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Biomedical subjects

F Alvarez

Publications and source records attributed to F Alvarez.

At least 253 records · Page 14Linked to original sources

Coxsackievirus induced myocarditis in mice: cardiac myosin autoantibodies do not cross-react with the virus.

After infection with Coxsackievirus B3 (CB3), H-2 congenic strains of mice on an A-background develop an immunologically mediated myocarditis associated with autoantibodies directed mainly against cardiac myosin. We tested these autoantibodies for cross-reactivity with the virus. Using immunoblotting and virus neutralizing assays with affinity purified antibodies and absorbed sera, we found that the autoantibodies to heart myosin did not cross react with CB3. In addition, myosin autoantibodies induced by immunization with cardiac myosin did not react with the virus. Western immunoblotting revealed that the anti-CB3 antibodies in the infected mice are directed against the capsid protein VP 2. We conclude that CB3 antigens do not stimulate an immune response that cross-reacts with cardiac myosin.

Animals↗

Behaviour of the contact phase of blood coagulation in the adult respiratory distress syndrome (ARDS).

In order to assess the role of the kallikrein-kinin (K-K) system in the pathogenesis of the adult respiratory distress syndrome (ARDS) we have prospectively determined coagulation contact phase, blood gas and hemodynamic parameters in patients with ARDS at 0, 36 and 72 h from diagnosis. Compared to normal values, significantly lower mean levels of factor XII (71.4 +/- 9.8%, p less than 0.0005), prekallikrein (PPK) (52 +/- 5.7%, p less than 0.0005), high molecular weight kininogen (HMWK) (73 +/- 2%, p less than 0.0005) and alpha 2-macroglobulin (alpha 2-M) (51 +/- 7.1%, p less than 0.0005) were found in ARDS patients. The functional kallikrein inhibitory activity (KKI) and C1-esterase inhibitor antigenic (CIINH) were significantly higher in these patients (113.2 +/- 5, p less than 0.005 and 124.7 +/- 7.6, p less than 0.0005 respectively) compared with normal values during the entire study period. The KKI/CIINH ratio decreased significantly in our ARDS patients at 0, 36 and 72 h (p less than 0.025; p less than 0.05 and p less than 0.005 respectively). We found a significant correlation between PPK levels and oxygenation index (r = 0.69, p less than 0.001), PPK and the static thoracic compliance values (r = 0.64, p less than 0.001). There was also a significant correlation between PPK levels and Qs/Qt (r = -0.89, p less than 0.001). ARDS patients that survived presented a stability in the PPK values in successive tests. Nevertheless non-survivors showed a progressive decrease in PPK levels during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Recovery of fertility after use of the levonorgestrel 20 mcg/d or Copper T 380 Ag intrauterine device.

Following use of either the Levonorgestrel 20 mcg/day or the TCu 380 Ag IUD in a randomized comparative study, 110 women stopped contracepting to have planned pregnancies. Pregnancy rates and recovery of fertility have been assessed. Age at acceptance, duration of use, parity and intervals between last pregnancy and IUD insertion or removal were similar for both groups. Life table pregnancy rates at one year were higher than 90 per cent for both device groups; but because some women quickly changed their minds or had been at risk of pregnancy only a short time before the analysis date, only 60.9 percent had actually become pregnant. Median time to planned pregnancy was 3 months for the TCu 380 Ag group and 4 months for the Levonorgestrel 20 group. Neither duration of use nor age at insertion or age at termination affected the pregnancy rates significantly.

Adult↗

Abnormal endocrine profile among women with confirmed or presumed ovulation during long-term Norplant use.

FSH, LH, estradiol and progesterone were serially assayed during 8 cycles of six subjects using six subdermal implants releasing levonorgestrel (NORPLANT) for a period of 2 to 6 years. All 8 cycles studied had a very low LH peak and a low or nonexistent FSH peak as compared to 8 control cycles. The mean LH peak for NORPLANT users was 33.9 mIU/ml as compared to 142 mIU/ml in the control group; and FSH was 13.0 mIU/ml as compared to 31.3 mIU/ml in controls. A subsequent rise in progesterone was observed in the 8 cycles studied, but the mean mid-luteal levels were significantly lower than in controls (9.0 ng/ml vs. 15.6 ng/ml). No differences were observed in the estradiol curve. Two of the subjects using NORPLANT had a laparotomy performed on days 17 and 20 of the cycle, for surgical sterilization purposes. A distinctive corpus luteum with a stigma was observed. Our results indicate that women under prolonged use of NORPLANT do not have normal endocrine cycles, even though they may ovulate. It is doubtful however, that these ovulatory cycles can be fertile under the abnormal endocrine conditions found in our subjects. In addition to the possible effect of luteal insufficiency, the normal maturation of the oocyte may be impaired.

Adult↗

Liver disease associated with anti-liver-kidney microsome antibody in children.

