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Biomedical subjects

H D Ochs

Publications and source records attributed to H D Ochs.

At least 145 records · Page 8Linked to original sources
PubMed1991

Home-based immunoglobulin infusion therapy: quality of life and patient health perceptions.

Thirty-seven antibody-deficient patients who were participating in a multicenter trial evaluating home-based, self-administered IVIG therapy anonymously completed questionnaires regarding beliefs concerning health control, quality of life, and attitudes toward active participation in medical care. Their responses were compared with a group of 29 patients undergoing traditional IVIG therapy in a medical clinic setting. A subsample of the home-based group who later returned to clinic-based IVIG therapy allowed comparison of responses given by the same patients in both settings. Home-based therapy was preferred to clinic-based therapy. Independence, convenience, comfort, decreased disruption of activities, travel time, and costs were specific factors rated most favorably. On the Health Belief Questionnaires, patients preferred informed, self-involved medical care regardless of the setting for their IVIG treatments.

Adult↗
PubMed1990

Origin of mutations in two families with X-linked chronic granulomatous disease.

The most common X-linked recessive form of chronic granulomatous disease (X-CGD) is characterized by the absence of cytochrome b558 in neutrophils. In a rare variant form of X-CGD, cytochrome b558 is present but not functional. The gene (locus symbol CYBB) was localized to band Xp21 by studies of patients with small chromosome deletions. The gene was cloned based on its location and found to encode the 91-Kd subunit of the cytochrome b558 complex. Most female carriers for X-CGD can be identified by their X-inactivation mosaicism; on average 50% of their neutrophils express the mutant phenotype and fail to reduce nitroblue tetrazolium (NBT). In 2 of 4 families studied, the maternal grandmothers had normal NBT tests, suggesting either nonrandom X-inactivation or new mutations. Restriction fragment length polymorphism analysis using closely linked flanking markers or the NsiI polymorphism detected by the CYBB probe itself, allowed us to identify the X chromosome carrying the mutation as derived from a healthy NBT-positive maternal grandfather. The mothers of the affected boys must have received a paternal X chromosome carrying a new mutation, consistent with the maternal grandmothers' normal NBT tests. In all of eight potential carriers studied, the results of the NBT and DNA marker testing were in complete agreement. Prenatal diagnosis by DNA testing can be performed in early gestation obviating the need for fetal blood sampling.

DNA↗
PubMed1990

Identification of surface proteins mediating adherence of CD11/CD18-deficient lymphoblastoid cells to cultured human endothelium.

Patients with the severe form of leukocyte adhesion deficiency syndrome do not express the CD11/CD18 adhesion complex on any of their leukocytes. Nevertheless, their lymphocytes, unlike their phagocytes, emigrate to extravascular sites of inflammation, demonstrating that surface proteins other than CD11/CD18 can mediate lymphocyte adherence to endothelium. Using a B-lymphoblastoid cell line (B-LCL) established from a CD11/CD18-deficient patient and cultured human umbilical vein endothelial cells (HEC), we investigated the CD11/CD18-independent mechanism(s) of lymphocyte adherence to endothelium. Monoclonal antibodies directed to the alpha 4 polypeptide (CD49d) and the beta 1 polypeptide (CD29) of the lymphocyte VLA-4 integrin receptor (CD49d/CD29), and to vascular cell adhesion molecule-1 (VCAM-1) on the endothelial cell significantly inhibited the adherence of the CD11/CD18-deficient B-LCL to untreated HEC and to HEC treated with recombinant human tumor necrosis factor-alpha. We suggest that the interaction of the lymphocyte receptor VLA-4 with the endothelial ligand VCAM-1 induced by cytokines at sites of inflammation or immune reaction represents a CD11/CD18-independent pathway of lymphocyte emigration.

Antibodies, Monoclonal↗
PubMed1990

Phorbol ester causes down-regulation of CD11/CD18-independent neutrophil adherence to endothelium.

