Search PubMed⌕ Search

Biomedical subjects

J R Wright

Publications and source records attributed to J R Wright.

At least 109 records · Page 6Linked to original sources
PubMed1996

Surfactant protein A protects growing cells and reduces TNF-alpha activity from LPS-stimulated macrophages.

In addition to its effect on surfactant lipids, surfactant protein (SP)-A promotes host defense. To define further the role of SP-A in regulating immune cell function, we evaluated the effect of SP-A on lipopolysaccharide (LPS)-activated alveolar macrophages in two settings. First, cocultured LPS-activated macrophages significantly inhibited lung fibroblast growth, but SP-A (added daily) attenuated this effect. Both LPS and SP-A acted via macrophages rather than directly on the fibroblasts, at least partially by affecting tumor necrosis factor (TNF)-alpha activity. TNF-alpha reproduced the growth suppression, anti-TNF-alpha antibodies attenuated the effect LPS-activated macrophages, and SP-A reduced TNF-alpha activity in conditioned medium. Second, SP-A reduced TNF-alpha activity in medium from isolated LPS-stimulated macrophages. The effects of SP-A were noted with or without serum, were dose-dependent and reversible, and were seen with two different serotypes of smooth LPS. Equimolar concentrations of immunoglobulin G and C1q had no effect. Thus SP-A both enhances host defense and modulates immune functions of alveolar macrophages.

Animals↗
PubMed1996

Human surfactant protein A enhances attachment of Pneumocystis carinii to rat alveolar macrophages.

Pneumocystis carinii (PC) pneumonia remains one of the most important opportunistic pulmonary infections. The alveolar macrophage (AM) is likely the primary cell for recognition and removal of PC. The histopathology of PC pneumonia is characterized by a surfactant-like alveolar exudate. We hypothesize that surfactant protein A(SP-A), the major apoprotein of surfactant, mediates attachment of PC to rat AMs by acting as a ligand between the organism and the AM. In this study, attachment of PC was determined using (51)Cr-labeled PC incubated at 4 degrees C with normal rat AM monolayers in the presence or absence of human SP-A. SP-A significantly enhanced attachment of PC from 14.2 +/- 1.2% to 42.0 +/- 3.8% (P<0.05). This enhanced attachment was visualized and quantified morphologically with confocal microscopy. PC attachment by SP-A was calcium- and mannose-dependent as SP-A-mediated attachment was significantly reduced in the presence of EGTA and mannose to 13.1 +/- 1.6% and 19.3 +/- 2.6%, respectively (P<0.05). Addition of type V collagen and antibodies to SP-A also significantly reduced SP-A-mediated attachment to 4.9 +/- 1.2% and 10.1 +/- 1.2%, respectively (P<0.05). We conclude that SP-A can function as a ligand between PC and the AM and may represent an important detection and clearance mechanism of PC from the alveolar spaces.

Animals↗
PubMed1996

Surfactant proteins A and D increase in response to intratracheal lipopolysaccharide.

Surfactant proteins A (SP-A) and D (SP-D) are "collectins": proteins with collagen-like region and lectin domain that bind carbohydrates in a calcium-dependent manner. Mannose-binding protein, a serum collectin, is an acute-phase protein. We hypothesized that SP-A and SP-D would respond to an acute stress, such as lung inflammation, in the same manner as does mannose-binding protein, with increased messenger ribonucleic acid (mRNA) and protein production. Rats received intratracheal lipopolysaccharide (LPS; 0.5 mg/kg) or vehicle and were killed 1, 6, 24, and 72 h later. Their lungs were lavaged and the lung tissue homogenized and analyzed for SP-A, SP-D, and phospholipids. Tissue levels of SP-A were increased by 6 h, peaked at 24 h, and were still elevated at 72 h in LPS-treated animals as compared with those given vehicle. SP-A and SP-D levels in lavage fluid were significantly elevated at 72 h. Message levels for SP-A and SP-D, but not SP-B, were significantly increased at 24 h. Lavage phospholipid levels first increased, then decreased in both the control and LPS-treated animals, and significantly less phospholipid was recovered in the lavage fluid of the LPS-treated animals than in that of controls at 72 h. Although other mechanisms, including altered surfactant metabolism, may be involved, these data are consistent with our hypothesis that SP-A and SP-D are upregulated by an acute inflammatory stress in a manner analogous to that of the structurally and functionally related serum acute-phase reactant, mannose-binding protein. We speculate that this upregulation may be a protective response for the lungs.

