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Biomedical subjects

G Lange

Publications and source records attributed to G Lange.

At least 55 records · Page 3Linked to original sources

Suppressive rod-cone interactions: evidence for separate retinal (temporal) and extraretinal (spatial) mechanisms in achromatic vision.

We investigated the influence of selective rod light and dark adaptation on cone-mediated sensitivity to monocular displays modulated sinusoidally in both spatial and temporal domains. Rod light adaptation (1) increased sensitivity to high spatial frequencies [> or = 8 cycles per degree (cpd)] flickered slowly (< or = 2 Hz), an effect that we refer to as grating suppressive rod-cone interaction (gSRCI); (2) increased sensitivity to low spatial frequencies (< or = 2 cpd) flickered rapidly (> or = 8 Hz), an effect that we refer to as flicker suppressive rod-cone interaction (fSRCI); and (3) had relatively little influence on intermediate temporal-spatial-frequency combinations. The magnitudes of both gSRCI and fSRCI increased as the retinal position of the test display was increasingly displaced parafoveally. In parafoveal retina, both forms of suppressive rod-cone interaction increased as the overall dimension of the test stimulus decreased. However, sensitivity to high spatial frequencies is equally well influenced by adaptation of the viewing and the contralateral eye, while the adapted state of the nonviewing eye negligibly influences sensitivity to rapid flicker. Moreover, gSRCI cannot be observed with a small (30-arcmin) grating restricted to the fovea, while fSRCI is a prominent effect with small foveal test stimuli. Collectively, these results and neurobiological evidence suggest that fSRCI reflects a mechanism restricted to distal retinal, while gSRCI involves extraretinal neural circuitry.

Adaptation, Ocular↗

[Penile metastasis of recto-sigmoid adenocarcinoma. Apropos of a case].

Metastases to the penis from rectocolic adenocarcinoma are extremely uncommon with 50 cases reported; the diagnosis is often delayed and the prognosis is very poor. The choice between an aggressive surgical approach and a palliative treatment is difficult, but surgery seems to give the best results in limited penile lesions. The authors report a case of metastatic involvement of the penis by a recurrent rectocolic adenocarcinoma in a 42 year old patient. A MR scan was performed before surgical treatment of both lesions.

Adenocarcinoma↗

The experiential facilitation of memory development in the home environment.

Relationships among young children's home experiences, their memory knowledge, and their memory-task performance were examined. The participants were 78 children in 2nd and 3rd grades and their families. The children were administered 2 study-recall memory tasks and a memory-knowledge questionnaire. Home experiences were assessed with data gathered during a home visit and from a parents' self-report questionnaire. Specific home experiences that relate to the development of memory knowledge and memory-task performance were identified. Regression analyses supported a hypothesized theoretical model in which the influence of home experiences on memory-task performance is, at least partially, a function of the relationship between parents' requirements for self-regulation and self-responsibility and the development of children's knowledge about memory requirements and memory strategies.

Child↗

Functional effects of myoblast implantation into histoincompatible mice with or without immunosuppression.

1. The goals of this study were to evaluate the immunogenicity of myogenic cells (MCs) (1) immediately after implantation into regenerating muscles, and (2) following their maturation under initial immunosuppression. Implanted mouse soleus muscles were evaluated by isometric tension recordings in vitro followed by histological investigations on frozen sections. 2. Implantation of non-histocompatible myoblasts into cryodamaged soleus muscles of CBA/J mice induced immune rejection which caused large and permanent deficits in muscle force: 4-42 weeks postimplantation maximal tetanic tension was 50-60% that of intact or regenerated cryodamaged control muscles without tendency for recovery or histological signs of muscle regeneration. Specific tension (force per unit muscle weight) was also significantly reduced. 3. On frozen sections, only 62 +/- 12% of the total area was desmin-positive, that is, occupied by muscle fibres, versus 90 +/- 4% in regenerated and 92 +/- 3% in intact muscles. Also, the total number of muscle fibre profiles was significantly reduced. 4. Under immune suppression with cyclosporin A (CsA), large muscles developed within 4 weeks. Following CsA withdrawal, muscle weight and force, in addition to desmin-positive areas on cross-sections, gradually declined over several months despite continual regeneration, indicating retarded immune rejection. 5. Initial application of CsA for 8 weeks after implantation, instead of 4 weeks, did not result in better survival of the implants, nor did a higher initial dose of CsA (100 instead of 50 mg kg-1 day-1). Prolonged continuous application of a reduced dose (25 mg kg-1 day-1) did not prevent muscle wasting but caused an additional delay. 6. It is concluded that histoincompatible myoblasts are highly immunogenic and that immune rejection causes large and permanent muscle deficits indicating elimination of host muscle tissue. Initial transient immunosuppression protects the incompatible cells, but after withdrawal, prolonged immune rejection and retarded muscle wasting occur.

