Sj?gren's syndrome in progressive systemic sclerosis

Thirty-five consecutive patients with progressive systemic sclerosis were prospectively evaluated for evidence of Sj?gren's syndrome. Six of the 35 (17%) were judged to have the disorder. This is a higher prevalence than in most reports, but much lower than that recently reportedly by Alarcón-Segovia and associates (7). An additional 17 of the 35 patients (48%) had significant fibrosis in the absence of sufficient mononuclear cell infiltrates to confirm the diagnosis of Sj?gren's syndrome. This group had particularly aggressive scleroderma with serious visceral features, and five died after a short duration of illness. No significant abnormalities were found in biopsies from six patients with the mixed connective tissue disease syndrome, five with Raynaud's phenomenon alone, or in 29 autopsy control subjects who had no evidence of connective tissue disease. Fibrosis in the absence of mononuclear infiltration in minor salivary glands of patients with progressive systemic sclerosis indicates a poor prognosis.     

Do substance abuse patients with more psychopathology receive more treatment?

The association between psychopathology at treatment entry and the amount of treatment services received was evaluated in 104 alcohol-dependent and 100 cocaine-dependent male veterans treated for 1 month in either a day hospital or inpatient program. Measures of psychopathology included the Addiction Severity Index psychiatric composite score, the presence or absence of an antisocial personality disorder diagnosis, and the total number of additional lifetime or current psychiatric diagnoses. Patients with higher admission Addiction Severity Index psychiatric composite scores received more medical, alcohol, family/social, and psychiatric services. There was also preliminary evidence that patients who received more treatment showed greater improvement 7 months after admission. The relationships between the other measures of psychopathology and treatment services failed to achieve overall statistical significance, although significant relationships were found in several individual areas.     

Cytogenetic analysis of aggressive meningiomas: possible diagnostic and prognostic implications

BACKGROUND: Published karyotypes from aggressive (atypical and malignant) meningiomas are few, but suggest clonal evolution from benign tumors with monosomy 22 to aggressive forms with additional abnormalities. The goal of this study was to identify the most frequent karyotypic abnormalities associated with aggressive histopathology and biologic behavior. METHODS: Eight intracranial meningiomas exhibiting histologically atypical features at the time of intraoperative diagnosis were chosen for cytogenetic analysis. The study set was comprised entirely of histologically atypical meningiomas. Four were considered malignant; three on the basis of brain invasion and one due to extracranial metastases. None was histologically anaplastic. RESULTS: Chromosomal abnormalities were demonstrated in 6 cases (75%), 5 of which were complex (63%). Loss of chromosome 22 was identified in two cases, both of which were associated with additional aberrations. Abnormalities most frequently involved chromosomes 1 (63%), 3 (50%), and 6 (63%). Four cases (50%) had dicentric or ring chromosomes. An additional 47 previously reported karyotypes from atypical and malignant meningiomas were reviewed. Comparison with published karyotypes of 200 histologically benign meningiomas served to underscore the increased frequency of complex karyotypes, chromosome 1, 3, and 6 abnormalities, and telomeric associations in the aggressive tumors. Apparently normal karyotypes as well as monosomy 22 alone were more frequently associated with benign, nonatypical histopathology. CONCLUSIONS: These findings suggest a possible role for cytogenetic analysis in determining the prognosis and perhaps in refining the diagnosis of atypical or aggressive meningiomas. Further studies are necessary to determine the significance of complex karyotypes, chromosome 1, 3, and 6 abnormalities, and telomeric associations, particularly whether they portend a more aggressive clinical course in meningiomas lacking features of histologic atypia.     

Exploration of the structural environment of the iron-sulfur cluster in putidaredoxin by nitrogen-15 NMR spectroscopy of selectively labeled cysteine residues

Putidaredoxin is a di-iron protein whose paramagnetic region is not well characterized by 1H detected NMR. We have studied the structure of this region in greater detail by directly observed 15N NMR of oxidized and reduced putidaredoxin preparations in which the six cysteine residues are selectively labeled with 15N. A new method for preparation of a stable form of reduced putidaredoxin has been developed for use in NMR. The 15N NMR spectra of the oxidized and reduced forms are characteristically different, and we have measured and compared 15N chemical shifts, spin-lattice relaxation times (T1), and chemical shift/temperature dependences for both forms. Evidence for localized valencies of the iron atoms in the reduced form is presented. From the 15N T1 values of the oxidized form, reduced distances of the cysteine backbone 15N nuclei from the center of the Fe2S2 cluster have been calculated. These distances are consistent with those calculated from X-ray crystal structure data for five ferredoxins, and confirm the structural similarity of the Fe2S2 clusters in putidaredoxin and in these ferredoxins in the oxidized state.     

