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Biomedical subjects

J Horowitz

Publications and source records attributed to J Horowitz.

At least 91 records · Page 5Linked to original sources

Serum and synovial fluid levels of serum amyloid A protein and C-reactive protein in inflammatory and noninflammatory arthritis.

Serum and synovial fluid (SF) levels of serum amyloid A (SAA) and C-reactive protein (CRP) were measured in 46 cases of various inflammatory arthritis (Group 1), and in 40 cases of noninflammatory arthritis: 18 cases of osteoarthritis (Group 2) and 22 cases of traumatic arthritis (Group 3). Serum and SF SAA levels were markedly elevated in Group 1: 126.4 micrograms/ml +/- 19.2 SEM and 46.4 micrograms/ml +/- 10.5 SEM, respectively; moderately elevated in Group 2: 10.1 micrograms/ml +/- 2.9 SEM, 4.0 micrograms/ml +/- 1.1 SEM and moderately elevated in Group 3: 10.4 micrograms/ml +/- 1.2 SEM, 4.0 micrograms/ml +/- 1.2 SEM, respectively. Serum/SF SAA ratios were similar in all 3 groups and ranged between 2.52-2.72. In comparison to SAA, the increment of serum and SF CRP above normal levels was moderate. A positive strong correlation was found between serum SAA and serum CRP: r = 0.64 (p less than 0.001) and between SF SAA and SF CRP: r = 0.59 (p less than 0.0001). SF SAA did not correlate with the number of SF white blood cells but did correlate with the percent of SF polymorphonuclear cells: r = 0.23 (p less than 0.05).

Arthritis↗

Mobility of individual 5-fluorouridine residues in 5-fluorouracil-substituted Escherichia coli valine transfer RNA. A 19F nuclear magnetic resonance relaxation study.

19F nuclear magnetic resonance (n.m.r.) relaxation parameters of 5-fluorouracil-substituted Escherichia coli tRNA(Val)1 were measured and used to characterize the internal mobility of individual 5-fluorouridine (FUrd) residues in terms of several models of molecular motion. Measured relaxation parameters include the spin-lattice (T1) relaxation time at 282 MHz, the 19F(1H) NOE at 282 MHz, and the spin-spin (T2) relaxation time, estimated from linewidth data at 338 MHz, 282 MHz and 84 MHz. Dipolar and chemical shift anisotropy contributions to the 19F relaxation parameters were determined from the field-dependence of T2. The results demonstrate a large chemical shift anisotropy contribution to the 19F linewidths at 282 and 338 MHz. Analysis of chemical shift anisotropy relaxation data shows that, relative to overall tumbling of the macromolecule, negligible torsional motion occurs about the glycosidic bond of FUrd residues in 19F-labeled tRNA(Val)1, consistent with the maintenance of base-base hydrogen-bond and/or stacking interactions at all fluorouracil residues in the molecule. The dipolar relaxation data are analyzed by using the "two-state jump" and "diffusion in a cone" formalisms. Motional amplitudes (theta) are interpreted as being due to pseudorotational fluctuations within the ribose ring of the fluorinated nucleoside. These amplitudes range from approximately 30 degrees to 60 degrees, assuming a correlation time (tau i,2) of 1.6 ns. By using available 19F n.m.r. assignment data for the 14 FUrd residues in 5-fluorouracil-substituted tRNA(Val)1, these motional amplitudes can be correlated directly with the environmental domain of the residue. Residues located in tertiary and helical structural domains show markedly less motion (theta approximately equal to 30 to 35 degrees) than residues located in loops (theta approximately equal to 45 to 60 degrees). A correlation between residue mobility and solvent exposure is also demonstrated. The amplitudes of internal motion for specific residues agree quite well with those derived from X-ray diffraction and molecular dynamics data for yeast tRNA(Phe).

Chemical Phenomena↗

19F nuclear magnetic resonance as a probe of anticodon structure in 5-fluorouracil-substituted Escherichia coli transfer RNA.

