Search PubMed⌕ Search

Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 307 records · Page 17Linked to original sources

Neutrophil activation detected by increased neutrophil elastase activity in type 1 (insulin-dependent) diabetes mellitus.

Neutrophils have been implicated in the development of vascular disease, and increased plasma neutrophil elastase indicates increased neutrophil activation. The aim of this study was to determine whether neutrophil elastase levels, measured by radioimmunoassay, are altered in diabetes. One hundred Type 1 (insulin-dependent) diabetic patients and 35 comparably-aged control subjects were studied. There was no difference in the total white cell count, but the diabetic group had a higher neutrophil count (p less than 0.05). Plasma neutrophil elastase (p less than 0.001) and total neutrophil elastase (p less than 0.02) were increased in the diabetic group. The total neutrophil elastase levels reflected the neutrophil count, but plasma neutrophil elastase was independent of the number of neutrophils. The increased plasma neutrophil elastase level was not related to age, duration of diabetes, plasma glucose or HbA1. The results suggest an association between diabetes and neutrophil activation which may play a role in the development of vascular disease.

Adult↗

Differential scanning calorimetric and Fourier transform infrared spectroscopic investigations of cerebroside polymorphism.

Calorimetric and Fourier transform infrared (FTIR) spectroscopic studies have been made of the polymorphism exhibited by bovine brain cerebroside-water systems, and the effect of cholesterol and dipalmitoylphosphatidylcholine (DPPC) upon this polymorphism was investigated. The conversion of the cerebroside from the thermodynamically stable to the metastable form is found to be accompanied by spectral changes, indicating a decrease in cerebroside headgroup hydration and a rearrangement of the hydrogen-bond network. The incorporation of low concentrations of cholesterol and DPPC into cerebroside bilayers broadens the thermal transitions associated with the cerebroside as a result of the disruption of cerebroside-cerebroside interactions. This disruption is evident in the spectra of cerebroside/cholesterol mixtures.

1,2-Dipalmitoylphosphatidylcholine↗

Opioid binding sites in the fish brain: an autoradiographic study.

Cryostat sections of trout brains were incubated with tritiated opioid ligands (5 nM [3H]etorphine or 4 nM D-[3H]Ala2, Met5 enkephalinamide) with the initial aim of locating opioid binding sites associated with the hypothalamo-pituitary axis. Naloxone-displaceable binding was observed in all regions of the brain, with a density ranking order of cerebellum greater than telencephalon greater than optic tectum greater than hypothalamus greater than brain stem greater than pituitary gland. Within the hypothalamus and pituitary gland binding was unexpectedly low, apart from a slightly enhanced binding anteriorly in the preoptic region and posteriorly associated with presumptive sensory fibres. A similar distribution of opioid binding sites was seen in the eel and lamprey brain. The high level of opioid binding in the cerebellum permitted a tentative identification of opioid subtypes using [3H]etorphine binding to membrane preparations from trout cerebellum. Scatchard analysis indicated the presence of a single class of high-affinity binding sites with a density of 0.38 pmol/mg protein and affinity constant (KD) of 2.6 nM. Displacement by unlabelled ligands suggested the existence of mu and/or kappa receptors.

Anguilla↗

Altered lung vascular permeability during intermittent haemodialysis.

Hypoxia is known to develop during intermittent haemodialysis. To investigate if increased pulmonary capillary permeability to protein contributes to this phenomenon, a dual-isotope technique using Indium-labelled transferrin and Technetium-labelled red blood cells was used. Lung vascular permeability was measured in eight patients with dialysis-dependent chronic renal failure immediately before and during intermittent haemodialysis with cuprophane membranes. As a group there was a significant increase in lung vascular permeability during the early stages of haemodialysis, compared to predialysis values (P less than 0.05) and this increase occurred during the period when the patients were leucopenic and maximally hypoxic. During the haemodialysis period, but not the predialysis period, the permeability index was also significantly increased compared to a group of eight controls (P less than 0.05). These results suggest that increased vascular permeability may contribute to dialysis-induced hypoxia and that this may relate to neutrophil activation within the pulmonary vascular bed.

Adolescent↗

First-trimester diagnosis of metachromatic leucodystrophy.

Two pregnancies at risk for late infantile metachromatic leucodystrophy were monitored by assaying arylsulphatase A at 0 degrees C in homogenates of chorionic villi. In one, the very low activity recorded indicated the fetus to be affected, and this was confirmed by demonstration of low arylsulphatase A activity in cultured villi and cultured fetal fibroblasts after termination. In the other pregnancy, normal activity was found in the villi and the pregnancy is continuing. This simple chromogenic assay appears to be reliable for first-trimester diagnosis of metachromatic leucodystrophy. However, there is a probability of mis-diagnosis if the standard assay at 37 degrees C is used.

