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Biomedical subjects

F Moro

Publications and source records attributed to F Moro.

At least 55 records · Page 3Linked to original sources

p53 expression in normal versus transformed mammalian cells.

To answer the question whether the level of p53 expression also reflects the status of a cell, with reference to transformation and genome stability, we have examined, by immunocytochemistry, the presence of p53 protein in a number of cell types including human diploid cells, Chinese hamster embryonal cells at different passages and gene amplified and/or transformed Chinese hamster cell lines. Primary human fibroblasts at early passage (LEO) and an established, non transformed, Chinese hamster cell line at early passage (CHEF/18) did not show any detectable p53 expression, either nuclear or cytoplasmic. All transformed human (Raji) and Chinese hamster cell lines (CHO, V79, V79/B7) showed a nuclear expression of p53, although at different intensities. Two cell lines selected from V79/B7 for their resistance to phosphonacetyl-L-aspartate or methotrexate and previously shown to bear gene amplification, showed p53 expression. In PALA L cells p53 expression was nuclear as in other positive cell lines tested, while in MTX M cells it was cytoplasmic. CHEF/18 cells at late passage in culture showed the typical behaviour of transformed cells and p53 was detected in several cells. Moreover, when transformed CHO cells were treated with compounds known to induce reverse transformation, both the disappearance of hallmarks of transformed phenotype and p53 reduction were observed. These results indicate a strong association within the same cell type between p53 expression and transformed status.

Animals↗

Early treatment of CMV infections in allogeneic bone marrow transplant recipients with foscarnet or ganciclovir.

Twenty-five patients with hematologic malignancies (n = 21) or aplastic anemia (n = 4) undergoing an allogeneic BMT from an HLA-identical sibling developed cytomegalovirus (CMV) antigenemia at a mean interval from BMT of 41 days (range 16-141 days). All patients were treated at the time of antigenemia in the absence of other signs of CMV disease with ganciclovir (n = 13) or foscarnet (n = 12) if the WBC count was < 2.5 x 10(9)/l or the patient had aplastic anemia. The two groups were comparable for age, sex and disease status. There were more patients receiving T cell-depleted grafts in the foscarnet group (58% vs 15%, p = 0.003). The first course of treatment was planned to last a minimum of 10 days: foscarnet was given at 180 mg/kg/day, and ganciclovir at 10 mg/kg/day. Patients still showing pp65-positive cells continued treatment in the absence of adverse effects such as cytopenia and/or increased creatinine levels. Maintenance treatment was given for 3-4 weeks. End-points of the study were (1) clearing of CMV antigenemia, (2) tolerance and side-effects, and (3) progression to CMV disease. Both agents were effective in clearing CMV antigenemia: 14 of 25 patients were CMV antigen-negative by day 14 of treatment and all surviving patients were negative by day +50. Renal toxicity was seen mainly in the foscarnet group but caused discontinuation of the drug only in one patient. Myelotoxicity was seen in the ganciclovir group and again could be controlled in 12 of 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

CMV prophylaxis with foscarnet in allogeneic bone marrow transplant recipients at high risk of developing CMV infections.

Eleven patients underwent bone marrow transplant (BMT) from an HLA-identical sibling following single dose total body irradiation (TBI), with in vivo and ex vivo T cell depletion (TCD). In spite of CMV prophylaxis with acyclovir and high-dose i.v. Ig, 10 of 11 patients developed CMV antigenemia, at a median interval from BMT of 34 days (range 16-72 days) and five died with CMV disease. Foscarnet was then given prophylactically in 11 additional TCD patients to test whether we could (1) prevent CMV reactivation, and (2) reduce transplant-related mortality. Foscarnet was given daily from days +10 to +15 (180 mg/kg/day), then thrice weekly (90 mg/kg/day) until day +100. Five patients developed CMV antigenemia at a median interval from BMT of 42 days (range 16-65 days); one progressed to CMV pneumonitis and died. The risk of developing CMV antigenemia within day 100 is currently 91% for the historical control group and 45% for the foscarnet group (p = 0.005). At diagnosis of CMV, the median number of CMV antigen-positive cells was 6.5 (range 1-13) vs 1 (range 1-5) in acyclovir vs foscarnet patients (p = 0.02) and the median highest number of CMV antigen-positive cells was 7 (range 3-110) vs 1 (range 1-12), respectively, (p = 0.03). The actuarial 1 year transplant-related mortality (TRM) is 49% and 13% in the two groups (p = 0.08). This study suggests that foscarnet prophylaxis starting on day +10 post-BMT may be helpful in reducing the risk of CMV disease and early mortality following TCD BMT.

Acyclovir↗

Fluorescence quenching at interfaces and the permeation of acrylamide and iodide across phospholipid bilayers.

Studies of fluorescence quenching in membrane proteins are complicated by the fact that the barrier effect of the bilayer towards the quenchers is not known with precision. Our studies show that (a) both acrylamide and iodide can permeate the membrane at comparable rates, (b) when quenchers are added externally to a vesicle suspension, the apparent Stern-Volmer quenching constants for the same fluorophores are lower in the inner than in the outer aqueous compartments, and (c) at least some non-polar fluorophores embedded in the bilayer are quenched by iodide, but not by acrylamide.

