Idiotypic networks and nature of molecular mimicry: an overview.
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Animals↗
Biomedical subjects
S Müller
Publications and source records attributed to S Müller.
Revised immune network concepts.
The idiotype network concept needs to be revised in order to be in agreement with current data on protein/protein interactions, with the phenomenon of T and B cell recognition of idiotopes, and with the failure of certain anti-idiotypes to stimulate a given immune response. It is proposed that the distinction among Ab2 alpha, beta, and gamma is abandoned, as well as the concept of an internal image idiotope which mimics the three-dimensional shape of nominal antigen. In place of these definitions, the concept of "network antigen" is introduced. Network antigens are potentially the entire repertoire of anti-idiotypes. However, their biological effectiveness is controlled and established by two factors: (i) the affinity to the idiotype Ig receptor; and (ii) the preexisting regulatory network segment that controls the outcome of immune stimulation or suppression. Screening for effective idiotype therapeutic agents has to be done with panels of anti-idiotype and idiotype antibodies in order to establish correlations between idiotope expression and disease progression. Recognizing the importance of network segments will be the first step in the direction toward a rational design of idiotype-based therapies.
Humans↗
Effect of aminophylline on cisplatin nephrotoxicity in the rat.
1. The effect of the methylxanthine aminophylline on cisplatin (5 mg kg-1 i.v.)-induced acute renal failure was investigated in the rat. Renal function was measured 5 days after cisplatin administration. 2. Cisplatin caused a polyuric acute renal failure. The creatinine clearance was significantly reduced. 3. Aminophylline (24 mg kg-1 12h-1) ameliorated the cisplatin nephrotoxicity when administered during the maintenance phase of acute tubular necrosis. However, it had no effect when only administered prophylactically before the cisplatin application. 4. Enprofylline (20 mg kg-1 4h-1 with dose adjustment), a methylxanthine lacking adenosine receptor antagonism in comparison to aminophylline, had no protective effect on cisplatin nephrotoxicity. 5. Adenosine is a renal vasoconstrictor and decreases glomerular filtration rate. Endogenous adenosine in the kidney is formed by degradation of ATP and is thought to be involved in various forms of acute renal failure. The results suggest that adenosine may be involved in the haemodynamic changes in the kidney induced by cisplatin.
Acute Kidney Injury↗
Immunotherapy of metastasizing renal cell carcinoma. Results of a multicentered trial.
119 patients with stage-IV renal cell carcinoma were treated using immunotherapy with autologous tumor vaccine. The immunization was carried out at monthly intervals, the patients were restaged every 3 months using X-ray, ultrasound scanning or computed tomography as well as bone scintigraphy in the follow-up. The patients' follow-up periods run from 6 to 66 months averaging in 38.5 months. 6 complete remissions, 4 partial responses and 29 stable diseases were seen, whereas 54 patients had progressive disease. Patients with a T1 primary tumor all survived the follow-up period irrespective of whether lymph node metastases (n = 2), venous invasion (n = 12) or distant metastases (n = 6) were present at the time of operation. Follow-up periods run from 12 to 48 months (averaging 23 months). Patients with T2 tumors showed survival up to 50 months postoperatively, of these only 3 died. Follow-up averages 30 months. The 3 patients died within the first year after operation. Patients with very large primary tumors showed the poor prognosis normally expected. 23 of these 40 patients died after a mean follow-up of 15 months. These results may indicate that immunotherapy can slow down tumor progression and induce objective responses. Those patients with small primary lesions apparently benefit from the treatment even though metastases are present at the time of diagnosis.
Carcinoma, Renal Cell↗
5-Hydroperoxyeicosatetraenoic acid (5-HPETE) enhances the synthesis of 1-O-alkyl-2-sn-acetyl-glycero-3-phosphocholine (PAF) in fMet-Leu-Phe-stimulated HL-60 cells: key role of diacylglycerol (DAG) in activation of protein kinase C (PKC).
We investigated the effect of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) on the PAF formation in fMet-Leu-Phe-stimulated HL-60 cells. 5-HPETE was found to enhance the PAF synthesis in fmlp-stimulated cells without causing additional mobilization of intracellular calcium. However, a significant increase in diacylglycerol (DAG) levels due to 5-HPETE was observed, which in turn activated the protein kinase C (PKC). Obviously, PKC is responsible for the activation of phospholipase A2 and the release of lyso-PAF and AA from complex lipid stores. Further, the dose-dependent increase in DAG production in absence of simultaneous increase in total inositol phosphates is indicative of an additional source for DAG besides PIP2.
Calcium↗
A one-year double-blind clinical study of the efficacy and tolerability of picumast dihydrochloride versus ketotifen in patients with bronchial asthma.
