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Biomedical subjects

W Olson

Publications and source records attributed to W Olson.

36 records · Page 2Linked to original sources
PubMed1992

Comparative contraceptive efficacy and mechanism of action of the norgestimate-containing triphasic oral contraceptive.

Norgestimate (NGM), a derivative of 19-nortestosterone with very specific affinity for the progesterone receptor, has been used in combination with ethinyl estradiol (EE) at low doses in both monophasic and triphasic oral contraceptives (OCs). An open-label comparative clinical trial was conducted with 4,234 healthy women using comparative clinical trial was conducted with 4,234 healthy women using triphasic levonorgestrel (LUG)/EE and NGM/EE through a total of 22,312 menstrual cycles. Contraceptive (LUG)/EE and NGM/EE through a total of 22,312 menstrual cycles. Contraceptive efficacy was excellent with both preparations, with no statistically significant between-regimen differences in pregnancy rates. The theoretical Pearl index was the NGM/EE triphasic, and 0.34 for the LNG/EE triphasic. Adverse experiences in groups were typical of those that may occur among women taking low-dose OC agents. was similar with the two preparations: 8.6% for the NGM/EE triphasic and 6.8% for the LNG/EE triphasic. In a separate mechanism of action study, specific endocrine parameters were investigated in 20 subjects using the NGM/EE triphasic for 4 cycles. Ovulation suppression was demonstrated in statistically significant decreases from pretreatment values in serum levels of luteinizing hormone, follicle-stimulating hormone, progesterone, and estradiol. Significant on-treatment increases in serum levels of sex hormone binding globulin evidenced minimal androgenicity. All hormonal values returned to or toward normal in the post-treatment cycle. The study results support those obtained in large noncomparative studies of the NGM/EE triphasic. This phased-dose combination suppresses ovulation and is a very effective, minimally androgenic contraceptive agent with a good safety profile.

Adolescent↗
PubMed1991

The v-rel oncogene of avian reticuloendotheliosis virus transforms immature and mature lymphoid cells of the B cell lineage in vitro.

Heavy chain gene rearrangements were analyzed in 67 independently derived reticuloendotheliosis virus (REV-T) transformed avian lymphoid cell lines. The status of the heavy chain genes in these REV-T transformed cell lines was determined, in part, by the age of the chicken whose spleen cells were transformed. Cell lines derived by the in vitro transformation of splenic lymphocytes obtained from embryos did not contain heavy chain gene Ig rearrangements. By contrast, splenic lymphocytes transformed by REV-T obtained from birds 1 week or older generally exhibited heavy chain gene rearrangements. The REV-T transformed lymphoid cell lines with heavy chain rearrangements also had light chain gene rearrangements. The Ig gene rearrangements in REV-T transformed cells were functional. The majority of the cells which had heavy chain rearrangements expressed a 2.2-kb mu transcript and synthesized and secreted IgM. An REV-T transformant was also identified which produced IgG, suggesting that v-rel can transform a terminally differentiated cell. Irrespective of their Ig chain gene status the REV-T transformed cell lines expressed variable amounts of some but not all normal B cell-specific markers and failed to express T cell markers. All the cell lines analyzed expressed the B-L (Ia-like) antigen as well as a common leukocyte antigen. Based on the expression of these surface molecules, the transformants with or without Ig gene rearrangements all appear to be committed to the B cell pathway.

Alleles↗
PubMed1990

Light chain gene conversion continues at high rate in an ALV-induced cell line.

We have analyzed immunoglobulin light chain sequences from avian leukosis virus (ALV) induced bursal and metastatic tumors and from cell lines derived from these tumors. Sequence data presented demonstrate that ALV-induced tumors and one cell line (DT40) derived therefrom continue to diversify their light chain genes outside of the bursal environment. Diversification within these tumor cells seems to occur by gene conversion events comparable with those observed in bursal B cells. Sequence analysis of spontaneously arising surface immunoglobulin negative subclones of the DT40 cell line revealed frameshifts within the rearranged light chain genes which most likely resulted from non-functional recombination events. Superimposed gene conversion events can repair these frameshifts leading to re-expression of surface immunoglobulin.

Animals↗
PubMed1987

A dumbbell-shaped, double-hairpin structure of DNA: a thermodynamic investigation.

