratios of these neurons were within the range of narrowly spatiotemporal-tuned neurons. Another group of reticular neurons, however, showed asymmetric bidirectional response sensitivity to CW and CCW rotations; a few of these neurons were responsive only to OVAR of one direction but not to both. For each of this second group of neurons, the spread of the delta values with velocity was large. These reticular neurons were described as exhibiting asymmetric and velocity-variable bidirectional response sensitivity. The gain tuning ratios of these latter neurons were found to be within the range of broadly spatiotemporal-tuned neurons. Single neurons of both groups displayed orientational tuning. Both the best response orientations of neurons that showed symmetric and velocity-stable bidirectional response sensitivity and the preferred orientations of neurons that showed asymmetric and velocity-variable bidirectional response sensitivity were found to point in all directions on the rotary plane. The response dynamics of the former group of neurons was also examined. All showed flat response gain across the entire velocity range. Some showed a flat response lead while others showed a progressive shift from small response lead at low velocity to phase close to zero at higher velocities. The functional significance of these medial medullary reticular neurons to the direction and orientation of head tilt is discussed.

Animals↗

Inhibition of stilbene estrogen-induced cell proliferation of renal epithelial cells through the modulation of insulin-like growth factor-I receptor expression.

In the present study, we have investigated the effects of stilbene estrogen, diethylstilbestrol (DES), on the proliferative activity and expression of insulin-like growth factor-I (IGF-I) receptor in Syrian hamster renal epithelial cells. DES exposure to renal epithelial cells caused both dose- and time-dependent increases in proliferative activity. We also tested the effects of antiestrogen ICI 182780 and insulin-like growth factor-I receptor (IGF-IR) antibody on cell proliferation. Cotreatment of cells with ICI 182780 (250 nM) and DES resulted in a 50% decrease in cell growth compared to DES alone. Treatment of cells with an anti-IGF-IR antibody (alpha IR3, 1 microgram/ml) also significantly reversed the growth-stimulatory effects of DES. A nuclear binding assay revealed that an enhanced level (approximately 2-fold) of [125I]IGF-I binding to nuclear protein occurred in DES treated renal epithelial cell nuclei compared to controls. IGF-I receptor gene expression analyzed by Northern blotting revealed that DES treatment increased the level of IGF-IR mRNA by 2-fold compared to controls. We also tested the effect of ICI compound on the induction of IGF-I receptor gene. The cotreatment of ICI 182780 strongly inhibited DES-induced IGF-I receptor gene expression (50-60% inhibition). Stimulation of the proliferative activity of renal epithelial cells by stilbene estrogen, its prevention by IGF-I receptor antibody, and inhibition of DES-induced proliferative activity and the expression of IGF-I receptors by ICI 182780 suggest the possibility that the stimulatory effect of DES on the proliferative activity of renal epithelial cells may be mediated through the up-regulation of IGF-I receptors.

Animals↗

Up-regulation of nuclear IGF-I receptor by short term exposure of stilbene estrogen, diethylstilbestrol.

In the present study we report the novel findings that IGF-I receptors are present in the nucleus based on the evidence from binding assay, detection of receptors by affinity labeling and Western blotting, and localization by immunofluorescence. The level of nuclear IGF-I receptors (nIGF-IRs) almost doubled in stilbene estrogen (diethylstilbestrol, DES) treated hamster kidneys compared to the controls. The binding constants Kd and Bmax of nIGF-IR of controls, 22.1 nM and 6.6 nmol/mg protein, respectively, were changed in response to DES treatment to 5.3 nM and 16.3 nmol/mg protein (P < 0.001), respectively. The enhanced level of IGF-IR in DES-treated nuclei was confirmed by both affinity labeling and Western blotting. These data suggest that IGFs may exert their biological effect through the IGF-I receptor present in the nucleus. Whether the up-regulation of nIGF-IR by exposure to a carcinogenic dose of DES may be a factor in the induction of renal cancer in Syrian hamsters, is not clear.

Animals↗

Prenatal detection of the separation of the great toe, toe syndactyly, and large bilateral choroid plexus cysts in a fetus with trisomy 18.

Prenatal sonographic presentation of toe deformities is associated with fetal aneuploidies. This report presents a second-trimester fetus with large bilateral choroid plexus cysts, clenched hands, separation of the great toe, toe syndactyly, abnormal double maternal serum biochemical screening results, and trisomy 18. We suggest a careful ultrasound screening of the fetal limbs and other organs once a choroid plexus cyst has been identified. If abnormal sonographic findings are present, or if the results of the maternal serum biochemical screening are abnormal, karyotyping should be recommended.

