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Biomedical subjects

S C Williams

Publications and source records attributed to S C Williams.

At least 181 records · Page 10Linked to original sources
PubMed1994

C/EBP-related protein 2 confers lipopolysaccharide-inducible expression of interleukin 6 and monocyte chemoattractant protein 1 to a lymphoblastic cell line.

C/EBP-related proteins 2 and 3 (CRP2 and CRP3) are differentially expressed by P388 lymphoblasts and their derivative P388D1(IL1) macrophages. We have ectopically expressed CRP2, the predominant CRP in macrophages, in P388 lymphoblasts. The expression of CRP2 is sufficient to confer the lipopolysaccharide (LPS)-inducible expression of interleukin 6 and monocyte chemoattractant protein 1 to lymphoblasts, which normally do not display LPS induction of inflammatory cytokines. Consistent with these findings, the expression of CRP2 antisense RNA blocks the LPS induction of IL-6 expression in P388D1(IL1) macrophages. This work clearly establishes the essential role of CRP2 in the induction of cytokine genes by LPS. Additionally, these data add MCP-1 to the list of cytokines showing an involvement of CRP2 in their expression.

Animals↗
PubMed1994

Isolation of high affinity human antibodies directly from large synthetic repertoires.

Antibody fragments of moderate affinity (approximately microM) can be isolated from repertoires of approximately 10(8) immunoglobulin genes by phage display and rounds of selection with antigen, and the affinities improved by further rounds of mutation and selection. Here, as an alternative strategy, we attempted to isolate high affinity human antibodies directly from large repertoires. We first created highly diverse repertoires of heavy and light chains entirely in vitro from a bank of human V gene segments and then, by recombination of the repertoires in bacteria, generated a large (close to 6.5 x 10(10)) synthetic repertoire of Fab fragments displayed on filamentous phage. From this repertoire we isolated Fab fragments which bound to a range of different antigens and haptens, and with affinities comparable with those of antibodies from a secondary immune response in mice (up to 4 nM). Although the VH-26 (DP-47) segment was the most commonly used segment in both artificial and natural repertoires, there were also major differences in the pattern of segment usage. Such comparisons may help dissect the contributions of biological mechanisms and structural features governing V gene usage in vivo.

Amino Acid Sequence↗
PubMed1994

The secondary structure of the von Willebrand factor type A domain in factor B of human complement by Fourier transform infrared spectroscopy. Its occurrence in collagen types VI, VII, XII and XIV, the integrins and other proteins by averaged structure predictions.

The type A domain of the von Willebrand Factor is found also in the complement proteins factor B (FB), C2, CR3 and CR4, the integrins, collagen types VI, VII, XII and XIV, and other proteins. FB is a component of the alternative pathway of the complement system of immune defence, and is cleaved into the fragments Bb and Ba during complement activation. Bb contains a von Willebrand Factor type A (vWF) domain of unknown secondary structure and a serine proteinase (SP) domain, whereas Ba contains three short consensus repeat/complement control protein (SCR/CCP) domains. Fourier transform infrared (FT-IR) spectroscopy on a recombinant vWF domain and on FB and its Bb and Ba fragments shows a broad amide I band. In H2O buffer, second derivative spectra of the amide I band show subcomponents at 1654 to 1657 cm-1, which is typical of alpha-helix, and at 1676 to 1685 cm-1 and 1636 to 1637 cm-1, which are typical of beta-strand. alpha-Helix was detected in the vWF domain, the Bb fragment and FB, and the proportion of alpha-helix present decreased in that order. This shows that the vWF domain contains appreciable amounts of alpha-helix, while the SP and SCR/CCP domains are almost entirely beta-sheet in their secondary structures. Quantitative integration of the vWF FT-IR spectrum showed that this contained 31% alpha-helix and 36% beta-sheet. In 2H2O buffer, the alpha-helix content in the vWF domain is sensitive to the solvent, while the beta-sheet content is less so. An alignment of 75 vWF type A sequences from 25 proteins was used for averaged secondary structure predictions of the total length of 206 residues by the Robson and Chou-Fasman methods. In support of the FT-IR analysis, a total of at least five well-predicted alpha-helices (35% of residues) and at least five well-predicted beta-strands (21% of residues) were identified by both predictive methods, all of which were interspersed by regions of coil or turn conformations. Eight of the ten predicted alpha-helices and beta-strands form an alternating arrangement with each other. Since the predicted alpha-helices are mostly amphipathic, and since the alpha-helix FT-IR band is sensitive to solvent, the alpha-helices are inferred to be on the protein surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1994

Identification of ethanolamine in rat and gerbil brain tissue extracts by NMR spectroscopy.

Some NMR resonances which have previously been observed but not identified in mammalian brain tissue extracts have been shown to arise from ethanolamine. This conclusion is drawn from a systematic study of the perchloric acid extracts of rodent brain tissue in which several NMR experiments were used to assign the peaks unambiguously. The extraction procedure used in this work gave samples with highly reproducible spectra, and ethanolamine was observed in all our extract samples. A localized increase in the concentration of ethanolamine was seen in the spectra of extracts produced from a cerebral infarct induced by occlusion of the middle cerebral artery in the rat.

