Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of L cells with 3 to 10 mM 3':5'-cyclic adenosine monophosphate (cAMP) in the presence of interferon was found to potentiate the development of antiviral activity. The dose response of interferon activity at various time periods in the presence and absence of cAMP indicated that potentiation of interferon activity by cAMP occurred at an early stage in the development of antiviral activity. Among the analogues of cAMP tested for interferon-potentiating activity, only the acylated derivatives were found to be active. Combined L-epinephrine and theophylline treatment of cells elevated cellular cAMP levels and also potentiated interferon-mediated antiviral activity. Interferon was also found to elevate cAMP levels in L cells. This activity was limited to biologically active interferon and antagonized the depression of cAMP associated with vesicular stomatitis virus (VSV) infection of L cells. These observations suggest that some aspects of interferon's biological activity is associated with an alteration in cellular levels of cAMP.
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PMID:Cyclic AMP potentiation of interferon antiviral activity and effect of interferon on cellular cyclic AMP levels. 17 Mar 77

Temperature-sensitive (ts) mutants of vesicular stomatitis virus belonging to complementation groups III and V were investigated for their in vivo RNA synthesis. The sucrose gradient patterns of the RNA species which they produced at nonpermissive temperature (39.2 degrees C) were systematically compared under different experimental conditions: variation of input multiplicity and of time of infection, superinfection with T particles, and temperature shifts. Finally, a more precise analysis of the various RNA species synthesized was carried out. It appeared that the characteristics of RNA synthesis specified at 39.2 degrees C by tsIII or tsV mutants differed from the normal RNA synthesis of vesicular stomatitis virus wild type. Their common depression at 39.2 degrees C in virion-like RNA (38S) production--i.e., so-called genome replication--was tentatively paralleled with the concomitant ts events which have been previously shown to affect the two viral envelope proteins. An overproduction of the RNA transcripts was described for mutants in group III and posed the question of a regulation process to determine the amount of RNA to be transcribed.
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PMID:Envelope proteins and replication of vesicular stomatitis virus: in vivo effects of RNA+ temperature-sensitive mutations on viral RNA synthesis. 21 12

Adriamycin was administered to 60 adults and 21 children by 3 different dosage schedules: 22.5 mg/sq m (0.6 mg/kg) daily for 4 days, 15 mg/sq m (0.4 mg/kg) every 8 hr for a total of 6 doses, and 50 to 120 mg/sq m as a single dose every 3 to 4 weeks. Objective responses lasting more than 1 month occurred in 5 subjects with acute leukemias or lymphoma, 3 with transitional cell carcinomas, 2 with sarcomas, 2 with Ewing's sarcoma and 1 each with bronchogenic carcinoma, orchidoblastoma, and thymoma. Toxic reactions included nausea, vomiting, stomatitis, alopecia, and hematopoietic depression, but significant cardiac toxicity occurred in only 1 patient. Pharmacokinetic data, collected in 25 patients by fluorometric and chromatographic assay, suggested a biphasic plasma clearance of drug with initial and secondary half-lives of about 1.5 and 14 to 21 hr, respectively. When drug was given every 8 hr there was evidence of loss of an initial very rapid phase of distribution of adriamycin and its metabolites. Urinary excretion accounted for 3.4 to 38.1% of administered fluorescence over a 72-hr period; in the first 24 hr, between 48.2 and 100% of this urinary material was in the form of adriamycin; leter, this fraction declined. No adriamycin or its fluorescent metabolites could be extracted from the stools.
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PMID:Clinical effects and pharmacokinetics of different dosage schedules of adriamycin. 94 83

Preliminary data are presented of a clinically feasible pilot study to select a significant subgroup of patients among those with muscle-invading bladder tumors for local cure and bladder preservation, while also to offer all patients the possibility of preventing the development of distant metastases. Transurethral debulking surgical resection was combined with neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy plus 2 additional courses of cisplatin and 4,000 cGy. If tumor was found on cystoscopic re-evaluation by biopsy and for cytology after cisplatin and partial irradiation (4,000 cGy.) immediate cystectomy was advised. If tumor was not found consolidation by a radiotherapy boost to a total of 6,480 cGy. plus 1 additional course of cisplatin was given. Of 53 consecutive patients the planned treatment was completed in 42 (79%). With a median followup of 26 months (range 15 to 42 months), 72% of all entered patients were alive, 70% have not required cystectomy and 74% have not had distant metastases. Among the 42 patients who completed the planned protocol chemotherapy dose reductions were required in 39% for stomatitis, bone marrow depression and/or renal dysfunction. There were 2 serious complications but no treatment-related sepsis, deaths or significant renal dysfunction. Eight patients underwent immediate radical cystectomy because of positive biopsy and/or cytology results after 4,000 cGy., while 34 completed full chemotherapy and radiotherapy without any significant bladder or bowel injury. Of 42 patients 22 (52%) have maintained the bladder without any recurrence, and of those selected for full chemotherapy and radiotherapy this number increased to 65%. To date 12 patients have persistent or recurrent bladder tumors: 5 (15%) had invasive tumors treated by cystectomy and 7 (21%) had carcinoma in situ treated by intravesical therapy. The true success of this or other selective bladder-preserving treatments will require 3 to 5 years of followup to be confident that such treatment has sterilized the bladder of cancer. This feasibility study has been clinically practical, modestly well tolerated and encouraging for the significant proportion of patients with a sustained complete response and for the 70% over-all survival rate at 2 years. To evaluate critically the efficacy of methotrexate, cisplatin and vinblastine chemotherapy in the prevention of occult distant micrometastases and in increasing the rate of successful bladder preservation, in May 1988 we began a randomized phase 3 trial with and without neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy.
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PMID:Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy and combined pelvic irradiation plus cisplatin chemotherapy. 212 7

