Biomedical subjects

B Ni

Publications and source records attributed to B Ni.

At least 37 records · Page 2Linked to original sources

PubMed1998

Radiculopathy after laminectomy for cervical compression myelopathy.

Postoperative radiculopathy is a complication of posterior cervical decompression associated with tethering of the nerve root. We reviewed retrospectively 287 consecutive patients with cervical compression myelopathy who had been treated by multilevel cervical laminectomy and identified 37 (12.9%) with postoperative radiculopathy. There were 27 men and ten women with a mean age of 56 years at the time of operation. The diagnosis was either cervical spondylosis (25 patients) or ossification of the posterior longitudinal ligament (12 patients). Radiculopathy was observed from four hours to six days after surgery. The most frequent pattern of paralysis was involvement of the C5 and C6 roots of the motor-dominant type. The mean time for recovery was 5.4 months (two weeks to three years). The results at follow-up showed that the rate of motor recovery was negatively related to the duration of complete recovery of postoperative radiculopathy (gamma=-0.832, p < 0.01) and that patients with spondylotic myelopathy had a significantly better rate of clinical recovery than those with ossification of the posterior longitudinal ligament (t=2.960, p < 0.01). Postoperative radiculopathy may be prevented by carrying out an anterior decompression in conjunction with spinal fusion, which will achieve stabilisation and directly remove compression of the cord at multiple levels.

Adult↗

PubMed1998

Diagnosis and treatment of acute central cervical cord injury.

OBJECTIVE: To clarify the diagnosis and management of acute central cervical cord injury. METHODS: Eighty-nine patients with acute cervical central cord injury were retrospectively reviewed. Sixty-three patients were treated conservatively and 26 were treated surgically. There were two acute deaths. Eighty-seven patients were followed up for 3 months to 15 years. RESULTS: Their average neurological score (ASIA) was increased from 41.7 at admission to 83.1 at follow-up. CONCLUSIONS: Acute central cervical cord injury should be differentiated from complete spinal cord injury, cervical myelopathy, cruciate paralysis and C8 nerve root injury. When compression of nerve tissue or cervical instability is identified, operative intervention should be indicated. The prognosis is less optimistic in the patients with severe primary injury and at old age.

Adult↗

PubMed1998

[Cervical spondylotic myelopathy: early diagnosis and timing of operation].

OBJECTIVES: To study early clinical characteristics and diagnosis of cervical spondylotic myelopathy and to search the timing of surgery. METHOD: Seventy-four cases of early diagnosed cervical spondylotic myelopathy (CSM) were treated with anterior cervical decompression and autologous ilium graft fusion. RESULT: The early stage of CSM was indistinct, and symptoms were mild. Neck pain, abnormality of motion and sensation of limbs, and hand and arm symptoms were shown frequently. Changes in neurological function could found during physical examination. Characteristic changes in imaging were helpful in early diagnosis of the disease. CONCLUSION: Early diagnosis and surgery of CSM are important in improving the therapeutic results.

Adult↗

PubMed1998

[Clinical significance of early diagnosis of cervical spondylotic myelopathy].

OBJECTIVE: To probe into the possibility of early diagnosis of cervical spondylotic myelopathy (CSM) prospectively and to screen the premorbid signs of CSM clinically, radiologically and electro-physiologically. METHOD: Twenty-nine items related to the occurring of CSM were chosen as common characteristics of CSM and considered as the criteria of prospective study. 81 patients who met the criteria were studied. All patients were followed up and observed for 2 - 6.5 years (mean 3.7 years). RESULT: Twenty-nine patients showed CSM during investigation. Thirteen items of the criteria were related to the occurring of CSM. The significant items include upper limb pain and abnormal sensation limb numbness, positive dynamic Hoffmann's sign, cervical canal stenosis, lower cervical instability, cervical intervertebral disc herniation, and delay of central motor conduct time. CONCLUSION: CSM can be early diagnosed. The patients who meet the established criteria should be followed up and observed closely. Early operation results in good effect.

