Hybrid Core-Shell (HyCoS) Nanoparticles produced by Complex Coacervation for Multimodal Applications.

Multimodal imaging probes can provide diagnostic information combining different imaging modalities. Nanoparticles (NPs) can contain two or more imaging tracers that allow several diagnostic techniques to be used simultaneously. In this work, a complex coacervation process to produce core-shell completely biocompatible polymeric nanoparticles (HyCoS) for multimodal imaging applications is described. Innovations on the traditional coacervation process are found in the control of the reaction temperature, allowing a speeding up of the reaction itself, and the production of a double-crosslinked system to improve the stability of the nanostructures in the presence of a clinically relevant contrast agent for MRI (Gd-DTPA). Through the control of the crosslinking behavior, an increase up to 6 times of the relaxometric properties of the Gd-DTPA is achieved. Furthermore, HyCoS can be loaded with a high amount of dye such as ATTO 633 or conjugated with a model dye such as FITC for in vivo optical imaging. The results show stable core-shell polymeric nanoparticles that can be used both for MRI and for optical applications allowing detection free from harmful radiation. Additionally, preliminary results about the possibility to trigger the release of a drug through a pH effect are reported.

Fusiform aneurysm of the proximal anterior cerebral artery (A1).

OBJECTIVE: Fusiform aneurysms of the A1 segment of the anterior cerebral artery (ACA) are exceptional, with only 15 reported cases. This article presents an additional case treated by microsurgical trapping. The aim is to discuss the treatment of these aneurysms based on the aneurysm morphology and the anatomy of the ACA complex. CASE REPORT: A 52-year-old woman with subarachnoid hemorrhage (Hunt-Hess grade II) showed an aneurysm of the proximal part of the A1 segment of the left ACA involving the whole circumference of the arterial wall on computerized tomography angiography and digital angiography. There was good collateral blood flow from the right ACA to the distal left ACA. A left pterional craniotomy allowed us to expose a large aneurysm of the proximal part of the A1 segment; the artery entered into the aneurysm sac and could not be identified at the level of the aneurysm. Trapping of the aneurysm was performed with a distal clip placed just before the origin of the artery of Heubner. No neurological deficits were observed postoperatively. CONCLUSION: Clipping of fusiform aneurysms of the A1 segment using an encircling clip is the treatment of choice but, more often, this is impossible. Trapping of the aneurysm with preservation of the perforating branches (mainly the Heubner artery) may be easily performed when collateral blood flow from the contralateral ACA is sufficient.

Multislice CT with single-phase technique in patients with suspected pancreatic cancer.

PURPOSE: The purpose of this study was to evaluate the role of multislice computed tomography (MSCT) with a single-phase technique in patients with suspected pancreatic cancer (PC). MATERIALS AND METHODS: Seventy-eight patients underwent MSCT with the following technical parameters: collimation: 4x1 mm; pitch 1; 120 kVp; 260 mAs. The pre-contrast scan was followed by a single acquisition phase in the caudocranial direction from the inferior hepatic margin to the diaphragm with a 60-s delay after IV administration of 150 ml of iodinated contrast material at a rate of 3 ml/s. Two radiologists assessed the single images independently. Receiver operating characteristics (ROC) curves were obtained for each of the two observers. RESULTS: The final diagnosis was pancreatic cancer in 46 cases and chronic pancreatitis in 32 cases. Areas under the curve (AZ) for diagnosis and evaluation of disease resectability were 0.97 and 0.93 for the first observer (p=ns), and 0.97 and 0.90 for the second observer (p=ns). The mean difference in tissue attenuation values between the cancer and normal pancreas was 72 +/- 3 Hounsfield units (HU). No statistically significant differences were observed in the degree of opacification between the peripancreatic arteries and veins. CONCLUSIONS: MSCT with a single-phase technique is an accurate and reproducible method for diagnosis and evaluation of disease resectability in patients with suspected PC, ensuring optimal tumour-to-pancreas contrast and maximal opacification of the main peripancreatic arterial and venous structures.

Cyclin D2 dysregulation by chromosomal translocations to TCR loci in T-cell acute lymphoblastic leukemias.