From June 1986 to November 1989, 7 patients (pts.) with transitional bladder cancer were treated with CDDP 70 mg/m2 i.v. on day 1 and MTX 40 mg/m2 i.v. on days 8 and 15. The initial stage was T2 N0 M0 (2), T2 N0 M0 (8), T4 N0 M0 (4) and T3-4 N+ M0 (3). The median age was 56 years. After a median number of two cycles (1-5) of CDDP-MTX, 3/17 pts. (17.6%) had a complete remission (CM), 9/17 pts. (53%) a partial response (PR) greater than 50%, 4/17 pts. (23.4%) a PR less than 50%, 1/17 pts. (6%) a stable disease. Nausea and vomiting occurred in almost all pts., 20% of pts. had grade 3 stomatitis, 35% of pts. had diarrhoea, 20% of pts. had conjunctivitis, 7% of pts. had a bone marrow depression and hair loss. One patient had severe renal and liver toxicity and grade 4 bone marrow suppression with sepsis, completely controlled after intensive care. The treatment after neoadjuvant chemotherapy was: radical cystectomy (11)- in one following radiotherapy -; partial resection + lymphoadenectomy (2); TUR (4) in 1 pt. with lymphoadenectomy. After a median follow-up of 28 months (6-36), 12/17, equivalent to 71% of pts. are disease free, 3/17 (17%) are alive with disease, 2/17 (12%) died. In conclusion the association of neoadjuvant CDDP-MTX can induce a high percentage of response, and can preserve bladder function in some patients. Further controlled trials and a longer follow-up are needed to better define the exact role of this combination in terms of disease free survival, total survival and quality of life.
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PMID:[Neoadjuvant chemotherapy using cisplatin (CDDP) and methotrexate (MTX) in carcinoma of the bladder]. 214 9

The amount of iododeoxyuridine (IdUrd) incorporated into DNA determines the degree of radiosensitization. Fluorodeoxyuridine (FdUrd) has been shown to biochemically modulate IdUrd incorporation into DNA in vitro and in vivo. In this Phase I study, these drugs were coadministered to patients during 14-day continuous i.v. infusion periods in order to investigate whether the incorporation of IdUrd into DNA in vivo could be increased without increasing the dose of IdUrd. IdUrd plasma concentrations and incorporation of IdUrd into DNA of granulocytes were measured by high-performance liquid chromatography. Up to 8.8% substitution of thymidine by IdUrd was observed. Even at 3.5 mg/m2/day FdUrd for 14 days (78% of the maximum-tolerated dose as a single agent), no clinically relevant enhancement of incorporation of IdUrd into DNA of granulocytes was observed. Also, no changes in plasma levels of IdUrd were observed with escalating doses of FdUrd. Toxicity patterns (stomatitis, diarrhea, and bone marrow depression) and isobologram analysis suggested that IdUrd and FdUrd had additive, rather than synergistic, effects.
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PMID:Fluorodeoxyuridine modulation of the incorporation of iododeoxyuridine into DNA of granulocytes: a phase I and clinical pharmacological study. 296 70

