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Biomedical subjects

S Burton

Publications and source records attributed to S Burton.

At least 55 records · Page 3Linked to original sources

Gene transfer into the rat renal glomerulus via a mesangial cell vector: site-specific delivery, in situ amplification, and sustained expression of an exogenous gene in vivo.

To evaluate the pathophysiological function of specific molecules in the renal glomerulus, selective, sustained, and modifiable expression of such molecules will be required. Towards achieving this end, we devised a gene transfer system using the glomerular mesangial cell as a vector for gene delivery. A reporter gene which encodes bacterial beta-galactosidase was introduced into cultured rat mesangial cells, and the stable transfectants were transferred into the rat kidney via the renal artery, leading to selective entrapment within the glomeruli. In the normal kidney, the reporter cells populated into 57 +/- 13% of glomeruli site specifically, and the expression of beta-galactosidase was sustained for 4 wk and declined thereafter. Within the glomerulus, some of the reporter cells remained in the glomerular capillaries, while others repopulated the mesangial area and, in part, extended their cytoplasmic processes toward the surrounding capillaries. When the cells were transferred into glomeruli subjected to transient mesangiolysis induced by monoclonal antibody 1-22-3, in situ expression of beta-galactosidase was amplified 7-12-fold, and the enhanced level of expression continued for up to 8 wk. The mesangial cell vector system thus achieves site-specific delivery of an exogenous gene into the glomerulus and is amenable to in situ amplification and sustained expression by preconditioning of the target site.

Animals↗

Pulmonary histopathologic findings, acid-base status, and absorption of colostral immunoglobulins in newborn calves.

A study was conducted to investigate whether aspiration of amniotic fluid is associated with a deleterious effect on absorption of colostral immunoglobulins or on blood gas and acid-base values of healthy newborn calves. Fourteen calves purchased from commercial sources were transported to a research facility immediately after birth and fed colostrum with known concentrations of immunoglobulins. Blood samples for gas analyses were collected within 5 hours of birth, 24 hours later, and prior to euthanasia. Between 3 and 5 days of age, calves were euthanatized by an overdose of barbiturates. Eleven calves had evidence of bronchoaspiration of amniotic fluid, as determined by presence of meconium, squamous epithelium, or keratin in histologic sections of fixed lung or by cytologic analysis of bronchoalveolar lavage fluid. Blood gas tensions and pH were within reference ranges in 11 of 14 calves. Aspiration of amniotic fluid could not be linked to any specific changes in blood gas tensions, acid-base status, or absorption of colostral immunoglobulins. Presence of keratin and meconium in the lungs often was accompanied by mild exudative alveolitis and focal atelectasis. It was concluded that aspiration of small amounts of amniotic fluid with or without meconium is common in calves and is not associated with hypoxemia, respiratory acidosis, or failure of passive transfer.

Acid-Base Equilibrium↗

Stereotactic core breast biopsy. An alternative.

Stereotactic core breast biopsy provides diagnostic accuracy equal to open surgical biopsy and is more comfortable and more cost effective than open surgical biopsy. A series of 75 patients is presented, of which 15 (20%) had positive findings, including 11 cancers and 4 atypical hyperplasias. The authors discuss indications, methods, patient preparation and results relating to this series of patients, including initial use of lateral compression for stereotactic core biopsies. This procedure promises to become the procedure of choice for nonpalpable, mammographically detected, indeterminate lesions of the breast and is likely to alter the conventional roles for the surgeon and radiologist regarding breast biopsy.

Adult↗

Screening for bacteriuria in urological patients using reagent strips.

A rapid and accurate ward-based method of diagnosing urinary infection would be of value in determining the prescription of antibiotics in pre-operative urological patients. This study describes the sensitivity and specificity of a screening technique based on commercially available reagent strips in the diagnosis of urinary infection. A total of 222 pre-operative samples and 83 post-operative samples was studied to compare the results of formal urine culture and reagent strips. Using a definition of a positive nitrite or a positive leucocyte esterase on the reagent strips as being suggestive of infection, it was found that the strips had a sensitivity of 91% and a specificity of 85% compared with formal culture in pre-operative samples. The results from post-operative samples were less satisfactory, the strips having a sensitivity of only 71% and specificity of 55%. The strips were insensitive but specific in the identification of pyuria in pre-operative specimens. These results suggest that reagent strips can be used as a ward-based method to identify men at risk of infection before urological procedures, and may allow selectivity in the use of peri-operative antibiotics.

Adolescent↗

Stabilisation and immobilisation of penicillin amidase.

Penicillin amidase was coupled to a periodate-oxidised dextran by reductive alkylation in the presence of sodium cyanoborohydride. A loss of activity (25%) was observed but the conjugate enzyme dextran was more thermostable than the native enzyme. Native and dextran-conjugated penicillin amidase were immobilised on amino activated silica (Promaxon, Spherosil, Aerosil) by a classical method using glutaraldehyde for the native enzyme and reductive alkylation for the modified enzyme. Good relative activity of the enzymes was obtained after insolubilisation. Immobilisation of both native and modified enzymes resulted in the thermostabilisation of the penicillin amidase.

Enzyme Stability↗

Cost control under the DRG system.

The change in the method of reimbursing hospitals from a retrospective to a prospective payment system known as diagnosis-related group (DRG) caused hospitals to increase control over their costs. This article details a system for cost control that gives timely feedback on the hospital's reimbursement position and allows the hospital to recognize areas that require their attention for proper control over costs. Three variances are discussed: controllable variance, standard variance, and total variance. The system was tested on a hospital found to have enough information for this purpose. The results of this application indicate that the system is as feasible in the hospital industry as it is in other industries.