Administration, Inhalation↗
PubMed1996

Phenotypic relationship of yield and type scores from first lactation with herd life and profitability.

Milk records from Ayrshire, Brown Swiss, Guernsey, Jersey, and Milking Shorthorn cows that first calved between 18 and 35 mo were combined with scores for linear type traits collected before 43 mo during first lactation to study herd life and lifetime profitability. Profitability (discounted relative net income) was the value of milk, calves, and cow salvage minus fixed costs, operating costs, and cow depreciation costs. Cows were included if they appeared only in a single herd and if the herd remained on test for 72 mo after birth date of the cow. Phenotypic correlations were computed for milk and fat yields and for 14 type traits during first lactation with nine variables for lifetime performance from 3895 Ayrshire, 7997 Brown Swiss, 20,179 Guernsey, 71,731 Jersey, and 628 Milking Shorthorn cows. Multiple correlations for predicting discounted relative net income for the four breeds with the most data were 0.43 to 0.46 from milk and fat yields (linear and quadratic effects) during first lactation, 0.11 to 0.29 from final score, and 0.21 to 0.33 from all type traits. Type scores had considerably less predictive ability than yield during first lactation for predicting profitability and had limited predictability after yield was included. Final score increased multiple correlations only 0.00 to 0.02 above that for yield for the same four breeds. Final score plus 13 type traits (linear, quadratic, and interaction effects) increased multiple correlations only 0.02 to 0.04 above that for yield. Because of the limited value of some of the linear type traits, an effort should be initiated to eliminate them from programs of breed associations.

Aging↗
PubMed1995

Prolongation of rat islet allograft survival by treatment with monoclonal antibodies against VLA-4 and LFA-1.

In this study, we investigated the effects of treatment with monoclonal antibodies against the VLA-4 and LFA-1 adhesion molecules on rat islet allograft rejection. TA-2 and TA-3 are function-blocking mAb against rat VLA-4 and LFA-1, respectively. Lewis rats were made diabetic (plasma glucose levels > 22.2 mmol/L) with streptozotocin. One week later, 1500 freshly isolated Wistar Furth rat islets were transplanted under the left kidney capsule of each rat. Monoclonal antibodies were administered intravenously at a dosage of 2 mg on the day of islet transplantation and then intraperitoneally every second day for 3 weeks or until graft rejection. Plasma glucose levels were monitored at least 3 times a week and blood leukocyte counts were monitored every 4 days. Rejection was defined as 2 plasma glucose levels > 11.1 mmol/L. Mean graft survival times in untreated and control mAb-treated rats were 5.3 and 6.0 days, respectively. Treatment with anti-VLA-4 or anti-LFA-1 resulted in only modest prolongation of mean graft survival time (9.3 and 7.4 days, respectively). However, treatment with the combination of anti-VLA-4 plus anti-LFA-1 resulted in long-term (i.e., 60-day) graft survival in 5 of 7 rats. Graft nephrectomy and histology confirmed islet graft survival at 60 days. A second Wistar Furth rat islet graft under the opposite renal capsule after graft nephrectomy did not show full tolerance; however, the function of the second graft was significantly prolonged without any immunosuppression. Combined blockade of VLA-4 and LFA-1 also markedly prolonged islet graft survival when islets were transplanted via the portal vein. In conclusion, both VLA-4 and LFA-1 play a role in islet allograft rejection and blockade of both prevents or greatly delays graft rejection.

Animals↗
PubMed1995

Surfactant protein a promotes attachment of Mycobacterium tuberculosis to alveolar macrophages during infection with human immunodeficiency virus.

