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Biomedical subjects

R J Anderson

Publications and source records attributed to R J Anderson.

At least 235 records · Page 13Linked to original sources

Human pheochromocytoma phenol sulfotransferase: biochemical properties and activities of thermolabile and thermostable forms.

To determine whether pheochromocytoma phenol sulfotransferase (PST) activities were similar to blood platelet PST activities, we established assay conditions and biochemical properties for the human pheochromocytoma enzymes. At least two forms of PST were present in high speed supernatant (HSS) preparations of the tumors. A thermolabile form (TL) and a thermostable form (TS) were similar to those of human platelet PST with regard to pH optima, apparent Km values, responses to 2,6-dichloro-4-nitrophenol and thermal stability. PST activities were measured in 74 tumors of neuroectodermal origin that had been stored at -80 degrees C for a mean of 37.9 months. Levels of TL and TS PST activities decreased in a nonlinear fashion with time of sample storage. TL and TS PST activities of 4 samples assayed after 1.08 +/- 1.95 (mean +/- SD) month of storage were 167 +/- 73 and 3,110 +/- 1,817 U/mg protein, respectively (mean +/- SEM). Our results indicated that the TL and TS forms of PST in pheochromocytoma HSS preparations were biochemically similar to platelet PST activities.

Adolescent↗

Electrophysiologic changes following treatment with organophosphorus-induced delayed neuropathy-producing agents in the adult hen.

Although clinical, pathological, and biochemical effects of organophosphorus-induced delayed neuropathy (OPIDN) have been intensively investigated in the adult hen, detailed electrophysiological studies are lacking. Adult white leghorn hens were treated with a single oral dose of either 30 mg/kg tri-2-cresyl phosphate (TOCP), 750 mg/kg TOCP, 4 mg/kg di-n-butyl-2,2-dichlorovinyl phosphate (DBCV), or 30 mg/kg di-n-butyl-2,2-dichlorovinyl phosphinate (DBCV-P). The 750 mg/kg TOCP and DBCV, but not the 30 mg/kg TOCP and DBCV-P, treatments resulted in clinical signs of OPIDN and mild to marked damage of the tibial nerve 21 days after dose. Twenty-four hr lymphocyte neurotoxic esterase (NTE) inhibition was used as an index of brain NTE inhibition for the various organophosphorus compound (OP) treatment. Twenty-four hr lymphocyte NTE inhibition for 30 mg/kg TOCP, 750 mg/kg TOCP, DBCV, and DBCV-P was 54.1, 87.1, 84.8, and 68.3%, respectively. Twenty-one days after dose, the TOCP-treated hens exhibited some abnormalities in conduction velocity and action potential duration in the tibial or sciatic nerves. No abnormalities were observed in action potential parameters of either the DBCV or DBCV-P treatments. Neurotoxic OP (TOCP and DBCV) treatment resulted in decreased refractoriness in the tibial nerve, increased refractoriness in the sciatic nerve, and elevated strength duration threshold for both nerves. These changes were not present in nerves from DBCV-P (a non-neurotoxic NTE inhibitor)-treated hens. These results suggest that refractory period and strength duration abnormalities in peripheral nerve correlate well with the production of OPIDN and are evident without coincident clinical signs or histopathology.

Action Potentials↗

The epidemiology of dental caries in relation to environmental trace elements.

This paper reviews the influence of the geochemical environment on the epidemiology of human dental caries. The best documented association is that between water borne fluoride and reduced caries prevalence. The influence of fluoride was first reported during the early decades of this century in Colorado, USA, and led to the fluoridation of some public water supplies in several countries. In all cases, fluoridation has been followed by significant improvements in dental health and no adverse effects in general health. Other trace elements in food and water have now been linked with dental caries. Molybdenum has been associated with reduced caries prevalence whereas selenium and lead appear to have adverse effects. Cavity formation in teeth probably involves a localised dissolution of the enamel surface by the products of bacterial activity. It is possible that the incorporation of trace metals into the apatite microcrystals of enamel may alter their physical properties, especially solubility, and hence their susceptibility to degradation.

Dental Caries↗

Cyclosporin A treatment of refractory rheumatoid arthritis.

Ten patients with rheumatoid arthritis were entered into a 24-week pilot study of oral cyclosporin A at a starting dosage of 6 mg/kg/day, followed by a 12-week washout period. Significant improvement in clinical parameters was observed at 12 weeks and 24 weeks (P less than 0.02 versus baseline for joint pain and joint swelling indexes and patient and physician assessments; P less than 0.04 versus baseline in the numbers of painful/tender joints and swollen joints). Adverse reactions were varied: renal impairment occurred in all patients and hypertension occurred in 7. All patients demonstrated an increase in defined disease activity at cessation of treatment and through the washout period. Cyclosporin A is clinically effective in the treatment of patients with refractory rheumatoid arthritis, but its value as an intervention therapy is limited by its toxicity.

