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Biomedical subjects

A Williams

Publications and source records attributed to A Williams.

At least 325 records · Page 18Linked to original sources
PubMed1996

Cross-infection of chicks by airborne transmission of Salmonella enteritidis PT4.

Airborne cross-infection by Salmonella enteritidis PT4 strains was demonstrated between sets of orally infected 1-d-old chicks and identical uninfected control chicks. Low numbers of Salm. enteritidis were detected in the air of the rooms housing the chicks. Sentinel mice within the rooms did not become infected. This study demonstrates that low levels of airborne Salm. enteritidis are a potential source of cross-infection in poultry houses.

Air Microbiology↗
PubMed1996

Use of whole gut perfusion to investigate gastrointestinal blood loss in patients with iron deficiency anaemia.

Iron deficiency anaemia may be due to occult bleeding into the gut. However, although clinical investigations may show a high frequency of gastrointestinal tract disease in these patients, the cause-effect relationship between the lesions detected and anaemia remain uncertain. This study aimed to establish whether lesions detected by endoscopy or imaging of the gastrointestinal tract in patients with unexplained iron deficiency anaemia are bleeding continuously. Routine clinical tests were performed in 42 patients with unexplained iron deficiency anaemia referred to this unit. Whole gut lavage and assay of haemoglobin in the gut perfusate were also performed. The main outcome measures were clinical diagnoses (by imaging and endoscopy of the upper gastrointestinal tract and colon); the concentration of haemoglobin in whole gut lavage fluid; and the calculated gastrointestinal blood loss per day. There were 73 clinical, dietary, or iatrogenic factors of possible aetiological importance in the 42 patients--poor diet (10), gross gastrointestinal abnormality (34 in 28 patients), malabsorption (14), coagulation problems (6), and NSAID use (9). The gut lavage test showed, however, that at the time the test was performed, only eight patients were losing more than 2 ml blood daily into the gut, including all four with colonic cancer, one with diffuse gastric vascular ectasia, and one with severe ulcerative oesophagitis. It is concluded that occult gastrointestinal bleeding sufficient to cause anaemia was evident in only 19% of 42 patients. There was a high frequency of other potential causes of iron deficiency in the remainder, suggesting that most of the gastrointestinal diseases and lesions detected in them were probably coincidental. Factors other than blood loss should be considered and treated in patients referred for anaemia assessment.

Adult↗
PubMed1996

The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study.

PURPOSE: To construct a breast cancer-specific quality-of-life questionnaire (QLQ) module to be used in conjunction with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and to test its reliability and validity cross-culturally. PATIENTS AND METHODS: Module construction took place after the EORTC guidelines for module development. The module--the QLQ-BR23--consists of 23 items covering symptoms and side effects related to different treatment modalities, body image, sexuality, and future perspective. This module was tested in 170 Dutch, 168 Spanish, and 158 American cancer patients at two points in time. The timing for the Dutch and Spanish patients was before and during treatment with radiotherapy or chemotherapy. For the American patients, the questionnaire was administered at admission at the breast clinic and 3 months after the first assessment. RESULTS: Multitrait scaling analysis confirmed the hypothesized structure of four of the five scales. Cronbach's alpha coefficients were, in general, lowest in Spain (range; .46 to .94) and highest in the United States (range; .70 to .91). On the basis of known-groups comparisons, selective scales distinguished clearly between patients differing in disease stage, previous surgery, performance status, and treatment modality, according to expectation. Additionally, selective scales detected change over time as a function of changes in performance status and treatment-induced change. CONCLUSION: These results lend support to the clinical and cross-cultural validity of the QLQ-BR23 as a supplementary questionnaire for assessing specific quality-of-life issues relevant to patients with breast cancer.

Adult↗
PubMed1996

Effects of prostaglandins on deoxyribonucleic acid and aggrecan synthesis in the RCJ 3.1C5.18 chondrocyte cell line: role of second messengers.

