Localized primary amyloidosis of axillary lymph nodes.
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Aged↗
Biomedical subjects
G Magro
Publications and source records attributed to G Magro.
The effects of a nonimmunogenic form of murine soluble interferon-gamma receptor on the development of autoimmune diabetes in the NOD mouse.
Previous studies have shown that in vivo treatment with antiinterferon-gamma (anti-IFNgamma) monoclonal antibodies (mAbs) prevents the development of autoimmune diabetes in NOD mice. Although these findings anticipate that specific anti-IFNgamma therapies may be useful for the prevention/treatment of human insulin-dependent diabetes mellitus, there are several reasons why the use of anti-IFNgamma mAb may be difficult in the clinical setting. With the aim to develop alternative forms of specific anti-IFNgamma therapies, we recently produced a nonimmunogenic form of the soluble IFNgamma receptor (sIFNgammaR) that binds and neutralizes murine IFNgamma with an affinity higher than that of anti-IFNgamma mAb. In this study we compared the efficacy of sIFNgammaR to that of two anti-IFNgamma mAbs (XMG 1.2 and AN-18) in the prevention of spontaneous and accelerated (cyclophosphamide-induced) forms of autoimmune diabetes in NOD mice. The results show that in the spontaneous model, sIFNgammaR could prevent histological and clinical signs of autoimmune diabetes as efficiently as the two mAbs. Under ex vivo conditions, sIFNgammaR exhibited a more powerful modulatory effect than XMG 1.2 mAb on cytokine secretion from splenic lymphoid cells, which resulted in a significant reduction of Concanavalin A-induced IL-2 secretion and an augmented release of both unstimulated and lipopolysaccharide-induced IL-6. Moreover, although both mAbs were immunogenic and elicited formation of high titers of anti-rat IgG, sIFNgammaR did not induce antibody formation. Unexpectedly, in the cyclophosphamide-induced model, sIFNgammaR turned out to be less effective than either of the two anti-IFNgamma mAbs. Taken together, these data support the role of IFNgamma in the pathogenesis of NOD mice, but, more importantly, suggest that a nonimmunogenic approach is possible to the diminution of the effects of IFNgamma in this model.
Animals↗
Ossifying fibroma of the skull in a patient with neurofibromatosis type 1. Case report.
Ossifying fibroma is a rare, benign, primary bone tumor that occurs most commonly in the mandible; a cranial vault location is extremely rare. In this report a case of symptomatic frontoparietotemporal ossifying fibroma with intracranial growth and cerebral displacement in a 12-year-old boy with neurofibromatosis type 1 (NF1) is described. Once excised the lesion did not recur. The skeletal system is frequently affected in NF1, and bone abnormalities are present in 50% to 70% of patients with this condition. The etiology of such lesions in NF1 is still controversial. To the authors' knowledge, ossifying fibromas of calvarial bones have not been described in NF1.
Child↗
Report of a case of congenital glioblastoma multiforme: an immunohistochemical study.
We report a rare case of congenital glioblastoma multiforme in a 13-day-old male neonate born at term who died from cardiocirculatory failure. The cerebral tumor was diagnosed in vivo by magnetic resonance imaging and confirmed histologically after autopsy. The histological and immunohistochemical features of this case were similar to those reported in the adult.
Brain↗
Co-ordinate expression of alpha 5 beta 1 integrin and fibronectin in Dupuytren's disease.
The expression of alpha 5 beta 1 (alpha 5 beta 1) integrin and its extracellular ligand fibronectin was studied immunohistochemically in 23 cases of Dupuytren's disease using an immunoperoxidase method for light microscopic visualization. All cases consisted of multiple nodules showing a variable degree of cellularity and fibrosis. Depending on the histological appearance of these nodules, each case was assigned to the three following phases: proliferative, involutional and residual. Alpha 5 beta 1 integrin was detected in the highly cellular areas of both proliferative and involutional phases where fibronectin was simultaneously expressed in the extracellular matrix (ECM). Diversely alpha 5 beta 1 and fibronectin disappeared from the hypocellular areas of involutional phase, undergoing fibrotic transformation, and from the fibrotic connective tissue of residual phases. These findings indicate that the expression pattern of alpha 5 beta 1 integrin correlates with the presence in the ECM of the corresponding ligand fibronectin during the different phases of Dupuytren's disease. We suggest that alpha 5 beta 1 integrin, linking fibronectin to stromal cells of both proliferative and involutional phases, may be involved in the contractile processes occurring in Dupuytren's disease.
