Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin's disease with emphasis on the expression of CD21 antigen

Based on observations of 66 cases, in which tissues were specially processed to optimize the simultaneous preservation of cell membrane antigens and morphology, we provide evidence in favor of a relationship between follicular dendritic reticulum cells (FDRC) and Reed-Sternberg (RS) cells of Hodgkin's disease (HD) other than the lymphocyte predominance subtype. RS cells were intimately related to the FDRC network (75% of cases), and the expression of CD21 antigen was frequent (41% of cases). Exclusive expression of CD21 antigen was found in 11 cases of HD, while the expression of other B-cell-associated markers (CD19, CD20, CD22) was both variable and inconsistent. The expression of T-cell antigens (CD3, CD4, CD8) was rare. Null phenotype of RS cells was observed in 27 of 66 cases (41%). Epstein-Barr virus (EBV) nucleic acids were found in 34 of 66 (51.5%) cases. Double labeling techniques showed the presence of EBV-positive RS cells within the FDRC network. A non-B-cell origin of RS cells was supported by the differential expression of EBV latent antigens in HD (latent membrane protein+, EB nuclear antigen 2-), which is unusual in EBV-driven lymphoblastoid cell lines and EBV-positive B-cell lymphomas. FDRC and RS cells are known to share morphological traits (binucleated cells), and both cell types possess Fc receptor for IgG. The hypothesis is further backed by the findings of CD15 antigen expression by occasional RS-like dysplastic FDRC in Castleman's disease (five cases), which is characterized by hyperplasia of FDRC. Whether FDRC might be the only cells involved in the conversion to RS cells by the loss or gain of antigens remains to be determined.     

Desmoplastic small round cell tumor: II: an ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers

The clinical and histological features of 39 cases of desmoplastic small round cell tumor (DSRCT) diagnosed at M.D. Anderson Cancer Center are presented. Thirty-two of the patients were men and seven were women ranging in age from 10 to 41 years (mean, 25 years). Twenty-five of the 35 patients for whom follow-up information was available died of widespread metastases 8 to 50 months (mean, 25.2 months) from the time of their diagnosis and the remaining 10 were alive with disease. With the exception of two cases that occurred in the liver and in the scrotum, respectively, all of the cases originated within the abdominal and/or pelvic peritoneum. Eight tumors also involved the retroperitoneum. Although the characteristic histologic pattern of "small, blue cells" embedded in a dense fibrous stroma was seen in most cases, about one third of the tumors exhibited a wide range of morphologic features. The recognition of these uncommon morphologic variants of DSRCT is of paramount importance to avoid a misdiagnosis because these tumors could potentially be confused with other neoplastic conditions.     

Detection of Helicobacter pylori associated antigen and heat shock protein 60 on follicular dendritic cells in the germinal centres of low grade B cell lymphoma of gastric mucosa associated lymphoid tissue (MALT)

AIMS: To investigate the localisation of Helicobacter pylori antigens and the expression of human heat shock proteins (HSP) in stomachs affected by MALT lymphoma. METHODS: Surgically resected stomachs from 24 patients with MALT lymphoma were immunostained with anti-H pylori rabbit antibodies (ORP-1 and ORP-2) and anti-human HSP60 mouse monoclonal antibodies (mAb) (LK-1 and LK-2). RESULTS: Follicular dendritic cells of germinal centres in the stomachs affected by MALT lymphoma were immunostained with anti-H pylori polyclonal antibodies and with anti-human HSP60 mAb, as were the epithelial cells. None of the lymph node samples reacted. CONCLUSIONS: Human HSP60, which cross reacts with anti-H pylori polyclonal antibodies, is often expressed on follicular dendritic cells in gastric MALT lymphoma tissues and may be aetiologically relevant to lymphomagenesis of MALT lymphoma.     

生发中心B细胞发育和淋巴瘤发生的分子机制研究进展

生发中心是B细胞成熟和发育的场所,生发中心B细胞的活化和分化受复杂的内在信号和转录因子网络调控.正常情况下,这些转录因子之间的相互作用维持着生发中心内B细胞的动态稳定.当机体细胞遗传学发生改变、病毒感染等,多种转录因子的异常表达引起B细胞内在信号网络调节失去平衡,表现为B细胞增殖异常,凋亡、分化受阻.B细胞恶性肿瘤常与B细胞的遗传学改变及生发中心转录因子异常表达有关.     

