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Biomedical subjects

D C Anderson

Publications and source records attributed to D C Anderson.

At least 343 records · Page 19Linked to original sources
PubMed1987

Mycobacterium paratuberculosis infection in a colony of stumptail macaques (Macaca arctoides).

Mycobacterium paratuberculosis infection was documented in a colony of stumptail macaque monkeys (Macaca arctoides), with 29 (76%) of 38 monkeys infected and shedding organisms in feces. Thirteen deaths have occurred during the past five years. Animals without overt clinical disease were shedding as many as 2 X 10(6) colony-forming units of M. paratuberculosis/g of feces. Intestinal tissues from animals dying of this disease contained up to 10(8) colony-forming units of M. paratuberculosis/g of tissue. The clinical and pathological features of paratuberculosis in this species were comparable to those reported for paratuberculosis in ruminants and Mycobacterium avium infections in primates. By enzyme-linked immunosorbent assay, antibodies to M. paratuberculosis were found in 79%-84% of the animals. Antibodies could not be detected in six animals with clinical disease. These findings extend the natural host range of M. paratuberculosis to include nonhuman primates and add support to current suggestions that M. paratuberculosis may be pathogenic for humans.

Animals↗
PubMed1987

Nosocomial cytomegalovirus infections within two hospitals caring for infants and children.

Using serology, virology, and molecular epidemiology, we investigated nosocomial transmission of cytomegalovirus (CMV) over a two-year period in two contrasting environments: a crowded, busy pediatric chronic care unit (337 patients, 43 nurses, and 76 therapists; average prevalence of CMV excretion in patients, 16%) and a small neonatal unit (293 patients and 69 nurses; average prevalence, 0.7%). In the chronic care unit no nurse or therapist acquired CMV, but two pairs of infants were infected with homologous strains of CMV, and patient-to-patient transmission was proven in one pair. In the neonatal unit no patients acquired CMV in the hospital, but two nurses seroconverted, with a nonoccupational source proven for one. Transmission from CMV-infected caretaker to patient did not occur in either environment. CMV was isolated from diapers as well as hands of patients and personnel but not from other environmental surfaces.

Adult↗
PubMed1987

Characterization of antibody-reactive epitopes on the 65-kilodalton protein of Mycobacterium leprae.

Twenty-three monoclonal antibodies (MAbs) prepared in seven different laboratories were studied, all of which recognized the 65-kilodalton (kDa) protein of Mycobacterium leprae as determined by Western blotting or gel radioimmunoassay or both. Fourteen of the MAbs recognized different epitopes, as evaluated by cross-competition studies using radiolabeled MAb and unlabeled inhibitors; the species specificity of these epitopes was defined by nitrocellulose dot blot immunoassays with bacterial sonic extract antigen preparations from 23 species of mycobacteria. Each of the 14 distinct MAbs recognized a 65-kDa protein produced by a lysogenized Escherichia coli Y1089 host containing cloned rDNA which included the gene for the M. leprae 65-kDa protein. Of the 14 distinct MAbs, 1 recognized an epitope found only on M. leprae, and the others recognized epitopes present on as few as 8 or as many as all 23 of the mycobacterial species studied. Identification of these distinct 65-kDa protein epitopes and use of the MAbs which recognize them should assist future structural studies of this protein and characterization of the T-cell reactive and serodiagnostically useful portions of the molecule.

Antibodies, Monoclonal↗
PubMed1987

Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins.

Leukocyte adhesion deficiency (LAD) is a recently recognized autosomal-recessive trait characterized by recurrent bacterial infections, impaired pus formation and wound healing, and abnormalities in a wide spectrum of adherence-dependent functions of granulocytes, monocytes, and lymphoid cells. Features of this disease are attributable to deficiency (or absence) of cell surface expression of a family of functionally and structurally related glycoproteins. These include Mac-1 (complement receptor type 3), lymphocyte function-associated antigen-1 (LFA-1), and p150,95. Defective biosynthesis of the beta chain shared by each molecule (comprised of alpha 1 beta 1 complexes) represents the fundamental molecular basis of this disease. Recognition of the molecular pathogenesis of this disorder has allowed rich insights into the role of cellular adherence reactions in inflammation and host defense.

