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Biomedical subjects

A Taylor

Publications and source records attributed to A Taylor.

At least 595 records · Page 33Linked to original sources
PubMed1988

Technetium-99m MAG3 kit formulation: preliminary results in normal volunteers and patients with renal failure.

Previous studies have shown that [99mTc]mercaptoacetyltriglycine (MAG3) purified by high performance liquid chromatography (HPLC) is a very promising new renal imaging agent which has characteristics very similar to [131I]orthoiodohippurate. An easily prepared kit formulation has been developed and evaluated in ten normal volunteers and three patients on hemodialysis. The average radiochemical purity was 96.6%. There were no adverse reactions. In the volunteers, the relative uptake +/- 1 s.d. was 49.1% +/- 2.6% for the right kidney and 50.9% +/- 2.6% or the left kidney. Urine activity was 71.4% +/- 6.4% of the injected dose at 30 min and 94.4% +/- 2.2% at 180 min. The 60-min plasma clearance was 340.0 +/- 79.0 ml/min and the volume of distribution was 5.15 +/- 1.1I. Approximately 0.5% of the injected dose was present in the gallbladder at 30-60 min postinjection. Gut activity was not present 30-60 min postinjection but reached 1% of the injected dose by 3 hr. In the hemodialysis patients, approximately 1% of the injected dose was present in the gallbladder and 0.5% in the gut at 30-60 min; gut activity increased to approximately 5% at 3 hr. In summary, results using the kit formulation compare favorably to previously published data using the HPLC purified material. Based on these preliminary results, the kit formulation is expected to have widespread clinical utility.

Adult↗
PubMed1988

Effects of altered physiologic states on clearance and biodistribution of technetium-99m MAG3, iodine-131 OIH, and iodine-125 iothalamate.

Technetium-99m mercaptoacetyltriglycine [( 99mTc]MAG3) is a new renal radiopharmaceutical with biologic properties similar to iodine-131 orthoiodohippuric acid [( 131I]OIH). MAG3 may be used as a replacement for [131I]OIH and/or [99mTc]DTPA. For this reason, we compared the effects of several potential adverse clinical conditions on the clearance and biodistribution of MAG3, OIH and a GFR marker. To simulate renal failure, five mice underwent bilateral renal pedical ligation. Twenty-four hours after surgery they were injected with MAG3 and OIH and killed 2 hr postinjection. Compared to sham operated controls, liver activity for MAG3 and OIH increased from 0.2% to 14.1% and 0.1% to 13.9%, respectively, while intestinal activity increased from 1.3% to 8.9% for MAG3 and 0.2% to 7.7% for OIH. Constant infusion studies were performed in rats to evaluate the effects of increased plasma organic acid levels, mannitol diuresis, dehydration, and acid/base imbalance on the clearance of OIH, MAG3, and [125I]iothalamate. No differences were noted between the OIH and MAG3 clearances following diuresis and dehydration and the differences involving acid/base imbalance were minimal. Dehydration depressed the clearance of [125I]iothalamate more than that of OIH or MAG3. Para-aminohippurate (PAH) infusion inhibited the clearance of MAG3 more than OIH supporting proximal tubular transport for MAG3; PAH had no effect on [125I]iothalamate. In summary HPLC purified MAG3 behaved similarly to OIH under adverse physiologic conditions and the data continue to support the use of MAG3 as a potential clinical substitute for OIH.

Acid-Base Imbalance↗
PubMed1988

Fracture of the penis--review with case report.

Fracture of the penis is a rare injury. Controversy exists regarding conservative versus operative management. A case of penile fracture managed conservatively is reported with a brief review of the literature.

Adult↗
PubMed1988

Radioimmunodetection of human melanoma with indium-111-labeled monoclonal antibody.

The purpose of the study was threefold: (1) to evaluate the efficacy of an 111In-labeled murine monoclonal antibody (ZME-018) directed against a heavy molecular weight melanoma associated glycoprotein in localizing metastatic disease; (2) to determine the effect of unlabeled antibody mass (2.5, 5, 10, 20, and 40 mg) on labeled antibody blood clearance, biodistribution and lesion detection; (3) to estimate radiation dosimetry. Twenty-five patients with previously documented disease received an intravenous infusion of 2.5 to 40 mg of monoclonal antibody with 1 mg of the antibody labeled with 5 mCi of 111In. There were no acute reactions. Patients were scanned without computer enhancement or background subtraction techniques at 24 and 72 hr after injection. Imaging detected tumor in 14/18 (78%) patients with active disease, identified 24/44 (77%) of lesions greater than 1 cm and changed or specifically directed patient management in 22% (4/18) patients with tumor. There was a prolongation in blood clearance associated with decreased liver and spleen activity following administration of 20 and 40 mg of antibody compared to the three lower antibody dose levels. Assuming a biodistribution similar to [111In]ZME-018, the radiation dose delivered to normal tissues by [90Y]ZME-018 would restrict its use as a routine vehicle for radioimmunotherapy; however, it may be possible to deliver substantial tumor doses in selected patients.

