Biomedical subjects
A Rios
Publications and source records attributed to A Rios.
Clinical, biological, and immunophenotypical characteristics of B-cell chronic lymphocytic leukemia with trisomy 12 by fluorescence in situ hybridization.
The clinical, biological, and immunophenotypical characteristics of B-cell chronic lymphocytic leukemia (B-CLL) patients with trisomy 12 detected by fluorescence in situ hybridization (FISH) using a chromosome 12 alpha-centromeric probe (D12Z3) were analyzed in the present study. From a total of 104 consecutive B-CLL patients, 21 (20%) displayed trisomy 12, the percentage of trisomic cells ranging from 13% to 76%. From the clinico-biological point of view, patients with trisomy 12 were associated with atypical CLL morphology (43% vs 10%, P = 0.04) and BM diffuse pattern (75% vs. 25%, P = 0.02) together with increased WBC counts (141 +/- 220 vs. 58 +/- 67 x 10(9)/L, P = 0.04). In contrast, no association was detected between the presence of trisomy 12 and other disease characteristics such as age, sex, clinical stage, hepatomegaly, lymphadenopathies, haemoglobin levels and platelet counts, and the cell cycle distribution of PB leukocytes in both groups of patients. Trisomy 12 patients had a significantly higher expression of the FMC7 antigen both in percentage (34 +/- 34% vs. 13 +/- 20%, P = 0.02) and absolute numbers (29 +/- 62 vs. 7 +/- 17 x 10(9)/L, P = 0.007). No major differences were found regarding the expression of mouse rosettes, CD19+, and CD19+/CD5+ lymphocytes. Upon analyzing the correlations between the disease characteristics of trisomy 12 cases, significant associations were found between the percentage of trisomic cells and both the WBC count (r = 0.52, P = 0.02) and the PB lymphocyte count (r = 0.60, P = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)
Arachidonic acid metabolism modulates vasopressin-induced renal vasoconstriction.
Previous studies have shown that cytochrome P450-Arachidonic Acid (P450-AA) metabolites modify the vascular tone of several vessels and that vasopressin (AVP) stimulates P450-AA metabolism. Thus, in the present study, we decided to investigate if the vasoconstrictor effect of AVP is related to activation of P450-AA metabolism. We used the isolated perfused kidney of a rat, to test this hypothesis. Bolus injection of AVP (5.5, 11, 22 and 45 ng) increased the perfusion pressure of the isolated kidney of a rat by 66 +/- 2, 87 +/- 4, 110 +/- 2 and 130 +/- 3 mmHg respectively. This AVP-induced vasoconstriction was significantly reduced by inhibition of AA metabolism with ETYA, or 7 ethoxyresorsorufin (7ER). Furthermore, in vivo induction of P450 system with dexamethasone, enhanced the AVP-induced vasoconstrictor effect. Conversely, depletion of P450 system with SnCl2 diminished the vasoconstrictor response to AVP. Measurement of P450-14cAA metabolites in the renal effluent, showed the presence of 3 radioactive peaks. The % of the recovered radioactivity was 0.12 +/- 0.05%, 0.11 +/- 0.03% and 1.13 +/- 0.5% and corresponded to Dihydroxyeicosatrienoic acids (DHTs), Hydroxyeicosatetraenoic acids (HETEs) and Epoxyeicosatrienoic acids (EETs) respectively, when kidneys were stimulated by AVP (300 ng) the % recovered were 0.34 +/- 0.01%, 0.38 +/- 0.01% and 3.11 +/- 0.7% for the DHTs, HETEs and EETs respectively. Treatment with dexamethasone or SnCl2 potentiated or inhibited the AVP-dependent release of the P450-AA metabolites. In conclusion, we suggest that AVP stimulates AA metabolism via P450 pathway in the kidney and that these AA metabolites participate in the vasoconstrictor effect of AVP in the renal circulation.
20-Hydroxyeicosatetraenoic acid is formed in response to EGF and is a mitogen in rat proximal tubule.
