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Biomedical subjects

C Klein

Publications and source records attributed to C Klein.

At least 289 records · Page 16Linked to original sources
PubMed1994

[High caloric parenteral nutrition in patients with mouth and oropharyngeal cancers--a clinical study].

Patients with carcinomas of the oral cavity and oropharynx often show signs of malnutrition. This is caused by reduced intake in patients due to chronic alcoholism resulting in suppressed appetite and disturbed gastrointestinal functions. Also the growth of the tumor can cause painful swallowing. The effects of chronic malnutrition reduce patients tolerance regarding surgical treatment, chemotherapy and radiation. A pretherapeutic parenteral balanced nutrition should achieve an anabolic metabolism. Changes in body cell mass (bcm) as a parameter of total protein synthesis can be estimated by bioelectrical impedance analysis in order to prove the success of this management. Twenty-eight patients participated in this study, divided into three groups: group 1 = 18 male subjects and group 3 = 3 female subjects, all able to be operated upon, and group 2 = 7 male subjects, not able to be operated. High caloric nutrition in group 1 lead to a higher increase of bcm than in group 2. The review of single cases showed that in both groups one part of the patients failed increasing bcm despite nutrition. The therapeutic response was correlated to survival by means of a Kaplan-Meier analysis and a Cox-model. Survival probability could positively be correlated to an increased bcm.

Adult↗
PubMed1993

Evidence for allosteric regulation of succinyl-CoA synthetase.

We have previously reported that distinctly different concentrations of GDP stimulate the phosphorylation and dephosphorylation of p36, the alpha-subunit of succinyl-CoA synthetase (SCS) in Dictyostelium discoideum. In this present study, we have investigated the mechanism underlying these dual effects of GDP. Dephosphorylation of p36 is induced by relatively high levels of GDP and is coincident with the formation of GTP. This indicates that, at high concentrations, GDP serves as a substrate of SCS. However, 100-fold lower concentrations of GDP, which do not bind to the catalytic site to induce SCS dephosphorylation, stimulate p36 phosphorylation. This stimulation is not diminished by dilution of the sample, and is retained during purification of the protein. Gel-filtration analyses indicate that SCS in our system behaves as a non-interacting alpha beta dimer, the hydrodynamic behaviour of which is not altered by the presence of added GDP. The data indicate that altered protein-protein interactions do not account for the stimulation of p36 phosphorylation by low GDP concentrations. We propose that GDP functions as an allosteric regulator of SCS, and experiments using guanosine 5'-[beta-thio]diphosphate (GDP[S]) are shown to distinguish further the allosteric and catalytic binding sites.

Allosteric Regulation↗
PubMed1993

P36, a Dictyostelium discoideum protein whose phosphorylation is stimulated by GDP, is homologous to the alpha-subunit of succinyl-CoA synthetase.

Previously, we reported the phosphorylation of a 36 kDa protein, p36, in crude membranes from the amoeba Dictyostelium discoideum (Anschutz, A.L., Howlett, A. and Klein, C. (1989) Proc. Natl. Acad. Sci. USA 86, 3665-3668). Here, we report the purification and identification of p36. The protein was purified approximately 35-40-fold with a yield of 8-10%. This material was then separated on 10% SDS-polyacrylamide gels and the band corresponding to p36 was isolated. Partial peptide sequencing of this band revealed p36 to be homologous to the alpha-subunit of succinyl-CoA synthetase. This identification of the protein was supported by the results of phosphorylation studies which examined the effects of substrates of succinyl-CoA synthetase on p36 phosphorylation. In crude sample preparations, p36 could be phosphorylated by both ATP or GTP and in either case, its phosphorylation was stimulated by low concentrations of GDP. Partially purified p36 retained its ability to be phosphorylated with GTP while exhibiting little or no phosphorylation with ATP. GDP still enhanced the rate of p36 phosphorylation with GTP. Therefore, the stimulation of p36 phosphorylation by GDP is not due to substrate conversion and is best explained by a regulatory mechanism.

Adolescent↗
PubMed1993

Agitation, aeration and perfusion modules for cell culture bioreactors.

