Search PubMed⌕ Search

Biomedical subjects

E Rossi

Publications and source records attributed to E Rossi.

At least 505 records · Page 28Linked to original sources
PubMedDate not supplied

Lead and the terminal mitochondrial enzymes of haem biosynthesis.

Lead exposure causes increases in urinary coproporphyrin excretion and the accumulation of zinc protoporphyrin in red cells. In the conventional view of the effect of lead on haem biosynthesis, the accumulation of these metabolites results from lead inhibition of two of the mitochondrial enzymes of haem biosynthesis, coproporphyrinogen oxidase (EC 1.3.3.3) and ferrochelatase (EC 4.99.1.1). This review critically assesses the evidence for the inhibition of these enzymes. We consider this evidence to be inconclusive and alternative explanations for the increased concentrations of coproporphyrin and zinc protoporphyrin are proposed.

Animals↗
PubMedDate not supplied

Autoantibody pattern in non-A, non-B hepatitis.

Acute and convalescent sera from 44 patients with non-A, non-B hepatitis were tested for organ and non-organ specific autoantibodies by indirect immunofluorescence. In the acute-phase sera, 36.4% of the patients were positive for smooth muscle antibodies. Brush border antibodies and anti-reticulin antibodies were detected in 13.6% of the patients. Only two patients (4.5%) were positive for anti-nuclear antibodies. The autoantibody pattern did not relate to the different epidemiology, sex, a previous hepatitis B virus infection or to the biochemical liver function tests. The autoantibody pattern did not differ statistically in patients who recovered (23 cases) and in patients who progressed to chronic liver disease (21 cases), even if a higher frequency of smooth muscle antibodies was detected in the latter group. Convalescent sera screening showed that the clinical course of the disease did not relate to the behaviour of smooth muscle antibodies, brush border antibodies and anti-reticulin antibodies. However, an increase (28.6%) in anti-nuclear antibodies in patients who progressed to chronic liver disease was observed. The clinical significance of the presence of serological markers of autoimmunity in patients with chronic sequelae following acute non-A, non-B hepatitis is discussed.

Acute Disease↗
PubMedDate not supplied

Congenital erythropoietic porphyria: skeletal manifestations and effect of pamidronate treatment.

Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis. Skeletal abnormalities have been described in patients with this disease. We report a 25-year-old woman with osteodystrophy from CEP. On examination, mild hepatosplenomegaly, multiple hyperpigmented scars, hypertrichosis, erythrodontia and red coloration of urine were found. Biochemical studies showed increased serum levels of alkaline phosphatase, fasting and total 24-h urinary calcium excretion. Serum 250H vitamin-D concentration was low due to avoidance of sun exposure. Skeletal radiographs disclosed marked vertical and horizontal trabecular pattern and biconcavity of most of the dorsal and lumbar vertebral bodies. Several round sclerotic lesions (1-3 cm in diameter) were seen in the skull, pelvis and one lumbar vertebrae. The sclerotic lesions were augmented in size and number compared to X-rays obtained 8 years before. Bone mineral density (evaluated by DEXA) was markedly reduced at the spine and moderately diminished at the proximal femur and total skeleton. Treatment for 11 months with pamidronate (and the addition of hydrochlorotiazide for the last 6 months) reduced to normal values the serum levels of alkaline phosphatase and fasting urinary calcium. The 24-h urinary excretion of calcium and hydroxyproline were also decreased. The BMD increased in all the skeletal areas with presumably hyperactive bone marrow: spine, head, ribs and pelvis (and total skeleton), but did not change at the extremities and diminished at the femoral neck. Patients with CEP may present osteodystrophy characterized by sclerotic lesions and osteopenia, most likely due to accelerated bone turnover in areas of active bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Variegate porphyria in Western Australian Aboriginal patients.

BACKGROUND: Survivors of shipwrecks along the Western Australian coast may have introduced a mutation for variegate porphyria into the Aboriginal population prior to first settlement. AIMS: To assess the mutations responsible for variegate porphyria in Western Australian Aboriginal patients, particularly the R59W mutation, which is the most common cause of variegate porphyria in South Africa. METHODS: New cases of porphyria were diagnosed by biochemical separation of porphyrin subtypes. Single-stranded conformation polymorphism analysis and DNA sequencing of the protoporphyrinogen oxidase gene was performed on Aboriginal patients to define possible causative mutation sites. RESULTS: Of the 296 new cases of porphyria diagnosed in Western Australia from 1978 to 1998, six had biochemically proven variegate porphyria. Three of those cases occurred in Aboriginal patients. Evidence for a possible fourth Aboriginal case of variegate porphyria is described. The R59W founder mutation responsible for over 90% of variegate porphyria in South Africa was excluded. Two new mutations that predicted amino acid substitutions with significant effects on enzyme function were detected in conserved regions of the protoporphyrinogen oxidase gene in one Aboriginal variegate porphyria patient and the possible fourth case. CONCLUSION: Results suggest that the mutations causing variegate porphyria in the Western Australian Aboriginal population occur sporadically and were not inherited from shipwrecked sailors.

