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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 685 records · Page 38Linked to original sources

Lysozyme kinetics in low water activity media. A possible hydration memory.

The influence of water activity on initial lysozyme kinetics is studied. Enzyme catalytic capacity exponentially increases with thermodynamical water activity of the reactant medium; this relation seems independent of the chemical structure of the water activity depressors but dependent on the structuration of water molecules they induce. This influence of water organization on initial enzyme activity is immediate and may be preserved even after a large dilution, thus lysozyme presents a "hydration memory" phenomenon. This effect is in accordance with sorption/desorption isotherms, an hysteresis loop being observed.

Culture Media↗

Scaffolding protein regulates the polymerization of P22 coat subunits into icosahedral shells in vitro.

Coat and scaffolding subunits derived from P22 procapsids have been purified in forms that co-assemble rapidly and efficiently into icosahedral shells in vitro under native conditions. The half-time for this reaction is approximately five minutes at 21 degrees C. The in vitro reaction exhibits the regulated features observed in vivo. Neither coat nor scaffolding subunits alone self-assemble into large structures. Upon mixing the subunits together they polymerize into procapsid-like shells with the in vivo coat and scaffolding protein composition. The subunits in the purified coat protein preparations are monomeric. The scaffolding subunits appear to be monomeric or dimeric. These results confirm that P22 procapsid formation does not proceed through the assembly of a core of scaffolding, which then organizes the coat, but requires copolymerization of coat and scaffolding. To explore the mechanisms of the control of polymerization, shell assembly was examined as a function of the input ratio of scaffolding to coat subunits. The results indicated that scaffolding protein was required for both initiation of shell assembly and continued polymerization. Though procapsids produced in vivo contain about 300 molecules of scaffolding, shells with fewer subunits could be assembled down to a lower limit of about 140 scaffolding subunits per shell. The overall results of these experiments indicate that coat and scaffolding subunits must interact in both the initiation and the growth phases of shell assembly. However, it remains unclear whether during growth the coat and scaffolding subunits form a mixed oligomer prior to adding to the shell or whether this occurs at the growing edge.

Capsid↗

Prevalence of patent foramen ovale in patients with stroke.

The cause of ischemic stroke in younger adults is undefined in as many as 35 percent of patients. We studied the prevalence of patent foramen ovale as detected by contrast echocardiography in a population of 60 adults under 55 years old with ischemic stroke and a normal cardiac examination. We compared the results with those in a control group of 100 patients. The prevalence of patent foramen ovale was significantly higher in the patients with stroke (40 percent) than in the control group (10 percent, P less than 0.001). Among the patients with stroke, the prevalence of patent foramen ovale was 21 percent in 19 patients with an identifiable cause of their stroke, 40 percent in 15 patients with no identifiable cause but a risk factor for stroke, such as mitral valve prolapse, migraine, or use of contraceptive agents, and 54 percent in 26 patients with no identifiable cause (P less than 0.10). These results suggest that because of the high prevalence of clinically latent venous thrombosis, paradoxical embolism through a patent foramen ovale may be responsible for stroke more often than is usually suspected.

Adult↗

A method for fixation of elastin demonstrated by stress/strain characterization.

In the process of examining the effects of oxidants on the mechanical properties of purified ligamentum nuchae elastin, it was found that sodium hypochlorite as constituted in Clorox will fix elastin at any preset extension. The treatments were carried out at a 1 to 5 dilution and at 0, 20 and 40% extensions. In each case, the new resting length was near the preset length and the elastic modulus increased remarkably, for example, from 1 to 5 x 10(7) dynes/cm2 for the sample preset at 20% extension. As reflected in the increased elastic modulus, the fixation was achieved by the formation of irreversible cross-links. Due to the near absence of side chains containing chemically reactive groups suitable for contributing to the formation of additional cross-links required in fixation, this is the first method whereby irreversible fixation of elastin has been achieved. The absence of a suitable fixative for elastic tissues such as lung, arteries, etc. has limited the microscopic characterization of functional extended states of these tissues.

Animals↗

Amino acid sequence determination and three-dimensional modelling of thioredoxin from the photosynthetic bacterium Rhodobacter sphaeroides Y.

The complete primary structure of thioredoxin from Rhodobacter sphaeroides Y has been determined by analysis of peptides after cleavage with cyanogen bromide, chymotrypsin and trypsin. Peptides were separated by HPLC and analyzed by liquid-phase and gas-phase sequencer degradations. The protein consists of 105 residues (Mr = 11,180); its amino acid sequence shows a clear homology to the five known thioredoxins from plant or bacterial sources, with 40-56% residue identity when the proteins are aligned at the active-site disulfide. Not only the active-site regions are conserved, but also residues which belong to the hydrophobic surface suggested to be important for binding of procaryote thioredoxins in redox interactions with other proteins (residues 75-76; 91-93 in Escherichia coli). A three-dimensional model of Rb. sphaeroides thioredoxin has been derived from the E. coli crystallographic structure with computer graphics. This model indicates that the overall structures as well as the active sites are closely similar; however, the residue substitutions allow both proteins to adopt different local folding as shown in the hydrophobic core.