Dupuytren Contracture↗
Distribution of extracellular matrix glycoproteins in the human mesonephros.
We analyzed the expression and distribution of collagen types IV and VI, laminin and fibronectin during the development and regression of the mesonephros in human embryos and fetuses ranging from 6 to 12 weeks of gestation by indirect immunoperoxidase methods. Type IV collagen, laminin and fibronectin were detected along the glomerular, tubular and capsular basement membranes of developing and mature nephrons. Only type IV collagen and fibronectin were found in the mesangium. Type VI collagen formed a delicate interstitial fibrillar network and a continuous basement membrane-like structure along the mesonephric nephrons. Basement membranes (GBM) of developing and mature glomeruli showed a distinct continuous staining for this collagen. The mesangial matrix was rich in type VI collagen. Mesonephric involution started during the 8th week of gestation and coincided with a moderate expansion of mesangial matrix and progressive collapse of the capillary walls, while the tubules became thinner and shorter. Staining for all extracellular matrix glycoproteins studied showed GBM wrinkling, gradual disintegration of some capillary loops and glomerulosclerosis. The sclerotic glomeruli were strongly positive for type IV collagen and less positive for type VI collagen and fibronectin. Laminin was absent. Our results indicate that collagen types IV, VI, laminin and fibronectin may be involved in the development and regression of the human mesonephros.
Collagen↗
Expression of cytokeratins, vimentin and basement membrane components in human fetal male müllerian duct and perimüllerian mesenchyme.
The expression and distribution of cytokeratins 8, 18, 19, pan-cytokeratin, vimentin, type IV collagen, laminin and fibronectin were investigated immunohistochemically in the Wolffian and Müllerian ducts and perimüllerian mesenchyme of human male fetuses ranging from 8 to 12 weeks of gestation. The epithelial cells of both genital ducts, the coelomic epithelium and the mesenchymal perimüllerian cells coexpressed cytokeratins 18, 19, pancytokeratin and vimentin. Type IV collagen, laminin, and fibronectin were detected in the basement membranes of both genital ducts, the coelomic epithelium and in the interstitium of the perimüllerian mesenchyme. The coelomic basement membrane adjacent to the müllerian duct showed interruptions and perimüllerian cells were in contact with the coelomic epithelium. The cytoskeletal immunophenotype of perimüllerian cells and their relationship with the coelomic epithelium suggested their coelomic origin. During the 12th week of gestation, müllerian duct began to regress with its basement membrane detaching from the surrounding mesenchyme. This coincided with the disappearance of vimentin from the ductal epithelial cells, as well as type IV collagen, laminin and fibronectin from perimüllerian mesenchyme. Thus müllerian ductal basement membrane dissolved. These findings indicate that the human müllerian duct regression is associated with changes in the interactions between Müllerian ductal and perimüllerian mesenchymal cells.
Basement Membrane↗
Immunohistochemical expression of type VI collagen in superficial fibromatoses.
The expression of type VI collagen was studied immunohistochemically in 26 cases of superficial fibromatoses (palmar, plantar and penile) using an immunoperoxidase method for light microscopic visualization. The polyclonal antibody against type VI collagen used in this study was isolated from human placenta and its specifity was tested by immunoblotting assay. All cases consisted of multiple nodules showing a variable degree of cellularity and fibrosis. Depending on the predominant histological appearance of these nodules, each case was assigned to the three following phases: proliferative, involutional and residual. Morphologically normal palmar and plantar aponeuroses were included as controls. Immunohistochemical findings showed that type VI collagen was present as longitudinal thin fibers in normal palmar and plantar aponeuroses. A differential expression of this collagen was found in the different stages of superficial fibromatoses. Type VI collagen was markedly expressed as a distinct fibrillar network in the extracellular matrix (ECM) surrounding proliferating stromal cells in proliferative and involutional phases. Its expression completely disappeared from the connective tissue undergoing fibrotic transformation during involutional and residual phases. The results of the present study suggest that type VI collagen is an extracellular marker of stromal tissue proliferation and is involved in the early phases of tissue remodelling occurring in the superficial fibromatoses.
Collagen↗
Misdiagnosis of Cushing's syndrome in a patient receiving rifampicin therapy for tuberculosis.