Neutrophils adhere to interleukin-1 (IL-1)-, tumour necrosis factor (TNF)- or lipopolysaccharide (LPS)-pretreated human umbilical vein endothelial cells (HEC) by CD11/CD18-dependent and independent mechanisms. We investigated CD11/CD18-independent neutrophil adherence to LPS-pretreated HEC by: (i) pretreating neutrophils with the anti-CD18 monoclonal antibody mAb 60.3; (ii) performing assays in the absence of Mg2; or (iii) using neutrophils isolated from a patient with leucocyte adhesion deficiency (CD11/CD18-deficiency). Under each of these conditions, CD11/CD18-independent neutrophil adherence to LPS-pretreated HEC was significantly greater than adherence to untreated HEC (15-18% versus 3-7%). In each case, however, stimulation of neutrophils with phorbol ester (PMA) abolished CD11/CD18-independent adherence to LPS-pretreated HEC (less than 5% adherence). Stimulation of neutrophils with bacterial chemotactic peptide (FMLP) or calcium ionophore (A23187) likewise reduced CD18-independent adherence to LPS-pretreated HEC. PMA also inhibited CD11/CD18-independent neutrophil adherence to HEC pretreated with IL-1 or TNF (80-90% inhibition). In contrast, PMA markedly enhanced CD11/CD18-dependent adherence to untreated or LPS-treated HEC. We conclude that stimulation of neutrophils with phorbol ester or other direct agonists down-regulates the CD11/CD18-independent mechanism of neutrophil adherence to IL-1, TNF- or LPS-pretreated HEC.

Antigens, CD↗
PubMed1990

Home self-administration of intravenous immunoglobulin therapy in children.

Twelve children with primary immunodeficiency, aged 2 to 17 years (mean +/- 1 SD = 9.8 +/- 5.3), were enrolled in a 9-month study to evaluate the feasibility and safety of home self-infusion of intravenous immunoglobulin (IVIg). An initial 2-month training and supervisory period was followed by a 6- to 7-month period during which the children or their parents infused IVIg in a home setting. Eight children received an average dose of 204 +/- 12 mg/kg every 2 weeks, two children received a dose of 400 mg/kg every month, and an additional two children received 240 to 250 mg/kg every 10 days. Peak and trough levels varied from 946 +/- 20 mg/dL and 627 +/- 16 mg/dL, respectively, in children receiving IVIg every 2 weeks. The peak-trough values for the children receiving IVIg every month were 1105 +/- 94 mg/dL and 457 +/- 78 mg/dL, while those of children receiving IVIg every 10 days were 840 +/- 24 mg/dL and 553 +/- 109 mg/dL. A total of 224 infusions were administered, with only two minor reactions occurring (reaction rate of 0.9%). There was no difference in the frequency of infections and antibiotic use during the study compared with the previous phase. The results demonstrate that home self-infusion of IVIg in children is safe and feasible.

Adolescent↗
PubMed1989

Heterogeneity of chromosomal breakage levels in epithelial tissue of ataxia-telangiectasia homozygotes and heterozygotes.

The objective of this study was to obtain an estimate of the frequency distribution of spontaneous chromosomal breakage occurring in vivo in oral epithelia of 20 ataxia-telangiectasia patients (A-T homozygotes) and 26 parents (A-T obligate heterozygotes). Samples of exfoliated cells were obtained from each individual by swabbing the oral cavity and preparing air-dried slides. The percentage of exfoliated cells with micronuclei (MEC frequency) was used as an in vivo indicator for the amount of chromosomal breakage occurring in the tissue. As a population group, MEC frequencies of the A-T patients differed significantly from controls (mean for A-T patients, 1.51; for controls, 0.29; P less than 0.01). However, the values observed in individual patients ranged from MEC frequencies 10- to 12-fold above control values, to frequencies overlapping the upper values observed in the controls. Similarly, MEC frequencies observed among the A-T heterozygotes differed significantly from controls (mean for A-T heterozygotes, 1.02, mean for controls, 0.29; P less than 0.01). However, only 16 of the 26 individuals sampled had MEC frequencies greater than 0.5%, the 90th percentile for controls (compared with 16 of the 20 A-T patients examined). Of the A-T patients 11 had been previously assigned to complementation groups on the basis of sensitivity to x-irradiation. Seven of the patients belonged to group A and had MEC frequencies ranging from 0.3% to 1.9% with the remaining patients belonging to group C with MEC frequencies of 0.2% to 0.9%. The data presented in this paper suggest that although levels of spontaneous breakage in epithelial tissues of A-T patients and A-T obligate heterozygotes are often significantly elevated, this is not the case in all individuals.

Adolescent↗
PubMed1989

Human antibody responses to bacteriophage phi X 174: sequential induction of IgM and IgG subclass antibody.

