Biomedical subjects

S Schulz

Publications and source records attributed to S Schulz.

At least 91 records · Page 5Linked to original sources

PubMed2000

Enantiomeric degradation of 2-(4-Sulfophenyl)Butyrate via 4-sulfocatechol in Delftia acidovorans SPB1.

Enrichment cultures with enantiomeric 2-(4-sulfophenyl)butyrate (SPB) as the sole added source(s) of carbon and energy for growth yielded a pure culture of a degradative bacterium, which was identified as Delftia acidovorans SPB1. The organism utilized the enantiomers sequentially. R-SPB was utilized first (specific growth rate [mu] = 0.28 h(-1)), with transient excretion of an unknown intermediate, which was identified as 4-sulfocatechol (4SC). Utilization of S-SPB was slower (mu = 0.016 h(-1)) and was initiated only after the first enantiomer was exhausted. Suspensions of cells grown in S-SPB excreted 4SC, so metabolism of the two enantiomers converged at 4SC. The latter was degraded by ortho cleavage via 3-sulfo-cis,cis-muconate. Strain SPB1 grew with 4SC and with 1-(4-sulfophenyl)octane (referred to herein as model LAS) but not with commercial linear alkylbenzenesulfonate (LAS) surfactant, which is subterminally substituted but nontoxic. It would appear that metabolism of the model LAS does not represent metabolism of commercial LAS.

Benzenesulfonates↗

PubMed2000

Cation transport and cell volume changes in maturing rat reticulocytes.

During maturation, reticulocytes lose membrane material, including transporters, and this is accompanied by a loss of cell water and volume. Here we determined a possible role of ion transport in adjusting cell volume during maturation. Reticulocytes and red blood cells of different ages were prepared from erythropoietin-treated rats by density gradient fractionation. Cell volume and ion transport were measured in freshly prepared cells and in reticulocytes during in vitro maturation. Reticulocytes had an increased K content and cell volume, whereas intracellular Na was decreased. All parameters approached whole blood values after 2 days in culture. Na-K pump was elevated in reticulocytes and decreased during maturation. Na-K-2Cl cotransport (NKCC) activity was lower in reticulocytes and was activated 8- and 20-fold by shrinkage and okadaic acid, respectively, whereas stimulation was barely detectable in high-buoyant density red blood cells. The ouabain- and bumetanide-insensitive Na flux in reticulocytes decreased on maturation. Most of it was inhibited by amiloride, indicating the presence of Na/proton exchange. Our results show that, although the Na-K-pump activity in reticulocytes is very much increased, the enhanced capacity of NKCC is essentially cryptic until stimulated. Both types of capacities (activities) decrease during maturation, indicating a possible loss of transport protein. The decrease was constrained to the period of reticulocyte maturation. Loss of transport capacity appears to exceed the loss of membrane surface area. Reticulocyte age-related changes in the net electrochemical driving force indicate that the increasing NKCC activity might contribute to the reduction in cell water.

Animals↗

PubMed2000

Immunohistochemical determination of five somatostatin receptors in meningioma reveals frequent overexpression of somatostatin receptor subtype sst2A.