We hereby describe a patient in whom chronic rifampicin treatment led to a misdiagnosis of Cushing's syndrome. He had long-standing insulin-dependent diabetes mellitus and active tuberculosis resistant to conventional treatment. The course was complicated by muscle weakness, lower limb atrophy, unstable glycemic control and hypokalemia. Ectopic Cushing's syndrome was suspected on the basis of high urinary free cortisol excretion (UFC) with a blunted circadian profile of serum cortisol and measurable plasma ACTH concentrations. Dynamic endocrine tests and imaging studies were compatible with occult ectopic ACTH syndrome. After substitution of rifampicin UFC excretion returned to normal within two weeks, as well as the 24-h cortisol profile and dynamic tests. The present case provides a practical example of the possibility to incorrectly suspecting Cushing's syndrome in patients treated with rifampicin, as previously envisaged by pharmacological studies.
Adrenocorticotropic Hormone↗
Placental thrombosis and fetal loss after passive transfer of mouse lupus monoclonal or human polyclonal anti-cardiolipin antibodies in pregnant naive BALB/c mice.
In the present study we evaluated the effect of passive transfer of a mouse monoclonal (CAM) or a human polyclonal anti-cardiolipin IgG on pregnancy outcome in BALB/c mice. The mice were immunized through the tail vein immediately after mating with 10 micrograms of monoclonal or polyclonal anti-cardiolipin antibodies. Two other groups of mice were given a mouse irrelevant monoclonal antibody or normal human polyclonal IgG respectively, at the same dose. In mice immunized with monoclonal or polyclonal anti-cardiolipin antibody we observed a significant increase in the number of fetal resorptions and a significant reduction of the mean weights of the embryos and the placentas. In mice immunized with CAM we also found a significant decrease in the number of healthy pups, while mice infused with human aCL antibody expressed a significant reduction in the fecundity rate. The histological examination showed widespread thrombosis and necrosis in the placentas derived from the mice immunized with the anti-cardiolipin antibodies. The model supports a possible direct pathogenetic effect of anti-phospholipid antibodies in recurrent fetal loss and points out that thrombotic events at placental level can be instrumental in the pathogenesis of the obstetric complications.
Animals↗
Effects of sodium fusidate in animal models of insulin-dependent diabetes mellitus and septic shock.
We have evaluated the effects of the novel immunosuppressant sodium fusidate (fusidin) in the non-obese diabetic (NOD) mouse and in D-galactosamine (D-Gal)-presensitized BALB/c mice challenged with the bacterial superantigen, Staphylococcus aureus enterotoxin B (SEB) or with the endotoxin, Escherichia coli lipopolysaccharide (LPS). The NOD mouse model has clinical and histoimmunological features similar to those of human insulin-dependent diabetes mellitus (IDDM). The SEB- and LPS-treated BALB/c mouse models exhibit pathogenic similarities with human septic shock conditions. In the NOD mouse, fusidin suppressed the spontaneous development of insulitis (mean inhibition 73%) and hyperglycaemia (IDDM incidence 25% versus 0%) when administered at 40 mg/kg five times weekly for 8 consecutive weeks from the fourth week of age; concurrently treated animals exhibited reduced percentages of splenic T lymphocytes. This anti-diabetogenic effect was confirmed in the accelerated model of diabetes induced in the NOD mouse with cyclophosphamide (CY) (IDDM incidence 55% versus 21-6% using dosages of fusidin from 40 to 80 mg/kg five times weekly); protection from IDDM development was achieved even when the drug (80 mg/kg/day) was first administered 7 days after CY challenge. In contrast, fusidin did not reverse hyperglycaemia when administered to CY-treated animals within 3 days of IDDM development. In the two models of septic shock, prophylactic treatment with fusidin, 80 mg/kg given three times for 2 days prior to D-Gal/SEB or D-Gal/LPS challenge, drastically reduced the lethality compared with D-Gal/buffer-treated mice. This effect may depend on the inhibitory action of fusidin on the secretion of cytokines such as interferon-gamma and tumour necrosis factor-alpha, the serum levels of which were greatly diminished in the fusidin-treated mice (mean inhibition 50-90%). These results demonstrate that fusidin may have a role in the treatment of cell-mediated autoimmune diseases and cytokine-mediated infectious diseases in humans.
Animals↗
Immunohistochemical distribution of S-100 protein and type IV collagen in human embryonic and fetal sympathetic neuroblasts.