For an optimized bioreactor design which is adapted to the cultivation of sensitive animal cells different modular bioreactor components for gentle agitation, sufficient aeration and long-term perfusion were developed and investigated with respect to their suitability from laboratory to production scale. Aeration systems have been designed for both shear sensitive cells and cells which tolerate bubbles. The systems are based on either membranes for bubble-free aeration or stainless steel sparger systems. They were characterized by determination of their oxygen transfer capacity and optimized in cultivation processes of different cell lines under process conditions such as batch and perfusion mode. Different impellers for suspension cells and cells grown on carriers were investigated for their suitability to ensure homogeneous gentle mixing. A large pitch blade impeller as well as a novel 3-blade segment impeller are appropriate for homogeneous mixing at low shear rates. Especially with the 3-blade segment impeller fluid mechanical stress can be reduced at a given stirrer speed which is advantageous for the cultivation of cells attached to microcarriers or extremely shear sensitive suspension cells. However, our results indicate that shear sensitivity of animal cells has been generally overestimated. Continuous perfusion of both suspension cell cultures and cells cultivated on microcarriers could be successfully performed over extended periods of time using stainless steel spinfilters with appropriate pore sizes and systems based on microporous hydrophilic membranes. Spinfilters are suitable cell retention systems for technical scale bioreactors allowing continuous perfusion cultures of suspension cells (pore size 10 to 20 microns) as well as anchorage dependent cells grown on microcarriers (pore size 75 microns) over six weeks to 3 months. Applying the developed modules for agitation, aeration and perfusion process adapted bioreactor set-ups can be realized which ensure optimum growth and product formation conditions in order to maximize cell and product yields.

Air↗
PubMed1993

[Lantibiotics, a class of ribosomally synthesized peptide antibiotics].

Lantibiotics are defined as peptide antibiotics containing the unusual amino acids mesolanthionine, 3-methyllanthionine, dehydroalanine, and dehydrobutyrine. They are synthesized by some gram-positive bacteria. Their inhibitory effect on certain other gram-positive bacteria is explained by detergent-like damage of cytoplasmic membranes. Prominent members of the lantibiotics are nisin of Lactococcus lactis, which can be used as a food preservative, subtilin of Bacillus subtilis, which is similar to nisin, and epidermin of Staphylococcus epidermidis, which is considered in the treatment of acne. Lantibiotics are ribosomally synthesized as prepeptides, which are posttranslationally modified. Genes probably encoding these biosynthetic enzymes and regulatory factors have been identified adjacent to the structural genes of the lantibiotics subtilin, nisin, and epidermin.

Amino Acid Sequence↗
PubMed1993

Common hemisphericity of language and music in a musician. A case report.

Aphasia coupled with amusia is reported in a 73-year-old male musician who was a lawyer by profession. This condition followed an ischemic stroke in the lateral aspect of the parieto-occipital region of the left hemisphere. The patient's music production exhibits jargon amusia, similar to that in his verbal production. This case supports the thesis that language and music may share a common hemisphere.

Aged↗
PubMed1993

Endogenous ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase that is not regulated by nitric oxide in Dictyostelium discoideum.

A 41,000 M(r) cytosolic protein (p41) in Dictyostelium discoideum was shown to be modified by ADP-ribosylation that was not regulated by nitric oxide (NO). This endogenous ADP-ribosylation was optimal at conditions distinct from those optimal for the NO-stimulated ADP-ribosylation of p41. These two activities were also differentially sensitive to reducing agents and modified different amino acids. The addition of haemoglobin, which sequesters NO, and of NO synthase inhibitors failed to block the endogenous ADP-ribosylation. P41 was purified to homogeneity. The N-terminal sequence of the purified protein was shown to be highly homologous to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Both endogenous and NO-stimulated activities ADP-ribosylated three isoforms of the protein, with pI values of 6.6, 6.8 and 7.0. In each case, the isoform with pI 6.8 was preferentially modified. Experiments using purified GAPDH indicate that both the endogenous and NO-stimulated ADP-ribosylation are self-catalysed modifications.

Adenosine Diphosphate↗
PubMed1993

Major histocompatibility complex class II deficiency: clinical manifestations, immunologic features, and outcome.

Major histocompatibility complex class II deficiency (bare lymphocyte syndrome) is a rare primary immunodeficiency disorder characterized by profound defects in human leukocyte antigen class II expression, inconsistent and incomplete expression of human leukocyte antigen class I molecules, and a complete lack of cellular and humoral immune responses to foreign antigens. To define the clinical and immunologic characteristics, outcome, and natural history of major histocompatibility complex class II deficiency, we retrospectively analyzed 30 consecutive patients. Clinical onset occurred in the first year of life, usually involving recurrent bronchopulmonary infections and chronic diarrhea. The clinical course was complicated by viral meningoencephalitis, hepatitis, cholangitis, and various autoimmune phenomena. Prognosis was very poor: the mean age at the time of death was 4 years. The main cause of death was overwhelming viral infection. Recent advances in bone marrow transplantation have raised hopes of curative treatment: 6 of 14 patients who underwent bone marrow transplantation were cured. Long-term survival after human leukocyte antigen-identical and haploidentical bone marrow transplantation seemed to depend primarily on the presence of preexisting viral infections.

