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Biomedical subjects

J Hua

Publications and source records attributed to J Hua.

At least 73 records · Page 4Linked to original sources
PubMed1997

The recognition potential, word difficulty, and individual reading ability: on using event-related potentials to study perception.

Ten observers detected words in a stream of random letters. The latency of the recognition potential (RP) was less for easier words. This implicated short latency processes in word detection. Reaction time (RT) and P3 latency decreases with training were attributed to improved motor preparation. The RT decrease with training was correlated with P3 (r = .67), but not RP (r = .04), latency reduction. P3 latency did not predict individual RT (r = .20), but RP latency did (r = .66). Twenty other subjects took the Verbal portion of a Graduate Record Examination to test whether the RP might be a better predictor of individual differences than P3. RP latency predicted a person's reading score (r = -.74), but P3 latency did not (r = .08). The word-difficulty effect and the shorter RP latency observed for superior readers supported the idea that the RP reflects perception that is based on language skill.

Adult↗
PubMed1997

Human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus Nef use distinct but overlapping target sites for downregulation of cell surface CD4.

Although the Nef proteins encoded by human immunodeficiency virus type 1 (HIV-1) and simian immuno-deficiency virus (SIV) are known to induce the efficient internalization and degradation of cell surface CD4, it remains unclear whether this process involves a direct interaction between Nef and CD4. Here, we report that CD4 downregulation by HIV-1 and SIV Nef requires distinct but overlapping target sites within the CD4 intracytoplasmic domain. In particular, mutation of a glutamic acid residue located at CD4 residue 405 or of arginine and methionine residues located, respectively, at residue 406 and 407 results in a mutant CD4 protein that is efficiently downregulated by HIV-1 Nef but refractory to downregulation by SIV Nef. However, both HIV-1 and SIV Nef require an isoleucine located at residue 410 and the dileucine motif found at CD4 residues 413 and 414. CD4 downregulation induced by the Nef protein encoded by HIV-2 is shown to require a CD4 target sequence that is similar to, but distinct from, that observed with SIV Nef. These data explain the previous finding that the murine CD4 protein, which has an alanine at residue 405, is refractory to downregulation by SIV, but not HIV-1, Nef (J. L. Foster, S.J. Anderson, A. L. B. Frazier, and J. V. Garcia, Virology 201:373-379, 1994). In addition, these observations provide strong genetic support for the hypothesis that the Nef-mediated downregulation of cell surface CD4 requires a direct Nef-CD4 interaction.

Alanine↗
PubMed1997

Neutral metoclopramide induces tumor cytotoxicity and sensitizes ionizing radiation of a human lung adenocarcinoma and virus induced sarcoma in mice.

Radiation induced cytotoxicity was potentiated by neutralized metoclopramide (nMCA; Neu-Sensamide, Oxigene Inc) when a human lung adenocarcinoma (H2981) transplanted into scid mice and an adeno-type 12 virus induced mouse sarcoma (A12B3) inoculated into CBA mice were exposed in vivo to low dose radiation at single doses of 1 and 2 Gy respectively. However, when the radiation dose was increased to 6, 10 or 18 Gy (single dose) and combined with a single dose nMCA (2 mg/kg), tumor cytotoxicity was not sensitized by the combination treatment. A fractionated dose of ionizing radiation (3 x 1 Gy) in combination with nMCA at a repeated dose of 3 x 10 mg/kg body weight (1 dose/day, i.m.) significantly increased cytotoxicity in H2981 compared with radiation given alone. nMCA alone also had a statistically significant dose dependent cytotoxic effect on H2981 growth when it was administered as repeated doses (8 doses) at 2 mg/kg or 10 mg/kg (1 dose every second day), and a similar result was achieved at 20 mg/kg but not at 2 and 10 mg/kg in the A12B3 tumor. In addition, the tumor volume at the start of treatment was important for the anti-tumor effect of nMCA (i.e. the larger initial tumor volume gave less effect on tumor growth). Taken together, our data propose that the mode of action of nMCA is different from radiation, and hence the two mechanisms are at least additive when in combination with lower radiation doses. The data further suggest that the cytotoxic mechanism is consistent with potentiating apoptosis because low and repeated doses of radiation (1-2 Gy), which are known to increase cytotoxicity by apoptosis, are sensitized by nMCA but not high doses and nMCA has more potent anti-tumor effects against H2981 tumors which have a higher constitutive apoptotic fraction of cells than A12B3.

