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Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 289 records · Page 16Linked to original sources
PubMed1989

Short cytoplasmic sequences serve as retention signals for transmembrane proteins in the endoplasmic reticulum.

The adenoviral transmembrane E3/19K glycoprotein is a resident of the endoplasmic reticulum. Here we show that the last six amino acid residues of the 15-membered cytoplasmic tail are necessary and sufficient for the ER retention. These residues can be transplanted onto the cytoplasmic tail of other membrane-bound proteins such that ER residency is conferred. Deletion analysis demonstrated that no single amino acid residue is responsible for the retention. The identified structural motif must occupy the extreme COOH-terminal position to be functional. An endogenous transmembrane ER protein, UDP-glucuronosyltransferase, also contains a retention signal in its cytoplasmic tail. We suggest that short linear sequences occupying the extreme COOH-terminal position of transmembrane ER proteins serve as retention signals.

Adenovirus E3 Proteins↗
PubMed1989

Fourier transform infrared spectroscopic studies on the secondary structure of the Ca2+-ATPase of sarcoplasmic reticulum.

Fourier transform infrared spectroscopy has been applied to the study of the secondary structure of the Ca2+-ATPase of sarcoplasmic reticulum. An attempt is made to quantitatively assess the various secondary structures present. Values of 45% alpha-helix, 32% beta-sheet and 23% turns were obtained. A comparison is made of these results and those obtained using other techniques such as CD and Raman spectroscopy. The various assumptions inherent in the present procedure are discussed. The effect of various ligands, e.g. Ca2+, vanadate, ATP and phosphate, upon the structure were investigated. Upon binding these ligands no marked spectral changes were observed.

Animals↗
PubMed1989

The use of fluorescein-conjugated lectins for visualizing atypical mycobacteria.

We investigated the feasibility of using fluorescein-conjugated lectins for visualizing and differentiating two species of atypical mycobacteria. Pure cultures of Mycobacterium fortuitum and Mycobacterium chelonei were established, as was an experimental model of infectious keratitis involving these two organisms. Samples from the pure cultures and corneal scrapings were placed on glass slides, fixed, and incubated with one of a panel of 22 fluorescein-conjugated lectins. The slides were examined using an epifluorescence microscope. Fluorescein-conjugated concanavalin A brightly stained both species of atypical mycobacteria, in both the pure culture and experimental keratitis samples. Several additional fluorescein-conjugated lectins (wheat germ agglutinin, succinylated wheat germ agglutinin, Phaseolus vulgaris erythroagglutinin, and Psophocarpus tetragonolobus agglutinin) brightly stained M chelonei, but only moderately stained M fortuitum. These staining patterns are consistent with the known carbohydrate compositions of the cell walls of atypical mycobacteria and suggest that fluorescein-conjugated lectins may be useful for the visualization of these organisms in corneal infections.

Abscess↗
PubMed1989

Effect of social drinking on neuropsychological performance.

The effects of social drinking on neuropsychological function have been assessed in a group of healthy male volunteers. Subjects were divided into three groups according to their daily alcohol consumption: (1) 40 g or less (n = 93), (2) 41-80 g (n = 22), (3) 81-130 g (n = 16). Group 1 had been drinking at the present level for a mean of 12.6 years, group 2 for 16.9 years and group 3 for 15.1 years; the differences are not significant. There are no significant differences on any neuropsychological tests variables between groups 1 and 2. However, subjects in group 3 were found to perform at a significantly lower level than groups 1 and 2 on the Rey Auditory Verbal Learning Test, the Austin Maze, and the Little Man and Spatial Memory Tests of the Bexley Maudsley Automated Psychological Screening Test. The pattern of deficits found in heavy social drinkers is less severe but otherwise similar to that found in alcoholics.

Adult↗
PubMed1989

T-cell recognition of the 18-kilodalton antigen of Mycobacterium leprae.

The 18-kilodalton (kDa) antigen of Mycobacterium leprae was expressed as a fusion protein with a 2-kDa leader peptide and used in proliferation assays with peripheral blood cells. Fifty percent of untreated tuberculoid leprosy patients and 93% of long-term leprosy contacts responded to the recombinant protein in lymphocyte transformation tests. Comparison of the stimulation indices in the two groups showed that the contacts responded more strongly than the tuberculoid leprosy patients. Seventy percent of Mycobacterium bovis BCG-vaccinated European donors responded, although with low stimulation indices. The isolation of 18-kDa antigen-responsive T-cell lines from a BCG-vaccinated British donor confirmed that the 18-kDa antigen contains at least one cross-reactive epitope. These results indicate that the 18-kDa protein is an important antigen in the immune response to leprosy.

Amino Acid Sequence↗
PubMed1989

Production of eosinophil-activating factor (EAF) by peripheral blood mononuclear cells from asthma patients.