Amino Acid Sequence↗

Distribution of glutamate decarboxylase-like immunoreactivity in the sixth abdominal ganglion of the cockroach Periplaneta americana.

An antiserum against glutamate decarboxylase (GAD) of the rat brain was used to locate GAD activity in sections of the nervous system of the cockroach, Periplaneta americana. The sixth abdominal ganglion was chosen because electrophysiological evidence suggests the presence of GABAergic inhibitory synapses in the cercal-giant interneuron system. Groups of somata and numerous fibres and tracts were positively labelled by the GAD antiserum. A posterior group of labelled somata could be identified close to the entry of the cercal nerves. A line of somata clusters lay along a ventro-lateral furrow. Another discrete row of GAD-like cells was located dorso-laterally. Some small cells among the dorsal unpaired neurons were labelled. A small central group appeared under these cells. An abundance of GAD-like processes and transversal tracts were found within the neuropile. The different systems of GABAergic inhibitors in the ganglion are discussed; in particular we show that the fibres of cercal nerve X are not labelled. This demonstrates that the latter act on the giant fibres via interneurons. We suggest that the group that sends axons into the overlapping region between the cercal nerve and the giant fibre could be the inhibitory interneurons involved in this system.

Abdomen↗

Plasma and synovial fluid meclofenamic acid concentrations in patients with rheumatoid arthritis of the knee.

We have measured plasma and synovial fluid concentrations of meclofenamic acid at 2, 4, 8, and 12 h during steady-state administration (100 mg three times daily for 4-7 days). Paired plasma and synovial samples were obtained pre-treatment and at one of the above times in twelve patients with a diagnosis of rheumatoid arthritis. In addition, the extent of protein binding of meclofenamic acid was assessed in vitro in the pre-treatment plasma and synovial fluid specimens. Peak total concentrations of 1.73 and 0.86 micrograms.ml-1 were observed in plasma (at 2 h) and synovial fluid (at 4 h) respectively. The extent of protein binding was 99.7 and 99.6% (not significantly different) in plasma and synovial fluid respectively. The results of this study are compared to those from similar reported studies of other nonsteroidal anti-inflamatory compounds.

Arthritis, Rheumatoid↗

Invasive squamous cell carcinoma of the cervix after recent negative cytologic test results--a distinct subgroup?

A study was conducted to determine if invasive cervical cancer diagnosed shortly after negative cytologic test results represents a demographically or epidemiologically distinct subgroup of these tumors. A total of 200 patients with invasive squamous cervical cancer and matched, neighborhood control subjects were interviewed. Cytology reports for smears taken 5 years before diagnosis were obtained, and reportedly negative smears were solicited and reevaluated. Thirty-three patients (group 1) had had one or more negative smears within 5 years and no previous abnormal cytologic results. At diagnosis cancers in group 1 had progressed further than those of patients with nondiagnostic positive smears (group 2, n = 43) but not as far as those of patients with no cytologic tests done within 5 years (group 3, n = 96). Age and social class were the same in groups 1 and 2, but both groups were younger and better educated than group 3. Otherwise group 1 did not differ from the other groups and the same risk factors prevailed roughly equally in all three groups. Therefore cervical tumors diagnosed soon after negative cytologic test results do not appear to differ etiologically from other squamous carcinomas at this site, and the failure of screening to detect these tumors is probably due to rapid progression through the preinvasive stages and/or failure to shed cancer cells in quantities sufficient for detection by routine cytologic screening.

Adolescent↗

Diagnosis of primary cardiac sarcoma. Report of 4 cases and review of the literature.

The authors report the most extensive series of malignant primitive cardiac tumours. The patients presented with pericarditis in three cases and with a ventricular rhythm disorder in one patient. The diagnosis was made by non-invasive imaging techniques in three of the four. Angiography was carried out in three cases and was the determining diagnostic procedure in one. Diagnosis of the cardiac tumour was made prior to death in all cases. A histological diagnosis was obtained surgically in two cases. From the therapeutic viewpoint, surgical excision followed by chemotherapy and/or radiotherapy may prolong life. The average survival period of our patients was 11 months. The prognosis appears to be better after early surgical intervention. In view of the variability of the clinical features of cardiac sarcomas, cardiac computed tomography scanning is a valuable complement to cross-sectional echocardiography and, in our opinion, essential for early diagnosis.

Adolescent↗

Image processing of electron micrographs of human alpha 2-macroglobulin half-molecules induced by Cd2+.