Antigens, Surface↗
PubMed1987

Effect of Haemophilus influenzae type b lipopolysaccharide on complement activation and polymorphonuclear leukocyte function.

Purified lipopolysaccharide (LPS) from Haemophilus influenzae type b (Hib) was examined for its capacity to interact with human hemolytic complement, generate conversion products of C3, C4, and factor B, stimulate C5a activity, and affect human neutrophil chemiluminescence and phagocytosis. Salmonella typhimurium LPS and Salmonella minnesota Rb LPS (R345 mutant) were examined for comparison. Incubation of Hib LPS with human serum deficient in gamma-globulin or with normal human serum containing 10 mM EGTA and 7 mM MgCl2 resulted in some depletion of hemolytic complement and conversion of C3 to degradation products (determined by inhibition of passive hemolysis and electrophoresis/immunofixation, respectively), indicating that complement activation occurred by the alternative pathway. Complement activation by Hib LPS and S. minnesota Rb LPS was similar, but significantly less effective than by S. typhimurium LPS (p less than 0.01). Solubilized Hib lipid A, but not LPS, induced conversion products of C4 in hypogammaglobulinemic serum, indicating activation of the classical pathway. Similar levels of C5a activity were generated by incubation of Hib LPS and S. typhimurium LPS in hypogammaglobulinemic serum, as determined by neutrophil shape change and neutrophil aggregation. Hib LPS directly stimulated neutrophil chemiluminescence, whereas S. typhimurium LPS had little effect. Phagocytosis of radiolabeled, opsonized Hib by neutrophils was diminished by S. minnesota Rb LPS, Hib LPS, or solubilized Hib lipid A (p less than 0.001), but was slightly increased by S. typhimurium LPS. Neither the oligosaccharide of Hib LPS or Hib capsular polysaccharide was capable of interacting with complement or altering neutrophil chemiluminescence or phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement Activation↗
PubMed1987

Periodontal manifestations of the heritable Mac-1, LFA-1, deficiency syndrome. Clinical, histopathologic and molecular characteristics.

The clinical, histopathologic and functional consequences of the genetic deficiency of leukocyte Mac-1, LFA-1 and p150,95 were assessed among three affected patients, heterozygotes and unaffected individuals among two generations of a single kindred. Longitudinal assessments of this family afforded the unique opportunity to characterize the natural history of severe periodontal manifestations associated with this disorder. Features uniformly observed among each patient included recurrent, necrotic soft tissue infections, impaired pus formation, delayed wound healing, constant granulocytosis, severe abnormalities of adhesion-dependent granulocyte functions and a profound deficiency (3%-6% of normal) of Mac-1 glycoproteins on granulocyte surfaces. Characteristic features of generalized prepubertal periodontitis including rapidly progressive alveolar bone loss affecting the primary and permanent dentitions (leading to premature tooth loss), recession, clefting and migration in association with intense gingival inflammation were uniformly observed. Biopsies of inflamed periodontal tissues in these individuals demonstrated dense infiltrates of mononuclear leukocytes but a striking absence of extravascular neutrophil granulocytes. Heterozygous family members demonstrated approximately half normal Mac-1 protein expression but no susceptibility to systemic infections and normal, adhesion-dependent leukocyte functions. Prepubescent heterozygotes demonstrated no periodontal manifestations but a 31-year-old heterozygous female exhibited clinical and radiographic features typical of postjuvenile periodontitis. The profound periodontal manifestations recognized in this clinical-pathologic model emphasize the physiologic importance of leukocyte adhesion reactions in defense of the periodontium and further suggest a possible pathologic role for Mac-1 proteins in other forms of early-onset periodontitis.

Adult↗
PubMed1987

Trial of 17-hydroxyprogesterone caproate (Proluton Depot) in women with long-standing infertility; failure of estrogen positive feedback the following cycle.