Morphological heterogeneity of myeloperoxidase-positive granules in normal circulating neutrophils: an ultrastructural study by cryosection

Ultrastructural localization of myeloperoxidase (MPO) in the granules of human circulating neutrophils was examined by cryosection. On careful comparison with the morphological characteristics of the granules by conventional transmission electron microscopic study, large MPO-positive granules were divided into five types by immunocryoultramicrotomy using monoclonal antibody. Double staining of MPO and lactoferrin (or lysozyme) was also performed. Lactoferrin was generally detected in MPO-negative granules. Lysozyme immunostaining was present in MPO-positive and -negative granules. These data may suggest different functions among large MPO-positive granules of human circulating neutrophils.     

Species barrier prevents an abnormal isoform of prion protein from accumulating in follicular dendritic cells of mice with Creutzfeldt-Jakob disease

The accumulation of abnormal prion protein in follicular dendritic cells did not occur in mice inoculated with materials from human Creutzfeldt-Jakob disease, whereas it always occurred in mice inoculated with mouse-adapted agents, suggesting an intense expression of the species barrier in the lymphoreticular system.     

Evidence for an important interaction between a complement-derived CD21 ligand on follicular dendritic cells and CD21 on B cells in the initiation of IgG responses

The addition of Ags to mononuclear leukocyte cultures typically elicits modest Ab responses, implying that cosignals beyond those provided by T cells and macrophages may be needed. Recently, we reported that Ab responses could be dramatically enhanced (10-1000-fold) by the addition of follicular dendritic cells (FDC), suggesting that FDC may provide an important costimulatory signal. This result prompted a study of molecules involved in FDC-mediated enhancement of Ab responses stimulated by specific Ag with memory T and B cells or nonspecifically by the addition of LPS. In this study, we report evidence supporting the concept that FDC bear a ligand that engages complement receptor II (CR2 or CD21) on B cells and provides a critical cosignal for both Ag-specific and polyclonal responses. A blockade of the CR2 ligand on FDC by the use of soluble CR2 or a blockade of CR2 on B cells by use of CR2 knockout mice (or B cells with CR2 blocked) reduced Ab responses from the microg/ml to the ng/ml range (10-1000-fold reductions). FDC from C3 knockout mice, which cannot generate the CR2-binding fragments (iC3b, C3d, and C3dg), were unable to provide costimulatory activity, suggesting the CR2 ligand on FDC consists of C3 fragments. FDC trap complement-activating Ag-Ab complexes, and it appears that FDC present B cells with both specific Ag to engage B cell receptors and a CR2 ligand to engage B cell-CR2. In short, optimal induction of specific Ab responses appears to require the combination of specific Ag and costimulatory molecules from both T cells and FDC.     

Synaptic organization of the human striatum: a postmortem ultrastructural study

Converging with psycho-social research findings, animal and human laboratory studies indicate that behavioral alternatives are important determinants of drug-taking. To investigate associations between how early adolescents spend their time, i.e. their behavioral repertoire and drug use (use of marijuana, crack/cocaine or inhalants), we analyzed data from an epidemiological sample of 1516 urban middle-school students who had completed private interviews in spring 1993. The interview included a 36-item questionnaire to assess how frequently the youth engaged in different activities; history of drug-taking was assessed separately. Multiple logistic regression was used to estimate associations between drug use and each of seven behavioral domains as well as sex, age and racial-ethnic status. Youths spending a great deal of time working for pay and assuming other adult-like roles were more likely to have initiated drug use (estimated odds ratio, OR = 3.49; p = 0.002). Those who spent much time in religious activities were less likely (OR = 0.2, p <0.001). An exploratory search for interactions disclosed other associations that merit attention in future research. These results corroborate evidence on the potential etiological significance of behavioral repertoire in relation to risk of drug use.     

