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Biomedical subjects

J Shannon

Publications and source records attributed to J Shannon.

At least 19 recordsLinked to original sources
PubMed2006

The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia.

The dual 5alpha-reductase inhibitor, dutasteride has been shown to suppress serum dihydrotestosterone (DHT) by >90%. In the present study, the effect of dutasteride 0.5 mg/day on intraprostatic DHT levels was investigated. In this multicenter, double-blind trial, 43 men with benign prostatic hyperplasia (BPH) scheduled to undergo transurethral resection of the prostate (TURP) were randomized to receive dutasteride, 0.5 mg/day or placebo for 3 months before surgery. Intraprostatic DHT, testosterone and dutasteride levels were determined at the time of TURP. Changes in serum DHT and testosterone from baseline, and both serum and intraprostatic dutasteride levels at the time of TURP were also assessed. Dutasteride reduced intraprostatic DHT by 94% relative to placebo (P<0.001); the adjusted mean intraprostatic DHT concentration was 3.23 and 0.209 ng/g in the placebo and dutasteride groups, respectively. In the dutasteride group, serum DHT was reduced from baseline by 93% at month 3, a significantly greater reduction (P<0.001) than the 15% decrease observed in the placebo group. There was a reciprocal increase in intraprostatic testosterone but the level of intraprostatic testosterone in the dutasteride group tended to be lower than the intraprostatic DHT level in the placebo group (P=0.06). Significant intraprostatic DHT suppression was achieved in all subjects who received dutasteride, regardless of the level of intraprostatic dutasteride. There was a strong positive correlation between serum and intraprostatic dutasteride concentrations (R(2)=0.73). After 3 months of treatment, dutasteride 0.5 mg/day provided near-complete suppression of both intraprostatic and serum DHT in men with BPH.

Aged↗
PubMed2006

Differences in proteoglycan deposition in the airways of moderate and severe asthmatics.

Excess deposition of proteoglycans (PGs) has been described in the subepithelial layer of the asthmatic airway wall. However, less is known about deposition in the airway smooth muscle (ASM) layer, and whether the pattern of deposition is altered depending upon disease severity. Endobronchial biopsies were performed in patients with severe or moderate asthma (defined using American Thoracic Society criteria) and in control subjects. Biopsies were immunostained for the PGs biglycan, lumican, versican and decorin. PG deposition was measured in the subepithelial and ASM layers, the former by calculating the area of positive staining, and the latter by determining the percentage area stained using point counting. Immunostaining for PGs was prominent in biopsies from both moderate and severe asthmatics, compared with control subjects. While there was no difference in the amount of PG in the subepithelial layer between the two asthmatic groups, the percentage area of biglycan and lumican staining in the ASM layer was significantly greater in moderate versus severe asthmatics. Differences in the deposition of proteoglycans within the airway smooth muscle layer of moderate versus severe asthmatics potentially impact on the functional behaviour of the airway smooth muscle in these two groups of patients.

Adult↗
PubMed2005

Gastric epithelioid haemangioendothelioma: a rare cause of upper gastrointestinal bleeding.

Vascular tumours of the stomach are rare, representing 0.9%-3.3% of all gastric neoplasms. A 58 year old man was admitted as an emergency with a one day history of haematemesis and melaena. He underwent an emergency laparotomy for a tumour in the lesser curve of the stomach. The tumour showed the characteristic histological and immunohistochemical features of epithelioid haemangioendothelioma. Surgery in the form of wide excision seems to be the treatment of choice for this rare neoplasm. This case highlights the difficulty in diagnosing this rare tumour preoperatively and emphasises the need for long term follow up in view of its uncertain metastatic potential.

Anastomosis, Roux-en-Y↗
PubMed2002

Mesenchymal-epithelial interactions in lung development and repair: are modeling and remodeling the same process?

We propose that lung morphogenesis and repair are characterized by complex cell-cell interactions of endodermal and mesodermal origin, leading to (or returning back to) an alveolar structure that can effectively exchange gases between the circulation and the alveolar space. We provide the developmental basis for cell/molecular control of lung development and disease, what is known about growth and transcription factors in normal and abnormal lung development, and how endodermal and mesodermal cell origins interact during lung development and disease. The global mechanisms that mediate mesenchymal-epithelial interactions and the plasticity of mesenchymal cells in normal lung development and remodeling provide a functional genomic model that may bring these concepts closer together. We present a synopsis followed by a vertical integration of the developmental and injury/repair mechanisms.

Aging↗
PubMed2001

Characterization of four new monoclonal antibodies that recognize mouse natural killer activation receptors.