Mononuclear cells from blood samples from asthmatic patients were tested for their ability to produce two eosinophil activating factors, EAF and TNF. High levels of EAF were produced by some but not by all patients. The influence of external factors on EAF production was evaluated. Patients receiving prednisolone (10-30 mg/day) tended to produce only low levels of EAF. Prednisolone has been shown to inhibit production of EAF in vitro by isolated mononuclear cells, at concentrations of 0.1-1 micrograms steroid/ml. Incubation of mononuclear cells with certain allergens enhances EAF production in sensitive individuals. Little or no production of TNF was observed in the patients examined.

Adult↗
PubMed1989

Development of human liver UDP-glucuronosyltransferases.

The development of multiple UDPGT activities towards eight substrates has been studied in fetal term and adult post-mortem (less than 5 h after death) liver samples. Most fetal and term liver activities were less than 14% of adult values, except that towards 5-hydroxytryptamine which was present in fetal and term liver at adult levels. The majority of UDPGT activities develop to adult levels within 10-20 weeks postnatally, and even premature (30 weeks) which survive for up to 10 weeks will develop these enzyme activities. Immunoblot analysis of human liver microsomes and cDNA cloning of human UDPGT shows the existence of the family of isoenzymes in man, and it is important to determine the developmental pattern of individual drug glucuronidating enzymes in liver. Immunoblot analysis of developing liver shows the presence of two major UDPGT polypeptides in fetal liver, whereas more than five are observed in adult liver. The investigation of substrate specificity of individual UDPGTs by expression of cloned genes in COS-7 cells and the use of antibodies will facilitate the identification of enzymes present in perinatal liver.

Cloning, Molecular↗
PubMed1989

Lung rejection and bronchial hyperresponsiveness to methacholine and ultrasonically nebulized distilled water in heart-lung transplantation patients.

Acute denervation of the lungs occurs after heart-lung transplantation (HLT), affecting both afferent and efferent nerves below the tracheal anastomosis. After surgery, the carina and main bronchi are perfused by mediastinal collaterals derived from the coronary arteries, and the intrapulmonary airways by retrograde blood flow from pulmonary artery collaterals. During acute rejection, the lungs are subjected to inflammation, particularly perivascular lymphocytic infiltrates. Rejection can be diagnosed by transbronchial biopsy (TBB). We report the bronchial responses to inhaled methacholine and ultrasonically nebulized distilled water (USNDW) in 16 HLT patients 2 wk to 43 months after surgery, relating them to the lung histopathology from concurrent TBB. Methacholine bronchial hyperresponsiveness was common, but it was not associated with airway epithelial or submucosal inflammation or perivascular lymphocytic infiltration. Six patients had a modest response to USNDW (fall in FEV1 greater than 10%). The responsiveness to USNDW was not associated with enhanced methacholine responsiveness or epithelial and mucosal inflammation. However, it was more commonly seen in patients with lung rejection and perivascular infiltrates. Methacholine hyperresponsiveness in HLT patients could therefore reflect denervation hypersensitivity of airway smooth muscle muscarinic receptors. The modest response to USNDW in some patients cannot be a result of a vagal reflex but could reflect a pathologic vascular response associated with lung rejection. These observations offer insight into the possible mechanisms of bronchial hyperresponsiveness in disease.

Adult↗
PubMed1989

The cough response to ultrasonically nebulized distilled water in heart-lung transplantation patients.

As a result of clinical heart-lung transplantation, the lungs are denervated below the level of the tracheal anastomosis. It has been questioned whether afferent vagal reinnervation occurs after surgery. Here we report the cough frequency, during inhalation of ultrasonically nebulized distilled water, of 15 heart-lung transplant patients studied 6 wk to 36 months after surgery. They were compared with 15 normal subjects of a similar age and sex. The distribution of the aerosol was studied in five normal subjects using 99mtechnetium diethylene triamine pentaacetate (99mTc-DTPA) in saline. In seven patients, the sensitivity of the laryngeal mucosa to instilled distilled water (0.2 ml) was tested at the time of fiberoptic bronchoscopy by recording the cough response. Ten percent of the aerosol was deposited onto the larynx and trachea, 56% on the central airways, and 34% in the periphery of the lung. The cough response to the aerosol was strikingly diminished in the patients compared with normal subjects (p less than 0.001), but all seven patients coughed when distilled water was instilled onto the larynx. As expected, the laryngeal mucosa of heart-lung transplant patients remains sensitive to distilled water. However, the diminished coughing when the distilled water is distributed by aerosol to the central airways supports the view that vagal afferent nerves do not reinnervate the lungs after heart-lung transplantation, up to 36 months after surgery.

