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Biomedical subjects

R Shapiro

Publications and source records attributed to R Shapiro.

At least 361 records · Page 20Linked to original sources
PubMed1985

Computed tomography of temporal bone pneumatization: 1. Normal pattern and morphology.

The pneumatization of 141 "normal" temporal bones on computed tomography (CT) was evaluated in 100 patients (age range, 6-85 years). Because of the controversy surrounding the sclerotic squamomastoid (mastoid), temporal bones with this finding were discarded. A CT index of pneumatization was based on the pneumatized area and the number of cells seen within a representative scanning section. Results suggest that squamomastoid pneumatization follows the classic normal distribution and does not correlate with age, gender, or laterality. A high degree of symmetry was found in 41 patients who had both ears examined. In 35% of all temporal bones, the petrous apex was pneumatized, concordant with the findings of other investigators. Pneumatization extending into other regions of the temporal bone corresponded linearly with squamomastoid pneumatization. Air-cell configuration was variable. Air-cell size tended to increase progressively from the mastoid antrum. The scutum "pseudotumor" appearance caused by incomplete pneumatization was seen frequently, and should not be mistaken for mastoiditis or an osteoma. Thick sections producing partial-volume effect may also produce this spurious finding. Therefore, when searching for mucosal thickening due to mastoiditis, large air cells should preferably be analyzed.

Adolescent↗
PubMed1985

Serum IgG and IgM rheumatoid factors and complement activation in extraarticular rheumatoid disease.

Rheumatoid factors (RF) may participate in both synovial and extraarticular (EA) inflammation in rheumatoid disease (RD). The relative roles of serum IgG RF and IgM RF in extraarticular rheumatoid disease (EARD) are unclear, as is the importance of complement (C) activation by these proteins. To investigate the relation of C activating properties of IgM RF (RF CAP) and total IgG RF and IgM RF to EARD we compared 18 patients with only articular disease to 27 patients with various EA manifestations (nodules, cutaneous vasculitis, neuropathy, Felty's syndrome) using radioimmunoassays for IgG and IgM RF and an established hemolytic assay for C activation by IgM RF. We calculated RF CAP by determining the mean hemolysis of sensitized SRBC/ml of RF serum (MH/ml). Normal volunteers and patients with other inflammatory arthritides served as controls. Controls had negligible amounts of IgG RF, IgM RF, and RF CAP. Mean IgG and IgM RF levels and RF CAP values were significantly higher in patients with EARD than those in the arthritis-only (AO) group. Mean IgM RF concentrations and IgM RF CAP correlated with each other and EARD. IgG RF also correlated with IgM RF and EARD, but did not contribute to RF CAP or EARD when adjusted for IgM RF. Further, some patients had high RF CAP values despite modest IgM RF levels. These data suggest that quantitative differences in IgM RF CAP and total IgM RF may be more important than IgG RF as determinants of EARD.

Arthritis, Rheumatoid↗
PubMed1984

Inhibition of angiotensin converting enzyme: mechanism and substrate dependence.

