Biomedical subjects

F Chen

Publications and source records attributed to F Chen.

At least 325 records · Page 18Linked to original sources

PubMed1998

Motoneurotrophins derived from limb buds protect the motoneurons in anterior spinal cord after nerve injury and promote nerve regeneration.

The effects of limb bud-derived motoneurotrophins (LBMNTs) as seen in the motoneurons in the anterior spinal cord and sciatic nerve regeneration of adult rats, were evaluated in the present study. A nerve regeneration chamber with a nerve gap of 9 mm was created by suturing the proximal and distal ends of a random sciatic nerve into a silicone tube after removal of a 5 mm piece of nerve in the distal end, The chamber of the experimental group was filled with 34.34 microg LBMNTs and PBS (0.01 mol/ml, pH 7.0),and the control group with PBS only. At 1 day, 4 days, 1 week, 2 weeks, 4 weeks and 6 weeks post surgery, the content of acetylcholine esterase (AchE) and acid phosphatase (ACP) of the anterior spinal cord (injured side) was quantified, and the corresponding motoneuron's ultrastructure and the existant ratio were also examined. Meanwhile, the regenerated nerve from within the silicone tube was examined at 2, 4 and 6 weeks post surgery for histological studies at both the light microscopic and ultrastructural levels. The experimental group showed a smaller decrease of AchE and an increase of ACP, a larger existant ratio of motoneurons, better ultrastructure and a more mature regenerated nerve based on a larger diameter of the regenerated nerve trunk, a greater number of axons and thicker myelin sheaths than the control group. So it was concluded that LBMNTs had a high activity of protecting motoneurons in the anterior spinal cord after nerve injury and promoting nerve regeneration, and it may be a new source of neurotrophic factors (NTFs).

Acetylcholinesterase↗

PubMed1998

Coding defect and a TATA box mutation at the bilirubin UDP-glucuronosyltransferase gene cause Crigler-Najjar type I disease.

Mutations at the bilirubin UDP-glucuronosyltransferase (transferase) gene in a severely hyperbilirubinemic Crigler-Najjar (CN) type I individual was compared with that in a moderately hyperbilirubinemic CN II individual. The CN-I (CF) patient in this study sustained a TATA box insertional mutation which was paired with a coding defect at the second allele, unlike all coding defects previously seen in CN-I patients. The sequence of the mutant TATA box, [A(TA)8A], also seen in the CN-II patient, was compared with that at the wild-type box, [A(TA)7A]. Transcriptional activity with [A(TA)8A] was 10-15% that with the wild-type box when present in the -1.7 kb upstream regulatory region (URR) of the bilirubin transferase UGT1A1 gene which was fused to the chloramphenicol acetyl transferase reporter gene, pCAT 1.7H, and transfected into HepG2 cells. Also, a construct with a TA deletion, [A(TA)6A], was prepared and used as a control; transcriptional activity was 65% normal. The coding region defect, R336W, seen in CF (CN-I) was placed in the bilirubin transferase UGT1A1 [HUG-Br1] cDNA, and its corresponding protein was designated UGT1A1*32. The UGT1A1*32 protein supported 0-10% normal bilirubin glucuronidation when expressed in COS-1 cells. The I294T coding defect seen at the second allele in SM (CN-II) generated the UGT1A1*33 mutant protein which supported 40-55% normal activity with a normal Km (2.5 microM) for bilirubin. The hyperbilirubinemia seen in SM decreased in response to phenobarbital treatment, unlike that seen in CF. Parents of the patients were carriers of the respective mutations uncovered in the offspring. The TATA box mutation paired with a deleterious missense mutation is, therefore, completely repressive in the CN-I patient, and is responsible for a lethal genotype/phenotype; but when homozygous, i.e. paired with itself, as previously reported in the literature, it is far less repressive and generates the mild Gilbert's phenotype.

Bilirubin↗

PubMed1998

The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin.

The presenilin (PS) genes associated with Alzheimer disease encode polytopic transmembrane proteins which undergo physiologic endoproteolytic cleavage to generate stable NH2- and COOH-terminal fragments (NTF or CTF) which co-localize in intracellular membranes, but are tightly regulated in their stoichiometry and abundance. We have used linear glycerol velocity and discontinuous sucrose gradient analysis to investigate the distribution and native conformation of PS1 and PS2 during this regulated processing in cultured cells and in brain. The PS1 NTF and CTF co-localize in the endoplasmic reticulum (ER) and in the Golgi apparatus, where they are components of a approximately 250-kDa complex. This complex also contains beta-catenin but not beta-amyloid precursor protein (APP). In contrast, the PS1 holoprotein precursor is predominantly localized to the rough ER and smooth ER, where it is a component of a approximately 180-kDa native complex. PS2 forms similar but independent complexes. Restricted incorporation of the presenilin NTF and CTF along with a potentially functional ligand (beta-catenin) into a multimeric complex in the ER and Golgi apparatus may provide an explanation for the regulated accumulation of the NTF and CTF.

