Biomedical subjects

T Cartwright

Publications and source records attributed to T Cartwright.

At least 19 recordsLinked to original sources

PubMed1999

An investigation of stress and pain perception during manual therapy in asymptomatic subjects.

Stress perceived by the patient during the application of a manual therapy treatment technique may account for the reported findings of sympathoexcitation and hypoalgesia immediately after its application. This study investigated whether there was a difference in the level of perceived stress and pain before, during and after the application of a treatment condition (treatment, placebo or control technique), or whether the difference related to the time course of subject involvement in the study.Twenty-four asymptomatic subjects participated in a double-blind, placebo-controlled, within-subjects study in which stress was measured with a stress rating scale and a stress visual analogue scale. Pain experienced by the subject during the application of the treatment technique was measured with a visual analogue scale and modified McGill pain questionnaire. There was no effect of the treatment condition on perceived stress, but there was a reduction in stress levels over the time course of involvement in the experiment, as demonstrated by pre-application levels of stress. Pain was not produced by the treatment technique.This study demonstrated that stress and pain were not features of the lateral glide manipulation of the cervical spine in asymptomatic subjects. If the dorsal periaqueductal grey region is responsible for the initial effects of manual therapy, as has been previously suggested, then stress and pain do not appear to play a role in activating this system during the application of a manual therapy treatment technique in asymptomatic subjects. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

PubMed1997

Interaction of human angiogenin with copper modulates angiogenin binding to endothelial cells.

Angiogenin is a potent inducer of blood-vessel formation with ribonucleolytic activity. Angiogenin binds to high affinity endothelial cell receptors and with lower affinity to extracellular matrix components. Here we report the effect of copper and zinc on these interactions. There was a 4.3-fold increase in angiogenin binding to calf pulmonary artery endothelial cells in the presence of Cu2+ in vitro. A 3.8-fold increase was observed with Zn2+, whereas Ni2+, Co2+, or Li+ had no effect. Specific angiogenin binding to the lower affinity matrix sites was increased by 2.7- and 1.9-fold in the presence of Cu2+ and Zn2+ respectively. Metal ion affinity chromatography and atomic absorption spectrometry were used to show the direct interaction of angiogenin with copper and zinc ions. Angiogenin bound 2.4 mol of copper per mole of protein. We suggest that copper, a modulator of angiogenesis in vivo, may be involved in the regulation of the biological activity of angiogenin.

Angiogenesis Inducing Agents↗

PubMed1994

Natural and structured baselines in the treatment of aggression following brain injury.

This single-case study describes the importance of presenting relevant baseline conditions in planning and evaluating treatment for aggression in a severely brain injured man 1 year after injury. An artificially low natural baseline resulted from staff reluctance to deliver instructions and corrective feedback needed for rehabilitation of self-care skill because these were frequently followed by aggression. A subsequent structured baseline presented these antecedents at the higher rates that were necessary for progress in the patient's rehabilitation. This resulted in an increase in aggressive behaviour, but also gave a more accurate representation of what his behaviour would be like under effective rehabilitation conditions. Intervention was based on data from the structured baseline, and included providing clear expectations, social reinforcement, and decelerative procedures. After reduction of aggression to zero, regular staff were reintroduced and presented instruction and corrective feedback as required. No further aggressive behaviour was noted, and self-care improved so that only minimal assistance was needed. Six months following reintroduction of regular staff, both baseline conditions were replicated. No aggressive behaviour was observed during either, suggesting that maintenance of gains could not be attributed to an artificially reduced rate caused by staff avoiding trigger antecedents.

Aggression↗

PubMed1993

Traumatic rupture of an aortic ulcerative atherosclerotic plaque producing aortic dissection: a complication of interscapular back blows used to dislodge objects from the esophagus.

Penetrating atherosclerotic ulcer of the aorta is a rare entity which usually occurs in the descending thoracic aorta. Herein, we report an unusual case of penetrating aortic ulcer which ruptured into the mediastinum. Interscapular back blows were performed on our patient in an attempt to dislodge an aspirin which she thought was lodged in her esophagus. Unlike previously reported cases of this entity, the penetrating aortic ulcer in our patient was located in the distal thoracic ascending aorta. Diagnosis of penetrating aortic ulcer can be made by utilizing aortography, contiguous dynamic contrast-enhanced computed tomography or magnetic resonance imaging. Treatment consists of adjunctive medical therapy until surgery can be performed.

