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Biomedical subjects

R J Williams

Publications and source records attributed to R J Williams.

At least 163 records · Page 9Linked to original sources
PubMed1994

Mechanistic insights aid the search for CFC substitutes: risk assessment of HCFC-123 as an example.

An international consensus on the need to reduce the use of chlorofluorocarbons (CFCs) and other ozone-depleting gases such as the halons led to the adoptions of the 1987 Montreal Protocol and Title VI of the 1990 Clean Air Act Amendments, "Protecting Stratospheric Ozone." These agreements included major provisions for reducing and eventually phasing out production and use of CFCs and halons as well as advancing the development of replacement chemicals. Because of the ubiquitous use and benefits of CFCs and halons, an expeditious search for safe replacements to meet the legislative deadlines is of critical importance. Toxicity testing and health risk assessment programs were established to evaluate the health and environmental impact of these replacement chemicals. Development and implementation of these programs as well as the structural-activity relationships significant for the development of the replacement chemicals are described below. A dose-response evaluation for the health risk assessment of the replacement chemical HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane) is also presented to show an innovative use of physiologically based pharmacokinetic (PBPK) modeling. This is based on a parallelogram approach using data on the anesthetic gas halothane, a structural analog to HCFC-123. Halothane and HCFC-123 both form the same metabolite, trifluoroacetic acid (TFA), indicative of the same metabolic oxidative pathway attributed to hepatotoxicity. The parallelogram approach demonstrates the application of template model structures and shows how PBPK modeling, together with judicious experimental design, can be used to improve the accuracy of health risk assessment and to decrease the need for extensive laboratory animal testing.

Air Pollutants↗
PubMed1994

Differential susceptibilities of enterococcal species to elfamycin antibiotics.

The elfamycins are a class of naturally occurring antibiotics not currently used in the therapy of human disease. Enterococcus faecium and closely related species (Enterococcus durans and Enterococcus hirae) are susceptible to these antibiotics, while isolates of Enterococcus faecalis and other enterococcal species are highly resistant. Among enterococci, susceptibility or resistance to elfamycins appears to be determined by the bacterial protein synthesis elongation factor EF-Tu. Elfamycin susceptibility may be a useful adjunct for rapidly distinguishing E. faecalis and E. faecium in the clinical microbiology laboratory and/or as a supplementary test for use in determining the species of enterococci.

Anti-Bacterial Agents↗
PubMed1994

Resource implications of head injuries on an acute surgical unit.

Head injuries are expensive and demanding in terms of resources. In the UK, most are cared for outside neurosurgical centres. In the absence of specialist rehabilitation services, patients with on-going disability add to those admitted for observation and treatment on acute surgical wards. We audited the workload pattern and financial implications related to head injuries on a general surgical unit in a central London teaching hospital. Data collected prospectively at the time of admission and derived from departmental computerized information systems included clinical outcome, hospital stay and its relationship to severity of injury and other factors. Ward, departmental (accident and emergency (A & E), intensive therapy unit (ITU), radiology, and theatre) and neurosurgical referral costs were derived. Long-term social and rehabilitation costs were not calculated. Over a 6 month period 899 patients with head injuries were treated in the A & E department, of whom 156 were admitted. Of the admitted patients 68% were classified as minor; 22% as moderate; and 10% as severe head injuries. Fifty-one per cent of adult admissions were intoxicated by alcohol. Prolonged hospital stay was related to age, severity of head injury, mechanism of injury, associated injuries and preexisting neuropsychiatric conditions (including alcoholism). Six patients died. The direct cost of these head injuries patients was estimated at 173,500 pounds, during which time they occupied 7.6% of our unit's adult inpatient capacity. Twenty-four hour observation of 76 patients with minor head injuries contributed 9700 pounds (5.6%) to this figure. Associated extracranial injuries cost a further 46,500 pounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Ultrasound scanning of the acute abdomen by surgeons in training.

Ultrasound is widely used in the investigation of abdominal symptoms. Its increasing popularity may lead to pressure on radiological services, diagnostic delay and prolonged hospital stay. Immediate imaging performed by radiologists can contribute useful information in acute emergencies. This study assessed the accuracy and value of abdominal ultrasonography when carried out by admitting surgeons. Three surgical registrars were first instructed for two half days by a consultant radiologist. Patients with acute symptoms were scanned at the time of initial presentation using an Aloka SSD-620 scanner with 3.5 and 5 MHz probes. A total of 205 scans was performed--124 of the upper and 81 of the lower abdomen. Immediate ultrasound provided information that contributed to the establishment or refutal of a diagnosis in 138 patients (67.3%), predominantly by confirming or excluding hepatobiliary disease, tubo-ovarian pathology or aortic aneurysms and in blunt abdominal trauma. The diagnosis was altered in a small proportion (7.8%). Scanning proved unhelpful in 62 patients and misleading in five. Findings concurred with those of a radiologist in 86% of the 139 patients subsequently scanned. Abdominal ultrasound is a useful tool in the hands of surgeons dealing with emergencies and may occasionally provide vital information. If access to radiological facilities is delayed, ultrasound by the admitting surgeon could lead to improved patient management and cost savings.