Adenocarcinoma↗
PubMed1997

Toxicity, antitumor and chemosensitizing effects of 3-chloroprocainamide.

3-Chloroprocainamide (3-CPA), an analog of metoclopramide (MCA), dose-dependently inhibited tumor growth in scid mice xenografted with a human brain astrocytoma (T24) when given intramuscularly to mice every third day for 14-20 days. 3-CPA was shown to have the same efficacy on tumor growth inhibition as neutral metoclopramide (neutral MCA) at the doses of 10-40 mg/kg when evaluated by tumor doubling time, tumor growth time for tumor volumes to reach 1000 mm3 and area under growth curve. 3-CPA at the dose of 3 x 40 mg/kg was also shown to enhance the cytotoxicity induced by a single dose of cisplatin at 7.5 mg/kg. A dose of < or = 160 mg/kg of 3-CPA did not show any notable extrapyramidal symptoms which was observed for neutral MCA treated mice at the dose of 20 mg/kg. The lethal response dose of 3-CPA for scid mice was 320 mg/kg which is 4 times higher than that determined for neutral MCA (80 mg/kg). These results support 3-CPA as a good candidate drug representing a new generation of benzamides for further clinical development as a cancer therapy drug.

Animals↗
PubMed1997

Interferon-alpha neutralizing antibodies in HIV and chronic HCV patients treated with natural-source human leukocyte-derived interferon-alpha n3.

Human leukocyte-derived IFN-alpha n3 (Alferon N Injection) was administered subcutaneously to treat 20 patients with asymptomatic human immunodeficiency virus type 1 (HIV-1) and 141 patients with chronic hepatitis C virus (HCV) infections. The treatment of HIV-1 and HCV patients, previously untreated with any IFN preparations, did not result in development of neutralizing antibodies to IFN-alpha n3. Among 69 HCV refractory patients who were unresponsive to previous treatment with rIFN-alpha 2b, 2 had neutralizing antibodies to rIFN-alpha 2b prior to IFN-alpha n3 therapy, with no or limited cross-reactivity to IFN-alpha n3. After retreatment with IFN-alpha n3, both patients had detectable neutralizing titers to IFN-alpha n3. Additionally, 2 other patients developed low and transient neutralizing titers to IFN-alpha n3. Interferon subtype specificity of these antibodies was tested against RP-HPLC purified fractions of IFN-alpha n3, as well as rIFN-alpha 2b and rIFN-alpha 8b. Sera from patients previously treated with rIFN-alpha 2b with high antibody titers to rIFN-alpha 2b strongly reacted with the natural IFN-alpha 2b, and to a limited extent with other iFN-alpha subtypes. Neutralizing activity against IFN-alpha 2b was significantly competed out by the presence of a small amount of other interferon subtypes present in IFN-alpha n3. One patient with prior presence of antibodies to IFN-alpha 2b developed a high antibody titer to IFN-alpha 8b with limited reactivity to IFN-alpha n3. Two of the HCV refractory patients with prior neutralizing antibodies to rIFN-alpha 2b responded to IFN-alpha n3 therapy. These data suggest that the presence of neutralizing antibodies to individual IFN-alpha species will not significantly diminish the biological activity and the clinical efficacy of multi-species IFN-alpha n3.

Antibodies↗
PubMed1996

Inhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model system.

