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Biomedical subjects

L S Chin

Publications and source records attributed to L S Chin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pediatric intracranial epidural abscess secondary to an infected scalp vein catheter.

The authors present a case of a 5-week-old infant developing a retrotorcular epidural abscess as a result of an infected scalp vein catheter. The abscess developed in the absence of sinusitis, otitis, trauma, or prior surgery. The diagnosis of epidural abscess was made on the basis of magnetic resonance imaging and ultrasound-guided aspiration of the fluid collection. An identified strain of Staphylococcus epidermidis was cultured from both the intravenous catheter and the abscess. The patient underwent a suboccipital craniectomy with drainage of the abscess and a 6-week total course of intravenous antibiotics. Magnetic resonance imaging 4 months after the procedure and 2.5-year pediatric clinic follow-up have demonstrated no evidence of neurologic deficit or recurrence. When present, a scalp vein catheter must be considered as an etiologic agent for an intracranial epidural abscess in this age-group.

Brain Abscess↗
PubMed1998

Distinct roles of synapsin I and synapsin II during neuronal development.

The synapsins are a family of neuron-specific proteins, associated with the cytoplasmic surface of synaptic vesicles, which have been shown to regulate neurotransmitter release in mature synapses and to accelerate development of the nervous system. Using neuronal cultures from mice lacking synapsin I, synapsin II, or both synapsins I and II, we have now found that synapsin I and synapsin II play distinct roles in neuronal development. Deletion of synapsin II, but not synapsin I, greatly retarded axon formation. Conversely, deletion of synapsin I, but not synapsin II, greatly retarded synapse formation. Remarkably, the deletion of both synapsins led to partial restoration of the wild phenotype. The results suggest that the synapsins play separate but coordinated developmental roles.

Animals↗
PubMed1997

Cell and molecular biology for neurosurgeons (or everything you wanted to know about molecular biology but were afraid to download).

We are fortunate to be physicians at a time when the molecular pathogenesis of disease is being unraveled. Beginning with the discovery of the structure of DNA to the Human Genome Project, molecular biology over the past 45 years has revolutionized medicine. Neurosurgery has a strong scientific tradition, but to remain active participants in this new era of medicine, we must understand the science of pathology at the molecular level, applying our unique perspective to its advancement. We will review most of the current techniques used today by cell and molecular biologists. Interwoven with these descriptions will be a brief discussion of pertinent molecular and cell biology concepts, a full review being beyond the scope of this article.

Journal Article↗
PubMed1997

Growth factors in central nervous system development and tumorigenesis.

Growth factors play an important role in the development of the normal central nervous system as well as in the genesis of central nervous system tumors. Some of the more important growth factors and growth factor receptors, as they pertain to neurooncology, are reviewed in this article.

Journal Article↗
PubMed1997

Current concepts of apoptosis.

Apoptosis is a carefully regulated process involved in developmental and immunological events. The alteration of apoptotic pathways is important in the establishment and progression of neoplasia. Apoptosis allows for the orderly removal of excess cells but, in contrast to necrosis, it is not an inflammatory process. Many of the molecular components and effectors of apoptosis have been described. In this review the authors briefly discuss the current understanding of apoptosis in the context of the two prevailing hypotheses, the "conflicting signal" and "dual signal" theories.

Journal Article↗
PubMed1997

4-Aminopyridine causes apoptosis and blocks an outward rectifier K+ channel in malignant astrocytoma cell lines.

Among the ion channels and pumps activated by growth factor stimulation, K+ channels have been implicated in the growth and proliferation of several cancer cell lines. The role of these channels in central nervous system tumors, however, has not been described. This study used the malignant astrocytoma cell lines U87 and A172. 4-Aminopyridine (4-AP) inhibition of proliferation was dose dependent, and assessment using a TUNEL in situ assay revealed that apoptosis occurred in U87 cells with wild-type p53 but not in A172 cells with mutant p53 (24-hr incubation with mM 4-AP). In patch clamp experiments, we identified two types of K+ currents in both cell lines, a charybdotoxin-sensitive Ca2(+)-activated K+ channel and a 4-AP-sensitive outward rectifier K+ current. The outward rectifier current was blocked by 4-AP in a dose-dependent manner, with half-maximal block occurring at 3.9 mM. The blocking effect of 4 mM 4-AP was noticeable at potentials as low as -65 mV and was statistically significant at -60 mV and above, suggesting that 4-AP-sensitive current is active at physiological potentials. By contrast, charybdotoxin (1 microM) and tetraethylammonium. Cl (2 mM) blocked the Ca2(+)-activated K+ channel in both cell lines but had no appreciable effect on cell growth. Our findings reveal that 4-AP inhibits proliferation and the outward rectifier K+ channel in both U87 and A172 cells. More studies are needed, however, to describe the mechanism by which K+ channels influence proliferation and induce apoptosis.