Strong expression of at least one of the three D-type cyclins is common in human cancers. While the cyclin D1 and D3 genes (CCND1 and CCND3) are recurrently involved in genomic rearrangements, especially in B-cell lymphoid neoplasias, no clear involvement of the cyclin D2 gene (CCND2) has been reported to date. Here, we identified chromosomal translocations targeting the CCND2 locus at 12p13, and the T-cell receptor beta (TCRB) or the TCRA/D loci in T-cell acute lymphoblastic leukemias (T-ALLs). Expression analysis demonstrated dramatic cyclin D2 overexpression in the translocated cases (n=3) compared to other T-ALLs (total, n=89). In order to evaluate dysregulation in T-ALL with respect to normal T-cell differentiation, we analyzed CCND2 expression in normal purified human thymic subpopulations. CCND2 levels were downregulated through progression from the early stages of human T-cell differentiation, further suggesting that the massive and sustained expression in the CCND2-rearranged T-ALL cases was oncogenic. Association with other oncogene expression (TAL1, HOXAs, or TLX3/HOX11L2), NOTCH1 activating mutations, and/or CDKN2A/p16/ARF deletion, showed that cyclin D2 dysregulation could contribute to multi-event oncogenesis in various T-ALL groups. This report is the first clear evidence of a direct involvement of cyclin D2 in human cancer due to recurrent somatic genetic alterations.

A complex pattern of recurrent chromosomal losses and gains in T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare malignant proliferation of lymphoid cells with a postthymic phenotype. Previous cytogenetic and molecular studies reported complex karyotypes with recurrent chromosomal abnormalities, including translocations involving either TCL1 at 14q32.1 or MTCP1 at Xq28, inactivation of the ATM gene by deletion and/or mutation, and isochromosomes 8. For extensive study of chromosomal imbalances in T-PLL, we analyzed 22 tumoral DNAs using comparative genomic hybridization (CGH). Abnormal CGH profiles were detected in all cases, demonstrating highly recurrent gains and losses and largely extending the abnormalities previously established. Only a few nonrecurrent abnormalities were observed, in contrast to the genetic instability anticipated from ATM inactivation. Nine recurrent regions of loss were identified at 8p (frequency 86%), 11q (68%), 22q11 (45%), 13q (41%), 6q (36%), 9p (27%), 12p (23%), 11p11-p14 (23%), and 17p (23%), as well as four regions of gain at 8q (82%), 14q32 (50%), 22q21-qter (41%), and 6p (23%). Several recurrent chromosomal abnormalities were simultaneously present in each case (mean, 5.7; up to 10), none being mutually exclusive of another. Fluorescence in situ hybridization analysis confirmed and extended 22q11 and 13q losses, giving final frequencies of 55% and 45%, respectively. Analysis of one case over a 7-year period confirmed the overall genetic stability of T-PLL and showed that tumor progression was associated with the onset of a few chromosomal abnormalities. This study establishes a complex pattern of highly recurrent chromosomal abnormalities in T-PLL, including some, such as chromosome 13 deletion, commonly found in other lymphoid malignancies.

Frequency locking of supermodes and stability of the out-of-phase-locked state in one-dimensional and two-dimensional arrays of vertical-cavity surface-emitting lasers.

In large arrays with equally pumped lasers the out-of-phase-locked state is a combination of several supermodes of the array that are locked to a common frequency. The far-field pattern is four lobed because the out-of-phase supermode is largely dominant. An approximated analytical expression for the locking threshold is found, and saturable dispersion is indicated as the physical mechanism that selects the out-of-phase-locked state.

Cytogenetic studies in acute promyelocytic leukemia: a survey of secondary chromosomal abnormalities.

A series of 105 patients with acute promyelocytic leukemia (APL) has been cytogenetically investigated at the Department of Hematology of the Saint-Louis Hospital (Paris) between 1977 and 1990. Sixty-two patients were examined at diagnosis, 32 in relapse, and 11 both at diagnosis and in relapse. The typical t(15;17)(q22;q12) or variants of this translocation were observed in all but four patients. The t(15;17) was the only change in 47 cases at diagnosis and in 21 examined in relapse. The most frequent secondary change was trisomy 8 (17% at diagnosis). More or less complex chromosomal abnormalities in addition to t(15;17) were present in six patients at diagnosis, and in 17 patients in relapse. Rearrangements of 2q35-q37 and del(11p) were observed only in relapse and may thus be nonrandom secondary changes. Cytogenetic studies performed on 19 patients treated with all-trans retinoic acid did not indicate that this treatment induces chromosomal abnormalities.