Adult↗

PubMed1997

Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granule neurons.

Neurotoxicity induced by overstimulation of N-methyl-D-aspartate (NMDA) receptors is due, in part, to a sustained rise in intracellular Ca2+; however, little is known about the ensuing intracellular events that ultimately result in cell death. Here we show that overstimulation of NMDA receptors by relatively low concentrations of glutamate induces apoptosis of cultured cerebellar granule neurons (CGNs) and that CGNs do not require new RNA or protein synthesis. Glutamate-induced apoptosis of CGNs is, however, associated with a concentration- and time-dependent activation of the interleukin 1beta-converting enzyme (ICE)/CED-3-related protease, CPP32/Yama/apopain (now designated caspase 3). Further, the time course of caspase 3 activation after glutamate exposure of CGNs parallels the development of apoptosis. Moreover, glutamate-induced apoptosis of CGNs is almost completely blocked by the selective cell permeable tetrapeptide inhibitor of caspase 3, Ac-DEVD-CHO but not by the ICE (caspase 1) inhibitor, Ac-YVAD-CHO. Western blots of cytosolic extracts from glutamate-exposed CGNs reveal both cleavage of the caspase 3 substrate, poly(ADP-ribose) polymerase, as well as proteolytic processing of pro-caspase 3 to active subunits. Our data demonstrate that glutamate-induced apoptosis of CGNs is mediated by a posttranslational activation of the ICE/CED-3-related cysteine protease caspase 3.

Animals↗

PubMed1997

Inorganic phosphate enhances phosphonucleotide concentrations in cultured fetal rat cortical neurons.

Our laboratory has recently characterized saturable Na(+)-dependent P(i) import into cultured fetal rat cortical neurons and shown that a substantial fraction of the P(i) so accumulated is incorporated into ATP. We now report that the ATP, NADPH and intracellular free P(i) ([P(i)]i) concentrations of cultured fetal rat cortical neurons are dependent on the extracellular P(i) concentration ([P(i)]e). [ATP], [NADPH] and [P(i)]i display a hyperbolic dependence upon [P(i)]e, being significantly increased after incubation with [P(i)]e of > or = 10 microM, and maximal at > or = 500 microM. Increases in both [ATP] and [NADPH] are abolished in the absence of glucose. In the absence of extracellular P(i), both [ATP] and [P(i)]i decline over time. Our data suggest that in cultured fetal rat cortical neurons [P(i)]e has a direct effect on glucose utilization, stimulating both ATP and NADPH synthesis via glycolysis and the pentose phosphate pathway.

Adenine Nucleotides↗

PubMed1997

Cloning and expression of a rat brain interleukin-1beta-converting enzyme (ICE)-related protease (IRP) and its possible role in apoptosis of cultured cerebellar granule neurons.

Several members of the IL-1beta-converting enzyme (ICE) family of proteases recently have been implicated in the intracellular cascade mediating the apoptotic death of various cell types. It is unclear, however, whether ICE-related proteases are involved in apoptosis of mammalian neurons and, if so, how they are activated. Here we report the cloning of an ICE-related protease (IRP) from rat brain, which displays strong sequence identity to human CPP32. In situ hybridization histochemistry reveals that this IRP mRNA is expressed in neuron-enriched regions of the developing and adult rat brain but is profoundly downregulated in the adult (compared with developing) brain. To investigate whether this IRP is involved in the death of neurons in the developing brain, we studied IRP expression in cultured cerebellar granule neurons. In cultured cerebellar granule neurons, reduction of extracellular K+ reliably induces apoptosis and stimulates overexpression of IRP mRNA. The latter is especially prominent 4 hr after switching from high K+ to low K+ medium. The expression of IRP mRNA was maintained at this level for at least 8 hr and was followed by apoptotic death of these neurons. Induction of IRP mRNA and cell death are blocked completely by adding depolarizing concentrations of K+ </=90 min after switching to low K+ medium (i.e., before the commitment point for apoptosis) and partially blocked by brain-derived neurotrophic factor (BDNF), which also partially rescues granule neurons from low K+-induced apoptosis. In addition, overexpression of IRP cDNA in HeLa cells results in cell death accompanied by strong internucleosomal cleavage of DNA, a typical feature of apoptosis. Finally, we detected cleavage of the putative death substrate poly (ADP-ribose) polymerase (PARP), beginning 8 hr after changing from high K+ to low K+ medium, coinciding with the time course of induced expression of the IRP gene. Our data suggest that transcriptional activation of IRP could be one of the mechanisms involved in the apoptotic death of cerebellar granule neurons.