Acrylamide↗

Palmitate transport through the blood-retina and blood-brain barrier of rat visual system during aging.

The permeability-surface area product (PA) of [1-14C]palmitate at the blood-retina (BRB) and blood-brain barrier (BBB) was determined after short carotid perfusion in male Sprague-Dawley rats at 4, 14 and 28 months of age. For the retina, optic nerve and tract, lateral geniculate body, visual and parietal cortex, there was no significant difference among mean PAs in any age group. For superior colliculus, frontal cortex, striatum, hippocampus and olfactory bulb, a slight but significant increase of PA values was observed between young (4-month-old) and senescent (28-month-old) rats. Our results indicate that aging does not affect influx into retina and other structures of rat visual system of the palmitate, a metabolic substrate for which carrier-mediated transport across the BRB and BBB has not been demonstrated.

Aging↗

Gout, uric acid and purine metabolism in paediatric nephrology.

Although gout and hyperuricaemia are usually thought of as conditions of indulgent male middle age, in addition to the well-known uricosuria of the newborn, there is much of importance for the paediatric nephrologist in this field. Children and infants may present chronically with stones or acutely with renal failure from crystal nephropathy, as a result of inherited deficiencies of the purine salvage enzymes hypoxanthine-guanine phosphoribosyltransferase (HPRT) and adenine phosphoribosyltransferase (APRT) or of the catabolic enzyme xanthine dehydrogenase (XDH). Genetic purine overproduction in phosphoribosylpyrophosphate synthetase superactivity, or secondary to glycogen storage disease, can also present in infancy with renal complications. Children with APRT deficiency may be difficult to distinguish from those with HPRT deficiency because the insoluble product excreted, 2,8-dihydroxyadenine (2,8-DHA), is chemically very similar to uric acid. Moreover, because of the high uric acid clearance prior to puberty, hyperuricosuria rather than hyperuricaemia may provide the only clue to purine overproduction in childhood. Hyperuricaemic renal failure may be seen also in treated childhood leukaemia and lymphoma, and iatrogenic xanthine nephropathy is a potential complication of allopurinol therapy in these conditions. The latter is also an under-recognised complication of treatment in the Lesch-Nyhan syndrome or partial HPRT deficiency. The possibility of renal complications in these three situations is enhanced by infection, the use of uricosuric antibiotics and dehydration consequent upon fever, vomiting or diarrhoea. Disorders of urate transport in the renal tubule may also present in childhood. A kindred with X-linked hereditary nephrolithiasis, renal urate wasting and renal failure has been identified, but in general, the various rare types of net tubular wasting of urate into the urine are recessive and relatively benign, being found incidentally or presenting as colic from crystalluria. However, the opposite condition of a dominantly inherited increase in net urate reabsorption is far from benign, presenting as familial renal failure, with hyperuricaemia either preceding renal dysfunction or disproportionate to it. Paediatricians need to be aware of the lower plasma urate concentrations in children compared with adults when assessing plasma urate concentrations in childhood and infancy, so that early hyperuricosuria is not missed. This is of importance because most of the conditions mentioned above can be treated successfully using carefully controlled doses of allopurinol or means to render urate more soluble in the urine. Xanthine and 2,8-DHA are extremely insoluble at any pH. Whilst 2,8-DHA formation can also be controlled by allopurinol, alkali is contraindicated. A high fluid, low purine intake is the only possible therapy for XDH deficiency.

Adolescent↗

[Lung abscess: evolution of a complication over 45 years].

143 patients with lung abscesses were hospitalised at the Department of Surgery at University Hospital Zurich from 1946 to 1990. Analysing our patients in a retrospective study we concluded as follows: 1. Lung abscesses have nearly disappeared in our patients. 2. Lung abscesses can be cured without lethality. 3. Cancers of the lung causing abscesses were not seen any more since 1960. 4. A compromised immunological system appeared as a new pathogenetical factor since the beginning of the 1980ies.

Cause of Death↗

New polymorphic HLA-DR epitopes recognized by three monoclonal antibodies produced against DR103 transfected L cells.