The interaction of angiotensin converting enzyme with six metal-coordinating [(D-3-mercapto-2-methylpropanoyl)-L-Pro (captopril), N-[1(S)-carboxy-3-phenylpropyl]-L-Ala-L-Pro (MK-422), N-(phenylphosphoryl)-L-Phe-L-Phe, N alpha-(3-mercaptopropanoyl)-L-Arg, N alpha-[1(S)-carboxy-3-phenylpropyl]-Ala-L-Lys, and N-[1(S)-carboxy-5-aminopentyl]-L-Phe-Gly] and three dipeptide inhibitors (Gly-L-Trp, L-Phe-L-Arg, and L-Ala-L-Pro) was examined at pH 7.5 in the presence of 300 mM NaCl. Inhibition modes, apparent Ki [Ki(app)] values, and shapes of 1/v vs. [I] plots were found to vary with the substrate employed. All inhibitors except Phe-Arg were competitive with the substrate furanacryloyl (Fa)-Phe-Gly-Gly, while five of seven tested with Fa-Phe-Phe-Arg as substrate produced mixed patterns. Ki-(app) values for N-[1(S)-carboxy-5-aminopentyl]-L-Phe-Gly, N-(phenylphosphoryl)-L-Phe-L-Phe, Gly-Trp, and MK-422 were 8.3-, 5.5-, 4.7-, and 2.6-fold lower, respectively, when Fa-Phe-Gly-Gly was substrate, compared with values measured with Fa-Phe-Phe-Arg. In contrast, Ki(app) values for Phe-Arg and (3-mercaptopropanoyl)-Arg were lower (2.8- and 2.2-fold, respectively) when Fa-Phe-Phe-Arg was the substrate. Plots of 1/v vs. [I] for most of the inhibitors were nonlinear, to an extent which was also substrate dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Inhibition of angiotensin converting enzyme: dependence on chloride.

In a previous report [Shapiro, R., Holmquist, B., & Riordan, J. F. (1983) Biochemistry 22, 3850], it was demonstrated that activation of angiotensin converting enzyme (ACE) by chloride is strongly dependent on substrate structure, and three substrate classes were identified on the basis of activation behavior. The present study examines the chloride dependence of the inhibition of ACE by nine inhibitors [(D-3-mercapto-2-methylpropanoyl)-L-Pro (captopril), N-[1(S)-carboxy-3-phenylpropyl]-L-Ala-L-Pro (MK-422), L-Ala-L-Pro, N-(phenylphosphoryl)-L-Phe-L-Phe, Gly-L-Trp, N-[1(S)-carboxy-5-aminopentyl]-L-Phe-Gly, L-Phe-L-Arg, N alpha-(3-mercaptopropanoyl)-L-Arg, and N alpha-[1(S)-carboxy-3-phenylpropyl]-L-Ala-L-Lys] containing structural features characteristic of the three classes of substrates. Apparent Ki values for all inhibitors are markedly (70-250-fold) decreased by 300 mM chloride. However, the enhancement of inhibition is achieved at significantly lower chloride concentrations with those inhibitors having an ultimate arginine or lysine than with the remainder. This variability parallels that previously found for activation of substrate hydrolysis. The effect of chloride on the individual steps in the formation and dissociation of the steady-state enzyme-inhibitor complexes was determined with the slow-binding inhibitor MK-422. Pre-steady-state analysis indicates that binding of both MK-422 and captopril follows a (minimally) two-step mechanism: (formula; see text) in which rapid formation of an enzyme-inhibitor complex is followed by a slow isomerization.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Oculomotor nuclear complex infarction. Clinical and radiological correlation.

We describe a patient with an isolated mesencephalic dorsal tegmental infarct affecting the oculomotor nuclear complex and medial longitudinal fasciculus, documented by high-resolution computed tomography, after undergoing percutaneous transluminal coronary artery angioplasty. Clinically, the patient exhibited bilateral ptosis, bilateral internuclear ophthalmoplegia, transient convergence retractory nystagmus, and minimal somnolence. We believe the combined clinical and radiological findings favor the presence of a caudal, dorsal, and paramedian embolic infarct in the territory of the paramedian branches of the mesencephalic artery as the most likely mechanism for these exceptional findings and correlate them with Warwick's scheme of the oculomotor subnuclei.

Cerebral Infarction↗
PubMed1984

The improbability of prebiotic nucleic acid synthesis.

Many accounts of the origin of life assume that the spontaneous synthesis of a self-replicating nucleic acid could take place readily. Serious chemical obstacles exist, however, which make such an event extremely improbable. Prebiotic syntheses of adenine from HCN, of D,L-ribose from adenosine, and of adenosine from adenine and D-ribose have in fact been demonstrated. However these procedures use pure starting materials, afford poor yields, and are run under conditions which are not compatible with one another. Any nucleic acid components which were formed on the primitive earth would tend to hydrolyze by a number of pathways. Their polymerization would be inhibited by the presence of vast numbers of related substances which would react preferentially with them. It appears likely that nucleic acids were not formed by prebiotic routes, but are later products of evolution.