We studied the appearance of antigen-specific immunoglobulin classes and IgG subclasses in normal adult human subjects in response to primary, secondary, and tertiary immunization with the T-cell-dependent neo-antigen bacteriophage phi X 174. To complete the study we developed a sensitive, specific, and reproducible ELISA assay which was closely comparable to the widely used neutralization assay for total antibody (r = +0.97) and for IgG antibody (r = +0.93), and reasonably comparable for IgM antibody (r = +0.76). We confirmed that the initial response to primary immunization was predominantly, but not exclusively, IgM antibody. The secondary and tertiary responses demonstrated memory, amplification, and switch from IgM to IgG antibody. There was an orderly appearance of phage-specific IgG subclasses. IgG3 and IgG1 antibodies appeared 2 to 6 weeks after primary immunization. In all subjects there was a marked increase in IgG1 and IgG3 antibody after secondary immunization, and IgG2 antibody followed closely; IgG4 antibody appeared in some subjects. IgM antibody persisted in significant amounts (approx 50%) throughout the secondary response period. Following tertiary immunization, IgG1, IgG2, and IgG3 antibody consistently increased, and IgG4 antibody appeared in all subjects; IgG1 antibody predominated. Low levels of IgM antibody (approx 1% of total) persisted during the tertiary response. The persisting antibody on long-term follow-up (median 4 years after immunization) was virtually all (greater than 90%) IgG1.

Adult↗
PubMed1989

Lymphocyte alterations in zinc-deficient calves with lethal trait A46.

Lymphocyte numbers and activities were evaluated at 2, 4, 8 and 12 weeks of age in two calves with lethal trait A46 (A46), a genetic disorder affecting intestinal zinc absorption. Plasma zinc concentrations declined to subnormal by 3 weeks of age, after which anorexia, diarrhea, alopecia and hyperkeratosis occurred. Lymphocyte response to phytohemagglutinin-P (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) stimulation was variably reduced. CD4+ T-lymphocytes were subnormal on at least one observation period following onset of zinc deficiency, and relative numbers of B lymphocytes were decreased at 8 weeks. Secondary antibody responses to bacteriophage phi X 174 were significantly reduced. The results demonstrate that calves homozygous for the A46 trait have normal numbers of functional lymphocyte subpopulations at birth, and that the activity of their lymphocytes is altered once the calves become zinc deficient.

Animals↗
PubMed1989

Immune dysfunction associated with graft-versus-host reaction in mice transplanted across minor histocompatibility barriers. I. Depressed antigen-specific antibody responses to bacteriophage phi chi 174.

The effect of the graft-versus-host reaction in response to minor histocompatibility antigens on the antibody response to a T-dependent antigen was studied in four strains of mice. Lethally irradiated mice were transplanted with bone marrow plus graded numbers of spleen cells from H-2-compatible donors. Recipients of syngeneic bone marrow transplants and recipients of allogeneic bone marrow depleted of T cells made normal antibody responses to bacteriophage phi chi 174 when immunized on day 28 (primary) and day 56 (secondary) after marrow transplantation. Recipients of allogeneic bone marrow plus spleen cells made only small amounts of specific antibody and failed to make IgG antibody after secondary immunization. The pattern of the depressed antibody response suggests that the primary mechanism of immune dysfunction in mice with the minor antigen GVHR is a lack of T helper cell function.

Animals↗
PubMed1989

CD11/CD18-independent neutrophil adherence to inducible endothelial-leucocyte adhesion molecules (E-LAM) in vitro.

