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Biomedical subjects

G Lange

Publications and source records attributed to G Lange.

At least 19 recordsLinked to original sources

Crystal structure of a chimeric Fab' fragment of an antibody binding tumour cells.

The crystal structure of a chimeric Fab' fragment of a monoclonal antibody is presented. The Fab' comprises the murine light chain and heavy chain variable domains of the carcinoma-binding antibody B72.3 fused to the constant domain of human kappa, and the first constant domain and hinge domain of human gamma 4, respectively. A model for the Fab' has been determined by molecular replacement and refined to a resolution of 3.1 A with an R-factor of 17.6%. The additional residues that distinguish a Fab' from a Fab fragment are seen to be disordered in the crystals. The H3 hypervariable loop is short and adopts a sharp hairpin turn in a conformation that results from an interaction between the lysine side-chain of H93 and the main-chain carbonyl group of H96. The remaining hypervariable loops display conformations similar to those predicted from the canonical structures approach, although loop H2 is apparently displaced by a salt-bridge formed between H55 Asp and the neighbouring H73 Lys. These and other features of the structure likely to be important in grafting the hypervariable loops to an otherwise human framework are discussed.

Amino Acid Sequence

Influence of rod adaptation upon cone responses to light offset in humans: I. Results in normal observers.

Dark-adapted rods exert a tonic suppressive influence upon cone-mediated sensitivity to rapid flicker, a phenomenon called suppressive rod-cone interaction (SRCI). However, rod dark adaptation has negligible influence upon cone-mediated thresholds measured with more usual psychophysical procedures. The present study separately examined the influences of rod light and dark adaptation upon cone-mediated sensitivity to transient increases or decreases in illumination using sawtooth flicker with rapid-on (ramp-off) or rapid-off (ramp-on) waveforms. In the parafoveal retina, cones alone were stimulated with flicker by spatially superimposing long- and short-wavelength stimuli presented in counterphase and matched in scotopic illuminance. Several different adaptation procedures were used. For higher (greater than 4 Hz) frequencies, sensitivity of cones to both waveforms is nearly identical under any condition of adaptation; sensitivity decreases as rods progressively dark adapt. A considerably different situation exists for slower frequencies (1-4 Hz). Sensitivity of cones to rapid-off flicker is appreciably greater under light-adapted conditions confirming recent observations by Bowen et al. (1989). But as rods progressively dark adapt, sensitivity of cones to rapid-off waveforms decreases considerably while sensitivity to rapid-on waveforms is much less affected; in the totally dark-adapted eye, sensitivity to both waveforms is identical. These results confirm and extend recent physiological observations in amphibian retina (Frumkes & Wu, 1990) suggesting that SRCI specifically involves responses to transient decreases in illumination.

Adaptation, Ocular

Influence of rod adaptation upon cone responses to light offset in humans: II. Results in an observer with exaggerated suppressive rod-cone interaction.

In normal observers, sensitivity of cones to rapid sinusoidal flicker decreases by about 0.7 log units as rods progressively dark adapt. However, Arden and Hogg (1985) described a night-vision disorder characterized by normal rod sensitivity but exaggerated suppressive rod-cone interaction (SRCI). We refer to this condition as the exaggerated SRCI syndrome (ESS). The present paper examines the influence of rod-adaptation upon cone-mediated responses to light onset and offset in an observer with ESS. Under all conditions of adaptation examined, sensitivity of cones to rapid-on waveforms is indistinguishable to that of a normal observer tested under identical circumstances; rod sensitivity is also normal. However, the sensitivity of cones to transient decreases in illumination is clearly subnormal under light-adapted conditions. This deficit in cone responsiveness to light offset becomes increasingly subnormal as rods dark adapt and, when completely dark adapted, the ESS observer is nearly blind to 1 Hz rapid-off sawtooth waveforms. These results strongly bolster previous results that suggest that suppressive rod-cone interaction is restricted to the response to transient decreases in illumination.

Adaptation, Ocular

The refined crystal structure of alpha-cobratoxin from Naja naja siamensis at 2.4-A resolution.