In open and double-blind studies 40 women with long-standing unexplained infertility were investigated and treated with 17 alpha-hydroxyprogesterone caproate (17HPC, Proluton Depot). In the open study, 16 women with a high index of suspicious abortions were given 500 mg 17HPC imtramuscularly (i.m.) weekly for 6-16 weeks. Six of the women received the drug from a time preceding the expected date of a period; 2 of these conceived that cycle and their pregnancies continued to term, while 4 were not pregnant. Ten women (9 with definite previous abortions) were given 17HPC when they suspected (correctly) that they were pregnant. Their pregnancies continued to term in all but 1, who had a premature delivery (still-birth) at 34 weeks. In the double-blind study 24 women were given injections of 17HPC or placebo i.m. at weekly intervals, from about 4 days before the expected period (day -4), provided that the level of progesterone (Prog) (on days -9 to -7) was greater than 10 nmol/l. After placebo no delay in menstruation or disruption of the succeeding cycle was observed. In 14 of 16 cycles in 14 women given 500 mg 17HPC the withdrawal period was delayed by a few days, and then followed by highly erratic bleeding over the next 1-3 months. The dose was therefore reduced to 250 mg 17HPC but the same problem resulted in 8 of 29 cycles in 16 women (including the above studied in later cycles). Regular cycles were eventually restored in all cases but in 3 this necessitated treatment with the contraceptive pill (Microgynon). In most of the post-treatment cycles there was a progressive and prolonged estradiol (E2) rise, which was not preceded by changes either in serum FSH concentration or in the LH/FSH ratio nor associated with the expected positive feedback rise in LH. We conclude that 17HPC disrupts the following cycle, probably by allowing follicular development while interfering with positive LH feedback. None of the patients of the double-blind study had conceived (as evidenced by undetectable hCG levels). Our study confirmed that this progestogen exerts no direct luteolytic effect. However, in order to establish the efficacy or otherwise of 17HPC given before the end of the cycle, women should be selected with a very high index of suspicion of recurrent early implantation failure or abortion.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1987

Inadequate luteal phase usually indicates ovulatory dysfunction: observations from serial hormone and ultrasound monitoring of 115 cycles.

We have studied 100 women with regular menstrual cycles and infertility and tried to assess how frequently an 'inadequate' luteal phase (defined by low-peak progesterone levels) follows 'normal' ovulation. Normal follicular growth on serial ultrasound scan and follicular disappearance or collapse within 48 hours of the recorded LH peak were taken together as convincing evidence of ovulation. Eighty-three of 115 cycles were judged to be ovulatory and 32 to be anovulatory. A peak mid-luteal phase maximum serum progesterone (Po) level of 32 nmol/L (10 ng/ml) was taken arbitrarily as the cut-off level of discrimination between 'adequate' and 'inadequate' corpus luteum function. Serum progesterone was undetectable (less than 2.5 nmol/L) throughout in 2 cycles while the maximum was above 32 nmol/L in 102 and detectable but less than 32 nmol/L in 11. Of the latter only 1 was ovulatory. We conclude that cycles with low luteal phase Po levels represent luteinization without ovulation.

Anovulation↗
PubMed1987

Abnormal stimulated adherence of neonatal granulocytes: impaired induction of surface Mac-1 by chemotactic factors or secretagogues.

