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Biomedical subjects

J C Lin

Publications and source records attributed to J C Lin.

At least 91 records · Page 5Linked to original sources

Granule cell raphes and parasagittal domains of Purkinje cells: complementary patterns in the developing chick cerebellum.

The extensive migration of granule cells and the parasagittal organization of Purkinje cells are two prominent features of cerebellar development. Using granule cell markers, we observed that the inward migration of a subset of granule cells occurs in streams that appear to be restricted to specific areas in the developing chick cerebellum. These streams are organized into a stereotypical series of parasagittal linear arrays, similar to the "granule cell raphes" described previously by . Similar raphes were found in the developing cerebellum of other avian species but not in the mouse cerebellum. During the period when granule cell raphes are apparent, Purkinje cells appear to be segregated into discrete parasagittal domains, interrupted by Purkinje cell-poor areas that correspond to the granule cell raphes. Purkinje cells in each domain exhibit a domain-specific expression profile of genes, including Bmp-7, EphA5/Cek-7, EphA4/Cek-8, and several chick homologs of Drosophila segmentation genes. From embryonic day 12 (E12) to E15, most of these genes gradually cease to be expressed differentially in parasagittal stripes, concurrent with the disappearance of the granule cell raphes by E15-E16. The spatial and temporal correlations of granule cell raphes and Purkinje cell parasagittal domains suggest a novel interaction between these two cell types and a potentially critical period of parasagittal patterning of the chick cerebellum.

Animals↗

Outpatient weekly chemotherapy in patients with nasopharyngeal carcinoma and distant metastasis.

BACKGROUND: Distant metastasis is a more common pattern of failure than locoregional recurrence after adequate radiotherapy in patients with nasopharyngeal carcinoma (NPC). The objective of this Phase II study was to assess the efficacy and toxicity of weekly chemotherapy in NPC patients with distant metastasis. METHODS: Patients with a histologic diagnosis of NPC and documented distant metastasis were eligible, including those who 1) had metastatic disease at presentation; 2) had developed metastatic disease during or at any time after local radiotherapy; or 3) had developed progressive disease or recurrence of metastasis after prior chemotherapy. The weekly chemotherapy regimen was comprised of 5-fluorouracil (5-FU), 1250 mg/m2, plus cisplatin, 25 mg/m2, as a 24-hour continuous intravenous infusion via a subcutaneous implanted port, using an ambulatory pump in an outpatient setting for the first 19 patients. Because of the low incidence and reduced severity of toxicity, the dosage of chemotherapy was escalated to 5-FU, 1667 mg/m2, plus cisplatin, 33.3 mg/m2, for the subsequent 25 patients. RESULTS: Between October 1992 and June 1996, a total of 44 patients with metastatic NPC were studied. They were 36 males and 8 females with a median age of 48 years (range, 30-72 years). Poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic types. Twenty-six patients had single organ metastasis, whereas 18 patients had multiple organ involvement. Locoregional disease existed simultaneously in 16 patients. The majority of patients had received previous radiotherapy (33 patients) and chemotherapy (23 patients: 16 as concurrent therapy for localized disease, 6 as salvage therapy for metastatic disease, and 1 for a postradiation adjuvant purpose). Among 38 patients with measurable disease, 8 obtained a complete response (CR) (21.1%), 12 obtained a partial response (PR) (31.6%), 17 had stable disease (SD) (44.7%), and 1 had progressive disease (2.6%). The median duration of CR, PR, and SD were 6.5 months, (range, 2-12 months), 5.5 months (range, 2-9 months), and 2.5 months (range, 1-6 months), respectively. Toxicity was found to be very mild. Only one patient developed a World Health Organization (WHO) Grade 1 mucositis. No visible alopecia and no treatment-related deaths occurred. WHO Grade 3-4 hematologic toxicities occurred in 1.0% of patients for leukopenia, 4.1% for anemia, and 2.9% for thrombocytopenia. CONCLUSIONS: Data from the current study indicate that 24-hour weekly infusion of 5-FU plus cisplatin has moderate activity but very low toxicity for NPC patients with distant metastasis. Further study is necessary to find more effective therapy.

