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Biomedical subjects

S C Williams

Publications and source records attributed to S C Williams.

At least 199 records · Page 11Linked to original sources
PubMed1993

The proton NMR spectrum in acute EAE: the significance of the change in the Cho:Cr ratio.

We have studied by nuclear magnetic resonance spectroscopy the evolution of the proton spectral changes in acute experimental allergic encephalomyelitis. We found an in vivo elevation in the ratio between the peaks assigned to "choline containing compounds" (Cho) and creatine plus phosphocreatine (Cr). This was associated with an increase in choline, betaine, and phosphorylcholine (PC) as well as a reduction in N-acetylaspartate (NAA), aspartate, N-acetylaspartatylglutamate and inositol in vitro. Histological examination revealed inflammation with no evidence of demyelination or neuronal loss. We conclude that the increase in the ratio of Cho:Cr was due to an increase in the concentrations of PC, betaine, and choline in association with inflammation, and not as others have suggested, with demyelination. The reported reduction in NAA may be due to dysfunction of neurones rather than their loss.

Animals↗
PubMed1993

A chemical shift selective inversion recovery sequence for fat-suppressed MRI: theory and experimental validation.

Fat-suppression techniques are used extensively in routine proton nuclear magnetic resonance imaging to produce images free from chemical shift artifacts and dynamic range problems. A hybrid fat-suppression sequence is studied which combines the principle of short time inversion recovery with chemical shift selective imaging. The aim of this study is to provide a theoretical understanding of the role of the sequence parameters, as well as to compare this hybrid sequence with its most closely related conventional fat-suppression techniques, namely selective pre-saturation and short time inversion recovery (STIR) imaging. The hybrid technique is shown to be robust in normal use, and more tolerant than the conventional methods to mis-settings of parameters such as inversion time, as well as tip angle and frequency bandwidth of the fat selective pulse.

Abdomen↗
PubMed1993

A new method for diffusion weighted imaging.

A new method for generating diffusion contrast in magnetic resonance imaging is presented. This technique is robust enough to allow implementation on conventional imaging systems without hardware modifications. Results from phantom measurements are reported. Qualitative contrast changes in magnetic resonance images derived from live mammalian brain are also demonstrated.

Animals↗
PubMed1993

Altered phosphorylation status, phospholipid metabolism and gluconeogenesis in the host liver of rats with prostate cancer: a 31P magnetic resonance spectroscopy study.

31P magnetic resonance spectroscopy (MRS) in vivo and in vitro was used to study modulation of host liver (HL) metabolism in rats bearing the MAT-LyLu variant of the Dunning prostate tumour. Animals were inoculated either with 10(6) or 10(7) MAT-LyLu cells, or with saline to serve as controls. Carcass weight in tumour-bearing (TB) animals decreased despite similar food and water intake in both groups. Absence of metastatic tumour cells from HL of all TB animals was confirmed by histological examination. Twenty-one days after inoculation, 31P MRS showed a 2.5-fold increase in [Pi]/[ATP] ratios in HL in vivo (P < 0.001) which was confirmed by 31P MRS of liver extracts in vitro (P < 0.005). Phosphodiester to ATP ratios were significantly increased (P < 0.05) in HL in vivo, but absolute PDE levels were similar in both groups. Phosphomonoester to ATP ratios did not change, although absolute phosphomonoester levels in HL were reduced by -41% (not significant). In HL extracts in vitro, sharp reductions in the levels of glucose-6-phosphate (P < 0.05), fructose-6-phosphate (P = 0.05), phosphocholine (P < 0.001), glycerophosphocholine (P < 0.001), and glycerophosphoethanolamine (P < 0.001) were observed. Electron microscopy revealed increased amounts and altered distribution of rough endoplasmic reticulum in HL. These findings show that experimental prostate cancer significantly affects hepatic phosphorylation status, phospholipid metabolism, and gluconeogenesis in the host animal, and demonstrate the value of combined MRS in vivo and in vitro in monitoring HL metabolism in cancer.

Animals↗
PubMed1992

MR imaging for measurements of ventricles and cerebral cortex in postnatal rats (H-Tx strain) with progressive inherited hydrocephalus.

