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Biomedical subjects

D Bruce

Publications and source records attributed to D Bruce.

At least 37 records · Page 2Linked to original sources
PubMed1999

Modulation of flash-induced photosystem II fluorescence by events occurring at the water oxidizing complex.

The mechanism of flash-induced changes with a periodicity of four in photosystem II (PSII) fluorescence was investigated with the aim of further using fluorescence measurements as an approach to studying the structural and functional organization of the water-oxidizing complex (WOC). The decay of the flash-induced high fluorescence state of PSII was measured with pulse amplitude modulated fluorometry in thylakoids and PSII enriched membrane fragments. Calculated QA- decay was well described by three exponential decay components, reflecting QA- reoxidation with halftimes of 450 and 860 micros, 2 and 7.6 ms, and 111 and 135 ms in thylakoids and PSII membranes, respectively. The effect of modification of the PSII donor side by changing pH or by removal of the extrinsic 17 and 24 kDa proteins on period four oscillations in both maximum fluorescence yield and the relative contribution of QA- reoxidation reactions was compared to flash-induced oxygen yield. The four-step oxidation of the manganese cluster of the WOC was found to be necessary but not sufficient to produce modulation of PSII fluorescence. The capacity of the WOC to generate molecular oxygen was also required to observe a period four in the fluorescence; however, direct quenching by oxygen was not responsible for the modulation. Potential mechanisms responsible for the periodicity of four in both maximum fluorescence yield pattern and flash-dependent changes in proportion of centers with different QA- reoxidation rates are discussed with respect to intrinsic deprotonation events occurring at the WOC.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗
PubMed1999

Splenectomy during partial remission in thrombotic thrombocytopenic purpura with prolonged plasma exchange dependency.

Some patients with thrombotic thrombocytopenic purpura (TTP) remain plasma-exchange-dependent for prolonged periods of time. This exposes patients to risk, uses substantial resources, and requires prolonged hospitalization. We have splenectomized 7 such patients following 25-42 plasma exchanges while patients were in partial remission only and were clinically stable. In 6 patients, including 1 with TTP secondary to mitomycin C, thrombocytopenia promptly resolved. Relapse has not occurred during 18 or more months of observation. The seventh patient did not respond. We conclude that splenectomy should be considered as an alternative to continued plasma-exchange therapy in such patients.

Adrenal Cortex Hormones↗
PubMed1999

Corpus callosum damage and interhemispheric transfer of information following closed head injury in children.

We evaluated the relationship of corpus callosum atrophy and/or lesions on magnetic resonance imaging (MRI) to functional hemispheric disconnection following closed head injury (CHI) in 51 pediatric patients, including mild CHI, moderate to severe CHI with extracallosal lesions, and moderate to severe CHI with callosal atrophy and/or lesions. Interhemispheric transfer of information was assessed using auditory, motor, tactile, and visual tests in patients and in 16 uninjured children. Total and regional callosal areas were measured from the midsagittal MRI slice by morphometry. The corpus callosum lesion group demonstrated a greater right ear advantage on verbal dichotic listening than all other groups. Areas of the posterior corpus callosum were negatively correlated with laterality indices of verbal dichotic listening performance and tachistoscopic identification of verbal material. The relationship of corpus callosum atrophy and/or lesions to asymmetry in dichotic listening is consistent with previous investigation of posttraumatic hemispheric disconnection effects in adults.

Adolescent↗
PubMed1999

Human apo-lipoprotein B from normal plasma contains oxidised peptides.

Oxidation of low density lipoprotein (LDL) may be atherogenic, but radical-initiated oxidation of its apoprotein B-100 (apoB) has been little studied. Transition metal ions iron and copper are candidates for mediating radical oxidation of LDL in vivo. Therefore, we studied the copper-ion-induced oxidation of apoB in human LDL. Using HPLC methods developed in our recent work, we studied the destruction of native and the generation of six oxidised amino acids; we also assessed the release of peptides from the LDL particle by FPLC. We observed time-dependent losses of apoB histidine, lysine and glycine. Long-lived reactive species, the reductant DOPA, and the oxidant hydroperoxides of valine and leucine (measured as hydroxides after reduction), were generated. Their relative abundance (mol/mol of parent amino acid) was DOPA > o- and m-tyrosine > dityrosine, valine-hydroxides, leucine hydroxides. Low molecular weight fragments were also released from the LDL in a time-dependent manner, contained hydroperoxides sensitive to GSH peroxidase, and generated radicals on reaction with iron-EDTA. The fragments contained peptides active in the quinone redox cycling procedure, comprising 0.25% of the supplied LDL amino acids. Characteristic peptides were present in each FPLC fraction containing the fragments, as judged by further HPLC fractionation. Some fragments were present in the unoxidised LDL preparations, and when these were largely removed by FPLC, copper oxidation could still generate fragments, suggesting that those present in the starting material might indicate prior oxidation. Concordantly, we found that fresh plasma LDL apoB contained 43% of total plasma protein-bound oxidised amino acids, and with the same relative abundance. We conclude that plasma proteins including apoB are subject to physiological oxidation, similar to that inflicted by copper ions; the latter may contribute to intimal LDL oxidation, which could be the source of oxidised plasma apoB.

