Search PubMed⌕ Search

Biomedical subjects

H Cai

Publications and source records attributed to H Cai.

At least 109 records · Page 6Linked to original sources

A model for binaural response properties of inferior colliculus neurons. II. A model with interaural time difference-sensitive excitatory and inhibitory inputs and an adaptation mechanism.

The inferior colliculus (IC) model of Cai et al. [J. Acoust. Soc. Am. 103, 475-493 (1998)] simulated the binaural response properties of low-frequency IC neurons in response to various acoustic stimuli. This model, however, failed to simulate the sensitivities of IC neurons to dynamically changing temporal features, such as the sharpened dynamic interaural phase difference (IPD) functions. In this paper, the Cai et al. (1998) model is modified such that an adaptation mechanism, viz., an additional channel simulating a calcium-activated, voltage-independent potassium channel which is responsible for afterhyperpolarization, is incorporated in the IC membrane model. Simulations were repeated with this modified model, including the responses to pure tones, binaural beat stimuli, interaural phase-modulated stimuli, binaural clicks, and pairs of binaural clicks. The discharge patterns of the model in response to current injection were also studied and compared with physiological data. It was demonstrated that this model showed all the properties that were simulated by the Cai et al. (1998) model. In addition, it showed some properties that were not simulated by that model, such as the sharpened dynamic IPD functions and adapting discharge patterns in response to current injection.

Acoustic Stimulation↗

The L-isoaspartyl protein repair methyltransferase enhances survival of aging Escherichia coli subjected to secondary environmental stresses.

Like its homologs throughout the biological world, the L-isoaspartyl protein repair methyltransferase of Escherichia coli, encoded by the pcm gene, can convert abnormal L-isoaspartyl residues in proteins (which form spontaneously from asparaginyl or aspartyl residues) to normal aspartyl residues. Mutations in pcm were reported to greatly reduce survival in stationary phase and when cells were subjected to heat or osmotic stresses (C. Li and S. Clarke, Proc. Natl. Acad. Sci. USA 89:9885-9889, 1992). However, we subsequently demonstrated that those strains had a secondary mutation in rpoS, which encodes a stationary-phase-specific sigma factor (J. E. Visick and S. Clarke, J. Bacteriol. 179:4158-4163, 1997). We now show that the rpoS mutation, resulting in a 90% decrease in HPII catalase activity, can account for the previously observed phenotypes. We further demonstrate that a new pcm mutant lacks these phenotypes. Interestingly, the newly constructed pcm mutant, when maintained in stationary phase for extended periods, is susceptible to environmental stresses, including exposure to methanol, oxygen radical generation by paraquat, high salt concentrations, and repeated heating to 42 degrees C. The pcm mutation also results in a competitive disadvantage in stationary-phase cells. All of these phenotypes can be complemented by a functional pcm gene integrated elsewhere in the chromosome. These data suggest that protein denaturation and isoaspartyl formation may act synergistically to the detriment of aging E. coli and that the repair methyltransferase can play a role in limiting the accumulation of the potentially disruptive isoaspartyl residues in vivo.

Bacterial Proteins↗

Photothrombotic middle cerebral artery occlusion in spontaneously hypertensive rats: influence of substrain, gender, and distal middle cerebral artery patterns on infarct size.

