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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 739 records · Page 41Linked to original sources

Calcium requirements for increased complement receptor expression during neutrophil activation.

It has recently been shown that human neutrophils rapidly increase surface expression of membrane receptors for C3b (CR1) and C3bi (CR3) in response to chemoattractants and other stimuli. In the present studies, we used monoclonal antibodies and flow cytometry to assess the role of Ca2+ in this process. Stimulation with ionophore A23187 in the presence of 1.2 mM Ca2+ increased CR1 330% and CR3 650% compared with unstimulated cells at 37 degrees C. Because this indicated that increasing the cytosolic free Ca2+ caused increased receptor expression, we examined the role of Ca2+ in the response to other stimuli as well. Adding 1.2 mM Ca2+ or 5 mM EDTA to the media in which the polymorphonuclear leukocytes were suspended had no effect on the CR1 response to f-MLP or LTB4, whereas Ca2+ slightly enhanced and EDTA markedly inhibited the CR3 response to these stimuli. The effects of Mg2+-EGTA and EDTA were identical. TMB-8 (200 microM), which inhibits the release of Ca2+ from intracellular stores, completely blocked the increased expression of both receptors induced by fMLP or LTB4. Increased expression of both receptors was also prevented by the calmodulin antagonists chlorpromazine (50 microM) and trifluoperazine (10 microM), but not by chlorpromazine sulfoxide. Phorbol myristate acetate (0.1 ng/ml) increased CR1 230% and CR3 265%. Again Ca2+ and EDTA did not alter the CR1 response, whereas Ca2+ increased CR3 to 287% and EDTA reduced CR3 to 187% of control. TMB-8 (250 microM) completely blocked both CR1 and CR3 responses to this stimulus as well. Thus, release of intracellular Ca2+ is necessary and sufficient for increased CR1 expression in response to diverse stimuli, but maximal increases in CR3 expression require an additional influx of extracellular Ca2+. These results indicate that the mechanisms by which the surface expression of the two different complement receptors increase are different in their requirements for extracellular Ca2+. In comparison with the work of others, we suggest that the processes of increased complement receptor expression and secretion of granular enzymes may also differ.

Calcimycin↗

[Psychodynamic relevance of sibling relations].

Sibling relations, including the relations of both parents and children with their siblings, are of as great importance in assessing the normal or abnormal development of a child as in understanding family psychodynamics. Sibling interaction is one of the "universals" in a biography; it was even dealt with in mythology. Despite numerous studies, there is little conclusive evidence about the subjective and psychodynamic significance of birth order. Diagnostic and therapeutic assessments must be made with the particular case in mind, which also presupposes that investigators take into account resistance they themselves may have to the topic of siblings. The author discusses the points that can be of importance with regard to siblings.

Birth Order↗

Absorption of subcutaneously administered regular human and porcine insulin in different concentrations.

The influence of the insulin concentration on its absorption from the subcutaneous tissues was studied by direct measurement of the appearance of insulin in the circulation after its subcutaneous administration. 10 units of regular insulin of semisynthetic human and porcine origin in strength of 15 units/ml, 40 units/ml, and 100/units/ml were administered as bolus to 9 healthy male volunteers, using switched-off, manually handled insulin pumps. Insulinaemia rose significantly higher (p less than 0.05) and insulin levels peaked earlier after the delivery of the 15 units/ml insulin solutions compared to the 100 units/ml insulin solutions. These findings might be of interest for type-I diabetic patients using insulin pumps that are to be loaded with regular insulin in varying concentrations.

Absorption↗

Complement-mediated serum cytotoxicity for Leishmania major amastigotes: killing by serum deficient in early components of the membrane attack complex.

Leishmania major, the agent of Oriental sore, is an obligate intracellular parasite of macrophages in mammalian hosts. Man's immune defense against this organism requires participation of specifically sensitized lymphocytes and activated macrophages. Recent studies, however, have demonstrated that as little as 1/120 concentration of normal human serum is highly cytotoxic for the amastigote form of L. major. Initiation of the lethal process occurs rapidly, requiring only 30 sec of parasite exposure to serum, and is mediated by antibody-independent activation of the alternate complement pathway. The molecular mechanism of cytotoxicity is not known, but may require participation of the membrane attack complex, C5b-9. We investigated this possibility by treating amastigotes with human sera genetically deficient in complement components C5, 6, 7, 8, or 9. We then measured viability of treated parasites by amastigote-promastigote conversion. Our results were quite unexpected: not only did C9-deficient serum kill organisms, but sera singly deficient in each of the preceding components C6 to C8 were also cytotoxic. The degree of cytotoxicity was related both to serum concentration and to the point in the complement cascade at which deficiency occurred. Sera lacking C6 or C7 were less cytotoxic than those deficient in C8, which were less toxic than those deficient in C9. Cytoxicity of deficient sera was abolished by heating serum to 56 degrees C for 30 min. These findings indicate that an incomplete membrane attack complex may mediate cytotoxicity for L. major amastigotes. Moreover, our results raise important questions regarding the mechanism by which the complex is assembled on the surface of a living, unicellular eukaryotic organism.

