Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pairs of frozen human patellar tendon-bone (PTB) ligament allografts were exposed to either 0 or 4 Mrad of gamma irradiation sterilization, the latter value based on recent reports suggesting higher dosage levels for adequate sterilization against the human immunodeficiency virus. All specimens were subjected to three levels of loading: lower functional loads, higher functional loads, and failure. Lower functional loads were simulated by performing in vitro static and cyclic creep tests, similar to loads that the surgeon and patient would apply before and after implantation, respectively. Higher functional loads, simulating moderate activities of daily living, were represented by the slope of the linear portion of the force-elongation curve or linear stiffness. Failure or trauma was then simulated by failing the grafts in tension at a high strain rate. We found that the irradiation treatment shortened the tendon by only 0.6 mm, which was nevertheless statistically significant (p < 0.01). By contrast, 4 Mrad did not significantly alter either static or cyclic creep (p > 0.05) at lower functional loads. Instead, irradiation produced the greatest changes during failure testing, reducing both the graft's linear stiffness by 12% (p < 0.025) and maximum force by 26% (p < 0.001). Although our data do not describe how an allograft might perform during the early healing and later collagen-remodelling phases, such in vitro studies remain important if we are to optimize allograft properties before arthroscopic anterior and posterior cruciate ligament reconstruction.
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PMID:The effects of 4 Mrad of gamma irradiation on the initial mechanical properties of bone-patellar tendon-bone grafts. 800 47

Rapidly accumulating evidence suggests that a proportion of patients with acquired immunodeficiency syndrome (AIDS) develop hypertensive pulmonary vascular disease reminiscent of primary pulmonary hypertension. As an initial step to explore the link between AIDS and hypertensive pulmonary vascular disease, the present study determined whether pulmonary hypertension is present in a well-characterized murine model of retrovirus-induced immunodeficiency. In agreement with previous reports, mice infected with the LP-BM5 murine leukemia virus developed polyclonal B and T cell activation followed by progressive and severe B and T cell immunodeficiency. At 12 wk postinfection, when persistent immunodeficiency was established, mice were anesthetized, and right ventricular systolic pressure was determined in open-chest, mechanically ventilated animals. Mean right ventricular systolic pressure was 14.7 +/- 1.3 mm Hg in control animals and was increased significantly to 22.5 +/- 3.2 mm Hg in virus-infected mice. Right ventricular hypertrophy was also present in infected mice as evidenced by a 27% increase in the ratio of right to left ventricular weights; there were no group-dependent differences in the left ventricular to total-body weight ratio. Morphometric evaluation indicated that medial thickness in muscularized pulmonary arteries, expressed as a percentage of the external diameter, was 9.6 +/- 0.4% in control lungs and increased to 14.4 +/- 0.5% in lungs from infected animals. Qualitative histopathologic analysis suggested increased perivascular collagen deposition in lungs from infected animals relative to control animals. Unlike AIDS patients with pulmonary hypertension, infected mice did not exhibit plexiform lesions or intimal fibrosis of the pulmonary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary hypertension in a murine model of the acquired immunodeficiency syndrome. 802 49

Susceptibility to collagen-induced arthritis (CIA) in mice is associated with a class II gene in MHC (Aq) but also with unknown genes outside MHC. Investigated here is the influence of genes on the X chromosome as well as the role of the X-linked immunodeficiency (xid) mutation. Reciprocal male F1 hybrids, bred to be heterozygous or homozygous for Aq, showed a genetic influence in their susceptibility to develop CIA. Crosses were made between B10.G, B10.Q, DBA/1, SWR/J, C3H.Q and CBA/Ca, and all F1 mice were castrated to avoid sex hormone modulation of the susceptibility. A differential timing of arthritis onset and severity were seen in the reciprocal F1 males. An exception was the reciprocal F1 male offspring from SWR/J and DBA/1 crosses which differed only in disease severity late in the course of the disease. The female F1 crosses did not show the same pattern of differential susceptibility to CIA as the F1 males. To exclude the possible influence of the Y chromosome, F1 males of reciprocal crosses were back-crossed to the parental strains creating offspring with equal X chromosomes but divergent Y chromosomes. No difference in development of arthritis was observed in these. The influence of the xid mutation was investigated next. The xid loci from the CBA/N mouse was bred into DBA/1 strain which is highly susceptible to CIA. The resulting congenic DBA/1-xid strain was resistant to induction of CIA and did not develop an antibody response to type II collagen. We conclude that polymorphic genes on the X chromosome modulate susceptibility to CIA. The results from the experiments with mice carrying xid mutations confirm that such immune modulating genes exist on the sex chromosomes.
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PMID:Genes on the X chromosome affect development of collagen-induced arthritis in mice. 825 7