The expression and distribution of S-100 protein and type IV collagen was studied immunohistochemically in sympathetic neuroblasts from the paravertebral region to the adrenal glands in human embryos and fetuses ranging from 7 to 12 weeks gestational age. From 7 weeks gestational age, S-100 protein was detected in round or oval cells mingling with sympathetic neuroblasts, and in spindle-shaped cells forming a continuous layer around them. The latter S-100 protein-positive cells were found in contact with the Schwann cells of nerve fibres entering the groups of sympathetic neuroblasts. Staining for type IV collagen showed that all groups of sympathetic neuroblasts were surrounded by a continuous basement membrane. By examining serial sections stained for type IV collagen and S-100 protein, a continuous basement membrane was found along the distribution pattern of the peripheral S-100 protein-positive spindle cells. The morphology of these cells, and their relationships with Schwann cells and with the basement membrane of the sympathetic neuroblasts, indicated that they were Schwann-like cells probably capable of synthesizing a continuous basement membrane separating the neuroblasts from the adjacent tissues. In contrast, the round or oval S-100 protein-positive cells, in contact with the sympathetic neuroblasts and not associated with nerve fibres, were considered as sustentacular or sustentacular precursor cells. At week 7 gestational age, the peri-adrenal sympathetic neuroblasts and their sustentacular and Schwann-like cells started to invade the adrenal glands and mingled with the adrenal cortical cells. These findings suggest the extra-adrenal origin of the sustentacular cells in embryonic and fetal adrenal glands.
Adrenal Glands↗
Parietal bone non-secreting solitary myeloma (plasmacytoma) with spread to the epidural space and scalp. Case report.
A case of solitary osteolytic lesion in the parietal bone in an otherwise asymptomatic patient is reported. Skull radiographs showed a radio-lucent lesion with well-defined margins without sclerotic reaction, CT scan demonstrated a mass that markedly enhanced extending from the epidural to the subcutaneous space of the parietal region. The patient underwent surgery and tumor was completely excised. Pathological examination showed tumor to be a plasmacytoma synthesizing kappa chains. Postoperatively the patient received radiotherapy. Four years after treatment there was no sign of local recurrence on CT can and of progression of multiple myeloma on clinical and laboratory studies. Our recommended treatment is that of a complete surgical excision followed by radiation to dose levels of 45-50 Gy. The patients should be followed carefully because of either local recurrence or possible progression to multiple myeloma. Radiotherapy and chemotherapy should started when signs of progression or other significant disease manifestations occur.
Aged↗
S-100 protein expression in a case of elastofibroma dorsi.
Elastofibroma is a rare tumorlike process that manifests as slowly growing, solid mass in the subscapular region of elderly persons. Histologically, it is characterized by the presence of fibrous connective tissue in which eosinophilic fibers and globular masses, stained by the elastic tissue stains, are interspersed. We report the immunohistochemical study of the cellular component in a case of subscapular elastofibroma in a 41-year-old man. An unexpected immunoreactivity for S-100 protein was detected in most fibroblast-like cells. S-100 protein expression may be related to a chondroid metaplasia of fibroblast-like cells in response to the continuous traumatic process occuring during the friction between the scapula and the underlying chest wall.
Adult↗
Protection from experimental autoimmune diabetes in the non-obese diabetic mouse with soluble interleukin-1 receptor.
We have evaluated the effects of a treatment with soluble interleukin-1 receptor (sIL-1R) in the accelerated model of autoimmune diabetes induced by cyclophosphamide (CY) in the non-obese diabetic (NOD) mouse. Prior to the CY challenge (350 mgkg body weight), female euglycemic NOD mice were randomly divided into three groups (A-C). Groups B and C were treated daily from 1 day before to 13 days after the CY challenge with sIL-1R at doses of 0.2 and 2 mg/kg body weight. Group A was treated with PBS. By 2 weeks after CY administration, an acute form of autoimmune diabetes with glycosuria, hyperglycemia and severe insulitis occurred in the majority (13/20, 65%) of the control mice (group A). In contrast, repeated injections with sIL-1R protected NOD mice from insulin-dependent diabetes mellitus (IDDM) development in a dose-dependent fashion; the incidence of IDDM was 53.3% (8/15) in the mice treated with 0.2 mg/kg and only 6.7% (1/15) in those treated with 2 mg/kg. However, none of the doses of the sIL-1R reduced the extent of insulitis in NOD mice. Importantly, the anti-diabetogenic property of sIL-1R may not involve major T cell function impairment; accordingly, in parallel experiments, splenic lymphoid cells from NOD mice not challenged with CY, but treated with 2 mg/kg sIL-1R for 5 consecutive days showed a normal distribution of mononuclear cell subsets and maintained their capacity to secrete interferon-gamma and IL-2 and to proliferate in response to polyclonal mitogenic stimulation with concanavalin A.
Animals↗
Expression and distribution of type VI collagen in gynecomastia.
