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Biomedical subjects

B Frame

Publications and source records attributed to B Frame.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative trait loci for callus initiation and totipotency in maize (Zea mays L.).

Induction of embryogenic callus in culture is an important step in plant transformation procedures, but response is genotype specific and the genetics of the trait are not well understood. Quantitative trait loci (QTL) were mapped in a set of 126 recombinant inbred lines (RILs) of inbred H99 (high Type I callus response) by inbred Mo17 (low Type I callus response) that were evaluated over two years for Type I callus response. QTL were observed in a total of eleven bins on eight chromosomes, including eight QTL with main effects and three epistatic interactions. Many of the QTL were mapped to the same or bordering chromosomal bins as candidate genes for abscisic acid metabolism, indicating a possible role for the hormone in the induction of embryogenic callus, as has previously been indicated in microspore embryo induction. Further examinations of allelic variability for known candidate genes located near the observed QTL could be useful for expanding the understanding of the genetic basis of induction embryogenic callus. The QTL observed herein could also be used in a marker assisted selection (MAS) program to improve the response of agronomically useful inbreds, but only if the resources required for MAS are lower than those required for phenotypic selection.

Chromosome Mapping↗
PubMed2001

Population pharmacokinetics of clinafloxacin in healthy volunteers and patients with infections: experience with heterogeneous pharmacokinetic data.

OBJECTIVE: Clinafloxacin is a new fluoroquinolone antibacterial with inhibitory activity against aerobic, anaerobic and atypical bacterial pathogens. The objectives of this study are to evaluate the pharmacokinetics of clinafloxacin in healthy volunteers and patients with infections and to describe our experience with mixed-effects modelling using heterogeneous pharmacokinetic data. DESIGN AND SETTING: Retrospective analysis of data from phase I to III trials. PATIENTS AND PARTICIPANTS: 204 healthy volunteers and 221 patients with infections. METHODS: Nonlinear mixed-effects modelling (MEM) was used to evaluate 3437 clinafloxacin plasma concentrations collected in 15 phase I to III trials. Models were developed separately for the healthy volunteers and patients, and then for the combined study population. RESULTS: The phase I data were best described with a 2-compartment linear model with first-order absorption. The absorption lag-time and absorption rate constant were 0.24h and 1.17h(-1), respectively. The volumes of distribution were found to be nonlinear functions of body surface area. Estimated creatinine clearance was the most important covariate for systemic clearance (CL). Interoccasion variability (IOV) in CL was observed in the patients in the phase II trial. In the combined study population, the variability in CL was best described by a model including IOV and distinct variabilities for healthy volunteers and patients. CONCLUSION: MEM was useful for evaluating data collected during different phases of drug development for this new fluoroquinolone agent.

Administration, Oral↗
PubMed1998

Non-steady state population kinetics of intravenous phenytoin.

This observational study explored the effects of demographics, sickness, and polypharmacy on the non-steady state population pharmacokinetics of intravenous phenytoin. One hundred fifteen patients were studied. Models were developed using the NONMEM program with hybrid first-order conditional estimation. A Michaelis-Menten model with delayed induction was preferred over a Michaelis-Menten model without induction, a Michaelis-Menten model with immediate induction, or a linear model with delayed induction. When the data were fit to a Michaelis-Menten model with delayed induction, the volume of distribution (Vd) was found to depend on weight and serum albumin. The Vd was estimated to be 0.95 l/kg, assuming an albumin level of 3 g/dl. The Michaelis-Menten constant (km) was estimated to be 7.9 mg/l. The baseline maximum metabolic rate was 580 mg/day for a 70-kg patient. The average time to onset of induction was 59.5 hours. If a fever developed after induction began, it increased the extent of induction. This model was evaluated retrospectively in 26 additional patients, yielding a mean prediction error of -0.4 mg/l (-3.0-2.2 mg/l) and a mean absolute prediction error of 4.7 mg/l (3.2-6.2 mg/l) based on two-level feedback. Given the large interindividual variances in maximum metabolic rate, phenytoin levels should be measured frequently.

Aged↗
PubMed1998

Population pharmacokinetics of ceftizoxime administered by continuous infusion in clinically ill adult patients.

