Biomedical subjects

A Onetti-Muda

Publications and source records attributed to A Onetti-Muda.

7 recordsLinked to original sources

PubMed2001

Primary effusion lymphoma in HIV-infected patients with multicentric Castleman's disease.

Multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL) are two B-cell lymphoproliferative diseases associated with Kaposi's sarcoma-associated herpes virus/human herpesvirus-8 (KSHV/HHV-8). Although MCD is considered a prelymphoma state, it is not known whether a pathogenetic link exists between MCD and PEL. This paper reports the clinico-pathological features of four cases of PEL (two pericardial, one pleural, and one peritoneal) developing in the context of HIV-associated MCD. Effusions, lymph nodes, spleen, and additional tissues from three autopsies were examined for morphology/immunophenotype, search for HHV-8 DNA, and assessment of immunoglobulin heavy chain gene (IgH) configuration using polymerase chain reaction (PCR)-based techniques. MCD and PEL samples contained HHV-8 DNA. Clonal IgH rearrangements were detected only in PEL, whereas MCD tissues were polyclonal. Light-chain immunostaining confirmed B-cell clonality in PEL (two lambda, one kappa, one not tested) and polyclonality in MCD. The autopsies revealed different morphological variants of visceral KS and multi-organ atypical infiltrates exhibiting immunoblastic/plasmablastic features reminiscent of PEL morphology, with a restriction of lambda-positive cells. In two cases, using microdissection and IgH PCR analysis, multiple/discrete bands were found in the infiltrates, compatible with polyclonality/oligoclonality. The case showing an oligoclonal IgH ladder contained a rearrangement of identical junctional size to the PEL clone; however, further analysis with PEL-derived clonotypic primers and sequencing of PCR products showed no amplification and nucleotide diversity, respectively, indicating that the two B-cell populations examined were clonally unrelated. These data show that MCD and PEL may co-exist in HIV-infected patients, suggesting a relevant association between these two HHV-8-related disorders. Although a definite clonal relationship between MCD and PEL was not demonstrated, it is hypothesized that in some MCD cases, within expanded polyclonal B-cell populations secondary to HHV-8 infection, clonal expansions may occur that localize into a body cavity, i.e. PEL.

Adult↗

PubMed2001

Acute cholestatic hepatitis induced by bupropion prescribed as pharmacological support to stop smoking. A case report.

We report the first case of acute cholestatic hepatitis induced by bupropion. This antidepressant was taken by a 49-year-old female as adjuvant treatment to stop smoking. After 20 days of bupropion, the patient presented a symptomatology characterized by asthenia, nausea and scleral icterus and biochemical analyses showed a dramatic increase in direct bilirubin (up to 28 mg/dl) and transaminases (up to 68-fold normal limits). Antinuclear antibodies were positive (title = 1:80; speckled pattern). Biochemical analyses and antinuclear antibodies were normal two years earlier. The histology showed a pattern of acute hepatitis with involvement of bile ducts and with features of centrolobular cholestasis. Treatment with methylprednisolone was commenced and continued for 20 days. Liver enzymes and bilirubin returned to normal within two months of withdrawal of bupropion and remained normal during the 4-month follow-up. Antinuclear antibodies also became negative. Other causes of liver damage were excluded. Considering the clinical diagnostic scale for hepatotoxic adverse drug reaction, our patient showed a score compatible with the final diagnosis of bupropion-related cholestatic hepatitis.

Acute Disease↗

PubMed2000

The ERK-1/2 signaling pathway is involved in the stimulation of branching morphogenesis of fetal mouse submandibular glands by EGF.

We have previously reported that epidermal growth factor (EGF) stimulates branching morphogenesis of the fetal mouse submandibular gland (SMG) (M. Kashimata and E. W. Gresik, 1997, Dev. Dyn. 208, 149-161) and that the EGF receptor (EGFR) is localized principally, if not exclusively, on the epithelial components of the fetal SMG (E. W. Gresik, M. Kashimata, Y. Kadoya, R. Mathews, N. Minami, and S. Yamashina, 1997, J. Histochem. Cytochem. 45, 1651-1657). The EGFR is a receptor tyrosine kinase, and after binding of its ligand, it triggers several intracellular signaling cascades, among them the one activating the mitogen-activated protein kinases (MAPK) ERK-1/2. Here we investigated whether EGF utilizes the ERK-1/2 signaling cascade to stimulate branching morphogenesis in the fetal mouse SMG. SMG rudiments were collected as matched pairs at E14, E16, and E18 (E0 = day of vaginal plug); placed into wells of defined medium (BGJb); and exposed to EGF for 5 or 30 min or to medium alone (controls). By Western blotting we found that EGF induced the appearance of multiple bands of phosphotyrosine-containing proteins, including bands at 170 kDa and 44 kDa/42 kDa, presumably corresponding to the phosphorylated forms of EGFR and ERK-1/2, respectively. Other blots showed the specific appearance of the phosphorylated EGFR and of phospho-ERK-1/2 in response to EGF. Immunohistochemical staining for phosphotyrosine increased at the plasma membrane after EGF stimulation for 5 or 30 min. Diffuse cytoplasmic staining for MEK-1/2 (the MAPK kinase that activates ERK-1/2) increased near the cell membrane after EGF stimulation. Phospho-ERK-1/2 was localized in the nuclei of a few epithelial cells after EGF for 5 min, but in the nuclei of many cells after EGF for 30 min. PD98059, an inhibitor of phosphorylation and activation of MEK-1/2, by itself inhibited branching morphogenesis and, furthermore, decreased the stimulatory effect of EGF on branching. Western blots confirmed that this inhibitor blocked phosphorylation of ERK-1/2 in fetal SMGs exposed to EGF. These results show that components of the ERK-1/2 signaling cascade are present in epithelial cells of the fetal SMG, that they are activated by EGF, and that inhibition of this cascade perturbs branching morphogenesis. However, EGF did not cause phosphorylation of two other MAPKs, SAPK/JNK or p38MAPK, in fetal SMGs. These results imply that the ERK-1/2 signaling is responsible, at least in part, for the stimulatory effect of EGF on branching morphogenesis of the fetal mouse SMG.

