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Biomedical subjects
Publications and source records attributed to M Riva.
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We have investigated the function of C3b receptor (CR1) in the malignant lymphocytes of B-chronic lymphocytic leukemia (B-CLL) mimicking the physiological ligand C3b with the anti-CR1 monoclonal antibody CB04 covalently linked to Sepharose CL-4B (CB04-S). The binding of insolubilized CB04-S to CR1 gave a progression signal to B-CLL cells which became B cell growth factor (BCGF)-responsive. The cells of 13 of 14 cases treated with CB04-S showed an active time-dependent proliferation when BCGF was added to the culture. After 72 hr of exposure to BCGF, the growth fraction evaluated with the Ki67 monoclonal antibody was 23.4 +/- 8.9 and the proportion of cells in S phase assessed by the bromodeoxyuridine incorporation technique was 18.6 +/- 8.5%. The proper sequence of CB04-S followed by BCGF was also important since the proliferation was halved when the sequence was reversed or the two signals were delivered concomitantly. CB04-S and BCGF alone failed to induce any significant proliferation; the percentage of cycling cells was less than 1% overlapping that of control culture cells. On the contrary, the proliferation of normal tonsil B cells was triggered both by CB04-S and by BCGF used as single agents (bromodeoxyuridine+ cells 12.7 +/- 5.1% and 20.0 +/- 7.3, respectively). Together these data indicate that malignant B-CLL cells need a sequential two-step signal based upon CR1 binding in order to be activated in vitro. This is a major difference with normal tonsil B lymphocytes whose proliferation is triggered both by CB04-S and by BCGF used as single agents.
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A lambda gt11 yeast genomic library was screened with antibodies directed against yeast RNA polymerases A, B, and C. Thirty-five individual recombinant phages that expressed proteins in Escherichia coli that were antigenically related to RNA polymerases A, B, or C were isolated by using 22 distinct antisera. Thus, all 22 genes for the RNA polymerase subunits were potentially cloned. In three cases (lambda A-43, lambda A-40, and lambda A-34.5), an antigenic protein was expressed in E. coli with the same molecular weight as the corresponding subunit. When lambda A-40 DNA was used to hybrid-select yeast mRNA, the protein translated in vitro was the expected size for the A-40 subunit, further supporting our isolation of the A-40 gene. However, mRNA hybrid selected by lambda A-27 DNA did not code for a protein of the correct size. The lengths of the mRNA that hybridized to phage lambda A-190 or lambda C-160 DNA on RNA blots were in agreement with the predicted sizes of the coding regions of the corresponding genes. As predicted by our previous immunological results, yeast DNA inserts of the lambda A-190 and lambda C-160 clones cross-hybridized to the B-220 subunit gene. The cloned genes for the RNA polymerase subunits will prove to be valuable tools for the study of the function, regulation, and genetics of the yeast RNA polymerases.
Subclavian-cortical middle cerebral artery bypass by saphenous vein interposition is an uncommon recent revascularization technique used for immediate volume flow to the brain or when donor arteries are unavailable or inadequate. We used this technique in four cases of symptomatic common carotid artery occlusion. In the last two cases, severe, reversible neurological complications occurred. We think that these complications are due to this particular technique, and more cautious indications than for traditional extra-intracranial arterial bypass are recommended.
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Some methionine derivatives with the amine group acylated with an aliphatic group bearing a free, esterified or etherified thiol group in the omega position were prepared and tested for protection against CCl4, paracetamol, ethyl alcohol and ethionine intoxication. Acid (XIV) (MG 28013) (Table I) and some of its alkyl derivatives (XVIII) (MG 28228) and (XIX) (MG 28226) proved to have significant activity in these tests. A more in-depth study on MG 28226 however indicated a slight intolerance when subacute toxicity was examined (90 gg).
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Yeast RNA polymerase C purified by a simple large scale method was resolved into multiple components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Specific antibodies directed against each polypeptide chain were prepared in rabbits and used as structural and functional probes. With minor exceptions, each antibody recognized specifically the corresponding polypeptide by blot-immunodetection. Cross-reactions with purified RNA polymerases A and B confirmed our previous description of the subunits shared by the three nuclear RNA polymerases. Immunoadsorption of RNA polymerase C at different stages of purification using antibodies to subunits C160 and C128 yielded the same collection of polypeptides as found in the purified enzyme: C160, C128, C82, C53, C40, C37, C34, C31, C27, C25, C23, C19, C14.5, C12.5, and C10. Subunit-specific antibodies were used to probe the activity of RNA polymerase C in a specific, reconstituted transcription system as well as on a nonspecific template. Transcription of the tRNAGlu3 gene in vitro was inhibited when RNA polymerase C was preincubated with antibodies directed to C128, C82, C53, C34, C23, or C19. Antibodies to C82, C53, and C34 were much less inhibitory in the nonspecific assay. Inhibition by anti-C128 or anti-C23 was relieved by preincubation of enzyme C with plasmid DNA prior to antibody addition. These results are discussed in terms of the participation of these polypeptides to the active enzyme molecule, and of their possible role in DNA binding or transcription factor recognition.
