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Biomedical subjects

A Price

Publications and source records attributed to A Price.

At least 109 records · Page 6Linked to original sources
PubMed1995

SecYEG and SecA are the stoichiometric components of preprotein translocase.

The transport of large preproteins across the Escherichia coli plasma membrane is catalyzed by preprotein translocase, comprised of the peripherally bound SecA subunit and an integrally bound heterotrimeric domain consisting of the SecY, SecE, and SecG subunits. We have now placed the secY, secE, and secG genes under the control of an arabinose-inducible promoter on a multicopy plasmid. Upon induction, all three of the proteins are strongly overexpressed and recovered in the plasma membrane fraction. These membranes show a strong enhancement of 1) translocation ATPase activity, 2) preprotein translocation, 3) capacity for SecA binding, and 4) formation of the membrane-inserted form of SecA. These data establish that SecY, SecE, and SecG constitute the integral membrane domain of preprotein translocase.

Adenosine Triphosphatases↗
PubMed1995

Isolated TSH deficiency with a partially empty sella.

Isolated TSH deficiency is rare. The diagnosis is based on (i) symptoms and signs of thyroid hormone deficiency, (ii) demonstration of an absent or impaired TSH response to TRH and (iii) other pituitary hormones remaining intact. We report a 60-year-old female in whom isolated TSH deficiency was found, with a free thyroxine - 7.0 pmol/L (11-20), total triiodothyronine level - 1.5 nmol/L (1.1-2.6) and thyroid stimulating hormone - 0.87 mU/L (0.38-4.3). A TRH test on two separate occasions demonstrated an inappropriately low TSH response. Computed assisted tomography revealed a partially empty sella and other pituitary hormones were demonstrated to be intact. We were unable to detect pituitary antibodies using indirect immunofluorescence on sections of monkey pituitary. Treatment with thyroxine improved this patient's symptoms and suppressed the TSH further.

Empty Sella Syndrome↗
PubMed1995

High-dose carboplatin and etoposide for salvage chemotherapy of germ cell tumours.

We evaluated high-dose carboplatin and etoposide with autologous bone marrow stem cell support in the salvage treatment of patients with metastatic germ cell tumours who had failed previous chemotherapy. The treatment programme comprised initial conventional dose chemotherapy. 23 patients received a first cycle of high-dose treatment, and 12 who showed no evidence of progression had a second cycle 2-3 months later. 8 of the 23 patients treated with high-dose chemotherapy are alive in remission 4-29 months from the start of high-dose treatment. 3 of these 8 required further treatment for recurrence. In the initial part of the study, the dose of carboplatin was escalated in successive patients. Grade 3/4 treatment-related toxicity occurred in 4 of 18 patients (1 fatal) who received carboplatin doses to give a AUC (area under the serum concentration/time curve) of 30 mg.min/ml or less and 3 of 5 patients (2 fatal) who received higher doses. We, therefore, recommend 30 mg.min/ml for further evaluation in chemotherapy sensitive patients.

Adolescent↗
PubMed1995

The renal medulla in acute renal allograft rejection: comparison with renal cortex.

A retrospective cohort study was undertaken to evaluate the diagnostic value of the renal medulla in acute renal allograft rejection (ARAR). One hundred and ninety-five biopsies from 98 patients were randomly selected out of 565 transplant biopsies. Biopsies were graded blindly from Grade 0 (no rejection) to Grade 3 (severe rejection) using standard criteria; ARAR was confirmed by a fall in all cases of mean serum creatinine concentration from 0.331 +/- 0.182 to 0.184 +/- 0.079 mmol/l, with anti-rejection therapy. In the 43 biopsies which contained both cortex and medulla, the ARAR grades and the intensities of mononuclear cell, plasma cell, polymorphonuclear cell and eosinophil infiltrates, and of interstitial oedema and haemorrhage, were similar in cortex and medulla (Spearman's Rank Correlation r = 0.55-0.81, P < 0.001). The sensitivity, specificity and overall accuracy of medullary changes in predicting ARAR changes in the cortex were 77%, 100% and 38%, respectively. Acute vascular rejection changes could not be compared between renal cortex and renal medulla because of the anatomical differences between cortex and medulla. Further evaluation of ARAR in the all 195 biopsies, of which 188 had cortical tissue and 50 had medullary tissue, showed no significant differences in histological features (P > 0.05), except for more cortical biopsies with plasma cells (29%) than medullary biopsies with plasma cells (10%; P < 0.02). It is concluded that: (1) ARAR histological changes are similar in cortex and medulla; (2) the predictive value of ARAR medullary changes for cortical rejection changes has low sensitivity (77%) and high specificity (100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Should thyroid function be assessed before cardiopulmonary bypass operations?