Cost Control↗

The role of the N-terminus of the large subunit of ribulose-bisphosphate carboxylase investigated by construction and expression of chimaeric genes.

The genes for the large and small subunits of ribulose bisphosphate carboxylase/oxygenase (Rubisco) from Anacystis nidulans have been expressed in Escherichia coli under the control of the lac promoter to produce active enzyme. The enzyme can be purified from the cells to yield up to 200 mg Rubisco/l cultured bacteria, and is indistinguishable from the enzyme extracted from A. nidulans. In order to investigate the role of the N-terminus of the large subunit in catalysis, chimaeric genes were constructed where the DNA coding for the 12 N-terminal amino acids in A. nidulans was replaced by DNA encoding the equivalent, but poorly conserved, region of either the wheat or maize large subunit. These genes, in constructs also containing the gene for the A. nidulans small subunit, were expressed in E. coli and produced enzymes with similar catalytic properties to the wild-type Rubisco of A. nidulans. In contrast, when the N-terminal region of the large subunit was replaced by unrelated amino acids encoded by the pUC8 polylinker, enzyme activity of the expressed protein was reduced by 90% under standard assay conditions, due to an approximately tenfold rise in the Km for ribulose 1,5-bisphosphate. This confirms that the N-terminus of the large subunit has a function in catalysis, either directly in substrate binding or in maintaining the integrity of the active site.

Chimera↗

Changes in oxytocin and vasopressin secretion during sexual activity in men.

We measured plasma oxytocin (OT) and arginine vasopressin (AVP) concentrations in 13 normal men during sexual arousal and ejaculation. Mean plasma AVP increased from 1.4 +/- 0.2 (+/- SE) to 5.3 +/- 1.7 pmol/L (P less than 0.05) during arousal, but there was no significant change in OT. In contrast, at ejaculation mean plasma OT rose from a basal value of 1.4 +/- 0.3 to 7.3 +/- 0.6 pmol/L (P less than 0.01) and then fell to basal concentrations in 30 min. AVP, however, had returned to basal levels at the time of ejaculation and remained stable thereafter. We conclude that in man AVP is secreted during sexual arousal, and there is, subsequently, a selective release of OT at the time of ejaculation.

Adult↗

Effectiveness of antiandrogens in the rat.

In order to determine the relative effectiveness of several antiandrogens, megace (megestrol acetate), flutamide and RU23908 were administered in optimal doses (20 mg./kg., 10 mg./kg. and 20 mg./kg.) subcutaneously daily to adult male Sprague-Dawley rats for 14 and 28 days and their effects on ventral prostate, seminal vesicles, and serum testosterone were determined. To avoid the possibility that these agents might also work through inhibition of testosterone production, all the treated animals were castrated and then implanted with a testosterone-filled silastic pellet to maintain a constant exogenous source of the androgen. A castrate placebo-treated group, an implanted placebo-treated group, and an intact placebo-treated group served as controls. The mechanisms and sites of action of the antiandrogens were thus limited to the target organs. Serum testosterone levels were equivalent at all time periods for all groups except the castrate controls which were significantly lower. The ventral prostates of the flutamide and RU23908 groups were similar and reduced 75% and 85% at 14 and 28 days respectively; the group receiving megace experienced prostatic regression of 49% and 65% which was significantly less of a reduction than that of the flutamide or RU23908 group. Results for seminal vesicle weights indicated similar trends. The administration of both steroidal (megace) and nonsteroidal (flutamide and RU23908) antiandrogens yielded a significant reduction of androgen dependent tissue weights relative to the intact control group and the implanted placebo group but still not as great a reduction as the effect produced by castration. In the rat, castration remains the optimal means of inducing regression of androgen dependent tissues.

Androgen Antagonists↗

Acute treatment with desipramine stimulates melatonin and 6-sulphatoxy melatonin production in man.

Acute administration of the antidepressant drug desipramine (DMI) in man, increased evening melatonin secretion, which reached peak plasma levels 2-4 h earlier than after placebo administration. The increase at set time points 21.00 h-22.00 h was directly proportional to an individual's integrated night-time secretion of melatonin. We have shown that this stimulation was not an effect of DMI inhibition on the hepatic metabolism of melatonin to 6-sulphatoxy melatonin (aMT6s), indeed aMT6s is in itself a good index of the evening melatonin rise. The stimulation of early evening melatonin by DMI might be exploited as a simple pineal function test.

Adult↗

Clinical studies of the effect of (+) and (-)-oxaprotiline upon noradrenaline uptake.

In six normal male subjects the mydriatic effect of tyramine eye drops was inhibited by 1 day's treatment with desipramine and the (+)- but not the (-)-enantiomer of oxaprotiline. In the same experiment, the secretion of melatonin was increased after treatment with (+)- but not with (-)-oxaprotiline. The effects of (+)-oxaprotiline and of desipramine treatment were similar, as were those of (-)-oxaprotiline and placebo. These findings extend to clinical studies the demonstration in animal experiments of stereo-specificity for the effects of (+)- and (-)-oxaprotiline upon noradrenaline uptake. A comparison of the effects of the two enantiomers should provide an ideal strategy for studying effects of noradrenaline uptake blockade in clinical studies.

Anthracenes↗