Ten risk factors (RF) were sought and compared in 100 patients with acute myocardial infarct (MI) and 50 with cerebrovascular disease (CVD) on their first admission. No other diseases were present. Only 3 subjects were free of the RF. At least three RF were noted in 71 MI (71%) and 32 CVD (64%), and four or more in 51 (51%) and 22 (44%) respectively. The most commonly observed in both groups were: high total: HDL cholesterol ratio, cigarette smoking, hypertriglyceridaemia, arterial hypertension, hyperuricaemia Total blood cholesterol was more frequently above normal in MI (52%) than CVD (28%). The difference between the means was significant (p less than 0.01). No significant differences, on the other hand, were noted for the other RF. These findings suggest that the definition of RF for MI and CVD patients is both practicable and important in the secondary prevention of these two diseases. They also show that their atherosclerotic risk profile is substantially the same.
Reference is made to a patient with an approximately 20-yr history of cluster headache and crises refractory to medical prophylaxis for 2 years prior to admission. Over the last 30 days, the picture had been complicated by resistance to ergotamine and motor deficiency in the right leg. Neuroradiological investigation revealed a lesion occupying the left parieto-occipital space. This remained undiagnosed. Its aetiology and clinical relations are discussed in the light of other cases of cluster headache associated with a demonstrated organic lesion described in the literature.
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A case of CT-diagnosed brain-stem haematoma associated with signs of dorsal medullary involvement is reported. The patient recovered completely within 1 month.
The purpose of this study was to teach two mentally retarded employees to perform tasks associated with their jobs. Typically, they served meals during lunch and dinner hours; however, they failed to wipe counters, and check and restock supplies. A self-instructional package, similar to the package introduced by Bornstein and Quevillon (1976), was incorporated to improve their performance in these areas. A multiple-baseline design was utilized in which training was sequentially introduced across subjects. The subjects were taught to ask questions about which tasks needed to be completed, answer their questions, and guide their performance in the task by self-instructing. The self-instructional strategies were introduced just prior to lunch and dinner (30-min period) and during the first 30 min of the lunch and dinner service periods, respectively. During training, both subjects demonstrated that they were capable of rehearsing each of the self-instructional strategies in a specific sequence. Following training, both subjects performed at least one of the three tasks (i.e., wiping counters, checking supplies, restocking supplies) during 84 and 88% of the observed work periods. Additionally, the results of the intervention indicated that both subjects spent more time working and met or exceeded nonprobationary, nonhandicapped coworkers' production standards (social validation measure). The results of this study are compared with those reported by others. Future areas of research are indicated.
The hypolipidemic activity of the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid (MG 28362) was assessed in various experimental conditions versus the corresponding activities of nicotinyl alcohol (NA), nicotinyl alcohol hemisuccinate (NAH), nicotinic acid (NAC), and pantethine tetranicotinate (PTN). In the normolipidemic rat, MG 28362 causes a more durable reduction of non-esterified fatty acids (NEFA) and serum triglycerides than the reference products. NEFA values return slowly to pretreatment levels without causing the rebound effect typical of most nicotinic acid derivatives. Likewise in the test of ethanol-induced hypertriglyceridemia, MG 28362 shows more pronounced and sustained activity compared to the reference products. It is also more effective on Triton hyperlipidemia and on diet-induced hypercholesterolemia; in the latter test, MG 28362 caused no triglyceride accumulation in the liver. Even at high dosage levels, MG 28362 did not cause the characteristic flushing of nicotinic acid congeners. Last, the new substance displays a fairly marked antiaggregating activity on blood platelets, some anti-hypoxic activity, and a generally low order of toxicity.
The preparation is reported of compounds with a free or esterified hydroxyisobutyric acid grouping characteristic of clofibrate, on various supporting molecules related to clofibrate itself or to probucol. Some compounds showed clear hypolipemic activity and for one compound (MG 6893) the effect was not accompanied by hepatomegalia.
We prepared several esters of pantetheine and pantethine, respectively, with 3-pyridineacetic acid and with 3-(3-pyridinemethoxycarbonyl)propionic acid, and we tested these products for their capacity to lower serum non-esterified fatty acids and triglycerides in normal animals. Among the products thus tested, the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid (MG 28362) displayed marked hypolipidemic activity, the action being of uncommonly long duration.
This study assessed the work behavior of five mentally retarded dishwashers. An ABCBC design was utilized with special educators initially observing the dishwashers (Overt measures). During the B phases these educators observed the same dishwashers' work behavior while a second group of observers, posing as kitchen laborers (coworkers), assessed work behavior, during other periods of the day (Overt or Covert). Finally, during C phases, special educators and coworkers recorded dishwashers working at the same time (Overt and Covert). Results indicated dishwashers worked more when educators observed them. Dishwashers spent less time working when these educators were absent. During the "Overt and Covert" observation phases (Phase C), where covert measures were taken in addition to overt measures (i.e., at the same time and on the same person), covert measures covaried with educators' measures of work performance. These results are discussed with suggestions to initiate a program of research to investigate the use of coworkers in the administration of behavior change methods, in work settings.