With the aim of identifying natural killer (NK) activation receptors, we immunized BALB/c mice with (BALB/cxB6)F1 NK LAK cells and made B-cell hybridomas. These were screened for monoclonal antibody (MAb) reacting with an NK activation receptor by using an antibody-induced redirected lysis (AIRL) assay against FcR-bearing P815 targets. Four hybridomas, clones 1C10, 1F10, 2D10 and 4G4, were selected for further characterization. Protein G-purified MAbs from these clones activated both resting and IL-2 activated B6 or F1 NK cells in the AIRL assay. 1F10 MAb, but not the other three MAbs, could compete for the binding of anti-NK1.1 (PK136) MAb to F1 NK cells. The four MAbs were screened for their ability to bind to or activate NK cells from the mouse strains SJL/J, DBA/2, 129/J, C3H/J, and BALB.K. None showed activity except IC10, which could bind to and activate SJL/J NK cells. When members of the NKR-P1 family from both B6 mice (A, B, and C genes expressed) and SJL mice (only A and B genes expressed) were expressed in Jurkat cells and tested for their antibody reactivity, PK136 MAb was found to recognize B6 NKR-P1C and SJL/J NKR-P1B; IC10 MAb was found to recognize NKR-P1-A, -B and -C from B6, but not NKR-P1A or -B from SJL/J; and 1F10 MAb was found to react only with B6 NKR-P1C.

Animals↗
PubMed2001

Co-localization of the inositol 1,4,5-trisphosphate receptor and calreticulin in the equatorial segment and in membrane bounded vesicles in the cytoplasmic droplet of human spermatozoa.

Modulation of the intracellular calcium concentration within mammalian spermatozoa is important in several pre-fertilization events including hyperactivated motility and the acrosome reaction. To identify calcium binding proteins (CBP) potentially regulating these processes, a (45)Ca overlay technique was employed on 2-D blots of human sperm extracts. Microsequencing by Edman degradation and CAD mass spectrometry identified a relatively abundant 60.5 kDa CBP with a pI of 4.2 as calreticulin (CRT). Immunofluorescent labelling with anti-CRT antibodies localized CRT to the acrosome, with highest fluorescence in the equatorial segment, and in the cytoplasmic droplets of 94 and 48% of human spermatozoa respectively. Double immunolabelling experiments demonstrated co-localization of CRT and the inositol 1,4,5-trisphosphate receptor (IP(3)R) in the acrosome, in the equatorial segment, and vesicular structures in the cytoplasmic droplets of the neck region. Electron microscopic immunogold labelling localized CRT to the equatorial segment of acrosome-reacted spermatozoa and to membrane-enclosed vesicles within the cytoplasmic droplet of both acrosome-intact and acrosome-reacted spermatozoa. Localization of the IP(3) receptor to the CRT-containing vesicles, in the sperm neck and to the acrosome, suggests that capacitative calcium entry in human spermatozoa may be regulated from these putative calcium storage sites.

Acrosome↗
PubMed2001

Conversion to core biopsy in preoperative diagnosis of breast lesions: is it justified by results?

AIMS: In recent years there has been increased use of core biopsy for the preoperative diagnosis of screen detected and symptomatic breast lesions. The aim of this study was to compare the quality assessment parameters for preoperative diagnosis by fine needle aspiration cytology (FNAC) before conversion to core biopsy with those for core biopsy after conversion in screening and symptomatic practice. Accuracy of typing and grading of tumours on core biopsy was assessed. METHODS: Correlation of FNAC (C1-5) and core biopsy (B1-5) results (total of 1768 cases) with subsequent available resection histology was performed for 473 FNAC samples in 1997/98, 349 core biopsies in 1998/99 performed in symptomatic practice, for 561 FNAC samples in 1997/98, and 385 core biopsies in 1998/99 performed in screening. Quality assessment parameters were calculated using the methodology detailed in the National Health Service Breast Screening Programme guidelines for cytology practice. RESULTS: Increased absolute and complete specificity, lower inadequate rates, and lower suspicious rates were found for core biopsy compared with FNAC in both symptomatic and screening practice. Typing of tumours was attempted in 86.7% of core biopsies in symptomatic practice and was accurate in 93.6% (132 of 141 where type was stated). Grading of tumours was attempted in 63.5% of invasive carcinomas, with the provisional grade on core biopsy being confirmed on later histology in 75% of grade 1 cases, in 70% of grade 2 cases, and in 86% of grade 3 cases. No case provisionally graded as 1 was subsequently found to be grade 3 and no provisionally grade 3 case was found to be grade 1. CONCLUSION: Conversion to core biopsy for the preoperative diagnosis of breast lesions increases specificity and reduces inadequate and suspicious rates. Grading and typing of tumours and assessment of oestrogen receptor status by immunocytochemistry is also possible in core biopsy, thereby increasing diagnostic information available when considering treatment options.

