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Biomedical subjects

J Power

Publications and source records attributed to J Power.

At least 19 recordsLinked to original sources

Modelling the growth and protein production by insect cells following infection by a recombinant baculovirus in suspension culture.

A mathematical model has been developed to describe the growth and infection of insect cells by recombinant baculoviruses. The model parameters were determined from a series of independent experiments involving batch suspension culture. The profiles generated by the model for cell growth, virus production and protein production agree with those observed in experiments. Presently, the model simulates only systems where cells are not growth-limited. The model is useful in aiding the design and optimization of large-scale systems for production of biological insecticides as well as recombinant proteins and in delineating those areas which are limiting the process and require further, more fundamental, investigation.

Animals

Extragenic suppressors of paralyzed flagellar mutations in Chlamydomonas reinhardtii identify loci that alter the inner dynein arms.

We have analyzed extragenic suppressors of paralyzed flagella mutations in Chlamydomonas reinhardtii in an effort to identify new dynein mutations. A temperature-sensitive allele of the PF16 locus was mutagenized and then screened for revertants that could swim at the restrictive temperature (Dutcher et al. 1984. J. Cell Biol. 98:229-236). In backcrosses of one of the revertant strains to wild-type, we recovered both the original pf16 mutation and a second, unlinked suppressor mutation with its own flagellar phenotype. This mutation has been identified by both recombination and complementation tests as a new allele of the previously uncharacterized PF9 locus on linkage group XII/XIII. SDS-PAGE analysis of isolated flagellar axonemes and dynein extracts has demonstrated that the pf9 strains are missing four polypeptides that form the I1 inner arm dynein subunit. The primary effect of the loss of the I1 subunit is a decrease in the forward swimming velocity due to a change in the flagellar waveform. Both the flagellar beat frequency and the axonemal ATPase activity are nearly wild-type. Examination of axonemes by thin section electron microscopy and image averaging methods reveals that a specific domain of the inner arm complex is missing in the pf9 mutant strains (see accompanying paper by Mastronarde et al.). When combined with other flagellar defects, the loss of the I1 subunit has synergistic effects on both flagellar assembly and flagellar motility. These synthetic phenotypes provide a screen for new suppressor mutations in other loci. Using this approach, we have identified the first interactive suppressors of a dynein arm mutation and an unusual bypass suppressor mutation.

Animals

Pharmacokinetics and serum protein binding of gestodene and 3-keto-desogestrel in women after single oral administration of two different contraceptive formulations.

Two low-dose oral contraceptives, both containing the same dose of ethinyl estradiol (EE2, CAS 57-63-6) but different progestins--gestodene (CAS 60282-87-3) and desogestrel (CAS 54024-22-5), respectively--were administered to 18 women in a single dose, cross-over study. The serum concentrations of gestodene (GEST, one of the components of Femovan) and 3-keto-desogestrel (KDG) have been measured by specific radioimmuno-assays and the pharmacokinetics of both progestins were assessed. The serum protein binding of both compounds was also investigated and although the free fraction was the same for GEST and KDG, the distribution with respect to the binding proteins albumin and sex hormone binding globulin (SHBG) was slightly different. GEST was mainly bound to SHBG, while KDG was predominantly bound to albumin. Maximum concentrations of GEST were observed after 0.7 +/- 0.2 h and amounted to 4.9 +/- 2.4 ng/ml. A biphasic pattern of disposition was observed, with half lives of 0.13 +/- 0.06 h and 14.6 +/- 4.2 h, respectively. The AUC was 32.9 +/- 18.3 ng.ml-1.h. For KDG, maximum serum levels of 1.7 +/- 0.8 ng/ml were observed 1.5 +/- 0.8 h post administration. Drug levels declined with half-lives of 0.5 +/- 0.2 h and 17.0 +/- 9.3 h, respectively, and the AUC was 15.2 +/- 10.9 ng.ml-1.h.

Adult

Pharmacokinetics and serum protein binding of 3-keto-desogestrel in women during three cycles of treatment with a low-dose combination oral contraceptive.