We examined the mechanisms involved in neutrophil adherence to cultured human umbilical vein endothelial cells (HEC) induced by direct stimulation of the neutrophils by phorbol myristate acetate (PMA), formylmethionyl-leucyl-phenylalanine (FMLP), or the calcium ionophore A23187 (neutrophil-dependent adherence), or by pretreatment of HEC with interleukin-1 (IL-1), tumour necrosis factor (TNF) or lipopolysaccharide (LPS) (endothelial-dependent adherence). Two distinct mechanisms for neutrophil adherence to HEC were demonstrated by performing adherence assays: (i) at 37 degrees versus 4 degrees; (ii) in the presence of Ca2+ only versus Mg2+ only; and (iii) in the presence or absence of monoclonal antibodies (mAb) to the CD11/CD18 adhesion complex of neutrophils. A CD11/CD18-dependent mechanism (i.e. inhibited by anti-CD18 mAb) was identified that was active in the presence of Mg2+ only but not of Ca2+ only, and at 37 degrees but not at 4 degrees. A CD11/CD18-independent mechanism (i.e. not inhibited by anti-CD18 mAb) was active at 4 degrees and at 37 degrees, and in the presence of Ca2+ only and of Mg2+ only. Neutrophil-dependent adherence induced by FMLP or PMA occurred solely via the CD11/CD18-dependent mechanism, whereas endothelial-dependent adherence induced by a 4-hr pretreatment with IL-1, TNF, or LPS involved both CD11/CD18-dependent and/independent mechanisms. CD11/CD18-deficient neutrophils isolated from a patient with leucocyte adherence deficiency (LAD) maintained the ability to adhere to LPS-pretreated HEC in the presence of Ca2+ only, indicating that this mechanism of adherence involves a receptor on the neutrophil distinct from CD11/CD18. Furthermore, the disappearance of the CD11/CD18-independent, but not of the CD11/CD18-dependent mechanism of adherence, in HEC treated with TNF for 24 hr suggests that the two mechanisms of neutrophil adherence also involve distinct inducible endothelial-leucocyte adhesion molecules (E-LAM).

Antigens, Surface↗
PubMed1989

IgM deficiency: clinical spectrum and immunologic assessment.

Selective IgM deficiency has been associated with recurrent infections and enteric protein loss. We have evaluated eight patients with IgM deficiency presenting with recurrent infections and manifestation of atopy. A variety of subtle immunologic aberrations were noted, including depressed IgM and elevated IgG responses to immunization with bacteriophage OX174. Despite normal quantitative IgG in most patients, IgG antibody responses to diphtheria-tetanus and/or pneumococcal polysaccharide antigens were generally depressed. No correlation could be made between antibody responses (or lack thereof) and the nature of infections in any given patient.

Adolescent↗
PubMed1988

Role of C3 in humoral immunity. Defective antibody production in C3-deficient dogs.

Previous studies have shown that animals pharmacologically depleted of C3 have impaired antibody responses. However, such C depletion is neither complete nor sustained, and the C3 cleavage products generated by C3 depletion can both enhance and inhibit the immune response. To clarify the role of C3 in humoral immunity, the antibody response of dogs with genetically determined total deficiency of C3 (C3D) was examined. Serum IgG levels of the C3D animals were within the normal range, but were significantly lower than levels seen in normal controls or C3D heterozygotes. Specific antibody production was defective: the antibody titers of C3D dogs in response to primary intravenous immunization with two different T cell-dependent Ag (sheep E and bacteriophage phi X-174) were markedly reduced when compared to either normal controls or C3D heterozygotes. After secondary immunization with T-dependent Ag, the total antibody titers were normal, but the C3D dogs made proportionately more IgM and less IgG antibody than did either control group. After i.v. immunization with a T cell-independent Ag (DNP-Ficoll), the C3D dogs had reduced levels of IgM and IgG antibody after primary and secondary immunization. Neither i.m. immunization nor the use of a 20-fold increase in Ag dose i.v. could correct the defect seen in the antibody response of C3D dogs. The results herein demonstrate that C3 plays a critical role in the generation of a normal humoral immune response.

Agammaglobulinemia↗
PubMed1988

Abnormal antibody responses in patients with persistent generalized lymphadenopathy.

Persistent, generalized lymphadenopathy (PGL) is a recognized component of human immunodeficiency virus (HIV) infection. We conducted longitudinal studies of B and T cell function in seven homosexual men with HIV infection and PGL. All seven had abnormal antibody-mediated immunity as studied by sequential assessment of in vivo antibody responses after immunization with the T-dependent neoantigens bacteriophage phi X 174 and keyhole limpet hemocyanin (KLH), the T-independent tetradecavalent pneumococcal polysaccharide vaccine, and the recall antigens diphtheria and tetanus toxoid. Compared to HIV-negative heterosexual controls, PGL patients responded with lower antibody titers and, following immunization with phage, failed to develop immunologic memory and to switch from IgM- to IgG-isotype antibody. In vitro antigen-induced antibody production was markedly diminished; and some patients showed depressed mitogen responses. There was a correlation between the degree of compromised immunity and the clinical condition; those with the most severe symptoms showed the most extensive immune deficiency. Yet despite obvious immunologic impairment five of the seven men have remained clinically stable over a 3-year follow-up period.