Methotrexate, Cisplatin, and Vinblastine (MCV) was followed by Cisplatin plus radiation therapy in 19 patients with muscle-invading clinical Stage T2-4NXM0 transitional cell carcinoma of the urinary bladder (including cystectomy candidates), to achieve local control and prevent distant metastases. Radical cystectomy was recommended for all patients who failed to reach a complete response (CR = biopsy negative and cytology not positive) following MCV and Cisplatin X 2 plus 4000 cGy. Completely responding patients, and those partially responding patients unsuited for cystectomy, were selected for bladder conservation treated with additional irradiation to the bladder tumor volume (total 6,480 cGy) plus one additional Cisplatin treatment. Dose reductions were required for stomatitis in 26%, mild bone marrow depression in 58%, and renal toxicity in 5% of the patients. During the Cisplatin/4000 cGy, mild dysuria occurred in 68% of patients and 36% had mild bowel hyperactivity. Serious complications have occurred in two patients to date. One patient had recurrent pulmonary emboli, marked reduction in bladder capacity, and diarrhea. A second had bladder perforation during cystoscopic evaluation after MCV and a small bowel obstruction after Cisplatin and 4000 cGy. There was no treatment-related sepsis. Three patients had initial complete transurethral resection of their tumors and therefore 16 patients are evaluable for tumor responsiveness to this protocol. Four patients (25%) were biopsy negative and cytology negative, whereas three additional patients (19%) were biopsy negative but cytology positive following initial MCV. Six patients (38%) were biopsy negative and cytology negative whereas three additional patients (19%) were biopsy negative and cytology positive following MCV and Cisplatin X 2 plus 4000 cGy pelvic radiation. Of the entire group, 9 patients were treated with full-dose radiotherapy. All of these patients are alive without evidence of tumor on rebiopsy of the original tumor site, but one has a persistent positive cytology. Seven patients had a radical cystectomy and 6 are disease free. The treatment of 3 patients deviated from the protocol. Overall, only one patient has developed distant metastases and currently 84% of the patients are disease-free, although follow-up is short. To date, this feasibility study has been clinically practical and well tolerated. The proportion of CR's suggests that this program may prove to be an organ-sparing and curative approach for a significant number of patients, but more experience and follow-up are required.
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PMID:Invasive bladder carcinoma: preliminary report of selective bladder conservation by transurethral surgery, upfront MCV (methotrexate, cisplatin, and vinblastine) chemotherapy and pelvic irradiation plus cisplatin. 318 28

Eighteen patients with advanced malignancies refractory to other forms of treatment were given dactinomycin (Act D) as continuous intravenous infusions. Their median age was 51 years (range, 36-67); their median performance status was 50 (range, 40-90) on the Karnofsky scale. Act D was administered continuously for 5 days, utilizing a central venous line and a perfusion pump. The starting dose was 0.1 mg/m2/24 hours X 5 days (total dose, 0.5 mg/m2) and was escalated according to a modified Fibonacci scale to 0.2, 0.33, and 0.5 mg/m2/24 hours X 5 days, respectively. Three, three, four, and eight patients were entered, respectively, in each dose level. Toxicities observed were: leukopenia in four patients (nadir leukocyte count less than 1000 cells/nm3 in one patient and 2000-3000 cells/mm3 in 3 patients); thrombocytopenia, with nadir platelet counts between 50,000 and 100,000 platelets/mm3 in 2 patients; stomatitis in four patients; and nausea in three patients. Vomiting was not observed during the infusions. Two patients may have had a radiation recall phenomenon. Blood count depression, nausea, and mucositis were transient, resolving after a few days. One patient at level IV died of sepsis, which was diagnosed on the fourth day of the infusion, before leukopenia intervened. No objective responses were seen. It was concluded that a higher dose of Act D can be given by continuous infusion than by a bolus injection; the authors recommended 0.5 mg/m2/day X 5 days (total dose, 2.5 mg/m2) for further studies.
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PMID:A phase I trial of dactinomycin intravenous infusion in patients with advanced malignancies. 400 96

9-beta-d-Arabinofuranosyladenine (Ara-A) effectively inhibited the production of infectious vesicular stomatitis virus (VSV) in MDBK cells. Furthermore, inhibition was shown to begin as early as the first 3 hr of infection. Studies employing (3)H-l-leucine indicated that Ara-A did not affect protein synthesis in uninfected cells, although it did cause a marked stimulation of protein synthesis in VSV-infected cells during the log phase of the growth cycle. Puromycin, an inhibitor of protein synthesis, was a more effective viral inhibitor than Ara-A. However, the combination of Ara-A and puromycin was less effective than puromycin alone except when present for long time periods. Short-term labeling experiments with (3)H-uridine demonstrated that Ara-A depressed ribonucleic acid (RNA) synthesis in uninfected cells, whereas periods of stimulation and depression of radioisotope incorporation occurred in infected cells. The results support the notion that Ara-A is incorporated into RNA early during viral replication.
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PMID:Inhibition of vesicular stomatitis virus replication by 9-beta-D-arabinofuranosyladenine. 436 72

Susceptibility of eight strains of influenza A and B viruses to interferon and to poly(I) . poly(C) were determined by the plaque reduction method. All strains tested were slightly less susceptible than vesicular stomatitis virus (VSV) in an established line of canine kidney (MDCK) cells. The 50% plaque depression doses (PD50) of poly(I) . poly(C) for influenza A and B viruses were as high as 3.0- to 4.5-fold and 6- to 18-fold that for VSV, respectively. The amounts of interferon required to inhibit plaque formation of influenza A and B viruses by 50% were 3.0-6.2 and 7.3-15.2 units/ml, respectively. The ratio of PD50 of poly(I) . poly(C) for each strain of influenza viruses tested to that for VSV in chick embryo cells was almost the same as in MDCK cells. Furthermore, in chick embryo cells, the strains of influenza virus tested were demonstrated to be much more susceptible to poly(I) . poly(C) than both Newcastle disease virus and vaccinia virus. It is suggested that influenza viruses may be relatively susceptible to interferon and to poly(I) . poly(C).
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PMID:Susceptibility of influenza viruses to interferon and to poly(I) . Poly(C) determined by the plaque reduction method. 615 60


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