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C Liu

Publications and source records attributed to C Liu.

At least 739 records · Page 41Linked to original sources
PubMed1993

Combination of aziridinylbenzoquinone and cis-platinum with radiation therapy in the 9L rat brain tumor model.

PURPOSE: We evaluated the potentiating effects of aziridinylbenzoquinone (AZQ) and cis-platinum on the prolongation of survival by radiation therapy in a rat brain tumor model. METHODS AND MATERIALS: On day 10 following intracranial inoculation of the 9L gliosarcoma, Fischer 344 rats were treated with radiation therapy (Cesium-137 source irradiator) and/or chemotherapy delivered either systemically (intraperitoneal or intravenous), or intracranially directly into the tumor in a volume of 5 microliters. Increased life spans were calculated relative to the median survival time for the control (ILS-C) or to the median survival time for radiation therapy only (ILS-RT) group. RESULTS: Median survival time for untreated rats was 22 +/- 3 days for seven experiments. Radiation therapy (16 Gy) produced a significant (p < 0.002) improvement in survival, with an average ILS-C of 75 +/- 19%. Systemic AZQ (1 or 5 intravenous injections of 0.5 mg/kg) produced ILS's of 0 and 23%, the latter being significant (p = 0.002). When added to radiation therapy, there were further improvements (ILS-RT's of 47 and 72%), but these were not significant. Intratumor AZQ (40 or 50 micrograms intracranially) produced significant ILS-C's of 30 and 33% (p = 0.01 and 0.0002, respectively). Added to radiation therapy, intracranial AZQ produced improvements (ILS-RT's of 5 and 102%), with only the latter being significantly improved (p = 0.009). Cis-platinum (3 micrograms intracranially) produced ILS-C's of 13 and 6%, neither significantly different from controls. Added to radiation therapy, cisplatinum caused improvements (ILS-RT's of 18 and 64%), with only the latter significant (p = 0.049). CONCLUSION: These results demonstrate that AZQ delivered systemically, and AZQ and cis-platinum delivered intracranially, can produce statistically significant improvements in the survival of rats burdened with the 9L brain tumor. The agents delivered intracranially significantly potentiated the prolongation of survival obtained by radiation therapy. This preclinical evidence suggests that combining radiation therapy with these cytotoxic chemotherapeutic agents may benefit patients with high-grade malignant brain tumors.

Animals↗
PubMed1993

Disialoganglioside GD2 anti-idiotypic monoclonal antibodies.

Disialoganglioside GD2 is widely expressed among neuroblastomas, melanomas, small-cell lung carcinoma, sarcomas and brain tumors. Immunity directed against this antigen may have anti-tumor utility. Since GD2 is poorly immunogenic, anti-idiotypic antibodies may serve as alternative tumor vaccines. Monoclonal antibody 3F8, a murine IgG3 specific for GD2, has shown excellent tumor-targeting ability in vitro and in vivo. LOU/CN rats were immunized with 3F8 and their spleens were used in somatic-cell hybridization, using SP2/0, P3 and Y3 as fusion partners. Six anti-idiotypic (anti-id) MAbs (C2D8, Idio-2, AIG4, C2H7, C4E4, A2A6) were selected based on their reactivity with 3F8 and non-reactivity with murine IgG3 myelomas. Specificity of each anti-id was demonstrated by using various ELISA: (i) lack of direct binding to solid phase myelomas and serum proteins; (ii) inability of other myelomas to inhibit anti-id binding to 3F8; (iii) absence of cross-reactivity of other myelomas to solid-phase anti-id; (iv) lack of inhibition by anti-id of binding of other ganglioside antibodies to their antigens. Antigen specificity was further examined by inhibition of binding of 3F8 to GD2 on immuno-thin-layer chromatography, and by inhibition of 3F8 immunostaining of neuroblastoma cell lines. These 6 antibodies were demonstrated to be distinct, in view of their cross-reactivity, fusion partners and relative strength of binding to 3F8. Anti-GD2 antibodies were induced after immunization with these anti-id antibodies in C57Bl/6 mice. These rat anti-3F8-idiotypic antibodies with exquisite specificity for anti-GD2 antibodies may be useful in vaccine construction.

Animals↗
PubMed1993

7S nerve growth factor has different biological activity from 2.5S nerve growth factor in vitro.

It is considered that two molecular forms of nerve growth factor (NGF), that is 7S NGF and 2.5S NGF have the identical neurotrophic effect on neurons. We now report that 7S NGF has different biological activities from 2.5S NGF in vitro. 7S NGF could promote the survival and neurite outgrowth of neurons from newborn rat hippocampus, cortex and cerebellum and stimulate the proliferation of astrocytes in vitro, but 2.5S NGF had no such effect.

Animals↗
PubMed1993

Selection and characterization of a neuraminidase-minus mutant of influenza virus and its rescue by cloned neuraminidase genes.

