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Biomedical subjects

A Morelli

Publications and source records attributed to A Morelli.

At least 109 records · Page 6Linked to original sources
PubMed1997

Gluten-free diet normalizes mouth-to-cecum transit of a caloric meal in adult patients with celiac disease.

The mechanisms responsible for bowel disturbances in celiac disease are still relatively unknown. Recent reports suggested that small bowel motor abnormalities may be involved in this pathological condition; however, there are no studies addressing small bowel transit in celiac disease before and after a gluten-free diet. We studied the mouth-to-cecum transit time of a caloric liquid meal in a homogeneous group of celiac patients presenting with clinical and biochemical evidence of malabsorption and complaining of diarrhea. Sixteen patients were recruited and investigated by means of hydrogen breath test through ingestion of 20 g lactulose together with an enteral gluten-free diet formula. A urinary D-xylose test was also done in each patient. Both breath tests and D-xylose tests were carried out basally and after a period of gluten-free diet. Twenty healthy volunteers were recruited as a control group and underwent the same breath testing. At the time of the diagnosis, mouth-to-cecum transit time was significantly prolonged in celiacs with respect to controls (243 +/- 10 vs 117 +/- 6 min, P = 0.0001). The D-xylose test was also abnormal (average urinary concentration 2.8 +/- 0.25 g, normal values >4.5). No correlation was found in patients between mouth-to-cecum transit time and urinary D-xylose output (r = 0.22). After the gluten-free diet period, mouth-to-cecum transit time in celiacs was significantly reduced compared to prediet transit (134 +/- 8 vs 243 +/- 10 min, P = 0.0001) and did not show statistical difference when compared to that found in controls (P = 0.1). The D-xylose test reverted to normal in all but two subjects, who were found to be noncompliant with the diet. Mouth-to-cecum transit time is significantly prolonged in patients affected by untreated celiac disease when compared to healthy controls. This alteration might not be correlated to intestinal malabsorption, and the prolonged orocecal transit could be due to impaired small bowel function (deranged motility?). Since intestinal transit returned to normal values after an adequate gluten-free period, a link with severe active mucosal lesions is suggestive.

Adult↗
PubMed1997

Ca(2+)-ATPase pump forms and an endogenous inhibitor in bovine brain synaptosomes.

Two forms of Ca(2+)-pump were identified in bovine brain synaptic membranes as aspartylphosphate intermediates and were characterized. The 140 kDa and 97 kDa phosphoproteins were digested by calpain, producing two phosphorylated fragments, of M.W. 124 and 80 kDa respectively, not inhibited by thapsigargin, and displayed a trypsin digestion pattern with the formation of one phosphorylatable fragment of about 80 kDa. These results suggest that both pumps belong to the Plasma Membrane-type of Ca2+ ATPases, differing from the Sarco- or Endoplasmic Reticulum kind. A plasma membrane Ca(2+)-ATPase proteinaceous inhibitor with molecular weight between 6,000 and 10,000 Da was resolved from synaptic terminal cytosol, where it is enriched by fourfold with respect to frontal cortex brain cytosol. Such enrichment is already evident in the correspondent crude fractions. The presence of calcium pump and its proteinaceous inhibitor inside the synaptic terminals from bovine brain is discussed in terms of free calcium level regulation in neuron synaptoplasm.

Animals↗
PubMed1997

NSAIDs upregulate beta 2-integrin expression on human neutrophils through a calcium-dependent pathway.