Amino Acid Sequence↗

PubMed1997

Effects of direct current on dog liver: possible mechanisms for tumor electrochemical treatment.

Mechanisms of tumor electrochemical treatment (ECT) were studied using normal dog liver. Five physical and chemical methods were used. Two platinum electrodes were inserted into an anesthetized dog's liver at 3 cm separation. A voltage of 8.5 V direct current (DC) at an average current of 30 mA was applied for 69 min; total charge was 124 coulombs. Concentrations of selected ions near the anode and cathode were measured. The concentrations of Na+ and K+ ions were higher around the cathode, whereas the concentration of Cl- ions was higher around the anode. Water contents and pH were determined near the anode and the cathode at the midpoint between the two electrodes and in an untreated area away from the electrodes. Hydration occurred around the cathode, and dehydration occurred around the anode. The pH values were 2.1 near the anode and 12.9 near the cathode. Spectrophotometric scans of the liver sample extract were obtained, and the released gases were identified by gas chromatography as chlorine at the anode and hydrogen at the cathode. These results indicate that a series of electrochemical reactions take place during ECT. The cell metabolism and its environment are severely disturbed. Both normal and tumor cells are rapidly and completely destroyed in this altered environment. We believe that the above reactions are the ECT mechanisms for treating tumors.

Animals↗

PubMed1997

Selective loss of neuronal Na+-dependent phosphate cotransporter mRNA in CA1 pyramidal neuron following global ischemia.

A recently identified neuronal Na+-dependent phosphate cotransporter (rBNPI) has been shown to import inorganic phosphate (P(i)) required for the production of high-energy phosphates which are vital to neuronal energy metabolism. In the present study, we have examined the expression of rBNPI mRNA in the hippocampus of rats subjected to 30 min of global ischemia by four-vessel occlusion. In situ hybridization reveals that transient forebrain ischemia results in a selective reduction in rBNPI mRNA expression in CA1 pyramidal neurons of the hippocampus. Expression of rBNPI is significantly reduced by 24 h and completely absent at 72 h following global ischemia when CA1 pyramidal neurons begin to show cell damage. By contrast, there is no change in the expression of Nedd2 mRNA, a developmentally regulated cell death gene, in CA1 pyramidal neurons at these same time points. The loss of rBNPI transcripts appears to be selective for CA1 pyramidal neurons since rBNPI mRNA expression is unchanged in neurons of the CA2-CA4 pyramidal cell layers following global ischemia. Our data indicate that an early reduction of rBNPI transcripts may contribute to a reduction in P(i)-dependent energy metabolism or signal transduction which has been reported in CA1 hippocampal neurons following global ischemia.

Animals↗

PubMed1997

alpha2-Macroglobulin as a beta-amyloid peptide-binding plasma protein.