Benchmarking↗
PubMed2000

Stress renders T cell blasts sensitive to killing by activated syngeneic NK cells.

Exposure of primary T cell blasts to stress in the forms of heat, hydrogen peroxide, or high-density growth conditions resulted in a state of enhanced susceptibility to killing by syngeneic IL-2-activated NK cells or lymphokine-activated killer cells, but not to killing by CTL. Cytotoxicity was perforin mediated and was not due to decreased target expression of total MHC class I. The levels of stress used had little effect on cell viability. For thermal stress, sensitization increased with temperature, required a minimum exposure time, and disappeared when cells were given a long enough recovery time. Our data support a model that predicts that activated NK cells play a role in the immunosurveillance of nontransformed stressed cells in normal animals.

Animals↗
PubMed2000

Dissociation between neural and vascular responses to sympathetic stimulation : contribution of local adrenergic receptor function.

Sympathetic activation produced by various stimuli, eg, mental stress or handgrip, evokes regional vascular responses that are often nonhomogeneous. This phenomenon is believed to be the consequence of the recruitment of differential central neural pathways or of a sympathetically mediated vasodilation. The purpose of this study was to determine whether a similar heterogeneous response occurs with cold pressor stimulation and to test the hypothesis that local differences in adrenergic receptor function could be in part responsible for this diversity. In 8 healthy subjects, local norepinephrine spillover and blood flow were measured in arms and legs at baseline and during sympathetic stimulation induced by baroreflex mechanisms (nitroprusside infusion) or cold pressor stimulation. At baseline, legs had higher vascular resistance (27+/-5 versus 17+/-2 U, P=0.05) despite lower norepinephrine spillover (0.28+/-0.04 versus 0.4+/-0.05 mg. min(-1). dL(-1), P=0.03). Norepinephrine spillover increased similarly in both arms and legs during nitroprusside infusion and cold pressor stimulation. On the other hand, during cold stimulation, vascular resistance increased in arms but not in legs (20+/-9% versus -7+/-4%, P=0.03). Increasing doses of isoproterenol and phenylephrine were infused intra-arterially in arms and legs to estimate beta-mediated vasodilation and alpha-induced vasoconstriction, respectively. beta-Mediated vasodilation was significantly lower in legs compared with arms. Thus, we report a dissociation between norepinephrine spillover and vascular responses to cold stress in lower limbs characterized by a paradoxical decrease in local resistance despite increases in sympathetic activity. The differences observed in adrenergic receptor responses cannot explain this phenomenon.

Adrenergic alpha-Agonists↗
PubMed2000

Seattle 5-a-Day Work-Site Project: process evaluation.

The Seattle 5-a-Day Work-Site Project developed a community-based intervention to increase fruit and vegetable intake, using both environmental (including cafeteria and work-site-wide events) and individual strategies. The Employee Advisory Board developed its own protocol from a common skeleton and a minimum set of activities. Small work sites and work sites with fewer female employees delivered more displays, posters, and table tents per employee (p < .01 and p < .05, respectively). Dose was neither related to use of the intervention nor to change in fruit and vegetable intake. Use of informational materials increased fruit and vegetable intake in the cohort of employees with both baseline and follow-up data (p = .05). The intervention was associated both with increased employee use of the intervention (activities and materials) and with increased intake of fruit and vegetables. Work sites with medium average baseline intake were the most responsive. These findings can guide the development of more efficient community-based dietary interventions.

Adult↗
PubMed1999

The NKR-P1B gene product is an inhibitory receptor on SJL/J NK cells.

The mouse NKR-P1 family includes at least three genes: NKR-P1A, -B, -C. Neither surface expression nor function of the NKR-P1B gene product has previously been shown. Here, we demonstrate that the SJL/J allele of the NKR-P1B gene product is expressed on SJL/J NK cells, and is recognized by PK136 mAb. Interestingly, the same mAb does not recognize the NKR-P1B gene product of C57BL/6. We have also generated a novel mAb, 1C10, that recognizes an activation receptor on SJL/J NK cells. Activation of the NKR-P1B receptor-inhibited 1C10 mAb induced redirected lysis and recruited SHP-1, indicating that NKR-P1B is an inhibitory receptor. Therefore, the mouse NKR-P1 gene family, like the Ly49 family, includes both activation and inhibitory receptors.

