Richter's syndrome in a case of atypical chronic lymphocytic leukaemia with the t(11;14)(q13;q32): role for a p53 exon 7 gene mutation.

Clinicobiological, histological, cytogenetic and molecular genetic studies were performed in a case of atypical B-cell chronic lymphocytic leukaemia (B-CLL) with the t(11;14)(q13;q32) evolving into Richter's syndrome (RS) in order (a) to determine the clonal relationship between the cell of origin for B-CLL and RS, and (b) to analyse genetic events underlying the disease progression in this patient. After 4 years following diagnosis, a rapid deterioration of the clinical picture occurred, concomitant with the appearance of large lymphoid blasts in peripheral blood (PB), bone marrow (BM) and ascites samples. A diagnosis of RS was made and cytogenetic analysis revealed karyotype evolution with trisomy 7 and del(17p) in addition to t(11;14).

Some new 3-methoxy-5-methyl-1,4-substituted pyrazoles.

A series of 3-methoxypyrazole derivatives was synthesized and tested as antifungal agents. The substituents were chosen on the base of their lipophylicity and for their presence in well-known antifungal drugs. The compounds displayed no significant activity in vitro.

Atypical chronic lymphocytic leukaemia with t(11;14)(q13;q32): karyotype evolution and prolymphocytic transformation.

In order to define better the cytological and clinical features of atypical B-cell chronic lymphocytic leukaemia (B-CLL) with t(11:14)(q13;q32), sequential morphologic immunological and cytogenetic studies were performed in seven patients belonging to a series of 72 consecutive cases presenting with a diagnosis of CLL or atypical CLL according to the FAB criteria. Cytologic diagnosis in these seven patients with t(11;14) was typical CLL in two cases presenting with < 10% large lymphocytes (LL) and prolymphocytes (PL) and atypical CLL in five cases in which LL and PL comprised between 10% and 55%. The diagnosis was supported by histologic findings on bone marrow biopsy (five cases) or splenectomy specimens (two cases).

Evolutionary analysis of cytochrome b sequences in some Perciformes: evidence for a slower rate of evolution than in mammals.

To obtain information relative to the phylogenesis and microevolutionary rate of fish mitochondrial DNA, the nucleotide sequence of cytochrome b gene in seven fish species belonging to the order of Perciformes was determined. Sequence analysis showed that fish mitochondrial DNA has a nucleotide compositional bias similar to that of sharks but lower compared to mammals and birds. Quantitative evolutionary analysis, carried out by using a markovian stochastic model, clarifies some phylogenetic relationships within the Perciformes order, particularly in the Scombridae family, and between Perciformes, Gadiformes, Cypriniformes, and Acipenseriformes.

Purification and characterization of a mitochondrial DNA-binding protein that binds to double-stranded and single-stranded sequences of Paracentrotus lividus mitochondrial DNA.

A mitochondrial protein, able to specifically bind two double-stranded homologous sequences of sea-urchin mitochondrial DNA, has been partially purified from Paracentrotus lividus eggs. This protein, present at a low concentration, is a polypeptide of 40 kDa. One of the binding sequences, located in the main non-coding region, contains the replication origin of the mitochondrial DNA H-strand.

Some new quinoline-based mono and dicarboxylic acids.

Some quinoline-based mono- and dicarboxylic acids structurally related to kynurenic acid have been synthesized and screened as antagonists of neurotransmission of NMDA, AMPA and KA excitatory amino acid receptors. Higher affinity for NMDA receptor was pointed out in the short series, but all the compounds, even those with key structural features of glutamic acid showed no significant activity.

Effects of diltiazem on the calcium accumulation and ATP synthesis simultaneously sustained by isolated rat heart mitochondria.

1. The effects of diltiazem have been investigated in isolated rat heart mitochondria exposed to conditions possibly attained in ischemia-damaged cells. 2.

Heterocyclic modulators of the NMDA receptor.

The design of new heterocyclic derivatives as modulatory agents at EAA receptors is described. In particular, the potent and selective activity at the NMDA receptor of trans-4-hydroxypipecolic acid-4-sulfate, as well as the neuroprotective properties of substituted thiokynurenates, a new class of competitive antagonists at the glycine site of the NMDA receptor complex, are reported.

Effects of diltiazem on liver mitochondria of rats: a reconsideration.

1. The effects of the Ca-channel blocker diltiazem (a drug of the benzothiazepine family) on bioenergetic metabolism have been assessed on isolated rat liver mitochondria. 2.

Biochemical and morphological observations on rat liver and kidneys six months after intravenous injection of a perfluorocompound emulsion.

The histological appearance of liver and kidneys and the energy metabolism of isolated liver and kidney mitochondria were evaluated in rats 6 months after intravenous administration of 1 ml of a perfluorocompound emulsion. Both liver and kidney specimens showed neither significant histological alteration nor the presence of intracytoplasmic perfluorocompound particles. A substantial depression of the rate of ATP synthesis was observed both in liver and kidney isolated mitochondria (with respect to control mitochondria) although the magnitude of the transmembrane electrical potential was unaltered.

Identification of two homologous mitochondrial DNA sequences, which bind strongly and specifically to a mitochondrial protein of Paracentrotus lividus.

Using a combination of band shift and DNasel protection experiments, two Paracentrotus lividus mitochondrial sequences, able to bind tightly and selectively to a mitochondrial protein from sea urchin embryos, have been found. The two sequences, which compete with each other for binding to the protein, are located in two genome regions which are thought to contain regulatory signals for mitochondrial replication and transcription. A computer analysis suggests that the sequence TTTTRTANNTCYYATCAYA, common to the two binding regions, is the minimal recognition signal for the binding to the protein.