BACKGROUND AND PURPOSE: To analyze the effects of substrain and gender differences in spontaneously hypertensive rats (SHR) and distal middle cerebral artery (MCA) branching patterns on infarct size, we compared infarct volumes produced by photothrombotic distal MCA occlusion using SHR/Kyushu and SHR/Izumo (Izm). METHODS: Twenty-four male and 8 female SHR/Kyushu, 15 male and 5 female SHR/Izm, and 6 male Wistar-Kyoto rats (WKY)/Izm (5 to 7 months old) were subjected to photothrombotic distal MCA occlusion, and infarct volumes were determined. RESULTS: Although blood pressure levels were essentially the same between the two substrains of hypertensive rats, infarct volumes were significantly larger in the SHR/Kyushu substrain than in SHR/Izm of either sex (P<0.001); infarct volumes in male and female SHR/Kyushu were 83.8+/-11.7 and 58.5+/-9.2 mm3, and those in male and female SHR/Izm were 61.5+/-10.7 and 34.8+/-7.9 mm3, respectively (values are mean+/-SD). Male SHR/Kyushu that had simple Y-shaped MCA showed smaller infarcts (75.8+/-14.6 mm3, n=11) than those with more branching (regular) MCA (93.2+/-19.1, n=13), the difference being significant (P=0.022). Male SHR/Izm with simple distal MCA also produced smaller infarctions than those with regular MCA (51.0+/-3.7 versus 68.9+/-8.7 mm3, P=0.0004). CONCLUSIONS: Photothrombotic occlusion of distal MCA in hypertensive rats provides a simple and reproducible model of focal ischemia. Most importantly, this study emphasizes the substantial variabilities in infarct sizes caused by the differences in substrains of SHR, gender, and distal MCA patterns.

Animals↗

The effect of bu shen sheng xue fang on beta-thalassemia at gene level.

Isoelectrofocusing electrophoresis, PCR-SSCP analysis with DNA direct sequencing and RT-PCR were used to analyze the constituents of hemoglobin, determine the pattern of globin gene mutation, and detect its mRNA transcription extent. The results indicated that Bu Shen Sheng Xue Fang (BSSXF) significantly increased the contents of hemoglobin (Hb) and fetal hemoglobin (HbF), and the chain ratio in patients with beta-thalassemia. The drug is markedly effective in heterozygous, but not effective in homozygous or genetic compound patients. It was suggested that the beta-globin gene defects were compensated by elevating the gamma/beta + gamma ratio, promoting the transcription and expression of gamma-globin gene in synthesizing HbF.

Adolescent↗

[Effects of mild hypothermia on Na(+)-K+ ATPase and lipid peroxidation in canine brain tissue following cardiac arrest and resuscitation].

The effect of mild hypothermia on Na(+)-K+ ATPase and lipid peroxidation in canine brain tissue following a 18-minute cardiac arrest and resuscitation for 8 hours were studied. Mild hypothermia improved the restoration of the activity of Na(+)-K+ ATPase, LDH, protect the activity of SOD, decrease the loss of GSH, but not completely blocked the ischemia reperfusion induced lipid peroxidation.

Animals↗

[Influence of cardiopulmonary bypass time on gastric intramucosal Pco2 and pH].

To determine the influence of cardiopulmonary bypass time on gastric intramucosal Pco2 and pH (pHi), 16 patients undergoing cardiopulmonary bypass (CPB) were divided into two groups according to the CPB time-- group A (n = 8) within 100 minutes and group B (n = 8) beyond 100 minutes. The gastric intramucosal Pco2 increased and the pHi decreased significantly (P< 0.01) at the end CPB compared with before operation, before bypass and 30 minutes after intermission of CPB in all patients. Between group B and A, there were significant differences in the gastric intramucosal Pco2 and in the pHi at the end of CPB. The patients of group A had no severe complications. In group B, three patients developed life-threatening complications, one of them died. The results indicate that the longer the CPB time, the greater the degree of gastric mucosal acidosis. It predicts the patients may develop life-threatening complication after cardiac operations.

Adolescent↗

[Influence of moderate hypothermia on the contents of 6-KETO-PGF1 alpha and TXB2 in brain tissues after cardiac arrest and resuscitation in dogs].

