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Biomedical subjects

G Magro

Publications and source records attributed to G Magro.

At least 55 records · Page 3Linked to original sources
PubMed1999

Unusual form of recurrent giant cell granuloma of the mandible and lower extremities in a patient with neurofibromatosis type 1.

We report on a girl with familial neurofibromatosis type 1 (Nf1) who at age 11 had multiple osteolytic lesions of the right mandible and the distal femoral and proximal tibial metaphyses bilaterally. No other skeletal component was affected, and no abnormalities were present on skeletal radiographs of her parents. Histologic examination of the mandibular and right femoral lesions revealed a "multinucleated giant cell process." Results of repeated routine laboratory and bone metabolic studies were within normal limits. The lack of reliable histologic criteria and the diagnostic problems in distinguishing among central giant cell granulomata, giant cell tumors of the jaw, cherubism, brown tumors resulting from (occult) hyperparathyroidism, Jaffe-Campanacci syndrome, McCune-Albright syndrome, Noonan-like/multiple giant cell lesion syndrome, and multiple nonossifying fibromas of bone are discussed.

Bone Diseases, Developmental↗
PubMed1999

Regulation of BAX and BCL-2 expression in breast cancer cells by chemotherapy.

Optimizing chemotherapeutic drug delivery strategies relies, in part, on identification of the most clinically effective sequence, dose, and duration of drug exposure. The combination of dose intensive etoposide (VP-16) followed by cyclophosphamide has clinical efficacy in the treatment of advanced breast cancer. However, molecular mechanisms that underlie the effectiveness of this combination of chemotherapeutic agents have not been investigated. In this study we investigated regulation of BAX and BCL-2 expression by VP-16 and cyclophosphamide as a potential mechanism for the induction of breast cancer cell death induced by this regimen. There was a dose and time dependent increase in BAX expression in the breast cancer cell lines MCF-7, MDA-MB-435S, and MDA-MB-A231 following in vitro treatment with 50-100 microM VP-16. Elevation of BAX protein expression in the presence of VP-16 alone did not correlate with reduced viability or induction of apoptosis in MCF-7, MDA-MB-435S, or MDA-MB-A231. VP-16 did effectively block the breast cancer cell lines evaluated (MCF-7 and MDA-MB-435S) at G2/M phase of the cell cycle, confirming activity of the drug in vitro. MCF-7 and MDA-MB-435S cells that were pre-treated with VP-16 and subsequently exposed to 1.0-12.0 microg/ml 4-hydroperoxycyclophosphamide (4HC), an active metabolite of cyclophosphamide, had markedly reduced viability when compared to matched controls treated with either VP-16 or 4HC individually. Consistent with this loss of viability, exposure of all three cell lines to the combination of VP-16 and 4HC resulted in higher BAX protein levels than those observed following treatment with either single agent. This combination of chemotherapeutic agents also resulted in reduced BCL-2 expression. These observations suggest that combination chemotherapy may derive its efficacy, in part, through coordinated regulation of specific gene products associated with apoptosis. Characterization of molecular events that underlie susceptibility of specific tumor cells to combination chemotherapeutic regimens may lead to additional improvements in treatment strategies for this disease.

Adenocarcinoma↗
PubMed1999

Endogenous interleukin-12 only plays a key pathogenetic role in non-obese diabetic mouse diabetes during the very early stages of the disease.

A rat monoclonal antibody (mAb) that neutralizes mouse interleukin-12 (IL-12) was administered to female non-obese diabetic (NOD) mice of different ages to dismantle the role of endogenous IL-12 in murine autoimmune diabetogenesis. This mAb was effective in preventing clinical, but not histological signs of spontaneous diabetes when treatment was started early in life at the age of 4 weeks and consecutively continued for 10 weeks. Delaying commencement of anti-IL-12 mAb prophylaxis until the age of 18 weeks, when NOD mice suffer from advanced insulitis, was ineffective. Anti-IL-12 mAb did not influence the course of the accelerated model of diabetes induced by cyclophosphamide. These data prove that the pathogenetic role of endogenous IL-12 in NOD mouse diabetes is restricted to the very early diabetogenic events presumably occurring prior to insulitis development.