Amino Acids↗
PubMed1999

Amplification of the inflammatory cellular redox state by human immunodeficiency virus type 1-immunosuppressive tat and gp160 proteins.

In the course of our studies on oxidative stress as a component of pathological processes in humans, we showed that microintrusion into cells with microcapillary and ultramicroelectrochemical detection could mimic many types of mechanical intrusion leading to an instant (0.1 s) and high (some femtomoles) burst release of H2O2. Specific inhibitors of NADPH enzymes seem to support the assumption that this enzyme is one of the main targets of our experiments. Also, human immunodeficiency virus type 1 (HIV-1) gp160 inhibits the cooperative response of uninfected T cells as well as Tat protein release by infected cells does. In this study, we analyzed in real time, lymphocyte per lymphocyte, the T-cell response following activation in relation to the redox state. We showed that the immunosuppressive effects of HIV-1 Tat and gp160 proteins and oxidative stress are correlated, since the native but not the inactivated Tat and gp160 proteins inhibit the cellular immune response and enhance oxidative stress. These results are consistent with a role of the membrane NADPH oxidase in the cellular response to immune activation.

Arsenicals↗
PubMed1999

Undergraduate students' misconceptions about respiratory physiology.

Approximately 700 undergraduates studying physiology at community colleges, a liberal arts college, and universities were surveyed to determine the prevalence of our misconceptions about respiratory phenomena. A misconception about the changes in breathing frequency and tidal volume (physiological variables whose changes can be directly sensed) that result in increased minute ventilation was found to be present in this population with comparable prevalence (approximately 60%) to that seen in a previous study. Three other misconceptions involving phenomena that cannot be experienced directly and therefore were most likely learned in some educational setting were found to be of varying prevalence. Nearly 90% of the students exhibited a misconception about the relationship between arterial oxygen partial pressure and hemoglobin saturation. Sixty-six percent of the students believed that increasing alveolar oxygen partial pressure leads to a decrease in alveolar carbon dioxide partial pressure. Nearly 33% of the population misunderstood the relationship between metabolism and ventilation. The possible origins of these respiratory misconceptions are discussed and suggestions for how to prevent and/or remediate them are proposed.

Adolescent↗
PubMed1999

Posterior fossa syndrome: identifiable risk factors and irreversible complications.

Cerebellar mutism was first described by Rekate et al. in 1985 as a transient condition which occurs after posterior fossa operations in children. Posterior fossa syndrome (PFS) and cerebellar mutism are often used interchangeably in the literature. In our experience, we found cerebellar mutism to be a reversible component of a persistent neurologic syndrome. The cause and identifiable risk factors have not been clearly elucidated in the literature. To further characterize PFS, we reviewed 253 children with posterior fossa tumors who underwent surgical resection. We documented 20 cases of PFS (8%), 12 males and 8 females. Age ranged from 1.5 to 13 years (mean = 6.5). Of the 20, 16 were medulloblastoma, 3 ependymoma and 1 astrocytoma. There was a 21 % incidence (16/76) of PFS in medulloblastoma of the posterior fossa. The incidence for ependymoma was 13% (3/24) and 1% (1/102) for astrocytoma. All 20 cases (100%) had brainstem involvement by the tumor. The most frequent postoperative findings included mutism, ataxia, 6th and 7th nerve palsies and hemiparesis. Mutism had a latency range of 1-7 days (mean = 1.7) and a duration of 6-365 days (mean = 69.2, median = 35). Although mutism resolved in all cases, the remaining neurologic complications which characterized our findings of PFS were rarely reversible. We describe potential risk factors for developing PFS after surgery with hopes of making neurosurgeons more aware of potential problems following the removal of lesions in this area. Early recognition of PFS would further promote patient and family understanding and coping with this syndrome.

Adolescent↗
PubMed1999

Evaluation of 18F-FDG positron emission tomography in gastric and oesophageal carcinoma.