Abdomen, Acute↗
PubMed1993

Hepatitis C virus antibody in alcoholic patients. Association with the presence of portal and/or lobular hepatitis.

OBJECTIVE: To evaluate the relationship between hepatitis C viral infection and alcoholic liver disease. DESIGN: Case-comparison study. SETTING: Bronx (NY) Veterans Affairs Medical Center. PARTICIPANTS: Forty-seven consecutive alcoholic patients undergoing diagnostic liver biopsy. MAIN OUTCOME MEASURES: Serum was obtained at the time of liver biopsy and assayed for antibodies to hepatitis C virus using enzyme-linked immunosorbent assay, recombinant immunoblot assay, and hepatitis C virus neutralization methods. RESULTS: Antibody to hepatitis C virus, as confirmed by the recombinant immunoblot assay, was strongly associated with the presence of portal and/or lobular inflammation (91% seropositivity) but was only present in 16% of patients without this histologic finding (P < .001). In patients without portal or lobular hepatitis, recombinant immunoblot assay seropositivity was seen in 27% of patients with cirrhosis and 20% of patients with alcoholic hepatitis and was absent in patients with steatosis and/or perivenular fibrosis. In the subgroup of alcoholic patients who were without known risk factors for hepatitis C virus infection (ie, no history of intravenous drug use or blood transfusions), antibody to hepatitis C virus was present in 78% of subjects with portal and/or lobular hepatitis but was absent in those with other types of alcoholic liver disease. Finally, anti-hepatitis C virus-seropositive patients had a significantly greater mean necroinflammatory score as compared with anti-hepatitis C virus-seronegative alcoholic patients (2.1 vs 1.2; P < .001). In contrast, there was no significant difference in the mean fibrosis score between the two groups. CONCLUSIONS: The presence of portal and/or lobular inflammation is strongly associated with antibodies to hepatitis C virus in alcoholic patients, even in the absence of known risk factors. This association indicates that hepatitis C virus is responsible, at least in part, for the portal and/or lobular hepatitis associated with alcoholic liver disease.

Adult↗
PubMed1993

Comparison of covalent and noncovalent labeling with near-infrared dyes for the high-performance liquid chromatographic determination of human serum albumin.

Noncovalent and covalent methods of labeling protein with near-infrared polymethine cyanine dyes were compared for use in analyzing human serum albumin (HSA) by high-performance liquid chromatography (HPLC) with near-infrared absorbance detection. While noncovalent labeling was faster than covalent labeling and took place in the physiological pH range, covalent labeling was more stable under conditions encountered in many of the widely used types of HPLC. Covalently labeled HSA protein peaks indicated uniform labeling of amino groups at both hydrophilic and hydrophobic binding sites, while noncovalent labeling showed a preference for hydrophobic binding sites.

Chromatography, High Pressure Liquid↗
PubMed1993

1H- and 13C-NMR investigation of redox-state-dependent and temperature-dependent conformation changes in horse cytochrome c.

The redox-state dependent changes in chemical shift, which have been measured for almost 100 CHn groups in the 13C-NMR spectra of horse cytochrome c [Santos, H., and Turner, D. L. (1992) Eur. J. Biochem. 206, 721-728], have been used to investigate the nature of the redox-related change in conformation. Apart from the haem and its axial ligands, the shifts are found to be dominated by the electron-nuclear dipolar coupling in the oxidised form, as was the case in 1H-NMR studies. These pseudocontact shifts are well described by using an empirically determined magnetic susceptibility tensor in conjunction with atomic coordinates for the horse cytochrome c. The groups which fit least well are located in the vicinity of Trp59. Comparison between 1H and 13C shifts and their temperature dependence shows that the differences from expectation based on a single structure for both oxidation states are caused largely by changes in the diamagnetic contribution to the chemical shifts. Since these are different for 1H and 13C resonances they indicate, independently from crystal structure data, some redox-related movement of the protein under the haem. The significance of these results for understanding electron transfer pathways is discussed. Finally, the temperature dependence of the pseudocontact shifts in the range 30-50 degrees C is shown to be anomalous. Approximately half of the anomalous effect may be attributed to Zeeman mixing of the electronic wavefunctions with a spin-orbit coupling constant lambda = 241 cm-1, while the other half is attributed to thermal expansion of the protein.

