Biomedical subjects
R Keller
Publications and source records attributed to R Keller.
Treatment of severe lower respiratory tract infections with ceftriaxone (Ro 13-9904). A pilot study.
Two pilot comparative trials in 29 patients suffering from severe lower respiratory tract infections are described. 15 patients received 7-10.5 g ceftriaxone as a total dose and 14 received 28 g amoxicillin, both antibiotics being given by intravenous route during 1 week. The local and systemic tolerance of the drugs were satisfactory; no adverse reactions or relevant laboratory changes were noticed. The clinical response was favourable in all patients. The mot relevant pathogens found in the sputum were Streptococcus pneumoniae in 11 cases and Haemophilus influenzae in 15 cases. Less relevant microorganisms such as Klebsiella pneumonia, Serratia, Pseudomonas sp. and Streptococcus viridans were cultivated prior to therapy. The two main pathogens disappeared from the sputum after therapy in 11 of 13 patients treated with ceftriaxone and in 10 of 13 treated with amoxicillin. The results of these pilot studies indicate that 7-10.5 g ceftriaxone are as active as 28 g amoxicillin in the treatment of severe lower respiratory tract infections.
Studies on the characterization of the linkage-region between polysaccharide chain and core protein in bovine corneal proteokeratan sulfate.
1) A new method of enrichment of the linkage-region in corneal proteokeratan sulfate is described, which consists of desulfation of peptidokeratan sulfate, followed by chromatography on Con A-Sepharose 4B and enzymatic degradation with beta-D galactosidase and beta-N-acetyl-D-glucosaminidase. 2) After permethylation, hydrolysis, reduction with sodium borohydrid and acetylation gas chromatography/mass spectrometry analyses were performed. The followings products could be detected as their peracetates: 2,3,4-tri-O-methylfucitol; 2,3,4,6-tetra-O-methylmannitol; 3,4,6-tri-O-methylmannitol; 2,4-di-O-methylmannitol; 2,3,4,6-tetra-O-methylgalactitol; 2,4,6-tri-O-methylgalactitol; 2,4-di-O-methylgalactitol. 3) The results point to the presence of a branched linkage region in the proteokeratan sulfate molecule with one mannose as the branching point and two mannose residues as the starting point of two disaccharide chains.
Studies on the polydispersity and heterogeneity of proteokeratan sulfate from calf and porcine cornea.
After proteolysis of the calf and porcine corneae with papain 66 (calf) and 56 (hog) polysaccharide-containing fractions were obtained by chromatography on Dowex 1X2 and fractionating precipitation with ethanol (calf) and by chromatography on Dowex 1X2 and CPC-cellulose (hog). The sulfatation degrees (mol sulfate/mol hexosamine) and molecular weights (Mw) of 13 peptidokeratan sulfate fractions from calf cornea and of 9 such fractions from porcine cornea were 0.41-1.25 (Mw 3200-21 500), and 0.42-1.41 (Mw = 4900-25 600), respectively. It was found that the sulfatation degree increases more than proportionally with the chain-length. More than 90% of total keratan sulfate in both cases contain 2-3 mannose and 5-9 amino acid molecules per peptidokeratan sulfate molecule. About 30% of the corepeptide amino acids were asparagine or aspartic acid. More than 90% of the peptidokeratan sulfates from porcine cornea exhibits chain lengths of 31-47 disaccharide units. Two oligosaccharide peptides were isolated from porcine cornea, both being sulfate-free. Besides a core peptide of about 9 amino acids (2 Asx) one of them showed a sugar composition very similar to that of the binding-region from corneal keratan sulfate accord. to Keller, R., Stein, T., Stuhlsatz, H.W., Greiling, H., Ohst, E., Müller, E., & Scharf, H.-D. (1981) Hoppe-Seyler's Z. Physiol. Chem. 362, 327-336: 3 Man, 2 Gal, 4 GlcNAc. The calculated molecular weight based on 3 mannose residues (Mw = 2 600) agrees with that determined by gel chromatography. The second oligosaccharide peptide was homogeneous on electrophoresis and contained the constituents of the linkage region from chondroitin sulfate beside those from keratan sulfate. Based on 4 mannose residues the calculated molecular weight (4 300) is in agreement with that from gel chromatography. The sequence Asn-X-Asx starting with the binding-Asn is postulated in the core protein of proteokeratan sulfate from amino acid analyses of the corneal peptidokeratan sulfate fractions.
[Adult respiratory distress syndrome (ARDS) (author's transl)].
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Induction of macroscopic metastases via surgery. The site of the primary tumor inoculum is critical.