We report the first calorimetric and spectroscopic investigation on a member of a new class of nucleic acid secondary structures in which both ends of a duplex core are closed by single-stranded loops. Such structures can be formed intramolecularly from appropriately designed base sequences. We have synthesized the 24-mer sequence shown, and we present calorimetric, spectroscopic, and electrophoretic (formula; see text) evidence that it adopts a dumbbell-shaped, double-hairpin structure. Our data allow us to reach the following conclusions: (1) The phosphodiester gap in the center of the core duplex of the dumbbell does not reduce the transition enthalpy relative to that measured for the corresponding octameric duplex d(GGAATTCC)2. (2) Incorporation of a 5'-phosphate group into the gap decreases the thermal stability of the dumbbell relative to its unphosphorylated sequence. On the basis of the salt dependence of this effect, we propose that the phosphorylation--induced decrease in thermal stability is electrostatic in origin. From the changes in the transition enthalpy and entropy, we suggest that the phosphorylation-induced decrease in thermal stability of the double hairpin arises from electrostatically induced based unstacking at the nick. (3) The thymine residues in the loop behave both electrostatically and enthalpically like denatured single strands. Published nuclear magnetic resonance studies reveal partial stacking of thymine residues in the loops of linear hairpin structures. If this feature persists in the double-hairpin structure, then the spatial overlap of thymine residues in the loops does not necessarily produce a favorable enthalpic contribution. (4) When both ends of the nicked octameric core duplex are constrained by loops of only four thymine residues, the dumbbell structure may adopt conformations in which the 5' and 3' ends at the nick are twisted relative to the helical axis and therefore are not in phase. Such conformations would account for the observed resistance of the double-hairpin structure to ligation, since the 3'OH and 5'P would no longer be collinear.

Base Sequence↗
PubMed1981

Increase in rabbit corneal curvature by heated ring application.

This study demonstrated that increases of corneal curvature in living rabbits could be induced through the application of heated brass rings. The peak increase averaged 10.5 D in a series of 19 eyes, as compared to the nontreated fellow eyes. This change tended to be transient, was not prolonged with the use of steroids locally, and tended to return to normal within two to three weeks. The mechanism of this change involved the creation of a rigid desiccated pseudo-limbus holding the cornea in the configuration of increased curvature. With the rehydration of the desiccated area, the cornea then reassumes its pretreated curvature and configuration. The application of the rings heated to about 98C produced a very low incidence of corneal ulceration. Further experiments showed that burn ulceration is a temperature-dependent phenomenon rarely found with application of heat less than 110C.

Animals↗
PubMed1979

Reactions of families to children with Duchenne muscular dystrophy.

Twenty-five families were interviewed to examine their adjustments to having a child with Duchenne muscular dystrophy (DMD). Chronic emotional stress experienced by families of DMD children was found to be a significant problem in the overall management of the illness. Based on information obtained from the assessment of families' adaptation to their child's illness, recommendations are made concerning parent education, school placement, facilitation of marital harmony, informing the child about his illness, and sensitivity to the responses of other family members.

Adaptation, Psychological↗
PubMed1978

Dose-dependent changes in sulfamethazine kinetics in rapid and slow isoniazid acetylators.

The pharmacokinetics of sulfamethazine (SMZ) was studied in 44 healthy volunteers. After an oral dose of 10 mg/kg we found the usual distribution of rapid and slow acetylators. The differences in the t1/2s between the phenotypes were not due to variations in renal clearance. Repeat studies at this dose showed very little intraindividual variation in t1/2s. After a 40 mg/kg dose there was an increase in the t1/2 of SMZ in every subject. The implications of these results on methods of phenotyping are discussed.

Acetylation↗
PubMed1975

Beneficial effects of penicillamine treatment on hereditary avian muscular dystrophy.

Hereditary muscular dystrophy in chickens of the New Hampshire strain was treated with penicillamine from the 9th day after hatching to the 425th day. The adult maintenance dose for males was 50 mg/kg per day and for females, 13-65 mg/kg per day. In avian dystrophy, deterioration of the muscle fibers is evidenced in the 2nd mo by an inability of the birds to rise after falling on their backs and by a progressive rigidity of the wings. The drug delayed the onset of symptoms and partially alleviated the debilitating aspects of the disease. Penicillamine produced three major improvements: (a) better righting ability when birds were placed on their backs; (b) greater wing flexibility; (c) and suppression of plasma creatine phosphokinase activity. The results are statistically analyzed and discussed in relationship to Duchenne dystrophy. Normal birds were not affected by penicillamine as judged by these parameters. The rationale for using penicillamine, a sulfhydryl compound with reducing properties, was (a) to attempt to protect essential thiol enzymes in the anabolic and glycolytic pathways against inactivation and (b) to prevent collagen cross-linking and deposition in muscle. Although the precise mechanism of drug action has not been determined. the possible role of penicillamine in mitigating the symptoms of genetic dystrophy in man is under consideration. Further, penicillamine may have a more generalized application i the prevention of contractures in a variety of neuromuscular disorders.

Animals↗
PubMed1975

Toxic epidermal necrolysis associated with allopurinol administration.

Allopurinol, now established as a standard form of therapy in hyperuricemia and gout, may be associated with life-threatening skin reactions. This study reports the occurrence of toxic epidermal necrolysis TEN) in three patients receiving Allopurinol. The patients receiving allopurinol. The patients had complicated medical illnesses and were receiving various other medications, but the most apparent common denominator was allopurinol ingestion. Two other cases of TEN and five cases of severe hypersensitivity reactions with vasculitis and extensive skin manifestations, secondary to this drug, have been described in the recent literature. Allopurinol has several unique biochemical and metabolic properties that may increase its ability to cause hypersensitivity or toxic skin reactions.

Aged↗