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Biomedical subjects

A Fields

Publications and source records attributed to A Fields.

29 records · Page 2Linked to original sources
PubMed1992

Systemic infusion versus bolus chemotherapy with 5-fluorouracil in measurable metastatic colorectal cancer.

From January 31, 1986 to January 31, 1989, 184 eligible patients were enrolled in a randomized study of either infusional or bolus 5-fluorouracil (5-FU) for the treatment of metastatic measurable colorectal cancer. Infusion was administered at an escalated dose schedule starting at 350 mg/m2 per day for 2 weeks with a 2-week rest period on a monthly basis, while bolus 5-FU was started at 400-450 mg/m2 for 5 days every 28 days. In these chemotherapy-naive patients with good performance status, the infusion arm produced a response in 11 of 88 patients versus 6 of 82 in the bolus arm (p = 0.384). Progression free survival was significantly longer (p = 0.0139) in the infusion group (3.8 versus 2.3 months), but no significant difference in survival was observed (p = 0.207). As expected, the toxicities of the regimens were different in character, but each had approximately a 20% incidence of significant toxicities. Neither of these methods of administering fluorouracil results in an exceptional response rate, nor does the infusion have an impact on survival as compared to the bolus route. If this type of complicated infusional approach is to continue, especially with increasing dosage (which could be accomplished on our schedule), randomized studies with survival as an endpoint must remain the gold standard.

Adult↗
PubMed1990

Identification of a novel transforming growth factor-beta (TGF-beta 5) mRNA in Xenopus laevis.

A novel transforming growth factor-beta (TGF-beta) mRNA of about 3.0 kilobases, which encodes a putative protein of 382 amino acids, has been identified in amphibians by cDNA cloning. This mRNA, which we designate as TGF-beta 5, is developmentally regulated and highly expressed beginning at early neurula (stage 14) and in many adult tissues in Xenopus laevis. Following the first methionine, the putative precursor protein has a hydrophobic region, approximately 22 amino acids long, which probably represents a signal sequence, similar to that found in TGF-beta s 1-3. The precursor also has potential sites for glycosylation, integrin binding (RGD), and a tetrabasic amino acid (RKKR) site for potential cleavage of the precursor peptide to a biologically active protein. The putative mature protein consists of 112 amino acids with 9 cysteines and has 76, 66, 69, and 72% identity to TGF-beta s 1-4, respectively.

Amino Acid Sequence↗
PubMed1984

D,L-alpha-difluoromethylornithine inhibits human cytomegalovirus replication.

D,L-alpha-Difluoromethylornithine (DFMO) is an inhibitor of ornithine decarboxylase, the first enzyme in the polyamine biosynthetic pathway. Exposure of human foreskin fibroblast cells to DFMO before their infection with human strains of cytomegalovirus (CMV) resulted in a reduction in the amount of infectious virus produced. A 3-day exposure to the drug was required to elicit maximal antiviral effect. Cells exposed to DFMO at the time of infection produced normal amounts of infectious virus. Preexposure to the drug for 1, 2, or 3 days before infection resulted in at least 10-, 100-, or 1,000-fold decreases, respectively, in the amount of infectious virus produced. This decrease paralleled the loss of intracellular spermidine and was partially spared by the addition of exogenous putrescine, spermidine, or spermine (10 microM). When added 3 days before infection, DFMO depressed production of herpes simplex virus and simian CMV, as well as wild-type and laboratory prototype strains of human CMV. Although some antiviral effect was observed at a drug concentration of 1 mM, 10 mM gave a stronger effect and was the amount routinely used. At 30 mM DFMO, growth of noninfected cells was slowed but not arrested. Studies to investigate the level at which DFMO interferes with CMV replication showed that DFMO-treated, infected cells (i) exhibit a typical CMV-specific cytopathic effect, (ii) synthesize both viral proteins and viral DNA, (iii) contain at least some capsid forms, and (iv) shed greatly reduced amounts of virus particles into the growth medium. Since CMV virions, like those of herpes simplex virus, contain the polyamines spermidine and spermine, and since DFMO essentially eliminates the pool of intracellular spermidine, the possibility is suggested that this drug may exert its antiviral effect by interfering with virus assembly, perhaps at the level of DNA packaging or capsid envelopment or both.

Cells, Cultured↗
PubMed1983

Infection in artificial blood pump implantation.

Infection has been observed in artificial heart experimentation to be of early onset and generally within the first 2 postoperative weeks. The organisms most often detected in blood cultures were Pseudomonas aeruginosa, Enterobacter cloacae, E. coli and Enterococcus, all of which are intestinal species. Contamination is thus thought to be the most plausible cause of perioperative infection. Absolute sterility must be maintained in animal care areas and blood access to these animals is to be minimized. Although prompt selection of a proper antibiotic therapy is essential, the eradication of infection maintains a poor prognosis. The time course of fibrinogen levels is a reliable index to determine the onset of infection.

Animals↗
PubMed1970

Opium in China.

Explore the source record for details and available documents.

China↗
PubMedDate not supplied

Experimental laser phototherapy of the Morris 7777 hepatoma in the rat.

