Glutamate-receptor genes in plants.
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Amino Acid Sequence↗
Biomedical subjects
J Chiu
Publications and source records attributed to J Chiu.
Vasopressin opposes locomotor stimulation by ethanol, cocaine and amphetamine in mice.
The effects of arginine8-vasopressin on the stimulation of locomotor activity induced by ethanol, cocaine and amphetamine were examined in DBA/2N mice. Locomotor activity was measured by photocell beam interruption for a period of 45 min following ethanol, cocaine or amphetamine administration. Pretreatment with vasopressin alone in a dose of 2 (but not 1) microg/mouse s.c. reduced locomotor activity. The low dose of vasopressin did not modify the stimulation of locomotor activity induced by i.p. administration of ethanol in doses of either 1.5 or 2 g/kg. The high dose of vasopressin reduced locomotor activity induced by both doses of ethanol, in an apparently additive manner. Cocaine in doses of 15 and 20 mg/kg strongly stimulated locomotor activity, but this stimulation was completely antagonized by pretreatment with 1 microg of vasopressin. Similarly, the stimulation of locomotor activity induced by amphetamine (5 mg/kg) was also blocked by pretreatment with vasopressin. These findings raise the possibility that the effect of vasopressin varies with the extent and nature of dopaminergic involvement in the drug-induced stimulation of activity. For drugs like cocaine or amphetamine which stimulate locomotor activity primarily through the mesolimbic dopaminergic system, vasopressin can completely antagonize the stimulation. For ethanol, which stimulates locomotor activity through action on a number of other neurotransmitters as well as dopamine, vasopressin treatment only reduces its stimulation of locomotor activity in an additive manner. These results suggest a close interaction between vasopressin and dopamine action.
Amphetamine↗
Motivation, recruitment, and screening of volunteers for a phase I/II HIV preventive vaccine trial in Thailand.
Data from recruitment and screening for a phase I/II preventive HIV-1 vaccine trial in Thailand were evaluated with respect to correlates of participation at each phase. Correlates included demographic variables, motivation for interest in the trial, and factors related to communication and contact. Participants were recruited at two sites through varied methods. The majority of prescreenees reported altruistic motives for interest in the trial and blood donors emerged as a group that may have been particularly altruistic. Findings indicated site differences in attrition during recruitment and screening, but not in enrollment into the vaccine trial. Blood donation and willingness to be contacted by phone at home were significantly related to making and keeping screening appointments.
AIDS Vaccines↗
Surface stiffness affects impact force during a fall on the outstretched hand.
Falls on the outstretched hand are among the most common causes of traumatic bone fracture. However, little is known regarding the biomechanical factors that affect the risk for injury during these events. In the present study, we explored how upper-extremity impact forces during forward falls are affected by modification of surface stiffness, an intervention applicable to high-risk environments such as nursing homes, playgrounds, and gymnasiums. Results from both experimental and linear biomechanical models suggest that during a fall onto an infinitely stiff surface, hand contact force is governed by a high-frequency transient (having an associated peak force Fmax1), followed by a low-frequency oscillation (having an associated lower magnitude peak force Fmax2). Practical decreases in surface stiffness attenuate Fmax1 but not Fmax2 or the magnitude of force transmitted to the shoulder. Model simulations reveal that this arises from the compliant surface's ability to decrease the velocity across the wrist damping elements at the moment of impact (which governs Fmax1) but inability to substantially reduce the peak deflection of the shoulder spring (which governs Fmax2). Comparison between model predictions and previous data on fracture force suggests that feasible compliant surface designs may prevent wrist injuries during falls from standing height or lower, because Fmax1 will be attenuated and Fmax2 will remain below injurious levels. However, such surfaces cannot prevent Fmax2 from exceeding injurious levels during falls from greater heights and therefore likely provide little protection against upper-extremity injuries in these cases.
Accidental Falls↗
Prediction of upper extremity impact forces during falls on the outstretched hand.
