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Biomedical subjects

F Alvarez

Publications and source records attributed to F Alvarez.

At least 235 records · Page 13Linked to original sources

A new antigen recognized by anti-liver-kidney-microsome antibody (LKMA).

Sera from 23 children with autoimmune chronic active hepatitis and positive for anti-liver-kidney-microsome antibody (LKMA), as defined by immunofluorescence, were analysed by Western blot (WB) and two-dimensional gel electrophoresis using rat liver microsomes as antigen, and by WB and dot-blot analysis with rat liver microsomal subfractions. Western blot analysis showed three patterns of reactivity: 13 sera recognized a 50 kD polypeptide, six sera a 66 kD polypeptide and four sera both of them. Two-dimensional gel electrophoresis, WB, and dot-blot analysis showed the 66 kD antigen to have a pI of 5.4 and to be located in the smooth domain of the endoplasmic reticulum. Western blot analysis using monospecific antisera against human IgG subclasses showed the LKMA directed against the 66 kD antigen to be mainly of the IgG1 subclass. These results indicate that LKMA associated with a subgroup of autoimmune hepatitis of children react with at least two different microsomal antigens in rat liver: (1) the 50 kD polypeptide, recently shown to be a cytochrome P-450 of the IID subfamily, and (2) a new antigen of 66 kD, the location of which suggests it may also be part of the mono-oxygenase complex.

Autoantibodies↗

Anti-liver kidney microsome antibody recognizes a cytochrome P450 from the IID subfamily.

Children with autoimmune hepatitis have high serum titers of antibodies directed against a 50-kD protein of rat liver endoplasmic reticulum. Affinity-purified anti-50-kD antibodies were used to screen a rat liver cDNA library in lambda GT-11 expression vector. 12 immunopositive clones were obtained. Crossreactivities between fusion proteins of these clones and the 50-kD protein was demonstrated, and four clones were analyzed by restriction mapping, one of them by nucleotide sequencing. Complete identity was found between the restriction maps of two clones (LKMC1 and LKMC2) and that of the 5' end of the rat cytochrome P450 db2. Sequence of a 608-bp fragment of LKMC1 showed complete homology with the rat P450 db2 form. The restriction map of the other two clones (LKMC3 and LKMC4) was identical to that of rat P450 db1. These results suggest that the antigen recognized by LKMA is a P450 of the IID subfamily.

Animals↗

An increment in unilateral carotid blood flow produces cerebral aneurysms in rats.

To study the effect of haemodynamic stress on cerebral aneurysm development, three groups of adult Wistar rats were used: 1) One group with ligation of the right common carotid artery; 2) One with an end-to-side common carotid artery anastomosis and 3) Another group that was sham-operated. Blood flow through the left common carotid artery was measured with an electromagnetic flow transducer (0.85 mm in diameter) in anesthetized animals. Before the experimental intervention, the mean carotid blood flow was 2.8 +/- 0.14 ml/min. Following carotid ligation the blood flow in the patent carotid artery increased 25 +/- 5% after 7 +/- 0.3 days and 37 +/- 18% after 149 +/- 23 days; whereas following carotid anastomosis, carotid blood flow increased 102 +/- 16% after 9.6 +/- 2 days and 103 +/- 35% after 169 +/- 15 days. The sham operation did not significantly affect carotid blood flow. Control values for mean arterial pressure (102 +/- 3 mmHg) and blood gases (PaO2 = 106 +/- 3.4 mmHg, PaCO2 = 38 +/- 1.2 mmHg and pH = 7.32 +/- 0.02) were similar in the three groups of rats and did not change significantly over time after the experimental procedure. Necropsy was carried out 149 +/- 15 days after the experimental intervention. No cerebral aneurysms were found in the rats with carotid ligation or which had been sham-operated, however, three of the eight rats (p less than 0.05) with carotid anastomosis presented single aneurysms in the anterior cerebral-anterior communicating arterial complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

Antibodies to liver/kidney microsome1 in chronic active hepatitis recognize specific forms of hepatic cytochrome P-450.

