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Biomedical subjects

R Invernizzi

Publications and source records attributed to R Invernizzi.

At least 91 records · Page 5Linked to original sources
PubMed1988

Recombinant gamma-interferon induces in vitro monocytic differentiation of blast cells from patients with acute nonlymphocytic leukemia and myelodysplastic syndromes.

gamma-Interferon (IFN-gamma) has previously been found to induce monocytic differentiation in established leukemic cell lines, such as HL-60 and U937. The aim of the present study was to evaluate the differentiative effect of highly purified recombinant (r)IFN-gamma on fresh bone marrow cells from patients with acute nonlymphocytic leukemia (n = 11) or myelodysplastic syndromes (n = 3). Blast cells were cultured in suspension in the presence or absence of rIFN-gamma (10-10(3) U/ml). While 6 out of 14 cases were unresponsive to rIFN-gamma in vitro, the remaining 8 patients showed a significant increase (0.05 greater than p greater than 0.001) in the percentage of cells expressing C3bi receptors, detected by OKM1 (median value in control cell, 9.5; median value in rIFN-gamma-treated cells, 31) and Mo1 (8.5 vs. 36), and in the percentage of cells expressing the monocytic antigens detected by Mo2 (8 vs. 28) and MY4 (6.5 vs. 32.5). In the responsive patients morphologic changes consistent with monocytic maturation, as well as a strong increase of alpha-naphthyl acetate esterase activity and of nitroblue tetrazolium reducing capability were observed upon culture with rIFN-gamma. We conclude that (a) rIFN-gamma may induce in vitro monocytic differentiation of blasts from acute nonlymphocytic leukemia and myelodysplastic syndrome patients, and that (b) this agent should be investigated for its capacity to be active in vivo.

Acute Disease↗
PubMed1988

Natural history of idiopathic refractory sideroblastic anemia.

We analyzed the natural history of idiopathic refractory sideroblastic anemia (IRSA) in 37 patients studied between 1969 and 1986. Although erythroid abnormalities were prominent in all, 12 patients also showed involvement of the granulocytic and/or megakaryocytic cell lines, and nonrandom chromosomal aberrations were observed in five of 23 patients studied for such defects. Measurements of erythroid marrow function showed in most cases erythroid expansion with ineffective erythropoiesis. In seven patients, however, the erythroid activity was found to be inappropriately low for the degree of anemia. Transfusion dependence occurred in 26 of 37 cases. Iron overload was a common feature at presentation but produced clinical manifestations of hemochromatosis only in those patients who subsequently had a regular need for blood transfusions. Five patients progressed to bone marrow failure, and another five patients (two of whom had monosomy 7) evolved into acute nonlymphocytic leukemia (ANLL). The median survival was 72 months, with a high transfusion requirement, multilineage defects, and inappropriately low erythroid proliferation being associated with a poor prognosis. The most common causes of death were complications of iron overload and evolution into ANLL. We conclude that (a) the natural history of IRSA is characterized by an initial phase of erythroid hyperplasia and ineffective erythropoiesis, which is usually stable for many years but in a subset of patients may be followed by a phase of marrow failure with or without the later emergence of leukemic blasts; (b) peripheral blood counts, measurement of erythroid marrow function, and chromosomal analysis are useful for identifying subjects at risk of evolution into marrow failure or ANLL; and (c) IRSA patients with no need for blood transfusions are very likely to be long survivors, whereas those who become transfusion dependent are at risk of death from the complications of secondary hemochromatosis.

Adult↗
PubMed1987

Cytochemistry of N-acetyl-beta-glucosaminidase in normal and leukemic T cells.

A cytochemical study of the N-acetyl-beta-glucosaminidase (NABG) activity in normal and leukemic T cells was carried out to ascertain any relationships between cytochemical reactivity and membrane phenotype. Under normal conditions, most T4-positive cells, defined on the basis of monoclonal antibodies and immunogold, were characterized by focal reactivity. In chronic T lymphoproliferative disorders, the reaction product of T4-positive cells consisted of a single coarse granule, while T8-positive cells demonstrated many scattered granules. In all cases of acute T cell malignancies, lymphoblasts were positive with a single coarse granule or many coarse and small granules located at one pole of the cell.

