AIDS case definitions in developing countries.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
M Pinto
Publications and source records attributed to M Pinto.
Standardization of prothrombin times in newborn infants.
The prothrombin time (PT) for patients receiving warfarin varies widely, reflecting the heterogeneity of thromboplastin reagents. The International Committee on Thrombosis and Haemostasis recommends that PT values for these patients be expressed as international normalized ratios. This study showed that thromboplastin reagents also significantly influence PT values in neonatal plasma and that expressing PT values as international normalized ratios decreases this variability.
Adult↗
Measurement of tissue carcinoembryonic antigen levels.
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Biomarkers, Tumor↗
Pulmonary surfactant inhibits interleukin-2-induced proliferation and the generation of lymphokine-activated killer cells.
The generation of lymphokine-activated killer (LAK) cell activity and the proliferative response to human recombinant interleukin-2 (IL-2) were significantly reduced when either human peripheral blood lymphocytes (PBL) or purified CD56+/CD3- lymphocytes were cultured in the presence of pulmonary surfactant. Surfactant concentrations ranging between 30 and 500 micrograms/ml produced increasing levels of inhibition ranging from 20 to 95%. For any given concentration of surfactant, increasing the IL-2 concentration produced increasing levels of LAK activity but never overcame the suppressive effects of the surfactant. Time course studies demonstrated that surfactant is inhibitory only if added to PBL during the first 2 days of IL-2 culture, suggesting a preferential action during the induction phase of LAK activity. Pretreatment of PBL with surfactant for as little as 2 to 4 h inhibited their subsequent response to IL-2 culture, suggesting that inhibition is rapid, persistent, and directly due to alterations in PBL responsiveness. To determine if surfactant alters cell membrane function, we measured the effects of surfactant exposure on LAK:tumor binding. Binding of LAK cells to both K562 and M14 tumor targets was inhibited in a concentration-dependent manner. Concurrently, we observed a reduced expression of IL-2 alpha-chain receptors on surfactant-treated CD56+/CD3- cells and a dramatic reduction in the expression of adhesion molecules including CD2, LFA-1, LFA-3, and ICAM-1. We conclude that pulmonary surfactant has the potential to suppress cytotoxic and proliferative responses to IL-2, alters cell-to-cell interactions, and reduces the expression of activation and adhesion molecules on LAK cells.
Adult↗
Mammalian heat shock protein families. Expression and functions.
When prokaryotic or eukaryotic cells are submitted to a transient rise in temperature or to other proteotoxic treatments, the synthesis of a set of proteins called the heat shock proteins (hsp) is induced. The structure of these proteins has been highly conserved during evolution. The signal leading to the transcriptional activation of the corresponding genes is the accumulation of denatured and/or aggregated proteins inside the cells after stressful treatment. The expression of a subset of hsp is also induced during early embryogenesis and many differentiation processes. Two different functions have been ascribed to hsp: a molecular chaperone function: chaperones mediate the folding, assembly or translocation across the intracellular membranes of other polypeptides, and a role in protein degradation: some of the essential components of the cytoplasmic ubiquitin-dependent degradative pathway are hsp. These functions of hsp are essential in every living cell. They are required for repairing the damage resulting from stress.
Animals↗
Denaturation of proteins during heat shock. In vivo recovery of solubility and activity of reporter enzymes.
Using beta-galactosidase and luciferase as reporter enzymes, we have previously shown that enzymatic inactivation occurring during a heat shock is concomitant with protein insolubilization (Nguyen, V. T., Morange, M., and Bensaude, O. (1989) J. Biol. Chem. 264, 10487-10492). In this paper, we observe that pretreatment of cells with D2O and glycerol, compounds known to stabilize protein structure, leads to a parallel decrease of protein inactivation and insolubilization, suggesting that these two phenomena result most probably from heat-induced protein denaturation. We found that heat shock-promoted inactivation and insolubilization are not irreversible processes, since even in the absence of protein synthesis, beta-galactosidase solubility and luciferase solubility and activity are recovered in vivo after a heat treatment. Cognate heat shock proteins might be involved in this renaturation process.
Animals↗
In vivo protective effect of lipopolysaccharide against Pseudomonas aeruginosa exotoxin A in mice.