4-Aminopyridine↗
PubMed1997

K252a inhibits proliferation of glioma cells by blocking platelet-derived growth factor signal transduction.

Growth factors are known to regulate glioma proliferation. The glioma cell lines U87 and T98G were examined for evidence of an autocrine stimulatory loop involving the neurotrophin family of growth factors. Although neurotrophin-3 and TrkC RNA were detected by reverse transcription-PCR, there was no evidence of significant interaction between neurotrophin-3 and its cognate receptor TrkC. The microbial alkaloid K252a has been described to inhibit both Trk tyrosine kinase activity and neuroblastoma cell proliferation. K252a inhibited proliferation in U87 (IC50 = 1170 nM) and T98G (IC50 = 529 nM) but induced apoptosis in U87 cells only. At concentrations of 500 nM to 1 microM, K252a blocked only platelet-derived growth factor (PDGF)-mediated receptor autophosphorylation. These results suggest that an autocrine loop involving PDGF is functional and important for maintaining tumor growth. There is no evidence to support the existence of a neurotrophin-mediated autocrine loop. K252a, through inhibition of PDGF signal transduction, may be a novel therapeutic agent in the treatment of human gliomas.

Apoptosis↗
PubMed1996

Early signaling events by endotoxin in PC12 cells: involvement of tyrosine kinase, constitutive nitric oxide synthase, cGMP-dependent protein kinase, and Ca2+ channels.

We studied the effects of endotoxin from Escherichia coli (E. coli) on Ca2+ channel activity in PC12 cells using the cell-attached patch clamp technique. Endotoxin (1-100 ng/ml) decreased channel availability (n x Po) to about one third of control values, an effect that required 3.5 +/- 1 min (mean +/- SD; n = 13) to reach steady state. The biophysical properties of the channel, including slope conductance (22 pS; 40 mM Ba2+), voltage dependence of n x Po, and open times (tau 1 = 0.78 ms, tau 2 = 8.9 ms) for the two open states at 0 mV, were not altered. The effect of endotoxin was blocked by polymyxin-B, indicating involvement of the lipid-A moiety of lipopolysaccharide, and by the tyrosine kinase (tk) inhibitor, tyrphostin. The effect of endotoxin was mimicked by 8-bromo-cGMP (100 microM), and was blocked by the inhibitor of cGMP-dependent protein kinase (PKG), H-8, suggesting involvement of the cGMP/PKG pathway. The effect of endotoxin also was blocked by the nitric oxide (NO) synthase inhibitor, NG-monomethyl-L-arginine monoacetate, suggesting involvement of nitric oxide synthase (NOS). The rapidity of the effect of endotoxin on Ca2+ channel activity suggested that constitutive NOS (cNOS) was involved, in accordance with our finding that endotoxin-induced transcriptional induction of NOS, as measured by nitrite production, required > 6 hr. We conclude that early signaling events by endotoxin in PC12 cells involve tk, cNOS, cGMP/PKG, and Ca2+ channels.

Animals↗
PubMed1996

Postsynaptic element contributes to the delay in synaptogenesis in synapsin I-deficient neurons.

In a previous study, we reported a retardation in process outgrowth and synapse formation in cultured hippocampal neurons from synapsin I-deficient mice. Here we investigated whether this delay in synaptogenesis was attributable to pre- or postsynaptic elements. The experimental paradigm used in this study involved the establishment of heterochronic cocultures of neurons from wild-type and synapsin I-deficient neurons established synapses with mature wild-type postsynaptic elements after 24 and 72 h, respectively. In contrast, synapsin I-deficient postsynaptic elements were able to receive synapses only after 9 days in culture, representing a 5-day delay compared to controls. The results suggest a broad role of synapsin I in the structural development of the synapse, participating directly or indirectly in the maturation of both presynaptic and postsynaptic sites.

Animals↗
PubMed1996

Chinese achondroplasia is also defined by recurrent G380R mutations of the fibroblast growth factor receptor-3 gene.

Achondroplasia is the most common form of dwarfism in humans. A recurrent glycine-to-arginine mutation at codon 380 (G380R) of the transmembrane domain of fibroblast growth factor receptor-3 (FGFR-3) was identified in the majority of Western and Japanese patients, which is uncommon in other autosomal dominant genetic diseases. To determine whether this mutation is also common in Chinese patients, we examined the G380R mutation in Chinese patients with achondroplasia. Of ten patients studied, including eight sporadic cases and one family with two affected members, all have the same G380R mutation with a G-to-A transition. Our results support the argument that the G380R mutation of FGFR-3 is the most frequent mutation causing achondroplasia across different populations.

