Improving current immunoglobulin therapy for patients with primary immunodeficiency: quality of life and views on treatment.

Background: Subcutaneous or intravenous immunoglobulin replacement is the mainstay of treatment for most patients with primary immunodeficiency disease (PID). The purpose of this study was to gain an understanding of how existing PID therapies affect patient lives and to identify desired improvements to immunoglobulin treatments.

Methods: An online questionnaire was made available through the International Patient Organisation for Primary Immunodeficiencies to patients with PID and their caregivers regarding current treatment satisfaction, living with PID, and patient preferences using a conjoint approach.

Primary ano-rectal malignant melanomas within a population-based national patient series in Sweden during 40 years.

Purpose: To analyze 251 patients (101 males and 150 females) diagnosed with ano-rectal malignant melanoma (ARMM) reported to the Swedish National Cancer Registry during 1960-1999.

Methods: Incidence, gender and age profiles, primary anatomical sites and density of the melanomas along with geographic distribution, and prognosis were investigated.

Results: The age-standardized incidence of ARMM was significantly higher for females (1.

p53 protein expression and TP53 mutations in malignant melanomas of sun-sheltered mucosal membranes versus chronically sun-exposed skin.

In this paper, we compare the expression of the TP53 gene product, p53 protein (p53p), in primary malignant melanomas from sun-shielded mucous membranes and from chronically sun-exposed skin. Archival tissues from 29 patients with mucosal melanomas and from 27 with cutaneous melanomas in facial skin were subjected to immunohistochemical procedures using the monoclonal antibody DO-1. p53p expression did not differ significantly between the two groups of melanomas.

Co-localization of neuroendocrine hormones in the human fetal pancreas.

Objective And Design: Co-localization of the four major pancreatic hormones, and also of islet amyloid polypeptide (IAPP), peptide tyrosine tyrosine (PYY), secretin and neurotensin, has been studied in the endocrine pancreas of human fetuses at 16, 18 and 22 weeks of gestation.

Methods: Double and triple immunofluorescence stainings have been used.

Results: All three fetal pancreata contained cells that showed insulin, glucagon, somatostatin, pancreatic polypeptide (PP), IAPP, secretin and PYY immunoreactivity.

p-Aminobenzoic acid, but not its metabolite p-acetamidobenzoic acid, inhibits thrombin induced thromboxane formation in human platelets in a non NSAID like manner.

We have previously shown that p-aminobenzoic acid (PABA) is acetylated by several cell lines and most peripheral blood cells, including platelets, to p-acetamidobenzoic acid (PACBA). The structural similarity of PABA and PACBA to local anesthetics and some non steroidal anti inflammatory drugs urged us to perform the present investigation. When human platelets were stimulated with thrombin to liberate AA, we found that PABA inhibited the production of thromboxane (TxB2) as measured with enzyme-linked immunosorbent assay.

Arachidonic acid is a preferred acetyl donor among fatty acids in the acetylation of p-aminobenzoic acid by human lymphoid cells.

We have previously reported that human lymphoid cells, such as peripheral blood mononuclear leukocytes (PBML) and the T-cell leukemia line Jurcat, synthesize p-acetamidobenzoic acid from p-aminobenzoic acid (PABA) and a two carbon fragment from arachidonic acid (AA), conceivably derived from beta-oxidation. Here we demonstrate that AA is a preferred substrate in this acetylation reaction over other common fatty acids such as palmitic (PA), oleic, linoleic or linolenic. This was unexpected because AA is not considered as a fuel fatty acid.

Identification of a substance, previously shown to enhance mitogenesis of human lymphocytes, as the acetamide of p-aminobenzoic acid.

We characterize here an arachidonic acid (AA)-derived metabolite previously found to have an adjuvant effect in phytohemagglutinin-induced mitogenesis of lymphocytes from mothers of newborn babies and from immunodeficient infants. We named the metabolite 'compound 4' due to its position in a thin-layer chromatography system developed for isolation of eicosanoids. The compound was originally found to be produced by peripheral blood mononuclear leukocytes and the T cell leukemia line Jurcat after long-term (18-24 h) incubation with [1-14C]AA.

Differential sensitivity to cAMP among human cord and maternal/adult peripheral lymphocytes discloses differences between PHA- and OKT3-induced activation pathways.

