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Biomedical subjects

R Gerber

Publications and source records attributed to R Gerber.

At least 37 records · Page 2Linked to original sources

Is weekly port filming adequate for verifying patient position in modern radiation therapy?

PURPOSE: The objective of this study is to use daily electronic portal imaging to evaluate weekly port filming in detecting patient set-up position. METHODS AND MATERIALS: A computer-based portal alignment method was used to quantify the field displacements on 191 digitized weekly port films and 848 daily electronic portal images in 21 radiation therapy patients. An electronic portal image data set as a control for actual daily treatment position was used to evaluate weekly port films with respect to same-day field displacement, rate of field placement error detection, and prediction of subsequent daily field displacements. RESULTS: The field displacements measured on a port film frequently deviated from the corresponding field displacements on the electronic portal image obtained in the same treatment set-up. A linear regression analysis showed that the curves fitted to the same-day field displacements had slopes that differed significantly from unity (p < 0.001). Overall, the respective frequencies of field placement error, beyond clinical tolerance limits of 5, 7, and 10 mm (corresponding to head and neck, thoracic, and pelvic sites) for port filming and electronic portal imaging were 11% and 14% (p = 0.4) in the X-direction (lateral or anteroposterior) and 24% and 13% (p = .0001) in the Y-direction (caphalad-caudad). When the data were broken down by anatomical region, this discrepancy was found to be mainly due to the differences in the thorax, and head and neck image data sets. For thoracic fields, error in Y-shifts was 28% by port filming, but only 9% by portal imaging (p = 0.01). In the head and neck region, 18% of the port films exceeded tolerance, whereas only 6% of the electronic portal images did (p = 0.0001). Field displacements on the treatment set-ups between the acquisition of port films were not predicted by those films. CONCLUSION: There are discrepancies between the field displacements and field placement errors detected by weekly port films and daily electronic portal images. This study suggests that improved methods of treatment verification may be necessary in modern radiation therapy.

Diagnostic Imaging↗

Soluble forms of the human T cell receptor CD4 are efficiently expressed by Streptomyces lividans.

We have developed a new gene expression and secretion system for Streptomyces lividans and used it to produce soluble forms of a human T-cell receptor CD4 at levels greater than 300 mg/l. The system uses the transcription, translation and secretion signals of the serine protease inhibitor gene STI-II which is naturally produced by S. longisporus. Using these signals, soluble derivatives of CD4 were secreted directly into the culture supernatant as correctly processed soluble, biologically active proteins. High level expression of the CD4 proteins depended on the transcription initiation signal, the amino acid sequence surrounding the signal peptide cleavage site and temporally controlled protease activities. We discuss these results in the context of the potential of this system for producing other eukaryotic proteins in Streptomyces.

Amino Acid Sequence↗

Complete heart block complicating retrograde left-heart catheterization of patients with cardiac allografts.

The development of complete heart block during left-sided cardiac catheterization is an uncommon event. We describe three cases of complete heart block complicating left-sided cardiac catheterization of patients with cardiac allografts. Review of the cases performed at our institution suggests that complete heart block during left-sided catheterization may be more common in patients with cardiac allografts.

Aged↗

Differentiated group professional practice in nursing: a demonstration model.

This innovative professional practice model was developed to assist in the redesign of the current nursing care delivery system in hospitals. It is expected that this model will facilitate the promotion of professional practice and that the results will be positive ones for patients, nurses, and hospitals. As Barry and Gibbons wrote recently, "Changing circumstances have become so compelling that it is no longer a question of whether familiar systems need redesigning, but rather how soon and by what means a different system will take place of the existing one."

Arizona↗

Effects of mutations altering SOS regulation on a nalidixic acid-inducible system for the production of heterologous proteins in Escherichia coli.

The major leftward early promoter of phage lambda pL, has frequently been used to drive expression of heterologous genes in Escherichia coli. pL is typically maintained fully repressed by the lambda cl protein. When induction of heterologous protein synthesis is desired, one of several potential mechanisms of destroying cl function is employed and the expression of the foreign gene commences. One method of derepressing pL involves exposing cells to nalidixic acid, which results in the "activation" of RecA protein and the subsequent RecA-mediated proteolytic cleavage of cl. Activated RecA also mediates the cleavage of the E. coli LexA protein, resulting in induction of the SOS regulon (at least 15 E. coli genes, including recA). We have examined the effect of two chromosomal mutations on the productivity of nalidixic acid inductions. One of the tested mutations (recA o) increased the intracellular concentration of RecA prior to induction; the other (lexAind-) resulted in a mutated lexA protein insensitive to RecA-mediated cleavage. These mutations were introduced into a strain carrying a cl+ defective lysogen. Synthesis of two heterologous proteins, human alpha 1-antitrypsin and a fusion protein partially derived from the Plasmodium falciparum circumsporozoite surface antigen, was examined in the wild-type and mutant strains. The maximum alpha-1 antitrypsin concentration achieved was improved by 50% when the recA o strain was used rather than the wild-type; however, only smaller changes (20% or less) in the maximum concentration of the malaria fusion protein were observed. Use of the lexAind- strain resulted in a decrease in the maximum concentration attained for both heterologous products.

