Multiple epithelial cysts of the spleen and on the splenic capsule, and high serum levels of CA19-9, CA125 and soluble IL-2 receptor

An 18-year-old woman with abdominal pain was diagnosed as having splenic cysts by computed tomography scan. She had high serum levels of CA19-9 (2886.8 U/mL; normal value, <35 U/mL), CA125 (131.1 U/mL; normal value, <35 U/mL) and soluble IL-2 receptor (1490 U/mL; normal range, 220-530 U/mL). The resected spleen weighed 1050 g, was 14 x 28 cm, and had more than 10 macroscopic cysts up to 10.3 x 9.5 cm. There were numerous microscopic cysts in the spleen and several on the splenic capsule. The levels of CA19-9 and CA125 in the cyst fluid were 2165550 U/mL and 160400 U/mL, respectively. After the surgery, the serum levels of the tumor markers decreased gradually. The inside of the largest cyst was mainly covered by granulation tissue with a focal lining of epithelial cells, and the other macroscopic cysts had stratified squamous epithelium. The microscopic splenic cysts and cysts on the splenic capsule were lined by either attenuated single-layered or multilayered epithelial cells. The lining epithelial cells of these cysts were positive for epithelial membrane antigen and cytokeratins. CA19-9 and CA125 were detected in the lining cells of the splenic cysts. In the present case, it is suspected that the splenic cysts were derived from the capsular lining cells that showed migration from the capsule or formed microcysts on the splenic capsule, as in the case of ovarian inclusion cysts.     

Retroperitoneal mucinous cystadenoma

Primary retroperitoneal mucinous cystadenoma is an uncommon tumor found exclusively in women. Herein, we describe a patient who had resection of a large retroperitoneal cystic mass. Histologic, immunohistochemical, and electron microscopic examination of the lining epithelial cells showed features of mesothelial cells in addition to ovarian mucinous cystadenoma. These findings suggest that these tumors arise from inclusions of mesothelial cells and subsequent mucinous metaplasia of the lining cells to form a cystadenoma. Estrogen receptors may be implicated in tumor promotion, explaining the occurrence exclusively in women.     

Long-term follow up studies of bronchial asthma in children. II. Prognosis and complications, treatment and allergic evaluations

A questionnaire on the prognosis of bronchial asthma was sent in 1988 to 1592 patients (1038 males, 554 females) averaging 20 years of age after 12 years' follow up. We reported on the prognosis and risk factors associated with asthmatic children in part I. The relation between prognosis and other allergic complications, treatment and laboratory data were investigated in this study. Eosinophil counts of more than 1000/mm3 and/or total serum IgE levels of more than 500 IU/ml (100 IU/ml in infants) indicated poor prognosis. However, the prognosis was not affected either by the allergens themselves or by the number of allergens determined by skin test and RAST. The prognosis was worse for patients with multiple allergic complications than for those without complications. Treatment may after the natural course of childhood asthma, but it has been difficult to evaluate the effect of each regimen over a long period. We compared the effect of hyposensitization (specific immunization) and non-bronchodilator antiasthmatic drugs (NBAAD), and found that hyposensitization alone gave better results than NBAAD and its combination. We had better results from hyposensitization over a period of 1 to 5 years than for less than 1 year or more than 5 years. We conclude that asthmatic children with risk factors should be kept under strict environmental control and given suitable therapeutic regimens to avoid the development of allergic diseases, the slow down of "allergic march", and to avoid intractable asthma.     

Neural mechanisms of chromatic adaptation in L-type cone horizontal cells of the carp retina

When a background light is delivered, the responsiveness of horizontal cells to light stimulus initially lowers but subsequently recovers gradually as shown by the increase in response amplitude to test light. These changes of responsiveness are observed when white or close wavelengths are used for both the background and test lights. However, the response amplitude to blue-green test light was initially enhanced but decreased and reached a steady state after the onset of red background illumination. The mechanism causing such a change of test responses was studied in the luminosity-type cone horizontal cells. The initial response enhancement was accompanied by an increase of the slope of hyperpolarizing phase, while the subsequent decrease of response amplitude was caused by the advancement of the recovery phase. The advancement of the recovery phase was eliminated by gamma-aminobutyric acid (GABA) or Co2+ (50 microM), which blocks GABA-induced currents in cone terminals. Dopamine, which inhibits GABA release from horizontal cells, stimulated the advancement of the recovery phase. The time course of the hyperpolarizing phase was not affected by these agents. The enhancement and the subsequent decrease of test responses were also observed in 6-hydroxydopamine-treated retinae. The results suggest that the GABAergic feedback pathway from horizontal cells to cones advances the recovery phase of response to test light. It appears, therefore, that the feedback modifies the responsiveness of horizontal cells to light stimulus under a red background illumination. The mechanism enhancing response amplitude will be also discussed.     

