A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.

Hematopoietic stem cell gene therapy (GT) using a γ-retroviral vector (γ-RV) is an effective treatment for Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency. Here, we describe a case of GT-related T-cell acute lymphoblastic leukemia (T-ALL) that developed 4.7 years after treatment.

The transcription factor HIF2α partakes in the differentiation block of acute myeloid leukemia.

One of the defining features of acute myeloid leukemia (AML) is an arrest of myeloid differentiation whose molecular determinants are still poorly defined. Pharmacological removal of the differentiation block contributes to the cure of acute promyelocytic leukemia (APL) in the absence of cytotoxic chemotherapy, but this approach has not yet been translated to non-APL AMLs. Here, by investigating the function of hypoxia-inducible transcription factors HIF1α and HIF2α, we found that both genes exert oncogenic functions in AML and that HIF2α is a novel regulator of the AML differentiation block.

How prostaglandins have changed the medical approach to glaucoma and its costs: an observational study of 2228 patients treated with glaucoma medications.

Purpose: The aim of the present study was to investigate how the medical treatment of glaucoma changed between 1997 and 2002, since the advent of prostaglandin derivatives, with regard to drug prescriptions and pharmaceutical costs.

Methods: A study was made of medical prescriptions for 2228 patients with glaucoma and/or ocular hypertension, in order to investigate the following: (i) the antiglaucoma drugs most commonly prescribed in 1997 and 2002, and any differences between the drugs prescribed in these 2 years; (ii) the number of drugs used per patient in 1997 and 2002, respectively, and (iii) any increase in the prescribing of antiglaucoma drugs and their relative costs from 1997 to 2002.

Results: From 1997 to 2002 there was a sharp drop in the prescribing of beta-blockers (79% in 1997 and 55% in 2002).

Anti-Trichomonas vaginalis monoclonal antibodies inducing complement-dependent cytotoxicity.

Hybridomas producing monoclonal antibodies (mAbs) directed against Trichomonas vaginalis (Tv) have been produced in three fusions using mice immunized with live or killed Tv. The ELISA technique was used to test the binding activity of six out of the 48 mAbs produced. It was found that acetone fixation enhanced the binding activity of the antibodies and revealed hidden antigenic determinants.

[Follow-up and prognosis of congenital hypothyroidism].

Neonatal screening of congenital hypothyroidism has been recently extended to the most of North America, Australia, Europe, and to several Italian areas. Before screening programs, several Authors reported neurological defects and behavioral disturbances also in patients whose treatment has been precocious, thus stressing the importance of an antenatal thyroidal defect. We have therefore setted up a follow-up program to evaluate the prevalence and to treat such disturbances in hypothyroid children.

The stimulation by epidermal growth factor (urogastrone) of the growth of neonatal rat hepatocytes in primary tissue culture and its modulation by serum and associated pancreatic hormones.

Epidermal growth factor (EGF) added in a single dose (between 10(-16) and 1.7 X 10(-9)M) to neonatal rat hepatocytes in primary culture with subsequent incubation for 12 and 24 hours in Eagle's MEM fortified with 10% (v/v) FBS stimulated their entry into S and M phases, as shown by (3H)thymidine labeling and autoradiography and by a 4-hour exposure to colchicine (0.1 mM).

Studies on the persistence of differentiated functions in rat hepatocytes set into primary tissue culture. II. Production of specific exportable proteins and the effect of purine cyclic nucleotides: an immunofluorescent study.

Immunofluorescent studies showed that even after 15 days in vitro primary neonatal rat hepatocytes contained in their cytoplasm detectable amounts of different adult rat serum proteins, including fibrinogen and proalbumin. Estimation of the intensity of specific fluorescence revealed that in untreated cultures the hepatocytic content of the various exportable antigens progressively diminished between the 5th and 15th day in vitro. Treatment with cAMP (10(-5) M daily) alone increased in hepatocytic cytoplasm, with respect to parallel controls, the content of total exportable proteins and of proalbumin.

Effects of ACTH and 3',5'-cyclic purine nucleotides on the morphology and metabolism of normal adult human adrenocortical cells in primary tissue culture.

Stereological studies showed that treatment of normal adult human adrenocortical cells in primary culture with ACTH or cyclic-AMP for 2 days results in similar increases in the volume of cells, of the mitochondrial and "membrane space" compartments and of the surface area of the smooth endoplasmic reticulum and mitochondrial cristae, and decrease in the lipid content of the cells. These changes were more marked after 8 days of treatment. Treatment for 2 days with cyclic-GMP had no striking effects on cell ultrastructure, whereas an 8-day treatment led to ultrastructural changes similar to those obtained after 2 days of ACTH- or cyclic-AMP-treatment.

