CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (I)

Occupational diseases Nos. 2108 and 2110 correspond to intervertebral disc-related diseases of the lumbar spine from many years of carrying or lifting heavy loads, occupations in extreme postures of full flexion or oscillation of the whole body when seated, and which compel the cessation of all activities which are or could be the cause for the origin, exacerbation or recurrence of the disease. These occupational diseases came into force at the start of 1993, but there have been considerable problems in their implementation. The present Part I of the contribution is the result of the work of an interdisciplinary study group and contains medical criteria for the assessment of possibly strain-related clinical characteristics and the evaluation of other possible causes. Part II is to be published in Volume 4/2005 and will deal with questions related to forced cessation and to the assessment of the loss of earning ability. Agreement was reached in many areas related to the assessment of occupational claims. This should allow for evidence-based decision making in the future for the occupational diseases Nos. 2108 and 2110.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (II)

The first part of this serial paper dealt with the medical criteria used in evaluation of the clinical picture caused by physical stress and the evaluation of other candidate causes and was published in issue no. 3/2005 (pp. 711–752) of Trauma and Berufskrankheit. This follow-up paper (II) presents criteria to be used in the evaluation of whether it is necessary to give up the occupations putting the spine at risk and in estimation of the degree of disability.     

Cutis Marmorata Telangiectatica Congenita Associated with a Double Aortic Arch

Abstract: We report a patient with cutis marmorata telangiectatica with the hitherto unreported anomaly of a double aortic arch. The presence of two major vascular anomalies in this patient may be secondary to a developmental defect of the mesoderm during embryogenesis.     

Phase I and pharmacologie study of liposomal daunorubicin (DaunoXome)

Summary We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial doseescalation steps from 10 to 60 mg/m². At 80 mg/m², two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m². Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m² in previously treated and 120 mg/m² of DaunoXome in previously untreated patients with solid tumors.EDW is supported in part by ACS award 92-14-1     

Simultaneous Pulmonary Leiomyosarcoma and Leiomyoma in Pediatric HIV Infection

The case of a 7-year-old girl with acquired immunodeficiency syndrome treated for 5 years with AZT and intravenous gamma globulin is reported. Shortly before her demise she developed a pulmonary leiomyosarcoma and leiomyoma. Does prolonged survival in pediatric acquired immune deficiency syndrome increase the incidence of secondary malignancies?     

Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake

Low brain uptake is a generally accepted problem in developing technetium-99m brain receptor imaging agents. For a class of potential 5-HT_2A receptorbinding agents we tried to improve the original low brain uptake of 0.4% injected dose (ID) in rats 5 min p.i. by modifying the lipophilic properties of the molecules. Because of the presence of a protonable nitrogen, which according to the pK _a value leads to ionization of the molecule at blood pH, the pK _a value was considered to be the parameter most suitable for adjustment of lipophilicity. Insertion of ether-oxygen in the molecule of five candidates lowers the apparent pK _a value from 10.0 to 8.3 and dramatically increases the brain uptake to 1.3% ID at 5 min. The direct relationship between brain uptake and apparent pK _a cannot be simply explained by the increase in the pK _a-governed proportion of the neutral species.     

A comprehensive survey for polymorphisms in the bovine IFN-gamma gene reveals a highly polymorphic intronic DNA sequence allowing improved genotyping of Bovinae.

This study aimed to identify interferon-gamma (IFN-gamma) gene variants in cattle for diagnostic purposes. Therefore, the entire bovine IFN-gamma gene (BoIFNG) and 2605 bp of its promoter DNA were sequenced. The BoIFNG DNA sequence conforms to the published part of Bo-IFN-gamma cDNA. Primer extension experiments show the presence of a 5' extension of exon 1 by 42 nucleotides (nt). One SINE element (Bov-A2) is located in the 5'-region, and two SINE elements (Bov-tA, Bov-B) are contained in the 3'-region of BoIFNG. The variants were detected by comparative sequence analysis of PCR amplicons from different bovine species. Four polymorphic mononucleotide repeats are situated in the promoter and in intron 1. Four distinct series of single nucleotide polymorphisms (SNP) were found in functionally important regions of BoIFNG. The region between the two intron 1 microsatellites contains the highest density of SNPs in Bos taurus breeds. One G-T transversion in the coding region of exon 1 causes a Gly(14) to Val(14) exchange in the BoIFNG signal peptide of different bovine species. A G-A transition in exon 2 encodes a Ser(19) to Asn(19) change in the mature protein of the Tibetan yak. Genotyping of randomly sampled Holstein Friesian cows at selected SNPs and of both intron 1 microsatellites revealed two dominant BoIFNG microhaplotypes. The detected SNPs improve the recently reported genotyping system of cattle.     

Testing for skin sensitization according to the notification procedure for new chemicals: the Magnusson and Kligman test

The notification procedure for new chemicals in the European Union (called the Chemicals Act in Germany) requires a skin sensitization test when the amount of a new chemical produced exceeds 100 kg/year. The preferred test is that of Magnusson and Kligman; more than 90% of the tests submitted are performed with it. Though the Magnusson and Kligman test is described in the literature, and in the test guidelines of the European Union and of the OECD, discrepancies do occur in the performance of the test between test laboratories. In this paper, recommendations are given for standardized performance of the Magnusson and Kligman test.