Search PubMed⌕ Search

Biomedical subjects

C J Watson

Publications and source records attributed to C J Watson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Capacity of insect (Manduca sexta) prothoracic glands to secrete ecdysteroids: relation to glandular growth.

The capacity of prothoracic glands to secrete ecdysteroids changes during the last larval stadium of the tobacco hornworm, Manduca sexta. In the present study, the protein content of prothoracic glands was observed to change significantly during this time period. Peaks in glandular protein content occurred on Day 4 (15.4 micrograms/gland) and Day 7 (14.6 micrograms/gland). These correspond to times of maximal ecdysteroid secretion in vitro. Ecdysteroid secretion in vitro was determined as a function of glandular protein content for Day 1, 3, and 7 glands. For unstimulated glands, secretion increased from 0.05 ng/microgram on Day 1, to 0.54 ng/micrograms on Day 3, to 1.37 ng/micrograms on Day 7. For glands incubated with big PTTH, secretion increased from 0.27 ng/micrograms on Day 1, to 2.05 ng/micrograms on Day 3, to 2.60 ng/micrograms on Day 7. The results suggested that developmental changes in secretory capacity are influenced by both the amount and type of glandular proteins. Glandular protein metabolism was assessed by monitoring the incorporation of [35S]methionine. A time course study revealed the rate of incorporation for Day 3 and Day 5 glands was significantly greater than the rate for Day 1 and Day 7 glands. Electrophoretic separation of radiolabeled glandular proteins revealed developmental changes in the pattern of protein synthesis. However, a band whose intensity changed in parallel with developmental changes in glandular secretory capacity was not detected. Finally, incorporation of BrdU by cells of the prothoracic glands was assessed using immunohistochemistry: Incorporation of BrdU was not observed on Days 1 or 7, occurred in only a few cells on Day 5, and was most pronounced on Day 3 (12.3% of the cells were labeled). The combined results indicate that changes in ecdysteroidogenic capacity are associated with (a) a change in glandular protein content, (b) a change in the types of proteins synthesized by prothoracic glands, and (c) a temporally restricted pulse of DNA synthesis, the latter being a possible indicant of cell proliferation.

Analysis of Variance↗
PubMed1995

The proximal milk protein binding factor binding site is required for the prolactin responsiveness of the sheep beta-lactoglobulin promoter in Chinese hamster ovary cells.

To identify cis-acting prolactin (PRL) response elements within the sheep beta-lactoglobulin (BLG) promoter, CHO cells were co-transfected with a rabbit PRL-receptor (PRL-R) expression plasmid and a number of BLG-CAT constructs. Resection through the 4200 bp BLG promoter diminished the PRL response. Mutation of the proximal binding site for milk protein binding factor (MPBF), a previously described mammary gland transcription factor, abolished the PRL inducibility of full length and shorter forms of the promoter. MPBF was shown to be similar to the Stat protein mammary gland factor (MGF) which has been shown to mediate PRL responsiveness of the rat beta-casein gene in mammary cells. MPBF binding activity was detected in the nucleus of CHO cells and was increased 2-6-fold in cells stably transfected with the PRL-R. The lactating mammary gland has high levels of MPBF binding activity and it is likely that this has an important role in the PRL induction of a variety of milk protein genes.

Animals↗
PubMed1995

Elevated levels of members of the STAT family of transcription factors in breast carcinoma nuclear extracts.

The transcription factor, milk protein binding factor (MPBF/Stat5), is a member of the STAT family of signalling molecules which mediates prolactin signal transduction in lactating mammary gland by binding to GAS (gamma-interferon activation site) DNA elements. We have determined the levels of STAT factors in nuclear extracts from a variety of human breast tissues including carcinoma and normal 'resting' breast by electrophoretic mobility-shift assay. The results show that the level of STAT binding activity is low in normal 'resting' breast and benign lesions while carcinoma samples have significantly higher (P < 0.01) amounts of STAT binding activity. Supershift analysis suggests that Stat1 and possibly other members of the STAT family of signalling factors, including Stat3, are activated in breast cancer tissues.

