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K Anderson

Publications and source records attributed to K Anderson.

At least 289 records · Page 16Linked to original sources

Presentation of viral antigen controlled by a gene in the major histocompatibility complex.

We describe a mutant human cell line (LBL 721.174) that has lost a function required for presentation of intracellular viral antigens with class I molecules of the major histocompatibility complex (MHC), but retains the capacity to present defined epitopes as extracellular peptides. The cell also has a defect in the assembly and expression of class I MHC molecules, which we show can be restored by exposure of the cells to a peptide epitope. This phenotype suggests a defect in the association of intracellular antigen with class I molecules similar to that described for the murine mutant RMA-S (ref. 5), but in the present case the genetic defect can be mapped within the MHC locus on human chromosome 6.

Antigen-Presenting Cells↗

Relation of pooled logistic regression to time dependent Cox regression analysis: the Framingham Heart Study.

A standard analysis of the Framingham Heart Study data is a generalized person-years approach in which risk factors or covariates are measured every two years with a follow-up between these measurement times to observe the occurrence of events such as cardiovascular disease. Observations over multiple intervals are pooled into a single sample and a logistic regression is employed to relate the risk factors to the occurrence of the event. We show that this pooled logistic regression is close to the time dependent covariate Cox regression analysis. Numerical examples covering a variety of sample sizes and proportions of events display the closeness of this relationship in situations typical of the Framingham Study. A proof of the relationship and the necessary conditions are given in the Appendix.

Adult↗

The respiratory syncytial virus subgroup B attachment glycoprotein: analysis of sequence, expression from a recombinant vector, and evaluation as an immunogen against homologous and heterologous subgroup virus challenge.

The attachment glycoprotein G of respiratory syncytial (RS) virus is important in both the antigenic and molecular diversity of the RS viruses. Previous work has shown that the glycoprotein G of a subgroup A RS virus expressed from a recombinant vaccinia virus provides significant protection against homologous but not heterologous subgroup virus challenge. We undertook the cDNA cloning and nucleotide sequencing of the G mRNA of a subgroup B RS virus (8/60) to extend molecular comparisons of the G protein both within and between subgroups. We also tested the ability of a subgroup B G protein to provide protection against challenge by A or B subgroup viruses. Sequence analysis showed a deduced amino acid sequence having a single major open reading frame encoding a protein of 292 amino acids with an elevated serine and threonine (30%) and proline (9%) content. The 8/60 G differed from a subgroup A virus (A2) G protein with only a 56% amino acid identity while the 8/60 G shared a 98% amino acid identity with the G protein of another subgroup B virus (18537). The 8/60 G cDNA was placed in a vaccinia virus vector (vvGB) which was shown to express the 8/60 G protein. Cotton rats immunized intradermally with vvGB and later challenged intranasally with 8/60 RS virus had a significant reduction in viral titers in the lungs relative to control animals whereas similarly immunized animals were not protected against heterologous subgroup challenge. Our results indicate that a RS virus subunit vaccine containing the G protein would require both A and B subgroup G proteins to afford protection against viruses of both subgroups.

Amino Acid Sequence↗

Impact on iron status of introducing cow's milk in the second six months of life.

To determine the impact on iron status of introducing cow's milk (CM) into the diet during the second 6 months of life, nutrient intake was assessed and iron status measured in 100 infants. Nutrient intake for 40 of the 45 infants, age 8 to 13 months, fed CM as the primary beverage for at least 3 months prior to the study and for 45 of 55 infants the same age fed a milk-based infant formula (FF) as the primary beverage for at least 3 months were assessed. All infants in the study were healthy, and the majority were taking no medications or supplements other than vitamins or fluoride for 3 weeks prior to the assessment. Blood drawn by peripheral venipuncture was analyzed by Coulter Counter for complete blood count; plasma albumin, iron, ferritin, transferrin saturation, and total iron-binding capacity were measured in all infants. CM-fed infants had significantly lower mean iron and vitamin C intakes, plasma albumin, transferrin saturation, and ferritin than did FF infants. The frequency of low plasma iron, low transferrin saturation, and low plasma ferritin was significantly greater in CM-fed than in FF infants. The percentage of subjects with three or more abnormal iron indices was more than twice as great in CM-fed infants (58%) as in FF infants (23%). Feeding infants iron-fortified formula to 12 months of age appears to deter iron deficiency.

