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Biomedical subjects

G J Williams

Publications and source records attributed to G J Williams.

At least 55 records · Page 3Linked to original sources
PubMed1992

Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity to substance P.

We investigated the effects of ozone exposure (3.0 ppm, 2 h) on airway neutral endopeptidase (NEP) activity and bronchial reactivity to substance P in guinea pigs. Reactivity after ozone or air exposure was determined by measuring specific airway resistance in intact unanesthetized spontaneously breathing animals in response to increasing doses of intravenous substance P boluses. The effective dose of substance P (in micrograms) that produced a doubling of baseline specific airway resistance (ED200SP) was determined by interpolation of cumulative substance P dose-response curves. NEP activity was measured in tracheal homogenates made from each animal of other groups exposed to either ozone or room air. By reverse-phase high-pressure liquid chromatography, this activity was characterized by the phosphoramidon-inhibitable cleavage of alanine-p-nitroaniline from succinyl-(Ala)3-p-nitroaniline in the presence of 100 microM amastatin. Mean values of the changes in log ED200SP were 0.27 +/- 0.07 (SE) for the ozone-exposed group and 0.08 +/- 0.04 for the air-exposed group. We found that phosphoramidon significantly increased substance P reactivity in the air-exposed animals (P less than 0.01), but it had no effect in the ozone-exposed group. This finding was associated with a significant reduction in tracheal homogenate NEP activity of ozone-exposed animals compared with controls: mean values were 18.1 +/- 1.9 nmol.min-1.mg protein-1 for the ozone-exposed group and 25.1 +/- 2.4 nmol.min-1.mg protein-1 for air-exposed animals (P less than 0.05). Inhalation of an aerosolized NEP preparation, partially purified from guinea pig kidney, reversed the substance P hyperreactivity produced by ozone exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1991

Left atrial clot in patients with mitral prostheses: increased rate of detection after recent systemic embolism.

We studied 70 patients with mitral valvar replacements by both transthoracic and transoesophageal echocardiography. Fifteen subjects had recently suffered a suspected embolic episode. The remainder (55) were studied for other clinical reasons. Transthoracic echocardiography demonstrated thrombus in only 1 of the 70 patients. By contrast, transoesophageal examination revealed thrombus in 8 out of 15 patients with recent suspected embolism and 3 out of 55 without. Thrombus was most commonly seen in patients with biological valvar prostheses whose anticoagulation had been discontinued. When patients with prosthetic mitral valves present with a suspected embolic episode, transoesophageal echocardiography is strongly recommended. This study also suggests that transoesophageal echocardiography may be useful for evaluating patients with biological valves if anticoagulation is withdrawn so as to identify formation of thrombus at the earliest possible stage.

Anticoagulants↗
PubMed1990

Cytogenetic studies of leukemic recurrence in recipients of bone marrow allografts.

Cytogenetic studies were made in 20 leukemic patients who relapsed after treatment by allogeneic bone marrow transplantation (BMT). Seven of the eight patients in whom no chromosomal abnormalities were detected in leukemic cells before BMT developed clonal abnormalities after BMT, and in two of these patients two independent clones were observed. Most patients in whom clones were detected before BMT showed evidence of clonal evolution after BMT. Nonclonal abnormalities were also observed in clonal cells. These additional abnormalities, both clonal and nonclonal, were attributed to the effects of total body irradiation received by the patient before BMT. There was no evidence of recurrence of leukemia in donor cells among these patients. We concluded that the cells found in leukemic recurrence were derived from the original leukemic clone.

Adolescent↗
PubMed1990

The value of transesophageal echocardiography in the investigation of acute prosthetic valve dysfunction.