Animals↗

[Economic, financial and social sequelae of successful kidney transplantations].

The effects were studied of successful kidney transplantation on 54 recipients of an isolated first kidney graft in 1986. The parameters studied were ability to work, dependence on disability insurance and physical well-being. We compared the conditions in the final months before and one year after transplantation. The data were derived from the case histories and by use of a questionnaire. A second questionnaire was sent to every patient. If data were still lacking, we contacted the patients by telephone. Graft function was good in 43 cases and in 3 cases poor but sufficient. 8 patients needed dialysis again. It is concluded that, concerning ability to work and quality of life, successful transplantation is superior to any kind of dialysis. One year after transplantation, 31 of 54 patients were able to work full time, while during the last months before transplantation only 7 were capable of this. In all 54 patients, average ability to work increased about 23%. The 16 former hospital hemodialysis patients with well functioning graft and with no other diseases or disturbances increased their average ability to work by around 50%. Dependence on disability insurance decreased to a corresponding extent. 35 of 54 patients reported improved general physical well-being after transplantation.

Follow-Up Studies↗

Effects of 5-HT1A agonists and 5-HT2 antagonists on haloperidol-induced dyskinesias in squirrel monkeys: no evidence for reciprocal 5-HT-dopamine interaction.

Dyskinetic movements and dystonic postures may be induced by neuroleptics in monkeys that have undergone previous neuroleptic treatment, and these motor abnormalities constitute a primate model of drug-induced extrapyramidal symptomatology. In view of previous suggestions that brain serotonergic systems may tonically inhibit dopamine neurons, the effects of several new and selective 5-HT2 receptor antagonists and 5-HT1A receptor agonists were investigated in this model. Setoperone, a dopamine D2 receptor antagonist with extremely potent 5-HT2 antagonism, caused dyskinetic movements. Although ritanserin is a potent 5-HT2 antagonist with very weak dopamine antagonist properties, this drug did not antagonize dyskinesias but induced them when administered at a high dose (30 mg/kg). Buspirone induced dyskinesias and blocked apomorphine-induced climbing, supporting prior reports that it has dopamine antagonist effects. Gepirone, a 5-HT1A agonist with less marked dopamine antagonist properties, induced dyskinesias in only one of six monkeys at 30 mg/kg and did not block haloperidol-induced dyskinesias. 8-OH-DPAT partly attenuated haloperidol-induced dyskinesias, an effect possibly attributable to its weak dopamine agonist properties. Tonic inhibition of brain extrapyramidal dopamine systems by serotonin systems does not appear to characterize neuroleptic-related dyskinesias in squirrel monkeys.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Rotational behavior induced by 8-hydroxy-DPAT, a putative 5HT-1A agonist, in 6-hydroxydopamine-lesioned rats.

Rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the ascending nigro-striatal pathway have been shown to rotate in response to dopamine (DA) agonists that are not considered to have postsynaptic DA stimulant properties in intact animals, suggesting a relative loss of DA receptor selectivity in the denervated striatum. The present experiments assessed the possibility that this loss of selectivity may extend to serotonin (5HT) agonist drugs. The 5HT-1a agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), at doses of 0.3-3 mg/kg SC, induced robust contralateral rotational behavior (RB) in 6-OHDA-lesioned rats that had been preselected on the basis of high responsiveness to the atypical DA agonists 3-PPP and SKF 38393. Rats with unilateral dorsal raphe lesions induced by 5,7-dihydroxytryptamine (5,7-DHT) showed contralateral RB in response to similar doses of 8-OH-DPAT but with a different behavioral pattern. The putative 5HT-1b agonist RU 24969 produced contralateral RB in 5,7-DHT-lesioned rats while showing a much weaker effect in 6-OHDA-lesioned rats. Striatal DA levels were depleted by 99% in representative 6-OHDA-lesioned rats but striatal 5HT levels were unaffected. The effects of 8-OH-DPAT in 6-OHDA-lesioned rats were therefore not attributable to destruction of ascending 5HT-containing neurons. These effects may result from indirect actions, mediated by 5-HT neurons or neuronal receptors, that result from asymmetry of brain DA systems.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

Heterogeneous rotational responsiveness in 6-hydroxydopamine-denervated rats: pharmacological and neurochemical characterization.