Anemia, Hypochromic↗

Differentiation of respiratory syncytial virus subgroups with cDNA probes in a nucleic acid hybridization assay.

A new approach to respiratory syncytial (RS) virus subgroup determination was developed by using a simple nucleic acid filter hybridization technique. By this method, virus-infected cells are bound and fixed in a single step, and the viral RNA in the fixed-cell preparation is characterized directly by its ability to hybridize to cDNA probes specific for either the A or B subgroups of RS virus. The subgroup-specific probes were constructed from cDNA clones that corresponded to a portion of the extracellular domain of the RS virus G protein of either a subgroup B RS virus (8/60) or a subgroup A RS virus (A2). The cDNA probes were labeled with 32P and used to analyze RS virus isolates collected over a period of three decades. Replicate templates of infected cell preparations were hybridized with either the subgroup A or B probe. The subgroup assignments of 40 viruses tested by nucleic acid hybridization were in agreement with the results of subgroup determinations based on their reactivities with monoclonal antibodies, which previously has been the only method available for determining the subgroup classification of RS virus isolates. The nucleic acid hybridization assay has the advantage of providing broad-based discrimination of the two subgroups on the basis of nucleic acid homology, irrespective of minor antigenic differences that are detected in assays in which monoclonal antibodies are used. The nucleic acid hybridization technique provides a reliable method for RS virus subgroup characterization.

Antibodies, Monoclonal↗

Nucleotide sequence analysis and expression from recombinant vectors demonstrate that the attachment protein G of bovine respiratory syncytial virus is distinct from that of human respiratory syncytial virus.

Bovine respiratory syncytial (BRS) virus causes a severe lower respiratory tract disease in calves similar to the disease in children caused by human respiratory syncytial (HRS) virus. While there is antigenic cross-reactivity among the other major viral structural proteins, the major glycoprotein, G, of BRS virus and that of HRS virus are antigenically distinct. The G glycoprotein has been implicated as the attachment protein for HRS virus. We have carried out a molecular comparison of the glycoprotein G of BRS virus with the HRS virus counterparts. cDNA clones corresponding to the BRS virus G glycoprotein mRNA were isolated and analyzed by dideoxynucleotide sequencing. The BRS virus G mRNA contained 838 nucleotides exclusive of poly(A) and had a major open reading frame coding for a polypeptide of 257 amino acid residues. The deduced amino acid sequence of the BRS virus G polypeptide showed only 29 to 30% amino acid identity with the G protein of either the subgroup A or B HRS virus. However, despite this low level of identity, there were strong similarities in the predicted hydropathy profiles of the BRS virus and HRS virus G proteins. A cDNA molecule containing the complete BRS virus G major open reading frame was inserted into the thymidine kinase gene of vaccinia virus by homologous recombination, and a recombinant virus containing the BRS virus G protein gene was isolated. This recombinant virus expressed the BRS virus G protein, as demonstrated by Western immunoblot analysis and immunofluorescence of infected cells. The BRS virus G protein expressed from the recombinant vector was transported to and expressed on the surface of infected cells. Antisera to the BRS virus G protein made by using the recombinant vector to immunize animals recognized the BRS virus attachment protein but not the HRS virus G protein and vice versa, confirming the lack of antigenic cross-reactivity between the BRS and HRS virus attachment proteins. On the basis of the data presented here, we conclude that BRS virus should be classified within the genus Pneumovirus in a group separate from HRS virus and that it is no more closely related to HRS virus subgroup A than it is to HRS virus subgroup B.