To investigate the effect of moderate hypothermia of whole brain (30 degrees C to 32 degrees C) on the levels of prostacyclin and thromboxane A2 in brain tissues after cardiac arrest and resuscitation. Twenty-one dogs were divided into four groups: Group A, nonischemic controls (n = 4); Group B, 15 minute cardiac arrest without reperfusion (n = 4); Group C, 15 minute cardiac arrest and standard resuscitation (n = 6); Group D, 15 minute cardiac arrest and moderate hypothermia (30 degrees C-32 degrees C). The results showed that as compared with those in Group A, the 6-Keto-PGF1 alpha levels remained substantially unchanged in Group C and D (P > 0.05), and the levels of TXB2 and TXB2/6-Keto-PGF1 alpha ratio increased significantly in Group C (P < 0.01), but both maintained basically stable in Group D (P > 0.05). In comparison with those in Group C, the levels of TXB2 and TXB2/6-Keto-PGF1 alpha ratio decreased dramatically (P < 0.01). It is concluded that the moderate hypothermia can depress the arachidonic acid metabolism and keep a certain balance between the activities of TXA2 and PGI2 during cerebral resuscitation.

6-Ketoprostaglandin F1 alpha↗

[Gene expression of messenger RNA coding for procollagen and tumour necrosis factor-alpha in lungs undergoing bleomycin-induced pulmonary fibrosis].

OBJECTIVE: mRNA for tumour necrosis factor-alpha(TNF-alpha) and procollagen I [pro alpha 1(I)] and III (pro alpha 1(III) was measured in bleomycin treated mice to evaluate their roles in pulmonary fibrosis. METHOD: 30 male Wistar rats were divided into normal control group and groups treated by bleomycin on days 3, 7, 14, 21, 30. Each group included 5 rats, and the rats were treated by single intratracheal instillation with sterile saline solution or with 5 mg/kg body weight of bleomycin. The rats were sacrificed at different days, and total RNA from the lungs of bleomycin or saline solution instilled rats was extracted. Expression of TNF-alpha, pro alpha 1 (I) and pro alpha 1 (III) mRNA was measured by dot blot and Northern blot hybridization. RESULT: The levels of TNF-alpha mRNA in lungs of bleomycin groups on days 3,7 were significantly higher than those of control group (t = 10.33 and 12.54 respectively; P < 0.01). The levels of pro alpha 1 (I) and pro alpha 1(III) mRNA in lungs of bleomycin group on day 7 were higher than those of control group(t = 10.56 and 24.23 respectively; P < 0.01), After reaching the peak levels in two weeks, the levels of pro alpha 1(III) mRNA in lungs of bleomycin group on day 30 declined slowly to approximately the values of normal control group (t = 1.95; P > 0.05); but the levels of pro alpha 1(I) mRAN on day 30 after bleomycin administration were higher than those of control group (t = 16.67; P < 0.01). The mRNA coding pro alpha 1(I) and pro alpha 1(III) in lungs of rats had two mRNA species. CONCLUSION: The results suggested that the metabolism of mRNAs for pro alpha 1 (I) and pro alpha 1 (III) may be preferentially perturbed, and that increase of collagen gene expression in the transcriptional level might be involved in the mechanism of collagen accumulation. The increased expression of TNF-alpha gene may play an important role in the early events of bleomycin-induced pulmonary fibrosis.

Animals↗

[Determination of levofloxacin in plasma and cerebrospinal fluid with HPLC and its pharmacokinetics in patients undergoing neurosurgical operations].

A RP-HPLC method was developed to determine the concentrations of levofloxacin in plasma and cerebrospinal fluid and its pharmacokinetics were studied in patients undergoing neurosurgical operations. C18H37 column was eluted with the mobile phase consisting of 10 mmol.L-1 KH2PO4-10 mmol.L-1(C4H9)4Br-CH3CN(45:45:10, pH 3.0) and the utraviolet absorbance was monitored at 295 nm. Ciprofloxacin was used as internal standard. The mean recoveries were 74.76% in plasma and 82.43% in cerebrospinal fluid, with the lowest detectable limits of 10 micrograms.L-1 and 6 micrograms.L-1, respectively. The RSD for the intra-day and inter-day were all less than 5%. A single oral administration of 300 mg levofloxacin tablet was given to 10 patients undergoing neurosurgical operations. The pharmacokinetic parameters in blood and in cerebrospinal fluid could be described by one compartment open model. The pharmacokinetic parameters were: blood Ke 0.12 +/- 0.04 h-1, T1/2 6.05 +/- 1.68 h, Tmax 1.05 +/- 0.29 h, Cmax 3.67 +/- 0.42 mg.L-1, AUC 33.43 +/- 7.32 mg.h.L-1, CLs 9.46 +/- 2.53 L.h-1, Vd 77.49 +/- 7.39 L; cerebrospinal fluid Ke 0.11 +/- 0.04 h-1, T1/2 6.95 +/- 1.88 h, Tmax 3.56 +/- 1.24 h, Cmax 1.68 +/- 0.25 mg.L-1, AUC 23.70 +/- 5.62 mg.h.L-1, CLs 13.70 +/- 5.11 L.h-1, Vd 126.61 +/- 13.20 L.

