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Biomedical subjects

B Gray

Publications and source records attributed to B Gray.

At least 73 records · Page 4Linked to original sources

Nitric oxide interaction with lactoferrin and its production by macrophage cells studied by EPR and spin trapping.

The production of nitrate (NO3-) and nitrite (NO2-) from macrophage-derived NO was studied using EPR and spin trapping. The formation of NO3- was determined via EPR in reactions involving the iron-binding protein, lactoferrin. The formation of NO2- was determined via EPR/spin trapping in the reaction between NO2- and H2O2. Dissolved nitric oxide (NO.) was reacted with lactoferrin yielding an EPR spectrum (77 degrees K) different from the normal EPR spectrum obtained for lactoferrin, suggesting that NO. interacts with the ferric ions bound to lactoferrin forming a ferric-nitrosyl type complex. The EPR spectrum (77 degrees K) of this ferric-nitrosyl type complex was also observed in the supernatant fluid of macrophage cell suspensions following their stimulation with lipopolysaccharide (LPS). During LPS stimulation of macrophages, these cells generate NO. which in turn produces NO3- and NO2-. The ferric-nitrosyl type complex is formed in a reaction mixture containing apolactoferrin and bicarbonate following the reaction of Fe+2 with NO3-, generated from macrophage-derived NO(.), to produce Fe+3 and NO(.). Furthermore, in an acidic medium, NO2- reacts with H2O2 forming peroxynitrous acid (HOONO) which rapidly decomposes into hydroxyl radicals (.OH) and the nitrogen dioxide (NO2.) radical. In the supernatant fluid of LPS-stimulated macrophage suspensions, the production of .OH was verified by spin trapping using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as the spin trap and ethanol as the .OH scavenger. The EPR spectra corresponding to the DMPO-OH and the DMPO-hydroxyethyl adducts were identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Kinetics of superoxide scavenging by dismutase enzymes and manganese mimics determined by electron spin resonance.

This study presents an e.s.r. assay for superoxide dismutase (SOD). Enzymic reactions were studied in which Cu,Zn-SOD, Mn-SOD and Fe-SOD each competed with the spin trap 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) for superoxide anion (O2-) at pH 7.8 O2- from dissolved KO2 (potassium superoxide) in dimethyl sulphoxide was added directly to the enzyme solutions containing DMPO. The results show that, in this competition reaction system, the kinetics of the reactions between the enzymes and O2- follow a function y = f[( SOD]0.5). The rate constant, kSOD = 6.4 x 10(9) M-1. S-1, determined for Cu,Zn-SOD is approximately an order of magnitude larger than those for Mn-SOD and Fe-SOD. A comparative study of reported SOD mimics, including Mn2+, MnO2-desferrioxamine mesylate (Desferal) and MnO2-Desferal-ascorbate, was done. The results show that solutions of these complexes are approximately three orders of magnitude less active than Cu,Zn-SOD and approximately two orders of magnitude less active than Mn-SOD or Fe-SOD. The results also suggest that the reactivity toward O2- in solutions of these complexes originates from the Mn2+ present and not from the MnO2-Desferal complexes.

Ascorbic Acid↗

Learning during general anaesthesia: implicit recall after methohexitone or propofol infusion.

Forty-four patients undergoing coronary artery surgery were allocated randomly to receive an infusion of propofol or methohexitone as a hypnotic supplement to a fentanyl-based anaesthetic technique. A taped message was played to the patients, consisting of 10 words associated with prompt sentences and a suggestion for a specific postoperative behavioural response. Twenty patients (10 propofol and 10 methohexitone) (perioperative group) were exposed to the taped message during surgery and in the immediate postoperative period and the other 24 patients (postoperative group) were exposed to the tape only in the postoperative period, after return to the intensive care unit (ICU). No patient had explicit recall of any events during the period when the tape was played. The patients in the propofol group who heard the tape during surgery had significant implicit recall of the word associations compared with the equivalent 10 methohexitone patients (P = 0.004), when tested 48 h after surgery. The patients who were played the tape whilst receiving identical infusion regimens for sedation in the ICU did not demonstrate implicit recall of the word associations in either the propofol or the methohexitone groups. There was no evidence of a response to the specific behavioural suggestion during the postoperative interview. The results confirm that auditory perception can occur during clinically adequate anaesthesia, and that suppression of auditory awareness or learning is a function of both the pharmacological degree of sedation and the degree of surgical stimulation.

