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Biomedical subjects

D Maas

Publications and source records attributed to D Maas.

At least 19 recordsLinked to original sources

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

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

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

[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

[Progressive systemic sclerosis - long-term treatment with azathioprin (author's transl)].

The study presents the results of an Azathioprin long-term therapy in 19 of 60 patients with progressive systemic sclerosis (PSS). Average treatment was 47 months (6 to 114 months). The patients received 2-2,5 Azathioprin/kg bodyweight daily. In 16 cases no further progression of PSS was noted. One patient showed minor deterioration. In particular no further deterioration in the lung and kidney manifestations were found. Two patients died. A female patient showed signs of osteomyelofibrosis after being treated for 70 months. She died 3,5 years after Azathioprin had been discontinued. The second patient died of right heart failure after recurrent pulmonary emboli. On the whole treatment with Azathioprin over a long period of time seems in most cases to hold the progression of the disease. The unfavourable prognosis can therefore be much improved.

Adolescent

[Wegener's granulomatosis. Roentgenographic signs and radiotherapeutic possibilities (author's transl)].

Pulmonary alterations and the clinical course of 8 patients with Wegener's granulomatosis are described. Knowledge of the variety of the clinical presentation and lung involvement is mandatory for the radiologist to achieve early diagnosis of this disease. Prognosis is better in Wegener's granulomatosis when adequate therapy is started in the first stage. Films of the nasal sinus are also important for the diagnosis. Besides immunsuppressiva radiation therapy can be helpful in local involvement of the ENT, skin, and orbital area as is demonstrated in 2 of our patients.

Adult

[Complex formation between monoclonal IgM and albumin in a patient with macroglobulinaemia (author's transl)].

A remarkable interaction between a monoclonal IgM(x) protein and autologous albumin was found in the serum of a 76 year old male patient (Ke.E) without morphological characteristics of Waldenströms disease. The components were bound noncovalently. Immunoelectrophoretic analysis of 50 additional monoclonal IgM and 10 IgA sera showed a complex formation with albumin in 62% (IgM) and in 90% (IgA). The degree of interaction was, however, less pronounced in comparison with that observed in the serum of Ke.E.

Aged

[On the question of drug-induced pseudo-LE syndrome: preliminary results in 58 cases (author's transl)].

Drug intake had been checked in 58 patients with pseudo-LE-syndrome. In view of the findings of the Zürich group a connection between the intake of Venopyronum¿ coated tablets and a pseudo-LE syndrome was strongly suspected in 45. In a further seven patients who also had taken the drug no definite connection could be shown because there was no temporal relationship between drug and disease. Three patients had taken Venopyronum-triplex capsules. Only three patients categorically denied ever having taken the drug in any form.

Acute Disease

[Heterogenicity of mitochondrial antibodies (author's transl)].

Sera from 137 patients with mitochondrial antibodies were tested against two different mitochondrial antigens. The mitochondrial antibodies from patients with pseudo-lupus erythematosus (PLE antigen) reacted exclusively with antigen which sedimented on moving-zone centrifugation at a density of 1.10, and contained no antigenic activity when tested against sera from patients with primary biliary cirrhosis (PBC). Purified PBC antigen had no PLE antigen activity at a density of 1.19, and all sera from patients with autoimmune liver disease fixed complement with this fraction. Sera from 54 of 55 patients with PLE reacted with the antigen of the PLE-gradient fraction. But 71 patients with liver disease had no such uniform reaction: sera from 39 patients fixed complement only with the PBC fraction, whereas 32 reacted stimultaneously with both the 1.10 and 1.19 density gradient fraction. The latter pattern was especially found in patients with chronic active hepatitis in whom antibodies to smooth muscle and nuclei were frequently detected.

Autoantibodies

[Polycystic disease of the kidneys and pregnancy (author's transl)].

A summary of pregnancy-developments of patients with polycystic disease of the kidneys is presented. The polycystic disease of the kidneys is a chronic progessive affection which takes both the kidneys in almost every case. The development of this disease can be divided in four stages. During the first, asymptomatic stage there is no disturbance of the pregnancy. In the second stage at the beginning of the decrease of the kidney-function therapy in pregnancy consists in confinement to bed and usual kidney-disease-diet. When complications as chronic recurrent pyelonephritis and hypertension rise and the final stage -- renal failure -- is achieved the pregnancy has to be finished as quick as possible in the early pregnancy by interruption and in the late pregnancy by sectio cesarian. Both methods should be followed by sterilisation of the patient.

Abortion, Therapeutic

[Mitochondrial antibodies induced by drug administration in patients with and without pseudo LE syndrome (author's transl)].

The pseudo LE syndrome was first described in 1972. It is a severe, sometimes fatal condition, in which high titres of mitochondrial antibodies are a constant feature. In the vast majority of cases detected, Venopyronum in dragée form (containing phenopyrazone, horse-chestnut extract, and cardiac glycosides from various plants), had been taken prior to onset of the clinical symptoms. It is probably commoner, that following intake of the drug mitochondrial antibodies appear without clinical manifestations. In both situations, disposition, dose and duration of treatment are important factors. There is reasonable ground to believe that not just a single component, but rather the combination of various substances in the preparation is responsible for the induction of an autoimmune process. At the present time it appears that an idiopathic form, without drug contact, also exists.

Adult