PGs play an important role in regulating articular chondrocyte function in both normal and pathological states. However, the mechanisms of the effects of PG on chondrocyte function remain undefined. We, therefore, examined the effects of PGE1, PGE2, and PGE2 alpha on second messenger generation in relation to DNA and aggrecan synthesis in the nontransformed rat RCJ 3.1C5.18 (RCJ) chondrocyte cell line. RCJ cells were grown under minimal attachment conditions on a composite collagen-agarose (0.15%/0.8%) gel to maintain a differentiated phenotype. PGE1 and PGE2 (0.001-100 microM) produced a similar dose-related increase in cAMP accumulation, with a maximal 8-fold increase over basal values, whereas PGF2 alpha produced a minimal 1.3-fold increase in cAMP levels only at 100 microM. On the other hand, both PGE2 and PGE2 alpha raised the intracellular free calcium ([Ca2+]i) concentration, derived primarily from extracellular sources, whereas PGE1 was without effect on [Ca2+]i. These three PGs also had divergent effects on DNA synthesis, as measured by [3H]thymidine ([3H]TdR) incorporation. PGF2 alpha (0.001-5 microM) produced a dose-related increase in [3H]TdR incorporation, with a maximal 1.6-fold increase over baseline values at 5 microM and a slight decline to below maximal levels at 10 microM. PGE2 exhibited a contrasting inverse biphasic response, with an initial small suppressive effect that was maximal at 0.1 microM and a secondary stimulatory phase producing a small increase over control values at 5 microM. PGE1 had a uniformly suppressive effect, producing a 30% decrease at 10 microM. Despite the divergent effects of PGE1, PGE2, and PGE2 alpha on second messenger generation and DNA synthesis, all three PGs produced a dose-related stimulation of aggrecan synthesis. PGF2 alpha was the most potent, producing significant stimulation at 0.001 microM and a maximal 104% increase at 5 microM. PGE1 and PGE2 were approximately equipotent and approximately 60% as effective as PGF2 alpha in stimulating aggrecan synthesis. Northern analysis demonstrated that the effects of PG on aggrecan synthesis were not accompanied by changes in aggrecan core protein steady state messenger RNA levels. Thus, the effects of PG on aggrecan production in RCJ cells appear to be regulated at the posttranscriptional level. Forskolin and (Bu)2cAMP mimicked the suppressive effects of PGE1 on [3H]TdR incorporation, as well as the stimulatory effect of PGE1 on aggrecan synthesis. In addition, the phorbol ester 12-O-tetradecanoyl phorbol acetate mimicked PGF2 alpha stimulation of [3H]TdR incorporation and aggrecan synthesis, and the effects of PGE2 alpha on these processes were blocked by protein kinase C inhibitors. Therefore, it appears that in mammalian chondrocytes, PGE1 primarily activates the cAMP-protein kinase A second messenger system, PGE2 alpha affects primarily the Ca2(+)-protein kinase C system, and PGE2 activates both pathways. Moreover, PG posttranscriptional regulation of aggrecan synthesis in chondrocytes involves both the cAMP-protein kinase A and Ca2(+)-protein kinase C second messenger systems.

Aggrecans↗
PubMed1996

Inhibition of vascular smooth muscle cell proliferation and arterial intimal thickening by a novel antiproliferative naphthopyran.