Adult↗
PubMed1987

The phosphorylation of nucleoplasmin by casein kinase-2 is resistant to heparin inhibition.

Highly purified preparations of casein kinase-2 from the nuclei of Xenopus laevis oocytes and from calf thymus can phosphorylate in vitro purified nucleoplasmin from X. laevis oocytes and eggs. The phosphorylation of nucleoplasmin by both kinase preparations is quite insensitive to heparin in contrast with casein phosphorylation which is completely abolished by heparin concentrations above 10 micrograms/ml. However, the phosphorylation of nucleoplasmin and casein are inhibited in a very similar fashion by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a well characterized specific inhibitor of casein kinase-2. Similarly, nucleoplasmin phosphorylation by the oocyte enzyme can be stimulated several-fold by spermine, another characteristic of this enzyme. These findings indicate that the phosphorylation of nucleoplasmin by purified casein kinase-2, while showing typical response to DRB and spermine, exhibits anomalous behavior in its resistance to heparin inhibition. It is possible that the large clusters of acidic amino acids in nucleoplasmin permit this substrate to interact with the enzyme more efficiently than other protein substrates. Heparin is generally considered a potent and specific inhibitor of casein kinase-2. This study, however, questions the validity of utilizing heparin inhibition as a criterion for casein kinase-2 involvement.

Animals↗
PubMed1987

The effect of sodium aurothiomalate (myochrysin) on the distribution of calcium, magnesium, copper, zinc and iron in the rat.

Sodium aurothiomalate was given to male Wistar rats (initial body weights: 150 g) by subcutaneous (s.c.) injection at doses of up to 7.5 mg/kg (corresponding to 4.27 mg gold/kg), twice a week, for 4-5 weeks. The concentrations of Ca, Mg, Fe, Cu and Zn were measured in serum, urine, faeces and in the liver, kidney, spleen, heart, lung, testis, bone and muscle. Kidney cytosol was separated by gel chromatography and the fractions analysed for protein, copper, zinc, iron and gold concentrations. The concentration of copper was increased 5-fold in kidney while smaller increases of zinc in kidney, copper in muscle, iron in muscle and testis and calcium in spleen were found. There was a significant reduction in the concentration of copper in serum. Kidney cytosol from gold-treated but not from control animals contained a low molecular weight protein which was associated with copper, zinc and gold. The rats developed proteinuria and microscopic changes to renal tubular cell structure were also observed. It is suggested that the gold-induced accumulation of copper may follow from an increased rate of synthesis of metallothionein and could be responsible for the renal dysfunction which develops in a proportion of rheumatoid arthritis patients who are treated with gold.

Animals↗
PubMed1987

Raised cerebrospinal-fluid copper concentration in Parkinson's disease.

The cerebrospinal-fluid copper concentration, measured by electrothermal atomisation/atomic absorption spectrophotometry, was significantly higher in 24 patients with untreated, idiopathic Parkinson's disease than in a control population of 34 patients (p less than 0.001). The difference in the in-vitro capacity of copper to damage DNA, measured by the phenanthroline assay was even greater. The high phenanthroline-copper concentration correlated with disease severity (p = 0.02) and with the rate of progression of disease (p less than 0.05). A possible role is suggested for copper-catalysed oxidative mechanisms in the pathogenesis of Parkinson's disease.

Adult↗
PubMed1987

Direct and relayed projection of periodontal receptor afferents to the cerebellum in the ferret.

Field potentials in the cerebellar cortex of the ferret have been studied in response to stimulation of alveolar, muscular and cutaneous branches of the trigeminal nerve. Responses from the alveolar nerves are unusual in their very short latency. Evidence based on latency analysis, frequency following and comparison with other well-known inputs supports the view that the earliest field potentials are due to direct, unrelayed afferents, which terminate as mossy fibres. There is, in addition, a monosynaptically relayed afferent path via mossy fibres. The alveolar nerve afferents concerned with the direct projection are shown to come from periodontal mechanoreceptors and not from cutaneous receptors. No such connections are found from jaw-muscle spindle afferents. The direct and relayed periodontal pathways are both ipsilateral and crossed. They terminate in the cerebellar cortex in the parvermal region of lobules IV, V and VI. The functional significance of the direct periodontal afferent projection is considered particularly in the light of parallels with the vestibular system, which also has direct and relayed cerebellar projections.

Afferent Pathways↗
PubMed1987

Focal synaptic potentials due to discrete mossy-fibre arrival volleys in the cerebellar cortex.