The aim of this study was to evaluate 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) in gastric and oesophageal carcinoma. 16 patients with biopsy proven oesophageal or gastric carcinoma had PET scans. Four patients had advanced disease and received palliative treatment. The remaining 12 patients were randomized to immediate surgery or neoadjuvant chemotherapy. Three patients had repeat PET scans following chemotherapy. PET detected the primary tumour in all cases including stage T1 lesions. Involved locoregional nodes (N1, N2) were not identified separately from the primary tumour. Semiquantitative analysis was performed in the form of tumour to liver activity ratios (TLR). In general, the TLR values were higher in the higher T stages, although there was only one case each of T1 and T2 lesions. PET scanning using 18F-FDG is a sensitive method for detecting primary oesophageal and gastric cancers but is limited in locoregional staging.

Adult↗
PubMed1998

Nonphotochemical quenching of excitation energy in photosystem II. A picosecond time-resolved study of the low yield of chlorophyll a fluorescence induced by single-turnover flash in isolated spinach thylakoids.

Chlorophyll a fluorescence emission is widely used as a noninvasive measure of a number of parameters related to photosynthetic efficiency in oxygenic photosynthetic organisms. The most important component for the estimation of photochemistry is the relative increase in fluorescence yield between dark-adapted samples which have a maximal capacity for photochemistry and a minimal fluorescence yield (F0) and light-saturated samples where photochemistry is saturated and fluorescence yield is maximal (Fm). However, when photosynthesis is saturated with a short (less than 50 micro(s)) flash of light, which induces only one photochemical turnover of photosystem II, the maximal fluorescence yield is significantly lower (Fsat) than when saturation is achieved with a millisecond duration multiturnover flash (Fm). To investigate the origins of the difference in fluorescence yield between these two conditions, our time-resolved fluorescence apparatus was modified to allow collection of picosecond time-resolved decay kinetics over a short time window immediately following a saturating single-turnover flash (Fsat) as well as after a multiturnover saturating pulse (Fm). Our data were analyzed with a global kinetic model based on an exciton radical pair equilibrium model for photosystem II. The difference between Fm and Fsat was modeled well by changing only the rate constant for quenching of excitation energy in the antenna of photosystem II. An antenna-based origin for the quenching was verified experimentally by the observation that addition of the antenna quencher 5-hydroxy-1,4-naphthoquinone to thylakoids under Fm conditions resulted in decay kinetics and modeled kinetic parameters very similar to those observed under Fsat conditions in the absence of added quinone. Our data strongly support the origin of low fluorescence yield at Fsat to be an antenna-based nonphotochemical quenching of excitation energy in photosystem II which has not usually been considered explicitly in calculations of photochemical and nonphotochemical quenching parameters. The implications of our data with respect to kinetic models for the excited-state dynamics of photosystem II and the practical applications of the fluorescence yield parameters Fm and Fsat to calculations of photochemical yield are discussed.

Chlorophyll↗
PubMed1998

Non-photochemical quenching of chlorophyll fluorescence in photosynthesis. 5-hydroxy-1,4-naphthoquinone in spinach thylakoids as a model for antenna based quenching mechanisms

In vivo mechanisms of non-photochemical quenching that contribute to energy dissipation in higher plants are still a source of some controversy. In the present study we used an exogenous oxidized quinone, 5-hydroxy-1,4-naphthoquinone to induce quenching of chlorophyll excited states in photosynthetic light-harvesting antenna and to elucidate the mechanism of non-photochemical quenching of chlorophyll fluorescence by this quinone. Excitation dynamics in isolated spinach thylakoids in the presence of an exogenous fluorescence quencher was studied by a combined analysis of data gathered from independent techniques (fluorescence yields, effective absorption cross-sections and picosecond kinetics). The application of a kinetic model for photosystem II to a combined data set of fluorescence decay kinetics and absorbance cross-section measurements was used to quantify antenna quenching by a model antenna quencher, 5-hydroxy-1,4-naphthoquinone. We observed depressions in F0 and photosystem II absorption cross-sections, paralleled with an increase of the rate constant for excitation decay in antenna. This approach is a first step towards quantifying the amount of antenna quenching contributing to non-photochemical quenching in vivo, evaluation of the contributions of antenna and reaction centre mechanisms to it and localization of the sites of non-photochemical energy dissipation in intact plant systems. Copyright 1998 Elsevier Science B.V.

Journal Article↗
PubMed1998

The Lashley-Hull debate revisited.