A neuraminidase (NA)-deficient mutant, designated NWS-Mvi, of the reassortant influenza virus A/NWS/33HA-A/tern/Australia/G70c/75NA (H1N9), was selected by passaging virus in MDCK cells in a medium containing neuraminidase from the bacterium Micromonospora viridifaciens and polyclonal antiserum against the influenza NA. Growth of the resulting mutant virus is dependent on the addition of neuraminidase to the medium. Western blot analysis showed that the neuraminidase protein was absent from the mutant virus particles, and Northern hybridization showed that RNA segment 6, which contains the coding information for the NA, had undergone massive deletion. Viral protein synthesis in cells infected with the mutant virus was not dependent on the addition of neuraminidase. In the absence of a functional NA, the NWS-Mvi mutant virus can infect MDCK cells with normal cytopathic effects. This neuraminidase-minus influenza virus serves as an excellent source of parent virus for reverse genetics experiments involving genes that encode a functional neuraminidase.

Animals↗
PubMed1993

Immune adjuvants for chemotherapy or radiotherapy in the 9L rat brain tumor model.

The therapeutic efficacy and toxicity of three biological response modifiers, Corynebacterium parvum (Cp), Chinese blister beetle extract (CBBE), recombinant human IL-1 alpha (rhIL-1 alpha), used alone or in combination with chemotherapy or radiotherapy, were investigated in the intracerebral (ic) rat 9L brain tumor model. Used alone, Cp (2 mg/rat, ip plus 70 micrograms/rat, ic), CBBE (5 microliters of an ethanol extract, ic), or IL-1 alpha (1 microgram/rat, ic or 1 microgram/rat x 3, q 3 d, ic), had no effect on animal survival compared to the untreated or saline treated controls. When combined with chemotherapy or radiotherapy, the three immunotherapeutic agents did not show any additive effects on survival compared to that observed with systemic BCNU (12 mg/kg), local ic bleomycin (0.25 unit), or local radiotherapy (16 Gy). While ic IL-1 alpha did not produce evident toxicity, there was fatal toxicity caused by ic Cp or CBBE treatment in a few animals. The combination of Cp and bleomycin produced severe neurotoxicity, resulting in the early death of animals. This study demonstrates a lack of efficacy of the nonspecific immune adjuvants IL-1 alpha, Cp or CBBE, used either alone or combined with cytotoxic chemotherapy or radiotherapy, in this rat brain tumor model.

Adjuvants, Immunologic↗
PubMed1993

The evolution of long interspersed repeated DNA (L1, LINE 1) as revealed by the analysis of an ancient rodent L1 DNA family.

All modern mammals contain a distinctive, highly repeated (> or = 50,000 members) family of long interspersed repeated DNA called the L1 (LINE 1) family. While the modern L1 families were derived from a common ancestor that predated the mammalian radiation approximately 80 million years ago, most of the members of these families were generated within the last 5 million years. However, recently we demonstrated that modern murine (Old World rats and mice) genomes share an older long interspersed repeated DNA family that we called Lx. Here we report our analysis of the DNA sequence of Lx family members and the relationship of this family to the modern L1 families in mouse and rat. The extent of DNA sequence divergence between Lx members indicates that the Lx amplification occurred about 12 million years ago, around the time of the murine radiation. Parsimony analysis revealed that Lx elements were ancestral to both the modern rat and mouse L1 families. However, we found that few if any of the evolutionary intermediates between the Lx and the modern L1 families were extensively amplified. Because the modern L1 families have evolved under selective pressure, the evolutionary intermediates must have been capable of replication. Therefore, replication-competent L1 elements can reside in genomes without undergoing extensive amplification. We discuss the bearing of our findings on the evolution of L1 DNA elements and the mammalian genome.

Animals↗
PubMed1993

MSR--a program for kinetic analysis of enzyme modification data on PC.

A computer program has been written for the kinetic method of substrate reaction (MSR) in enzyme modification studies. The program analyses a series of progress curves that continuously record signals (absorbance, fluorescence emission, etc.) reflecting the concentration changes of substrate or product during enzyme modification in the presence of substrate. After the apparent kinetic parameters are calculated by graphdrawing or curve-fitting method, a series of relevant plots is shown, from which information about the enzyme-inhibitor interaction can be deduced and microscopic kinetic constants calculated.

Animals↗
PubMed1993

An mRNA homologous to interleukin-1 receptor type I is expressed in cultured rat sympathetic ganglia.