Qualitative differences in pharmacological responsiveness to various types of dopamine agonists have been reported in rats that have undergone unilateral 6-hydroxydopamine (6-OHDA)-induced denervation of the nigro-striatal pathway. The present experiments further characterize these differences, pharmacologically and neurochemically. Rats were classified as having high rotational sensitivity (0.03 mg/kg SC apomorphine sufficient to induce more than 100 rotations/20 min) or low sensitivity (0.3 mg/kg SC apomorphine required to meet this criterion). High sensitivity rats showed marked contralateral rotational behavior (approximately 150 rotations/20 min) in response to apomorphine (ED50 = 0.08 mg/kg IP), CGS 15855A (ED50 = 0.07 mg/kg), CGS 15873A (ED50 = 0.43 mg/kg), (+)-3-PPP (ED50 = 2.3 mg/kg), (-)-3-PPP (ED50 = 0.87 mg/kg) and quinpirole (peak effective dose, 0.03 mg/kg). In low sensitivity rats, 3- to 10-fold higher doses of apomorphine induced a maximal rate of rotational behavior, but only partial effects were produced by quinpirole, CGS 15855A, CGS 15873A, (+)-3-PPP, and (-)-3-PPP (40-80 rotations/20 min). Because apomorphine is a nonselective D1 and D2 agonist, it is proposed that activation of either D1 or D2 receptors suffices to induce high rates of rotation in high sensitivity rats, whereas in low sensitivity rats, D1 or D2 agonism alone induces submaximal rotation rates. The ipsilateral rotational behavior induced by d-amphetamine was more pronounced and occurred at lower doses in the high-sensitivity rats. Striatal dopamine depletion on the lesioned side did not differ between the groups, but low sensitivity rats showed two-fold higher DOPAC/DA ratios on the lesioned side than did high-sensitivity rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Injections of deuterated tryptamine into the nucleus accumbens of the rat: effects on locomotor activity and monoamine metabolism.

Previous studies have shown that the systemic injection of tryptamine stimulates locomotion in rats and that the nucleus accumbens, a region involved in locomotion, contains the largest concentrations of binding sites for tryptamine in the brain of the rat. The present study examined the behavioral and neurochemical effects of bilateral injections into the accumbens of a deuterated analog of tryptamine, a,a-[2H]tryptamine. Injections of 25 micrograms a,a-[2H]tryptamine increased movements in rats at 25-70 min after injection and increased vertical (rearing) activity at 25-40 min. Injections of 50 micrograms of a,a-[2H]tryptamine produced a transient suppression of movement and vertical activity at 5-15 min, followed by increases in these activities at 40-65 min after injection that were comparable to the increases elicited by 10 micrograms of d-amphetamine. At 30 min after the injection of 50 micrograms a,a-[2H]tryptamine the concentration of dopamine in the nucleus accumbens was increased by 87%, and was preceded by a transient decrease in the level of the metabolite of dopamine homovanillic acid. The levels of 5-hydroxytryptamine and its major metabolite, 5-hydroxyindoleacetic acid in the nucleus accumbens were not changed. Thus, a,a-[2H]tryptamine may interact with tryptamine receptors in the nucleus accumbens to modulate locomotor behavior through mesolimbic dopamine neurons.

Animals↗

Glycopeptide antibiotics: a mechanism-based screen employing a bacterial cell wall receptor mimetic.

The evolution of a highly targeted screening program for the discovery of antibiotics of the glycopeptide (vancomycin) class is described. A holistic approach was utilized which optimized not just screening techniques but also the selection of candidate producer cultures and their growth under conditions which enhanced production of target compounds. Two screen techniques were utilized; differential inhibition of a vancomycin-resistant strain and its susceptible parent, and a specific antagonism screen using the reversal of glycopeptide activity by a tripeptide analog of the glycopeptide receptor, diacetyl-L-lysyl-D-alanyl-D-alanine. The latter screen was 2- to 32-fold more sensitive to known glycopeptides than the former, and was absolutely specific, yielding no false positive responses. The use of the tripeptide antagonism assay, combined with optimized culture selection and growth conditions yielded novel glycopeptide antibiotics at a rate of 1 per 320 cultures screened. With a holistic approach to screening and properly optimized techniques, large numbers of cultures do not need to be examined in order to discover novel antibiotics.

Actinomycetales↗

Biosynthetic studies of aridicin antibiotics. II. Microbial transformations and glycosylations by protoplasts.

In connection with the biosynthetic studies of the aridicin antibiotics in Kibdelosporangium aridum, various microorganisms, known to produce related glycopeptide antibiotics, have been examined for their glycosylating activity. A number of strains were found to mannosylate the aridicin aglycone, while Actinoplanes teichomyceticus was found to have deacylating activity as well. A protoplast system of K. aridum was developed and was found to possess novel glycosylating activity in addition to the mannosylating activity which was also present in the whole cells. Effects on the glycosylating activity by various membrane solubilizing agents have been discussed.

Actinomycetales↗