Animals↗
PubMed1999

Fatal biphasic brainstem and spinal leptomeningitis with Cryptococcus neoformans in a non-immunocompromised child.

Cryptococcal meningitis is one of the most common life-threatening, invasive fungal infections of the central nervous system in patients with defective T-lymphocyte function. It is, however, unusual in children. We report on a non-immunocompromised 10-y-old boy without evidence of immunological abnormality who developed headache, vomiting, disturbances of consciousness and areflexia. Magnetic resonance imaging of the brain and the spinal cord revealed enlargement of the ventricles and high signal lesions in the leptomeninges at the level of the cerebral peduncles and the cervical and thoracic cord. Cerebrospinal fluid analysis was positive for Cryptococcus neoformans. He was treated with amphotericin B and was symptom-free within 1 wk. Despite an extended course of therapy his symptoms suddenly relapsed and he succumbed to the medical complications of cardiac and respiratory failure. Central nervous system appearances at postmortem were those of cryptococcal leptomeningitis.

Arachnoid↗
PubMed1999

Cortical benign fibromatous tumor (fibroma) of the kidney.

Benign fibromatous tumor (BFT), also named 'fibroma', is a distinctive clinico-pathologic entity occurring in epididymis, spermatic cord, paratesticular structures, testis, renal peripelvis and rarely in renal parenchyma. We report the first case of a BFT (fibroma) located in the cortex of the kidney, and a critical review on the topic is provided. Tumor was found incidentally at autopsy as a small cortical nodule. With the increasing use of radiological imaging of the abdomen, it is likely that an increased number of incidental and asymptomatic benign renal tumors will be diagnosed. We underline that BFT (fibroma) should be considered in the preoperative differential diagnosis of renal cortical nodules.

Actins↗
PubMed1999

Failure of exogenously administered interferon-gamma or blockage of endogenous interleukin-4 with specific inhibitors to augment the incidence of autoimmune diabetes in male NOD mice.

Interferon (IFN)-gamma and interleukin (IL)-4 are prototypic type 1 and type 2 cytokines which are known to play pathogenetic and protective roles, respectively, in NOD mouse IDDM. The capacity of male NOD mice to produce more IL-4 and less IFN-gamma within the insulitic lesions than females has been suggested to contribute to their lower incidence of diabetes. In this study we have tested the effects of prolonged prophylactic treatment of male NOD mice with rat IFN-gamma, mouse IFN-gamma, anti-IL-4 monoclonal antibody (mAb) and recombinant murine soluble IL-4 receptor (smIL-4R) on the diabetogenic events leading to insulitis and diabetes. None of these treatments influenced spontaneous and/or cyclophosphamide-induced autoimmune diabetogenesis in male NOD mice. Control mice exhibited comparable histological signs of insulitis and incidence of diabetes to those treated with either mouse/rat IFN-gamma or specific IL-4 inhibitors. On the contrary, both clinical and histological signs of diabetes were suppressed by prophylactic treatment with anti-IFN-gamma mAb. These findings indicate that the autoimmune diathesis of male NOD mice towards IDDM cannot be augmented by manipulation of endogenous IFN-gamma or IL-4.

Animals↗
PubMed1998

Cloning and expression of the programmed cell death regulator Bad in the rat brain.

The Bcl-2 family of proteins consists of both antagonists (e.g. Bcl-2) and agonists (e.g. Bax) that regulate apoptosis and compete through dimerization. In the present study we cloned the cDNA encoding the rat brain BAD, a distant member of the Bcl-2 family that was shown to promote cell death. The cloned cDNA encoded a protein of 205 amino acids, containing three putative Bcl-2 homology domains (BH1, BH2 and BH3) and no C-terminal signal-anchor sequence. The predicted amino acid sequence was identical to the Bad-cDNA recently cloned from the rat ovary with the exception of a stretch of six amino acids, thus indicating the existence of two Bad alternative splice variants or a sequence artifact in the rat ovary Bad-cDNA. Immunohistochemical analysis in the rat brain revealed the exclusive expression of Bad in the epithelial cells of the choroid plexus, a result which is consistent with a very specialized function of Bad in the brain.