Distribution and heterogeneity of mast cells in the human uterus

Mast cells (MCs) are widely distributed in most human tissues. Those cells that contain only tryptase are designated as T-MCs, while those that also contain chymase are referred to as TC-MCs. This study uses immunohistochemical staining for tryptase and chymase to assess the distribution and heterogeneity of these two types of MCs in the human uterus. The greatest number of MCs was found in the inner (i.e. luminal) half of the myometrium, with this area containing approximately equal proportions of T-MCs and TC-MCs. There were fewer MCs in the outer half of the myometrium and the cervix, but the proportion of TC-MCs in both of these areas was substantially higher. In contrast, the endometrium contained significantly fewer MCs, but proportionally more T-MCs. There was no change in the number of MCs between the proliferative and secretory phases of the menstrual cycle; however, there was a significantly lower number in all areas after menopause. Most of the MCs were observed in close association with uterine smooth muscle cells, as well as in the vicinity of fibroblasts and collagen, and it appears they may play an important role in the reconstruction of uterine tissues during the menstrual cycle.     

Fluoride stimulation of the rat parathyroid gland: an ultrastructural study

The parathyroid glands of rats given 150 ppm fluoride in the drinking water for 10 weeks are evaluated ultrastructurally and compared to the parathyroid glands of untreated rats. As a result of fluoride ingestion, the majority of the parathyroid cells are dark chief cells, indicating that these cells are in the active stages of the secretory cycle. More significantly, in the fluoride-treated rats, the cytoplasmic organelles of the dark chief cells are even more developed that those seen in the dark chief cells of untreated rats. The dark cells contain an electron-dense cytoplasm with abundant lamellar arrays of rough endoplasmic reticulum, spiral aggregations of free ribosomes, multiple dilated Golgi complexes, and increased numbers of secretory granules. The cells are at a minimum dimension with maximum tortuosity of the plasma membranes; and, as a result, large intercellular spaces are often seen between contiguous cells. Based on these observations, it is suggested that, in the fluoride-treated rat, a type of secondary hyperparathyroidism develops resulting in an increase in the organelles involved in protein synthesis and secretion.     

Penetration of M cells and destruction of Peyer's patches by Yersinia enterocolitica: an ultrastructural and histological study

Yersinia enterocolitica is enteropathogenic for man and rodents. Previous studies provided evidence that Y. enterocolitica invades the lymphoid follicles of the Peyer's patches (PP) of the small intestine. In this study Y. enterocolitica-induced tissue alterations of the follicle-associated epithelium (FAE) and the underlying PP tissue were analysed by scanning (SEM) and transmission electron microscopy (TEM) as well as by conventional histological examination. For this purpose, an experimental mouse infection model including orogastric infections as well as ileal loop experiments were used. A rapid and selective colonisation of the FAE after orogastric yersinia infection was observed by SEM. TEM studies confirmed that Y. enterocolitica adhered closely to the FAE including M cells and enterocytes. Histological studies and TEM revealed that Y. enterocolitica selectively invaded the PP via M cells but not via other cells of the FAE. One day after Y. enterocolitica infection the FAE was altered and small micro-abscesses comprising yersiniae expressing the major outer-membrane protein YadA were observed immediately beneath the FAE. Adjacent villi were dilated from lymphangiectasis and transmigrating polymorphonuclear leucocytes (PMNL) were found within the epithelium. At 5-7 days after infection the FAE and parts of PP were destroyed. Profound alterations of the cyto-architecture of the PP were due to the enormous recruitment of PMNL. By day 5 after infection, abscesses were found in the mesenteric lymph nodes. However, TEM studies revealed evidence that Y. enterocolitica may disseminate from the PP not only via the lymphatics but also by invasion of blood vessels. Taken together, the results of this study demonstrate that the FAE is the primary site of host-pathogen interaction in Y. enterocolitica infection and that this pathogen penetrates M cells and subsequently induces destruction of the PP.     

