Biomedical subjects
Publications and source records attributed to A Pinto.
A 20-year-old man with massive ileal enterolithiasis was investigated with plain radiography, ultrasound, computed tomography, barium follow through and double contrast barium enema. Ileocecal valve agenesis was found at surgery. The enteroliths were located in the distal ileum, which communicated with the large intestine via an ileotransverse fistula.
Intrarenal manometry (IRM) using the Salaman fine-needle technique was routinely performed in 28 renal transplant patients in order to make the differential diagnosis of acute tubular necrosis, cyclosporin nephrotoxocity, and acute rejection. A total of 246 IRM determinations with simultaneous percutaneous renal biopsies were obtained in cases of acute renal failure following a renal transplant. Normal IRM values were 21.4 +/- 1.3 mm Hg. After collecting the clinical data, cyclosporin levels, ultrasound information, response to therapy, and renal biopsy results, we retrospectively obtained 49 IRM measurements in acute rejection, 9 in cyclosporin nephrotoxicity, and 26 in acute tubular necrosis. The values in acute rejection (41.3 +/- 9.5 mm Hg) were significantly different from the normally functioning kidneys, cyclosporin nephrotoxicity, or acute tubular necrosis. The values in cyclosporin nephrotoxicity were slightly elevated when compared to the normal or acute tubular necrosis determinations (p < 0.04) but were still significantly lower than the acute rejection. Our results suggest that IRM represents a useful technique in the approach to the acute renal dysfunction in renal transplant recipients.
CD40 is a 48 Kd integral membrane protein expressed by cells of B cells, origin, dentritic cells, monocytes, epithelial cells, endothelial cells and tumor cells including carcinomas, B cell lymphomas/leukemias and Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD). CD40 has been clustered as a member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily with the corresponding counterstructure, the CD40 ligand (L) being mainly expressed by activated CD4+ T cells, but also some activated CD8+ T cells, basophils, eosinophils, mast cells and stromal cells. CD40L shares significant amino acid homology with TNF particularly in its extracellular domain ("TNF homology region") and is therefore viewed as a member of the TNF ligand superfamily. Binding of CD40L+ T cells to CD40+ B cells is thought to play a major role in T cell-dependent B cell activation, B cell proliferation, Ig isotype switching, memory B cell formation and rescue of B cells from apoptotic death in germinal centers. Mutations of the CD40L gene have been associated with the X-linked hyper-IgM immunodeficiency syndrome, pointing to the critical role of the CD40/CD40L interaction in the T cell-B cell interplay. Accordingly, expression of CD40 by human lympho-hematopoietic tumors has been shown in most of the B cell neoplasias, H-RS cells and HD and some carcinomas. In contrast, CD40L+ tumor cells are almost invariably restricted to CD4+/CD8- T cell lymphomas. Overall, functional CD40/CD40L interactions appear to be critical for cellular activation signals during immune responses and neoplastic tumor cell growth. The understanding of the biology of CD40L has improved our diagnostic and therapeutic repertoire in the management of several human diseases, including CD40+ tumors.
A serological survey for antibodies to Leptospira spp. was conducted on sheep, goat and dog serum samples collected in three localities in Cordillera province in the southern part of the Santa Cruz Department (Bolivia) in 1992. A total of 98 sheep, 218 goats and 43 dogs were tested against 29 leptospiral serovars using the microscopic agglutination test. At the time of blood collection all of the examined animals appeared healthy and presented no clinical sign suggestive of leptospirosis. Antibody prevalences, as determined by positive results at a 1:100 dilution or higher, was 14.3% in sheep, 19.7% in goats, and 14.0% in dogs. Agglutinins against six serovars (poi. shermani, pomona, canicola, javanica, djasiman) were found in positive animals. The highest serological prevalence in sheep and goats was recorded for serovar poi, followed by pomona in sheep and shermani in goats. Titres to shermani were the commonest in dogs. The results of this survey indicate that leptospiral infection is common in south-east Bolivia and that serovars of several serogroups concur in the etiology.