Aged↗

PubMed1993

Process economics of animal cell and bacterial fermentations: a case study analysis of tissue plasminogen activator.

One link in the complex chain of medical economics is the cost of bringing new drugs and biologicals to the market. Advances in recombinant-DNA technology permit production of therapeutically active proteins in effectively unlimited quantities. Nevertheless, each expression system has a characteristic influence on the nature of the product produced and the process required to obtain it. In this case study we compare experiences with recombinant-tissue plasminogen activator (rtPA) produced in Chinese hamster ovary (CHO) cells and in Escherichia coli, with the aim of understanding the roles of some of the parameters that affect process economics. tPA belongs to the group of highly specific serine proteases that convert plasminogen to plasmin, which in turn degrades several protein substrates including fibrin, thus making it an effective thrombolytic agent. The treatment of acute myocardial infarction with such thrombolytic agents can result in early discharge of patients and decreased medical costs. However, there are major differences in the prices of the various available agents. The price of the FDA-licensed tPA product is $2,200 per dose or $22,000 per gram. It is believed that a significant portion of this price relates to manufacturing costs. We examine by way of case study illustration the cost breakdown for the two processes, and highlight important process, design and economic considerations that ultimately define a particular protein product.

Animals↗

PubMed1992

Moral philosophy and nursing curricula: indoctrination of the new breed.

A sizable proportion of nursing curricula subtly indoctrinate students with a particular normative ethic. Seldom is there adequate philosophical justification for the ethic, and students are rarely invited to subject that ethic to a rigorous philosophical analysis. Nursing curricula are replete with philosophical positions treated as moral imperatives to which all, students and faculty, owe their allegiance. This unsatisfactory situation warrants urgent attention. One problem is that of failing to justify the school's moral philosophy; another is the question of philosophically indoctrinating students to adhere to an ethic that advocates the individual's freedom and responsibility, a practice inconsistent with the predominant proposition advanced by the ethic.

Curriculum↗

PubMed1991

Identification of the main epitope on human cytochrome P450 IID6 recognized by anti-liver kidney microsome antibody.

Antibodies present in the sera of a group of children with autoimmune hepatitis react with human cytochrome P450 IID6. cDNA constructions of various fragments of human P450 IID6 were made and expressed and the resulting peptides were tested in immunoblot with patients' sera. These allowed identification of at least two antigenic sites on the P450 molecule. The main one, recognized by all sera tested, is located between amino acids 239 and 271. Synthesis of three peptides covering this area of the molecule allowed identification of a sequence of three amino acids (tyrosine-tryptophane-asparagine) located at position 261-263 that constitutes the essential part of the epitope. A protein sequence data-base search revealed homologies between this region of human P450 and proteins from Salmonella typhimurium, from human T lymphotropic virus types 1 and 2 and Herpes simplex virus type 1.

Amino Acid Sequence↗

PubMed1990

Low molecular weight, sequence based, collagenase inhibitors selectively block the interaction between collagenase and TIMP (tissue inhibitor of metalloproteinases).

Sequence-based inhibitors of collagenase bearing an hydroxamate group capable of chelating the active site zinc atom were synthesized and tested. The effect of one of these molecules (RP 59794; Ki about 10(-8) M) on the formation of the TIMP: collagenase complex was also tested. RP 59794 blocks complex formation and can partially dissociate established TIMP: collagenase complexes. It exhibits the same stereospecificity in this activity as in its inhibition of collagenase suggesting that TIMP and RP 59794 both interact with the active site region of collagenase.

Amino Acid Sequence↗

PubMed1990

Hypoglycaemic effect of Momordica charantia extracts.

The hypoglycaemic effect of orally administered extracts of fruits of cultivated Momordica charantia (karela) was examined in normal and streptozotocin diabetic mice. In normal mice, an aqueous extract (A) lowered the glycaemic response to both oral and intraperitoneal glucose, without altering the insulin response. This aqueous extract (A) and the residue after alkaline chloroform extraction (B) reduced the hyperglycaemia in diabetic mice at 1 hour. Material recovered by acid water wash of the chloroform extract remaining after an alkaline water wash (D) produced a more slowly generated hypoglycaemic effect. The results suggest that orally administered karela extracts lower glucose concentrations independently of intestinal glucose absorption and involve an extrapancreatic effect. Two types of hypoglycaemic substances with different time dependent effects are indicated.

Animals↗

PubMed1990

Oncogenic proteins new targets for chemotherapeutic agents against cancer.

