Molecular and cellular aspects of the secretory immunoglobulin system *Brandtzaeg, PER
doi: 10.1111/j.1699-0463.1995.tb01073.xpmid: 7695886
Adaptive immunological protection of mucous membranes is provided mainly by secretory IgA antibodies. Such “first line” defence is accomplished through a unique cooperation between the mucosal B‐cell system and the secretory component (SC) expressed basolaterally on glandular epithelial cells. This transmembrane glycoprotein is quantitatively the most important receptor of the immune system because it is responsible for external transport of locally produced polymeric IgA (plgA), which is the major product of humoral immunity. Transmembrane SC belongs to the Ig supergene family and functions as a general pig receptor, also mediating the external translocation of pentameric IgM to form secretory IgM. The B cells responsible for local pig production are intitally stimulated in lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine, from which they migrate as memory cells to exocrine tissues all over the body. Mucous membranes are thus furnished with secretory antibodies in an integrated way, ensuring a variety of specificities at every secretory site. There is currently great interest in exploiting this integrated or “common” mucosal immune system for oral vaccination against pathogenic infectious agents. However, much remains to be learned about mechanisms for antigen uptake and processing necessary to elicit mucosal immunity as well as the molecular biology and cytokine regulation of SC‐dependent pig transport. Moreover, evidence is emerging for the existence of subcompartmentalization in the mucosal immune system, particularly a dichotomy in cellular migration between the gut and the upper airway, which may complicate the design of efficient local vaccines.
Immunohistochemical study of estrogen receptors in primary breast carcinomas and their lymph node metastases including comparison of two monoclonal antibodiesNedergaard, LOTTE; Haerslev, TORBEN; Jacobsen, GRETE KRAG
doi: 10.1111/j.1699-0463.1995.tb01074.xpmid: 7695887
Estrogen receptors (ER) status was investigated in 101 primary breast carcinomas and their axillary lymph node metastases to determine if the malignant cells retained or changed this phenotypic feature during the metastatic process. Immunohistochemistry with the ER‐ICA kit (Abbott Laboratory) on formalin‐fixed paraffin‐embedded tissue was used (paraffin ER‐ICA). The ER status in primary and secondary tumours was concordant in 80 patients (79%) and discordant in 21 (21%). Eighteen of these twenty‐one patients had ER‐positive primary tumours and ER‐negative lymph node metastases. This discordance, which may be due to loss of ERs in the metastatic cells or tumour heterogeneity, could explain the well‐known failure of endocrine treatment in some of the patients with ER‐positive primary tumours. A new monoclonal antibody ID5 (DAKO) against ERs was applied on formalin‐fixed paraffin‐embedded tissue from 83 of these 101 primary carcinomas. These analyses and paraffin ER‐ICA analyses were compared to prior analyses of the same 83 tumours using the ER‐ICA kit on fresh frozen tissue (“gold standard”, frozen ER‐ICA). Kappa coefficient, sensitivity and specificity were 0.74, 0.96 and 0.75 for ID5 antibody, and 0.59, 0.72 and 0.96 for ER‐ICA antibody on paraffin sections.
