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R Rodriguez

Publications and source records attributed to R Rodriguez.

At least 127 records · Page 7Linked to original sources

Homology modeling, model and software evaluation: three related resources.

MOTIVATION: Homology modeling is rapidly becoming the method of choice for obtaining three-dimensional coordinates for proteins because genome projects produce sequences at a much higher rate than NMR and X-ray laboratories can solve the three-dimensional structures. The quality of protein models will not be immediately clear to novices and support with the evaluation seems to be needed. Expert users are sometimes interested in evaluating the quality of modeling programs rather than the quality of the models themselves. RESULTS: Three servers have been made available to the scientific community: a homology modeling server, a model quality evaluation server and a server that evaluates models built of proteins for which the structure is already known, thereby implicitly evaluating the quality of the modeling program. AVAILABILITY: The modeling-related servers and several structure analysis servers are freely available at http://swift.embl-heidelberg.de/servers/ CONTACT: gert.vriend@embl-heidelberg.de

Computational Biology↗

Double modulation of 5-fluorouracil by methotrexate and high-dose L-leucovorin in advanced colorectal cancer.

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and L-leucovorin (L-LV) in patients with advanced recurrent (inoperable) or metastatic colorectal carcinoma (ACC). Between July 1993 and October 1995, 41 patients with ACC received a regimen that consisted of MTX 150 mg/m2 i.v., infused over a 20-minute period at hour 0, followed 19 hours later by L-LV 250 mg/m2 in a 2-hour i.v. infusion. 5-FU, 900 mg/m2, was administered by i.v. push injection at hour 20. Beginning 24 hours after MTX administration, all patients received four doses of L-LV, 15 mg/m2 i.m., every 6 hours. Cycles were repeated every 15 days. Two patients were not assessable for response. Objective regression was observed in 11 of 39 (28%) patients, [95% confidence interval (CI), 14-42%]. One (2%) patient achieved complete response (CR) and 10 (26%) partial response (PR). No change was recorded in 15 (39%) patients and progressive disease was noted in 13 (33%) patients. The median time to treatment failure was 6 months and the median survival time was 10 months. Toxicity was within acceptable limits, but one therapy-related death due to severe leukopenia was observed. The dose-limiting toxicity was mucositis. Eight episodes of grade 3 or 4 stomatitis were observed, and were responsible for dosage modifications of MTX and 5-FU. In conclusion, further in experimental and clinical studies are clearly necessary in order to design the best modulatory strategy of 5-FU.

Adult↗

Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma.

A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.

Adult↗

Influence of genistein (4',5,7-trihydroxyisoflavone) on the growth and proliferation of testicular cell lines.

The effects of genistein on testicular cells, TM3, TM4, and GC-1 spg, were studied in vitro. First, each cell line was cultured with pre-determined concentrations of genistein for a maximum of 72 h to assess the effects of genistein on in vitro growth of the test cells. A second series of experiments were performed to determine the degree of genistein-induced apoptosis in these cells, using Apop-Tag kit reagents, to detect apoptotic cells in situ by specific end labeling, and detection of DNA fragments produced by the apoptotic process. The results obtained indicate that: i) genistein inhibits the growth and proliferation of testicular cells; ii) growth inhibition and proliferation is dose- and exposure-time dependent; iii) there is significant difference in sensitivity of the different testicular cells to genistein; iv) genistein induces apoptosis in testicular cells in a concentration-dependent manner. Genistein-induced apoptosis identifies genistein as a potential diagnostic and therapeutic tool in testicular pathophysiological research.

Animals↗

Care for Canada's frail elderly population: fragmentation or integration?

Budget constraints, technological advances and a growing elderly population have resulted in major reforms in health care systems across Canada. This has led to fewer and smaller acute care hospitals and increasing pressure on the primary care and continuing care networks. The present system of care for the frail elderly, who are particularly vulnerable, is characterized by fragmentation of services, negative incentives and the absence of accountability. This is turn leads to the inappropriate and costly use of health and social services, particularly in acute care hospitals and long-term care institutions. Canada needs to develop a publicly managed community-based system of primary care to provide integrated care for the frail elderly. The authors describe such a model, which would have clinical and financial responsibility for the full range of health and social services required by this population. This model would represent a major challenge and change for the existing system. Demonstration projects are needed to evaluate its cost-effectiveness and address issues raised by its introduction.

Aged↗

Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells.

Prostate-specific antigen (PSA) is a widely used marker for the diagnosis and management of prostate cancer. Minimal enhancer/promoter constructs derived from the 5' flank of the human PSA gene (prostate-specific enhancer) were inserted into adenovirus type 5 DNA so as to drive the E1A gene, thereby creating a prostate-specific enhancer-containing virus, CN706. E1A was expressed at high levels in CN706-infected human PSA-producing LNCaP cells but not in CN706-infected DU145 cells, which are human prostate cells that do not express PSA. The titer of CN706 was significantly higher in LNCaP cells compared to several human cell lines that do not produce PSA (HBL100, PANC-1, MCF-7, DU145, and OVCAR3). Furthermore, in LNCaP cells, the yield of CN706 was dependent on exogenous androgen (R1881). CN706 destroyed large LNCaP tumors (1 x 10(9) cells) and abolished PSA production in nu/nu mouse xenograft models with a single intratumoral injection.