Abnormalities, Multiple↗

FGF induces new feather buds from developing avian skin.

Induction of skin appendages involves a cascade of molecular events. The fibroblast growth factor (FGF) family of peptide growth factors is involved in cell proliferation and morphogenesis. We explored the role of the FGFs during skin appendage induction using developing chicken feather buds as a model. FGF-1, FGF-2, or FGF-4 was added directly to the culture medium or was released from pre-soaked Affigel blue beads. Near the midline, FGFs led to fusion of developing feather buds, representing FGFs' ability to expand feather bud domains in developing skin. In lateral regions of the explant where feather placodes have not formed, FGF treatment produces a zone of condensation and a region with an increased number of feather buds. In ventral epidermis that is normally apteric (without feathers), FGFs can also induce new feather buds. Like normal feather buds, the newly induced buds express Shh. The expression of Grb, Ras, Raf, and Erk, intracellular signaling molecules known to be downstream to tyrosine kinase receptors such as the FGF receptor, was enriched in feather bud domains. Genistein, an inhibitor of tyrosine kinase, suppressed feather bud formation and the effect of FGF. These results indicate that there are varied responses to FGFs depending on epithelial competence. All the phenotypic responses, however, show that FGFs facilitate the formation of skin appendage domains.

Animals↗

Peptide nucleic acids stimulate gamma interferon and inhibit the replication of the human immunodeficiency virus.

BACKGROUND: Peptide nucleic acids (PNAs) are newly appreciated molecules consisting of both amino acids and nucleotides that already have been shown to have interesting properties; for example, they are very stable and have antisense activity. Reticulose, a peptide nucleic acid preparation that had been used for many years to treat human viral infections such as influenza, was investigated for inhibitory effects on the replication of the human immunodeficiency virus (HIV) in cell culture systems. METHODS: H9 and peripheral blood mononuclear cells (PBMCs) were treated with reticulose before, during, and after infection with HIV-1 at various multiplicities. Treatment of cells with PNA significantly inhibited replication of HIV-1 as measured by synthesis of viral mRNA and p24 protein, reverse transcriptase activity, and syncitial cell formation. Exposure of cells to PNA under conditions that favor transfection of DNA, such as electroporation, markedly enhanced the inhibition of HIV replication. RESULTS: In experiments to examine the mechanism of inhibition, it was found that PNA stimulated production of a distinctive cassette of chemokine mRNAs in PBMC cultures. Cytokines stimulated by reticulose included gamma interferon, interleukin-6, interleukin-1, and tissue necrosis factor-alpha. CONCLUSIONS: These results offer new tools for the study of immune functions and, moreover, open new approaches to the therapy of HIV infection and AIDS.

Antiviral Agents↗

Isoniazid-induced fever.

A rare case of isoniazid (INH)-induced fever is described. A 27-year-old woman diagnosed with miliary tuberculosis (TB) began to receive combined anti-TB treatment including INH, ethambutol, rifampicin and pyrazinamide on the second day of hospitalization. A spiked fever developed in the afternoon of the seventh hospital day. There was no evidence of a hypersensitivity reaction. All examinations including liver function tests, routine biochemistry tests, serum titer of antinuclear antibody and rheumatoid factor were within normal limits. The blood leukocyte count was also within normal range and no evidence of infection at other sites was found. Following the discontinuance of anti-TB agents, the patient's body temperature gradually returned to normal. When the patient was rechallenged with INH, the high fever recurred. The fever subsided again after the discontinuance of INH, and her recovery followed a smooth course thereafter, on combination therapy with rifampicin, ethambutol and pyrazinamide. This experience demonstrates the potential of INH to cause an isolated fever without other manifestations, which may be misdiagnosed as an infectious process. Though it is very rare, INH-induced fever must be considered when fever develops during anti-TB treatment.

Adult↗

The cutRS signal transduction system of Streptomyces lividans represses the biosynthesis of the polyketide antibiotic actinorhodin.

The nucleotide sequence of a two-component signal transduction operon (cutRS) of Streptomyces lividans TK64 was elucidated. Transcription of the operon was detected during the transition and stationary phases of growth, initiating at a single site upstream of cutR. This promoter region also possessed promoter activity directed away from cutRS, which appears to be responsible for the previously observed suppression of the translational deficiency of a melC1 mutation. Mutations in cutR and cutS were generated by gene replacement. The resulting mutants exhibited accelerated and increased production of the polyketide antibiotic, actinorhodin, which could be reversed by introduction of cutR on a plasmid. cutRS was also shown to repress actinorhodin production in the closely related species, Streptomyces coelicolor A3(2). The cutRS operon is the second two-component system found in Streptomyces that negatively regulates secondary metabolism.