Acetylglucosaminidase↗
PubMed1986

High-degree abnormalities of nuclear DNA distribution in SIg negative acute lymphoblastic leukemia with vacuolated blasts.

Among 65 consecutive patients with untreated adult acute lymphoblastic leukemia (ALL), six had peculiar clinical and cytologic features. Bone marrow and circulating blasts were large and showed prominent vacuolization, with variable degree of granular periodic acid-Schiff positivity in the cytoplasm. All patients had marked spleen and liver enlargement with cholestasis and without either lymph node or central nervous system disease. They achieved complete response to chemotherapy, and their median survival was longer than 12 months. Blast cells were studied for immunologic markers, propidium iodide flow cytofluorometric DNA content, and in vitro tritiated thymidine labeling index (3H-TdR LI). These showed a "null" phenotype in two cases, contained intracytoplasmic immunoglobulins (Cy mu) in two and were positive for CALL and Ia antigens in two others (one of which also contained Cy mu). Surface immunoglobulins (SIg) were found on less than 12% of cells, and T-cell markers were absent. In five cases, one or two stem lines with highly abnormal modal DNA content were found to coexist with diploid blasts. The 3H-TdR LI was high (8.5%-15.5%). Abnormal cell lines, after being cleared by chemotherapy, were found again at relapse. Additional cell lines appeared during the course of the disease in one patient, having different sensitivity to cytostatics. These cases of ALL apparently derive from B-cells not yet expressing SIg and have an exceptionally high incidence of aneuploid cell lines.

Adolescent↗
PubMed1986

d- and l-isomers of fenfluramine differ markedly in their interaction with brain serotonin and catecholamines in the rat.

Various doses of fenfluramine isomers were compared for their ability to affect monoamine levels, metabolism and synthesis in the rat brain. d-Fenfluramine was more potent than l-fenfluramine in reducing serotonin (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) at 4 h after their administration. After decarboxylase inhibition, a low dose of d-fenfluramine (2.5 mg/kg) reduced 5-HT synthesis, assessed as 5-hydroxytryptophan (5-HTP) accumulation, in the hypotalamus and lower brain-stem only, whereas a higher dose (5 mg/kg) reduced 5-HT synthesis in all brain regions examined except the striatum. A higher dose of l-fenfluramine (10 mg/kg) was required to reduce 5-HT synthesis. Metergoline, a 5-HT antagonist, did not modify the effects of fenfluramine isomers on 5-HT synthesis. One h after its administration l-fenfluramine 5-20 mg/kg significantly increased brain 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MHPG-SO4), striatal homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) levels, while after 4 h only the highest dose raised HVA levels. No change of striatal HVA and DOPAC levels was seen 1 or 4 h after any dose of d-fenfluramine while the highest dose raised brain MHPG-SO4 levels. Neither l- nor d-fenfluramine changed striatal 3-methoxytyramine (3-MT) levels. The noradrenaline (NA) and dopamine (DA) levels were decreased 4 h after 10 and 20 mg/kg l-fenfluramine or 20 mg/kg d-fenfluramine. The results show that the d- and l-isomers of fenfluramine at relatively low doses have a specific action on brain 5-HT and catecholamines, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1986

Selective involvement of dopamine in the nucleus accumbens in the feeding response elicited by muscimol injection in the nucleus raphe dorsalis of sated rats.

Muscimol injection (100 ng) in the nucleus raphe dorsalis (NRD) caused intense eating in non-food-deprived rats. At a dose (10 micrograms) blocking dopamine mediated responses (examined by increased locomotion or stereotypy caused by systemically injected d-amphetamine), fluphenazine injected in the n. accumbens, but not in the striatum, significantly reduced the eating response elicited by muscimol in the NRD while food intake of deprived rats was not significantly modified by fluphenazine injected in either area. Fluphenazine (20 micrograms) in the striatum reduced eating in both conditions, but the animals showed marked sedation which obviously interfered with the feeding response. Dopamine release and synthesis, measured respectively by 3-methoxytyramine and accumulation of dihydroxyphenylalanine after aromatic amino acid decarboxylase inhibition, were significantly reduced in the n. accumbens, but not in the striatum, of muscimol treated animals. The metabolism of serotonin was reduced in both areas of muscimol treated rats. It is suggested that changes in dopamine receptor sensitivity, together with changes in serotonin function, might be involved in the feeding response caused by muscimol injection in the NRD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Cytochemistry of circulating lymphocytes in diabetes mellitus with and without retinopathy and in newly diagnosed type I (insulin dependent) diabetes.