The crystal structure of the "long" alpha-neurotoxin alpha-cobratoxin was refined to an R-factor of 19.5% using 3271 x-ray data to 2.4-A resolution. The polypeptide chain forms three loops, I, II, III, knotted together by four disulfide bridges, with the most prominent, loop II, containing another disulfide close to its lower tip. Loop I is stabilized by one beta-turn and two beta-sheet hydrogen bonds; loop II by eight beta-sheet hydrogen bonds, with the tip folded into two distorted right-handed helical turns stabilized by two alpha-helical and two beta-turn hydrogen bonds; and loop III by hydrophobic interactions and one beta-turn. Loop II and one strand of loop III form an antiparallel triple-pleated beta-sheet, and tight anchoring of the Asn63 side chain fixes the tail segment. In the crystal lattice, the alpha-cobratoxin molecules dimerize by beta-sheet formation between strands 53 and 57 of symmetry-related molecules. Because such interactions are found also in a cardiotoxin and alpha-bungarotoxin, this could be of importance for interaction with acetylcholine receptor.

Amino Acid Sequence

[Investigations of centrifugal penetration of the tooth root hard substances by hydrogen peroxide].

After application of hydrogen peroxide into the root canal of extracted teeth of patients between the ages of 18 and 30 years the antiseptic could be detected on the root surface by means of iodometry and in tooth cross sections in dentine and cementum by means of staining reaction (benzidine-peroxidase solution). Out of the root canals which were apically not passable and coronally closed the first traces of the instilled 5% hydrogen peroxide appeared after 14 min 45 sec on the root surface. In the dentine a mean penetration depth of hydrogen peroxide up to 1.28 mm (apical root area), 1.45 mm (middle root third) and 1.95 mm (coronal root area) could be measured. Best results were obtained after rinsing/suction treatment of the root canal, especially in combination with low-frequency ultrasound.

Adolescent

Microtubule oscillations. Role of nucleation and microtubule number concentration.

Microtubules are capable of performing synchronized oscillations of assembly and disassembly which has been explained by reaction mechanisms involving tubulin subunits, oligomers, microtubules, and GTP. Here we address the question of how microtubule nucleation or their number concentration affects the oscillations. Assembly itself requires a critical protein concentration (Cc), but oscillations require in addition a critical microtubule number concentration (CMT). In spontaneous assembly this can be achieved with protein concentrations Cos well above the critical concentration Cc because this enhances the efficiency of nucleation. Seeding with microtubules can either generate oscillations or suppress them, depending on how the seeds alter the effective microtubule number concentration. The relative influence of microtubule number and total protein concentrations can be varied by the rate at which assembly conditions are induced (e.g. by a temperature rise): Fast T-jumps induce oscillations because of efficient nucleation, slow ones do not. Oscillations become damped for several reasons. One is the consumption of GTP, the second is a decrease in microtubule number, and the third is that the ratio of microtubules in the two phases (growth-competent and shrinkage-competent) approach a steady state value. This ratio can be perturbed, and the oscillations restarted, by a cold shock, addition of seeds, addition of GTP, or fragmentation. Each of these is equivalent to a change in the effective microtubule number concentration.

Guanosine Diphosphate

Relationships between study organization, retrieval organization, and general and strategy-specific memory knowledge in young children.

The present study examined relationships between young children's memory knowledge and their use of taxonomic and color memory organization. Forty-eight 5-, 6-, and 7-year-olds were administered metamemory tests of organization-strategy knowledge and general memory knowledge, and were tested on two study-recall tasks before, and two study-recall tasks after, training in the use of color or taxonomic organization. Study organization (grouping) scores were low before training, but improved significantly in post-training tasks. Training effects were less pronounced for retrieval organization (clustering) and did not occur for item recall. Relationships between taxonomic study and retrieval organization were apparent only for the 7-year-olds, while relationships between color organization at study and retrieval were not apparent at any age level. Relationships between metamemory, strategy-use, and recall proficiency were evident on some tasks for 7-year-olds, but not for younger children. Although teacher ratings of the children's mastery orientations were also found to be related to recall proficiency for the older subjects, specific strategy knowledge was a more consistent correlate of strategy use and amount recalled.