Neonatal rat hepatocytes in primary tissue culture free from density-dependent regulation of growth.

Studies employing [3H]thymidine and radioautography as well as colchicine and Feulgen staining of DNA showed that up to 19-fold increases in the degree of cell crowding in vitro, i.e. from 1.

Effect of glucagon and insulin on the growth of neonatal rat hepatocytes in primary tissue culture.

Commercial (bovine-porcine) glucagon added in a single dose between 10(-12) and 10(-7) M to neonatal rat hepatocytes in primary cultures with subsequent incubation for 20-24 h, stimulated their entry into the DNA synthesis phase as revealed by [3H]thymidine-labeling and radioautography; about 14 h of incubation was required before an effect was observed. Commercial (bovine) insulin at doses between 10(-11) and 10(-7) M apparently stimulated the entry of hepatocytes into S phase. However, insulin's effect, which needed 20 h for induction, was due to the release of a wave of synchronized hepatocytes from an earlier produced block near the G1/S boundary of their growth-division cycle.

Investigations on the turnover of adrenocortical mitochondria. IX. A stereological study of the effects of chronic treatment with acth on the size and number of mitochondria from adult human adrenocortical cells cultured in vitro.

The effects of ACTH on the mitochondria of adult human adrenocortical cells cultured in vitro were investigated by electron microscopic and stereological methods. It was found that ACTH induces increase in the volume of the mitochondrial compartment, which is due to both a hypertrophy and an increase in number of the organelles. The hypothesis that ACTH controls the growth and proliferation of human adrenocortical mitochondria is discussed.

Stimulation by N6,O2'-dibutyrul andenosine 3',5'-cyclic monophosphate of RNA and DNA synthesis and of cell proliferation of rat hepatocytes in primary tissue culture.

The effects of DBcAMP in doses from 1.5 x 10(-8) to 1.5 x 10(-3) M on the compartmental apparent surface area (ASA) and (5(-3H)uridine radioactivity concentration (URC), (methyl-3H)thymidine labelling index per 1 hour ([Me-3H]Tdr LI/h) and per cent mitotic index (MI%) and colchicine metaphase index (CMI%) of young rat differentiated hepatocytes in primary tissue culture were investigated by morphometric and radioautographie methods.

Effect of adenosine 3',5'-cyclic monophosphate on the RNA and DNA synthesis and cell proliferation of rat hepatocytes in primary culture: a radioautographic study.

The effect of a 24-h treatment with various doses (from 1.5-10-minus 8 to 3.0-10-minus 3 M) of adenosine 3',5'-cyclic monophospahte (cAMP) on morphometric parameters, [5--3H]uridine radioactivity concentration (URC), [methyl--3H]thymidine [Me--3H]-Tr) labelling index per hour (L.

Studies on the persistence of differentiated functions in rat hepatocytes set into primary tissue cultures. Specific binding of 3H-bilirubin after eight days of staying in vitro.

Preliminary experiments were performed which indicate that even after 8 days of staying in primary in vitro tissue culture rat hepatocytes are still able to take up and bind tritiated, unconjugated bilirubin in a specific fashion and much more intensely than do connective tissue cells present in the same cultures. The data are suggestive of the maintenance in 8-day cultured hepatocytes of at least some of the specific pathways bound to bilirubin metabolism.

Cyclic AMP induces ultrastructural differentiation of normal adult human adrenocortical cells cultured in vitro.

Electron microscopic studies have revealed that cyclic AMP, like ACTH, induces structural differentiation of adult human adreno-cortical cells cultured in vitro. These findings support the hypothesis that cyclic AMP can function as an intracellular mediator of the action of ACTH on the human adrenal gland.

Primary tissue culture of normal adult human decapsulated adrenal cortex: radioautographic studies on the metabolic effects of ACTH1-24.

ACTH-deprived primary normal adult human adrenocortical cells on the 23rd day in vitro were found to lack any DNA synthetic and proliferative activity, but incorporated uridine-3H and 1-leucine-3H actively. In cortical cells of the same age treated for 2 and 7 days with ACTH1-24 (3 X 10(-6) M) the incorporation of the precursors for RNA and DNA synthesis and the cell proliferation were found to be markedly stimulated. The apparent uptake of leucine-3H was instead reduced in 2-day and, less still, in 7-day treated cells.