The incidence of tuberculosis is increasing on a global scale, in part due to its strong association with human immunodeficiency virus (HIV) infection. Attachment of Mycobacterium tuberculosis to its host cell, the alveolar macrophage (AM), is an important early step in the pathogenesis of infection. Bronchoalveolar lavage of HIV-infected individuals demonstrated the presence of a factor which significantly enhances the attachment of tubercle bacilli to AMs 3-fold relative to a normal control population. This factor is surfactant protein A (SP-A). SP-A levels are increased in the lungs of HIV-infected individuals. SP-A levels and attachment of M. tuberculosis to AMs inversely correlate with peripheral blood CD4 lymphocyte counts. Elevated concentrations of SP-A during the progression of HIV infection may represent an important nonimmune risk factor for acquiring tuberculosis, even before significant depletion of CD4 lymphocytes in the peripheral blood occurs.

AIDS-Related Opportunistic Infections↗
PubMed1995

Association of surfactant protein C with isolated alveolar type II cells.

Surfactant protein C (SP-C) is a small hydrophobic protein that is synthesized and secreted by alveolar type II cells. The mechanism of clearance of SP-C from the alveolar airspace is not well understood, although previous studies demonstrated that recombinant SP-C instilled into the lungs of spontaneously breathing anaesthetized rats was taken up by type II cells and incorporated into lamellar bodies. The current investigation was undertaken to characterize the interaction of a complex of SP-C and surfactant-like lipids with freshly isolated rat alveolar type II cells under conditions in which the extracellular milieu can be regulated. SP-C was isolated from alveolar proteinosis lavage fluid and radiolabeled with 125I-Bolton-Hunter reagent. The radiolabeled protein retained its ability to facilitate adsorption of phospholipids to an air/liquid interface. Labeled human SP-C associated with isolated type II cells in a concentration-dependent manner that was also dependent upon temperature and time. The association of labeled SP-C with isolated type II cells did not saturate up to 150 micrograms/ml. SP-A significantly enhanced the association of SP-C with isolated type II cells. Under the experimental conditions tested, SP-C was not degraded to TCA-soluble products. These results are consistent with the hypothesis that association or uptake of SP-C by type II cells may be enhanced by SP-A and that like SP-A, SP-C is recycled by type II cells.

Animals↗
PubMed1995

Essential fatty acid deficiency prevents multiple low-dose streptozotocin-induced diabetes in naive and cyclosporin-treated low-responder murine strains.

We have previously shown that essential fatty acid (EFA) deficiency prevents diabetes and ameliorates insulitis in low-dose streptozotocin (LDS)-treated male CD-1 mice. The effects of EFA deficiency on the incidence of diabetes after LDS treatment has not been examined in other strains. In contrast to highly susceptible CD-1 mice, several other strains of mice are only partially susceptible to LDS treatment and do not develop appreciable insulitis; however, the susceptibility of these strains can be markedly increased by cyclosporin A (CsA) pretreatment to reduce suppressor cell function. Weanling male BALB/cByJ, DBA/2J, and C57BL/6J mice were placed on EFA-deficient (EFAD) or control diets for 2 months and then divided into experimental and control groups. Ten EFAD and 10 control mice from each strain received LDS treatment (40 mg/kg/d 5 d); an additional 10 EFAD BALB/cByJ and another 10 control BALB/cByJ mice received subcutaneous CsA injections (20 mg/kg/d) for 14 days prior to and for 5 days simultaneous with LDS treatment (40 mg/kg/d 5 d). Plasma glucose levels for all mice were determined 3 times per week for 3 weeks after LDS treatment. Mean plasma glucose levels (+/- SEM) at the end of the experiment were significantly lower in the EFAD groups vs control groups in BALB/cByJ (P < 0.001), DBA/2J (P < 0.00001), and C57BL/6J (P = 0.012) mice. CsA supplementation increased the severity of diabetes in LDS-treated BALB/cByJ mice (P < 0.0005); however, EFA deficiency also prevented diabetes in CsA-supplemented BALB/cByJ mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Characterization of the pancreatic hormones from the Brockmann body of the tilapia: implications for islet xenograft studies.