Meningioma is one of a variety of human tumors that exhibit a very high density of somatostatin receptors and in many cases show a true positive somatostatin receptor scintigraphy. However, the level of expression of individual somatostatin receptor proteins in meningioma has not been investigated. We have recently developed a panel of somatostatin receptor subtype-specific antibodies that effectively stain formalin-fixed, paraffin-embedded tumor tissue (S. Schulz et al., Clin. Cancer Res., 4: 2047-2052, 1998). In the present study, we have used these antibodies to determine the somatostatin receptor status of 40 randomly selected meningiomas. Immunoreactive staining for all somatostatin receptors was clearly located at the plasma membrane of the tumor cells and completely blocked with antigenic peptide. The vast majority of tumors (29 cases; 70%) were positive for sst2A immunoreactivity; among these, 20 (69%) tumors showed high levels of sst2A immunoreactivity. In contrast, all other somatostatin receptors were only detected sporadically, and none of these cases revealed a particularly strong staining. However, it is uncertain to what extent somatostatin receptor-immunoreactive staining intensity may translate into somatostatin receptor protein expression on the tumor cells. Therefore, in a prospective study, 16 surgically removed meningiomas were collected, and the level of sst2A expression was determined using Western blot analysis. Whereas sst2A was readily detectable as a broad band migrating at Mr 70,000 in 12 (75%) of these tumors, 8 tumors (50%) showed particularly high levels of immunoreactive sst2A receptors. There was an excellent correlation (P < 0.001) between the level of sst2A protein expression detected in Western blots and the sst2A- immunoreactive staining seen in tissue sections. Thus, the frequent overexpression of the sst2A receptor may explain the high tracer uptake often observed in meningioma patients during somatostatin receptor scintigraphy. Moreover, this simple immunohistochemical method could prove useful in identifying those cases of recurrent disease that may possibly respond to therapy with sst2-selective agonists.

Adult↗

PubMed2000

A lumped parameter model of left ventricular filling-pressure waveforms.

Assessment of left-ventricular function and quantification of valve stenosis are important in clinical practice as well as in physiological research. This paper describes a mathematical model of diastolic ventricular filling and flow across the mitral valve. The model primarily consists of a system of three first-order, non-linear ordinary differential equations. The equations are solved in MATLAB using the ode45 command. The model generates pressure versus time waveforms for the atrium and ventricle, and flow versus time waveforms for mitral valve flow. Comparisons between model outputs and in-vivo data collected in two porcine experiments show excellent agreement.

Diastole↗

PubMed2000

Guanylyl cyclases and signaling by cyclic GMP.

Guanylyl cyclases are a family of enzymes that catalyze the conversion of GTP to cGMP. The family comprises both membrane-bound and soluble isoforms that are expressed in nearly all cell types. They are regulated by diverse extracellular agonists that include peptide hormones, bacterial toxins, and free radicals, as well as intracellular molecules, such as calcium and adenine nucleotides. Stimulation of guanylyl cyclases and the resultant accumulation of cGMP regulates complex signaling cascades through immediate downstream effectors, including cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. Guanylyl cyclases and cGMP-mediated signaling cascades play a central role in the regulation of diverse (patho)physiological processes, including vascular smooth muscle motility, intestinal fluid and electrolyte homeostasis, and retinal phototransduction. Topics addressed in this review include the structure and chromosomal localization of the genes for guanylyl cyclases, structure and function of the members of the guanylyl cyclase family, molecular mechanisms regulating enzymatic activity, and molecular sequences coupling ligand binding to catalytic activity. A brief overview is presented of the downstream events controlled by guanylyl cyclases, including the effectors that are regulated by cGMP and the role that guanylyl cyclases play in cell physiology and pathophysiology.

Animals↗

PubMed2000

Automated coding of diagnoses--three methods compared.

In Germany, new legal requirements have raised the importance of the accurate encoding of admission and discharge diseases for in- and outpatients. In response to emerging needs for computer-supported tools we examined three methods for automated coding of German-language free-text diagnosis phrases. We compared a language-independent lexicon-free n-gram approach with one which uses a dictionary of medical morphemes and refines the query by a mapping to SNOMED codes. Both techniques produced a ranked output of possible diagnoses within a vector space framework for retrieval. The results did not reveal any significant difference: The correct diagnosis was found in approximately 40% for three-digit codes, and 30% for four-digit codes. The lexicon-based method was then modified by substituting the vector space ranking by a heuristic approach that capitalizes on the semantic structure of SNOMED, thus raising the number of correct diagnoses significantly (approximately 50% for three-digit codes, and 40% for four-digit codes). As a result, we claim that lexicon-based retrieval methods do not perform better than the lexicon-free ones, unless conceptual knowledge is added.

Abstracting and Indexing↗

PubMed2000

MedSynDiKATe--design considerations for an ontology-based medical text understanding system.