Among the most common causes of upper extremity fracture is a fall on the outstretched hand. Yet few data exist on the biomechanical factors which affect injury risk during this event. In this study, we measured impact forces during low-height (0-5 cm), forward falls onto the outstretched hand, and found that these are governed by an initial high-frequency peak and a subsequent, lower-frequency oscillation. This behavior was well-simulated by a two-degree-of-freedom, lumped-parameter mathematical model. Increases in body mass caused greater increases in the peak magnitude of the low-frequency component (Fmax2) than the high-frequency component (Fmax1). However, increases in fall height more strongly influenced Fmax1, which exceeded Fmax2 for all but very low fall heights. Model predictions suggest that fall heights greater than 0.6 m carry significant risk for wrist fracture, since above this height, peak forces surpass the average fracture force of the distal radius. Finally, while the shoulder experiences lower peak force than the wrist (since Fmax1 is not transmitted proximally), it undergoes considerably greater deflection, and thereby absorbs the majority of impact energy during a fall.
Accidental Falls↗
Activation of human herpesvirus 8 (HHV-8) thymidine kinase (TK) TATAA-less promoter by HHV-8 ORF50 gene product is SP1 dependent.
Human herpesvirus 8 (HHV-8) is a newly discovered virus closely associated with Kaposi's sarcoma and primary effusion lymphomas. When they occur in patients with AIDS, these B-cell lymphomas frequently harbor another human herpesvirus, Epstein-Barr virus (EBV). To determine the molecular mechanisms of the regulation of early gene expression by the immediate-early gene products of HHV-8 and to assess possible molecular interactions between HHV-8 and EBV, we studied the regulation of the HHV-8 thymidine kinase (TK) promoter in cell lines harboring either or both viruses. The constitutive chloramphenicol acetyltransferase (CAT) activity of the TK promoter was low in all six cell lines tested. A putative immediate-early gene product of HHV-8 ORF50, which is a homolog of EBV BRLF1, was cloned into an expression vector and tested for its transactivating capacity. In the presence of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), the CAT activity of the TK promoter was increased 7- to 720-fold by cotransfection with the ORF50 clone in EBV-producing cell lines (Ramos/AW, P3HR-1, and BC-1) but not in EBV-negative cell lines (BCBL-1 and Ramos), nor in the latently EBV-infected cell line Raji. The TK promoter contains three consensus SP1- and two AP1-binding sites. In electrophoretic mobility shift assays, the cellular factor SP1, but not AP1, was found to bind specifically to the TK promoter. To determine whether the increased CAT activity resulted from the interaction of SP1 with the ORF50 gene product, we introduced mutations into two SP1-binding sites. Both mutated SP1 sites had reduced SP1-binding activity and greatly decreased TK promoter responsiveness to ORF50 transactivation, suggesting that upregulation of TK promoter by ORF50 is SP1 dependent.
Base Sequence↗
Breast reconstruction in previously irradiated patients using tissue expanders and implants: a potentially unfavorable result.
There exists a paucity of definitive information on the suitability of implant reconstructions in previously irradiated breast cancer patients. This controversial topic prompted a review of our prosthetic reconstructions in this select group of patients. A retrospective study of patients treated between 1976 and 1993 with lumpectomy and radiation therapy for early breast cancer revealed 67 patients with local recurrences. Nine of these patients (10 breasts) underwent a two-stage prosthetic reconstruction following a salvage mastectomy. The average age was 47.9 years. The mean dose of irradiation was 6,070 cGy. The average interval from radiation therapy to placement of a tissue expander was 4.6 years. In one patient (10%) the tissue expander extruded. The average follow-up for 8 patients (9 breasts) who underwent exchange to a permanent prosthesis was 5.1 years. In four reconstructions (40%) there was an uneventful postoperative course. Two cases (20%) were difficult to expand and the final result lacked projection. One patient (10%) developed an infection requiring removal of the permanent prosthesis. Two patients (20%) developed Baker class III or IV capsular contractures. Overall, in our group of 10 implant reconstructions, 60% of the patients resulted in either a complication or an unfavorable result.
Breast Implantation↗
Immunolocalization of androgen receptor and estrogen receptor in the developing testis and excurrent ducts of goats.