Adenovirus E1A Proteins↗

An unusual effect of application of the amino acid L-arginine on cat visual cortical cells.

Iontophoretic application of L-arginine (L-Arg) resulted in a profound decrease in visually elicited and spontaneous activity in 22 of 77 (29%) cells in area 17 of the anaesthetized/paralysed cat. Duration was long, and cells did not recover pre-application activity levels, indicating permanent decline. This effect was obtained without change in the extracellularly recorded wave-form, demonstrating that this did not result from depolarization block. In the remaining 55 cells, application of L-Arg alone, at levels capable of eliciting inhibition as described above, was without effect. In 29 cells, L-Arg application was able to reverse the effect of inhibition of nitric oxide (NO) production. Populations of cells showing the depressive effect described above and those affected by NO modulation levels were mutually exclusive.

Action Potentials↗

Follow-back study of oldest workers with emergency department-treated injuries.

The aging of the U.S. workforce highlights the need to address issues affecting older workers specifically. Telephone surveys were conducted with injured workers identified through a surveillance system based in a sample of emergency departments in the United States. The 176 interviewed cases correspond to a national estimate of 8,263 (s.e. = 1,258) injuries to workers aged 63 years and older during May 15-September 30, 1993. Five percent reported limitations in the types or amount of work they could perform prior to the injury. Ninety-four percent reported familiarity with the task resulting in injury. Fifty-one percent returned to work without missing any workdays; however, 69% required return visits to a health care provider. Thirty-four percent reported receiving training in injury prevention. Twenty percent of the injured workers were self-employed and 43% worked for small businesses. Data from this study provide insight into routinely collected statistics and have implications for future research and intervention efforts.

Accidents, Occupational↗

Perirenal MR high signal--a new and sensitive indicator of acute ureteric obstruction.

PURPOSE: This study was carried out to determine the incidence of perirenal magnetic resonance (MR) high signal in acute ureteric obstruction as demonstrated by half-Fourier acquisition single shot turbo spin-echo (HASTE) MR. In addition, we evaluated the sensitivity of this perirenal MR high signal as a predictor of acute ureteric obstruction. MATERIALS AND METHODS: A prospective evaluation of 55 consecutive patients with suspected ureteric obstruction was carried out using the HASTE MR sequence. Images were compared to concurrent IV urography (IVU) or to computed tomography (CT) where these were available. Acute and chronic ureteric obstruction were differentiated by clinical evaluation. RESULTS: Forty-one patients had obstructed kidneys. HASTE MR accurately predicted the presence of acute ureteric obstruction in 20/23 (87%) based on presence of perirenal MR high signal. None of these showed evidence of contrast medium extravasation on the concurrent i.v. urogram. 15/18 (83%) chronically obstructed kidneys demonstrated no perirenal high signal on HASTE MR, and the remaining three showed only a trace of perirenal high signal. CT showed perirenal stranding in only 2/8 patients with acutely obstructed kidneys. CONCLUSION: In acute ureteric obstruction, HASTE MR shows perirenal high signal intensity much more commonly than IVU shows extravasation or CT showing perirenal stranding. The origin of this MR signal is uncertain but may represent oedema, lymphatic distension or free fluid from forniceal rupture. HASTE MR can accurately distinguish between acute and chronic ureteric obstruction based on the degree of perirenal high signal.

Acute Disease↗

Temporary balloon protection as an adjunct to endosaccular coiling of wide-necked cerebral aneurysms: technical note.

OBJECTIVE: We present an endovascular technique for treating wide-necked cerebral aneurysms using Guglielmi detachable coils (Target Therapeutics, Fremont, CA) and simultaneous temporary balloon protection. The temporary balloon serves as a mechanical external force to mold the microcoils away from the parent artery. METHODS: Two illustrative cases of wide-necked cerebral aneurysms treated with Guglielmi detachable coils and a temporary balloon are presented. Emphasis is placed on the technical aspects of the approach, with several variations. The first case involves a left posterior cerebral artery aneurysm at the P1/P2 segment, and the second case involves a left paraclinoid internal carotid artery aneurysm. Both patients suffered from subarachnoid hemorrhage, but neither was a candidate for craniotomy. In each case, the coils, when used alone, protruded into the parent artery and were therefore removed. Then a temporary balloon was inflated for mechanical protection during coil deployment. RESULTS: The use of simultaneous temporary balloon protection allowed more dense intra-aneurysmal coil packing, especially in the neck, without parent artery compromise, than did the use of Guglielmi detachable coils alone. CONCLUSION: Endovascular treatment of wide-necked cerebral aneurysms can be facilitated by simultaneous temporary balloon protection.