Adenofibroma↗
PubMed1995

Physical therapy management of isolated serratus anterior muscle paralysis.

This case report presents a patient who developed right shoulder pain following strenuous upper-extremity exercise. Approximately 6 weeks later his pain resolved, he noticed persistent right upper-extremity weakness. He was referred to physical therapy for evaluation and treatment. Physical therapy evaluation revealed isolated serratus anterior muscle paralysis. A long thoracic neuropathy was subsequently confirmed by electromyographic testing. The etiology, pathophysiology, and pathokinesiology of serratus anterior muscle paralysis are reviewed. A case is presented, illustrating how the clinical decision making is based on the pathokinesiology and pathophysiology. The patient was followed over the course of 17 months and has recovered full right shoulder active range of motion. His serratus anterior muscle strength has increased to Good minus, and he reports significantly improved functional use of the upper extremity.

Adult↗
PubMed1995

IL-4 mRNA expression by peritoneal cells during episodes of peritonitis in patients on continuous ambulatory peritoneal dialysis.

Peritoneal cells were isolated from dialysates drained from nine patients on continuous ambulatory peritoneal dialysis (CAPD) during episodes of peritonitis. Levels of expression of mRNA for the regulatory cytokines, interferon-gamma (IFN-gamma) and IL-4, were investigated daily, where possible, during the first 5 days of peritonitis. Cytokine mRNA levels were compared with those of peripheral blood mononuclear cells (PBMC) stimulated in vitro with phorbol 12-myristate 13-acetate (PMA) plus phytohaemagglutinin (PHA). Peritoneal cells expressed low levels of IFN-gamma mRNA; for four of nine patients, IL-4 mRNA levels greater than those expressed by stimulated PBMC were detected. There was no pattern of cytokine mRNA expression associated with the types of organisms detected in dialysates at initiation of peritonitis. However, in contrast to those patients with a transient, resolving peritonitis, significant IL-4 mRNA expression was detected in cells isolated early in the episodes of peritonitis in patients who suffered recurrent peritonitis within 30 days of the initial peritonitis episode. These results suggest an association between early IL-4 mRNA expression and susceptibility to further infections. The known anti-inflammatory effects of IL-4 may explain this association.

Adult↗
PubMed1995

Cis-urocanic acid synergizes with histamine for increased PGE2 production by human keratinocytes: link to indomethacin-inhibitable UVB-induced immunosuppression.

There is considerable evidence that suppression of the immune system by UVB (280-320 nm UV) irradiation is initiated by UVB-dependent isomerization of a specific skin photoreceptor, urocanic acid (UCA), from the trans to the cis form. Previous studies have confirmed that cis-UCA administration to mice 3-5 days prior to hapten sensitization at a distant site, suppresses the contact hypersensitivity (CHS) response upon challenge. This study demonstrates in mice that cis-UCA, like UVB, suppresses CHS to trinitrochlorobenzene by a mechanism partly dependent on prostanoid production. In vitro experimentation showed that human keratinocytes, isolated from neonatal foreskin, increased prostaglandin E2 (PGE2) production in response to histamine but not UCA alone. However, cis-UCA synergized with histamine for increased PGE2 production by keratinocytes. Cis-urocanic acid also increased the sensitivity of keratinocytes for PGE2 production in response to histamine. Prostaglandin E2 from keratinocytes exposed to cis-UCA and histamine may contribute directly, or indirectly, to the regulation of CHS responses by UVB irradiation.

Animals↗
PubMed1995

Molecular genetic analysis of a family with a history of Hodgkin's disease and dyschondrosteosis.

