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Biomedical subjects

J Han

Publications and source records attributed to J Han.

At least 127 records · Page 7Linked to original sources

In situ dehydration of carbamazepine dihydrate: a novel technique to prepare amorphous anhydrous carbamazepine.

The purposes of this project were to prepare amorphous carbamazepine by dehydration of crystalline carbamazepine dihydrate, and to study the kinetics of crystallization of the prepared amorphous phase. Amorphous carbamazepine was formed and characterized in situ in the sample chamber of a differential scanning calorimeter (DSC), a thermogravimetric analyzer (TGA), and a variable temperature x-ray powder diffractometer (VTXRD). It has a glass transition temperature of 56 degrees C and it is a relatively strong glass with a strength parameter of 37. The kinetics of its crystallization were followed by isothermal XRD, under a controlled water vapor pressure of 23 Torr. The crystallization kinetics are best described by the three-dimensional nuclear growth model with rate constants of 0.014, 0.021, and 0.032 min-1 at 45, 50, and 55 degrees C, respectively. When the Arrhenius equation was used, the activation energy of crystallization was calculated to be 74 kJ/mol in the presence of water vapor (23 Torr). On the basis of the Kissinger plot, the activation energy of crystallization in the absence of water vapor (0 Torr water vapor pressure) was determined to be 157 kJ/mol. Dehydration of the dihydrate is a novel method to prepare amorphous carbamazepine; in comparison with other methods, it is a relatively gentle and effective technique.

Algorithms↗

Fibrous dysplasia with barely increased uptake on bone scan: a case report.

Fibrous dysplasia, in general, appears as an area of markedly increased uptake on bone scintigraphy. Therefore, the possibility of fibrous dysplasia is likely to be excluded when the lesion shows no or slightly increased uptake. The authors report a case of incidentally detected fibrous dysplasia that appeared as slightly increased uptake on bone scintigraphy and was found to harbor a bone infarction along with typical fibrous dysplasia by pathologic examination of a specimen sampled by curettage. Barely increased bone uptake in fibrous dysplasia may be associated with decreased vascularity and osteoblast activity of the lesion as a result of concurrent bone infarction. The authors suggest that not every case of fibrous dysplasia appears as an area of intensely increased uptake on a bone scan. Clinicians should be cautious in interpreting bone scans of radiographically indicated fibrous dysplasia.

Diphosphonates↗

Trapeziometacarpal joint instability affects the moment arms of thumb motor tendons.

This study measured the changes in moment arm length of thumb motor tendons after simulated ligamentous instability and subsequent reconstruction of the trapeziometacarpal joint. Excursions of thumb motor tendons were measured simultaneously with the trapeziometacarpal joint angulation during flexion to extension and abduction to adduction motion. Tendon moment arms were calculated based on joint and tendon displacement techniques in the intact joint, after sequential sectionings of the capsuloligamentous restraints, and after the reconstruction procedure of Eaton and Littler. The results showed that moment arms of the abductor pollicis longus and extensor pollicis brevis tendons increased significantly as compared with those for normal joints during flexion to extension motion after sectioning the palmar capsuloligamentous components. After the ulnopalmar structures were cut, the moment arm of the extensor pollicis longus tendon had a statistically significant increase during abduction to adduction motion, and those of the extensor and flexor pollicis longus tendons decreased significantly during flexion to extension motion. Changed moment arms were restored to a normal level after the ligamentous reconstruction. These results indicate that ligamentous disruptions alter the mechanical balance of thumb motor tendons, which may contribute to joint deformities observed in trapeziometacarpal joint arthritis. Restoring joint stability is important to correct mechanical imbalance of the tendons.

Aged↗

Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest.

The p38 group of kinases belongs to the mitogen-activated protein (MAP) kinase superfamily with structural and functional characteristics distinguishable from those of the ERK, JNK (SAPK), and BMK (ERK5) kinases. Although there is a high degree of similarity among members of the p38 group in terms of structure and activation, each member appears to have a unique function. Here we show that activation of p38gamma (also known as ERK6 or SAPK3), but not the other p38 isoforms, is required for gamma-irradiation-induced G(2) arrest. Activation of the MKK6-p38gamma cascade is sufficient to induce G(2) arrest in cells, and expression of dominant negative alleles of MKK6 or p38gamma allows cells to escape the DNA damage-induce G(2) delay. Activation of p38gamma is dependent on ATM and leads to activation of Cds1 (also known as Chk2). These data suggest a model in which activation of ATM by gamma irradiation leads to the activation of MKK6, p38gamma, and Cds1 and that activation of both MKK6 and p38gamma is essential for the proper regulation of the G(2) checkpoint in mammalian cells.