Over the past 10 years, more than 40 potentially oncogenic genes, termed protooncogenes, have been identified in the human genome. Little is known of the physiological role of the proteins encoded by these genes, but they seem to be involved in the reception and transmission of hormonal and other environmental information from the cell membrane to the nucleus. These proteins may acquire transforming properties when over-expressed or if structurally altered following partial deletions or point mutations. Cytogenetic analysis shows loss of genetic material from specific chromosomal loci in many human tumors, suggesting that the absence of a functional gene at these loci may permit tumor development. The genes involved have been termed "anti-oncogenes". Understanding the control mechanisms of cell proliferation is essential in order to understand how cancer cells escape from this control. To this end, numerous oncogenes have been cloned, permitting the production of modified forms of oncogenic proteins and identification of the regions essential for their biological activity. Availability of large amounts of protein also allows the production of specific antibody which can be used to verify whether blockage of a given protein results in reversion of the transformed phenotype. If it can be shown that the expression of an oncogenic protein is essential for transformation, it should be possible to search for molecules that inhibit its action or which mimic the effects of an anti-oncogene. This type of research is already well advanced for the oncogenic ras proteins, and models have been established that permit both screening for potential inhibitors and design of specific antagonists.

Animals↗

PubMed1989

Specific binding of angiogenin to calf pulmonary artery endothelial cells.

Specific binding of angiogenin (ANG) to calf pulmonary artery endothelial cells was demonstrated. Cellular binding at 4 degrees C of 125I-labeled human recombinant ANG was time and concentration dependent, reversible, and saturable in the presence of increasing amounts of the unlabeled molecules. The interaction was shown to be specific since a large excess of unlabeled ANG reduced labeled ANG binding by 80%, whereas similar doses of RNase A, a structurally related protein, had no effect. Scatchard analyses of binding data revealed two apparent components. High-affinity sites with an apparent dissociation constant of 5 x 10(-9) M were shown to represent cell-specific interactions. The second component, comprising low-affinity/high-capacity sites with an apparent dissociation constant of 0.2 x 10(-6) M, was essentially associated with pericellular components. High-affinity ANG binding sites varied with cell density and were found on other endothelial cells from bovine aorta, cornea, and adrenal cortex capillary but not on Chinese hamster lung fibroblasts. Divalent copper, a modulator of angiogenesis, was found to induce a severalfold increase in specific cell-bound radioactivity. Placental ribonuclease inhibitor, a tight-binding inhibitor of both ribonucleolytic and angiogenic activities of ANG, abolished 125I-labeled human recombinant ANG binding only in the absence of copper.

Angiogenesis Inducing Agents↗

PubMed1989

[Inhibition of synovial collagenase by actinonin. Study of structure/activity relationship].

Actinonin is a pseudopeptide antibiotic which inhibits collagenase at micromolar concentrations [10]. In this study, Actinonin analogs were tested to investigate "structure/activity" relationships for this class of molecule. The results indicate that distance between the hydroxamate carbonyl group and that of the first amide bond is important, since increasing this distance by a methylene group, decreases inhibition by a factor of 100. The amide bonds of this inhibitor must be in the peptide bond orientation. Different N terminal amide derivatives and different hydrophobic substituents adjacent to the hydroxamate residue, had little effect on inhibitory activity. However, in this series of molecules, two hydrophobic groups separated by an amide bond seem to be necessary for potent inhibition.

Animals↗

PubMed1989

[Natural inhibitor of metalloproteinases: structural and functional study].

A potent collagenase inhibitor was purified from cells of calf aorta medial tissue maintained in culture. This molecule was characterized and identified as TIMP (Tissue Inhibitor of Metalloproteinases). Formation of a TIMP--collagenase complex was demonstrated chromatographically using pure TIMP and pure pig synovial cell collagenase. The N-terminal aminoacid sequence of TIMP was determined and, using appropriate oligonucleotide probes the human genes was cloned from a human cDNA bank. This gene was expressed in E. coli, and fully active TIMP was obtained after a denaturation renaturation process. The interest of TIMP as a model for the design of novel collagenase inhibitors is discussed.

Amino Acid Sequence↗

PubMed1988

Monoclonal antibodies against synovial collagenase: use for immunopurification and characterization of the latent and active enzyme.