Human alpha 2-macroglobulin is a tetrameric plasma inhibitor of proteinases. Its dissociation by Cd2+ gives functional dimers. Electron microscopy of negatively stained dimers shows their round-ended cylindrical shape with furrows delimiting 3 main stain-excluding domains. Image processing of electron micrographs shows the existence of 2 main orientations of the dimers on the carbon support film. The dimer is composed of 2 curved monomers linked in a central domain, and related by a 90 degree rotation. Taking into account the known primary structure of alpha 2-macroglobulin and the linkage of the 2 constitutive monomers by 2 disulfide bonds, the molecular organization of the dimer is discussed, extended to the tetrameric molecule and compared to the published models of human alpha 2-macroglobulin.

Cadmium↗

Electrical excitability of artificial enzyme membranes. IV. Theoretical approach of the membrane potential of synthetic proteinic films.

This paper deals with the theoretical approach of the membrane potential of artificial proteinic film. Programming techniques using finite difference simulations for the steady state and transient solutions of the Nernst-Planck and Poisson equations were used and solved by the collocation and corrector methods. This approach allows one to calculate the membrane potential without any discontinuity between the Donnan and the diffusion potentials, the thickness of the boundary layers being automatically determined by the intrinsic properties of the solution and of the membrane. The theoretical results are compared with experimental potentials measured on proteinic artificial films.

Enzymes↗

Intraoperative radiation therapy of hepatic metastases: technical aspects and report of a pilot study.

Surgical resection of hepatic metastases offers long-term survival, and possible cure, for selected patients with colorectal carcinoma. Fifty percent of patients considered candidates for resection are found to have disease confined to the liver. The resections necessary are often more extensive than predicted preoperatively, which provides an opportunity for innovative approaches using radiation therapy. The intraoperative radiation therapy technique presented here offers the ability to control multiple metastatic deposits in patients not deemed resectable. This is achieved using remote afterloading interstitial (Ir-192) radiation therapy to deliver tumoricidal radiation doses to limited volumes within the liver. The technique was used to treat 11 patients in a pilot study, delivering radiation doses of 20 Gy to the periphery of predetermined target volumes in a single treatment. The number of metastatic deposits treated ranged from 2 to 11 separate tumors with maximum diameters from 3 to 9 cm (median 6 cm). Hospitalizations were from 6 to 23 days (median 8) with only one patient experiencing a surgically related complication (wound dehiscence and pneumonia). There were no radiation related complications on follow-up to 18 months. Biopsies of two treated sites in a patient undergoing reoperation confirmed control of tumors by this procedure. This technique is offered as a standby procedure to patients undergoing exploration for hepatic resection at our institution.

Aged↗

The spectrum of closed-head injuries in facial trauma victims: incidence and impact.

Little is known of the incidence of closed-head injury (CHI) associated with facial trauma. To study this problem, we conducted a retrospective review of 200 consecutive admissions to the University of Michigan Medical Center Emergency Department from 1980 to 1985 for treatment of acute facial fractures. All patients were admitted within 48 hours of injury (93% within 24 hours). Medical records were reviewed for age, sex, description, and circumstances of facial injury; assessment of loss of consciousness and anterograde amnesia; and associated intracranial or extracranial injuries. Seventy-three percent of the patients were men (mean age, 27.8 years). Etiologies, in descending order, were road traffic accidents (52%), assaults (22%), sports (14%), falls (7%), other injuries (3%), and gunshot wounds (2%). The incidence rate of CHI in our study was 55%. More than 90% of the head injuries were associated with the loss of consciousness of less than one hour. Risk factor analysis failed to demonstrate that an increased risk of CHI is associated with age, sex, or number of facial fractures. However, there was a one and one-halffold increased risk associated with patients involved in automobile accidents.

Accidents, Traffic↗

Evaluation of a mutual help network for the elderly residents of planned housing.

We set up a mutual help network among the elderly residents of a government-subsidized apartment building and evaluated its impact on their social ties, social support satisfaction, and depression. A quasi-experimental design was used, with the residents of a similar building located in the same neighborhood serving as the control group. A total of 230 individual services were exchanged, and 28 group activities were organized during the study period. There was almost no difference between experimental and control groups with respect to the change over the study period in the number of social ties with other residents of the building. Support satisfaction decreased in both groups, but the decrease was larger in the experimental group. The control group had a slight decrease in the frequency of their depressive symptoms, whereas the experimental group had a moderate increase. More research is needed on the ability of social support interventions to produce beneficial effects on mental health among individuals who are not experiencing a particular life stress.

Aged↗

Activity of spiramycin against chlamydia, in vitro and in vivo.

In-vitro and in-vivo studies were performed to assess the activity of spiramycin against chlamydiae. In tissue culture spiramycin exhibited very good activity against Chlamydia trachomatis but less against C. psittaci. C. psittaci was also studied in a mouse experimental model. There was 100% clinical cure of the mice with 50 mg/kg, demonstrating excellent in-vivo activity. The livers of mice recovering after therapy showed less chlamydial antigen than controls. These results show good in-vitro and in-vivo activity of spiramycin against chlamydiae, suggesting that clinical trials are warranted.

Animals↗