Lipopolysaccharide (LPS) treatment of mice 1 to 5 days prior to administration of Pseudomonas aeruginosa exotoxin A (PA) induced full or partial protection against PA intoxication. The optimal LPS dose that induced resistance was 50 to 100 micrograms per mouse. Simultaneous administration of LPS and PA to mice, however, increased their sensitivity to PA two- to fourfold. Mice pretreated with LPS demonstrated a markedly enhanced clearance rate of 125I-labeled PA from peripheral blood, livers, and kidneys. In mice exposed to LPS and PA simultaneously, the rate of elimination of labeled PA was lower than that in control mice. While protein synthesis was inhibited significantly in livers and other organs of PA-exposed mice, in LPS-pretreated mice, PA-induced inhibition of protein synthesis was either diminished or totally prevented and elongation factor 2 (EF2) levels were normal. In mice treated only with LPS, enhanced protein synthesis and increased levels of EF2 were observed, suggesting that LPS protection against PA intoxication was perhaps a consequence of excessive amounts of EF2 induced by LPS.
ADP Ribose Transferases↗
Cystic fibrosis in the Portuguese population: haplotype distribution and molecular pathology.
The aim of this study was to obtain an estimate of the frequency of the delta F508 mutation in the Portuguese population, and of the tightness of its association with specific haplotypes. Furthermore, the genotype/clinical phenotype relationship and the feasibility of prenatal diagnosis were also investigated. The analysis of 42 cystic fibrosis (CF) families revealed that (1) 52% of CF chromosomes carry the deletion of codon 508; (2) there seems to be a positive correlation between the occurrence of the delta F508 mutation and the severity of the disease; and (3) fully informative prenatal diagnosis can be offered in 76% of at-risk pregnancies by using both genomic and allele specific oligonucleotide probes.
Chromosome Deletion↗
Heterogeneity of laboratory test results for antiphospholipid antibodies in patients treated with chlorpromazine and other phenothiazines.
Ninety-seven psychiatric patients who have been treated with the antipsychotic drug chlorpromazine or another phenothiazine have been investigated for the presence of antiphospholipid antibodies. A variety of coagulation studies and specific antiphospholipid immunoassays were performed to define the spectrum of antigen specificity of these antibodies. Coagulation studies showed an increasing sensitivity for the lupus anticoagulant with reagents of differing phospholipid content. Prolonged activated partial thromboplastin times (APTTs) were found in five patients with the use of an insensitive APTT reagent and in 14 patients with a lower phospholipid content reagent. In every case, attempted correction of the clotting time with normal plasma was unsuccessful. Twenty-one patients had abnormal kaolin clotting time profiles. In seven of these patients, test results with both APTT reagents had been normal. Antibody reactivity was tested against three negatively charged phospholipids, phosphatidyl-serine, cardiolipin, and phosphatidylinositol. Only five patients demonstrated reactivity against phosphatidylinositol, whereas high antibody titers were observed in 28 patients against one or both of phosphatidylserine and cardiolipin. Twenty-three of these patients were found to have elevated anticardiolipin-specific IgM antibodies. Overall, 41 of the patients had at least one laboratory abnormality suggestive of antiphospholipid antibody activity. Seven of the 26 patients, taking phenothiazines other than chlorpromazine, had positive test results for antiphospholipid antibodies. No clinical thromboembolic events were recorded in any patient. These findings demonstrate the heterogeneity of antiphospholipid antibody specificity induced in patients treated with various phenothiazine drugs and indicate that none of these patterns of reactivity marks a predisposition for thromboembolism in this population.
Adult↗
Osteoblastomas of the cervical spine.
Osteoblastomas of the cervical spine frequently occur with anterior vertebral body involvement despite the classical teaching, which suggests that involvement is usually confined to the posterior elements. A review of osteoblastomas that involved the cervical spine was conducted at a single institution over 20 years. Four patients were identified with osteoblastoma of the cervical spine from a total of 13 spinal osteoblastomas, and their conditions were assessed to determine the anatomic extent of neoplastic involvement, the surgical margins obtained at resection, methods of spinal stabilization, and local recurrence rate. A mean follow-up time of 11.4 years was obtained. Posterior surgical extirpation of the neoplasm can successfully be accomplished with good long-term results by achieving intralesional margins. Patients with cervical spine osteoblastomas represent a separate subset from patients with other spinal osteoblastomas because of their unique appearances.
Adolescent↗
Natural autoantibodies against Tamm-Horsfall glycoprotein in normal individuals in relation to age and in adult patients with kidney diseases.