The use of 19F nuclear magnetic resonance (n.m.r.) spectroscopy as a probe of anticodon structure has been extended by investigating the effects of tetranucleotide binding to 5-fluorouracil-substituted Escherichia coli tRNA(Val)1 (anticodon FAC). 19F n.m.r. spectra were obtained in the absence and presence of different concentrations of oligonucleotides having the sequence GpUpApX (X = A,G,C,U), which contain the valine codon GpUpA. Structural changes in the tRNA were monitored via the 5-fluorouracil residues located at positions 33 and 34 in the anticodon loop, as well as in all other loops and stems of the molecule. Binding of GpUpApA, which is complementary to the anticodon and the 5'-adjacent FUra 33, shifts two resonances in the 19F spectrum. One, peak H (3.90 p.p.m.), is also shifted by GpUpA and was previously assigned to FUra 34 at the wobble position of the anticodon. The effects of GpUpApA differ from those of GpUpA in that the tetranucleotide induces the downfield shift of a second resonance, peak F (4.5 p.p.m.), in the 19F spectrum of 19F-labeled tRNA(Val)1. Evidence that the codon-containing oligonucleotides bind to the anticodon was obtained from shifts in the methyl proton spectrum of the 6-methyladenosine residue adjacent to the anticodon and from cleavage of the tRNA at the anticodon by RNase H after binding dGpTpApA, a deoxy analog of the ribonucleotide codon. The association constant for the binding of GpUpApA to fluorinated tRNA(Val)1, obtained by Scatchard analysis of the n.m.r. results, is in good agreement with values obtained by other methods. On the basis of these results, we assign peak F in the 19F n.m.r. spectrum of 19F-labeled tRNA(Val)1 to FUra 33. This assignment and the previous assignment of peak H to FUra 34 are supported by the observation that the intensities of peaks F and H in the 19F spectrum of fluorinated tRNA(Val)1 are specifically decreased after partial hydrolysis with nucleass S1 under conditions leading to cleavage in the anticodon loop. The downfield shift of peak F occurs only with adenosine in the 3'-position of the tetranucleotide; binding of GpUpApG, GpUpApC, or GpUpApU results only in the upfield shift of peak H. The possibility is discussed that this base-specific interaction between the 3'-terminal adenosine and the 5-fluorouracil residue at position 33 involves a 5'-stacked conformation of the anticodon loop. Evidence also is presented for a temperature-dependent conformational change in the anticodon loop below the melting temperature of the tRNA.

Anticodon↗

Structure of tobacco genes encoding pathogenesis-related proteins from the PR-1 group.

Infection of Samsun NN tobacco with tobacco mosaic virus (TMV) was found to induce the synthesis of mRNA encoding a basic protein with a 67% amino acid sequence homology to the known acidic pathogenesis-related (PR) proteins 1a, 1b and 1c. By Southern blot hybridization it was shown that the tobacco genome contains at least eight genes for acidic PR-1 proteins and a similar number of genes encoding the basic homologues. Clones corresponding to three of the genes for acidic PR-1 proteins were isolated from a genomic library of Samsun NN tobacco. The nucleotide sequence of these genes and their flanking sequences were determined. One clone was found to correspond to the PR-1a gene; the two other clones do not correspond to known TMV-induced PR-1 mRNA's and may represent silent genes. Compared to the PR-1a gene, these genes contain an insertion or deletion in the putative promoter region and mutations affecting the PR-1 reading frame.

Amino Acid Sequence↗

Blood clearance of Streptococcus pneumoniae by C-reactive protein.