Animals↗
PubMed1993

The effects of bone cement powder on human adherent monocytes/macrophages in vitro.

This study reports the effects of Simplex bone cement powder (BC) on the proliferation and production of bone resorbing factors in vitro by human adherent monocytes/macrophages. Adherent peripheral blood cells were isolated from seven healthy individuals and exposed to a dispersion of BC powder (1 mg/mL), phytohemagglutinin (PHA, 40 micrograms/mL), or medium alone at different periods of cell incubation (days 0-2, 0-7, 5-7, or 10-12). Cell proliferation was quantified by incorporation of 3H-thymidine uptake. Culture supernatants were evaluated for levels of interleukin 1-like activity (IL-1) by murine thymocyte proliferation assay, prostaglandin E2 (PGE2) by radioimmunoassay, lysosomal enzyme activity (N-acetyl-beta-D-glucosaminidase and beta-glucuronidase using fluorometry, and collagen and casein degrading activity using radioactive substrates. Human adherent peripheral blood cells showed a proliferative response to PHA that coincided with cell maturation; BC did not inhibit PHA-induced cell proliferation of either adherent or nonadherent blood cells, indicating the non-toxic nature of these particles at the concentrations tested. BC stimulated increased release of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase; the levels of PGE2, IL-1, collagenase, and caseinase were unchanged.

Adult↗
PubMed1993

The history of proton-driven ATP formation.

This article sets down the beginnings of some thoughts in bio-energetics. It illustrates how difficult it is in science as elsewhere to know how a new idea is generated. The literature needs very careful examination and separation from personalities.

Adenosine Triphosphate↗
PubMed1993

The binding of a complex cobalt ruthenium polyamine by deoxyribonucleic acid and a lipopolysaccharide: a model for a novel class of drugs.

In this paper we discuss the following: 1. Synthesis of [Co(H3CsarNHCH2pyRu(NH3)5)] (PF6)5, (CoRu). 2. Interaction of CoRu with calf thymus DNA and with lipopolysaccharide from Escherichia coli C (LPS) has been estimated using the absorption of the complex at 242 and 420 nm. 3. DNA and LPS increase the rate of fall of absorption at 420 nm due to autooxidation of the complex. 4. The fall in absorption of CoRu(II) at 420 nm can be used to give an approximate measure of binding to DNA and to LPS. 5. Both macromolecules are aggregated by CoRu at high concentrations and the cation and macromolecule complex can be removed by low speed centrifugation. 6. The DNA-CoRu complex can also be removed by high speed centrifugation when the cation concentration is too low to cause aggregation (20 microM CoRu/155 microM DNA-P). Absorption of redissolved complex at 420 nm is restored by reduction with ascorbic acid. 7. At saturation the ratio of mole CoRu bound/mole DNA-P is 0.16.

Ascorbic Acid↗
PubMed1993

Frequency of seasonal affective disorder among individuals seeking treatment at a northern Canadian mental health center.

The frequency of seasonal affective disorder (SAD) was examined in clients receiving treatment for recurrent mood disturbances in a northern Canadian site. Approximately one-fifth of these individuals were identified as having SAD when file histories and a statistical criterion were used as the basis for assessment. The failure to find a higher prevalence rate at this latitude may be due to other studies' reliance on client self-report, a tendency for individuals with SAD to relocate south, or a greater tendency for clients with SAD to be seen by general practitioners and alcohol treatment centers in the north.

Adult↗
PubMed1993

Chronic ethanol reduces immunologically detectable Gq alpha/11 alpha in NG108-15 cells.

Recent work has shown that chronic ethanol treatment inhibits receptor-stimulated phosphoinositide hydrolysis in NG108-15 cells and that ethanol exerts this effect primarily at the level of the guanine-nucleotide binding protein (G protein). Here we investigated the effects of ethanol exposure on the expression of Gq alpha/11 alpha, two highly homologous G protein alpha-subunits that have been implicated as regulators of phosphoinositidase C. Addition of ethanol (10-200 mM) to the culture medium for 48 h caused a concentration-dependent decrease in the immunologically detectable levels of Gq alpha/11 alpha. A small (approximately 15%) reduction in Gq alpha/11 alpha was observed after only 6 h of exposure to 200 mM ethanol, but membrane levels were reduced by 31% at 48 h. The ethanol-induced loss of Gq alpha/11 alpha was apparently independent of factors present in the foetal calf serum component of the culture medium. These results suggests that the decrease in receptor-mediated phosphoinositide hydrolysis following chronic ethanol treatment of NG108-15 cells may be mediated in part by a reduction in the membrane levels of Gq alpha/11 alpha.