Smooth muscle cell proliferation plays an important role in neointimal thickening after vascular injury and may contribute to restenosis after angioplasty. Development of suitable pharmacological agents modulating smooth muscle cell proliferation is critical for further investigation of vascular hyperplasia and its prevention. In the present study, we report a novel series of compounds that inhibit smooth muscle cell proliferation and arterial intimal thickening after balloon angioplasty. LY290181 (2-amino-4-[3-pyridyl]-4H-naphtho [1, 2-b]pyran-3-carbonitrile) and LY290293 (2-amino-4-[3-pyridyl]-4H-naphtho [1, 2-b]pyran-carbonitrile) produced a dose-dependent inhibition of DNA synthesis and proliferation of vascular smooth muscle cells in culture. Fifty percent inhibition (IC50) of cell proliferation was produced by 20 nM LY290181 or LY290293. Cell growth inhibition was not due to cell death, as demonstrated by the release of intracellular lactate dehydrogenase and by the reversibility of inhibition upon washing. Inhibition of smooth muscle cell proliferation was achieved in cells stimulated by either serum or individual growth factor such as platelet-derived growth factor, fibroblast growth factor or epidermal growth factor. In the rat model of balloon injury to carotid artery, LY290181 and LY290293 produced 61% (P < .005) and 48% (P < .005) inhibition of intimal thickening when administered p.o. at 100 and 120 mg/kg/day, respectively, over a 2-week period. Inhibition of intimal thickening (70%, P < .005) by LY290293 was also demonstrated when the compound was administered s.c. at 10 mg/kg/day. These studies demonstrate that naphthopyrans LY290181 and LY290293 are potent inhibitors of smooth muscle cell proliferation in vitro and that they produce substantial reduction in arterial intimal thickening in a balloon injury model when administered systemically.

Angioplasty, Balloon↗
PubMed1996

Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first two years of life.

A total of 200 children were followed from birth through 2 years of age with nasopharyngeal (NP) cultures to determine the normal colonization pattern of nontypeable H. influenzae (NTHI) in young children. NP cultures were obtained routinely at 13 scheduled visits. 44% of children became colonized by 2 years; acquisition was greatest in the first year. Colonization with the initial strain, as determined by outer membrane proteins, persisted from 1-5 months, median 2 months. Children carried one predominant strain at a time but became colonized with up to 7 different strains, mean 2.2, over 2 years. Three patterns of colonization were observed: i) rapid elimination of the initial strain, ii) prolonged colonization with the initial strain, and iii) colonization with different strains. Reacquisition of a previously carried strain was rare. Changes in outer membrane protein patterns reflected acquisition of new strains rather than phenotypic changes of old strains. Children colonized with 1 strain for < or = 2 months generated a greater mucosal antibody response, log 2.35, U/ng/ml SIgA, than children colonized with different strains, log 1.89, U/ng/ml SIgA, p <0.01. These data suggest that duration of colonization with one strain and the acquisition of a new strain is regulated by the local specific SIgA.

Bacterial Outer Membrane Proteins↗
PubMed1995

Detection of apoptosis in murine scrapie.

In order to determine whether apoptosis contributes to the neuronal loss in scrapie, in situ end labeling was applied on brains of mice showing clinical signs of the disease. Positively labeled, apoptotic neurons were observed in the cerebellum, cerebral cortex and hippocampus, areas known to show characteristic scrapie-related vacuolation, and were absent in the brains of control mice. We conclude that apoptosis plays a role in the neuronal loss that occurs in scrapie. The importance of apoptosis as a predominant cell death mechanism in scrapie, however, remains to be determined.

Animals↗
PubMed1995

Bioactivation of dinitrobenzamide mustards by an E. coli B nitroreductase.

A nitroreductase isolated and purified from Escherichia coli B has been demonstrated to have potential applications in ADEPT (antibody-directed enzyme prodrug therapy) by its ability in vitro to reduce dinitrobenzamides (e.g. 5-aziridinyl 2,4-dinitrobenzamide, CB 1954 and its bischloroethylamino analogue, SN 23862) to form cytotoxic derivatives. In contrast to CB 1954, in which either nitro group is reducible to the corresponding hydroxylamine, SN 23862 is reduced by the nitroreductase to form only the 2-hydroxylamine. This hydroxylamine can react with S-acetylthiocholine to form a species capable of producing interstrand crosslinks in naked DNA. In terms of ADEPT, SN 23862 has a potential advantage over CB 1954 in that it is not reduced by mammalian DT diaphorases. Therefore, a series of compounds related to SN 23862 has been synthesized, and evaluated as potential prodrugs both by determination of kinetic parameters and by ratio of IC50 against UV4 cells when incubated in the presence of prodrug, with and without the E. coli enzyme and cofactor (NADH). Results from the two studies were generally in good agreement in that compounds showing no increase in cytotoxicity in presence of enzyme and cofactor were not substrates for the enzyme. None of the analogues were activated by DT diaphorase isolated from Walker 256 carcinoma cells. For those compounds which were substrates for the E. coli nitroreductase, there was a positive correlation between kcat and IC50 ratio. Two compounds showed advantageous properties: SN 25261 (with a dihydroxypropylcarboxamide ring substituent) which has a more than 10-fold greater aqueous solubility than SN 23862 whilst retaining similar kinetic characteristics and cytotoxic potency; and SN 25084, where a change in the position of the carboxamide group relative to the mustard resulted in an increased cytotoxicity ratio and kcat compared with SN 23862 (IC50 ratios 214 and 135; kcat values of 75 and 26.4 sec-1, respectively). An analogue (SN 25507) incorporating both these structural changes had an enhanced kcat of 576 sec-1. This study elucidates some of the structural requirements of the enzyme and aids identification of further directions in the search for suitable prodrugs for an ADEPT nitroreductase system.

