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Biomedical subjects

A L Thomas

Publications and source records attributed to A L Thomas.

At least 55 records · Page 3Linked to original sources

D-penicillamine and polymyositis: the significance of the anti-Jo-1 antibody.

A 57-yr-old lady developed polymyositis whilst taking D-penicillamine for RA. D-Penicillamine-induced polymyositis occurs in RA with a greater frequency than idiopathic polymyositis. Anti-acetyl choline receptor antibodies and ANA were positive, consistent with drug-induced disease. Anti-Jo-1 antibodies are considered specific for idiopathic myositis, and their presence was unexpected. Following withdrawal of the drug, the disappearance of the anti-Jo-1 and other antibodies coincident with clinical improvement, suggested that D-penicillamine was responsible for inducing antibody production.

Antibodies↗

Renin and angiotensin converting enzyme concentrations in the fetal and neonatal guinea-pig.

1. Plasma renin concentration (PRC) and plasma and pulmonary angiotensin converting enzyme (ACE) concentration were measured in fetal and neonatal guinea-pigs from 45 days gestational age (GA) until 21 days post-partum. 2. Fetal PRC increased towards term to reach values greater than those measured in normal adult males. Pentobarbitone anaesthesia of the mother resulted in significant elevation of fetal PRC after 66 days GA but not before this time. 3. PRC were very high in the newborn guinea-pig, decreased rapidly during the first 24 h after birth and then more gradually, to reach approximately adult values by day 21. 4. Fetal plasma ACE concentration increased towards term to reach values greater than those measured in adult males and decreased subsequently. 5. Pulmonary ACE concentrations were very low throughout gestation but increased considerably between days 3 and 14 post-partum. Low concentrations of ACE were measured in other fetal tissues but placental concentrations were relatively high. 6. Propranolol (0.1 mg I.P.) or saline was administered (under halothane-nitrous oxide anaesthesia) to fetuses of litters of various GA from 55 days to term. Fetal PRC were measured 3 h later. Propranolol treatment resulted in significantly lower fetal PRC than saline treatment in litters aged 63 days to term but not in younger litters. 7. These data indicate that the renin-angiotensin system is functional in the fetal guinea-pig during the last third of gestation. Fetal plasma renin concentrations near term are greater than those measured in normal adult males. This may, in part, reflect an increased influence of the fetal sympathetic nervous system.

Angiotensin I↗

Chronic central vein catheterization for intraoperative and long-term venous access in swine.

Chronic venous access and repeated blood sampling for research purposes in large swine ideally should be possible without sedation, restraint or direct venipuncture of deep vessels. An operative technique of cranial vena cava catheterization and chronic catheter maintenance methods are described which were used successfully in the placement of 11 silicone rubber catheters in 10 animals. All were used for repeated blood sampling, as well as intraoperative infusion of medications and large fluid volumes. Long term patency was excellent with 10 catheters patent at the end of the study interval, up to 14 weeks after insertion. Serial blood sampling was accomplished easily without restraint. Catheter damage, infection or malfunction was rare. Proper maintenance and careful aseptic blood sampling render the cranial vena cava catheter a safe and reliable alternative to direct venipuncture in swine.

Animals↗

Serial prostatic histology. A valid marker of response to hormone treatment.

Serial transrectal needle biopsies were taken from 146 patients (657 specimens) with advanced prostatic cancer (T3/T4, M1/MO) admitted to a trial of two forms of oestrogen therapy. Histological grading by Gleason and Mostofi techniques on the initial biopsy showed no correlation either with extent of disease or its eventual outcome on treatment. Change in grade was dissociated from the response of bone metastases to hormone treatment and did not appear to influence survival. However, the prognosis of 16 patients showing clearance of tumour from their serial biopsies was generally good.

Aged↗

A case of sarcoid arthritis in a child.

An 8-year-old girl presented with dyspnoea, weight loss, erythema nodosum, and an arthritis. A diagnosis of sarcoidosis with joint involvement was made. The clinical features of this unusual arthritis in a child and the response to corticosteroid therapy are described.

Arthritis↗

Preliminary studies with azapropazone in gout and hyperuricaemia.

Eight patients with acute gouty arthritis were treated with high dose oral azapropazone 600 mg qds in an open study in order to evaluate its therapeutic potential in acute gout. The drug appeared to be as effective as previous agents used in the management of individual patient's acute gout with resolution of pain in 2-21 days, and it had a potent hypouricaemic and uricosuric effect. The uricosuric effect of azapropazone 300 mg qds and phenylbutazone 100 mg tds was compared in a seven day cross-over study in seven asymptomatic patients with gout and hyperuricaemia. Azapropazone had a more rapid uricosuric effect than phenylbutazone. There was a statistically significant fall in serum uric acid and rise in uric acid clearance 24 hours after starting azapropazone and 72 hours following phenylbutazone.

Adult↗

A soybean seed urease-null produces urease in cell culture.

