Biomedical subjects

K Hsu

Publications and source records attributed to K Hsu.

At least 37 records · Page 2Linked to original sources

PubMed1996

Fenestration in the myelin sheath of nerve fibers of the shrimp: a novel node of excitation for saltatory conduction.

Giant nerve fibers of the shrimp family Penaeidae conduct impulses at the velocity highest among all animal species (approximately 210 m/s; highest in mammals = 120 m/s). We examined these giant and other small nerve fibers morphologically using a differential interference contrast microscope as well as an electron microscope, and found a very specialized form of excitable membrane that functions as a node for saltatory conduction of the impulse. This node appeared under the light microscope as a characteristic pattern of concentrically aligned rings in a very small spot of the myelin sheath. The diameter of the innermost ring of the node was about 5 microns, and the distance between these nodes was as long as 12 mm. Via an electron microscope, these nodes were characterized by a complete lack of the myelin sheath, forming a fenestration that has a tight junction with an axonal membrane. Voltage clamp measurements by a sucrose gap technique demonstrated that the axonal membrane at these fenestration nodes is exclusively excitable and that the large submyelinic space is a unique conductive pathway for loop currents for saltatory conduction through such fenestration nodes.

Animals↗

PubMed1996

Neuropharmacological characterization of local ibogaine effects on dopamine release.

Local perfusion with ibogaine (10(-6) M-10(-3) M) via microdialysis probes in the nucleus accumbens or striatum of rats produced a biphasic dose-response effect on extracellular dopamine levels. Lower doses (10(-6) M-10(-4) M) produced a decrease while higher doses (5 x 10(-4) M-10(-3) M) produced an increase in dopamine levels. Dihydroxyphenylacetic acid (DOPAC) levels were not effected. Naloxone (10(-6) M) and norbinaltorphimine (10(-6) M-10(-5) M) did not affect dopamine levels, but when co-administered with ibogaine (10(-4) M) blocked the decrease in dopamine levels produced by ibogaine. Ibogaine (10(-3) M) stimulation of dopamine levels in the striatum was calcium independent and not blocked by tetrodotoxin (10(-5) M). Pretreatment with cocaine (15 mg/kg), reserpine (5 mg/kg) or alpha-methyl-para-tyrosine (250 mg/kg) given intraperitoneally significantly reduced ibogaine (10(-3)M) stimulation of striatal dopamine levels. In striatal synaptosomes, both ibogaine and harmaline (10(-7)-10(-4) M) produced dose-dependent inhibition of [3H]-dopamine uptake. These findings suggest that ibogaine has both inhibitory and stimulatory effects on dopamine release at the level of the nerve terminal. It is suggested that the inhibitory effect is mediated by kappa opiate receptors while the stimulatory effect is mediated by interaction with the dopamine uptake transporter.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

Pulmonary edema induced by phorbol myristate acetate is attenuated by compounds that increase intracellular cAMP.

We have investigated the effect of terbutaline, aminophylline and dibutyryl cyclic AMP (DBcAMP) on phorbol myristate acetate (PMA)-induced acute lung injury in isolated, blood-perfused rabbit lungs. Pulmonary arterial pressure and lung weight were measured for 30 min after a bolus injection of PMA (10 mu g/kg). In the group exposed to PMA alone, the mean pulmonary arterial pressure (PAP) increased from 16.33 + or - 1.28 to 77.30 + or - 6.40 mmHg (P <0.001), and lung weight increased by 70.69 + or - 10.94 g during the 30 min after PMA challenge (P<0.001). Pretreatment with terbutaline, aminophylline or DBcAMP prevented the increases in both PAP and lung weight (P <0.001). Each of the three drugs also prevented the increase in pulmonary vascular permeability induced by PMA: terbutaline, aminophylline, and DBcAMP all significantly reduced the pulmonary capillary filtration coefficient (KfC) as well as the albumin concentration in the lung lavage fluid after PMA exposure. Post-treatment with terbutaline 5 min after PMA administration also had a protective effect. The mechanisms responsible for these protectivp3 effects may all involve an increase in intracellular cAMP, since all three drugs increase cAMP in the lung (though by different mechanisms). Our data further indicate that the inhibition of tumor necrosis factor production may likewise play an important role in the protective effect exerted by these drugs.

