Biomedical subjects

C V Smith

Publications and source records attributed to C V Smith.

184 records · Page 11Linked to original sources

PubMedDate not supplied

Structural origins of bulky oxidative DNA adducts (type II I-compounds) as deduced by oxidation of oligonucleotides of known sequence.

Bulky DNA adducts, previously termed type II I-compounds, are detected by 32P-postlabeling following treatment of DNA with several Fenton-type oxygen radical-generating reagents, i.e., mixtures of Fe(II) or Ni(II) and H2O2. In an attempt to characterize the chemical nature and mechanism(s) of formation of these novel adducts, 16 single-stranded deoxyribooligonucleotides (20- and 21-mers) of known sequence were oxidized with Fe(II) or Ni(II) and H2O2, and the products were analyzed by 32P-postlabeling. Eight adducts were obtained reproducibly by oxidation of DNA and test oligonucleotides in a sequence-dependent manner. One major adduct (2) was formed only if the test oligonucleotide contained two adjacent adenine residues. Similarly, adducts 3 and 8 specifically originated in AC and CA sequences, respectively. Adduct 6 required a 5'-C-purine-3' sequence. On the other hand, GN sequences (where N is any normal nucleotide) gave rise to adduct 1, another major product, and adduct 7. Similarly, adducts 4 and 5 were produced by the oxidation of AN sequences. These observations are most readily explained if the oxidation reactions caused intrastrand cross-links between adjacent nucleotides, leading to dimer formation. The observation that adducts 1, 4, 5, and 7 did not require a specific 3'-nucleotide was consistent with the notion that these nucleotides lacked a 3'-base, suggesting the presence of a 5'-->3' purine-sugar cross-linked in the oxidized products. The majority of the lesions came from AA and 5'-purine-N-3' sequences. The effects of Fe(II) and Ni(II) were qualitatively similar; however, higher yields of products were observed with Fe(II) as the catalyst. The definition of the chemical origins of these bulky DNA modifications, which represent a new type of DNA damage, is expected to contribute to a better understanding of the mechanism of metal carcinogenesis and to shed light upon the origins of certain endogenous DNA lesions. Recently, some of the major oxidative DNA adducts characterized here were detected by 32P-postlabeling in the renal DNA of male rats treated with ferric nitrilotriacetate, a known potent prooxidative kidney carcinogen in these animals.

Autoradiography↗

PubMedDate not supplied

Comparison of patient-controlled and nurse-administered analgesia using intravenous fentanyl during labor.

Preliminary observations have shown that fentanyl citrate, a potent narcotic, is helpful during labor without undue side effects. This randomized prospective investigation compared the patient-controlled administration of fentanyl with that of administration by nurses on request. Eighty healthy women beginning active labor (cervical dilation 4 cm) at term were assigned to receive fentanyl intravenously by either patient-controlled administration (n=37) or nurse administration on demand (n=43). Pain intensity measurements during early and late labor revealed the degree of analgesia to be the same in both groups. The delay in setting up the infusion system and the short time between requesting analgesia and vaginal delivery were limitations with self-administration. Maternal oversedation and vomiting did not occur. Neonatal naloxone therapy was used infrequently, umbilical serum levels of fentanyl were the same in both groups, and postnatal neuroadaptive testing revealed comparable results in both groups. Despite the usefulness of fentanyl during labor, administration by the patient had no advantages over administration by the nurses in significantly reducing drug use, improving pain relief, or avoiding drowsiness.

Adult↗

PubMedDate not supplied

Combined continuous and demand narcotic dosing for patient-controlled analgesia after cesarean section.

New patient-controlled analgesia devices can deliver an analgesic by continuous infusion along with demand dosing. This prospective investigation involving postcesarean-section patients was undertaken to determine whether a combination of continuous infusion and demand dosing of meperidine would provide more effective analgesia than would demand dosing alone during the first 24 hours. During a 12-month period, 171 patients were prescribed meperidine postoperatively, using a 5- to 10-mg demand dose no more frequently than every 10 minutes. Patients were assigned to groups receiving no continuous infusion or infusion at rates of 10, 20, or 30 mg/h. The groups receiving continuous infusion showed more immediate and sustained pain relief, with no serious complications. All patients were able to understand the nurse, became ambulatory, and tolerated liquids on the first postoperative day. The infusion rate of 20 mg/h was most acceptable in requiring fewer demand doses while providing satisfactory pain relief without undesired sedation. In conclusion, a system combining continuous infusion and demand dosing was preferable to demand dosing alone, and added no apparent hazards.

Adult↗

PubMedDate not supplied

Induction of specific tolerance to MHC-disparate allografts through genetic engineering.

The potential for induction of transplantation tolerance through genetic engineering of allogeneic MHC genes is being studied in two animal models. The first system involves a congenic mouse strain combination differing by a single class I locus. Using a retroviral vector, cDNA encoding one allele of this locus was introduced into bone marrow of the congenic partner strain, and the transduced bone marrow was used to reconstitute autologous animals. Skin-grafting data indicate that this reconstitution led to tolerance for the allelic products of this class I locus. The second system involves similar manipulations of miniature swine bone marrow, with the goal of inducing tolerance to class II antigens, since these antigens have been shown to be of overwhelming importance in determining the fate of vascularized allografts in this model. In vitro data in a bone marrow culture system indicate that an appropriate vector for this purpose has been produced.

Animals↗