The Brockmann body of the teleost fish, the tilapia (Oreochromis nilotica) has been considered as a potential source of islet xenograft tissue for patients with insulin-dependent diabetes. This study describes the purification from an extract of tilapia Brockmann bodies of insulin and several peptides arising from different pathways of post-translational processing of two proglucagons, two prosomatostatins and proPYY. The primary structure of tilapia insulin is similar to insulins from other teleosts (particularly the anglerfish, Lophius americanus) except that the strongly conserved glutamine residue at position 5 in the A-chain, a residue that is important in the binding of insulin to its receptor, is replaced by glutamic acid. In common with other teleosts, the tilapia Brockmann body expresses two non-allelic glucagon genes. Alternative pathways of post-translational processing lead to glucagons with 29 and 36 amino acid residues derived from proglucagon I and glucagons with 29 and 32 residues derived from proglucagon II. Glucagon-like peptides with 30 and 34 residues derived from proglucagon II were also isolated. In each case, the longer peptide is a C-terminally extended form of the shorter. Tilapia peptide tyrosine-tyrosine (PYY) was isolated in a C-terminally alpha-amidated from with 36 amino acid residues that is structurally similar (89% sequence identity) to anglerfish PYY. A 30-amino acid peptide, representing the C-terminal flanking peptide of PYY, was also isolated that shows only 53% sequence identity with the corresponding anglerfish peptide. Tilapia somatostatin-14 is identical to mammalian somatostatin but the [Tyr7, Gly10] somatostatin-containing peptide derived from prosomatostatin II contains the additional substitution (Phe11-->Leu) compared with the corresponding peptide from other teleosts.

Adipose Tissue↗
PubMed1995

Investigative approach to frog gastrocnemius laboratory: potential impact on animal use in teaching laboratories.

With growing concern over the use of animal experimentation in the teaching of physiology, many biology departments are reassessing the use of animal experiments in the teaching lab. However, it may be just as important to assess how animal experimentation is used in the undergraduate teaching laboratory rather than simply assessing if animal experimentation should be used at all. In our study, sophomore-level life science students enrolled in a core organismal biology course undertook a laboratory exercise designed to elucidate properties of muscles and neuromuscular communication following two protocols: 1) a standard demonstrational model wherein students were told to undertake the exercise as a means to understand physiological processes that they had been exposed to previously in lecture or 2) an investigative model wherein the use of the gastrocnemius preparation was a logical next step in an ongoing investigation, the content of which was driven by student-generated hypotheses. We have observed a significant decrease in a number of the negative comments concerning the use of animals in experimentation (25.6 vs. 3.6%) since the implementation of the investigative approach to the laboratory, suggesting that curricular approaches to the use of animals in the teaching laboratory may have an impact on student attitudes concerning animal experimentation.

Animal Welfare↗
PubMed1995

Degradation of surfactant lipids and surfactant protein A by alveolar macrophages in vitro.

Pulmonary surfactant is synthesized and secreted into the airspaces by the alveolar type II cell. After it is secreted, surfactant undergoes a series of poorly understood transformations resulting in formation of a surface tension-reducing surface at the air-liquid interface. The by-products of the surface film and/or other products of surfactant metabolism are eventually cleared from the alveolar space. Both the alveolar type II cell and the macrophage are thought to be involved in surfactant clearance and have been shown to internalize surfactant lipid in vitro. The goal of the current investigation was to characterize further and to quantitate the role of the macrophage in surfactant clearance by investigating the uptake and metabolism of surfactant lipids and surfactant protein A (SP-A) by macrophages in vitro. SP-A enhanced the uptake of lipids by macrophages in a time-, temperature-, and concentration-dependent manner. In contrast, neither of the collagen-like proteins SP-D or C1q enhanced the uptake. Phosphatidylcholine was rapidly degraded by macrophages and the degradation occurred both in the presence and absence of SP-A. In addition, macrophages degrade SP-A by a process that is time- and temperature-dependent. These results and calculations of uptake and degradation rates suggest that macrophages may contribute significantly to the process of surfactant clearance.