Amino Acid Sequence↗
PubMed1998

Gastric carcinoma with ovarian metastases in an adolescent.

Gastric carcinoma represents only 0.05% of malignant paediatric gastrointestinal tumours. This condition is associated with a poor prognosis because its rarity and non-specificity of the symptoms usually delay its diagnosis. The authors present a 16-year-old girl with a poorly differentiated gastric carcinoma (signet-ring-cell type) with bilateral ovarian metastases who died of peritoneal carcinomatosis despite extensive surgery and chemotherapy. The epidemiological, clinical, and pathological features of gastric carcinoma in childhood are discussed.

Adolescent↗
PubMed1998

Multilocular cystic epithelioid leiomyoma of the uterus with focal lymphangioma-like pattern: report of a case with immunohistochemical study.

We report a rare case of epithelioid leiomyoma of the uterus presenting as a multilocular cystic mass containing clear fluid. The histologic basis of cysts was the diffuse intratumoral cystic degeneration. Histologically, the presence of numerous cystic cavities of variable size raised the possibility that vascular abnormalities, such as hemangioma, lymphangioma, and diffuse cavernous angiomatosis, could be associated with epithelioid leiomyoma. An immunohistochemical study using endothelial cell and basement membrane markers, was helpful in excluding the vascular nature of the cystic cavities and revealed an unexpected focal lymphangioma-like pattern as a peculiar component of tumor.

Adult↗
PubMed1998

Correlated expression of BCL-2 protein, estrogen receptor, cathepsin D and low growth fraction (PCNA) in intracystic papillary breast carcinoma.

The expression of BCL-2 protein was evaluated immunohistochemically in 23 intracystic papillary carcinomas (IPCs) of the breast. Twenty-two patients were female and one male, aged 49-90 years (median 72). Twenty-one cases had a benign behaviour, while two cases developed local recurrence. Of the 23 tumours, 19 (82%) were immunoreactive for BCL-2, the majority of positive carcinomas showing intense cytoplasmic staining of more than 50% neoplastic cells. The intensity of BCL-2 expression was significantly correlated with prognostic markers such as estrogen receptor (ER) positivity (p = 0.001), cathepsin D (CD) reactivity in the neoplastic cells (p = 0.001) and low growth fraction, evaluated by proliferating cell nuclear antigen (PCNA) immunostaining (p = 0.008). An inverse relationship was also found between BCL-2 and p53 protein (p = 0.001). Three cases of high grade (G3) IPC expressed p53, high PCNA index, and CD (the latter only in the stromal cells), but no immunostaining for BCL-2 and ER. Thus, absence of BCL-2 expression in high grade IPC was associated with ER-negative, rapidly proliferating and p53-positive immunophenotype. All high grade tumours showed invasion of the cystic wall. Local recurrence developed in one of these. The authors conclude that BCL-2 immunoreactivity in IPC is related with tumour grade and with a range of molecular markers of favourable prognosis such as ER positive status, CD expression in the neoplastic cells, and low PCNA index. These findings are consistent with the indolent clinical course and the very favourable prognosis of IPC of the breast.

Aged↗
PubMed1998

Muscular hamartoma of the breast. Case report and review of the literature.

Muscular hamartoma (MH) is a rare tumor-like lesion of the breast, and only 22 cases have been reported in the literature. We report an additional case of MH of the breast, giving a new immunocytochemistry-based insight into the histogenesis of the smooth muscle component. The expression of CD34 antigen in smooth muscle cells suggested that MH originates from stromal cells via leiomyomatous metaplastic changes. This hypothesis was supported by the evidence that stromal cells in the normal parenchyma nearby the hamartoma were positive for CD34 antigen and, focally, also positive for smooth muscle markers (alpha-smooth muscle actin and desmin). A complete list of differential diagnoses and a review of the literature on the topic are provided. Although the use of the term "muscular hamartoma" could be considered inappropriate because of the absence of smooth muscle tissue in the normal breast, the authors underline that this designation can be easily accepted if the histogenesis of the heterologous component is regarded as a result of a stromal cell metaplastic change.

