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Biomedical subjects

M Federico

Publications and source records attributed to M Federico.

At least 127 records · Page 7Linked to original sources

Human lymphoblastoid interferon for hairy cell leukemia: results from the Italian Cooperative Group.

Since April 1985, 82 patients with HCL entered a multicenter study using lymphoblastoid alpha-interferon; 51 (including 15 who failed splenectomy and 24 with substantial splenomegaly) enrolled before April 1986 are evaluated in this study. The patients were treated with 3 mega units daily subcutaneously until complete or partial response and were thereafter randomly allocated to a maintenance regime of 3 mega units/week or to observation only. Ten cases had a complete response, 18 a partial response, and 15 a minimal response. Two patients had no response, two interrupted therapy due to major toxicity (toxic hepatitis and thrombocytopenia), six died before completing 1 month of therapy of sepsis, and two died of myocardial infarction. In the two groups of splenectomized and nonsplenectomized patients the mean time to hemoglobin recovery was 8.5 and 6.5 weeks, respectively, the neutrophil count recovery was 6.5 and 9.3 weeks, and the time to platelet count recovery was 4.0 and 5.4 weeks, respectively. No significant differences in recovery time and response rate were observed between the two groups. In 31 out of 32 patients with substantial splenomegaly the spleen became either inpalpable (18) or significantly smaller (13). This study confirms the responsiveness of HCL to IFN in nonsplenectomized patients with high tumor burdens and is therefore recommended as a first-line therapy.

Humans↗

Anti-tumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. V. Comparisons with the action of tumor necrosis factor.

A number of similarities and dissimilarities in the anti-tumor effects of TNF and interferon alpha/beta have been observed in DBA/2 mice injected with Friend erythroleukemia cells (FLC). Mouse TNF exerted marked anti-tumor effects in mice injected either s.c. or i.p. with FLC lines 3C18 or 3 gamma R8 resistant in vitro to the cytotoxic effects of TNF. Likewise, mouse interferon alpha/beta had anti-tumor activity in mice injected with these FLC, resistant to the action of interferon alpha/beta or gamma in vitro. The results of histopathologic examination and 31P nuclear magnetic resonance analyses of 3C18 FLC s.c. tumors injected with TNF resembled the results previously obtained for 3C18 FLC tumors injected with interferon alpha/beta, although the effects of TNF occurred more rapidly. Injection of mice with antibody to mouse interferon alpha/beta or gamma did not abrogate the anti-tumor effects of TNF in mice injected i.p. with FLC. Our results suggest that in this experimental system the anti-tumor effects of TNF, like interferon alpha/beta, do not result from a direct effect on the tumor cells themselves but are host-mediated.

Animals↗

Natural resistance in mice against Friend leukemia cells. I. Studies with in vitro passaged interferon-sensitive and interferon-resistant cell clones.

Anti-lymphoma natural resistance (NR) has been detected in DBA/2 mice inoculated intravenously (iv) with syngeneic Friend leukemia cells (FLC). Interferon-sensitive 745 or interferon-resistant 3Cl-8 clones, passaged in vitro and exhibiting "low" tumorigenicity in syngeneic DBA/2 mice, were used. NR, measured as rapid clearance of radiolabeled cells from lung and liver of recipient mice, was age-dependent, was boosted by host pretreatment with polyinosinic-polycytidylic (poly I:C) acid or Friend leukemia virus, and was decreased by mice pretreatment with cyclophosphamide or i-carrageenan. Treatment of "target" FLC with interferon suppressed the susceptibility of 745 FLC, but not that of 3Cl-8 FLC to host's NR. These data suggest that the "low" in vivo tumorigenicity of in vitro passaged FLC is, at least in part, due to host's NR directed against target structures associated with leukemia cells.

Aging↗

2',5'-Oligoadenylate synthetase-uninducible alpha/beta-interferon-resistant Friend cells develop an antiviral state when permeabilized with lysolecithin and treated with 2',5'-oligoadenylate oligomers.

