Revisiting the prognostic role of gallium scintigraphy in low-grade Non-Hodgkin’s lymphoma

The purpose of this study was threefold: to evaluate the role of gallium-67 scintigraphy in the staging of low-grade non-Hodgkin’s lymphomas (LGNHL), to assess the relationship between the expression of CD71 on the surface of the neoplastic cells and the ⁶⁷Ga uptake by the tumour, and to establish the contribution of ⁶⁷Ga scan in defining the prognosis of LGNHL. Forty-eight patients with untreated LGNHL diagnosed in a single institution over a decade were reviewed. The end point of the study was survival of the patients according to the scintigraphic ⁶⁷Ga score at diagnosis. In addition to ⁶⁷Ga scan, other prognostic variables were studied, relating to the neoplastic burden, the biology of the tumour and the host. Univariate and multivariate analyses were used. ⁶⁷Ga scan identified only 116/286 (41%) nodes involved by lymphoma that were detected by clinical examination or computed tomography scan. A scintigraphic scoring system with an arbitrary cut-off value of 3 (high scan score) was able to predict patients with a dismal prognosis: with a mean follow-up of 47 months (range: 1–146 months) the median survival time was 28 months in patients with a high scan score and 74 months in patients with a low scan score (P=0.002). CD71 values were 27.4%±14.9% (mean ±SD) in the former and 8.9%±7.2% in the latter (P=0.0001). Only performance status and extranodal sites were significant variables for prognosis in multivariate analysis. It is concluded that ⁶⁷Ga scan is inaccurate in staging but might be very important in defining the prognosis in LGNHL, in association with other prognostic variables. Received 1 May and in revised form 6 August 1997     

Prognostic value of pharmacological stress echocardiography in diabetic and nondiabetic patients with known or suspected coronary artery disease.

OBJECTIVES: We sought to compare the prognostic value of pharmacological stress echocardiography (SE) in diabetic and nondiabetic patients with known or suspected coronary artery disease. BACKGROUND: Although SE is a useful tool for risk stratification of patients with diabetes, it has not been established whether it retains the same prognostic information in diabetic patients compared with nondiabetic patients. METHODS: A total of 5,456 patients (749 diabetics) undergoing dipyridamole (n = 3,306) or dobutamine (n = 2,150) SE were prospectively followed up for the occurrence of hard events (death and/or nonfatal myocardial infarction). RESULTS: During a median time of 31 months, 411 deaths and 236 infarctions occurred. There were 132 events in diabetic patients and 515 in nondiabetic patients (18% vs. 11%, respectively; p < 0.0001). Moreover, 1,607 (29%) patients underwent coronary revascularization and were censored. Ischemia at SE, resting wall motion score index, and age were independent predictors of death and hard events in both diabetic and nondiabetic patients. Compared with a normal test, ischemia and scar test patterns were associated to significantly lower age-corrected five-year hard event-free survival in diabetic as well as nondiabetic patients. However, a normal test was associated with a greater than two-fold annual event rate in diabetic patients as compared with nondiabetics who were either younger (2.6% vs. 1.0%) or older (5.5% vs. 2.2%) than 65 years of age. CONCLUSIONS: Stress echocardiography is equally effective in risk stratifying diabetic and nondiabetic patients independently of age. However, the normal test result predicts a less favorable outcome in diabetic than in nondiabetic patients.     

Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study

BACKGROUND: Infertile women positive for thyroid antibodies suffer from a poor pregnancy/delivery outcome, although conflicting data have been published. Our objective was to investigate if levothyroxine (LT4) exerts any effect on pregnancy and/or delivery rates in thyroid peroxidase antibody (TPOAb)-positive (+) women undergoing assisted reproductive technologies. METHODS: Patients undergoing treatment were screened for TPOAb, thyroid-stimulating hormone (TSH) and free thyroxine (FT4). A total of 72 (15%) out of the 484 euthyroid women selected were TPOAb (+). These 72 patients were randomly divided into two groups: group A (n = 36) underwent LT4 treatment, group B (n = 36) placebo. Group C consisted of 412 women (85%) who were TPOAb negative (-). All patients received controlled ovarian stimulation. The endpoints of treatment were pregnancy rate, miscarriage rate and delivery rate. RESULTS: No differences in pregnancy rate were observed between the three groups. Miscarriage rate was higher in TPOAb (+) in comparison to TPOAb (-) [relative risk: 2.01 (95% CI = 1.13-3.56), P = 0.028]. CONCLUSIONS: The pregnancy rate is not affected either by presence of TPOAb or treatment with LT4. However, TPOAb (+) women show a poorer delivery rate compared to TPOAb (-). LT4 treatment in TPOAb (+) does not affect the delivery rate.     

Metallothionein (I+II) confers, via c-myc, immune plasticity in oldest mice: model of partial hepatectomy/liver regeneration

Because of its similarity to ageing in impaired immune efficiency 48 h after surgical procedures on young partially hepatectomised mice, partial hepatectomy/liver regeneration (pHx) provides a good model for the study of inflammation in ageing. In old age, high metallothionein (I+II) (MT) sequesters a substantial number of intracellular zinc ions consequently leading to low zinc ion bioavailability for an adequate immune response. Corticosterone and IL-6 affect MTmRNA induction in inflammation and after pHx against oxidative damage. The aim of this study was to investigate the role played by MT in conferring immune plasticity in ageing and in very old age using the pHx model. 48 h after their partial hepatectomy, the crude zinc balance was negative in young, old and very old mice coupled with increased MT, corticosterone, sIL-6R and IL-6. Concomitantly, Natural Killer (NK) cell activity and IL-2 production decreased. Complete restoration of the nutritional-endocrine-immune parameters occurred 15 days from the surgical procedures in young and very old mice, but not in old or transgenic mice overexpressing MT. A significant positive or inverse correlation among nutritional-endocrine-immune parameters exists in young and very old mice, but not in old mice during liver regeneration. Since MT also affects c-myc, the gene expression of c-myc declines from 48 h to days 7 and 15 after pHx in young and very old mice, but remains constantly high in old pHx mice for the same days. This circumstance leads to the appearance of tumours in the long run in old pHx mice and survival times that are shorter than old sham controls. Because complete remodelling also occurs in IL-6 and in sIL-6R in very old mice during liver regeneration, the pre-existing inflammation is not detrimental in very old age. As such, very old mice are still responsive to large inflammation, such as pHx, thanks to correct MT homeostasis. Correct MT homeostasis, via c-myc, is therefore pivotal in both suitable liver regeneration and in conferring immune plasticity with subsequent successful ageing. High MT plays an extremely harmful role in ageing: on one hand it lowers zinc ion bioavailability levels required for immune efficiency and on the other hand it increases c-myc expression. The combination of immune depression and enhanced c-myc, via high MT, may trigger the appearance of age-related degenerative diseases.     

Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity

Anaplastic large cell lymphomas are associated with chromosomal aberrations involving the anaplastic lymphoma kinase (ALK) gene at 2p23 that result in the expression of novel chimeric ALK proteins with transforming properties. In most of these tumors, the t(2;5)(p23;q35) generates the NPM-ALK fusion gene. However, several studies have now demonstrated that genes other than NPM may be fused to the ALK gene. We have recently described two different ALK rearrangements involving the TRK-fused gene (TFG) in which the same portion of ALK was fused to different length fragments of the 5' TFG region. These two rearrangements encoded chimeric proteins of 85 kd (TFG-ALK(S)) and 97 kd (TFG-ALK(L)), respectively. In this study, we have identified a new ALK rearrangement in which the catalytic domain of ALK was fused to a larger fragment of the TFG gene (TFG-ALK(XL)), encoding for a fusion protein of 113 kd. Genomic analysis of these three TFG-ALK rearrangements revealed that the TFG breakpoints occur at introns 3, 4, and 5, respectively, whereas the ALK breakpoints always occur in the same intron. No homologous regions or known recombination sequences were found in these regions. Transfection experiments using NIH-3T3 fibroblasts showed a similar transforming efficiency of TFG-ALK variants compared with NPM-ALK. In addition, in common with NPM-ALK, the TFG-ALK proteins formed stable complexes with the signaling proteins Grb2, Shc, and PLC-gamma. In conclusion, these findings indicate that the TFG may use a variety of intronic breakpoints in ALK rearrangements generating fusion proteins of different molecular weights, but with similar transforming potential than NPM-ALK.     