Adult↗
PubMed1989

Airway mucosal bioelectric potential difference in cystic fibrosis after lung transplantation.

Bioelectrical potential difference (PD) across the respiratory mucosa is raised in cystic fibrosis (CF). We have recorded airway potentials from seven patients with CF who had undergone heart-lung transplantation and from eight patients without CF who had had transplants for cardiovascular disease; comparison of these populations controls for the effects of denervation and immunosuppressive treatment. Six patients without CF who had not had transplants formed an additional control. PD was recorded during routine fiberoptic bronchoscopy, using a Ringer's-perfused exploring bridge connected across a high impedance amplifier to an intravenous reference bridge. Bronchial lavage and sputum culture revealed no evidence of infection. Bronchial PD was similar in all three groups of patients at equivalent sites. However, nasal PD was raised in the CF group (mean value, 44 mV +/- 3.9 SE) compared with the patients who had transplants for cardiovascular disease (mean, 18 mV +/- 1.1 SE), and the control patients (mean, 15 mV +/- 1.2 SE). We conclude that the epithelial defects that result in raised airway potentials in CF do not recur in the transplanted lung.

Adolescent↗
PubMed1989

Recombinant TGF-beta 1 is synthesized as a two-component latent complex that shares some structural features with the native platelet latent TGF-beta 1 complex.

The entire coding region of the human transforming growth factor beta 1 (TGF-beta 1) precursor cDNA has been stably expressed in a human renal carcinoma cell line. Like platelet TGF-beta 1, the recombinant TGF-beta 1 is secreted in a biologically latent form. Immunoblot analysis and gel-filtration indicate that the recombinant latent TGF-beta 1 is a 100-kDa complex in which active 25-kDa TGF-beta 1 is noncovalently associated with the remaining 75 kDa of the processed precursor. Unlike the platelet latent complex, the recombinant latent complex contains no 135-kDa component. Thus, the processed precursor peptide alone is sufficient to confer latency on active TGF-beta 1, and the 135-kDa platelet component has a different role. The processed precursor is similarly glycosylated in recombinant and platelet complexes, and in both has an exposed heparin binding site that may be involved in targeting of the latent complex. Finally, acid activation of recombinant and platelet complexes is reversible, suggesting that the activation process does not cause major structural modifications in the components of the latent complex.

Binding Sites↗
PubMed1989

Pacidamycins, a novel series of antibiotics with anti-Pseudomonas aeruginosa activity. I. Taxonomy of the producing organism and fermentation.

The pacidamycins are a new complex of nucleosidyl-peptide antibiotics with highly specific activity against Pseudomonas aeruginosa. They are produced by Streptomyces coeruleorubidus AB 1183F-64 which was isolated from a soil sample collected at Offenburg in the FRG. The mature spore masses of the producing organism are greenish gray to blue, and the spore chains are arranged in spirals. After the structures of the pacidamycins were determined, the fermentation medium was supplemented with component amino acids. This resulted in the directed biosynthesis of several members of the complex. The overall antibiotic recovered was increased from 1 approximately 2 mg/liter to more than 100 mg/liter through a combination of strain selection, medium manipulation and amino acid feeding experiments.

Anti-Bacterial Agents↗
PubMed1989

Head scan appearances and cognitive function in renal failure.

Cognitive function was assessed, and unenhanced CT head scans were carried out in 44 patients with renal failure. Thirteen had been on regular hemodialysis for 5 years or more (long-term hemodialysis group, LTHD), 12 had received hemodialysis for less than 5 years (short-term hemodialysis, STHD), 9 were on continuous ambulatory peritoneal dialysis (CAPD group) and 10 had severe chronic renal failure and were near to-but had not reached-dialysis dependence (chronic renal failure group, CRF). Employing an index of deterioration (the "discrepancy score") based on the discrepancy between current reading skills and current performance on the Wechsler Adult Intelligence Scale, 6 LTHD patients, 2 STHD patients, 2 CAPD patients and 5 CRF patients were identified as functioning below their predicted premorbid optimum level. Cerebral sulci were abnormally wide in 22 patients (8 LTHD, 2 STHD, 6 CAPD and 6 CRF) and one of the STHD group also had cerebral ventricular dilatation. Nine patients had both an abnormal scan and evidence of cognitive deterioration, 13 had an abnormal scan in the absence of such evidence and 6 had evidence of cognitive deterioration and a normal scan. Both cognitive deterioration and the CT scan finding of widening of cerebral sulci were commoner in these patients than would be expected in an age-matched sample of the general population, but no simple relationship was found between anatomical abnormality and cognitive functioning. Statistically significant correlations were found between discrepancy score and the cumulative amount of aluminum prescribed to be taken orally in both LTHD and CAPD groups.

Adult↗