When patients present with suspected prosthetic valve dysfunction, investigation is usually instituted to delineate the site and cause thereof. Precordial cross-sectional echocardiography is often helpful in this respect, but in the patient with acute pulmonary edema, imaging may be impaired because of discomfort and respiratory distress. The information obtained may also be suboptimal as a result of concomitant obesity, chest wall deformity, and pulmonary disease. In addition, further difficulties may relate to the acoustic shadowing produced by the metallic portion of the valve and its sewing ring, especially with valves in the mitral position. In such patients, cardiac catheterization may cause further decompensation and is associated with a recognized increase in morbidity and mortality. Angiography does not accurately site regurgitant jets in relation to the prosthetic valve concerned and will not detect the presence of vegetations. Transesophageal echocardiography circumvents many of these imaging difficulties and we evaluated its use in five patients with prosthetic heart valves who presented acutely ill, in severe pulmonary edema and suspected prosthetic heart valve failure. In each case, the diagnosis of valve dysfunction was established, and precise information regarding the site and cause of the failure was obtained. No complications or deterioration in patient condition resulted from the procedure and the findings were confirmed at surgery performed within 24 hours in all five patients. Transesophageal echocardiography should be included in the assessment of acute prosthetic heart valve failure.

Acute Disease↗
PubMed1990

A system for ambulatory monitoring and computerised analysis of oesophageal motility and luminal pH.

It is often desirable to monitor physiological events from subjects free to participate in their normal daily activities. This is especially so where clinical symptoms are elusive or precipitated by specific activities. Through ambulatory monitoring, evidence of a causal relationship between recorded parameters and the spontaneous onset of symptoms may be revealed. We describe an ambulatory monitoring system which permits continuous 24-hour recording of oesophageal motility from three levels within the oesophagus together with luminal pH. Computerised analysis of the recorded data addresses many of the problems associated with processing the information accrued through long-term monitoring by providing an automatic comparison of patient data against either preselected values or those of the program's algorithm. Motility is quantified in terms of wave frequency, amplitude, duration and temporal relationship together with an integration of the wave area and mean pressure baseline. The corresponding pH data is quantified as frequency, duration and integrated area of pH excursions throughout a range of pH1-8. This system provides access to the entire patient record which may either be viewed on screen, analysed or output to a printer. Analysis yields a tabulated breakdown of motility and pH events from any section of the patient's record. Selective analysis readily permits statistical comparison of discrete time-matched samples corresponding to different patient circumstances.

Algorithms↗
PubMed1990

Eating disorders, perceived control, assertiveness and hostility.

There are anecdotal claims that eating disorder patients perceive themselves as highly controlled by the family and by society, but that they do not show assertive behaviour towards controllers. Anorexic and bulimic females were compared with female psychiatric patients, dieters and non-dieting controls on measures of eating disorder symptomatology, locus of control, assertiveness, inwardly directed hostility, family control and family encouragement of independence. Eating disorder patients reported significantly more external control, more inwardly directed hostility, less self-assertion and less family encouragement of independence than dieters and non-dieting controls, but they did not differ from psychiatric controls. Most of the characteristics seen in eating disorder subjects were also reported by psychiatric controls.

Adolescent↗
PubMed1990

Cellular metabolism of 3'-azido-2',3'-dideoxyuridine with formation of 5'-O-diphosphohexose derivatives by previously unrecognized metabolic pathways for 2'-deoxyuridine analogs.

