Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine

BACKGROUND: The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. METHODS: Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n=2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4). RESULTS: Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. CONCLUSIONS: Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.     

Relationship between A-3826G polymorphism in the promoter of the uncoupling protein-1 gene and high-density lipoprotein cholesterol in Japanese individuals: a cross-sectional study

BACKGROUND: A-3826G polymorphism within the promoter region of the uncoupling protein-1 (UCP-1) gene is possibly involved in the pathophysiology of obesity and metabolic disorders. However, the effects of UCP-1 A-3826G polymorphism on high-density lipoprotein cholesterol (HDL-C), a major contributor to atherosclerotic disease, still have not been established. METHODS: A total of 298 healthy Japanese subjects (144 males and 154 females, mean age: 45.2 years) with a body mass index (BMI) of 20.0-30.0 kg/m(2), regular lifestyles, and receiving no medication were enrolled in the cross-sectional study to estimate the relationship of serum HDL-C levels with UCP-1 A-3826G polymorphism by genomic PCR and Bcl1-restriction fragment length polymorphism analysis. We used 1.04 mmol/L of HDL-C in Japanese males and 1.29 mmol/L in Japanese females as cut-off values of low HDL-cholesterolemia. RESULTS: The genotype and allele frequencies of UCP-1 A-3826G polymorphism were similar to those previously reported in the Japanese population. In males, HDL-C levels of the GG genotype (1.75+/-0.49 mmol/L) were significantly higher than those found in the AA genotype (1.45+/-0.34 mmol/L, p=0.015). In females, the occurrence rate of low HDL-cholesterolemia was significantly different by genotype: a low prevalence in the GG genotype (15.4% in the AA, 4.8% in the AG, 15.4% in the GG genotype, p=0.022). Logistic regression analysis was used to identify risk factors for low HDL-cholesterolemia, with adjustments for age, gender, smoking, alcohol intake, BMI, hypertriglyceridemia, and genotype. The GG genotype was detected as being a significant associated factor (odds ratio =0.11 [95% confidence interval =0.01-0.90], p=0.01), in addition to BMI and the presence of hypertriglyceridemia. CONCLUSIONS: These results suggest that the GG genotype may be an independent protective factor associated with low HDL-cholesterolemia in this population, although the role of the UCP-1 A-3826G polymorphism in HDL-C is complex and remains controversial. This hypothesis needs further investigation.     

Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors

Context  Very little is known about the frequency of generation and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. Furthermore, transmission of resistant virus, whether influenza A or B, has not been recognized to date. Objective  To assess the prevalence and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. Design, Setting, and Patients  Investigation of the neuraminidase inhibitor sensitivity of influenza B isolates from 74 children before and after oseltamivir therapy and from 348 untreated patients with influenza (including 66 adults) seen at 4 community hospitals in Japan during the 2004-2005 influenza season. Four hundred twenty-two viruses from untreated patients and 74 samples from patients after oseltamivir therapy were analyzed. Main Outcome Measure  Sialidase inhibition assay was used to test the drug sensitivities of influenza B viruses. The neuraminidase and hemagglutinin genes of viruses showing reduced sensitivity to neuraminidase inhibitors were sequenced to identify mutations that have the potential to confer reduced sensitivity to these drugs. Results  In 1 (1.4%) of the 74 children who had received oseltamivir, we identified a variant with reduced drug sensitivity possessing a Gly402Ser neuraminidase substitution. We also identified variants with reduced sensitivity carrying an Asp198Asn, Ile222Thr, or Ser250Gly mutation in 7 (1.7%) of the 422 viruses from untreated patients. Review of the clinical and viral genetic information available on these 7 patients indicated that 4 were likely infected in a community setting, while the remaining 3 were probably infected through contact with siblings shedding the mutant viruses. Conclusions  In this population, influenza B viruses with reduced sensitivity to neuraminidase inhibitors do not arise as frequently as resistant influenza A viruses. However, they appear to be transmitted within communities and families, requiring continued close monitoring.      

Application of Isolite system during treatment of dental caries identified in submerged mandibular second primary molar

We used the Isolite system for treatment of dental caries identified in a submerged mandibular right primary second molar. A 5-year-6-month-old girl was referred to our clinic for close examination of an impacted mandibular right second primary molar. An intraoral examination showed a slight pit extending inside the gingiva and on the occlusal surface of the tooth. X-ray photographic examination revealed that the affected tooth was severely submerged and had a radiolucent area on the occlusal surface, which extended close to the pulp cavity. Most of the periodontal ligament space could not be clearly identified except for the distal side of the distal root. We considered that the area of the tooth was partially ankylosed and consulted with oral surgeons, who decided to postpone extraction, due to the presence of the permanent successor close to the affected tooth. Thus, we treated the dental caries, which appeared to be technically difficult because of the deep location of the tooth. The Isolite system was utilized in this case, as we considered that adjacent soft tissue and saliva could be excluded with its use. Under infiltration anesthesia, gingival tissue covering the occlusal surface was removed with an electric knife, and the carious lesion was removed, which resulted in pulp exposure. Severe inflammation of the pulp was revealed and pulpectomy was performed. There were no signs and symptoms after the treatment. At 1 year after treatment, the occlusal surface remained exposed and no inflammatory findings were observed in adjacent gingival tissue.     