Previous studies have demonstrated that human cord blood lymphocytes are resistant to the anti-proliferative action of prostaglandin E2 (PGE2) in phytohaemagglutinin (PHA)-induced mitogenesis, whereas the same cells activated by OKT3 are at least as sensitive to PGE2 as the corresponding cells from their mothers or other adults. In the present investigation it was found that: (i) PHA-induced proliferation of cord peripheral blood mononuclear leucocytes (PBML) is less sensitive to inhibition by forskolin--a direct activator of adenylate cyclase (AC)--and dibutyryl cAMP--a permeant cAMP analogue--than the proliferation of the corresponding maternal cells; (ii) OKT3-induced proliferation of cord as well as maternal PBML is highly sensitive to inhibition by forskolin and dibutyryl cAMP; (iii) cord PBML show an overall lower rate of AC activity compared with maternal PBML, in response to PGE2 and other autacoids as well as to receptor-independent stimulation; (iv) cord PBML also display a significantly lower rate of degradation of cAMP through cAMP-phosphodiesterase compared with maternal cells; (v) unbroken cord and maternal PBML show comparable rates of cAMP accumulation after stimulation with PGE2. The results suggest a lower sensitivity to the effect of cAMP in cord compared with maternal/adult lymphocytes in PHA-induced proliferation.

Inflammatory cells in transplanted kidneys are infected by human cytomegalovirus.

To determine which cells in kidney grafts are infected with human cytomegalovirus (HCMV) before and after transplantation, kidney specimens were studied by in situ hybridization with 35S-labeled DNA probes representing HCMV immediate-early and late genes. Pretransplantation biopsies and serial posttransplantation biopsies were obtained from 7 renal grafts. All of the transplant recipients were HCMV-seronegative at the time of transplantation and all developed primary HCMV infections.

A novel arachidonic acid metabolite with stimulatory effect on PHA-induced mitogenesis of lymphocytes.

The isolation of a novel arachidonic acid (Aa) metabolite from the supernatant of unstimulated human cord blood mononuclear leucocytes is reported. The metabolite, arbitrarily named 'compound 4' is neither a known lipoxygenase nor a cyclooxygenase product. 'Compound 4' was added to PHA-stimulated peripheral blood mononuclear leucocytes (PBML) from healthy blood donors, from mothers at term and from patients with immunodeficiency.

A prostaglandin-mediated suppressive activity of cord as compared to maternal or other adult adherent cells in OKT3 antibody-induced proliferation.

In a previous study we reported that cord blood lymphocytes show lower OKT3 responses as compared to their mothers and to other, unrelated adults. In the study reported here, we investigated the interactions between lymphocytes and adherent accessory cells in OKT3-stimulated cultures of newborn (cord), maternal, and other adult peripheral blood mononuclear leukocytes (PBML) and determined the following. (1) Removal of adherent cells (AC), by two cycles of plastic adherence or by nylon wool columns, impaired the OKT3-induced proliferation of maternal/adult cells, but significantly enhanced the OKT3 responsiveness of cord cells.

Monocyte-regulated hyporesponsiveness of human cord blood lymphocytes to OKT3-monoclonal-antibody-induced mitogenesis.

OKT3 monoclonal antibody recognizes surface antigenic structures present on all human mature T lymphocytes and is mitogenic for resting peripheral T cells. Recent reports suggest that these structures are linked to the specific antigen receptor of the T cells and play an important role in T-cell activation. We have tested the mitogenic action of OKT3 on resting lymphocytes from human newborns, their mothers, and unrelated adults.

Conditions for the immunohistochemical demonstration of complement factor C3 in formaldehyde-fixed and paraffin-embedded renal tissues.

Paraffin sections of formaldehyde-fixed renal biopsies were labeled for complement C3 by a polyclonal rabbit antibody to human complement C3, by the peroxidase-antiperoxidase complex (PAP) and the avidin-biotin peroxidase complex (ABC) techniques, respectively. All tissues had C3 deposits according to direct immunofluorescence on fresh frozen sections. Staining for muramidase was introduced as an intrinsic control for the degree of tissue proteolysis after the necessary trypsin digestion prior to the immunoenzyme labeling.

Blood transfusions generate/increase previously absent/weak blocking antibody in women with habitual abortion.