Child↗
PubMed1993

Blinking, alpha brain waves and smoking in schizophrenia.

Blink rates (BR) and alpha brain waves were studied in 13 schizophrenic and 13 healthy smokers under conditions of smoking deprivation as well as smoking saturation and under different task conditions of smooth pursuit eye movements. Task conditions significantly changed BR and alpha power; smoking enhanced BR and alpha frequency, the latter effect being especially pronounced in schizophrenics for F3-F4 leadings. Concerning BR, groups differed significantly as long as smoking quantity was not statistically controlled. BR, alpha power and smoking quantity were consistently correlated above chance levels. Results are discussed with respect to the blink alpha neurocircuit model.

Adult↗
PubMed1993

Biosynthesis of the lantibiotic subtilin is regulated by a histidine kinase/response regulator system.

Subtilin is a lanthionine-containing peptide antibiotic (lantibiotic) which is produced by Bacillus subtilis ATCC 6633. Upstream from the structural gene of subtilin, spaS, three genes (spaB, spaT, and spaC) which are involved in the biosynthesis of subtilin have been identified (C. Klein, C. Kaletta, N. Schnell, and K.-D. Entian, Appl. Environ. Microbiol. 58:132-142, 1992). By using a hybridization probe specific for these genes, the DNA region downstream from spaS was isolated. Further subcloning revealed a 5.2-kb KpnI-HindIII fragment on which two open reading frames, spaR and spaK, were identified approximately 3 kb downstream from spaS. The spaR gene encodes an open reading frame of 220 amino acids with a predicted molecular mass of 25.6 kDa. SpaR shows 35% similarity to positive regulatory factors OmpR and PhoB. The spaK gene encodes an open reading frame of 387 amino acids with a predicted molecular mass of 44.6 kDa and was highly similar to histidine kinases previously described (PhoM, PhoR, and NtrB). Hydrophobicity blots suggested two membrane-spanning regions. Thus, spaR and spaK belong to a recently identified family of environmentally responsive regulators. These results indicated a regulatory function of spaR and spaK in subtilin biosynthesis. Indeed, batch culture experiments confirmed the regulation of subtilin biosynthesis starting in the mid-logarithmic growth phase and reaching its maximum in the early stationary growth phase. Gene deletions within spaR and spaK yielded subtilin-negative mutants, which confirms that subtilin biosynthesis is under the control of a two-component regulatory system.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Nitric oxide-releasing compounds inhibit Dictyostelium discoideum aggregation without altering cGMP production.

The effects of nitric oxide-releasing compounds on Dictyostelium discoideum cell development and guanylyl cyclase activity were studied. The addition of SNP (sodium nitroprusside) or SIN-1 (3-morpholino-syndnonimine) to starved cells inhibited their differentiation and aggregation in a concentration-dependent manner. In contrast to mammalian systems, SNP did not significantly affect guanylyl cyclase activity in cell lysates of D. discoideum, nor did it stimulate cGMP production in intact cells. The results suggest that the inhibitory effects of NO on D. discoideum cell aggregation are through a mechanism independent of an effect on guanylyl cyclase activity.

Animals↗
PubMed1992

Catalytic center of cyclodextrin glycosyltransferase derived from X-ray structure analysis combined with site-directed mutagenesis.

An X-ray structure analysis of a crystal of mutant Asp229----Ala of cyclodextrin glycosyltransferase from Bacillus circulans (Ec 2.4.1.19) that had been shortly exposed to beta-cyclodextrin showed density corresponding to a maltose bound at the catalytic center. The crystal structure was refined to an R-factor of 18.7% at 2.5-A resolution. The catalytic center is defined by homology with the structurally known alpha-amylases and by the observation that mutants Asp229----Ala and Asp328----Ala are almost inactive. By model building, the density-defined maltose was extended to a full beta-cyclodextrin, which then indicated the general locations of seven subsites for glucosyl units. The catalytically competent residues Asp229, Glu257, and Asp328 are at the reducing end of the density-defined maltose. In the unligated wild-type structure, Glu257 and Asp328 form a 2.6-A hydrogen bond between their carboxylates in an arrangement that resembles those of the catalytically competent carboxylates in acid proteases. Presumably, the first catalytic step is an attack of the proton between Glu257 and Asp328 on the oxygen of the glycosidic bond.

Bacillus↗
PubMed1992

Nitric oxide stimulates the ADP-ribosylation of a 41-kDa cytosolic protein in Dictyostelium discoideum.

