Biomedical subjects
Publications and source records attributed to M Lozano.
Sclerosing sweat duct carcinoma is an infrequent adnexal tumor, locally aggressive and with a high incidence of local recurrences. Its location is preferably cephalic and its clinical presentation often unspecific. We present a new case with an atypical location and the clinical appearance of a benign cutaneous lesion. Diagnosis was established after a histological and immunohistochemical study. A terminological review was done.
BACKGROUND AND OBJECTIVE: Serum alanine-aminotransferase (ALT) is being used as a surrogate test for preventing post-transfusion viral hepatitis. However, ALT elevation is influenced by many factors. We have studied ALT levels in 1,036 consecutive blood donors to determine their association with gender, obesity, and hepatitis virus infection markers. DESIGN AND METHODS: In each donation aspartate-aminotransferase (AST), lactate dehydrogenase (LDH) and gamma-glutamyl transferase (gamma GT) activity were also determined and body mass index (BMI) was calculated. RESULTS: Five hundred seventy-nine men and 457 women donated blood; ALT activity was 25.3 +/- 14.5 IU/L (mean +/- SD) for men and 16.3 +/- 7.9 IU/L for women (p < or = 0.0005). The upper normal value for men was 56 IU/L and 34 IU/L for women. On applying this value to the study group 4.8% of the men and 2% of the women had values greater than the cutoff. Among the men with increased ALT levels, 53.5% had a BMI > 27, 7.1% also had an increased level of GGT and 7.1% had increased levels of AST and LDH. None of them were HBsAg nor anti-HCV positive. Among the women with increased ALT, 33.3% had BMI > 27, 33.3% had increased levels of LDH and AST, and 11.1% were anti-HCV positive (only 1 donor). INTERPRETATION AND CONCLUSIONS: It seems clear that different cutoff values should be considered for men and women. Factors such as obesity, may account for more than 50% of the cases with increased ALT values, indicating the low specificity of the test.
BACKGROUND AND OBJECTIVE: alpha-thalassemia is very common on all thalassemic geographical regions. The present work aimed at analyzing the relationship between the degree of microcytosis and hematological parameters and the type of alpha-thalassemic mutation. DESIGN AND METHODS: Five hundred and thirty-six subjects with 4 kinds of alpha-thalassemia were examined using established techniques that determined all hematological parameters, and globin synthesis and molecular biological techniques to study the DNA of globin genes by Southern blotting. RESULTS: Adult carriers of alpha (+)-thalassemia (-alpha/alpha alpha) present very few hematological alterations. In a statistical comparison with normal individuals (alpha alpha/alpha alpha), significant differences were found between the hemocytometric data and the MCV and MCH of heterozygous alpha + thalassemia and the heterozygous alpha zero or homozygous alpha + genotype. Hb H disease was detected in 15 patients, presenting a severe degree of anemia, a significant increase in RDW and globin chain synthesis with an alpha/beta ratio of 0.5 +/- 0.1. INTERPRETATION AND CONCLUSIONS: These data provide reference values for geographical areas where alpha + thalassemia is common. These hematocytometric data, together with hemoglobin analysis, could be useful as a future reference data for new patients diagnosed with alpha-thalassemia.
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After implementing a new nursing care delivery system, evaluating its outcomes is essential. An evaluation process answers key questions: (1) Were planned outcomes achieved? (2) Were the users satisfied? (3) Does the delivery system need to be modified?
Extracts of Helicobacter pylori (HP) have been shown to induce leukocyte adhesion in mesenteric venules, but the effects of HP infection on gastric microvessels are unknown. Inflammatory cell interactions in the gastric microcirculation were studied by intravital videomicroscopy in mice inoculated with either saline or fresh isolates of HP. Platelet aggregates were detected and quantified in murine portal blood, while endothelial P-selectin expression was determined using the dual radiolabeled mAb technique. Platelet activation and aggregation were studied in HP-infected patients and controls by measuring the platelet-aggregate ratio and platelet P-selectin expression. HP infection induced a marked increase in the flux of rolling leukocytes and the appearance of platelet and leukocyte- platelet aggregates in murine gastric venules. The HP-induced rolling and platelet aggregate formation was abrogated by mAbs against L- or P-, but not E- selectin. Endothelial cell expression of P-selectin was not altered, but platelet P-selectin expression was enhanced in HP-infected mice. Circulating platelet aggregates and activated platelets were also detected in HP-infected patients. These findings indicate that platelet activation and aggregation contribute to the microvascular dysfunction and inflammatory cell recruitment associated with HP infections.