Interleukin-1 (IL-1) induces substance P (SP) gene expression in cultured rat superior cervical ganglion (SCG) explants. In order to study the molecular mechanism of this action of IL-1, the presence of an interleukin-1 receptor (IL-1R) activity and the identity of an mRNA homologous to known IL-1R sequence was determined in SCG. The SP increase is blocked by recombinant IL-1 receptor antagonist protein, so IL-1 must be interacting with a specific receptor. We have cloned cDNA homologous to IL-1R type I from rat SCG using a reverse transcription-polymerase chain reaction (RT-PCR). The resulting cDNA sequence is strongly homologous with mouse and human IL-1R cDNA of the T cell and fibroblast type (type I; encoding an 80-kDa protein). mRNA specific for IL-1R can be readily detected in intact SCG by quantitative RT-PCR and S1 hybridization. However, the level of IL-1R mRNA increases 3-6-fold by 2 days in culture. This increase is independent of the presence of dexamethasone, IL-1 beta or IL-1 receptor antagonist protein ligands. The increase of IL-1R following explantation, a model of nerve injury, may provide a mechanism linking inflammatory signalling to neuronal phenotypic changes.

Amino Acid Sequence↗
PubMed1993

Use of sodium hyaluronate in treating temporomandibular joint disorders: a randomized, double-blind, placebo-controlled clinical trial.

This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporomandibular joint (TMJ) disorders. One hundred twenty-one patients were studied at three test sites using a randomized, double-blind, placebo-controlled experimental design. Patients were selected on the basis of 1) confirmed diagnosis of either degenerative joint disease (DJD), reducing displaced disc (DDR), or nonreducing displaced disc (DDN); 2) nonresponsiveness to nonsurgical therapies; and 3) severe dysfunction as established by the Helkimo indices (HI), visual analog scales (VASs), and physical measurements of joint movement and joint noise (arthrophonometry [APM]). Subjects received a unilateral upper joint space injection of either 1) 1% sodium hyaluronate in physiologic saline (MedChem Products, Woburn, MA) or 2) USP physiologic saline. Clinical evaluations were performed using HI, VAS, and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection. Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval. For DJD, no difference in outcome was seen between treatment groups. For DDN, significant between-group differences were seen through 1 month; however, beyond this time point, the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy. For DDR, statistically significant within-group and between-group improvement in all three measures (HI, VAS, APM) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period. At the month-2 and month-3 examination intervals, twice as many patients treated with hyaluronate (90%) showed improvement compared to patients given placebo. Further, only 3% of patients with DDR who were treated with hyaluronate relapsed compared with 31% of patients with DDR given placebo.

Adult↗
PubMed1993

Management of symptomatic latent nystagmus.

Most patients with latent nystagmus are asymptomatic and do not require treatment. We discuss the management by botulinum toxin injection and surgery of five cases of latent nystagmus in which the patients suffered loss of visual acuity on certain manoeuvres as a consequence of an exacerbation of the nystagmus amplitude. The importance of eye movement recordings for accurate diagnosis is stressed and the investigative role of botulinum toxin injection is discussed. Extraocular muscle surgery is helpful in some cases of symptomatic latent nystagmus.

Adult↗
PubMed1993

Limbal transplantation in the management of chronic contact-lens-associated epitheliopathy.

We describe the clinical management of 6 patients who developed a chronic corneal epitheliopathy 1-18 years after commencing soft contact lens wear. All had a history of exposure to thiomersal in contact lens fluids. The corneal changes were characterised by epithelial haze and superficial stromal vascularisation which extended from the limbus towards the visual axis. Five patients were observed for a minimum of 18 months after stopping contact lens wear before undergoing limbal transplantation. A good result was obtained in 1 patient who had worn a contact lens in one eye only. Recurrent epithelial changes were observed on the recipient eyes of the remaining patients who had previously worn contact lenses bilaterally, and in 1 patient epithelial haze also developed adjacent to the donor site in the previously clinically normal donor eye. All 5 patients experienced an improvement in symptoms post-operatively but in 2 patients the visual acuity later deteriorated because of epithelial irregularity. The sixth patient has not had surgery. We conclude that limbal stem cell dysfunction in chronic contact-lens-associated epitheliopathy may be subclinical and that autograft transplantation in bilaterally exposed patients may fail to restore the epithelial phenotype of the host eye whilst jeopardising the epithelial integrity of the donor eye by depleting its stem cell reserve.

Adolescent↗
PubMed1993

Geographic variation of procedure utilization. A hierarchical model approach.

In this study, an abbreviated introduction to hierarchical statistical models for quantifying and explaining variations in the utilization of medical care is presented. The illustrative example was derived from an analysis of interstate variation in coronary angiography utilization for Medicare patients with a recent acute myocardial infarction. The hierarchical model distinguished within-from between-states variation: the former was modeled via a separate logistic regression for each state, with age and sex as the independent variables, while the latter was modeled via a multivariate normal distribution for the coefficients of the state-specific logistic models. Alternative computation approaches were compared and model fit was assessed. Estimates of the distribution of state rates of angiography for an average patient and for age-by-sex strata were obtained. The results showed substantial interstate variation in angiography utilization, but only moderate interstate variation in the effects of age and sex on the decision to perform angiography. This analytic approach allows substantially more detailed results than those by standardization, and accounts for sample size differences between units of aggregation. The next major step in the analysis would be to derive smoothed estimates of the individual state logistic models by pooling data across states. The analysis can also be extended to incorporate other patient characteristics, such as race and comorbidity, and state characteristics, such as geographic location and availability of the procedure.

