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PubMed1979

17 alpha-Hydroxylase deficiency. A combination of hydroxylation defect and reversible blockade in aldosterone biosynthesis.

We have studied the hormonal secretion and excretion patterns in a patient with the XX type of 17 alpha-hydroxylase deficiency. In the untreated state, the patient's urine contained only those steroids which do not require 17-hydroxylation in their biosynthesis. Aldosterone was not produced in the patient and the metabolic product of its immediate precursor, 18-hydroxy-11-dehydro-tetrahydrocorticosterone, was excreted in markedly elevated amounts. This apparent complete block in 18 oxidation was reversible upon long-term ACTH suppression within 27 days. Direct in vitro incubation of the patient's adrenal gland removed at operation demonstrated, 1) the complete lack of 17 alpha-hydroxylase activity, 2) the functional block in the ability to oxidize the hydroxyl group at the 18 methyl side chain. The addition of physiological concentrations of angiotensin to the incubation medium further showed, 3) angiotensin mildly stimulated the entire aldosterone biosynthetic pathway, 4) angiotensin directly stimulated the conversion of 18-hydroxycorticosterone to aldosterone. We propose that in this patient, 17-hydroxylase deficiency produced a decreased plasma concentration of cortisol, followed by stimulation of deoxycorticosterone production by ACTH. The resultant increase in extracellular fluid volume suppressed plasma renin activity. This resulted in a low plasma concentration of angiotensin II which directly suppressed oxidation of 18-hydroxycorticosterone to aldosterone. This defect has been called corticosterone methyl oxidase defect type 2.

18-Hydroxycorticosterone↗

PubMed2000

In situ hybridization detection of human herpesvirus 6 in brain tissue from fatal encephalitis.

A 23-month-old girl died after 2 days' illness with rash, fever, and convulsions. Neuropathologic findings were consistent with viral hemorrhagic encephalitis in pontine tegmentum and medial thalamic areas. Human herpesvirus 6 (HHV-6) DNA was detected in pontine nuclei by in situ hybridization. In addition, polymerase chain reaction for HHV-6 of serum and paraffin-embedded pontine tissue was positive, and serology indicated an acute primary infection. This is the first case showing HHV-6 DNA in the brain cells of an immunocompetent patient with acute encephalitis.

Brain↗

PubMedDate not supplied

Comparison of a putative second serotype of chicken infectious anemia virus with a prototypical isolate II. Antigenic and physicochemical characteristics.

A putative new serotype of chicken infectious anemia virus (CIAV) isolated from 17-wk-old broiler breeder pullets was compared with a known, previously characterized CIAV isolate, the Del-Ros strain. Physicochemical characteristics evaluated induded thermal stability, size, pH, and chloroform sensitivity. Physicochemically, CIAV-7 was identical to CIAV. The virus isolates were compared antigenically by enzyme-linked immunosorbent assay, virus neutralization, immunofluorescence assay, and western blot. All four serologic assays demonstrated that CIAV-7 is antigenically distinct from the Del-Ros strain of CIAV. Additionally, polymerase chain reaction (PCR) and Southern blot were used to determine if there were similarities in genome sequence between the two viruses. CIAV-7 could not be detected with CIAV-specific PCR primers or a with CIAV-specific probe by Southern hybridization.

Animals↗

PubMed1986

A comparison of peer-initiation and teacher-antecedent interventions for promoting reciprocal social interaction of autistic preschoolers.

We compared two procedures for improving the social interactions of three autistic children. In a peer-initiation condition, confederates were taught to initiate interaction with the autistic children. In a teacher-antecedent condition, teachers prompted the autistic children to initiate with confederates, who had been taught to reciprocate. Using an alternating treatment design, differential effects were found. The peer-initiation procedure reliably increased the social responses of the autistic children, whereas the teacher-antecedent condition increased the initiations and responses of the autistic children. In addition, longer chains of social interaction occurred during the teacher-antecedent condition.