Itachi, a soybean (Glycine max [L.] Merr.) variety with 0.2% normal seed urease activity, was recovered from a screen of 6,000 entries in the United States Department of Agriculture soybean germplasm collection. No urease antigen in Itachi seed extracts was detected by double diffusion or by rocket immunoelectrophoresis. Native gels stained for protein or ureolytic activity revealed no detectable urease holoenzyme. An anti-urease antibody affinity column was used to remove all detectable urease activity and antigen from ;wild type' (cv. Prize) seed extracts. Affinity column effluent and nonchromatographed Itachi extracts both lack a species which comigrates with purified urease subunits in sodium dodecylsulfate polyacrylamide gels. Inability to detect urease antigen or urease protein suggests that during development of Itachi seeds there is no synthesis of urease protein or that, at most, its synthesis is 0.2% of wild type (Prize).No urease activity or only traces of urease activity were detected in cotyledons of developing or germinating Itachi seeds. In contrast, callus cultures induced from cotyledon, shoot tip, root, or root tip tissues of Itachi seedlings exhibited ureolytic activity equivalent to that of Prize cultures. Shoot tip cultures of both Prize and Itachi grew with urea as sole nitrogen source. Most or all of the ureolytic activity in crude extracts of Prize and Itachi suspension culture cells is seed-like urease in thermal stability, recognition by antibodies to the seed enzyme, hydroxyurea sensitivity, and nickel requirement for synthesis. It has been reported previously (Polacco, Havir 1979 J Biol Chem 254: 1707-1715; Polacco, Sparks, Jr, Havir 1979 Genet Eng 1: 241-259) that partially purified cell culture urease is identical to seed urease by immunological and electrophoretic criteria. These results suggest that urease is under different developmental controls in the seed and in cell culture.In both Prize and Itachi cultures, utilization of the ureide allantoin, unlike that of urea, is not dependent on nickel. This suggests that ureide catabolism does not require urease.

Journal Article↗

Obliterative bronchiolitis in rheumatoid arthritis.

Two patients with rheumatoid arthritis who developed obliterative bronchiolitis are described. Both patients had received penicillamine. The first patient died in respiratory failure 4 months after the onset of her breathlessness and the diagnosis was confirmed at post-mortem. The second patient was diagnosed with appropriate lung function tests and has been started on azathioprine. Although she is still disabled by breathlessness 12 months after presentation, her condition has stabilised.

Arthritis, Rheumatoid↗

Fetal and adult hemoglobin in the chronically catheterized sheep fetus.

The switch from fetal to adult hemoglobin (Hb) has been investigated in fetal and newborn lambs. In the period between 125 and 145 days gestation, the proportion of fetal cells containing adult Hb increased significantly in catheterized fetuses. This increase paralleled the rise in fetal plasma cortisol under several different experimental conditions. However, infusion of synthetic adrenocorticotropin (ACTH1-24) into the fetus, which increased fetal plasma cortisol concentrations to levels slightly higher than observed at term, did not bring about any increase in the proportion of cells containing adult Hb. Increasing fetal plasma prolactin (PRL) concentration either by infusion of PRL or by stimulating endogenous PRL release with thyrotropin-releasing hormone (TRH) did not influence the time or rate of the switch. The fetal reticulocyte count was significantly higher in blood samples taken at the time of catheterization in fetuses of 103-115 days gestation than at 116-128 days gestation. In one repeatedly sampled fetus of adult type Hb AB, Hb C was observed at the time when the fetus was anemic. At birth the number of cells containing adult Hb was significantly higher in catheterized lambs than in nonoperated controls.

Animals↗

Thyroid hormone relationships in the fetal and newborn lamb.

Plasma thyroxine (T4) and reverse triiodothyronine (rT3) concentrations have been measured in chronically catheterised sheep fetuses during the last third of gestation. In some animals T4 and rT3 concentrations fell before delivery but there was no change in the t4/rT3 ratio. In several serially sampled fetuses a small rise in plasma triiodothyronine concentration has been demonstrated in the days preceding delivery. Infusion of cortisol to fetuses commencing at 130 days of gestation (term 147 days) with the simultaneous administration of progesterone to delay labour resulted in changes in T4 and rT3 concentrations which were similar to those normally seen at term. The nature of the changes in the peripheral metabolism of T4 around the time of birth are discussed.

Animals↗

Circulating plasma protein concentrations in the fetal and neonatal sheep.

Fetal and neonatal ovine plasma protein and lactate dehydrogenase concentrations have been measured between 124 and 146 days gestation in th chronically catheterized fetal sheep and in the newborn lamb. Fetal plasma protein concentration ranged from 24.7 to 77.0 mg . ml-1 and increased at a rate of 1.65 mg . ml-1 . day-1. In contrast, in the first 10 days of neonatal life plasma protein concentration fell steadilyu at a rate of 2.64 mg . ml-1 . day-1. Fetal plasma lactate dehydrogenase concentration increased at a rate of 0.014 IU . ml-1 . day-1 during the period of study. The increase correlated significantly with the rise of fetal plasma protein concentration. In contrast, in the newborn lamb no significant change in plasma lactate dehydrogenase concentration was observed during ther first 10 days after birth.