Animals↗
PubMed1994

A sodium magnetic resonance imaging study of acute cerebral ischaemia in the gerbil.

23Na magnetic resonance imaging has been used to investigate sodium changes during and after cerebral ischaemia in a gerbil model. The sodium signal decreased within 4 minutes of the onset of ischaemia, and subsequently increased between 4 and 8 minutes after the onset of reperfusion. These observations may be reflecting the redistribution of tissue sodium resulting from energy failure and recovery.

Animals↗
PubMed1994

Effect of fish oil on cancer cachexia and host liver metabolism in rats with prostate tumors.

The aim of this study was to investigate whether tumor-induced cachexia and aberrations in host liver metabolism, induced by the MAT-LyLu variant of the Dunning prostate tumor, could be prevented by omega 3 fatty acids from fish oil. On day 0, adult Copenhagen-Fisher rats fed normal chow ad libitum were inoculated with 10(6) MAT-LyLu cells (n = 14) or saline (n = 9). On day 7, when tumors were palpable, four tumor-bearing (TB) and four nontumor-bearing (NTB) rats were put on isocaloric diets with 50% of total energy as fish oil. The introduction of fish oil-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7-14 (difference by dietary group: NTB, P < 0.001; TB, P < 0.001). During days 14-21, energy intake in fish oil-fed animals returned to approximately 75% of energy intake by animals fed normal diets (difference by dietary group: NTB, P < 0.003; TB, P = 0.001). Carcass weight of animals on day 21, when the study was terminated, was significantly related to initial weight (P = 0.05) and mean food intake during the study (P = 0.01). When data were adjusted for these variables using analysis of covariance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on normal diets only (mean +/- SEM 58 +/- 10 g loss, P < 0.001), but not in TB animals on fish oil diets (8 +/- 18 g loss, P = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The effects of sodium bicarbonate and a mixture of sodium bicarbonate and carbonate ("Carbicarb") on skeletal muscle pH and hemodynamic status in rats with hypovolemic shock.

Rats rendered hypotensive and acidotic by withdrawal of blood were treated by infusion of either an equimolar mixture of sodium bicarbonate and sodium carbonate ("Carbicarb"), sodium bicarbonate alone, or sodium chloride. Skeletal muscle intracellular pH (pHi) was measured using magnetic resonance spectroscopy from the chemical shift of the carbon-2 (C2) proton resonance of the imidazole ring of anserine. In the groups treated with alkali, arterial blood pH (pHa) was restored to normal, but no change was observed in the sodium chloride-treated animals. Despite an elevation of arterial blood partial pressure of CO2 (PaCO2) in the group treated with sodium bicarbonate, no significant change in pHi was observed in any group. Blood lactate levels, initially elevated in all groups, underwent only minor changes. In all three groups a transient and similar elevation of arterial blood pressure was observed after infusion. Differential effects of Carbicarb and sodium bicarbonate in metabolic acidosis may be dependent on the model of metabolic acidosis used, and an alteration in PaCO2 induced by alkali therapy may not be a major determinant of changes in pHi.

Acidosis↗
PubMed1994

Early changes in cerebral sodium distribution following ischaemia monitored by 23Na magnetic resonance imaging.

23Na magnetic resonance imaging has been used in this preliminary study to investigate early changes in brain sodium signal intensity during and after cerebral ischaemia in a gerbil model. The total sodium signal in selected brain regions decreased between 15 and 30% within 4 min of the onset of ischaemia, and then remained constant throughout the ischaemic period. The same pattern was observed in the eyes. On reperfusion, there was no significant change in the sodium signal over the first 4 min, but by 8 min the signal intensity had returned to or passed through control levels in all regions measured, with the exception of the eyes. These observations are consistent with the loss and resynthesis of ATP as seen in this model, and may be reflecting the redistribution of tissue sodium resulting from energy failure and recovery.

Acute Disease↗
PubMed1994

Preliminary analysis of elasmobranch tissue using magnetic resonance imaging.

High resolution NMR images of sixgill shark (Hexanchus griseus) tissue from both horizontal and sagittal orientations are presented. Structures normally radiographically undetectable are visualised here with NMR. Proton density, spin-lattice and spin-spin relaxation time maps as well as various relaxation weighted images show selective enhancement of different tissue types. Quantitative analysis of major anatomical features in the shark head is provided.

Animals↗
PubMed1994

Vigabatrin-induced lesions in the rat brain demonstrated by quantitative magnetic resonance imaging.

