Search PubMed⌕ Search

Biomedical subjects

R Swanson

Publications and source records attributed to R Swanson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Species variants of the IsK protein: differences in kinetics, voltage dependence, and La3+ block of the currents expressed in Xenopus oocytes.

We have compared the slowly activating K+ currents (IsK) resulting from the expression of the human, mouse, or rat IsK proteins in Xenopus oocytes, utilizing natural, species-dependent sequence variations to initiate structure-function studies of this channel. Differences were found between the human and rodent currents in their voltage dependence, kinetics, and sensitivity to external La3+. The current/voltage relationships of the human and rat IsK currents differed significantly, with greater depolarizations required for activation of the human channel. The first 30 s of activation during depolarizations to potentials between -10 and +40 mV was best described by a triexponential function for each of the three species variants. The activation rates were, however, significantly faster for the human current than for either of the rodent forms. Similarly, deactivation kinetics were best described as a biexponential decay for each of the species variants but the human currents deactivated more rapidly than the rodent currents. The human and the rodent forms of IsK were also differentially affected by external La3+. Low concentrations (10, 50 microM) rapidly and reversibly reduced the magnitude of the mouse and rat currents during a test depolarization and increased the deactivation rates of the tail currents. In contrast, the magnitude and deactivation rates of the human IsK currents were unaffected by 50 microM La3+.

Animals↗
PubMed1993

Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy.

BACKGROUND: This report consists of a retrospective analysis of 50 patients with primary invasive and 17 with recurrent histologically confirmed vulvar carcinoma treated with radiation therapy for locoregional disease. METHODS: Of the patients with primary tumors, 13 were treated with wide local excision plus radiation therapy; 13 had radical vulvectomy followed by irradiation to the operative fields and inguinal-femoral/pelvic lymph nodes; 8 received similar postoperative radiation therapy after partial or simple vulvectomy; 16 patients had radiation therapy alone after biopsy; and 17 had recurrent tumors treated with radiation therapy alone. RESULTS: In patients treated with biopsy/local excision, local tumor control was 92-100% in T1-3N0 disease, 40% in similar stages with N1-3, and 27% in recurrent tumors. Among patients treated with partial/radical vulvectomy and radiation therapy, primary tumor control was 90% in those with T1-3 tumors and any nodal stage, 33% in those with any T stage and N3 lymph nodes, and 66% in patients with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for patients with T1N0 disease, 62% for those with T2-3N0 disease, 30% for those with T1-3N1 disease, and 11% for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 disease. Four of 17 patients treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and radiation therapy. In patients with T1-2 tumors treated with biopsy/wide tumor excision and radiation therapy with doses less than 50 Gy, the local tumor control was 75% (three of four patients), in contrast to 100% (13 of 13 patients) with 50.01-65 Gy. With T3-4 tumors treated with local excision and radiation therapy, tumor control occurred in none of three patients with doses less than 50 Gy and 66% (six of nine) with 50.01-65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and radiation therapy, local tumor control was 75% (six of eight), regardless of dose level; in T3-4 tumors, it was 67% (four of six patients) with 50-60 Gy and 86% (six of seven) with 65-70 Gy. Differences were not statistically significant. There was no significant dose response for tumor control in the inguinal-femoral lymph nodes, with doses of 50 Gy being adequate for elective treatment of nonpalpable lymph nodes and 60-70 Gy controlling tumor growth in 75-80% of patients with N2-3 nodes when administered postoperatively, after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess. CONCLUSIONS: Wide local tumor excision and radiation therapy or irradiation alone in T1-2 tumors is an alternative treatment to radical vulvectomy in controlling vulvar carcinoma, with significantly less morbidity. In comparison with reported rates for surgery alone, radiation therapy after radical vulvectomy for locally advanced tumors improves tumor control at the primary site and regional lymphatics. Indications and techniques of radiation therapy are discussed.

Adenocarcinoma↗
PubMed1993

The effect of noise on entropy.

A complementary relationship between the entropy (S) and the variance (sigma(2)) of an electron-density map is derived by approximating the logarithmic term in the entropy expression by a series expansion around the average map density. The resulting expression is S approximately ln N - 1/2sigma(2), where N is the number of grid points and sigma is the r.m.s. deviation from the mean in a map normalized to unit mean. The algebraic expression is of interest because it is consistent with and allows numerical evaluation of the surprising argument that noise decreases the entropy of a map. The argument is that a noise contribution by itself generates a certain variance that is independent of the atomic structure and that adds to the variance due to the structure. Increased variance corresponds to decreased entropy. This property of noise provides an intuitively reasonable justification for maximizing the entropy of an electron-density map in the quest for more readily interpretable maps of macromolecules. The entropy-variance relationship also extends the range of applicability of the entropy concept to maps with a limited amount of negative density. The approximation which leads to the entropy-variance relationship is most applicable where it is most likely to be useful - in experimental maps of relatively low structure definition.