Child

Form characteristics of category-retrieval relationships in children and adults.

Subjects from Grades 2, 4, 6, and college performed a sort-recall task with 24 noncategorized items, using two 12-item sorts, four 6-item sorts, or six 4-item sorts. Among the children, the effects of increasing unitization at study were uneven across the category size conditions used and did not resemble the linear patterns shown by adults. Second graders showed retrieval advantages only for the smallest categories used, whereas fourth and sixth graders benefited from the use of moderately sized sorting categories but failed to show additional improvements for smaller sorting categories. An examination of subjects' sorting explanations suggested that different category-retrieval patterns may reflect better and poorer item relations established in smaller and larger categories, respectively. Sort conditions affording the best recall at the different grade levels were those in which subjects established the greatest number of contextual and categorical (taxonomic) relations among sorted items.

Adolescent

Gentamicin and other ototoxic antibiotics for the transtympanic treatment of Menière's disease.

Severe unilateral cases of Menière's disease can be successfully treated with ototoxic antibiotics. Among them gentamicin sulfate gives the safest results. With the aid of a small syringe this antibiotic is introduced into the external auditory canal 5 times/day. From there it reaches the middle ear through a ventilating tube by using a Politzer bag. Gentamicin then penetrates the round and oval windows, where it influences inner ear function. Of 92 patients treated during the past 20 years, more than 90% have had no further attacks after therapy.

Auditory Threshold

["Tertiary" lymphedema--procedures in lymph drainage therapy].

In patients with malignant tumours (with or without secondary lymphedema) a so-called tertiary lymphedema may develop. This edema is mostly caused by exacerbation of the primary tumor, by local recurrences or by loco-regional metastases. If a tertiary lymphedema is suspected oncologic diagnostic investigations must be immediately performed. During this period lymphatic drainage therapy is stopped. In patients with safely established hopeless prognosis drainage therapy may be continued if necessitated by pain or functional decrease. Otherwise, oncologic therapy should be completed before lymphatic drainage is continued.

Aged

[Escape of hydrogen peroxide and oxygen from the root canal].

In vitro investigations demonstrate that hydrogen peroxide, like the oxygen emitted from the root canal, escapes into the area around the root. The amount measurable was dependent on the concentration, the amount of time that the hydrogen peroxide was left in the root canal and the patency of the foramen apicale. The growth of the Staphylococcus aureus (SG 511) was restricted in the area around those roots whose root canal contained a 5% solution of hydrogen peroxide.

Dental Pulp Cavity

[Sensitivity of microorganisms of infected root canals to disinfectants].

The bactericidal and growth inhibiting effects of disinfectants on Streptococcus and Candida strains were tested in vitro. Chlorhexidine, when used in tiny concentrations (0.0001-0.0039%) inhibits the growth of Streptococci. With Wofasteril 0.32%) all Streptococci and Candida were killed within a minute. Next to a good bacteria inhibitor (0.001-0.032%), a sufficient bactericidal effect on Streptococci is shown by hydrogen peroxide when used in a 4% concentration and warmed to 45 degrees Centigrade (degrees C).

Anti-Infective Agents, Local

The anti-proteolytic behavior of lathyrogens.

The lathyrogens, beta-aminopropionitrile and alpha-aminoacetonitrile inhibit both the esterolytic and proteolytic activity of trypsin at a concentration of 100 mM. Lineweaver-Burk plots demonstrate that inhibition is competitive, with alpha-aminoacetonitrile being the more potent inhibitor. The enzyme associated with and capable of digesting tropoelastin is inhibited by both lathyrogens when tested against its natural substrate, tropoelastin. Administration of alpha-aminoacetonitrile-HCl to the diet of young chicks (0.1% w/w) resulted in a 62% increase in the yield of tropoelastin and significant reduction in fatality as compared to beta-aminopropionitrile-fumarate.

Acetonitriles