BACKGROUND: Because of the significance of androgens and estrogens in prenatal and postanatal differentiation of the testis and excurrent ducts, it is important to understand the developmental pattern of androgen receptor (AR) and estrogen receptor (ER) in these organs. METHODS: Tissues from 1-23-week-old goats were fixed in 4% paraformaldehyde and embedded in Paraplast-plus. Antigenic sites for AR and ER were immunolocalized using the PG-21 rabbit anti-rat/human antibody and the H-222 rat anti-human monoclonal antibody, respectively. The avidin-biotin horseradish peroxidase procedure was used to identify positive immunoreactivity. Controls included incubation of sections with irrelevant IgG in place of primary antibody. RESULTS: Within the testis, immunostaining for AR in the nuclei of Sertoli cells increased gradually from mild at week 1 to strong at week > or = 19. In contrast, nuclei of peritubular myoid cells and Leydig cells exhibited moderate to strong reaction for AR in all animals. Germ cells were negative. Within the rete testis, efferent ductules, regions I-V of the epididymis, and ductus deferens, nuclei of all epithelial cells, peritubular myoid cells, and intertubular connective tissue cells expressed moderate to strong staining for AR at all ages. ER were confined to nonciliated cells of the efferent ductules, which displayed moderate staining in all animals, beginning from week 1. CONCLUSIONS: Nuclear AR staining, found in all testicular cells (except germ cells) and excurrent duct cells examined, was observed to change in an age-related manner only in Sertoli cells, where staining intensity increased between week 1 and week 19. Staining for ER, confined to nonciliated epithelial cells of the efferent ductules, was not affected by postnatal age.
Animals↗
Identification of a pathogenicity locus, rpfA, in Erwinia carotovora subsp. carotovora subsp. carotovora that encodes a two-component sensor-regulator protein.
A mutant of Erwinia carotovora subsp. carotovora, AH2552, created by a Mud1 insertion was found to be reduced in plant pathogenicity and deficient in extracellular protease and cellulase activity, although it produced normal levels of pectate lyase and polygalacturonase. A cosmid clone, pEC462, was isolated from a wild-type E. carotovora subsp. carotovora DNA library that concomitantly restored pathogenicity and protease and cellulase activities of AH2552 to wild-type levels when present in trans. The genetic locus that was disrupted in AH2552 by insertion of Mud1 has been designated rpfA, for regulator of pathogenicity factors. Sequencing of the rpfA region identified an open reading frame of 2,787 bp, and the predicted 929-amino acid polypeptide shared high identity with several two-component sensor-regulator proteins: BarA from Escherichia coli, ApdA from Pseudomonas fluorescens, PheN from P. tolaasii, RepA from P. viridiflava, LemA from P. syringae pv. syringae, and RpfC from Xanthomonas campestris pv. campestris. The RpfA locus described in this study encodes a putative sensor kinase protein that is involved in both extracellular protease and cellulase production and the pathogenicity of E. carotovora subsp. carotovora on potato tubers.
Aconitate Hydratase↗
A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells.
Mammalian cells accumulate reduced folates and methotrexate, a folate antagonist, through the reduced-folate carrier (RFC) (Goldman, I.D., Lichtenstein, N.S., and Oliverio, V.T. (1968) J. Biol. Chem. 243, 5007-5017). This study describes the isolation and expression of a cDNA clone that restores RFC activity to human breast cancer cells defective in this transporter. The cDNA cancer cells defective in this transporter. The cDNA codes for a peptide (mRFC1) of 58 kDa, whose hydropathy plot, resembling those of mammalian sugar transporters, predicts that it may be a member of a superfamily of transporter genes. Transfection of methotrexate-resistant (MTXR) ZR-75-1 cells with an expression vector, pRFC1, that codes for this peptide restores their ability to accumulate methotrexate. Furthermore, transport of methotrexate into pRFC1-transfected cells is blocked by a 10-fold molar excess of the reduced folate, 5-formyltetrahydrofolic acid, but is unaffected by folic acid. The increase in methotrexate uptake that is observed in pRFC1-transfected MTXR ZR-75-1 cells reverses their resistance to this antitumor agent.
Amino Acid Sequence↗
Identification, characterization, and physical mapping of 14 polymorphic simple sequence repeat markers on human chromosome 21.
Fourteen new dinucleotide repeat polymorphisms specific for human chromosome 21 have been identified, mapped, and characterized. The average heterozygosity of all markers was 0.66. The average PIC value was 0.61. The markers were mapped by STS content mapping of YACs previously assigned to chromosome 21. The correlation of polymorphic genetic markers with substantially complete physical maps should facilitate the identification of loci of interest on chromosome 21.