Oligodendroglioma with signet-ring cell morphology: a case report with an immunohistochemical and ultrastructural study

Clinical reports have suggested an unusual frequency in the number of patients with food allergy to snails who are also allergic to the house-dust mite (HDM). As allergy to HDM is one of the most frequent sensitizations in atopic patients of Western countries, evaluation of the relevance of the concomitant sensitization to Dermatophagoides pteronyssinus and to snails is an important consideration. To evaluate the responsibility of different snail components and of snail mites for inducing in vivo hypersensitivity in patients allergic to HDM, the in vivo reactivity of patients with clinical symptoms after ingestion of snails was assessed by skin prick tests with extracts and hemolymph from four different Helix species snails, and extracts from the snail parasitic mite, Riccardoella limacum. In addition, to obtain epidemiologic data on cosensitization to HDM and snails in allergic patients, the frequency of snail sensitization and its relationship to HDM sensitization were determined in a population of 169 allergic children. All patients allergic to snails had positive skin prick tests to the snail extracts and none to R. limacum extract. The number of positive skin reactions did not significantly differ whatever the species, snail part, or heating procedure used. The strongest reactions were obtained with Helix pomatia (Burgundy snail). Among the 169 prospectively tested children, 38 had a positive prick test to snail extracts; 79% of the snail-sensitized children had sensitization to HDM; and 31% of the children allergic to HDM were found to be sensitized to snails. These results show that snail components, and not the mite R. limacum, were responsible for the in vivo hypersensitivity. These snail components reacting in vivo are present in different parts of snails, including the hemolymph. One-third of the children allergic to HDM were sensitized to snails without any previous ingestion of snails: this observation suggests that HDM was the sensitizing agent and that the cross-reaction could be clinically relevant in countries where eating snails is common.     

Melanotic neuroectodermal tumour of infancy: an immunohistochemical and ultrastructural study

Two cases of melanotic neuro-ectodermal tumour of infancy (MNTI)--a rare neoplasm arising in the first year of life--are reported, with the results of immunohistochemical and ultrastructural examination. The tumours consisted of a biphasic cell population in a fibrous stroma. The small, darkly staining cells comprising the first population stained positively for synaptophysin, showing them to be neuroblasts, and the large epithelioid cells comprising the second cell population stained positively with the antibodies HMB-45 and NKI-Beteb, showing them to be melanocytes. Ultrastructural examination of the second case confirmed the biphasic nature of the tumour cells, with secretory granules and neurofilaments in the neuroblastic population, and melanosomes in the epithelioid population. These results add to the evidence supporting the neural crest origin of MNTI and confirm its formation from two distinct cell lines. Both cases have responded to local excision, with no recurrence more than a year after initial treatment.     

Layer-specific dendritic regression of pyramidal cells with ageing in the human prefrontal cortex

Huntingtin is the protein product of the gene for Huntington's disease (HD) and carries a polyglutamine repeat that is expanded in HD (>36 units). Huntingtin-associated protein (HAP1) is a neuronal protein and binds to huntingtin in association with the polyglutamine repeat. Like huntingtin, HAP1 has been found to be a cytoplasmic protein associated with membranous organelles, suggesting the existence of a protein complex including HAP1, huntingtin, and other proteins. Using the yeast two-hybrid system, we found that HAP1 also binds to dynactin P150(Glued) (P150), an accessory protein for cytoplasmic dynein that participates in microtubule-dependent retrograde transport of membranous organelles. An in vitro binding assay showed that both huntingtin and P150 selectively bound to a glutathione transferase (GST)-HAP1 fusion protein. An immunoprecipitation assay demonstrated that P150 and huntingtin coprecipitated with HAP1 from rat brain cytosol. Western blot analysis revealed that HAP1 was enriched in rat brain microtubules and comigrated with P150 and huntingtin in sucrose gradients. Immunofluorescence showed that transfected HAP1 colocalized with P150 and huntingtin in human embryonic kidney (HEK) 293 cells. We propose that HAP1, P150, and huntingtin are present in a protein complex that may participate in dynein-dynactin-associated intracellular transport.     