Matrix metalloproteinases (MMPs) have been implicated in tumor progression, but the exact roles that each member of this family may play in contributing to the behavior of malignant tumors are only beginning to be understood. MMP-9 (gelatinase B or the 92-kDa gelatinase/type IV collagenase) expression has been associated with metastasis in a variety of model systems including that of rat sarcomas generated by transformation of rat embryo cells with rasH and myc. To determine the effect that expression of MMP-9 has in this system, we inhibited the expression of MMP-9 using a hammerhead ribozyme. Introduction of an expression vector for a ribozyme directed against the rat MMP-9 mRNA sequence into a metastatic rat embryo cell line transformed by rasH and myc (2.10.10) that constitutively secretes MMP-9 resulted in the absence of detectable MMP-9 mRNA and loss of released 92-kDa gelatinase activity. These cells were no longer metastatic in a lung colonization assay but retained tumorigenicity. Introduction of an expression vector for a control hammerhead ribozyme had no effect. These data document the requirement for MMP-9 expression in metastasis in this system.

Animals↗
PubMed1996

A nuclear role for the Fragile X mental retardation protein.

Fragile X syndrome results from lack of expression of a functional form of Fragile X mental retardation protein (FMRP), a cytoplasmic RNA-binding protein of uncertain function. Here, we report that FMRP contains a nuclear export signal (NES) that is similar to the NES recently identified in the Rev regulatory protein of human immunodeficiency virus type 1 (HIV-1). Mutation of this FMRP NES results in mis-localization of FMRP to the cell nucleus. The FMRP NES is encoded within exon 14 of the FMR1 gene, thus explaining the aberrant nuclear localization of a natural isoform of FMRP that lacks this exon. The NES of FMRP can substitute fully for the Rev NES in mediating Rev-dependent nuclear RNA export and specifically binds a nucleoporin-like cellular cofactor that has been shown to mediate Rev NES function. Together, these findings demonstrate that the normal function of FMRP involves entry into the nucleus followed by export via a pathway that is identical to the one utilized by HIV-1 Rev. In addition, these data raise the possibility that FMRP could play a role in mediating the nuclear export of its currently undefined cellular RNA target(s).

Amino Acid Sequence↗
PubMed1996

Functional consequences of natural sequence variation in the activation domain of HIV-1 Rev.

Initial infection with an attenuated form of human immunodeficiency virus type 1 (HIV-1) may give rise to some of the rare asymptomatic infections that have been observed. Recently, data have been presented suggesting that a persistent mutation in the essential activation domain of the HIV-1 Rev regulatory protein might have contributed to the maintenance of the asymptomatic state in one individual. Here, we have used a range of assays for in vivo Rev function to examine whether natural sequence variation in the normally highly conserved Rev activation domain can indeed affect Rev function. Analysis of five distinct natural sequence variants of the Rev domain demonstrated that each produced a two- to fourfold drop in Rev function when compared to the consensus activation domain sequence A sixth sequence, reported for the MN isolate of HIV-1, proved entirely inactive. However, resequencing of this region of the MN genome revealed that this isolate actually encodes a consensus Rev activation domain. Overall, these data reveal that even natural sequence variation in the essential Rev activation domain can result in significantly reduced Rev function and suggest that isolates containing such sequence variation are likely to replicate less effectively.

Amino Acid Sequence↗
PubMed1996

A binding factor for interleukin 2 mRNA.

Jurkat cells, a human T lymphocyte line that can be induced to synthesize and secrete interleukin 2, contain a factor that binds interleukin 2 mRNA. Binding can be demonstrated by formation of a complex detectable by gel electrophoresis. The binding is sequence specific and occurs in the 3'-non-coding region, within 160 nt of the end of the coding region, at or near a site on the mRNA that is rich in A and U residues. However, it appears not to be due to known AU binding factors. The factor is protease sensitive and binds non-covalently to interleukin 2 mRNA. It behaves like a protein of molecular weight 50 000-60 000 after UV-induced cross-linking to the mRNA. Preparations of the binding factor also protect interleukin 2 mRNA against degradation by a recently described RNasin-resistant endoribonuclease activity in Jurkat cells. Protection occurs under the same conditions required to generate the gel-retarded complex.