Patients with human immunodeficiency virus (HIV) infection are prone to the development of focal segmental glomerulosclerosis, a lesion in which increased mesangial cell proliferation and matrix synthesis may play a role. We undertook the present study to determine whether HIV sera may affect mesangial cell proliferation and matrix synthesis either directly or indirectly via effects on macrophage supernatants. Pooled HIV sera was found to significantly enhance (P < 0.01) mesangial cell proliferation in a concentration-related manner. Mesangial cell proliferation was significantly suppressed by two medications commonly utilized in HIV-infected patients, azidothymidine and trimethoprim/sulfamethoxazole, and was not significantly altered by lipopolysaccharide, suggesting that these medications as well as recurrent infection are unlikely to account for the proliferative effect of HIV sera. Supernatants from HIV sera-treated macrophages were found to significantly enhance (P < 0.01) mesangial cell incorporation of [3H]proline, a marker for synthesis of the matrix component collagen, compared to supernatants from control sera-treated macrophages. These results suggest that HIV sera may directly enhance mesangial cell proliferation and may indirectly increase mesangial cell matrix synthesis by altering macrophage secretory products. These effects may play a role in the development of glomerulosclerosis in patients with HIV infection.
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PMID:Effects of human immunodeficiency virus sera and macrophage supernatants on mesangial cell proliferation and matrix synthesis. 836 79

Several neuropathologic findings in infants and children with human immunodeficiency virus type-1 (HIV-1) infection are different from those observed in adults, probably related to the fact that the retroviral infection occurs in the setting of neuro-development. This report describes the interaction and biologic activity of tat, the HIV-1 trans-activating protein on human neuroblasts. Two human neuroblastoma cell lines, LAN-5 and GI-CA-N, have been studied for their capability to adhere to tat (full recombinant protein) and to two different peptide residues of it. Both cells adhere to tat and tat46-60 basic domain, although not to tat65-80 residue, which contains the RGD (arginine-glycine-aspartic acid) motif. Adhesion to collagen I was inhibited by preincubating GI-CA-N cells with tat,46-60 although not with tat,65-80 indicating the capability of the basic residue to interfere with collagen I-induced cellular adhesion. The expression of 200-kD neurofilaments induced by collagen I was not induced by tat,46-60 indicating that neural differentiation along the same pathway is not mimicked by this peptide. Neuroblast cell proliferation was not affected by adhesion to tat46-60 nor to tat.65-80 GI-CA-N cells are not permissive to HIV-1 infection. However, proviral DNA was documented in the cell lysate for 14 consecutive in vitro passages, whereas HIV-1 transcription was never detectable. This would exclude the possibility that tat would be transduced by these cells. GI-CA-N stained negative for CD4, although positive for Gal-C, which may explain HIV-1 entry. Results show that immature human neural cells interact with tat protein and/or its basic residue in vitro. A mechanism similar to that herein described would possibly be active in vivo, which may help in clarifying the pathogenic mechanisms of neurologic dysfunction and destruction of the CNS observed in infants infected with HIV-1.
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PMID:Adhesion of human neuroblasts to HIV-1 tat. 855 50