A novel mechanism for bradykinin production at inflammatory sites. Diverse effects of a mixture of neutrophil elastase and mast cell tryptase versus tissue and plasma kallikreins on native and oxidized kininogens

Coprocessing of kininogens by a mixture of human mast cell tryptase and neutrophil elastase was explored as a potential substitute for the kallikrein-dependent pathway for kinin generation during inflammation. Tryptase easily excised bradykinin from the synthetic heptadecapeptide, ISLMKRPPGFSPFRSSR, but was unable to produce significant amounts of kinin by proteolysis of kininogens. However, a mixture of tryptase and elastase released bradykinin from each protein with a yield comparable to that of human plasma kallikrein. Significantly, neither plasma nor tissue kallikrein was able to effectively process N-chlorosuccinimide-oxidized high molecular weight kininogen, an effect attributed to the oxidation of a methionine residue upstream from the N terminus of the kinin domain. In support of these results the model heptadecapetide, ISL(MO)KRPPGFSPFRSSR, was also resistant to hydrolysis by either kallikrein. In contrast, the release of bradykinin from oxidized peptide or protein substrates by the tryptase/elastase mixture was not altered. Because kininogen modification may occur at inflammatory sites, as a result of the oxidative burst of recruited neutrophils and macrophages, these results suggest an alternative pathway for kinin production and the necessity for the novel utilization of two specific proteinases known to be released from these cells during inflammatory episodes.     

Accessing the scientific literature. The reality of virtual scholarship

OBJECTIVE: The purpose of this study was to evaluate HDL-C values and their relationship to high total cholesterol values during childhood. PATIENTS AND METHODS: We have studied 4,547 children and adolescents of both sexes between 4 and 6 years of age. RESULTS: We found HDL-C values > 50, 65 and 75 mg/dl in 66.28%, 26.17% and 7.81%, respectively. Of the cases studied, 44.8% had TC > 174.9 mg/dl and 15.17% higher than 199.9 mg/dl. The positive predictive value (PPV) to detect LDL-C > 129.9 mg/dl was 67.1 and 26.4 for values of TC > 199.9 and 174.9, respectively. The PPV to detect a LDL-C/HDL-C > 2.19 of the TC > 199.9 and 174.9 mg/dl was 54.78 and 23.95, respectively. CONCLUSIONS: The HDL-C of children and adolescents is often high and this could be responsible for the high TC values. Most of the children with TC values between 174.9 and 199.9 mg/dl have neither an increase in LDL-C nor in the LDL-C/HDL-C ratio.     

Using matrix-assisted laser desorption ionization mass spectrometry to map the quinol binding site of cytochrome bo3 from Escherichia coli

The cytochrome bo3 ubiquinol oxidase contains at least one and possibly two binding sites for ubiquinol/ubiquinone. Previous studies used the photoreactive affinity label 3-[3H]azido-2-methyl-5-methoxy-6-geranyl-1,4-benzoquinone (azido-Q), a substrate analogue, to demonstrate that subunit II contributes to at least one of the quinol binding sites. In the current work, mass spectroscopy is used to identify a peptide within subunit II that is photolabeled by the azido-Q. Purified cytochrome bo3 was photolabeled as previously described using azido-Q that was not tritiated (i.e., not radiolabeled). Subunit II was then isolated from an SDS-PAGE gel and proteolyzed in situ with trypsin. The resulting peptides were eluted from the gel and then identified using matrix-assisted laser desorption ionization mass spectrometry. The resulting mass spectrum was compared to that obtained by analysis of subunit II that had not been exposed to the photolabel. Using the amino acid sequence, each peak in the mass spectrum of the unlabeled subunit II could be assigned to an expected trypsin fragment. Two additional peaks were observed in the mass spectrum of the photolabeled subunit with m/z 1931.9 and 2287.7. Subtraction of the mass of azido-Q from the peak at m/z 1931.9 results in a mass equivalent to that of a peptide consisting of amino acids 165-178. The assignment of the peak at m/z 2287.7 cannot be made unequivocally and may correspond either to the covalent attachment of azido-Q to peptide 254-270 or to a peptide resulting from incomplete proteolysis. The labeled peptide, 165-178, is within the water-soluble domain of subunit II, whose X-ray structure is known. This peptide is located near the site where CuA is located in the homologous cytochrome c oxidases and can be placed near the interface between subunits I and II.