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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 1,459 records · Page 81Linked to original sources

Characterization of different tumor antigens present in cells transformed by simian virus 40.

In addition to large T and small t antigens, cells transformed by simian virus 40 (SV40) commonly contain other proteins which specifically immunoprecipitate with SV40 anti-T serum and which are not detected in untransformed cells. The additional tumor antigens (T-Ags) fall into two groups: those having a close structural relationship with normal SV40 T-Ags, and those unrelated to large T and small t. The latter are probably nonviral T-Ags (NVT-Ags). The NVT-Ags comprise a family of proteins of molecular weight 50,000-55,000. Fingerprint analysis shows that NVT-Ags have few if any peptides in common with large T or small t, and that they lack the amino terminal tryptic peptide and the peptides unique to small t. NVT-Ags from different species have different fingerprints, but those isolated from different transformants of the same cell line are identical. The size of NVT is unaltered in cells transformed by mutants of SV40 with deletions in the region 0.60-0.55 map units. The mRNA for NVT does not hybridize to SV40 DNA. The other forms of T-Ag isolated from transformed cells fall into three classes: shortened forms of large T (truncated large T); multiple species of T-Ag with molecular weights very similar to, but distinct from, those of normal large T (large T doublets and triplets); and elongated forms of large T (super T). These proteins all contain the normal amino terminus of SV40 T-Ags, and the truncated forms of large T lack peptides from the carboxy terminal half of large T. One species of super T (molecular weight 130,000) contains only those methionine tryptic peptides present in normal large T, although it may contain some peptides in more than one copy.

Animals↗

Changes in blood glucose and plasma insulin after intravenous galactose in human injury.

1. The increase in blood glucose after intravenous galactose was measured at 6--8 h and 14 days after hip replacement (14 patients) and accidental injury (14 patients). 2. After hip replacement there was a greater rise of glucose after galactose on the day of the operation than on recovery, despite basal hyperglycaemia. This earlier period was also associated with inappropriately low insulin concentrations for the prevailing glucose concentration, and hyperketonaemia (13 out 14 patients). 3. After accidental injury patients with initial hyperketonaemia (nine out of 14) also had a greater rise of blood glucose after galactose than on recovery and had relative insulin deficiency; in contrast those who were initially normoketonaemic (five out of 14) showed a rise in glucose comparable with that after recovery and basal insulin concentrations more appropriate to the existing glucose concentration. 4. It is concluded that in most subjects after injury hepatic glucose release after galactose administration is not suppressed despite hyperglycaemia.

Adolescent↗

Effect of vitamin D deficiency on sarcoplasmic reticulum function and troponin C concentration of rabbit skeletal muscle.

1. Weanling rabbits were made rachitic either by a vitamin D-deficient diet or by parenteral administration of ethane 1-hydroxy-1,1-diphosphonate (EHDP) in amounts sufficient in other species to block the formation of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]. 2. The uptake of calcium into the isolated sarcoplasmic reticulum from mixed striated quadriceps muscle, and the amount of troponin C (the calcium-binding component of the troponin complex) in relation to other proteins from the same muscle, were measured. 3. In muscle from animals made rachitic by a dietary deficiency of vitamin D, the rate of uptake of calcium by the sarcoplasmic reticulum and the troponin C concentration were both significantly less (P less than 0.02) than in control littermates. In EHDP-treated animals no significant differences from controls were found. 4. These results show that dietary deficiency of vitamin D in such animals can affect muscle physiology. Since no changes are found in animals made rachitic with EHDP, who presumably have a selective deficiency of 1,25-(OH)2D3, it is possible that the effect of vitamin D on muscle is mediated through metabolites other than 1,25-(OH)2D3 such as 25-hydroxycholecalciferol.

Animals↗

The 3-methylhistidine content of human tissues.

1. The amount of 3-methylhistidine (3-MeH) has been measured in eighty-eight samples of tissue taken post-mortem from five adults. 2. The highest concentration (mumol/g fat-free dry weight) of 3-MeH was in skeletal muscle (3.31 +/- 0.05); intermediate values (2-3) were found in cardiac muscle and those tissues containing smooth muscle; and low values (less than 1) occurred in parenchymal tissues such as liver and kidney. 3. There was little variation between the mean 3-MeH content of striated muscles in different individuals, and no significant difference between the 3-MeH concentrations of striated muscles taken from six different sites. 4. The results suggest that it is justifiable to use values obtained from single muscles to calculate the rate of myofibrillar breakdown from urinary 3-MeH excretion.

Adult↗

Herpes zoster oticus. Uncommon but recognizable cause of facial paralysis.

