Biomedical subjects

D Maas

Publications and source records attributed to D Maas.

At least 19 recordsLinked to original sources

PubMed2001

The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome.

Here we present the first genetic analysis of adiponectin levels, a newly identified adipocyte-derived protein. Recent work has suggested that adiponectin may play a role in mediating the effects of body weight as a risk factor for coronary artery disease. For this analysis we assayed serum levels of adiponectin in 1100 adults of predominantly northern European ancestry distributed across 170 families. Quantitative genetic analysis of adiponectin levels detected an additive genetic heritability of 46%. The maximum LOD score detected in a genome wide scan for adiponectin levels was 4.06 (P = 7.7 x 10(-6)), 35 cM from pter on chromosome 5. The second largest LOD score (LOD = 3.2; P = 6.2 x 10(-5)) was detected on chromosome 14, 29 cM from pter. The detection of a significant linkage with a quantitative trait locus on chromosome 5 provides strong evidence for a replication of a previously reported quantitative trait locus for obesity-related phenotypes. In addition, several secondary signals offer potential evidence of replications for additional previously reported obesity-related quantitative trait loci on chromosomes 2 and 10. Not only do these results identify quantitative trait loci with significant effects on a newly described, and potentially very important, adipocyte-derived protein, they also reveal the emergence of a consistent pattern of linkage results for obesity-related traits across a number of human populations.

Adiponectin↗

PubMed1999

HLA-DR/DQ interaction in patients with erosive rheumatoid arthritis presenting articular and extraarticular disease manifestations.

In the present study we have analysed the effect of HLA-DRB1 and -DQB1 alleles on disease progression and genetic predisposition among 201 RA patients. We clearly confirm the association of RA with HLA class II alleles sharing the (Q)R/KRAA amino acid (AA) cassette in the third hypervariable region (HVR3) of the DR beta-chain. The HVR3 (Q)R/KRAA motif was significantly overrepresented among RA patients (79% vs. 40%, P < 0.001), with one third of the patients homozygous (28% vs. 6.7%, P < 10(-9)) and the number of rheumatoid factor positive (RF+) patients was significantly increased among HVR3 (Q)R/KRAA homozygous in comparison to HVR3 (Q)R/KRAA negative individuals. Erosive disease defined by the Larsen Score and personal disability determined using the Health Assessment Questionnaire (HAQ) was significantly increased among patients positive for the HVR3 motif with the worst outcome among HVR3 (Q)R/KRAA homozygous patients. In contrast, there was no association of the shared HVR3 AA cassette and disease severity in the majority of patients presenting systemic (extraarticular) disease. Homozygosity for the shared HVR3 motif was only marginally increased among patients presenting 'severe' extraarticular disease in comparison to patients with articular disease (33% vs. 43%, P = ns). Similarly, patients with nodular disease were not more often homozygous for the HVR3 (Q)R/KRAA motif. Furthermore, we observed no HLA-DR independent association of DQB1 alleles among HVR3 (Q)R/KRAA positive patients and controls. Our analysis supports the predominant role of HLA-DR for genetic susceptibility to RA. In the clinical setting, however, HLA-DR typing may be limited to assess the individual risk of patients for disease progression.

Adult↗

PubMed1997

Age-related changes in male gonadal function. Implications for therapy.

In contrast with women, who experience a complete and abrupt cessation of ovarian function during the menopause, aging men largely maintain their testicular androgen production. Nevertheless, most cross-sectional studies indicate that there is a partial decrease in testosterone levels with aging, although this has not been confirmed by other studies. The disparity among studies stems from differences in study design, patient numbers, assay techniques and inclusion criteria. Proposed mechanisms for an age-associated decline in testosterone production include: (i) defects in the hypothalamic-pituitary-testicular axis; (ii) an increase in sex hormone binding globulin levels; (iii) environmental factors; (iv) medication use; and (v) chronic illness. The potential beneficial effects of testosterone replacement therapy in hypogonadal men include increased bone density, increased muscle strength, an improved feeling of well-being and an improved metabolic profile. These benefits need to be weighted against the potential risks of androgen therapy, such as erythrocytosis, sleep apnoea, and the stimulation of benign prostatic hypertrophy or an occult prostate malignancy. Consequently, androgen replacement should be used with caution in elderly men with hypogonadism until the results of well-controlled prospective studies are available.

Aged↗

PubMed1996

Vaccination against hydatidosis using a defined recombinant antigen.