Journal Article↗
PubMed1992

An evaluation of the Thermafil endodontic obturation technique.

The purpose of this study was to evaluate the Thermafil endodontic obturation technique and to compare it with laterally condensed gutta-percha. Thirty-seven maxillary central incisors were similarly prepared and divided into groups. Seventeen were obturated with Thermafil and 17 with lateral condensation. Three served as controls. After vacuum staining, all teeth were cleared and apical dye penetration was evaluated by two independent observers. Average leakage values were 0.24 mm and 1.32 mm for Thermafil and 0.47 mm and 1.18 mm for lateral condensation. There was no significant difference between the techniques, although a difference between evaluators was noted. Final results point to the relative subjectivity of in vitro leakage studies. When comparing the obturation times of both techniques, the Thermafil technique averaged 2 min 56 s while lateral condensation took 3 min 26 s. Statistical analysis showed no significant difference in obturation times.

Analysis of Variance↗
PubMed1992

Analysis of a measles outbreak in Kent County, Michigan in 1990.

New recommendations from the Immunization Practices Advisory Committee call for a second dose of measles vaccine for school age children. The purpose of this paper is to demonstrate the need for additional measures for the protection of preschool age children. A hospital-based measles outbreak of 25 cases in Kent County, MI, in 1990 provided an opportunity to study measles transmission to preschool age children. Twenty-two (88%) were people who had never received measles vaccine. Twelve of the cases were unvaccinated preschoolers, seven of whom were older than 15 months. Three nonvaccinated, but eligible people (one philosophic exemption and two vaccine-eligible preschoolers) were the source of most of the other cases. One school age unvaccinated child died of measles pneumonitis. A telephone survey indicated that improved public education regarding indications and contraindications to vaccination might encourage vaccination of children according to public health recommendations.

Adolescent↗
PubMed1991

Alternative splicing contributes to K+ channel diversity in the mammalian central nervous system.

In an attempt to define the molecular basis of the functional diversity of K+ channels, we have isolated overlapping rat brain cDNAs that encoded a neuronal delayed rectifier K+ channel, K,4, that is structurally related to the Drosophila Shaw protein. Unlike previously characterized mammalian K+ channel genes, which each contain a single protein-coding exon, K,4 arises from alternative exon usage at a locus that also encodes another mammalian Shaw homolog, NGK2. Thus, the enormous diversity of K+ channels in mammals can be generated not just through gene duplication and divergence but also through alternative splicing of RNA.

Amino Acid Sequence↗
PubMed1991

Do CK-MB results affect chest pain decision making in the emergency department?

STUDY OBJECTIVE: To analyze the effect of creatine kinase isoenzyme (CK-MB) results on decision making in the evaluation of emergency department patients with chest pain. DESIGN: Prospective, controlled observational study of clinical decision making. SETTING: EDs of two teaching hospitals, a Veterans Affairs medical center, and a medical school university hospital. TYPE OF PARTICIPANTS: Patients more than 30 years old complaining of chest discomfort warranting an ECG. Excluded were hemodynamically unstable patients and patients with ECG evidence of an acute myocardial infarction (AMI). INTERVENTIONS: After the initial assessment including ECG but not CK-MB data, physicians answered questions regarding estimated probability of AMI and disposition plans. CK-MB levels were drawn every hour for as long as three hours (from one to four CK-MBs) with results readily available. Physicians could admit their patients into the hospital at any time. At disposition after reviewing a second ECG and all available CK-MB data, the physicians answered the same questions and rank ordered the contribution to disposition of the following six factors: initial and serial clinical evaluations, initial and serial ECGs, and initial and serial CK-MB enzymes, respectively. The absolute log likelihood ratio test measured the contribution of CK-MB to decision certainty. MEASUREMENTS AND MAIN RESULTS: Three hundred seventy-six patients were studied: 29 (7.7%) with AMI and 347 without AMI (nonAMI). Physicians indicated that CK-MB levels were useful for more than one third of study patients. When considered useful, CK-MB results strengthened the impression of AMI in AMI patients and decreased the impression of AMI for nonAMI patients; CK-MB also correlated with the perceived need for cardiac care unit admission in AMI patients and with a reduced need to admit nonAMI patients. The use of CK-MB results did not significantly increase ED release rates. CONCLUSION: The rapid availability of serial CK-MB results appears to affect decision making in one third of ED patients with chest pain and nondiagnostic ECGs. CK-MB levels appear to complement clinical evaluation of the ED chest pain patient in a manner analogous to the ECG.