Aged↗
PubMed1993

RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae.

To investigate the role of the yeast telomere-, silencing-, and UAS-binding protein RAP1 in telomere position effects, we have characterized two sets of mutant cells: (1) a set of rap1 alleles (termed the rap1t alleles) that produce truncated RAP1 proteins missing the carboxy-terminal 144-165 amino acids; and (2) null mutants of the RIF1 gene, encoding a protein capable of interaction with the carboxyl terminus of RAP1. The data presented here indicate that loss of the carboxyl terminus of RAP1 abolishes position effects at yeast telomeres and diminishes silencing at the HML locus. Elimination of position effects in these cells is associated with increased accessibility to the Escherichia coli dam methylase in vivo. Thus, the carboxy-terminal domain of RAP1 is required for telomere position effects. In contrast, rif1 deletion alleles increase the frequency of repressed cells. Using the rap1t alleles to generate wild-type cells differing only in telomere tract lengths, we also show that telomere position effects are highly sensitive to changes in the size (or structure) of the telomeric tract. Longer poly(G1-3T) tracts can increase the frequency of transcriptional repression at the telomere, suggesting that telomeric poly(G1-3T) tracts play an active role in the formation or stability of subtelomeric transcriptional states.

Chromatin↗
PubMed1993

Genetic evidence that promoter P2 is the physiologically significant promoter for the pyrBI operon of Escherichia coli K-12.

The pyrBI operon of Escherichia coli K-12 encodes the two nonidentical subunits of the pyrimidine biosynthetic enzyme aspartate transcarbamylase (ATCase). Expression of this operon is negatively regulated by pyrimidine availability primarily through UTP-sensitive transcriptional attenuation and, to a lesser extent, at the level of transcriptional initiation. Previous studies indicated that the pyrBI operon was transcribed from tandem sigma 70 promoters designated P1 and P2, with the large majority of transcription initiated at the more downstream promoter P2. To more clearly define the roles of these promoters, mutations that severely impair or inactivate individual promoters were constructed in the chromosomal pyrBI operon, and their effects on ATCase synthesis were measured. In cells grown under conditions of either pyrimidine excess or pyrimidine limitation, more than 99% of all ATCase synthesis was directed by transcripts initiated at promoter P2, indicating that it is the only physiologically significant pyrBI promoter. However, mutations that effectively inactivate promoter P1 caused a 15% reduction in ATCase levels, apparently by inhibiting transcription from promoter P2 by an unknown mechanism. Support for this explanation was provided by the demonstration that little, if any, transcriptional initiation occurred at promoter P1 in a transcriptional fusion vector whereas a high level of transcription was initiated at promoter P2 in an equivalent construction. Our results also provide evidence for pyrimidine-mediated regulation of transcriptional initiation at promoter P2 over a severalfold range and show that cells can grow reasonably well with very low levels of ATCase, apparently because of changes in the concentration of allosteric effectors that increase the specific activity of the enzyme.

Aspartate Carbamoyltransferase↗
PubMed1993

Do the suprachiasmatic nuclei oscillate in old rats as they do in young ones?

The basis of the decline in circadian rhythms with aging was addressed by comparing the patterns of three behavioral rhythms in young and old rats with the in vitro rhythm of neuronal activity in the suprachiasmatic nuclei (SCN), the primary circadian pacemaker. In some old rats, rhythms of body temperature, drinking, and activity retained significant 24-h periodicities in entraining light-dark cycles; in others, one or two of the rhythms became aperiodic. When these rats were 23-27.5 mo old they were killed, and single-unit firing rates in SCN brain slices were recorded continuously for 30 h. There was significant damping of mean peak neuronal firing rates in old rats compared with young. SCN neuronal activities were analyzed with reference to previous entrained behavioral rhythm patterns of individual rats as well. Neuronal activity from rats with prior aperiodic behavioral rhythms was erratic, as expected. Neuronal activity from rats that were still maintaining significant 24-h behavioral rhythmicity at the time they were killed was erratic in most cases but normally rhythmic in others. Thus there was no more congruence between the behavioral rhythms and the brain slice rhythms than there was among the behavioral rhythms alone. These results, the first to demonstrate aberrant SCN firing patterns and a decrease in amplitude in old rats, imply that aging could either disrupt coupling between SCN pacemaker cells or their output, or cause deterioration of the pacemaking properties of SCN cells.

Aging↗