Amino Acid Sequence↗

The 22,000-kilodalton protein of respiratory syncytial virus is a major target for Kd-restricted cytotoxic T lymphocytes from mice primed by infection.

Recombinant vaccinia viruses containing the 22-kilodalton protein (matrixlike or 22K protein) or phosphoprotein gene from respiratory syncytial virus were constructed. These recombinant viruses expressed proteins which were immunoprecipitated by appropriate respiratory syncytial virus antibodies and comigrated with authentic proteins produced by respiratory syncytial virus infection. The new recombinant viruses (and others previously described containing the attachment glycoprotein, fusion, or nucleoprotein genes of respiratory syncytial virus) were used to infect target cells for cultured polyclonal cytotoxic T lymphocytes generated from the spleens of BALB/c or DBA/2 mice primed by intranasal infection with respiratory syncytial virus. Respiratory syncytial virus-specific cytotoxic T lymphocytes (CTL) showed strong Kd (but not Dd)-restricted recognition of the 22K protein. As previously reported, the fusion protein and nucleoprotein were both seen by CTL, but recognition of these proteins was comparatively weak. There was no detectable recognition of other respiratory syncytial virus proteins tested (including phosphoprotein). 22K protein-specific splenic memory CTL persisted for at least 11 months after infection of BALB/c mice. Priming BALB/c mice with recombinant vaccinia virus containing the 22K protein gene induced respiratory syncytial virus-specific memory CTL at lower levels than that previously reported following infection with a similar recombinant containing the fusion protein gene. These data identify the 22K protein as a major target antigen for respiratory syncytial virus-specific CTL from H-2d mice primed by respiratory syncytial virus infection.

Animals↗

Variation of breath sound and airway caliber induced by histamine challenge.

Inspiratory breath sounds were recorded from the chest wall during histamine challenge in five subjects with mild asthma (baseline FEV1 greater than 60% of predicted normal). The median frequency of the power spectrum of the breath sounds was found to correlate with the percentage change in FEV1 induced by histamine and with FEF50. The analysis suggests that for a decrease in FEV1 of 20%, the median frequency of breath sound would increase by 80 Hz. Variation in airway caliber produced a consistent alteration in the distribution of energy in inspiratory breath sound in the absence of wheeze. Spectral analysis of breath sound may be a useful addition to conventional spirometry in identifying changes in airway diameter.

Adult↗

Recovery of an epitope recognized by a novel monoclonal antibody from airway lavage during experimental induction of chronic bronchitis.

Prolonged exposure of dogs to high concentrations of SO2 gas results in a syndrome with many of the characteristics of human chronic bronchitis, including cough and chronic mucous hypersecretion as well as airway obstruction. We developed and used a novel monoclonal antibody, GB-4B, raised against epithelial glycoprotein isolated from human hypersecretory mucus to probe airway lavage samples from dogs before and during prolonged exposure to SO2 gas. There were relatively low mean titers of the epitope recognized by GB-4B in airway lavage fluid as evidenced by enzyme-linked immunosorbent assay before exposure to SO2 gas. After 25 to 50 wk of SO2 exposure, the dogs showed a significant increase in pulmonary resistance and there was a significant increase in the titer of the epitope in the airway lavage fluid. Using the same antibody immunohistochemical analysis of airway tissues from SO2-exposed dogs revealed patchy staining of the mucous glands and airway secretory cells and dense staining along the airway surface; airway tissue from control dogs and one SO2-exposed dog whose lavage fluid did not contain the epitope showed little or no staining. These data demonstrate that similar mucin epitopes appear in airway lavage fluid under hypersecretory conditions in both animals and humans. The epitope may have utility as a marker of chronic mucous hypersecretion.

Animals↗

"Anger attacks": possible variants of panic and major depressive disorders.

The authors report a series of illustrative cases in which patients presented with sudden "spells" of anger with physical features that resembled panic attacks but lacked the affects of fear and anxiety. These spells or "attacks" of anger were experienced as uncharacteristic and were inappropriate to the situations in which they occurred. Since treatment of these attacks with antidepressants produced in each case marked improvements in behavior, the authors also formulate some hypotheses as to the nature of these episodes.

