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Biomedical subjects

A Marcus

Publications and source records attributed to A Marcus.

At least 55 records · Page 3Linked to original sources

Effects of age, neuropsychological impairment, and medication on regional cerebral blood flow in schizophrenia and major affective disorder.

Reports of abnormalities of regional cerebral blood flow (rCBF) in patients with schizophrenia and major affective disorder are contradictory. To gain a better understanding of the possible sources of these contradictions, the rCBF and neuropsychological functioning of 15 schizophrenics, 15 patients with major affective disorder, and 15 age-matched controls were studied. No group differences in overall rCBF, percent frontal deviation in flow, or rCBF asymmetries were observed. Both overall rCBF and percent frontal deviation of rCBF were reduced with greater age and with increasing neuropsychological impairment. Dosage of neuroleptic medication was associated with reduced whole brain flow, not with percent frontal deviation flow. Previously reported differences in the resting rCBF of schizophrenics might be more closely related to the age of the subjects and to their neuropsychological impairment rather than the inherent progression of the disorder.

Adult↗

[Evaluation of a transitional group home for psychiatric patients during and after adolescence].

A report is given on a 6-year follow-up study of a project involving outpatient treatment of adolescents and young adults (16-21 years of age) coupled with group living following inpatient treatment for psychiatric disorders. During the period studied 45 of the 53 participants completed treatment. The mean duration of treatment was 46 weeks for both the group with and without psychotic symptoms.

Adolescent↗

Ribosome binding to inosine-substituted mRNAs in the absence of ATP and mRNA factors.

Incubating ribosomes and eukaryotic initiation factor eIF3 with an inosine-substituted mRNA (where the mRNA secondary structure is strongly reduced) in the absence of ATP and other protein synthesis factors produces a 40 S ribosome.mRNA complex. When Met-tRNAMeti and eIF2 are added, a 60 S ribosome subunit attaches forming an 80 S ribosome.mRNA complex. ATP and the three mRNA factors, eIF4B, cap-site factor, and eIF4A, strongly stimulate the attachment of the 60 S subunit. In the absence of Met-tRNAMeti, the 60-S subunit does not attach, and adding ATP and the mRNA factors inhibits the accumulation of 40 S ribosome.inosine mRNA complexes. These results indicate that a 40 S ribosome, probably in a complex with eIF3, has an intrinsic capacity to attach to mRNA. Further, they suggest that Met-tRNAMeti may interact in a subsequent step to stabilize the 40 S ribosome.mRNA complex and allow the attachment of a 60 S ribosome subunit. Although seen most clearly with the inosine-substituted mRNAs, the 40 S ribosome reaction is also obtained with "guanosine" mRNA. A 40 S ribosome attaches to guanosine mRNA without ATP and mRNA factors when an incubation mixture containing ribosomes, eIF3, and mRNA is fixed with glutaraldehyde. In addition, a 40 S ribosome.guanosine mRNA complex can be obtained without glutaraldehyde in incubations containing ATP and the three mRNA factors in the absence of Met-tRNAMeti. The latter reaction is limited because of the instability of the 40 S ribosome.mRNA complex in the absence of Met-tRNA. Nevertheless, its authenticity is indicated by its full dependence upon ATP and the three mRNA factors. The lack of factor requirement for the formation of 40 S ribosome complexes with inosine-substituted mRNAs indicates that ATP and the three mRNA factors function primarily to unwind the secondary structure of a guanosine mRNA. Data relevant to a role for ATP in facilitating ribosome migration on an mRNA are also discussed.

Adenosine Triphosphate↗

Characterization of two soybean repetitive proline-rich proteins and a cognate cDNA from germinated axes.

We have resolved and analyzed two proline-rich proteins isolated from the walls of soybean cells in culture. The proteins are similar in amino acid content, containing 20% proline, 20% hydroxyproline, 20% lysine, 16% valine, 10% tyrosine, and 10% glutamate. The proteins undergo a rearrangement or a limited cleavage in dilute NaOH, but are otherwise remarkably stable to a high concentration of alkali. We have cloned and sequenced a cDNA from soybean axes germinated for 31 hours (1A10-2) coding for a protein that closely corresponds in its amino acid content to that of the proline-rich proteins. The cDNA sequence predicts a decameric repeat of Pro-Pro-Val-Tyr-Lys-Pro-Pro-Val-Glu-Lys. Consequently, this class of proteins is referred to as repetitive proline-rich proteins, i.e., RPRP2 and RPRP3. We have also analyzed RNA gel blots with probes that discriminate between the new cDNA clone and a related cDNA previously reported [SbPRP1; Hong, Nagao, and Key (1987). J. Biol. Chem. 262, 8367-8376]. Messenger RNAs from young seedlings and from soybean suspension cultures correspond primarily to the new RPRP clone (1A10-2), whereas the predominant mRNA accumulating later in the roots corresponds to SbPRP1.