The beta-amyloid peptide (A beta) is a normal proteolytic processing product of the amyloid precursor protein, which is constitutively expressed by many, if not most, cells. For reasons that are still unclear, A beta is deposited in an aggregated fibrillar form in both diffuse and senile plaques in the brains of patients with Alzheimer's disease (AD). The factor(s) responsible for the clearance of soluble A beta from biological fluids or tissues are poorly understood. We now report that human alpha2-macroglobulin (alpha2M), a major circulating endoproteinase inhibitor, which has recently been shown to be present in senile plaques in AD, binds 125I-A beta(1-42) with high affinity (apparent dissociation constant of 3.8 x 10(-10) M). Approximately 1 mol of A beta is bound per mole of alpha2M. Both native and methylamine-activated alpha2M bind 125I-A beta(1-42). The binding of 125I-A beta(1-42) to alpha2M is enhanced by micromolar concentrations of Zn2+ (but not Ca2+) and is inhibited by noniodinated A beta(1-42) and A beta(1-40) but not by the reverse peptide A beta(40-1) or the cytokines interleukin 1beta or interleukin 2. alpha1-Antichymotrypsin, another plaque-associated protein, inhibits both the binding of 125I-A beta(1-42) to alpha2M as well as the degradation of 125I-A beta(1-42) by proteinase-activated alpha2M. Moreover, the binding of 125I-A beta(1-42) to alpha2M protects the peptide from proteolysis by exogenous trypsin. These data suggest that alpha2M may function as a carrier protein for A beta and could serve to either facilitate or impede clearance of A beta from tissues such as the brain.

Amyloid beta-Peptides↗

PubMed1996

Lumbar disc herniation in patients with developmental spinal stenosis.

Lumbar spinal stenosis and lumbar disc herniation are usually regarded as two pathogenetically different conditions, but in the literature lumbar disc herniation in patients with developmental spinal stenosis has been rarely documented. In a clinical retrospective study, 42 lumbar disc herniations with developmental spinal stenosis were reported and analyzed. Discectomy was performed after laminotomy. The patients were followed-up for an average of 4.4 years (range 2-7 years). The preoperative symptoms disappeared completely in 28 patients, in 13 patients some degree of backache remained although their nerve root pain had been relieved, and in 1 patient intermittent claudication reappeared after 6 years resolution of their preoperative pain. We conclude that when developmental spinal stenosis is combined with disc herniation, discectomy through laminotomy rather than laminectomy is usually sufficient for decompression.

Adult↗

PubMed1996

Molecular cloning, expression, and chromosomal localization of a human brain-specific Na(+)-dependent inorganic phosphate cotransporter.

We describe the molecular cloning of a cDNA encoding a human brain Na(+)-dependent inorganic phosphate (P(i)) cotransporter (hBNPI). The nucleotide and deduced amino acid sequences of hBNPI reveal a protein of 560 amino acids with six to eight putative transmembrane segments. hBNPI shares a high degree of homology with other Na(+)-dependent inorganic P(i) cotransporters, including those found in rat brain and human and rabbit kidney. Expression of hBNPI in COS-1 cells results in Na(+)-dependent P(i) uptake. Northern blot analysis demonstrates that hBNPI mRNA is expressed predominantly in brain and most abundantly in neuron-enriched regions such as the amygdala and hippocampus. Moderate levels of expression are also observed in glia-enriched areas such as the corpus callosum, and low levels are observed in the substantia nigra, subthalamic nuclei, and thalamus. In situ hybridization histochemistry reveals relatively high levels of hBNPI mRNA in pyramidal neurons of the cerebral cortex and hippocampus and in granule neurons of dentate gyrus. The level of hBNPI mRNA is quite low in fetal compared with adult human brain, suggesting developmental regulation of hBNPI gene expression. Southern analyses of nine eukaryotic genomic DNAs probed under stringent conditions with hBNPI cDNA revealed that the hBNPI gene is highly conserved during vertebrate evolution and that each gene is most likely present as a single copy. Using fluorescent in situ hybridization, we localized hBNPI to the long arm of chromosome 19 (19q13) in close proximity to the late-onset familial Alzheimer's disease locus.

Animals↗

PubMed1995

Purification and binding properties of the Mal63p activator of Saccharomyces cerevisiae.