MedSynDiKATe is a natural language processor for automatically acquiring knowledge from medical finding reports. The content of these documents is transferred to formal representation structures which constitute a corresponding text knowledge base. The general system architecture we present integrates requirements from the analysis of single sentences, as well as those of referentially linked sentences forming cohesive texts. The strong demands MedSynDiKATe poses to the availability of expressive knowledge sources are accounted for by two alternative approaches to (semi)automatic ontology engineering.

Evaluation Studies as Topic↗

PubMed2000

Modeling anatomical spatial relations with description logics.

Although spatial relations are essential for the anatomy domain, spatial reasoning is only weakly supported by medical knowledge representation systems. To remedy this shortcoming we express spatial relations that can intuitively be applied to anatomical objects (such as 'disconnected', 'externally connected', 'partial overlap' and 'proper part') within the formal framework of description logics. A special encoding of concept descriptions (in terms of SEP triplets) allows us to emulate spatial reasoning by classification-based reasoning.

Anatomy↗

PubMed2000

Semantic analysis of medical free texts.

The semantic interpretation of natural language utterances is usually based on a large number of transformation rules which map syntactic structures (parse trees) onto some kind of meaning representation. However, those interpretation rules exhibit an insufficient degree of abstraction so that the scalability and portability of such natural language processing systems is hard to maintain. In this paper, we introduce an approach that is able to cope with a wide variety of semantic interpretation patterns in medical free texts by applying a small inventory of abstract semantic interpretation schemata. These schemata address generalized graph configurations within syntactic dependency parse trees, which abstract away from specific syntactic constructions.

Computer Graphics↗

PubMed2000

Knowledge engineering the UMLS.

In order to transform a major portion of the Unified Medical Language System (UMLS) into a formally sound description logics system we have developed a four-step knowledge engineering approach. We report on experiments with a Loom knowledge base which consists of 164,000 concepts and 76,000 relations covering human anatomy and pathology. We discuss the fully automatized as well as interactive semiautomatic steps. The latter ones focus on the manual work necessary to render the formal target representation structures complete and adequate.

Artificial Intelligence↗

PubMed1999

A novel Ggamma isolated from Drosophila constitutes a visual G protein gamma subunit of the fly compound eye.

Visual transduction in the compound eye of flies is a well established model system for the study of G protein-coupled transduction pathways. To characterize key components of the phototransduction cascade we performed substractive hybridization screening. We cloned the cDNA coding for the visual Ggamma (Ggamma(e)) subunit from Drosophila which had so far eluded identification at the molecular level. Northern blot analysis revealed the presence of a major, 1.4-kilobase(kb) Ggamma(e) transcript and two minor transcripts of 1.8 and 6 kb in size. The major 1.4-kb mRNA is expressed preferentially in the eye. The spatial expression pattern determined for Ggamma(e) as well as co-immunoprecipitation experiments demonstrated that Ggamma(e) dimerizes with Gbeta(e) to form the heterodimeric Gbetagamma subunit which functions in visual transduction in the Drosophila compound eye. Ggamma(e) shares common characteristics with the visual Ggamma subunits of human rod and cone photoreceptors although different classes of Galpha subunits are employed in vertebrate and invertebrate phototransduction. By the molecular cloning and characterization of the visual gamma subunit of Drosophila one of the few missing links in the well studied Drosophila phototransduction cascade has been characterized to complete our knowledge about the Drosophila visual transduction pathway.

Amino Acid Sequence↗

PubMed1999

Targeted disruption of the orphanin FQ/nociceptin gene increases stress susceptibility and impairs stress adaptation in mice.

The neuropeptide orphanin FQ (also known as nociceptin; OFQ/N) has been implicated in modulating stress-related behavior. OFQ/N was demonstrated to reverse stress-induced analgesia and possess anxiolytic-like activity after central administration. To further study physiological functions of OFQ/N, we have generated OFQ/N-deficient mice by targeted disruption of the OFQ/N gene. Homozygous mice display increased anxiety-like behavior when exposed to a novel and threatening environment. OFQ/N-null mice show elevated basal pain threshold but develop normal stress-induced analgesia. Interestingly, these mice show impaired adaptation to repeated stress when compared with wild-type mice, whereas their performance in spatial learning remained unaffected. Basal and poststress plasma corticosterone levels were found to be elevated in OFQ/N-deficient animals. Thus, OFQ/N appears to be crucially involved in the neurobiological regulation of stress-coping behavior and fear.