In the past 10 years we have examined 20 children with inflammatory liver disease associated with high serum titers of anti-liver-kidney microsome antibody (anti-LKM). The first hepatic symptoms were progressive fatigue and jaundice, the fortuitous finding of hepatomegaly or splenomegaly with raised transaminase activity, or an acute hepatitis-like illness. At the time of diagnosis, hepatomegaly was present in 18 children, splenomegaly in 16, jaundice in nine, and ascites in two. Serum alanine transferase activities were elevated in all but two, who had already received steroids. Serum total gammaglobulin values were greater than 2.0 gm/dl in 16 children, prothrombin activity less than or equal to 60% in six, and serum titer of anti-LKM between 1:100 and 1:100,000. All children but one had cirrhosis, and histologic signs of aggressivity were present in 14. In 11 children one or more extrahepatic diseases were present, including type 1 diabetes, vitiligo, glomerulonephritis, autoimmune hemolytic anemia, hypoglycemia with hyperinsulinism, autoimmune thyroiditis, chronic mucocutaneous candidiasis with hypoparathyroidism, and multiple cutaneous and visceral telangiectasias. Treatment with prednisone and azathioprine improved the liver condition in 16 of the 18 patients given treatment. In eight of them discontinuation of treatment resulted in rapid relapse; 14 are still receiving treatment and have stable hepatic function with follow-up from 8 months to 6 1/2 years. Only two are free of treatment. Four children died, two in spite of immunosuppressive therapy, one during a relapse, and one of extrahepatic disease. These results indicate that this autoimmune inflammatory liver disease may have onset early in life, with several clinical patterns; is frequently associated with certain types of extrahepatic manifestations of autoimmune origin; and is a potentially fatal disease for which immunosuppressive treatment must be started early.

Adolescent↗

Small basic proteins of myelin from central and peripheral nervous systems are encoded by the same gene.

Peripheral nervous system (PNS) and central nervous system (CNS) rodent myelins, which are produced by different cell types, share common morphological and functional characteristics although their major integral membrane proteins are completely different. Both types of myelin however, contain sets of four myelin basic proteins (MBPs), which share similar immunochemical and electrophoretic properties. We have isolated and characterized cDNA clones corresponding to the rat mRNAs encoding the small MBPs (SMBPs) found in both CNS and PNS myelin. Sequence analysis of these clones indicate that SMBPs in both divisions of the nervous system are encoded by the same nucleotide sequences, which suggests that they are the products of the same gene expressed in both oligodendrocyte and Schwann cells. In dot-blot hybridization experiments with the CNS SMBP cDNA as a probe, it was shown that there is a 20-fold higher level of MBP mRNA in a CNS myelin fraction than in total brainstem mRNA. It also was found that in optic and sciatic nerves, which contain oligodendrocytes and Schwann cells respectively, there are higher levels (4-fold and 2-fold, respectively) of MBP mRNA than in brainstem. Blot-hybridization experiments showed that a probe derived from the coding region of the rat SMBP cDNA hybridizes to an homologous mRNA (approximately equal to 2.6 kilobases) present in human optic nerve, which is not detectable with a probe derived from the 3' untranslated region. This conservation of coding-region sequences is in accord with the highly homologous amino acid sequences reported for the MBPs in the two species.

Animals↗

Isolation and partial characterization of neurofibrillary tangles and amyloid plaque core in Alzheimer's disease: immunohistological studies.

Fractions enriched in neurofibrillary tangles (NFT) and amyloid fibrils were isolated from the cerebral cortex of three cases of senile dementia of the Alzheimer type. Distilled water suspensions of these fractions were excluded from all pore size gels and resisted digestion with various proteolytic enzymes. Formic acid/chloroform treatment of each fraction resulted in the appearance of 4,000-6,000, 15,000-17,000 and 24,000 molecular weight proteins, with concomitant diminution in the amount of excluded material at the top of each gel. The 4,000-6,000 dalton band was best seen in fractions containing randomly arranged amyloid fibrils, and its amino acid composition resembled that of the recently reported "beta" protein. A polyclonal antiserum to purified NFT reacted with tangles in neurons and in dystrophic neurites around plaques by immunoperoxidase staining. No reaction was obtained with cerebrovascular or plaque core amyloid immunohistologically, or with the 4-6 kD protein on immunoblots. Cross-reactivity with the neurofibrillary lesions occurring in Pick's disease, progressive supranuclear palsy, postencephalitic Parkinsonism and dementia pugilistica was also seen. Specific binding of this antiserum to the double filamentous structure was confirmed by immunoelectron microscopy. Although the presence of "beta" protein in both NFT and amyloid-containing fractions suggests that it may be an important constituent of both, cross-contamination cannot be excluded.

Alzheimer Disease↗

Monoclonal antibody studies defining the origin and properties of autoantibodies in Graves' disease.