Autistic Disorder↗

PubMed2001

Does investor ownership of nursing homes compromise the quality of care?

OBJECTIVES: Two thirds of nursing homes are investor owned. This study examined whether investor ownership affects quality. METHODS: We analyzed 1998 data from state inspections of 13,693 nursing facilities. We used a multivariate model and controlled for case mix, facility characteristics, and location. RESULTS: Investor-owned facilities averaged 5.89 deficiencies per home, 46.5% higher than nonprofit facilities and 43.0% higher than public facilities. In multivariate analysis, investor ownership predicted 0.679 additional deficiencies per home; chain ownership predicted an additional 0.633 deficiencies. Nurse staffing was lower at investor-owned nursing homes. CONCLUSIONS: Investor-owned nursing homes provide worse care and less nursing care than do not-for-profit or public homes.

Activities of Daily Living↗

PubMed1992

Simultaneous insulinlike growth factor I and insulin resistance in obese Zucker rats.

It has recently been shown that the ability of insulinlike growth factor I (IGF-I) to stimulate glucose uptake and to lower circulating amino acid levels is retained in insulin-resistant diabetic BB rats. To examine in vivo effects of IGF-I in obese Zucker rats (another model of insulin resistance) 6 obese and 6 lean rats received euglycemic IGF-I infusions (0.65 nmol.kg-1.min-1). IGF-I-stimulated glucose uptake in obese rats was 50% lower than lean control rats (45.0 +/- 2.8 vs. 92.2 +/- 6.1 mumol.kg-1.min-1, respectively), even though the rise in circulating IGF-I levels was greater in the obese group during IGF-I infusion. In addition, branched chain amino acid concentrations that declined by 45% in lean controls were not suppressed significantly in obese rats (392 +/- 33 basal vs. 327 +/- 29 microM at 90 min). Equivalent results were observed during euglycemic insulin clamps (12 pmol.kg-1.min-1) in 7 obese and 11 lean rats. These studies demonstrate that obese Zucker rats are resistant to the effects of IGF-I and insulin on glucose and amino acid metabolism.

Aging↗

PubMed1987

Isolation and characterization of a pentameric amino acid from elastin.

An unknown amino acid was purified from bovine ligament elastin. The compound was shown by proton NMR to have a pyridinium ring structure similar to isodesmosine, yet containing an olefinic double bond on one additional side chain which was not attached to the pyridinium ring. Mass spectral analysis confirmed the NMR data and indicated a parent compound with a mass of 653. A structure is proposed that is derived from the condensation of five lysine residues. The trivial name of pentasine is proposed for this compound.

Amino Acids↗

PubMed2006

CDw78 defines MHC class II-peptide complexes that require Ii chain-dependent lysosomal trafficking, not localization to a specific tetraspanin membrane microdomain.

MHC class II molecules (MHC-II) associate with detergent-resistant membrane microdomains, termed lipid rafts, which affects the function of these molecules during Ag presentation to CD4+ T cells. Recently, it has been proposed that MHC-II also associates with another type of membrane microdomain, termed tetraspan microdomains. These microdomains are defined by association of molecules to a family of proteins that contain four-transmembrane regions, called tetraspanins. It has been suggested that MHC-II associated with tetraspanins are selectively identified by a mAb to a MHC-II determinant, CDw78. In this report, we have re-examined this issue of CDw78 expression and MHC-II-association with tetraspanins in human dendritic cells, a variety of human B cell lines, and MHC-II-expressing HeLa cells. We find no correlation between the expression of CDw78 and the expression of tetraspanins CD81, CD82, CD53, CD9, and CD37. Furthermore, we find that the relative amount of tetraspanins bound to CDw78-reactive MHC-II is indistinguishable from the amount bound to peptide-loaded MHC-II. We found that expression of CDw78 required coexpression of MHC-II together with its chaperone Ii chain. In addition, analysis of a panel of MHC-II-expressing B cell lines revealed that different alleles of HLA-DR express different amounts of CDw78 reactivity. We conclude that CDw78 defines a conformation of MHC-II bound to peptides that are acquired through trafficking to lysosomal Ag-processing compartments and not MHC-II-associated with tetraspanins.