Base Sequence↗
PubMed1996

Cytokines induced by Sendai virus in human peripheral blood leukocytes.

Human peripheral blood leukocytes (hPBL) are a rich source of natural leukocyte interferon (IFN-alpha) when treated with Sendai virus. Sendai virus treatment of hPBL will also result in significant production of several chemokines and cytokines such as macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8, in a time-dependent way. A significant amount of MCP-1 is constitutively produced in overnight culture of leukocytes. The most abundant cytokine is IFN-alpha, which is induced to its maximum level approximately 11-15 h after addition of Sendai virus. The amount of IFN-alpha induced at 15 h after Sendai virus treatment is more than 16-fold higher than those of MIP-1alpha, MIP-1beta, and RANTES. IFN-alpha is also induced more than 60-fold higher than TNF-alpha and IL-8. The amount of IL-6 induced is approximately 400-fold less than IFN-alpha. Limited amounts of other cytokines such as IL-1alpha, IL-1beta, macrophage colony-stimulating factor, TNF-beta, and IFN-gamma are also induced in Sendai virus-treated hPBL. No measurable amount of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, leukemia inhibitory factor, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-11, or IL-12 was induced in the supernatant of Sendai virus-treated hPBL.

Chemokine CCL2↗
PubMed1996

The recognition potential and conscious awareness.

The idea that conscious awareness of a recognizable image is necessary for it to evoke the recognition potential (RP) was tested by asking bilingual subjects to selectively attend to superimposed English and Chinese word images. The subjects detected most of the words in the attended language, but were largely oblivious of words in the non-attended language. Attended word images evoked the RP. Non-attended words did not. RP latency was less for Chinese than for English words. This provided a basis for inferring which language a subject was trying to read when valid English and Chinese words were both present. A subject was looking for Chinese if the latency was short and for English if it was long. The results showed that selective attention had a powerful effect on the RP. They supported the idea that conscious awareness is necessary for evoking it, though they did not rule out the theoretical possibility that some method not yet tested could be found that would block conscious awareness without blocking the RP. The sensitivity of the RP to what a subject is trying to see and its low variance seem to provide advantages for studying visual perception. It provides a short latency indicator of image processing that merits further investigation. Use of it may lead to a better understanding of visual perceptual processes.

Adult↗
PubMed1996

Analysis of sinusoidal-shaped frequency-selective RF pulses.

RODEO (rotating delivery of excitation off resonance), which can be represented as an delta [symbol: see text] pulse where delta is an 2 pi-sinusoidal waveform and [symbol: see text] = - delta, has been used as a frequency-selective rf pulse for fat-suppressed three-dimensional magnetic resonance imaging. This study systematically compared several sinusoidal-shaped pulses with different combinations of delta and [symbol: see text]. The sinusoidal-shaped pulses were also compared with the Gaussian-shaped and binomial-shaped pulses. The overall performances for fat suppression can be rated as "delta [symbol: see text] delta > 1331 > delta [symbol: see text] = 121," where 121 and 1331 are second- and third-order binomial pulses, respectively.

Adipose Tissue↗
PubMed1996

Accuracy of using radiographs for custom hip stem design.

If the shape of the femoral canal could be predicted with sufficient accuracy for the design of custom femoral stems, this would reduce the cost and provide a simpler design method than using computed tomography scans. Five groups of femurs were used for the study. The first two groups were used to determine an average femur shape, described by 25 transverse sections. In the next group of femurs, the shape was predicted from radiographs by distorting the shape of the average femur to conform to the radiographic outlines. The profiles were accurate to within 1 mm on average, the larger errors being in the trochanteric regions. In the proximomedial region, and in the distal canal, the accuracy was better than 0.3 +/- 0.8 mm. When femoral stems were designed from the actual and predicted canals, there was minimal difference in the sections of the two stems. The stems had a particular geometric form with a straight distal end, and flares at the proximomedial and proximoanterior locations; however, when stems designed by either method were inserted into canals prepared by distal reaming and proximal rasping, there was an error in fit in certain regions of approximately 1 mm. It was concluded that for femurs without serious abnormality of shape, a biplane radiographic method was sufficiently accurate for the prediction of canal shape and for the design of a standard type of custom uncemented stem.

