Search PubMed⌕ Search

Biomedical subjects

A Ernst

Publications and source records attributed to A Ernst.

At least 73 records · Page 4Linked to original sources

The number of identical kringle IV repeats in apolipoprotein(a) affects its processing and secretion by HepG2 cells.

A variable number of 5.6-kilobase kringle IV repeats in the human apolipoprotein(a) (apo(a)) gene results in a size polymorphism of the protein and correlates inversely with the plasma levels of the atherogenic lipoprotein(a) (Lp(a)). In order to analyze whether this association reflects a direct effect of kringle IV repeat number on Lp(a) plasma concentration, we have studied the expression of recombinant apo(a) (r-apo(a)) isoforms in the human hepatocarcinoma cell line HepG2. Following transient transfection of apo(a) cDNA expression plasmids that differed only in the number of kringle IV repeats, we observed a gradual decrease of Lp(a) in the medium of the cells with an increasing number of kringle IV repeats, mimicking the relationship present in humans in vivo. The analysis of apo(a) protein in the lysate and in the medium of cells that were transfected with a plasmid encoding an apo(a) isoform with 22 kringles revealed a predominant intracellular precursor with little secretion of the mature apo(a) protein. In contrast, transfection of a plasmid encoding an isoform with 11 kringles led to effective secretion of the mature peptide into the medium, indicating differential processing rates of apo(a) isoforms in the secretory path way. The intracellular accumulation of an apo(a) precursor in the endoplasmic reticulum was demonstrated by cell fractionation and [35S]Met metabolic labeling/temperature block experiments using HepG2 cells stably transfected with recombinant apo(a). The direct and causal effect of kringle IV repeat number on the expression of recombinant apo(a) in HepG2 cells, and presumably liver cells, provides a novel mechanism for the genetic regulation of the concentration of a protein.

Apolipoproteins A↗

[Tooth discoloration as a rare complication of septorhinoplasty].

BACKGROUND: Surgeons should thoroughly consider the clinical implications of elective surgery such as septorhinoplasty for functional and cosmetic improvement of the appearance of the nose. Complications may jeopardize the intended result of this surgery. CASE REPORT: We report on the rare complication of devitalization of two incisors in the maxilla with disturbing discoloration after performing a septorhinoplasty in a 23-year-old woman. The patient underwent a serial hydrogen peroxide bleaching and a root canal procedure. CONCLUSION: The osteotomy of a huge basal crista that compromised neurovascular dental supply could be a possible mechanism of this event. Even though such a complication after septorhinoplasty is extremely rare, patients should be informed of this eventually prior to surgery, if only for legal reasons.

Adult↗

[Distant metastasis of renal cell carcinomas to the head-neck area].

BACKGROUND: Metastases of hypernephroma to the head and neck, especially to the larynx, are rare occurrences. PATIENTS: We report on two cases with solitary spread in the head and neck. A 73-year-old woman who underwent nephrectomy because of a hypernephroma six years ago had a manifestation in the right false vocal cord, which was resected by laser surgery. The specimen of the strumectomy in the other patient revealed a metastasis of an asymptomatic hypernephroma to the thyroid gland and finally led to correct diagnosis of the primary tumor. RESULTS: The female patient refused any further treatment and died of cachexia with tumor dissemination four months later. The other patient is still living with a local recurrence after palliative irradiation and administration of interleukin-2 and alpha-interferon. CONCLUSIONS: In absence of other tumor manifestations, choosing an adequate therapy can be difficult because of the long survival rates in some patients even after hematogenous spread and the unpredictable behavior of this malignancy.

Aged↗

An insertion element prevents phycobilisome synthesis in N2-fixing Synechocystis sp. strain BO 8402.

The unicellular diazotrophic cyanobacterium Synechocystis sp. strain BO 8402, isolated from Lake Constance, contains a novel insertion sequence, IS8402, in the apcA gene encoding a pigmented protein of phycobilisomes. IS8402 comprises 1,322 bp, flanked by two inverted repeats of 15 bp. Upon insertion in the target DNA, direct duplications of 8 nucleotides were generated. One open reading frame, potentially coding for a protein of 399 amino acids, was found. The deduced amino acid sequence shows homology to putative transposases of the IS4 family. Precise excision of the insertion element resulted in a spontaneous revertant, Synechocystis sp. strain BO 9201, that had regained the ability to form hemidiscoidal phycobilisomes. Apart from the unique insertion of IS8402 into apcA in strain BO 8402 both strains contain at least 12 further homologous insertion elements at corresponding sites in the genomes. The unique insertion in strain BO 8402 prevents the expression of apcABC operon and hence abolishes the formation of intact phycobilisomes. This decreases the quantum efficiency of photosystem II and promotes anaerobic N2 fixation in a unicellular cyanobacterium with a highly oxygen-sensitive nitrogenase.