Effects of heparins on platelet function are controversial, but perfusion studies, that simulate physiological conditions, might help to explain their clinical behaviour. We used a perfusion system to test the effect unfractionated heparin and a low-molecular-weight heparin (dalteparin, Fragmin) on platelet adhesion promoted by a damaged vascular surface. Normal blood samples containing increasing concentrations of unfractionated heparin and dalteparin were perfused through annular chambers containing enzymatically denuded rabbit aorta segments (5 min at 800 sec-1). Segments were evaluated morphometrically measuring the total surface covered by platelets and by large aggregates (thrombi). Unfractionated heparin inhibited platelet interaction with subendothelium in a lesser extent than dalteparin in both covered surface and thrombi (p < 0.01). At heparin doses that caused maximal inhibition covered surface was 10.0% +/- 3.1% with dalteparin and 18.3% +/- 4.2% with unfractionated heparin, and thrombi were 5.6% +/- 3.2% and 12.3% +/- 3.0%, respectively. These results may collaborate to explain some differences observed in the clinical results obtained with unfractionated heparin and with dalteparin.
We report a 65-year-old man who presented with a Merkel cell carcinoma on his right ear, a small satellite nodule and regional lymph node metastases. No treatment was given because of his generally poor state of health. Spontaneous regression of all the lesions was observed within a month. Merkel cell carcinoma is a potentially aggressive tumour. Only four cases of spontaneous regression have been reported previously.
The nuclear matrix has been implicated in several cellular processes, including DNA replication, transcription, and RNA processing. In particular, transcriptional regulation is believed to be accomplished by binding of chromatin loops to the nuclear matrix and by the concentration of specific transcription factors near these matrix attachment regions (MARs). A number of MAR-binding proteins have been identified, but few have been directly linked to tissue-specific transcription. Recently, we have identified two cellular protein complexes (NBP and UBP) that bind to a region of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) previously shown to contain at least two negative regulatory elements (NREs) termed the promoter-proximal and promoter-distal NREs. These NREs are absent from MMTV strains that cause T-cell lymphomas instead of mammary carcinomas. We show here that NBP binds to a 22-bp sequence containing an imperfect inverted repeat in the promoter-proximal NRE. Previous data showed that a mutation (p924) within the inverted repeat elevated basal transcription from the MMTV promoter and destabilized the binding of NBP, but not UBP, to the proximal NRE. By using conventional and affinity methods to purify NBP from rat thymic nuclear extracts, we obtained a single major protein of 115 kDa that was identified by protease digestion and partial sequencing analysis as the nuclear matrix-binding protein special AT-rich sequence-binding protein 1 (SATB1). Antibody ablation, distamycin inhibition of binding, renaturation and competition experiments, and tissue distribution data all confirmed that the NBP complex contained SATB1. Similar types of experiments were used to show that the UBP complex contained the homeodomain protein Cux/CDP that binds the MAR of the intronic heavy-chain immunoglobulin enhancer. By using the p924 mutation within the MMTV LTR upstream of the chloramphenicol acetyltransferase gene, we generated two strains of transgenic mice that had a dramatic elevation of reporter gene expression in lymphoid tissues compared with reporter gene expression in mice expressing wild-type LTR constructs. Thus, the 924 mutation in the SATB1-binding site dramatically elevated MMTV transcription in lymphoid tissues. These results and the ability of the proximal NRE in the MMTV LTR to bind to the nuclear matrix clearly demonstrate the role of MAR-binding proteins in tissue-specific gene regulation and in MMTV-induced oncogenesis.
The Bernard-Soulier syndrome (BSS) is characterized by thrombocytopenia with giant platelets, a prolonged bleeding time with defective platelet adhesion to the subendothelium related to a defect in platelet membrane glycoprotein Ib (GPIb) and a decreased prothrombin consumption. The mechanism of the latter abnormality remains unknown. In this study, we showed that this defect was corrected by the addition of purified human factor VIII (FVIII) to blood from four patients with BSS. The correction of prothrombin consumption was almost complete at concentrations between 1.5 and 3 IU/ml of FVIII procoagulant activity (VIII:C) and partially abolished by a monoclonal antibody which neutralizes VIII:C. This correction was specific for FVIII and was not observed after addition of purified human FIX. It was obtained, in the same magnitude range, with FVIII complexed to von Willebrand factor (vWF) but not with free vWF. These data provide a new insight into the knowledge of the physiological interaction between the platelet membrane and the vWF-FVIII complex facilitating plasma coagulation activation and may lead to helpful therapeutic advances.