BACKGROUND: Margination of circulating neutrophils (PMN) into the gastric microcirculation is an early and critical event in the pathogenesis of non-steroidal antinflammatory drug (NSAID)-induced gastropathy. This effect is mediated through the upregulation of beta 2 integrins on the PMN surface. AIMS: To investigate whether indomethacin modulates: (1) Mac-1 expression; (2) Ca2+ mobilization ([Ca2+]i), protein kinase C and nitric oxide accumulation; and (3) mitogen-associated protein kinase phosphorylation in human PMN. METHODS: Human PMN were isolated by centrifugation through a double Ficoll gradient. [Ca2+]i was measured in PMN loaded with fura-2 and Mac-1 expression by flow cytometry. RESULTS: Indomethacin caused a concentration- and time-dependent upregulation of CD11b and CD18 expression and PMN adhesion to endothelial cells. Maximal upregulation of Mac-1 expression (40-50%) occurred after a 30-min incubation with 0.1mM indomethacin. The effect was prevented by removing the Ca2+. Ionomycin and thapsigargin caused a 7-10-fold increase in [Ca2+]i and a 2-4-fold increase in Mac-1 expression. Indomethacin induced a concentration-dependent phosphorylation of a 41-kDa mitogen-associated protein kinase. Tyrosine kinase inhibitors prevented the effect of indomethacin on Mac-1 expression and Ca2+ mobilization. Indomethacin and ionomycin increased superoxide generation, myeloperoxidase secretion and PMN adherence to endothelial cells and stimulated nitric oxide production. Indomethacin-induced Mac-1 upregulation was prevented by a nitric oxide synthase inhibitor. CONCLUSIONS: Indomethacin-induced upregulation of Mac-1 is mediated by changes in [Ca2+]i and nitric oxide. Phosphorylation of the 41-kDa mitogen-associated protein isoform is a previously unreported target of NSAID action. These effects might help to explain the ability of indomethacin to cause gastric neutrophil margination.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Autonomic dysfunction and upper digestive functional disorders in untreated adult coeliac disease.

There is recent evidence that upper-gut motor abnormalities may be present in coeliac disease. However, to date, the pathophysiological mechanisms responsible for the above have not been explored. The purpose of the present study was to investigate upper-gut motor activity in coeliac disease and explore the role played by the autonomic nervous system in motility disturbances. Thirty untreated adult coeliac patients were recruited into the study. Oesophageal manometry and cardiovascular autonomic tests were performed in all patients; oesophageal pH-metry was carried out in 20 patients, gastrointestinal manometry in eight and scintigraphic gastric emptying in 13. Oesophageal motor abnormalities were detected in about 50% of patients, pH-metry was abnormal in 30% of them, and up to 75% of coeliac patients displayed gastrointestinal motility alterations. Delayed gastric emptying was documented in about 50% of patients and was correlated with manometric post-prandial hypomotility. Autonomic tests were positive in 45% of patients as a group, and reached pathological score in 19% of them. Autonomic score correlated significantly with the percentage of bi-peaked waves and with the number of fasting intestinal clusters. This study confirms that upper-gut motor abnormalities are frequently present in adult coeliac disease. Extrinsec autonomic neuropathy may play a role, although other pathophysiological mechanisms are likely to occur.

Adolescent↗
PubMed1997

Expression of transgenes in normal and neoplastic anterior pituitary cells using recombinant adenoviruses: long term expression, cell cycle dependency, and effects on hormone secretion.