Adrenergic beta-Agonists↗

PubMed1996

Two neurotoxins (BmK I and BmK II) from the venom of the scorpion Buthus martensi Karsch: purification, amino acid sequences and assessment of specific activity.

Two neurotoxins, BmK I and BmK II, were purified from the venom of the Chinese scorpion Buthus martensi Karsch. The complete amino acid sequences of both toxins, each containing 64 amino acid residues, were determined by the automatic sequencing of reduced and S-carboxymethylated toxins and their peptides, obtained after cleavage with TPCK-treated trypsin and Staphylococcus aureus V8 protease, respectively. Toxicity as minimum lethal dose tested by i.c.v. injection in mice showed that BmK I was six times more potent than BmK II. Only two amino acid replacements were found: at position 59 Val in BmK I was replaced by Ile in BmK II, and at position 62 a basic Lys residue in BmK I was substituted by a neutral Asn residue in BmK II. These features suggest that the positively charged residue (Lys or Arg) in the C-terminal position 62 (or 61 or 63) may also play an important role in facilitating the interaction between scorpion neurotoxins and the receptor on sodium channels. The effects of BmK I on nerve excitability were examined with the crayfish axon using intracellular recording and voltage-clamp conditions. The results indicate that BmK I preferentially blocks the sodium channel inactivation process. Thus, functional and structural similarities suggest that BmK I and BmK II belong to group 3 of scorpion alpha-type toxins.

Amino Acid Sequence↗

PubMed1996

Depression and academic impairment in college students.

Impairment from depression and its impact on productivity are of profound societal importance. We report the results of an evaluation of depression and academic impairment in university students, using standardized measures. Sixty-three students completed the Beck Depression Inventory and the work role section from the Social Adjustment Scale-Self Report. Academic impairment, manifested as missed time from class, decreased academic productivity, and significant interpersonal problems at school, was seen in 92% of the students. More severe depression was related to a higher level of impairment. At all levels of depression, affective impairment-inadequacy, distress, and disinterest in school-was more prevalent than was academic impairment. The risk of academic impairment became likely at only moderate-to-severe levels of depression. Discussing the implications of depression with students and aggressively pursuing both medication and nonmedication therapies are essential in preventing the high morbidity associated with untreated depression.

Achievement↗

PubMed1996

Evidence for the involvement of phospholipase A2 mechanisms in the development of stimulant sensitization.

Evidence suggests that phospholipase A2 (PLA2) activation is involved in numerous neuroplastic phenomena, including long-term potentiation. Considering the pharmacological similarities between long-term potentiation and stimulant sensitization, it seems possible that PLA2 inhibition activity also might have a role in the induction of stimulant sensitization. In this study, we have investigated whether PLA2 inhibition, by quinacrine, has any effects on stimulant-induced behavioral sensitization. Both locomotor and stereotypic behavioral sensitization were dose-dependently blocked in rats pretreated with quinacrine (8-25 mg/kg i.p.) 15 min before cocaine (30 mg/kg i.p.), when tested with cocaine (15 mg/kg i.p) 72 hr later. Similar results also were found with d-amphetamine (2 mg/kg i.p.) sensitization using a 10-day treatment regimen with testing on day 11. The ability of PLA2 activation, by melittin, to produce cocaine sensitization also was tested. Local injections of melittin (0.1 microgram/0.4 microliter) into the ventral tegmental area sensitized the subsequent stimulation of locomotor activity, stereotypy and nucleus accumbens dopamine release by cocaine, when tested 72 hr later. Local injections of melittin (0.1-1.0 microgram/0.8 microliter) into the nucleus accumbens had a moderate sensitizing effect on locomotion. Quinacrine (16 mg/kg) pretreatment 45 min before intraventral tegmental area melittin injection significantly decreased melittin-induced sensitization of the locomotor and stereotypy response to cocaine. These results indicate that PLA2 activation may play a role in the induction of stimulant sensitization. It is proposed that PLA2 activity in mesolimbic dopamine neurons, at the level of the cell bodies and perhaps the nerve terminals, is involved in the biochemical mechanisms mediating the development of stimulant sensitization.