Ontogeny of the endocrine cells of the intestine and rectum of sea bass (Dicentrarchus labrax L.): an ultrastructural study

Several endocrine cell types were ultrastructurally characterized during the differentiation of the intestine and rectum of sea bass (Dicentrarchus labrax L.) larvae. Only one cell type (type I) was found in the posterior region of the undifferentiated gut of 5-day-old larvae (phase I). Types V and VI were found in both the intestine and rectum, types II, III and IV in the intestine, and types VII and VIII in the rectum of 9- and 12-day-old larvae (phase II), the rectum alone showing signs of functional differentiation. In phase III larvae, in which both the intestine and rectum were differentiated, types IX, X, XI, XII, XIII, XIV and XV were found in the intestine, only types X, XI and XII being seen in the rectum. Besides these, a new cell type, XVI, was observed in the intestine of 55- and 60-day-old larvae (phase IV), in which the digestive tract was completely differentiated. The endocrine cells appearing in phases I and II showed very scarce secretory granules and the ultrastructural features of undifferentiated cells. Some endocrine cell types in the earliest developmental stages were related to some of those found later. A maturational process of the endocrine cell types paralleled the differentiation of the intestine and rectum, with an apparent increase in the number of secretory granules accompanying organelle development.     

Testicular effects of vasectomy in rats: an ultrastructural and immunohistochemical study

Onset and offset of calcium current in response to short, depolarizing voltage pulses were studied in giant synaptic terminals of goldfish bipolar neurons. Tail-current decays were extremely rapid (80 micros at -70 mV), and exponentially slowed at more positive repolarization potentials. The amplitude of tail current following voltage pulses varied with the pulse amplitude, according to a Bolzmann distribution with a V1/2 of -27.6 mV and a slope factor of 13.8 mV. When interpreted with a Hodgkin-Huxley model, calcium-current onset was best described by m2 kinetics and a time constant (tau(m)) of 0.62 ms at -10 mV. The kinetics of calcium-current onset and offset are at least two- to threefold faster than those described in other native cells. Combined with other recent data, the results suggest that the rapid kinetics may participate in a fast signaling mode in the goldfish ON-center pathway.     

Expression of MUC-1 glycoprotein in plasma cells, follicular dendritic cells, myofibroblasts and perineurial cells: immunohistochemical analysis using three monoclonal antibodies

Normal and malignant plasma cells (PC), follicular dendritic cells (FDC), myofibroblasts (MFB) and perineurial cells (PNC) were investigated for the expression of MUC-1 glycoprotein (MUC-1gp) by immunohistochemical and immunoelectron microscopic techniques using monoclonal antibodies E29, 115D8, DF3 and a combination of the three. MUC-1 glycoprotein-positive PC detected by the combined antibodies were frequently seen in a variety of pathological lesions tested, including chronic cervicitis, chronic synovitis, Hodgkin's disease, allergic rhinitis and sinusitis, tuberculous lymphadenitis, foreign body granuloma, multiple myeloma, and chronic tonsillitis. In the lesions containing MUC-1gp-positive PC, the infiltration of immunoglobulin (Ig) E PC and/or IgE-bound mast cells was significantly increased, but MUC-1gp-positive PC did not contain any specific immunoglobulin heavy or light chains. The findings suggest that the expression of MUC-1 gp in PC, although not restricted to IgE-class cells, may be induced in an allergic status. Plasma cells and PNC mainly reacted with the antibodies E29 and 115D8, while FDC and MFB were principally reactive with the antibody DF3. In some cases of multiple myeloma, the neoplastic PC were predominantly immunoreactive with DF3. The results indicate: (i) the epitopic variability of MUC-1gp molecules expressed on the non-epithelial cells; and (ii) the epitopic alterations during malignant transformation. It should also be noted that the expression of MUC-1gp in the non-epithelial cells represents a pitfall in histopathological diagnosis.     

Toxoplasma gondii: an ultrastructural study of host-cell invasion by the bradyzoite stage

The invasion of Toxoplasma gondii tachyzoites and bradyzoites was followed in bovine kidney cells via electron microscopy. The process of invasion differed between bradyzoites and tachyzoites. In the early stages of entry there was evidence of localised formation of membrane projections in the host cell adjacent to the parasite. Parasite reorientation and rhoptry release appeared to be necessary for invasion; however, the tight junction could not be clearly discerned and there was no evidence of constriction or of any membrane shedding from the parasite. The resulting parasitophorous vacuole was smaller than the tachyzoite vacuole and parasites were frequently found to lie immediately under the host cell membrane. The vacuole was rapidly adapted by the release and formation of an intra-phagosomal membrane network, while the parasitophorous vacuole formed a relationship with host-cell endoplasmic reticulum.