Three cases of herpes zoster oticus illustrate the manifestations of this relatively uncommon cause of facial paralysis. Topographic analysis, in which functions of facial nerve branches are assessed, helps establish the level of facial nerve involvement. Sequential faradic stimulation testing often is a sensitive prognostic indicator of recovrey of facial nerve function, particularly if nerve excitability persists. A few recent reports support the use of systemic steroid therapy for herpes zoster oticus; opinions vary regarding the efficacy of surgical decompression for facial paralysis. Although general principles cannot be deduced from three cases, each case discussed exemplifies an important aspect of management. The prognostic significance of results of nerve stimulation tests is illustrated by the complete return of facial nerve function in our first patient. Our second patient's response to systemic steroid therapy supports recent reports of the value of such agents in herpes zoster oticus. Partial return of facial nerve function in our third patient two months after onset of paralysis accentuates the importance of a period of observation before a nerve graft or other rehabilitative procedures are undertaken.

Adult↗

Studies on pregnancy-associated plasma protein A in the third trimester of pregnancy.

The plasma concentration of pregnancy-associated plasma protein A (PAPP-A) was measured in 34 women during the last 10 weeks of pregnancy. From 30 to 36 weeks the concentration of this protein increased steadily. Thereafter the concentration of PAPP-A rose more steeply, the highest amounts being found in early labour. The concentration of PAPP-A in peripheral venous blood and in the uterine vein was much the same. It was less in the retroplacental blood and a great deal less in the peritoneal fluid. The day-to-day variation was small; the coefficient of variation at 38 weeks was only 7.3 per cent. After delivery, the concentration of PAPP-A fell more slowly than other placental proteins and steroids, the average half-life being 51 hours. Although there is no doubt that PAPP-A is a product of the syncytiotrophoblast, our findings suggest that it is not simply secreted by the chorionic villi directly into the intervillous space but makes its way into the maternal circulation by a more circuitous route.

Ascitic Fluid↗

Suppression of chronic ventricular arrhythmias with propranolol.

The antiarrhythmic efficacy of propranolol was evaluated in 32 patients with chronic high frequency ventricular arrhythmias in a placebo-controlled protocol. After a placebo control period, propranolol was begun and the dosage increased sequentially until arrhythmia suppression was achieved, side effects appeared, or a maximum dosage of 960 mg/day was reached. Computerized analysis of ambulatory recordings was used to quantify the arrhythmias. Twenty-four patients had 70--100% arrhythmia suppression at plasma levels ranging from 12--1100 ng/ml (end of dosing interval). Eight patients in this group had frequent episodes of ventricular tachycardia that were totally suppressed at or below the dosage that produced greater than or equal to 70% suppression of ventricular ectopic depolarizations (VEDs). A biphasic dose-response curve was seen in five patients who responded with a decrease in arrhythmia frequency in the lower ranges of dosages but had increased frequency of ectopic rhythms as the dosage was increased above the optimal level. Only one-third of patients responded at doses less than or equal to 160 mg/day. However, with dosages of 200--640 mg/day, an additional 40% responded. Propranolol appears to control ventricular arrhythmias safely and effectively in many patients. The finding that the antiarrhythmic effect in many patients required plasma concentrations greater than those that produce substantial beta-adrenergic blockage raises a question whether blockade of cardiac beta receptors can directly account for all of the antiarrhythmic actions of propranolol.

Adult↗

Whole body hyperthermia: a phase-I trial of a potential adjuvant to chemotherapy.

Fourteen patients with a variety of neoplasms not responsive to standard forms of therapy underwent whole body hyperthermia for a maximum 4 h at 41.8 degrees C. This was a phase-I cancer trial designed to develop whole body hyperthermia as an adjuvant to systemic chemotherapy. Intravenous analgesia was used to sedate patients, obviating the need for general endotracheal anesthesia. Hyperthermia was induced by means of a high-flow water perfusion suit. Cardiovascular performance was evaluated using a flow-directed pulmonary artery catheter. Patients developed a twofold mean increase in cardiac index without evidence of cardiac damage by ECG or creatine phosphokinase (CPK) isoenzymes. An acute fall in serum magnesium and phosphate and an acute rise in arterial pH, serum CPK values, and granulocyte count occurred in all patients. There were no clotting abnormalities. Toxicity included fatigue, diarrhea, nausea, and transient elevations in liver enzymes. Four patients were febrile for 36 h after initial defervescence. Peripheral neuropathy developed in four. These results show that with carefully monitored conditions whole body hyperthermia is feasible.

Adolescent↗

Renal anomalies in mice prenatally exposed to ethanol.

The current observations confirm and extend earlier data demonstrating the deleterious effects of ethanol in the C57BL/6J mouse. Ethanol given to pregnant mice from gestation-day 5 to gestation-day 11 reduced the number of mice going to full term, decreased the number of pups per litter, and lowered the birthweight of the live pups. Prenatal exposure to ethanol also produced a high incidence of hydronephrosis in the offspring.

Abnormalities, Drug-Induced↗