Malignant peripheral nerve sheath tumor of small round cell type with pleomorphic spindle cell sarcomatous areas

An unusual case of malignant peripheral nerve sheath tumor (MPNST) arising in the posterior mediastinum of a 59-year-old man is reported. Histopathologically, the tumor showed an admixture of a dense proliferation of small round cells resembling a primitive neuroectodermal tumor (PNET) and a pleomorphic spindle cell sarcomatous area. Abortive rosettes, primitive neural tube-like structures, and a few glandular structures were found in the small round cell area. Small round cells were immunoreactive for neural cell adhesion molecule and synaptophysin, but were not immunoreactive for MIC2 and neuron-specific enolase. Pleomorphic spindle cells were occasionally arranged in a storiform pattern and were diffusely immunoreactive for S-100 protein. The MPNST of small round cell type is distinguishable from PNET by its negative immunoreactivity for MIC2, and the present tumor is assumed to be derived from primitive neuroectodermal cells in the peripheral nerve capable of bidirectional (neuron and Schwann cell) differentiation.     

The Serum Factor from Patients with Ulcerative Colitis that Induces T Cell Proliferation in the Mouse Thymus Is Interleukin-7

The disturbance of immune regulatory T cells is related to the pathogenesis of ulcerative colitis. Here we demonstrated and characterized the serum factor from ulcerative colitis patients that induced proliferation of intrathymic T cells. The factor isolated from the patient sera by a combination of gel filtration and anion-exchange chromatography induced proliferation of CD4⁺CD8^– intrathymic T cells in the organ-cultured embryonic mouse thymus. Purification and amino acid sequence analysis of the serum factor demonstrated that the N-terminal 12 sequence was homologous to that of interleukin-7. SDS-PAGE and Western blot confirmed that purified serum factor was interleukin-7. Enzyme immunoassay demonstrated that the serum interleukin-7 concentration was significantly increased in the patients. PCR and Southern blot hybridization demonstrated that interleukin-7 mRNA expression was increased in the thymus tissues from patients but decreased in the colonic mucosa. Since interleukin-7 is a crucial cytokine for proliferation and differentiation of T cells in the thymus, the present study indicates that interleukin-7 may contribute to the disturbance of immune regulatory T cells in ulcerative colitis.     

The effect of prednisolone on substance P-induced vascular permeability in mice

The effect of prednisolone on the substance P (SP)-induced vascular permeability increase in male ddY, WBB6 F₁–+/+ (control) and WBB6 F₁-W/W^v (no mast cell in skin or internal organs) mice was investigated. 1) SP (1–10 000 pg/site) increased vascular permeability in ddY, WBB6 F₁–+/+ and WBB6 F₁-W/W^v mice ears. 2) SP (100 pg/site)-induced vascular permeability was inhibited by prednisolone (10 mg/kg) administered intraperitoneally 3 to 12 hours prior to the elicitation of the reaction in ddY mice. When dexamethasone at a dose of 1 mg/kg was administered intraperitoneally 2 to 24 hours prior to the elicitation of the reaction, significant inhibition was observed. When prednisolone was administered intraperitoneally 8 hours prior to the elicitation of the reaction, the SP-induced capillary permeability increase in both ddY and WBB6 F₁-W/W^v mice was clearly inhibited by the drug at doses of 5 and 10 mg/kg. 3) Diphenhydramine (1 and 10 mg/kg) inhibited SP-induced vascular reaction in ddY mice but not in WBB6 F₁-W/W^v mice. 4) Atropine (10 mg/kg) inhibited SP-induced vascular reaction in both ddY and WBB6 F₁-W/W^v mice. But acetylcholine did not cause an increase of vascular permeability in ddY and WBB6 F₁-W/W^v mice ears. 5) Prednisolone (5 mg/kg) inhibited histamine- and serotonin-induced vascular permeability in ddY and WBB6 F₁-W/W^v mice ears. 6) Prednisolone (5 and 10 mg/kg) inhibited the SP-induced histamine release from ddY mice peritoneal mast cells. These results suggest that the vascular effect of SP is mediated by both mast cell dependent (release of histamine from mast cells) and mast cell independent mechanisms. Prednisolone inhibits the SP-induced vascular permeability mediated by both mechanisms in mice.     

Coexistence of peptides (corticotropin releasing factor/neurotensin and substance P/somatostatin) in the bed nucleus of the stria terminalis and central amygdaloid nucleus of the rat

Coexistence of corticotropin releasing factor and neurotensin and also of substance P and somatostatin was demonstrated in the lateral bed nucleus of the stria terminalis and the central amygdaloid nucleus of the rat, by means of a light microscopic mirror method or immunofluorescent double staining. Using the former technique, a major proportion of corticotropin releasing factor-like immunoreactive cells were found to display neurotensin-like immunoreactivity in the dorsal subdivision of the lateral bed nucleus of the stria terminalis and the lateral subdivision of the central amygdaloid nucleus. On the other hand, the immunofluorescent method showed that a significant number of neurons with both substance P- and somatostatin-like immunoreactivity were located in the ventral subdivision of the lateral bed nucleus of the stria terminalis and the medial subdivision of the central amygdaloid nucleus. Distribution patterns of such co-localized peptides may indicate that there are morphological and biochemical similarities between the dorsal subdivision of the lateral bed nucleus of the stria terminalis and the lateral subdivision of the central amygdaloid nucleus, as well as between the ventral subdivision of the lateral bed nucleus of the stria terminalis and the medial subdivision of the central amygdaloid nucleus. Previous studies have demonstrated that peptide-containing neurons in the lateral bed nucleus of the stria terminalis and central amygdaloid nucleus, such as corticotropin releasing factor-, neurotensin-, substance P- and somatostatin-like immunoreactive cells, project to the lower brainstem. The results of the present study suggest that corticotropin releasing factor/neurotensin and substance P/somatostatin neurons may be part of the lateral bed nucleus of the stria terminalis/central amygdaloid nucleus-lower brainstem pathways.     