N. Weidman (1994) claimed that "Karl Lashley and Clark Hull had a long and unresolved controversy about the structure and function of the brain, its relationship to the mind, and the use of machine metaphors to explain intelligence" (p. 162). The record contained in published articles and unpublished correspondence indicates otherwise. The clash was explicitly about continuity versus noncontinuity in discrimination learning, stimulus generalization, and the development of quantitative and mathematical psychological theory and its relation to neurophysiological data. Weidman also contended that the subtext of the debate was whether heredity or environment was more important in determining intelligence and behavior. This is doubtful. It is more probable that the debate stemmed from Lashley's career-long opposition to connectionism.

Brain↗
PubMed1998

Early diagnosis of subependymal giant cell astrocytoma in patients with tuberous sclerosis.

We present 19 patients with tuberous sclerosis complex and subependymal giant cell astrocytoma. The mean age at the time of tumor diagnosis was 9.4 years (range, 1.5 to 21 years). Computed cranial tomography (CT) or cranial magnetic resonance imaging (MRI) identified the lesion which was resected in all cases. Seven patients had hydrocephalus and there was an interval increase in the tumor size or a large tumor without hydrocephalus in 12 patients. Surgical criteria included: (1) presence of hydrocephalus; (2) interval increase in tumor size; (3) new focal neurologic deficit attributable to the tumor; and/or (4) symptoms of increased intracranial pressure. Eight patients were identified through a surveillance program involving annual computed cranial tomography. All of these eight patients had their tumor removed prior to the development of symptoms, none had neurologic deficits which persisted after surgery, and none has so far developed recurrent subependymal giant cell astrocytoma. In contrast, of the 11 patients from the non-surveillance group 7 were symptomatic at tumor diagnosis, 1 had a complicated postoperative course, 2 developed recurrent giant cell astrocytoma, and 1 had an extensive lesion that could not be completely excised. Periodic cranial imaging may help to identify subependymal giant cell astrocytomas in tuberous sclerosis patients before they become symptomatic. Earlier diagnosis and treatment could reduce surgical morbidity and the risk of tumor recurrence.

Adolescent↗
PubMed1997

Preparative induction and characterization of L-antithrombin: a structural homologue of latent plasminogen activator inhibitor-1.

The inhibitory mechanism of the serpin family of serine protease inhibitors is characterized by a remarkable degree of conformational flexibility. Various conformational states have been elucidated by X-ray crystallography and indicate that the inhibitory loop, the central A-beta-sheet, and the outside edge of the C-beta-sheet are particularly mobile. However, no crystal structure of a serpin-enzyme complex is yet available, and the likely nature of the protease-complexed serpin remains for biochemical and biophysical researchers to examine. Here, we show that the biochemical induction of the latent state of antithrombin is slow relative to polymer formation, and infer that this may reflect structural features that are important for the regulation of the initial docking and subsequent locking of serpins with cognate proteases. L-Antithrombin was induced by incubation of native antithrombin at 60 degrees C for 10 h in the presence of citrate to prevent polymerization. L-Antithrombin was more stable to denaturation by both heat and urea than native antithrombin. Whereas native antithrombin formed binary complexes with synthetic peptide homologues of the inhibitory loop, biochemically induced L-antithrombin did not, indicating that the inhibitory loop of L-antithrombin is probably fully inserted into the A-beta-sheet as in the crystal structure. This was confirmed by limited proteolysis studies which demonstrated that the inhibitory loop of L-antithrombin could not be cleaved by five proteases which do cleave the loop of native antithrombin. The limited proteolysis studies also indicated that the "gate" region (residues 236-248) of the biochemically induced L-antithrombin was in a conformation substantially different from that of the native antithrombin. This again is similar to L-antithrombin in the crystal structure in which the gate has "opened" away from the body of the molecule by a rotation of 24 degrees to facilitate the relocation of strand 1C from its ordered position in the C-beta-sheet to a disordered surface loop. At 60 degrees C in the absence of citrate, antithrombin (and other serpins) rapidly polymerizes. In the presence of citrate, the formation of L-antithrombin is slow and increases with time, indicating that the inhibition of polymer formation by citrate allows the time necessary for the much slower formation of the L form. We therefore suggest that L-antithrombin formation is a two-step process: an initial rapid conformational change, probably including partial incorporation of the reactive loop into the A-sheet (as in the active molecule in the crystal structure) and displacement of s1C from the C-beta-sheet which supports polymer formation, and a much slower transition to complete loop insertion within the A-beta-sheet. It is likely that both the first rapid transitional step and the structural features that impose resistance to the second more extensive conformational change reflect the optimization of the unique inhibitory function in the serpins.

Amino Acid Sequence↗