Animals↗

Analysis of electronically pulsed versus quasi-continuous wave carbon dioxide lasers in an animal model.

In this study we sought to compare laser tissue interaction in both the quasi-continuous waveform and electronically pulsed waveform of the carbon dioxide laser. An intramode analysis of the electronically pulsed form (at 350 and 650 pulses per second) was also undertaken. Intraperitoneal laser incisions were made on New Zealand white female virginal rabbits and tested at days 0, 5, 15, and 20. Testing involved proximal and midsection analysis of the laser sites to evaluate total area of vaporization, total area of tissue thermal damage, maximum diameter of injury at epithelial surface, maximum depth of laser penetration, angle of vaporization crater edges, and angle of tissue thermal injury of the three modes. Analysis of proximal versus midsection preparation revealed different zones of vaporization and injury within the same laser site. The zone of injury with respect to time was nonuniform, suggesting that the laser output in the electronically pulsed mode was not constant. An in vivo tissue lens phenomenon was also detected, resulting in a compound thermal vaporization and injury pattern.

Animals↗

[Quality control of the self-measurement of blood sugar in unselected type I diabetics. The importance of patient training].

Unselected type I diabetics were hospitalized for group training and treatment programme during which blood-sugar was self-monitored with the Haemo-Glukotest 20-800; quality of self-monitoring improved appropriately. The patients had taken part in either the standard training programme (67 patients) or in the "intensive" training programme (101 patients). At the beginning of the training week, after the first theoretical and practical instructions, the quality of blood-sugar self-monitoring was equally poor among patients of both programmes. At the end of the "standard" training week, self-monitoring results were still unsatisfactory, though slightly better than at the onset. Because of these poor results, the training programme was intensified. Optimal quality of self-monitoring was then achieved at the end of the training period. In 69 others, also unselected, type I diabetics the quality of self-monitoring was determined 14 months after their participation in the training programme. Using the Haemo-Glukotest 20-800 (57 patients), self-monitoring gave excellent results; using a blood-glucose measuring instrument (12 patients) it was slightly worse. Assuming intensive training, even unselected type I diabetics can obtain accurate blood-sugar measurements using test-strips.

Adult↗

Cell-free fatty acid acylation of Semliki Forest viral polypeptides with microsomal membranes from eukaryotic cells.

Using [14C]palmitoyl-CoA as donor and deacylated (fatty acid-free) structural proteins of Semliki Forest virus as exogenous acceptors, palmitic acid was incorporated into polypeptide in a cell-free system with microsomes of baby hamster kidney cells, chicken embryo fibroblasts, and rat liver cells. Out of the four viral proteins (E1, E2, E3, and C) only E1 becomes acylated enzymatically. The protein bound fatty acids of the in vitro product are resistant to detergents and to organic extractions but can be released with hydroxylamine thus affording the typical features of acyl-proteins. Fatty acid transfer to E1 requires the presence of microsomes and is abolished when microsomal membranes are omitted or boiled prior to the incubation. Exogenous acceptor protein E1 had to be deacylated prior to the incubation in order to function during acylation in vitro since no fatty acid chains were transferred into untreated viral E1. Acylation of E1 is time- and temperature-dependent and can be stimulated by increasing the concentrations of acceptor protein, microsomal membranes, or of exogenous fatty acid donor. While Mg2+ does not influence the transfer reaction, Mn2+ leads to a dose-dependent inhibition commencing at a concentration of 1 mM. The cell-free acylation activity fails to show high specificity with regard to the chain length or degree of saturation of the acyl chain used as lipid substrate since palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), and myristic acid (C14:0) are all transferred onto E1 as long as ATP is present in the incubation mixture. The type of detergent and its concentration were found to be critical for this acylation in vitro. Nonidet P-40 or Triton X-100 both up to a 0.2% concentration allowed the reaction while no enzymatic transfer of palmitic acid onto E1 was detected in the presence of octyl-beta-D-glucoside and Tween 20 at the conditions used for the in vitro incubation. However, when acyl transfer onto lipid acceptors was monitored, the incorporation of fatty acids into the neutral- and phospholipids functioned normally in octyl-beta-D-glucoside only, while Nonidet P-40 and Triton X-100 inhibited the acylation of all neutral lipids and of most of the phospholipids completely.(ABSTRACT TRUNCATED AT 400 WORDS)

Acylation↗

Target fasting glycaemia for pump-treated type-I diabetics.

In 17 type-I diabetic patients on continuous s.c. insulin infusion (CSII) therapy, potential interrelationships between fasting levels of blood glucose (BG), serum free insulin (free IRI), total (free and bound) insulin (total IRI) and insulin-binding immunoglobulin G ( IgGI ) were evaluated. There was no consistent relationship between the basal s.c. infused insulin dosages and the associated insulinaemia or glycaemia. A significant inverse correlation was found between the fasting levels of serum free IRI and BG (P less than 0.005). On the basis of this interrelationship, a target range of 90-110 mg/dl for fasting BG during CSII treatment is proposed.