We describe a family in which two sisters with the autosomal dominant skeletal dysplasia, Leri-Weill dyschondrosteosis (LWD), developed Hodgkin's disease (HD) in late adolescence. In a preliminary attempt to identify HD susceptibility gene(s), HLA-typing and linkage analysis were carried out in the family. Using HLA molecular typing, both sisters were found to have inherited a variant of the HD-susceptibility allele, DPB1*0301, known as DPB1*2001. Following a previous report of a constitutional chromosome translocation (t(2q;8p)) in a family with LWD, preliminary linkage studies were carried out using chromosome 2q and 8p molecular markers. Regions covered by 7/10 chromosome 2 markers and 4/8 chromosome 8 markers were excluded as the location of a candidate LWD gene. Given the rarity of LWD and HD, their simultaneous occurrence is unlikely to have been due to chance. We suggest that a mutation in the LWD gene itself, or a gene closely linked to it, perhaps acting with increased susceptibility to infection conferred by DPB1*2001, resulted in HD in the two sisters.

Adolescent↗
PubMed1994

The mammary factor MPBF is a prolactin-induced transcriptional regulator which binds to STAT factor recognition sites.

Site-directed mutagenesis of the three binding sites for the mammary factor MPBF in the beta-lactoglobulin (BLG) promoter demonstrates that MPBF is a transcriptional activator of the BLG gene in mammary cells. MPBF requires phosphorylation on tyrosine for maximum binding activity and binds to GAS (interferon gamma-activation site) elements which are similar to the MPBF binding sites. Prolactin induces MPBF binding activity in CHO cells and is not antigenically related to Stat1 (p91) and Stat2 (p113), suggesting that this transcription factor is likely to be another member of the STAT family of cytokine/growth factor-induced transcription factors.

Animals↗
PubMed1994

Tolerance of porcine renal allografts induced by donor spleen cells and seven days' treatment with cyclosporine.

Liver allografts in pigs and in rats elicit a substantial cellular immune response that can resolve spontaneously with the induction of donor-specific systemic tolerance. Self-limiting interactions between host and donor (graft)-derived leukocytes may be the basis for tolerogenesis. We have attempted to reproduce this effect of liver grafting in pigs by peroperative infusion of donor leukocytes into kidney graft recipients given an interrupted short course of CsA designed to promote donor leukocyte survival and interaction with host cells. This protocol can secure long-term kidney graft survival resistant to challenge by donor skin grafting. Donor skin is, however, rejected, but more slowly than third-party skin, indicating a degree of systemic specific unresponsiveness in these long-term kidney graft recipients.

Animals↗
PubMed1994

Immunosuppression of canine renal allograft recipients by CD4 and CD8 monoclonal antibodies.

A state of tolerance to MHC mismatched allografts can be generated in rodents by treatment with CD4 and CD8 monoclonal antibodies (mAb). In order to transpose this type of therapy to large animals and ultimately to the clinic, a suitable model is required. To this end we have generated a series of mAb to the canine CD4, CD8, and Thy-1 antigens and have tested their ability to prevent rejection of renal allografts. Donor-recipient pairs were selected from a colony of mongrel dogs in which untreated rejection of two haplotype-mismatched kidneys occurred by day 7 (defined as a serum creatinine > 300 mumol/l). Therapy with either the CD4 or the CD8 mAb, using no other immunosuppression, did not prolong graft survival. Depletion of T cells by a Thy-1 mAb prior to surgery only extended graft survival to day 9. However, treating with combinations of mAb up to day 10 (CD4 plus Thy-1; CD4 plus CD8; or CD4 plus CD8 plus Thy-1) prolonged renal allograft function up to 25 days. Combination of the triple mAb therapy with a sub-therapeutic immunosuppressive drug regimen (cyclosporin A plus azathioprine that alone gave a median survival of 15 days) favored survival to a median of 38 days. This protocol also inhibited the antiglobulin response that had curtailed the effects of mAb treatment, opening the way to more extended, and potentially tolerizing, mAb plus drug regimens.

Animals↗