Adult↗

Dietary selenium intakes and plasma selenium concentrations of formula-fed and cow's milk-fed infants.

The plasma selenium concentrations of 57 infants 8 to 12 months of age were assessed using flameless atomic absorption spectrophotometry. The infants ingested either cow's milk or whey-predominant milk-based infant formula as their primary beverage as part of a mixed diet for at least 3 months. The calculated mean +/- standard deviation (SD) daily dietary selenium intake of 26 infants fed cow's milk (34 +/- 13 micrograms), assessed by a 3-day diet record and/or a 24-hour diet recall, was significantly (p less than or equal to .001) greater than that of 31 formula-fed infants (22 +/- 11 micrograms). The mean +/- SD plasma selenium concentration of infants fed cow's milk (39 +/- 11 micrograms/L) was also significantly (p less than or equal to .05) greater than that of infants fed formula (31 +/- 12 micrograms/L). Both groups of infants ingested similar amounts of total energy; however, the infants fed cow's milk received more total protein and selenium and a greater percentage of protein and selenium from their primary beverage than did the infants receiving formula. Both groups of infants were consuming a mixed diet with similar sources of selenium. To examine the selenium status of infants as well as other individuals better, further analysis of foods is clearly needed to provide more information on dietary selenium sources. The influence of variables such as body size and ethnicity, intake, sources and forms of dietary protein, and dietary forms of selenium on plasma selenium concentrations must also be investigated.

Animals↗

A study on primiparous sows of the ability to show standing oestrus and to ovulate after weaning. Influences of loss of body weight and backfat during lactation and of litter size, litter weight gain and season.

The ability to show standing oestrus and to ovulate within 10 days of weaning was studied in 240 purebred Swedish Yorkshire primiparous sows, fed according to a conventional feeding regime during lactation. The sows were weighted and backfat depth was recorded at farrowing and at weaning. Oestrus control was performed daily and blood samples for determination of plasma progesterone were drawn regularly in 205 sows. The distribution among the sows of the first standing oestrus after weaning had 2 peaks. The first peak occurred within 10 days of weaning and the second 24-30 days after weaning. Twelve per cent of the sows ovulated without showing standing oestrus within 10 days of weaning and 4% had an anovulatory first oestrus within the same time. Significant differences in age at farrowing and in loss of weight and backfat during lactation were found between sows which both showed standing oestrus and ovulated within 10 days of weaning and sows which neither showed standing oestrus, nor ovulated within the same time. The season during which weaning occurred significantly influenced the ability to show standing oestrus and ovulate within 10 days of weaning. Among the sows which both showed standing oestrus and ovulated within 10 days of weaning, significant positive correlations were found between weight loss, litter size, litter weight gain and the interval from weaning to first standing oestrus.

Adipose Tissue↗

Acute and chronic pulmonary complications following autologous bone marrow transplantation in non-Hodgkin's lymphoma.

Whereas intensive chemoradiotherapy with bone marrow salvage may be the only chance for cure in a number of patients with non-Hodgkin's lymphoma, high complication rates with subsequent mortality have been detrimental to our ability to cure many patients. Prominent among these complications is pulmonary toxicity, in the form of acute and infectious complications and interstitial pneumonitis. We report here our experience with 100 patients receiving autologous bone marrow transplants for non-Hodgkin's lymphoma. The incidence of interstitial pneumonitis (IP) was 7.6% and our mortality from IP was 1%, the lowest reported.

Acute Disease↗

Flocculation of serum lipoproteins with cyclodextrins: application to assay of hyperlipidemic serum.