Thyroid function is depressed during and after cardiopulmonary bypass surgical procedures, and this may adversely affect myocardial performance. There is known to be a high prevalence of thyroid abnormalities in the elderly population, and many patients undergoing cardiac operations fall into this category. We have assessed thyroid function in 116 patients admitted for elective open heart procedures to determine the value of preoperative testing. Abnormalities in thyroid function were present in 13 (11.2%) of the patients studied, 3 of whom were receiving thyroxine therapy. One patient who had overt hypothyroidism died postoperatively of a large cerebral infarct; 11 had elevated thyrotropin levels with normal serum thyroxine levels; and 1 who had overtreated hypothyroidism suffered fast atrial fibrillation postoperatively. No other complications were observed. These findings indicate that thyroid function should be assessed preoperatively in patients already on thyroxine therapy. Whether thyroid function should be evaluated routinely in all patients before operations involving cardiopulmonary bypass is not clear. Although there is a high incidence of abnormal laboratory results, there were no apparent adverse effects on the surgical outcome.

Aged↗
PubMed1994

Haematological toxicity of radiotherapy following high-dose chemotherapy and autologous bone marrow transplantation in patients with recurrent Hodgkin's disease.

17 patients with recurrent Hodgkin's disease received 21 courses of radiotherapy (RT) 1-23 months after high-dose chemotherapy and autologous bone marrow transplantation. WHO grade III-IV haematological toxicity, of median duration 38 days (range 4-236), was observed following 10 courses of radiotherapy in 9 patients. This haematological morbidity could be predicted with an 80.0% sensitivity when the pre-RT white cell count was < 5 x 10(9)/l or the platelet count < 100 x 10(9)/l. It occurred in 9/11 patients with initial stage III-IV disease, including all 6 given extended radiotherapy fields, but in no patients with initial stage II disease (chi 2 = 9.35, P < 0.005). Age, histology, the presence of B symptoms, performance status, previous radiotherapy or chemotherapy, the interval between autologous bone marrow transplantation and radiotherapy, the high-dose regimen used, and the radiotherapy dose or field size, did not appear to affect haematological toxicity. The median survival was 18 months from the date of starting radiotherapy. 7 patients remain alive and progression-free 8-51 months (median 21 months) after radiotherapy. Radiotherapy may contribute to durable remissions in patients with relapsed or residual Hodgkin's disease after autologous bone marrow transplantation, but significant haematological toxicity may be expected in those with mild pancytopaenia prior to radiotherapy, particularly with initial stage III or IV disease.

Adolescent↗
PubMed1994

Eosinophils in acute renal allograft rejection.

Tissue eosinophils have been previously implicated in allograft rejection and graft loss. The aim of this study was to evaluate the role of eosinophils in acute renal allograft rejection. Data from 71 patients with 114 renal biopsies with acute allograft rejection were compared with those from 26 controls. The median tissue eosinophil density (0.4-1.1 eosinophils per micron2 x 10(6)) and the median peripheral blood eosinophilia (1.5-3.0%) in all grades of acute interstitial rejection and in acute vascular rejection were higher than in controls (0.0 eosinophils per micron2 x 10(6), p < 0.0023, and 0.9%, p < 0.035). In all grades of rejection, 36-54% of biopsies had tissue eosinophil density > or = 1 eosinophil per micron2 x 10(6), and 20-36% of patients had peripheral blood eosinophilia > or = 4%, compared with 0% and 4%, respectively, in controls (p < 0.000 and p = 0.0245). The sensitivity, specificity and overall accuracy of predicting acute rejection with tissue eosinophil density > or = 1 eosinophil per micron2 x 10(6) is 41%, 100% and 52%, and for peripheral blood eosinophila > or = 4% is 23%, 96% and 40%, respectively. The median tissue eosinophil density in acute rejection with graft loss was 1.9 eosinophils per micron2 x 10(6) compared to 0.2 eosinophils per micron2 x 10(6) in acute rejection without graft loss (p = 0.014), and 67% of acute rejection with graft loss had tissue eosinophil density > or = 1 eosinophil per micron2 x 10(6) compared with 28% of acute rejection without graft loss (p = 0.028).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Observer variation and discriminatory value of biopsy features in inflammatory bowel disease.

If skilled histopathologists disagree over the same biopsy specimen, at least one must have an incorrect interpretation. Thus, disagreement is associated with, although not the cause of, diagnostic error. The present study aimed to determine the magnitude of variation among 10 observers with a special interest in gastrointestinal histopathology. They independently interpreted the same biopsy specimens for morphological features which may discriminate between patients with Crohn's disease and ulcerative colitis and normal subjects. Thirty of 41 features had agreement measures significantly better than expected by chance (p < 0.05). The range of agreement in the 45 observer pairs over the final diagnosis was 65-76%. There was good agreement in discriminating between normal slides and those showing confirmed inflammatory bowel disease. For normal slides, however, the term nonspecific inflammation was often applied and without any consistency. In addition, true Crohn's disease slides were often and consistently thought to be ulcerative colitis. Having identified 11 important discriminatory morphological features, two multiple regression analyses were then carried out to produce a scoring system for inflammatory bowel disease. These results suggest there is considerable room for improvement in the reliability of colonic biopsy specimen interpretation and that this could probably be achieved using more exact definitions of morphological features and diseases.

Colitis, Ulcerative↗
PubMed1994

Production of bioactive and immunoreactive interleukin-6 (IL-6) and expression of IL-6 messenger ribonucleic acid by human pituitary adenomas.