To identify possible secretory determinants of impaired hyperadherence and stimulated migration of neonatal granulocytes (NGs), we performed correlative studies of: (a) specific granule content and exocytosis, (b) secretago-gue-mediated upregulation of f-met-leu-phe (fMLP) receptors, (c) the chemotactic induction of the adhesive glycoproteins Mac-1 alpha (complement receptor 3) and beta, and (d) morphometric assessments of specific (peroxidase negative) granule depletion following chemotactic stimulation. Lactoferrin (LF) content of NG suspensions (cord blood or peripheral blood cells) was profoundly diminished (mean +/- SD 51% +/- 18% of normal) as compared with healthy adult granulocytes (AGs). Despite diminished cellular content, LF release by NG suspensions in response to fMLP was comparable to that of AGs. In contrast, LF release by NG suspensions was significantly diminished in response to phorbol myristate acetate (PMA) or calcium ionophor A23187 and/or during stimulated cell spreading, experimental conditions promoting overall greater LF depletion than chemotactic stimuli. In addition, NGs demonstrated an impaired capacity to upregulate fMLP receptors in response to PMA or A23187 when tested under the same experimental conditions. Baseline expression of the adhesive glycoproteins Mac-1 alpha and beta on NG surfaces was normal, but induction or upregulation of these proteins by chemotactic concentrations of fMLP, C5a as well as secretory (high) concentrations of PMA and A23187, was significantly diminished as compared with AGs. In contrast, chemotactic induction of the surface expression of the complement receptor-1 (CR-1) on NGs was normal. An impaired induction of Mac-1 alpha or beta was directly related to an impaired enhancement of adherence of NG in response to fMLP over a chemotactically relevant concentration range (10(-10) to 10(-7) mol/L). Moreover, in blocking-incubation experiments using anti-Mac-1 alpha/beta monoclonal antibodies (MAbs), significantly less inhibition of adherence by these MAbs was evident with fMLP-stimulated NG as compared with AG suspensions. Under selected chemotactic conditions, ultrastructural assessments of NGs demonstrated diminished peroxidase-negative granule loss in association with diminished granule-membrane fusion and the "addition" of plasma membrane. These studies suggest that abnormal expression of multiple surface determinants derived from peroxidase-negative granules or other intracellular pools may contribute to deficient chemotaxis or other inflammatory functions of NGs.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Surface↗
PubMed1986

LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells.

Lymphocyte function associated antigen 1 (LFA-1) is a leukocyte cell adhesion protein. We have studied a novel human immunodeficiency disease in which LFA-1 and two other proteins which share the same beta subunit are lacking from the surface of leukocytes. The basis of the inherited defect in cell surface expression of both the alpha and beta subunits of LFA-1 was determined by somatic cell fusion of patient or normal human cells with an LFA-1+ mouse T cell line. Human LFA-1 alpha and beta subunits from normal cells could associate with mouse LFA-1 subunits to form interspecies hybrid alpha beta complexes. Surface expression of the alpha but not the beta subunit of patient cells was rescued by the formation of interspecies complexes. The findings show that the LFA-1 alpha subunit in genetically deficient cells is competent for surface expression in the presence of an appropriate beta subunit, and suggest that the genetic lesion affects the beta subunit. The human LFA-1 alpha and beta subunits were mapped to chromosomes 16 and 21, respectively. The genetic defect is inferred to be on chromosome 21.

Animals↗
PubMed1986

The genetic deficiency of leukocyte surface glycoprotein Mac-1, LFA-1, p150,95 in humans is associated with defective antibody-dependent cellular cytotoxicity in vitro and defective protection against herpes simplex virus infection in vivo.

The role of the Mac-1, LFA-1, p150,95 leukocyte glycoprotein family in mediating antiviral host defense was investigated by utilizing mononuclear cells (MC) obtained from eight patients with a genetic deficiency of Mac-1, LFA-1, and p150,95, and normal MC incubated with subunit-specific monoclonal antibodies (MAb) directed against these glycoproteins. As shown with an in vitro chromium-release cytotoxicity assay to herpes simplex virus (HSV)-infected Chang liver target cells, MC of these patients with the severe phenotype or normal MC preincubated with a combination of MAb against Mac-1 glycoprotein subunits were deficient in antibody-dependent cellular cytotoxicity (ADCC). When used individually, MAb directed at LFA-1-alpha or -beta also inhibited ADCC and natural killer cytotoxicity (NKC). In a single cell agarose assay, MC of Mac-1-deficient patients formed fewer effector-target cell conjugates in the presence of specific anti-HSV antibody. To investigate the in vitro contributions of these glycoproteins to cytotoxic host defense mechanisms, two in vivo adoptive transfer models were explored in which neonatal mice are protected against a lethal HSV challenge by normal human MC plus anti-HSV antibody (in vivo ADCC) or human interferon-alpha (NKC stimulated in vivo). In each model, MC from patients with "severe" or "moderate" phenotypes of Mac-1 deficiency, or normal MC incubated with a combination of anti-LFA-alpha, Mac-1-alpha, p150,95-alpha plus -beta MAb failed to protect neonatal mice against lethal HSV infection. These studies further indicate requirements for adhesion-dependent mechanisms in the mediation of MC-ADCC, and suggest that Mac-1-dependent cellular adhesive properties are necessary for normal cytotoxic functions in vivo in experimental models of human ADCC or interferon-stimulated NKC. These findings, in addition to the recognized occurrence of severe or even lethal viral infections in some Mac-1-deficient patients, suggest that glycoproteins of the Mac-1 family may be important determinants of antiviral host defense.