The efficacy and tolerability of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) (2 mg twice daily orally) in comparison with ketotifen (1 mg twice daily orally) was investigated in 400 patients with bronchial asthma (picumast dihydrochloride n = 202, ketotifen n = 198) in a double-blind, controlled, parallel group study. Assessment of therapeutic and preventative efficacy was by means of symptom scores, quantitative measurements (accumulatory threshold dose) of the bronchial hyperreactivity by means of inhalatory acetylcholine provocation, measurements of peak expiratory flow, vital capacity (VC) and 1-s capacity (FEV1) as well as global assessment of efficacy by the doctor and patient. Tolerability was assessed by recording side effects and global assessment of tolerance on a rank scale at the end of the treatment as well as by means of clinico-chemical parameters. Picumast dihydrochloride and to a lesser extent ketotifen both led to a clinically relevant and statistically significant increase in the inhalatory provocation dose (PD50) for acetylcholine. There was a moderate improvement in the symptom scores and a rise in peak flow values in both treatment groups. The mean total score of asthmatic symptoms of both drugs showed a clear but quantitatively low improvement after 12 months' treatment. The differences in efficacy between picumast dihydrochloride and ketotifen were not statistically significant. During the course of the study, adverse reactions were recorded on 117 occasions (picumast dihydrochloride n = 41, ketotifen n = 76).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Treatment of fetal hemolytic disease using plasmapheresis].
Report about the therapy of severe Morbus haemolyticus fetalis in 15 pregnant women by plasmapheresis alone. Fetal survival rate was 67%. One of three children with hydrops fetalis survived. Plasmapheresis may be used in combination with intrauterine transfusion and improves treatment of Morbus haemolyticus fetalis.
Erythroblastosis, Fetal↗
[The effect of climatic and meteorologic factors on bronchial hyperreactivity and the course of bronchial asthma diseases and their potential significance in asthma prevention: hypotheses, methodologic approaches and initial results].
Bronchial hyperresponsiveness (BHR) as the main condition for the development of asthma may be modulated either by intrinsic or by extrinsic stimuli as well as by climatic and meteorologic factors. Proinflammatory mediators in combination with alterations of airway mucosa induce or amplify BHR. Upper airway viral infections, exposure to allergens in atopic subjects, chronic hyperplastic changes of the upper airways, airway irritants and analgesics are supposed to be the most likely asthma triggers in predisposed children and adults. There is the suggestion that BHR can be improved not only by treatment with steroidal and nonsteroidal antiinflammatory drugs but also by maritime climatotherapy. The latter could be the result not only of the reduction of inhalative irritants, e.g. of allergen concentration, but also by the involvement or more complex mechanisms. Possible theoretic approaches and hypotheses regarding the mode of action of maritime climatic cures are discussed. First preliminary results obtained in a mediterranean region have demonstrated a negative impact of metereologic events like passages of cold weather fronts or increase of wind velocity on the course of asthma disease. An improvement of BHR assessed by histamine challenge test has been observed at the end of climatotherapy in the Baltic sea area. Prospective studies about asthma prevention in subjects at risk with BHR and atopy that have been starting should contribute to the evaluation of the therapeutic effects and the prognostic importance of maritime climatotherapy for getting exact scientific indications for climatotherapy in patients with bronchial asthma.
Adult↗
[Electrophysiologic findings in so-called latent cardiomyopathies].
In the framework of a diagnostic cardiac catheterization for the confirmation or exclusion of an idiopathic myocardial disease 72 patients with latent cardiomyopathy (LCM) and 51 patients without pathological haemodynamic parameters (Non-CM) were examined electrophysiologically. Intraventricular and His-Purkinje conduction defects were essentially more frequently to be proved in patients with LCM than in the non-CM group, whereas an increased ventricular vulnerability in the two groups of patients was existing in about 20% of the cases. The disturbances of rhythm anamnestically frequently mentioned by patients with LCM might above all be traced back to atrial dysrhythmias, since in about one third of the examined patients an increased atrial vulnerability could be proved. Prospective studies of the course must explain, whether the pathological electrophysiological parameters are of prognostic importance in patients with LCM.
Adult↗
Modulation of Ig gene expression by Ig binding factors. Suppression of alpha-H chain and lambda-2-L chain mRNA accumulation in MOPC-315 by IgA-binding factor.
