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K Bridges

Publications and source records attributed to K Bridges.

34 records · Page 2Linked to original sources
PubMed1985

Effects of alterations in cellular iron on biosynthesis of the transferrin receptor in K562 cells.

Treatment of K562 cells, a human erythroleukemia cell line, with desferrioxamine raised the levels of the receptor for transferrin (Tf) two- to threefold over that of the control cells. The levels of receptor were reduced by at least 50 and 35% of that of the control in cells treated with diferric Tf and ferric ammonium citrate, respectively. These changes were of total cellular receptors with no alteration in the proportion of receptors found on the cell surface. The half-lives of the receptor were identical in cells treated with desferrioxamine, diferric Tf, or ferric ammonium citrate. Cells metabolically labeled with [35S]methionine showed a 2.5-fold increase in the rate of receptor synthesis when treated with desferrioxamine and a 35 and 65% decrease when treated with ferric ammonium citrate and diferric Tf, respectively. In vitro translations of polyadenylated mRNA isolated from cells incubated with desferrioxamine showed a 2.5-fold increase in translatable mRNA for the receptor, whereas treatment of cells with ferric ammonium citrate and diferric Tf resulted in a 25 and 50% reduction, respectively, in translatable mRNA for this receptor.

Cell Line↗
PubMed1985

Douglas House: a new type of hostel ward for chronic psychotic patients.

A new type of hostel ward is described in which domestic activities take the place of attendance at a day centre or industrial workshop. Residents no longer depend on the institution for meals, cleaning, or social activities. The programme is resident-orientated, and individual treatment plans are designed and effected using a points system. The emphasis of group activities is on communication and living skills. The hostel ward is able to care for our most disabled patients who are thought to need 24-hour nursing care.

Activities of Daily Living↗
PubMed1985

Clonal separation of mature melanocytes from premelanocytes in a diploid human cell strain: spontaneous and induced pigmentation of premelanocytes.

Strains of pigmented melanocytes can be derived reproducibly from normal human skin. Published procedures have been modified here to yield a strain, 'Nohm-1', comprising many unpigmented cells as well as cells with various degrees of pigmentation observable by light microscopy. The unpigmented cells contain early melanosomes (pigment organelles) and the specific enzyme tyrosinase. They are on average smaller and less dendritic than the pigmented cells. Nohm-1 cells show normal chromosomal banding patterns and normal proliferative behaviour, including senescence. They form no tumours in immunodeficient (nude) mice. Nohm-1 cells have been cloned and yield two distinct types of colony, depending on the progenitor cell. Well-pigmented melanocytes engender pure colonies of pigmented cells, but cells with little or no pigment can produce both unpigmented and pigmented progeny. Thus there is a separate cell type, or premelanocyte, which can differentiate spontaneously and stably in culture; this cell type includes both unpigmented and faintly pigmented cells. Usefully, most premelanocytes are viable after frozen storage, unlike well-pigmented melanocytes. Some components of the culture medium affect the proportion of pigmented cells in Nohm-1 cultures, and hence probably the ratio of mature melanocytes to premelanocytes. Rapid pigmentation can be induced artificially and simply, by using a medium with increased extracellular pH and tyrosine concentration.

Cell Differentiation↗
PubMed1985

Long-term efficacy of deferoxamine iron chelation therapy in adults with acquired transfusional iron overload.

Transfusional iron overload in adult patients with acquired anemias may result in widespread organ dysfunction. Long-term deferoxamine mesylate therapy was administered by continuous subcutaneous infusion to six such patients, who have been followed up for up to 66 months of therapy while continuing to be transfusion-dependent. During deferoxamine therapy, liver density by computed tomographic scan decreased in four of five patients, liver iron content decreased in two of three patients, and liver function normalized in two patients. Plasma cortisol response to insulin-induced hypoglycemia improved in three of five patients receiving therapy. Pituitary growth hormone reserve normalized in two patients and remained normal in the other three tested. One patient, treated concurrently with ascorbic acid, died suddenly. The other five patients have had no cardiac deterioration by noninvasive testing. We conclude that long-term deferoxamine iron chelation therapy is effective not only in retarding but, in some cases, even reversing organ damage caused by transfusional iron overload.