Amino Acid Sequence↗

Somatic findings in children and adolescents with anorexia nervosa.

94 patients (mean age 15,4 years) with anorexia nervosa were investigated. We found cardiovascular parameters in correlation with body weight. ECG-changes had no connection with weight and concentration of potassium. Pulse and systolic blood pressure decreased, concentration of urea and SGOT and SGPT increased with weight decreases. Compared with the results of the adults of Fichter (1985), pulse and blood pressure changed more often, whereas the concentration of potassium often rested unchanged. Therapy with neuroleptics calls for ECG-controls. Interesting was the finding that we found less raised levels of cortisol in the group with extremely low weight on admission.

Adolescent↗

A hydroxyproline-rich protein in the soybean cell wall.

A cDNA clone that hybridizes to an mRNA (1A10) that accumulates to a substantial level in the axis of the germinating soybean seed was sequenced. The amino acid sequence of the clone indicates an almost perfect repeat of Pro-Pro-Val-Tyr-Lys resulting in a protein containing 40% proline and lacking serine and histidine. On the likelihood that such a protein might be a hydroxyproline-rich cell-wall glycoprotein (HRGP), cell walls of a soybean cell culture were extracted by procedures used to obtain soluble basic cell-wall glycoproteins, and the proteins were fractionated and purified. A 33-kDa protein (and possibly a 28-kDa protein) was obtained that has an amino acid distribution similar to that of the cDNA clone. The protein lacks histidine and serine and contains 20% hydroxyproline and 20% proline. The HRGP is thus distinct both in its amino acid content and in its pentameric repeat of Pro-Pro-Val-Tyr-Lys, with half of the prolines being hydroxylated.

Amino Acid Sequence↗

Workplace smoking policies: attitudes of union members in a high-risk industry.

We surveyed members of a medium-size national union representing workers in high-risk industries to assess workers' support for union and company programs to help smokers break the habit and policies that restrict smoking. Two surveys were conducted that involved 690 respondents in 1984 and 593 respondents in 1985. Respondents overwhelmingly (82%) favored restrictions on smoking in the workplace but less than half agreed that companies or unions should be concerned about workers smoking off the job. For both smokers and nonsmokers, beliefs that cancer has specific causes and can be prevented strongly predict support for workplace smoking control policies. Exposure to company occupational health training also influenced smokers and nonsmokers to support selected smoking control policies. These and other findings led to the conclusion that: (1) educating workers about cancer may promote support for smoking control policies, and (2) smoking control policies are more acceptable in the context of a strong company health and safety program.

Attitude↗

A wheat germ cap-site factor functional in protein chain initiation.

Component C1 from wheat germ, a factor that functions in attaching ribosomes to mRNA, has been resolved into a fraction that does not bind to m7GDP-agarose (referred to as eIF4B) and one that binds and is eluted specifically by m7GDP. Both components are required for the attachment of ribosomes to [3H]methyl-labeled reovirus RNA and for the translation of a number of mRNAs, including the noncapped RNA of satellite tobacco necrosis virus. The component that binds to m7GDP-agarose, referred to as CSF (cap-site factor), contains primarily proteins of Mr 24,000, 26,000, and 75,000. Crosslinking studies with oxidized [3H]methyl-labeled reovirus RNA show that one of the lower molecular weight polypeptides of CSF interacts specifically with the 5'-cap of the mRNA in the absence of any other components. Incubation of component C1 and eIF4A in the presence of ATP results in the additional crosslinking of a 51- and a 65-kDa protein. In the absence of eIF4A, there is only the crosslinking of the lower molecular mass polypeptide (24 or 26 kDa). Attempts to reconstitute the C1 reaction with CSF and eIF4B result in a considerably diminished reaction. Crosslinking of eIF4A, however, is obtained in an incubation containing only CSF and eIF4A, suggesting that CSF may bring about an initial interaction of eIF4A with the 5' end of the mRNA.

Adenosine Triphosphate↗

Initiation factors eIF4A and C1 from wheat germ and the formation of mRNA X ribosome complexes.