Mydriasis with Light-Near Dissociation in Fisher's Syndrome

Background

Approximately 50% of patients with Fisher's syndrome show involvement of the pupillomotor fibers and present with mydriasis and light-near dissociation. However, it is uncertain whether this phenomenon is induced by an aberrant reinnervation mechanism as in tonic pupil, or is based on other mechanisms such as those associated with tectal pupils.

Cases

We evaluated the clinical course and the pupillary responses in four of 27 patients with Fisher's syndrome who presented with bilateral mydriasis.

Observations

The pupils of both eyes of the four patients were involved at the early stage of Fisher's syndrome. The pupils in patients 1 and 2 showed mydriasis with apparent light-near dissociation lasting for a significant period and had denervation supersensitivity to cholinergic agents. On the other hand, the pupils of patients 3 and 4 were dilated and fixed to both light and near stimuli.

Conclusions

Our observations indicate that the denervated iris sphincter muscles, which are supersensitive to the cholinergic transmitter, may play an important role in the expression of light-near dissociation in Fisher's syndrome.?Jpn J Ophthalmol 2007;51:224–227 © Japanese Ophthalmological Society 2007

     

Immunolocalisation of E-cadherin and beta-catenin in human pterygium

AIM: The pterygium represents an invasion of a wing of altered ocular surface tissue into the normal cornea. The head itself is slightly elevated and white, which is the only site of firm adhesion to the globe. The mechanisms of cell proliferation and adhesion in pterygium epithelium, however, are unknown. The aim of this study was to analyse the expression of cell adhesion molecules in pterygium tissues. METHODS: Six pterygia were surgically removed using the bare-sclera procedure, and two normal corneas and a normal bulbar conjunctiva were also obtained. Formalin-fixed, paraffin-embedded tissues were analysed by immunohistochemistry with anti-E-cadherin and beta-catenin antibodies. RESULTS: Immunoreactivity for E-cadherin was not detected in the normal cornea and conjunctiva. In contrast, all corneal and conjunctival epithelial cells showed a weak homogeneous immunoreaction for beta-catenin on the cell membrane. In the pterygium head, the thickness was relatively marked compared with the body, and normal conjunctival and corneal epithelia. E-cadherin as well as beta-catenin was heterogeneously expressed in the cell membrane and cytoplasm of a variety of epithelial cells, whereas the expression was less marked in the body. Several epithelial cells showed intense nuclear immunoreactivity for beta-catenin. Immunoreactivity of beta-catenin, but not E-cadherin, was detected in only a few stromal cells, which were less marked than in epithelial cells. CONCLUSION: It is suggested that E-cadherin and beta-catenin are concentrated in pterygium tissue, and are possibly involved with epithelial proliferation and adhesion.     

Autoantibodies to the heat-shock protein hsp73 in localized scleroderma

We determined the presence of antibodies to the heat-shock protein hsp73 (anti-hsp73) in 57 serum samples from patients with localized scleroderma using an enzyme-linked immunosorbent assay (ELISA). In addition, 30 samples from healthy individuals, 30 from patients systemic lupus erythematosus (SLE) and 32 from patients with systemic sclerosis were assessed. IgG and/or IgM anti-hsp73 antibodies were detected in 33% (19/57) of the patients with localized scleroderma. Among the three subtypes of localized scleroderma, generalized morphoea showed the highest incidence of anti-hsp73 antibodies (40%, 6/15). IgG and/or IgM anti-hsp73 antibodies were also detected in 9/30 samples (30%) from patients with SLE and in 13/32 samples (41%) from patients with systemic sclerosis, while the samples from the healthy controls were all negative for anti-hsp73. By immunoblotting, specific binding of antibodies to hsp73 was confirmed with representative serum samples that were positive for anti-hsp73 in the ELISA. Our findings indicate that the presence of anti-hsp73 is an additional immunological abnormality in localized scleroderma.     

A case of scleroderma spectrum disorder with anticentriole antibody and pulmonary hypertension

We describe the case of a patient with anticentriole antibody-positive scleroderma spectrum disorder (SSD) who developed pulmonary hypertension. A 54-year-old woman had noticed Raynauds phenomenon and digital ulcers during the winter for the past 10 years. Although sclerodactyly was not present, digital ulcers, swelling of her hands, and phalangeal contracture were observed. An indirect immunofluorescence test revealed anticentriole antibody. Other SSc-specific antoantibodies were negative. An echocardiogram demonstrated that the estimated right ventricular systolic pressure was increased to 51 mmHg. She was diagnosed as SSD with pulmonary hypertension. This is the first case of SSD with anticentriole antibody to develop pulmonary hypertension.Abbreviations SSD Scleroderma spectrum disorder - SSc Systemic sclerosis