Amino Acid Sequence↗
PubMed1999

Osteolymphoma (primary bone lymphoma): an Australian review of 70 cases. Australasian Radiation Oncology Lymphoma Group (AROLG).

BACKGROUND: To examine prognostic factors, treatment outcomes and design future studies for Osteolymphoma (OL)--also known as primary bone lymphoma. METHODS: Between 1979 and 1993, 70 patients with OL were treated in nine Australian centres. The effect of patient-, tumour-, and treatment-related factors on local control, distant disease-free survival and overall survival were assessed by multivariate analysis. RESULTS: Most patients (94%) received radiotherapy (RT) (median dose 40 Gy) and 56% received chemotherapy. Multifocal disease was present in 20% of patients. The five year rates of overall survival and local control were 59% and 82%. Although there was a trend towards better results with the addition of chemotherapy, on multivariate analysis, there were no factors identified which appeared to impact upon overall and disease-free survival. Among the distant recurrences, there was a high proportion in bone (33%). Six patients suffered pathological fractures after treatment. CONCLUSION: High rates of local control were achieved by RT, but the overall survival remains relatively poor, worse than nodal lymphoma. The natural history of the disease suggests that OL may be a distinct entity, different to nodal lymphomas, so the results of clinical trials in nodal lymphoma may not be relevant to OL. Prospective studies could define the outcome of combined modality therapy and set a benchmark for testing further proposals, as well as improving our knowledge of the clinical features of OL.

Adult↗
PubMed1997

The hypertension of autonomic failure and its treatment.

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.

Aged↗
PubMed1997

Self-efficacy as a predictor of dietary change in a low-socioeconomic-status southern adult population.

There is an increasing emphasis on designing health promotion interventions for low-socioeconomic-status (SES) individuals. However, many previously developed behavior change tools have not been tested in this population. Self-efficacy was measured at pre- and postintervention as part of a randomized clinical trial to reduce cholesterol levels in rural low-SES Southern adults. A 22-item scale was designed and validated to measure subjects' confidence in their abilities to make dietary changes. High mean self-efficacy was noted in both control and intervention subjects at pre- and postintervention. Mean self-efficacy score was a significant predictor of dietary change at both preintervention and postintervention. This study demonstrates that self-efficacy is a predictor of ability to make dietary changes in a low-SES rural population. This finding is of significance to researchers and practitioners wishing to design theory-based health promotion interventions in this population.

Diet↗
PubMed1997

Using a brief household food inventory as an environmental indicator of individual dietary practices.

OBJECTIVES: This study examined whether foods in household pantries are an indicator of house-hold members' diet. METHODS: In a random-digit-dial survey, the presence in the house of 15 high-fat foods was assessed with whoever answered the phone. A randomly selected household member was surveyed about diet-related behaviors (n = 1002). RESULTS: Individuals in the precontemplation stage of dietary change had more high-fat foods in their pantry than those in maintenance (means of 7.4 and 5.8, respectively). Individuals with low-fat pantries had an intake of 32% energy from fat vs 37% for those with high-fat pantries. CONCLUSIONS: Household food inventories are a practical and valid approach to monitoring dietary behaviors in community-based studies.

Adult↗
PubMed1997

Application of a behavioral approach to measuring dietary change: the fat- and fiber-related diet behavior questionnaire.

This study reports the validity, reliability, and responsiveness of a 33-item fat- and fiber-related behavior questionnaire (FFB) and describes how this instrument provides insight into the process of adopting healthy diets. Data are from the Eating Patterns Study, a randomized clinical trial of a physician-delivered, self-help intervention to reduce fat and increase fiber intake. Intervention (n = 850) and control participants (n = 945) completed both a food frequency questionnaire and the FFB at baseline and at 3 and 12 months postintervention. Validity, as assessed by correlation of the FFB with the food frequency questionnaire at baseline, was 0.53 for fat (fat scale with percentage energy from fat) and 0.50 for fiber (fiber scale with fiber g/1000 kcal; both P < 0.001). Reliability, as assessed by the intraclass correlation in controls across all three time points, was 0.77 for the fat scale and 0.74 for the fiber scale (both P < 0.001). The largest changes in fat-related behavior were in avoiding fat as a flavoring and in using specially manufactured low-fat foods, and the largest changes in fiber-related behavior were in substituting high-fiber versions of common foods. Overall, the FFB was a reasonably valid and reliable measure of dietary intake, which provided insight into the behavioral effects of the dietary intervention.

Behavior Therapy↗