Hydroxyeicosatetraenoic acid (20-HETE) is a major cytochrome P-450-arachidonic acid metabolite in the rat kidney, and its synthesis along the nephron is specifically localized to the proximal tubule, where receptor density for epidermal growth factor (EGF) is the highest. EGF stimulated endogenous 20-HETE formation in a concentration and time-dependent manner, i.e., from 1.6 to 2.6 +/- 0.3 and 3.0 +/- 0.6 pmol 20-HETE.mg-1.min-1 at 10(-8) and 10(-7) M EGF, respectively. The effect of 20-HETE on proximal tubular cell proliferation was examined using primary cultures of rat proximal tubular cells and proximal tubular-derived cell lines, LLC-PK1 and opossum kidney OK. In both cell lines, 20-HETE increased thymidine incorporation into DNA with maximal effect at 10(-9) M. Addition of 20-HETE to serum-deprived LLC-PK1 or OK cells for 48 h caused a concentration-dependent increase in cell number with maximal effect at 10(-9) M. This effect was specific, as structurally similar eicosanoids such as 20-COOH-arachidonic acid, 19(R)-HETE, and 19(S)-HETE did not increase cell number. In 4-day primary cultures of proximal tubular cells, EGF (10(-9) M) and 20-HETE (10(-9) M) increased bromodeoxyuridine (BrdU) incorporation by 40 and 28%, respectively. Addition of both resulted in a twofold increase in BrdU incorporation. Although 20-HETE synthesis in cultured cells is greatly diminished with time, significant picomolar concentrations can be obtained in 4-day cultures. Addition of 17-octadecynoic acid (17-ODYA), an inhibitor of 20-HETE synthesis, significantly inhibited EGF-stimulated BrdU incorporation. The demonstrations that EGF stimulates proximal tubular 20-HETE production and that the latter is a potent mitogen to these cells suggests that 20-HETE may act as a mediator of the EGF effect on cellular growth in the proximal tubule.
HIV-1 p17 synthetic peptide vaccine HGP-30: induction of immune response in human subjects and preliminary evidence of protection against HIV challenge in SCID mice.
An HIV-1 p17 subunit vaccine, HGP-30, was evaluated in 38 HIV-1 seronegative individuals in phase I clinical trials in U.K. and U.S.A. The vaccine preparation induced cytotoxic T-cell (CTL) (11/25) and lymphocyte proliferation responses to KLH (19/20) and HGP-30/p17 (24/29) as well as antibody responses to HGP-30 (29/38) and KLH (38/38). The CTL activity was observed in a higher number of vaccine recipients (9/18) in the lower dose groups (10 and 25 micrograms/kg) than the vaccine recipients (2/7) in the 50 and 100 micrograms/kg dose group. These observations suggest that the 10-25 micrograms/kg vaccine dose may preferentially induce TH1 cell responses. TH1 cell responses have been suggested as important in inducing protective cell mediated immunity. The CTL response has been shown to be CD8+. In a pilot study in SCID mice, HIV-1 virus challenge studies in mice reconstituted with cells from an HGP-30 immunized individual showed protection against virus challenge as compared to SCID mice reconstituted with cells from a non-immunized subject. These studies suggest that HGP-30 is capable of inducing protective cellular immunity.
Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine. A randomized, double-blind clinical trial. The Bristol-Myers Squibb AI454-010 Study Group.
