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Biomedical subjects

B J Jenkins

Publications and source records attributed to B J Jenkins.

At least 19 recordsLinked to original sources
PubMed2002

Venous thromboembolic prophylaxis for transurethral prostatectomy: practice among British urologists.

Venous thromboembolism (VTE) is an occasional cause of death after transurethral prostatectomy but there are no established guidelines for its prevention in relation to this operation. We assessed practice in the UK by mailing a questionnaire to 460 consultant members of the British Association of Urological Surgeons. 362 (79%) completed questionnaires were received. 280 of 362 (77%) respondents routinely used VTE prophylaxis with transurethral prostatectomy; 82 (23%) did not. 230 of the 280 urologists who took precautions used mechanical methods; 50 used low dose heparin, either with stockings or alone. This survey indicates that, despite a lack of clear evidence, most British urologists favour some form of precaution against VTE in patients undergoing transurethral prostatectomy.

Anticoagulants↗
PubMed2000

Traumatic priapism: an unusual cycling injury.

A case is reported of a 35 year old man who sustained an injury to the perineum in a cycling accident which resulted in a traumatic priapism. After confirmation of the diagnosis by Doppler sonography and angiography, therapeutic selective arterial embolisation was followed by successful detumescence of the penis and subsequent return of normal erectile function. It is suggested that percutaneous embolisation of the lacerated cavernosal artery is a safe and effective minimally invasive treatment for this uncommon condition.

Adult↗
PubMed2000

Epidermoid cysts of the testis: the case for conservative surgery.

The series comprises 6 patients (mean age, 21 years) who presented with an epidermoid cyst of the testis between 1991 and 1998. Pre-operative ultrasonography suggested the presence of a testicular cancer in 3 patients who underwent a radical orchidectomy. The ultrasound successfully predicted the true diagnosis in 3 patients who had a wedge excision of the cyst together with a cuff of normal surrounding tissue. All patients are free of disease with a mean follow-up of 3 years. With increasing awareness of the condition coupled with accurate pre-operative radiological imaging, local excision of an epidermoid cyst with preservation of the remainder of the testis is now a feasible and rational alternative to more radical surgery.

Adolescent↗
PubMed1999

A cell type-specific constitutive point mutant of the common beta-subunit of the human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 receptors requires the GM-CSF receptor alpha-subunit for activation.

The high affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a cytokine-specific alpha-subunit (hGMRalpha) and a common signal-transducing beta-subunit (hbetac) that is shared with the interleukin-3 and -5 receptors. We have previously identified a constitutively active extracellular point mutant of hbetac, I374N, that can confer factor independence on murine FDC-P1 cells but not BAF-B03 or CTLL-2 cells (Jenkins, B. J., D'Andrea, R. J., and Gonda, T. J. (1995) EMBO J. 14, 4276-4287). This restricted activity suggested the involvement of cell type-specific signaling molecules in the activation of this mutant. We report here that one such molecule is the mouse GMRalpha (mGMRalpha) subunit, since introduction of mGMRalpha, but not hGMRalpha, into BAF-B03 or CTLL-2 cells expressing the I374N mutant conferred factor independence. Experiments utilizing mouse/human chimeric GMRalpha subunits indicated that the species specificity lies in the extracellular domain of GMRalpha. Importantly, the requirement for mGMRalpha correlated with the ability of I374N (but not wild-type hbetac) to constitutively associate with mGMRalpha. Expression of I374N in human factor-dependent UT7 cells also led to factor-independent proliferation, with concomitant up-regulation of hGMRalpha surface expression. Taken together, these findings suggest a critical role for association with GMRalpha in the constitutive activity of I374N.

Amino Acid Sequence↗
PubMed1999

Effect of oral and i.v. tenoxicam in postoperative pain after total knee replacement.

