Long-term treatment with thalidomide for severe recurrent hemorrhage from intestinal angiodysplasia in Glanzmann Thrombasthenia.

Gastrointestinal angiodysplasia (GIA) is the most common cause of occult gastrointestinal bleeding (GIB) requiring often hospitalization and transfusions, especially in patients with hemorrhagic disorders. Thalidomide, impairing neo-angiogenesis, has been successfully used in the management of bleeding in patients with GIA and in particular in patients with inherited bleeding disorders. Only one case of short-term treatment with thalidomide in a patient with Glanzmann thrombasthenia (GT) and recurrent GIB due to GIA has been reported so far.

Sunitinib inhibits tumor vascularity and growth but does not affect Akt and ERK phosphorylation in xenograft tumors.

Sunitinib is a multikinase inhibitor approved for use in some human solid malignancies, including renal clear cell and gastrointestinal stromal cancer, and under investigation for many other neoplasias. In many preclinical cancer models sunitinib has shown anti-angiogenic and antitumor effects, acting mainly by inhibiting the activity of pro-angiogenic growth factor receptors. However, a percentage of tumors develop resistance to this treatment.

Recent advances in adrenal autoimmunity.

Autoimmune Addison's disease (AAD) results from the immune-mediated destruction of adrenocortical cells. AAD is a major component of the autoimmune polyendocrine syndromes type 1 (APS 1) and type 2. The adrenal autoimmune process is made evident by the apperance of circulating autoantibodies against the steroidogenic enzyme 21-hydroxylase.

Radioiodine uptake in non-lactating mammary glands: evidence for a causative role of hyperprolactinemia.

Context: Radioiodine uptake is rarely observed in normal non-lactating breast tissue. Investigation of the in vivo regulation of iodide uptake in breast tissue may be useful for the induction of radioiodine uptake in breast cancer tissue for diagnostic and therapeutic purposes.

Case Reports: We report the cases of two post-menopausal women who underwent radioiodine therapy for papillary thyroid carcinoma and in whom breast uptake of radioiodine on post-therapy whole body scan (WBS) was observed.

Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse.

Aims/hypothesis: Recent observations suggest the involvement of the gastrointestinal tract in the pathogenesis of islet autoimmunity. Thus, the modulation of gut-associated lymphoid tissue may represent a means to affect the natural history of the disease. Oral administration of probiotic bacteria can modulate local and systemic immune responses; consequently, we investigated the effects of oral administration of the probiotic compound VSL#3 on the occurrence of diabetes in non-obese diabetic (NOD) mice.

Improved in planta expression of the human islet autoantigen glutamic acid decarboxylase (GAD65).

The smaller isoform of the enzyme glutamic acid decarboxylase (GAD65) is a major islet autoantigen in autoimmune type 1 diabetes mellitus (T1DM). Transgenic plants expressing human GAD65 (hGAD65) are a potential means of direct oral administration of the islet autoantigen in order to induce tolerance and prevent clinical onset of disease. We have previously reported the successful generation of transgenic tobacco and carrot that express immunoreactive, full-length hGAD65.

Expression of endocrine autoantibodies in chronic hepatitis C, before and after interferon-alpha therapy.

Interferon-alpha (IFN-alpha) treatment for chronic hepatitis C (CHC) has been associated with thyroid autoimmunity and/or dysfunction. Only a few data concerning the prevalence of islet-cell or adrenal cortex autoantibodies in IFN-alpha-treated subjects are currently available. The aims of our study were to evaluate in CHC, 1) the prevalence and association of thyroid, islet-cell and adrenal autoantibodies, and 2) the appearance of endocrine dysfunction, before and after a 6 month IFN-alpha treatment.

CTLA-4-Ig regulates tryptophan catabolism in vivo.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a critical role in peripheral tolerance. However, regulatory pathways initiated by the interactions of CTLA-4 with B7 counterligands expressed on antigen-presenting cells are not completely understood. We show here that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4-immunoglobulin (CTLA-4-Ig) is contingent upon effective tryptophan catabolism in the host.

Autoantibody profile and epitope mapping in latent autoimmune diabetes in adults.

The presence of islet cell autoantibodies in adult diabetic subjects who do not require insulin treatment for at least six months after the initial clinical diagnosis identifies the so-called latent autoimmune diabetes in the adult (LADA). Glutamic acid decarboxylase autoantibodies (GAD65Ab) are the best immune marker to identify LADA patients, while other islet autoantibodies, such as IA-2 autoantibodies, have a very low diagnostic sensitivity. Islet cell antibodies, as detected by indirect immunofluorescence, may improve the diagnostic specificity of the immune analysis when detected in GAD65Ab-positive patients.

Autoantibody recognition of COOH-terminal epitopes of GAD65 marks the risk for insulin requirement in adult-onset diabetes mellitus.

Some type 2 diabetic subjects develop secondary failure to sulphonylurea treatment and require insulin therapy. To test the diagnostic sensitivity and specificity of epitopes of GAD65 autoantibodies (GAD65Ab) for insulin requirement, in patients with latent autoimmune diabetes of the adult, we studied 569 adult subjects with a clinical diagnosis of type 2 diabetes mellitus. All the patients had been initially treated with hypoglycemic agents and/or diet for at least 1 yr.