Adult↗
PubMed1986

Contributions of the Mac-1 glycoprotein family to adherence-dependent granulocyte functions: structure-function assessments employing subunit-specific monoclonal antibodies.

MAb directed at the alpha-subunits of Mac-1 (alpha M), LFA-1 (alpha L), p150,95 (alpha X), or their common beta-subunit were used to characterize the contributions of the Mac-1 glycoprotein family to granulocyte adherence reactions. Inhibitory effects of these MAb in incubation experiments with normal granulocytes indicated distinct adhesive contributions of each subunit. Significantly greater adherence, and inhibition of adherence by anti alpha M, alpha X, and beta MAb, was observed under chemotactic conditions designed to "up-regulate" the surface expression of the alpha M beta and alpha X beta complexes. Adherence to protein-coated glass and binding of albumin-coated latex beads were significantly inhibited by anti-beta greater than anti-alpha M (OKM-10, M1/70, LM2/1.6 and OKM-1) greater than anti-alpha X greater than anti-alpha L MAb, but no effects of anti-HLA, AB, or anti-CR-1 MAb were evident. A similar rank order of inhibition was observed in granulocyte aggregation assays in response to C5a, PMA, or f-Met-Leu-Phe. Significant inhibition of directed migration by anti-beta or anti-alpha M (OKM-1 or OKM-10) MAb was observed in subagarose but not Boyden chemotaxis assays; inhibition was dependent on a continuous cell exposure to anti-Mac-1 alpha or beta during the assay, suggesting that a continuum of new Mac-1 expression is required for directed translocation. Phagocytosis of Oil-Red-O paraffin or zymosan selectively opsonized with C3-derived ligands was significantly inhibited by anti-alpha M MAb (OKM-10 greater than LM2/1.6 greater than M1/70 greater than OKM-1) or by combinations of anti-alpha M + anti-CR-1 MAb, but only minimal inhibitory effects of anti-beta MAb and no effects of anti-alpha L or anti-alpha X MAb were seen. Similarly, complement-dependent phagocytosis-associated lactoferrin release, ingestion, and intracellular killing of Staphylococcus aureus 502A, and binding of iC3b-opsonized SRBC, were significantly inhibited by anti-alpha M (OKM-10, M1/70) or combinations of anti-alpha M + anti-CR-1 MAb, but not by anti-beta, alpha L, or alpha X MAb. Notably, none of the anti-Mac-1 MAb demonstrated inhibitory effects in assays of adherence-independent functions including shape change, specific f-Met-Leu-3H-Phe binding, O-2 generation, chemiluminescence evolution, or lactoferrin release in response to PMA.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Lipoprotein abnormalities in insulin-dependent diabetes mellitus.

Despite the increased risk of atherosclerosis in diabetes mellitus, levels of serum cholesterol, triglycerides, low-density-lipoprotein (LDL) cholesterol, and high-density-lipoprotein (HDL) cholesterol were similar in 57 men with insulin-dependent diabetes mellitus (IDDM) and 81 non-diabetic controls. However, substantially lower serum levels of apolipoprotein B, the principal apolipoprotein of LDL, and a concomitant increase in the cholesterol-loading of apolipoprotein B were found in IDDM. The likely changes in LDL density and particle size resulting from this compositional abnormality might lead to accelerated atherogenesis analogous to that seen in type III hyperlipoproteinaemia. In addition, there was an increase in the concentration of cholesterol in the smaller, denser, HDL3 subfraction of serum HDL in IDDM.

Adult↗