Mal63p is a transcriptional activator for maltose fermentation in Saccharomyces cerevisiae. We have purified it to homogeneity from a yeast strain in which the MAL63 gene is under the control of the GAL1-GAL10 promoter. Purification included fractionation of a whole-cell extract by ion-exchange chromatography, chromatography using both non-specific DNA-affinity (calf thymus), and sequence-specific DNA-affinity chromatography. Mal63p activity was assayed by its binding to a fragment of the MAL61-MAL62 promoter, using both filter-binding and electrophoretic-mobility shift assays. DNase-I footprinting identified a new binding site (site 3) between the two previously known sites (sites 1 and 2). Mal63p is a dimer, and methylation-protection experiments identify the recognition motif as: c/a GC N9 c/a GC/g.

Base Sequence↗

PubMed1995

Heterologous expression systems for P-glycoprotein: E. coli, yeast, and baculovirus.

Chemotherapy, though it remains one of the front-line weapons used to treat human cancer, is often ineffective due to drug resistance mechanisms manifest in tumor cells. One common pattern of drug resistance, characterized by simultaneous resistance to multiple amphipathic, but otherwise structurally dissimilar anticancer drugs, is termed multidrug resistance. Multidrug resistance in various model systems, covering the phylogenetic range from bacteria to man, can be conferred by mammalian P-glycoproteins (PGPs), often termed multidrug transporters. PGPs are 170-kD polytopic membrane proteins, predicted to consist of two homologous halves, each with six membrane spanning regions and one ATP binding site. They are members of the ATP-binding cassette (ABC) superfamily of transporters, and are known to function biochemically as energy-dependent drug efflux pumps. However, much remains to be learned about PGP structure-function relationships, membrane topology, posttranslational regulation, and bioenergetics of drug transport. Much of the recent progress in the study of the human and mouse PGPs has come from heterologous expression systems which offer the benefits of ease of genetic selection and manipulation, and/or short generation times of the organism in which PGPs are expressed, and/or high-level expression of recombinant PGP. Here we review recent studies of PGP in E. coli, baculovirus, and yeast systems and evaluate their utility for the study of PGPs, as well as other higher eukaryotic membrane proteins.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Characterization of Na(+)-dependent phosphate uptake in cultured fetal rat cortical neurons.

Our laboratory has recently cloned and expressed a brain- and neuron-specific Na(+)-dependent inorganic phosphate (P(i)) cotransporter that is constitutively expressed in neurons of the rat cerebral cortex, hippocampus, and cerebellum. We have now characterized Na(+)-dependent 32Pi cotransport in cultured fetal rat cortical neurons, where > 90% of saturable P(i) uptake is Na(+)-dependent. Saturable, Na(+)-dependent 32Pi uptake was first observed in primary cultures of cortical neurons at 7 days in vitro (DIV) and was maximal at 12 DIV. Na(+)-dependent P(i) transport was optimal at physiological temperature (37 degrees C) and pH (7.0-7.5), with apparent Km values for P(i) and Na+ cf 54 +/- 12.7 microM and 35 +/- 4.2 mM, respectively. A reduction in extracellular Ca2+ markedly reduced (> 60%) Na(+)-dependent P(i) uptake, with a threshold for maximal P(i) import of 1-2.5 mM CaCl2. Primary cultures of fetal cortical neurons incubated in medium where equimolar concentrations of choline were substituted for Na+ had lower levels of ATP and ADP and higher levels of AMP than did those incubated in the presence of Na+. Furthermore, a substantial fraction of the 32Pi cotransported with Na+ was concentrated in the adenine nucleotides. Inhibitors of oxidative metabolism, such as rotenone, oligomycin, or dinitrophenol, dramatically decreased Na(+)-dependent P(i) import rates. These data establish the presence of a Na(+)-dependent P(i) cotransport system in neurons of the CNS, demonstrate the Ca(2+)-dependent nature of 32Pi uptake, and suggest that the neuronal Na(+)-dependent P(i) cotransporter may import P(i) required for the production of high-energy compounds vital to neuronal metabolism.

Adenosine Triphosphate↗

PubMed1995

[An ultrastructural study on resting cyst of Euplotes encysticus].