Adult↗

[Direct collection with graphite probe filters and determination of trace cadmium in atmospheric particulate matter by graphite probe furnace atomic absorption spectrometry].

After atmospheric particulate matter was directly collected with graphite probe filters, the trace cadmium in APM was determined by graphite probe furnace atomic absorption spectrometry. The results showed that the absorbance (peak-area mode)and the concentration of cadmium had a excellent linearity in the range of 0-50 microg/L. The characteristic mass and detection limit (3 sigma) were 2.48 and 1.86 pg, respectively. Its relative standard deviation was 2.06% (n = 11). The results of analysis of the National Bureau of standards of America, Standard Reference Material (SRM) No. 1648, Urban Particulate Matter, gave a recovery of 90.15-99.29% with RSD of 4.09%. The method proved to be accurate, sensitive, rapid and simple.

English Abstract↗

Identification of metalloprotease/disintegrins in Xenopus laevis testis with a potential role in fertilization.

Proteins containing a membrane-anchored metalloprotease domain, a disintegrin domain, and a cysteine-rich region (MDC proteins) are thought to play an important role in mammalian fertilization, as well as in somatic cell-cell interactions. We have identified PCR sequence tags encoding the disintegrin domain of five distinct MDC proteins from Xenopus laevis testis cDNA. Four of these sequence tags (xMDC9, xMDC11.1, xMDC11.2, and xMDC13) showed strong similarity to known mammalian MDC proteins, whereas the fifth (xMDC16) apparently represents a novel family member. Northern blot analysis revealed that the mRNA for xMDC16 was only expressed in testis, and not in heart, muscle, liver, ovaries, or eggs, whereas the mRNAs corresponding to the four other PCR products were expressed in testis and in some or all somatic tissues tested. The xMDC16 protein sequence, as predicted from the full-length cDNA, contains a metalloprotease domain with the active-site sequence HEXXH, a disintegrin domain, a cysteine-rich region, an EGF repeat, a transmembrane domain, and a short cytoplasmic tail. To study a potential role for these xMDC proteins in fertilization, peptides corresponding to the predicted integrin-binding domain of each protein were tested for their ability to inhibit X. laevis fertilization. Cyclic and linear xMDC16 peptides inhibited fertilization in a concentration-dependent manner, whereas xMDC16 peptides that were scrambled or had certain amino acid replacements in the predicted integrin-binding domain did not affect fertilization. Cyclic and linear xMDC9 peptides and linear xMDC13 peptides also inhibited fertilization similarly to xMDC16 peptides, whereas peptides corresponding to the predicted integrin-binding site of xMDC11.1 and xMDC11.2 did not. These results are discussed in the context of a model in which multiple MDC protein-receptor interactions are necessary for fertilization to occur.

Amino Acid Sequence↗

AMPA receptor antagonist, YM90K, reduces infarct volume in thrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.