Amino Acid Sequence↗

Increased IL-5 and IL-10 transcription in bronchial cells after Sauropus androgynus ingestion.

An outbreak of rapidly progressive obstructive lung disease in Taiwan was noted in some patients regularly ingesting the vegetable Sauropus androgynus because of its perceived weight reducing properties. Bronchoalveolar lavage (BAL) prior to administration of medication was performed in two women who had regularly ingested this vegetable and had developed obstructive ventilatory defects. Both patients showed a significant increase in neutrophils and, to a lesser extent, of eosinophils in the lavage fluid as compared to two unrelated controls. Interleukin (IL)-1 beta, IL-2, IL-5, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha in cells recovered from BAL fluid were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Augmented expression of the IL-10 gene was detected in only two patients who had regularly ingested S. androgynus. Our results suggest that altered cytokine expression and infiltration of eosinophils and neutrophils may be involved in the pathology of obstructive lung disease caused by regular ingestion of S. androgynus.

Adult↗

Segmentation and feature extraction techniques, with applications to MRI head studies.

To obtain a three-dimensional reconstruction of the hippocampus from a volumetric MRI head study, it is necessary to separate that structure not only from the surrounding white matter, but also from contiguous areas of gray matter--the amygdala and cerebral cortex. At present it is necessary for a physician to manually segment the hippocampus on each slice of the volume to obtain such a reconstruction. This process is time consuming, and is subject to inter- and intraoperator variation as well as large discontinuities between slices. We propose a novel technique, making use of a combination of gray scale and edge-detection algorithms and some a priori knowledge, by which a computer may make an unsupervised identification of a given structure through a series of contiguous images. This technique is applicable even if the structure includes so-called false contours or missing contours. Applications include three-dimensional reconstruction of difficult-to-segment regions of the brain, and volumetric measurements of structures from series of two-dimensional images.

Algorithms↗

Morphological factors influencing transepithelial conductance in a rabbit model of ileitis.

BACKGROUND & AIMS: Infection of rabbits with coccidia (Eimeria magna) causes chronic ileal inflammation and diarrhea. Inflamed ileum also shows decreased transmural conductance. The aim of this study was to characterize morphological factors known to affect paracellular permeability that may alter transmural conductance in inflamed ileum. METHODS: Ileal mucosa was mounted in Ussing chambers for study of [3H]mannitol and [3H]inulin fluxes. Light and electron microscopy were used for morphometric studies. Alterations in the zonula occludens of epithelial cells were evaluated in freeze-fracture replicas. RESULTS: Inflamed ileum showed diminished paracellular fluxes. Inoculated rabbits showed marked lymphoplasmocytic infiltration and villus blunting in ileum. Villus linear junctional density was unaffected. However, total villus apical surface area per square centimeter of tissue was reduced in inflamed ileum, causing a diminished total villus linear junctional pathway per square centimeter of apical surface. Villus zonula occludens strand number was reduced in inflamed ileum, whereas the frequency of both villus and crypt lateral surface extrajunctional strands increased. CONCLUSIONS: Chronic inflammation exerts a profound effect on ileal paracellular permeability. Morphological data suggest that this effect may be caused in part by alterations in inflamed ileal mucosal structure and tight junctional organization and density, particularly on villi.

Animals↗

Contact areas and pressure distributions in the subtalar joint.

We investigated how foot position and ankle arthrodesis affect the contact characteristics of the subtalar joint. Nine fresh-frozen specimens of amputated lower legs were used. Pressure-sensitive films were inserted into the anterior and posterior articulation of the subtalar joint. The contact areas and pressure for various foot positions and under axial loads of 600, 1200, and 1800 N were determined based on the gray level of the digitized film. In neutral position and under a 600 N load, the maximum contact pressure in the subtalar joint was 5.13 +/- 1.16 MPa. The contact area (1.18 +/- 0.35 cm2) was only 12.7% of the whole subtalar articulation area (9.31 +/- 0.66 cm2), and the total force (348.5 +/- 41.7 N) transmitted via this contact area was about 58% of the applied load (600 N). Dorsiflexion of the foot increased the contact area and the force transmitted, but decreased the average contact pressure in the subtalar joint, while the reverse occurred in plantar flexion. Eversion increased the subtalar contact stress, whereas inversion up to 10 degrees decreased it. Ankle joint arthrodesis shifted the contact areas in the subtalar joint posteriorly in all inversion/eversion positions. Moreover, total force transmitted through the subtalar joint as well as the contact pressure increased.

Adult↗