Base Sequence↗
Posttranscriptional control of glutathione S-transferase pi gene expression in human breast cancer cells.
The glutathione S-transferase pi gene (GST pi) is highly expressed in estrogen receptor negative (ER-) but not expressed in ER+ human breast cancer cell lines. To define regulatory mechanisms of GST pi gene expression, we analyzed both the activity of the GST pi promoter and the posttranscriptional fate of GST pi RNA sequences in three ER+ and three ER- breast cancer cell lines. Expression of a transiently transfected CAT reporter gene driven by the GST pi promoter and 2203 nucleotides of 5'-flanking sequences were similar in all six cell lines regardless of ER status. Endogenous GST pi transcription rates in nuclei isolated from ER- cells were quite low despite high steady state levels of cytoplasmic mRNA. Furthermore, the endogenous GST pi gene was transcribed in ER+ nuclei at rates similar to those obtained in ER- nuclei. We determined the stabilities of mRNAs transcribed from the endogenous GST pi gene (ER- cells) and from a stably transfected GST pi cDNA expression vector (ER+ and ER- cells). The endogenous GST pi mRNA was extraordinarily stable in ER- cells. Comparisons between transfected ER+ and ER- cells revealed no significant differences in the stabilities of transfection-derived GST pi mRNA sequences. We conclude that GST pi mRNA stability contributes significantly to the high levels of cytoplasmic mRNA observed in ER- cells, but that the differential expression of GST pi in ER+ versus ER- cells is governed by other posttranscriptional processes.
Breast Neoplasms↗
Treatment of Mycobacterium avium complex bacteremia in AIDS with a four-drug oral regimen. Rifampin, ethambutol, clofazimine, and ciprofloxacin. The California Collaborative Treatment Group.
OBJECTIVE: To determine the quantitative microbiologic response and the clinical response of patients with Mycobacterium avium complex bacteremia and AIDS to an oral antimycobacterial regimen. DESIGN: A phase II, multicenter clinical trial. SETTING: Four university-affiliated medical centers. PATIENTS: Forty-one patients with HIV infection who had at least two consecutive blood cultures positive for M. avium complex and who had not received previous antimycobacterial therapy were enrolled in the study. Thirty-one patients were evaluable with regard to the efficacy of the oral regimen. INTERVENTIONS: Patients received a combination of orally administered rifampin (600 mg), ethambutol (15 mg/kg body weight), clofazimine (100 mg once daily), and ciprofloxacin (750 mg twice daily) for 12 weeks. Parenterally administered amikacin, 7.5 mg/kg daily for 4 weeks after the first 4 weeks of oral therapy, was used at the discretion of the individual investigator. MEASUREMENTS: Clinical symptoms, Karnofsky scores, and adverse events were monitored. Colony counts for M. avium complex were determined. MAIN RESULTS: The mean logarithmic (log) baseline colony count decreased from 2.1 to 0.7 after 4 weeks of oral therapy (P less than 0.001). Suppression of bacteremia was sustained throughout therapy. Thirteen patients (42%) became culture negative during therapy. The mean duration of treatment was 9.7 weeks. Nineteen evaluable patients (61%) completed 12 weeks of therapy. Adverse reactions to one or more agents were common. CONCLUSIONS: A rapid reduction in symptoms and bacteremia can be achieved as early as week 2 of therapy using an oral regimen of rifampin, ethambutol, clofazimine, and ciprofloxacin. Colony counts rose dramatically after therapy was discontinued, suggesting that more prolonged periods of therapy are necessary to eradicate systemic infection.
Acquired Immunodeficiency Syndrome↗
Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. The California Collaborative Treatment Group.
