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Biomedical subjects

B J Allen

Publications and source records attributed to B J Allen.

At least 19 recordsLinked to original sources

TGF-beta blocks early but not late differentiation-specific gene expression and morphologic differentiation of 3T3 T proadipocytes.

Transforming growth factor-beta (TGF-beta) inhibits morphologic differentiation of BALB/c 3T3 T cells as well as other proadipocyte models. Our prior studies suggested that TGF-beta may act only during the early stages of differentiation induction. However, we did not determine whether TGF-beta was differentially effecting expression of any of the various differentiation-specific genes or if it could cause down-regulation of these genes in differentiated cells. Therefore, in the current study we tested the effects of exogenous TGF-beta (0.01-5.0 ng/ml) on morphologic differentiation and on differentiation-dependent gene expression (Northern and slot blot analyses) at various times during differentiation. When induced to differentiate, 3T3 T cells first undergo predifferentiation growth arrest and from this state molecular, biochemical, and morphological differentiation proceeds. Here it was found that when added prior to the onset of differentiation, TGF-beta was a potent inhibitor or morphologic differentiation as well as of the expression of differentiation-specific genes such as lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPD). However, once morphologic differentiation began, TGF-beta was ineffective in blocking differentiation. In addition, exposure of fully differentiated cells to TGF-beta for up to 72 hours caused no decrease of differentiation-specific genes and even a 7-day treatment caused no morphologic dedifferentiation. Tumor necrosis factor also had no detectable effect on fully differentiated cells.

3T3 Cells

Adjuvant metoprolol improves efficacy of class I antiarrhythmic drugs in patients with inducible sustained monomorphic ventricular tachycardia.

Inducible ventricular tachycardia frequently persists despite solitary class I antiarrhythmic drug therapy. To determine the effect of metoprolol as adjuvant therapy, 19 patients with clinical ventricular tachycardia with baseline inducible sustained monomorphic ventricular tachycardia and persistently inducible ventricular tachycardia despite class I drugs were evaluated. Eight of 19 patients (42%) became noninducible when metoprolol was added to class I drug therapy. Sixteen of 19 patients (84%) were harder to induce or noninducible on a regimen of adjuvant metoprolol therapy. In evaluating the clinical characteristics of the 19 patients, no significant differences were found between patients who were persistently inducible and those rendered noninducible. In evaluating the electrophysiologic characteristics, the group eventually rendered noninducible had a significantly shorter baseline induced cycle length (259 +/- 27 vs 305 +/- 53 msec). Combination class I drug and metoprolol therapy significantly lengthened the ventricular effective refractory period in both groups compared with baseline. The long-term follow-up was excellent in all patients remaining on metoprolol in the noninducible group. Therefore adjuvant metoprolol therapy creates a significant improvement in a number of patients with persistently inducible ventricular tachycardia despite class I drug therapy.

Adult

Local control of subcutaneous murine melanoma xenografts in nude mice by neutron capture therapy.

The systemic administration of enriched [10B]D,L-p-boronophenylalanine results in the selective uptake of boron by Harding-Passey melanoma xenografts in the nude mouse model. The boron-10 located in the tumour cells acts as a radiation sensitizer for thermal neutron irradiation. The nude mouse model can be successfully used to demonstrate that regression and local control of melanoma can be achieved by neutron capture therapy. Control is a manifestation of the high linear energy transfer radiation released after neutron capture by boron-10, and does not result from an equal fluence of neutrons alone. Histological examination of remnant tumour beds 300 days after treatment shows the presence of isolated melanoma cells. However, these cells are few in number and appear incapable of division.

Animals

A total body nitrogen facility for paediatric use.

The design, calibration and evaluation of a facility for in vivo prompt gamma neutron capture analysis of total body nitrogen in children is described. The patient is scanned in both supine and prone positions, across a vertically collimated beam from a 1 GBq 252Cf fission source. Two NaI(T1) detectors are placed on either side of the patient, perpendicular to both the neutron beam and the scanning direction. The effective dose equivalent delivered to a child during an 840 s scan is approximately 0.14 mSv (QF = 10). Correction factors for nitrogen background (width-dependent), hydrogen background (1-4% of hydrogen gamma ray peak) and the differential attenuation of nitrogen and hydrogen gamma rays (width-dependent) can be applied to the measured nitrogen-to-hydrogen gamma ray counts ratio. By using the mass of hydrogen (based on body mass and fat mass) as an internal standard, the nitrogen mass can then be determined. Measurements with a urea-containing box phantom show that the current precision (CV) of the net nitrogen counts and of the nitrogen-to-hydrogen counts ratio is +/- 2.0% and +/- 1.5%, respectively. Using small anthropomorphic and other phantoms, estimation of the mass of nitrogen has a precision of +/- 1.4 to 5.4% and an accuracy of 97.1 to 101.5%.

Australia

Nitrogen deposition in malnourished children with cystic fibrosis.

To determine the protein nutritional status of 21 malnourished children with cystic fibrosis (CF), total body nitrogen (TBN) was measured and the results were compared with 21 control subjects. CF patients demonstrated a lower TBN (P less than 0.001). When matched for height (n = 10) or bone age (n = 13), the CF patients still had a depressed TBN/height or TBN/lean body mass (P less than 0.05). To assess nitrogen deposition during nutritional rehabilitation, repeat TBN measurements were performed on the 21 CF patients. Nitrogen deposition ranged from -230 to 550 g/y and correlated with weight velocity (r = 0.78, P less than 0.001). Increased nitrogen deposition (greater than 150 g/y) was generally associated with normal height gain (height velocity SD score greater than -2.00) and weight gain (greater than 2.0 kg/y). Decreased nitrogen deposition was associated with poor weight gain but did not preclude normal linear growth. These data suggest an important role for TBN estimations in defining protein nutritional status in children and indicate that skeletal growth can continue in the presence of minimal nitrogen deposition.