Amino Acid Sequence↗

GlbN (cyanoglobin) is a peripheral membrane protein that is restricted to certain Nostoc spp.

The glbN gene of Nostoc commune UTEX 584 is juxtaposed to nifU and nifH, and it encodes a 12-kDa monomeric hemoglobin that binds oxygen with high affinity. In N. commune UTEX 584, maximum accumulation of GlbN occurred in both the heterocysts and vegetative cells of nitrogen-fixing cultures when the rate of oxygen evolution was repressed to less than 25 micromol of O2 mg of chlorophyll a(-1) h(-1). Accumulation of GlbN coincided with maximum synthesis of NifH and ferredoxin NADP+ oxidoreductase (PetH or FNR). A total of 41 strains of cyanobacteria, including 40 nitrogen fixers and representing 16 genera within all five sections of the cyanobacteria were screened for the presence of glbN or GlbN. glbN was present in five Nostoc strains in a single copy. Genomic DNAs from 11 other Nostoc and Anabaena strains, including Anabaena sp. strain PCC 7120, provided no hybridization signals with a glbN probe. A constitutively expressed, 18-kDa protein which cross-reacted strongly with GlbN antibodies was detected in four Anabaena and Nostoc strains and in Trichodesmium thiebautii. The nifU-nifH intergenic region of Nostoc sp. strain MUN 8820 was sequenced (1,229 bp) and was approximately 95% identical to the equivalent region in N. commune UTEX 584. Each strand of the DNA from the nifU-nifH intergenic regions of both strains has the potential to fold into secondary structures in which more than 50% of the bases are internally paired. Mobility shift assays confirmed that NtcA (BifA) bound a site in the nifU-glbN intergenic region of N. commune UTEX 584 approximately 100 bases upstream from the translation initiation site of glbN. This site showed extensive sequence similarity with the promoter region of glnA from Synechococcus sp. strain PCC 7942. In vivo, GlbN had a specific and prominent subcellular location around the periphery of the cytosolic face of the cell membrane, and the protein was found solely in the soluble fraction of cell extracts. Our hypothesis is that GlbN scavenges oxygen for and is a component of a membrane-associated microaerobically induced terminal cytochrome oxidase.

Aerobiosis↗

A second nitrogenase in vegetative cells of a heterocyst-forming cyanobacterium.

In many filamentous cyanobacteria nitrogen fixation occurs in differentiated cells called heterocysts. Filamentous strains that do not form heterocysts may fix nitrogen in vegetative cells, primarily under anaerobic conditions. We describe here two functional Mo-dependent nitrogenases in a single organism, the cyanobacterium Anabaena variabilis. Using a lacZ reporter with a fluorescent beta-galactoside substrate for in situ localization of gene expression, we have shown that the two clusters of nif genes are expressed independently. One nitrogenase functions only in heterocysts under either aerobic or anaerobic growth conditions, whereas the second nitrogenase functions only under anaerobic conditions in vegetative cells and heterocysts. Differences between the two nif clusters suggest that the nitrogenase that is expressed in heterocysts is developmentally regulated while the other is regulated by environmental factors.

Acetylene↗

Identification of two functionally distinct lysine-binding sites in kringle 37 and in kringles 32-36 of human apolipoprotein(a).

The well documented association between high plasma levels of lipoprotein(a) (Lp(a)) and cardiovascular disease might be mediated by the lysine binding of apolipoprotein(a) (apo(a)), the plasminogen-like, multikringle glycoprotein in Lp(a). We employed a mutational analysis to localize the lysine-binding domains within human apo(a). Recombinant apo(a) (r-apo(a)) with 17 plasminogen kringle IV-like domains, one plasminogen kringle V-like domain, and a protease domain or mutants thereof were expressed in the human hepatocarcinoma cell line HepG2. The lysine binding of plasma Lp(a) and r-apo(a) in the culture supernatants of transfected HepG2 cells was analyzed by lysine-Sepharose affinity chromatography. Wild type recombinant Lp(a) (r-Lp(a)) revealed lysine binding in the range observed for human plasma Lp(a). A single accessible lysine binding site in Lp(a) is indicated by a complete loss of lysine binding observed for r-Lp(a) species that contain either a truncated r-apo(a) lacking kringle IV-37, kringle V, and the protease or a point-mutated r-apo(a) with a Trp-4174-->Arg substitution in the putative lysine-binding pocket of kringle IV-37. Evidence is also presented for additional lysine-binding sites within kringles 32-36 of apo(a) that are masked in Lp(a) as indicated by an increased lysine binding for the point mutant (Cys-4057-->Ser), which is unable to assemble into particles. An important role of these lysine-binding site(s) for Lp(a) assembly is suggested by a decreased assembly efficiency for deletion mutants lacking either kringle 32 or kringles 32-35.