Antigen Presentation↗

PubMed1999

Nomenclature of immunoglobulin A and other proteins of the mucosal immune system. IUIS/WHO subcommittee on IgA nomenclature.

The predominant immunoglobulin found in exocrine secretions of humans and most other mammals is secretory IgA, a polymeric form of IgA containing an additional glycoprotein chain designated "secretory component". In this article recommended abbreviations are proposed for the following forms of human IgA and other proteins of related interest: secretory IgA, secretory IgM, secretory component, polymeric immunoglobulin receptor, polymeric IgA, monomeric IgA, IgA subclass 1, IgA subclass 2, A2 allotype marker 1, and A2 allotype marker 2.

Animals↗

PubMed2000

Pasteurized, monoclonal antibody factor VIII concentrate: establishing a new standard for purity and viral safety of plasma-derived concentrates.

A factor VIII concentrate (Monoclate-P) manufactured using a combination of pasteurization and immunoaffinity chromatography has been chosen to compare and contrast manufacturing aspects of plasma-derived factor VIII concentrates. Pasteurization is a virucidal method with a long safety record in clinical practice, while immuno-affinity chromatography selectively isolates and purifies the procoagulant protein of factor VIII, and partitions potential viral contaminants and nonessential proteins to the unbound fraction. The complete Monoclate-P production process reduces human immunodeficiency virus by > or = 10.5 log10, Sindbis (a model for hepatitis C virus) by > or = 6.5 log10, and murine encephalomyocarditis virus (a non-enveloped model virus) by 7.1 log10. The viral safety of Monoclate-P has been further demonstrated in clinical studies in patients not previously treated with blood or plasma-derived products. Additionally, the manufacture of Monoclate-P includes careful donor screening and plasma testing for antibodies to syphilis and human immunodeficiency, hepatitis B, and hepatitis C viruses to enhance source plasma safety. Combined with donor selection and plasma testing, multiple viral reduction steps effectively eliminate both lipid-enveloped viruses (e.g. human immunodeficiency, hepatitis B and C) and non-lipid-enveloped viruses (e.g. hepatitis A). In addition, polymerase chain reaction-based nucleic acid detection tests for hepatitis B and C viruses and for human immunodeficiency virus-1 have been introduced as part of an investigational new drug mechanism.

Antibodies, Monoclonal↗

PubMed2000

High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia.

Deficiency of functional deoxycytidine kinase (dCK) is a common characteristic for in vitro resistance to cytarabine (AraC). To investigate whether dCK is also a target for induction of AraC resistance in patients with acute myeloid leukemia (AML), we determined dCK messenger RNA (mRNA) expression in (purified) leukemic blasts and phytohemagglutinin-stimulated T cells (PHA T cells) from patients with chemotherapy-sensitive and chemotherapy-resistant AML. In control samples from healthy donors (PHA T cells and bone marrow), only wild-type dCK complementary DNA (cDNA) was amplified. Also, in (purified) leukemic blasts from patients with sensitive AML, only wild-type dCK cDNAs were observed. These cDNAs coded for active dCK proteins in vitro. However, in 7 of 12 (purified) leukemic blast samples from patients with resistant AML, additional polymerase chain reaction fragments with a deletion of exon 5, exons 3 to 4, exons 3 to 6, or exons 2 to 6 were detected in coexpression with wild-type dCK. Deletion of exons 3 to 6 was also identified in 6 of 12 PHA T cells generated from the patients with resistant AML. The deleted dCK mRNAs were formed by alternative splicing and did code for inactive dCK proteins in vitro. These findings suggest that the presence of inactive, alternatively spliced dCK mRNA transcripts in resistant AML blasts may contribute to the process of AraC resistance in patients with AML. (Blood. 2000;96:1517-1524)

Acute Disease↗

PubMed2000

The chemical and biological versatility of riboflavin.