3'-Azido-2',3'-dideoxyuridine (AzdU, CS-87) is a potent inhibitor of human immunodeficiency virus replication in human peripheral blood mononuclear cells (PBMC) with limited toxicity for human bone marrow cells (BMC). In the present study, metabolism of AzdU was investigated in human PBMC and BMC after exposure of cells to 2 or 10 microM [3H]AzdU. 3'-Azido-2',3'-dideoxyuridine-5'-monophosphate (AzdU-MP) was the predominant metabolite, representing approximately 55 to 65% of intracellular radioactivity in both PBMC and BMC at all times. The AzdU-5'-diphosphate and -5'-triphosphate intracellular levels were 10- to 100-fold lower than the AzdU-MP levels and, of note, AzdU-5'-triphosphate was not detected in human BMC. Using anion exchange chromatography, a new peak of radioactivity, distinct from any known anabolites, was detected. This chromatographic peak was found to be resistant to alkaline phosphatase but was hydrolyzed by 5'-phosphodiesterase, yielding AzdU-MP. Incubation of [3H]AzdU and D-[1-14C]glucose in PBMC and BMC produced a double-labeled peak with the same retention time as the anabolite, suggesting formation of a hexose derivative of AzdU. A novel high performance liquid chromatography method was developed that allowed for the separation of nucleosides, nucleotides, and carbohydrate derivatives thereof. Using this highly specific method, the putative AzdU-hexose actually was separated into two chromatographic peaks. These novel metabolites were identified as 3'-azido-2',3'-dideoxyuridine-5'-O-diphosphoglucose and 3'-azido-2',3'-dideoxyuridine-5'-O-diphospho-N-acetylglucosamine. Following 48 hr of incubation with [3H] AzdU, as much as 20 and 30% of these AzdU metabolites accumulated in PBMC and BMC, respectively. When AzdU was removed from the cell cultures, intracellular AzdU diphosphohexose concentrations decayed in a monophasic manner, with an elimination half-life of 14.3 hr. By 48 hr, levels of 0.3 pmol/10(6) cells were still detected, reflecting a gradual anabolism of these metabolites. Elimination of AzdU-MP and AzdU-5'-diphosphate was characterized by a two-phase process, with a short initial half-life of 0.83 and 0.24 hr and a long terminal half-life of 14.10 and 8.24 hr, respectively. Similar diphosphohexoses of deoxyuridine (dUrd) were also detected in human PBMC and BMC after exposure to [3H]dUrd, suggesting that dUrd derivatives are metabolized in a similar manner. In summary, the discovery of novel metabolic pathways for dUrd analogs demonstrates that AzdU has unique metabolic features that may contribute to the low toxicity of this anti-HIV agent in human BMC and also affect its mechanism of action.(ABSTRACT TRUNCATED AT 400 WORDS)

Antiviral Agents↗
PubMed1989

Cytogenetic studies of 103 patients with acute myelogenous leukemia in relapse.

In order to investigate the cytogenetic patterns in relapsed acute myelogenous leukemia (AML), a clinical and cytogenetic follow-up of patients newly diagnosed for the Fourth International Workshop on Chromosomes in Leukemia (4IWCL) was evaluated at the 6IWCL. Information was received on 103 patients in relapse who were then classified into seven groups according to the diagnostic karyotype. These groups were: normal, t(8;21), t(15;17), +8, a single specific abnormality either numerical or structural other than those already listed, a single nonrandom or miscellaneous abnormality again either numerical or structural, and complex abnormalities. The patient's age, diagnostic FAB type, the number of relapses, the total survival time, and the karyotype in relapse were considered in each of these cytogenetic groups. The remission and survival rates were comparable in all groups except the +8 group, where patients relapsed earlier and had a shorter survival time. Multiple relapses occurred most frequently in the t(8;21) group, whereas none of the patients with t(15;17) relapsed more than once, although the total survival time was similar to the two groups. Thirty-nine percent of the patients relapsed with the same karyotype as at diagnosis. A more complex karyotype showing evolution was found in 53%, and 8% showed either a less-complicated karyotype or appeared to have reverted to normal. Numerical abnormalities in relapse frequently involved trisomy of chromosomes 8 and/or 21. There was a nonrandom development of 9q- with relapse in patients with t(8;21). A pericentric inversion of chromosome 4, and abnormality infrequently reported at diagnosis, was found in relapse in association with t(15;17), t(8;21), and +8 karyotypes. Changes considered to be typically secondary in nature involving 5q, 7q, and 12p were seen in only seven cases. Twenty-one patients who had an apparently normal karyotype at diagnosis remained normal in relapse, indicating that absence of clonal chromosome abnormality is a real observation in AML rather than a failure of detection.

Adolescent↗
PubMed1989

Structure of cycloguanil hydrochloride by neutron diffraction.