Adenovirus vectors have recently been used to transfer genes into a variety of cell types, including neurons, glial cells, Schwann cells, and epithelial cells. To evaluate the efficiency of gene transfer into pituitary cells using viral vectors, we used replication-deficient recombinant adenovirus vectors (RAds) encoding beta-galactosidase driven by various viral promoters. We tested the ability of RAds to infect and express beta-galactosidase within the different identified cell populations of the anterior pituitary anterior pituitary gland and also in tumor cells of anterior pituitary origin, i.e. GH3 and AtT20 cells. Our results demonstrate that transgenes encoded by RAds are expressed within all cell types of the adenohypophysis in vitro and also within AtT20 and GH3 endocrine tumor cells. Our long term expression studies indicate that long term expression with low cytotoxicity can be achieved, but that the longevity of transgene expression from RAds depends on the proliferative status of the target cells. Slowly dividing cells (endocrine population) express transgenes for longer than actively dividing cells (tumor cells and nonendocrine anterior pituitary cells). The ability of anterior pituitary cells to secrete ACTH or LH through the regulated secretory pathway decreased after infection with RAds at high multiplicity of infection (> or = 20 plaque-forming units/target cell), whereas cell viability was not affected. We also demonstrate that a higher percentage of cells expressed the transgene beta-galactosidase when we infected actively dividing GH3 cells compared with the infection of growth-arrested GH3 cells. This could reflect differential virus entry or differential activity of the individual promoters during different stages of the cell cycle. This work demonstrates that high efficiency gene transfer into all pituitary cell types can be achieved with RAds, and that this system can be exploited to characterize and experimentally manipulate pituitary-specific gene expression. The higher efficiency of infection and transgene expression in actively dividing cells compared to that in their growth-arrested counterparts could also be exploited for the treatment of pituitary adenomas that do not respond to classical treatment strategies, using suicide or cytotoxic gene therapy.

Adenoviridae↗
PubMed1997

Allelic loss in parathyroid tumors from individuals homozygous for multiple endocrine neoplasia type 1.

Homozygosity for the multiple endocrine neoplasia type 1 (MEN1) gene mutation was described in two of three affected siblings of a kindred in which both parents and the third daughter were heterozygotes. Surprisingly, in the two homozygotes, the disease history did not differ from the one of the heterozygotes. In the attempt to unravel genetic differences in parathyroid tumorigenesis between homozygotes and heterozygotes, restriction fragment length polymorphism analysis and microsatellite PCR analysis for loss of heterozygosity (LOH) at the MEN1 gene region on chromosome 11q13 was performed in parathyroid tissues removed at surgery from the mother, her heterozygous sister, and the three siblings. Allelic losses were evidenced in the larger glands of each patient, with a similar pattern of chromosome 11q12-13 losses. The somatic mutation consisted of a large lose of genetic material from chromosome 11. No gross differences exist in the 11q12-13 LOH observed between homozygous and heterozygous carriers. Interestingly, one of the parathyroid tumors from one heterozygote exhibited region of skipped LOH at the 11q12-13 region. The region in the depth of the critical interval retained heterozygosity, whereas those flanking it shared LOH. These findings indicate that inactivation of both copies of the MEN1 gene are not sufficient for parathyroid tumor development in MEN 1 patients and that tumor suppressor genes, other than the MEN1 gene on chromosome 11 or on other chromosomes, can be involved in the pathogenesis of parathyroid tumorigenesis in MEN 1 syndrome.

Chromosome Deletion↗
PubMed1997

Interferon plus ursodeoxycholic acid versus interferon in the treatment of chronic C viral hepatitis.

BACKGROUND: The aim of as study was to ascertain whether the association of interferon alpha-2a and ursodeoxycholic acid (IFN+UDCA) was more efficacious in ameliorating liver parameters than interferon (IFN) alone in patients with chronic hepatitis C. METHODS: Forty-one chronic hepatitis C patients, who had at least twice the normal value of one transaminase, were randomly assigned to treatment with IFN + UDCA (n = 21) or IFN alone (n = 20). IFN was administered subcutaneously at a dose of 3 MU thrice weekly, UDCA orally at 10 mg/kg bw/day. IFN therapy was terminated 6 months later and the responders (normalized transaminases) of both groups were treated with UDCA alone for a further 12 months. RESULTS: In the IFN + UDCA group there were 2 drop-outs from therapy and 11 responders, while in the IFN group they were, respectively, 3 and 10. Transaminases normalized after the first month of treatment in 7/11 responders with IFN + UDCA compared with 3/10 in the IFN responders group. The trend to normalization was more rapid with IFN + UDCA than with IFN alone (chi 2t = 3.95; p < 0.05). Disease relapse (defined as at least one transaminase > x 1.5 the normal value) was 3/11 in the IFN + UDCA group and 4/10 in the IFN group. 2/11 responders in the IFN + UDCA and 1/10 in the IFN group were HCV RNA negative by PCR. The total Knodell histological score decreased more in the IFN+UDCA than in the IFN group (-2.67 +/- 3.44. vs -1.67 +/- 2.16, mean +/- SD). CONCLUSIONS: The administration of UDCA determine an earlier normalization-time of transaminases in the patients responders to IFN therapy and could be useful to reduce the relapse into disease after the IFN therapy.