Alzheimer Disease↗

PubMed1998

Identification and cloning of an orphan G protein-coupled receptor of the glycoprotein hormone receptor subfamily.

Mining of the EST database identified a human EST that was predicted to encode a novel member of the glycoprotein hormone receptor subfamily. Based on the sequence information, the full-length coding region of this gene was isolated and sequenced. This gene, designated HG38, is predicted to encode a polypeptide of 907 amino acid residues with a putative signal peptide sequence at its very N-terminus. HG38 is most closely related to members of the glycoprotein hormone receptor subfamily with approximately 35% overall identity at the protein sequence level. As with the glycoprotein hormone receptors, HG38 contains a long extracellular domain with a total of 16 leucine-rich repeats. Northern blot analysis showed that HG38 was expressed in skeletal muscle, placenta, spinal cord, and various regions of the brain. Radiation hybrid mapping placed HG38 into human chromosome 12q22-23. HG38 is most likely to be a receptor for a novel class of glycoprotein ligands.

Amino Acid Sequence↗

PubMed1998

Auxiliary downstream elements are required for efficient polyadenylation of mammalian pre-mRNAs.

We have previously identified a G-rich sequence (GRS) as an auxiliary downstream element (AUX DSE) which influences the processing efficiency of the SV40 late polyadenylation signal. We have now determined that sequences downstream of the core U-rich element (URE) form a fundamental part of mammalian polyadenylation signals. These novel AUX DSEs all influenced the efficiency of 3'-end processing in vitro by stabilizing the assembly of CstF on the core downstream URE. Three possible mechanisms by which AUX DSEs mediate efficient in vitro 3'-end processing have been explored. First, AUX DSEs can promote processing efficiency by maintaining the core elements in an unstructured domain which allows the general polyadenylation factors to efficiently assemble on the RNA substrate. Second, AUX DSEs can enhance processing by forming a stable structure which helps focus binding of CstF to the core downstream URE. Finally, the GRS element, but not the binding site for the bacteriophage R17 coat protein, can substitute for the auxiliary downstream region of the adenovirus L3 polyadenylation signal. This suggests that AUX DSE binding proteins may play an active role in stimulating 3'-end processing by stabilizing the association of CstF with the RNA substrate. AUX DSEs, therefore, serve as a integral part of the polyadenylation signal and can affect signal strength and possibly regulation.

Adenoviruses, Human↗

PubMed1998

Chromatin remodeling of the interleukin-2 gene: distinct alterations in the proximal versus distal enhancer regions.

Known transcription factor-DNA interactions in the minimal enhancer of the murine interleukin-2 gene (IL-2) do not easily explain the T cell specificity of IL-2 regulation. To seek additional determinants of cell type specificity, in vivo methodologies were employed to examine chromatin structure 5' and 3' of the 300 bp IL-2 proximal promoter/enhancer region. Restriction enzyme accessibility revealed that until stimulation the IL-2 proximal promoter/enhancer exists in a closed conformation in resting T and non-T cells alike. Within this promoter region, DMS and DNase I genomic footprinting also showed no tissue-specific differences prior to stimulation. However, DNase I footprinting of the distal -600 to -300 bp region revealed multiple tissue-specific and stimulation-independent DNase I hypersensitive sites. Gel shift assays detected T cell-specific complexes binding within this region, which include TCF/LEF or HMG family and probable Oct family components. Upon stimulation, new DNase I hypersensitive sites appeared in both the proximal and distal enhancer regions, implying that there may be a functional interaction between these two domains. These studies indicate that a region outside the established IL-2 minimal enhancer may serve as a stable nucleation site for tissue-specific factors and as a potential initiation site for activation-dependent chromatin remodeling.

Animals↗

PubMed1998

Metal-mediated oxidative DNA damage induced by nitro-2-aminophenols.