Partial deletion of chromosome 2 in non-Hodgkin lymphoma.

Six patients with non-Hodgkin malignant lymphoma (NHL) in a series of 151 cases showed partial deletion of chromosome 2 when studied cytogenetically. Three had deletions of bands 2p14-p22 and three others had a deletion of bands 2q22-q24 in common. The deletions were associated with other abnormalities in each case and were not associated with a particular subtype of NHL. These deletions are secondary, apparently nonrandom, new abnormalities associated with NHL.

Loss of genetic material from the short arm of chromosome 12 is a frequent secondary abnormality in non-Hodgkin's lymphoma.

Abnormalities of the short arm of chromosome 12 have been detected in a wide variety of hematopoietic disorders. Seven cases of non-Hodgkin's lymphoma (NHL) are reported with various rearrangements involving bands 12p13 or 12p11, associated with other chromosome changes. A review of the literature confirms that rearrangements of 12p, mainly at band 12p13, are nonrandom chromosomal abnormalities in all subtypes of NHL, as in other malignant blood disorders. No common translocation could, however, be detected, and 12p abnormalities may be considered as secondary chromosomal events. Most of the 12p rearrangements involving translocation of genetic material of unknown origin, suggest that they result in loss of 12p segment.

Deletion of (7p13p14) in non-Hodgkin's lymphoma.

Deletion of the short arm of chromosome 7 at 7(p13p14) has been occasionally reported in non-Hodgkin's malignant lymphoma (NHL). The inclusion of this abnormality within the list of nonrandom changes awaited further data. We report three partial deletions of 7p with breakpoint at 7p13, found in various subtypes of NHL, and one deletion covering these bands (7p11 to 7p15). The association of 7p- with other chromosomal changes in the same NHL suggests that partial 7p deletion is a nonrandom secondary abnormality.

Cytogenetic studies of 44 T-cell acute lymphoblastic leukemias.

Cytogenetic studies on 44 patients with T-cell acute lymphoblastic leukemia (ALL) were reported. The incidence of leukemia without detectable chromosomal changes was 25%. Hyperdiploidy with more than 50 chromosomes was found in only one patient. Previously described nonrandom abnormalities like 6q-, 9p-, and 12p- were observed, and it was confirmed that they are not specific for a particular type of ALL. The incidence of chromosomal rearrangements on chromosomes 7 and 14 where the T-cell receptor gene loci are located was 36% of those with abnormal karyotypes and 27% of the total. This was clearly different from the frequency of rearrangements of these bands found in T-cell lymphoma. Finally, a rearrangement on bands 11q14-q21 was detected in five cases.

Secondary nonrandom chromosomal abnormalities of band 13q34 in Burkitt lymphoma-leukemia.

Clonal abnormalities of the long arm of chromosome 13 were detected in 9 of 54 patients with Burkitt lymphoma-leukemia. All abnormalities involved band 13q34, in three patients as t(1;13). The 13q34 abnormalities are thus the second most frequent secondary chromosomal abnormalities, after those of chromosome I, in these lymphoid proliferations.

Chromosomal rearrangement on chromosome 11q14-q21 in T cell acute lymphoblastic leukemia.

Deletion and translocation involving the bands 11q14 and 11q21 have been detected in five patients with T cell acute lymphoblastic leukemia (ALL). The breakpoint on chromosome 11 was on the same band as that previously described in some acute nonlymphocytic leukemias: monocytic or myelomocytic. The existence of a new nonrandom rearrangement involving bands 11q14-q21 is postulated in ALL. An unusual rearrangement on 11q13 in a patient with T cell ALL is also reported.

Cytogenetic studies on acute nonlymphocytic leukemia in relapse.

Karyotypic abnormalities were compared in 42 acute nonlymphocytic leukemia patients at diagnosis and in relapse. Clonal changes were observed in 21 cases. The types of changes were the appearance of clonal abnormalities in relapse in four patients without clonal changes at diagnosis, the detection of new abnormalities superimposed on preexisting ones in 11 cases, and the selection of an abnormal clone in six others. Nonclonal structural abnormalities, mainly involving chromosomes 17 and 12p, were detected in relapse in 17 patients, compared to seven at diagnosis. The appearance of totally new clonal changes at relapse and the role of individual sensitivity to chemotherapy are discussed.

