CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells.

Homing of chronic lymphocytic leukemia (CLL) cells to sites favoring growth, a critical step in disease progression, is principally coordinated by the CXCL12/CXCR4 axis. A cohort of 62 CLL patients was divided into migrating and nonmigrating subsets according to chemotaxis toward CXCL12. Migrating patients phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) proteins more than nonmigrating patients (P<0.0002). CD38 expression was the parameter most strongly associated with heightened CXCL12 signaling (P<0.0001), confirmed by independent statistical approaches. Consistent with this observation, CD38(-) CLL cells in samples with bimodal CD38 expression responded less to CXCL12 than the intact clone (P=0.003). Furthermore, lentivirus-induced de novo expression of CD38 was paralleled by increased responses to CXCL12, as compared with cells infected with a control virus. CD38 ligation with agonistic monoclonal antibodies (mAbs) enhanced CXCL12 signaling, whereas blocking anti-CD38 mAbs inhibited chemokine effects in vitro. This is attributed to physical proximity on the membrane between CD38 and CXCR4 (the CXCL12 receptor), as shown by (i) coimmunoprecipitation and (ii) confocal microscopy experiments. Blocking anti-CD38 mAbs significantly compromised homing of CLL cells from blood to lymphoid organs in a mouse model. These results indicate that CD38 synergizes with the CXCR4 pathway and support the working hypothesis that migration is a central step in disease progression.

Measurement of bile acid half-life using [75Se]HCAT in health and intestinal diseases. Comparison with [75Se]HCAT abdominal retention methods.

The diagnostic values in detecting terminal ileum dysfunction using [75Se]HCAT have been assessed for two different scintigraphic techniques in 58 subjects. The measurement of [75Se]HCAT T1/2 in the enterohepatic circulation by daily gallbladder scintigraphy showed 78% sensitivity, 96% specificity, 96% positive predictive value, and 78% negative predictive value at the optimal cutoff level of 2.0 days; lower--but not significantly different--figures were observed for [75Se]HCAT total abdominal retention four and seven days after isotope administration, at the optimal cutoff levels of 40% and 22%, respectively. [75Se]HCAT T1/2 was then evaluated in 60 patients with various intestinal diseases. Sixty-nine percent (9/13) of patients with diarrhea of obscure origin showed abnormal [75Se]HCAT T1/2. Bile acid malabsorption using [75Se]HCAT can be investigated by the noninvasive measurement of its enterohepatic T1/2 and may play a pathogenetic role in patients with diarrhea of obscure origin.

[Diagnosis of bacterial contamination of the small intestine using the 1 g [14C] xylose breath test in various gastrointestinal diseases]. / La diagnosi di contaminazione batterica del tenue mediante il test respiratorio con 1 g di [14C] xilosio in varie patologie gastrointestinali.

The prevalence of the small intestine bacterial overgrowth syndrome has been assessed in 109 in-patients affected by various gastrointestinal disorders using the 1 g [14C]-xylose breath test; 18 healthy subjects acted as a control group: none of them showed abnormal results (100% specificity). None of 14 patients with colonic disease had abnormal results, whereas in 44 patients with ileal diseases the test was positive in 12% to 39% of the cases. Abnormal results were found in 46% of patients who underwent partial gastric resection greater than 20 years before, 29% of patients with irritable bowel syndrome without diarrhoea (faecal wet weight less than or equal to 600 g/72 h), 56% of those with diarrhoea of obscure origin, and 25% of celiac patients. Eight out of 8 patients with altered results showed normalization of the test after antibiotic therapy. Despite its high diagnostic value in the setting of clinical research, the 1 g [14C]-xylose breath test cannot as yet be proposed as a routine investigation.

An association of primary hyperparathyroidism and non medullary thyroid carcinoma.

A 40-year-old woman was admitted because of long-lasting asymptomatic hypercalcaemia. About 2 years earlier she underwent thyroidectomy and further 131 I therapy because of well-differentiated non medullary thyroid carcinoma. On admission biochemical data and hormonal values (serum calcium, serum phosphorus, i-PTH) were consistent with primary hyperparathyroidism; ultrasonography, computed tomography, thallium-technetium scintiscanning disclosed right paratracheal mass; on surgical procedure a right parathyroid adenoma was removed. The coexistence of non medullary thyroid carcinoma and primary hyperparathyroidism is rare: the prior 131 I therapy might be linked to subsequent development of parathyroid adenoma.