BACKGROUND: Even though the presence of a prominent tissue eosinophilia represents a common histopathologic feature of Hodgkin's disease (HD), eosinophils have been mainly regarded as 'innocent' bystanders recruited and activated during the cellular reaction typical of HD. To evaluate the putative role of eosinophils or eosinophil-derived cytokines on tumor-cell regulation in HD, we have analyzed these cells for the functional expression of surface ligands (L) of the tumor necrosis factor (TNF) superfamily, whose specific receptors are known to transduce proliferation signals at the surface of Hodgkin (H) and Reed-Sternberg (RS) cells. MATERIALS AND METHODS: Eosinophils from peripheral blood of healthy donors and patients with HD, primary hypereosinophilic syndrome (HES), or secondary hypereosinophilia (HE), were purified by density gradient centrifugation and immunomagnetic depletion of residual granulocytes. RESULTS: By immunostaining and mRNA analysis, we were able to show that eosinophils from normal donors and patients with HD, HES, and HE express a number of receptors and ligands of the TNF superfamily, including CD40, CD40L, CD30L, CD95/Fas, CD95/FasL and 4-1BB. In addition, we provide evidence that cytokines regulating eosinophil proliferation and activation, i.e., interleukin (IL)-5, IL-3, and granulocyte-macrophage colony-stimulating factor, are able to enhance the cellular density of several TNF superfamily ligands and/or receptors at the surface of cultured eosinophils. Finally, we have shown that native CD40L and CD30L at the surface of purified eosinophils are functionally active and able to transduce proliferative signals on CD40+ and CD30+ target cells, including cultured H-RS cells. CONCLUSIONS: Our data suggest that eosinophils may act as important elements in the pathology of HD by providing cellular ligands for TNF-superfamily receptors (CD40, CD30, CD95/Fas) able to transduce proliferation and antiapoptotic signals at the surface of H-RS cells. The presence on eosinophils of receptors for TNF ligands expressed by activated T cells (i.e., OX40L, FasL, CD40L, 4-1BBL), also suggest that eosinophils may contribute to the deregulated network of interactive signals between H-RS cells, T cells, and other surrounding reactive cells.
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The hypoglycemic effect of a Copalchi extract (Sucontral) was tested in 60 adult-male and female-Wistar rats in the present randomized, placebo-controlled, parallel-comparative animal study. A control group receiving only an Altromin standard chow was compared to treatment groups which received an Altromin chow enriched with Copalchi dry substance at 0.028% m/m or at 0.28% m/m. The study period was 30 days. The distinctly significant blood glucose lowering effect of the Copalchi extract could be demonstrated in both treatment groups. No significant difference in the antidiabetic effect was seen between the two concentrations. The onset of action of the Copalchi extract was observed between treatment day 1 and 3. A 20-25% decrease in the blood glucose concentration was achieved between the 7th and 15th day of treatment and remained at this level thereafter. This plateau was reached in the female rats already between treatment day 3 and 5. The parallel observed increase in the mean body weight was not striking and generally was the same between the test animals and the control animals.
After considering the clinical and physiopathological aspects of Raynaud's phenomenon, the authors have evaluated the medium effects of therazosine in 2 groups of patients, respectively with idiopathic and secondary Raynaud's phenomenon. The results show that the therazosin determines a decrease of number, intensity and duration of vasospastic attacks to the hands as well as an improvement of telethermographic and ultrasonographic findings.