Animals↗

PubMed1996

Carcinosarcoma of the renal pelvis: a case report with immunohistochemical study.

The clinicopathologic feature of one carcinosarcoma of the renal pelvis is reported. The tumor occurred in a 51-year-old woman with a long standing history of renal calculi. The epithelial component was consistent with squamous cell carcinoma, whereas the sarcomatous component was composed of pleomorphic spindle cells. The immunohistochemical studies demonstrated obvious epithelial and mesenchymal reactivity respectively. The tumor progressed rapidly with widespread metastases and the patient died one month after operation.

Carcinosarcoma↗

PubMed1995

Pentoxifylline attenuates acute lung injury induced by microemboli.

Pentoxifylline (PTX), a methylxanthine derivative, effectively prevents acute lung injury in different animal models. To investigate whether PTX would attenuate acute lung injury induced by microemboli resulting from treatment with calcium chloride (CaCl2) suspension, an isolated blood-perfused rat lung model was used. Pretreatment with PTX prevented the increase in pulmonary arterial pressure (PAP), lung weight gain and protein concentration in the lavage fluid after CaCl2 treatment.

Acute Disease↗

PubMed1995

Human signal recognition particle (SRP) Alu-associated protein also binds Alu interspersed repeat sequence RNAs. Characterization of human SRP9.

Nearly 1 million interspersed Alu elements reside in the human genome. Alu retrotransposition is presumably mediated by full-length Alu transcripts synthesized by RNA polymerase III, while some polymerase III-synthesized Alu transcripts undergo 3'-processing and accumulate as small cytoplasmic (sc) RNAs of unknown function. Interspersed Alu sequences also reside in the untranslated regions of some mRNAs. The Alu sequence is related to a portion of the 7SL RNA component of signal recognition particle (SRP). This region of 7SL RNA together with 9- and 14-kDa polypeptides (SRP9/14) regulates translational elongation of ribosomes engaged by SRP. Here we characterize human (h) SRP9 and show that it, together with hSRP14 (SRP9/14), forms the activity previously identified as Alu RNA-binding protein (RBP). The primate-specific C-terminal tail of hSRP14 does not appreciably affect binding to scAlu RNA. Kd values for three Alu-homologous scRNAs were determined using Alu RBP (SRP9/14) purified from HeLa cells. The Alu region of 7SL, scAlu, and scB1 RNAs exhibited Kd values of 203 pM, 318 pM, and 1.8 nM, respectively. Finally, Alu RBP can bind with high affinity to synthetic mRNAs that contain interspersed Alus in their untranslated regions.

Amino Acid Sequence↗

PubMed1995

Measurement of nitric oxide release in the isolated perfused rat lung.

In this study we have continuously measured real-time production of nitric oxide (NO) in the isolated, perfused rat lung by using an NO monitor (model NO-501, Inter Medical Co., Nagoya, Japan) with an NO-selective resin microsensor. A stable NO response was obtained when the sensor was placed in the pulmonary artery or the pulmonary vein; in contrast, the tracings obtained from the lung periphery were unstable. Furthermore, the NO release was higher when the isolated lungs were perfused with physiological salt solution rather than whole blood perfusion. Changes in NO production were also monitored in acute hypoxia and reoxygenation. Pretreatment with endotoxin (10 mg/kg) potentiated the NO release observed, and this effect of endotoxin was further potentiated by arginine (1 x 10(-4) M) and acetylcholine (1 x 10(-5) M) and countered by the NO synthase inhibitor, L-NG-nitro-arginine methyl ester (L-NAME; 1 x 10(-3) M).