Cytochemical studies have been performed on peripheral blood lymphocytes of 68 diabetic subjects, with various conditions of metabolic control, and 15 newly diagnosed insulin-dependent diabetic patients. 20 patients of the 1 group had diabetic retinopathy. In diabetic patients periodic acid Schiff positivity, acid phosphatase, and N-acetyl-beta-glucosaminidase activities of lymphocytes are fairly impaired, particularly in insulin-dependent diabetes. Concerning the alpha-naphthyl-acetate-esterase activity, the percentage of positive cells with coarse granules is significantly reduced (p less than 0.001) in diabetic patients as compared to controls, without difference related to age and sex. These abnormalities are more evident in patients with poor glyco-metabolic control. In patients with newly diagnosed insulin-dependent diabetes we have found a further decrease in alpha-naphthyl-acetate-esterase activity, and an increase in acid phosphatase and N-acetyl-beta-glucosaminidase activities. Cyto-enzymatic activities are not significantly different in subjects with diabetic retinopathy. The results of peripheral lymphocyte enzymatic activities in diabetics could be related to a depression of the cell-mediated immunity and could enhance the infections risk of these patients. Furthermore our data show an altered immunological balance in subjects with newly diagnosed type I diabetes.

Acid Phosphatase↗
PubMed1986

Neurochemical mechanism of action of drugs which modify feeding via the serotoninergic system.

The neurochemical mechanisms by which drugs acting on central serotoninergic system modify feeding were reviewed. Fenfluramine, a clinically effective appetite suppressant, releases serotonin from nerve terminals and inhibits its reuptake, and considerable evidence suggests that these effects mediate its anorectic activity. The D isomer of fenfluramine is particularly specific in affecting serotonin mechanisms and causing anorexia. Transmitters other than serotonin such as acetylcholine, catecholamines and GABA are also affected by systemic administration of fenfluramine, but some of these effects are secondary to fenfluramine's action on serotoninergic mechanisms. Moreover, there is no evidence that these brain substances are involved in fenfluramine's ability to cause anorexia. Several studies with drugs affecting different serotonin mechanisms such as release and uptake or mimicking the action of serotonin at post-synaptic receptors suggest that increase serotonin release and direct stimulation of postsynaptic receptors are the most effective mechanisms for causing depression of food intake, although inhibition of serotonin uptake may also contribute in appropriate conditions. Development of serotonin receptor hyposensitivity and, in some instances, decreased serotonin levels may lead to tolerance to the anorectic activity of drugs enhancing serotonin transmission, the degree of this depending critically on the type of effect on serotonin mechanisms and intensity and duration of serotonin receptor activation. Recent evidence suggests that a decrease in serotonin function causes stimulation of feeding. This may lead to development of new strategies for the treatment of clinical anorexias.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Chronic treatment with iprindole reduces immobility of rats in the behavioural 'despair' test by activating dopaminergic mechanisms in the brain.

Iprindole, 10 mg kg-1 i.p., once daily for 21 days, enhanced the metabolism of dopamine in the frontal cortex and striatum of rats with no effect in the nucleus accumbens 1 h after the last injection. Noradrenaline metabolism in the brainstem and telencephalon was also increased in these conditions. No effect on dopamine or noradrenaline metabolism was seen 24 h after the last injection. The same repeated treatment schedule with iprindole markedly reduced the immobility of rats in the behavioural 'despair' test 1 h after the last injection and the effect was prevented by 0.5 mg kg-1 i.p. haloperidol and 100 mg kg-1 i.p. sulpiride but not by 3 mg kg-1 s.c. prazosin or 5 mg kg-1 i.p. (+/-)-propranolol. The data show that enhanced metabolism of brain dopamine and noradrenaline is associated with the presence of iprindole during repeated treatment and the effect on dopamine mechanism is important in iprindole's ability to reduce rats' immobility in the behavioural 'despair' test.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Treatment of infections during hematologic malignancies with aztreonam, a new antibiotic.