Animals↗
PubMed1995

Age and seasonal effects on Holstein yield for four regions of the United States over time.

Multiplicative factors to adjust Holstein yield for age and season of calving were calculated and analyzed from 20 data files for region and time. Regions were 1) California, 2) Minnesota and Wisconsin, 3) New York and Pennsylvania, and 4) six southern states (Texas, Louisiana, Mississippi, Alabama, Georgia, and Florida). Time periods were calving years of 1964 to 1968, 1971 to 1975, 1976 to 1980, 1981 to 1985, and 1986 to 1990. The same statistical model was used that had been used to derive current USDA factors from 1964 to 1968 data. The number of lactation records for each data file ranged from 81,394 to 2,238,201 and increased with time. Effect of calving season on milk yield generally decreased with time; the largest decrease was for the southern region. Effect of calving age also generally decreased for recent data, and the largest decreases were for California. Updated factors to adjust yield for calving age and season are indicated for some regions.

Aging↗
PubMed1995

Role of surfactant protein A in the pathogenesis of tuberculosis in subjects with human immunodeficiency virus infection.

Human immunodeficiency virus (HIV)-infected subjects are at increased risk for tuberculosis even before there is a significant loss of CD4 lymphocytes. A factor was found to be present in the bronchoalveolar lavage (BAL) of HIV-infected subjects that promoted the attachment of M. tuberculosis (MTB) organisms to alveolar macrophages (AMs). Using 51Cr-labeled MTB organisms, BAL from control subjects resulted in MTB attachment to AMs at 11.6% +/- 1.0%; in contrast, BAL from HIV-infected subjects increased attachment to 33.1% +/- 3.8% (P < 0.001). Surfactant protein A (SP-A) levels in BAL of normal controls was 1.9 +/- 0.3 micrograms/ml and was 5.5 +/- 0.4 micrograms/ml in the BAL of HIV-infected subjects (P < 0.01). When SP-A was removed by immunoprecipitation from the BAL of HIV-infected subjects, MTB attachment decreased from 33.1% +/- 3.8% to 11.3% +/- 0.4% (P < 0.001), a value identical to control levels. Exogenous human SP-A (5 micrograms/ml) was added back to the immunoprecipitated BAL and the enhanced attachment of MTB was restored. These data suggest that BAL from HIV-infected subjects contain a factor that facilitates MTB attachment to AMs, the first critical step in the establishment of infection. This factor appears to be SP-A.

Animals↗
PubMed1994

Adaptation of enteroendocrine cells in response to jejunal-ileal transposition in the rat.

BACKGROUND/AIMS: Enteroendocrine cell subpopulations are uniquely distributed along the crypt-villus and cephalocaudal axes of the small intestine. These regional differences in enteroendocrine cell expression, which are maintained in spite of rapid turnover of the epithelium, serve as descriptive markers of physiological differences along the length of the bowel. This study aimed to determine the influence of luminal contents on the maintenance of regional differentiation patterns of enteroendocrine and enterocytic phenotypes. METHODS: Sections of jejunum and ileum were surgically transposed in rats, leaving the innervation and blood supply to the transposed segments intact. The animals were killed 1, 4, and 8 weeks after surgery. Enteroendocrine cell subpopulations and enterocytic cell markers were studied immunohistochemically. RESULTS: No change in regional expression patterns was seen in response to the altered luminal environment by any of the enterocytic markers and four of the five enteroendocrine cell subpopulation markers. Eight weeks after surgery, the number of gastrin-expressing enteroendocrine cells increased in ileal segments transplanted proximally. CONCLUSIONS: Although luminal signals can affect intestinal stem cells to alter their proliferation rates, the luminal environment has only limited effects on the regional-specific expression of enteroendocrine or enterocytic products.

Adaptation, Physiological↗