Biomedical subjects

F Pan

Publications and source records attributed to F Pan.

At least 37 records · Page 2Linked to original sources

PubMed1999

The absence of resurgent sodium current in mouse spinal neurons.

The Scn8a gene encodes a neuronal, voltage-gated sodium channel, which is highly expressed in both cerebellar Purkinje neurons and spinal motoneurons [D.L. Burgess, D.C. Kohrman, J. Galt, N.W. Plummer, J.M. Jones, B. Spear, M.H. Meisler, Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease', Nature Genetics 10 (1995) 461-465; K.L. Schaller, D.M. Krzemien, P.J. Yarowsky, B.K. Krueger, J.H. Caldwell, A novel, abundant sodium channel expressed in neurons and glia, J. Neurosci. 15 (1995) 3231-3242]. Sodium channels in Purkinje cells produce an unusual, "resurgent" current when the cells are repolarized to intermediate potentials (-60 to -20 mV) following a strong depolarization that completely inactivates transient sodium current [I.M. Raman, L.K. Sprunger, M.H. Meisler, B.P. Bean, Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice, Neuron 19 (1997) 881-891; I.M. Raman, B.P. Bean, Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons, J. Neurosci. 17 (1997) 4517-4526]. Here, we have examined whether large spinal neurons (predominantly motoneurons), isolated from P6-P8 mice and cultured overnight, produce sodium currents resembling those either of Purkinje cells or of Xenopus oocytes after heterologous expression of Scn8a. We found that P10-P14 Purkinje cells exhibited resurgent current (ranging from -3.6 to -15.4 pA/pF in 16 cells at -40 mV), but cultured spinal neurons had little or no such current (<0.5 pA/pF in 13 of 16 cells; -1.2 to -2.3 pA/pF in three of 16 cells). Furthermore, unlike Scn8a channels heterologously expressed in Xenopus oocytes [M.R. Smith, R.D. Smith, N.W. Plummer, M.H. Meisler, A.L. Goldin, Functional analysis of the mouse Scn8a sodium channel. J. Neurosci. 18 (1998) 6093-6102], there was not a prominent component of persistent sodium current in either Purkinje neurons or large spinal neurons. Based on analysis of cells from mice with a Scn8a null mutation, Scn8a channels appear to contribute significantly to total sodium current in both in P10-P14 Purkinje cells (approximately 40%; [21]) and cultured P7-P8 spinal motoneurons (approximately 70% [K.D. García, L.K. Sprunger, M.H. Meisler, K.G. Beam, The sodium channel Scn8a is the major contributor to the postnatal developmental increase of sodium current density in spinal motoneurons, J. Neurosci. 18 (1998) 5234-5239]). Thus, the presence or absence of resurgent current, and of persistent sodium current, appears to depend on cellular factors other than the mere presence of the Scn8a transcript.

Action Potentials↗

PubMed1999

Properties of coralline hydroxyapatite and expanded polytetrafluoroethylene membrane in the immature craniofacial skeleton.