Primary subcutaneous inoculation of fibrosarcoma cells into syngeneic rats leads to progressive local tumor growth. In this experimental model, the incidence of macroscopic metastases is critically dependent on the site of the primary tumor implant. Inoculation of tumor cells into the back is only exceptionally followed by macroscopic metastases; in sharp contrast, inoculation of tumor cells into the thigh gives rise to spontaneous metastatic tumor growth in a high proportion of the animals. Surgical intervention involving excision of the primary tumor either gives frequently rise to macroscopic metastases (when the primary tumor was inoculated in the back) or markedly enhances the growth of metastatic foci (when the primary tumor was inoculated in the thigh).
[Therapy of chronic respiratory insufficiency].
In patients with chronic respiratory insufficiency the treatment of the underlying pulmonary disease is of primary importance. However, many patients often also need symptomatic management to recompensate or stabilize impaired pulmonary gas exchange. The most suitable measures for this purpose are (1) ventilatory support by periodic intermittent positive pressure breathing (IPPB), (2) long-term oxygen administration and (3) respiratory stimulant drugs. IPPB provides good results if restricted to well defined indications (paO2 below 60 mm Hg, paCO2 above 45 mm Hg, forced expiratory volume [FEV1] below 40% of vital capacity or below 1000 ml). Long-term domiciliary oxygen therapy for at least 15 h daily prevents the early decompensation of cor pulmonale and improves physical performance. With the introduction of industrial O2-concentrators this form of therapy becomes more practicable and less expensive compared with the conventional method delivering compressed oxygen. However, the indication should be confined to patients with chronic and severe hypoxemia (paO2 below 50 mm Hg), pulmonary hypertension and secondary polycythemia. Respiratory stimulant drugs are useful in protecting patients from central respiratory depression during oxygen breathing. Aminophylline seems to be the most suitable drug simultaneously acting as a bronchodilator and vasodilator in the pulmonary circulation. To achieve a potent stimulant effect, serum theophylline levels above 10 microgram/ml through repeated intravenous administrations of aminophylline are required. Individual differences in the pharmacokinetic action of theophylline may sometimes need drug monitoring to prevent toxic side effects.
Regulatory functions of macrophages.
Recent findings, based predominantly on cell culture studies, indicate that, apart from their long established role as scavenger cells, mononuclear phagocytes have a key position in the regulation of varied basic cellular functions. Thus far, major effects on cell differentiation, proliferation and/or viability have been described. These basic cellular properties can either be enhanced or suppressed by macrophages, thus attesting their important role in regulating other cell populations. Present knowledge concerning these interactions is briefly summarized.
[Water balance in Germany (author's transl)].
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Suppression of natural antitumour defence mechanisms by phorbol esters.
Chemical carcinogenesis in certain tissues occurs in at least two stages: initiation, producing irreversible tissue alterations, and promotion (by agents, themselves non-carcinogenic), enhancing the outgrowth of transformed cells. Among the various tumour-promoting compounds isolated from croton oil, phorbol-12-myristate-13-acetate (PMA), is the most potent. Cell culture studies have shown that the phorbol diesters and structurally related substances induce a variety of dramatic changes in diverse eukaryotic cells. Spreading, differentiation, metabolism, DNA synthesis, expression of cell surface glycopeptides, deoxyglucose transport, as well as polyamine, plasminogen activator and ornithine decarboxylase activity are altered. These findings indicate that tumour promoters potentiate expression of the transformed phenotype in cells already malignantly transformed and also induce reversible manifestations of the transformed phenotype in normal cells. It is not known whether these agents additionally influence host effector systems involved in antitumour resistance. The present study is concerned with the effects of PMA on spontaneous in vitro cytotoxicity by macrophages and/or natural killer (NK) cells, and on the resistance to rat fibrosarcoma in vivo considered to depend on these normal effectors, in particular on mononuclear phagocytes.
[Chronic respiratory insufficiency in general practice].