Ceftizoxime is a widely used beta-lactam antimicrobial agent, but pharmacokinetic data for use with clinically ill patients are lacking. We studied the population pharmacokinetics of ceftizoxime in 72 clinically ill patients at a community-based, university-affiliated hospital. A population pharmacokinetic model for ceftizoxime was created by using a prospective observational design. Ceftizoxime was administered by continuous infusion to treat patients with proven or suspected bacterial infections. While the patients were receiving infusions of ceftizoxime, serum samples were collected for pharmacokinetic analysis with the nonlinear mixed-effect modeling program NONMEM. In addition to clearance and volume of distribution, various comorbidities were examined for their influence on the kinetics. All 72 subjects completed the study, and 114 serum samples were collected. Several demographic and comorbidity variables, namely, age, weight, serum creatinine levels, congestive heart failure, and long-term ventilator dependency, had a significant impact on the estimate for ceftizoxime clearance. A mixture model, or two populations for estimation of ceftizoxime clearance, was discovered. One population presented with an additive clearance component of 1.6 liters per h. In addition, a maximizer function for serum creatinine levels was found. In summary, two models for ceftizoxime clearance, mixture and nonmixture, were found and are presented. Clearance for ceftizoxime can be estimated with commonly available clinical information and the models presented. From the clearance estimates, the dose of ceftizoxime to maintain the desired concentration in serum can be determined. Work is needed to validate the model for drug clearance and to evaluate its predictive performance.

Adult↗
PubMed1994

Structure and function of selectable and non-selectable transgenes in maize after introduction by particle bombardment.

Zea mays transformants produced by particle bombardment of embryogenic suspension culture cells of the genotype A188 x B73 and selected on kanamycin or bialaphos were characterized with respect to transgene integration, expression, and inheritance. Selection on bialaphos, mediated by the bar or pat genes, was more efficient than selection on kanamycin, mediated by the nptII gene. Most transformants contained multicopy, single locus, transgene insertion events. A transgene expression cassette was more likely to be rearranged if expression of that gene was not selected for during callus growth. Not all plants regenerated from calli representing single transformation events expressed the transgenes, and a non-selectable gene (uidA) was expressed in fewer plants than was the selectable transgene. Mendelian inheritance of transgenes consistent with transgene insertion at a single locus was observed for approximately two thirds of the transformants assessed. Transgene expression was typically, but not always, predictable in progeny plants--transgene silencing, as well as poor transgene transmission to progeny was observed in some plant lines in which the parent plants had expressed the transgene.

Cells, Cultured↗
PubMed1992

Effect of allogeneic blood transfusion on solid tumor growth and pulmonary metastases in mice.

The effect of allogeneic blood transfusions on solid tumor growth and pulmonary metastases was examined in two different strains of mice. Recipient mice (C57B1 or DBA/2) were given transfusions from allogeneic donors (Balb/c or B6AF1, respectively). The effect of allogeneic blood transfusion on solid tumor growth (B16 in C57B1 mice and P815 in B6AF1 mice) as well as the number of pulmonary metastases (B16 in C57B1 mice) was examined utilizing inoculations of varying numbers of tumor cells. In both solid tumor models, allogeneic transfusion resulted in significant enhancement of tumor growth when smaller (1.25 x 10(5), 2.5 x 10(5)) numbers of tumor cells were inoculated into the host animal. In contrast, no effect of allogeneic transfusion on tumor growth was observed when higher (4.5 x 10(5)) numbers of tumor cells were inoculated. Similarly, increased numbers of pulmonary metastases following allogeneic blood transfusion were observed when lower numbers (1 x 10(5)) of B16 tumor cells were administered; whereas no effect was observed with higher (4.5 x 10(5)) tumor cell numbers. The data in the present study suggest that the number of tumor cells inoculated into the recipient animal has a strong bearing in the allogeneic blood-transfusion-induced tumor growth effect.

Animals↗
PubMed1991

Effect of blood transfusion on survival in a mouse bacterial peritonitis model.

Allogeneic blood transfusions can result in alloimmunization or immunosuppression. A previous study demonstrated a deleterious effect of allogeneic blood transfusion on tumor growth in mice that was dependent, in part, on the dose of tumor cells with which the host animal was inoculated. The current study examined the effect of a similar allogeneic blood transfusion protocol on survival in a mouse bacterial peritonitis model. C57Bl/6J mice were transfused with 0.2 mL of heparinized fresh whole blood from C57Bl/6J (syngeneic) or Balb/c (allogeneic) mice. Transfusions were given on Days -10 and -7. On Day 0, mice were injected intraperitoneally with 10(7) Escherichia coli. Survival at Day 7 was 61 percent in the allogeneic blood transfusion group and 55 percent in the syngeneic blood transfusion group (p = 0.52). Experiments using different strains of mice, different transfusion protocols, and different doses of bacteria also failed to demonstrate an effect of allogeneic blood transfusion on survival. The results demonstrate that blood transfusion does not influence survival after a septic challenge with bacteria. The data obtained in the present study, together with those obtained in the tumor model, suggest that the mechanisms by which the allogeneic blood transfusion impedes host defense against bacterial infections is different from the mechanisms involved in tumor growth.

Animals↗
PubMed1990

Effect of blood transfusions on experimental pulmonary metastases in mice.