Echinococcus granulosus is the causative agent of hydatid disease in humans and animals. Natural transmission of the parasite occurs between dogs as definitive hosts and animal intermediate hosts. There is an urgent need for improved methods to control the parasite's transmission. Here we describe the development of a vaccine based on a cloned recombinant antigen from the parasite egg (oncosphere). Sheep-vaccinated with the antigen, designated EG95, are protected (mean 96-98%) against hydatidosis developing from an experimental challenge infection with E. granulosus eggs. The vaccine will provide a valuable new tool to aid in control of transmission of this important human pathogen. It also has the potential to prevent hydatid disease directly through vaccination of humans.

Amino Acid Sequence↗

PubMed1992

Transsynaptic regulation of galanin, neurotensin, and substance P in the adrenal medulla: combinatorial control by second-messenger signaling pathways.

The adrenomedullary content of neurotensin and substance P was examined 1, 6, and 12 days after hypoglycemic shock. The neurotensin content was increased 60-fold within 24 h and remained elevated for up to 12 days, whereas the substance P content was increased approximately sevenfold within 24 h of insulin treatment and returned to control levels by 12 days poststimulation. Because protein kinase A, protein kinase C, and calcium influx in the rat adrenal medulla are all stimulated following splanchnic nerve stimulation, the differential regulation of neurotensin and substance P biosynthesis following stimulation of these three pathways was examined in bovine chromaffin cells in vitro. Neurotensin levels were up-regulated by elevated potassium, forskolin, and phorbol ester in bovine chromaffin cells. Substance P levels were up-regulated by elevated potassium and forskolin but not by phorbol ester treatment. When chromaffin cells were treated with phorbol ester in combination with forskolin, neurotensin levels were increased in a synergistic fashion, whereas phorbol ester antagonized the forskolin-induced elevation of substance P levels. Earlier, it was reported that galanin biosynthesis, like neurotensin biosynthesis, is upregulated by depolarization, phorbol ester stimulation, and forskolin treatment in chromaffin cells in vitro. Here we report that galanin is also, like neurotensin, increased greater than 60-fold after stimulation of the rat adrenal medulla in vivo. Neuropeptide-specific combinatorial effects of stimulating the calcium, protein kinase A, and protein kinase C signaling pathways may underlie the quantitative differences between galanin and neurotensin compared with substance P up-regulation in rat adrenal medulla after splanchnic nerve stimulation in vivo.

Adrenal Medulla↗

PubMed1991

Enhanced rate of expression and biosynthesis of neuropeptide Y after kainic acid-induced seizures.

Recent studies have shown marked increases in brain content of neuropeptide Y (NPY) after seizures induced by intraperitoneal injection of kainic acid and after pentylenetetrazole kindling in the rat. We have now investigated possible changes in the rate of biosynthesis of NPY after kainic acid treatment, by using pulse-labeling of the peptide and by determining prepro-NPY mRNA concentrations. For pulse labeling experiments, [3H]tyrosine was injected into the frontal cortex, and the incorporation of the amino acid into NPY was determined after purifying the peptide by gel filtration chromatography, antibody affinity chromatography, and reversed-phase HPLC. At 2 and 30 days after kainic acid treatment, the rate of tyrosine incorporation was enhanced by approximately 380% in the cortex. In addition, concentrations of pre-pro-NPY mRNA were determined in four different brain areas by hybridization of Northern blots with a complementary 32P-labeled RNA probe 2, 10, 30, and 60 days after kainic acid treatment. Marked increases were observed in the frontal cortex (by up to 350% of controls), in the dorsal hippocampus (by 750%), and in the amygdala/pyriform cortex (by 280%) at all intervals investigated. In the striatum only a small, transient increase was observed. The data demonstrate increased expression of prepro-NPY mRNA and an enhanced rate of in vivo synthesis of NPY as a result of seizures induced by the neurotoxin kainic acid.

Amygdala↗

PubMed1990

Cholinergic deficit induced by ethylcholine aziridinium (AF64A) transiently affects somatostatin and neuropeptide Y levels in rat brain.