Animals↗

PubMed1995

Protective effect of mepacrine on hypoxia-reoxygenation-induced acute lung injury in rats.

Mepacrine, a cell membrane stabilizer and inhibitor of phospholipase A2 (PLA2), exerts a protective effect on ischemia-reperfusion injury in heart; however, its effect in lungs has not been examined. This study aimed to determine whether mepacrine pretreatment attenuates ischemia-reperfusion lung injury simulated by hypoxia reoxygenation and to identify possible mechanisms for such protection. Acute lung injury was induced in Sprague-Dawley rats by ventilation with 5% CO2-95% N2 and 5% CO2-95% air. Pretreatment with 0.06 mM mepacrine significantly attenuated the acute lung injury. Capillary filtration coefficient, lung weight gain, and protein concentration of lung lavage fluid were significantly lower in mepacrine-treated rats than in rats exposed to hypoxia reoxygenation alone. Steroid dexamethasone, another potential PLA2 inhibitor, had almost no protective effect. Mepacrine but not dexamethasone caused dose-dependent attenuation of the increase in leukocyte chemiluminescence produced by exposure to phorbol myristate acetate. Mepacrine also dose-dependently inhibited production of tumor necrosis factor-alpha (TNF-alpha) by human monocytes; dexamethasone was much less effective in decreasing TNF-alpha production. We conclude that mepacrine but not dexamethasone can significantly attenuate a hypoxia-reoxygenation-induced injury of the lung. This protective effect of mepacrine may not be the result of its inhibition of PLA2 but rather of its downregulation of oxygen radical production by circulating or resident leukocytes or its attenuation of TNF-alpha production by macrophages.

Animals↗

PubMed1994

A human Alu RNA-binding protein whose expression is associated with accumulation of small cytoplasmic Alu RNA.

Human Alu sequences are short interspersed DNA elements which have been greatly amplified by retrotransposition. Although initially derived from the 7SL RNA component of signal recognition particle (SRP), the Alu sequence has evolved into a dominant transposon while retaining a specific secondary structure found in 7SL RNA. We previously characterized a set of Alu sequences which are expressed as small cytoplasmic RNAs and isolated a protein that binds to these transcripts. Here we report that biochemical purification of this protein revealed it as the human homolog of the SRP 14 polypeptide which binds the Alu-homologous region of 7SL RNA. The human cDNA predicts an alanine-rich C-terminal tail translated from a trinucleotide repeat not found in the rodent homolog, which accounts for why the human protein-RNA complex migrates more slowly than its rodent counterpart in RNA mobility shift assays. The human Alu RNA-binding protein (RBP) is expressed after transfection of this cDNA into mouse cells. Expression of human RBP in rodent x human somatic cell hybrids is associated with substantial increase in endogenous small cytoplasmic Alu and scB1 transcripts but not other small RNAs. These studies provide evidence that this RBP associates with Alu transcripts in vivo and affects their metabolism and suggests a role for Alu transcripts in translation in an SRP-like manner. Analysis of hybrid lines indicated that the Alu RBP gene maps to human chromosome 15q22, which was confirmed by Southern blotting. The possibility that the primate-specific structure of this protein may have contributed to Alu evolution is considered.

Amino Acid Sequence↗

PubMed1994

Ischemia-reperfusion lung injury attenuated by ATP-MgCl2 in rats.

The protective effect of ATP-MgCl2 on ischemia-reperfusion lung injury has been reported in kidney, liver, heart, and muscle but has not been examined in lungs. The aim of this study was to determine whether ATP or ATP-MgCl2 pretreatment would attenuate ischemia-reperfusion-induced acute lung injury and to identify the possible mechanisms for such protection. Typical acute lung injury was successfully induced in Sprague-Dawley rats by 10 min of hypoxia followed by 75 min of ischemia and 50 min of reperfusion. Pretreatment with ATP-MgCl2 (or adenosine) but not ATP or MgCl2 (all at 10(-6) M) significantly attenuated the acute lung injury. All the protective effects of ATP-MgCl2 were nearly undetectable when promazine (an ecto-adenosinetriphosphatase inhibitor) or 3,7-dimethyl-1-propargylxanthine (an A2-receptor antagonist) was added before ATP-MgCl2 pretreatment. These observations support our hypothesis that the protective effect of ATP-MgCl2 is in part mediated through adenosine, the degradation product of ATP, which is produced by the Mg(2+)-dependent ecto-adenosinetriphosphatase on the surface of neutrophils and reacts with neutrophil A2 receptors to inhibit the production of O2 radicals.