Adult↗
PubMed1991

Individual and combined activities of clarithromycin and its 14-hydroxy metabolite in a murine model of Haemophilus influenzae infection.

Clarithromycin is metabolised in man mainly to the 14-hydroxy derivative, which is also biologically active. As this metabolite is not produced in rodents, we used a murine model of Haemophilus influenzae pulmonary infection to compare the in-vivo activity of clarithromycin and 14-hydroxy clarithromycin, alone and in combination, and erythromycin. In terms of bacterial killing, clarithromycin's 14-hydroxy metabolite was much more active than clarithromycin and erythromycin at doses of 100 mg/kg. For the combination tests, low doses of 14-hydroxy clarithromycin (12, 16 and 24 mg/kg) were ineffective alone but potentiated the bactericidal activity of clarithromycin (100 mg/kg) (P less than 0.01-0.001). The in-vivo results can be explained by in-vitro and pharmacokinetic data: the MIC and MBC of 14-hydroxy clarithromycin are half those of clarithromycin and erythromycin, while the combination of clarithromycin and its metabolite was synergistic in terms of bacteriostatic and bactericidal activities. Potentially useful levels of 14-hydroxy clarithromycin were found after oral administration of low doses, with a prolonged half-life compared with that of the parent compound. On the basis of these results it appears that the 14-hydroxy metabolite may have an important role to play in the treatment of bronchopulmonary infections in man due to H. influenzae.

Administration, Cutaneous↗
PubMed1990

Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain.

Rat brain cDNA and genomic clones encoding three K+ channels, Kv1, Kv2, and Kv3, have been isolated by screening with Shaker probes and encode proteins of 602, 530, and 525 amino acids. Each of the deduced protein sequences contains six hydrophobic domains (including an S4-type region characteristic of many voltage-gated channels) and are 68%-72% identical to each other overall. Transcripts of approximately 3.5, approximately 6.5, and approximately 9.5 kb encode Kv1, Kv2, and Kv3, respectively. The Kv2 mRNA is expressed only in brain, whereas the Kv1 and Kv3 transcripts are found in several other tissues as well. There is a marked increase in the amount of Kv1 mRNA in cardiac tissue during development and a similar, but less pronounced, increase of both this mRNA and the Kv2 transcript in brain. RNAs synthesized in vitro from the three clones induce voltage- and time-dependent, delayed rectifier-like K+ currents when injected into Xenopus oocytes, demonstrating that they encode functional K+ channels.

Amino Acid Sequence↗
PubMed1990

Cloning and expression of the delayed-rectifier IsK channel from neonatal rat heart and diethylstilbestrol-primed rat uterus.

cDNAs encoding a delayed-rectifier-type K+ channel were cloned from both neonatal rat heart and ovariectomized, diethylstilbestrol-primed rat uterus by using the polymerase chain reaction. Both clones have nucleotide sequences identical to that encoding the rat kidney IsK channel [Takumi, T., Ohkubo, H. & Nakanishi, S. (1988) Science 242, 1042-1045] and encode a putative protein of 130 amino acids. Injection of RNA transcripts of the cDNAs into Xenopus oocytes resulted in the expression of a slowly activating, voltage-dependent K+ current. An antisense oligonucleotide, derived from the sequence of the clone, specifically inhibited the expression of the slow, outward current observed in cells injected with mRNAs isolated from the parent tissues (i.e., kidney, heart, and uterus), indicating that the cloned gene underlies the major K+ current expressed from RNA isolated from these tissues.

Amino Acid Sequence↗
PubMed1988

Accuracy of in vivo aminoacylation requires proper balance of tRNA and aminoacyl-tRNA synthetase.

The fidelity of protein biosynthesis in any cell rests on the accuracy of aminoacylation of tRNA. The exquisite specificity of this reaction is critically dependent on the correct recognition of tRNA by aminoacyl-tRNA synthetases. It is shown here that the relative concentrations of a tRNA and its cognate aminoacyl-tRNA synthetase are normally well balanced and crucial for maintenance of accurate aminoacylation. When Escherichia coli Gln-tRNA synthetase is overproduced in vivo, it incorrectly acylates the supF amber suppressor tRNA(Tyr) with Gln. This effect is abolished when the intracellular concentration of the cognate tRNA(Gln2) is also elevate. These data indicate that the presence of aminoacyl-tRNA synthetase and the cognate tRNAs in complexed form, which requires the proper balance of the two macromolecules, is critical in maintaining the fidelity of protein biosynthesis. Thus, limits exist on the relative levels of tRNAs and aminoacyl-tRNA synthetases within a cell.