A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis

Synovial T cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA) synovitis. We have quantitatively analyzed the T cell receptor (TcR) variable (V) region gene repertoire of freshly isolated synovial fluid (SF) T cells, comparing it with that of peripheral blood (PB) T cells in RA. The TcR V gene repertoire of PB and SF T cells in RA and osteoarthritis was heterogeneous. In contrast, Vail in SF was expressed to a greater degree in three of five RA patients, and increased levels of Vp6, 1-3 were found in the SF of four of six RA, compared with paired PB. Of note, Vβ6, 1–3 was universally used in four RA patients with a disease duration of less than 10 years, irrespective of their HLA-DR types. This was in contrast to two other RA patients, suffering for more than 20 years, who showed different Vα and Vβ usages. β-chain sequence analysis in RA patients with a preference for Vβ6, 1–3 has shown that a few clones dominated in SF, whereas polyclonality was observed in PB. These findings suggest oligoclonal expansion of T cells in response to specific antigen(s) in the SF of these patients with RA of relatively short duration. Concomitant use of two hydrophobic amino acids, leucine and valine, in the Dβ region was noticeable among the predominant SF clones. These two amino acids might directly contact a peptide specific for the induction of synovitis in RA patients. TcR-directed therapy may, therefore, be useful for the treatment of early RA synovitis.     

Synergistic effect of gelatin microspheres incorporating TGF-beta1 and a physical barrier for fibrous tissue infiltration on skull bone formation

The objective of this study is to examine whether or not bone formation at a skull bone defect induced by gelatin microspheres incorporating transforming growth factor (TGF)-beta1 is promoted by prevention of fibrous tissues into the defect. The 6-mm diameter bone defect of rabbit skulls was applied with gelatin microspheres incorporating TGF-beta1 or free TGF-beta1 and physically covered by a barrier membrane. When the bone formation at the defect was assessed 6 weeks postoperatively, combinational application of gelatin microspheres incorporating 0.1 microg of TGF-beta1 with the barrier membrane induced bone formation at the skull defect, in marked contrast to that of 0.1 microg of free TGF-beta1 and empty gelatin microspheres. Complete defect closure was histologically observed by the newly formed bone tissue. Without the barrier membrane, gelatin microspheres incorporating TGF-beta1 were less effective in inducing bone formation, whereas free TGF-beta1 and empty gelatin microspheres were ineffective. The skull defect was occupied by fibrous tissue infiltrated in place of bone tissue. The bone mineral density at the skull defect applied with gelatin microspheres incorporating TGF-beta1 plus the membrane was significantly higher than that of gelatin microspheres incorporating TGF-beta1 alone. The present data indicated that physical protection from the soft tissue infiltration enabled gelatin microspheres incorporating TGF-beta1 to synergistically enhance the osteoinductive ability at the skull defect.     

Non-adhesive cyanoacrylate as an embolic material for endovascular neurosurgery

Endovascular neurosurgery is now becoming available as one of strategies for the treatment of cerebro-spinal arterio-venous malformations and aneurysms. For this treatment, a microcatheter is advanced into or close to a lesion and then an embolic material is administered through it to obliterate the lesion. N-butyl-2-cyanoacrylate (NBCA) has preferentially been used as an embolic material in Europe and America. However, its exceptionally strong adhesive force sometimes causes adhesion between the tip of the microcatheter and the artery. In this study, a new non-adhesive cyanoacrylate, isostearyl-2-cyanoacrylate (ISCA), was developed. It carries a long hydrophobic side isostearyl group with lower reactivity and adhesion than other cyanoacrylates. Its polymerization rate is, however, too low to obliterate a vascular lesion with a rapid blood flow. To increase the polymerization rate. ISCA was mixed with NBCA. As a result, the adhesive force of the mixture became extremely low, compared with that of NBCA. The viscosity of the mixture was low enough to allow its' use as an embolic material. Tissue reactions against the mixture was milder than those against NBCA. Radio-angiography became possible by mixing further with Lipiodol. The evaluation of this new embolic material with a rabbit renal artery showed that the obliteration effect of the mixture of ISCA and NBCA was excellent to use as an embolic material for clinical applications.     

A possible pathogenic role of CD8+ T cells and their derived cytokine, IL-16, in SLE

Current investigations into the role of CD8+ T cells and their derived cytokine, interleukin (IL)-16, in the induction of CD4+ T cell abnormalities in systemic lupus erythematosus (SLE) were reviewed and discussed on the basis of results mainly obtained in our laboratory.