PubMed HealthSearch

Biomedical subjects

M Davison

Publications and source records attributed to M Davison.

At least 19 recordsLinked to original sources

Dihydrolipoamide dehydrogenase from the halophilic archaebacterium Haloferax volcanii: characterization and N-terminal sequence.

Dihydrolipoamide dehydrogenase, a flavin disulfide reductase, has been purified and characterized from Haloferax volcanii. The enzyme is a dimer of relative mass 128,000, with an optimal activity at pH 9.0 in 1 M NaCl. Following reduction with its substrate, dihydrolipoamide, the enzyme is inactivated through covalent bond formation with the trivalent arsenical p-aminophenyl arsenoxide. The amino acid composition and the amino acid sequence of the first 49 residues of the N-terminus have been determined.

Amino Acid Sequence

Heterogeneity of chromogranin A-derived peptides in bovine gut, pancreas and adrenal medulla.

Chromogranin A is produced in many endocrine cell types, and is widely used as a marker in endocrine-cell pathology and secretory-cell biology. There is some evidence that it may be proteolytically processed to yield the putative pancreatic regulatory peptide, pancreastatin, and, in order to characterize the relevant pathways in gastrointestinal and pancreatic endocrine cells, we have used, in radioimmunoassay, site-directed antibodies to pancreastatin itself (L331) and to a sequence of chromogranin A immediately C-terminal to pancreastatin (L300). The latter antibody revealed three major forms of immunoreactivity of 8 kDa and five peptides of approx. 3 kDa in bovine pancreas and gut extracts. The 8 kDa peptides were characterized as chromogranin A-(248-313)-peptides, i.e. C-terminally extended forms of pancreastatin; two of the 8 kDa variants differed in two positions, confirming a polymorphism predicted from cDNA sequencing. One of the 3 kDa peptides was characterized as chromogranin A-(297-313)-peptide, i.e. the C-terminal heptadecapeptide of the 8 kDa peptide that would be liberated after cleavage to yield pancreastatin. On the basis of chromatographic studies, immunohistochemistry and the stoichiometry of different immunoreactive peptides, three different pathways of chromogranin A processing were identified: in adrenal chromaffin cells chromogranin A existed mainly as the unmodified intact protein, in pancreatic islet and gastric antral endocrine cells pancreastatin and the 3 kDa peptides were major products, but in small intestine and gastric corpus endocrine cells there was little nor no pancreastatin and the 8 kDa cleavage product predominated. There are therefore important differences in the distribution of chromogranin A-derived peptides between quite closely related populations of endocrine cells that are attributable not only to variable post-translational cleavage but also to the expression of different primary sequences. It seems possible that in different cell types chromogranin A-derived peptides might subserve a variety of different functions.

Adrenal Medulla

Identification of 3- and 4-repeat tau isoforms within the PHF in Alzheimer's disease.

The microtubule associated protein tau is incorporated into the pronase resistant core of the paired helical filament (PHF) in such a way that the repeat region is protected from proteases, but can be released as a major 12 kDa species from the PHF core by formic acid treatment and by boiling in SDS. This fragment retains the ability to aggregate in the presence of SDS. Detailed sequence analysis of the 12 kDa species shows that it consists of a mixture of peptides derived from the repeat region of 3- and 4-repeat tau isoforms comigrating as a single electrophoretic band. However, the 4-repeat isoforms released from the core lack either the first or the last repeat. The pronase-protected region of tau within the PHF core is therefore restricted to three repeats, regardless of isoform. The alignment of cleavage sites at homologous positions within tandem repeats after protease treatment indicates that the tau-core association is precisely constrained by the tandem repeat structure of the tau molecule.

Alzheimer Disease

The interaction between stimulus and reinforcer control on remembering.