The previously described direct and relayed projections of periodontal afferents to the cerebellar cortex have been examined in detail by extracellular field-potential analysis. Advantage is taken of the very small temporal dispersion of the afferent volleys to permit identification of the presynaptic spike potential of mossy fibres, the subsequent synaptic potential and the firing of granule cells. Changes in form of the presynaptic potential with depth are compared with published descriptions of presynaptic potentials elsewhere. The negative synaptic potential in the granular layer is shown to have a positive aspect in the molecular layer. Granule-cell firing can, under some conditions, yield a population spike interrupting the synaptic potential wave. Records are presented showing all-or-none complex waves, which appear to be single glomerular potentials, not previously described in the mammalian cerebellum. Their distinction from cellular spike potentials is emphasized.

Afferent Pathways↗
PubMed1987

Structure, assembly, and secretion of octameric invertase.

Yeast invertase forms a homo-octamer of core glycosylated subunits during assembly in the lumen of the endoplasmic reticulum. This form has been purified from mutant cells (sec18) in which transport of secreted proteins from the endoplasmic reticulum is blocked. No heterologous protein subunits are found in the purified material. Analysis of invertase derived from wild type cells or from mutant cells blocked at subsequent stages in secretion demonstrates that invertase remains a homo-octamer throughout the pathway even though the extent of subunit glycosylation increases. Purified octameric invertase is dissociated into dimer units that reassociate in the presence of polyethylene glycol. Negatively stained preparations show the dissociated enzyme as individual spheres, whereas octameric invertase appears as four associated spheres. Assembly of the octamer in vitro and in vivo is facilitated by the presence of N-linked carbohydrate. Selective release of dimeric glycosylated invertase from intact yeast cells suggests that oligomerization helps retain the enzyme in the periplasmic space.

Acid Phosphatase↗
PubMed1987

Effect of glycosylation on yeast invertase oligomer stability.

Yeast external invertase is a glycoprotein that exists as a dimer that can associate to form tetramers, hexamers, and octamers (Chu, F., Watorek, W., and Maley, F. (1983) Arch. Biochem. Biophys. 223, 543-555; Esmon, P. C., Esmon, B. E., Schauer, I. E., Taylor, A., and Schekman, R. (1987) J. Biol. Chem., 262, 4395-4401), a process that is facilitated by the attached oligosaccharide chains. We have studied this association by high performance liquid chromatography on a gel filtration matrix, by which procedure wild-type bakers' yeast invertase gives two peaks, and invertase from a core mutant (mnn1 mnn9) of Saccharomyces cerevisiae X2180 gives three peaks. Concentration of an invertase solution by freezing drives the dimers into higher aggregates that, at 30 degrees C, re-equilibrate to a mixture of smaller forms, the composition of which depends on pH, concentration, and time. The invertase from a mutant, mnn1 mnn9 dpg1, which underglycosylates its glycoproteins and produces invertase with 4-7 oligosaccharide chains, forms oligomers of much lower stability than the mnn1 mnn9 invertase, which has 8-11 carbohydrate chains. Both of these mutants release external invertase from the periplasm into the medium during growth, but we conclude that defects in the cell wall structure may be more important in this release than an altered tendency of the invertases to aggregate. Investigation of aggregate formation by electron microscopy revealed that all invertases, including the internal nonglycosylated enzyme, form octamers under appropriate conditions.

Chromatography, Gel↗
PubMed1987

Distinct patterns of glycosylation of colligin, a collagen-binding glycoprotein, and SPARC (osteonectin), a secreted Ca2+-binding glycoprotein. Evidence for the localisation of colligin in the endoplasmic reticulum.

Mouse parietal endoderm PYS cells were labelled with [2-3H]mannose for 16-24 h. Colligin, an Mr-47000 collagen-binding protein, and SPARC, a Mr-43000 protein, highly homologous to the Ca2+-binding protein osteonectin, were isolated from labelled cell extracts and culture medium respectively. Glycopeptides obtained by exhaustive digestion with pronase were analysed by lectin-affinity, ion-exchange, and gel-filtration chromatography and by paper chromatography of high-mannose oligosaccharides after endo H release. The results show that the N-linked carbohydrate chains of colligin are exclusively the high-mannose type, of which (Man)8(GlcNAc)2 and (Man)9(GlcNAc)2 make up 77%. This carbohydrate structure provides strong evidence that colligin is a component of the endoplasmic reticulum, and argues against a role in cell-surface interactions. By contrast to colligin, SPARC secreted by PYS cells contains predominantly a diantennary complex type of chain containing a variable number of sialic acid and core-substituted fucose residues. Similar glycosylation patterns to those discussed above were seen in colligin isolated from primary mouse embryonic parietal endoderm cells and the murine 3T3 cell line, and in SPARC secreted by bovine corneal endothelial cells. Unlike the type-IV-collagen-binding glycoprotein studied by Dennis, J., Waller, C. and Schirrmacher, V. [J. Cell Biol. 99, 1416-1423 (1984)], removal of N-linked oligosaccharides from colligin had no effect on its binding to native type IV collagen.