Ataxia Telangiectasia Mutated Proteins↗

PKCepsilon modulates NF-kappaB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes.

We have previously shown that protein kinase C (PKC)-epsilon, nuclear factor (NF)-kappaB, and mitogen-activated protein kinases (MAPKs) are essential signaling elements in ischemic preconditioning. In the present study, we examined whether activation of PKCepsilon affects the activation of NF-kappaB in cardiac myocytes and whether MAPKs are mediators of this signaling event. Activation of PKCepsilon (+108% above control) in adult rabbit cardiomyocytes to a degree that has been previously shown to protect myocytes against hypoxic injury increased the DNA-binding activity of NF-kappaB (+164%) and activator protein (AP)-1 (+127%) but not that of Elk-1. Activation of PKCeta did not have an effect on these transcription factors. Activation of PKCepsilon also enhanced the phosphorylation activities of the p44/p42 MAPKs and the p54/p46 c-Jun NH(2)-terminal kinases (JNKs). PKCepsilon-induced activation of NF-kappaB and AP-1 was completely abolished by inhibition of the p44/p42 MAPK pathway with PD98059 and by inhibition of the p54/p46 JNK pathway with a dominant negative mutant of MAPK kinase-4, indicating that both signaling pathways are necessary. Taken together, these data identify NF-kappaB and AP-1 as downstream targets of PKCepsilon, thereby establishing a molecular link between activation of PKCepsilon and activation of NF-kappaB and AP-1 in cardiomyocytes. The results further demonstrate that both the p44/p42 MAPK and the p54/p46 JNK signaling pathways are essential mediators of this event.

Animals↗

Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis.

Neural crest cells are multipotential stem cells that contribute extensively to vertebrate development and give rise to various cell and tissue types. Determination of the fate of mammalian neural crest has been inhibited by the lack of appropriate markers. Here, we make use of a two-component genetic system for indelibly marking the progeny of the cranial neural crest during tooth and mandible development. In the first mouse line, Cre recombinase is expressed under the control of the Wnt1 promoter as a transgene. Significantly, Wnt1 transgene expression is limited to the migrating neural crest cells that are derived from the dorsal CNS. The second mouse line, the ROSA26 conditional reporter (R26R), serves as a substrate for the Cre-mediated recombination. Using this two-component genetic system, we have systematically followed the migration and differentiation of the cranial neural crest (CNC) cells from E9.5 to 6 weeks after birth. Our results demonstrate, for the first time, that CNC cells contribute to the formation of condensed dental mesenchyme, dental papilla, odontoblasts, dentine matrix, pulp, cementum, periodontal ligaments, chondrocytes in Meckel's cartilage, mandible, the articulating disc of temporomandibular joint and branchial arch nerve ganglia. More importantly, there is a dynamic distribution of CNC- and non-CNC-derived cells during tooth and mandibular morphogenesis. These results are a first step towards a comprehensive understanding of neural crest cell migration and differentiation during mammalian craniofacial development. Furthermore, this transgenic model also provides a new tool for cell lineage analysis and genetic manipulation of neural-crest-derived components in normal and abnormal embryogenesis.

Animals↗

Elucidating tumor necrosis factor signaling pathway using a functional gene identification approach.

Functional identification of genes is an efficient way to study many biological processes in lower eukaryotes. However, an effective approach in mammalian cells is still under development. We designed a functional gene identification procedure and applied it in a study of tumor necrosis factor (TNF)-induced cell killing. This procedure employed a specially designed retroviral vector that allows random truncation of genes, efficiently selecting clones in which a gene was disrupted and quickly identifying disrupted genes. We have identified several novel genes by a preliminary test of this approach and confirmed by reconstitution that the genes we identified are required for TNF cytotoxicity in L929 cells. Because of the efficient identification of these components in TNF-induced cell killing, we have already been able to outline the killing pathway of TNF in L929 cells. Application of this method could be widespread because it can be used in studying any cellular responses if a specific selection assay can be set up.

Animals↗

Semiinvasive pulmonary aspergillosis: CT and pathologic findings in six patients.