Animals↗

PubMed1991

Demonstration of oestrogen and progesterone receptors in freeze-dried, paraffin-embedded sections of breast cancer.

Immunohistochemical evaluation of oestrogen and progesterone receptors is of importance in evaluating human breast tumours. Staining techniques can be performed on snap-frozen, cryostat-cut tissues or, as recently reported, on formalin-fixed, paraffin-embedded tissues. These methods are, however, limited by several drawbacks, including difficulties in retrospective studies and in storage of the material, and the relatively high frequency of false negative results for chemically fixed specimens. We therefore investigated the application of freeze-drying technology to assess the feasibility and reliability of this technique as an alternative method for diagnostic breast pathology. Morphological and immunohistochemical studies were performed on snap-frozen, freeze-dried and paraffin-embedded tissue obtained from 16 cases of benign and malignant breast neoplasms. Our results showed good preservation of tissue morphology, similar to standard formalin fixation, and excellent preservation of antigenic reactivity of nuclear receptors, comparable to that obtained with cryostat sections. We therefore suggest that freeze drying and paraffin embedding of frozen tissue blocks is equivalent or even preferable to formalin fixation for the demonstration of oestrogen and progesterone receptors, at least in the case of small tumours.

Breast Neoplasms↗

PubMed1986

Effect of advanced age on the induction by androgen or thyroid hormone of epidermal growth factor and epidermal growth factor mRNA in the submandibular glands of C57BL/6 male mice.

We have compared the responsiveness of the submandibular glands of mature (12 month old) and senescent (26-28 month old) male C57BL/6 mice to dihydrotestosterone (DHT) or triiodothyronine (T3) in terms of steady state levels of epidermal growth factor (EGF) protein and EGF mRNA. Northern blot analyses did not disclose any differences with age in the apparent sizes of EGF mRNA species. In untreated animals, submandibular glands of 26-28-month-old mice contained approximately 50% less EGF, and 75% less EGF mRNA than those of 12-month-old males. With advanced age, there was a 20% reduction in the absolute volume of the granular convoluted tubule (GCT) compartment, which is the exclusive site of EGF and EGF mRNA in the gland. In general, GCTs of old mice were composed of smaller cells with fewer secretion granules, but there was considerable cell-to-cell variation. In addition, there was greater variation in the intensity of immunocytochemical staining for EGF in senescent GCT cells, which also gave a lower and more variable in situ hybridization signal for EGF mRNA. After hormonal stimulation for 1 week with either tri-iodothyronine (T3) or dihydrotestosterone (DHT), EGF protein concentration in the glands was induced to the same level at both ages. However, EGF mRNA was 50% less abundant in old hormonally stimulated glands, compared to similarly treated young ones. Although many GCT cells in treated glands of senescent males respond to hormonal stimulation by increases in size and in content of secretion granules, there was cell-to-cell variation in responsiveness, especially after treatment with T3. These findings indicate that the decreases seen in the entire gland in EGF and EGF mRNA are caused by a wide-spread deterioration of the GCT cells themselves, which apparently can be reversed in many but not all GCT cells by stimulation with supraphysiologic doses of either T3 or DHT.

Aging↗

PubMed1986

Epidermal growth factor gene expression is regulated differently in mouse kidney and submandibular gland.

The concentration of the peptide mitogen epidermal growth factor (EGF) is hormonally and developmentally regulated in the granular convoluted tubule cells of the mouse submandibular gland. Using a labeled EGF nucleic acid probe, we have demonstrated that submandibular gland EGF mRNA concentrations increase during postnatal development of the gland and after the administration of testosterone or thyroid hormone. Recently, it was reported that EGF mRNA is present in kidney as well as a number of other mouse tissues. A comparison of EGF gene regulation in submandibular gland and kidney revealed that kidney EGF mRNA levels also increase during the postnatal period. Opposite sex differences were observed, with submandibular gland levels being about 16-fold higher in the male than in the female and kidney levels being 2- to 4-fold higher in the female than in the male. Renal EGF mRNA concentrations are less responsive to hormones than those in the submandibular gland. Renal EGF was localized immunocytochemically to the cells of distal convoluted tubules.

Adrenalectomy↗

PubMedDate not supplied

Thin glomerular basement membrane disease.

The term thin glomerular basement membrane disease (TBMD) refers to a condition characterised by thinning of the GBM at electron microscopy examination and, clinically, by isolated hematuria, frequently occurring in other family members, with no extra-renal manifestations. Progression towards chronic renal failure (CRF), although rare, has been reported and blood pressure is high in 30-35% of cases during follow-up. TBMD is generally considered different from Alport syndrome since immunohistological investigation does not show abnormalities of type IV collagen alpha chains in the GBM, as frequently observed in Alport patients; moreover, in familial cases, the disease is transmitted as autosomal dominant trait, rarely observed in Alport syndrome. Genetic studies suggest that TBMD is a heterogeneous disease, but some cases may be related to mutations of COL4A3/COL4A4 genes, thus belonging to the spectrum of type IV collagen diseases. TBMD may arise with other glomerular diseases, most frequently IgA nephropathy, and it remains to be established whether these cases are a casual occurrence or whether a thinner than normal GBM predisposes to immune complex deposition.

Anti-Glomerular Basement Membrane Disease↗