Pathoanatomical aspects of malignant haematological disorders among Danish patients exposed to thorium dioxideVisfeldt, JAKOB; Andersson, MICHAEL
doi: 10.1111/j.1699-0463.1995.tb01076.xpmid: 7695889
The Danish Thorotrast Study was recently reestablished and improved. The cohort has been reidentified and followed up, and now comprises 1003 Thorotrast‐exposed patients. For all suspected haematological cases, cytological and histological material has been revised and malignant diseases have been reclassified. The numbers of cases of leukemia and other related haematological disorders were as follows: 16 acute myeloid leukemia (AML); 8 myelodysplasia syndrome (MDS); 1 acute lymphatic leukemia (ALL); 3 chronic myeloid leukemia (CML); 4 non‐Hodgkin's lymphoma (NHL); 2 multiple myeloma (MM); 2 myelofibrosis (MF); 2 chronic lymphatic leukemia (CLL). Except for CLL, all cases might be Thorotrast‐induced. (Expected number of leukemias: <2.5.) The findings in the German, Japanese, Portuguese and Danish studies are very similar. Some of the characteristic features include a high incidence of AML with several erythroleukemias, many cases of MDS, and a relatively low incidence of CML. In several studies of leukemia induced by alkylating agents, erythroleukemia is also described as a prominent feature. The possibility exists that a phase of relative predominance of erythroid elements in the bone marrow may be a common and not an unusual feature in the pathogenesis of these secondary leukemias. The findings are also compared with histopathological data from a Danish control group of de novo leukemia patients and from atomic bomb survivors with radiation‐induced leukemia. The relative frequency of AML is higher among the Thorotrast‐exposed patients than among the Danish control group and the A‐bomb survivors. In contrast, low relative frequencies are seen for ALL and CML in Thorotrast cases in comparison with de novo leukemia cases and A‐bomb survivors. It can be concluded that differences in relative and absolute frequency of leukemias and myelodysplastic syndrome exist not only between the irradiated populations and the unexposed control group, but even between groups exposed to low‐LET (linear energy transfer) and high‐LET radiation.
The impact of the first notification of positive blood cultures on antibiotic therapySchØNheyder, H. C.; HØJbjerg, T.
doi: 10.1111/j.1699-0463.1995.tb01077.xpmid: 7695890
The impact on antibiotic therapy of the first notification of positive blood cultures was assessed for 735 episodes of bacteraemia detected during 1992 in the County of Northern Jutland, Denmark. A primary focus of infection was defined in 498 episodes, the urinary tract being the most frequent (n = 182, 25%). Twenty‐nine patients (3.5%) had died prior to the initial contact. In 12 episodes antibiotic therapy had either been stopped or data were not available, leaving 694 episodes for further assessment. In 567 episodes antibiotic therapy had been started prior to the initial contact, the most frequent regimen being ampicillin or an ampicillin‐aminoglycoside combination (295 episodes), whereas cephalosporins, thienamycin, and fluoroquinolones were seldom used (41 episodes). The ongoing antibiotic coverage was deemed appropriate in 418 episodes (60%), non‐optimal in 90 (13%), and lacking in 186 (27%). The notification of positive blood cultures elicited changes in antibiotic therapy in 315 episodes (45%), including commencement of antibiotic therapy in 127 (18%). Thus, blood culture results have a measurable impact on antibiotic therapy.
MUM‐4, a monoclonal antibody reacting with resident peritoneal mouse macrophagesAgger, RALF; Rhodes, JOAN M.
doi: 10.1111/j.1699-0463.1995.tb01078.xpmid: 7535062
A new rat monoclonal antibody, MUM‐4, which recognizes a murine antigen/epitope that is absent on monocytes, strongly expressed on resident peritoneal macrophages and almost completely absent from peritoneal macrophages 4 days after an intraperitoneal injection of thioglycollate or heat‐killed Propionibacterium acnes organisms, is described. Immunocytochemistry and flow cytometry have been used to characterize the specificity of the antibody. MUM‐4 did not react with blood granulocytes, peritoneal exudate granulocytes, lymphocytes from blood or peritoneum, isolated spleen dendritic cells, or veiled cells from the thoracic duct of mesenteric lymphadenectomized mice. The MUM‐4 antibody reacted with resident peritoneal macrophages from all the mouse strains studied. MUM‐4 appears to represent a new specificity. The MUM‐4 antibody is of the rat IgG2c isotype and exhibits complement‐mediated cytotoxicity with rabbit complement. The staining achieved with MUM‐4 by FACS or immunocytochemical methods is intense on most resident peritoneal macrophages and the antibody should be a valuable addition to the panel of monoclonal antibodies available for studies on mouse macrophages.