OBJECTIVE: To compare pyrimethamine plus clindamycin (PC) to pyrimethamine plus sulfadiazine (PS) as a treatment for toxoplasmic encephalitis (TE) in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized, unblinded phase II, multicenter trial with provision for crossover for failure or intolerance of the assigned regimen. SETTING: University hospitals. PATIENTS: Eighty-four patients with presumptive TE were entered. Thirteen were excluded when they were found to have another diagnosis, and 12 were excluded because they did not meet entry criteria. The baseline characteristics in the remaining 26 patients randomized to PC and 33 randomized to PS were comparable. INTERVENTIONS: Patients were treated for 6 weeks with pyrimethamine and folinic acid plus either sulfadiazine or clindamycin. Clindamycin was given intravenously during the first 3 weeks. MEASUREMENTS AND MAIN RESULTS: There was a trend toward greater survival in patients randomized to PS (hazard ratio, 3.25; 95% CI, 0.63 to 16.8; P = 0.13), but most study deaths were not directly related to TE. In contrast, patients randomized to PC appeared more likely to achieve complete clinical (odds ratio, 0.67; CI, 0.2 to 1.97; P greater than 0.2) and radiologic responses (odds ratio, 0.28; CI, 0.08 to 0.96; P = 0.02). Multivariate analysis revealed drug effects to be largely independent of other variables. Similar efficacy of the treatments was also suggested by a hazard analysis of resolution of abnormal mental status, fever, and headache. Skin rash was the most common adverse event in both treatment arms. Because of toxicity, six patients randomized to PC and 11 patients randomized to PS had to switch to the alternate treatment, but only three were unable to complete therapy after crossover. CONCLUSIONS: The results of several end points of efficacy, taken together, suggest that the relative efficacy of PC approximately equals that of PS. PC appears to be an acceptable alternative in patients unable to tolerate PS.
Acquired Immunodeficiency Syndrome↗
Length of stay and survival after intensive care for severe Pneumocystis carinii pneumonia. A prospective study. California Collaborative Treatment Group.
Survival rates for persons receiving intensive care for Pneumocystis carinii pneumonia have improved. However, the utility of prolonged intensive care for patients who do not show initial improvement remains unclear. We assessed survival in a nested cohort study of patients receiving intensive care while participating in a randomized trial of early adjunctive corticosteroids for Pneumocystis pneumonia. Twenty-eight of 251 (11 percent) participants were admitted to an intensive care unit. Fourteen (50 percent) of these were discharged alive from the intensive care unit and 11 (39 percent) were discharged alive from the hospital. Survivors and nonsurvivors were similar demographically and with respect to treatment received but differed in the mean days of intensive care received (4.5 vs 8.6 [p = 0.02]). The conditional probability surviving to hospital discharge after intensive care dropped steadily from 39 percent at intensive care unit admission to 17 percent after one week and to 0 percent after two weeks.
Adrenal Cortex Hormones↗
Fluconazole treatment of persistent Cryptococcus neoformans prostatic infection in AIDS.
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Acquired Immunodeficiency Syndrome↗
A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group.
BACKGROUND AND METHODS: In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high. We conducted a controlled, double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole. At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis. The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase. RESULTS: Of 84 patients initially enrolled, 16 (19 percent) were found to have silent, persistent infection on the basis of cultures that became positive after entry into the study; 7 other patients were lost to follow-up shortly after entry. Of the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34 assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to 53). Of the 11 recurrent infections, 7 were detected in urine obtained after prostatic massage. There were four recurrent meningeal infections in the patients taking placebo, but none in those taking fluconazole (mean duration of follow-up, 164 days) (P = 0.03). In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1). Survival and toxicity were similar in the two maintenance-treatment groups. CONCLUSIONS: In patients with AIDS, silent persistent infection is common after clinically successful treatment for cryptococcal meningitis. Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection.
Acquired Immunodeficiency Syndrome↗
Treatment of acute toxoplasmosis with intravenous clindamycin. The California Collaborative Treatment Group.
The interim results are presented of an ongoing large-scale, prospective, randomized study to determine the potential role of clindamycin in the treatment of toxoplasmic encephalitis. Patients were seropositive for Toxoplasma gondii antibodies and had clinical signs compatible with toxoplasmic encephalitis. Data was available on 33 patients, 15 of whom received pyrimethamine p.o./clindamycin i.v. and then p.o., and 18 of whom received pyrimethamine p.o./sulfadiazine p.o. The interim evaluation did not reveal a remarkable difference between the two regimens in the clinical or radiologic response. Adverse reactions to both regimens were common and frequently multiple, there being more adverse gastrointestinal reactions in patients on pyrimethamine/clindamycin and more adverse hematological reactions in those on pyrimethamine/sulfadiazine.
Acquired Immunodeficiency Syndrome↗