IgM and IgG natural antibodies to Tamm-Horsfall glycoprotein (THP) were found in serum samples of all healthy individuals tested by the ELISA technique. The IgM anti-THP antibody level was higher in the group 1-20 years old than the IgG anti-THP. The IgG anti-THP rose with increase in age (greater than 21 years old groups) and then the IgG and IgM anti-THP activity over aging remained constant. The natural anti-THP antibodies possess a lower degree of specificity and/or avidity than induced antibodies. The antibody titers against THP determined in 61 adult patients with chronic kidney diseases was significantly lower than that in adult controls. This low level of naturally occurring THP antibodies appears to be a general phenomenon. In these patients, diminished antibody levels appeared against a panel of self (collagen, fibronectin, THP) and non self (bovine gamma globulin (BGG), ovalbumin (OVA)) antigens as compared with normal controls. The low levels of these antibodies are not associated with a concomitant drop of IgG and IgM in their sera.
Adolescent↗
Differential roles of splanchnic and peripheral tissues in determining diurnal fluctuation of glucose tolerance.
To identify the mechanisms and the sites of the diurnal fluctuation in glucose tolerance in humans, we selectively quantitated the components of net splanchnic glucose balance, i.e., splanchnic glucose uptake and hepatic glucose output, as well as peripheral glucose uptake, by combining tritiated glucose infusion with hepatic and femoral venous catheterization. The studies were carried out in 11 healthy volunteers at 8:00 A.M. and at 6:00 P.M. on different days after 12 h of fasting. After intravenous glucose infusion (6.5 mg.kg-1.min-1 for 120 min) blood glucose rose twofold at 8:00 A.M. and threefold at 6:00 P.M. (P less than 0.01). Insulin levels did not differ significantly between the two series of tests. Splanchnic glucose balance switched from the net output of the basal state to a net uptake in both morning and afternoon studies. However, this effect was more marked at 6:00 P.M. than at 8:00 A.M. (at 60-120 min, P less than 0.05). The different pattern of splanchnic glucose balance was entirely accounted for by a greater rise in splanchnic glucose uptake in the afternoon, as the suppression of endogenous glucose output by the glucose load was practically complete in both series of studies. In contrast, glucose uptake by leg tissues increased less at 6:00 P.M. than at 8:00 A.M. (at 30-60 min, P less than 0.05; at 75 and 90 min, P less than 0.01; at 105 and 120 min, P less than 0.005). These data indicate that the mechanism responsible for the reduced glucose tolerance later in the day resides in the peripheral tissues whose ability to dispose of a glucose load is drastically decreased.
Adult↗
Thermal injury-induced non-specific resistance to fatal Pseudomonas aeruginosa burn-infection in mice.
Nonlethal thermal injury in mice results in rapid death by immediate injection of 10(3) viable P. aeruginosa in the skin of the burn sites. Resistance to the lethal burn combined with P. aeruginosa infection developed 24 h after initial thermal injury and reached maximal effect 7 days later; it then continued for at least 21 days. The optimal survival was achieved when the first thermal injury was made for 7 seconds at 350 degrees C. Increased resistance, but for a short period could also be obtained by injection of lipopolysaccharide (LPS) 1-4 days prior to the burn-P. aeruginosa infection. However, when the LPS was injected immediately after the burn-infection, the lethal effect was increased. The induction of late protection after thermal injury and bacterial infection was demonstrated with P. aeruginosa organisms only. Under similar schedule of thermal injury resistance was not induced by infection with Semliki forest virus. On the contrary viral infection increased the susceptibility of burned mice to a fatal outcome. Immune or natural antibodies were not elevated in the sera of post burn mice. Furthermore, delayed type hypersensitivity response, as evaluated by a footpad weight assay was inhibited and this inhibition persisted at least for 7 days post burn. The thymus weight and its lymphoid cell content in thermally injured mice decreased significantly 7 days post burn, whereas the weight of the spleen increased and it contained fewer lymphocytes per gram tissue. We suggest that endotoxin entering the systemic circulation post-burn might be one of the factors contributing to the early sensitivity and the late protection against the fatal P. aeruginosa burn-infection.
Animals↗
[Antiemetic effect of the levo isomer of sulpiride (L-sulpiride) in humans].