Animals↗

[27 years experiences with transtympanic aminoglycoside treatment of Menière's disease].

BACKGROUND: Severe unilateral Menière's disease is successfully treated intratympanically with ototoxic antibiotics. Gentamicin sulfate (Refobacin) gives the best results. The only disadvantage is that gentamicin may damage hearing in the treated side. Therapy is easier in patients with marked hearing loss prior to treatment. PATIENTS AND METHOD: Since 1976 we treated 61 patients by injecting 8-12 mg Refobacin (0.2-0.3 ml) into the external auditory meatus between two and five times per day. By creating slight pressure (Politzer bag) the liquid is transported into the middle ear via a ventilating tube. From here it penetrates through the windows. The slightest indication of inner ear reaction was grounds for immediately terminating treatment. RESULTS: In 54 of our 61 patients (follow-up 2-17 years) we were completely successful. Three further patients continued having very rare and weak spells, yet we regard them as being practically healed. We did not succeed in four of our cases. Twenty-nine patients suffered hearing loss. Hearing was mostly poor prior to therapy. CONCLUSIONS: Transtympanic gentamicin therapy provides very good results in severe cases of unilateral Menière's disease. Spells of vertigo and vomiting are controlled. We propose individual dosage depending on hearing threshold and intensity of symptoms.

Administration, Topical↗

The effects of category distinctiveness and stimulus relations on young children's use of retrieval clustering strategies.

The influence of category distinctiveness and the associative relatedness of within-category items on young children's use of an organizational clustering strategy at retrieval was examined. Children from preschool and Grades 1 and 3 studied and recalled 9-item sets of pictured items representing either distinctive categories (e.g., numbers, letters, animals) or standard categories (e.g., furniture, clothing, animals). Half of the children at each grade level and in each category-type condition received category exemplars that were high associates. The results showed that each of the grade levels exhibited above-chance clustering for the distinctive categories but not for the standard categories. However, preschool participants attained above-chance clustering only for high-associate items, suggesting that their retrieval may have been driven automatically by natural word associations inherent in the stimuli. For older participants, above-chance clustering obtained for the low-associate as well as for the high-associate items, suggesting that they may have engaged in strategic retrieval activity.

Association Learning↗

Transtympanic gentamycin in the treatment of Ménière's disease.

Severe cases of Ménière's disease are successfully treated with ototoxic antibiotics. Gentamycin sulphate gives the best results. With the aid of a small syringe the drug is introduced into the external auditory canal 3-5 times per day. From there it is transported into the middle ear through a ventilating tube (Grommet) under slight pressure (Politzer bag). The liquid then penetrates the round and oval windows and influences inner-ear function. More than 90% of our patients in 25 years after therapy had no further attacks.

Ear, Middle↗

The human saphenous vein in pharmacology: effect of a new micronized flavonoidic fraction (Daflon 500 mg) on norepinephrine induced contraction.

Local acidosis (pH 6.4) depresses reactivity of vascular smooth muscle and especially the response of human isolated saphenous veins to exogenous norepinephrine. Experiments were performed to study, under acidosis conditions, the interaction between Daflon 500 mg, a micronized fraction of 90% diosmin and 10% hesperidin, and norepinephrine on human rings of veins. Varicose veins were obtained by conservative varicose veins surgery and normal veins from patients undergoing coronary artery bypass graft surgery. Isometric tension was recorded from venous rings in organ chambers filled with Krebs-Henseleit solution (pH 7.4; 37 degrees C). Metabolic acidosis (from pH 7.4 to 6.4) was obtained by lowering the HCO3- concentration of the Krebs-Henseleit solution. Cumulative concentration-response curves for norepinephrine (10(-7) to 10(-5)M) were obtained at pH 6.4 in the presence or in the absence of Daflon 500 mg (10(-5)M) added 20 min previously to the organ bath. Under acidotic conditions, Daflon 500 mg induced a shift to the left of the concentration-response curves for norepinephrine. This potentiation was significant in both normal and varicose veins and was increased in proportion with the pathological status of the venous rings. These results support the therapeutic benefits of Daflon 500 mg in chronic venous insufficiency.

Acidosis↗

Crystallographic studies of Savinase, a subtilisin-like proteinase, at pH 10.5.