4,6-Diamino-1-(p-chlorophenyl)-1,2-dihydro-2,2-dimethyl-s-triazine hydrochloride, C11H15-CIN5+.Cl-, Mr = 288.20, monoclinic, P21/c, a = 8.783 (2), b = 10.267 (2), c = 17.234 (3) A, beta = 115.72 (1) degrees, U = 1400.1 (5) A3, Z = 4, Dx = 1.337 Mg m-3, lambda = 1.15882 (7) A for unit-cell determination and 1.04702 (7) A for collection of intensity data, mu = 0.191 mm-1, T = 15.0 (5) K, final R(F2) = 0.050 and wR(F2) = 0.063 for 3099 independent reflections. Five atoms of the triazine ring are nearly coplanar. The sixth, the quaternary C(2), is displaced from this plane (P1) so that the bond to one of its methyl substituents is nearly perpendicular to P1 while the other methyl substituent lies almost in the plane. The chlorophenyl-ring plane is nearly perpendicular to P1. The heterocycles form cyclic dimers via hydrogen bonds from the 6-amino group to ring atom N(5) of an adjacent molecule. All other N-H units are hydrogen bonded to the Cl- counter ion. The ring is protonated at position N(3).

Chemical Phenomena↗
PubMed1989

Recombinant human interferon-beta suppresses the replication of HIV and acts synergistically with AZT.

The in vitro effects of recombinant human interferon-beta ser (rIFN-beta ser) and 3'-azido-3'-deoxythymidine (AZT) alone and in combination on human immunodeficiency virus (HIV) replication were examined. rIFN-beta ser inhibited HIV progeny virus synthesis in cell cultures chronically infected with HIV. When used in combination, suboptimally effective concentrations of rIFN-beta ser and AZT synergistically inhibited HIV-mediated syncytium formation in HeLa T4 cell cultures. Whereas AZT alone reduced HIV replication in human MT-2 cells, addition of low concentrations of rIFN-beta ser reduced by 4- to 1,000-fold the amount of AZT required to maximally block HIV p24 antigen synthesis and HIV-mediated cell lysis. No drug-related cytoxicity was observed when the two agents were used together at and above maximally effective concentrations. These results suggest that a safer, yet effective, therapy for HIV infections may be achieved with reduced doses of AZT in combination with rIFN-beta ser.

Cells, Cultured↗
PubMed1989

Fatal acute left ventricular outflow obstruction due to interventricular septal haematoma--diagnosis by transoesophageal echocardiography.

We describe a case of fatal left ventricular outflow obstruction detected by intraoperative transoesophageal echocardiography. This resulted from acute haematoma formation within the interventricular septum following internal mammary artery grafting to the left anterior descending coronary artery. This unusual case highlights the emerging role of transoesophageal echocardiography in the diagnosis and management of the complications of cardiac surgery.

Echocardiography, Doppler↗
PubMed1988

Doppler ultrasound of normally functioning mechanical mitral and aortic valve prostheses.

Doppler ultrasound flow velocities across clinically normally functioning mitral (Bjork-Shiley, Medtronic Hall, Lillehei-Kaster, Duromedic and Starr-Edwards) and aortic (Bjork-Shiley, Medtronic Hall, Lillehei-Kaster and Duromedic) valve prostheses are described. To enable ease of reference for the echocardiographer and to avoid the need for time-consuming calculations of pressure drops and effective valve orifice areas, peak flow velocities and, where relevant, pressure half times across valves of different types and sizes are tabulated. In the mitral position, there was significant negative correlation between peak velocity and valve size and between pressure half time and valve size only when a large number and a wide range of sizes of a given type of mitral prosthesis was studied. Similarly, there was significant negative correlation between peak velocity and aortic valve size for Bjork-Shiley and Duromedic valves. Regurgitant jets were detected across 18.4% of mitral and 42% of aortic prostheses.