Amino Acid Sequence↗

Noninvasive assessment of the intralabyrinthine pressure. A new technique applied to patients with X-linked progressive mixed deafness syndrome with perilymphatic gusher during stapes surgery.

In this report, we describe the findings of a noninvasive assessment of the intralabyrinthine pressure in two patients from a family with X-linked progressive, mixed deafness syndrome in whom a perilymphatic gusher occurs during stapes surgery. The so-called tympanic membrane displacement measurement technique could be successfully applied in these two patients (from a total of five patients who were studied) because they still showed a stapedial reflex at 1 kHz, which is mandatory for application of the tympanic membrane displacement measurement technique. The findings were compared with those of age-related control subjects and indicated a significantly elevated intralabyrinthine pressure in the two patients who were observed. The results suggest that the tympanic membrane displacement measurement technique may serve as a screening test in audiological diagnostic studies of perilymphatic hypertension.

Acoustic Impedance Tests↗

Tobacco prevention education in a pediatric residency program.

OBJECTIVE: To report the impact of a tobacco intervention in a pediatric residency program. DESIGN: Residents and faculty took pretests and posttests and follow-up surveys 6 months later. SETTING: An urban, university-affiliated, county medical center. INTERVENTION: An educational program of three presentations, written materials, and a bulletin board. RESULTS: Significant improvement in counseling and confidence in counseling. Perceptions of barriers to counseling, specifically expertise, time limitation, and doubts regarding counseling effectiveness diminished. Residents changed less than faculty in particular areas. There were no differences between the posttests and the follow-up survey 6 months later. CONCLUSIONS: Pediatric health professionals in an academic setting, given an educational program, will change their behaviors and attitudes about their role in counseling patients about tobacco use.

Adult↗

Acute hyperpolarization and elongation of cochlear outer hair cells on superfusion with cis-platinum.

The acute effects of cis-platinum on isolated cochlear outer hair cells (OHC) were investigated with whole-cell patch-clamps and measurements of cell length changes. Our findings demonstrated that cis-platinum reversibly induced a hyperpolarization and cellular elongation. These results suggest that the effects produced are the result of an interaction between cis-platinum and transduction channels in OHC. These acute effects are distinctly different from the chronic, irreversible ones that are followed by death of the OHC. The exact mechanism of these chronic effects remains unknown as yet.

Animals↗

Human plasma DSIP decreases at the initiation of sleep at different circadian times.

Nocturnal plasma delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) was determined serially in seven healthy male subjects. Time courses during nocturnal sleep (2300-0800 h), nocturnal sleep deprivation (2300-0500 h), and morning recovery sleep (0500-0800 h) after sleep deprivation were compared. A significant decrease in plasma DSIP-LI was found at the transition from wakefulness to sleep in both evening sleep (2300 h) and morning recovery sleep (0500 h). Time courses were accompanied by physiological changes in sleep electroencephalographic slow-wave activity, and in plasma concentrations of cortisol and human growth hormone. No sleep stage specificity was found. It is concluded that DSIP is influenced by the initiation of sleep.

Adult↗

[Noninvasive evaluation of intracochlear pressure. II. Study findings in patients with Meniere's disease, fluctuating deep tone hearing and peripheral vestibular vertigo].

The tympanic membrane displacement technique (TMD) is aimed at evaluating intracochlear and intracranial pressure changes non-invasively. Therefore, the present paper describes the findings in patients with Ménière's disease where an increase in volume of the endolymphatic spaces is discussed. It should be investigated to which extent a change in the intracochlear pressure corresponds to different stages of the disease. It could be described that the intracochlear pressure does change over a certain period of persisting Ménière's, but that there is no extensive increase in intracochlear pressure between the attacks. The glycerol test as well as the acute attack (case report on one patient) are, however, characterised by distinct patterns. The same holds true for the late-stage Ménière's. It could be demonstrated that the functional patency of the cochlear aquaeduct in patients with long-term Ménière's history is reduced. This finding is surprising and should be investigated further. In essence, the TMD technique enables to better characterise Ménière patients, but it should not be a tool of routine diagnosis of the disease. In some audiological patients, it can also be beneficially applied (10).

Adolescent↗

[Noninvasive assessment of intracochlear pressure. III. Case reports of patients with intracochlear hyper- and hypotension].