We examined the effect of allogeneic blood transfusions (BT) on pulmonary metastases in a mouse model. Recipient (C57B1/6J) mice were transfused with either saline, syngeneic blood or allogeneic (Balb/c) blood on two occasions, days 0 and 3. One week after the last transfusion, recipient mice were injected intravenously with varying numbers of methylcholanthrene-induced fibrosarcoma cells. Twenty days later the number of pleural nodules was counted as an index of pulmonary metastasis. The data demonstrate that the inoculation of 2.5 x 10(5) or 1 x 10(5) tumor cells resulted in significantly higher numbers of pulmonary metastases in mice that received allogeneic BT than the mice that received syngeneic blood or saline. In contrast, allogeneic BT caused significant inhibition of pulmonary metastases in mice that received 3.5 x 10(5) tumor cells. The data suggest that the immunomodulatory (stimulatory or inhibitory) effect of BT is dependent on the numbers of tumor cells inoculated. It is likely that the conflicting reports in the literature on the effects of BT on tumor growth may be due to inoculation of different numbers of tumor cells. These results have an important bearing in understanding the effect of allogeneic BT on tumor growth both in experimental animals and in cancer patients.

Animals↗
PubMed1987

Hormonal influences on osteoporosis.

Osteoporosis has recently received increased attention in both the medical and lay literature. It is estimated that there are more than one million osteoporosis-related fractures yearly in the United States, which are responsible for between three and four billion dollars in health care expenditures. A discussion of osteoporosis requires consideration of both the physiology and pathophysiology of bone tissue. In a structural sense, bone exists in two forms, the outer compact cortex accounting for 80 percent of total bone volume, and the more porous inner trabecular bone. Bone-forming osteoblasts and bone-resorbing osteoclasts are responsible for the ongoing, life-long process of formation and resorption of bone. Sex hormone deficiency, as well as chronic illness, malnutrition, and childhood immobilization, has deleterious effects on growth and modeling, ultimately reducing peak bone mass and setting the stage for osteoporosis in later life. Estrogen is known to have a protective effect on the female skeleton. The mechanisms of this effect are unknown, although estrogen may protect against parathyroid hormone-mediated bone loss. There may be a particular subset of postmenopausal women who are particularly susceptible to estrogen deficiency. Calcitonin levels, which decrease postmenopausally, return to normal with estrogen; other hormones may also play important roles. Osteoporosis is not the result of a single hormonal deficiency or excess; it must be considered in relation to other pathogenetic and risk factors.

Bone Marrow↗
PubMed1987

Atypical insufficiency fractures confused with Looser zones of osteomalacia.

Six women, aged 24-67 years, had osteopenia and insufficiency fractures, which suggested a diagnosis of osteomalacia. The insufficiency fractures occurred at traditional sites for Looser zones, were multiple in number, were symmetrically distributed in three patients, and did not heal promptly. Bone mass was low, as assessed by single-energy photon absorptiometry at the midshaft of the radius. Two postmenopausal women had vertebral compression fractures. Biochemical indices and bone histomorphometric analysis excluded osteomalacia, and in vivo double tetracycline labeling in five patients revealed both high and low bone turnover states. We propose more stringent radiographic criteria for the designation of the term "Looser zone" that retains the customary association between the radiologic event and osteomalacia. This paper also outlines a diagnostic strategy for future cases of atypical insufficiency fractures and proposes reasons for their resemblance to true Looser zones.

Adult↗
PubMed1987

Bone histomorphometry in hypogonadal and eugonadal men with spinal osteoporosis.

We present iliac bone histomorphometric data after in vivo double tetracycline labeling and related biochemical data from 14 nonalcoholic men referred for evaluation of symptomatic spinal osteoporosis. Six patients had previously undiagnosed hypogonadism, and 8 had normal gonadal function and no evident etiology for osteoporosis. Bone histomorphometry revealed no differences in structural measurements or resorption indices between the 2 groups. However, compared to reference values for normal postmenopausal women, osteoblast surface, mineralizing surface, and formation rate were normal or modestly increased in the hypogonadal men and significantly reduced in the idiopathic group. There were significant corresponding differences between the 2 groups in the fasting urinary hydroxyproline to creatinine ratio, an index of bone resorption, and serum total alkaline phosphatase, an index of bone formation. Plasma 25-hydroxyvitamin D levels did not differ between the 2 groups and were above 10 ng/mL in all patients. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels were normal in the hypogonadal group and significantly reduced in the idiopathic group, but did not correlate with any histological measurements. The formation indices fell substantially in 3 of 4 hypogonadal men after 7-14 months of therapy with testosterone and a calcium supplement. We conclude the following. In vitamin D-replete hypogonadal men with osteoporosis, 1,25-(OH)2D synthesis is normal, and bone remodeling is modestly increased and correctable by hormone replacement therapy, as in normal postmenopausal women. In middle-aged men with idiopathic osteoporosis, there is impairment of 1,25-(OH)2D synthesis and of the recruitment and activity of teams of osteoblasts, as in postmenopausal osteoporosis.

Adult↗