We describe the complexation of isolated and native lipoproteins by natural macrocyclic polymers of glucose ("cyclodextrins"). Treatment of serum with cyclodextrin produces an immediate flocculation of the lipoproteins. The formation of cyclodextrin-lipoprotein complexes was evident on agarose electrophoresis gels. The concentration-dependent ability of alpha-cyclodextrin to precipitate chylomicrons and very-low-, low-, and high-density lipoproteins was used for clarifying lipemic serum. Results for normal and lipemic patients' specimens for some routinely measured analytes showed a good correlation between cyclodextrin treatment and ultracentrifugation. Unlike the use of organic solvents or ultracentrifugation, the proposed system provides a simple, mild, non-hazardous, and effective means for removing interfering lipid particles from biological specimens.

Chemical Precipitation↗

Expression of a novel 3.5-kb macrophage colony-stimulating factor transcript in human myeloma cells.

Macrophage CSF (M-CSF) induces proliferation of monocyte/macrophage progenitor cells and can also activate some functions of mature cells. Three different human M-CSF cDNA (4.0, 3 to 3.5, and 1.5 kb) which are the result of alternative splicing of the single M-CSF gene have been cloned. Each of these cDNA encode a biologically active M-CSF. M-CSF transcripts are expressed in normal fibroblasts and other mesenchymal cells, and also in some hematopoietic cells such as monocytes. Normal human cells examined to date express only the 4.0-kb transcript. In contrast, a 3.5-kb M-CSF transcript was continuously expressed in two multiple myeloma cell lines (RPMI 8226 and U266/AF10) and in a bone marrow specimen of a patient with multiple myeloma. The myeloma cell lines secreted biologically active M-CSF. Resting and activated normal B lymphocytes and other B cell neoplasms examined did not express the 3.5-kb transcript, but could be induced to express the 4.0-kb transcript and to secrete M-CSF. Myeloma cells appear to be unique among hematopoietic cells in their expression of the 3.5-kb M-CSF transcript.

B-Lymphocytes↗

Anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation for B-cell non-Hodgkin's lymphoma: phenotypic reconstitution and B-cell function.

In the present report we have attempted to examine immunologic reconstitution following high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-purged autologous bone marrow transplantation (ABMT). By cell-surface phenotypic analysis, the majority of patients had normal percentage of natural killer cells (NK), monocytes, and CD8+ T cells at one month post-ABMT. In contrast, the percentage of CD4+ T cells was reduced for at least 3 years, and the CD4:CD8 ratio reflected this imbalance. B-cell reconstitution was slightly prolonged, with normal percentage and absolute numbers of CD20+ B cells evident by 3 months. Although B cells returned by 3 months, in vitro assessment of B-cell function demonstrated impairment of proliferative responses to either anti-immunoglobulins bound to beads (anti-Ig), Epstein-Barr virus (EBV), or interleukin-2 (IL-2) for approximately 1 year and low molecular B-cell growth factor (BCGF) for approximately 2 or more years. Moreover, in vivo B-cell reconstitution demonstrated a more selective defect, with normal levels of immunoglobulin IgM returning at 6 months, IgG at 12 months, and IgA after 2 years. Despite normal numbers of B cells and relative normal levels of Ig early following ABMT, our in vitro data suggest an intrinsic defect in B-cell responsiveness. Moreover, these defects are similar to those observed following nonpurged autologous and allogeneic BMT, although the interval of immune impairment appears more prolonged.

Antibodies, Monoclonal↗

Cardiovascular risk factors in the elderly.

The relation of total plasma cholesterol to the incidence of coronary heart disease (CHD) was one of the first findings of the Framingham Heart Study. The Framingham data established that a 1% increase in total cholesterol produced a 2% increase in CHD incidence. This relation has now been shown to apply to persons aged 60 to 70 years as well as to younger persons. The risk of CHD associated with various factors, including total cholesterol, low- and high-density lipoprotein and triglyceride levels, uric acid, blood glucose level, fibrinogen level and hypertensive blood pressure, is discussed with particular reference to the elderly. New data from the Framingham group show that increased left ventricular mass may be a significant risk factor for CHD, particularly among the elderly.

Adult↗