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Biomedical subjects

R W Williams

Publications and source records attributed to R W Williams.

At least 145 records · Page 8Linked to original sources
PubMed1985

Immunochemistry, physical chemistry and biology of 2',5'-oligoadenylates.

Monoclonal antibodies directed against 2-5A were developed and characterized. 2',5'-Oligoadenylate-protein complexes possess at least three distinct antigenic surfaces defined primarily by the ribose-phosphate backbone. A schematic model for the three epitopes is presented. Antibodies directed against 2-5A, in conjunction with other techniques, were employed to quantify 2-5A in various tissues of pathogen-free mice. Levels of 2-5A were in the range of 400-800 fmole/gm. Mice injected with poly(I).poly(c) or encephalomyocarditis virus (EMCV) showed elevated levels of 2-5A. Administration of poly(I).poly(C) or EMCV increased the level of 2-5A in different tissues to different extents. Raman spectroscopy was employed to explore the conformation of 2-5A. Distinct differences were observed in bands arising from the backbone portion of 2-5A relative to those of 3-5A. The most striking finding was the appearance of a strong, sharp band at 1460 cm-1 in spectra of 5'-monophosphorylated 2-5A's. This band was barely detectable in core and triphosphorylated 2-5A. Its presence suggests that 5'-monophosphorylated 2-5A's possess a unique conformational feature that distinguish them from cores and 5'-triphosphorylated forms.

Adenine Nucleotides↗
PubMed1984

Raman spectroscopy of homologous plant toxins: crambin and alpha 1- and beta-purothionin secondary structures, disulfide conformation, and tyrosine environment.

The Raman spectrum of crambin crystals is different from the spectrum of crambin in solution. The amide I spectrum of crambin in solution is not different from the solution spectra of proteins homologous (greater than 40%) with crambin, alpha 1- and beta-purothionins. We have two interpretations of these results. One is that helical segments in crambin and the purothionins in solution are more irregular than those in crystalline crambin. Comparative analyses of amide I and amide III spectra, and of the conformational preferences of the amino acid sequences of these proteins, are consistent with this interpretation. The other is that, due to the way helical segments in crambin are stacked end on end along the same axis in the crystal, transition dipole coupling along the axis of these extended helixes enhances the amide I intensity of helical residues. On the basis of a combined Raman and sequence conformational analysis, we propose that the structure of the purothionins is the same as that of crambin in solution and that residues 7-12 in crystalline crambin are somewhat more regular and ordered than they are in solutions.

Antimicrobial Cationic Peptides↗
PubMed1984

Raman spectroscopy and deuterium exchange of the filamentous phage fd.

The filamentous phage fd has been investigated using the techniques of Raman spectroscopy and deuterium exchange. Despite the rather uniform secondary structure of the fd phage coat protein, which is predominantly alpha-helix, the deuterium exchange is complex. A substantial fraction of the helical peptides exchange deuterium by 8 h at room temperature, yet another substantial fraction does not exchange following an additional 5 months at 4 degrees C. Heating the phage to 70 degrees C for several hours leads to additional deuterium exchange compared to samples soaked for 5 months in heavy water. We suggest that the wide variation in peptide exchange rates may be related to the phage protein quaternary structure, which has been shown to be a double layer of tightly packed helices. The accomplishment of enhanced exchange by reaction at high temperature combined with digital difference spectroscopic methods has enabled us to define the structure of the amide III and III' bands. The complexity of these bands is unexpected for a simple helical protein, but we suggest that the complexity arises at least in part from end-effects that become important in short alpha-helices.

Amides↗
PubMed1984

Binocular interaction in the fetal cat regulates the size of the ganglion cell population.

During fetal development of the cat's visual system there is a marked overproliferation of optic nerve axons. In utero binocular interaction contributes to the severity of fiber loss since removal of an eye during gestation attenuates axon loss in the remaining optic nerve. The purpose of the present study was to determine whether this reduced loss of optic nerve fibers is due to a failure of retraction by supernumerary axon branches or to a reduction in ganglion cell death. To resolve this issue, we compared the number of ganglion cells and optic nerve fibers in adult cats which had one eye removed at known gestational ages. Retinal ganglion cells were backfilled with horseradish peroxidase and counts were made from retinal wholemounts. The axon complement was assessed with an electron microscopic assay. In the retinas of a normal cat we estimated 151,000 and 152,000 ganglion cells. The optic nerves of two other normal cats contained approximately 158,000 and 159,000 axons. In comparison, an animal enucleated on embryonic day 42 had 180,000 ganglion cells and 178,000 optic nerve fibers, while in an animal enucleated on embryonic day 51 the corresponding estimates were 182,000 and 190,000. The close agreement between cell and fiber counts indicates that axonal bifurcation does not contribute appreciably to the axon surplus in the optic nerve of prenatally enucleated cats. These results demonstrate that prenatal binocular interaction regulates the size of the mature retinal ganglion cell population.