Chemical Phenomena↗
PubMed1984

Polyamino acid enhancement of bacterial phagocytosis by human polymorphonuclear leukocytes and peritoneal macrophages.

Cationic polyamino acids are known to enhance a variety of cell-cell interactions by virtue of their ability to alter electrostatic forces of cell surfaces. In this study, the effect of polyamino acids on phagocytosis of 3H-labeled bacteria by human polymorphonuclear leukocytes (PMNs) and peritoneal macrophages was investigated. Negatively charged and neutral polyamino acids did not influence phagocytosis of unopsonized Staphylococcus epidermidis, whereas protamine, poly-L-arginine, and poly-L-lysine stimulated phagocytosis in a dose-dependent manner. At 50 micrograms/ml, greater than 30% uptake by PMNs was seen with each of these cationic polyamino acids. Although cationic polyamino acids promoted PMN and peritoneal macrophage phagocytosis of unopsonized S. epidermidis, Staphylococcus aureus M (encapsulated) and M variant (unencapsulated), and Escherichia coli J5, little effect was seen with the parent E. coli O111:B4 or a serotype O222:H16 strain. Pretreatment of bacteria and phagocytes separately demonstrated that the phagocytosis-promoting property of polyamino acids is manifest predominantly on the bacteria. Bacteria pretreated with cationic polyamino acids also elicited a PMN chemiluminescent response, and PMN-associated bacteria were killed, as determined by a fluorochrome microassay. Thus, cationic polyamino acids promote the phagocytosis and killing of many but not all bacterial strains, and in this respect polyamino acids function as opsonins.

Escherichia coli↗
PubMed1984

Protein-enhanced fluorescein chemiluminescence used in an immunoassay for rubella antibody in serum.

The chemiluminescence of fluorescein derivatives is greatly enhanced when they are conjugated to proteins. We exploited this property in devising a chemiluminescence immunoassay for rubella antibodies. In this sequential "sandwich"-type assay, tubes coated with rubella antigen are used for antibody separation and goat antibody to human IgG conjugated with fluorescein isothiocyanate is used for detection of bound rubella antibodies.

Antibodies, Viral↗
PubMed1983

Critical lysine residue at the chloride binding site of angiotensin converting enzyme.

Pulmonary angiotensin converting enzyme has been reductively methylated by using formaldehyde and sodium cyanoborohydride. This modification virtually eliminates enzyme activity toward some substrates (e.g., furanacryloyl-Phe-Gly-Gly) while less drastically affecting activity toward others (e.g., furanacryloyl-Phe-Phe-Arg). Affinity chromatography and analysis of radiolabeled reaction products reveal that this effect is due to methylation of a single critical lysine residue. Loss of activity primarily represents an increase in Km values, indicating that the critical lysine plays a role in substrate binding. This lysine can be protected by a competitive inhibitor, suggesting that it is at or near the active site. Addition of chloride at pH 6.1 specifically protects against methylation of this lysine. These findings support the idea that the critical lysine is part of the binding site for chloride and other monovalent anions which are strong activators of the enzyme.

Animals↗
PubMed1983

Anion activation of angiotensin converting enzyme: dependence on nature of substrate.