Nitric oxide-releasing compounds were shown to activate an ADP-ribosyltransferase activity in the cytosol of Dictyostelium discoideum. The enzyme ADP-ribosylated a cytosolic protein of approximately 41 kDa, p41. Neither cGMP nor GTP and its analogues affected this ADP-ribosylation. p41 differs from other substrates ADP-ribosylated by cholera, pertussis, or diphtheria toxins. Treatment of ADP-ribosylated p41 with snake venom phosphodiesterase released adenosine 5'-monophosphate, indicating a mono-ADP-ribose-protein linkage. This linkage was stable to neutral hydroxylamine but was sensitive to mercury ions and iodomethane, suggesting an attachment to a cysteine residue. Treatment of intact cells with nitric oxide-releasing compounds appeared to stimulate the ADP-ribosylation of p41 and this modification was reversible.

ADP Ribose Transferases↗
PubMed1992

Foreign body perforation of the normal oesophagus.

Over an 11-year period, 12 patients with foreign body perforation of a previously normal oesophagus were treated in our institution. The foreign bodies were most commonly bones (10 cases), 5 of which were chicken bones; other species were pigeon, rabbit, veal, pork and fish (one each); 2 perforations were due to swallowed dentures. The mean age was 60 years (range 42-73) and 6 patients were female. A degree of psychosocial dysfunction was present in 3 patients. Seven patients presented late (> 48 h after ingestion). The commonest presenting symptoms were fever and pain (8 patients). Other symptoms included dysphagia (7), respiratory distress (3), and late cervical abscess formation (3). The diagnosis was established by contrast oesophagography or rigid oesophagoscopy. A third of the perforations were cervical, the remainder intrathoracic. All patients were treated by surgical drainage with or without primary closure of the perforation. There were no operative deaths. Five patients developed postoperative oesophageal leaks which required reoperation in 1 patient. All patients were well and swallowing normally on discharge from hospital. Follow-up endoscopy or oesophagography was carried out in all patients and confirmed the absence of oesophageal disorders. Foreign body perforation of the oesophagus is a rare but important subentity of oesophageal perforation which responds well to surgical treatment.

Adult↗
PubMed1992

[Magnetic resonance tomography and magnetic resonance angiography in lymphangiomatosis].

Generalised lymphangiomatosis is a rare benign congenital abnormality of the lymphatic vessels with a complex pattern. 3 patients with different types of lymphangiomatosis were studied by MRT and MRA and histopathologically. All patients had multiple organ involvement in the abdomen, the skeleton and the skull. The basis in each case was lymphangiomatosis of capillary-cavernous, cystic or cavernous type. The results of MRT and MRA in diagnosing splenic, vascular and skeletal changes correlated accurately with operative findings and with the histopathological classification. In summary, MRT combined with MRA and using paramagnetic contrast media are the diagnostic methods of choice for the investigation of generalised lymphangiomatosis with multiple organ involvement.

Abdomen↗
PubMed1992

Analysis of genes involved in biosynthesis of the lantibiotic subtilin.

Lantibiotics are peptide-derived antibiotics with high antimicrobial activity against pathogenic gram-positive bacteria. They are ribosomally synthesized and posttranslationally modified (N. Schnell, K.-D. Entian, U. Schneider, F. Götz, H. Zähner, R. Kellner, and G. Jung, Nature [London] 333:276-278, 1988). The most important lantibiotics are subtilin and the food preservative nisin, which both have a very similar structure. By using a hybridization probe specific for the structural gene of subtilin, spaS, the DNA region adjacent to spaS was isolated from Bacillus subtilis. Sequence analysis of a 4.9-kb fragment revealed several open reading frames with the same orientation as spaS. Downstream of spaS, no reading frames were present on the isolated XbaI fragment. Upstream of spaS, three reading frames, spaB, spaC, and spaT, were identified which showed strong homology to genes identified near the structural gene of the lantibiotic epidermin. The SpaT protein derived from the spaT sequence was homologous to hemolysin B of Escherichia coli, which indicated its possible function in subtilin transport. Gene deletions within spaB and spaC revealed subtilin-negative mutants, whereas spaT gene disruption mutants still produced subtilin. Remarkably, the spaT mutant colonies revealed a clumpy surface morphology on solid media. After growth on liquid media, spaT mutant cells agglutinated in the mid-logarithmic growth phase, forming longitudinal 3- to 10-fold-enlarged cells which aggregated. Aggregate formation preceded subtilin production and cells lost their viability, possibly as a result of intracellular subtilin accumulation. Our results clearly proved that reading frames spaB and spaC are essential for subtilin biosynthesis whereas spaT mutants are probably deficient in subtilin transport.

Amino Acid Sequence↗