Although extensive research regarding the treatment of calvarial defects has been done in adult models, little is known about the response in the maturing skeleton. The role of coralline hydroxyapatite and expanded polytetrafluoroethylene membrane in augmenting bone growth and repair of calvarial defects in a neonatal model is explored. Utilizing a 3-week-old neonatal swine model, bone growth into 28 calvarial defects was measured. After exposure of the calvaria in seven animals, four defects of 10 mm in diameter were created. In each animal, one defect was treated with a 10-mm disc of porous hydroxyapatite alone (Interpore 500, Interpore International), and a second defect was covered with an expanded polytetrafluoroethylene membrane (Gore-Tex OV-6) secured by four 3-mm microscrews (Luhr Microsystem, Howe-Medica Inc.). The third defect combined an implanted hydroxyapatite disc covered by an expanded polytetrafluoroethylene membrane, whereas the fourth defect served as an untreated control. Histology and histomorphometry were performed on undecalcified specimens harvested at 6 weeks after surgery. In both hydroxyapatite groups, the bone growth into the inorganic matrix provided complete osseous union in all specimens, and the amount of fibrosis was significantly lower (p < 0.02) in comparison with the control. Unexpectedly, there was significant osteoclastic resorption of the hydroxyapatite matrix (35.1 percent decrease) with simultaneous bone deposition and remodeling. The addition of an expanded polytetrafluoroethylene membrane covering the hydroxyapatite implant provided an insignificant advantage in bone growth (27.3 percent versus 28.3 percent, respectively). Finally, the expanded polytetrafluoroethylene membrane alone afforded no qualitative advantage secondary to intrusion of brain and dura into the defect as well as displacement of the membrane inward during appositional growth, leading to incomplete healing of the defect with thinning of the surrounding cranial bone. Unique in this maturing model was morphologic evidence of complete union at the calvaria-hydroxyapatite interface in all specimens as well as active remodeling of the hydroxyapatite matrix. The results of this study suggest that porous hydroxyapatite may be a suitable bone substitute in maturing calvarial bone defects, achieving superior osseous integration and volumetric bone gain while undergoing concurrent resorption and remodeling.

Animals↗

PubMed1999

The direct effect of intraorbital pressure on orbital growth in the anophthalmic piglet.

Tissue expanders placed within the orbit can have a positive effect on orbital and ipsilateral midfacial growth. To date, there is no precise method for controlling and monitoring expansion to induce normal growth in the developing facial skeleton. The present study was undertaken to determine the optimal physiologic pressure required to stimulate normal orbital growth and to determine whether above-normal growth could be achieved with higher intraorbital pressures. Using a neonatal swine model, an accurate method of monitoring intraorbital pressure, precisely controlling intraorbital expansion, and achieving normal orbital growth was explored. Sixteen male, 3-week-old Yorkshire piglets were randomly divided into three surgical groups. In each group, the left orbit was the experimental side, and the contralateral right orbit served as an untreated control. Group 1 (n = 6) underwent enucleation only. Group 2 (n = 5) underwent enucleation and orbital expansion at a near-normal physiologic pressure of 20 mmHg. Group 3 (n = 5) underwent enucleation and orbital expansion at a supernormal pressure of 60 mmHg. Spherical tissue expanders (10 cc) with a separate injection port were utilized as the orbital expanders. Pressure was monitored by an electronic manometer that was calibrated daily. Morphology of the orbits was documented by photography, the dimensions of the orbits were quantitated by three-dimensional mechanical digitization, and orbital volumes were calculated. In the unexpanded, anophthalmic control group, a significant reduction in radial growth after evisceration was seen. In group 2, the orbit stimulated with a consistent pressure of 20 mmHg, just above the physiologic normal pressure of 17 mmHg, showed an increase in radial dimension of 8 percent compared with the unoperated side. In the high-pressure group of 60 mmHg, an increase of 16 percent in the radius was observed over the 4-week period. This led to a corresponding increase in orbital volumes with increased pressure. Utilizing a paired t test, these differences in the radial and volumetric growth of the orbit were statistically significant (p < 0.005). The results obtained demonstrated a direct relationship between intraorbital pressure and the growth of the bony orbit in the radial dimension. On the basis of this study, we concluded that orbital expansion maintained at normal physiologic pressure can stimulate normal orbital growth in the neonatal facial skeleton. In addition, application of above-normal pressures for expansion can induce accelerated orbital growth.

Animals↗

PubMed1999

[Combination of high-dose chemotherapy with autologous hematopoietic stem cell transplantation for recurrent and high-risk breast cancer: a pilot study].