Adult↗

Intron-exon structure of the MET gene and cloning of an alternatively-spliced Met isoform reveals frequent exon-skipping of a single large internal exon.

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional factor that stimulates epithelial cell mitogenesis, motility, invasion, and morphogenesis. Its receptor is encoded by the MET proto-oncogene, a transmembrane receptor tyrosine kinase. Several studies have suggested a role for MET as a dominant oncogene in tumor development and progression. Conversely, MET is located at a region on chromosome 7q31 frequently deleted in carcinomas, suggesting that recessive mutations in MET may exist in certain cancers. To facilitate a search for mutations in MET, we have obtained the intron-exon structure of the human MET gene. We present the genomic structure of the first member of the Met receptor family to be characterized. Interestingly, MET contains a large second exon of 1214 nucleotides. We show that this exon, containing the AUG for the Met receptor, is frequently skipped in normal human tissues and cell lines, and corresponds to a ubiquitously expressed 7 kb Met transcript. This transcript yields no detectable protein product in vivo. Thus, unlike other genes, in which alternative splicing often gives rise to proteins with distinct activities, exon-skipping of MET exon 2 is predicted to decrease the abundance of a Met mRNA encoding a functional Met receptor.

Alternative Splicing↗

[Computer-assisted structure analysis of trabecular bone in the diagnosis of osteoporosis].

Osteoporosis is characterized by reduced bone mass and a deterioration of bone structure which results in an increased fracture risk. The purpose of this review is to evaluate structure analysis techniques in the diagnosis of osteoporosis. Several imaging techniques were applied to analyze trabecular bone, such as conventional radiography, high-resolution computed tomography (HR-CT) and high-resolution magnetic resonance imaging (HR-MRI). The best results were obtained using high-resolution tomographic techniques. The highest spatial resolutions in vivo were achieved using HR-MRI. These studies show that texture parameters and bone mineral density predict bone strength and osteoporotic fractures in a complementary fashion. Combining both techniques yields the best results in the diagnosis of osteoporosis.

Calcaneus↗

Heterogeneity of trabecular bone structure in the calcaneus using magnetic resonance imaging.

The purpose of this study was to quantify the heterogeneity in the trabecular bone structure in the calcaneus. Magnetic resonance (MR) images of the calcaneus were obtained in the sagittal plane at an in-plane resolution of 195 microns and a slice thickness of 1000 microns in 12 young normal subjects. Regions of interest (ROI) were selected to cover the calcaneus using a grid of square boxes (10 mm per side). A thresholding technique based on the regional intensity histogram was used to segment the images into trabecular bone and marrow phases and to calculate measures such as apparent trabecular bone area fraction, apparent trabecular spacing, apparent trabecular thickness and apparent trabecular number. Bone mineral density (BMD) of the calcaneus was assessed using dual-energy X-ray absorptiometry (DXA). Histological sections of three calcanei were also analyzed using transmission light illumination, and the results used to calibrate our computational software. For a relatively narrow inter-subject variation in posterior BMD, a significant inter-subject variation was seen in MRI-derived structural parameters. Furthermore, the spatial heterogeneity of the structural parameters in the posterior region was as high as 40%. Thus, the posterior tuberosity of the calcaneus, a typical site for BMD and single-point ultrasound assessments, can demonstrate significant regional variation in trabecular bone structure.

Absorptiometry, Photon↗

T-cell malignant lymphoma with conjunctival involvement.

PURPOSE: To report a rare case of T-cell malignant lymphoma involving the conjunctiva. METHODS: A 63-year-old woman had rapid onset of bilateral perilimbal congestion and chemosis. Perilimbal thickening with corneal infiltration developed 20 days later. Computed tomography incidentally disclosed a right maxillary sinus mass. Biopsy specimens from the maxillary sinus mass and the left limbus were subjected to histopathologic examination and immunohistochemical study. RESULTS: T-cell malignant lymphoma of diffuse large cell type, stage IV, was diagnosed. The patient was treated with combination chemotherapy plus 13-cis-retinoic acid and remained in remission 1 1/2 years after diagnosis. CONCLUSION: Conjunctival involvement with T-cell lymphoma may present as episcleritis and chemosis.