Animals↗
PubMed1984

Affinity-labeled somatomedin-C receptors and binding proteins from the human fetus.

We investigated the ontogeny of the human placental membrane somatomedin-C (Sm-C)/insulin-like growth factor I (IGF-I) receptor by affinity labeling with the cross-linking agent disuccinimidyl suberate (DSS). Specific Sm-C receptors, identified from as early as 6 weeks gestation, demonstrated no apparent structural changes through the course of gestation. Second trimester human fetal brain membranes cross-linked to [125I]Sm-C exhibited an identical pattern of receptor binding. These findings in both placenta and fetal brain membrane are consistent with the proposed heterotetrameric structure of the Sm-C/IGF-I receptor. Using a similar DSS cross-linking technique, we identified Sm-C-binding proteins in second trimester amniotic fluid [apparent molecular mass (Mr), 38,000 and 35,000] and term cord plasma (Mr, 41,000, 38,000, and 35,000). Identically sized binding components (Mr, 35,000-45,000) were also found in membrane preparations of preterm placenta and brain after cross-linking. Evidence that these binding species represent contamination of preterm membrane preparations with soluble amniotic fluid and/or fetal plasma Sm-C-binding proteins and that they are not derived from membrane receptors is as follows: (1) these binding species, like amniotic fluid and cord plasma binding proteins, were insensitive to competition with insulin (in concentrations as high as 0.6 mg/ml), a characteristic not shared with membrane receptor binding components; (2) these binding species were largely removed from placental membranes by extensive washing and appeared in the supernate when membrane preparations were incubated at 4 C for 18 h, indicating that they were soluble and not an integral part of the particulate membrane; (3) limited proteolysis of placental membrane preparations did not result in the appearance of similar binding species; and (4) preparation of preterm placental membranes in the presence of protease inhibitors did not eliminate these binding species. Use of traditional methodology to study binding of somatomedin to receptors in membranes prepared from preterm human tissues may be misleading because of contamination by amniotic fluid and/or plasma-derived binding proteins.

Affinity Labels↗
PubMed1984

Organization of the cat's lateral geniculate nucleus following interruption of prenatal binocular competition.

In adult cats which had an eye removed at least two weeks before birth the remaining retina projects to the entire ipsilateral and contralateral lateral geniculate nucleus. In these prenatally enucleated animals, all lateral geniculate neurons responded apparently normally to visual stimuli and retinotopy also appeared to be normal. These findings demonstrate that termination of in utero binocular competition induces marked morphological changes in the visual system, but the functional organization of the major retino-recipient structure develops normally.

Animals↗
PubMed1983

Estimation of protein secondary structure from the laser Raman amide I spectrum.

A new method for estimating protein secondary structure from the laser Raman spectrum has been developed whereby the amide I Raman band of a protein is analyzed directly as a linear combination of amide I bands of proteins whose secondary structures are known. For 14 proteins, analyzed by removing each one from the reference set and analyzing its structure in terms of the remaining proteins, the average correlation coefficients between the Raman and X-ray diffraction estimates of helix, beta-strand, turn, and undefined were 0.98, 0.98, 0.82 and 0.35, respectively. Significant correlations were also observed for distinctions between alpha-helix (0.98) and disordered helix (0.82), and between parallel (0.82) and antiparallel (0.97) beta-sheets. The average standard deviation of these Raman estimates from the X-ray values is less than 4%. In addition, a singular value analysis of 20 Raman amide I spectra indicates that there may be as many as nine significant independent pieces of information present in the amide I region.

Amides↗
PubMed1983

Development of the retinal pathway to the pretectum of the cat.

