Descripción: 1. 1. This paper confirms the increase in sensitivity obtained for erythrocyte UIS measurement by pre-incubation of the red cells in a 0.2% Triton-X 100 solution containing 1 mmol/1 ZnSO4 and dithiothreitol as described by Piepkorn et al. (1978). 2. 2. To achieve optimal precision in this assay a substrate concentration of delta aminolaevulinic acid (ALA) of 1000nmol/ml is required. Interpretation of the results obtained by this method is discussed and its use in the detection of both latent and acute intermittent porphyria is demonstrated. Comparative studies were carried out by using the Batlle et al. (1978) method and a modification employing ALA as substrate. © 1980.

Descripción: 1. 1. A family investigation was performed in eleven cases of Porphyria Cutanea Tarda (PCT). 2. 2. By using clinical findings, quantitative measurements and thin layer chromatography (TLC) of urinary porphyrins, overt and subclinical PCT patients have been identified. 3. 3. In the overt type, skin manifestations are present, excretion of urinary porphyrins is increased and the TLC pattern of porphyrins in urine is characteristic for PCT. 4. 4. In the subclinical type, patients have no clinical symptoms, excretion of porphyrins in urine might be normal or enhanced and TLC pattern of urinary porphyrins is typical for PCT. 5. 5. By applying these criteria a clear distinction between hereditary and non-hereditary PCT was possible. 6. 6. Among the 11 families studied, in four families where PCT was hereditary, four members have the overt type and ten relatives the subclinical type. 7. 7. In seven families where PCT was non-hereditary only the propositus has overt PCT and not a single relative showed any clinical or biochemical abnormality. © 1980.

Descripción: The major natural reservoir of Junin virus, the aetiological agent of Argentine haemorrhagic fever, is the cricetid Calomys musculinus. Neonatal animals experimentally infected with Junin virus (XJCl3 strain) developed typical disease and approximately 80% of them died. Most survivors become persistently infected. Antigenically variant viruses were isolated from the blood and brain of infected cricetids during the acute and chronic stages of the disease. These variants could be distinguished from the parental strain by kinetic neutralization assays using polyclonal antibodies. Some biological properties were shared with the parental virus strain including its virulence for newborn C. musculinus. These variant viruses may play a major role in chronic disease since we have shown that a viral isolate from an infected brain was poorly neutralized by serum obtained from the same animal.

Descripción: 1. 1. Studies on porphyrin biosynthesis from exogenus ALA, at various time intervals as well as direct enzyme measurements (aminolevulimc acid dehydratase (ALA-D); porphobilinogenase (PBG ase) and deaminase were carried out in hemolysates of human erythrocytes from healthy controls and patients with lead poisoning (Pb), acute intermittent porphyria (AIP), porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP), variegate porphyria (VP) and congenital erythropoietic porphyria (CEP). 2. 2. Inhibited ALA-D in Pb, reduced PBGase and deaminase in AIP, lower uroporphyrinogen decarboxylase in PCT, and diminished isomerase in CEP, were confirmed. In addition, ALA-D was found, reduced in AIP, unchanged in PCT and increased in EPP, VP and CEP. PBGase and deaminase were, on the other hand, increased in Pb and PCT, unchanged in VP and diminished in EPP and CEP. 3. 3. Total porphyrin biosynthesis is a function of time; compared to normals, is lower in CEP and AIP, but higher in PCT. 4. 4. The porphyrin profile changes along the time; uroporphyrin increases at longer intervals while that of coproporphyrin concomitantly diminished. A significance enhancement of octacarboxylic porphyrins was observed during the entire duration of the incubation in PCT hemolysates. In CEP the main porphyrin was always uroporphyrin I. 5. 5. Studies on both total porphyrins formed and their distribution were performed in hemolysates from cases of non-hereditary and hereditary PCT and AIP, before and after therapy. © 1980.

Descripción: Glucocorticoids are potent regulators of the innate immune response, and alteration in this inhibitory feedback has detrimental consequences for the neural tissue. This study profiled and investigated functionally candidate genes mediating this switch between cell survival and death during an acute inflammatory reaction subsequent to the absence of glucocorticoid signaling. Oligonucleotide microarray analysis revealed that following lipopolysaccharide (LPS) intracerebral administration at striatum level, more modulated genes presented transcription impairment than exacerbation upon glucocorticoid receptor blockage. Among impaired genes we identified ceruloplasmin (Cp), which plays a key role in iron metabolism and is implicated in a neurodegenative disease. Microglial and endothelial induction of Cp is a natural neuroprotective mechanism during inflammation, because Cp-deficient mice exhibited increased iron accumulation and demyelination when exposed to LPS and neurovascular reactivity to pneumococcal meningitis. This study has identified genes that can play a critical role in programming the innate immune response, helping to clarify the mechanisms leading to protection or damage during inflammatory conditions in the CNS. © 2007 Glezer et al.

Descripción: The role of oxidative stress in prostate cancer has been increasingly recognised. Acute and chronic inflammations generate reactive oxygen species that result in damage to cellular structures. Haeme oxygenase-1 (HO-1) has cytoprotective effects against oxidative damage. We hypothesise that modulation of HO-1 expression may be involved in the process of prostate carcinogenesis and prostate cancer progression. We thus studied HO-1 expression and localisation in 85 samples of organ-confined primary prostate cancer obtained via radical prostatectomy (Gleason grades 4-9) and in 39 specimens of benign prostatic hyperplasia (BPH). We assessed HO-1 expression by immunohistochemical staining. No significant difference was observed in the cytoplasmic positive reactivity among tumours (84%), non-neoplastic surrounding parenchyma (89%), or BPH samples (87%) (P=0.53). Haeme oxygenase-1 immunostaining was detected in the nuclei of prostate cancer cells in 55 of 85 (65%) patients but less often in non-neoplastic surrounding parenchyma (30 of 85, 35%) or in BPH (9 of 39, 23%) (P<0.0001). Immunocytochemical and western blot analysis showed HO-1 only in the cytoplasmic compartment of PC3 and LNCaP prostate cancer cell lines. Treatment with hemin, a well-known specific inducer of HO-1, led to clear nuclear localisation of HO-1 in both cell lines and highly induced HO-1 expression in both cellular compartments. These findings have demonstrated, for the first time, that HO-1 expression and nuclear localisation can define a new subgroup of prostate cancer primary tumours and that the modulation of HO-1 expression and its nuclear translocation could represent new avenues for therapy. © 2007 Cancer Research UK.