Cytogenetic studies on 519 consecutive de novo acute nonlymphocytic leukemias.

Cytogenetic studies were performed in the same laboratory on 519 untreated cases of de novo acute nonlymphocytic leukemia (ANLL) between 1977 and 1985. The overall incidence of clonal chromosome abnormalities was 54.3%; higher in children (67.5%) than in adults (50.4%). The distribution of chromosome abnormalities was uneven, according to the categories of the FAB nomenclature. The highest frequency of chromosome changes was observed in ANLL-M3 and the lowest in M1 and M6. The frequency of specific chromosome abnormalities and of their associated changes were also estimated. Monosomy 7 was detected in three patients with acute megakaryocytic leukemia (M7). Six cases with two abnormal chromosomally unrelated clones were observed and six constitutional chromosome abnormalities were detected. A clearer knowledge of the incidence of various chromosomal changes in ANLL seems necessary for better differentiation between the so-called primary and secondary chromosome abnormalities and for prognostic evaluation.

Cytogenetic studies on patients with medullary carcinoma of the thyroid.

Cytogenetic studies were carried out on stimulated lymphocyte cultures of patients with medullary carcinoma of the thyroid. Of 32 patients studied, seven had a hereditary carcinoma, and five had multiple endocrine neoplasia type 2A and two had type 2B. Neither a constitutional chromosome abnormality nor an increase in chromosomal breakage were detected in these patients.

Abnormalities of the short arm of chromosome 12 in acute nonlymphocytic leukemia and dysmyelopoietic syndrome.

Abnormalities of the short arm of chromosome #12 (12p) were found in 18 patients, 7 with previously untreated acute nonlymphocytic leukemia (ANLL) and 11 with dysmyelopoietic syndromes (MDS) or ANLL following treatment for another malignant disease. The chromosome #12 abnormality was a partial deletion in 15 patients and a translocation in 3. The 12p- was the sole chromosomal abnormality in seven patients (four with de novo ANLL) and was associated with other chromosome abnormalities in eight patients. Thus, partial monosomy for 12p was often associated with other chromosomal changes and was a secondary abnormality in some cases. The consequences of this hemizygosity for genes located at 12p are discussed with references to the possible expression of a potentially mutated recessive gene. The study of c-K-ras 2, normally located at 12p, must be done in such cases, as the association of secondary blood disorders and multiple chromosome abnormalities suggests a possible mutation of this c-oncogene on chromosome #12.

Chromosome studies in polycythemia vera patients.

One hundred thirty-five polycythemia vera (PV) patients (30 untreated by chemotherapy and 105 treated) were studied cytogenetically . The incidence of clonal chromosomal abnormalities was 20.7% (28 patients in nonleukemic phase). The incidence of 20q - was 3.7% (5 patients). The presence of cytogenetically abnormal clones did not allow prediction of the evolution of the disease. In a few cases, abnormal clones disappeared at the time of later studies. Although nonrandom, the majority of clonal chromosomal abnormalities are believed to be secondary events in PV patients.

[Cytogenetics and acute non-lymphoblastic leukemias. Value of short-term cultures]. / Cytogénétique et leucémies aiguës non lymphoblastiques. Intérêt des cultures à court terme.

Normal and abnormal results of chromosome studies performed on 101 acute nonlymphoblastic leukemia (ANLL) patients were compared according to the bone marrow and/or blood cell culture times. A higher proportion of abnormal karyotypes was observed after culture than on direct preparations in acute promyelocytic leukemia and in acute myeloblastic leukemia with t(8-21) translocation; in some cases the chromosome abnormality seen after culture was not detected with the direct technique. No clear-cut differences in chromosome studies resulted when the differing techniques were applied to other forms of ANLL. In contrast the classification of individual patients into AA and AN categories differed in some cases when determined by direct or culture techniques. These results have to be taken into consideration in the study of relationships between chromosome anomalies and prognosis.

C-banding studies in acute nonlymphocytic leukemia.

C-Banding studies were performed on cells of 100 acute nonlymphocytic leukemia (ANLL) patients. No differences were found among patients in regard to age or sex. When compared to 70 healthy controls, an excess of a symmetrical distribution of 9qh was found, mainly due to an increased incidence of changes at level 2 according to the Patil and Lubs classification.