Synthesis, antibacterial activity and structure-activity relationships of N-substituted 4-diazo-pyrazole-5-carboxamides. 2.

A series of 4-diazopyrazole-5-carboxamides 1 d-n has been synthesized and their antibacterial activity against a number of Gram-negative and Gram-positive strains has been tested. Some of the compounds resulted quite active and the whole set allowed to further study the SAR of the class. Substituents in position 5 affect Gram-negative and Gram-positive activities via bulk and electronic properties respectively; position 3 mostly affects the Gram-negative activity, while the presence of the charged diazo group in position 4 is crucial for both antibacterial activities.

Uncoupling effect of the general anesthetic 2,6-diisopropylphenol in isolated rat liver mitochondria.

2,6-Diisopropylphenol, a general anesthetic, was previously reported to reduce the transmembrane electrical potential in isolated rat liver mitochondria without affecting the rate of ATP production. This effect appeared to contrast with the generally accepted chemiosmotic mechanism for oxidative phosphorylation. In this study we further examined the influence of 2,6-diisopropylphenol on the production of ATP by isolated mitochondria and we studied its effect on the permeability of the inner mitochondrial membrane to protons.

Influence of the anesthetic 2,6-diisopropylphenol on the oxidative phosphorylation of isolated rat liver mitochondria.

Isolated rat liver mitochondria have been incubated in the presence of the general anesthetic 2,6-diisopropylphenol (0-100 microM) and the efficiency of oxidative phosphorylation has been evaluated by measuring the respiratory rates, the rates of ATP synthesis or hydrolysis and the magnitude of the transmembrane electrical potential. The results obtained indicate that: (a) in mitochondria energized either by succinate or by ATP, 2,6-diisopropylphenol decreased the transmembrane electrical potential and increased the rates of either electron transfer or ATP hydrolysis; (b) in succinate-energized mitochondria 2,6-diisopropylphenol, at concentrations causing substantial depression of the transmembrane electrical potential, did not modify either the rate of phosphorylation of added ADP or the rate of ADP-stimulated respiration: (c) in succinate-energized mitochondria 2,6-diisopropylphenol caused a concentration-dependent inhibition of the uncoupler-stimulated rate of succinate oxidation. These findings suggest that under the experimental conditions reported 2,6-diisopropylphenol affected the generation and/or maintenance of the transmembrane electrical potential while leaving unchanged the coupling between the electron flow in the respiratory chain and the synthesis of ATP.

Techniques for experimental rat kidney (and liver) perfusion.

The technique described here allows to perfuse in situ either the left kidney alone, both kidneys or both kidneys and the liver of rats with few operations, without danger of organs damage and with a good control of temperature and pressure. This technique allows a good maintainance of the metabolic activity of the perfused tissues and offers the possibility to collect urine by cannulating the bladder.

The cytochrome b of the sea urchin Paracentrotus lividus is naturally resistant to myxothiazol and mucidin.

The ubiquinol:cytochrome c reductase activity of Paracentrotus lividus mitochondria is relatively insensitive to the specific inhibitors myxothiazol and mucidin. The I50 of myxothiazol and mucidin are three and two orders of magnitude higher, respectively, in P. lividus than in bovine heart mitochondria.

Mapping and characterization of Paracentrotus lividus mitochondrial transcripts: multiple and overlapping transcription units.

This paper reports the mapping of both mature and precursor Paracentrotus lividus mitochondrial transcripts. Several mtRNAs were found to have 5' and 3' termini which differ from those inferred through DNA sequencing (Cantatore et al. 1989).

Synthesis, antibacterial activity and structure-activity relationships of N-substituted 3-methyl-4-diazo-5-pyrazolecarboxamides.

A number of N-substituted 3-methyl-4-diazo-5-pyrazolecarboxamides (IVa-p) have been synthesized and tested for their in vitro antibacterial activity. All the compounds have been assayed against several representative Gram-negative and Gram-positive bacteria, as well as against some intestinal bacterial species. Some of the 4-diazopyrazoles IVa-c have shown a quite interesting broad-spectrum activity, while they are ineffective against the "protective" intestinal flora.

The complete nucleotide sequence, gene organization, and genetic code of the mitochondrial genome of Paracentrotus lividus.

The 15,697-nucleotide sequence of Paracentrotus lividus mitochondrial DNA is reported. This genome codes for 2 rRNAs, 22 tRNAs, and 12 mRNAs which specify 13 subunits of the mitochondrial inner membrane respiratory complexes. The gene arrangement differs from that of other animal species.

[The use of 3-dimensional CT reconstruction in childhood. Technics and dosimetry].

A new computer method has been developed that allows the reprocessing of standard CT scans to produce 3D surface images. We employed the 3D reconstruction program developed by Hitachi Medical System using an Ansaldo A-TOM XR 1200 scanner. The process requires only standard CT scanner hardware, and reconstruction time is comparable to that of sagittal and coronal reconstructions.

Effects of unilateral ureteric occlusion on renal necrosis occurring in rats fed a methyl-deficient diet.

Wistar male rats were fed from weaning a methyl-deficient diet (groups I and II) or a standard commercial diet (groups III and IV). At the day 3 the left ureter was tied and divided in animals of groups I and III, while those in groups II and IV were sham operated. Rats of all groups were killed on days 8 and 10 to evaluate the incidence and extent of tubular necrosis (day 8) and tubular and cortical necrosis (day 10).