Women who suffered recurrent spontaneous abortions of unknown cause were studied for cellular reactivity and blocking antibody in a one-way mixed lymphocyte culture. A defined group of 20 women whose serum displayed no blocking capacity was given three transfusions of leukocyte-rich erythrocyte concentrates. Serum from all women displayed significant blocking capacity 2 months after the third transfusion.

Human fetal/neonatal suppressor activity: relation between OKT phenotypes and sensitivity to prostaglandin E2 in maternal and neonatal lymphocytes.

T lymphocytes from human fetuses and newborns strongly and spontaneously suppress various adult cell functions (i.e. T-cell proliferation, B-cell differentiation, and Ig synthesis).

Gastrointestinal carcinoma-associated antigen detected by a monoclonal antibody in dysplasia and adenocarcinoma associated with chronic ulcerative colitis.

Colorectal tissue specimens from 13 patients with chronic ulcerative colitis, of whom all had epithelial dysplasia and 2 had adenocarcinoma, were tested for the presence of gastrointestinal carcinoma-associated antigen (GICA), using an immunoperoxidase technique with a monoclonal antibody (MAb) against this antigen. GICA was present in the formaldehyde-fixed and paraffin-embedded sections of dysplastic and cancer tissue but absent from normal or hyperplastic epithelium. However, the pattern and extent of staining with the antibody did not correlate with the degree of dysplasia, i.

Strong prostaglandin associated suppression of the proliferation of human maternal lymphocytes by neonatal lymphocytes linked to T versus T cell interactions and differential PGE2 sensitivity.

Lymphocytes from human fetuses and newborns strongly, regularly, and non-specifically suppress the proliferation of PHA stimulated peripheral blood mononuclear leucocytes. The suppression is prostaglandin (PG)-dependent. Our present investigation clearly indicates that the suppression is associated with neonatal T versus maternal T lymphocyte interactions, independent of monocytes.

Expression of gastrointestinal carcinoma-associated antigen (GICA) detected in human fetal tissues by monoclonal antibody NS-19-9.

The expression of a gastrointestinal carcinoma-associated antigen (GICA), a monosialoganglioside, was investigated in tissues from human fetuses of various gestational ages (10-40 weeks). Mouse monoclonal antibody NS-19-9, generated in mice immunized with SW1116 human colon carcinoma cells, was used along with a second polyclonal antibody to mouse IgG to detect antigen expression as visualized by means of the biotin-avidin-peroxidase assay. Sections of snap-frozen tissues or tissues fixed in 4% formaldehyde, in mercury chloride-formaldehyde, or in Bouin's solution were used.

Habitual abortion: parental sharing of HLA antigens, absence of maternal blocking antibody, and suppression of maternal lymphocytes.

The immunologic responsiveness of eight women who habitually abort has been investigated. All shared an HLA-A or B antigen with their husbands. Sharing of an HLA-DR antigen was found in seven couples, one of which also had a second DR antigen in common.

Strong suppression by mononuclear leukocytes from cord blood of human newborns on maternal leukocytes associated with differences in sensitivity to prostaglandin E2.

We have tested peripheral mononuclear leukocytes (PML) from the cord blood of newborns, from sera of their mothers, and from sera of nonrelated nonpregnant adult women for sensitivity to suppressive exogenous prostaglandin E2 (PGE2). Endogenous PG production was simultaneously inhibited by indomethacin 2.8 microM.

Conversion of arachidonic acid in human maternal and neonatal mononuclear leukocytes.

The metabolism of exogenous [1-14C]arachidonic acid in neonatal and maternal peripheral mononuclear leukocytes was studied. Both neonatal and maternal leukocytes converted arachidonic acid to hydroxy acids and to prostaglandin E2, but small amounts of PGF2 alpha and thromboxane B2 were also found. In addition a polar arachidonic acid metabolite with conjugated double bonds was identified in the supernatant from both maternal and neonatal leukocytes.

Differences in binding sites for prostaglandin E2 on mononuclear leucocytes from human newborns and from their mothers.

Binding of [3H]prostaglandin E2 (PGE2) to peripheral mononuclear leucocytes (PML) from newborns and their mothers was studied. Specific binding of PGE2 to both maternal and neonatal PML was found. The binding was maximal after 15 min of incubation at 37 degrees C and specific for PGE1 and PGE2 versus PGA1, PGF1 alpha, and PGF2 alpha.