The question whether during the process of cholinergic degeneration somatostatin- and/or neuropeptide Y-containing neurons in rat hippocampus and cortex react to the withdrawal of cholinergic function was addressed. After bilateral intracerebroventricular injection of the cholinotoxin ethylcholine aziridinium (AF64A; 1 or 2 nmol/ventricle) in rats, the activity of choline acetyltransferase (ChAT) started to decline in the hippocampus within 24 h. The reduction of ChAT activity reached its maximum within 4 days (34 and 55% after 1 and 2 nmol of AF64A/ventricle, respectively) and persisted during the observation period of 14 days. In the parietal cortex, ChAT activity decreased by 23% 4 days after 2 nmol of AF64A/ventricle. The loss in ChAT activity was accompanied by a transient decline in the levels of somatostatin and a transient increase in the levels of neuropeptide Y in both brain areas. In the hippocampus, the reduction in somatostatin content was most pronounced after 2 days (by 22 and 33% after 1 and 2 nmol of AF64A/ventricle, respectively). Within 14 days, somatostatin levels returned to control values. Neuropeptide Y levels increased slightly by approximately 25% of control values in the hippocampus. The changes described were present in both the dorsal and ventral subfields of the hippocampus. Similar but less pronounced changes in levels of both neuropeptides were observed in the parietal cortex. The present data provide further evidence for a close neuronal interrelationship between cholinergic and somatostatin- and/or neuropeptide Y-containing neurons in rat hippocampus and parietal cortex.

Animals↗

PubMed1988

Effect of local injection of cysteamine and cystamine on somatostatin and neuropeptide Y levels in the rat striatum.

Cysteamine and its dimeric form cystamine have been applied to the rat striatum by local injection. Both compounds resulted in a dose-dependent decrease of somatostatin levels. Maximal reduction of somatostatin (by about 50%) was obtained at a dose of 50 micrograms of cysteamine or cystamine after about 6 h. All three molecular weight forms of somatostatin--somatostatin-14, somatostatin-28, and the 13,000 molecular weight form of somatostatin--were reduced, as shown by size exclusion HPLC. Injection of radiolabeled cystamine revealed a fast conversion of the compound to cysteamine, suggesting it is active in the monomeric form. The levels of neuropeptide Y, which is colocalized with somatostatin in striatal neurons, failed to be changed by local or intraperitoneal injection of cysteamine, suggesting that this treatment does not affect vesicles of somatostatin/neuropeptide Y neurons.

Animals↗

PubMed1987

HLA-DR4 and Gm 1;21 haplotypes are associated with pseudolupus induced by venopyronum dragées.

The phenotypic frequencies of human major histocompatibility complex class I, II, and III antigens and immunoglobulin allotypes (Gm factors) were determined in 56 patients (55 women, 1 man) who had lupus-like disease induced by venopyronum dragées. The findings in these patients were compared with those of a control group. We found a significant increase of HLA-DR4 (57.1% versus 26.5%, relative risk [RR] 3.7) and a decrease of HLA-DR3 (3.6% versus 19.1%, RR 0.16) in the patient group. In addition, the haplotype Gm 1;21 (60.7% versus 32.9%, RR 3.2), and the phenotype Gm 1,3;5,21 (46.4% versus 25.8%, RR 2.5) were significantly increased. Both the haplotype Gm 1;21 and the phenotype Gm 1,3;5,21 are associated with HLA-DR4 in pseudolupus patients but not in controls. The coincidence of HLA-DR4 and Gm 1;21 markedly increases the risk of acquiring pseudolupus (RR 6.9). We conclude that the pathogenesis of pseudolupus is influenced by at least 2 independent genetic factors. A similar HLA association has been described in hydralazine-induced lupus, and this suggests a common pathogenic mechanism.

Adult↗

PubMed1986

A new serological reaction in patients with polymyalgia rheumatica and/or giant cell (temporal) arteritis: deposition of complement C4 and C3 components on rat kidney structures detected by indirect immunofluorescence.

Using indirect immunofluorescence deposition of complement C4 and C3 components to rat kidney medullary structures was demonstrated. This serological reaction (C4/C3-IFT) is regularly obtained with fresh sera of patients suffering from active polymyalgia rheumatica (PMR) and/or giant cell (temporal) arteritis (GCA). Sera of normal controls and of steroid-treated PMR and/or GCA patients in clinical remission have a negative C4/C3-IFT reaction. A positive conversion of the test in steroid-treated patients indicates enhanced disease activity. Because of its technical simplicity, C4/C3-IFT can be routinely used first, as a reliable serological marker in the primary diagnosis of PMR and/or GCA and second, as a sensitive criterion of disease activity in these patients. C4/C3-IFT reactivity is, however, not specific for GCA and/or PMR. Various systemic inflammatory diseases may have a positive reaction as well (e.g., certain viral and bacterial infections, malignant tumors, vasculitides, inflammatory joint diseases of different etiology). Recent experimental findings suggest that C-reactive protein (CRP) in patients' sera mediates an activation of the classical complement pathway resulting in a deposition of C4 and C3 complement components to certain rat kidney structures.