Rats treated with 250 mg/kg/day vigabatrin showed lesions detected by magnetic resonance imaging (MRI) in the cerebellar white matter in vivo. No lesions were seen in any control animal. As well as these visually apparent lesions, quantitative T2 relaxation time measurements showed a 12 ms increase in cerebellar white matter from 66 +/- 4 ms (SD, n = 5) to 78 +/- 2 ms (SD, n = 7). This region, as expected from previous studies, showed microvacuolation on post-mortem pathology. Additionally, significant increases in T2 relaxation times of 4-9 ms were found in the cerebral cortex, thalamus and hippocampus. Microvacuolation was not detected by post-mortem histopathology in the cerebral cortex or hippocampus, however, immunohistochemical staining for glial fibrillary acidic protein and for macrophages (ED1) showed reactive astrocytes (gliosis) and in more severe cases, microglial proliferation in these regions; such changes were also seen in association with the microvacuoles. No T2 increase was found in the cerebellar grey matter or olfactory bulbs. MRI techniques, including T2 relaxometry, are therefore sensitive for detecting vigabatrin-induced changes, including reactive astrocytosis, microglial proliferation and vacuolation in the rat brain. These results suggest that quantitative MRI should be a useful method for evaluating whether vigabatrin has neuropathological effects when given to patients.

Animals↗
PubMed1994

Perirenal liposarcoma containing extramedullary hematopoiesis associated with renal cell carcinoma.

We present the first reported case of a perirenal well-differentiated liposarcoma containing extramedullary hematopoiesis associated with an ipsilateral T2N0M0 renal cell carcinoma. This patient, a seventy-one-year-old white male, had no known hematologic disorder and on preoperative evaluation had similar radiographic findings identified within the contralateral perirenal space. Pathologic evaluation after radical nephrectomy reported the perirenal mass to consist only of myelolipomatous change, however, further review identified liposarcoma.

Aged↗
PubMed1994

Utilization of uniformly labeled 13C-polyunsaturated fatty acids in the synthesis of long-chain fatty acids and cholesterol accumulating in the neonatal rat brain.

Polyunsaturated fatty acids are needed for normal neonatal brain development, but the degree of conversion of the 18-carbon polyunsaturated fatty acid precursors consumed in the diet to their respective 20- and 22-carbon polyunsaturates accumulating in the brain is not well known. In the present study, in vivo 13C nuclear magnetic resonance spectroscopy was used to monitor noninvasively the brain uptake and metabolism of a mixture of uniformly 13C-enriched 16- and 18-carbon polyunsaturated fatty acid methyl esters injected intragastrically into neonatal rats. In vivo NMR spectra of the rat brain at postnatal days 10 and 17 had larger fatty acid signals than in uninjected controls, but changes in levels of individual fatty acids could not be distinguished. One day after injection of the U-13C-polyunsaturated fatty acid mixture, 13C enrichment (measured by isotope ratio mass spectrometry) was similar in brain phospholipids, free fatty acids, free cholesterol, and brain aqueous extract; 13C enrichment remained high in the phospholipids and cholesterol for 15 days. 13C enrichment was similar in the main fatty acids of the brain within 1 day of injection but 15 days later had declined in all except arachidonic acid while continuing to increase in docosahexaenoic acid. These changes in 13C enrichment in brain fatty acids paralleled the developmental changes in brain fatty acid composition. We conclude that, in the neonatal rat brain, dietary 16- and 18-carbon polyunsaturates are not only elongated and desaturated but are also utilized for de novo synthesis of long-chain saturated and monounsaturated fatty acids and cholesterol.

Aging↗
PubMed1994

Gardner's syndrome. Case report and discussion of the manifestations of the disorder.

Extracolonic manifestations of Gardner's syndrome are common and may precede the detection of colonic polyps. Tc-MDP bone scintigraphy performed on a patient with Gardner's syndrome demonstrated intense uptake of radiotracer within the maxilla and mandible as a result of the dental anomalies associated with this disorder. Nuclear scintigraphy has a role in the imaging of these patients for skeletal anomalies, the detection of thyroid carcinoma, and for skeletal metastases when colon carcinoma is detected.

Adult↗
PubMed1993

Dye-ligand affinity purification of human complement factor B and beta 2 glycoprotein I.

The rapid purification of human factor B using dye-ligand chromatography is described. The 50% ammonium sulphate supernatant of fresh human serum is equilibrated in pH 7.4, 25 mM Tris buffer containing 0.5 mM CaCl2 and 0.5 mM MgCl2, with 25 mM sodium caprylate and chromatographed on Cibacron Blue F3GA-agarose. Caprylic acid binds to the fatty acid binding site of albumin, preventing it from binding to the resin which thus retains a high capacity for binding factor B. Factor B together with the homologous protein beta 2I are eluted from the column by a linear gradient of KCl. Subsequent NaCl gradient FPLC on Hiload S-Sepharose, equilibrated in 10 mM potassium phosphate, 5 mM EDTA, pH 7.0, provides both factor B and beta 2I in homogeneous form.

Chromatography, Affinity↗
PubMed1993

Cloning and sequencing of human immunoglobulin V lambda gene segments.

To provide the building blocks for making synthetic antibody fragments we have used the polymerase chain reaction (PCR) to clone human variable (V) gene segments of lambda light chains. The PCR primers were based on the sequences of known human V lambda segments, and were used to isolate 14 new V lambda segments (including 4 pseudogenes) from a single individual. We have compiled a sequence directory from this data and other sources to include all known human V lambda segments with open reading frames and we have identified a new V lambda family (V lambda IX). Almost all of the segments (22/24) have different sequences in the complementarity-determining regions, setting a lower limit to the structural diversity of the antigen binding sites encoded by human V lambda genes in the human population.

Base Sequence↗