Development of an ELISA test for determination of the urinary trypsin inhibitor: analytical performance and applications

Increased urinary excretion of urinary trypsin inhibitor (UTI) has been reported in various inflammatory conditions and in Alzheimer's subjects, but its diagnostic potential remains to be elucidated. A reliable and specific enzyme-linked immunosorbent assay (ELISA) test for the determination of the UTI in human urine was developed. This assay was performed using 96-well microtiter plates. The plate surface is coated with an anti-UTI polyclonal antibody, the urine sample was added in a dilution range, and the detection was achieved using the enzyme-conjugated antibody. The assay was quantified by the build-up of colored product upon the addition of the substrate. Recoveries were 93%, and the intra- and inter-assay CVs were 4.25% and 21%, respectively. The ELISA showed parallelism of standard and urine samples and no significant interference by the biological matrix. The usefulness of the assay has been demonstrated by applying it to urine samples from Alzheimer's disease patients, and comparing with negative controls. UTI urinary levels are significantly increased in Alzheimer's subjects.     

Limb anomalies: Developmental and evolutionary aspects

In this review we describe the developmental mechanisms involved in the making of a limb, by focusing on the nature and types of interactions of the molecules that play a part in the regulation of limb patterning and characterizing clinical conditions that are known to result from the abnormal function of these molecules. The latter subject is divided into sections dealing with syndromal and nonsyndromal deficiencies, polydactylies, and brachydactylies. Conditions caused by mutations in homeobox genes and fibroblast growth factors and their receptor genes are listed separately. Since the process of limb development has been conserved for more than 300 millions years, with all the necessary adaptive modifications occurring throughout evolution, we also take into consideration the evolutionary aspects of limb development in terms of genetic repertoire, molecular pathways, and morphogenetic events.     

Prevalences, genotypes, and risk factors for HIV transmission in South America

HIV cross-sectional studies were conducted among high-risk populations in 9 countries of South America. Enzyme-linked immunosorbent assay screening and Western blot confirmatory testing were performed, and env heteroduplex mobility assay genotyping and DNA sequencing were performed on a subset of HIV-positive subjects. HIV prevalences were highest among men who have sex with men (MSM; 2.0%-27.8%) and were found to be associated with multiple partners, noninjection drug use (non-IDU), and sexually transmitted infections (STIs). By comparison, much lower prevalences were noted among female commercial sex workers (FCSWs; 0%-6.3%) and were associated mainly with a prior IDU and STI history. Env subtype B predominated among MSM throughout the region (more than 90% of strains), whereas env subtype F predominated among FCSWs in Argentina and male commercial sex workers in Uruguay (more than 50% of strains). A renewed effort in controlling STIs, especially among MSM groups, could significantly lessen the impact of the HIV epidemic in South America.     

Isolation and characterization of the thermoresistant gluconokinase from Escherichia coli

It is known that two gluconokinases are inducibly expressed during the utilization of gluconate by E. coli. One is thermoresistant (activity stable for 3 h at 30 °C) and the other thermosensitive (losses 75% or more of its activity under the above conditions). The thermoresistant gluconokinase (EC 2.7.1.12) was isolated, purified and characterized for the first time from the E. coli mutant Ca26, a K12 derivative which lacks the thermosensitive activity. The enzyme was purified 43 fold with a recovery of 11%. The M_r of the enzyme was 100 kDa with three equal subunits of approximately 29.5 kDa. The enzyme exhibited Michaelis-Menten kinetics and the K_m values for gluconate and ATP were 0.02 mM and 0.045 mM respectively.