Adolescent↗
PubMed1988

Reproducibility and persistence of abnormal transmitral flow velocity patterns detected by pulsed Doppler ultrasound.

This prospective study examines the reproducibility and persistence of abnormal transmitral flow detected using pulsed Doppler ultrasound on 2 separate occasions between 2 days and 6 weeks apart. The 22 patients included were accepted consecutively from those having an abnormal diastolic flow pattern at initial examination. Abnormal flow velocity patterns were defined as those exhibiting reversal of the ratio of the passive filling velocity (E) and active atrial transport velocity (A). There was no significant difference between the separately recorded values for the ratio of the peak E and A velocities or of the ratio of the planimetered areas beneath each of the velocity waves, with positive correlations for both sets of values (r = 0.68, r = 0.67). Significant positive correlation also existed between the mean rates of acceleration to each of the E and A velocity peaks of the transmitral waveform recorded on separate occasions (r = 0.68, r = 0.95). Interobserver variation for the analysis of hard-copy pulsed Doppler recordings between two trained observers was less than 5% and intraobserver error for recording analysis was less than 2% for both observers. Abnormal transmitral flow velocity patterns persist unchanged in the absence of therapeutic intervention and the acceptably small observer error in the recording and analysis of such flow patterns allows consistent and clinically reliable data to be obtained.

Adolescent↗
PubMed1988

Can left ventricular end-diastolic pressure be estimated non-invasively?

The relationship between the velocity waveforms due to the early and late phases of ventricular filling recorded by pulsed Doppler changes with abnormalities of left ventricular diastolic function and it has previously been suggested that quantitative assessment of these changes may provide a clinically useful estimate of left ventricular end-diastolic pressure. Pulsed Doppler ultrasound was used to record transmitral blood flow velocities simultaneously and on the same recorder as left ventricular pressure measurements in 30 patients undergoing cardiac catheterisation for the investigation of ischaemic heart disease. Contrary to previous reports we found no relationship between transmitral flow and left ventricular end-diastolic pressure. Caution is required in the conclusions drawn from transmitral flow velocity patterns whose relationship to left ventricular end-diastolic pressure remains uncertain.

Blood Flow Velocity↗
PubMed1986

Inhibition of 2',5'-oligo(A)-dependent endoribonuclease by 2',5'-oligo(A) degradation products.

Addition of extract of interferon (IFN)-treated HeLa cells to transcription reactions containing activated reovirion cores decreases the yield of viral mRNA (C. Baglioni, A. De Benedetti, and G. J. Williams, 1984, J. Virol. 52, 865-871). The 2'5'-oligo(A) (2-5A)-dependent endonuclease (RNase L) cleaves specifically viral mRNA, but little 5'-triphosphate 2-5A is recovered from these reactions by DEAE-cellulose chromatography. However, in the present study we detected microM concentrations of 2-5A derivatives by binding to RNase L. Similar results were obtained when the synthetic double-stranded RNA poly(I) X poly(C) was incubated with extract from IFN-treated cells: microM concentrations of 2-5A were detected by the binding assay, but little rRNA was degraded by RNase L. 2-5A derivatives which inhibited the activation of RNase L by authentic 2-5A were eluted from DEAE-cellulose with 90 mM KCl. These inhibitors were also formed by incubating purified 2-5A with HeLa cell extract. These results indicated that 2-5A was synthesized in the incubations with reovirion cores or poly(I) X poly(C), but that it was in large part degraded to compounds inhibitory for RNase L. IFN-treated HeLa cells were incubated with poly(I X C), but little rRNA degradation was detected in spite of the presence of high concentrations of 2-5A in these cells. Most of this 2-5A was eluted with 90 mM KCl from DEAE-cellulose and was inhibitory for RNase L. This indicated that 2-5A was degraded to inhibitory derivatives also in intact cells. The structure of the degradation products of 2-5A has not been established, but they contain free terminal phosphate(s), since their binding to RNase L and the inhibition of this enzyme is abolished by digestion with phosphatase.

Adenine Nucleotides↗