Two hair dye components, carcinogenic 4-nitro-2-aminophenol and 5-nitro-2-aminophenol, induced Cu(II)-dependent DNA cleavage frequently at thymine and guanine residues in DNA fragments obtained from the c-Ha-ras-1 protooncogene. When the p53 tumor suppressor gene was used, 4-nitro-2-aminophenol caused Cu(II)-dependent piperidine-labile sites at poly G sequences. In the presence of Cu(II), both components increased 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in DNA. The inhibitory effects of catalase and bathocuproine on DNA damage suggest the involvement of H2O2 and Cu(I). It is speculated that nitro-2-aminophenols undergo Cu(II)-mediated autoxidation to generate active oxygen species causing DNA damage which leads to their carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1998

Germ cell nuclear factor is a response element-specific repressor of transcription.

We have shown that the orphan receptor Germ Cell Nuclear Factor (GCNF) binds to a direct repeat of the sequence AGGTCA with zero base pair spacing (DR0). Here, we further characterize the binding characteristics of GCNF. We demonstrate that GCNF binds specifically to DR0s as a homodimer, and does not bind with high affinity to DR1-DR6 sequences. GCNF is the first nuclear receptor shown to bind specifically to DR0s. The wild type GCNF is unable to transactivate the reporter plasmid DR0(2)tkCAT. Lacking a ligand to activate GCNF, we fused the activation domain from the viral protein VP16 to GCNF, and observed activation of DR0(2)tkCAT. This activation is specifc to DR0s, and is not observed when that sequence is replaced by DR1-DR6 sequences. In addition GCNF does not transactivate through an SF-1 response element. At increasing concentrations, wild type GCNF is able to repress basal transcription. Repression is again specific to DR0s. The preference of GCNF for the DR0 sequence both in vitro and in transfections suggests that GCNF defines a novel nuclear receptor signaling pathway.

DNA-Binding Proteins↗

PubMed1998

Glycoprotein IIb Leu214Pro mutation produces glanzmann thrombasthenia with both quantitative and qualitative abnormalities in GPIIb/IIIa.

Glanzmann thrombasthenia is an inherited bleeding disorder due to a functional reduction or absence of platelet GPIIb/IIIa (alphaIIbbeta3) integrin receptors. Based on a prolonged bleeding time and absence of platelet aggregation in response to physiologic agonists, a 55-year-old white man was diagnosed as having Glanzmann thrombasthenia. The patient's platelet fibrinogen level was approximately 5% of normal. As judged by complex-dependent monoclonal antibody (MoAb) binding, surface expression of platelet GPIIb/IIIa receptors was less than 5.5% of normal, whereas the binding of an anti-GPIIIa specific MoAb (7H2) was approximately 12% of normal. Immunoblot analysis of the patient's platelet lysates showed approximately 35% of normal levels of GPIIIa, approximately 30% of normal levels of GPIIb, and an abnormally migrating fragment of GPIIb. Biotinylation of the surface proteins on the patient's platelets followed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed only GPIIb and GPIIIa subunits of normal size. Surface expression of platelet alphavbeta3 receptors was 192% of normal, suggesting that the patient's' defect was in GPIIb. Sequence analysis of the patient's GPIIb cDNA identified a T to C transition at nucleotide 643, predicting a Leu214Pro substitution. Direct sequencing of GPIIb exon 6 indicated that the patient is homozygous for the mutation. The nature of the Leu214Pro mutation was analyzed by expression in Chinese hamster ovary (CHO) cells. As judged by subunit-specific MoAb binding, surface expression of mutant receptors was approximately 60% of normal, but these receptors were not recognized by the complex-dependent monoclonal antibodies, 10E5 and 7E3. In addition, mutant receptors pretreated with the ligand-induced binding site MoAb AP5 were not recognized by the activation-dependent MoAb PAC-1 and mutant expressing CHO cells did not adhere to immobilized fibrinogen. These data suggest that the Leu214Pro mutation in GPIIb disrupts the structural conformation, and either directly or indirectly, the ligand binding properties of the heterodimeric complex. This is in accord with studies from other integrins that have implicated a beta-turn in a homologous region as important in ligand binding. Thus, the Leu214Pro mutation appears to produce the Glanzmann thrombasthenia phenotype by both qualitative and quantitative abnormalities. In addition, the mutation appears to confer susceptibility of the GPIIb subunit to proteolysis.

Animals↗

PubMed1998

Identification of an IL-7-associated pre-pro-B cell growth-stimulating factor (PPBSF). I. Production of the non-IL-7 component by bone marrow stromal cells from IL-7 gene-deleted mice.