Aniline Mustard↗
PubMed1995

Can we distinguish between benign versus malignant compression fractures of the spine by magnetic resonance imaging?

STUDY DESIGN: The authors investigate the usefulness of magnetic resonance imaging in differentiating benign versus malignant compression fractures by reviewing patients and a fracture model in a canine model. OBJECTIVES: To determine the sensitivity and specificity of magnetic resonance imaging in differentiating benign versus malignant compression fractures of the spine and to obtain distinguishing features in magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: The differentiation between benign and abnormal compression fractures of the thoracolumbar spine has important implications regarding patient treatment and prognosis. Plain radiographs, bone scans, and computed tomography are not accurate imaging modalities for this purpose. METHODS: Magnetic resonance imaging scans of 22 patients with confirmed lesions of the thoracolumbar spine were studied. There were 11 malignant and 11 benign lesions. Two experienced neuroradiologists blindly reviewed the magnetic resonance imaging scans and determined benign or malignant lesions. A canine study was performed to simulate a compression fracture model with a vertebral osteotomy in two dogs, and serial contrast-enhanced magnetic resonance imaging scans were performed 15, 30, 60 and 90 days after surgery. RESULTS: The correct interpretation between two neuroradiologists was 77% and 95%. The combined sensitivity rate was 88.5%, and the specificity rate was 89.5%. Magnetic resonance imaging reliably distinguished benign versus malignant lesions based on the anatomic distribution and intensity of signal changes of bone and adjacent tissues, contrast enhancement characteristics, and changes over time. Only one malignant lesion was misinterpreted by both neuroradiologists as benign, whereas there was one additional missed malignant lesion and three misinterpreted benign lesions by one radiologist. In the canine study, signal changes and enhancement were found 60 days after surgery, but no signal changes or enhancement were noted on the scan 90 days after surgery. CONCLUSIONS: Magnetic resonance imaging scans can detect malignant vertebral lesions early, but acute healing compression fractures may mimic the findings of metastatic lesions. The use of contrast-enhanced magnetic resonance imaging scans and serial magnetic resonance imagings are helpful for additional differentiation between benign and malignant compression fractures. In addition to magnetic resonance imaging scans, other diagnostic tests and clinical findings should be correlated before biopsy or surgery of the suspected lesion.

Adult↗
PubMed1995

Down-regulation but not phosphorylation of stathmin is associated with induction of HL60 cell growth arrest and differentiation by physiological agents.

Stathmin is a cytosolic phosphoprotein that has an important but, as yet, undefined role in cell proliferation and differentiation. Induction of growth arrest and differentiation of HL60 cells to monocytes by phorbol 12-myristate 13-acetate is associated with rapid phosphorylation of the protein. Stathmin phosphorylation was not seen when HL60 cells were induced to differentiate to monocytes, by 1 alpha, 25-dihydroxyvitamin D3, and to neutrophils, by all-trans retinoic acid and granulocyte colony stimulating factor. In all the above instances, stathmin expression was down-regulated. Thus, increased stathmin phosphorylation is not required for cell growth arrest or differentiation or down-regulation of stathmin expression.

Blotting, Western↗