Vomiting represents one of the most dangerous complications of general anesthesia. L-sulpiride has been able to control this complication very effectively. We studied the effect on vomiting of two doses of L-sulpiride (50/100 mg). Both these doses have been effective in reducing the episodes of vomiting other than in preventing nausea and retching if considered versus controls and also versus droperidol at the doses of 5 mg (50 mg L-sul = 12%, 100 mg = 4%, droperidol = 20%, controls = 28%). L-sulpiride is an antagonist of dopamine on D2 receptors therefore inhibits the action of dopamine increasing the secretion of prolactin. During the surgical distress per se prolactin levels are increased. Together with the increment of catecholamines, high concentration of prolactin can evoke arrhythmias. In view of this possibility we studied the time course of the administration of the two doses of L-sulpiride and of droperidol on prolactin secretion. Both of the drugs increased the plasma levels of prolactin. Droperidol-induced increase in prolactin secretion was significant already at ten minutes after the administration reaching the peak after 20 minutes. L-sulpiride increased prolactin secretion reaching the maximum increase 20 minutes after the administration of 50 mg of the drug, and 30 minutes after the administration of 100 mg doses. The hyperprolactinemizing action of droperidol lasts for at least 8 hours, whereas L-sulpiride action lasts 4 hours.
Adolescent↗
Origin of the excess capacitance at intimate Schottky contacts.
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Journal Article↗
Translocation t(1;7) revisited. Report of three further cases and review.
Three white patients, two with myelofibrosis and one with refractory anemia, presented with a t(1;7). The clinical and cytogenetic findings are discussed in the context of 45 cases already published. Rather than the specific association of t(1;7) with a particular hematologic disorder, a review of the literature strongly suggests correlation with therapeutic or environmental exposure to toxic substances. The proposed mechanisms to explain the origin of t(1;7) are briefly reviewed.
Adolescent↗
B-cell chronic lymphatic leukemia in Hodgkin's disease. A report of two patients with unusual chromosome features.
The development of B-cell chronic lymphatic leukemia in two patients who had previously been treated for Hodgkin's disease is described. In both cases aneuploidy and multiple chromosome aberrations of hemopoietic cells were evident. In one patient these changes included a clonal 14q + abnormality in association with other complex rearrangements, interpreted as translocation abnormalities involving t(6;14), 5(1;15), and t(17;19). Although the chromosome abnormalities in the other patient were nonclonal, a 14q abnormality also was detected, namely t(14q+;18q-). Other chromosome abnormalities (all nonclonal) in the two patients included translocations involving chromosome 5 and deletion of 7q in one patient and trisomy of chromosome 8 in the other. Although these abnormalities have been associated with the presence or development of non-Hodgkin's lymphoma, acute nonlymphoblastic anemia, or myelodysplastic disorders, the findings in these patients suggest that the detection of clones and potential clones with these abnormalities may be only one stage in the development of secondary malignancy.
Adult↗
Effects of partial hepatectomy on the immune responses in mice.
Experiments were performed to investigate the immune responses occurring as a result of partial hepatectomy (HEP) in mice. On Day 12 mice subjected to HEP showed a twofold rise in serum levels of IgG when compared with sham-operated (ShO) controls. The effects of HEP on specific antibody production following a single immunization with sheep red blood cells (SRBCs) were investigated. An early appearance of direct (IgM) splenic plaque-forming cells (PFCs) and significantly elevated indirect (IgG) PFCs were found in HEP mice. Elevated, early-appearing mercaptoethanol-resistant (IgG) hemagglutinating antibodies were also demonstrated in the sera of HEP mice. In addition to these findings our study showed that humoral and cell-mediated responses are affected by HEP in opposing fashion. Partial hepatectomy performed immediately after skin grafting suppressed a first set allograft rejection in mice. Furthermore, inhibited delayed-type hypersensitivity (DTH) response against SRBCs, as evaluated by a footpad weight assay, was demonstrated in HEP mice compared with the ShO controls. When SRBC-primed mice were partially hepatectomized 15 days later, they responded in a manner typical of the secondary immune response, showing an increased production of indirect (IgG) splenic PFCs. A similar anamnestic response was observed in mice sensitized with leptospiral antigen 50 days prior to HEP or exposed to carbon tetrachloride (CCl4) hepatotoxin. The mice responded by elevated serum IgG-specific antibodies as measured by solid-phase enzyme-linked immunosorbent assay (ELISA). Since HEP induced in mice immunological disturbances similar to those associated with liver disease, it is suggested that partial hepatectomy creating liver deficiency followed by regeneration may be a useful experimental model to study the immune status of various forms of hepatic damage.
Animals↗