AIDS-Related Complex↗
PubMed1988

Inoculation of baboons and macaques with simian immunodeficiency virus/Mne, a primate lentivirus closely related to human immunodeficiency virus type 2.

A primate lymphotropic lentivirus was isolated on the human T-cell line HuT 78 after cocultivation of a lymph node from a pig-tailed macaque (Macaca nemestrina) that had died with malignant lymphoma. This isolate, originally designated M. nemestrina immunodeficiency virus (MnIV) and now classified as simian immunodeficiency virus (SIV/Mne), was inoculated intravenously into three juvenile rhesus monkeys (Macaca mulatta), three juvenile pig-tailed macaques (M. nemestrina), and two juvenile baboons (Papio cynocephalus). All six macaques became viremic by 3 weeks after inoculation, whereas neither of the baboons developed viremia. One pig-tailed macaque died at 15 weeks with suppurative peritonitis secondary to ulcerative, necrotizing colitis. Immunologic abnormalities included a marked decrease in CD4+ peripheral blood lymphocytes. Although five macaques mounted an antibody response to SIV/Mne, the animal that died at 15 weeks remained antibody negative. Three other macaques (two rhesus and one pig-tailed) died 66 to 87 weeks after inoculation after exhibiting progressive weight loss, anemia, and diarrhea. Histopathologic findings at necropsy included various manifestations of immune deficiency, nephropathy, subacute encephalitis, pancreatitis, adenocarcinoma, and lymphoid atrophy. SIV/Mne could be readily isolated from the spleens and lymph nodes of all necropsied macaques, and from the cerebrospinal fluid, brains, bone marrow, livers, and pancreas of some of the animals. SIV antigens were localized by avidin-biotin immunohistochemistry to pancreatic islet cells and to bone marrow endothelial cells. The data suggest that African baboons may be resistant to infection by SIV/Mne, whereas Asian macaques are susceptible to infection with this pathogenic primate lentivirus.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Mechanism of immune dysfunction associated with minor antigen graft-vs-host disease in mice.

A well-characterized murine model of graft-vs-host disease (GVHD) that develops in response to minor histocompatibility antigens was used to study the mechanism of an immunodeficiency syndrome that is associated with GVHD. Lethally irradiated mice were transplanted with a combination of bone marrow and spleen cells from H-2 compatible donors that differed at multiple minor histocompatibility antigens, or from syngeneic donors. Four to 12 weeks later, the humoral responses of transplanted and control mice to the T dependent antigens bacteriophage phiX174 and TNP-sheep red blood cells (TNP-SRBC), and to the T independent antigen TNP-Brucella abortus (TNP-BA) were determined. The results demonstrate that mice with GVHD have relatively intact B Cell function and a profound defect in T helper cell function. The immune response to T dependent antigens normalized with repeated immunization. We conclude that immune dysfunction in mice with GVHD is due to a reversible defect in T helper cell function.

Animals↗
PubMed1988

Use of thymic grafts or thymic factors to augment immunologic recovery after bone marrow transplantation: brief report with 2 to 12 years' follow-up.

Thymus tissue implants, thymic epithelial cells obtained from third party donors sharing one HLA-A and -B locus with the recipient, or the thymic hormones thymosin fraction 5 and thymopentin were given to recipients of HLA-identical sibling bone marrow to prevent chronic graft-versus-host disease (GVHD) and accelerate immunologic reconstitution. The clinical courses of 17 patients receiving thymus tissue and 18 patients receiving thymic hormones were reported initially 5 years ago and showed no difference in the incidence of chronic GVHD or immunologic recovery from those of concurrent or historical controls. We report here for the first time nine new patients who received thymus tissue implants with modifications of the culture method to lower the number of lymphocytes in the transplanted tissue with the intent of reducing rejection of the thymus tissue grafts. The clinical outcomes and immunologic functions of these nine patients were similar to those of the recipients of the earlier thymus tissue implants. With follow-up now ranging from 2.2 to 12.3 years (median 6.7) for the total group, 16 patients are alive. Seven never developed chronic GVHD. Nine were treated for chronic GVHD, seven of whom recovered and are leading normal lives, one has chronic pulmonary insufficiency, and one is disabled from chronic GVHD. We conclude that thymus tissue grafts or thymic epithelial cells partially HLA-matched to the recipient, thymosin fraction 5, or thymopentin used as described were not effective in reducing the incidence of chronic GVHD, improving immunologic recovery, or altering long-term survival.

Adolescent↗