Electrophoresis, Polyacrylamide Gel↗
PubMed1993

Involvement of adenosine in ethanol-induced changes in G-protein expression in NG108-15 cells?

Previous work has suggested that adenosine may be involved in ethanol-induced heterologous desensitization of adenylate cyclase in NG108-15 cells. It was proposed that chronic ethanol causes adenosine to accumulate extracellularly, activating adenosine A2 receptors and so leading to a reduction in Gs alpha mRNA and Gs alpha protein (Nagy et al., 1989). In this study we further investigated the effect of chronic ethanol on G-protein expression in NG108-15 cells. Pretreatment of NG108-15 cells with ethanol (200 mM, 48h) reduced membrane levels of Gs alpha and Gi alpha but increased Go alpha expression. The effects of ethanol on alpha-subunit expression were not reversed by adenosine deaminase and could not be mimicked by the adenosine agonist 5'- (n-ethyl)-carboxamidoadenosine (NECA). Chronic ethanol pretreatment did not appear to reduce the levels of Gs alpha or Gi alpha 2 mRNA. This same ethanol pretreatment reduced cell proliferation and increased differentiation without altering cell viability. Adenosine deaminase did not reverse any of these effects. These results indicate that ethanol differentially regulates G-protein alpha-subunit expression and induces morphological alterations in these cells independently of extracellular adenosine.

Adenosine↗
PubMed1993

Ethanol differentially regulates guanine nucleotide-binding protein alpha subunit expression in NG108-15 cells independently of extracellular adenosine.

Recent work has suggested that chronic ethanol treatment induces heterologous desensitization of adenylate cyclase in a number of cell lines maintained in culture and that this phenomenon is mediated by adenosine. It has been proposed that ethanol induces the accumulation of extracellular adenosine, which then down-regulates the Gs alpha protein and leads to heterologous desensitization. Here we investigated the effects of chronic ethanol treatment on the expression of Gs alpha, Gi alpha, and Go alpha, as well as cAMP signal transduction, in NG108-15 cells and further examined the role of adenosine in mediating these effects. Pretreatment of NG108-15 cells with 200 mM ethanol for 2 days reduced membrane levels of Gs alpha and Gi alpha and increased those of Go alpha. However, ethanol did not reduce the levels of Gs alpha and Gi alpha 2 mRNA in these cells. The ability of ethanol to alter alpha subunit expression was not reversed by removal of extracellular adenosine and could not be mimicked by an adenosine agonist. Chronic ethanol treatment increased both basal and agonist-stimulated cAMP accumulation in NG108-15 cells. Whereas the increase in basal cAMP was abolished by acute addition of adenosine deaminase, the increase in agonist-stimulated cAMP accumulation was not. Morphological examination of the cells indicated that ethanol inhibited cell division and promoted the apparent differentiation of the cells. These results indicate that ethanol induces complex alterations in guanine nucleotide-binding protein alpha subunit expression and cAMP signal transduction in NG108-15 cells and that it is unlikely that these effects are mediated simply by adenosine.

Adenosine↗
PubMed1993

Acute renal failure in the llama (Lama glama).

This clinical report describes 2 cases of acute renal failure in the llama (Lama glama). Both llamas presented with histories of administration of potentially nephrotoxic agents prior to hospitalization. It is suggested that renal function be carefully monitored in all llamas treated with nephrotoxic agents, especially when history or clinical signs indicate increased risk for renal failure.

Acute Kidney Injury↗
PubMed1993

Splenic cysts: changes in diagnosis, treatment and aetiological concepts.

Splenic cysts are generally considered as either true epidermoid cysts or false pseudocysts. The former are thought to be congenital while the latter are reputedly post-traumatic. However, a number of important features are common to both types of cysts and this classification may need revision. The recognition of the importance of the spleen, together with developments in imaging and operative surgery have led to significant changes in the management of splenic cysts. Accurate preoperative diagnosis and localisation together with increasing awareness of splenic conservation techniques should now ensure that, whenever possible, cysts can be eradicated without resort to total splenectomy. We present four patients who illustrate various aspects of this condition.

Adult↗