Mouse bone marrow (BM) stromal cell conditioned medium (CM) from our long-term lymphoid culture system selectively induces the in vitro proliferation and presumptive differentiation of pre-pro-B cells (B220+, HSA-, TdT- or TdT+, c[mu-]) from adult rat, mouse, and human BM. However, the responsible growth factor(s) has not yet been identified. Inasmuch as IL-7 is one of the cytokines most closely associated with early B-lineage development, we utilized BM adherent cells and stromal cell lines from IL-7 gene-deleted (-/-) mice in combination with rIL-7 and anti-IL-7 mAb to investigate its possible regulatory role in our culture system. The results show that, although rIL-7 and IL-7 (-/-) CM each can maintain the viability of freshly harvested pre-pro-B cells in vitro, neither induces them to proliferate and/or differentiate, even in the presence of recombinant stem cell factor (rSCF) and/or recombinant insulin-like growth factor (rIGF). The results also show that anti-IL-7 mAb fails to neutralize the pre-pro-B cell growth-stimulating activity in IL-7 (+/+) CM. Yet rIL-7 enables IL-7 (-/-) CM to induce proliferation of pre-pro-B cells, and to "prime" them to respond directly to monomeric IL-7. Furthermore, anti-IL-7 mAb adsorbs the pre-pro-B cell growth-stimulating activity from both IL-7 (+/+) CM and rIL-7-supplemented IL-7 (-/-) CM; but rIL-7 does not restore this activity. Lastly, both pre-pro-B cell growth-stimulatory activity and IL-7 are quantitatively recovered by ultrafiltration in the 50 to 100 kDa, rather than the 10 to 50 kDa, apparent molecular mass fraction. These results suggest that the pre-pro-B cell growth-stimulating activity in our culture system is the property of a self-associating complex of IL-7 and a second BM stromal cell-derived cofactor.

Animals↗

PubMed1998

Identification of an IL-7-associated pre-pro-B cell growth-stimulating factor (PPBSF). II. PPBSF is a covalently linked heterodimer of IL-7 and a Mr 30,000 cofactor.

Evidence is provided in a companion paper for an IL-7-associated molecular complex that selectively stimulates the proliferation and presumptive differentiation of pre-pro-B cells in our long-term bone marrow culture system and "primes" them to proliferate in response to monomeric IL-7. Here, Western immunoblot analysis reveals that this pre-pro-B cell growth-stimulating factor (PPBSF) is a self-assembling heterodimer of IL-7 and a cofactor with a M(r) of 30,000. Thus, when developed with anti-IL-7 mAb, PPBSF migrates electrophoretically as a covalently bound approximately 55-kDa molecule under nonreducing conditions but dissociates under reducing conditions. Furthermore, the addition of rIL-7 or native IL-7 to medium conditioned by stromal cells from IL-7 gene-deleted (-/-) mice results in the formation of active 45-kDa and 55-kDa molecular complexes, respectively. Antiserum prepared in IL-7(-/-) mice against affinity-purified PPBSF contained separable reactivities for IL-7 and the non-IL-7 component of PPBSF. The PPBSF cofactor detected by this antiserum migrates as an approximately 30-kDa molecule and is able to maintain the viability, but not the proliferation, of pre-pro-B cells. Furthermore, the cofactor is produced constitutively by IL-7(-/-) and IL-7(+/+) bone marrow stromal cells under pro-B- but not pre-B-type culture conditions. Consequently, IL-7 appears to exist almost entirely as a heterodimer (i.e., PPBSF) in pro-B-type cultures, whereas it exists almost entirely as a monomer in pre-B-type cultures. Although the identity of the PPBSF cofactor remains to be determined, it does not appear to be stem cell factor, insulin-like growth factor-1, thymic stromal-derived lymphopoietin, flt3, stromal cell-derived factor-1, or IL-7R.

Animals↗

PubMed1998

A central region of Ku80 mediates interaction with Ku70 in vivo.