Preliminary studies have demonstrated that some pituitary adenomas secrete immunoreactive interleukin-6 (irIL-6) when cultured in vitro. We have extended these studies by investigating 100 pituitary adenomas of different types measuring immunoreactive and bioactive IL-6. Tumors were cultured either as explants without fetal calf serum or as dispersed cells with 10% total calf serum. Fifty-three of the 100 (53%) pituitary cultures were found to release irIL-6 and in 44 adenomas examined, 32 (72.7%) secreted bioactive IL-6. In 61 explant cultures, 30 adenomas released IL-6, indicating autonomous secretion. The amount of IL-6 released by adenomas in cell culture was generally higher, although the incidence was similar to explant cultures. IrIL-6 was released by 7 of 14 prolactinomas, 15 of 27 somatotrophinomas, 5 of 7 corticotrophinomas (including 2 Nelson's adenomas), 1 of 1 thyrotrophinomas, 2 of 2 gonadotrophinomas, and 23 of 49 clinically non-functioning adenomas. Periadenomatous tissue removed from a patient with a corticotrophinoma was found to secrete IL-6 but in much lower concentration than from the adenoma tissue. Tumor necrosis factor-alpha and -gamma-interferon were not detected in the conditioned media. Four IL-6-secreting adenomas were examined by in situ hybridization for IL-6 messenger RNA, and three of these were positive with fluorescence present throughout the tissue examined. We have provided evidence that over half of pituitary adenomas secrete IL-6 which is bioactive and that IL-6 is synthesized within the tumor by the adenoma cells.

Adenoma↗
PubMed1994

Lower extremity static and dynamic relationships with rearfoot motion in gait.

Twenty nonsymptomatic subjects were assessed while walking at a photoelectronically monitored place (2 +/- 0.1 m.s-1) using high speed cinematography (200 Hz) to record the rearfoot motion in the frontal plane, and electrogoniometry (100 Hz) to measure joint kinematics in the lower extremity. The foot type of the subjects was determined statically by using a podiascope and digitization techniques. The results demonstrated that no foot type variables contributed significantly to the variance in either rearfoot angle at foot strike or maximum rearfoot angle (p > 0.05). Regression equations were developed using kinematic variables: rearfoot angle at foot strike = 3.81 + (0.06*time to hip internal rotation) - (0.46*tibia internal rotation) + (0.14*plantarflexion); (R = 0.87, SE = 1.23 degrees); maximum rearfoot angle = 4.02 + (0.52*hip internal rotation) - (0.11*time to hip internal rotation); (R = 0.66, SE = 2.07 degrees). This study identifies hip joint movements as being the most significant contributors to prediction of rearfoot angles produced during walking.

Adult↗
PubMed1994

Midwifery portfolios: supporting the midwife.

The UKCC has made clear recommendations for the development of Professional Profiles (portfolios). Senior midwives should recognise the importance of their responsibility in assisting junior colleagues in the preparation of portfolios. Midwives preparing portfolios need assistance in identifying their aspirations and in reflecting on current practice. Those assisting should consider themselves as facilitators of growth rather than judges of incompetence. Goals should be limited to four, and half of these should be short-term.

Humans↗
PubMed1993

Pituitary adenomas with high and low basal inositol phospholipid turnover; the stimulatory effect of kinins and an association with interleukin-6 secretion.

OBJECTIVE: We examined basal inositol phospholipid turnover and the response to the kinin, kallidin, in human pituitary adenomas and determined whether or not there was an association between these parameters and interleukin (IL-6) secretion status by the tumours. DESIGN: Pituitary adenoma tissue was dispersed and cells were cultured in monolayer for 96 hours. The medium was then removed and assayed for IL-6 and anterior pituitary hormones. The cells were labelled with 3H-myoinositol for 24 hours and then incubated under basal conditions with kallidin and, in some cases, with TRH and GnRH for 60 minutes. Total inositol phosphate accumulation and pituitary hormone secretion were assessed. PATIENTS: Tissue was collected from 29 consecutive patients being treated surgically for pituitary adenomas. MEASUREMENTS: Total 3H-inositol phosphates, growth hormone, prolactin, LH, FSH, TSH and immunoreactive IL-6. RESULTS: Two groups of pituitary adenomas were identified, one with high and one with low basal inositol phospholipid turnover. Kallidin stimulated inositol phosphate accumulation in seven of the 29 adenomas studied. The kallidin-responsive adenomas were associated with high basal phosphoinositide turnover. All seven kallidin-responsive adenomas secreted IL-6. The adenomas studied with high basal inositol phosphate production were also responsive to TRH and in two tumours to GnRH. Kallidin stimulated GH release in one GH-secreting adenoma but had no effect on hormone secretion from any other tumour. CONCLUSION: Two groups of pituitary adenomas have been identified with high and low basal inositol phosphoinositide turnover. Phosphoinositide metabolism is readily stimulated by kallidin and TRH in adenomas with high but not low turnover. Kinin-responsive adenomas secreted IL-6 but IL-6 secretor status does not preclude that they will respond to kallidin.

Adenoma↗