It was the scope of two previous papers to outline the basics and possible neurotological applications of the tympanic membrane displacement technique (TMD). The present paper is aimed at briefly reviewing five distinct cases where a sudden sensorineural hearing loss with/without tinnitus could be monitored by the TMD technique. These features include a sudden hearing loss upon lumbar puncture, the audiological manifestation of an internal hydrocephalus, stapes gusher and the round window rupture. All symptoms are based on a change in intracranial and intracochlear pressure which in turn leads to the manifestation of the previously unknown sensorineural hearing loss and/or tinnitus.

Adult↗

[Langerhans cell histiocytosis of the temporal bone].

BACKGROUND: The localized form of the Langerhans cell histiocytosis was referred to earlier as eosinophilic granuloma, which has the best prognosis of all histiocytosis syndromes concerning survival. The non-malignant proliferative disorder of the histiocytic system is still of unknown etiology. Characteristic radiographic signs are osteolytic lesions. PATIENT: We report on an otologic manifestation of a 20-year-old man's temporal bone, which developed three years after a successful treatment of an eosinophilic granuloma of the mandible. RESULTS: Surgery and low-dose irradiation led to a complete remission of the disease. Other manifestations of the disease were not detected until now. CONCLUSIONS: In the presence of chronic aural discharge, Langerhans cell histiocytosis must bei considered in differential diagnosis and a histopathological examination should be performed.

Adult↗

Effect of pressure on echocardiographic videodensity from sonicated albumin: an in vitro model.

The effect of different pressures (0, 10, 30, 60, 80, 100, 120, or 180 mm Hg) on the ultrasound contrast effect obtained from sonicated albumin was evaluated by videodensity decay curves in an in vitro model immersed in a water tank. Decay rates and half-times were calculated from the videodensity decay curves at each pressure. A significant (P < 0.0001) relation was found between contrast disappearance and pressure: the higher the pressure the more rapid the contrast disappearance. Release of pressure did not result in contrast reappearance. Contrast decrease with pressure may result from microbubble destruction or alteration in acoustic properties by pressure. These findings may help explain the limited success of sonicated albumin for systemic ultrasonographic arteriography and myocardial perfusion imaging after intravenous injection. An ideal contrast agent for contrast echo studies should be stable at physiologic pressures.

Albumins↗

Randomized comparison of fluorouracil and leucovorin therapy versus fluorouracil, leucovorin, and cisplatin therapy in patients with advanced colorectal cancer.

BACKGROUND: Because of experimental and preliminary clinical evidence that additional modulation of the biochemical pharmacology and cytotoxicity of 5-fluorouracil (5-FU) and leucovorin (LV) may be possible by combination of these agents with cisplatin (CDDP), the authors undertook a prospective randomized trial in patients with colorectal cancer. METHODS: Between 1989 and 1992, 138 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either 5-FU (425 mg/m2) and LV (20 mg/m2) for 5 days, or the combination of 5-FU and LV in the same daily dose plus cisplatin (20 mg/m2), each drug given for 4 consecutive days. In both treatment arms, courses were administered every 28 days, if toxicity allowed, for a total of 6 months or until evidence of tumor progression. RESULTS: The overall responses (complete and partial response) were 19% and 28% for the 5-FU/LV and the 5-FU/LV/CDDP treatment arms, respectively. Although the three-drug combination appeared superior to 5-FU/LV for time to progression or death (8.5 versus 5.2 months; P = 0.042), there was no evidence that the adoption of cisplatin will translate into a definite survival advantage. A comparative analysis of the toxicities experienced by the patients in the two treatment groups showed a comparable rate, although severe side effects (P < 0.05), specifically stomatitis (P = 0.013), were noticed more frequently in patients treated with 5-FU/LV for 5 days. CONCLUSIONS: These results suggest that the therapeutic index of 5-FU/LV in metastatic colorectal cancer may be improved with the addition of cisplatin. However, the somewhat better therapeutic activity and lower incidence of severe gastrointestinal side effects have to be weighed against additional pharmaceutical charges and the need for a more intense antiemetic regimen.

Adult↗

Acute gentamicin ototoxicity in cochlear outer hair cells of the guinea pig.

The acute effects of the aminoglycoside antibiotics gentamicin on isolated cochlear outer hair cells (OHC) was investigated by whole-cell patch-clamp and measurements of the intracellular potassium level by means of the potassium-sensitive dye PBFI. In addition, the accompanying length changes of OHC are described. It could be shown that gentamicin at different concentrations reversibly induces a hyperpolarization by about 5-10 mV, potassium outflow from the cytoplasm (by about 22 mM) and a cellular elongation (by about 10%). It is suggested that these effects are the result of an interaction between gentamicin and the cochlear transduction channels in OHC as suggested earlier. These acute effects are distinctly different from the chronic gentamicin effects which are based on the metabolization of the antibiotics to cause the death of the OHC by interaction with the phosphoinositide signalling cascade.

Animals↗