Ischemic bowel disease is a rare disorder whose incidence is increasing as the mean age of the population increases. Diagnosis by clinical, laboratory and radiologic means is often difficult, and delay in definitive therapy results in substantial morbidity and mortality. A series of 26 consecutive patients, with proved acute superior mesenteric ischemia, was retrospectively reviewed: the authors report the diagnostic methods performed preoperatively, the site and the cause of infarction and the time passed between the first radiograph ans surgery. Plain abdominal radiographs were performed in 25 of 26 patients, screening abdominal US in 23 cases and CT in 19 cases. All radiological examinations were retrospectively reviewed by three authors, independently, to recognize the different signs of infarction. On plain abdominal films, the findings warranting a presumptive diagnosis of bowel infarction were air-fluid levels (84% of cases), dilated bowel loops (48%), thickened and unchanging loops (20%), gastric distension and gasless abdomen (12%), small bowel pseudo-obstruction (8%). Screening abdominal US demonstrated intraperitoneal free fluid (26%) and dilated bowel loops (22%). Abdominal CT showed air-fluid levels (79%), dilated loops and free intraperitoneal fluid (47%), intramural gas and thickened bowel loops (36.8%), engorgement of the mesenteric vessels (31%), mesenteric-portal gas, mesenteric thrombus and marked reduction in the volume of gas in the small bowel (10.5%) and paper-thin bowel loops (5%). The authors conclude that air-fluid levels, dilated loops and intraperitoneal free fluid are the most frequent findings, even though they are not specific. While abdominal plain film and screening ultrasonography can be negative, CT detects at least one abnormal finding and at least three abnormal findings in 73% of cases.
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The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-6 on clonogenic growth of blast-cell progenitors from 19 immunologically defined CD10-positive B-lineage acute lymphoblastic leukemias (ALL) coexpressing (My+ALLs) or not (My-ALLs) myeloid antigens have been studied. Our results demonstrate that GM-CSF was able to support the clonogenic growth of blast cells from My+ALLs, being totally ineffective on My-All samples. Accordingly, both alpha and beta chains of GM-CSF receptor (R) were expressed by My+ALL blasts, as investigated by reverse-transcriptase polymerase chain reaction (RT-PCR). Colony cells from GM-CSF-stimulated My+ALL cultures displayed the same immunophenotype as primary leukemic cells at diagnosis (CD10+, CD19+, CD22+), and retained the expression of myeloid-associated antigens and of GM-CSF-R transcripts. Moreover, My+ALL blasts showed a preferential sensitivity to the growth-promoting activity of IL-3 and IL-6, as compared with My-ALL cells. In addition to rearrangements of the JH region of immunoglobulin genes, My+ALL cells showed aberrant rearrangements of gamma (three cases) and beta (two cases) T-cell receptor genes, as well as of bcr sequences (three cases). Our data, showing an unexpected cross-lineage response of My+ALLs to GM-CSF, and their preferential stimulation by IL-3 and IL-6, as compared with My-ALLs, further support the concept that My+ALLs represent a separate entity with unique biological features.
BACKGROUND: DNA methylation and DNA cytometric parameters were evaluated in the rectal mucosa from patients with extensive and long-standing ulcerative colitis. METHODS: Twenty-six patients with extensive disease for more than 7 years and 11 healthy controls were included. Global DNA methylation was assessed as the capacity of the DNA test to incorporate [3H]methyl groups from [3H]-S-adenosyl-methionine in the presence of Sss1 methylase. A higher incorporation reflects a lower state of intrinsic methylation. DNA ploidy, S-phase fraction, and proliferative index (PI = S + G2M) of the cell cycle were analyzed by flow cytometry. RESULTS: Incorporation of the [3H]methyl groups into DNA was 10-fold higher in patients compared with controls (P < 0.001) and was significantly higher in patients with histologically active disease (P = 0.02). With regard to flow cytometry, all samples showed a diploid pattern, but S-phase fraction and the proliferative index values were significantly increased in patients compared with controls (P = 0.0007 and P = 0.003, respectively). A positive correlation was found between S-phase fraction and proliferative index and the number of exacerbations of the disease (P < 0.005), and there was a trend among those patients who had disease for longer than 20 years to present with increased cellular proliferation compared with those with a shorter evolution of disease (P > 0.05). CONCLUSIONS: DNA hypomethylation and proliferative activity are increased in this group of patients, supporting the concept that their colonic mucosa undergoes epigenetic and kinetic changes that might predispose these individuals to develop colorectal neoplasms. However, it cannot be ruled out that these markers solely reflect hyperproliferation associated with active inflammation.