Adult↗
PubMed1996

Effect of postoperative treatment with a combination of chuangxiong and electret on functional recovery of muscle grafts: an experimental study in the dog.

Clinical experiences have shown that simultaneous use of constitutional and local treatments postoperatively may increase recovery of transplanted muscle function more than any single treatment. In the present experiment, 27 adult dogs had orthotopic replantation of their bilateral rectus femoris muscles by microneurovascular anastomoses with different therapeutic methods postoperatively for 22 weeks grouped as local implantation of an electret substance (n = 14), intramuscular injection of chuangxiong (Ligusticum wallichii franch) (n = 12), combined use of these two treatments (n = 14), or control (n = 14) to evaluate the influence of these different treatments on muscle function and morphology; electromyography, maximal tetanic tension, and histologic and histochemical examinations showed that the results in all the treatment groups were superior to those in the nontreatment group and that simultaneous use of constitutional and local treatments was superior to any single treatment. At week 22, the maximal tetanic tension of the three treatment groups returned to 57.68 +/- 1.67, 53.64 +/- 3.28, and 64.94 +/- 3.28 percent of control values (before transplantation), respectively, versus 47.99 +/- 2.21 percent in the nontreatment group. These results suggest that treatment with local electret and systemic chuangxiong simultaneously has a favorable effect on nerve regeneration and on muscle function after muscle transplantation.

Animals↗
PubMed1996

Protein sequence requirements for function of the human T-cell leukemia virus type 1 Rex nuclear export signal delineated by a novel in vivo randomization-selection assay.

The Rex protein of human T-cell leukemia virus type 1, like the functionally equivalent Rev protein of human immunodeficiency virus type 1, contains a leucine-rich activation domain that specifically interacts with the human nucleoporin-like Rab/hRIP cofactor. Here, this Rex sequence is shown to function also as a protein nuclear export signal (NES). Rex sequence libraries containing randomized forms of the activation domain/NES were screened for retention of the ability to bind Rab/hRIP by using the yeast two-hybrid assay. While the selected sequences differed widely in primary sequence, all were functional as Rex activation domains. In contrast, randomized sequences that failed to bind Rab/hRIP lacked Rex activity. The selected sequences included one with homology to the Rev activation domain/NES and a second that was similar to the NES found in the cellular protein kinase inhibitor alpha. A highly variant, yet fully active, activation domain sequence selected on the basis of Rab/hRIP binding retained full NES function even though this sequence preserved only a single leucine residue. In contrast, nonfunctional activation domain mutants that were unable to bind Rab/hRIP had also lost NES function. These data demonstrate that NES activity is a defining characteristic of the activation domains found in the Rev/Rex class of retroviral regulatory proteins and strongly support the hypothesis that the Rab/hRIP cofactor plays a critical role in mediating the biological activity of these NESs. In addition, these data suggest a consensus sequence for NESs of the Rev/Rex class.

Amino Acid Sequence↗
PubMed1996

The recognition potential and word priming.

The effect of priming on the latency of the recognition potential (RP) was tested using rapid stream stimulation. Subjects detected five-letter words in a stream of nonword images. Lifting the right index finger signalled detection of a word. Rapid responses were rewarded and false alarms were penalized. Just before generating an image stream, a computer briefly displayed either the specific target word or or five-letter string that indicated the target was any one of ten previously studied words. Precise target specification was expected to produce more rapid detection than the provision of less definite information. Since the RP was thought to reflect the speed of perception, it was predicted that its latency would be less when the target word was beforehand than when less specific information was provided. The results for 10 subjects confirmed the hypothesis.

Adult↗