Variant sublines of Friend erythroleukemia cells (FLC) that do not respond to alpha/beta-interferon (IFN-alpha/beta) by developing an antiviral state but respond partially to IFN-gamma with an induced antiviral state, lack the ability to induce the 2',5'-oligoadenylate (2-5A) synthetase pathway. Exposure of wild-type and variant cells to exogenous 2-5A oligomers made permeable with lysolecithin resulted in 50-70% inhibition of protein synthesis. Further, the replication of vesicular stomatitis virus in IFN-resistant 2-5A synthetase-deficient FLC exposed to 2-5A trimer was inhibited to the same extent as in wild-type cells. Last, a significant cleavage of ribosomal RNA was observed in samples of total RNAs extracted from variant and wild-type permeabilized FLC, but only if they were exposed to 2-5A. These data are compatible with the conclusion that (i) the activation of the 2-5A-dependent endoribonuclease is not impaired in the variant cells, and (ii) the uninducibility of 2-5A synthetase can be bypassed by exogenously introducing its products, which leads to the establishment of a bona fide antiviral state.

2',5'-Oligoadenylate Synthetase↗

Reevaluation of prognostic significance of symptoms in Hodgkin's disease.

The prognostic value--at diagnosis--of fever, sweating and weight loss, which enter the Ann Arbor B category, and of pruritus, whose influence on survival is still debated, were systematically reevaluated in 635 patients with Hodgkin's disease, observed between 1972 and 1982. By means of multivariate analysis an intrinsic, more negative prognostic value was demonstrated for each of the following symptoms: fever over 38 degrees C, weight loss more than 10% of body weight in the 6 months before admission, and severe pruritus, which is defined as being generalized, causing multiple excoriations and resisting local and systemic antipruritics. Patients with the mild counterparts of these symptoms, as well as sweats, were found to have a survival rate quite comparable with that of fully asymptomatic patients. A rearrangement of the Ann Arbor B constitutional symptoms which would replace sweats with severe pruritus might be more correct and more suitable for better selecting the patients who require more aggressive therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Establishment of the antiviral state in alpha, beta-interferon-resistant Friend cells treated with gamma-interferon. Induction of 67-kilodalton protein kinase activity in absence of detectable 2-5A synthetase.

Treatment with murine gamma-interferon (IFN) preparations of variant sublines of Friend leukemia cells resistant to the alpha, beta IFN-induced antiviral state (Affabris, E., Jemma, C., and Rossi, G.B. (1982) Virology 120, 441-452; Affabris, E., Romeo, G., Belardelli, F., Jemma, C., Mechti, N., Gresser, I., and Rossi, G. B. (1983) Virology 125, 508-512) results in the establishment of a bona fide antiviral state. In fact, gamma IFN preparations are able to induce a dose-dependent reduction of endogenous virus release and of vesicular stomatitis or encephalomyocarditis viruses yields (up to 1.5 log). Under these experimental conditions, no inducible 2-5A synthetase activity is detectable in cell extracts. The 67-kDa protein kinase, uninducible by treatment with alpha, beta IFN (up to 13,000 units/ml), is instead induced upon treatment with gamma IFN at a similar rate of activity as in wild-type Friend leukemia cells, both when assayed in solution and after immobilization on poly(rI) X poly(rC)-agarose.

2',5'-Oligoadenylate Synthetase↗

Serum albumin in Hodgkin's disease.

Serum albumin levels were measured by electrophoresis in 552 evaluable patients with Hodgkin's disease. Determinations were made on all patients at onset, on 224 after induction therapy and on 78 in relapse after remissions of variable length. At onset a discrete hypoalbuminemia was evident, inversely related to stage and more marked in symptomatic cases and elder patients. Little or no differences in albumin levels were found with relation to histologic subtypes, sex and presence of weight loss or hepatic damage. Posttherapeutic normalization of serum albumin occurred only after achievement of complete remission and failed after partial remission, while a new clear decrease became evident in relapse. On the basis of 799 albumin measurements during active disease and in remission, the albumin/alpha 2-globulin ratio demonstrated a clear and useful clinical advantage over either albumin or alpha 2-globulin fractions alone as indicator of active disease and relapse. If defective synthesis is the most accepted mechanism for hypoalbuminemia in Hodgkin's disease, these results suggest a casual factor somehow related to the tumoral mass.