We have evaluated the effect of oral and i.v. tenoxicam on postoperative pain after unilateral total knee replacement in a double-blind, randomized, controlled study. Tenoxicam was administered to two groups of patients, either before (40 mg orally) or after (40 mg i.v.) surgery, then at 24 h after surgery (40 mg i.v.) and at the end of each day for 8 days (20 mg orally). A third group were given placebo at all times. All patients had access to PCA morphine for the first 48 h and then co-dydramol tablets for the duration of the study. We studied 101 patients, mean age 67 yr. There was no significant reduction in the requirement for PCA morphine for the duration of the study in either of the treatment groups, or for co-dydramol in the first 2 days, but tenoxicam significantly reduced the need for co-dydramol over the remaining 7 days. There were no significant differences in mobility between groups. There was a high incidence of adverse events reported, with a similar number in each of the three groups.

Administration, Oral↗
PubMed1998

Saturation mutagenesis of the beta subunit of the human granulocyte-macrophage colony-stimulating factor receptor shows clustering of constitutive mutations, activation of ERK MAP kinase and STAT pathways, and differential beta subunit tyrosine phosphorylation.

The high-affinity receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are heterodimeric complexes consisting of cytokine-specific alpha subunits and a common signal-transducing beta subunit (hbetac). We have previously demonstrated the oncogenic potential of this group of receptors by identifying constitutively activating point mutations in the extracellular and transmembrane domains of hbetac. We report here a comprehensive screen of the entire hbetac molecule that has led to the identification of additional constitutive point mutations by virtue of their ability to confer factor independence on murine FDC-P1 cells. These mutations were clustered exclusively in a central region of hbetac that encompasses the extracellular membrane-proximal domain, transmembrane domain, and membrane-proximal region of the cytoplasmic domain. Interestingly, most hbetac mutants exhibited cell type-specific constitutive activity, with only two transmembrane domain mutants able to confer factor independence on both murine FDC-P1 and BAF-B03 cells. Examination of the biochemical properties of these mutants in FDC-P1 cells indicated that MAP kinase (ERK1/2), STAT, and JAK2 signaling molecules were constitutively activated. In contrast, only some of the mutant beta subunits were constitutively tyrosine phosphorylated. Taken together, these results highlight key regions involved in hbetac activation, dissociate hbetac tyrosine phosphorylation from MAP kinase and STAT activation, and suggest the involvement of distinct mechanisms by which proliferative signals can be generated by hbetac.

Animals↗
PubMed1997

A family of cytokine-inducible inhibitors of signalling.

Cytokines are secreted proteins that regulate important cellular responses such as proliferation and differentiation. Key events in cytokine signal transduction are well defined: cytokines induce receptor aggregation, leading to activation of members of the JAK family of cytoplasmic tyrosine kinases. In turn, members of the STAT family of transcription factors are phosphorylated, dimerize and increase the transcription of genes with STAT recognition sites in their promoters. Less is known of how cytokine signal transduction is switched off. We have cloned a complementary DNA encoding a protein SOCS-1, containing an SH2-domain, by its ability to inhibit the macrophage differentiation of M1 cells in response to interleukin-6. Expression of SOCS-1 inhibited both interleukin-6-induced receptor phosphorylation and STAT activation. We have also cloned two relatives of SOCS-1, named SOCS-2 and SOCS-3, which together with the previously described CIS form a new family of proteins. Transcription of all four SOCS genes is increased rapidly in response to interleukin-6, in vitro and in vivo, suggesting they may act in a classic negative feedback loop to regulate cytokine signal transduction.

Amino Acid Sequence↗
PubMed1996

Interacting residues in the extracellular region of the common beta subunit of the human granulocyte-macrophage colony-stimulating factor, interleukin (IL)-3, and IL-5 receptors involved in constitutive activation.