Adult↗
PubMed1983

Intracellular dissociation of receptor-bound asialoglycoproteins in cultured hepatocytes. A pH-mediated nonlysosomal event.

The binding, internalization, and degradation of 125I-asialo-orosomucoid were studied in primary monolayer cultures of rat hepatocytes. Ligand entered the cell bound to the asialoglycoprotein receptor and subsequently dissociated from the receptor intracellularly. Rate coefficients for each of the transitions that constitute the endocytic pathway were computed. Subcellular fractionation on Percoll gradients revealed that prior to localization in lysosomes, 125I-asialo-orosomucoid resided in a fraction of slightly lower buoyant density than plasma membranes. Neither ammonium chloride (20 mM) nor leupeptin (0.1 mg/ml) affected ligand binding or internalization of prebound ligand. However, both reagents inhibited degradation of ligand by greater than 95%. Of the two, only ammonium chloride inhibited receptor-ligand dissociation. Ammonium chloride treatment resulted in the accumulation of ligand in the prelysosomal fraction. In contrast, exposure of cells to leupeptin led to accumulation of ligand within lysosomes. The results are interpreted in terms of pH-mediated dissociation of ligand-receptor complex within a nonlysosomal endocytic vesicle.

Animals↗
PubMed1982

Fate of receptor and ligand during endocytosis of asialoglycoproteins by isolated hepatocytes.

The endocytosis leading to degradation of 125I-labeled asialo-orosomucoid specifically bound to the surface of freshly isolated hepatocytes was monitored as a function of time at 37 degrees C. Experimental values were determined for the rates of internalization, dissociation of the receptor-ligand complex, and degradation of the labeled ligand. Compartmental analysis and computer modeling revealed that the data were compatible with dissociation of ligand from receptor preceding ligand degradation. The rate coefficient for internalization was calculated to be an order of magnitude greater than that for receptor--ligand dissociation. Ligand internalization did not result in concomitant depletion in the total number of cell surface receptors. Our data are taken to indicate that ligand remains associated with the receptor after internalization, that the complex is dissociated prior to degradation, and that new, unoccupied receptors are promptly returned to the cell surface from an internal pool.

Animals↗
PubMed1981

Calcium regulates the commitment of murine erythroleukemia cells to terminal erythroid differentiation.

An alteration in the rate of calcium transport appears to be the rate-limiting event for the commitment of murine erythroleukemia (MEL) cells to initiate a program of terminal erythroid differentiation. The dimethyl sulfoxide (DMSO)-induced commitment of MEL cells to erythroid differentiation can be inhibited by treatment of cells with the calcium-chelating agent EGTA. Upon removal of EGTA, cells initiate commitment without the 12-h lag normally observed after treatment with DMSO alone. Treatment of cells with DMSO in the presence of calcium ionophore A23187 causes cells to initiate commitment from time zero with no lag. These results suggest that the lag is the time required for DMSO to alter the calcium transport properties of the cell.

Animals↗
PubMed1980

Reconstitution of the hepatic asialoglycoprotein receptor with phospholipid vesicles.

A solubilized detergent-free preparation of the hepatic binding protein specific for asialoglycoproteins associates spontaneously with small unilamellar lipid vesicles. This process is independent of the phase transition of the lipid and effectively restores the specific binding activity of the receptor protein. The insensitivity of the resulting lipid-protein complex to ionic strength provides evidence for a hydrophobic interaction. There is a perturbation of the lipid phase transition concomitant with addition of the protein. Circular dichroism studies indicate that the protein undergoes a conformational change on association with lipid. Binding of specific ligand produces further physical changes in the receptor as indicated by alterations in the tryptophan fluorescence quenching pattern.

Animals↗
PubMed1979

Gentamicin- and silver-resistant pseudomonas in a burns unit.