C-reactive protein (CRP) has long been known to be an acute phase protein associated with infection and various forms of tissue damage. Recent studies have shown that human CRP can be used to passively protect mice from lethal infection with Streptococci pneumoniae. In this study we have undertaken a detailed examination of the ability of human CRP and rabbit CRP (CxRP) to mediate the blood clearance of pneumococci in mice. We have shown that the optimal activity of these acute-phase proteins requires a functioning complement system, and it can take place even in the xid mouse, which has virtually no naturally occurring anti-pneumococcal antibody in its serum. These studies provide additional evidence that CRP may play a protective role in pneumococcal infections, and it may help postpone the development of fatal levels of pneumococci in the blood, long enough for an effective anti-pneumococcal antibody response to be generated.

Animals↗

Cardiovascular manifestations of ankylosing spondylitis.

In a retrospective study, 40 patients with ankylosing spondylitis were assessed for extraspinal manifestations. Cardiovascular complications were found in 17 patients (42.5%): 5 (12.5%) had aortic insufficiency, 3 (7.5%) had atrioventricular block and 5 (12.5%) had bundle branch block. Wolff-Parkinson-White syndrome was diagnosed in one case and short PR syndrome in another. Cardiovascular complications were more common in patients with longer disease duration. Ischemic heart disease was found in 17.5% of the cases and pulmonary fibrosis in 15%. Peripheral arthritis was found in 42.5% and its prevalence did not differ in patients with or without cardiac involvement.

Adolescent↗

Low serum antimycobacterial glycolipid antibody titers in the sera of patients with systemic lupus erythematosus associated with central nervous system involvement.

Antibodies which bind to glycolipids derived from Mycobacterium tuberculosis were sought in the sera of patients with systemic lupus erythematosus (SLE), with and without neurological disease, patients with active tuberculosis and normal controls. A significantly lower activity against the mycobacterial glycolipids was detected in the sera of patients with SLE with neurological involvement compared to other patients with SLE or controls. We suggest that low antibody levels against mycobacterial glycolipids may be useful in the diagnosis of patients with SLE in whom involvement of the central nervous system is suspected.

Antibodies, Bacterial↗

Quinidine-induced lupus erythematosus-like syndrome: three case reports and a review of the literature.

Three patients with an LE-like syndrome secondary to quinidine are described. Twenty-two similar cases are reviewed. The clinical picture is characterized mainly by polyarthritis, pleuritis, fever and dermatitis. The common laboratory findings are positive antinuclear antibodies, absence of anti-DNA antibodies, thrombocytopenia, leukopenia and abnormal liver function tests. This LE-like syndrome may appear within days or up to several years after the start of quinidine treatment and disappears completely a few weeks after discontinuation of the drug.

Aged↗

Erythema nodosum in the Negev area--a survey of 50 patients.

Fifty patients in the Negev area with erythema nodosum (EN) were studied retrospectively. The clinical picture and demographic characteristics did not differ markedly from those in the literature. In contrast to most European studies but like those from Egypt, we found streptococcal pharyngitis to be the major cause of EN. Conspicuously, sarcoidosis is a rare cause of EN in the Negev. The low incidence of EN in the Negev--2 cases/100,000 people per year--as opposed to Europe--14 cases/100,000 people per year--is hardly explained by the low occurrence of sarcoidosis in Israel. Other factors, unknown at present, may account for this low incidence.

Adolescent↗

Limited joint mobility and other rheumatological manifestations in diabetic patients.

Limited joint mobility was diagnosed in 42.9% of Type I and 37.3% of Type II diabetic patients. Abnormally thick skin was detected in 31.4% of Type I and 33.7% of Type II diabetic patients. Skin abnormalities were observed mainly in patients with L.J.M. There was a high prevalence of hand flexor tendon abnormalities (18.6%). Decreased range of shoulders and hips and flexor tendon abnormalities were significantly more common in patients with LJM. No significant association was found between LJM and grip strength, joint complaints, family history of rheumatic diseases, hypoglycemic attacks, cardiovascular diseases and autonomic neuropathy.

Adolescent↗

Fluorine-19 nuclear magnetic resonance studies of the structure of 5-fluorouracil-substituted Escherichia coli transfer RNA.

