T cell responses to orbital antigens in thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is most likely to be a T cell-mediated disease, in which cytokines released in the extraocular muscles activate fibroblasts, increasing glycosaminoglycan production. The nature of the orbital antigen recognized by the infiltrating T cells is unclear, although it is possible that there is cross-reactivity between this and a thyroid autoantigen to explain the close association with thyroid autoimmunity. We have tested the ability of human and porcine eye muscle antigen preparations to stimulate proliferation of circulating T cells from healthy subjects and patients with TAO or Graves' disease without clinical TAO. Occasional responses were seen, particularly after depletion of CD8+ T cells, and two out of 10 TAO patients responded to eye muscle proteins of 25-50 kD after fractionation of antigens on gels and subsequent elution. There was no disease-specific response of T cells to R1, R14, D1 and 1D3, recombinant proteins identified from screening an eye muscle cDNA library with sera from patients with autoimmune thyroid disease. We have also found that interferon-gamma (IFN-gamma) production by T cells from TAO patients was not stimulated by eye muscle membrane antigens or by 1D3. These results suggest that the frequency of circulating T cells responding to eye muscle antigens in TAO is low, and that several candidate orbital antigens, including the 64-kD protein 1D3, are unlikely to be important T cell autoantigens in this condition.     

A novel pancreatic endocrine tumor suppressor gene locus on chromosome 3p with clinical prognostic implications.

The molecular pathogenesis of pancreatic endocrine tumors is largely unknown. Such tumors are more likely to develop in individuals with the von Hippel-Lindau (VHL) syndrome. We sought to determine whether allelic loss of the recently identified VHL tumor suppressor gene on chromosome 3p25-26 occurs in the more common sporadic forms of these tumors. Allelic loss on chromosome 3p was identified in 33% of 43 patients with endocrine tumors of the pancreas. The smallest common region of allelic loss, however, centered not at the VHL locus, but rather at 3p25, centromeric to VHL. Furthermore, no mutations of the VHL gene were identified in these tumors. Loss of alleles on chromosome 3p was associated with clinically malignant disease, whereas tumors with retained 3p alleles were more likely to be benign. Thus, the VHL gene does not appear to play a pathogenic role in the development of sporadic pancreatic endocrine tumors. Instead, a locus at chromosome 3p25 may harbor a novel pancreatic endocrine tumor suppressor gene, and allelic loss of this chromosomal region may serve as a molecular marker that helps distinguish benign from clinically malignant disease.     

The effects of prior exposure to silicone on capsule formation, histology, and pressure

Investigations into the effects of prior silicone exposure on subsequent capsule formation around silicone implants assume particular relevance in light of the exponential increase in the medical application of polymers such as silicone. The inert nature of silicone has been in question with regard to its effects on the immune system, specifically whether or not it may act as a hapten or antigen. The present study analyzes the effects of prior silicone exposure on subsequent capsule formation, histological consistency, and pressures when an animal is reexposed to a silicone implant. Twelve female Lewis rats (body weight 250 g) were randomly divided into two groups. Group 1 (n = 6) rats were subcutaneously injected with 2.5 ml of Freund's Complete Adjuvant, Group 2 (n = 6) rats were injected with an equal volume of adjuvant sonicated with silicone gel. At 4 weeks a gel-filled silicone implant was placed subcutaneously in each animal. Capsule pressures were obtained at 4 months and the capsules from 3 rats from Group 2 were excised and examined microscopically. Pressures were measured again at 8 months and all remaining capsules were excised and examined. No statistically significant differences were noted when comparing two profiles over time between silicone-exposed and nonexposed animals in regard to capsule thickness or capsule pressure. However, capsule pressures were significantly lower at 8 months than at 4 months in both groups (p less than 0.034). In this model, significant reductions in capsule pressure were noted in both groups over time, but prior exposure to silicone did not appear to alter capsule histology, thickness, or pressure.     

New reference allelic ladders to improve allelic designation in a multiplex STR system

This paper reports the composition of a new reference allelic ladder mixture for use with a multiplex DNA profiling system consisting of six short tandem repeat loci. The loci included in this mixture are HUMTH01, D21S11, D18S51, D8S1179, HUMVWAF31/A, HUMFIBRA/FGA and an amelogenin sex test. Sequence analysis of individual ladder alleles was carried out and allelic designations made in accordance with the recommendations of the International Society of Forensic Haemogenetics (1992; 1994). A series of rare alleles which increase the range of alleles previously reported were identified. By including some of the rare alleles into the ladder marker system, we have significantly improved the ability to identify new alleles in unknown samples. Received: 12 August 1997 / Received in revised form: 7 November 1997     

Asbestos fiber type in malignant Mesothelioma: An analytical scanning electron microscopic study of 94 cases

Although the association between asbestos exposure and malignant mesothelioma is indisputable, controversy continues regarding the relative contribution of the various types of asbestos fibers to the development of mesothelioma. We examined the types of asbestos fibers recovered from lung parenchyma in more than 90 cases of malignant mesothelioma from the United States, using an analytical scanning electron microscope. Almost half of the patients were former asbestos insulators or shipyard workers. The fibers were recovered from lung tissues obtained at autopsy or surgical resection by means of a sodium hypochlorite digestion procedure. Amosite absestos was identified in 81% of the cases and accounted for 58% of all fibers 5 μm or greater in length. Tremolite/actinolite/anthophyllite were identified in 55% of the cases and accounted for 10% of all fiber types. Chrysotile was identified in 21% of the cases and accounted for 3% of fibers exceeding 5 μm in length. Crocidolite was found in 16% of the cases and accounted for 3% of fibers exceeding 5 μm in length. Nonasbestos mineral fibers (commonly found in the lungs of the general population) were observed in 71% of the cases and accounted for 25% of all fibers 5 μm or greater in length. The findings in this study are at odds with the assertion that crocidolite asbestos is responsible for most mesotheliomas in the United States. © 1993 Wiley-Liss, Inc.     

Genesis of papillar pit. Microscopy study in a newborn infant

The rare microscopic picture of a pit of the optic disk is described. The recess extended from the physiological cup of the optic disk to the former cleft of the optic stalk at the point of entry of the ophthalmic artery. There was no disk coloboma. This result is in good agreement with von Szily's paper on the genesis of crater-like holes in the optic disk as a residue of the cavity of the primordial epithelial papilla. In this case there was no communication of the vitreous cavity with a subretinal space, which is suspected of being the cause of the frequent concomitant serous detachment of the macula.