The factors contributing to unequal mortality rates following Pneumocystis carinii pneumonia (PCP) in different groups at risk are poorly understood. We therefore compared the first episodes of PCP without prophylaxis in human immunodeficiency virus infected (HIV) and otherwise immunosuppressed patients in this retrospective study. A total of 58 HIV-infected and 16 otherwise immunosuppressed patients were analysed. The comparison included epidemiological, clinical, laboratory, radiological and microbiological data, as well as therapy and clinical course. A prognostic analysis was performed using a logistic regression model. The mortality was significantly different in the two groups (HIV group 17 versus non-HIV group 50%). Renal transplant patients had a higher survival rate as compared to malignancy or collagen vascular disease as underlying diseases at risk. Acute respiratory failure was more common in the non-HIV group. Variables found to be significantly associated with lethal outcome in univariate analysis were alveolar to arterial pressures difference for oxygen (P(A-a),O2), haemoglobin, platelet count, total protein, serum albumin, and gamma-globulins in the HIV-group, and serum albumin in the non-HIV group. In the multivariate analysis of the HIV group, platelet count and gamma-globulins remained independent prognostic factors. In conclusion, in the HIV-group, mortality is closely related to the severeness of PCP as well as to the severeness of the acquired immune deficiency syndrome (AIDS) disease. In the non-HIV group, malignancy and collagen vascular disease as underlying conditions at risk account for the high mortality rate. Its severeness was mainly reflected by serum albumin, which represented the only variable found to be significantly associated with death in both groups.
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PMID:Clinical characteristics and outcome of Pneumocystis carinii pneumonia in HIV-infected and otherwise immunosuppressed patients. 857 83

Given the similarities between the two viruses, the feline immunodeficiency virus (FIV) is becoming an interesting animal model for human immunodeficiency virus (HIV) studies. To explore the still controversial role of the liver in the development of HIV infection, sinusoidal endothelial cells (SEC) were isolated, and primary cultures were infected with the FIV Villefranche IFFA strain. The isolated cells were characterized by their typical fenestrations, the presence of von Willebrand factor (vWf), and their ability to take up acetylated low-density lipoproteins and denatured collagen. Two weeks after infection, significant amounts of FIV p24 antigen were detected by immunofluorescence in both multinucleated giant and single cells and by enzyme-linked immunosorbent assay in the culture medium. High amounts of viral particles were observed together with different steps of budding at the plasma membrane or at the membrane of intracytoplasmic vacuoles. The released viral particles were shown to be infectious for a permissive cell line. During the first 3 weeks of infection, the only cytopathic effect of FIV was syncytia formation. No noticeable impairment of the pattern of fenestrations and the modulation of their number by a cytoskeleton-mediated process occurred. The productive infection of SEC may contribute to the progression of the infection.
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PMID:Productive infection of primary cultures of endothelial cells from the cat liver sinusoid with the feline immunodeficiency virus. 862 Nov 76

In human immunodeficiency virus 1 (HIV-1)-infected patients, a hypoperfusion is seen by SPECT analyses in different brain regions but a specific pattern for the predominance of a specific brain region has not been found. The vessels of the cerebral cortex of the frontal, temporal, parietal, and occipital lobes of acquired immunodeficiency syndrome (AIDS) brains and control brains were analyzed by immunohistochemistry and lectin histochemistry. Immunohistochemistry was performed for collagen IV, laminin (basal lamina), and factor VIII (endothelial cell) and lectin histochemistry [Ricinus communis agglutinin (RCA-I), Ulex europaeus agglutinin (UEA-I), wheatgerm agglutinin (WGA) and soybean agglutinin (SBA)] was used to study changes of glycoproteins in the endothelial cell membrane. Vessels were counted in the gray and white matter, and their staining intensity for the different antibodies and lectins was rated using a three-point scale. Immunoreactivity for collagen IV was reduced in AIDS brains, which may be related to thinning of the basal lamina of cerebral vessels, as has previously been shown by electron microscopy. Lectin histochemistry with SBA, UEA-I and WGA indicated loss of glycoproteins in the membrane of endothelial cells. The data from the present study show morphological changes of the endothelial cells and of the basal lamina in the brain of individuals with AIDS, and might represent the morphological sequelae of a disturbed blood-brain barrier, or may account for the hypoperfusion seen in SPECT analyses.
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PMID:Vascular changes in the cerebral cortex in HIV-1 infection. II. An immunohistochemical and lectinhistochemical investigation. 881 Nov 23

