Biomedical subjects

R C Newton

Publications and source records attributed to R C Newton.

71 records · Page 4Linked to original sources

PubMed1987

The activation of human fibroblast prostaglandin E production by interleukin 1.

We have examined the induction of prostaglandin E2 (PGE2) release from fibroblasts by human interleukin 1 (IL-1). A number of fibroblast cell lines appear to respond to IL-1 in a fashion similar to that seen with synovial fibroblast cultures. Using the Gin-1 primary fibroblast cell line, the earliest time where a significant increase in PGE2 release can be detected is 2 hr. Thereafter PGE2 appears to increase dramatically, with levels after 5 hr increased over 50-fold above baseline. IL-1 appears to directly induce the increase in PGE2 since removal of other proteins from culture medium does not affect induction. PGE2 induction by IL-1 also does not require cell proliferation. The induction appears to involve the synthesis of new protein since the enhanced release can be completely blocked by addition of actinomycin D or cycloheximide. Arachidonic acid mobilization in cells does not appear to be altered following IL-1 addition. However, the ability to convert arachidonic acid to PGE2 is increased following 5 hr of culture with IL-1. While increasing the release of PGE2, the addition of phorbol esters, alone or in combination with calcium ionophores, does not mimic the protein synthesis-dependent increase seen with IL-1. Taken together these results suggest that IL-1 induction of fibroblast PGE2 involves the synthesis of new protein or proteins involved in the conversion of free arachidonic acid to PGE2.

Arachidonic Acid↗

PubMed1987

Scarring alopecia.

The scarring alopecias are a diverse group of diseases characterized by the combination of follicular destruction and dermal scarring. In this article we divide scarring alopecias into three broad categories, pediatric diseases, perifollicular lymphocytic diseases, and folliculopustular diseases, and discuss selected entities from each category.

Adult↗

PubMed1987

High-level expression in Escherichia coli of a soluble and fully active recombinant interleukin-1 beta.

A complementary DNA sequence encoding monocyte interleukin-1 (IL-1), beta form/pI7, was expressed in Escherichia coli. Recombinant plasmid pDP516 was constructed by cloning and rebuilding the mature IL-1 coding sequence into an E. coli expression vector. Bacteria transformed with pDP516 constitutively produced recombinant IL-1 (r-IL-1) at 15-20% of total E. coli protein. The r-IL-1 was found to be in the soluble fraction of sonicated E. coli Bacterial r-IL-1 (DP516) has been purified to homogeneity by anion exchange and sizing column chromatography, with an apparent molecular weight of 17,500. The identity of the purified r-IL-1 was confirmed by amino acid and DNA sequencing analyses. Purified recombinant IL-1 DP516 exhibits biological activity similar to that of native monocyte IL-1 (3 approximately 4 X 10(7) units/mg). An amino-terminal deletion mutant completely abolishes the biological activity, indicating that the integrity of the IL-1 molecule might be important for its function.

Amino Acid Sequence↗

PubMed1986

Human monocyte production of interleukin-1: parameters of the induction of interleukin-1 secretion by lipopolysaccharides.

The role of lipopolysaccharide (LPS) as an activator of human monocyte interleukin-1 (IL-1) synthesis and secretion has been examined in this study. The results demonstrate that when blood monocytes are prepared under low endotoxin conditions, they do not spontaneously secrete IL-1 activity. When cells are exposed to LPS extracted from different bacterial species, there is variation seen in the potency, with LPS from Salmonella species being the most potent in inducing IL-1 activity from human monocytes. This material is tenfold more potent than LPS obtained from three different strains of Escherichia coli and 10,000-fold more potent than material obtained from two other bacterial species. Detoxified endotoxins are inefficient activators for IL-1 secretion. When monocytes are exposed to LPS, there is a rapid rise in the level of IL-1 activity detected. Activity can be detected in cell lysates after 1 hr with appreciable accumulation seen over the first 6 hr of culture. This is accompanied by IL-1 release into the surrounding medium after 2 hr of culture with subsequent accumulation. Monocyte synthesis of IL-1 activity appears to be sensitive to fg/ml levels of Salmonella minnesota LPS, while appreciable secretion of this activity by monocytes requires pg/ml levels.