We investigated the distribution of type VI collagen in 36 cases of routinely fixed and paraffin-embedded gynecomastia using an immunoperoxidase method for light microscopic visualization. Four samples of normal male mammary gland tissue were also included as controls. A protease predigestion was essential for the visualization of this extracellular matrix (ECM) glycoprotein. In normal male breast, no immunoreaction for type VI collagen was detected in the stroma surrounding the ducts. Gynecomastia was classified into three histological types: florid (type I), fibrous (type II), and intermediate (type III). Type VI collagen was differentially expressed in the periductal stroma of all types. This collagen was markedly expressed at the early disease stage (type I) when the periductal stroma is highly cellular and vascular. Its expression decreased when periductal stroma undergoing fibrotic transformation (type III) and completely disappeared from the dense periductal stroma of fibrous stage (type II). These findings suggest that type VI collagen is involved in the ECM remodelling occurring in gynecomastia.
Adult↗
The effects of thymopentin on the development of SLE-like syndrome in the MRL/lpr-lpr mouse.
Thymopentin (TP-5) is a synthetic pentapeptide that corresponds to the active 32-36 amino acid sequence of the thymic hormone thymopoietin, of which it retains all the immunomodulatory properties. In this study, we have evaluated the effects of long term prophylactic treatment with TP-5 on the clinical, immunological and histological parameters of the SLE-like syndrome that spontaneously occurs in MRL/lpr-lpr (MRL-lpr) mice. TP-5, administered (s.c.) to these mice at the doses of 1, 10 and 100 mg/kg, was given daily, five times a week, from the 9th to the 26th weeks of life. The prophylactic treatment with TP-5 prolonged in a clear dose-dependent fashion the lifespan of MRL-lpr mice as compared with PBS-treated control mice, and the effect reached statistical significance at the doses of 10 and 100 mg/kg. In parallel ex vivo studies, this clinical effect was associated with multiple profound modifications of the immune system including: (i) the reduction of the spontaneous and Con A-induced release of interleukin-4 (IL-4); (ii) the increased secretion of interferon-gamma (IFN-gamma) and IL-6 upon polyclonal mitogenic stimulation, and (iii) the amelioration of the defective Con A-induced lymphoproliferative response. In contrast, although the drug diminished the severity of proteinuria in MRL-lpr mice, it neither reduced histological signs of lupus nephritis nor diminished the serum titres of anti-native DNA and anti-histone autoantibodies. These results indicate that TP-5 displayed powerful immunodulatory activities in a well known model of human SLE.
Amino Acid Sequence↗
Endocrine evaluation of incidentally discovered adrenal masses (incidentalomas)
Since 1989, 45 patients [pts; 26 females and 19 males, aged 19-79 yr (median, 58)] bearing incidentally discovered adrenal masses were studied. The aim of the study was to verify the prevalence of hormone activity in clinically silent adrenal masses. Endocrine work-up included determination of urinary catecholamines and their metabolites, measurement of PRA and aldosterone levels in clino- and orthostatic posture, and basal and dynamic [dexamethasone (dex) suppression and ovine CRH stimulation] evaluation of hypothalamic-pituitary-adrenal axis. The most frequent finding was the reduction of dehydroepiandrosterone sulfate (DHEA-S) levels below the third percentile of controls in 19 (42%) pts. DHEA-S levels were significantly lower in pts than in controls [68 (range, 5-1000) vs. 208 (34-326) micrograms/dL; 1.8 (0.1-27.1) vs. 5.6 (0.9-8.8) mumol/L; P < 0.001]. Three pts (7%) had high 24-h mean serum cortisol levels, and 6 (14%) had blunted day-night amplitude of cortisol rhythm. Defective dex suppressibility was found in 15% of pts vs. 8% of controls (P < 0.05). ACTH and cortisol responses to ovine CRH did not significantly differ between pts and controls, although blunted ACTH responses were found in 22% of the cases. The above-mentioned endocrine alterations could be accounted for by autonomous cortisol secretion by the adrenal nodule at a rate not sufficient to give clinical expression, but able to inhibit to some extent the hypothalamic-pituitary-adrenal axis. These results indicate that silent cortisol hypersecretion is frequently observed in pts with adrenal incidentaloma even if progression to overt Cushing's syndrome seems unlikely. Indeed, the size of the mass and the hormone pattern remained substantially unchanged in 9 pts followed up for 12 months. From merely a cost/benefit ratio, the evaluation of DHEA-S levels and dex suppression has sufficient sensitivity to identify the occurrence of silent hypercortisolism.
Adenoma↗