OBJECTIVE: To determine the benefits of switching to didanosine compared with continuing zidovudine among patients infected with human immunodeficiency virus (HIV) who have previously used zidovudine and have signs of clinical deterioration. DESIGN: Randomized, double-blind, two-armed, parallel, comparative clinical trial with a blinded, compassionate crossover provision at 12 weeks. SETTING: Outpatient clinics at 19 tertiary care medical centers. PATIENTS: 312 patients infected with HIV who had received zidovudine for 6 months or more, had CD4 cell counts of 300/mm3 or less, and had signs of clinical deterioration within 12 weeks before study entry. INTERVENTION: Peroral didanosine tablets (600 mg/d adjusted for weight, "high dose") or zidovudine capsules (600 mg/d). MEASUREMENTS: Primary study end points were death, a new acquired immunodeficiency syndrome (AIDS)--defining event, or the combination of two new or recurrent HIV-related diagnoses with a 50% decrease in CD4 cells. RESULTS: Switching to didanosine was associated with fewer end points than continuing zidovudine (relative risk [RR] for zidovudine:didanosine = 1.5; 95% Cl, 1.1 to 2.0). This benefit was consistent across subgroups of patients with either AIDS-related complex or AIDS and was most apparent among those with a CD4 count at entry of 100/mm3 or more (RR = 2.2; Cl, 1.1 to 4.4). CONCLUSIONS: This study shows a positive treatment effect for switching from zidovudine to didanosine among patients with either AIDS-related complex or AIDS and validates the common practice of using clinical signs or a decrease in the CD4 count as an indication for changing therapy.
Effect of dietary nucleotides on small intestinal repair after diarrhoea. Histological and ultrastructural changes.
The effects of specific nutrients on intestinal maturation and repair after injury are practically unknown. The purpose of this work was to study the effects of dietary nucleotides on the repair of the intestinal mucosa after chronic diarrhoea induced by a lactose enriched diet in the weanling rat. One group of weanling rats was fed with a standard semipurified diet (control group), and another group was fed with the same diet containing lactose as the only soluble carbohydrate (lactose group). After 14 days the lactose group was allowed to recover for four weeks with the control diet (lactose-control group) or with the control diet supplemented with AMP, GMP, IMP, CMP, and UMP 50 mg/100 g each (lactose-nucleotide group). The control group was divided into two subgroups, which were fed with the control diet and the nucleotide supplemented diet for the same period (control-control group and control-nucleotide group). The lactose diet induced diarrhoea after 24 hours of feeding. Two weeks later there were changes in intestinal structure with loss of enterocyte microvillar surface, significant lymphocyte infiltration, supranuclear cytoplasmic vesiculation, decreased number of goblet cells, and enlarged mitochondria with low density and few cristae. After recovery from diarrhoea, animals fed the nucleotide enriched diet showed an intestinal histology and ultrastructure closer to that of the normal control group. Mitochondrial ultrastructure was closer to normal in comparison with the lactose-control diet group. In this second group the number of goblet cells as well as the villous height/crypt depth ratio was reduced and the number of intraepithelial lymphocytes increased compared with the nucleotide supplemented group. These results suggest that dietary nucleotides may be important nutrients for intestinal repair.
Recombinant human erythropoietin and health-related quality of life of AIDS patients with anemia.
To evaluate the effect of recombinant human erythropoietin on anemia and health-related quality of life in patients with acquired immunodeficiency syndrome (AIDS), we initiated an observational study with an open-label multicenter treatment protocol that involved multiple academic and community physicians in the United States. Our subjects comprised 251 anemic (i.e., hematocrit < 30%) patients with a clinical diagnosis of AIDS using 1987 CDC criteria, age > or = 12 years, and serum erythropoietin level < or = 500 IU/L. The initial dosage of recombinant human erythropoietin was 4,000 units subcutaneously for 6 days each week. Based on the patient's response to therapy, the dosage was increased sequentially to 8,000 units subcutaneously for 6 days per week. Our measurements included changes in mean hematocrit and health-related quality of life. The interview included measures of energy/fatigue; physical, social, role and cognitive function; depression; health perceptions; and life satisfaction. Adverse experiences were also documented to assess safety. Changes in mean hematocrit level from a baseline of 27.9% to 33.6% at week 12 (p < .0001) and 34.5% at week 24 (p < .0001) were observed in patients treated with recombinant human erythropoietin. Adverse experiences, not clearly associated with AIDS, were reported by 10% of patients. Increases in energy (p < .05) were observed after 12 and 24 weeks of drug therapy, and increases in health perceptions were seen after 24 weeks (p < .05). No statistically significant increases or decreases were observed on measures of physical functioning, cognitive functioning, depression, social functioning, or home management activities over the 24-week follow-up. Anemia correctors (defined as hematocrit > or = 38%) showed greater improvement in energy, health perceptions, home management, and role function than noncorrectors. Study dropouts and those who died had significantly worse scores for health-related quality of life at baseline compared to study completers. Thus, the AIDS patients with anemia and serum erythropoietin levels < or = 500 IU/L treated with recombinant human erythropoietin showed increased mean hematocrit and improved health perceptions and energy levels. The drug therapy was associated with increased feelings of energy, but it was not associated with other changes in health status and well-being in the AIDS patients completing the study. These observations need to be confirmed in randomized clinical trials.