Ku, the DNA binding component of DNA-dependent protein kinase (DNA-PK), is a heterodimer composed of 70 and 86 kDa subunits, known as Ku70 and Ku80 respectively . Defects in DNA-PK subunits have been shown to result in a reduced capacity to repair DNA double-strand breaks. Assembly of the Ku heterodimer is required to obtain DNA end binding activity and association of the DNA-PK catalytic subunit. The regions of the Ku subunits responsible for heterodimerization have not been clearly defined in vivo . A previous study has suggested that the C-terminus of Ku80 is required for interaction with Ku70. Here we examine Ku subunit interaction using N- and C-terminal Ku80 deletions in a GAL4-based two-hybrid system and an independent mammalian in vivo system. Our two-hybrid study suggests that the central region of Ku80, not its C-terminus, is capable of mediating interaction with Ku70. To determine if this region mediates interaction with Ku70 in mammalian cells we transfected xrs-6 cells, which lack endogenous Ku80, with epitope-tagged Ku80 deletions carrying a nuclear localization signal. Immunoprecipitation from transfected cell extracts revealed that the central domain identified by the GAL4 two-hybrid studies stabilizes and co-immunoprecipitates with endogenous xrs-6 Ku70. The central interaction domain maps to the internally deleted regions of Ku80 in the mutant cell lines XR-V9B and XR-V15B. These findings indicate that the internally deleted Ku80 mutations carried in these cell lines are incapable of heterodimerization with Ku70.

Amino Acid Sequence↗

PubMed1998

Uncoupling protein-3: a muscle-specific gene upregulated by leptin in ob/ob mice.

We identified and partially characterized another member of the uncoupling protein termed UCP3. Human and mouse UCP3 protein sequences are 86% identical to each other, and 73% and 59% identical to UCP2 and UCP1, respectively. Expression of human UCP3 in yeast resulted in a drastic decrease of mitochondria membrane potential. Northern analysis showed that UCP3 was highly expressed in skeletal muscle in human, rat, and mouse. Mapping of UCP3 placed it to the same chromosomal region of UCP2 in both human and mouse, a region that is linked to obesity and hyperinsulinemia. Furthermore, adenovirus-mediated leptin expression in obese ob/ob mice led to increased expression of UCP3 in skeletal muscle. The data indicate that UCP3 encodes a muscle-specific uncoupling protein that may play an important role in the regulation of energy expenditure and development of obesity.

Adenoviridae↗

PubMed1998

Embryonic limb buds derived neurotrophins on the survival of neurons and the growth of axons in culture in vitro.

Bioactive proteins from SD rat limb buds were extracted and purified. Fractions of 22 ku, 34 ku and 95 ku were proved to have neurotrophic activity to neurons, and the combined activity of these three fractions was the highest. So they were combinedly added into the culture medium of sensor neurons in dorsal root ganglia and motor neurons of anterior spinal cord from 2-week-old embryonic rats, and PBS was added as control. Phase-contrast microscopic and electron microscopic observations, and true cholinesterase measurements were performed to evaluate the survival and changes in growth, function, and ultrastructure of these cultured neurons. In the experimental group, it was found that the AchE activity was higher (P < 0.01), ultrastructural changes in mitochondria, Gorgi's complex and other cell organs were milder than those in the control group. The results showed limb buds derived neurotrophins played an important role in maintaining the survival of the neurons and promoting the growth of axons. It was concluded that embryonic limb buds derived neurotrophins had high neurotrophic activities on neurons' survival and axon growth.

Animals↗

PubMed1998

Biodegradation of tricalcium phosphate ceramics by osteoclasts.

Biodegradation of tricalcium phosphate (TCP) ceramics was observed through mixed culture of osteoclasts and TCP discs in vitro in this study. Osteoclasts were isolated from newborn SD rat's marrow of long bone and cultured on TCP discs. The culture terminated at the 48th h and 96th h respectively. Under an inverted microscope, the osteoclasts imparted round or oval body with multinuclear and many thin processes. These cells were positively stained for tartrate-resistance acid phosphatase (TRAP). Scanning electron microscope showed that many resorption lacunae on TCP disc surface and their diameters were smaller than 20 microns. Osteoclasts were located in the lacunae. At the 96th h, the resorption lacunae become larger and osteoclasts showed degeneration. It is suggested that osteoclasts possess ability to re-absorb TCP ceramics under in vitro culturing condition.

Animals↗

PubMed1998

Effects of acute ethanol on GABA release and GABA(A) receptor density in the rat mesolimbic system.

The present study has addressed whether acute ethanol administration mediates changes in GABA release and GABA(A) receptor density in the rat mesolimbic system. In vivo microdialysis was performed in the ventral pallidum and between the ventral tegmental area and substantia nigra of conscious ethanol-naive rats. Extracellular levels of endogenous GABA were stable in both brain regions and not significantly affected following administration of 5 ml of 20% ethanol by gavage, despite clear overt behavioral signs of intoxication. Two hours following ethanol administration, animals were decapitated and the brains processed for autoradiography. Adjacent tissue sections were incubated with [3H]SR95531 or [3H]muscimol and the resulting autoradiograms quantified. Binding of both radioligands was significantly reduced in the striatum of rats treated with ethanol compared to vehicle (15 +/- 2% for [3H]SR95531 and 33 +/- 6% for [3H]muscimol). In contrast, ethanol had no effect on [3H]SR95531 binding in hippocampus, while that of [3H]muscimol was increased by 100 +/- 30%. Ethanol had no effect on the binding of either radioligand in all other areas examined. Therefore, while acute ethanol had no effect on the release of GABA in either the ventral pallidum or ventral tegmental area, changes in the binding density of GABA(A) ligands were observed in selected brain regions.