Previous reports by a number of laboratories have shown that Ig-binding factors may play a role in the regulation of Ig production by B cells. Although numerous studies have addressed the specificity and biologic function of Ig-binding factors at the cellular level, little information is available regarding the mechanism whereby Ig-binding factor modulates Ig production by B cells at the molecular level. Herein we have examined the specificity and molecular mechanism of the suppression of IgA production mediated by IgA-binding factor. Using the IgA-secreting plasmacytoma, MOPC-315, as a target cell, we have demonstrated that: 1) IgA-binding factor binds to IgA, but not to IgG, IgM, or BSA; 2) IgA-binding factor can suppress proliferation as well as IgA production by MOPC-315; 3) soluble IgA, but not IgG or IgM can inhibit the action of IgA-binding factor; 4) suppression of Ig production by IgA-binding factor is maximal within 8 to 12 h after exposure to the factor and is reversible; 5) IgA-binding factor suppresses IgA production by selectively down-regulating synthesis of IgA H and L chain proteins; 6) IgA-binding factor selectively suppresses transcription of alpha-H chain and lambda-2-L chain genes; 7) IgA-binding factor suppresses accumulation of c-myc mRNA. These findings suggest that IgA-binding factor binds selectively to surface IgA on MOPC-315 and suppresses IgA production by down-regulating transcription of H and L chain genes. Suppression of MOPC-315 proliferation by IgA-binding factor may be related to the concomitant down-regulation of the expression of the c-myc gene. c-myc is deregulated in MOPC-315 by virtue of the reciprocal 15:12 chromosomal translocation present in MOPC-315 where the c-myc gene is translocated and rearranged into the alpha-H chain gene complex. Simultaneous suppression of the expression of c-myc and alpha-H chain genes suggests that these two genes may be coordinately modulated, in plasmacytomas, by IgA-binding factor.
Animals↗
[Hand metastases--a rare metastatic form of colorectal carcinoma].
24 years after the diagnosis of ulcerative colitis had been made a now 77-year-old man was found to have carcinoma of the rectum. One year after its resection lung metastases and a sacral recurrence became apparent. Two years later swelling of the left hand was at first diagnosed as Sudeck's atrophy, but subsequent tests revealed a metastasis of the known adenocarcinoma to the hand. Palliative telecobalt radiation quickly brought about symptomatic relief.
Adenocarcinoma↗
Multifrequency selective rf pulses for multislice MR imaging.
A method is described for multislice imaging by means of rf pulses which contain a multifrequency excitation spectrum. These pulses label each slice by an individual signal phase and allow the separation of the signals from all the slices by subsequent add/subtract procedures. The image sensitivity corresponds to the total number of acquisitions. Sequences for the imaging of an arbitrary number of slices with a minimum number of experiments are described.
Magnetic Resonance Imaging↗
The polyamine metabolism of filarial worms as chemotherapeutic target.
Parasite-specific putrescine-N-acetyltransferase and polyamine oxidase, both involved in the reversed pathway of polyamine metabolism, were demonstrated for Ascaris suum and Onchocerca volvulus. Berenil-treatment was found to be correlated with accumulation of polyamines, especially spermine, obviously due to blockaded polyamine interconversion. Furthermore it was shown that added spermine to the culture medium led to the death of worms. These specificities might be exploited for chemotherapy of filarial infections. Polyamines are widely distributed in the nature. They are found in higher and lower eucaryotes and in procaryotes as well as in viruses (Tabor and Tabor, 1984). During the last years there have been many approaches to examine the role of polyamines in cell growth and differentiation in vertebrates (Tabor and Tabor, 1984; Pegg, 1986). The polyamine metabolism of parasites also has attracted increasing interest, e.g. in African trypanosomes the initial enzyme of polyamine synthesis - ornithine decarboxylase - has been exploited as a target for chemotherapy by using DFMO (DL alpha-difluoromethylornithine) (Bacchi et al., 1980; Bacchi et al., 1983; Fairlamb et al., 1985; Giffin et al., 1986). The polyamine metabolism of filaria and other helminths is still a neglected area of research, although there are reports about distribution pattern of polyamines and some peculiarities of polyamine metabolism in filarial worms (Srivastava et al., 1980; Wittich et al., 1987; Walter, 1988). DFMO and MGBG (methylglyoxal bis-(guanylhydrazone], both of which are potent inhibitors of polyamine synthesis in mammals, do not significantly effect the viability of filarial worms (Wittich et al., 1987).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Sexual dimorphism of the scapula].
Studies on 96 male and 53 female human right scapulas confirmed a highly significant sexual dimorphism. This sexual dimorphism could also be ascertained for 23 pairs of scapulas from male and female individuals with identical body height. It therefore depends not only on the different average stature of men and women. Using the presented quantitative criteria, the sex of 88% of the bones could be determined correctly, while 4% were misclassified.
Adolescent↗
Suppression of humoral immune response against herpes simplex virus induced by defective strains, ts- and TK- mutants.