Animals↗

PubMed1986

Mechanism-oriented assessment of isotretinoin in chronic or subacute cutaneous lupus erythematosus.

Eight of ten patients with chronic or subacute cutaneous lupus erythematosus completed 16 weeks of oral isotretinoin therapy (80 mg/day). All eight patients noted an excellent clinical response without significant side effects. (Two patients did not return to initial two-week follow-up.) Peripheral blood B- and T-cell counts were unaffected by therapy. Therapy was associated with resolution of routine histopathologic abnormalities, conversion of abnormal lesional direct immunofluorescence microscopy to normal, normalization of the epidermis on electron microscopy, and reduction of all T cells near the dermoepidermal junction without change in ratio of T-helper/inducer cells to T-suppressor/cytotoxic cells. Isotretinoin is a clinically effective short-term therapy for chronic or possibly for subacute cutaneous lupus erythematosus. The primary mechanism of action remains unestablished.

Administration, Oral↗

PubMed1986

Giant Mycobacterium fortuitum abscess associated with systemic lupus erythematosus.

A 36-year-old woman with a 1 1/2-year history of systemic lupus erythematosus was first seen in October 1984 with a six-month history of several ulcerated and scarred lesions on the lower extremities. A biopsy specimen showed a granulomatous infiltrate of deep dermis and subcutaneous tissue. Over the next three weeks, the patient developed a violaceous, warm, indurated, tender, fluctuant lesion involving most of the left buttock. A culture showed a rapidly growing atypical acid-fast bacteria, which was later identified as Mycobacterium fortuitum. The patient was treated with surgical drainage of the left hip abscess, followed by a three-week treatment with doxycycline hyclate and amikacin sulfate. She was discharged while receiving oral doxycycline and ethambutol hydrochloride.

Abscess↗

PubMed1985

Domiciliary nebulisers in asthma: a district survey.

Fifty three patients who were found to be using a home nebuliser for asthma completed a questionnaire. The results showed some confusion about the criteria for recommending whether a patient should buy a nebuliser and for its correct use. Twelve patients had not received any instruction on the use of their nebuliser, and only 11 of those old enough used a peak flow meter in conjunction with it. Eight patients aged 7-15 were using inhaled sympathomimetic aerosols only at the time of buying a nebuliser as compared with most of the older patients, who were using regular oral steroids. Forty nine patients assessed their asthma as moderate to severe, but eight of these were not attending a hospital clinic. Several patients were using 20 mg salbutamol or more every day, and on occasion doses of up to 50 mg a day were reported. It is recommended that patients should be assessed before they buy a nebuliser and advice given on correct use by a district nebuliser service, organised either by respiratory function technicians or in physiotherapy departments for adults together with a paediatric health visitor for children.

Adolescent↗

PubMed1985

Effect of interferon on the induction of human monocyte secretion of interleukin-1 activity.

This study investigates the effect of interferons on the induction of human monocyte secretion of interleukin-1 (IL-1) activity by lipopolysaccharides (LPS). Monocytes do not spontaneously produce IL-1 and the addition of interferons to the culture does not lead to detectable secretion. Addition of LPS alone induces the release of measurable amounts of IL-1 activity. The addition of low doses (1-10 units/ml) of alpha, beta, or gamma interferon to the LPS-stimulated cultures further increases this secretion by 50%. The addition of 1000 units/ml of alpha or beta interferon leads to inhibition of IL-1 release. By contrast, gamma interferon is a dose dependent enhancer of IL-1 release. The effect of gamma interferon is on the production of IL-1 and is not an enhancement of IL-1 activity in the biological assay. Results demonstrate that addition of gamma interferon to monocytes increases the rate of secretion of IL-1 by these cells. Gamma interferon also appears to abrogate the loss in the ability of monocytes to produce IL-1 activity after overnight culture. This last result parallels the maintainence of the expression of the HLA-DR surface marker on monocytes by gamma interferon. These results may help define a mechanism involving IL-1 generation which could have bearing on the in vivo pyrogenic effects of purified gamma interferon.