Pharmacokinetics of liposomal nystatin in patients with human immunodeficiency virus infection.
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To purge or not to purge: the neuroblastoma experience.
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Magnetic resonance imaging in full-term infants with repetitive focal seizures.
We report two full-term infants who developed repetitive focal seizures within the first 48 hours of life. Neither infant had predisposing factors and there were no abnormalities on a computed tomography (CT) scan performed on day 2 of life. Magnetic resonance imaging (MRI) performed during the second week of life showed a focal hemorrhagic infarction in both patients. We conclude that either an MRI or a contrast-enhanced CT scan should be obtained within 1 week in patients in whom the initial imaging technique failed to reveal a focal lesion, at which time a cerebral infarction can be diagnosed with greater sensitivity.
Delayed onset right-sided diaphragmatic hernia secondary to group B streptococcal infection.
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Down-regulation of bone marrow stem cell formation by T cell subsets. Effect of CD8+ cells on colony formation in peripheral blood and bone marrow.
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Biocompatibility of dialysis membranes: a comparative study.
White blood cell counts and plasma C5a anaphylatoxin values were studied during haemodialysis with cuprophane, ethylenevinylalcohol, polycarbonate, polymethylmethacrylate, acrylonitrile, polysulphone and polyacrylonitrile membrane dialysers. Cuprophane induced marked leukopenia with striking plasma generation of C5a. Ethylenevinylalcohol, polycarbonate, polymethylmethacrylate and acrylonitrile promoted an intermediate degree of leukopenia with mild but significant complement activation; however, leukopenia and C5a generation were not time-related with some of these membranes. In contrast, polysulphone and polyacrylonitrile showed neither leukopenia nor C5a increase. These data suggest that although there must be further factors involved, complement-derived anaphylatoxin C5a generation may have a relevant role in the mechanism of haemodialysis-induced leukopenia. At the present time evaluation of the leukopenic effect and the C5a generation capability of a membrane seem worthwhile for estimating its degree of biocompatibility.
B-cell chronic lymphocytic leukaemia: prognostic value of the immunophenotype and the clinico-haematological features.
Sixty-two previously untreated patients with B-cell chronic lymphocytic leukaemia were analysed to study the prognostic value of both the immunologic phenotype and the clinicobiologic characteristics. Univariate studies showed that none of the immunological markers analysed, sheep-rosette, mouse-rosette, slg, and HLA/DR, CD20, FMC7, CD5, and CD9 antigens, had a significant influence on survival. On the other hand, several clinical and haematological characteristics were identified as being associated with survival: 1) clinical features--presence of lymphadenopathies (P less than .05) and hepatomegaly and/or splenomegaly (P less than .04); 2) haematologic parameters--presence of anaemia and/or thrombopenia (P less than .05), the absolute peripheral blood lymphocyte count (P less than .03), and the presence of hypogammaglobulinemia (P less than .08); 3) biochemical parameters--serum uric acid (P less than .03); and 4) bone marrow histopathological features--biopsy pattern (P less than .04) and the percentage of lymphocytes in bone marrow aspirate (P less than .03). Both the Rai staging and the International Workshop on CLL staging systems were effective in identifying groups of patients with significantly different prognoses (P less than .05). Multivariate regression analysis demonstrated that the combination of three clinicopathologic characteristics (bone marrow histopathologic pattern, absolute peripheral blood lymphocyte count, and the presence or not of hypogammaglobulinaemia) had the strongest predictive relationship with survival time. In summary, our findings show that the clinicobiological and anatomopathologic parameters have much more prognostic relevance than the immunological markers analysed in the present study.