Achondroplasia↗
PubMed1996

Synaptic vesicle recycling in synapsin I knock-out mice.

The synapsins are a family of four neuron-specific phosphoproteins that have been implicated in the regulation of neurotransmitter release. Nevertheless, knock-out mice lacking synapsin Ia and Ib, family members that are major substrates for cAMP and Ca2+/ Calmodulin (CaM)-dependent protein kinases, show limited phenotypic changes when analyzed electrophysiologically (Rosahl, T.W., D. Spillane, M. Missler, J. Herz, D.K. Selig, J.R. Wolff, R.E. Hammer, R.C. Malenka, and T.C. Sudhof. 1995. Nature (Lond.). 375: 488-493; Rosahl, T.W., M. Geppert, D. Spillane, D., J. Herz, R.E. Hammer, R.C. Malenka, and T.C. Sudhof. 1993. Cell. 75:661-670; Li, L., L.S. Chin, O. Shupliakov, L. Brodin, T.S. Sihra, O. Hvalby, V. Jensen, D. Zheng, J.O. McNamara, P. Greengard, and P. Andersen. 1995. Proc. Natl. Acad. Sci. USA. 92:9235-9239; see also Pieribone, V.A., O. Shupliakov, L. Brodin, S. Hilfiker-Rothenfluh, A.J. Czernik, and P. Greengard. 1995. Nature (Lond.). 375:493-497). Here, using the optical tracer FM 1-43, we characterize the details of synaptic vesicle recycling at individual synaptic boutons in hippocampal cell cultures derived from mice lacking synapsin I or wild-type equivalents. These studies show that both the number of vesicles exocytosed during brief action potential trains and the total recycling vesicle pool are significantly reduced in the synapsin I-deficient mice, while the kinetics of endocytosis and synaptic vesicle repriming appear normal.

Animals↗
PubMed1996

Two primitive neuroectodermal tumor cell lines require an activated insulin-like growth factor I receptor for growth in vitro.

OBJECTIVE: To determine the expression of the insulin-like growth factors (IGFs) and the IGF-I receptor in primitive neuroectodermal tumor cell lines and to assess the importance of these proteins in the growth of cell lines in vitro. METHODS: Ribonucleic acid blotting and reverse transcriptase-polymerase chain reaction were used for detection of IGF and IGF-I expression. Ribonucleic acid blotting was used for detection of up-regulation of c-fos in the presence of exogenous growth factor. Immunoprecipitation was used to demonstrate autophosphorylation of the receptor in the presence of exogenous growth factor. Ligand binding analysis was used to determine the binding affinity of the receptor and the number of receptors per cell. Growth of curves in the presence of monoclonal antibody that blocks binding of ligand to receptor was measured to determine the requirement for an activated receptor during growth. RESULTS: Expression of IGF-II was identified in one cell line. No expression of IGF-I was seen in any cell line. Expression of IGF-I receptor was detected in all three cell lines. Immunoprecipitation experiments demonstrated autophosphorylation of the receptor after addition of IGF-I to growing cells. Ligand binding analysis revealed 9.2 x 10(4) and 4 x 10(4) receptors per cell in the Daoy and PFSK cell lines, respectively. Addition of either IGF alone or in combination to serum-starved cells was not able to restore growth of the cell lines. A blocking monoclonal antireceptor antibody decreased growth of Daoy and PFSK cells in a dose-dependent fashion. Complete arrest of growth occurred at 1 microgram/ml antibody in both cell lines. CONCLUSION: The IGF-I receptor is expressed by primitive neuroectodermal tumor cell lines in vitro. An activated receptor is important for cell proliferation in vitro. Additional work will establish the importance of these findings for tumors in vivo.

Antibodies↗
PubMed1996

Anterior tibia spine fracture in children: follow-up evaluation by biomechanical studies.

BACKGROUND: The treatment of anterior tibial spine (ATS) fracture in children is in controversy. Previous studies have shown that most of the children who sustained ATS fractures have objective evidence of the anterior cruciate ligament (ACL) laxity at follow-up, but detailed biomechanical analysis of the knee joint has seldom been performed. METHODS: Eight ATS fractures in children at a mean age of 12 years were treated from 1989 to 1994. Two were of Meyer's classification type I, 3 were of type II, and 3 were of type III. The treatment varied from casting to open reduction & internal fixation (ORIF) by pulling through suture or biofix absorbable screw. Patients were followed with radiological, clinical and biomechanical analysis. KT 1000 knee arthrometer was used to evaluate the laxity of ACL. Cybex isokinetic machine was used to evaluate knee extensor and flexor strength. RESULTS: During an average follow-up period of 47 months, all fractures showed to unite well on X-ray except 1 untreated type I fracture who had malunion. Only one had subjective complaint of instability, but 3 had clinical signs of instability. Objective evidence of laxity, determined by KT-1000 arthrometer, was noted in 4 patients. Decreased muscle strength, determined by Cybex isokinetic machine, was more prominent in hamstrings than in quadriceps. CONCLUSIONS: Patients with milder ATS fracture (type I & II), if treated inappropriately, may still result in ACL laxity and knee muscle strength deficiency. Type III ATS fractures, if treated well by ORIF, tend to recover nearly normal ACL function and muscle strength.

