Analysis of a large pedigree with elliptocytosis, multiple lipomatosis, and biological false-positive serological test for syphilis

Elliptocytosis, multiple lipomatosis, and biological false-postive serological test for syphilis (BFPSTS) were found in a single individual. One hundred eighty relatives were tested for the three diseases: 74 were typed for seven blood group antigens, and 58 were typed for four electrophoretic enzyme markers. Likelihood analysis of the pedigree data confirmed independent dominant inheritance for elliptocytosis and lipomatosis. BFPSTS appears dominant, but the analysis was inconclusive. No linkages were found between any disease gene and any marker gene. Two female pedigree members with BFPSTS developed systemic lupus erythematosus, a finding in agreement with the previously described association. The analysis did not lead to any conclusions about the causal relationship between the two traits.     

Prednisolone disposition in steroid-dependent asthmatics

A 40-mg intravenous dose of prednisolone was given as prednisolone phosphate to seven severe steroid-dependent asthmatics and to 13 healthy volunteers to determine if the large prednisone requirements of these patients were a function of the disease, cellular response, or rapid clearance of prednisolone. Plasma concentrations of prednisolone, prednisone, and cortisol were determined by high-performance liquid chromatography over an 8-hr test period. Circulating eosinophil concentrations were monitored concurrently. The apparent half-lifes of prednisolone in the asthmatics and normals were 3.33 +/- 0.71 and 3.25 +/- 0.58 hr (mean +/- SD). The apparent plasma clearances of prednisolone were 201 +/- 54 and 198 +/- 38 ml/min/1.73 m2 and the apparent volumes of distribution were 50.8 +/- 11.7 and 53.5 +/- 13.5 L/1.73 m2 for the asthmatic and normal groups, respectively. When the concentration-dependent binding of prednisolone to plasma protein was examined, no differences in the apparent clearances of unbound drug were found between the two groups. The eosinopenic response to prednisolone was similar in the steroid-dependent asthmatics and healthy normal volunteers. These studies indicate that binding, distribution, and clearance of prednisolone are not responsible for the large prednisone requirement of some steroid-dependent asthmatics. Differences in steroid-receptor sensitivity or in severity or pathophysiology of the disease state more likely account for the need for large prednisone dosages in these patients.     

An evaluation of procedures used in staging carcinoma of the cervix

A review of 227 cases of invasive carcinoma of the cervix was undertaken to determine the efficacy of procedures using in the staging of this disease. All patients had a pretreatment chest radiography and intravenous pyelogram. 96.5% had pretreatment cystoscopy, 98.6% had pretreatment proctoscopy, and 92% had a pretreatment barium enema. These patients were retrospectively staged on the findings of physical examination only. Each additional procedure was then evaluated by comparison with the initial staging. Cystoscopy and chest film findings each would have changed the clinical stage in fewer than 1% of cases, barium enema in 1.4%, and proctoscopy in 2.2%. No patient had a positive barium enema without a positive proctoscopy, while two patients had positive proctoscopies with negative barium enemas. The overall yield of positive findings by pretreatment intravenous pyelography was 7.3%. Lymphangiography, although inconsistently done, yielded positive findings in all stages. Chest radiographs, intravenous pyelography, proctoscopy, and lymphangiography are recommended as part of the pretreatment workup of patients with carcinoma of the cervix. Routine barium enema is no longer recommended, and cystoscopy is only recommended in patients with clinical stage IIB disease or greater.     

A new quinoline-carbamate aphicide

We found that it was nearly impossible to apply the quinoline-carbamate aphicide per os by means of synthetic diets, owing to its high feeding-deterrent-effect. After application via the roots of the host plant, this systemic compound is deposited on the leaf surface. The results suggest that the toxic effect is not the result of the oral uptake of phloem sap, but of the tarsal contact with the toxicant. Sensitivity of aphids to this compound and LD50-values were determined after topical applications.     

Tetrahydroisoquinolinecarboxylic acids and catecholamine metabolism in adrenal medulla explants

In a study of the relationship of the tetrahydroisoquinolinecarboxylic acids (TIQCAs) to catecholamine metabolism, we have investigated their effects on cultured rat adrenal medulla explants. Medullae were incubated in medium containing norlaudanosolinecarboxylic acid (NLCA) or 3',4'-deoxynorlaudanosolinecarboxylic acid (DNLCA) (0.5 mM) in the presence and absence of [3H]tyrosine. By paired-ion reverse-phase high pressure liquid chromatography, tissue epinephrine (EPI), norepinephrine (NE), dopamine (DA) and TIQCA were resolved. Endogenous concentrations were measured with electrochemical detection, and radioactivity was assayed by collecting appropriate effluents. Tissue levels of the TIQCAs reached saturating levels of 0.36 mM by about 20 hr. DNLCA elicited a significant decrease (60%) in endogenous DA, NE and EPI at 40 hr, whereas only DA was depressed at 30 hr. NLCA had little effect after 30 or 40 hr. When tissues were maintained in the presence of alpha-methyltyrosine (0.5 mM) for 40 hr, catecholamine levels were depressed to an extent similar to that observed with DNLCA. Incubation with [3H]tyrosine in the presence of TIQCAs revealed inhibition of tyrosine uptake and suggested a reduction in the rate of catecholamine synthesis. These results are consistent with previous data on the inhibition of tyrosine 3-monooxygenase by DNLCA in vitro.     

Some Implications of a Sample of Practical Turing Tests

A series of imitation games involving 3-participant (simultaneous comparison of two hidden entities) and 2-participant (direct interrogation of a hidden entity) were conducted at Bletchley Park on the 100th anniversary of Alan Turing’s birth: 23 June 2012. From the ongoing analysis of over 150 games involving (expert and non-expert, males and females, adults and child) judges, machines and hidden humans (foils for the machines), we present six particular conversations that took place between human judges and a hidden entity that produced unexpected results. From this sample we focus on features of Turing’s machine intelligence test that the mathematician/code breaker did not consider in his examination for machine thinking: the subjective nature of attributing intelligence to another mind.     

Dissociation between the potency and reversibility of the insulinotropic action of two meglitinide analogues

The non-sulphonylurea hypoglycaemic agent repaglinide is about one order of magnitude less potent, in terms of insulinotropic efficiency, than S3075, another meglitinide analogue. In the present study, the effects of these two drugs upon 86Rb outflow, 45Ca efflux and insulin release from prelabelled rat pancreatic islets were investigated in a perifusion system. At a concentration of 10 microM, which is sufficient to evoke a maximal secretory response in incubated islets, both agents inhibited 86Rb efflux from islets perifused in the absence of D-glucose, and stimulated both 45Ca efflux and insulin release from islets perifused in the presence of 6 mM D-glucose. The stimulation of 45Ca efflux from prelabelled islets was suppressed in the absence of extracellular Ca2+. The cationic and secretory response to repaglinide differed, however, from that evoked by S3075, in persisting for at least 20 min after removal of the drug from the perifusion medium, whilst the changes in 86Rb outflow, 45Ca efflux and insulin release caused by S3075 were rapidly reversible. These findings indicate that there is no parallel between the insulinotropic efficiency of distinct meglitinide analogues, and the reversibility of their functional effects. Since a comparable dissociation was recently documented in the case of hypoglycaemic sulphonylureas, the present observations reinforce the view that distinct molecular determinants may rule the relative insulinotropic potency of sulphonylureas and structurally related meglitinide analogues, on one hand, and the reversibility of their biological action, on the other hand.