Breast Neoplasms↗
PubMed1998

Benign fibromatous tumor (fibroma) of the kidney: a case report.

Benign fibromatous tumor (fibroma) of the urogenital tract is a distinctive pathologic entity occurring in the testis, paratesticular structures and renal peripelvis. We report a well-circumscribed tumor replacing the cortex and the medulla of more than half of the upper kidney, radiographically thought to be renal cell carcinoma. Histologically, the tumor was characterized by a variable cellularity and was composed of bland spindle-shaped cells loosely dispersed in a fibromyxoid to densely fibrous stroma in which calcifications and chronic inflammation were not observed. Immunocytochemistry showed that cells were positive for vimentin and, only focally, stained positive for desmin and alpha-smooth muscle actin. Differential diagnosis included a wide spectrum of benign and malignant spindle cell tumors. The clinicopathologic features were consistent with benign fibromatous tumor (fibroma) of the kidney. To our knowledge, this is the first case of benign fibromatous tumor (fibroma) of the kidney reported in the English literature.

Aged↗
PubMed1998

Breast and pectoralis musculo-aponeurotic fibromatosis: two independent lesions occurring in the same patient. A case report.

We report the first case of primitive breast fibromatosis associated with a synchronous independent musculo-aponeurotic fibromatosis of the omolateral pectoralis major muscle in an otherwise healthy 29-year-old woman without clinical evidence of any genetic syndrome. The primary occurrence of the two lesions was supported by the absence of any macroscopic and microscopic connection. The present case suggests that a pre- or intraoperative frozen section diagnosis of breast fibromatosis should lead the surgeon and pathologist to exclude an independent fibromatosis of the underlying musculo-aponeurotic fascia.

Actins↗
PubMed1998

Benign spindle cell tumor of the breast with prominent adipocytic component.

We report a rare case of "benign spindle cell tumor of the breast with prominent adipocytic component" and present a review of the literature on the topic. The close morphologic resemblance with myofibroblastoma and spindle cell lipoma of the breast is emphasized and used as a starting point for diagnostic and histogenetic considerations. Although immunocytochemistry and electron microscopy showed features favoring a diagnosis of spindle cell lipoma, they were not conclusive. The tumor described here contributes to widen the spectrum of the benign spindle cell tumors of the breast variously named "benign spindle cell tumor," myofibroblastoma, spindle cell lipoma, and fibroma. It is important to distinguish this lesion from spindle cell metaplastic carcinoma and aggressive fibromatosis.

Adipocytes↗
PubMed1998

Type VI collagen in glomeruli of short- and long-term experimental diabetic rats.

Type VI collagen was revealed by high-resolution immunocytochemistry in renal glomeruli from short- and long-term streptozotocin-injected hyperglycaemic rats and from their age-matched normoglycaemic controls. The labellings obtained over the glomerular basement membrane and the mesangial matrix were assessed by quantitative evaluations. The labellings over the glomerular basement membrane were low and sparse in the young normoglycaemic animals but became consistent and increased in intensity with age and in both the short- and long-term diabetic animals. For the mesangial matrix, this was labelled more systematically, and its intensity increased with age and in the short-term hyperglycaemic animals. For the long-term hyperglycaemic animals, the intensities of labelling resembled those of their age-matched controls. These results indicate that type VI collagen appears to be a minor constituent of the extracellular matrix of the rat glomeruli, rather concentrated in the mesangial area in the young control animal. Concomitant with the general modifications of the extracellular matrix occurring with age and diabetes, this component increases, but apparently not with the length of the hyperglycaemic state.

Age Factors↗