OBJECTIVE: We describe the chest CT and pathologic findings of semiinvasive pulmonary aspergillosis in six patients. CONCLUSION: Semiinvasive pulmonary aspergillosis should be considered in the mildly immunocompromised patient with CT findings that reveal persistent parenchymal abnormalities. Patterns include consolidation and mass.

Adult↗

Induction of CD36 expression by oxidized LDL and IL-4 by a common signaling pathway dependent on protein kinase C and PPAR-gamma.

CD36, a class B scavenger receptor, is a macrophage receptor for oxidized low density lipoprotein (OxLDL) and may play a critical role in atherosclerotic foam cell formation. We have previously demonstrated that OxLDL, macrophage-colony stimulating factor (M-CSF), and interleukin-4 (IL-4) enhanced expression of CD36. The effect of OxLDL on CD36 is due, in part, to its ability to activate the transcription factor, PPAR-gamma (peroxisome proliferator activated receptor-gamma). Other PPAR-gamma ligands (15-deoxyDelta(12,14) prostaglandin J(2) (15d-PGJ(2)) and the thiazolidinedione class of antidiabetic drugs) also increase CD36 expression. We have now evaluated signaling pathways involved in the induction of CD36. Treatment of RAW264.7 cells (a murine macrophage cell line) with protein kinase C (PKC) activators (diacylglycerol and ingenol) up-regulated CD36 mRNA expression. Specific inhibitors of PKC reduced CD36 expression in a time-dependent manner, while protein kinase A (PKA) and cyclic AMP agonists had no effect on CD36 mRNA expression. PKC inhibitors reduced basal expression of CD36 and blocked induction of CD36 mRNA by 15d-PGJ(2), OxLDL and IL-4. In addition, PKC inhibitors decreased both PPAR-gamma mRNA and protein expression and blocked induction of CD36 protein surface expression by OxLDL and 15d-PGJ(2) in human monocytes, as determined by FACS. 15d-PGJ(2) had no effect on translocation of PKC-alpha from the cytosol to the plasma membrane. These results demonstrate that two divergent physiological or pathophysiological agonists utilize a common pathway to up-regulate of CD36 gene expression. This pathway involves initial activation of PKC with subsequent PPAR-gamma activation. Defining these signaling pathways is critical for understanding and modulating expression of this scavenger receptor pathway.

Animals↗

Asymmetric synthesis of 2,3-methanoleucine stereoisomers from common intermediates.

2,3-Methanoamino acids are useful probes for studying the bioactive conformation of peptides and for investigating the effect of local conformational constraints on the activity of peptidomimetics. We synthesized all four stereoisomers of Cbz-protected 2, 3-methanoleucine for incorporation into peptidomimetic inhibitors of calpain. While the synthesis of 2,3-methanoamino acids has been previously reported, our procedure offers a versatile route in which the pair of diastereomers of each geometric isomer was synthesized from a common intermediate.

Amino Acids↗

CD36 in atherosclerosis. The role of a class B macrophage scavenger receptor.

CD36, an 88 kD transmembrane glycoprotein, is an important receptor for oxidized lipoproteins. Unlike the LDL receptor, expression of CD36 is upregulated by this pro-atherogenic particle, and binding and uptake perpetuates a cycle of lipid accumulation and receptor expression. This effect is, in part, mediated by the transcription factor, peroxisome proliferator activated receptor-gamma (PPAR gamma), and its ligands. We have found that specific inhibitors of protein kinase C (PKC) reduce basal mRNA expression of CD36 and block induction of CD36 mRNA and protein by oxidized LDL (OxLDL) and a PPAR gamma ligand. In addition, PKC inhibitors block both PPAR gamma mRNA and protein expression. These results suggest that activation of CD36 gene expression by OxLDL involves activation and translocation of PKC with subsequent PPAR gamma activation. More recently, we have generated a mouse null for CD36, and crossed it with the atherogenic Apo E null strain. Evaluation of lesion development in these animals will allow us to assess the in vivo contribution of CD36 to the pathogenesis of atherosclerosis.

Animals↗

Iron deficiency alters H- and L-ferritin expression in rat brain.