Neuronal degeneration in subacute necrotizing encephalomyelopathy (Leigh's disease)Lindboe, C. F.; Lie, A. K.; Aase, S. T.; Schjetne, O. B.; Haave, I.
doi: 10.1111/j.1699-0463.1995.tb01079.xpmid: 7695891
We report clinical, radiological and pathological findings in a 5‐year‐old girl who died of subacute necrotizing encephalomyelopathy (SNE) after 4 weeks of illness. Autopsy revealed endothelial swelling and vacuolar degeneration of the neuropil in the brain, brain stem and cerebellum. In addition, the affected areas showed degeneration of the neurons which was different from anoxic nerve cell damage both with regard to morphological picture and topographical distribution. This neuronal degeneration was probably due to the underlying metabolic defect in SNE per se and resembled in several aspects the nerve cell changes seen in the thalami and inferior olives in active Wernicke's encephalopathy. It is our opinion that more attention should be paid to the nerve cell degeneration in SNE rather than focusing on the relative preservation of these cells.
Characterization of an erythromycin resistance (erm) plasmid in Streptococcus pyogenesSchalen, CLAES; Gebreselassie, DANIEL; StÅHl, STEN
doi: 10.1111/j.1699-0463.1995.tb01080.xpmid: 7695892
Three erythromyxin‐resistant Swedish isolates of Streptococcus pyogenes, representing different T‐types, were studied. Two of the strains showed constitutive high‐level (MIC>200 μg/ml) and one showed moderate (MIC 6.4 μg/ml) resistance; the latter strain was sensitive to lincosamide and clindamycin, and resistance was not induced by erythromycin. In each of the strains, a plasmid with an estimated Mw of 17.6±0.9×106 was isolated in addition to smaller cryptic plasmids. The three plasmids pSE701, pSE702 and pSE703 had very similar restriction enzyme cleavage patterns. Novobiocin curing of the high‐level resistance strain ER559 showed the resistance to be linked to its 17.6×106 plasmid, pSE703. Furthermore, by electroporation this rather large plasmid was reintroduced into an erythromycin‐sensitive cured derivative, acquiring resistance, and the plasmid was again recovered from the transconjugant. One of the plasmids, pSE702, was shown by filter mating to be conjugative within S. pyogenes. DNA‐DNA hybridization showed that the resistance determinant of the present three isolates was related to the erm gene on plasmid pAMpl of Enterococcus faecalis but not to that of plasmid pE194 of Staphylococcus aureus. The copy numbers of pSE702 and pSE703, derived from the two high‐level resistant strains, were 11±3 and 17±5 compared to 2±1 for pSE701, derived from the moderately resistant strain, possibly accounting for the phenotypic variation observed. The plasmids pSE702 and pAMpM showed about 80% homology in DNA‐DNA hybridization tests and high similarity in their restriction maps.
Acinar cell carcinoma of the pancreasKuopio, TEIJO; Ekfors, TAUNO O.; Nikkanen, VÄINÄMÖ; Nevalainen, TIMO J.
doi: 10.1111/j.1699-0463.1995.tb01081.xpmid: 7695893
Pancreatic acinar cell carcinoma is a rare neoplasm (comprising about 1% of pancreatic tumours). We studied three cases (61‐year‐old female; 42‐year‐old male; 57‐year‐old male), whose survival after diagnosis ranged from 1 year 2 months to 6 years 8 months. There were widespread metastases in each case. The tumours had acinar, trabecular and solid growth patterns. By immunohistochemistry, pancreatic acinar cell markers including carboxyl ester lipase, pancreatic secretory trypsin inhibitor and pancreatic phospholipase A2 (group I PLA2) gave a strong positive reaction in all three cases. By electron microscopy, zymogen granules were seen in the cytoplasm of the tumour cells. Immunostaining for prostate‐specific antigen was positive in all three cases. Above‐normal concentrations of pancreatic PLA2 were measured in the serum of one patient and the values decreased during chemotherapy concomitantly with the reduction in the size of the tumour mass. In conclusion, immunohisto‐chemical demonstration of the secretory products of acinar cells including the new marker pancreatic PLA2 is useful in the differential diagnosis of pancreatic acinar cell carcinoma. Determination of the concentration of pancreatic group I PLA2 in serum may be helpful in the evaluation of therapy.