Proliferative funiculitis with a prominent infiltration of mast cells

A surgical case of proliferative funiculitis (pseudosarcomatous myofibroblastic proliferation of the spermatic cord) with a prominent mast cell infiltration is reported. A 67-year-old man with a history of right inguinal herniorrhaphy 7 years earlier was operated on for diffuse swelling of the inguinal region and scrotum. A large lipoma was found in the inguinal region, and a nodular lesion, measuring 2.7 cm in maximal dimension, was firmly attached to the right spermatic cord. The nodular lesion showed diffuse proliferation of fibroblasts and myofibroblasts associated with the deposition of collagen. A diffuse infiltration of numerous mast cells was found throughout the lesion. Lesions that belong to the group of inflammatory pseudotumors are rarely accompanied by a prominent mast cell infiltration, and the differentiation from mast cell neoplasms is often problematic in such cases. The present case is the first example of proliferative funiculitis associated with this rare phenomenon.     

The effect of immunoglobulin G1 structure on macrophage binding to supported planar lipid monolayers.

We have studied the antibody-dependent binding of macrophages to supported planar lipid monolayers containing haptenated phospholipids (Tnp-Cap-DPPE). Eight monoclonal anti-TNP IgG1s, which had similar affinities to the TNP residues in solution and in the membranes, were used in the experiment. The results showed that mouse macrophages (P388D1 and J774.1) bound with different affinities to these IgG1-coated lipid monolayers. The monoclonal antibody shown to be deficient in macrophage binding was also relatively ineffective in activating complement. These results indicated that individual monoclonal antibodies of a given subclass may prove deficient in terms of the biological activities associated with the group as a whole.     

Immunohistological study on malignant fibrous histiocytoma

Malignant fibrous histiocytoma (MFH) shows a mixed proliferation of both fibroblastic and histiocytic cells. Because of their complex morphologic appearances, the nature of truly neoplastic cells in MFH has been controversial. In the present study, immunoperoxidase method (PAP method) was used to examine the intracytoplasmic lysozyme (LY), alpha-1-antitrypsin (A1AT), fibronectin (FN), and polyvalent immunoglobulin (PI) in the fibroblastic and histiocytic cells. Twenty-three cases with MFH were histologically divided into three groups; predominantly fibroblastic type (Group I; 5 cases), mixed fibroblastic and histiocytic type (Group II; 15 cases), and almost pure histiocytic type (Group III; 3 cases). Fibroblastic cells showed a strong positive reaction for LY and A1AT, suggesting the histiocytic nature, while the proliferating cells in Group II were more intensely stained by each of the antibodies than in Groups I and III. Enzyme histochemical examinations on fresh materials were available in 3 cases. These findings suggest that proliferating cells in MFH possess a histiocyte nature.     

Quantitative Analysis of Mycobacterial and Propionibacterial DNA in Lymph Nodes of Japanese and European Patients with Sarcoidosis

The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.     

Quantitative ultrastructure of synapses on functionally identified primary afferent neurons in the cat trigeminal mesencephalic nucleus

Though a number of studies have reported the presence of synapses on neurons in the trigeminal mesencephalic nucleus (Vmes), there have been no quantitative studies of either the density of innervation, or the ultrastructure, of the synapses on single, physiologically identified neurons in this nucleus. In this study we recorded from single neurons in the Vmes, identified them as being either muscle spindle afferents (MS) or periodontal ligament mechanoreceptor afferents (PL), and then labeled the neurons by intra-axonal injection of horseradish peroxidase (HRP). The material was first processed to reveal the HRP activity, following which ultrathin sections through the labeled somata were cut and examined under the electron microscope. Complete serial reconstructions were made through the soma of one MS neuron and one PL neuron, and the contacts on the neurons reconstructed. Boutons were found on the soma, spines, appendages and the axon hillock and the initial segment of the axon. The numbers of boutons terminating on the two neurons were 198 (PL) and 424 (MS), giving a packing density of 4.4 and 10.7 boutons respectively (i.e., number of boutons/100 micron 2 of the postsynaptic membrane). Boutons could be separated into two types on the basis of their vesicles: those containing clear, round vesicles (i.e., S-type) and those containing a mixture of round, oval and flattened vesicles (P-type). Ninety-five (PL neuron) and 99% (MS neuron) of terminals on the two neurons were P-type. All the S-type boutons and 80% of the P-type boutons formed asymmetric synaptic contacts while 10% of the P-type boutons made symmetric contacts. Quantitative measurements of the P-type boutons on the labeled neurons, in which the data of MS and PL neurons were pooled, revealed that bouton volume was highly correlated with bouton surface area, active zone number, total active zone area, vesicle number, and mitochondrial volume. However, comparing the quantitative measurements of the P-type boutons with those of previously reported vibrissa afferent terminals and their associated axon terminals revealed that all the parameters were smaller for the P-type boutons (on Vmes neurons) than those of the vibrissa afferent terminals but similar to those of axon terminals presynaptic to the vibrissa afferents. Taken together, our results emphasize the wide scope for synaptic interactions in the Vmes and suggest that it may be more fruitful to view the Vmes as an integrating center.     