Since their discovery and chemical characterization in the 1930s, flavins have been recognized as being capable of both one- and two-electron transfer processes, and as playing a pivotal role in coupling the two-electron oxidation of most organic substrates to the one-electron transfers of the respiratory chain. In addition, they are now known as versatile compounds that can function as electrophiles and nucleophiles, with covalent intermediates of flavin and substrate frequently being involved in catalysis. Flavins are thought to contribute to oxidative stress through their ability to produce superoxide, but at the same time flavins are frequently involved in the reduction of hydroperoxides, products of oxygen-derived radical reactions. Flavoproteins play an important role in soil detoxification processes via the hydroxylation of many aromatic compounds, and a simple flavoprotein in liver microsomes catalyses many reactions similar to those carried out by cytochrome P450 enzymes. Flavins are involved in the production of light in bioluminescent bacteria, and are intimately connected with light-initiated reactions such as plant phototropism and nucleic acid repair processes. Recent reports also link them to programmed cell death. The chemical versatility of flavoproteins is clearly controlled by specific interactions with the proteins with which they are bound. One of the main thrusts of current research is to try to define the nature of these interactions, and to understand in chemical terms the various steps involved in catalysis by flavoprotein enzymes.

Animals↗

PubMed1975

Membrane penicillinase of Bacillus licheniformis 749/C, a phospholipoprotein.

The hydrophobic membrane penicillinase of Bacillus licheniformis 749/C has been characterized in view of its possible role in secretion of the hydrophilic exoenzyme. It differs from exoenzyme in carrying an additional phospholipopeptide chain of 25 amino acids that contains only Asx, Glx, Gly, and Ser residues. The NH2-terminal residues is phosphatidylserine. since the extra peptide chain is probably relatively polar, the phospholipid group may well be directly responsible for the hydrophobic properties of the membrane enzyme.

Amino Acid Sequence↗

PubMed1975

Complement activation by a univalent hapten-antibody complex.

The univalent hapten, nonadeca lysyl epsilon-Dnp-lysine, binds tightly to rabbit anti-2,4-dinitrophenyl antibody, and the complex has a sedimentation coefficient of 6.7, characteristic of a single antibody molecule. In this communication, we show that this complex is a good activator of the serum complement system. For activation to occur, the univalent hapten must contain the specific group which binds to the antibody, and also the polycationic chain. In addition, activation requires a functional complement-binding region on the intact antibody molecule. The classical pathway appears to be involved since the first, fourth, and second components of complement are markedly depleted when the complement system is activated by this univalent hapten-antibody complex.

Animals↗

PubMed2002

[Update on Acinetobacter baumannii].

RESISTANCE TO IMIPENEM: The increase in the prevalence of A. baumannii resistance is worrying because of the diversity of the enzymes implicated in the resistance and its epidemic diffusion that is always difficult to handle. BROAD SPECTRUM BETA-LACTAMASE: Still rare in Acinetobacter, a broad spectrum beta-lactamase has been demonstrated in a strain isolated during a urinary infection and at the origin of an outbreak. RISK FACTORS: Other than the classic risk factors, a survey regrouping the data from 28 Spanish hospitals showed that hospitalisation in an intensive care unit and the administration of an inappropriate antibiotherapy are two risk factors of mortality during Acinetobacter infections. DEPENDING ON THE PRODUCTION OF SLIME: An antibiotherapy must be administered earlier in strains producing slime than in strains that do not. TO FIGHT ACINETOBACTER: It is essential to break the epidemic chain. In addition to this priority measure, a policy of correct antibiotic use must be installed.

Acinetobacter Infections↗

PubMed1992

Structural analysis of low TCR-CD3 complex expression in T cells of an immunodeficient patient.