Adolescent↗
PubMed1996

Clonal analysis by chromosome 11 microsatellite-PCR of microdissected parathyroid tumors from MEN 1 patients.

Loss of heterozygosity (LOH) at chromosome 11q13 loci has been described in the majority of larger parathyroid tumors from patients affected by Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome. Since classical histology of the whole parathyroid gland does not permit a clear morpho-genetic correlation, the clonal composition of abnormal parathyroid tissue was analyzed in DNA obtained from single nodules and non-nodular areas within MEN 1 parathyroid lesions. Microdissected sections were analyzed by chromosome 11q13 microsatellite-PCR for LOH and by patterns of X-inactivation. We detected LOH for chromosome 11q13 loci in at least one microdissected area for each familial MEN 1 patient, but not in the single sporadic case. X-inactivation pattern of two "clonal" tumors exhibited a polyclonal cell composition of these microdissected samples, indicating the existence of a genetic heterogeneity in MEN 1 parathyroid microareas exhibiting a "clonal" pattern for allelic losses.

Adolescent↗
PubMed1996

Upper gastrointestinal motor activity in patients with slow-transit constipation. Further evidence for an enteric neuropathy.

Recent evidence indicates that patients complaining of severe chronic idiopathic constipation may have motor abnormalities not limited to the colon. We studied by manometric means gastric and small bowel motility in a homogeneous group of patients with chronic idiopathic constipation, ie, the slow transit type. Twenty-one patients were recruited for the study and compared to 33 healthy subjects. Manometric examination was carried out for about 5 hr fasting and 1 hr after a standard meal. Analysis of the manometric tracings revealed during fasting no abnormalities in number and configuration of migrating motor complex with respect to controls. However, in 70% of patients motor abnormalities were detected, represented by bursts of nonpropagated contractions and discrete clustered contractions. After feeding, the patient group displayed a significantly shorter antral motor response to the meal with respect to controls; moreover, intestinal bursts of nonpropagated contractions were found in 19% of patients, and 14% of them had an early return of the activity fronts. We conclude that patients with slow transit constipation frequently display motor abnormalities of the upper gut. These findings further strengthen the concept that this condition may represent a panenteric disorder.

Adult↗
PubMed1996

Flatus-related colorectal and anal motor events.

Although complaints of excessive "gas" symptoms are frequently encountered in clinical practice, the physiologic and pathophysiologic grounds of flatus events are poorly understood, partly because of the social taboos associated with the topic and partly because of technical difficulties in measuring flatus. For these reasons, we studied the colorectal and anal motor events occurring during artificially evoked flatus events and compared them to those that occurred spontaneously. Five healthy male volunteers were studied by multilumen probes placed in the left colon and rectum and across the anal canal, to observe the flatus-related motor events that occurred after instillation of air into the colon. Flatus-related spontaneously occurring motor events were also checked in 24-hr motility tracings obtained in three patients with functional bowel disorders. Analysis of the tracings showed that both artificially induced and spontaneously occurring flatus-related motor phenomena were characterized by colonic propagated contractions associated with a rise in rectal pressure and early relaxation of the anal sphincter, in a sequence resembling that observed following swallowing. Spontaneous flatus events were associated with colonic waves of lesser amplitude than those following insufflation of air into the colon.

Adult↗
PubMed1996

Characterization and function of the receptor for IGF-I in human preosteoclastic cells.