The presence of a prominent tissue eosinophilia represents a typical histopathologic hallmark of Hodgkin's disease (HD). To evaluate the putative role of eosinophils on tumor cell regulation in HD, we have analyzed these cells for the functional expression of CD30 ligand (CD30L), a surface molecule able to transduce CD30-mediated proliferation signals on Hodgkin's (H) and Reed-Sternberg (RS) cells. The results demonstrate that circulating and tissue eosinophils from normal donors and patients with HD or hypereosinophilic syndrome (HES), display CD30L mRNA and express CD30L protein, as shown by immunostaining with a specific monoclonal antibody (M80) and with a biotinylated soluble CD30-Fc fusion protein. The surface density of CD30L on eosinophils from HD and HES patients was remarkably higher compared with healthy donors, probably reflecting a cytokine-mediated upregulation in these pathologic conditions. Accordingly, we provide evidence that cytokines regulating eosinophils proliferation and activation, ie, interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF), are able to enhance the cellular density of CD30L on purified eosinophils from normal subjects. Finally, we show that native CD30L on human eosinophils is a functionally active surface structure able to transduce proliferative signals on CD30+ target cells, including cultured H-RS cells. Our data suggest that eosinophils may not merely represent innocent bystanders, but rather act as important elements in the pathology of HD by contributing to the deregulated network of CD30/CD30L-mediated interactive signals between H-RS cells and surrounding reactive cells.
The block of terminal differentiation is a prominent feature of acute promyelocytic leukemia (APL) and its release by retinoic acid correlates with disease remission. Expression of the APL-specific PML/RARalpha fusion protein in hematopoietic precursor cell lines blocks terminal differentiation, suggesting that PML/ RARalpha may have the same activity in APL blasts. We expressed different PML/RARalpha mutants in U937 and TF-1 cells and demonstrated that the integrity of the PML protein dimerization and RARalpha DNA binding domains is crucial for the differentiation block induced by PML/RARalpha, and that these domains exert their functions only within the context of the fusion protein. Analysis of the in vivo dimerization and cell localization properties of the PML/RARalpha mutants revealed that PML/RARalpha--PML and PML/RARalpha--RXR heterodimers are not necessary for PML/RARalpha activity on differentiation. We propose that a crucial mechanism underlying PML/RARalpha oncogenic activity is the deregulation of a transcription factor, RARalpha, through its fusion with the dimerization interface of another nuclear protein, PML.
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The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein is rearranged in about 30% diffuse large B-cell lymphomas and is expressed predominantly in normal germinal center B cells and related lymphomas. These findings suggest that BCL-6 may play a role in regulating differentiation of normal germinal center B cells and that its deregulated expression caused by rearrangements may contribute to lymphomagenesis. This prompted us to investigate the expression of the BCL-6 protein in Hodgkin's disease (HD), focusing on the nodular lymphocyte predominance subtype (NLPHD), which differs from classical HD by virtue of the B-cell nature of the malignant cell population (so-called L&H cells) and its relationship with germinal centers. Forty-one HD samples (19 NLPHD, 12 nodular sclerosis, and 10 mixed cellularity) were immunostained with the monoclonal antibodies PG-B6 and PG-B6p that react with a fixative-sensitive and a formalin-resistant epitope on the aminoterminal region of the BCL-6 gene product, respectively. Strong nuclear positivity for the BCL-6 protein was detected in tumor (L&H) cells in all cases of NLPHD. In contrast, BCL-6 was expressed only in a small percentage of Hodgkin and Reed-Sternberg cells in about 30% of classical HD cases. Notably, the nuclei of reactive CD3+/CD4+ T cells nearby to and rosetting around L&H cells in NLPHD were also strongly BCL-6+, but lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed from that of classical HD, whose cellular background was made up of CD3+/CD4+ T cells showing the BCL-6-/CD40L+ phenotype. These results further support the concept that NLPHD is an histogenetically distinct, B-cell-derived subtype of HD and suggest a role for BCL-6 in its development.
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