Adult↗

PubMed1986

[A new serologic reaction in patients with polymyalgia rheumatica and/or giant cell arteritis].

Fresh sera from patients with active polymyalgia rheumatica and/or giant cell arteritis are fixing the complement components C4 and C3 to structures of the medulla of rat kidney tissue as demonstrated by the indirect immunofluorescent technique. This PMR-associated reaction is also a useful tool in monitoring disease activity, as it becomes negative under effective treatment with steroids.

Animals↗

PubMed1985

[Autoimmune hemolytic anemia in ulcerative colitis. Report on 7 cases, possible treatment and review of the literature].

Warm-antibody autoimmune hemolytic anemia (AIHA) is a rare but typical extraintestinal complication of ulcerative colitis. Seven cases with this condition are reported here and 24 further cases from the literature are reviewed. There were no essential differences between the two groups of patients with respect to clinical and immuno-hematological findings. However, the introduction of immunosuppressive drugs has led to a change in therapy and prognosis in recent years. Our observations suggest that treatment with steroids and azathioprine is to be recommended, with accompanying therapy of the underlying disease. In patients failing to respond to this immunosuppressive regimen, splenectomy or surgical treatment of the affected intestines must be considered. For every patient with ulcerative colitis and hyperregenerative anemia the possibility of warm autoantibody formation must be ruled out by performing the direct antiglobulin test.

Adult↗

PubMed1985

High-dose intravenous immunoglobulin for post-transfusion purpura.

Five patients with post-transfusion purpura (four due to Zw(a), one presumably due to HLA antibodies) were treated with intravenous immunoglobulin (IgG) at doses of 0.4 g per kg body weight. IgG therapy was immediately effective as indicated by cessation of bleeding and rise of platelet counts in four out of five cases.

Adult↗

PubMed1985

[In vitro and in vivo studies with interleukin 2 (IL-2) and various immunostimulants in a patient with AIDS].

We report on a lethal course of an acquired immunodeficiency syndrome (AIDS) in a young female patient. She had spent her vacancies six years before diagnosis in Haiti, where a sexual intercourse with a Haitian man had occurred. Leading clinical symptoms consisted of recurrent Herpes simplex infections of the genital and perianal region as well as unexplained high temperatures. There were some typical laboratory and immunologic features of this disease with leukopenia, hypergammaglobulinemia, cutaneous anergy, a reduction of peripheral T-lymphocytes (OKT 3) and an almost complete loss of OKT 4 (helper cells) positive lymphocytes. The mitogenic response upon stimulation with allogeneic cells (MLC) or with the mitogens PHA, Con A and PWM was significantly reduced. There was no measurable interleukin-2 (IL-2) secretion of peripheral blood lymphocytes. Several immunostimulators (thymopentin, inosiplex, bestatin) were tested in lymphocyte proliferation assays in vitro. The mitogenic response could not be enhanced by neither of these substances. A clinical trial with Delimmun (inosiplex) for 14 days did not show any clinical or immunologic improvement in this patient. The intravenous application of high dose immunoglobulin G was without any observable effect. The proliferation inducing capacity of a highly purified IL-2 preparation on the AIDS cells in vitro led us to a clinical trial with this substance. We applied 100 Bödeker units of IL-2 per kg body weight and day subcutaneously for 16 days. A therapeutical effect, however, could not be observed. Cell marker analyses did not show significant changes in lymphocyte subpopulation composition under IL-2 therapy. There was an increase in the spontaneous cell proliferation 14 days after start of IL-2 therapy. The PHA- and IL-2 response of the AIDS cells, however, was unchanged. It cannot be excluded that an administration of IL-2 in earlier stages of AIDS may have beneficial effects.

Acquired Immunodeficiency Syndrome↗

PubMed1984

Differential generation of chemiluminescence--detectable oxygen radicals by normal polymorphonuclear leukocytes challenged with sera from systemic lupus erythematosus and rheumatoid arthritis patients.