OBJECTIVE: To evaluate the therapeutic effectiveness and safety of combined high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (AHSCT) for recurrent and high-risk breast cancer. METHODS: Thirteen patients with recurrent or high-risk breast cancer underwent HDC with AHSCT. Seven cases had relapsed metastasis who had failed in the previous chemotherapy. Two cases had stage IV disease who had received palliative excision. Four cases had stage II or III breast cancer with over 10 positive axillary lymph nodes who had received radical surgical resection. Four cases received autologous bone marrow transplantation, and six received autologous peripheral blood stem cell transplantation. The consolidation regimen was Thiotepa 500 (250-604) mg/m2, Cyclophosphamide 4.9 (3.3-6.0) g/m2. Eight cases were also given Carboplatin 800 (400-800) mg/m2, and two received Etoposide 830 (800-830) mg/m2 instead of Thiotepa in the consolidation regimen. Twelve cases underwent endocrinotherapy after HDC with AHSCT, six operated cases underwent radiotherapy in the area of chest wall and regional lymph nodes after HDC with AHSCT. RESULTS: After a median follow-up of 8(1-47) months, four cases achieved complete remission (CR) and 3 achieved partial remission (PR) in the 7 cases with relapsed metastasis after induction of chemotherapy, PR patients achieved CR after HDC with AHSCT. The disease free survival (DFS) was 1-31 months in these 7 cases. One of two stage IV cases achieved CR and the other had progressive disease (PD) after induction chemotherapy, but the PD patient achieved PR after HDC with AHSCT, they underwent local radiotherapy after HDC with AHSCT and DFS was 5 and 22 months, respectively. The DFS was from 1-47 months in 4 cases with stage II or III disease. CONCLUSION: HDC with AHSCT is a highly potential therapeutic means for recurrent and high-risk breast cancer paitents.

Adult↗

PubMed1998

Donor pretreatment with Flt-3 ligand augments antidonor cytotoxic T lymphocyte, natural killer, and lymphokine-activated killer cell activities within liver allografts and alters the pattern of intragraft apoptotic activity.

BACKGROUND: Liver allografts are accepted across major histocompatibility complex (MHC) barriers in mice and induce donor-specific tolerance without requirement for immunosuppressive therapy. There is evidence that passenger leukocytes may play a key role in tolerance induction. Flt-3 ligand (FL) is a recently cloned hematopoietic cytokine that strikingly augments functional dendritic cells (DCs) within lymphoid and nonlymphoid tissue. METHODS: The expression of costimulatory molecules and MHC class II antigen on DCs isolated from livers of FL-treated B10 (H2b) mice (10 microg/day; 10 days) was examined by flow cytometric analysis, and their allostimulatory activity assessed in primary mixed leukocyte cultures. B10 livers from FL-treated donors were transplanted orthotopically into naive C3H (H2k) recipients. Donor cells (MHC class II+) in recipient spleens were identified by immunohistochemistry. Antidonor cytotoxic T lymphocyte activity, and both natural killer and lymphokine-activated killer cell activities of graft nonparenchymal cells and host splenocytes were determined using isotope release assays. Apoptotic activity within liver grafts was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling. RESULTS: DCs isolated from livers of FL-treated donor mice exhibited increased cell surface expression of CD40, CD80, CD86, and IAb, and augmented T cell allostimulatory activity compared with controls. Within 24 hr of organ transplantation, the numbers of donor IAb+ cells within recipient spleens was augmented substantially compared with normal liver recipients. Livers from FL-treated donors were rejected acutely (median survival time, 5 days), whereas control B10 liver allografts survived >100 days. Nonparenchymal cells from rejecting grafts 4 days after transplantation exhibited increased antidonor cytotoxic T lymphocyte, natural killer, and lymphokine-activated killer cell activities compared with cells from spontaneously accepted grafts. This augmented cytotoxic reactivity was associated with histologic evidence of injury to bile duct epithelium and vascular endothelium that was not readily evident in controls. CONCLUSION: Thus, although normal livers provide allostimulatory signals sufficient to elicit an antidonor immune response, regulatory mechanisms that may include apoptosis of graft-infiltrating T cells, and that are overcome by augmenting the number of functional donor DCs, may account for inherent liver tolerogenicity.

Animals↗

PubMed1998

[Ceruloplasmin gene expression in silicotic rat lung].

