Inhibition of IL-2 synthesis by donor-pecific suppressor T cells in a renal transplant recipient

Abstract A study was conducted to elucidate the mechanism of donor-pecific Mixed Lymphocyte Reaction (MLR and Cell Mediated Lymphotoxicity (CML) unresponsiveness in a renal transplant recipient with a long-term well-functioning kidney. The peripheral blood lymphocytes (PBL) of the recipient, who had not shown rejection since his transplantation 5 years previously, and those of his mother (donor), his father and two healthy third parties were examined. MLR, CML, semimicro MLR in a double chamber, interleukin-2 (IL-2) synthesis assay and limiting dilution assay were performed. This recipient showed donor-pecific MLR and CML unresponsiveness. IL-2 assay showed that the PBL of the recipient produced less IL-2 against the donor than against the father and the third parties. The addition of exogenous recombinant IL-2 (rIL-2; Takeda Co.) to the priming MLR caused a recovery of CML against the donor. A limiting dilution assay indicated that cytotoxic T cell precursor (CTLp) frequencies against the donor and father did not differ. The suppressor assay in a double chamber indicated that the PBL of the recipient stimulated by the donor PBL had a non-pecific suppressive effect on MLR, CML and IL-2 synthesis of the PBL across the Major Histocompatibility Complex (MHC) barrier. This suppressive effect was abolished by OKT3 or OKT8 monoclonal antibody and complement. Thus, the recipient had donor-pecific suppressor T cells that produced a humoral non-pecific suppressive factor only when stimulated by the donor PBL, and this factor suppressed PLR and CML by inhibiting IL-2 synthesis of the PBL.     

Preoperative therapeutic embolization for massive hemoptysis from bronchial collaterals in tetralogy of Fallot--a case report successfully treated by total correction

Hemoptysis from bronchial collateral arteries in cyanotic heart diseases is a troublesome complication. We report a case of Tetralogy of Fallot presented with massive hemoptysis which was successfully treated with transcatheter therapeutic embolization prior to the radical operation. A 28-years old man was admitted to our hospital because of hemoptysis and dyspnea. On the day of admission, he had a massive hemoptysis and became asphyxic. Diagnostic cardiac catheterization performed next day revealed Tetralogy of Fallot. Bronchial arteriogram demonstrated large bronchial collateral arteries with heavy staining around the right lower lobe bronchus. Therapeutic embolization with Gelfoam was performed and the hemostasis was obtained. The radical operation was performed 4 months later. Before cardiopulmonary bypass, the right bronchial artery was ligated. He was weaned from the extracorporeal circulation under the stable circulatory condition, and respirator on the first post operative day without any complications, and he was discharged on the 57th day after the operation. We emphasize the efficacy of therapeutic embolization of the well developed bronchial collateral arteries as a pretreatment of hemoptysis in the cyanotic heart disease.     

Retention fluids of chronic sinusitis induce neutrophil adherence to microvascular endothelial cells.

The adherence of circulating leukocytes to the vascular endothelium is a critical step in the emigration of leukocytes through blood vessel walls to inflammatory lesions. The influence of nasal secretions on the adherence of neutrophils to the vascular endothelium was investigated using monolayers of human mucosal microvascular endothelial cells derived from the inferior turbinate. Preincubation of vascular endothelial cells with retention fluids from the maxillary sinus of the patients with chronic sinusitis showed increased neutrophil adherence. Recombinant IL-1 beta was also tested and found to induce adherence of neutrophils to human mucosal microvascular endothelial cells. However, no adhesive effect was observed with the nasal secretions of nasal allergy. An enzyme-linked immunosorbent assay detected considerable amounts of IL-1 beta in the chronic sinusitis retention fluids, while the amounts of IL-1 alpha and TNF-alpha were very low. The increased adhesion of the neutrophils by the retention fluids of chronic sinusitis was also neutralized by the incubation with anti-IL-1 beta antibody in a dose dependent manner. These findings suggest that IL-1 beta in the paranasal secretion of chronic sinusitis induces the adherence of neutrophils to vascular endothelium and subsequent infiltration of neutrophils in the paranasal sinuses, thus contributing to the persistence of chronic sinusitis.     

The effects of intranasal application of low dose buserelin in women with hypothalamic amenorrhea]

Low doses of the Gn-RH agonist (buserelin, 30 micrograms) were given intranasally to 14 women with clomiphene ineffective hypothalamic amenorrhea three times daily for three weeks in order to study pituitary responses and to induce follicular maturation and ovulation. Clomiphene ineffective hypothalamic amenorrhea patients were classified into two groups by LH-RH stimulation test before the treatment. Group 1 was defined as having basal serum LH and FSH levels lower than 1.5 mIU/ml, LH and FSH peaks lower than 3mIU/ml by LH-RH stimulation test. Group 2 consisted of cases other than those in Group 1. While a significant increase in basal LH and FSH (p less than 0.01, p less than 0.001) and improvement in pituitary response to LH-RH stimulation test were observed in group 1, the basal levels of LH and FSH did not increase significantly and pituitary response to a LH-RH stimulation test was decreased in group 2. It is suggested that pituitary priming occurred in group 1 and pituitary desensitization occurred in group 2. None of 14 patients showed signs of follicular maturation during or after the treatment. The results demonstrated that the biphasic pituitary response to intranasal buserelin spray and the limit of its therapeutic use for the treatment of hypothalamic amenorrhea.     

Cleft lip-nose repair technique: Sequential repair

The results of repairing cleft lip by aesthetic plastic surgery are now excellent. However, the cleft lipnose deformity is still very difficult to repair with the present techniques. A technique that can repair the cleft lip-nose deformity with good results is presented. The technique is divided into three parts: Part I consists of nasal repair of the primary cleft lip. Part II is nasal reconstruction as a secondary operation with or without lip repair. For example, nasal reconstruction may be secondary to repair of deformities of the sill, rim, limen nasi, septum, or nasal bones. Part III is an aesthetic nasal operation such as rhinoplasty, mentoplasty, or zygomaplasty.     

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.