Adenosine Triphosphate↗

PubMed1993

Multiple dispersed loci produce small cytoplasmic Alu RNA.

Alu repeats are short interspersed elements (SINEs) of dimeric structure whose transposition sometimes leads to heritable disorders in humans. Human cells contain a poly(A)- small cytoplasmic transcript of -120 nucleotides (nt) homologous to the left Alu monomer. Although its monomeric size indicates that small cytoplasmic Alu (scAlu) RNA is not an intermediary of human Alu transpositions, a less abundant poly(A)-containing Alu transcript of dimeric size and specificity expected of a transposition intermediary is also detectable in HeLa cells (A. G. Matera, U. Hellmann, M. F. Hintz, and C. W. Schmid, Mol. Cell. Biol. 10:5424-5432, 1990). Although its function is unknown, the accumulation of Alu RNA and its ability to interact with a conserved protein suggest a role in cell biology (D.-Y. Chang and R. J. Maraia, J. Biol. Chem. 268:6423-28, 1993). The relationship between the -120- and -300-nt Alu transcripts had not been determined. However, a B1 SINE produces scB1 RNA by posttranscriptional processing, suggesting a similar pathway for scAlu. An Alu SINE which recently transposed into the neurofibromatosis 1 locus was expressed in microinjected frog oocytes. This neurofibromatosis 1 Alu produced a primary transcript followed by the appearance of the scAlu species. 3' processing of a synthetic -300-nt Alu RNA by HeLa nuclear extract in vitro also produced scAlu RNA. Primer extension of scAlu RNA indicates synthesis by RNA polymerase III. HeLa-derived scAlu cDNAs were cloned so as to preserve their 5'-terminal sequences and were found to correspond to polymerase III transcripts of the left monomeric components of three previously identified Alu SINE subfamilies. Rodent x human somatic cell hybrids express Alu RNAs whose size, heterogeneous length, and chromosomal distribution indicate their derivation from SINEs. The coexpression of dimeric and monomeric Alu RNA in several hybrids suggests a precursor-product relationship.

Animals↗

PubMed1993

The effects of hypothermia on the intracellular pH of erythrocytes studied using 31P NMR and endogenous compounds.

The effects of hypothermia on the intracellular pH of human erythrocytes were studied non-invasively using 31P NMR spectroscopy and the endogenous phosphorus-containing compounds glycerate 2,3-bisphosphate and inorganic phosphate. Specifically, the pH dependence of the 31P NMR chemical shifts of these compounds was used to measure the intracellular pH at 25 and 37 degrees C. The possibility of a non-pH-dependent change on the chemical shifts of the 2-P and 3-P resonances of glycerate 2,3-bisphosphate due to the presence of paramagnetic deoxy-haemoglobin (i.e., a pseudo-contact interaction) was investigated and found to have negligible effect under the present experimental conditions. The most probable reasons for this are that the deoxy-haemoglobin concentration was too small and/or the glycerate 2,3-bisphosphate does not get sufficiently close to the paramagnetic centre to be affected. The change in intracellular pH with temperature was consistent with that predicted by the alphastat hypothesis.

2,3-Diphosphoglycerate↗

PubMed1993

Protamine-induced acute lung injury and the protective effect of agents that increase cAMP.