The clinical entity of chronic respiratory insufficiency involves a variety of lung diseases with different etiology. Diagnosis, treatment and follow-up are mainly a problem of ambulatory medicine. The most common representative is the patient with chronic obstructive lung disease. The wide array of diagnostic tools makes the selection of appropriate tests difficult for the general practitioner. The clinical findings, as the most important aspect, together with a simple spirometric test (VC and FEV1), however, provide the physician with sufficient parameters to evaluate the current status. Blood gas analysis are indispenable, but can be performed at lengthy intervals. The main therapy relies on selective beta-agonists in combination with steroids. For long-term administration of steroids, however, inhaled steroids should be preferred. Antibiotics should be used liberally and without delay. Cardiac therapy is an important cornerstone in the treatment of chronic respiratory insufficiency. The frequency of glycoside intolerance makes diuretics the ideally suited drug for treatment of concomitant cardiac insufficiency. It is advantageous to use consistent inhalation therapy for drug administration, mainly due to the milder systemic side-effects. A choice must be made between the simple electric nebulizer or the more demanding IPPB-respirator, which requires more demanding patient selection. Both types can be leased through Cantonal institutions, which also provide for regular control of inhalation techniques and maintenance of the inhalation devices. Physiotherapy plays an important part in the instruction of patients as well as providing them with psychological assistance and support in everyday problems. Regular monthly controls by a physician with a standardized questionnaire have proven most useful in guiding the patients and adjusting therapy to individual needs. The frequency of hospitalization can only be reduced by observing all the above mentioned factors.
[The respiratory intensive unit. Requirements for the treatment of patients with acute respiratory insufficiency].
Patients with acute severe respiratory insufficiency can only be correctly monitored, treated and nursed in a well-equipped intensive care unit staffed with well-trained personnel. Qualified doctors and nursing staff are more important for the monitoring and assessment of the patient's symptoms than highly sophisticated electronic monitoring systems. Continuous controls of vital and mechanical functions are however essential , as are the services of well-run laboratories. Treatment calls, above all, for the use of efficient and reliable respirators capable of adjustment to suit the impaired breathing. The quality of nursing and the success of intensive medical care measures are best ensured by well-designed layouts, strict adherence to sensible and appropriate hygienic techniques, continuous and practice-related further education for personnel, and unrestricted communication inside and outside the intensive care unit.
Radioimmunoassay of an invertebrate peptide hormone - the crustacean neurosecretory hyperglycemic hormone.
Antibodies against hyperglycemic hormone (CHH) of Carcinus were raised in rabbits by injection of extract from sinus glands which contain high concentrations of CHH. The antiserum neutralizes the biological activity of CHH and binds 125-J-CHH. A RIA for CHH was established and was used to measure the hormone content of sinus glands.
Immunocytochemical identification of hyperglycemic hormone-producing cells in the eyestalk of Carcinus maenas.
Antiserum raised in rabbits against extracts of sinus glands from Carcinus annd shown by several criteria to contain antibodies directed against the neurosecretory hyperglycemic hormone was used to locate the hormone-producing perikarya in the optic ganglia. By means of the double antibody fluorescence technique, selective staining of the large neurosecretory perikarya of the medulla terminalis ganglionic X-organ (MTGXO) and their axons is obtained. The axon endings of the sinus gland are also stained. None of the other groups of neurosecretory cells in the eyestalk shows fluorescence. Preabsorption of the antiserum with pure hyperglycemic hormone abolishes the fluorescence.
Postoperative spontaneous breathing with CPAP to normalize late postoperative oxygenation.
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In vitro expression of spontaneous macrophage cytotoxicity is independent of substratum adhesiveness.
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Competition between foetal tissue and macrophage-dependent natural tumour resistance.
Prolonged interaction in vitro between C. parvum-induced adherent predominantly phagocytic rat peritoneal cells and syngeneic or xenogeneic tumour targets consistently produces marked cytotoxicity. In the presence of irradiated foetal liver cells, expression of cytotoxicity is blocked in a dose-dependent manner. The ability of liver cells to compete with tumour targets is rapidly lost after birth. Irradiated liver cells from adult donors showed no such competition with tumour cells. The in vivo growth in ascites form of rat fibrosarcoma cells of low immunogenicity is significantly enhanced by irradiated foetal liver cells administered locally shortly before or on the day of tumour-cell challenge. The findings may provide an indication as to the nature of the structures recognized as non-self by mononuclear phagocytes.
In vitro expression of cytotoxicity by macrophages is independent of the actual serum concentration.
In utilizing the same effector and target cells, similar arrangement and population density of cells but varying the actual serum concentration in the range between 1 and 50% fetal calf serum, it was attempted to accurately assess the dependence of in vitro cytolysis expressed by adherent, predominantly phagocytic mononuclear cells ('macrophages') on the actual serum concentration. The results show that the extent to which cytotoxicity by activated macrophages against a given target cell type was expressed, was within a comparable range independent of the actual serum concentration. This holds true for each of the 9 target cell lines examined although with some of the cell lines there was a certain tendency towards high cytotoxicity in the range between 5 and 20% serum.