Monoclonal antibodies have been produced against porcine synovial collagenase which recognize both the active enzyme and its inactive precursor. These antibodies inhibited the collagenolytic activity of collagenase, but not its activity with a synthetic peptide substrate. The antibodies were also able to recognize human synovial, human skin fibroblast and human chondrocyte collagenase but not the enzyme from human granulocytes. One of the monoclonal antibodies was successfully used for the immunopurification of the porcine enzyme and these experiments led to the demonstration of an endogenous activator of procollagenase in the synovial cell culture medium.

Animals↗

PubMed1988

Arrhythmia and late mortality after Mustard and Senning operation for transposition of the great arteries. An eight-year prospective study.

Arrhythmia and late sudden death are recognized complications of intraatrial repair of transposition of the great arteries. We performed a prospective study over 8 years in 100 consecutive hospital survivors who underwent Mustard (46 patients) or Senning (54 patients) operations between 1978 and 1982. Arrhythmia was analyzed by preoperative, postoperative, and serial follow-up Holter monitoring and standard electrocardiograms and was related to clinical outcome. Before repair, all patients were in sinus rhythm with a low incidence of arrhythmia. After repair, there was a gradual decrease in stable sinus rhythm during follow-up so that at a mean of 7 years after operation only 56% of patients having the Senning operation and 66% having the Mustard, with simple transposition, were in stable sinus rhythm on Holter monitoring. There was no significant difference between the two operations. Eleven patients (five after Senning [two simple, three complex], six after Mustard [five simple, one complex]) died during follow-up, four suddenly (two after Senning, two after Mustard). However, loss of sinus rhythm or the presence of arrhythmia on standard electrocardiograms or Holter recordings did not identify patients at risk for increased morbidity or mortality. Thus, even with current surgical techniques, gradual loss of sinus rhythm occurred after both Mustard and Senning operations. Because late death could not be predicted by electrocardiographic analysis, an alternative approach involving detailed hemodynamic and electrophysiologic measurements may be required to identify high-risk patients.

Arrhythmias, Cardiac↗

PubMed1987

Effect of peptide chain length on absorption of egg protein hydrolysates in the normal human jejunum.

The influence of the peptide chain length of partial enzymic hydrolysates of protein on nitrogen and amino acid absorption was studied in 12 subjects using a jejunal perfusion technique. Three hydrolysates of egg white and an equivalent amino acid mixture were perfused at 30 mmol/L and 100 mmol/L in two separate experiments. Two hydrolysates (OH1 and OH2) contained mainly dipeptides and tripeptides, whereas the third (OH3) comprised tripeptide to pentapeptides as judged chromatographically. Nitrogen absorption was significantly slower from the higher chain length mixture, OH3, than from the short chain mixtures, OH1 and OH2, at both concentrations. Similarly, several amino acid residues were absorbed less well from OH3 than from OH1 and OH2. These data demonstrate that the chain length of heterogeneous mixtures of peptides affects absorption of nitrogen and individual amino acid residues, and suggest that brush border hydrolysis of tetrapeptides and pentapeptides limits absorption from enzymic hydrolysates of protein which simulate the composition of the postprandial luminal contents.

Amino Acids↗

PubMed1987

Chemical synthesis of a gene coding for human angiogenin, its expression in Escherichia coli and conversion of the product into its active form.

A synthetic gene coding for human angiogenin was synthesized by solid support phosphoramidite chemistry as eight long oligodeoxynucleotides which were subsequently assembled and cloned in Escherichia coli. The gene was designed to use codons found in highly expressed E. coli proteins. A pBR322-derived expression vector was constructed containing the E. coli trp promoter, the ribosome-binding site of the bacteriophage lambda cII gene, the angiogenin coding sequence, and the transcription terminator region of the E. coli rrnB operon. Under tryptophan deprivation, angiogenin was strongly expressed in E. coli cells at a yield of 5-10% of total protein. The eukaryotic protein was found to be insoluble but could be easily renatured and purified. The purified angiogenin was demonstrated to be active as an angiogenic factor and exhibited a characteristic RNase activity.

Amino Acid Sequence↗

PubMed1987

An inhibitor of mammalian collagenase active at micromolar concentrations from an actinomycete culture broth.

Anti-collagenase activity was detected in the culture supernatant of an Actinomycete strain S 4373. The molecule was purified by solvent extraction, medium pressure and high pressure reverse phase chromatography and finally by HPLC gel filtration. The pure product was analyzed by mass spectroscopy and was identified as actinonin, a known pseudopeptide antibiotic. The Ki was determined as 1.4 microM and this value was confirmed using pure synthetic actinonin.

Actinomycetales↗