In a symbolic matching-to-sample task, 6 pigeons obtained food by pecking a red side key when the brighter of two white lights had been presented on the center key and by pecking a green side key when the dimmer of two white lights had been presented on the center key. Across Part 1 and Parts 6 to 10, the delay between sample-stimulus presentation and the availability of the choice keys was varied between 0 s and 25 s. Across Parts 1 to 5, the delay between the emission of a correct choice and the delivery of a reinforcer was varied between 0 s and 30 s. Although increasing both types of delay decreased stimulus discriminability, lengthening the stimulus-choice delay produced a greater decrement in choice accuracy than did lengthening the choice-reinforcer delay. Additionally, the relative reinforcer rate for correct choice was varied across both types of delay. The sensitivity of behavior to the distribution of reinforcers decreased as discriminability decreased under both procedures. These data are consistent with the view, based on the generalized matching law, that sample stimuli and reinforcers interact in their control over remembering.

Animals

Effects of varying stimulus disparity and the reinforcer ratio in concurrent-schedule and signal-detection procedures.

The present study measured the effects of stimulus and reinforcer variations on pigeons' behavior in two different choice procedures. Two intensities of white light were presented as the stimuli on the main key in a switching-key concurrent schedule and as the sample stimuli in a signal-detection procedure. Under both procedures, the scheduled rate of reinforcement was varied across conditions to produce various ratios of obtained reinforcement. These ratios were obtained for seven pairs of light intensities. In the concurrent schedules, the effects of reinforcer-ratio variations were positively correlated with the physical disparity between the two light intensities. In the signal-detection procedure, changes in the reinforcer ratio produced greater effects on performance when stimulus disparity was very low or very high compared to those found at intermediate levels of stimulus disparity. This discrepancy creates a dilemma for existing behavioral models of signal-detection performance.

Animals

Obstetrical practice survey report. Healthy Futures Program, May 2, 1991.

Oklahoma physicians in three specialty areas (ob/gyn, family practice, and general practice) were surveyed in regard to their practice of obstetrics. The 611 physicians who responded included a representative sample in regard to county of practice, rural vs urban, age, degree (DO & MD), specialty, and type of practice. Respondents accounted for 51% of the total 1989 births in Oklahoma during calendar year 1989. The vast majority (greater than 90%) of respondents report that they normally provide delivery services and prenatal care in combination. Cesarean sections are performed by almost all ob/gyns (97.6%), more than half of the family practitioners (56.5%), and a very few general practitioners (18.9%). Half of all physicians responding have made changes in their obstetric practice in the last 3 years. The most common changes are: reducing care of medically high risk, uninsured, and/or Medicaid patients. The most important reasons for these changes are: fear of obstetric malpractice suits, inconvenience of obstetrics and excessive professional liability insurance premiums. Specific reasons for reducing care to medically high risk patients were reported to be: increased medical legal liability, belief that high risk patients should be cared for by specialists, and lack of Medicaid reimbursement for diagnostic services. Almost 90% of the physicians responding to the survey are required to carry a minimum amount of professional liability insurance by the hospital where they practice with the most frequently stated amount being $1,000,000. Current average "global fees" reported by the respondents were $1,202 for a spontaneous vaginal delivery and $1,543 for a cesarean delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Lexical capture: a developmental disorder of reading and spelling.

We report a case of a 35-year-old teacher, Louise, with a history of learning difficulties and current evidence of developmental phonological dyslexia and dysgraphia. Her reading, spelling, and remembering of novel stimuli written in conventional alphabetic script was poor, but she performed significantly better when the same items were written in the International Phonetic Alphabet, a system that she learned when studying linguistics. Her impaired performance in tasks of phonemic segmentation and short-term memory, which are generally associated with impaired reading and spelling of unfamiliar material, could not account for her specific difficulty with alphabetic stimuli. Instead, her problems appear to result from a lexical strategy, which we have called "lexical capture".

Adult

Outcome of mechanical ventilation in Central Africa.

The outcome of mechanical ventilation is reported in a prospective series of 200 patients managed in an intensive care unit in Zambia. Fifty two patients survived (26%), and 46 patients were subsequently discharged from hospital (23%). Ten patients died in whom a complication of ventilation was a factor. Patients not expected to survive by the authors had a 96.3% mortality whereas patients with a chance of survival had a mortality rate of 58.8%. Two diagnostic groups were found to have a high mortality: head injury (85.1%) and non-traumatic coma (76.4%). This series is compared with similar series from developed countries and recommendations are made for the institution of mechanical ventilation in the developing world.