Polycations, such as protamine sulfate and polylysine, have been implicated in acute lung injury. We studied the vascular effect of protamine sulfate and the protective effect of agents that increase cAMP in isolated rat lungs perfused with a cell- and plasma-free solution. Protamine sulfate (3 mg) markedly increased pulmonary artery pressure (PAP) from 15.6 +/- 0.5 to 30.8 +/- 1.2 mmHg (P < 0.01) and lung weight gain (LWG) by 7.8 +/- 1.5 g within 30 min (P < 0.001). The protective effects of pharmacological agents that increase intracellular cAMP were investigated. These agents included dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, a cAMP analogue), aminophylline and pentoxifylline (both are phosphodiesterase inhibitors). Pretreatment with these agents 5 min before protamine administration largely attenuated the increases in PAP and LWG. Because DBcAMP, aminophylline and pentoxifylline all share the effects of increasing intracellular cAMP and were effective on the protamine-induced lung changes, the intracellular level of cAMP could be a major determinant of lung injury. Since there is no blood in the perfusate, the mechanism of cAMP on cellular components in the blood such as neutrophils, can be ruled out. The endothelial cells are likely to be the target cells because charge interaction is believed to occur on the endothelial surface. This result will be very important in the elucidation of the protective effect of cAMP in acute lung injury.

Aminophylline↗

PubMed1992

Dimethylthiourea ameliorates acute lung injury induced by phorbol myristate acetate in dogs.

BACKGROUND AND METHODS: The protective effects of dimethylthiourea, a potent scavenger of hydroxy radical (.OH) and hydrogen peroxide, in experimental lung injury in large animals remain controversial. The present study was designed to determine whether dimethylthiourea can ameliorate the acute lung injury produced in dogs by phorbol myristate acetate. Six dogs were infused with dimethylthiourea (0.75 g/kg in saline) for 1.5 hrs, beginning 1 hr before an i.v. bolus injection of phorbol myristate acetate (17 micrograms/kg); six dogs received phorbol myristate acetate (17 micrograms/kg) alone; and six dogs were infused with saline alone. Hemodynamic changes, arterial oxygenation, and the development of lung edema were monitored for 4 hrs after phorbol myristate acetate injection to assess the extent of lung damage. RESULTS: As compared with the dogs that received phorbol myristate acetate alone, the edematous lung damage was significantly reduced in those dogs that received dimethylthiourea as well as phorbol myristate acetate. In the dimethylthiourea-treated dogs, the lung wet/dry weight ratios were smaller (p less than .01); protein concentrations in lung lavage fluid were lower (p less than .01); the decrease in PaO2 was significantly reduced (p less than .01); and there were significant reductions in the alveolar-arterial oxygen tension difference (P[A-a]O2) (p less than .01) and shunt (Qsp/Qt) (p less than .05). Also, dimethylthiourea significantly lowered the increased mean pulmonary arterial pressure levels during the second half of the experiment. CONCLUSIONS: These experimental data suggest that dimethylthiourea is capable of reducing the neutrophil-mediated lung injury produced by the release of hydroxy radical and/or hydrogen peroxide in dogs exposed to phorbol myristate acetate.

Acute Disease↗

PubMed1992

Response to steroid and duration of radicular pain as predictors of surgical outcome.

Prolonged structural compromise of spinal nerve roots can lead to chronic changes that surgical decompression might not be able to reverse. In this study, it was hypothesized that if there were a reversible structural pain component, a steroid injected into the patient's symptomatic nerve root should provide temporary pain relief and that these patients should have a favorable surgical outcome. It also was hypothesized that duration of radicular symptoms would correlate inversely with surgical outcome. For postoperative relief of radicular pain, the results showed that patients with pain lasting less than 1 year had a positive surgical result (89%), regardless of response to steroid. Patients with pain lasting more than 1 year and who have had a positive response to steroid injected into the symptomatic nerve root (roots) had a positive surgical outcome of 85%. Patients who did not respond to the steroid and had pain for more than 1 year (95%) generally had a poor surgical outcome. Although the poor outcome in the last group might be explained in some cases by an inadequate structural correction, inadequate stabilization, or functional reasons, the majority of these failures represented irreversible changes in the neural structures.

Betamethasone↗