Anion activation of pulmonary angiotensin converting enzyme has been examined by using 23 furanacryloyl- and 3 benzoyl-tripeptides as substrates. Chloride stimulates hydrolysis of all substrates at least 24-fold. However, the kinetic mechanism, the amount of chloride required, and the effect of pH on activation, plus the relative activating potencies of various anions, are all strongly dependent on the substrate employed. Three substrate classes have been identified. Class I substrates appear to be hydrolyzed at pH 7.5 by an ordered bireactant mechanism in which anion must bind before substrate. The apparent activation constant (KA') for Cl- ranges from 75 to 150 mM at pH 7.5, doubles at pH 9.0, and decreases to about 3 mM at pH 6.0. Class II substrates, in contrast, are hydrolyzed by a nonessential activator mechanism. The kinetically determined KA' for Cl- at pH 7.5 ranges from 2.9 to 5.0 mM and changes only slightly with pH. Class III substrates are also hydrolyzed by a nonessential kinetic mechanism but one different from that followed by class II peptides. KA' values for Cl- at pH 7.5 measured with class III substrates are 18-30 mM. Class II substrates have Arg or Lys at the ultimate or penultimate position. The features distinguishing class I and III peptides are less clear, although all class III substrates identified have penultimate alanine residues. Possible explanations for this substrate dependence are offered.

Acetates↗
PubMed1983

Complement activity in the cord blood of term neonates with the amniotic fluid infection syndrome.

Cord blood samples from 11 term neonates whose placentas showed histological changes typical of the amniotic fluid infection syndrome were analysed in order to determine haemolytic activity of the classic and alternative complement pathways and serum levels of complement proteins and immunoglobulins. Although the mean values of all these parameters were higher in this group than in an age-related control group, only classic haemolytic pathway activity was significantly elevated (P less than 0,025).

Amniotic Fluid↗
PubMed1983

The effects of bisulfite on growth and macromolecular synthesis in Escherichia coli.

Bisulfite reversibly inhibits the growth of a variety of microorganisms and has been used as a preservative in foods and beverages for that reason. We have now measured macromolecule synthesis in Escherichia coli K12 after bisulfite treatment. RNA synthesis, the synthesis of total protein, and of an inducible enzyme, beta-galactosidase, stopped almost immediately upon addition of 2 mM (or higher concentrations) of bisulfite. These functions resumed after a lag whose duration depended on the concentration of bisulfite added. The synthesis of DNA was slowed upon bisulfite addition, but did not stop entirely. The inhibition of RNA synthesis by bisulfite took place in both stringent and relaxed strains of E. coli and was not relieved upon addition of chloramphenicol. Stringent control was therefore not involved in this effect. No effect on protein synthesis was observed in the cell-free system of E. coli (using poly(U) or MS2 RNA as messenger) at bisulfite concentrations up to 10 mM. Protein synthesis inhibition in vivo was apparently not due to a reaction of bisulfite with a component of this system. In additional experiments, RNA polymerase was not impaired by bisulfite, and the growth inhibition effect was shown to proceed in the presence of inhibitors of free radical chain reactions.

Escherichia coli↗
PubMed1983

Reversal of growth inhibition in Escherichia coli by bisulfite.

Bisulfite inhibits growth, protein synthesis and RNA synthesis in micro-organisms. These inhibitory effects, in Escherichia coli K12, were diminished when certain amino acids were added to the minimal growth medium. The effects of individual amino acids were additive, synergistic and independent of their concentration. At 10 or 5 mM bisulfite, the presence of tyrosine had the greatest importance, while phenylalanine, glycine and methionine played a lesser role. E. coli cultures resume growth subsequent to bisulfite inhibition, after a lag whose duration is proportional to the initial concentration of added bisulfite. This resumption of growth was shown not to result from the depletion of bisulfite (by air oxidation or metabolism), but rather to adaptation to the presence of bisulfite concentrations that previously were inhibitory. The inhibitory effects of bisulfite were duplicated by lesser concentrations of cysteine. Both substances inhibited RNA synthesis by a mechanism that was independent of the stringent control system. A sulfite reductase deficient mutant was more resistant to inhibition by both bisulfite and cysteine. The various results indicate that growth inhibition by bisulfite is not due to covalent reactions with cellular target molecules, but to conversion of bisulfite to other substances, probably including cysteine, which in turn inhibit bacterial growth.

Amino Acids↗