The generation of chemiluminescence (CL)-detectable oxygen radicals by normal human polymorphonuclear leukocytes (PMN) after challenging with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) sera is described. CL was measured in a luminol-dependent assay and referred to a standard obtained when performed immune complexes (Ic) (human tetanus toxoid-antitoxoid Ic resuspended in normal pooled serum) were tested on PMN. Normal sera gave rise to CL activity by PMN between 0% and 50% of the standard Ic (mean +/- standard error of the mean (SEM): 20.7 +/- 4.8). Sera from SLE and RA patients induced strikingly different biological effects on PMN. SLE sera generally induced a high CL-detectable generation of oxygen metabolites which may be causally related to the intense tissue damage (vasculitis) frequently observed in this disease. In contrast to SLE, RA sera induced a CL-detectable respiratory burst by PMN that was included in the normal range. Thus, the biological effects of these sera in terms of stimulation of toxic oxygen radical generation by phagocytes are quite different. This generation of oxygen radicals might reflect a different clearance of circulating Ic by PMN in SLE and RA disease.

Antigen-Antibody Complex↗

PubMed1984

[Variable immune deficiency syndrome with antibody deficiency--long-term substitution with immunoglobulins].

We report on our experience with intravenous serum immunoglobulin therapy in five patients with common variable hypogammaglobulinemia. Our results support earlier observations that the immunoglobulin preparations used by us, namely Sandoglobulin and Polyglobin, are both effective in preventing severe infections and free of severe side effects. Essential clinical and laboratory findings of our patients are shown. We also point to the pathogenetic heterogeneity of these diseases as demonstrated by cell marker studies of lymphocyte subpopulations (anti immunoglobulin antisera and monoclonal OKT-antibodies). Finally we show in preliminary kinetic studies that the reduction of serum IgG-levels varies after administration of the same dose of IgG intraindividually in long-term follow-up. Further studies are required to demonstrate whether this variability is due to variable immunoglobulin synthesis and/or variable catabolism or elimination of administered immunoglobulin.

Adolescent↗

PubMed1983

Reticulocytopenia in severe autoimmune hemolytic anemia (AIHA) of the warm antibody type.

A patient with severe AIHA of the warm antibody type, absence of reticulocytes and red cell hyperplasia of the bone marrow is described. In order to maintain a reasonable hemoglobin level 38 units of washed packed red cells were required within 24 days. The treatment with high doses of steroids showed no permanent beneficial effect. After splenectomy the red cell destruction was immediately reduced and the patient went into a remission. Bone marrow culture studies during the acute phase of the disease and at the time of complete hemato- and immunological remission, i.e. 4 months after splenectomy suggested a circulating autoantibody directed to early erythroid progenitors (BFU-E). The inhibitory activity in the patient's plasma did not influence granulocytic or mixed colony formation (CFU-GEMM). In addition to autoantibodies directed to erythroblasts and erythropoietin involved in the pathogenic mechanisms leading to red cell aplasia type I and II the culture studies suggest an unusual autoantibody that might cause the observed reticulocytopenia and erythropoietic hyperplasia of the bone marrow in AIHA. After the splenectomy the patient recovered, he required no further blood transfusions and his disease has not recurred.

Adult↗

PubMed1983

[Clinical significance and pathogenesis of drug- or microbe-induced autoimmune hemolytic anemias].

Methyldopa and several other drugs, continuously taken over months or years, may induce autoimmunity in persons having a probably genetic predisposition. The autoimmunity is reversible after discontinuation of the drug. A number of infectious agents may lead to the same effect. The autoantibodies can react with different autologous targets, for instance red blood cells. This may occasionally cause an autoimmune haemolytic anaemia. The two pathogenetic cardinal points are discussed in the case of the methyldopa-induced autoimmune haemolytic anaemia: the induction of the process results very probably by inhibiting or blocking of the competent suppressor-T-lymphocytes, which normally prevent an autoantibody production, representing a form of chemical "contrasuppression". This has been demonstrated in cultures of peripheral human blood lymphocytes of patients on methyldopa therapy. The second pathogenetic cardinal point is the effect of the autoantibody after its binding to the drugs investigated up to now. Rarely it is pathogenic. This relation is exactly contrary to the idiopathic warm autoantibody anaemia and remains an unsolved problem. A reversible selective deficiency of suppressor-T-cells has also to be postulated for other autoimmune haemolytic anaemias and autoimmune diseases induced by drugs or infectious agents.

Adult↗