Animals↗
PubMed1987

1,25(OH)2D levels in dihydrotachysterol-treated patients: influence on 1,25(OH)2D assays.

Many clinicians continue to prefer dihydrotachysterol (DHT) as the initial vitamin D agent of choice in hypoparathyroidism and renal osteodystrophy because of its long history of efficacy and safety. Assessment of the factors influencing the clinical response to DHT treatment should include measurement of vitamin D metabolite profiles, but investigators have heretofore been unable to measure 1,25(OH)2D because levels have been found to be falsely elevated when employing the chick intestinal cytosol receptor assay. After converting from the chick cytosol receptor assay to the calf thymus receptor assay for measuring 1,25(OH)2D, we did not note falsely elevated levels of 1,25(OH)2D in DHT-treated patients. The design of this study, therefore, was aimed at determining whether or not the calf thymus receptor measured authentic 1,25(OH)2D in such patients. We controlled for the possibility that freezing and thawing or prolonged storage might have either lowered 1,25(OH)2D levels or degraded a metabolite(s) of DHT that would have otherwise been recognized as "1,25(OH)2D" by the calf receptor. Similarly, technical differences between the two assays, source of thymus, and potential interference by other cytosolic proteins were eliminated as causes for the difference between the 1,25(OH)2D levels in the two assays. Our experiments do not provide an explanation for why the thymus receptor does not "see" the interfering metabolite(s) of DHT. This could reflect either a tissue difference or perhaps a species difference. Our results do provide the first opportunity to expand the investigation of the metabolic effects of DHT therapy to include changes in intrinsic 1,25(OH)2D metabolism.

Biological Assay↗
PubMed1987

Multigated radionuclide study of the total artificial heart.

A permanent total artificial heart, the Jarvik-7, was implanted into a 61-year-old male with a severe cardiomyopathy. Gated radionuclide studies were performed in the patient both prior to surgery and following implantation. Preoperative gated radionuclide cardiac studies revealed marked left ventricular enlargement, severe hypokinesis and a left ventricular ejection fraction of 10%. The right ventricle was moderately enlarged with a 27% ejection fraction. Following implantation of the Jarvik-7 artificial heart, gated cardiac studies were performed with a computer gated by a signal from the heart controller. The left ventricular ejection fraction was 69% and the right ventricular ejection fraction was 62%. This compared to a theoretical ejection fraction of 74% for each ventricle based on chamber anatomy. There was excellent ventricular emptying. Phase analysis showed uniform diaphragm motion. The use of gated cardiac studies in humans may prove helpful in evaluating mechanical problems with the artificial heart, such as malfunction of the diaphragm, before they become clinically apparent.

Heart↗
PubMed1987

99mTc-MAG3, a new renal imaging agent: preliminary results in patients.

99mTc-mercaptoacetyltriglycine (MAG3) is a new renal radiopharmaceutical which has been shown to have biological properties similar to 131I-hippurate (OIH) in animals and volunteers. 99mTc-MAG3 has now been compared with 131I-orthoiodohippurate (OIH) in a group of patients with varying degrees of renal impairment. In all cases, the 99mTc-MAG3 images were superior regardless of serum creatinine. Selected examples are illustrated including scans and renogram curves in a normal volunteer, transplant patients with creatinines of 9.8 mg/dl and 2.6 mg/dl respectively, and a furosemide study in a patient with questionable obstruction. Our preliminary results suggest that 99mTc-MAG3 performs well in patients with impaired renal function and may well provide an acceptable replacement for OIH. A kit formulation has been developed and will soon be undergoing clinical evaluation.

Adult↗
PubMed1987

Measures of leucine aminopeptidase can be used to anticipate UV-induced age-related damage to lens proteins: ascorbate can delay this damage.

This paper focuses on damage to soluble lens proteins during ultraviolet (UV) light exposure and its prevention by ascorbate (Vitamin C). Using 2.3 X 10(-3) W/cm2 UV A and 0.4 X 10(-4) W/cm2 UV B, aminopeptidase inactivation in lens supernatants is significant after 60 min. Protein aggregation and decreases in tryptophan levels, phenomena associated with UV-induced and cataract-related damage, are observed only after longer (6 h) UV exposure. Thus, it would appear that measurements of aminopeptidase activity can be used to anticipate damage to lens structural proteins. Ascorbate (15 mM) added to soluble lens proteins prior to photoirradiation can prevent some of these changes. The data presented suggest plausible relationships between impaired proteolysis and cataract formation.

Aging↗