Anesthesia, General↗

Fractures caused by falling from a wheelchair in patients with neuromuscular disease.

This report discusses the occurrence of fractures caused by falling from a wheelchair. 13 distal femur, two proximal humerus and three distal tibia fractures were seen in 13 patients, of whom 11 had Duchenne muscular dystrophy, one had Becker muscular dystrophy and one had spinal muscular atrophy. All were non-ambulant and had been wheelchair-dependent for at least one year before the fall occurred. Six patients sustained fractures between 1976 and 1982, and five more between 1983 and 1985. Eight subsequent fractures from wheelchair falls have occurred since 1986. Although wheelchair design, controls and adaptations have continued to improve, wheelchair safety has not.

Accidental Falls↗

Plasma ferritin concentration and physical work capacity in athletes.

This investigation aimed to determine whether the physical work capacity of nonanemic athletes could be improved when plasma ferritin concentrations of below 30 ng/ml were raised at least 15 ng/ml. The experimental group consisted of 15 training athletes, each of whose plasma ferritin concentration was less than 30 ng/ml (mean and SD of 19.8 +/- 8.4 ng/ml). In a control group of 16, each was measured with a plasma ferritin concentration of more than 40 ng/ml (mean and SD of 83.3 +/- 37.6 ng/ml). All participated in submaximal and maximal tests for aerobic and anaerobic power. Following iron supplementation, plasma ferritin concentration in each experimental subject increased by at least 15 ng/ml to more than 30 ng/ml, to a new mean of 46.3 +/- 15.5 ng/ml. The performance measures were also repeated, but no significant overall effects were associated with the increased plasma ferritin concentrations. These data provide no sound evidence that physical work capacity of athletes is enhanced when plasma ferritin concentrations of around 20 ng/ml are increased by at least 15 ng/ml.

Female↗

Angelman syndrome: clinical profile.

To further delineate the clinical and developmental features of Angelman syndrome, we collected data through three sources of information: (1) physical examinations; (2) laboratory data and family questionnaire data of affected individuals; and (3) literature review. The questionnaire data describes a generally normal prenatal and birth history. Feeding difficulties, developmental delay, or seizures were the presenting problems in all infants. The diagnosis of Angelman syndrome, however, was not made in any infant prior to 1 year of age. Except for seizures, no medical or surgical complication was common, although a variety of visual complaints or findings were common. Sixty percent of Angelman syndrome children had a cytogenetically demonstrated deletion of chromosome 15q11-q13. The individuals with and without a deletion could not be differentiated clinically. Diagnosis in early childhood is therefore difficult, and a high index of suspicion is recommended.

Adolescent↗

Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a severely disabling illness of uncertain aetiology. It is characterized by a chronic, sustained or fluctuating sense of debilitating fatigue without any other known underlying medical conditions. It is also associated with both somatic and neuropsychological symptoms. Both physical and laboratory findings are usually unremarkable. Regional cerebral blood flow (rCBF) was assessed in 60 clinically defined CFS patients and 14 normal control (NC) subjects using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomography (SPECT). Compared with the NC group, the CFS group showed significantly lower cortical/cerebellar rCBF ratios, throughout multiple brain regions (P < 0.05). Forty-eight CFS subjects (80%) showed at least one or more rCBF ratios significantly less than normal values. The major cerebral regions involved were frontal (38 cases, 63%), temporal (21 cases, 35%), parietal (32 cases, 53%) and occipital lobes (23 cases, 38%). The rCBF ratios of basal ganglia (24 cases, 40%) were also reduced. 99Tcm-HMPAO brain SPECT provided objective evidence for functional impairment of the brain in the majority of the CFS subjects. The findings may not be diagnostic of CFS but 99Tcm-HMPAO SPECT may play an important role in clarifying the pathoaetiology of CFS. Further studies are warranted.

