Thymic lesions in fatal infectious mononucleosis

Thymic lesions were studied in 35 patients with fatal infectious mononucleosis (FIM) including 21 males with the X-linked lymphoproliferative syndrome (XLP) and 14 non-XLP patients. Six patterns based on the lymphocyte content and status of Hassall's bodies were observed: massive lymphoproliferation effaced the architecture and Hassall's bodies (HB) in 6 cases. Epstein-Barr virus (EBV)-laden B cells surrounded by cytotoxic T cells and natural killer cells were found in one of these cases. Only 5 of the 35 thymuses contained normal-appearing HB. Seven showed a moderate reduction in HB. Rarely, multinucleated giant cells and hyaline globules were seen where one might expect HB to reside. Plasma cells and macrophages were generally abundant. Eight displayed a marked depletion of HB. In 7, no HB were recognized. Massive necrosis was seen in one of these cases. Stress involution was encountered in only two patients, both of whom had sporadic fatal IM. Thymic lesions and alterations were similar but less extensive in sporadic FIM. These morphological studies, taken in context with clinical and experimental reports, suggest that destruction of thymic epithelium may contribute to the progression of immune defects seen in XLP following EBV infection. The destruction of HB that we observed was similar in appearance to lesions in several other immune deficiency disorders.     

Prevalence of HBsAg carriers in native and immigrant pregnant female populations in Israel and passive/active vaccination against HBV of newborns at risk.

Israel has no official prevention policy at present against perinatal and horizontal transmission of hepatitis B virus (HBV) infection in newborns and children at risk. The present study was designed to assess the prevalence of HBV carrier state in a population of 11,123 pregnant women at term. Among this population (mean age 29.7 +/- 5.9), 98 women (0.88%) were found to be asymptomatic HBsAg+ carriers, and 97% of these carriers were anti-HBe+. Evidence for HBV replication, as determined by serum HBV-DNA, was established in 6.6% of the HBsAg+/anti-HBe+ population. The HBsAg carrier rate was strongly influenced by religion, continent, and country of birth of the carrier mothers. The highest relative carrier rate was found among women of Moslem origin (4.3%), as compared to Jewish women (0.67%). Most carrier women were born in Israel (56.1%) to mothers who had emigrated from regions with intermediate or high endemicity of HBV, such as North Africa or the Middle East. In these groups, the HBsAg carrier rate ranged between 1.2 and 3.0%. Ninety-three percent of newborns receiving passive/active vaccination against HBV developed protective levels of anti-HBs. Finally, evidence for horizontal transmission of HBV was found in 19.3% of 83 non-vaccinated children in families of HBsAg carriers. The present study therefore establishes HBsAg prevalence rates in specific risk groups of women at term and confirms the need for an official policy on immunization against HBV in Israel. Since over 50% of women at term belong to the defined risk groups, universal active vaccination of the entire newborn population each year is suggested as the most rational and needed policy in Israel.     

Cellular origin and differentiation of renal carcinomas. A fluorescence microscopic study with kidney-specific antibodies, antiintermediate filament antibodies, and lectins

Frozen sections of human renal carcinomas were studied in indirect immunofluorescence using antibodies against intermediate filaments of cytokeratin, desmin and vimentin type, and against proximal tubular brush border and distal tubular Tamm-Horsfall glycoprotein antigens, as well as with fluorochrome-labeled lectins in an attempt to study the origin and stage of differentiation of renal carcinomas. Eighty per cent of the renal carcinomas expressed the brush border antigens, whereas the Tamm-Horsfall glycoprotein could not be found. Antibodies against epidermal cytokeratins reacted only with collecting ducts in normal kidney, whereas antibodies against cytokeratins of Madin-Darby canine kidney epithelial cell line also reacted with glomerular and tubular epithelium. In 93% of the carcinomas tumor cells showed reactivity with both types of antikeratin antibodies. Vimentin, the cytoskeletal protein of mesenchymal cells, was present in the carcinoma cells of 53% of the tumors, although it was not present in normal tubular epithelium. Moreover, vimentin was expressed together with cytokeratin in the carcinoma cells in 57% of the keratin-positive samples as judged by double immunostaining, whereas the muscle type of intermediate filament protein, desmin, was not seen in the malignant cells. Binding sites for Lotus tetragonolobus agglutinin and soybean agglutinin, normally present in the cells of proximal tubules, were lacking or only faintly detectable in the neoplastic cells. Dolichos biflorus agglutinin, normally present in collecting ducts, was not detected in the tumors. The results show that most renal carcinomas express cytokeratin antigens as a sign of their epithelial origin and also show characteristics of proximal tubular cells. On the other hand, the results indicate that lectin-binding sites typical for normal differentiated tubular cells are profoundly modified in renal carcinomas. Ulex europaeus agglutinin did not bind to the malignant cells but decorated the endothelial cells of the tumors.     

