Follicular hyperplasia presenting with a marginal zone pattern in a reactive lymph node lesion

Histologically, the marginal zone pattern of the lymph node is characterized by lymphoid follicles with three distinct layers. The inner layer is composed of follicular center zones, the middle layer of darkly stained mantle zones, and the outer layer of marginal zones. However, the marginal zone pattern is rarely seen in reactive lymph nodes except for mesenteric lymph nodes. We describe the clinicopathologic, immunohistochemical and genotypic findings of six cases of reactive follicular hyperplasia exhibiting the marginal zone pattern. The patients comprised three males and three females (age range 24 to 63 years; medium 56 years). Follow-up data were obtained from five patients. None of them developed malignant lymphomas during the follow-up period of from 5 to 204 months (median 68 months). Histologically, the lesion was characterized by numerous lymphoid follicles and partial distortion of lymph node structure. Varying degrees of progressive transformation of the germinal center (PTGC) were noted in the four cases. The marginal zone pattern was observed in some or most of the lymphoid follicles including PTGC. The marginal zone B cells were small to medium-sized lymphocytes with round or slightly indented nuclei and a broad rim of pale cytoplasm. Some of them had a monocytoid appearance. They were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD10-, CD21-, CD23-, CD43-, CD45RO-, Bcl-6-, cyclin D1-, EMA- and p53-. A portion of them were Bcl-2 positive. Occasional large lymphoid cells with round or indented nuclei and moderate amounts of cytoplasm were observed in the marginal zone in four cases. These large lymphoid cells were usually CD20 positive, but Bcl-6 negative. A small number of them contained polytypic intracytoplasmic immunoglobulins. The polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Recognition of unusual marginal zone hyperplasia in reactive lymph node lesions is important to avoid confusion with nodal involvement in various low-grade B cell lymphomas presenting a marginal zone distribution pattern.     

Inflammatory pseudotumor of lymph nodes: clinicopathologic and immunohistological study of 11 Japanese cases

We report 11 Japanese cases of inflammatory pseudotumor (IPT) of the lymph node. There were 7 males and 4 females with ages ranging from 5 to 68 years (median; 48). Only 2 patients had systemic lymphadenopathy, and all others had involvement of only 1 lymph node group. Constitutional symptoms such as fever were present in 8 patients and laboratory abnormalities were detected in 5. All patients recovered and were alive and well after 2 to 180 months (median; 32 months). Histologically, the process mainly involved the connective tissue framework of the lymph node, secondarily spreading into the lymph node parenchyma and the perinodal tissue. It was characterized by a storiform growth pattern of myofibroblasts, marked vascularity with associated vascular lesions, and a polymorphous reactive cellular infiltrate in a collagen-rich stroma. An immunohistochemical study revealed numerous myofibroblasts, histiocytes, and vascular endothelial cells expressing vascular endothelial growth factor (VEGF) in 6 cases. It was suggested that VEGF may be involved, in part, in the induction of the angiogenesis of IPT. Moreover, the present study indicates that follicular dendritic cell sarcoma, nasal T/natural killer cell lymphoma, and anaplastic large cell lymphoma should be added to the differential diagnosis from IPT of the lymph node. Int J Surg Pathol 9(3):207-214, 2001     

F-waves of the facial muscles in healthy control subjects and in patients with peripheral facial nerve disturbance

F-waves were recorded from the mentalis muscles with surface electrodes following stimulation of the marginal mandibular branch of the facial nerve in healthy control subjects during wakefulness, non-REM (rapid eye movement) sleep and voluntary contraction and in patients with Bell's palsy and acoustic neurinoma. The F-wave of the facial muscles results from the backfiring of antidromically activated alpha motoneurons in the facial motonucleus. Therefore, first, the F-waves were not easily elicited in patients with any disturbance in the proximal segment of the facial nerve (Bell's palsy and acoustic neurinoma). Second, the F-waves were affected by excitability of the facial motonucleus; the F-waves were inhibited significantly during sleep and enhanced significantly during voluntary contraction compared with those at rest during wakefulness. When the stimulation strength was set submaximum for M-waves, F-waves were elicited but H-waves, which have lower threshold than M-waves, were not elicited in the facial muscles, unlike the case of the extremities. Measurement of the F-waves of facial muscles is a new method for estimating excitability of the facial motonucleus unless there is any disturbance of the proximal segment. Fundamental characteristics of the facial F-waves were shown in the present study and measuring facial F-waves is clinically applicable for investigation of both excitability of the facial motonucleus and facial peripheral nerve disturbance.     

Fine mapping of a gene responsible for regulating dietary cholesterol absorption; founder effects underlie cases of phytosterolaemia in multiple communities

Sitosterolaemia (also known as phytosterolaemia, MIM 210250) is a rare recessive autosomal inherited disorder, characterised by the presence of tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. The defective gene is hypothesised to play an important role in regulating dietary sterol absorption and biliary secretion, thus defining a molecular mechanism whereby this physiological process is carried out. The disease locus was localised previously to chromosome 2p21, in a 15 cM interval between microsatellite markers D2S1788 and D2S1352 (based upon 10 families, maximum lodscore 4.49). In this study, we have extended these studies to include 30 families assembled from around the world. A maximum multipoint lodscore of 11.49 was obtained for marker D2S2998. Homozygosity and haplotype sharing was identified in probands from non-consanguineous marriages from a number of families, strongly supporting the existence of a founder effect among various populations. Additionally, based upon both genealogies, as well as genotyping, two Amish/Mennonite families, that were previously thought not to be related, appear to indicate a founder effect in this population as well. Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM.     