The effect of high pH (pH 10.5) on Savinase, a subtilisin-like serine proteinase, has been investigated using X-ray crystallography. The structures of two Savinase mutants were determined at two different pH values, namely pH 6.0, where the enzyme is inactive (this is the pH at which most of the structural work has been carried out on other serine proteinases), and pH 10.5, where Savinase is active. Comparison of these high resolution (0.16 nm) structures showed four related sets of changes between the two pH values. First, the difference in protonation state of the active-site histidine leads to a change in conformation of the active-site triad. Secondly, there are resulting changes in the water structure around this histidine residue with much increased mobility of the water in the active-site at pH 10.5. Thirdly, the two substrate-binding loops on either side of the binding site are less well linked by ordered water molecules at pH 10.5 and show substantially increased flexibility. Finally, the first substrate-binding loop, residues at positions 99-104, moves slightly so as to widen the substrate channel.

Amino Acid Sequence↗

Crystal structure of an extracellular fragment of the rat CD4 receptor containing domains 3 and 4.

BACKGROUND: CD4 is a transmembrane protein on the surface of T lymphocytes that interacts with MHC class II proteins at the surface of accessory cells, and is involved in the triggering of the lymphocytes by foreign antigens. It is also the major receptor for the human immunodeficiency virus. The extracellular portion of CD4 was predicted to contain four immunoglobulin superfamily domains and this has been confirmed by X-ray crystallography, but no detailed structure of domains 3 and 4 has been available. RESULTS: We now report the expression of a form of rat CD4 containing only domains 3 and 4, its crystallization, and the refinement and analysis of its structure by X-ray crystallography with 2.6 A spacing data. Both domains show variations in core residues when compared with immunoglobulin domains. Features of the structure are discussed with respect to the structure of the complete extracellular part of CD4 and its function. CONCLUSIONS: Domains 3 and 4 of CD4 show considerable similarity to domains 1 and 2, although there is a 25 degrees rotation in the relative positions of the domains with respect to one another. The absence of the disulphide bond in domain 3 is associated with an alteration in the packing of the beta-sheets, which may be important for interactions with domain 2 in the overall receptor structure. The location of N-linked glycosylation on one face of domain 3 appears to preclude the dimerization that is observed in antibodies.

Amino Acid Sequence↗

CD4 and the immunoglobulin superfamily.

The CD4 membrane glycoprotein was one of the first cell surface antigens to be identified using monoclonal antibodies. It was shown to have a central role in the control of the recognition of foreign proteins by T lymphocytes and later as a receptor for the human immunodeficiency virus (HIV). The analysis of the amino acid sequence of CD4 showed that the extracellular region comprised four regions with sequence similarities to immunoglobulin domains. The structure of domains 3 and 4 of CD4 has been determined by X-ray crystallography and, like domains 1 and 2 previously determined, these have typical immunoglobulin-like folds. The results are discussed with respect to the identification of other domains with immunoglobulin-like folds from amino acid sequence data, and the evolution of CD4.

Amino Acid Sequence↗

Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-terminal domains.

The CD4 antigen is a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigens and is also a receptor for the human immunodeficiency virus. the extracellular portion of CD4 is predicted to fold into four immunoglobulin-like domains. The crystal structure of the third and fourth domains of rat CD4 was solved at 2.8 angstrom resolution and shows that both domains have immunoglobulin folds. Domain 3, however, lacks the disulfide between the beta sheets; this results in an expansion of the domain. There is a difference of 30 degrees in the orientation between domains 3 and 4 when compared with domains 1 and 2. The two CD4 fragment structures provide a basis from which models of the overall receptor can be proposed. These models suggest an extended structure comprising two rigid portions joined by a short and possibly flexible linker region.

Amino Acid Sequence↗

Distal vein graft reconstruction for isolated tibioperoneal vessel occlusive disease in diabetics with critical foot ischaemia--does it work?

Since 1986, 75 distal vein bypass procedures have been performed in 72 diabetics with isolated tibioperoneal vessel occlusive disease for limb salvage. Fifty-six grafts were anastomosed proximally to the below-knee popliteal artery and 19 to the anterior tibial artery. Autologous vein was used in all patients. One patient died within the first postoperative month. Of the occluded grafts, only two which failed during hospitalisation were salvaged. In six patients progressive plantar gangrene necessitated below-knee amputation in spite of graft patency. Using life-table analysis, primary and secondary patency rates were 84 and 86% at 1 year and 71 and 76% at 5 years. One- and five-year limb salvage rates were 81 and 72%, respectively. Distal vein graft reconstruction for limb threatening ischaemia produces excellent patency rates and contributes significantly to limb salvage in these patients.

Aged↗