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A Stauffer

Publications and source records attributed to A Stauffer.

17 recordsLinked to original sources
PubMed1999

The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane.

11beta-Hydroxysteroid dehydrogenase enzymes (11beta- HSD) regulate the ratio of active endogenous glucocorticoids to their inactive keto-metabolites, thereby controlling the access of glucocorticoids to their cognate receptors. In this study, the topology and intracellular localization of 11beta-HSD1 and 11beta-HSD2 have been analyzed by immunohistochemistry and protease protection assays of in vitro transcription/translation products. 11beta-HSD constructs, tagged with the FLAG epitope, were transiently expressed in HEK-293 cells. The enzymatic characteristics of tagged and native enzymes were indistinguishable. Fluorescence microscopy demonstrated the localization of both 11beta-HSD1 and 11beta-HSD2 exclusively to the endoplasmic reticulum (ER) membrane. To examine the orientation of tagged 11beta-HSD enzymes within the ER membrane, we stained selectively permeabilized HEK-293 cells with anti-FLAG antibody. Immunohistochemistry revealed that the N terminus of 11beta-HSD1 is cytoplasmic, and the catalytic domain containing the C terminus is protruding into the ER lumen. In contrast, the N terminus of 11beta-HSD2 is lumenal, and the catalytic domain is facing the cytoplasm. Chimeric proteins where the N-terminal anchor sequences of 11beta-HSD1 and 11beta-HSD2 were exchanged adopted inverted orientation in the ER membrane. However, both chimeric proteins were not catalytically active. Furthermore, mutation of a tyrosine motif to alanine in the transmembrane segment of 11beta-HSD1 significantly reduced V(max). The subcellular localization of 11beta-HSD1 was not affected by mutations of the tyrosine motif or of a di-lysine motif in the N terminus. However, residue Lys(5), but not Lys(6), turned out to be critical for the topology of 11beta-HSD1. Mutation of Lys(5) to Ser inverted the orientation of 11beta-HSD1 in the ER membrane without loss of catalytic activity. Our results emphasize the importance of the N-terminal transmembrane segments of 11beta-HSD enzymes for their proper function and demonstrate that they are sufficient to determine their orientation in the ER membrane.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

The Embryonics Project: a machine made of artificial cells.

It is possible to trace the origins of biological inspiration in the design of electronic circuits to the very dawn of the field of computer engineering, with the work of John von Neumann in the 1940s. To his brilliance we owe not only the first methodical attempts to define the electronic equivalents of many fundamental biological process, but also the development of the first self-replicating computing machines. Unfortunately, the electronic technology of the time would not allow a physical realization of von Neumann's machines, and it was not until the introduction of new programmable circuits in the 1980s that the field of bio-inspired machines gained new momentum. In this article, we describe the Embryonics (embryonic electronics) Project, an attempt to draw inspiration from the ontogenetic processes that determine the growth of multicellular organisms in the design of new, massively parallel arrays of processors (the artificial cells). Our cells are simple processors, all based on an identical hardware structure and all containing the same program (our artificial genome), but executing different parts of the genome depending on their spatial coordinates within the array. As in living beings, the presence of the genome in every cell allows the introduction of features such as self-replication and self-repair (cicatrization). In addition, the cells are implemented using an array of programmable elements (the artificial molecules), which allows their structure to be adapted to a given application. Through the parallel operation of many of these simple processors, we hope to realize highly complex systems, the equivalent of multicellular organisms in the natural world.

Animals↗
PubMed1998

Increased expression of erbB3 in colorectal cancer is associated with concomitant increase in the level of erbB2.

ErbB3 is a transmembrane signaling molecule that shares close structural homology with epidermal growth factor receptor (EGFR), erbB2, and erbB4. They have all been implicated in cell transformation and tumor pathogenesis, but very little is known about the role of erbB3 in normal colon and colorectal cancer. Therefore, in the current study, we determined whether erbB3 is found in normal human colon and whether its expression is altered in colorectal cancer. Because of some evidence that erbB3 might interact with erbB2 and EGFR, respectively, by heterodimerization, we also included erbB2 and EGFR analysis with special regard to coexpression. The study was performed on 35 patients operated on for colorectal carcinoma. The normal human colon showed weak erbB3 and erbB2 immunostaining, predominantly in surface epithelial cells. EGFR immunoreactivity in normal colon varied from weak to strong. In contrast, in 31 of 35 (89%) and in 29 of 35 (83%) colonic cancers, moderate to strong immunoreactivity for erbB3 and erbB2, respectively, was present in most epithelial cancer cells. A concomitant erbB3 and erbB2 immunostaining advantage could be found in 77% of cancerous tissues in comparison with the normal colon. No difference in EGFR immunostaining was evident between normal colon and cancer. Northern blot analysis showed an increase in erbB3 and erbB2 mRNA levels in 64% of cancers in comparison with normal colon samples. By densitometry, 2.3-fold and a 1.5-fold significant increases in erbB3 and erbB2 mRNA levels, respectively, were calculated in the cancerous tissues. Eighty-five percent of cancers with erbB3 mRNA overexpression showed an increase in erbB2 mRNA. Southern blot analysis did not indicate any gene amplification or rearrangement responsible for erbB2 or erbB3 overexpression. EGFR, however, was decreased in cancer on mRNA level. These findings indicate that erbB2 and erbB3, but not EGFR, may contribute to tumor growth and disease progression in colon cancer. The correlation between increased erbB2 and erbB3 expression in both Northern blots and immunohistochemical analysis suggests a co-overexpression of erbB2 and erbB3 and might support the hypothesis that these two growth factor receptors act together by heterodimer formation.