Antineoplastic Combined Chemotherapy Protocols↗

Enhanced antinociception of clonidine in spontaneously hypertensive rats involves a presynaptic noradrenergic mechanism.

We and others previously reported that the antinociceptive effect of clonidine, measured by the hot plate method, was greater in spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto rats (WKYs). In the present study, we found that the difference in clonidine-induced analgesia between these two strains was abolished after lesioning the presynaptic noradrenergic neurons with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). Previous studies indicated that clonidine increases tissue norepinephrine (NE) content by inhibiting NE release. We found that the basal NE concentration in locus coeruleus (LC), as measured by HPLC-ECD, was not different between WKYs and SHRs. Systemic application of clonidine (0.69 mg/kg, I.P.) significantly increased the tissue content of NE in the SHRs, but not in WKYs. Using pressure microinjection and high-speed chronoamperometric recording techniques, we found that local application of KCl to the LC brain slices increased extracellular NE levels in both strains. Perfusion of slices with clonidine (1 microM) selectively attenuated KCl-evoked NE release in SHRs, suggesting that clonidine-induced presynapitc inhibition is more effective in SHRs than in WKYs. In conclusion, our data indicate that SHRs possess augmented sensitivity to clonidine to inhibit presynaptic NE release, which may be responsible for the enhanced antinociceptive effect of clonidine in this strain.

Adrenergic Agents↗

Anisotropy of the elastic modulus of trabecular bone specimens from different anatomical locations.

To associate the mechanical anisotropy of trabecular bone with the relationship between bone mineral density (BMD) and mechanical properties, 97 cubic specimens of human trabecular bone were imaged with computed tomography. Bone cubes from the spine, the calcaneus, the distal, and the proximal femur were tested multidirectionally to measure their compressive stiffness and to calculate their ratios of mechanical anisotropy. The ultimate strength was determined in a destructive test in cephalo-caudal (c-c) direction. Compressive stiffness was largest in the c-c direction for the specimens from the spine, as well as the distal and the proximal femur, but not the calcaneus. Anisotropy ratios in c-c direction were larger at the distal femur and the spine than in the proximal femur. The predictive power of BMD for the mechanical properties varied with anatomical location and strongly depended on the loading direction. While at the spine the c-c stiffness was highly correlated to BMD (r2 = 0.73), the perpendicular directions showed only modest correlations (r2 < 0.53). The correlations of mechanical properties with BMD were greatest at locations where the anisotropy was less pronounced (proximal femur) or rather uniform (spine). The data suggest that BMD can be most successfully applied to determine the mechanical properties in the principal loading direction, which from a clinical perspective may be most relevant.

Adult↗

High-resolution magnetic resonance imaging: three-dimensional trabecular bone architecture and biomechanical properties.