The serum concentrations of 3-keto-desogestrel have been measured in 43 women who took a low-dose oral contraceptive containing 30 micrograms ethinyl estradiol (CAS 57-63-6) together with 150 micrograms desogestrel (CAS 54024-22-5) for a period of 3 months. Basic pharmacokinetic parameters, like Cmax, tmax and AUC, as well as the serum protein binding of 3-keto-desogestrel were determined on days 1, 10 and 21 of the first and the third treatment cycle, respectively. During cycle one, Cmax, AUC(0-4h) and AUC(0-24h) values on day 1 were 1.9 +/- 0.7 ng/ml, 3.9 +/- 1.3 ng.ml-1.h and 12.4 +/- 5.7 ng.ml-1.h, respectively. These values increased to 4.7 +/- 2.0 ng/ml, 12.1 +/- 5.6 ng.ml-1.h and 47.3 +/- 26.0 ng.ml-1.h on day 21. Within cycle 3, a similar, although less steep increase was observed for these parameters and there was practically no difference in the values of corresponding parameters on day 21 of both cycles. Throughout treatment, there was a redistribution of 3-keto-desogestrel with respect to the binding proteins albumin and sex hormone binding globulin (SHBG). During cycle 1, the free fraction decreased from 1.8% on day 1 to 1.1% on day 21, and the SHBG-bound fraction increased at the same time from 40% to 62%, mainly at the expense of the albumin-bound fraction. During cycle 3, there were only minor changes as compared to cycle one. The observed changes in the serum protein binding were related to an increase in SHBG levels during the treatment period.

Adult

Concentration of ethinyl estradiol in the serum of 31 young women following a treatment period of 3 months with two low-dose oral contraceptives in an intraindividual cross-over design.

Two low-dose oral contraceptives, both containing the same dose of ethinyl estradiol (EE2) but different progestins (gestodene and desogestrel, respectively), were compared with respect to the relative bioavailability of EE2. The study was conducted with 31 women as an open intraindividual comparison with the ingestion of both preparations for 3 months, respectively. On days 1, 10 and 21 of the 1st, 3rd and 6th cycle, blood was sampled at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 h following administration. The concentrations of EE2 were determined in the serum samples of each individual and the area under the serum concentration versus time curves, AUC (0-4 h) and AUC (0-24 h), were calculated. Corresponding parameters obtained on days 1, 10 and 21 of the 3rd and 6th month of treatment were compared on a statistical basis, and no differences were found. This result was in concordance with a previously performed study, where both formulations were administered to 18 women in a single-dose cross-over design. However, the results of the previous and the present study are at variance with the result of one other study, reporting higher EE2 levels in the serum of women taking the gestodene-containing formulation as compared to those taking the desogestrel-containing formulation.

Adult

The effect of peritoneal dialysate on pulmonary function and blood gasses in C.A.P.D. patients.

There have been many reports showing diminished vital capacity (VC), total lung capacity (TLC), and functional residual capacity (FRC), after the infusion of peritoneal dialysate in patients on continuous ambulatory peritoneal dialysis (C.A.P.D.) for chronic renal failure. We also examined the effects of the infusion of two litres of dialysate on airways resistance (Raw) using total body plethysmography and on arterial blood gasses. Ten patients on C.A.P.D. were selected. The mean results of dialysate infused (in) and dialysate drained (out) are as follows: FVC 3.66 l (in) and 3.73 l (out) (not significant); VC 3.81 l (in) and 3.99 l (out) (p less than 0.05); FEV1 3.02 l (in) and 2.94 (out) (n.s.); TLC 5.89 l (in) and 6.33 l (out) (p less than 0.05); FRC 3.56 l (in) and 3.78 l (out) (p less than 0.05); Raw 4.79 cmsH21/l/s (in) and 4.72 cmsH20/l/s (out) (n.s.); Pa02 11.03 kPA (in) and 11.35 kPA (out) (p less than 0.001). We conclude that two litre dialysate causes significant reduction of TLC, VC and FRC, and a reduction in Pa02 and A-a02 but has no effect on airways resistance.

Airway Resistance

Human alveolar type II cells: stimulation of DNA synthesis by insulin and endothelial cell growth supplement.

Proliferation of type II cells is important for the recovery of the alveolar epithelium after acute lung injury. However, the factors that regulate the proliferation of human type II cells are unknown. Human alveolar type II cells were isolated from resected lung by dissociation with porcine pancreatic elastase and crystalline trypsin and purified by density-gradient centrifugation and serial differential adherence. The purity of the type II cells in the final adherent preparation was 84.4 +/- 1.1% type II cells by alkaline phosphatase and 87.7 +/- 2.8% by cytokeratin (n = 7). The medium MCDB-151 with 0.4% fetal bovine serum (FBS) was used to demonstrate the stimulatory effect of individual growth factors. Under these conditions, thymidine incorporation was stimulated by insulin, epidermal growth factor, endothelial cell growth supplement (ECGS), and acidic and basic fibroblast growth factors. Cholera toxin did not stimulate thymidine incorporation. The most effective stimulation was by the combination of insulin and ECGS. The incorporation of bromodeoxyuridine was used to identify the proportion of cells that were active in DNA synthesis. Insulin and ECGS increased the percentage of cells that incorporated bromodeoxyuridine from 8.5 +/- 1.3% to 21.3 +/- 2.4% (n = 6). Mitotic figures were seen in smears prepared from cultures incubated with insulin and ECGS. This observation was confirmed by electron microscopy, which demonstrated type II cells in metaphase. Increasing the concentration of FBS or human serum in the culture medium to 10% decreased the stimulatory effect of insulin and ECGS.(ABSTRACT TRUNCATED AT 250 WORDS)