Production of monoclonal antibodies directed against polymorphic epitopes of HLA class II molecules using whole human cells as immunogen has often proved ineffective, because most of the antibodies produced are directed against non-MHC human cell surface molecules. One approach to overcome this problem is the use of transfected mouse L cells expressing a single HLA class II allele as immunogen. By immunizing C3H mice with DR103-transfected L cells, we obtained 3 mAb, OHA TM901, OHA TM902, and OHA TM903, that recognize different polymorphic epitopes of the HLA-DR molecule. The molecular specificities of the 3 mAb were determined on a large panel of B-lymphoblastoid cell lines (B-LCL), peripheral blood cells and HLA class II transfectants from the XIth International Histocompatibility Workshop. Interestingly, the 3 polymorphic mAb detect new HLA-DR epitopes shared by several specificities: OHA TM901 reacts with DR1 (DR101, DR103), DR9 (DR901) and DR10 (DR1001) molecules; OHA TM902 recognizes the same molecules but also DR8 (DR801, 802, 803); OHA TM903 reacts with all DR types except DR3 (DR301, 302), DR7 (DR701, 702) and DR52. Surprisingly, OHA TM901 reacts with DR9 transfectants and B-LCL but not with DR9 peripheral blood lymphocytes. Biochemical analyses indicate that the 3 mAb immunoprecipitate HLA-DR products and react in western blots with DR alpha/beta-dimer but not with free alpha- or beta-chains. This study shows that transfected L cells are very useful tools for the production and the fine characterization of mAb recognizing polymorphic epitopes of HLA class II molecules.

Animals↗

Bone marrow harvest for marrow transplantation: effect of multiple small (2 ml) or large (20 ml) aspirates.

The aim of this study was to evaluate the yield of nucleated cells and CFU-GM and the T cell composition in bone marrow harvested by means of multiple small (2 ml) or large (20 ml) aspirations. Eleven marrow donors were studied: each donated 1000 ml of bone marrow in two aliquots of 500 ml for an HLA identical sibling transplant. In six cases the first 500 ml were harvested by means of multiple 2 ml aspirations (A) and the second 500 ml by means of 20 ml aspirations (B). In five cases the opposite was done: 20 ml aspirates first (C) and 2 ml afterwards (D). From each 500 ml aliquot a sample was taken for enumeration of nucleated cells and CD3+ lymphocytes and for CFU-GM growth. Small volume aspirations (groups A and D) yielded more nucleated cells (p = 0.02), more CFU-GM (p = 0.03) and fewer CD3+ cells (p = 0.1) when compared with large volume aspirations (groups B and C). This study shows that marrow harvesting by means of multiple small volume aspirations minimizes the dilution with peripheral blood and results in greater numbers of cells and hemopoietic progenitors.

Adult↗

Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease.

This paper reports investigations in a young woman with renal disease and six other seemingly healthy young members of a new kindred (four male:two female) with familial juvenile gouty nephropathy (McKusick 16200). The family had previously been known to have a "familial" renal disease, but came to attention through an isolated episode of gout in the propositus when renal function was already impaired. A reduced GFR was found in three of the other six subjects. Hyperuricemia associated with a grossly reduced fractional uric acid clearance (Cur/Ccr x 100) was present in the propositus and five kindred members, three of whom were children. The finding of this abnormality in two subjects with normal GFR suggests that this apparent hallmark of the disease precedes the onset of renal damage. The results confirm the dominant nature of the disorder, and highlight the need to investigate all kindred members of patients with juvenile gout and renal failure. Early recognition is important, since allopurinol therapy in doses adjusted to the reduced renal function may ameliorate the progression of the renal lesion.

Adolescent↗

Optic neuropathies: therapeutic approach.

The review deals with therapeutic aspects of optic nerve diseases. Attention is given to the lack of established guidelines for treatment of different optic neuropathies. In fact, there are no sure protocols in the literature for infective, inflammatory and vascular disorders. The authors present some new drugs and discuss the efficacy of related therapy, in particular for vascular disorders. The differentiated therapy for arteritic and non-arteritic AION is discussed. Treatment of vascular occlusion in the acute phase, in the post-occlusive state and prophylaxis is reported. The usefulness of anticoagulants is examined. In the conclusion, the authors stress the necessity to carry out properly controlled multicenter trials to obtain valid knowledge that allows rational and effective therapy protocols.

Arteritis↗

Ischemic optic neuropathies.

Primary or secondary impairment of blood supply to the optic nerve results in a spectrum of ischemic optic neuropathies with multiple etiopathogenesis. Among these the clinical features of traumatic and radiation optic neuropathy are outlined. Diagnostic criteria, associated conditions, risk factors and functional prognosis of anterior ischemic optic neuropathy are reviewed and discussed in the light of the contribution of recent literature.

Humans↗

Retinoblastoma. Combined treatment of 21 cases. Critical review of the results.

The authors report their experience in the treatment of 21 children affected by retinoblastoma. There were 14 bilateral and seven unilateral cases of retinoblastoma; mean age at diagnosis was 16 months in males (16 patients) and 30 months in females (five patients). They were all staged according to Howarth et al. (1980) and treatment was correlated to the various stages. The treatment protocol was determined by a group of co-workers at the University of Padova. Among the 35 affected eyes, 26 were enucleated and the others were treated without surgery. One patient died of cerebral metastases and two patients are affected by a second tumor with an unfavorable prognosis for survival. Two other patients are affected by chronic liver disease, probably due to chemotherapy. The authors confirm the importance of early diagnosis and prompt and effective treatment in children affected by retinoblastoma. They also stress that recently developed genetic techniques allow diagnosis of retinoblastoma even before the symptoms appear.

Antineoplastic Combined Chemotherapy Protocols↗