Eosinophilic neuronal inclusion bodies in the temporal lobe.

Intracytoplasmic neuronal inclusion bodies were found in the temporal lobe of an elderly woman. The oval or rod-shaped inclusion bodies were eosinophilic, showed bright red staining with azan, and were about half the size of the nucleus of a large neuron. They were non-argyrophilic and non-congophilic. Ultrastructurally, the inclusion bodies consisted of aggregates of filamentous materials showing partial periodicity. Among inclusion bodies reported up to now, the present ones resembled some described previously as "thalamic inclusions", but were different with regard to their partial filament periodicity, and unusual in that they were located in the deep layer of the temporal lobe and not in the thalamic nuclei.     

Substance P stimulates release of RANKL via COX-2 expression in human dental pulp cells

Objective: Our previous study found that substance P (SP), a sensory neuropeptide, was expressed in the dental pulp of rats during experimental tooth movement. We examined the effects of SP on the production of prostaglandin (PG) E₂ and the receptor activator of nuclear factor- B ligand (RANKL) by human dental pulp fi broblast-like (HDPF) cells. Materials and methods: SP was added to cultured HDPF cells at concentrations ranging from of 10⁻⁴ to 10⁻¹² mol/L. PGE₂ and soluble RANKL (sRANKL) levels were determined using enzyme-linked immunosorbent assay kits. Gene expression was confi rmed by RT-PCR analysis. Pit formation assays using dentin slices were carried out to examine the effect of SP on osteoclastogenesis. Results: The levels of PGE₂ and sRANKL increased in the presence of SP, though the increases were greater in the experimental groups in both a time- and concentration-dependent manner, and the increase of RANKL was partially mediated by PGE₂ . The gene expression of cyclooxygenase (COX)-2 and RANKL was up-regulated, and conditioned medium samples obtained from HDPF cells treated with SP induced bone resorption. Conclusions: SP stimulated the production of PGE₂ and RANKL, and promoted bone resorption. Therefore, SP may be involved in pulpal inflammation and root resorption during orthodontic tooth movement. Received 11 April 2005; returned for revision 27 July 2005; returned for final revision 20 September 2005; accepted by M. Katori 2 November 2005     

Aplastic anemia: lack of increase of in vitro colony formation after T cell depletion with monoclonal antibodies and complement

To detect suppressor T cells to hematopoietic stem cells, growth of granulocyte-macrophage colony-forming cells (CFU-GM) and burst-forming unit (BFU-E) was compared before and after treatment of bone marrow cells with anti-T monoclonal antibodies and complement in 29 patients with aplastic anemia. The anti-T monoclonal antibodies used were 35.1 (CD2), Tp120 (CD6) and ATL27 (not clustered). Treatment of normal bone marrow with anti-T monoclonal antibodies and complement resulted in complete (greater than 99%) lysis of T cells with negligible effects on colony growth. Preincubation of marrow samples with monoclonal antibodies and complement did not enhance CFU-GM or BFU-E colony growth in patients with aplastic anemia. Using this assay, there was no evidence of T cell-mediated inhibition of colony proliferation in any of 29 patients.     

Characterization of a helper T cell epitope recognized by mice of a low responder major histocompatibility type.

Most known helper T cell (Th) epitopes studied have naturally been immunodominant epitopes recognized by T cells from animals of high responder major histocompatibility complex (MHC) haplotype. We have previously found that most such immunodominant Th epitopes tend to be amphipathic alpha helices, that is, helices with hydrophobic residues on one side and hydrophilic residues on the other, and the corresponding peptide can usually elicit a response to the native protein. However, very few epitopes seen by MHC low responder T cells have been identified. Within the CNBr fragment of residues 1-55 of sperm whale myoglobin (SwMb), a Th epitope is known to exist that stimulates T cells from low responder H-2k mice, but it has not yet been localized to a length of 8-12 residues, the usual length of a Th epitope. To determine whether this low responder epitope would have similar properties, we located it using 10 evenly overlapping 15-residue peptides that span the region. Analysis of this region by the computer program predicted the site covered by two peptides (residues 26-40 and 31-45 which overlap by 10 residues) to be the most likely site for a Th epitope. Of the 10 peptides tested experimentally, only one peptide (residues 26-40) was able to stimulate two low responder Th clones that are specific for the 1-55 region. The peptide was able to prime T cells of low responder B10.BR mice in vivo for in vitro response to the native SwMb as well as to the peptide fragment of residues 1-55. Immunization of low responder mice with SwMb showed that, of the 10 overlapping peptides, the major site of response within the 1-55 region is to the identified peptide. Finally, an extended peptide of residues 24-42 was made to increase the amphipathic score. This extended peptide induced greater proliferation of the clones. Thus, this low responder epitope has properties similar to those of immunodominant epitopes recognized by high responders.