Adolescent↗

An unusual complication of tracheal intubation.

We report a previously undescribed complication of tracheal intubation. The complication arose as a result of tracheal intubation performed as an emergency procedure in a patient with an abnormal anteriorly placed larynx. Subsequent corrective laryngeal surgery was required after a temporary tracheostomy had been performed.

Adult↗

Intraperitoneal 5-fluorouracil infusion for treatment of both peritoneal and liver micrometastases.

Pharmacokinetic studies indicate that intraperitoneal administration of 5-fluorouracil (5-FU) has the potential to reduce the locoregional recurrence rate of gastrointestinal cancer. We have tested this hypothesis in a rat model, in which liver and peritoneal micrometastases were induced by the injection of cultured colonic cancer spheroids into both the portal vein and peritoneal cavity, respectively. Sixty-seven tumor-bearing animals were randomized to receive either no treatment, superior mesenteric vein 5-FU, or intraperitoneal 5-FU. Infusions were begun 2 days after tumor inoculation at a dose of 45 mg/kg/day and continued for 5 days. All untreated animals had advanced liver and peritoneal metastases 1 month after tumor implantation. Intraperitoneal 5-FU totally prevented the development of macroscopic tumor on peritoneal surfaces in 57% of animals. Paradoxically, rats treated with portal vein 5-FU had significantly more tumor or peritoneal surfaces than did the untreated group (p = 0.038). Both intraperitoneal and portal vein chemotherapy resulted in approximately a 50% reduction in total liver metastases compared with untreated animals (p = 0.78). Comparison of hepatic tumor growth within different lobes or segments demonstrated that although intraperitoneal 5-FU produced a homogeneous reduction in liver metastases, the effect of portal vein chemotherapy was unevenly distributed. We conclude that intraperitoneal chemotherapy was not only effective in eradicating peritoneal micrometastases but also received the same overall reduction in liver metastases as did portal vein chemotherapy. Moreover, regional differences in hepatic tumor responses as a result of drug streaming during portal vein 5-FU infusion were not observed after intraperitoneal chemotherapy.

Animals↗

The blocked bed.

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Bed Occupancy↗

Cross-reactive monoclonal antibodies for diagnosis of pneumococcal meningitis.

A diagnostic test for the detection of Streptococcus pneumoniae meningitis was developed using monoclonal antibodies (MAbs) to phosphocholine (PC) and non-PC determinants of pneumococcal teichoic acids. These MAbs do not recognize other bacteria that commonly cause meningitis. By using a dot blot assay, these MAbs were compared with a polyvalent pneumococcal capsular omniserum and an antiserum made to whole cells for their ability to detect pneumococci in infected spinal fluids. An immunoglobulin M (IgM) anti-PC antibody gave a positive reaction with 16 of 22 (73%) pneumococcal culture-positive spinal fluids. One false-positive result out of 45 pneumococcal culture-negative spinal fluids was also observed. D3114/63, an IgM MAb to non-PC determinants of teichoic acids, detected 15 of 22 of the pneumococcal culture-positive spinal fluids with one false-positive result. IgG2b and IgG3 anti-PC MAbs were less efficient than the IgM anti-PC MAb at detecting pneumococci in spinal fluids. Like the IgM anti-PC MAb, omniserum detected 73% of the culture-positive pneumococcal spinal fluids, with one false-positive result. The use of anti-PC or D3114/63 MAbs instead of a pooled serum such as omniserum has several advantages: (i) use of a single cross-reactive antibody rather than 83 pooled antibodies; (ii) possibility of a higher concentration of reactive antibody, which may increase the sensitivity of the test; (iii) a standardized antibody preparation; (iv) ease of preparation of the antibody; and (v) less expense.

Antibodies, Monoclonal↗

Role of attachment for the virulence of Streptococcus pneumoniae.