A previous study using random mutagenesis identified an activating mutation in the common beta subunit (hbetac) of the human granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5 receptors in which an isoleucine residue (Ile374) in the extracellular region of hbetac is replaced by asparagine (Jenkins, B. J., D'Andrea, R., and Gonda, T. J. (1995) EMBO J 14, 4276-4287). To investigate the mechanism by which this mutation (I374N) acts, we employed site-directed mutagenesis to explore predictions based on a structural model of hbetac. We focused on possible interactions between Ile374 and other hydrophobic residues in its vicinity and found that replacement of two such residues, Leu356 and Trp358, with asparagine resulted in constitutive activation of hbetac. Hydrophilic substitutions at both of these positions and at position 374 resulted in the greatest degree of activation, as measured by the growth rate of factor-independent cells, while hydrophobic substitutions had lesser or no effects. Moreover, these "weak" substitutions appeared to synergize, since factor-independent cells expressing the double mutants I374F/W358F and I374F/L356A showed substantially higher growth rates than the single mutants. Taken together, these results suggest that Ile374 normally interacts with Leu356 and Trp358, and that disruption of these interactions results in a conformational change in hbetac that leads to constitutive activity. A model relating this notion to the predicted structure and to ligand- and alpha subunit-dependent activation of hbetac is proposed.

Amino Acid Sequence↗
PubMed1995

Activating point mutations in the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors suggest the involvement of beta subunit dimerization and cell type-specific molecules in signalling.

We have combined retroviral expression cloning with random mutagenesis to identify two activating point mutations in the common signal-transducing subunit (h beta c) of the receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5 by virtue of their ability to confer factor independence on the haemopoietic cell line, FDC-P1. One mutation (V449E) is located within the transmembrane domain and, by analogy with a similar mutation in the neu oncogene, may act by inducing dimerization of h beta c. The other mutation (I374N) lies in the extracellular, membrane-proximal portion of h beta c. Neither of these mutants, nor a previously described mutant of h beta c (FI delta, which has a small duplication in the extracellular region), was capable of inducing factor independence in CTLL-2 cells, while only V449E could induce factor independence in BAF-B03 cells. These results imply that the extracellular and transmembrane mutations act by different mechanisms. Furthermore, they imply that the mutants, and hence also wild-type h beta c, interact with cell type-specific signalling molecules. Models are presented which illustrate how these mutations may act and predict some of the characteristics of the putative receptor-associated signalling molecules.

Amino Acid Sequence↗
PubMed1995

Non-invasive estimation of venous admixture: validation of a new formula.

We have developed a computer program that estimates venous admixture (intra-pulmonary shunt) from four measurements: haemoglobin concentration, end-tidal carbon dioxide tension (PE'CO2), fractional inspired oxygen concentration (FIO2) and pulse oximetry (SpO2). The formula was tested on patients in an intensive therapy unit by using it to estimate shunt while it was measured simultaneously by a standard, invasive method. A total of 101 measurements were made in 29 patients. After correcting the systematic errors in the assumed differences between PE'CO2 and arterial PCO2, and between SpO2 and co-oximetrically measured SaO2, and correcting for a trend in the arteriovenous oxygen concentration difference (C(a-v))2) with shunt, the bias of the non-invasive minus invasive shunt differences was negligible, with no significant dependence on shunt. The limits of agreement were then +/- 16% shunt overall (+/- 13% within patients). When SaO2 was used instead of SpO2, the limits were +/- 11% (+/- 8% within patients).

Carbon Dioxide↗
PubMed1995

Substitution cystoplasty for intractable interstitial cystitis.

OBJECTIVE: To assess the results of substitution cystoplasty for the treatment of intractable interstitial cystitis (IC). PATIENTS AND METHODS: Thirty-two patients (29 women and three men; mean age 58 years, range 24-74) with intractable IC resistant to conservative therapy who had undergone substitution cystoplasty between 1983 and 1992 were reviewed. Their bladder capacities were measured pre-operatively and related to the outcome of treatment. RESULTS: All but two of the 22 women with a bladder capacity of < 250 mL under anaesthetic were improved (five) or cured (15) of their symptoms. The results in women with larger bladder capacities were much less reliable, with only two of seven being cured of their symptoms. The three men all had a good result. Those who had undergone supratrigonal cystectomy were more likely to void spontaneously, but four patients developed pyelonephritis from associated reflux. Subtotal cystectomy reduced the likelihood of reflux and, although there were too few patients for statistical significance, probably increased the chance of cure at the expense of increasing the need for intermittent self-catheterization (ISC). CONCLUSIONS: Pre-operative bladder capacity under anaesthetic is the most reliable predictor of outcome of substitution cystoplasty for treating intractable IC in women. It is contra-indicated if bladder capacity is > 250 mL. Supratrigonal cystectomy is a quick and easy operation and is preferable in the older patient. Subtotal cystectomy with reimplantation of the ureters is preferable in the younger patient, even though it may increase the need for ISC.