Antigens, Surface↗

PubMed1985

Pigmented purpuric eruptions.

The pigmented purpuras comprise a group of dermatoses that are most commonly located on the lower extremities and share related clinical and histopathologic appearances. Included is a discussion of the following entities: progressive pigmentary disease of the skin (Schamberg's disease), purpura annularis telangiectodes (Majocchi's disease), pigmented purpuric lichenoid dermatosis (Gougerot and Blum's disease), and lichen aureus.

Adolescent↗

PubMed1984

Discrimination between nonmalignant and malignant cells by combinations of IFN-gamma and IFN-alpha/beta.

Combination treatment with interferon (IFN)-gamma and either IFN-alpha or IFN-beta synergistically enhances (potentiates) the anticellular effects of the IFNs. IFNs have been shown to have anticellular activity against normal as well as malignant cells. To study the relative effectiveness of IFN's anticellular activity against nonmalignant and malignant cells in the mouse system, two paired sets of nonmalignant/malignant cells (JB-1/JB-8; D-1/D-11a) were studied using 3-day kinetics of cell growth experiments. Treatment of the nonmalignant cells with IFN-gamma or IFN-alpha/beta employed separately had little or no effect on the growth of the cells at the IFN concentrations employed. Combination IFN treatment had only a slight effect on the growth of these cells. Treatment of the malignant cells with IFN-gamma or IFN-alpha/beta employed separately had low levels of effect on the growth of the cells. In contrast, treatment of these malignant cells with combined IFN-gamma and IFN-alpha/beta had a very marked anticellular effect, dramatically showing the growth of, or even killing, the malignant cells. These observations appeared to be independent of the growth status of the cells, since stationary-phase and log-phase malignant cells maintained their relatively greater sensitivity to the IFNs. Thus, IFN treatment, particularly combination IFN treatment, had a differential effect on the growth of the paired sets of nonmalignant and malignant cells and appeared to sharply differentiate between nonmalignant and malignant cells.

Animals↗

PubMed1980

Genetic control of the immune response of mice to highly dinitrophenylated human gamma-globulin (DNP56HGG).

The immune response to highly dinitrophenylated human gamma-globulin (DNP56HGG) was tested in inbred strains of mice. Significant differences in the anti-DNP response among inbred strains were found, including the magnitude of serum antibody and the location of plaque-forming cells (spleen or lymph nodes). The strain differences persisted when the dose and adjuvant were changed. The genetic control of the anti-DNP response to DNP56HGG was investigated. The analysis of the response of congenic and F1 hybrid mice to DNP56HGG suggests that at least two genes are involved in the control of the anti-DNP response. The two genes are demonstrated by complementation in the F1 generation, and show no correlation with H-2 haplotype or IgG2a allotype. A third gene may be implicated by differences in response observed between male and female mice.

Adjuvants, Immunologic↗

PubMed1978

The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody.