Suppression of humoral antibody formation against HSV is not only induced by replicating Herpes simplex virus type 2 (HSV-2) but also by the defective strain ANG and the deletion mutant 1301 of Herpes simplex virus type 1 (HSV-1). Moreover, ts-mutants A, H, K, S, 1201 and 1208 of HSV-1 as well as some ts-mutants of HSV-2 and "defective-interfering" particles of HSV-1 after high multiplicity of infection-passages induced suppression. Treatment of infected mice with ACG reduced antibody-formation but did not result in suppression. UV-irradiation of the antibody producing strain Len of HSV-1 strongly reduces antibody formation and induces suppression. Experiments using a series of intertypic recombinants showed the suppressing activity to be spread over the whole genome of HSV-2. It is concluded that suppression is induced by more than one region of the genome of HSV-2 and by incomplete replication of HSV-1 and 2.
Animals↗
Peptide neuroanatomy of adjuvant-induced arthritic inflammation in rat.
The influence of adjuvant-induced arthritis of the rat on central and peripheral peptide neuroanatomy was investigated by immunohistochemistry. The most striking feature of arthritic rats was the differential intensification of neuronal proenkephalin- and prodynorphin-related staining in dorsal horn. Changes were ipsilateral in monoarthritic and bilateral in polyarthritic rats as compared to controls. Opioid responsive neurons were target of substance P (SP) and calcitonin gene-related peptide (CGRP) fibers. Changes of SP and CGRP predominated in peripheral inflamed tissue and consisted of intensified immunostaining and an apparent sprouting of sensory fibers particularly around venules, in the epidermis and in areas infiltrated by immunocompetent cells. Opioid staining was absent from primary afferents but present in some immune cells of inflamed tissue. Endogenous antinociceptive opioids and pro-nociceptive/pro-inflammatory SP and CGRP may be crucial in the concerted response of the neuroimmune system to chronic inflammatory pain.
Animals↗
Complete and partial ureteral obstruction: evaluation of renal effects with P-31 MR spectroscopy and Tc-DMSA scintigraphy.
Phosphorus-31 magnetic resonance (MR) spectroscopy was used to study the effects of partial and complete ureteral obstruction on the porcine kidney; results were compared with renal tubular function as determined with technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy. Twenty-seven pigs were used: nine as sham-operated controls, six with partial ureteral obstruction, and 12 with complete ureteral obstruction. P-31 MR spectra and Tc-DMSA scintiscans were obtained weekly over 3 weeks. Partial obstruction caused no significant change in P-31 MR spectra, whereas Tc-DMSA scintiscans showed a 74% decrease in tubular function by the end of 3 weeks. Complete obstruction caused a 43% reduction in the mean adenosine triphosphate (ATP) to inorganic phosphate (Pi) ratio, which paralleled the 96% decrease in Tc-DMSA uptake over 3 weeks. The difference in ATP/Pi ratios between control and completely obstructed kidneys was significant (P less than .01) at 2 and 3 weeks after ligation. These results indicate that radionuclide Tc-99m DMSA uptake is very sensitive to the pathophysiologic changes in renal tubular function, while the organ average cellular bioenergetic state (ATP/Pi) is not as strongly affected.
Adenosine Triphosphate↗
Effect of systemic pH on pHi and lactic acid generation in exhaustive forearm exercise.
To investigate whether changes in systemic pH affect intracellular pH (pHi), energy-rich phosphates, and lactic acid generation in muscle, eight normal volunteers performed exhaustive forearm exercise with arterial blood flow occluded for 2 min on three occasions. Subjects ingested 4 mmol/kg NH4Cl (acidosis; A) or NaHCO3 (alkalosis; B) or nothing (control; C) 3 h before the exercise. Muscle pHi and phosphocreatine (PCr) content were measured with 31P-nuclear magnetic resonance (31P-NMR) spectroscopy during exercise and recovery. Lactate output during 0.5-7 min of recovery was calculated as deep venous-arterial concentration differences times forearm blood flow. Before exercise, blood pH and bicarbonate were lower in acidosis (7.303 +/- 0.009, 18.6 +/- 0.5 meq/l) than alkalosis (7.457 +/- 0.010, 32.2 +/- 0.7 meq/l) and intermediate in control (7.389 +/- 0.007, 25.3 +/- 0.6 meq/l). Lactic acid output during recovery was less with A (245 +/- 39 mumol/100 ml) than B (340 +/- 55 mumol/100 ml) (P less than 0.05) and intermediate in C (293 +/- 31 mumol/100 ml). PCr utilization and resynthesis were not affected by extracellular pH changes. pHi did not differ before exercise (A, 7.04 +/- 0.01; B, 7.09 +/- 0.01; C, 7.06 +/- 0.01) or at its end (A, 6.28 +/- 0.07; B, 6.28 +/- 0.11; C, 6.31 +/- 0.09). Hence systemic acidosis inhibited and alkalosis stimulated lactic acid output. These findings suggest that systemic pH regulates cellular acid production, protecting muscle pH, at the expense of energy availability.
Adult↗