Using a coculture system, we have recently demonstrated that insulin-like growth factor I (IGF-I) is a mediator of preosteoclastic cell migration toward bone-derived endothelial cells. To better characterize the mechanisms of IGF-I action on preosteoclastic cells we evaluated the expression of type I IGFs receptor in the human leukemic cell line, FLG 29.1, which differentiates toward the osteoclastic phenotype following phorbol ester (TPA) treatment. Scatchard analysis of 125I-labeled IGF-I to FLG 29.1 cells revealed the presence of a single high affinity binding site in both untreated and TPA-treated cells with a similar Kd value (0.3 +/- 0.2 nmol/L and 0.4 +/- 0.1 nmol/L, respectively). In untreated cells, IGF-I binding capacity (1.43 +/- 0.41 fmol/10(6) cells) was significantly (p < 0.05) lower than in TPA-treated cells (2.62 +/- 0.87 fmol/10(6) cells). Competition analyses and crosslinking studies revealed the presence of type I IGF receptor both in untreated and TPA-treated cells. Northern analysis demonstrated that mRNA for IGF-I receptor was expressed by both untreated and TPA-treated FLG 29.1 cells. In addition, FLG 29.1 cells released in the conditioned medium IGFBP-2 and IGFBP-4, whose expression was increased by TPA treatment as demonstrated by ligand and immunoblot analyses. The previous observations of chemotactic action of IGF-I on FLG 29.1 cells was confirmed by ultrastructural observations. Indeed, these cells revealed a marked migratory activity in response to nanomolar concentrations of IGF-I. In addition, the IGF-I receptor alpha IR-3 antiserum inhibited the IGF-I-induced FLG 29.1 cell's migratory activity. These findings clearly show that type IIGF receptor is expressed by osteoclast precursors and that IGF-I induces migration of these through the binding to type I IGF receptors. Binding proteins expressed by osteoclast precursors may play an autocrine role in modulating the IGF-I bioeffects.

Adult↗
PubMed1996

Epidermal growth factor modulates pepsinogen secretion in guinea pig gastric chief cells.

BACKGROUND & AIMS: Although epidermal growth factor (EGF) inhibits gastric acid secretion, the effects it exerts on gastric chief cells are unknown. The aim of this study was to investigate whether EGF modulates pepsinogen release and intracellular Ca2+ concentrations ([Ca2+]i) and whether the effect involves mitogen-activated protein (MAP) kinase, eicosanoid generation, and nitric oxide. METHODS: Chief cells were obtained by sequential digestion with collagenase and Ca2+ chelation. [Ca2+]i was measured in cells loaded with Fura-2 and NO generation by the NO coproduct citrulline. RESULTS: In situ hybridization, immunohistochemistry, and immunoblotting showed that EGF receptor and MAP kinases were constitutively expressed in chief cells. EGF caused a concentration-dependent stimulation of pepsinogen secretion and MAP kinase activity and determined a 2.5-7.0-fold increase in [Ca2+]i, inositol 1,4,5-tryphosphate, prostaglandin E2, and leukotriene B4. Tyrosine kinase inhibitors and cyclooxygenase and lipoxygenase inhibitors reduced pepsinogen secretion and eicosanoid generation induced by EGF. EGF increased citrulline generation and guanosine 3',5'-cyclic monophosphate accumulation sixfold; the effect was blocked by NG monomethyl-L-arginine, which is an NO synthase inhibitor. CONCLUSIONS: EGF stimulates pepsinogen secretion by activating eicosanoid generation, tyrosine kinases, MAP kinases, Ca2+, NO, and guanosine 3',5'-cyclic monophosphate.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1996

Flow cytometric analysis of cytokine receptors on human Langerhans' cells. Changes observed after short-term culture.