Adult↗
PubMedDate not supplied

Case report: hypoparathyroidism and iron storage disease. Treatment with 25-hydroxy-vitamin D3.

A patient in whom hypoparathyroidism developed as a complication of posttransfusional iron storage disease is described. The hypoparathyroidism occurred after more than 15 years of receiving blood transfusions at frequent intervals. In this patient with thalassemia major the serum PTH levels were undetectable. 25-hydroxy-vitamin D3 corrected the hypocalcemia that was resistant to vitamin D2, probably due to the associated liver dysfunction. Other cases reported in the literature are reviewed. It is suggested that hypoparathyroidism occurs more frequently than usually suspected in patients with iron storage disease.

Adult↗
PubMedDate not supplied

Adenosinergic modulation of homocysteine-induced seizures in mice.

Homocysteine thiolactone (HTL) elicits seizures in mice at a dose of 850 mg/kg (95-100% of animals) with an average latency time of 19.5 min. These seizures are reversed by both 5' N-ethylcarboximide adenosine (NECA) and flunitrazepam, with respective ED50 doses of 0.025 and 0.20 mg/kg. NECA was approximately four-fold more potent as an inhibitor of HTL-induced seizures than of seizures induced by pentylenetetrazol (PTZ, 75 mg/kg). Flunitrazepam was equipotent in both seizure paradigms. The purine precursor 5-amino-4-imidazole carboxamide riboside, (AICAr), although virtually ineffective against PTZ-induced seizures at doses greater than 1 g/kg, was able to inhibit HTL-induced seizures with an ED50 of approximately 350 mg/kg. The anticonvulsant effect of AICAr was dose and time dependent. The anticonvulsant potency of AICAr was increased by simultaneous administration of the adenosine uptake blocker Mioflazine, whereas the central nervous system (CNS)-impermeable adenosine uptake blocker dipyridamole had no effect. The ability of AICAr to permeate the blood-brain barrier (BBB) is limited (less than 1%) and may explain its low potency as an anticonvulsant. AICAr also has very low potency at brain adenosine A1 and A2 receptors as well as adenosine uptake sites (IC50 greater than 10(-3) M), suggesting that its anticonvulsant properties are not mediated by direct action at these sites. The results indicate that AICAr does have frank anticonvulsant effects and further suggest that HTL-induced seizures may represent a useful paradigm for evaluation of adenosinergic agents. AICAr or more potent derivatives thereof may represent a new class of anticonvulsants with the ability to target seizure foci selectively.

Adenosine↗
PubMedDate not supplied

High-level detection of gene amplification and chromosome aneuploidy in extracted nuclei from paraffin-embedded tissue of human cancer using FISH: a new approach for retrospective studies.

A novel application of fluorescence in situ hybridization (FISH) to isolated nuclei is described. The method detects gene amplification and chromosome aneuploidy in extracted nuclei from paraffin-embedded tissue of human cancer with greater sensitivity and specificity than existing FISH methods. In this study, the method is applied to signal detection of the HER-2/neu (c-erbB-2) gene, whose amplification is one of the most common genetic alterations associated with human breast cancer. Nuclei were extracted and isolated from formalin fixed, paraffin embedded tissue of 43 different carcinomas (breast, ovary, endometrium, gastrointestinal stromal tumor and malignant mesothelioma). FISH was performed both on sections and extracted nuclei of each tissue using chromosome enumeration probes (CEP) for the centromeric regions of chromosomes 8 and 17, and a locus specific identifier (LSI) for the HER-2/neu oncogene. Differences between ploidy calculated in sections and extracted nuclei were seen in 3 breast carcinomas and 1 gastrointestinal stromal tumor (GIST). Furthermore, 1 breast cancer, previously considered to be borderline for HER-2/neu gene amplification turned out to be clearly amplified. Nuclei extraction and isolation bypass all the problems related to signal interpretation in tissue sections, and the adoption of this new technique, which improves the signal quality in several neoplastic samples, is suggested.

Aneuploidy↗