The purpose of this study was to use high-resolution magnetic resonance (MR) imaging combined with image analysis to investigate the three-dimensional (3D) trabecular structure, anisotropy, and connectivity of human vertebral, femoral, and calcaneal specimens. The goal was to determine whether: (a) MR-derived measures depict known skeletal-site-specific differences in architecture and orientation of trabeculae; (b) 3D architectural parameters combined with bone mineral density (BMD) improve the prediction of the elastic modulus using a fabric tensor formulation; (c) MR-derived 3D architectural parameters combined with BMD improve the prediction of strength using a multiple regression model, and whether these results corresponded to the results obtained using higher resolution depictions of trabecular architecture. A total of 94 specimens (12 x 12 x 12 mm cubes) consisting of trabecular bone only were obtained, of which there were 7 from the calcaneus, 15 from distal femur, 47 from the proximal femur, and 25 from the vertebral bodies. MR images were obtained using a 1.5 Tesla MR scanner at a spatial resolution of 117 x 117 x 300 microm. Additionally, BMD was determined using quantitative computed tomography (QCT), and the specimens were nondestructively tested and the elastic modulus (YM) was measured along three orthogonal axes corresponding to the anatomic superior-inferior (axial), medial-lateral (sagittal), and anterior-posterior (coronal) directions. A subset of the specimens (n=67) was then destructively tested in the superior-inferior (axial) direction to measure the ultimate compressive strength. The MR images were segmented into bone and marrow phases and then analyzed in 3D. Ellipsoids were fitted to the mean intercept lengths, using single value decomposition and the primary orientation of the trabeculae and used to calculate the anisotropy of trabecular architecture. Stereological measures were derived using a previously developed model and measures such as mean trabecular width, spacing, and number were derived. Because the spatial resolution of MR images is comparable to trabecular bone dimensions, these measures may be subject to partial volume effects and were thus treated as apparent measures, such as BV/TV, Tb.Sp, Tb.N, and Tb.Th rather than absolute measures, as would be derived from histomorphometry. In addition, in a subset of specimens, the Euler number per unit volume was determined to characterize the connectivity of the trabecular network. There were significant differences in the BMD, trabecular architectural measures, elastic modulus, and strength at the different skeletal sites. The primary orientation axes for most of the specimens was the anatomic superior-inferior (axial) direction. Using the fabric tensor formulation, in addition to BMD, improved the prediction of YM (SI), while including some of the architectural parameters significantly improved the prediction of strength. In comparing MR-derived 3D measures with those obtained from 20 microm optical images (n=18; 9 vertebrae, 9 femur specimens), good correlations were found for the apparent Tb.Sp and Tb.N, moderate correlation was seen for the apparent BV/TV, and poor correlation was found for the apparent Tb.Th. Using these higher resolution images, the fabric tensor formulation for predicting the elastic modulus also showed improved correlation between the measured and calculated modulus in the axial (SI) direction. In summary, high-resolution MR images may be used to assess 3D architecture of trabecular bone, and the inclusion of some of the 3D architectural measures provides an improved assessment of biomechanical properties. Further studies are clearly warranted to establish the role of architecture in predicting overall bone quality, and the role of trabecular architecture measures in clinical practice. (ABSTRACT TRUNCATED)

Anatomy, Cross-Sectional↗

Impact of spatial resolution on the prediction of trabecular architecture parameters.

Although the efficacy of various measures for the assessment of trabecular bone architecture has been widely studied, the impact of spatial resolution on the estimation of these measures has remained relatively unexplored. In this study, ten cubes each of human trabecular bone from the femur and vertebral bodies were obtained from nine cadavers (four males and five females), aged 23-67 years (mean 42.3 years). These specimens were serially milled and imaged at a resolution of 40 microm to produce three-dimensional digitizations from which traditional morphometric and structural anisotropy measures could be computed based on a three-dimensional approach. The cubes were then artificially degraded to an in-plane resolution of 100 microm and an out-of-plane (slice) resolution of 100-1000 microm. These resolutions mimicked in vivo resolutions as seen using magnetic resonance (MR) imaging. All images, original and degraded, were individually segmented using a thresholding algorithm, and both the traditional morphometric and structural anisotropy measures were recomputed. The choice of slice direction was varied along the superior-inferior (axial), anterior-posterior (coronal), and medial-lateral (sagittal) directions to minimize the impact of the lower slice resolution on the architectural measures. It was found that traditional morphometric measures such as trabecular spacing and trabecular number showed weak resolution dependency; measures such as trabecular thickness, however, showed strong resolution dependency and required very high resolutions for precise measurement. In the case of the femur specimens, both structural anisotropy as well as the preferred orientation showed a strong resolution dependency. The resolution dependency of these parameters could be minimized for the femur and the vertebral body specimens if the slice direction was taken along the superior-inferior direction.

Adult↗

Unusually high frequency of a 69-bp deletion within the carboxy terminus of the LMP-1 oncogene of Epstein-Barr virus detected in Burkitt's lymphoma of Turkish children.