Analgesia↗

PubMed1999

Direct evidence for biphasic cAMP responsive element-binding protein phosphorylation during long-term potentiation in the rat dentate gyrus in vivo.

Phosphorylation of the transcription factor cAMP responsive element-binding protein (CREB) is thought to play a key role in synaptic plasticity and long-term memory. However, direct evidence for CREB phosphorylation during hippocampal long-term potentiation (LTP) in vivo is sparse. Here, we show that, in the intact animal, CREB is rapidly phosphorylated in response to high-frequency stimulation but not low-frequency stimulation of the perforant pathway. CREB phosphorylation occurred in a biphasic manner, with a first peak at 30 min and a second long-lasting peak beginning 2 hr after tetanic stimulation and lasting for at least 24 hr. Only stimuli that generated nondecremental LTP promoted a sustained hyperphosphorylation of CREB but not stimuli that produced decremental LTP. CREB phosphorylation was specifically triggered in the dentate gyrus, as well as the CA1, but not the CA3, hippocampal region. Pretreatment with the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate completely prevented activation of CREB. Together, we have resolved the spatial and temporal dynamics of CREB phosphorylation during hippocampal LTP, showing that the transcription factor CREB is specifically recruited at two distinct time points in some forms of hippocampal synaptic plasticity in vivo.

Animals↗

PubMed1999

Tyramide signal amplification in brain immunocytochemistry: adaptation to electron microscopy.

The tyramide signal amplification (TSA) technique is well-established in light microscopic immunohistochemistry and in situ hybridization to improve the signal-to-noise ratio. The present study deals with its adaptation to the electron microscopic level using the pre-embedding technique and a modified protocol. The outcome of immunolabeling of most of the antigens tested in brain tissue, including endothelial and neuronal nitric oxide synthase, glial fibrillary acidic protein, and isolectin B4, was greatly improved. If signal amplification is required, the TSA-technique proved to be reliable with high specificity and good ultrastructural resolution.

Antibody Specificity↗

PubMed1999

Targeted gene disruption in the development of mouse models to elucidate the role of receptor guanylyl cyclase signaling pathways in physiological function.

The physiological role of receptor guanylyl cyclases (GCs), which transduce a signal via the generation of intracellular cyclic GMP, has been somewhat speculative since there are few specific inhibitors that discriminate among various receptor isoforms. Although the natriuretic peptide receptors have been thought to regulate cardiovascular and renal function, the exact contribution of the receptor subtypes has not been clarified. The normal role of the heat-stable enterotoxin receptor guanylyl cyclase remains undefined, and several orphan members of the family await the identification of ligands as well as function. Targeted gene disruption, familiarly known as gene knockout, has emerged during the past decade as a powerful technique for probing the function of gene products, and has been used to develop animal models of inherited human diseases. We are just beginning to apply gene targeting technology to the guanylyl cyclase receptor family. Reviewed here is the information gained to date from the targeted disruption of several members of the guanylyl cyclase receptor family, their ligands, or effector molecules.

Animals↗

PubMed1999

Urine flow rates and residual urine volumes in urogynecology patients.