Aneurysm, Ruptured↗

Dystonia associated with crack cocaine use.

Cocaine is a substance that has significant central stimulant action in the central nervous system. As cocaine abuse spreads throughout society, many neurologic side effects are appearing with increasing frequency. These side effects include seizures, tremor, focal neurologic deficits, headache, and dizziness. Recently, there have been reports of movement disorders associated with cocaine use. Cocaine use increases the incidence of acute dystonic reactions in patients being treated with dopamine blocking agents. There have also been rare reports of cocaine causing dystonia in patients who were taking no other street drugs or medications. Our report describes the case of a patient who had an acute dystonic reaction 12 hours after a crack cocaine binge.

Adult↗

Syphilis in injecting drug users: clues for high-risk sexual behaviour in female IDUs.

The objective was to measure the gender-specific differences for syphilis and for the sexual transmission of human immunodeficiency virus (HIV) in a cross-sectional analysis of injecting drug users (IDUs) admitted to detoxification between February 1987 and January 1990. HIV was determined by enzyme-linked immunosorbent assay (ELISA) and confirmed with Western blot. For syphilis reactive samples to a rapid plasma reagent (RPR) were confirmed with treponemal tests (FTA-ABS or MHA-TP). Of the 386 heterosexual IDUs, 68% were HIV-positive and 4.7% had serologic syphilis (RPR and FTA-ABS or MHA-TP positive). Syphilis was higher in women (12%) than in men (3%), and women reported a significantly (P < 0.001) higher number of sex partners. Men had an IDU as a sex partner more often than women did (P = 0.001). Serologic syphilis in women was associated with having had more than one sexual partner in the previous year (P = 0.028) but this association was not present in men. HIV infection was not associated with syphilis in male IDUs. However, HIV was present in all women with syphilis that reported more than one partner.

Adolescent↗

Cloning and characterization of RAD17, a gene controlling cell cycle responses to DNA damage in Saccharomyces cerevisiae.

Mutants of the yeast Saccharomyces cerevisiae defective in the RAD17 gene are sensitive to ultraviolet (UV) and gamma radiation and manifest a defect in G2 arrest following radiation treatment. We have cloned the RAD17 gene by complementation of the UV sensitivity of a rad17-1 mutant and identified an ORF of 1.2 kb encoding a predicted gene product of 45.4 kDa with homology to the Schizosaccharomyces pombe rad1+ gene product and to Ustilago maydis Rec1, a known 3'->5'exonuclease. The RAD17 transcript is cell cycle regulated, with maximum steady-state levels during late G1. The rad17-1 mutation represents a missense mutation that maps to a conserved region of the gene. A rad17 disruption mutant grows normally and manifests levels of UV sensitivity similar that of the rad17-1 strain. As previously observed with other genes involved in G2 arrest (such as RAD9 and RAD24), RAD17 regulates radiation-induced G1 checkpoints at at least two possible arrest stages. One is equivalent to or upstream of START, the other at or downstream of the Cdc4 execution point. However, the temperature sensitivity of the cell cycle mutant dna1-1 (a G1 arrest mutant) is not influenced by inactivation of RAD17.

Amino Acid Sequence↗

Radiation therapy for renal transplant rejection refractory to pulse steroids and OKT3.

PURPOSE: To determine the response rate and kidney graft survival following local irradiation to the transplanted renal graft undergoing persistent rejection after medical management including pulse steroids and OKT3. The role of radiation for renal transplant rejection after failure of OKT3 has not been previously reported. METHODS AND MATERIALS: From July 1, 1988 to July 1, 1994, 72 consecutive patients with kidney graft rejection were treated with local irradiation to the transplanted renal graft following failure of medical management. All patients received pulse steroids and OKT3, an anti-CD3 immunosuppressant. Patients who failed to respond to methylprednisolone and OKT3 therapy were referred for radiation therapy. The median time from the diagnosis of rejection to irradiation was 8 days. All kidney grafts received local graft irradiation to a total of 8 Gy delivered in four daily fractions. RESULTS: Sixty (83%) patients initially responded to radiotherapy at 7 days after completion of radiotherapy, as defined by a decrease in serum creatinine. Thirty-five responding patients have not experienced a second episode of graft rejection. Overall, 43 (60%) patients have renal graft survival, with a median follow-up of 16 months (range of 6-73 months)> CONCLUSION: It is concluded that there is a subgroup of kidney graft patients undergoing graft rejection who are refractory to pulse steroids and OKT3 therapy where irradiation may be an effective modality with high rates of response and a moderate rate of graft survival. However, a prospective, randomized trial in these medically refractory patients is needed to ascertain whether these results are clinically significant.

Cohort Studies↗