Adenocarcinoma↗
PubMed1998

Self-replicating and self-repairing multicellular automata.

Biological organisms are among the most intricate structures known to man, exhibiting highly complex behavior through the massively parallel cooperation of numerous relatively simple elements, the cells. As the development of computing systems approaches levels of complexity such that their synthesis begins to push the limits of human intelligence, engineers are starting to seek inspiration in nature for the design of computing systems, both at the software and at hardware levels. We present one such endeavor, notably an attempt to draw inspiration from biology in the design of a novel digital circuit: a field-programmable gate array (FPGA). This reconfigurable logic circuit will be endowed with two features motivated and guided by the behavior of biological systems: self-replication and self-repair.

Cell Physiological Phenomena↗
PubMed1997

Ontogenetic hardware.

Ontogeny is the process by which a single mother cell, the zygote, gives rise, through successive divisions, to a complete organism, possibly containing trillions of cells (e.g. in humans). This paper describes research whose inspiration is drawn from the process of ontogenetic development. By adopting certain features of cellular organization, and by transposing them to the world of integrated circuits on silicon, we show that certain properties unique to the living world, such as self-replication, self-repair, and growth, can also be attained in artificial objects (integrated circuits). Specifically, we identify and describe three classes of ontogenetic hardware: (1) self-replicating hardware; (2) embryonic hardware; and (3) L-systems based hardware, dubbed L-hardware. For each class we present an example of a hardware realization, along with a discussion of possible applications. Continued research on ontogenetic hardware may yield novel bio-inspired systems endowed with replicative, growth, and regenerative capabilities.

Cell Differentiation↗
PubMed1995

Psychogenic seizures: video telemetry observations in 27 patients.

Psychogenic seizures are unusual during the first decade of life. To compare the clinical features of psychogenic seizures in young children with those of teenagers, the long-term electroencephalographic and video monitoring studies of all patients younger than 18 years of age with recorded episodes diagnosed as psychogenic seizures were reviewed from a single hospital during the past 7 years. The 27 patients were divided into 2 age groups: group A, 6-9 years (n = 5), and group B, 10-17 years (n = 22). All patients had habitual episodes recorded during monitoring. Although the adolescents displayed clinical patterns similar to adult patients with psychogenic seizures, the children demonstrated a clinical pattern characterized mainly by prolonged staring and unresponsiveness. The most common behaviors in the adolescent group were tremor (45%), intermittent stiffening (41%), and out-of-phase movements of the extremities (36%). Fifteen percent of the patients had a history of seizures. This study suggests that young children with psychogenic seizures have clinical profiles different from that of teenagers.

Adolescent↗
PubMed1992

MR imaging in the evaluation of SLAP injuries of the shoulder: findings in 10 patients.