Anti-liver/kidney microsome1-positive sera from children with chronic active hepatitis were studied in an effort to identify the microsomal antigens selected during induction and progression of this autoimmune disease. Immunoblot analysis of sodium dodecyl sulfate gel-resolved microsomal proteins from human and rat liver using anti-liver/kidney microsome1-positive sera revealed a single polypeptide of 48 kilodaltons (human microsomes) or 50 kilodaltons (rat microsomes). Levels of the 50-kilodalton rat microsomal polypeptide were suppressed in vivo by several drugs known to modulate expression of individual forms (enzymes) of hepatic cytochrome P-450, with the largest decrease effected by phenobarbital. Dot blot analysis using a panel of 10 electrophoretically homogeneous rat liver cytochrome P-450 forms under nondenaturing conditions established that the two methylcholanthrene-inducible forms, P-450 BNF-B and P-450 ISF-G (P-450 gene subfamily IA), are selectively recognized by the anti-liver/kidney microsome1 antibodies. These findings demonstrate that sera associated with autoimmune (anti-liver/kidney microsome1) chronic active hepatitis are specifically reactive with select rat hepatic P-450 forms and suggest that these autoantibodies may be principally directed against one or more constitutive forms of the corresponding human liver cytochromes.

Autoantibodies↗

The role of the levonorgestrel intrauterine device in the prevention and treatment of iron deficiency anemia during fertility regulation.

Hematocrit and blood ferritin were assayed in 43 women using a levonorgestrel intrauterine device (LevoNg-IUD), 49 using the Copper T-380 Ag (T-Cu 380 Ag), 27 using the Lippes loop and 30 non-IUD users as controls. The mean duration of use was 41 months for the three IUD groups. Women not using IUDs and with similar age, parity, years of schooling and family income as users had a normal mean hematocrit and ferritin, but 30% had low hematocrit (below 38%) and 43% had low ferritin (below 11 ng/ml). After prolonged use of the IUDs, 26% of users of Lippes loop, 22% of users of T-Cu 380 Ag and only 2% of users of LevoNg-IUD had subnormal hematocrit; 70%, 55% and 14%, respectively, had low ferritin. Thus, in a population with high incidence of anemia, the use of LevoNg-IUD appears to reduce the proportion of women with clinical anemia and with depletion of their iron store.

Adult↗

Alterations in the peripheral lymphoid organs and differential leukocyte counts in Saprolegnia-infected brown trout, Salmo trutta fario.

The number of circulating leukocytes and the structure of splenic and renal lymphoid tissue were comparatively analysed in healthy and Saprolegnia-infected wild brown trout, Salmo trutta fario. Sick trout showed lymphopenia, mainly due to decreased numbers of circulating small lymphocytes, and heterophilia. The splenic and renal lymphoid tissue of infected trout exhibited similar changes, consisting of cellular depletion, lymphoid cell degeneration, and vascular alterations with blood vessel enlargement and hypertrophy of sinusoidal endothelial cells. Furthermore, the endothelial cells in the spleen and kidney of the infected trout contained cytoplasmic vesicles filled with material of possible fungal origin. The absence of a reticular sheath was also evident in the splenic ellipsoids. These results suggest some immunodepression in Saprolegnia-infected trout which might favour the course of the disease.

Animals↗

Short- and long-term vitamin A treatment in children with cholestasis.

Newborns have limited reserve supplies of vitamin A. Infants with chronic cholestasis are in a precarious nutritional state because of their limited ability to build these stores even though the vitamin is present in their diet. In this study, we investigated liver concentrations of vitamin A in 30 children with extrahepatic biliary atresia. We demonstrate that correction of the deficiency occurs after intramuscular administration of a water-miscible solution of retinyl palmitate (100,000 IU, or 30 mg retinol equivalent). Furthermore, we evaluated the effect of vitamin A injections on liver and blood concentrations in nine children with chronic cholestasis over a 1-y period. We conclude this treatment is efficient and is well tolerated.

Biliary Atresia↗

Allergenic cross-reactivity of several strains of Trichinella in mice and rats by the passive cutaneous anaphylaxis technique.

The cross-reactivity of antiparasite IgE antibody responses induced by allergenic antigens obtained from Trichinella spiralis and Trichinella pseudospiralis was determined by the passive cutaneous anaphylaxis (PCA) technique in BCF1 mice infected with T. spiralis, Trichinella nelsoni, Trichinella nativa, and T. pseudospiralis and in rats infected with T. spiralis and T. pseudospiralis. Our results demonstrate that when the antigen used for the PCA challenge is derived from muscular L1 larvae of T. spiralis, high IgE antibody titres can be detected from sera of animals infected with T. spiralis, T. nelsoni, or T. nativa, but not with T. pseudospiralis, during the entire life cycle of the parasite. However, when homologous antigens are used in the PCA test, we obtained comparable values of IgE titres in rats and mice infected with both T. spiralis and T. pseudospiralis strains. These results suggest the existence of a high degree of immunologic identity between the allergenic antigens of T. spiralis, T. nelsoni, and T. nativa strains, but not T. pseudospiralis.