For resting cysts of Euplotes encysticus, in their various ciliatures, most of the ciliary shafts above the cilia kinetosomes are degenerated, or preserve their kinetosomes only. Sometimes, kinetosomes of certain frontal and ventral cirri are also disintegrated and disappeared. For remaining cilia, on their shafts, peripheral doublet microtubule (MT) and central pair of MTs still possess their structural pattern of "9 + 2". In few ciliary shafts, the phenomena of 2 sets of "9 + 2" structures surrounded by a common sheath can also be seen. At the center of kinetosomal peripheral triplets (triplet MTs), aggregates of MT-like structures are formed. For kinetosomal accessory structures, only residues of inter-kinetosomal connections and ciliature brackets can be seen. No MT layers can be seen under the pellicles of non-ciliated cortex. At the ciliated cortex, there are peripheral MT layers (corresponding to sub-pellicular MT layers) within the ciliature cavity, MT ribbons at (and near) the deeper parts of ciliature, and scattered MT groups. Besides, various shapes of ciliary shafts structures are seen within cortical vesicles of ciliated regions. Nuclear pores of macronucleus enlarged apparently, reduced in number, and, chromatin attached on the inner membrane of these nuclear pores.

Animals↗

PubMed1995

Regional expression and cellular localization of the Na(+)-dependent inorganic phosphate cotransporter of rat brain.

We have recently isolated and identified a brain specific Na(+)-dependent inorganic phosphate (Pi) cotransporter cDNA (rBNPI) from a rat brain cDNA library (Ni, et al., 1994). We now report the regional and developmental expression, as well as the cellular localization, of rBNPI mRNA in the rat brain. In situ hybridization histochemistry reveals that rBNPI mRNA is selectively expressed in neuron-enriched regions of the adult rat brain, such as the cerebral cortex, hippocampus, and cerebellum. Cellular localization of rBNPI transcripts reveals expression in both pyramidal and granule neurons in these regions. By contrast, little to no hybridization signal was observed in white matter-enriched areas such as the corpus callosum. The expression of rBNPI mRNA was determined during pre- and postnatal development of the rat CNS. From embryonic day 17 to early postnatal day 10 (PND 10), there is a rather widespread but diffuse pattern of rBNPI expression in brain. During late postnatal development, however, the expression of rBNPI mRNA becomes confined to discrete populations of neurons in the cerebral cortex, hippocampus, and cerebellum. Thus, rBNPI expression is developmentally regulated and abundant levels of mRNA are found in rather discrete populations of neurons in the adult rat brain. The latter suggests that rBNPI may serve to selectively regulate intracellular Pi transport in certain neurons for either metabolic and (or) signaling events.

Aging↗

PubMed1994

Depolarization or glutamate receptor activation blocks apoptotic cell death of cultured cerebellar granule neurons.

Cerebellar granule neurons can be readily maintained in culture if depolarized with high concentrations of K+ or subtoxic concentrations of various excitatory amino acids. We now report that these depolarizing stimuli promote cerebellar granule neuron survival by blocking their programmed death via apoptosis. Cerebellar granule neurons maintained in depolarizing conditions and then changed to non-depolarizing conditions, exhibit the morphological and biochemical features of apoptosis, including cytoplasmic blebbing, condensation and aggregation of nuclear chromatin and internucleosomal DNA fragmentation. Inhibitors of RNA or protein synthesis greatly attenuate cell death induced by non-depolarizing culture conditions. In contrast, cerebellar granule neurons, when exposed to fresh serum-containing medium or to high concentrations of glutamate, exhibit a delayed-type of neurotoxicity which is non-apoptotic in nature. Given the actions of excitatory amino acid receptor agonists in preventing apoptosis of cultured cerebellar granule neurons, we hypothesize that the functional innervation of postmigratory granule neurons during cerebellar development may prevent further elimination of these neurons by blocking their programmed death.

6-Cyano-7-nitroquinoxaline-2,3-dione↗