The binding of ribosomes to mRNA is analyzed in a fractionated system from wheat germ with [3H]uridine-labeled poly(A)+ RNA prepared from germinating wheat embryos. The reaction requires factors eIF3, eIF4C, and eIF5; Met-tRNA and the Met-tRNA binding system; either GTP or GMP-PNP; ATP; and factors C1 and eIF4A. These requirements are identical to those previously found to be necessary for formation of ribosome X Met-tRNAMeti complexes, with the exception of ATP, and factors C1 and eIF4A. The function of factors C1 and eIF4A is therefore specifically related to the mRNA attachment reaction. The presence of GTP in the mRNA binding reaction results in the formation of 80 S ribosome complexes, while with GMP-PNP only 40 S ribosome complexes are formed. Ribosome binding to native reovirus RNA in the fractionated wheat germ system is similar to the reaction with poly(A)+ RNA, strongly requiring ATP and factors C1 and eIF4A. Binding to inosine-substituted reovirus RNA, however, is only partially dependent upon ATP, and both the ATP-dependent and the ATP-independent binding reactions strongly require factor C1 and are substantially stimulated by factor eIF4A. The ATP-independent reaction is inhibited by pm7GDP, has a strong requirement for Met-tRNAMeti, and the 40 S ribosome complex is stable to RNase. These results indicate that the ATP-independent binding of ribosomes to inosine-substituted reovirus RNA proceeds through the normal initiation process. They further suggest that neither factor C1 nor eIF4A function exclusively to unwind mRNA secondary structure. Since eIF4A is required for the ATP-independent binding to inosine mRNA, and at the same time interacts with ATP in the reaction with ATP-requiring mRNAs, this factor may have two roles in protein chain initiation, one related to the mRNA X ribosome interaction, and one related to the function of ATP.

Adenosine↗

Omaha childhood blood lead and environmental lead: a linear total exposure model.

The majority of experimental and population studies of blood lead (PbB) and environmental lead, including the Omaha study, have utilized the Goldsmith-Hexter log-log or power function model. Comparison was made of the log-log model and a linear model of total exposure to describe the Omaha Study of 1074 PbBs from children ages 1-18 years as related to air (PbA), soil (PbS), and housedust (PbHD) lead. The data fit of the linear model was statistically equivalent to the power model and the predicted curves were biologically more plausible. The linear model avoids the mathematical limitations of the power model which predicts PbB zero at PbA zero. From the Omaha data, this model, ln PbB = ln (beta 0 + B1 PbA + B2 PbS + beta 3 PbHD) predicts that PbB increases 1.92 micrograms/dl as PbA increases 1.0 microgram/m3. Since PbS and PbHD increase with PbA, however, the increases in total exposure predict a PbB increase of 4-5 micrograms/dl as PbA increases 1.0 microgram/m3.

Adolescent↗

Evaluation of hospital care in one trauma care system.

To evaluate the effectiveness of the trauma care system in the Hudson Valley Emergency Medical Services (EMS) Region, (with no designated regional trauma care center) 421 consecutive trauma autopsy reports for 1979-80 were analyzed. Of the 421 trauma patients, 194 died at the scene (DAS), most from vehicular accidents. The remaining 227 patients were triaged into the EMS system. Ninety-five were dead on arrival (DOA) at medical facilities; of 132 (31 per cent) who arrived alive at hospitals, 35 died in emergency rooms and 97 died later as inpatients. Nearly 60 per cent of the deaths involved brain injuries. A panel of five physician-evaluators examined the pathologist's analysis of those deaths considered to have been possibly preventable and concluded that 10 deaths (7.6 per cent) of in-hospital cases were preventable. The study showed the need for primary prevention of accidents to decrease the number of victims (46 per cent) who died at the scene and those (23 per cent) who were dead on arrival at hospitals.

Accidents, Traffic↗

Wheat germ eIF2 and CoeIF2. Resolution and functional characterization in in vitro protein synthesis.

A factor that binds Met-tRNAiMet in a ternary complex (eucaryotic initiation factor (eIF2) ) and an auxiliary component that strongly stimulates the activity of the binding factor (CoeIF2) have been purified from extracts of wheat germ. The molecular weights of the two factors, as determined by glycerol gradient centrifugation and sodium dodecyl sulfate gel electrophoresis, are 88,000 and 20,000, respectively. Incubation of wheat germ eIF2 with gamma-[32P]ATP and alpha-subunit kinase results in the phosphorylation of a Mr = 40,500 subunit, while no specific phosphorylations are found when the eIF2 is incubated with the beta-kinase. These data are interpreted to suggest that CoeIF2 is a monomer of Mr = 20,000 while eIF2 may be a dimer, containing subunits of Mr = 40,000 and 50,000. Both eIF2 and CoeIF2 are strongly required for in vitro amino acid polymerization, providing the first direct demonstration of the function of CoeIF2 in protein synthesis.

