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Biomedical subjects

R Barker

Publications and source records attributed to R Barker.

At least 55 records · Page 3Linked to original sources
PubMed1991

Substance P and neurodegenerative disorders. A speculative review.

The causes of the neurodegenerative disorders of Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are unknown. It is proposed that all these disorders result primarily from a loss of trophic peptidergic neurotransmitter, possibly Substance P (SP). This loss in turn produces the classical neuronal degeneration seen in each of these diseases and occurs due to a combination of natural aging and chronic autoimmune destruction following a viral infection of the CNS, early in life. The loss is therefore slow and by the time of clinical presentation the inflammatory process is disappearing as the antigenic stimulus lessens with its removal. The implications of the theory in terms of future research and therapy are briefly discussed.

Alzheimer Disease↗
PubMed1990

Primary care internal medicine: a challenging career choice for the 1990s.

A career in primary care internal medicine can be challenging and rewarding, yet during the last decade fewer medical students have selected training in internal medicine. We wish to inform medical students, their advisors, and other physicians about the field of primary care internal medicine. We define the discipline, compare it with traditional internal medicine and with family practice, and describe features of strong primary care internal medicine training programs. We discuss common misconceptions and concerns about training programs and the career and give examples of career paths chosen by graduates of primary care programs. We encourage students to consider the option of primary care internal medicine when making career decisions and provide faculty advisors unfamiliar with primary care internal medicine training programs with a reference resource.

Career Choice↗
PubMed1990

Membrane processes associated with the osmotic-pulse incorporation of inositol hexaphosphate.

In previous studies (Biochem. Biophys. Res. Commun. 144, 779-786 (1987); Prog. Clin. Biol. Res. 292, 65-75 (1989)), we showed that inositol hexaphosphate (IHP), when added to erythrocyte membrane ghosts in the range 0.6-2.5 mM, caused a large disruption of skeletal protein-protein interactions as monitored by electron paramagnetic resonance techniques. IHP incorporated into intact cells by an osmotic-pulse method (J. Cell. Physiol. 129, 221-229 (1986)) leads to cells with markedly decreased oxygen affinity. Exposure of the red cells to higher levels of IHP during the osmotic pulse leads to less lysis and more normal cellular indices after healing of the transiently-disrupted membrane (J. Lab. Clin. Med. 113, 58-66 (1989)). In order to determine what effect higher levels of IHP had on skeletal proteins and bilayer lipids of membrane ghosts, spin labeling studies were performed. The main findings were: (a) There was a concentration-dependent alteration in skeletal protein interactions. At concentrations greater than 25 mM IHP, the effectiveness of IHP to disrupt skeletal protein interactions was diminished. (b) No apparent alteration of the motion or order of phospholipids or the lipid water interface of intact cells into which IHP was incorporated occurred, suggesting that higher levels of IHP do not alter the physical state of the lipid bilayer.

Electron Spin Resonance Spectroscopy↗
PubMed1989

Adrenal grafting for Parkinson's disease: a role for substance P.

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the primary pathology is thought to be a loss of dopaminergic neurons in the substantia nigra (SN). The mainstay of treatment has been the use of the drug L-DOPA, a drug that crosses the blood-brain barrier and is converted to dopamine. Recently, intracerebrally implanted grafts of adrenal tissue to promote functional recovery in nigral-damaged recipient animals and patients have been successfully performed. The recovery in these cases is said to be due to the dopamine present in the grafted adrenal tissue. This explanation has several fallacies, however. It is the contention of this paper that substance P is the active agent in the grafted tissue. This raises the possibility of improving the treatment for PD by the use of grafted tissue that is a purer source of SP or SP agonists.

Adrenal Medulla↗
PubMed1988

How does the brain control its own activity? A new function for the basal ganglia.

It has long been a problem in neuroscience to known how the brain controls its own activity, how it is able to control the level of CNS excitability and how it is able to select and act on some information as opposed to some other information. In this paper I propose a new theory in which the basal ganglia play a role in selecting information ("selective attention") and in controlling the general level of excitability of the CNS ("state control"), the two processes being to some extent interdependent. The basal ganglia achieve these functions by actions on the thalamic-frontal cortical axis and on the brainstem mesencephalic reticular formation.

Arousal↗
PubMed1987

Electron spin resonance (ESR) studies of skeletal protein interactions in human erythrocyte membranes exposed to polyanions and in membranes prepared from inositol hexaphosphate (IHP)-incorporated low-affinity erythrocytes.