It is well established that granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1 and tumour necrosis factor-alpha (TNF-alpha) are involved in Langerhans' cell (LC) development and dendritic cell traffic. However, little is known about the pattern of cytokine receptors on human LC and their modulation during different stages of maturation. The expression of cytokine receptors was studied by flow cytometry on both freshly isolated LC (fLC) and 72-hr cultured LC (cLC). Epidermal cell suspensions enriched in LC were obtained after skin trypsinization and Ficoll-Hypaque gradient. LC were identified by their CD1a positivity. Although the majority of fLC were positive for the alpha chain of GM-CSF receptor (GM-CSFR), the beta chain of GM-CSFR was detected only on 15% of CD1a+ cells. fLC were also positive for IL-1 receptor (IL-1R) type 1, IL-1R type 2, 75,000 molecular weight TNF receptor (TNFR) and interferon-gamma receptor (IFN-gamma R). IL-6R and its transducing signal gp130 were present in a subset of fLC. Granulocyte colony-stimulating factor receptor (G-CSFR), macrophage colony-stimulating factor receptor (M-CSFR), the alpha and beta chain of IL-2R, IL-4R, IL-7R, IL-8R and 55,000 molecular weight TNFR were not detected on fLC. After culture, LC up-regulated the expression of both the alpha and beta chains of GM-CSFR, IL-1R type 2, alpha and beta chains of IL-2R, IL-6R and gp130. In contrast, IL-1R type 1 and 75,000 molecular weight TNFR were down-modulated and the expression of IFN-gamma R was not affected by culture. These results suggest that LC undergo changes in the cytokine receptor repertory during in vitro maturation.

Antibodies, Monoclonal↗
PubMed1996

Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells.

Although it is known that dendritic cells (DC) migrate in response to inflammatory stimuli. There is little information about the expression of receptors for chemotactic factors on DC. The present study has demonstrated by double immunostaining and flow cytometry of Langerhan's cell (LC)-enriched epidermal cell suspensions that a small subpopulation (5-6%) of epidermal resident DC (rLC) expresses receptors for C5a (C5aR). Epidermal rLC positive for C5aR show a round-shape morphology, were located next to the basement membrane and express HLA-DR molecules higher than C5aR negative rLC. These observations suggest that rLC would express C5aR as part of their process of maturation during tissue trafficking. To investigate whether epidermal LC up-regulate C5aR along their differentiation pathway. LC were differentiated in vitro after culture in epidermal cell suspensions supplemented with granulocyte macrophage colony-stimulating factor (GM-CSF). As a result, in vitro differentiated LC increased the expression of C5aR up to 69% of the DC population. In accordance with this observation, interdigitating DC of secondary lymphoid organs (lymph node and tonsil) also expressed (5aR. Migratory CD1a positive DC that spontaneously migrated out of dermal or split-skin organ explants were also positive for C5aR and were used for chemotaxis and chemokinesis assays in response to human recombinant C5a (rC5a). Optimum migration to rC5a was observed at 10(-8)M with a sigmoidal dose response curve. Checkboard analysis demonstrated that locomotion in response to rC5a was chemotaxis and not chemokinesis.

Antigens, CD↗
PubMed1996

Interleukin 10 reduces lethality and hepatic injury induced by lipopolysaccharide in galactosamine-sensitized mice.

BACKGROUND & AIMS: Tumor necrosis factor alpha (TNF-alpha) release plays a pivotal role in the pathogenesis of liver injury induced by lipopolysaccharide (LPS) administration in D-galactosamine (GalN)-sensitized mice. Interleukin (IL) 10 is an anti-inflammatory cytokine that inhibits TNF-alpha synthesis and release both in vitro and in vivo and prevents lethality from experimental endotoxemia. The present study was designed to ascertain whether in vivo treatment with IL-10 protects mice against LPS/GalN-induced liver injury. METHODS: Mice were treated with an intraperitoneal dose of LPS/GalN with or without IL-10 pretreatment. Liver injury was assessed biochemically and histologically, and plasma TNF-alpha levels, liver myeloperoxidase activity, and adhesion molecule expression were determined. RESULTS: Administration of LPS in GalN-sensitized mice caused lethal shock and massive hepatic necrosis in almost 100% of the mice. The effect was associated with a significant increase in plasma TNF-alpha concentrations, liver myeloperoxidase activity, and up-regulation of adhesion molecules on liver specimens and circulating neutrophils. Pretreatment with IL-10 reduced plasma TNF-alpha concentrations and LPS/GalN-induced liver injury and lethality. Moreover, IL-10 reduced the LPS/GalN-induced liver neutrophil margination and up-regulation of adhesion molecules both on liver specimens and circulating neutrophils. CONCLUSIONS: The present results suggest that IL-10 therapy could be useful in the treatment of TNF-alpha-mediated liver diseases.