Electrophoresis, Polyacrylamide Gel↗

Fractionation and partial characterization of the protein synthesis system of wheat germ. I. Resolution of two elongation factors and five initiation factors.

Wheat germ S100 supernatant was resolved into 10 components, all of which are required for tobacco mosaic virus RNA-directed incorporation of amino acid into protein. Two of the components, C2b and C2a, are, respectively, elongation factors 1 and 2, having molecular weights of 51,000 and 72,000. A third factor (C2e) binds Met-tRNA in a GTP-requiring reaction and is absolutely required for the formation of both 40 S ribosome.Met-tRNAiMet and 80 S ribosome.Met-tRNAiMet complexes. This factor is considered to be eucaryotic initiation factor 2. Formation of 80 S ribosome Met-tRNAiMet complexes is augmented 2 to 3-fold by the simultaneous addition of an mRNA, factor C1, and fraction D2(a + b). Factor C1 also reverses the inhibition of translation by an increased concentration of monovalent cations and promotes the translation of a "competitively inhibited" mRNA. These observations suggest that factor C1 and either factor D2a and D2b (or both) function in mRNA attachment reactions. Factor C1 has a molecular weight of 115,000 and appears to be made up of two or three subunits. Factor D2b has been purified to essential homogeneity and has a molecular weight of 55,000. Its interaction with mRNA and its molecular weight suggest that this factor is the wheat germ equivalent of reticulocyte eucaryotic initiation factor 4A.

Amino Acids↗

Fractionation and partial characterization of the protein synthesis system of wheat germ. II. Initiation factors D1 (eucaryotic initiation factor 3), D2c (eucaryotic initiation factor 5), and D2d (eucaryotic initiation factor 4C).

This report characterizes three components of the fractionated wheat germ protein synthesizing system, factors D1, D2c, and D2d. FActor D1 has a molecular weight of about 420,000 and is comprised of 7-10 components varying in molecular mass between 28,000 and 105,000 daltons. The factor is absolutely required for the formation of both 40-S ribosome.Met-tRNAiMet and 80 S ribosome.Met-tRNAiMet complexes except at low Mg2+ concentration, where significant 40 S ribosome complex formation can be obtained without D1, provided the reaction products are fixed with glutaraldehyde. Factor D1 can be shown to interact with the 40-S ribosome subunit in two ways: the change in sedimentation of the ribosome subunits that occurs when ribosomes are incubated with the factor under dissociating conditions and the prevention of the reformation of 80 S ribosomes by a prior incubation of ribosome subunits with the factor. Factor D2c has a molecular mass of about 100,000 daltons and is absolutely required for the conversion of 40 S ribosome.Met-tRNAiMet complexes to 80 S ribosome.Met-tRNAiMet. Factor D2d strongly augments the D2c-dependent formation of 80S ribosome.Met-tRNAiMet complexes, with the requirement for D2d most apparent when the complexes are fixed with glutaraldehyde, a treatment that labilizes the 80 S ribosome-bound Met-tRNAiMet. Addition of factor D2d to a 40 S ribosome.Met-tRNAiMet synthesizing system also increases the amount of complex obtained 2-5-fold. Consideration of these characteristics establishes components D1, D2c, and D2d as wheat germ eucaryotic initiation factors 3, 5, and 4C, respectively.

Eukaryotic Initiation Factor-1↗

Eukaryotic initiation factor 4A is the component that interacts with ATP in protein chain initiation.

Protein synthesis in a resolved homogenate of wheat germ requires ATP and eight factors functioning at the level of protein chain initiation. To identify the component(s) interacting with ATP, the different factors were treated with the ATP affinity analogue 5'-p-fluorosulfonylbenzoyladenosine (FSBA) and tested for their function in protein synthesis. The activity of eukaryotic initiation factor 4A (eIF4A) was strongly curtailed, whereas all other factors were unaffected. At a concentration of 250 microM, AMP, ADP, and ATP protected eIF4A against FSBA inactivation, whereas at a concentration 50 microM, protection was afforded only by ATP. GTP did not protect at a concentration of 250 microM. In another approach, the substrate analogue 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP) was found to inhibit protein synthesis in a manner, at least in part, competitive with ATP. Supplementing a TNP-ATP inhibited reaction with eIF4A substantially reversed the inhibition. Except for a small effect by factor C1, no reversal was obtained with any other component. Finally, a preincubation of ribosomes with ATP, mRNA, and eIF4A resulted in the formation of a complex capable of TNP-ATP-resistant amino acid incorporation. These data are interpreted to indicate that the primary interaction of ATP is with eIF4A. A model is proposed reconciling this conclusion with other observations relevant to the mRNA . ribosome attachment reaction.

Adenosine Triphosphate↗