Bromodeoxyuridine

Short course chemotherapy for pulmonary tuberculosis. A randomised controlled trial of a six month versus a nine month oral regimen.

We report on the first trial in the Republic of Ireland to look at chemotherapy for TB. This management trial, carried out in single unit, which treats a third of all TB cases in the Republic of Ireland compared to effectiveness of a three drug/nine month regimen (Rifampicin (R), Isoniazed (R), supplemented with Ethambutol (E) for the first two months = RHE9) with a four drug six months regimen (R, H supplemented with E and Pyrazinamide (Z) for the first two months = RHEZ6). Two hundred and eighty eight patients (288) were entered into the study. A total of 143, (76 were in the RHE9 group and 67 in the RHEZ6 group) completed the trial as planned. At the end of the third month, significantly more patients in the RHEZ6 regimen (98%) were culture negative compared to the RHE9 regimen (88%). All were culture negative at the end of chemotherapy. Drug intolerance was seen in 35 (12%) patients with no significant difference in hepatitis between the two regimens. Toxicity from Pyrazinamide was minimal. One hundred and forty five (145) patients were invalid for analysis for the following reason:- bacteriologically negative TB (41), drug intolerance (35), death (23), non-compliance (19), diagnosis not TB (10), drug resistance (7), extrapulmonary disease (4), consent withdrawn (3), Mycobacteria other than tuberculosis (3). All patients are being followed to monitor relapse rates.

Administration, Oral

Temporal lobectomy for partial complex seizures: evaluation, results, and 1-year follow-up.

Twenty-six patients were evaluated for temporal lobectomy. Fourteen underwent initial monitoring with electrodes in the amygdala and hippocampus bilaterally. Twelve had initial monitoring with scalp and sphenoidal electrodes. Four had conclusive localization without depth electrodes. Twenty-three patients underwent lobectomy. At 1-year minimum follow-up, 15 were seizure free. Five had greater than 90% reduction in seizure frequency. Complications of depth electrodes were one hemorrhage and one abscess. One patient developed impaired memory following surgery. Temporal lobectomy is effective in well-selected patients. Depth electrodes localize seizure onset from mesial temporal structures. Scalp and sphenoidal recording may be sufficient in some cases.

Adolescent

Arachidonic acid metabolites and small airways disease in non-smoking sarcoidosis patients.

The present study was designed to assess the occurrence of small airways disease (SAD) in non-smoking sarcoidosis patients by pulmonary function measurement; and to investigate the possible mechanisms of SAD by measuring the in vitro production of arachidonic acid metabolites (PGE2 and LTB4) by peripheral blood mononucleocytes from sarcoidosis patients. SAD did in fact occur in 15 of the 32 sarcoid patients studied. The increase in LTB4 and decrease in PGE2 observed in SAD patients could imply a causative role for these arachidonic acid metabolites in SAD.

Arachidonic Acids

A comparison of the virulence of three strains of Mycoplasma gallisepticum and one strain of Mycoplasma gallinarum in chicks, turkey poults, tracheal organ cultures and embryonated fowl eggs.

The virulence of three strains of Mycoplasma gallisepticum (S6 of low broth passage, S6 of high broth passage and A514) and of one strain of M gallinarum was investigated in specific pathogen free chicks, turkey poults, chick embryo tracheal organ cultures and embryonated fowl eggs. One strain of M gallisepticum, S6, of low passage, caused high mortality in newly hatched chicks, and turkey poults, high embryo mortality, and rapid suppression of ciliary activity in tracheal organ cultures. The other strains of M gallisepticum and M gallinarum had relatively less effect. In view of its greater sensitivity, chick embryo mortality is preferable to tracheal organ culture for assessing the virulence of experimental strains of M gallisepticum.

Animals