The present report summarizes experiments with monoclonal antibodies to the TSH receptor. The data provide further insight into the TSH receptor structure and into the basis of autoimmune antibodies implicated in the pathogenesis of Graves' disease. They resolve many clinical questions and provide new approaches to enhance our understanding of autoimmune disease. In one new approach, it has been noted that the 11E8 TBIAb can precipitate the phosphorylated beta subunit of the insulin and IGF1 receptor. This cross-reactivity or recognition of determinants adjacent to the TSH receptor may not be random. Insulin, IGF1, alpha 1 adrenergic, and TSH receptors have been linked to a synergistic cascade response system of the thyroid involving growth, thyroglobulin biosynthesis, iodination of thyroglobulin, and thyroid hormone formation. Future studies with the monoclonals may help unravel this cascade system and its regulatory relationships, along with the relationships between autoimmune thyroid disease and autoimmune diseases of other organs.

Antibodies, Anti-Idiotypic↗

Experimental model for induction of cerebral aneurysms in rats.

Two groups of rats with induced arterial hypertension were studied. One group underwent section of the left common carotid artery with an end-to-side anastomosis of the proximal segment to the right common carotid artery. The second group was subjected to ligation of the left common carotid artery. The number of aneurysms caused by the procedure in the first group was higher, the difference being statistically significant (p less than 0.05, chi-square).

Animals↗

Anti-liver-kidney microsome antibody recognizes a 50,000 molecular weight protein of the endoplasmic reticulum.

Children with autoimmune chronic active hepatitis may have high titers of antibodies detected by immunofluorescence staining of hepatocytes and tubular cells in rat liver and kidney sections, respectively. These antibodies are directed against antigens contained in microsomal fractions prepared from these two organs. We have found that sera from these patients recognized a 50,000 mol wt protein present in higher concentration in smooth microsome subfractions compared with rough microsome subfractions. This protein is an integral membrane protein and is not glycosylated. It is exposed on the cytoplasmic face of the endoplasmic reticulum and is rather resistant to proteolysis with proteinase K. Since patients with liver disease of different etiology and similar severity of cell lysis do not give rise to liver-kidney microsome antibody (LKMA), lysis of hepatocytes is apparently not a sufficient condition for their development.

Animals↗

Anovulation, inadequate luteal phase and poor sperm penetration in cervical mucus during prolonged use of Norplant implants.

Blood samples for progesterone assay were collected for a total of 49 cycles, from 27 volunteers using the NORPLANT system. Levonorgestrel determinations were carried out in the same samples. A group of 12 women with normal cycles were studied in the same manner to serve as controls. Of the 49 cycles studied, 20 (41%) were ovulatory. The mean levonorgestrel level in ovulatory patients was 0.34 +/- 0.11 ng/ml (S.D.) compared to 0.42 +/- 0.14 ng/ml (S.D.) in anovulatory cycles. Compared to the control group, progesterone levels were significantly lower for users of NORPLANT implants during days -12 to -10 (p less than 0.025), -9 to -7 (p less than 0.05), -6 to -4 (p less than 0.0005) and days -3 to -1 (p less than 0.01). Cervical mucus evaluations and post-coital tests were done around mid-cycle in 29 of the cycles studied. All samples of cervical mucus were of poor quality, viscous and scarce, with a mean SPK of 4.1 +/- 2.3 cm. Most had absent or atypical ferning. Twenty-one subjects (73%) had a post-coital score of 1, and 4 (14%) of zero. Thus, anovulation, inadequate luteal phase and the direct effect of the continuous administration of levonorgestrel over cervical function, all seem to contribute to the effectiveness of NORPLANT implants.

Anovulation↗

Peripheral nerve involvement in children with chronic cholestasis and vitamin E deficiency. A clinical, electrophysiological and morphological study.

Seven children with early onset cholestasis who developed signs of peripheral neuropathy were investigated before and after one and a half to three years of treatment by vitamin E. This neuropathy appeared to be due to neuronoaxonal degeneration, but unusual Schwann cell inclusions were also observed. Although the treatment stabilized or improved the condition of all patients, no striking changes were noted neither in the EMG nor in the second nerve biopsy of a patient treated for three years. As the pathological process concerned it is probably both a developmental disorder and a degenerative phenomenon, substitutive vitamin E treatment should be proposed very early in life.

Adolescent↗

[Results of portasystemic shunts in cirrhosis in children].

A surgical porto-systemic shunt was carried out in 37 children and adolescents (age: 2 yrs-18 yrs) who presented with cirrhosis and portal hypertension. All patients were classified "A" or "B" according to Child's criteria. Proof of the patency of the shunt was obtained by endoscopy and/or angiography in 31 children. Two children died in the early postoperative period. Thrombosis of the shunt occurred in 4 children. With a follow-up of 6 months to 11 years, none of the 31 children operated on successfully presented with gastro-intestinal bleeding due to portal hypertension. Nine presented with one or several episodes of porto-systemic encephalopathy. Five of these were transient allowing for a normal diet to be resumed later. These results indicate that porto-systemic shunts are effective to prevent gastro-intestinal bleeding, even in young children with cirrhosis. However, in addition to Child's criteria, indications for shunt surgery must take into account the degree of hemorrhage risk and the possible need for a liver transplantation later.

Brain Diseases↗