19F nuclear magnetic resonance has been used to study fully active Escherichia coli tRNA1Val in which 5-fluorouracil has replaced more than 90% of all uracil and uracil-derived modified bases. The 19F spectrum of the native tRNA contains resolved resonances for all 14 incorporated 5-fluorouracils. These are spread over a 6 ppm range, from 1.8 to 7.7 ppm downfield of the standard free 5-fluorouracil. The 19F resonances serve as sensitive monitors of tRNA conformation. Removal of magnesium or addition of NaCl produces major, reversible changes in the 19F spectrum. Most affected is the lowest field resonance (peak A) in the spectrum of the native tRNA. This shifts 2-3 ppm upfield as the Mg2+ concentration is lowered or the NaCl concentration is raised. Thermal denaturation of the tRNA results in a collapse of the spectrum to a single broad peak centered at 4.7 ppm. Study of the pH dependence of the 19F spectrum shows that five incorporated fluorouracils with 19F signals in the central, 4-5.5 ppm, region of the spectrum, peaks C, D, E, F, and H, are accessible to titration in the pH 4.5-9 range. All have pKa's close to that of free 5-fluorouridine (ca. 7.5). Evidence for a conformation change in the tRNA at mildly acidic pHs, ca. 5.5, is also presented. Four of the titratable 5-fluorouracil residues, those corresponding to peaks D, E/F, and H in the 19F spectrum of fluorine-labeled tRNAVal1, are essentially completely exposed to solvent as determined by the solvent isotope shift (SIS) on transfer of the tRNA from H2O to 2H2O. These are also the 5-fluorouracils that readily form adducts with bisulfite, a reagent that reacts preferentially with pyrimidines in single-stranded regions. On the basis of these results, resonances D, E, F, and H in the middle of the 19F spectrum are attributed to 5-fluorouracils in non-base-paired (loop) regions of the tRNA. Evidence from the ionic strength dependence of the 19F spectrum and arguments based on other recent studies with fluorinated tRNAs support earlier suggestions [Horowitz, J., Ofengand, J., Daniel, W. E., & Cohn, M. (1977) J. Biol. Chem. 252, 4418-4420] that the resonances at lowest field correspond to tertiary hydrogen-bonded 5-fluorouracils. Consideration of ring-current effects and the preferential perturbation of upfield 19F resonances by the cyclophotoaddition of 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen, which is known to react most readily with pyrimidines in double-stranded regions, permits initial assignment of upfield resonances to 5-fluorouracils in helical stems.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗

Fluorine-19 nuclear magnetic resonance study of codon-anticodon interaction in 5-fluorouracil-substituted E. coli transfer RNAs.

Codon-anticodon interaction was investigated in fully active 5-fluorouracil-substituted E. coli tRNAVal1 (anticodon FAC) by 19F NMR spectroscopy. Binding of the codon GpUpA results in the upfield shift of a 19F resonance at 3.9 ppm in the central region of the 19F NMR spectrum, whereas trinucleotides not complementary to the anticodon have no effect. The same 19F resonance shifts upfield upon formation of an anticodon-anticodon dimer between the 19F-labeled tRNA and E. coli tRNATyr2 (anticodon QUA). These results permit assignment of the peak at 3.9 ppm to the 5-fluorouracil at position 34 in the anticodon of fluorouracil-substituted tRNAVal1. The methionine codon ApUpG also causes a sequence-specific upfield shift of a peak in the central part of the 19F NMR spectrum of fluorinated E. coli tRNAMetm. However, ApUpG has no effect on the 19F spectrum of 19F-labeled E. coli tRNAMetf, indicating possible conformational differences between the anticodon loop of initiator and chain-elongating methionine tRNAs. 19F NMR experiments detect no binding of CpGpApA to the complementary FpFpCpG (replaces Tp psi pCpG) in the T-loop of 5-fluorouracil-substituted tRNAVal1, in the presence or absence of codon, suggesting that the tertiary interactions between the T- and D-loops are not disrupted by codon-anticodon interactions.

Anticodon↗