Arthritis, Rheumatoid↗

2,000-centiGray total lymphoid irradiation for refractory rheumatoid arthritis.

Because toxicity with the use of 3,000 centiGray (cGy) of total lymphoid irradiation (TLI) was observed in an earlier study, 2,000-cGy treatments were delivered in a 2-portal format to 7 patients and in a modified 3-portal fashion to 6 patients, as part of a randomized, investigator-blinded trial of TLI treatment for refractory rheumatoid arthritis. Analysis of combined data from the 13 patients revealed statistically significant improvement in 5 clinical indicators of disease activity at the end of TLI and 6 and 12 months later, accompanied by T4-specific immunosuppression. Management considerations resulted in the introduction of prednisone therapy in 5 patients, methotrexate in 4, and azathioprine in 1 during the interval of 8-12 months post-TLI. Herpes zoster occurred in 5 patients prior to the initiation of this additional therapy. These data indicate that, in patients with rheumatoid arthritis, a TLI dose of 2,000 cGy is sufficient to produce measurable benefit that lasts for 6 months, and that the improvement can be maintained at 12 months by the use of prednisone and methotrexate.

Adult↗

Retention of differentiated characteristics by cultures of defined rabbit kidney epithelia.

Rabbit nephron segments of proximal convoluted tubules (PCT); proximal straight tubules (PST); cortical and medullary thick ascending limbs of Henle's loop (CAL, MAL); and cortical, outer medullary, and inner medullary collecting tubules (CCT, OMCT, IMCT) were individually microdissected and grown in monolayer culture in hormone supplemented, defined media. Factors favoring a rapid onset of proliferation included young donor age, distal tubule origin, and the addition of 3% fetal calf serum to the medium. All primary cultures had polarized morphology with apical microvilli facing the medium and basement membrane-like material adjacent to the dish. Differentiated properties characteristic of the tubular epithelium of origin retained in cultures included ultrastructural characteristics and cytochemically demonstrable marker enzyme proportions. PCT and PST were rich in alkaline phosphatase; CAL stained strongly for NaK-ATPase; CCT contained two cell populations with regard to cytochrome oxidase reaction. A CCT-specific anti-keratin antibody (aLEA) was immunolocalized in CCT cultures, and a PST cytokeratin antibody stained PST cultures. The biochemical response of adenylate cyclase to putative stimulating agents was the same in primary cultures as in freshly isolated tubules. In PCT and PST adenylate cyclase activity was stimulated by parathyroid hormone (PTH) but not by arginine vasopressin (AVP); CAL and MAL adenylate cyclase was stimulated by neither PTH nor AVP; CCT, OMCT, and IMCT adenylate cyclase was stimulated by AVP but not by PTH. NaF stimulated adenylate cyclase activity in every cultured segment. It is concluded that primary cultures of individually microdissected rabbit PCT, PST, CAL, MAL, CCT, OMCT, and IMCT retain differentiated characteristics with regard to ultrastructure, marker enzymes, cytoskeletal proteins, and hormone response of adenylate cyclase and provide a new system for studying normal and abnormal functions of the heterogeneous tubular epithelia in the kidney.

Adenylyl Cyclases↗

Chronic recurrent Goodpasture's syndrome.

A distinctive case of Goodpasture's syndrome characterized by multiple recurrences occurring over 14 years was observed. Each recurrence followed cessation of prednisone and azathioprine therapy, and reinstitution of this therapy resulted in prompt remission. Initially, both glomerulonephritis and hemoptysis were prominent clinical features. In recent years, hemoptysis has been the predominant clinical problem. This and other cases suggest that Goodpasture's syndrome may comprise a wider disease spectrum than generally appreciated.

Adult↗

Clinical assessment of extracellular fluid volume in hyponatremia.

Assessment of the status of extracellular fluid volume is important in evaluating the cause and selecting appropriate therapy for hyponatremic disorders. Since the sensitivity and specificity of clinical assessment of extracellular fluid volume status in hyponatremic states remain unknown, 58 non-edematous patients with serum sodium less than 130 meq/liter were prospectively evaluated. Patients were judged to be either normovolemic (no response of serum sodium to saline infusion) or hypovolemic (saline infusion significantly corrected hyponatremia). Hypovolemic patients had significantly higher plasma renin activity (5.0 +/- 1.5 versus 2.5 +/- 0.5 ng/ml per three hours, p less than 0.05) and norepinephrine (1,054 +/- 252 versus 519 +/- 55 pg/ml, p less than 0.05) concentrations than did normovolemic patients. Clinical assessment correctly identified only 47 percent of hypovolemic patients and 48 percent of normovolemic patients. Thus, clinical assessment was of limited sensitivity and specificity in identifying extracellular fluid volume status in these hyponatremic patients. However, the concentration of sodium in a spot urine sample clearly separated hypovolemic (mean UNa = 18.4 +/- 3.1 meq/liter) from normovolemic (mean UNa = 72 +/- 3.7 meq/liter, p less than 0.001) hyponatremic patients.