Amino Acyl-tRNA Synthetases↗
PubMed1988

Overproduction and purification of Escherichia coli tRNA(2Gln) and its use in crystallization of the glutaminyl-tRNA synthetase-tRNA(Gln) complex.

We describe the genetically engineered overproduction of Escherichia coli tRNA(2Gln), its purification by high pressure liquid chromatography (HPLC), and its subsequent use in the growth of crystals of the E. coli glutaminyl-tRNA synthetase-tRNA(Gln) complex. The overproduced tRNA represents 60 to 70% of the total tRNA extracted from the engineered strain. A single anion exchange HPLC column is then sufficient to increase the purity of this isoacceptor to 90 to 95%. Crystals of this material complexed with the monomeric E. coli glutaminyl-tRNA synthetase enzyme were obtained by vapor diffusion from solutions containing sodium citrate as the precipitating agent. The crystals diffract to beyond 2.8 A resolution (1 A = 0.1 nm) and are of the orthorhombic space group C222(1) with unit cell parameters a = 240.5 A, b = 93.9 A, c = 115.7 A. Gel electrophoresis of dissolved crystals demonstrates the presence of both protein and tRNA.

Amino Acyl-tRNA Synthetases↗
PubMed1988

Expression of a bovine rhodopsin gene in Xenopus oocytes: demonstration of light-dependent ionic currents.

Xenopus oocytes express a gene encoding bovine rhodopsin as well as its SP6 RNA polymerase-derived transcripts and total retinal mRNA. The opsin produced is in unglycosylated (30 kDa) and two glycosylated (35 kDa and 41 kDa) forms. Incubation of the cells expressing the above proteins with 11-cis-retinal generates rhodopsin, which was purified by immunoaffinity chromatography. The purified protein shows the expected UV/visible absorption spectrum and characteristic light-dependent activation of the rod outer segment GTP binding protein. Oocytes expressing rhodopsin exhibit light-dependent ionic currents that are detected by voltage-clamp techniques.

Animals↗
PubMed1988

Site-directed mutagenesis to fine-tune enzyme specificity.

We have used a combination of a genetic selection and oligonucleotide-directed mutagenesis to introduce a series of amino acid replacements for a single residue into Escherichia coli glutaminyl-tRNA synthetase. The mutant enzymes mischarge supF tRNA(Tyr), with glutamine, to varying degrees depending on the polarity of the side chain introduced but apparently not depending on the size or shape of the side chain. These results indicate that repulsive charge-charge interactions may be important for specific recognition of nucleic acids by proteins and illustrate how a mutant, derived from genetic selection, may be further modified in activity by oligonucleotide-directed mutagenesis.

Amino Acid Sequence↗
PubMed1987

Susceptibility testing of macrolide antibiotics against Haemophilus influenzae and correlation of in vitro results with in vivo efficacy in a mouse septicemia model.

There is poor correlation between the MICs and zone sizes obtained for erythromycin against Haemophilus influenzae. The effect of two media, Mueller-Hinton medium supplemented with 3% lysed horse blood and 10 micrograms of NAD per ml (MHA + LYHB) and Mueller-Hinton agar supplemented with 1% bovine hemoglobin and 1% IsoVitaleX (MHA + HGB), on the MICs and zone sizes of erythromycin against H. influenzae was determined. The effect of three different methods for inoculum preparation on the susceptibility of H. influenzae was also determined. The MICs were independent of the method of inoculum preparation, but the zone sizes were smaller if the inoculum was carefully adjusted to contain approximately 10(8) CFU/ml. MICs were higher and zone sizes were smaller when MHA + HGB was used instead of MHA + LYHB. Good correlation was found when MHA + LYHB was used for determining the MIC and MHA + HGB was used for determining susceptibility by the disk method. When the inoculum was adjusted to match a McFarland 0.5 standard, the viable counts had to be approximately 10(8) CFU/ml for good correlation between MICs and zone sizes. A-56268, a new macrolide antibiotic, was tested against H. influenzae, and its MICs and tentative breakpoints against this organism were determined. The MICs obtained by various methods were correlated with in vivo efficacy by using a mouse septicemia model. MICs obtained on MHA + HGB or MHA + LYHB incubated without a 5% CO2 atmosphere showed the best correlation with in vivo efficacy.

Animals↗