Aging↗

Continuous variability of fetal PO2 in the chronically catheterized fetal sheep.

A method of continuous monitoring of fetal intravascular PO2 at various sites in the circulation in the chronically catheterized fetal sheep for up to 41 days (mean 11.1 days) has been compared with values obtained in blood samples measured extracorporeally in a standard blood gas analyzer. A double-blind comparison of the two methods showed that there was no bias between the two methods and correlation was 0.94. The stability of the electrodes was superior to that of a conventional blood gas analyzer. In every animal there was continuous variability of fetal vascular PO2. In the period from 105 to 126 days' gestation we noted the presence of slow increases in basal uterine tone that we have called "contractures". The frequency of these contractures was very regular at approximately one per hour. The frequency of these contracutres was very regular at approximately one per hour. There is a statistically significant related fall in fetal vascular PO2 in relation to these contractures. Well-coordinated uterine contractions during labor also produced a fall in fetal vascular PO2 that was related to the uterine activity.

Animals↗

The effect of prostaglandin E2 infusion in the fetal lamb on fetal plasma ACTH, prolactin and cortisol concentrations.

PGE2 (2 micrograms/min) has been infused for 1h into the fetal jugular vein of 8 chronically catheterized fetuses on 13 occasions from 112 to 138 days gestation. Infusion of ethanol vehicle alone was conducted in fetuses from 111-139 days gestation. PGE2 administration produced a significant increase in fetal plasma cortisol after 30 min. No significant change was observed in fetal plasma prolactin concentration. Fetal plasma ACTH concentration was significantly elevated above resting concentration after 30 min. of PGE2 infusion. Metabolic clearance rate of PGE2 was 860 ml/min or 350 ml/kg/min. Intrauterine pressure was not changes during the infusion at any gestational age.

Adrenocorticotropic Hormone↗

Ultrastructural changes in the placenta of the ewe after long-term intravascular infusion of 2-bromo-alpha-ergocryptine (CB154) into mother or fetus.

The fine structural appearance of the placenta of the ewe has been examined following long-term infusion of CB154 into either the fetus or the pregnant ewe. Binucleate cells which usually contain aggregations of spherical membrane-bound electron-dense inclusions, are a characteristic component of the chorionic epithelium of the sheep. Following CB154 infusion into either the fetus or ewe at 111 to 137 days of gestation, binucleate cells were partially or completely depleted of the droplets which are present in binucleate cells of control animals at a similar gestational age. No obvious changes in the maternal epithelial syncytium were observed after CB154 administration. Infusion of CB154 into the fetus alone was also followed by degenerative changes in some binucleate cells which ranged from condensation of nuclei to complete cell fragmentation. Either a direct or an indirect action of CB154 on binucleate cells is suggested by these observations. Hypoprolactinaemia followed CB154 infusion in all treated animals; its possible influence on binucleate cell activity is discussed.

Animals↗

Pituitary stalk-section and some of its effects on endocrine function in the fetal lamb.

A detailed description is given of a method to section the pituitary stalk of the fetal lamb after 105 days gestational age. The approach to the stalk is made through a window in the frontal bone. In order to prevent regeneration of the hypothalamo-pituitary connections a silicone plate is introduced through the probe used to fracture the stalk. The surgical outcome and viability of 11 pituitary stalk sectioned fetuses is described over periods of up to 23 days. The presence of pituitary infarction following stalk section was related to damage of the anterior hypophysial vesssels if the probe was deviated from the mid-line at any time in its course. The effect of this procedure on fetal plasma T4 and PRL concentrations and the initiation of premature labour by the continuous infusion of cortisol into the fetus is described.

Animals↗

Ultrastructural changes in the placenta of the ewe after fetal pituitary stalk section.

Binucleate cells are a normal component of the ovine chorionic epithelium, but are usually separated from the fetal-maternal interface by a thin layer of cytoplasm derived from the principal or uni-nucleate cells of the trophoblast. They are distinguished not only by two distinct and separate nuclei, but also by conspicuous membrane-bound cytoplasmic inclusions in the form of haloed droplets. After fetal pituitary stalk section binucleate cells move up to and participate in the formation of the fetal-maternal interface; furthermore they extend clear blunt-ended pseudopodia into the maternal epithelial syncytium. These activities do not appear to be supppressed by fetal infusion of cortisol or ACTH. The apparent motility of binucleate cells, together with the presence of haloed droplets within the maternal epithelial syncytium, suggests that after fetal pituitary stalk section binucleate cells invade the uterine syncytium, lose their limiting membranes and discharge their contents into the syncytial cytoplasm. Large molecules such as ovine placental lactogen may be transported from fetal to maternal tissues by this mechanism.

Adrenocorticotropic Hormone↗