OBJECTIVE: Injuries to the superior portion of the glenoid labrum, called SLAP (superior labrum, anterior and posterior) injuries, are recently recognized injuries consisting of tears of the long head of the biceps tendon anchor/superior labral complex. The purpose of this study was to determine if the MR imaging findings in patients with surgically proved SLAP injuries correspond to the abnormalities found at arthroscopy. MATERIALS AND METHODS: Four variants of SLAP lesions have been described; they are based on the degree of compromise of the superior portion of the glenoid labrum, biceps tendon, and labral-biceps anchor. A type I lesion has superior labral fraying in the region of the biceps anchor. A type II lesion has superior labral fraying and stripping of the superior part of the glenoid labrum and attached biceps off the underlying glenoid fossa. A type III lesion has a bucket-handle tear of the superior portion of the glenoid labrum in the region of the biceps anchor. A type IV lesion has a bucket-handle tear of the superior part of the glenoid labrum with extension of the tear into the proximal biceps tendon. Standard spin-echo MR imaging studies in 10 patients with surgically proved SLAP lesions were evaluated retrospectively. Correlations were made between MR imaging findings and the SLAP injury type determined from descriptions in the surgical report. MR imaging studies in a control group of seven symptomatic patients surgically proved not to have SLAP injuries also were evaluated. RESULTS: MR imaging examinations of two patients with type I lesions showed irregularity of the labral contour and a slight increase in signal intensity on all imaging sequences. MR imaging examinations of two patients with type II lesions showed globular high signal interposed between the superior part of the glenoid labrum and the superior portion of the glenoid fossa. One case showed high signal in the labral-biceps anchor. The other case showed paired cleavages in the superior and inferior aspects of the superior part of the glenoid labrum at the labral-biceps anchor. MR imaging examinations of two patients with type III lesions showed superior labral tears identified as high signal intensity within the superior part of the labrum separate from the normal superior part of the labral cavity. MR imaging examinations of the four patients with type IV lesions showed diffuse high signal intensity within the superior part of the glenoid labrum with marked abnormal high signal intensity extending into the proximal high signal intensity within the superior part of the labrum separate from the normal superior part of the labral cavity. MR imaging examinations of the four patients with type IV lesions showed diffuse high signal intensity within the superior part of the glenoid labrum with marked abnormal high signal intensity extending into the proximal biceps tendon. None of the MR imaging studies of patients in the control group showed findings seen on MR imaging studies of patients with surgically proved SLAP lesions. CONCLUSION: Although prospective data are required to document accuracy, these preliminary data suggest that an MR examination can be useful in detecting SLAP abnormalities and establishing the type of SLAP lesion before surgery, thereby permitting better operative planning.

Adult↗
PubMed1990

[Mucin histochemistry of the digestive tract in the human fetus].

Mucin secretion was studied in the gastric, intestinal, left colic and/or rectal mucosa of 42 human fetuses ranging in age from 10 to 41 weeks of gestation (menstrual age). Several histochemical techniques were used at different pH to demonstrate neutral mucins, sialomucins and sulphomucins (Periodic Acid Shiff (PAS) with and without amylase, Alcian Blue (BA) pH 2.5, pH 1 with and without hyaluronidase, BA/PAS pH 2.5 and High Iron Diamine (HID)/BA). The gastric mucosa showed mixed neutral/acid secretions during the second term. The neutral mucins increased during the 3rd term when acid mucins fell and represented only 20 percent of the secretions by the end of gestation, as during the neonatal period. These mixed secretions closely reassembled the intestinal metaplasia described in inflammatory or tumoral lesions of the stomach. The intestinal mucosa secreted mucins as early as 10 weeks before the gastric and rectal mucosa. There were neutral and acid mucins, but unlike in adults, the sulphomucins were secreted by the goblet cells of the villous and crypt epithelia. The secretions of the rectal mucosa were acid and the sulphomucins increased in quantity from 14 to 26 weeks of gestation. The HID positive sulphomucins diffused into the meconium, and probably modified the physical and chemical properties of meconium and influenced anal continence.

Age Factors↗
PubMed1988

Early developmental progress of preterm twins discordant for birthweight and risk.

Studies of developmental progress in high-risk twins have disparate findings. In this study, we report the outcome of 45 twin pairs born between 26 and 37 weeks gestation, and whose birthweights ranged from 840 to 2000 g. No significant differences were found for weight, risk and birth order. However, earlier preterm infants were found to have significantly lower mental scores on the Bayley Scales of Infant Development at 24 months, and lower IQ scores on the Stanford Binet Intelligence Scale at 36 months. These findings imply that gestational age is a powerful variable in determining developmental outcome.

Birth Weight↗
PubMedDate not supplied

Comparison of conventional and computed arthrotomography with MR imaging in the evaluation of the shoulder.

To compare conventional arthrography and computed arthrotomography (CAT) with magnetic resonance (MR) imaging in the evaluation of the shoulder, we studied 18 patients who underwent conventional double contrast arthrography and CAT, and T1-, balanced, and T2-weighted MR imaging. The arthrograms were independently reviewed by two of the authors and the MR images were independently reviewed by three other authors in a systematic fashion with the aid of a prewritten evaluation form. The findings were compared among reviewers and between imaging methods. We found MR comparable to conventional arthrography in the evaluation of the rotator cuff; however, MR also enabled evaluation of tendonitis, which could not be accomplished with conventional arthrography. Because of MR's superior soft tissue imaging capability, we were able to stage the impingement syndrome. Magnetic resonance also allowed evaluation of the glenoid labrum and capsuloligamentous structures and assessment of instability in a fashion similar to CAT. In most cases, information obtained from MR equaled or exceeded that obtained from conventional arthrography and CAT. With refinement in technique and increased experience, we believe that MR may replace arthrography in the evaluation of the shoulder.

Adolescent↗