Adherence of microorganisms to mucosal surfaces is a general phenomenon among microorganisms infecting the human host. Its role for persistence and colonization as well as production of local inflammation is well established. This paper describes the adhesion of Streptococcus pneumoniae to human epithelial cells. Strains from various anatomical sites or diseases are compared for attaching capacity. Isolates from the same host but at different times are also compared. The molecular mechanisms, the so-called adhesin-receptor interactions, are partially described. The pneumococcus recognizes a sugar sequence; GlcNAc beta 1-3Gal; on the surface of the host epithelial cell. Glycoconjugates containing this disaccharide act as receptors for adhering pneumococci. The adhesin in pneumococcal attachment is less well characterized. It is a heat and trypsin sensitive component, most likely a peptide, which forms a bridge between the receptor and an anchoring site in the pneumococcal cell wall. Receptor active saccharides are part of the adhesion-inhibitory activity found in human milk.

Bacterial Adhesion↗

The effect of inhaled bronchoconstrictors on transcutaneous gas tensions in normal adult subjects.

The administration of histamine and leukotriene D4 (LTD4) by nebulised aerosol in logarithmically increasing doses to normal subjects resulted in significant bronchoconstriction. Transcutaneous oxygen tension (tcPO2) was monitored during and after the bronchial challenge tests. Following histamine challenge there was significant hypoxaemia in all subjects (mean fall in tcPO2, 20 mmHg). However, following LTD4 administration, there was a small and insignificant fall in tcPO2. Transcutaneous carbon dioxide tension (tcPCO2) was also monitored throughout bronchial challenge, but showed no significant change. We suggest that the hypoxaemia following histamine challenge was due to increased ventilation/perfusion (V/Q) mismatching in the lung induced by histamine deposition.

Administration, Inhalation↗

A protective monoclonal antibody that reacts with a novel antigen of pneumococcal teichoic acid.

D3114/63 is a hybridoma cell line producing a monoclonal antibody that appears to recognize a common antigenic determinant associated with the teichoic acids of Streptococcus pneumoniae. This hybridoma was produced in a fusion of splenic lymphocytes from an X-linked immunodeficient (xid) male (CBA/NxBALB/c)F1 mouse hyperimmunized with a heat-killed type 6A strain EF-3114. Treatment of EF-3114 with periodate, but not with protease, destroyed its ability to bind D3114/63. The specificity of D3114/63 for teichoic acids was suggested by the ability of both C-polysaccharide and F-antigen to inhibit its binding to EF-3114. Inhibition studies indicated that D3114/63 does not bind the PC determinant of teichoic acids. As in the case with anti-PC antibodies, the presence of an intact pneumococcal capsule significantly reduced the binding of D3114/63 to viable pneumococci. By means of a colony immunoblot procedure, it was determined that D3114/63 bound to all 97 pneumococcal strains tested including representatives of 24 different serotypes. Both D3114/63 and anti-PC antibodies were able to detect pneumococcal antigen in spinal fluids of 3 out of 4 patients with pneumococcal meningitis. D3114/63 protected mice from fatal infection with type 3 strain WU2 pneumococci but not from type 5 strain DBL5 or type 6A strain EF-3114.

Animals↗

Naturally occurring antibodies to phosphocholine as a potential index of antibody responsiveness to polysaccharides.

Naturally occurring antibodies reactive with the phosphocholine (PC) determinant of pneumococcal teichoic acids may be useful for evaluating the potential of patients to make antibodies to polysaccharides. Antibodies to PC are present in most adults under the age of 60 years, are absent in very young children, and are present at low levels in Wiscott-Aldrich patients and in IgG2-deficient adults. These last three groups respond very poorly to polysaccharide antigens. Antibodies to PC are also found at low levels in the elderly, a group that has previously been shown to have low levels of antibody to blood groups A and B carbohydrates. The levels of antibody to PC over time were constant in most individuals and, in adults, seemed to show slightly less variation than did titers of antibody to blood group B. Our findings suggest that titers of antibody to PC may be superior to titers of antibody to blood group A or B for monitoring responsiveness to carbohydrate antigens.

ABO Blood-Group System↗