Ferritin (Ft) H and L subunits are independently regulated proteins with both transcriptional and translational regulation in response to cellular iron levels. While the heterogeneous distribution of ferritin and iron in the brain is now well established, the relative response of each subunit to iron deficiency and iron supplementation, is not well defined. Weanling male Sprague-Dawley rats (n=12 per group) were randomly assigned to an iron deficient (3.5 mg Fe/kg diet), control (35 mg Fe/kg diet) or supplemented (350 mg Fe/kg diet) diet for six weeks. The H-/L-ferritin subunit ratio and mRNA levels were determined. Overall, the protein ratio in control rats of H to L was approximately 45:1 compared to a ratio >60:1 in iron deficiency but the absolute amounts of each subunit varied greatly from one brain region to another. The ratio of H-:L-ferritin mRNA was 6:1 and was not affected by dietary iron deficiency in contrast to a potent effect on mRNA levels in liver. Severe iron deficiency reduced brain ferritin H protein levels significantly in all regions, whereas only ferritin L levels in striatum, substantia nigra and pons were affected by iron deficiency. Supplemental dietary iron increased both ferritin subunits, with the largest increase (50%) in the hippocampus. These data indicate that ferritin H and L subunits within the brain respond differently to iron status and suggest post transcription regulation as a key event.

Animals↗

Changes in stroke index measured by impedance cardiography in a human model of moderate acute blood loss

Early detection of acute hemorrhage is problematic because changes in traditional parameters such as heart rate and blood pressure are notoriously unreliable. OBJECTIVE: To observe the effect of acute, moderate blood loss on stroke index (SI) as measured non-invasively by impedance cardiography. METHODS: Five healthy, adult volunteers were phlebotomized 590 mL over ten minutes. The volume of blood loss was expressed as a percent of estimated total blood volume (TBV) according to the formula TBV = (weight in kg) x (70 mL/kg). Stroke index was measured in a fixed, reclining position before (SI #1) and after (SI #2) phlebotomy, using the BioZ.com (Cardiodynamics International Corporation, San Diego, CA) thoracic bioimpedance monitor. Absolute and relative changes were calculated. RESULTS: In each volunteer, a fall in SI was noted after phlebotomy. The percent change in SI ranged from 8% to 18% (table 15-1). There appeared to be a correlation between blood loss as a percent of estimated total blood volume and the percent decline in SI among these volunteers. CONCLUSIONS: Impedance cardiography reliably detected moderate acute blood loss in this small set of healthy, adult volunteers. If these results can be quantified and validated prospectively in a larger population, SI may prove to be a valuable, non-invasive parameter for detection of early hemorrhage shock.

Journal Article↗

[Study of an in-vivo and real-time method to measure blood viscosity].

The traditional methods to measure blood viscosity are out-line. They have the disadvantages of long measurement time, many disturbance factors during measurement, the damage to blood sample, and etc. So rapidity, accuracy and repeatability are not satisfactory. A new method to measure blood viscosity is proposed in this paper, which uses needle instead of capillary and can measure blood viscosity during collecting blood. Owing to the advantages of small amount of blood sample, rapidity and repeatability, the new method is of value for clinical application.

Animals↗

[A functional evaluation on peripheral nerve regeneration enhanced by targeted muscular injection of ciliary neurotrophic factor].

OBJECTIVE: To investigate the effects of targeted muscular injection of ciliary neurotrophic factor (CNTF) on the regeneration of injured peripheral nerves. METHODS: The left sciatic nerves of 80 Sprague-Dawley rats were excised to form 6 mm defect and the two ends were bridged by silicone tubes, they were randomly divided into two groups, CNTF group and normal saline (NS) group. The CNTF group was given recombinant human CNTF, 1 mg/kg every other day for 30 days, and the NS group was given equal quantity of normal saline as NS group. The sciatic nerve functional index (SFI), electrophysiological assessment, morphometric analysis of axons, and choleratoxin horseradish peroxidase (CB-HRP) retrograde-labelling were measured postoperatively. RESULTS: The SFI, electrophysiological parameters (nerve conduction velocity, latency and amplitude of compound muscle action potentials), myelinated axons counts, mean axons diameters and myelin sheath thickness, number of CB-HRP labelled ventral horn motor neurons of spinal cord were significantly higher in CNTF group than that of NS group. CONCLUSION: Targeted muscular injection of CNTF can promote the regeneration of peripheral nerve and improve the nerve functional recovery.

Animals↗

[Effect of 2/100 Hz transcutaneous electrical nerve stimulation on sexual dysfunction and serum sex hormone of heroin addicts].