The tumoricidal effect of the activation of hematoporphyrin derivative (HpD), by an argon-ion-dye-laser (wavelength 630 nm), was investigated in the Buffalo rat bearing subcutaneous implants of the Morris 7777 hepatoma. Tumor growth was monitored by measuring the tumor volume with constant force calipers. In control animals and those that were pretreated with HpD alone (10 or 20 mg per kg by i.p. injection) or laser light alone (2,000 J at 100 mW), a predictable exponential growth pattern of the cancer was observed. Animals were pretreated with HpD (10 mg per kg by i.p. injection) 48 hr prior to the fiberoptic, intratumor delivery of laser radiation (2,000 J at 100 mW), when the tumor had reached a volume greater than 1.5 cm3. Forty-eight hours after combined laser and HpD treatment, the hepatoma underwent coagulation necrosis, and the tumor volume rapidly increased from a mean value of 1.8 +/- 0.7 cm3 S.D. to a value of 5.8 +/- 1.5 cm3 S.D., compared with a mean of 3.7 +/- 0.7 cm3 S.D. in animals who had not received laser phototherapy. Rats treated with HpD and laser light survived longer (mean survival time 48 +/- 12 days S.D.) than did the other animals treated with the laser alone or HpD alone (mean survival time 31 +/- 16.5 S.D.). Tissue biodistribution studies with tritiated hematoporphyrin derivative, given with doses of 10 and 20 mg per kg of HpD, showed higher concentrations of the dye in the liver, kidneys and spleen than in the tumor at 48 hr after administration of the dye.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Dose response and time course of carboplatin-induced micronucleated polychromatic erythrocytes in the cat: implications for combination carboplatin chemotherapy.

The dose response and time course of micronucleated polychromatic erythrocytes (mPCE) in cat peripheral blood induced by various doses (150-250 mg/m2) of carboplatin in vivo was determined. The data indicate that carboplatin produced a significant (p < 0.05) dose-dependent increase in the number of mPCE over baseline values; however, the times following carboplatin administration when mPCE were first observed differed significantly (p < 0.05) between the three carboplatin dose groups. mPCE were present in significantly greater numbers (p < 0.05) on smears at an earlier time interval following a single carboplatin dose of 150 mg/m2 than for a dose of either 200 or 250 mg/m2. The peak number of mPCE occurred on days 7, 14 and 17.5 following administration of a carboplatin dose of 150, 200 and 250 mg/m2, respectively. The pattern of time course delay following carboplatin administration suggests that the block of erythropoietic stem cells in G2 is dose dependent. Indeed, the administration of carboplatin arrested the cell cycle in the G2 phase and, at higher doses, diminished the number of cycling erythroid precursor cells. mPCE were apparent in blood smears only after recovery from this arrest and resumption of replication. This observation has implications for the scheduling of carboplatin administration when used in combination with other anticancer drugs.

Animals↗
PubMedDate not supplied

Preliminary phase II clinical and pharmacokinetic study of 9-cis retinoic acid in advanced cervical cancer. New York Gynecologic Oncology Group.

PURPOSE: 9-cis retinoic acid (ALRT 1057; 9cRA) is a promising new retinoid that binds to all known retinoic acid receptors (RAR and RXR), potentially providing it with a broader spectrum of biologic activity than either 13-cis retinoic acid or all-trans retinoic acid. It has been shown to be at least as active as all-trans retinoic acid as a differentiation-inducing and antiproliferative agent in both in vivo and in vitro tumor model systems. METHODS: The New York Gynecologic Oncology Group undertook a prospective, multi-institutional phase II clinical and pharmacokinetic trial of 9cRA in patients with advanced or recurrent squamous cell or adenosquamous cell carcinoma of the uterine cervix. Patients received daily oral doses of 140 mg/m2 of 9cRA. 9cRA and its metabolites were determined by reversed-phase HPLC in plasma samples drawn at 0.5 to 8 hours. RESULTS: Sixteen patients with advanced or recurrent carcinoma of the cervix were enrolled. Therapy was well tolerated with no unexpected toxicities. There were no complete or partial responses observed, indicating that a response rate of 20% or greater to this agent could be ruled out with 95% confidence. Pharmacokinetic parameters for 9cRA on day 1 were in agreement with previous studies. The area under the plasma versus time curves for 9cRA declined by 69% between days 1 and 8 with daily 9cRA dosing and remained at this low level in those patients evaluated on day 28. 4-oxo-9-cis retinoic acid (4-oxo-9cRA) was identified as a major plasma metabolite of 9cRA. Plasma levels of 4-oxo-9-cRA were initially 71% of those of 9cRA, but in contrast to 9cRA, there was no decline in plasma levels on days 8 and 28. The ratio of the area under the curve for the 4-oxo metabolite relative to that of the parent compound increased from less than 1 on day 1 to approximately 2.4 on days 8 and 28. Thus, despite early induction of its own metabolism, levels of total retinoid metabolites persisted at pharmacologic levels at day 28. CONCLUSIONS: 9cRA with this dose and schedule was inactive in women with advanced carcinoma of the cervix. Despite a decline in plasma levels of 9cRA over time, levels of the 4-oxo metabolite tended to persist. While the 4-oxo metabolite is less potent than the parent compound, these data nevertheless suggest that the lack of clinical activity in this patient population may not be attributable exclusively to suboptimal pharmacokinetic parameters.

Adult↗