Multifactorial study of prognostic factors in differentiated thyroid carcinoma.

Using survival corrected for intercurrent deaths as an endpoint, the prognostic significance of age, sex, histology, clinical extent of disease, size of primary tumor, type and result of treatment, was assessed in a series of 133 patients with differentiated thyroid carcinomas treated over a 16-year period. The following parameters were shown to be unfavourably related to survival: old age, follicular moderately-differentiated histological type, extrathyroid growth of the primary tumor and/or presence of distant metastases at diagnosis. In patients not cured after surgery, postoperative radioiodine therapy was correlated with, better survival rates. A multivariate statistical analysis (Cox model) showed that tumor stage and age at diagnosis were the major determinants of prognosis. Based on this data a risk index was worked out and three low/intermediate/high risk subgroups, characterized by significantly different survival rates, were identified in the study population.

[Treatment of differentiated carcinoma of the thyroid gland]. / Il trattamento del carcinoma differenziato della tiroide.

In this paper the Authors, after a description of the prognostic factors in patients with differentiated thyroid carcinoma, propose a rationale for the therapy. The role of surgery, radioiodine treatment, endocrine therapy, radiotherapy and chemotherapy is described. The follow-up for the disease is briefly outlined. The authors suggest that treatment and follow-up protocols should be in accordance with the prognostic factors.

Comparison of chromosome aberration frequency before and after administration of 131I in two groups of thyroid cancer patients.

The chromosome aberration frequencies of 10 thyroid cancer patients, before and after their first radioiodine treatment (group A), were compared to the frequencies found in another 10 subjects previously treated with two or more radioiodine administrations (group B). Our data show that the relative increase in chromosome-type aberrations was similar in the two groups: from 2.0% to 3.7% (group A) and from 4.7% to 9.0% (group B). However, the increase in the number of cells with aberrations was greater in group A. Moreover, the higher frequency of aberrations in group B, even before the radioiodine treatment, points out the effect of previous treatments and demonstrates the persistence of this type of lesion. The sister chromatid exchange frequency in the two groups was also analysed, but no effect bound to the radioiodine treatment could be demonstrated.

131I-metaiodobenzylguanidine treatment in neuroblastoma: report of two cases.

Poor results with 131I-meta-iodobenzylguanidine (MIBG) therapy have been obtained in two children with stage IV neuroblastoma treated after partial surgery and unsatisfactory combination chemotherapy. Both patients' response to treatment (four and three 1-month-spaced courses, respectively; cumulative administration of 11.9 and 9.2 GBq) has been characterized by a low isotope concentration in the primary tumor and in the multiple bone metastases and by bone marrow uptake with final severe hematological toxicity. A slight decrease in the primary tumor's volume was observed in one patient at a cumulative dose of 85 Gy; there was no change in the other's at 42 Gy. At an initial, greater isotope concentration delivering 103 Gy, some bone metastases displayed a sharp decrease in uptake that persisted in the successive courses. For both patients a progressive spreading of new tumor localisation in the bones and finally in the soft tissues was observed.

[Current clinical use of radioisotopes in the study of platelet kinetics]. / Attualità sull'utilizzazione clinica delle indagini radioisotopiche nello studio della cinetica piastrinica.

Radioisotopic study of platelet kinetics can provide a preliminary orientation in the diagnosis of thrombocytopenia. A study of the platelet kinetics in thrombocytopenic and normal subjects using the Cr51 isologous platelet labelling technique and subsequent in vivo injection of the labelled platelets was conducted. The results obtained confirm the reliability and usefulness of the technique. The identification of the limitations involved and the recognition of their significance in processing data allows the hematologist and the general practitioner to allow the right amount of room for the study of platelet kinetics in the diagnosis of thrombocytopenia.

Analysis of cell kinetics, chromosome aberration frequency and sister chromatid exchanges in lymphocyte "in vitro" cultures of patients irradiated by 131I. Preliminary note.

In the present note we analyse the possible effect of 131I administration on lymphocyte cultures or patients previously subjected to thyroidectomy because of carcinoma. Three parameters were taken into consideration: cell kinetics, SCE frequency and chromosome aberrations frequency before and after treatment. It is possible to point out only an increase of chromosome aberrations. Our data stress the importance of considering several variables at the same time when we are faced with the problem of evaluating possible DNA damage.