Eosinophil cationic protein and myeloperoxidase in nasal secretion as markers of inflammation in allergic rhinitis

The inflammatory component of allergic rhinitis was studied by measuring the concentration and content of eosinophil cationic protein (ECP, specific for eosinophils) and myeloperoxidase (MPO, specific for neutrophils) in samples of nasal secretion from 20 pollen-allergic subjects. All secretion samples contained measurable concentrations of both proteins. The mean ECP concentrations on two occasions without pollen exposure were 950 and 1170 micrograms/l. The ECP concentration during the pollen season without any therapy (mean 1160 micrograms/l) did not differ significantly from the baseline values, but intranasal corticosteroid therapy resulted in a significant decrease (mean 530 micrograms/l). The concentration of MPO was about 10 times higher than that of ECP, but the changes in MPO were nonsignificant throughout the observation period. An inverse correlation was found between the threshold dose in histamine challenges and the ECP level expressed either as concentration or as content. Furthermore, the ECP concentration and content 1 day after a positive allergen challenge were both significantly correlated with the strength of the challenge reaction. Measurements of ECP in nasal secretions are useful for studying the presence and activity of eosinophils in the nasal mucosa, and may prove of value in clinical investigations on patients with allergic rhinitis.     

The DQA1*0104 allele is carried by DRB1*1001- and DRB1*1401-positive haplotypes in Caucasians, Africans and Orientals

Abstract: The DQA1*0104 allele is known to differ from DQA1*0101 by a single nucleotide in the sequenced part of the first exon. DQA1*0104 has a guanine in the second position of the second expressed codon, whereas DQA1*0101 and all other sequenced DQA1 alleles have an adenine in that position, changing aspartic acid to glycine. The DQA1*0104 allele was originally described in African Americans with the DRB1*12, DRB3*0101, DQA1*0104, DQB1*0501, DRB1*12, DRB3*0202, DQA1*0104, DQB1*0605 or DRB1*14, DQA1*0104, DQB1*0503 haplotypes. When developing DQA1 typing by PCR amplification with sequence-specific primers (PCR-SSP), we observed that all DR10- and DR14-positive samples carried the DQA1*0104 allele, wheres all DRB1*01 -positive DNAs carried the closely related DQA1*0101 allele. In the present study, samples representing the major ethnic groups with DR-DQ haplotypes known to carry the DQA1*0104 allele or the very similar DQA1*0101 allele were investigated by Taq I RFLP analysis, PCR-SSP typing and nucleotide sequencing. The DQA1*0104 allele was found to differ from DQA1*0101 not only in the second expressed codon, but also by a productive mutation in the signal peptide. All investigated DRB1*1001 -(n = 24) and DRB1*1401 -positive (n = 25) haplotypes, defined by homozygosity or association, of Caucasian, African or Oriental origin carried the DQA1*0104 allele, whereas the DQA1*0101 allele was found on all DRB1*01 -positive (n = 32) haplotypes. These findings demonstrate that in the assignment of HLA class II alleles, polymorphism outside the second exon sometimes must be considered. The maintenance of the DQA1*0104 allele on a few distinct haplotypes indicates that the allele is old and might also be compatible with a functional difference between the DQA1*0101 and DQA1*0104 alleles.     

Identification of cyclophilin A from human decidual and placental tissue in the first trimester of pregnancy

The protein patterns of tissue homogenates from human deciduaand placenta of first trimester pregnancies were investigated.Particular attention was paid to the low molecular weight componentsof these tissues, since substantial evidence has accumulatedthat some of these smaller proteins show a characteristic cyclicand pregnancy expression. Two specific bands were purified fromhomogenates of first trimester decidua and placenta using gelfiltration and anion exchange chromatography. These bands wereseparated by gel electrophoresis and blotting onto polyvinylidendifluoridemembrane. Partial amino acid sequencing of both proteins revealedsequences identical to human cyclophilin A. One protein wassequenced V-N-P-T-V-F-F-D-I-A-V-D-G-E-P-L-G-R-(X)-S-F-E-L-F-A-D-K-V-Pand identified as the 17 kDa isoform of cyclophilin A. The otherprotein was sequenced V-N-P-T-V-F-F-D-I-A and identified asthe 18 kDa isoform of cyclophilin A. cyclophilin A/decidua/placenta/progesterone/progesterone receptor