Isolation and mapping of a polymorphic CA repeat sequence at the human VRK1 locus

VRK1 is a novel human putative serine/threonine kinase, and is located on chromosome 14 at band q32 where an autosomal recessive congenital microphthalmia (CMIC) is mapped. We isolated a polymorphic dinucleotide CA repeat marker from a genomic clone containing the human VRK1 gene. This polymorphism will be useful in genetic studies of disorders localized at the 14q32 region, such as CMIC. Received: October 8, 1998 / Accepted: October 16, 1998     

Proliferative cell nuclear antigen expression in follicular tumours of the thyroid with special reference to oxyphilic cell lesions

The expression of proliferative cell nuclear antigen (PCNA) in follicular tumours of the thyroid was examined by immunohistochemistry. Both usual nonoxyphilic cell follicular tumours (non-OCT) and oxyphilic cell tumours (OCT) were subdivided into benign, indeterminate, encapsulated carcinoma, and widely invasive carcinoma types. Among non-OCT the percentages of PCNA-positive cells in benign tumours, encapsulated carcinomas, and widely invasive carcinomas was 2.5%–8.6%, 11.8%–39.1%, and 18.6%–20.0%, respectively. There was a statistically significant difference between benign tumours and encapsulated or widely invasive carcinomas, as in previous studies. A value of 10% was appropriate to distinguish benign from malignant lesions. PCNA-positive cells in indeterminate-type non-OCT were not significantly different from those in benign tumours, ranging from 4.3%–19.6%, and occurring at more than 10% in three of six tuours. Among OCT the positivity was less than 10% in benign tumours (4.5%–7.8%) and more than 10% in malignant tumours (14.1%–35.9%) and all the eight indeterminate tumours (12.5%–27.3%), with a statistically significant differences between the benign tumour and each of the latter types. These results indicate that the examination of PCNA is valuable in diagnosis of thyroid follicular tumours and that the use of similar diagnostic criteria may be warranted in both non-OCT and OCT.     

Histopathologic study of partial hydatidiform moles and DNA triploid placentas

Sixty-two placentas with a triploid DNA content, which were analyzed by flow cytometry using paraffin-embedded tissues, were histologically investigated. These placentas were histologically classified as follows: 51 partial hydatidiform moles (PM), two hydropic abortuses and nine non-hydropic placentas. The DNA indices of the triploid peaks were between 1.41 and 1.60. Histologically, two populations of normal and edematous villi, vesicular villous edema with cistern formation, focal syncytiotrophoblastic hyperplasia with vacuola-tion, and villous scalloping with trophoblastic inclusion were almost always observed in the PM, but no single pathologic feature was specific for PM. The two entities, PM and triploid placenta, overlapped. Not all triploid gestations are PM and not all PM moles are triploid as shown in previously reported diploid or tetraploid PM. Although no patient with triploid PM developed persistent disease in this series, follow up of triploid PM is required as long as its true biological potential remains unclear. Flow cytometry is a reliable aid in the diagnosis of PM.     

Activation of natural killer T cells by alpha-galactosylceramide impairs DNA vaccine-induced protective immunity against Trypanosoma cruzi

Innate immunity as a first defense is indispensable for host survival against infectious agents. We examined the roles of natural killer (NK) T cells in defense against Trypanosoma cruzi infection. The T. cruzi parasitemia and survival of CD1d-deficient mice exhibited no differences compared to wild-type littermates. NK T-cell activation induced by administering alpha-galactosylceramide (alpha-GalCer) to T. cruzi-infected mice significantly changed the parasitemia only in the late phase of infection and slightly improved survival when mice were infected intraperitoneally. The combined usage of alpha-GalCer and benznidazole, a commercially available drug for Chagas' disease, did not enhance the therapeutic efficacy of benznidazole. These results suggest that NK T cells do not play a pivotal role in resistance to T. cruzi infection. In addition, we found that the coadministration of alpha-GalCer with DNA vaccine impaired the induction of epitope-specific CD8(+) T cells and undermined the DNA vaccine-induced protective immunity against T. cruzi. Our results, in contrast to previous reports demonstrating the protective roles of NK T cells against other infectious agents, suggest that these cells might even exhibit adverse effects on vaccine-mediated protective immunity.     

The influence of social environmental condition on the production of stress-induced 22 kHz calls in adult male Wistar rats

Adult rats emit 22 kHz ultrasonic vocalizations (USVs) in response to aversive stimuli, and these sounds are suggested to have communicative information among conspecifics. It is conceivable that social environment during development of rats has relevance to the emission of 22 kHz USVs. To examine the effects of social environment after weaning on production of stress-induced USVs, we compared the amount of emission of USVs among three groups of rats reared under different conditions after weaning. One group of rats was housed individually, and the other two groups were housed in pairs, in which social hierarchy of the pair was determined by social dominance-subordination relationships. The USVs were induced by acute mild somatic stimuli on the back and neck. Individually reared rats emitted much fewer USVs than pair-reared rats. In addition, socially subordinate rats emitted more USVs compared with socially dominant ones. These results suggest that not only social interaction but also the status in social hierarchy may play an important role in the process of the development of USVs induced by somatic stimuli.