Animals↗
PubMed1996

All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells.

Leukemic cells spontaneously secrete cytokines involved in the proliferation of the clone; in this study we evaluated the effects of all-trans retinoic acid (ATRA) on the in vitro autocrine production of cytokines by acute myeloid leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20 ANLL of other cytotypes than APL) were studied; the in vitro secretions of IL-1 alpha, IL-3, IL-4, IL-6, IL-10, G-CSF, GM-CSF, TNF-alpha were tested with and without ATRA addition. After 5 d exposure to ATRA 10(-6) M APL-treated samples showed a significant reduction of IL-6 (p = 0.008) and GM-CSF (p = 0.03) and a significant increase of IL-1 alpha (p = 0.01) production, if compared to untreated APL samples. No difference was seen in IL-3, IL-10 and IL-4 productions; G-CSF production resulted absent in all but 3 APL cases, in which addition of ATRA determined increase in the production. Interestingly, the 3 G-CSF-producing cases did not obtain clinical remission with ATRA; GM-CSF and IL-6 were spontaneously produced by all the cases, and 7 of 10 APL patients subsequently obtained complete remission after induction. TNF-alpha was produced only in 1 case. No statistical difference was seen in all the productions obtained from other than promyelocytic acute leukemic cells, both with and without ATRA addition. However, it is noteworthy that the production of IL-6 was more than twice as high in ANLL non-APL than in APL cases. In conclusion, these data could thus suggest possible complementary mechanisms of the exhaustion of the leukemic clone upon treatment with ATRA.

Bone Marrow↗
PubMed1996

Clinical implications of serum levels of soluble CD23 and tumor necrosis factor alpha in low-grade non-Hodgkin's lymphoma.

In the last few years the research for new biological features in low-grade non-Hodgkin's lymphoma has provided important results. Several biological parameters are under evaluation and, in particular, cytokines and soluble receptors levels are showing their importance as prognostic parameters. In the present study, serum levels of tumor necrosis factor alpha (TNF-alpha) and soluble CD23 (sCD23) were measured at the time of diagnosis and after induction polychemotherapy in 40 patients with newly diagnosed low-grade non-Hodgkin's lymphoma (LG-NHL). The treatments were CIOP (cyclophosphamide, idarubicin, vincristine, prednisone) regimen for 28 patients and FMP (fludarabine, mitoxantrone, prednisone) scheme for 12 patients. Pretreatment levels of TNF-alpha were highly elevated in patiets with LG-NHL compared with healthy controls (p = 0.005) and were significantly correlated with the Ann Arbor stage (p = 0.001). sCD23 was detected in 35 patients at diagnosis and were markedly increased in LG-NHL patients when compared to healthy controls (p = 0.005); patients with advanced stage presented higher values than those with early stage disease (p = 0.002). All the complete responders (20/40, 50%) showed a decrease of TNF-alpha and sCD23 levels. By contrast, the combination of high levels of TNF-alpha and sCD23 correspond to a group of non-responders. Our results suggest that TNF-alpha and sCD23 are specific prognostic parameters for LG-NHL, and that they could be used as tumor markers within a potential biological prognostic index.

Adolescent↗