The introduction of molecular therapy through the delivery of nucleic acids either as oligonucleotides or genetic constructs holds enormous promise for the treatment of renal disease. Significant barriers remain, however, before successful organ-specific molecular therapy can be applied to the kidney. These include the development of methods to target the kidney selectively, the definition of vectors that transduce renal tissue, the identification of appropriate molecular targets, the development of constructs that are regulated and expressed for long periods of time, the demonstration of efficacy in vivo, and the demonstration of safety in humans. As the genetic and pathophysiologic basis of renal disease is clarified, obvious targets for therapy will be defined, for example, polycystin in polycystic kidney disease, human immunodeficiency virus (HIV) type 1 in HIV-associated nephropathy, alpha-galactosidase A in Fabry's disease, insulin in diabetic nephropathy, and the "minor" collagen IV chains in Alport's syndrome. In addition, several potential mediators of progressive renal disease may be amenable to molecular therapeutic strategies, such as interleukin-6, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and transforming growth factor-beta(TGF-beta). To test the in vivo efficacy of molecular therapy, appropriate animal models for these disease states must be developed, an area that has received too little attention. For the successful delivery of genetic constructs to the kidney, both viral and nonviral vector systems will be required. The kidney has a major advantage over other solid organs since it is accessible by many routes, including intrarenal artery infusion, retrograde delivery through the uroexcretory pathways, and ex vivo during transplantation. To further restrict expression to the kidney, tropic vectors and tissue-specific promoters also must be developed. For the purpose of inhibition of endogenous or exogenous genes, current therapeutic modalities include the delivery of antisense oligodeoxynucleotides or ribozymes. For these approaches to succeed, we must gain a much better understanding of the nature of their transport into the kidney, requirements for specificity, and in vivo mechanisms of action. The danger of a rush to clinical application is that superficial approaches to these issues will likely fail and enthusiasm will be lost for an area that should be one of the most exciting developments in therapeutics in the next decade.
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PMID:Molecular therapy for renal diseases. 884 Sep 36

Although very little is known about the aetiology of sarcoidosis, its immunopathogenesis is now better known. The interaction of alveolar macrophages and T cells may play a role in the pathomechanism of the disease. To infiltrate the tissue, lymphocytes have to migrate through the subendothelial basement membrane and interstitium, rich in extracellular matrix (ECM). The interaction of lymphocytes with proteins of the ECM may play an important role in the migration, accumulation and activation of these cells. The aim of our study was to estimate the ability of the ECM components (collagen I, collagen IV and fibronectin) to co-stimulate T-cells in patients with sarcoidosis. The peripheral blood was obtained from 14 sarcoid patients. The disease was confirmed histologically in 9 cases and in 5 patients on clinical grounds. In radiological findings 4 persons were at the first stage of the disease, 4 at the second, in three cases interstitial changes were found and in three patients, the fibrosis on the X-ray was noticed. No one of those patients were treated with steroids during last 2 months. Normal peripheral blood T cells are strongly co-stimulated by ECM proteins. In contrast, lymphocytes from patients with sarcoidosis were inhibited by the ECM proteins. The mean co-stimulation ratios (OKT3 + ECM proteins:OKT3 alone) were significantly lower for all ECM proteins (collagen I: p < 0.00009; collagen IV: p < 0.02; fibronectin: p < 0.04). Our data shed a new light on the nature of sarcoidosis associated immunodeficiency and suggest that disturbed T cells: ECM interactions may play a role in the pathogenesis.
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PMID:[Co-stimulating effect of extracellular matrix proteins on T lymphocyte proliferation in patients with sarcoidosis. Preliminary tests]. 899 64


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