Burkitt's lymphoma (BL) in Turkish children is commonly associated with Epstein-Barr virus (EBV) infection. The C-terminus of the latent membrane protein 1 (LMP-1) of EBV is essential for transformation and the 30-bp deletion detected in this region has been implicated to be associated with a more aggressive malignant phenotype. To understand the molecular mechanisms underlying EBV pathogenesis in BL of Turkish children, we analyzed 30-bp deletion and 33-bp variable repeat regions of the LMP-1 gene from paraffin-embedded tumor tissues of 30 BL patients (mean age 5.9 years). Primer pairs spanning the 30-bp deletion and 33-bp repeat regions were designed for amplification by polymerase chain reaction (PCR). The PCR-amplified products were analyzed by gel electrophoresis, Southern blot hybridization, and DNA sequencing. Twenty-eight (93%) of 30 BL biopsy samples were EBV positive as determined by PCR. Variable copy numbers (ranging from 4.5 to 7) of the 33-bp repeat of LMP-1 gene were detected in these EBV-containing tumor samples. To determine the frequency of the 30-bp deletion of the LMP-1 gene, we sequenced the amplimers encompassing this region. Analyses of DNA sequence of 28 Turkish BLs have disclosed four patterns: the first (32% (9/28)) is identical to B95-8 with no deletion, the second (11% (3/28)) is identical to Asian NPC CAO strain with 30-bp deletion, the third (46% (13/28)) is prevalent in Turkish BLs with a longer deletion (69 bp), and the fourth (11% (3/28)) consists of a mixture of 30-bp and 69-bp deletion. The occurrence of high frequency of the 69-bp deletion appears to have no correlation with the disease site. Mutations found in the CAO strain were also detected in the Turkish BL clustering at the amino acids 322, 334, 338 and 342; whereas mutations specific for Turkish BL were clustered at amino acids 326, 352 and 361. To assess the EBV genotype with the changes in C-terminus of LMP-1 gene, we performed genotyping by PCR to differentiate type A and B strain. All 28 patients were infected by type A EBV. Such a high frequency of the larger size (69 bp) deletion has never been reported. Ascertaining the role of this deletion in BL pathogenesis will require further study.

Amino Acid Sequence↗

Activation of human herpesvirus 8 (HHV-8) thymidine kinase (TK) TATAA-less promoter by HHV-8 ORF50 gene product is SP1 dependent.

Human herpesvirus 8 (HHV-8) is a newly discovered virus closely associated with Kaposi's sarcoma and primary effusion lymphomas. When they occur in patients with AIDS, these B-cell lymphomas frequently harbor another human herpesvirus, Epstein-Barr virus (EBV). To determine the molecular mechanisms of the regulation of early gene expression by the immediate-early gene products of HHV-8 and to assess possible molecular interactions between HHV-8 and EBV, we studied the regulation of the HHV-8 thymidine kinase (TK) promoter in cell lines harboring either or both viruses. The constitutive chloramphenicol acetyltransferase (CAT) activity of the TK promoter was low in all six cell lines tested. A putative immediate-early gene product of HHV-8 ORF50, which is a homolog of EBV BRLF1, was cloned into an expression vector and tested for its transactivating capacity. In the presence of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), the CAT activity of the TK promoter was increased 7- to 720-fold by cotransfection with the ORF50 clone in EBV-producing cell lines (Ramos/AW, P3HR-1, and BC-1) but not in EBV-negative cell lines (BCBL-1 and Ramos), nor in the latently EBV-infected cell line Raji. The TK promoter contains three consensus SP1- and two AP1-binding sites. In electrophoretic mobility shift assays, the cellular factor SP1, but not AP1, was found to bind specifically to the TK promoter. To determine whether the increased CAT activity resulted from the interaction of SP1 with the ORF50 gene product, we introduced mutations into two SP1-binding sites. Both mutated SP1 sites had reduced SP1-binding activity and greatly decreased TK promoter responsiveness to ORF50 transactivation, suggesting that upregulation of TK promoter by ORF50 is SP1 dependent.

Base Sequence↗

Successive order scattering transport approximation for laser light propagation in whole blood medium.

An analytical solution method of the radiative transport equation, describing light scattering distribution in whole blood, is derived by applying successive order scattering approximation and transport approximation. By separating coherent components of scattered fluxes, the transport equation can be represented in terms of each order scattering flux, and the equations for each order scattering flux have a simplified integration term of scattering contribution that usually makes the solution complicated or even impossible. Also, actual phase function can be used for calculation of angular dependent scattering distribution that is approximated by the sum of the zeroth- and first-order Legendre polynomial in diffusion theory, or the sum of isotropic and coherent components in transport approximation. The method is then used to calculate reflectance from a half-space blood medium. It is found that first-order scattering flux alone produces a good agreement with experimental data and higher-order scattering fluxes are negligible in whole blood.