The development of retinal projections to the pretectal complex of prenatal and early postnatal cats has been examined using the anterograde transport of horseradish peroxidase and tritiated amino acids. As early as embryonic day 38, the entire dorsal pretectum is penetrated by retinal ganglion cell axons. At this stage the bilateral complement of retinal efferents appears to be dispersed uniformly within the pretectal anlage. A week later, on embryonic day 46, indistinct foci of peroxidase reaction product can be discerned within 2 of the primordial nuclei: the nucleus of the optic tract and the olivary nucleus. By embryonic day 56, five distinct bilateral fields of retinal fiber termination are apparent within the following regions: (i) the nucleus of the optic tract; (ii) the pretectal olivary nucleus; (iii) the posterior pretectal nucleus; (iv) the anterior pretectal nucleus; and (v) the medial pretectal nucleus. Four days before birth, on embryonic day 61, crossed and uncrossed retinal arbors are partially segregated within the nucleus of the optic tract and the pretectal olivary nucleus. The early postnatal retinal connection to the pretectum has an overall pattern virtually indistinguishable from that of the mature cat. The ontogeny of the retinal influx to the pretectum is similar to that of the retinocollicular projection. However, the development of retinal projections to the pretectum and superior colliculus appears to lag behind those to the dorsal lateral geniculate nucleus. These differences may reflect temporal and spatial gradients in the maturation of three major classes of retinal ganglion cells.

Animals↗
PubMed1983

Microcervical foraminotomy. A surgical alternative for intractable radicular pain.

Utilizing a microsurgical technique that minimizes laminectomy and facet trauma, simple posterior foraminotomy has been used for the treatment of intractable radicular pain in 235 patients with 585 symptomatic cervical nerve roots during the past ten years. The procedure was initially applied as an alternative treatment for patients unresponsive to anterior discectomy and/or laminectomy procedures. The operation accomplishes a thorough decompression of the posterior and inferior walls of the foraminal tube from entrance to exit, without disturbance of the intervertebral disc. All patients in the series experienced resolution of radicular pain by this technique. Correlation between preoperative myelographic defects and surgical pathology became less rewarding as the series matured since the majority of foraminal lesions apparently responsible for root irritation lie outside the spinal canal.

Cervical Vertebrae↗
PubMed1983

Facilitating patient understanding in the treatment of growth delay.

Effective physician-patient communication is often critical to the success of therapy of an illness. It has been shown that childrens' understanding of their illness is related to their stage of cognitive development, emotional maturity, and the level of communication between doctor and patient. Using a simple visual technique, we have demonstrated that nearly 45 percent of growth delayed children and their families overestimated their height in relation to peers and nearly 80 percent have unrealistic expectations of hGH therapy. This could be corrected to a significant degree by using the same visual aid in combination with family conferences. The results of this study have implications for the nature of physician-patient communications in other disorders.

Adolescent↗
PubMed1983

The exchange of calcium in larvae of the mosquito Aedes aegypti.

The exchange of labelled calcium between the external medium and the whole body was investigated in the larva of Aedes aegypti (L.) using a closed, two-compartmental model. The transport system for the uptake of Ca2+ was found to be saturable and obeyed Michaelis-Menten kinetics. The efficiency of the inward transport of calcium from dilute solutions was markedly reduced by starvation or by ruthenium-red, a selective inhibitor of Ca2+ activated ATPase, indicating that this transport system is energy dependent. Unlike transport systems for the major monovalent ions, the Ca2+ transport system is not located in the anal papillae, since removal of these organs resulted in enhanced Ca2+ fluxes. While over 95% of the calcium in the larva appeared to be distributed in the extracellular haemolymph, only 16% of the total calcium was readily exchangeable with the external medium; thus the majority of the calcium is apparently bound to haemolymph constituents. The results suggest that calcium pumps consisting of Ca2+ activated ATPases play an important role in the absorption of Ca2+ from dilute solutions in the gut and its reabsorption from the urine in the rectum.

Aedes↗
PubMed1983

Visual response properties in the tectorecipient zone of the cat's lateral posterior-pulvinar complex: a comparison with the superior colliculus.