The question of whether or not lymphoid cells can cooperate across a histocompatibility difference barrier has been studied in several laboratories. Using an adoptive transfer system, Katz et al. (1) first showed that T cells from (low responder x high responder) F(1) mice, primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT), could collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from a high responder, but not a low responder strain, in response to DNP-GLT. The response to GLT is under H- 2-1inked Ir gene control. In contrast, studies with mouse bone marrow chimeras have shown that T cells can interact with H-2-histoincompatible B cells in response to antigens not under Ir gene control (2-4). Another type of chimera, the allophenic mouse, has been used to study possible histoincompatible cell interactions to a number of antigens, including DNP-L- glutamic acid, L-lysine, L-alanine; L-glutamic acid, L-alanine, L-tyrosine; L-glutamic acid, L-lysine, L-phenylalanine; and poly-L (Tyr, Glu)-poly D,L- Ala-poly-L-Lys[T,G)-A-L] (5-9). The response to each of these antigens is under H-2-1inked Ir gene control. It was initially reported (8, 9) that in allophenic mice containing both high and low responder cells, the antibody to (T,G)-A-L was of both the high and low responder allotype. This was interpreted to mean that high responder T cells had cooperated with low responder B cells across a histocompatibility difference barrier in the environment of the allophenic mice. However, Press and McDevitt (10) have recently reported that additional and more accurate analyses of these allophenic mouse sera failed to detect any anti-(T,G)-A-L antibody of the low responder allotype. Moreover, in an experiment using bone marrow chimeras, there was no low responder allotype antibody produced in response to (T,G)-A- L(10). The present study was undertaken to test the immune response of allophonic mice to an antigen, DNP-bovine gamma globulin (DNP(56)BGG), known to be controlled by genes both inside and outside the H-2 complex (11, 12).(1) When high and low responder cells to DNP(56)BGG are present in allophenic mice, only antibody of the high responder allotype is produced. The results suggest that cell cooperation in allophenic mice cannot occur across a histocompatibility difference barrier in response to an antigen whose genetic control is at least partially within the H-2 complex.

Animals↗

PubMed1972

Uncomplicated HL-A matched sibling bone marrow graft for combined immune deficiency.

When an apparently identical HL-A donor can be found and satisfactorily checked by the mixed lymphocyte reaction, it is worth attempting simple bone marrow grafting in a patient with combined immune deficiency syndrome who otherwise would die. Immunocompetence was given in this way to a baby girl by her 4-year-old brother and was confirmed by the presence of Y-chromosome in most of the transforming lymphocytes. IgA was late to emerge, presumably owing to the immaturity for IgA of the donor's bone marrow.

Bone Marrow Transplantation↗

PubMed1968

Coeliac syndrome.

Explore the source record for details and available documents.

Celiac Disease↗

PubMedDate not supplied

The total chemical synthesis of monocyte chemotactic protein-1 (MCP-1).

The affinity-based N (alpha)-amino protecting group tetrabenzo[a,c,g,i]fluorenyl-17 methoxycarbonyl (Tbfmoc) has been utilized as a hydrophobic probe to allow the simple, quick and highly effective isolation of a 76 residue cysteine-containing protein (MCP-1). The base-labile Tbfmoc group can be removed under very mild conditions, which preserve the thiol-containing protein in the reduced state. Oxidative folding was then used to furnish the biologically active beta-chemokine MCP-1.

Amino Acid Sequence↗

PubMedDate not supplied

The Charing Cross Hospital Child Development Centre: a description of its work ad an evaluation of its first 385 patients.

Charing Cross Hospital provides facilities for the study of handicapped children in a normal nursery which forms part of its Child Development Centre. The period of assessment varies from one day to three weeks; the advantages of prolonged assessment are discussed. Parental involvement and support, and the teaching of medical students are emphasized. A study of the Centre's first 385 patients is presented.

Child Day Care Centers↗

PubMedDate not supplied

Repigmentation of vitiliginous skin by cultured cells.

Epidermal cells from pigmented areas of a patient with vitiligo were cultured in MCDB-153 medium, which supports the clonal growth of undifferentiated keratinocytes and melanocytes. The cells were grown on collagen-coated substrata. After the cells reached semiconfluence, the composite of substratum and cells was emplaced onto dermabraded vitiliginous areas as a graft. Re-epithelialization of the grafted areas was complete after 2 weeks. Repigmentation was evident after 1 month and continued over the observation period of several months. There was complete and normal differentiation of the graft, including a normal distribution of melanocytes in the basal layer. Ultrastructural studies showed a normal distribution of melanosomes in the melanocytes and showed keratinocytes that were indistinguishable from the uninvolved skin.

Antibodies↗