Anisotropy↗

Proximal femur: assessment for osteoporosis with T2* decay characteristics at MR imaging.

PURPOSE: To use T2* measurements at magnetic resonance (MR) imaging to investigate the trabecular structure of the hip in women with and women without osteoporotic hip fractures and to compare this technique with bone mineral density (BMD) measurements in the diagnosis of fractures. MATERIALS AND METHODS: T2* maps of the proximal femur were obtained at 1.5 T in 23 postmenopausal study patients with osteoporotic hip fractures, 27 age-matched healthy postmenopausal control subjects, and five healthy premenopausal control subjects. A modified gradient-recalled acquisition in the steady state, or GRASS, sequence was used with echo times of 4-40 msec at 4-msec increments. T2* values were measured in five regions of interest: femoral neck, the Ward triangle, trochanter, intertrochanteric region, and total proximal femur. Additionally, BMD measurements of the hip were obtained with dual x-ray absorptiometry. RESULTS: Significant differences between T2* measurements were obtained in all three groups (P < .05). BMD measurements of the hip also showed significant differences (P < .05). For T2* and BMD measurements, odds ratios and areas under the curve in receiver operating characteristic analysis were comparable. Correlations between 1/T2* values and BMD were significant (P < .05). T2* measurements in the proximal femur showed regional variations. CONCLUSION: MR imaging decay characteristics of bone marrow could be used to differentiate between postmenopausal women with and those without osteoporotic hip fractures.

Absorptiometry, Photon↗

A comparative study of trabecular bone properties in the spine and femur using high resolution MRI and CT.

The purpose of this study was to use high resolution (HR) magnetic resonance (MR) and computed tomography (CT) images combined with texture analysis to investigate the trabecular structure of human vertebral and femoral specimens and to compare these techniques with bone mineral density (BMD) in the prediction of bone strength. Twenty-nine bone cubes were harvested from 12 proximal femur cadaver specimens and 29 from 8 spines. HR MR and CT images were obtained, and texture analysis techniques were used to assess trabecular structure. Additionally, BMD, elastic modulus (EM), and maximum compressive strength were determined. R2 for EM versus texture measures computed in the MR images was higher (R2 = 0.27-0.64, p < 0.01) in the spine than in the femur specimens (R2 = 0.12-0.22, p < 0.05). R2 values were similar in the CT images. R2 for EM versus BMD was 0.66 (p < 0.01) in the spine and 0.61 (p < 0.01) in the femur specimens. In the MR images, texture measures combined with BMD in a multivariate-regression model significantly increased R2, while improvement was less significant in the CT images. Thus, texture analysis may provide additional information needed to analyze bone strength and quality.

Adult↗

In vivo high resolution MRI of the calcaneus: differences in trabecular structure in osteoporosis patients.

The purpose of this study was to use high resolution (HR) magnetic resonance (MR) images of the calcaneus to investigate the trabecular structure of patients with and without osteoporotic hip fractures and to compare these techniques with bone mineral density (BMD) in differentiating fracture and nonfracture patients. Axial and sagittal HR MR images of the calcaneus were obtained in 50 female (23 postmenopausal patients with osteoporotic hip fractures and 27 postmenopausal controls). A three-dimensional gradient-echo sequence was used with a slice thickness of 500 micron and in plane resolution of 195 x 195 micron. Texture analysis was performed using morphological features, analogous to standard histomorphometry and fractal dimension. Additionally, BMd measurements of the hip (dual-energy X-ray absorptiometry) were obtained in all patients. Significant differences between both patient groups were obtained using morphological parameters and fractal dimension as well as hip BMD (p < 0.05). Odds ratios for the texture parameters apparent (app.) bone volume/total volume and app. trabecular separation were higher than for hip BMD. Receiver operator characteristic values of texture measures and hip BMD were comparable. In conclusion, trabecular structure measures derived from HR MR images of the calcaneus can differentiate between postmenopausal women with and without osteoporotic hip fractures.

Absorptiometry, Photon↗

Gadolinium-enhanced MRI in neuro-Behçet disease.

Gadolinium-enhanced MRI is a practical method to evaluate the active lesion of Behçet disease and the response to treatment. This case was presented as a slow-growing brainstem tumor clinically and radiographically.

Adult↗