As part of a wider investigation on brain structure and function in young rats with inherited hydrocephalus, this study was undertaken to develop a technique to monitor, and quantify, progressive changes in ventricle and cortical dimensions in hydrocephalic rats in vivo. Magnetic resonance images were obtained with a T1-weighted protocol and a multislice variant of the inversion recovery sequence which displayed optimal contrast between cerebrospinal fluid and brain parenchyma. Rats were imaged at 7, 14, and 21 days after birth by taking 10 contiguous 2.0-mm coronal slices. Area and distance measurements were taken from the displayed images, enabling calculation of ventricle volumes, cortical length, and cortical thickness. The lateral ventricle volume, which was already 100-fold larger than control at 7 days, increased to over 1000 mm3 at 21 days. The anterior-posterior length of the cortex was up to 27% larger in hydrocephalics and the cortical mantle was up to 75% thinner, particularly in the posterior cortex. Subsequent fixation and histological sectioning of two 21-day-old rats showed that the smaller dimensions, which were obtained from analysis of the sections, could be accounted for by shrinkage of the tissue during dehydration and wax embedding.

Aging↗
PubMed1991

In vivo detection of metabolic changes in a mouse model of scrapie using nuclear magnetic resonance spectroscopy.

In vivo proton nuclear magnetic resonance (NMR) spectroscopy studies of scrapie in a mouse model have shown the appearance of an abnormal peak in the brain early in the incubation period. This abnormal peak was detected weeks before the detection of a protease-resistant form of a membrane protein and vacuolar histopathology in vitro, and several months before clinical signs, and the signal increased in intensity as the disease progressed. In the chronic stage of the disease, a reduction in N-acetyl aspartate levels was observed using in vivo and in vitro proton NMR spectroscopy.

Animals↗
PubMed1991

A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro.

Mouse and rat genomic DNA libraries were screened by reduced stringency hybridization with the DNA-binding domain of the c/ebp gene as a probe. Three genes were isolated that encode bZIP DNA-binding proteins (designated CRP1, CRP2, and CRP3) with strong amino acid sequence similarities to the C/EBP-binding domain. CRP2 is identical to the protein described recently by other groups as NF-IL6, LAP, IL-6DBP, and AGP/EBP, whereas CRP1 and CRP3 represent novel proteins. Several lines of evidence indicate that these three proteins, along with C/EBP, comprise a functional family. Each bacterially expressed polypeptide binds to DNA as a dimer with recognition properties that are virtually identical to those of C/EBP. Every member also bears a conserved cysteine residue at or near the carboxyl terminus, immediately following the leucine zipper, that at least in vitro allows efficient disulfide cross-linking between paired zipper helices. We developed a gel assay for covalent dimers to assess leucine zipper specificities among the family members. The results demonstrate that all pairwise combinations of dimer interactions are possible. To the extent that we have examined them, the same heterodimeric complexes can be detected intracellularly following cotransfection of the appropriate pair of genes into recipient cells. All members are also capable of activating in vivo transcription from promoters that contain a C/EBP-binding site. Our findings indicate that a set of potentially interacting C/EBP-like proteins exists, whose complexity is comparable to that of other bZIP protein subfamilies such as Jun, Fos, and ATF/CREB.

Amino Acid Sequence↗
PubMed1991

Differential Regulation of beta-1,3-Glucanase Messenger RNAs in Response to Pathogen Infection.

The acidic, extracellular, glucan endo-1,3-beta-glucosidases (EC 3.2.1.39; beta-1,3-glucanases), pathogenesis-related proteins-2, -N, and -O (i.e. PR-2, PR-N, and PR-O) were purified from Nicotiana tabacum (tobacco) and their partial amino acid sequences determined. Based on these data, complementary DNA (cDNA) clones encoding the proteins were isolated. Additional cDNAs were isolated that encoded proteins approximately 90% identical with PR-2, PR-N, and PR-O. Although the proteins encoded by these cDNAs have not been identified, their deduced amino acid sequences have slightly basic or neutral calculated isoelectric points, as well as carboxy-terminal extensions. These physical characteristics are shared by the vacuolar form of beta-1,3-glucanase and other vacuolar localized analogs of PR proteins, suggesting that the unidentified proteins may be similarly localized. A preliminary evolutionary model that separates the beta-1,3-glucanase gene family from tobacco into at least five distinct subfamilies is proposed. The expression of beta-1,3-glucanase messenger RNAs (mRNAs) in response to infection by tobacco mosaic virus was examined. Messages for the acidic glucanases were induced similarly to the mRNAs for other PR proteins. However, the basic glucanase showed a different response, suggesting that different isoforms are differentially regulated by tobacco mosaic virus infection at the mRNA level.