Adult↗
PubMed1994

Differential expression of genes encoding a cysteine-rich keratin family in the hair cuticle.

In the hair follicle the cuticle develops as a thin layer of cells between the hair shaft cortex and the inner root sheath. Once the cuticle cells begin to differentiate they accumulate cysteine-rich granules in their cytoplasm but the identity of their constituent proteins has remained largely an enigma. In this report we show differential expression of a family of genes encoding cysteine-rich, glycine-rich keratins in the cuticle. Two clones of the sheep KAP5 gene family were isolated: the KAP5.4 cDNA encodes a protein of 190 amino acids (M(r) = 16,936) containing 32 mol% cysteine, 26 mol% glycine and the partial KAP5.5 cDNA encodes a protein of at least 197 amino acids (M(r) > or = 17,474) containing 29 mol% cysteine, 28 mol% glycine. The predicted amino acid sequences of the KAP5 family show extensive sequence conservation and all the proteins are composed almost entirely of cysteine-rich and glycine-rich repeats. Each KAP5 gene produces an approximately 1.5-kb mRNA species but the KAP5.4 and KAP5.5 mRNA levels appear to be severalfold greater than the KAP5.1 mRNA. Comparative tissue in situ hybridizations reveal a positive correlation between the onset of expression and follicle depth. For a given KAP5 gene two widely different cuticle expression patterns were noted amongst the follicle populations, and on the basis of follicle bulb cell kinetics they are consistent with expression in either sheep primary or secondary follicle types.

Amino Acid Sequence↗
PubMed1994

The accuracy of conventional and three-dimensional thallium-technetium scans in patients with hyperparathyroidism resulting from multiglandular hyperplasia.

25 patients with hyperparathyroidism resulting from multiglandular hyperplasia were studied prior to cervical exploration. 43% of abnormal glands were correctly localized by preoperative thallium-technetium scintigraphy. In the 11 patients who underwent three-dimensional scanning, all glands already identified by scintigraphy were also localized in a third plane. In one patient an additional gland, not detected by the conventional scan, was visible.

Adult↗
PubMed1994

Junior doctors' hours: what do they really think?

Junior doctors' hours are one of the most controversial topics under debate in the health service today. We undertook a detailed postal questionnaire of hospital doctors in training within a major teaching unit in order to assess the awareness and perceived implications of the incipient changes and to elucidate how it was felt these changes would affect both the doctors and patients. The questionnaire focused specifically on the effect of the changes on quality and continuity of patient care, junior training and socio-economic factors relating to the medical staff. The questionnaire was entirely anonymous and carried only the first author name but provision was made to determine current grade, specialty, age, sex and career plans of the respondents. Importantly, space was included at the end for pertinent comments. All junior staff in training in all specialties in the Cardiff area were circulated. Three hundred and twenty-six questionnaires were sent out and 202 were returned of which 192 were properly completed (59%). Almost everyone was au fait with the proposed changes. There was a surprisingly high level of support for changes among non-surgical trainees, and half felt that quality of care would improve, though the more senior the trainee, the less enthusiastic they were in all aspects. Many felt that far too little consultation with junior staff had taken place and there was generalized criticism of general practitioner trainees by their specializing counterparts, partly because of a perceived lack of commitment and partly because of blame of this group for the inception of the changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