Allergens↗

New insights on the mode of action of intrauterine contraceptive devices in women.

To gain a better understanding of the mechanism of action of intrauterine devices (IUDs), a search was made for ova in the genital tracts of 115 women using no contraception and of 56 women using IUDs, all of whom volunteered for study in conjunction with surgical sterilization. Ova were recovered from tubal flushings between 48 and 120 hours after the midcycle peak of luteinizing hormone in 39% of the IUD users compared with 56% of women in the control group (0.05 less than P less than 0.10). This suggests an action of the IUD before the ovum reaches the uterus. Eggs with a microscopic appearance consistent with fertilization were recovered from the fallopian tubes of half of the women using no contraception who had intercourse within the fertile period of the reproductive cycle and from whom ova were recovered. In contrast (P less than 0.01), no eggs with this appearance were recovered in IUD users who had intercourse within the fertile period. No ova were recovered from the body of the uterus of any of the IUD users. Fertilized ova are less likely to reach the uterine cavity containing an IUD. Thus, the principal mode of IUDs is by a method other than destruction of live embryos.

Fallopian Tubes↗

Subjective perception of bleeding and serum ferritin concentration in long-term users of Norplant.

UNLABELLED: Serum ferritin was measured in 4 groups of long-term users of NORPLANT implants. The users were divided according to their own subjective perception of bleeding: a random sample of 46 one year active users; 30 active users who had increased bleeding; 39 women who had increased bleeding and had the implants removed; 28 active or terminated users who had reduced bleeding. These four groups were compared with a control group of 68 new acceptors of any method at the same clinic who met the criteria for use of NORPLANT. The mean age, parity, years of schooling and family income were similar for the 5 groups. Mean hematocrit for all NORPLANT groups were significantly higher than the control group. About half of the NORPLANT subjects and controls with normal hematocrit had ferritin levels below 11 ng/ml. The proportion of subjects with ferritin less than 11.0 ng/ml were: Group 1) 48%; 2) 63%; 3) 77%; 4) 36% and CONTROLS: 57%. Mean iron stores for all NORPLANT users did not differ significantly from those of a demographically similar control group. Significant differences were, however, observed in two subgroups of NORPLANT users. Those women who had increased bleeding and requested implant removal had lower mean ferritin levels and those who perceived decreased bleeding as a result of NORPLANT use had higher ferritin concentration.

Adult↗

Malignant and atypical meningiomas: a reappraisal of clinical, histological, and computed tomographic features.

A series of 21 patients with atypical and malignant meningiomas is presented. Histological criteria such as high cellularity, typical and atypical mitosis, necrosis, infiltration of the underlying brain, poor differentiation, and distant metastasis define nonbenign meningiomas. Male predominance in this nonbenign group is significant when compared to a group of 205 benign meningiomas, which were also operated on. The malignant and atypical meningiomas are compared with the benign meningiomas, and special emphasis is placed on their computed tomographic features. The presence of tumor fringes (suggesting invasion of the brain substance) and intratumoral hypodense areas were both significant signs of malignancy of atypia. Radical surgical excision is still considered the treatment of choice.

Adolescent↗

Molecular cloning of a 2',3'-cyclic nucleotide 3'-phosphodiesterase: mRNAs with different 5' ends encode the same set of proteins in nervous and lymphoid tissues.

Antibodies raised to a mixture of the 46 and 48 kDa rat CNS 2',3'-cyclic nucleotide 3-phosphodiesterases (CNPs) recognized apparently identical proteins in peripheral nervous system (PNS), thymus, and circulating blood lymphocytes. These antibodies were used to identify, in a rat brain phage lambda gt11 expression library, cDNA clones encoding beta-galactosidase-CNP fusion proteins, some of which showed CNP activity. In RNA blots, the subcloned CNP cDNA inserts hybridized to mRNAs of approximately 2400 and approximately 2800 nucleotides (nts), and to a approximately 2500 nt mRNA from thymus. Several nonexpressing CNP cDNAs were identified by plaque hybridization, and the mRNA transcribed in vitro from one of these cDNAs (pCNP7) encoded a complete 46 kDa CNP polypeptide. Examination of the deduced amino acid sequence revealed an apparent homology to cAMP binding sites in several other proteins. A 373 bp segment from the 5' end of this pCNP7 hybridized only to the 2800 nt nervous system mRNAs, thus revealing that not all CNP mRNAs share the same 5'-ends. Genomic DNA blots probed with CNP cDNAs suggest that there is a single gene which can be alternatively spliced to produce the various mRNA transcripts in the nervous and lymphoid tissues.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