Administration, Oral↗

PubMed1998

Distribution of GABAA receptors in the limbic system of alcohol-preferring and non-preferring rats: in situ hybridisation histochemistry and receptor autoradiography.

The present study has employed quantitative receptor autoradiography and in situ hybridisation histochemistry to compare the expression of the mRNA encoding the alpha 1 and alpha 2 subunits of the GABAA receptor and the binding density of mature GABAA receptors in the limbic system of alcohol-preferring Fawn-Hooded rats (FH) with Wistar-Kyoto rats (WKY). Quantifiable levels of mRNA encoding the alpha 1 subunit were found in cortical regions, ventral pallidum, substantia nigra, horizontal limb of the diagonal band and the hippocampus of both rat strains. Interestingly, expression of the alpha 1 subunit mRNA was decreased by approximately 30% in the hippocampus of FH compared to WKY rats. Following a 28-day period with free access to 10% ethanol, expression of the alpha 1 subunit transcript, was significantly increased in the piriform cortex and horizontal limb of the diagonal band, unaltered in the hippocampus but decreased in the substantia nigra of FH rats. Quantifiable levels of mRNA encoding the alpha 2 subunit were found in nucleus accumbens, amygdala, cortical regions, lateral septal nucleus, hippocampus, medial habenula and ventral pallidum of both strains. Expression of the alpha 2 subunit mRNA was decreased by approximately 35% in both the hippocampus and occipital cortex of FH compared to WKY rats. However, consumption of 10% ethanol in FH rats had no impact upon expression of the mRNA encoding the alpha 2 subunit in any region examined. Mature GABAA receptors were studied by autoradiography utilising the antagonist radioligand [3H]SR95531 and the agonist radioligand [3H]muscimol. Topographic binding throughout the limbic system of both strains was observed for both radioligands. Specifically, [3H]SR95531 binding was higher in the occipital cortex, hippocampus, lateral septal nucleus, superior colliculus and ventral pallidum of the FH rats compared to WKY rats; however, in the nucleus accumbens [3H]SR95531 binding was lower in FH compared to WKY. Ethanol consumption had no measurable effect on the binding of [3H]SR95531 in FH rats. In the case of [3H]muscimol, binding was higher in the cortex, lateral septum and ventral pallidum of FH compared to WKY. Furthermore, ethanol consumption resulted in a 25-30% increase in [3H]muscimol binding in the lateral septum and striatum of FH rats. These data provide evidence for differential expression of GABAA receptor subunits in FH and WKY rats, and additionally indicate anatomically defined variations in GABAA receptor binding between the two rat strains.

Alcohol Drinking↗

PubMed1998

Revision of the ununited one-bone forearm.

Between 1975 and 1995, 7 patients were surgically treated for persistent forearm pain following previously unsuccessful attempts of constructing a radioulnar synostosis using interosseous bone grafting with either cross screw or pin fixation. These prior reconstructive procedures were salvage operations to address symptomatic radioulnar instability. The time interval between index operation and revision surgery was a mean of 12.6 months (range, 4-36 months). The postoperative follow-up period averaged 29.7 months (range, 11-61 months). To address these failed radioulnar arthrodeses, plate osteosynthesis and aggressive bone grafting were used in 5 of 7 patients (group 1) (4 with autologous graft and 1 with demineralized bone matrix). Union was achieved in all 5 patients after a single revision operation. Radiographic evidence of solid union was seen at approximately 4 months. In the remaining 2 patients (group 2), revision synostosis procedures were performed; these involved local bone grafting and repeat transverse screw fixation in 1 patient and iliac crest bone grafting alone in the other. One of these 2 patients progressed to union; the other had a persistent symptomatic fibrous union. The 5 patients in group 1 reported symptomatic relief, while the 2 patients in group 2 were dissatisfied. There were no postoperative complications in our series. Based on our findings, we advocate abundant bone grafting and plating for rigid internal fixation in failed radioulnar synostosis procedures.

Adult↗