Previous biophysical investigations, including those from our laboratories, have reported that polyphosphates weaken RBC membrane skeletal protein-protein interactions and decrease hemoglobin affinity for oxygen. We have additionally demonstrated that low-affinity intact RBC's may be produced by inositol hexaphosphate (IHP) incorporation via an osmotic pulse method. In the present electron spin resonance (ESR) study, IHP was shown to cause a concentration-dependent increase in the segmental motion of ghost membrane skeletal proteins, but no alterations in spin-labeled terminal sialic acid. Pyrophosphate and inositol hexasulfate were significantly less effective in altering the physical state of skeletal proteins than was IHP. Additional ESR studies of both the interaction of IHP with membrane skeletal proteins in the presence of hemoglobin and of membranes obtained from osmotic pulse-treated intact cells were performed. The results of all these studies are discussed in terms of previous biophysical investigations of the effects of polyphosphates on membranes and of possible molecular events that occur during the osmotic pulse procedure.

2,3-Diphosphoglycerate↗
PubMed1987

Fusion glycoprotein of measles virus: nucleotide sequence of the gene and comparison with other paramyxoviruses.

The sequence of the fusion (F) glycoprotein mRNA of the Hallé strain of measles virus was determined from a cDNA clone representing the entire length of the mRNA. It contained 2384 nucleotides, excluding poly(A), with a 5' consensus sequence typical of paramyxoviruses and a 3' terminus found in measles virus mRNAs. The coding sequence was preceded by an unusually long (580 nucleotide) 5' non-translated region, which contained 44% cytosine. The longest open reading frame coded for a polypeptide of 553 amino acids with a predicted molecular weight of 59.84 K. Comparison of the sequence with that of the Edmonston strain of measles virus showed that the gene is highly conserved. No amino acid differences were observed between the two strains. The F polypeptide had three regions of high hydrophobicity: an N-terminal signal peptide, the N-terminus of F1 and a C-terminal membrane-spanning region. The four potential asparagine-linked glycosylation sites (one in the signal peptide) were all in the F2 subunit. Comparison of the measles virus F amino acid sequence with other paramyxoviruses revealed homologies with these viruses. Certain regions such as the N terminus of F1 and ten cysteine residues which probably impose structural restraints were highly conserved.

Amino Acid Sequence↗
PubMed1986

Leishmaniasis and malaria: new tools for epidemiologic analysis.

Parasitic diseases are still prevalent in many parts of the world, causing both human suffering and economic loss. Recent developments in biotechnology, such as the use of monoclonal antibodies and recombinant DNA, have the potential for providing both more extensive and detailed information on the parasite in the infected human and in insect vectors. New methods of detection, both in man and insect vectors, have been developed for two parasitic diseases, leishmaniasis and malaria. These new methodologies will be important in epidemiologic studies on the prevalence and transmission of these parasitic diseases.

Antibodies, Monoclonal↗
PubMed1986

General methods for enriching aldoses with oxygen isotopes.

Synthetic methods are described for enriching 4-, 5-, and 6-carbon aldoses with oxygen isotopes. The general approach includes exchange between H2(1)8O and the aldehyde group of an aldose, exchange of O-1 onto C-2 of both of the 2-epimeric aldoses formed by molybdate-resin epimerization, and chain extension using cyanide addition. These methods make possible the production of all 16 aldohexoses enriched at 5 of the 6 oxygen atoms, all 8 aldopentoses enriched at 4 of the 5 oxygen atoms, and the four aldotetroses enriched at 2 of the 4 oxygen atoms. The general applicability of these methods is illustrated by the synthesis of a group of 22 different, 18O-enriched, biologically important D-aldoses having 4, 5, and 6 carbon atoms. The group includes D-[1-, 2-, 3-, 4-, O]glucose, D-[1-, 2-, 3-, 4-, and 6-18O]mannose, D-[1-, 2-, 3-, and 5-18O]arabinose, D-[1- abd 2- 18O] erythorose, and D-[1- and 2-18O]threose. The g.l.c.-m.s. characterization of these sugars with respect to the position and degree of 18O-enrichment is reported. The potential of the methods for producing aldoses having oxygen labels at multiple positions, or aldoses labeled simultaneously with oxygen, hydrogen, and carbon isotopes is discussed.

Gas Chromatography-Mass Spectrometry↗
PubMed1986

Paramolybdate anion-exchange resin, an improved catalyst for the C-1-C-2 rearrangement and 2-epimerization of aldoses.

Aqueous solutions of molybdate at 90 degrees bring about the inversion of the C-1-C-2 fragment of aldoses having four or more carbon atoms, generating thermodynamically equilibrated mixtures of the starting aldose and its 2-epimer. In some cases, notably with the aldopentoses, substantial proportions of the 3-epimers are produced, as well as 2-epimers that have not undergone inversion of the C-1-C-2 fragment. These side-reactions can be controlled by using the paramolybdate form of an anion-exchange resin (AG MP-1) together with the formate form of the same resin. The latter acts to scavenge unbound molybdate and paramolybdate anions that appear to be responsible for the side reactions.

Anion Exchange Resins↗