Activation of CD44 induces ICAM-1/LFA-1-independent,Ca2+, Mg2+, —independent adhesion pathway in lymphocyte-endothelial cell interaction

We have established an endothelial cell line KOP2.16 from pooled mouse lymph nodes. Resting lymphocytes avidly bound to KOP2.16 and migrated underneath the cytoplasm. The binding was partly mediated by VLA-4 and VCAM-1, but apparently independent of CD44 since anti-CD44 antibody examined failed to inhibit the binding. However, pretreatment of lymphocytes with anti-CD44 resulted in the rapid appearance of Ca²⁺-, Mg²⁺-independent, LFA-1/ICAM-1-, CD2/LFA-3,VLA-4/VCAM-l-independent lymphocyte binding, indicating that a novel adhesion pathway was induced by the anti-CD44 treatment. Interestingly, the elicited adhesion was observed only when anti-CD44 that block hyaluronate recognition of CD44 were used for lymphocyte pretreatment. Neither hyaluronate itself nor non-blocking anti-CD44 up-regulated the adhesion. Fab fragment of the blocking anti-CD44 did not induce the up-regulation unless cross-linked with a second antibody, indicating that cross-linking of surface CD44 is necessary for induction of a novel adhesion pathway. We propose that the agonistic anti-CD44 antibodies induce a novel adhesion pathway by mimicking ligand binding to CD44 on the lymphocyte surface and that non-hyaluronate ligand(s) is involved in regulation of adhesive function of CD44. Potential involvement of such a regulatory mechanism in lymphocyte homing is discussed.     

A role for the P1 anchor residue in the thermal stability of MHC class II molecule I-Ab

The thermal stability of the murine MHC class II molecule, I-A(b), in complex with invariant chain-derived peptide (CLIP) and an antigenic peptide derived from the alpha subunit of the I-E molecule (Ealpha) at mildly acidic and neutral pH were analyzed using circular dichroism (CD). The stability of I-A(b)-CLIP was increased by a single amino acid substitution in the P1 anchor residue, from Met of CLIP to Phe of Ealpha, similar, in this respect, to I-A(b)-Ealpha. This indicates that hydrophobic interaction in the P1 pocket is critical and plays a primary role in the stability of the complex. The structural models of I-A(b)-peptides based on the crystal structure of I-A(d) might explain the increased stability and the preference for hydrophobic residues in this site. Taken together with what is known of the resident stability at a mildly acidic pH, the difference in stability would closely correlate with the ability of MHC class II to exchange peptides from CLIP to antigenic peptides in the endosome.     

Acetaminophen-induced immunosuppression associated with hepatotoxicity in mice

We investigated the influence of acetaminophen (APAP), an analgesic and hepatotoxic agent, on the immune system in mice. The activity of serum glutamic-pyruvic transaminase was markedly increased by about 200 fold compared to that of the vehicle control following intraperitoneal injection of 400 mg/kg of APAP. In vivo antibody-producing responses to SRBC was significantly inhibited by APAP in a dose-dependent manner, while in vivo T cell-independent antibody-producing responses to TNP-Ficoll was not inhibited. The addition of thymocytes from APAP-treated mice suppressed the response to SRBC in vitro. Thymocyte blastogenesis following mitogenic stimulation with concanavalin A was also inhibited by injection of APAP. The delayed-type hypersensitivity response and mixed lymphocyte reaction, which are used to evaluate cell-mediated immunity, were also significantly reduced after treatment with APAP. These results indicate that APAP suppresses the humoral and cell-mediated immune responses at a dose that causes liver injury.