Adult↗

Reduced free radical activity detected by decreased diene conjugates in insulin-dependent diabetic patients.

Free radicals are unstable chemical species which react with and oxidize adjacent molecules, particularly polyunsaturated lipids. The diene-conjugated non-peroxide isomer of linoleic acid (PL-9,11-LA') has been identified as the main diene-conjugated compound in plasma, and is a probable marker of free radical activity. The aim of the current study was to determine whether the level of PL-9,11-LA', measured by HPLC, is altered in insulin-dependent diabetes, and to investigate whether any abnormality demonstrated correlated with microvascular disease in the form of retinopathy. There was no difference in the concentrations of linoleic acid between the diabetic and control groups (422(129) vs 402(81) (SD) mumol l-1). However, the concentration of PL-9,11-LA' was significantly reduced in the diabetic group compared with control group (15.6(6.7) vs 19.3(3.9) mumol l-1, p less than 0.01), with the molar ratio of PL-9,11-LA':linoleic acid x 100 similarly reduced (3.8(1.3) vs 5.0(1.6)%, p less than 0.005). This study does not support the concept that free radicals play a significant role in the development of diabetic vascular disease.

Adult↗

Arizonins, a new complex of antibiotics related to kalafungin. I. Taxonomy of the producing culture, fermentation and biological activity.

The arizonins, a novel complex of antibiotics related to kalafungin, were discovered in the fermentation broth of Actinoplanes sp. AB660D-122. Comparative taxonomic studies indicated that the culture is a new species and therefore has been designated Actinoplanes arizonaensis sp. nov. Two members of the complex, arizonins A1 and B1, exhibit moderate to potent in vitro antimicrobial activity against pathogenic strains of Gram-positive bacteria.

Actinomycetales↗

Development of wound infections among women undergoing cesarean section.

Sixty consecutive wound infections were studied among 1104 women undergoing cesarean section. Wound infections caused by cervical-vaginal flora were associated with prolonged labor, particularly with greater duration of fetal monitoring and number of vaginal examinations, and with organisms isolated from the endometrium at cesarean section. In contrast, women with wound infections caused by Staphylococcus aureus had neither prolonged labor nor S aureus isolated at cesarean section. The 25% of wound infections associated with S aureus represent potentially preventable conditions that presumably arise from exogenous sources.

Cesarean Section↗

Role of SecA and SecY in protein export as revealed by studies of TonA assembly into the outer membrane of Escherichia coli.

The growth of secAts or secYts mutants at the restrictive temperature has been shown to inhibit the export of many outer membrane proteins. We report here that in two secAts strains the rate of incorporation of newly synthesized protein into both inner and outer membrane fractions decreased by about 70% at the restrictive temperature. The export of the outer membrane protein TonA was used as a model system in which to study the effects of SecA or SecY inactivation. pre-TonA that accumulated at the restrictive temperature was found to co-sediment with the outer membrane fraction. However, the precursor was sensitive to protease and did not float up a sucrose gradient with the membrane fractions. It was therefore concluded that pre-TonA was not integrated into the outer membrane fraction but probably accumulated in the cytoplasm. Studies on the rate of processing of pre-TonA, pulse-labelled at the restrictive temperature then chased at the permissive temperature, revealed differences between secA and secY mutants. In the secAts mutant the great majority of cytoplasmic pre-TonA was not apparently processed to the mature form, whereas in the secYts mutant significant amounts of precursors were rapidly chased into mature TonA, which appeared in the outer membrane. These results suggest that SecA and SecY may act sequentially in the export of proteins to the outer membrane. In particular these data indicate that SecA is required to maintain pre-TonA in a translocationally competent form prior to interaction with the SecY export site.

Bacterial Outer Membrane Proteins↗

Metabolism and DNA binding of 1-nitro[14C]pyrene by isolated rabbit tracheal epithelial cells.

The metabolism of 1-nitro[14C]pyrene (1-NP) and the binding of its reactive intermediates to DNA and protein was examined in rabbit tracheal epithelial cells. The tracheal cells isolated by two protease digestion methods had normal cellular morphology and viability. The digestion method which demonstrated the highest rate of 1-NP metabolism and DNA binding used a 1 h incubation of the tracheas with 1% protease at 37 degrees C. Metabolites from the incubation medium and cell lysates were extracted, analyzed and quantitated by h.p.l.c. The majority of the metabolites produced by tracheal cells were EA:AC extractable and were released to the surrounding incubation medium. The predominant metabolites identified and quantified in the medium were the ring oxidation products, a 1-NP-diol, 1-NP phenols (6- or 8-OH-1-NP), 10-OH-1-NP and 3-OH-1-NP. Major metabolites formed by nitroreduction were NAAP and 1-AMP. The metabolites retained by tracheal cells were qualitatively identical to those identified in the medium but were present at one-seventh to one-tenth of the amounts. The rate of both 1-NP metabolism and DNA binding was very high. After 4 h, 62% of the 1-NP was metabolized and 198 DNA adducts/10(6) nucleotides were formed. The rate of [14C]1-NP-DNA adducts formation was highest at 30 min of incubation (124 adducts/10(6) nucleotides/h). These high rates of metabolism and DNA binding are consistent with the possibility that tracheal cells may be a particular target tissue for tumor induction by nitrosubstituted polycyclic aromatic hydrocarbons associated with diesel and other combustion emission particles. The preponderance of highly mutagenic 1-NP phenols as metabolites suggest that ring oxidation as well as nitroreduction may result in intermediates which form DNA adducts.