We examined the effects of a potent and selective antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptor, YM90K, on brain infarction using a newly developed stroke model of thrombotic distal middle cerebral artery occlusion. Male spontaneously hypertensive rats (5-7 months old) were subjected to photochemically-induced distal middle cerebral artery occlusion as previously described [Stroke 26 (1996) 333-336]. Intravenous infusion of YM90K (n = 8) (5 mg/kg per h for 1 h) or the same amount of vehicle (n = 8) (alkaline saline) was started 5 min after distal middle cerebral artery occlusion. Penumbral cerebral blood flow was determined with laser-Doppler flowmetry. Three days after the ischemic insult, brains were stained with 2,3,5-triphenyltetrazolium chloride and infarct volumes were determined. One hour infusion of YM90K significantly reduced infarct volume by 34% (93 +/- 23 mm3 in control group vs. 61 +/- 25 mm3 in YM90K-treated group, P = 0.017). There were no significant differences in the degrees of cerebral blood flow reduction after distal middle cerebral artery occlusion between the YM90K treated and control groups. YM90K reduces infarct volume in experimental ischemia produced by photothrombotic distal middle cerebral artery occlusion in rats. The present results demonstrated beneficial effects of AMPA receptor blockade on acute ischemic stroke.

Animals↗

N-methyl threonine analogues of deglycobleomycin A2: synthesis and evaluation.

The synthesis of 5 and its D-allo-threonine epimer 6 and the comparison of their DNA cleavage efficiency and selectivity with that of deglycobleomycin A2 (3) are detailed. The studies illustrate that N-methylation of the L-threonine subunit within deglycobleomycin A2 dramatically reduces the DNA cleavage efficiency (10-15-fold), weakens and nearly abolishes the inherent DNA cleavage selectivity, but has little effect on the inherent oxidation capabilities of the activated Fe(III) complexes. The results are consistent with a previously unrecognized prominent role for the threonine NH and the potential importance of a hydrogen bond to the Fe(III) hydroperoxide complex of bleomycin or a subsequent activated complex implicated in recent structural models.

Bacteriophage phi X 174↗

Role of diacylglycerol-regulated protein kinase C isotypes in growth factor activation of the Raf-1 protein kinase.

The Raf protein kinases function downstream of Ras guanine nucleotide-binding proteins to transduce intracellular signals from growth factor receptors. Interaction with Ras recruits Raf to the plasma membrane, but the subsequent mechanism of Raf activation has not been established. Previous studies implicated hydrolysis of phosphatidylcholine (PC) in Raf activation; therefore, we investigated the role of the epsilon isotype of protein kinase C (PKC), which is stimulated by PC-derived diacylglycerol, as a Raf activator. A dominant negative mutant of PKC epsilon inhibited both proliferation of NIH 3T3 cells and activation of Raf in COS cells. Conversely, overexpression of active PKC epsilon stimulated Raf kinase activity in COS cells and overcame the inhibitory effects of dominant negative Ras in NIH 3T3 cells. PKC epsilon also stimulated Raf kinase in baculovirus-infected Spodoptera frugiperda Sf9 cells and was able to directly activate Raf in vitro. Consistent with its previously reported activity as a Raf activator in vitro, PKC alpha functioned similarly to PKC epsilon in both NIH 3T3 and COS cell assays. In addition, constitutively active mutants of both PKC alpha and PKC epsilon overcame the inhibitory effects of dominant negative mutants of the other PKC isotype, indicating that these diacylglycerol-regulated PKCs function as redundant activators of Raf-1 in vivo.

3T3 Cells↗

Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27KIP1.

Activation of growth factor receptors by ligand binding initiates a cascade of events leading to cell growth and division. Progression through the cell cycle is controlled by cyclin-dependent protein kinases (Cdks), but the mechanisms that link growth factor signaling to the cell cycle machinery have not been established. We report here that Ras proteins play a key role in integrating mitogenic signals with cell cycle progression through G1. Ras is required for cell cycle progression and activation of both Cdk2 and Cdk4 until approximately 2 h before the G1/S transition, corresponding to the restriction point. Analysis of Cdk-cyclin complexes indicates that Ras signaling is required both for induction of cyclin D1 and for downregulation of the Cdk inhibitor p27KIP1. Constitutive expression of cyclin D1 circumvents the requirement for Ras signaling in cell proliferation, indicating that regulation of cyclin D1 is a critical target of the Ras signaling cascade.

3T3 Cells↗