A pilot study of diethyldithiocarbamate in patients with acquired immune deficiency syndrome (AIDS) and the AIDS-related complex.
We investigated the use of diethyldithiocarbamate (DTC, or Imuthiolr, Merieux Institute) as a therapeutic agent in patients with Acquired Immune Deficiency Syndrome (AIDS) and AIDS-Related Complex (ARC). Patients were prospectively stratified and randomized to receive DTC 200 mg/m2 intravenously weekly for 16 weeks or no therapy, followed by crossover to the opposite arm for an equal period. Forty-four patients were entered and forty were evaluable. There was a statistically significant decrease in symptoms in the DTC treated patients compared to the controls (p = .002). There was a significant improvement in lymphadenopathy in the treated patients compared to the controls (p = .005). One patient showed disappearance of splenomegaly, one clearing of antifungal agent-resistant perianal moniliasis, and one clearing of hairy leukoplakia. No significant differences in progression were noted. No changes were seen in any of the immunological parameters measured. There was no significant toxicity. Because of the changes in symptoms and in lymphadenopathy, we suggest that further study of DTC, both alone and in combination with other agents, may be indicated.
Spatial and temporal correlation between early nerve fiber growth and neuroepithelial cell death in the chick embryo retina.
The distribution of cell death in the ventral pycnotic zone of the chick embryo retina was studied in Hamburger-Hamilton's stages 16 to 25 (2 1/2 to 4 1/2 days of incubation). The number of fragments appearing in the retina increases notably from stage 20 at which stage they are limited almost exclusively to the optic disc region. At the same time optic fibers are seen in this area for the first time. In stage 24 cell death phenomena are numerous in the ventral retina, and become even more extensive in the following stage. Stage 25 meanwhile sees a drop in cell death in the dorsal retina. The overall picture presented by cell remains and young ganglion cells indicates that in stages 19-23 cell death occurs mainly in the zone between the ganglion cells of the posterior pole and the optic stalk. In the stage 25 retina most of the cell fragments of the ventral retina are found on either side of the fissure, while ganglion cells in the process of sending out axons toward the fissure appear laterally (nasally and temporally) to these zones of degeneration. Hence a spatial and temporal correlation is established between fiber growth and neuroepithelial cell degeneration, allowing us to construct a hypothesis with regard to the role that cell death might play in setting up an initial pattern of optic fiber growth.
Bone marrow histopathologic patterns and immunologic phenotype in B-cell chronic lymphocytic leukaemia.
The present work analyzes the clinicobiological and immunological characteristics - the latter hitherto unexplored - of the different bone marrow histopathological patterns of the B-cell chronic lymphocytic leukaemia (B-CLL). In addition, we studied whether any or some of these parameters were able to predict the probability of a particular pattern of bone marrow involvement appearing. Of the 100 B-CLL cases studied 41 had a diffuse pattern and 59 were non-diffuse - interstitial 27, nodular 11 and mixed 21 -. Neither clinical nor immunological differences were observed among the distinct non-diffuse patterns. The patients in the diffuse group displayed an increased incidence of mu+ isotype and a higher proportion of HLA-DR and HAN-PC 1 positive cells while, conversely, reactivity with the FMC 8 McAb was lower. In addition, patients with a diffuse pattern of BM involvement displayed features of a more extensive disease: a higher incidence of adenopathies (p less than 0.05), hepatomegaly (p less than 0.01), splenomegaly (p less than 0.01), anaemia (p less than 0.01) and thrombopenia (p less than 0.01) as well as higher levels of peripheral blood lymphocytosis (p less than 0.05) and a higher percentage of BM lymphocytic infiltration (p less than 0.001). Multiple regression analysis showed that thrombopenia and splenomegaly were the two most important features in predicting the probability of a diffuse pattern.