The medial portion of the cat's lateral posterior-pulvinar complex (LPm) receives a prominent ascending projection from the superficial layers of the superior colliculus. This region of the thalamus has been suggested to serve as a relay by which visual information from the midbrain could be conveyed to extrastriate cortex. In order to determine how the functional organization within the LPm compares with that of the superior colliculus, visual response properties of LPm and superior collicular neurons were examined under identical experimental conditions. The majority of neurons in the LPm, as in the superior colliculus, respond vigorously to moving stimuli, and a substantial proportion of these cells also exhibit a preference for movements in a particular direction. Furthermore, most cells in the LPm, in common with those of the tectum, respond only in a phasic manner to flashed stimuli, have homogeneous receptive field organization, and show response suppression to stimuli larger than the activating region of the receptive field. As in the colliculus, the ipsilateral visual field is represented in the LPm. In spite of these similarities, there are also some striking differences between the visual responses of LPm and collicular neurons. First, the average size of receptive fields of neurons within the LPm is at least twice that of units in the superficial gray layers of the tectum. Second, more cells in the colliculus are directionally selective than those in the LPm, and the distribution of preferred directions is different in the two regions. Third, an appreciable proportion (27%) of the cells in the LPm are orientation selective, whereas this response property is only rarely encountered in the cat's tectum. Fourth, many LPm neurons can only be activated by binocular stimulation, whereas most collicular units respond equally well to stimulation of either eye. Collectively, these findings indicate that there is a substantial transformation in the lateral posterior-pulvinar complex of the ascending visual influx provided by the superior colliculus.

Acetylcholinesterase↗
PubMed1983

Loss of axons in the cat optic nerve following fetal unilateral enucleation: an electron microscopic analysis.

Between the 48th day of gestation (E-48) and maturity, the number of axons in the cat optic nerve is reduced by approximately 50%. On the basis of an electron microscopic assay, the axon population of the E-48 nerve was estimated to be 328,000. In contrast, estimates from two normal adults were 159,000 and 158,000. In utero unilateral enucleation (at E-45 and E-46) attenuated the severity of this loss since the optic nerves of the experimental animals contained 200,000 and 198,000 fibers. These results indicate that prenatal binocular competition is involved in the elimination of ganglion cell axons during the normal development of the cat's visual system. The increased number of axons in the optic nerve of the prenatally enucleated animals could be due to reduced ganglion cell death or a failure to retract supernumerary axon collaterals. It is suggested that the former explanation is more consistent with what is currently known about the development of retinofugal projections.

Animals↗
PubMed1983

An analysis of axon caliber within the optic nerve of the cat: evidence of size groupings and regional organization.

Axon size in the optic nerves of three adult cats was measured using an accurate planimetric method. A sample of the axon complement was obtained from sets of more than 125 electron micrographs taken at each nerve. In contrast to previous reports, the distribution of axon diameter, as estimated from measurements of axonal cross-sectional area was clearly bimodal. The group of finest axons had a mode at approximately 1 micrometer, and the mode of the group of intermediate size axons was approximately 2 micrometers. Fibers with diameters larger than 3.5 micrometers formed the extensive tail of the distribution. The proportions of large, intermediate, and small axons were estimated to be 5%, 45%, and 50%. These groups probably correspond to the alpha, beta, and gamma classes of retinal ganglion cells. Regional distributions of axon caliber were also bimodal and, in a few instances, even trimodal. A peripheral crescent of each nerve contained a large number of fine fibers. Mean fiber diameter within discrete regions of the optic nerve varied inversely with the density of axon packing. The thickness of the myelin sheath was highly correlated with the inner fiber diameter, hence, myelin sheath width was also distributed in a bimodal manner. These results furnish the first clear evidence that the distribution of fiber caliber within the cat's optic nerve mirrors the principal classes of retinal ganglion cells.

Animals↗
PubMed1982

Raman spectroscopy of avidin: secondary structure, disulfide conformation, and the environment of tyrosine.

An analysis of the amide I region of Raman spectra indicates that avidin has 10 +/- 5% and 55 +/- 4% of its residues in helical and beta-strand conformations, respectively. Predictions of secondary structure on the basis of the sequence of avidin are consistent with the high percentage of residues in the beta conformation. We observe no differences between the spectra of avidin in solution and in crystals nor is there a significant difference between the secondary structures of avidin and the complex of avidin with biotin. In addition, the ratio of the intensities of the tyrosine doublet at 826 and 855 cm-1 indicates the lone tyrosine side chain of an avidin subunit is in a strong hydrogen bond as a proton acceptor. The Raman data also indicate the single disulfide of an avidin subunit has dihedral angles of 0-50 degrees for each of its two C beta-S bonds and a dihedral angle of 85 +/- 20 degrees for its disulfide bond. We discuss the significance of these results in relation to findings of earlier work on avidin.

Avidin↗