In 1977-8 gentamicin-resistant strains of Pseudomonas aeruginosa became very common in a burns unit, over 90% being resistant at the peak of the outbreak. Some strains were also resistant to silver nitrate, though silver resistance was not found in any other strains of Ps aeruginosa isolated. Unlike the gentamicin resistance, the silver resistance was unstable, and strains became sensitive on repeated subculture. All the gentamicin-resistant strains of Ps aeruginosa were of the same serotype (O:11, H:2,5). Though gentamicin resistance could be transferred in vitro from resistant strains of Ps aeruginosa to one sensitive strain of Ps aeruginosa, there was no evidence of in-vivo transfer of gentamicin resistance between strains of pseudomonas in the patients' burns, nor was there evidence of transfer of gentamicin resistance between Ps aeruginosa and enterobacteria. Carbenicillin-resistant and gentamicin-resistant Ps aeruginosa were sometimes found in the same burns, but no gentamicin-carbenicillin (doubly) resistant strains were found among the 986 strains tested during the outbreak. The outbreak of gentamicin-resistant Ps aeruginosa from burns was not reduced by stopping treatment with gentamicin and its analogues but only by segregating all patients with Ps aeruginosa in one of the two wards of the unit and admitting new patients only to the other ward.

Burns↗
PubMed1977

Drug resistance in relation to use of silver sulphadiazine cream in a burns unit.

Topical chemoprophylaxis of extensive burns with silver sulphadiazine cream led to a large increase in the proportion of sulphadiazine-resistant Gram-negative bacilli in a burns unit. When all sulphonamide treatment in the ward was stopped; the incidence of sulphonamide-resistant strains fell back to levels similar to those recorded when silver sulphadiazine treatment was introduced. This was associated with a large reduction in the incidence of resistance of certain Gram-negative bacilli (especially Klebstella sp) to several antibiotics. Transferable resistance to sulphadiazine, shown by conjugation experiments with Escherichia coli K12, was found in a majority of the strains of Klebsiella sp tested, and in other species. A pattern of transferable resistance to tetracycline, cephaloridine, chloramphenicol, ampicillin, carbenicillin, and sulphadiazine (T Ce Cl A Ca S) was found in four of the 22 strains of Klebsiella tested, and closely related patterns were transferred by five other strains. These patterns of resistance were commonly found in Klebsiella sp isolated from burns in the period before the withdrawal of sulphonamides from the ward but were found in none of the Klebsiella strains isolated in the first six months after that period. Strains of Acinetobacter and Proteus, in which transferable resistance was not found, showed no appreciable fall or rise in sulphadiazine resistance; there was no fall in resistance of these organisms to tetracycline, cephaloridine, chloramphenicol, ampicillin or carbenicillin on withdrawal of sulphonamides from the ward, but there were substantial falls in resistance of Acinetobacter to kanamycin, gentamicin, trimethoprim, and tetracycline which were probably not caused by the withdrawal of sulphonamides.

Acinetobacter↗
PubMed1976

Topical chemoprophylaxis with silver sulphadiazine and silver nitrate chlorhexidine creams: emergence of sulphonamide-resistant Gram-negative bacilli.

Controlled trials of 0.5% silver nitrate compresses (SN), 1% silver sulphadiazine cream (SSD), and a cream containing 0.5% silver nitrate and 0.2% chlorhexidine digluconate (SNC) showed that all were comparably effective in protecting burns from infection. SN compresses were much less active against miscellaneous Gram-negative bacilli than the other preparations, and the mean morning and evening temperatures and respiration rates in the patients treated with SN compresses were higher then those of patients treated with SSD. Pseudomonas aeruginosa and Proteus spp, though rare in all groups, were less often found in the patients treated with SN compresses. Sulphonamide-resistant Gram-negative bacilli became predominant during the trial of SSD cream on extensive burns and the prophylactic effectiveness of that preparation was thus reduced in the later stages of the trial.

Administration, Topical↗
PubMed1976

A source isolator for infected patients.

A plastic, mechanically ventilated source isolator with filters in the air effluent was designed to enable infected patients to be nursed and treated in a general ward or to be transported without risk to staff or other contacts. Two models of isolator were developed. Their potential value was tested by the challenge of heavy dispersal, inside the isolator, of bacteria (a) from patients with burns, during the change of dressings, (b) from contaminated bedding during simulated bed-making, and (c) from the dispersal of a suspension of Bacillus subtilis var. globigii. Sampling of air by slit samplers outside the isolator and, in comparable control patients, from the air of the room in which dressings were changed, showed consistently lower counts of bacteria and of Staph. aureus during dressings when the isolator was used; on removal of the isolator canopy there was, in some experiments, a considerable increase in airborne bacteria, due to residual bacteria in the isolator of to the re-dispersal of bacteria which settled on the patient and his bedding during the dressing. Simultaneous sampling with slit samplers inside and outside the isolator during and after bed-making or dispersal of B. subtilis var. globigii showed an almost complete protection of the air outside the isolator against contamination by bacteria released inside the isolator.