Adult↗

[Bronchial asthma, nasal polyposis and analgesic intolerance (the ASA triad). A successful computer based analysis of free texts].

In the period 1977 to 1980 the case histories were collected of 1731 asthmatics and 3590 non-asthmatics and stored in free text form in a computer data bank. Analyzing the data, 1643 primary asthmatics were selected comprising 537 seasonal and 417 perennial asthmatics. The incidence of nasal polyposis and chronic sinusitis on the one hand, and intolerance to analgesics on the other, was, at 9.5% and 4.5% respectively, higher in asthmatics than in non-asthmatics. In perennial asthmatics the particularly high incidences of 16% and 7.2% were observed for the two symptoms. As expected, the ASA triad (common occurrence of nasal polyposis, intolerance to analgesics and asthma) was found to be particularly frequent in perennial asthma (3.1%). A higher rate of coincidence of nasal polyposis and intolerance to analgesics was found in asthma patients than pure chance would suggest. This association is statistically significant for all asthma subpopulations. The mechanism which leads to the ASA triad is still unknown. Computer-aided analysis of free text information proved of great assistance in this study.

Analgesics↗

Identification of acyl donors and acceptor proteins for fatty acid acylation in BHK cells infected with Semliki Forest virus.

The modification of viral glycoproteins through the covalent attachment of fatty acids was studied in baby hamster kidney (BHK) cells infected with Semliki Forest virus (SFV). Comparative pulse-chase experiments with [3H]palmitic acid and [35S]methionine revealed that a precursor polypeptide, designated p62, of the structural SFV glycoprotein and E1 serve as the primary acceptors of acyl chains. Acylation of p62 occurs immediately prior to its proteolytical cleavage to E2 and E3 emphasizing the post-translational and specific nature of this hydrophobic modification. To trace the acyl donor(s) for protein acylation the covalent attachment of fatty acids to p62 was studied after extremely short labeling periods with [3H]palmitic acid and correlated to the metabolism of the exogenous tritiated fatty acid. The shortest possible labeling time, a 10 s pulse with [3H]palmitic acid, was sufficient to acylate SFV p62. Analysis of the labeled lipids extracted from the same cells revealed that palmitoyl-CoA and phosphatidic acid showed the highest specific radioactivity among the tritiated lipid species. Out of these lipid species palmitoyl-CoA was identified as the functional acyl donor lipid in a cell-free system for the acylation of polypeptides.

Acylation↗

Analysis of cancer pain by the neurologist.

Pain intensity and the importance of pain for the cancer patient depend on a variety of individual factors and show considerable divergence (Bonica and Ventafridda 1979). They are greatly influenced by the enigma of the cancer disease as well as the consequential psychiatric problems (Frey 1980). An effective neurological analysis of the cancer pain, although demanding for the physician, is important for further specific diagnostic procedures and for the indication of appropriate therapy. Sometimes thorough neurological examination can lead to the first diagnosis of the carcinoma; when there is already evidence of metastases, the unfavorable prognosis can be made at the same time.

Antineoplastic Agents↗

Hyperinsulinaemia in non-cirrhotic haemochromatosis: impaired hepatic insulin degradation?

This study investigated early alterations of glucose metabolism in idiopathic haemochromatosis. Circulating concentrations of glucose, insulin, C-peptide, glucagon, and gastric inhibitory polypeptide (GIP) were measured after a 100-g oral glucose load in 10 men with idiopathic haemochromatosis in the non-cirrhotic stage of the disease. All had normal glucose tolerance and normal body weight. Ten matched healthy subjects were studied as controls. Insulin concentrations increased to significantly higher levels in patients with idiopathic haemochromatosis than in the control subjects from 30 to 180 min after the glucose load (p less than or equal to 0.01), while fasting insulin concentrations were not significantly different (p greater than 0.05). Concentrations of glucose, glucagon, C-peptide, and GIP were not significantly different at any time (p greater than 0.05). Thus, patients with idiopathic haemochromatosis show hyperinsulinaemia and hence insulin resistance without impaired glucose tolerance in the non-cirrhotic stage. Since pancreatic insulin secretion (C-peptide), glucagon secretion, and the entero-insulinar axis (GIP) are not impaired in these non-cirrhotic patients with idiopathic haemochromatosis, iron accumulation in the hepatocytes may be responsible for the impaired insulin effect and may cause impaired hepatic insulin extraction.

Adult↗

[Dexamethasone suppression test: a biologic marker of endogenous depression?].

In the past few years there have been numerous publications, which have stressed the value of the Dexamethasone Suppression Test (DST) as a diagnostic marker of endogenous depression. Our own studies in 333 psychiatric inpatients and 121 healthy subjects did not reveal a differential diagnostic use for the DST. This result is in good agreement with recent results published in the literature. Our own data demonstrate, however, that intervening variables, such as severity of illness, weight loss, sleep disturbances, situational stress, drug and alcohol withdrawal and the pharmacokinetics of dexamethasone, have an important influence on the DST results, regardless of the diagnostic classification.

Depressive Disorder↗