Nineteen patients with hematological malignancies (5 malignant lymphomas, 9 acute leukemia and 5 other hematological diseases) were treated with aztreonam alone or in combination for infection. Four out of five patients in the lymphoma group, 6/9 in the leukemia group and 4/5 in the last group were considered cured of their infection. No important clinical side effects or consistent deterioration of hematology and chemistry tests were observed.

Acute Disease↗
PubMed1985

Cytochemistry of dipeptidylaminopeptidase IV and II in normal and neoplastic lymphoid cells.

Cytochemical methods were used to determine the distribution of dipeptidylaminopeptidase IV (DAP IV) and II (DAP II) in lymphoid cell populations from patients with lymphoproliferative diseases. Special attention was paid to unusual intracellular distribution patterns which might correlate with the presence of various membrane markers. In healthy patients, about 50% of the circulating lymphocytes were found to be positive to both reactions, the intracellular distribution patterns being variable. The DAP IV reaction was negative in all B-CLL cases. In 2 cases of T-CLL with phenotype E+ OKT3+T4-T8+ one was negative and one was weakly positive, while two cases of T-CLL with phenotype E+ OKT3+T4+T8- were both strongly positive. The other non-T lymphoproliferative diseases studied were negative for DAP IV, while one T-ALL and three T-lymphoma cases showed a strong granular or diffuse distribution. The DAP II reaction was strongly positive in all the T lymphoproliferative diseases studied, irrespective of their immunological phenotype. This reaction was also weakly positive in some cases of plasmocytoma and lymphoplasmacytoid lymphoma.

Antibodies, Monoclonal↗
PubMed1985

Ultrastructural patterns of the alpha-naphthyl butyrate esterase activity in normal and leukaemic peripheral blood leucocytes.

The activity of alpha-naphthyl butyrate esterase was investigated at the ultrastructural level in normal human peripheral blood and in a few cases of hairy cell leukaemia, B-chronic lymphocytic leukaemia and acute monocytic leukaemia. A membrane reactivity was detected in most normal monocytes and lymphocytes. The activity in monocytes was very strong and was inhibited by NaF. It was NaF-resistant and less intense in lymphocytes. The reaction product was localized in the cytoplasm only in a small percentage of lymphocytes. In lymphocytes and monoblasts from pathological samples the pattern of reactivity was similar to that found in their normal counterparts, except for a lower intensity. The hairy cells showed a discrete distribution of the NaF-resistant reaction product on their cell surface. The different patterns of enzyme distribution are discussed critically.

Carboxylic Ester Hydrolases↗
PubMed1985

Cytochemical pattern of alpha-mannosidase, alpha-fucosidase and neutral maltase in normal blood cells.

The activity of alpha-mannosidase, alpha-fucosidase and neutral maltase was studied by cytochemical techniques in blood cells of 20 controls and of 4 T and B lymphocyte concentrates. All granulocytes, monocytes and platelets showed fine or coarse reaction product deposition, whereas lymphocytes were negative or showed various positivity patterns. A significant difference of the positivity between T and B subpopulations was observed only for the fucosidase reaction. It is possible that the different positivity patterns of the lymphoid cells are related to different functional activities. Further studies will probably confirm the interest of the alpha-fucosidase reaction for the characterization of normal and pathological lymphoid cells.

Adolescent↗
PubMed1984

Castleman's disease with coagulation defect. A case report.

The case of a young man with the plasma cell type of Castleman's disease is described. Beyond the well known systemic manifestations the coagulation tests showed a decrease in the activity of factors V, VIII and X due to the presence of lupus-like circulating anticoagulants. After surgical excision of the mediastinal mass both hematochemical pathological data and the coagulation defect disappeared. It is suggested that the lupus-like anticoagulant was secreted by the tumor.

Adult↗