Mouse mammary tumor virus (MMTV) causes mammary carcinomas and T-cell tumors in mice. MMTV variants that induce T-cell tumors have a large deletion within the U3 region of the long terminal repeat (LTR) compared to MMTV strains that induce mammary tumors. We provide evidence here that T-cell tropic MMTV strains lack a redundant binding site for a cellular protein called NBP (negative regulatory element binding protein). The lack of NBP-binding sites in T-cell tropic MMTV strains presumably leads to higher levels of transcription in T-cells during the MMTV life cycle and an increased incidence of mutagenic integration events.
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Seven-three patients diagnosed with vascular dementia (VD) left to their natural evolution have been observed during a period of time of one year. The objective of this study is to find an index to quantify the degree of loss of cognitive capabilities in patients affected by VD, as well as to define the minimum loss of punctuation in this index, that can only be caused by an unfavourable evolution of the disease. This index, which we call Percentual Variation Index (PVI), is based on the evolution of the punctuations of the Cognoscitive Mini-Exam (CME) after a follow-up of one year. Our definition states that in order to consider patients as having cognitive impairment of vascular origin, they must lose more than 10% of their basal CME score in one year. This method could be useful in assessing the therapeutic efficacy of drugs used in treating such illnesses.
Bacterial contamination of blood components is an infrequent although potentially fatal event. Bacterial contamination rate of platelet concentrates (PC) varies between 1/900 to 1/2,000 random donor units. However the risk of symptomatic bacteriemias is lower (between 1/2,000 to 1/12,000 random donor units). The organisms most commonly implicated in contaminated PC are gram-positive bacteria such as coagulase negative Staphylococci, Bacillus cereus or Propionibacterium acnes, although gram-negative organisms are also found that generally are associated to a higher mortality. Here, a fatal case of sepsis due to Staphylococcus carnosus associated to transfusion of a contaminated random donor platelet unit is reported.
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We studied the effect of increasing concentrations of protein C (PC) and activated protein C (APC) on haemostasis in an in vitro thrombosis model. Blood from healthy donors was anticoagulated with citrate-phosphate-dextrose (final citrate concentration 19 mM) or a low molecular weight heparin (LMWH, 20 IU/ml). Enzymatically denuded rabbit aorta segments were exposed to flowing blood for 10 min in an annular perfusion chamber. PC and APC were added to the perfusate immediately prior to exposure. In citrated blood at a shear rate of 800/s, PC and APC induced a statistically significant decrease in platelet deposit at 16 micrograms/ml and 32 micrograms/ml. In perfusions performed with blood anticoagulated with LMWH, there was no effect on platelet deposition at 16 and 32 micrograms/ml either at shear rates of 300/s or 800/s. Addition of PC showed no effect on fibrin deposition at a shear rate of 300/s; in contrast, a nonstatistically significant 40% reduction was seen at a shear rate of 800/s, compared to controls. Addition of APC caused a 100% reduction in fibrin formation at 16 and 32 micrograms/ml at both shear rates studied. PC and APC inhibited platelet deposition on the exposed subendothelial surface, in a dose-dependent manner. Effects of PC and APC on platelet function might be mediated through inhibition of thrombin generation at the platelet microenvironment.
A reduction in the ability of GPIb to bind specific MoAbs or ligands (vWF) has been reported in platelets exposed to thrombin in suspension. We have analyzed modifications in the presence of glycoproteins (GPs) on platelets activated under flow conditions in a system which allows limited thrombin and fibrin generation. Normal blood anticoagulated with low molecular weight heparin (LMWH, Dalteparin 20 IU/ml) was recirculated for up to 10 min at 800 s-1 through annular chambers containing denuded arterial segments. Aliquots of blood were removed from the reservoir at 0, 1, 5 and 10 min and immediately mixed with paraformaldehyde. Membrane glycoproteins: GPIb (CD42b), GPIIb-IIIa (CD41a), GPIV (CD36); and activation dependent antigens: P-selectin (CD62P) and lysosomal glycoprortein (CD63), were detected in whole blood by dual color flow cytometry. Circulation of through the perfusion system resulted in platelet activated as demonstrated by the increased percentage of platelets positive for antigens CD62P and CD63. A gradual increase in the binding of MoAbs directed against GPIb, GPIIb-IIIa, and GPIV epitopes was noted during the entire perfusion period. Observed differences in mean fluorescence intensities at all the observation times were statistically significant (P < 0.001). Our results obtained on platelets in an experimental thrombosis system indicate that GPIb, GPIIb-IIIa and GPIV remain on the surface of activated platelets and actually increase their expression. Alterations detected at the level of GPIb in platelets activated by thrombin in suspension may not take place under in vivo situations.