Adolescent↗
PubMed1996

Acute monteggia fractures in children.

BACKGROUND: Monteggia fracture rarely occurs in children. If it occurs, type I fracture is most commonly seen. We study the functional results of nonsurgical management in acute cases. METHODS: From July, 1988 through October, 1994, we encountered 15 cases of acute Monteggia fractures, accounting for 2.3% of forearm fractures. Twelve were males and three were females, at an average age of 7 years and 10 months. Nine fractures occurred on left non-dominant side, six occurred on right dominant side. There were eleven type I (73.3%), no type II, three type III (20%), and one type IV (6.7%) fractures. All of these patients received closed reduction with long arm casting, and the most stable position of fracture was supination of the forearm and flexion of the elbow. RESULTS: After follow-up for an average of 45.9 months, all fractures were found to unite without residual deformity of ulna or dislocation of the radial head. The functional results were excellent. Posterior interosseous nerve palsy occurred in one patient before treatment, and recovered spontaneously. CONCLUSIONS: Unlike adults, children with Monteggia fractures can get excellent results from closed reduction with long arm casting.

Casts, Surgical↗
PubMed1995

Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin I-deficient mice.

Synapsin I, the most abundant of all neuronal phosphoproteins, is enriched in synaptic vesicles. It has been hypothesized to regulate synaptogenesis and neurotransmitter release from adult nerve terminals. The evidence for such roles has been highly suggestive but not compelling. To evaluate the possible involvement of synapsin I in synaptogenesis and in the function of adult synapses, we have generated synapsin I-deficient mice by homologous recombination. We report herein that outgrowth of predendritic neurites and of axons was severely retarded in the hippocampal neurons of embryonic synapsin I mutant mice. Furthermore, synapse formation was significantly delayed in these mutant neurons. These results indicate that synapsin I plays a role in regulation of axonogenesis and synaptogenesis.

Animals↗
PubMed1995

Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice.

Synapsin I has been proposed to be involved in the modulation of neurotransmitter release by controlling the availability of synaptic vesicles for exocytosis. To further understand the role of synapsin I in the function of adult nerve terminals, we studied synapsin I-deficient mice generated by homologous recombination. The organization of synaptic vesicles at presynaptic terminals of synapsin I-deficient mice was markedly altered: densely packed vesicles were only present in a narrow rim at active zones, whereas the majority of vesicles were dispersed throughout the terminal area. This was in contrast to the organized vesicle clusters present in terminals of wild-type animals. Release of glutamate from nerve endings, induced by K+,4-aminopyridine, or a Ca2+ ionophore, was markedly decreased in synapsin I mutant mice. The recovery of synaptic transmission after depletion of neurotransmitter by high-frequency stimulation was greatly delayed. Finally, synapsin I-deficient mice exhibited a strikingly increased response to electrical stimulation, as measured by electrographic and behavioral seizures. These results provide strong support for the hypothesis that synapsin I plays a key role in the regulation of nerve terminal function in mature synapses.

Animals↗
PubMed1995

Neuromuscular injury during limb lengthening: a longitudinal follow-up by rabbit tibial model.

Limb lengthening has been used for many years to correct congenital anomalies and unequal leg length. Some surgeons focus on bone genesis and anatomical alignment, and pay less attention to potential damage to muscles, nerves, and vessels during the gradual stretching. In an attempt to identify the presence and extent of neuromuscular abnormalities during leg elongation, a rabbit tibial osteotomy model was used for 17 male rabbits, and fixation-distraction apparatuses were applied at a rate of 1 mm lengthening per day. Electrophysiological test was used to investigate both hindlegs every 2 weeks for 8 weeks after surgery. Needle electromyography (EMG) showed denervation in the elongated legs with 14 limbs having peroneal nerve damage and 12 limbs having damage to the posterior tibial nerve. Nerve regeneration signs were found in ankle extensors and flexors beginning 2 weeks postoperatively. The results of nerve conduction studies revealed significant differences (P < .05) in CMAP amplitude (mV) and area (mV.mS) in ankle extensors and flexors between elongated and nonelongated legs. There was no significant side-to-side difference with respect to distal latency. The incidence of neuromuscular injury was common in these rabbits. These findings suggest that early detection of neuromuscular involvement by electrophysiological test is a practical way to assess neuromuscular function during limb lengthening.

Animals↗