In order to investigate the existence of extrahepatic ceruloplasmin (Cp) gene expression during silicotic process, molecular hybridization technique including dot blotting, in situ hybridization and Northern blotting was used. Twenty one days after silica dust intratracheal injection, Cp mRNA was detectable in lung, which was nearly double the content of that in the control (saline injection). In situ hybridization and Northern blotting revealed that the alveolar macrophages in silicosis could express Cp mRNA. It is concluded that lung is a prominent site for Cp gene expression during silicosis and Cp may play a previously unknown role in pulmonary injury or repair.

Animals↗

PubMed1998

[Detection of type 6 human herpesvirus (HHV-6) specific DNA sequence in lymphoma tissues by PCR].

OBJECTIVE: To study the relationship between human herpesvirus-6 (HHV-6) and lymphoma in China. METHODS: The specimens of paraffin-embedded lymphoma tissue, leukemia cell lines and normal blood donor peripheral blood lymphocytes(PBL) were examined for the presence of HHV-6 DNA sequence by polymerase chain reaction (PCR). RESULTS: Of the 52 cases lymphoma studied, HHV-6 DNA sequence was detected in 21 cases; of 43 normal PBL, HHV-6 DNA sequence was detected in 8 cases. The difference was statistically significant (P < 0.05). HHV-6 DNA sequence was also present in two leukemia cell lines. CONCLUSION: The results suggest that HHV-6 may be related to lymphoma in China.

DNA, Viral↗

PubMed1996

Tacrolimus pretreatment attenuates preexisting xenospecific immunity and abrogates hyperacute rejection in a presensitized hamster to rat liver transplant model.

In the hamster to rat liver transplant model, we determined the efficacy of tacrolimus in attenuating natural xenospecific humoral immunity and in abrogating the hyperacute liver rejection that is produced by presensitizing the Lewis rat recipient. Hamster livers, transplanted orthotopically into naive rats (controls), were rejected with animal death after 6.4.+/- 0.5 (SD) days. The infusion on (day -6) of 1.5 x 10(7) hamster hepatocytes, or of 1.5 x 10(8) nonparenchymal cells (NPC), resulted in hyperacute rejection and death in < or = 1.9 days. However, when the rats were pretreated with 1 mg/kg/day tacrolimus from days -6 to -1, survival of non-presensitized animals was prolonged to 25 +/- 20 days and that of recipients presensitized with hamster hepatocytes to 36 +/- l6 days or with NPC to 32 +/- 1.7 days. The tacrolimus pretreatment significantly reduced the hamster-specific complement-dependent cytotoxic antibodies response directed to liver NPC but not to lymph node cell targets. These observations suggest that the prolongation of survival by appropriately timed treatment with this T cell directed drug model is caused by the inhibition of humoral as well as cellular xenograft rejection.

Animals↗

PubMed1996

Ginkgo biloba L.: history, current status, and future prospects.

In this paper, we describe the status of the exploration and use of the Ginkgo biloba leaves in China. We emphasize the need for careful studies of the intra-specific genetic diversity of Ginkgo biloba since genetic variation within this species may result in significant differences between the chemical and pharmacological properties of the different sub-species. It is therefore imperative that we catalog the intraspecific diversity of Ginkgo biloba L., and we stress that it is important to conserve this diversity since different subspecies may have different pharmacochemical properties resulting in differential medical usages.

Cycadopsida↗

PubMed1996

The superior auricular artery and retroauricular arterial island flaps.

This paper reports the finding of the superior auricular artery, which is a fairly large arterial branch, about 1 mm in diameter, arising from the superficial temporal artery anterior to the auricular helix. It is covered by skin, the anterior auricular muscle, and the fascia of the parotid gland. It runs together with its concomitant vein posteriorly in the groove between the cartilage of the ear and the temporal bone and anastomoses with the posterior auricular artery. This artery has been used successfully to raise large retroauricular arterial island flaps for one case of total nose reconstruction and seven cases of reconstruction of the severely constricted anophthalmic socket. These operative procedures are described in detail.

Anophthalmos↗

PubMed1996