Animals↗

Progressive mental regression in siblings with Morquio disease type B (mucopolysaccharidosis IV B).

A brother and sister with clinical and radiological features of Morquio disease, but with atypical mental regression, are described. Leucocyte and fibroblast beta-galactosidase activity was deficient in the siblings, while N-acetylgalactosamine 6-sulphate sulphatase and neuraminidase were normal. Study of the residual fibroblast beta-galactosidase activity towards 4-methylumbelliferyl and p-nitrophenyl beta-D-galactosides indicated that the mutation resembles that in typical Morquio B disease (increased Km and similar pH maximum) rather than that in GM1-gangliosidosis. The patients have therefore been classified as having Morquio B disease with atypical mental regression rather than GM1-gangliosidosis variants with particularly severe bony abnormalities. The mutation was, however, distinct from that in Morquio B disease since residual activity towards the alternative artificial substrate 4-methylumbelliferyl-beta-D-fucoside was increased. The patients represent further examples of the heterogeneity that can result from mutation at the beta-galactosidase locus.

Bone Diseases, Developmental↗

The acute inflammatory response to myocardial infarction: imaging with indium-111 labelled autologous neutrophils.

The uptake of indium-111 labelled neutrophils was examined in 30 patients with acute myocardial infarction by planar imaging and single photon emission computed tomography. The time from venepuncture to reinjection of the autologous labelled neutrophils was less than 2.5 hours and imaging was carried out 24 hours later. Twenty three patients had a positive uptake of neutrophils in the myocardium and imaging was improved by single photon emission computed tomography. There was a significant difference between the intervals from the onset of chest pain to injection of labelled neutrophils between patients with positive and negative images; early reinjection was more likely to produce a positive image. Indeed, all nine patients reinjected within 18 hours of the onset of symptoms had positive images. The results suggest that the stimulus for activation and migration of neutrophils is transient; this is an important factor if neutrophil release products play a role in cell damage after coronary occlusion.

Acute Disease↗

Effect of N6-(L-2-phenylisopropyl)adenosine and insulin on cAMP metabolism in 3T3-L1 adipocytes.

The antilipolytic effect of N6-(L-2-phenylisopropyl)-adenosine (PIA), an adenosine analogue thought to act via cell surface receptors, was investigated in 3T3-L1 adipocytes. PIA (1 microM) was as effective as 1 nM insulin in reducing lipolysis stimulated by 1 nM isoproterenol and more effective than insulin at higher isoproterenol concentrations. In intact adipocytes, PIA reduced isoproterenol-induced cyclic AMP (cAMP) accumulation and increased particulate cAMP phosphodiesterase. In particulate preparations PIA suppressed isoproterenol stimulation of adenylate cyclase. PIA was more effective than 5'-N-ethylcarboxamide adenosine (NECA) or adenosine in inhibiting adenylate cyclase and activating phosphodiesterase. In intact adipocytes, two agents with so-called "insulin-like" activities, i.e., anti-insulin receptor antibodies and wheat germ agglutinin (WGA), also increased particulate cAMP phosphodiesterase. Pertussis toxin, which inhibits stimulation of the particulate cAMP phosphodiesterase by insulin (but not by isoproterenol), also inhibited the effects of PIA, anti-insulin receptor antibodies, and WGA. In 3T3-L1 cells, PIA appears to inhibit lipolysis by inhibiting adenylate cyclase and stimulating phosphodiesterase; these effects of PIA, as well as those of anti-insulin receptor antibodies and WGA on phosphodiesterase, may be mediated via guanyl nucleotide-binding proteins.

3',5'-Cyclic-AMP Phosphodiesterases↗

Coloradocin, an antibiotic from a new Actinoplanes. I. Taxonomy, fermentation and biological properties.

Coloradocin was discovered in a screen for anti-anaerobe activity. The producing organism was determined to be a new species of Actinoplanes, designated Actinoplanes coloradoensis sp. nov. Coloradocin inhibits Bacteroides, Clostridium and other anaerobes. It does not inhibit most aerobic bacteria but is effective against Neisseria gonorrhoeae and Haemophilus influenzae. Coloradocin has low acute toxicity.

Actinomycetales↗