Normal membrane expression of the T cell receptor (TCR) depends on the coordinated synthesis and assembly of all seven proteins composing the complex, i.e. the TCR alpha and beta chains, the CD3 gamma, delta, and epsilon chains, and the zeta-zeta or zeta-eta dimer. In an experimental TCR membrane-defective T cell variant (Sussman, J. L., Bonifacino, J. S., Lippincott-Schwartz, J., Weissman, A. M., Saito, T., Klausner, R. D., and Ashwell, J. D. (1988) Cell 52, 85-95) and in two siblings whose lymphocytes express only a low level of the TCR/CD3 complex (Alarcon, B., Berkhout, B., Breitmeyer, J., and Terhorst, C. (1988) N. Engl. J. Med. 319, 1203-1208), a defect in zeta chain synthesis and/or assembly was thought to account for the defective membrane synthesis of the whole complex. We report on another immunodeficient patient whose T lymphocytes express the T cell receptor at one-tenth of normal fluorescence intensity and are not triggered to proliferate in vitro by anti-CD3 or anti-CD2 antibodies. Biochemical analysis of the patient's surface-iodinated peripheral blood lymphocytes failed to detect TCR alpha and beta, or CD3 gamma, delta, and epsilon proteins but revealed the presence of the zeta homodimer (probably as a result of the high proportion of natural killer cells). In the cytoplasm, TCR alpha and beta proteins and the zeta chain were detected, but, using monoclonal anti-CD3 antibodies, the CD3 gamma, delta, and epsilon chains were not. In addition, the CD3 epsilon chain was not detected with polyclonal antiserum in a very sensitive Western blotting detection system. The zeta chain was shown to be synthesized by the patient's T and natural killer cells. Northern blot analysis revealed normal levels of normal-size TCR beta and CD3 gamma, delta gene-specific mRNAs and decreased levels of TCR alpha mARN; CD3 epsilon gene transcripts were of abnormal size and present in lower than normal amounts. These findings suggest that this defect in T cell receptor-CD3 expression involves a mutation in the CD3 epsilon gene leading to the synthesis of an abnormal and unstable CD3 epsilon subunit.

Antigens, CD↗

PubMed1977

[Secretory immunoglobulin A].

Secretory IgA is the prevailung immunoglobulin on the mucous membranes of different tissues. It is a polymer immunoglobulin and in comparison to the serum IgA the secretory IgA has a additional polypeptide chain, the secretory component. The secretory IgA is synthesized locally in the mucosa. Secretory IgA is a very important factor in the immune defence of the mucous membranes. Secretory antibodies are regulated independently from serum antibodies. They show a virus neutralizing effect and activities against bacteria and lifeless noxa. The mechanism is not yet clear. It is possible, that the reaction of the secretory IgA with the antigen prevents settlement of microorganisms on the mucous membranes. The clinical importance of secretory IgA is undoubted especially the deference of the mucosa in cases of a virus infection.

Antibodies↗

PubMed2005

Is cytomegalovirus associated with human colorectal tumorigenesis?

Despite the rapid advance in the understanding of molecular pathways underlying human colorectal tumorigenesis, the causes that initiate dysregulation of the pathways remain largely unknown. Human cytomegalovirus (CMV) has been implicated as a potential etiopathogenetic agent. To further investigate whether CMV participates in human colorectal tumorigenesis, we examined 23 colorectal hyperplastic polyps, 65 colorectal adenomas, and 51 colorectal adenocarcinomas by immunohistochemical analysis using 2 antibody mixtures that recognize CMV immediate early, early, and delayed gene products. The results show that while typical nuclear staining (with or without cytoplasmic positivity) was observed in control cases of CMV colitis, no nuclear positivity was detected in any cases studied. Focal and weak cytoplasmic staining was noted in a subset of cases, particularly when a higher antibody concentration was used. This staining was believed to be nonspecific, however, because it also was observed in normal-appearing colonic mucosa. In addition, polymerase chain reaction failed to detect the presence of CMV DNA in 24 selected cases showing nonspecific cytoplasmic immunostaining. These observations demonstrate an absence of CMV proteins and DNA in human colorectal adenocarcinomas and their precursor lesions.

Adenocarcinoma↗