Extracellular Space↗

Effect of diisopropylfluorophosphate and soman on rat skeletal muscle contracture during tetanic stimulation.

A number of reports have documented the myopathy that accompanies exposure to irreversible acetylcholinesterase inhibitors. However, less information is available on the functional consequences of the myopathy. The purpose of this study was to examine the effects of diisopropylfluorophosphate (DFP) and soman on skeletal muscle contracture. Rats were given daily doses of DFP or soman, and the tetanic contracture of the triceps surae muscles was recorded at various exposure periods up to 20 d. DFP decreased tetanic contracture during 5-Hz stimulation. Increased stimulation up to 50 Hz did not enhance the effect. The muscles showed the greatest deficit on d 5. Continued dosing produced a slightly attenuated effect. Soman produced a frequency-dependent increase in muscle contracture. The increase was greatest on d 2 and 4, but remained elevated over the 20-d study. These results show that two drugs that presumably both raised levels of transmitter in the synaptic cleft as a result of esterase inhibition can produce either enhanced or decreased muscle contraction.

Animals↗

Calcium modulates vasopressin effect in rabbit cortical collecting tubule.

The calcium ion has been proposed to be an important mediator of the hydroosmotic response to arginine vasopressin (AVP). We examined the effect of reducing basolateral calcium activity on hydraulic conductivity (Lp) in response to AVP in rabbit cortical collecting tubules (CCT) perfused in vitro. Each tubule served as its own control. Reducing bathing fluid calcium from 0.94 mM to 4.6 microM reduced Lp in each tubule (mean decrease from 146 +/- 13 to 106 +/- 7 cm X s-1 X atm X 10(-7), n = 11, P less than 0.025). To determine whether this inhibitory effect was due to a decrease in cellular calcium uptake, we measured the effect of adding 10(-4) M lanthanum to bathing fluid on AVP-stimulated Lp. Lanthanum decreased Lp (from 109 +/- 13 to 80 +/- 10 cm X s-1 X atm X 10(-7), P less than 0.05) in each tubule. To examine the site at which low peritubular calcium activity regulates AVP action, we measured the effect of decreasing bathing fluid calcium on 8-[p-chlorophenylthio]-adenosine 3',5'-cyclic monophosphate (ClPheS-cAMP)-stimulated Lp (n = 5). Decreasing bathing fluid calcium significantly decreases (P less than 0.025) Lp response to ClPheS-cAMP. Since these results suggest that cellular calcium uptake can exert a post-cAMP effect to modulate AVP action, we examined the effect of the calcium ionophore A23187 (10(-7) M) on AVP- and ClPheS-cAMP-stimulated Lp A23187 reversibly potentiates (25-30%, P less than 0.025) the Lp response to both AVP and ClPheS-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Flow dependence of vasopressin-stimulated hydraulic conductivity in rabbit collecting tubule.

Flow rate dependence of both electrolyte and nonelectrolyte transport in various nephron segments has been described. Prior studies have used relatively leaky epithelia in which the flow rate-dependent transport phenomena can be explained in terms of alterations in axial and radial concentration profiles. In this study, the flow rate dependence of either vasopressin or cyclic adenosine monophosphate-stimulated water flux (Jv), hydraulic conductivity (Lp), and osmotic permeability (Pf) were measured in isolated perfused rabbit cortical collecting tubules. Increasing perfusion rate from 6.0 +/- 0.4 to 20.7 +/- 1.2 nl/min results in highly significant increases in Jv (131%) and in Lp and Pf (120%). In this relatively tight epithelium, osmotic equilibrium did not occur. Although the mechanism of this effect remains to be elucidated, the present results mandate maintenance of constant flow rates when examining the perfused cortical collecting tubular response to vasopressin.

Animals↗

Effect of pyridostigmine on tetanic contracture of innervated and denervated rat skeletal muscle.

Pyridostigmine has been reported to cause histological damage and decrements in tetanic contracture of skeletal muscle. Cholinesterase inhibition, decreased transmitter release and desensitization of postsynaptic receptors have all been proposed as mechanisms for these effects. The purpose of the present study was to determine whether the effect of pyridostigmine to decrease tetanic contracture was due to pre- or postsynaptic action. Rats with innervated or chronically denervated hindlimbs were given pyridostigmine (25 mg/kg) s.c. by infusion for four days. Tetanic contracture (20, 50, 100 Hz) was evoked by sciatic nerve stimulation in the innervated muscles and direct muscle stimulation in the denervated muscles. Pyridostigmine significantly decreased the contracture of innervated triceps surae muscle in a frequency dependent manner. Post-tetanic potentiation was reduced from control muscle responses. In denervated muscle pyridostigmine had no effect on contracture or post-tetanic potentiation. These results show that innervation is required for the detrimental effect of pyridostigmine and that the drug has no effect on skeletal muscle.

Animals↗