Adolescent↗
PubMed1975

Comparison of two methods for assessing the removal of total organisms and pathogens from the skin.

A standard hand-wash sampling technique was compared with a simple finger-streak sampling method in assessing the relative effectiveness of a number of alternative preparations used for disinfecting the surgeon's hands (alcoholic 0.5% chlorhexidine, alcoholic 0.1% tetrabrom-o-methyl phenol, a 4% chlorhexidine detergent solution, aqueous 0.5% chlorhexidine, 2% 'Irgasan' detergent solution and, as control, bar soap). There was a fairly good correlation between the results of assessment by the two methods after a single disinfection and after six disinfections, three on one day and three on the next. Significant differences were shown in 21 comparisons between treatments when the hand-wash sampling test was used, and 16 of these comparisons also showed a significant difference by the finger-streak test. Staphylococcus aureus was found in hand samplings from 5 out of 8 nurses in the Burns Unit of Birmingham Accident Hospital by the hand-wash sampling method and from 2 of the same 8 nurses by the finger-streak method; the numbers were small, and no Staph. aureus were isolated from the same hands after 1 min. wash in 70% ethyl alcohol. Similar sampling on 29 nurses in other wards showed Staph. aureus on 3 nurses (one in large numbers) by the hand-wash technique and on 1 nurse by the finger-streak test; in only 1 nurse whose hands showed Staph. aureus before disinfection was the organism found, by hand-wash sampling, after disinfection. Parallel sampling of nurses' hands after washing with soap and water and after disinfection with 95% ethanol showed larger numbers of Staph. aureus in a hospital for skin diseases than in a general hospital, and a lower incidence and somewhat lower density of Staph. aureus after ethanol treatment than after washing with soap and water; Gram-negative bacilli, on the other hand, were commoner on hands in the general than in the skin hospital, and present in much smaller numbers after disinfection with ethanol than after washing with soap and water. Antibiotic sensitivity tests showed the frequent recurrence on the hands of some nurses of multi-resistant Staph. aureus with resistance patterns similar to those found in infective lesions in some of the patients; different sensitivity patterns were usually found in staphylococci isolated from the nose. Even in wards where many patients were infected, carriage by nurses' hands of a particular strain of Staph. aureus did not seem to last for more than a few days.

Anti-Bacterial Agents↗
PubMedDate not supplied

In vitro generation of Epstein-Barr virus-specific cytotoxic T cells in patients receiving haplo-identical allogeneic stem cell transplantation.

Use of a partially mismatched related donor (PMRD) is an option for patients who require allogeneic transplantation but do not have a matched sibling or unrelated donor. Epstein-Barr virus (EBV)-induced lymphoma is a major cause of mortality after PMRD transplantation. In this study, we present a clinical grade culture system for donor-derived EBV-specific cytotoxic T cells (CTLs) that do not recognize haplo-identical recipient cells. The EBV-specific CTLs were tested for cytolytic specificity and other functional properties, including ability to transgress into tissues, propensity for apoptosis, degree of clonality, stability of dominant T-cell clones, and Tc and Th phenotypes. The EBV-specific CTLs were routinely expanded to greater than 80 x 10(6) over a period of 5 weeks, which is sufficient for clinical application. A CD8+ phenotype predominated, and the CTLs were highly specific for donor lymphoblastoid cell lines (LCLs) without killing of recipient targets or K562. Vbeta spectratyping showed an oligoclonal population that was stable on prolonged culture. The EBV-specific CTLs were activated (D-related human leukocyte antigen [HLA-DR+], L-selectin+/-) and of memory phenotype (CD45RO+). Expression of the integrin VLA-4 suggested that these CTLs could adhere to endothelium and migrate into tissues. The Bcl-2 message was upregulated, which may protect the CTLs from the apoptosis. The first demonstration of overexpression of bcl-2 in human memory CTLs. In addition, we show that lymphoblastoid cell lines used to generate CTLs are readily genetically modified with recombinant lentivirus, indicating that genetically engineered antigen presentation is feasible.

Adolescent↗