Adult↗

A report of seven long survivors for evidence of prognostic factors in hairy cell leukemia.

The clinical hematologic and pathologic findings of 30 patients with hairy cell leukemia observed between 1966 and 1979 were studied. Twelve patients had long-lasting course of the disease. Seven of them displayed a survival greater than or equal to 120 months, whereas 18 patients died within 36 months of the diagnosis. Their clinical and laboratory characteristics (age of onset, sex, ESR, hemoglobin, WBC, neutrophils, monocytes, platelets, spleen and liver size) were analyzed to ascertain possible prognostic features. Multivariate discriminant analysis, performed both with a direct method and with a stepwise method (Wilks' method), provided a discriminant function able to correctly predict the prognosis of the disease in 83.3% of the examined cases. Spleen size, neutrophil count, age of onset, ESR and liver size turned out to be the most important prognostic factors; in contrast, splenectomy did not significantly affect the prognosis in our cases.

Adult↗

Morphological characterization of stationary reticulum cells of the stromal in the mesenteric lymph node of the guinea pig.

The large mesenteric lymph node taken from guinea pigs in a period of time ranging from the 10th day prepartum till the 26th day postpartum has been examined in order to study: the morphological features of the stromal stationary reticulum cells with particular regard to recognize their stages of development; the possible ontogenetic relationship between these cells during the maturation of the lymphoid tissue. Our data support the hypothesis that from local mesenchymal cells originates a pool of poorly differentiated reticulum cells that can give rise to stromal stationary reticulum cells (myofibroblast-like cells, fibroblast-like cells, pericyte-like cells and dendritic cells). These elements have a characteristic distribution pattern likely related to different local functional requirements.

Aging↗

New clinical criteria for the assessment of liver involvement in Hodgkin's disease.

The hepatic involvement in Hodgkin's disease, histologically verified in 133 patients who underwent laparotomy or laparoscopy, proved to be singly related to the following clinical findings: result of the liver isotopic scan, liver and/or spleen enlargement, serum albumin less than or equal to 3.5 g/dl, GOT and/or GPT greater than or equal to 20 mU/ml, serum alkaline phosphatase (SAP) greater than or equal to 210 mU/ml, BSP retention at 45 min greater than or equal to 6.5% and ESR greater than or equal to 51 mm at 1 hr. Such clinical findings were jointly evaluated and further selected by means of a logistic discriminant analysis, and the simplest function with the best discriminant ability between involved and non-involved liver was made by liver scan, spleen enlargement, BSP retention and GOT (89.5% of correct diagnoses). Since the Ann Arbor clinical criteria for liver involvement showed correct diagnoses in 69-80% of the cases, more reliable criteria can be proposed. So, liver involvement is highly probably (a) when three or more of the five variables indicated above are abnormal, or (b) when a markedly abnormal liver scan is associated with alteration of at least one of the other four parameters: otherwise liver will be non-involved.

Adolescent↗

Tonsillectomy: a prognostic factor in Hodgkin's disease?

The clinical features and course of Hodgkin's disease (HD) were investigated in 160 previously tonsillectomized patients and compared with 375 nontonsillectomized ones. In both groups, sex, social class, histologic type, stage and symptoms were almost identically distributed. Tonsillectomized patients showed a higher incidence of initial cervical forms (p less than 0.05) and more frequently developed the disease under 35 years of age (p less than 0.001), thus also reflecting the different policies of the otolaryngologists in the past few decades. Moreover, the tonsillectomized patients enjoyed a significantly better survival (p approximately equal to 0.01) than the nontonsillectomized ones. Adjusted survival curves for age and site of initial involvement proved that the favorable prognostic value of tonsillectomy was not due to the altered distribution of these 2 factors in the 2 groups; in addition, an earlier diagnosis in tonsillectomized patients could be excluded. The favorable effect of tonsillectomy in HD patients might be related specifically to the reduced portion of immunologically reacting oropharyngeal lymphoid tissue remaining after tonsillectomy. A decreased output of the specific immune-complexes, which are responsible for the disease, according to Vianna's theory, might be hypothesized in tonsillectomized patients.

Adolescent↗