Levels of adrenocortical autoantibodies correlate with the degree of adrenal dysfunction in subjects with preclinical Addison's disease.

To test the hypothesis that levels of adrenal autoantibodies correlate with the degree of adrenal dysfunction, we followed up adrenal cortex autoantibody (ACA) titers and 21-hydroxylase (21OH) autoantibody (21OHAb) levels in 19 ACA-positive subjects with preclinical Addison's disease. On enrollment, all the 19 ACA-positive subjects were positive for 21OHAb. At follow-up, the concordance rate for simultaneous presence/absence of both ACA and 21OHAb was as high as 91% and a strong, positive correlation between 21OHAb levels and ACA titers was observed (P < 0.

Etiological diagnosis of primary adrenal insufficiency using an original flowchart of immune and biochemical markers.

Approximately 70-80% of cases of primary adrenal insufficiency are classified as idiopathic. An effective protocol for the etiological diagnosis of primary adrenal insufficiency is needed to ensure correct patient management. With the aim of developing an algorithm for the etiological diagnosis of primary adrenal insufficiency, we studied 56 Italian patients with nonsurgical primary adrenal insufficiency and 24 French patients with X-linked adrenoleukodystrophy (ALD) for serum levels of adrenal cortex, steroid-21-hydroxylase (21OHAb), islet cell (ICA), glutamate decarboxylase (GAD65Ab), IA2/ICA512 (ICA512Ab), thyroid peroxidase (TPOAb) autoantibodies, and plasmatic concentrations of very long chain fatty acids (VLCFA).

Protection from autoimmune diabetes by adjuvant therapy in the non-obese diabetic mouse: the role of interleukin-4 and interleukin-10.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by the destruction of insulin-producing beta-cells in the pancreatic islets. A single administration of CFA prevents clinical hyperglycaemia in non-obese diabetic (NOD) mice. We have previously shown that CFA administration does not eliminate insulitis in the pancreas of the treated animals, but diverts the disease process from a destructive to a non-destructive pathway.

Effect of adjuvant therapy on development of diabetes in mouse and man.

Freund's complete adjuvant (CFA) and BCG vaccine modulate the development of type 1 diabetes in animal models. In non-obese diabetic mice, CFA and BCG significantly reduced the proportion developing diabetes compared with controls. Histological examination showed that autoimmune disease still developed but had been diverted to become nondestructive.

Preventive effects of azathioprine (AZA) on the onset of diabetes mellitus in NOD mice.

We have studied the effects of long-term treatment with azathioprine (AZA) vs cyclosporin A (CSA) vs placebo (PL), in three groups of 10 week old, prediabetic NOD mice. One of 8 AZA, none of 8 CSA and 7 of 11 PL treated mice developed overt diabetes (IDDM). Quantitative morphometric analysis conducted on mouse pancreatic histologic sections documented that extent and degree of islet beta-cell damage were incomparably less severe in the mice that received AZA or CSA compared to those treated with PL.

Detection of cell-mediated immunity in type I diabetes mellitus.

Type I insulin dependent diabetes mellitus (IDDM) is thought to result from chronic, cell-mediated, 'autoimmune' islet damage. Antibody testing is extensively used to define and follow the pre-diabetic population. However, the assay for cell mediated immunity (CMI) should be more predictive of impending disease.

Facilitation of specific tolerance induction in adult mice by RS-61443.

RS-61443 is an immunosuppressive agent that facilitates pancreatic islet allograft acceptance in two mouse strain combinations (BALB/c----CBA and C57Bl/6J----BALB/c). A remarkable feature of this agent is its ability to facilitate long-term graft acceptance after a short (30 days) period of treatment; following withdrawal of the agent 40-70% of islet allografts are maintained for an indefinite period. This long-term graft acceptance has been shown to result from specific tolerance induction in the recipient animal.

Immunoprotection of pancreatic islet grafts within artificial microcapsules.

To circumvent pancreatic islet graft-directed immune destruction we enveloped porcine islets within highly biocompatible and selectively permeable algin/polyaminoacid microcapsules. These special microspheres were deposited between the inner (permeable) and the outer (impermeable) layers of an artificial, coaxial vascular prosthesis, directly anastomized to blood vessels. Five dogs with spontaneous, insulin-dependent diabetes received microencapsulated porcine islets in arterio-vein iliac prosthesis by-passes.

[Islands of Langerhans transplant in the treatment of diabetes mellitus: current status, indications, future perspectives].

Islet cell transplantation is a potential and attractive alternative to exogenous insulin administration for the therapy of IDDM. Large scale clinical applicability of this approach has been hampered, so far, by technical problems such as separation of massive islet concentrations and immune rejection. Microencapsulation within algin/polyaminoacids has provided islets with selective permeable biomembranes thus allowing prevention of the host's immune response and circumvention of general immunosuppression of the recipient.

A method for the massive separation of highly purified, adult porcine islets of Langerhans.

A method for the massive and reproducible isolation of highly purified, adult porcine islets of Langerhans is described. The successful combination of donor animal-strain selection with original procedures for pancreas retrieval and enzymatic digestion permitted us to separate uniquely massive concentrations of pure porcine islets with no need for mechanical disruption of the pancreatic tissue. Following our procedure, porcine islets, which fully retain viability and function, can be harvested easily and rapidly.