OBJECTIVE: To evaluate the effect of 2/100 Hz electrical stimulation produced by Han's acupoint nerve stimulator (HANS) in treating heroin induced sex dysfunction. METHODS: Thirty-three heroin addicts were randomly divided into 2 groups to receive either buprenorphine (BPN group, n = 16) or HANS plus small dose of BPN (HANS group, n = 17) for 14 days. The doses of BPN were tailored according to individual requirement that could totally abolish withdrawal syndrome. The frequency of HANS was 2 Hz and 100 Hz shifting automatically, each lasting for 3 seconds. The stimulation was applied to 8 acupoints, the Hegu and Laogong of one upper limb, Neiguan and Waiguan of another limb, Sanyinjiao and Xingjian of both lower limbs, for 30 min. The therapy was carried out 3-4 times per day in the initial two weeks of treatment, and reduced to 1-2 times per day in the following 2 weeks. RESULTS: (1) The urine analysis for morphine in both groups turned to negative 14 days after treatment. (2) After 2 weeks of treatment, the composite score (Visual Analog Scale, VAS) of sexual function in HANS group showed a 102% increase (P < 0.01) compared with before treatment and was 107% of that in the BPN group (P < 0.01). (3) After 4 weeks treatment the serum concentration of luteinizing hormone (LH) and testosterone (T) in the HANS group showed a 137% and 118% increase respectively compared with those before treatment (P < 0.05), and the level of LH was 79.6% of that in the BPN group (P < 0.05). CONCLUSION: The 2/100 Hz transcutaneous electrical stimulation produced by Han's acupoint nerve stimulator could improve the recovery of sexual function and raise the serum concentration of LH and T in heroin addicts.

Adult↗

[Modified vascular endothelia growth factor receptor-mediated targeting nonviral gene delivery system and in vivo beta-gal transducing experiment].

OBJECTIVE: To investigate whether the modified vascular endothelial growth factor (VEGF) receptor-mediated targeting nonviral gene delivery system is efficient in transducing exogenous gene. METHODS: We detected the expression of VEGF receptor on some tumor models by immunohistochemistry at first and selected nine models, i.e. SMMC-7721, SK-OV-3, H128, SPC-A1, LoVo, MKN-45, BCaP-37, A375, cervical cancer xenograft and hepatoma xenograft. Then we prepared two complexes, GV1-P.L./beta-gal and GV2-P.L./beta-gal, and injected the two complexes subcutaneously into nude mice around the tumor. The expression of the reporter gene was observed in the vascular endothelial cells and some tumor cells with highly expressed VEGF receptor. RESULTS: GV2 gene delivery system could transduce exogenous gene into vascular endothelial cells and subcutaneously transplanted tumors such as SK-OV-3, and cervical xenograft which were rich of VEGF receptor on the surface of the tumor cell. The expression reached a high level at day 3 and decreased eventually until the 3(rd) week. There was no expression in the heart and lung but low expression was seen in the spleen. GV1 gene delivery system also transduced exogenous gene into the endothelial cells but with low efficiency. CONCLUSION: This system can specifically transduce beta-gal to cells rich of VEGF receptor but not to cells with undetectable VEGF receptor. The targetability of this modified system is increased as compared to the system previously reported.

Animals↗

[Comparison of TIPS, a modified Sugiura procedure and TIPS plus a modified Sugiura procedure for portal hypertension].

OBJECTIVE: Transjugular intrahepatic portosystemic shunts (TIPS), a modified Sugiura procedure and TIPS plus a modified Sugiura procedure were compared to evaluate their clinical results in treatment of portal hypertension. METHODS: Ninety patients with portal hypertension respectively underwen TIPS (group I, n = 30), a modified Sugiura procedure (group II, n = 30) and TIPS plus a modified Sugiura procedure (group III, n = 30). The rates of rebleeding and encephalopathy, and the mortality of patients with portal hypertension were observed. RESULTS: The early postoperative complications were observed in 23.33% of the patients in group I, in 30.0% of those in group II, and in 20.0% of those in group III. The early postoperative rates of rebleeding were 6.67% in group I, 10% in group II, and 0% in group III. Hepatic encephalopathy was seen in 16.67% of the patients in group I, 0% in group II and 13.33% in group III. The early mortality was 3.33% in group I. During follow-up for 1 - 36 months, the rates of rebleeding were 34.48% in group I, 33.33% in group II, and 3.33% in group III. The rates of encephalopathy and mortality were respectively 17.20% and 20.69% in group I, 3.33% and 13.33% in group II, 3.33% and 3.33% in group III. The shunt patency in group III was higher than that in group I. CONCLUSION: Combination of TIPS and a modified Sugiura procedure can be effective to prevent and treat variceal bleeding.

Adult↗