Journal Article↗
PubMed1989

cis-acting determinants of basal and lipid-regulated apolipoprotein A-IV expression in mice.

The levels of apolipoprotein A-IV (apoA-IV) mRNA are regulated by dietary lipid in the liver of both the mouse and rat. Thirteen different inbred mouse strains were fed a high lipid diet, and the effect on apoA-IV liver mRNA levels was examined. It was found that each strain responded in one of two ways. Mice of four strains had higher liver apoA-IV mRNA levels as compared with syngeneic mice fed a normal chow diet. Mice of the other nine strains had decreased liver apoA-IV mRNA levels as compared with syngeneic mice fed a normal chow diet. Using F1 hybrids between mice from BALB/c, C3H, and C57BL/6 and between 129 and C57BL/6, as well as recombinant inbred strains derived from a cross between BALB/c and C57BL/6, we have shown that both the normal level of liver apoA-IV mRNA in the chow-fed mice and the lipid-dependent regulation of apoA-IV mRNA levels are controlled by cis-acting genetic elements. The apoA-IV mRNA levels in mice fed a normal diet varied dramatically among strains, with the largest difference (90-fold) being between the 129/J inbred strain and the C57BL/6J strain. In addition, we have examined the expression of apoA-IV during mouse development. ApoA-IV mRNA is expressed early in mouse liver (16 days postcoitum), whereas others have shown previously that rat liver apoA-IV mRNA is undetectable until 14 days after birth. ApoA-IV mRNA levels in the intestine and apoA-I mRNA levels in the liver and intestine, by contrast, mirror the pattern seen in the rat.

Animals↗
PubMed1989

True water and fat MR imaging with use of multiple-echo acquisition.

The original Dixon method for chemical shift imaging of a two-component system is extended to a multiple-echo technique. Four echoes are used to gain all the information required to remove non-chemical shift-dependent phase changes and produce true fat and water images. Applications of the method both to a phantom and to human tissue are shown. This technique results in information comparable to that obtained from the Dixon method in half the imaging time and also gives an equivalent, if not slightly improved, signal-to-noise ratio.

Arm↗
PubMed1986

Mouse apolipoprotein A-IV gene: nucleotide sequence and induction by a high-lipid diet.

Apolipoprotein A-IV (apo A-IV) functions in conjunction with other apolipoproteins to form lipoprotein particles which are involved in lipid homeostasis. In this report we present the nucleotide sequence of the mouse apo A-IV gene and demonstrate its induction in the liver by chronically high dietary lipid. The apo A-IV gene consists of three exons and two introns. The introns separate evolutionarily conserved and functional polypeptide domains. Intron 1 divides most of the apo A-IV signal peptide from the amino terminus of the mature plasma protein. The second intron separates a highly evolutionarily conserved, variant amphipathic peptide repeat from the remainder of the mature apo A-IV protein. The 5' flanking region has several interesting features. The apo A-IV gene has variant TATA and CAT box sequences, TTTAAA and CCAACG, respectively. There are five G-rich direct repeats of 10 nucleotides and a short inverted repeat in the 5' flanking region. We speculate that these sequence elements in the 5' flanking region may be involved in the regulation of apo A-IV gene expression. We also show that chronically high dietary lipid induces liver apo A-IV levels 10-fold in C57BL/6 mice, a strain susceptible to atherosclerotic lesions, while we observed no induction in nonsusceptible BALB/c and C3H mice.

Amino Acid Sequence↗
PubMed1985

IgG subclass antibodies to herpes simplex virus.

Several mouse monoclonal antibodies specific for human IgG1, IgG2, IgG3, and IgG4 were evaluated by enzyme-linked immunosorbent assay to detect human IgG subclass antibodies to herpes simplex virus (HSV) antigens. The variable results with different monoclonal antibodies point to the need for well-characterized reagents in the study of antibody responses to infectious agents. The 204 sera tested were obtained from 157 patients with various forms of clinically manifest HSV infections and from several controls. IgG1 antibodies were demonstrated in almost all HSV-infected subjects and were the first antibodies to appear in primary genital infections. IgG2, IgG3, and IgG4 antibodies were detected in acute-phase sera, most often in patients with recurrent genital herpes but in none of those with primary infections. IgG4 antibodies occurred significantly more frequently in sera from men than in those from women with recurrent genital infections.

Adult↗