Coma

The interaction of stimulus and reinforcer control in complex temporal discrimination.

Six pigeons were trained in a discrete-trials signal-detection procedure to discriminate between a fixed-duration stimulus (5 s or 20 s) and a set of variable durations ranging from 2.5 s to 57.5 s in steps of 5 s. For each fixed-duration stimulus, the ratio of reinforcer frequencies contingent upon reporting the fixed versus the variable stimulus was systematically manipulated. Detection performance was well controlled by both the stimulus value and the reinforcer ratio. Both the discriminability between the fixed duration and the set of variable durations, and the discriminability between the fixed duration and each of the variable durations, were independent of the reinforcer-frequency ratio when discriminability was measured as log d. The sensitivity of response bias to reinforcement-ratio changes was independent of the value of the fixed duration, but was not independent of the discriminability of the variable durations from the fixed durations. Under current models, discriminability measures in complex temporal discrimination may be independent of biasing manipulations, but bias measures are not independent of stimulus values.

Animals

Partial separation and functional characterization of guinea pig basophil-stimulating factor.

We have previously described T lymphocyte dependent guinea pig basophil growth from bone marrow precursors in vitro. In the current studies, basophil-stimulating factor (BSF) present in mitogen-stimulated splenic conditioned medium (CM) has been functionally characterized, utilizing an assay for BSF on nonadherent bone marrow target cells. BSF was found to be heat stable, nondialyzable, and inactivated by proteases. Monosaccharides known to inhibit guinea pig lymphokines yielded a unique profile of inhibition of BSF activity and nonidentity of BSF with guinea pig migration inhibition factor, interleukins 1 or 2, and granulocyte-macrophage colony-stimulating activity, from which BSF could be separated after gel filtration. BSF-containing CM also had no detectable interleukin-3 activity as measured in a murine assay. An inverse relation was found between interleukin 2 and BSF production by peritoneal exudate T cells (PEL) stimulated with antigen. Fractionation of serum-containing and serum-free CM demonstrated a molecular size for BSF of 50,000-65,000 daltons. Guinea pig BSF is a distinct T cell dependent lymphokine with an active protein moiety which may interact with target bone marrow cells through a cell surface carbohydrate receptor.

Animals

A system for solar radiation data storage and analysis.

It is important for photodermatologists to have an accurate and continuous measurement of the ultraviolet radiation reaching the ground. This implies the establishment of a network of detectors, but for this to be a practical reality, it is essential that an accurate and convenient system be adopted for data storage and analysis. To this end we have developed a system which meets the following criteria: it is automatic; component costs are low: it uses a home microcomputer costing 400 pounds (less than $600); because processing is done by a computer, it is flexible; also, for the same reason, there is the facility for on-line display and on-line analysis; there are no significant errors: a modified computer circuit produces a temperature coefficient of 30 ppm/degrees C; reliability is good: 12 d of data were lost from all causes, including development, during 12 months of continuous use. The system described could form the basis of a practical UV-recording network.

Data Collection

The structure of mammalian rod opsins.

Ovine rhodopsin is organised in disc membranes as a monomer. The determination of its amino acid sequence has permitted the utilisation of structure prediction programmes which indicate the probable disposition of the polypeptide chain in the bilayer. This putative model is consistent with labelling data using the chemical probes, [14C]succinic anhydride, [125I]diazodiido sulphanilic acid and [125I]iodophenyl azide, and with the cleavage points for several proteases. More surprisingly the predicted structure points to the occurrence of breaks/distortions in the transmembrane helical segments. These distorted regions may be of primary functional importance to the protein and at least one is associated with the attachment point of the chromophore. This particular part of the structure is also identified as a "mutational hot spot", for bovine, equine, ovine and porcine opsins exhibit different sequences (but conserved molecular volumes) in the four residues following the retinyllysine. In an otherwise highly conserved protein with no obvious functional differences between the four species, the high substitution rate in this region is unexplained.

Amino Acid Sequence