Two hundred and fifty consecutive women referred because of symptoms of lower urinary tract dysfunction underwent a full clinical and urodynamic assessment. Their urine flow rates and residual urine volumes were analyzed. The urine flow rates of the urogynecology patients were found to be significantly less than those of an asymptomatic population. There were significant declines in urine flow rates in the presence of a previous hysterectomy and with increasing grades of prolapse, particularly uterine prolapse, cystocele and enterocele. Unlike the normal female population, there was also deterioration with increasing parity and age, the latter largely due to the increasing incidence of hysterectomy and prolapse with age. The 10th centile of the Liverpool Nomogram for the maximum urine flow rate was found to be the most useful discriminant for a final urodynamic diagnosis of voiding difficulties. Most urogynecology patients have no or small residual urine volumes, 74% <10 ml and 81% <30 ml (vs 95% <30 ml in asymptomatic women). In urogynecology patients residuals were larger where there had been a prior hysterectomy or with grade 2 or higher uterine prolapse, cystocele and enterocele. Mean residual was 14.8 ml (vs 4.8 ml in asymptomatic women). These data indicate a higher incidence of voiding difficulties (abnormally slow urine flow (under 10th centile) and/or abnormally high residual urine volume (over 30 ml) in urogynecology patients, particularly those with higher grades of prolapse and with prior hysterectomy.

Female↗

PubMed1999

Evaluation of ozonated oxygen in an experimental animal model of osteomyelitis as a further treatment option for skull-base osteomyelitis.

The standard treatment of chromic skull-base osteomyelitis is antibiotics and surgical removal of sequestrums. Hyperbaric oxygen therapy has been found to be a useful method for managing refractory cases of chronic osteomyelitis. Since a minimal blood supply is needed for hyperbaric oxygen therapy, chronic osteomyelitis can produce necrotic infected areas that are not nutrified and therefore not assessable for hyperbaric oxygen therapy. Ozone is known to be an oxidizing medium with a strong bactericidal effect. We investigated the influence of locally applied ozonated oxygen on the development of chronic osteomyelitis in an experimental animal model using the femur of the rabbit. The proximal sides of the femurs of 40 rabbits were prepared and a needle inserted into the intramedullary cavity. Osteomyelitis was induced with an infusion of Staphylococcus aureus and sodium morrhuate into the bone. The needle was left in a intramedular location. After a 4-week delay animals were randomly separated into treatment and control groups. The infected femur of treated animals was flushed three times a day with 20 ml of ozonated oxygen at an ozone concentration of 107 micrograms/ml O2 over periods of 2 or 4 weeks. Clinical, radiographic and microbiological findings were documented. Chronic osteomyelitis occurred in all animals. Ten rabbits were excluded from further study during the investigation because of excessive weight loss (> 15% of the original weight). Bacterial cultures showed no significant reduction of S. aureus concentrations in the ozone-treated group, although comparison of radiographic results revealed less serious osteomyelitis-related bone damage in these animals (P < 0.01). These findings indicate that refractory osteomyelitis in the head and neck may benefit from locally applied "flush" therapy with ozonated oxygen in addition to treatment with antibiotics, surgery and hyperbaric oxygen.

Animals↗

PubMed1999

Simulation of arterial hemodynamics after partial prosthetic replacement of the aorta.

BACKGROUND: Replacing parts of the aorta with a non-compliant vascular prosthesis results in marked alterations of the aortic input impedance and influences arterial hemodynamics. We propose a mathematical model of circulation that can predict hemodynamic changes after simulation of vascular grafting. METHODS: A new mathematical model of the human arterial system was developed on a 75-MHz Pentium personal computer using Matlab software. The human arterial tree was delineated according to a 128-branch design encompassing bifurcations and physical properties of the arterial wall. A digitized aortic flow wave was chosen as the input signal to the system. After determination of the modules of elasticity of native vascular tissue and standard prostheses in technical experiments, replacement of any part of the aorta with a prosthesis was simulated by increasing the elasticity in the parts desired. RESULTS: During control conditions, the model displayed a physiologic distribution of flow and pressure waves throughout the arterial system. Simulated replacement of the aorta resulted in an increase in pressure amplitude and a partial loss of the aortic "Windkessel" function. Calculation of the aortic input impedance showed an increase in the characteristic impedance, whereas the peripheral resistance remained unaltered. CONCLUSIONS: This mathematical model of the arterial circulation is useful for simulating hemodynamic changes after implantation of vascular grafts. The results of the model analysis are consistent with those in previous experimental work.

Aorta↗