Adolescent

Monte Carlo study of thermal flux profiles and body correction factors for body protein measurements of obese subjects.

In previous calculations for Total Body Nitrogen measurements of children, the anterior/posterior thermal neutron flux profile with depth was found to be fairly flat after an initial rise. However, for obese adults significant variations are found in the flux profile with the central flux value being as low as 20% of the peak value. The significance of these flux variations is examined. Correction factors are calculated for the varying attenuation of the nitrogen and hydrogen photons by a range of obese bodies. The calculations included the effect of the thermal flux profile as well as that of an outer layer of low nitrogen content adipose tissue. The bodies are assumed to have a homogeneous hydrogen content. A study of four obese body models with varying sex and fat content shows that the correction factors do not vary much between males and females. This is surprising since the female models are assumed to have a surface fat layer twice as thick as for the male models. The correction factors are found to be only slightly sensitive to the thermal flux variations with depth.

Adipose Tissue

Total-body nitrogen by neutron activation in maintenance dialysis.

The nutritional status of 35 patients on continuous ambulatory peritoneal dialysis (CAPD) was assessed by the traditional methods of dietary history and anthropometric measurements, and was compared with simultaneous measurements of dietary protein intake (DPI) calculated from urea generation rate and total-body nitrogen (TBN) assessment by prompt neutron activation analysis (PNAA). DPI as determined by dietary recall was significantly higher than calculated DPI (1.04 +/- 0.42 v 0.84 +/- 0.28 g/kg/d; P less than 0.001). Anthropometric measurements did not differ significantly from the predicted normal values for sex, height, and age. However, PNAA measurements of TBN demonstrated significant nitrogen depletion, being 88.2% of normal for males (P less than 0.001) and 87.5% of normal for females (P less than 0.002); TBN correlated significantly with DPI calculated from urea generation rate (P less than 0.05). Assessment of these 35 patients 17.5 +/- 4.4 months later, demonstrated that patients who died or suffered serious morbidity requiring transfer from CAPD (n = 10) had significantly lower TBN than those who remained on CAPD or underwent successful renal transplantation (n = 25): 80.0% v 93.2% of normal (P less than 0.01). No difference in anthropometric measurements was observed between the two groups of patients. Eleven patients on maintenance home or satellite hemodialysis underwent identical dietary, anthropometric, and TBN assessments and results were similar to those obtained in the CAPD population, although no correlation with calculated DPI and TBN was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption

The potential of neutron capture therapy in the management of uncontrollable localised tumours.

The role of Neutron Capture Therapy for the treatment of uncontrollable, localised tumours is examined. Several boron carrier biochemicals are already in use for the selective accumulation of boron in cancer cells, and therapeutic boron concentrations have been achieved in glioblastoma and melanoma in animal models and in patients. Local control of glioblastoma and subcutaneous melanoma has been reported after thermal neutron irradiation. Different neutron beam requirements apply for the treatment of these cancers, in the former case a thermal beam is adequate but a more penetrating epithermal beam is needed for the treatment of deep-seated tumours. A thermal facility for small animal irradiations is available in Australia, and the development of a patient thermal/epithermal facility is under active consideration.

Boron

Body protein of patients undergoing haemodialysis.

The total body protein status of 18 patients undergoing regular haemodialysis was assessed by measuring total body nitrogen (TBN) using in vivo neutron activation analysis (NAA). Eighteen healthy controls, who were selected according to their height, age and sex match with the patients were also measured. The male and female patients were both found to have lower mean values for total body protein (P less than 0.01, P less than 0.025 respectively) although they had similar weights compared with their matched controls. Seven patients were measured on further occasions and only two patients showed a change in their body protein. One female showed an increase of 11 per cent in body protein (with an increase of 25 per cent in body weight) after intensive nutritional repletion therapy. In vivo NAA provides a direct means of measuring body protein and is a reliable method to monitor changes with treatment regimes.

Adult

Determination of total body water by Fourier transform infrared analysis.

A new technique for determining body water using deuterium isotope dilution and Fourier transform infrared (FTIR) analysis is described. The advantages of the FTIR over conventional dispersion and filter infrared instruments include greater flexibility through computer controlled operations and availability of 'on-line' analytical software. The technique was further improved by the development of a simple procedure for determining D2O concentration in untreated serum samples. A validation study of six normal adults showed that the fat-free-mass determined from the deuterium-space (total body water) correlated well with the results obtained by total body nitrogen (r = 0.997), total body potassium (r = 0.996) and anthropometric (r = 0.995) measurements.

Adult

Changes in body protein composition following aortic reconstruction.

Major surgery initiates a stress response due to the body's neuroendocrine reaction which leads to a breakdown of muscle protein with an increased urinary nitrogen excretion and a negative nitrogen balance. In vivo neutron activation analysis (IVNAA) is a technique which measures total body nitrogen. A total of 23 IVNAA studies were performed in six patients having aortic reconstruction to assess the effect of this major operation on body nitrogen and to determine the time required for a return to the pre-operative state. Aortic surgery caused a mean decrease of 2.9% in bodyweight (from a mean of 65.4 kg to 63.5 kg) but a much greater decrease of 9.9% in total body nitrogen (from a mean of 1778 g to 1602 g). Only two of six patients had recovered to pre-operative values by the end of the study period which extended for a mean of 92 days.

Aged