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  • Cell & Developmental Biology  (51)
  • Ultrastructure  (10)
  • pharmacokinetics  (10)
  • 1
    Electronic Resource
    Electronic Resource
    Differences of Ca2+ regulation in skin fibroblasts from blacks and whites (1989)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 138 (1989), S. 367-374 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Black people have a higher propensity than caucasions toward essential hypertension. To explore the possibility that this racial difference relates to cellular Ca2+ metabolism, we measured 45Ca2+ washout and uptake and cytosolic free concentration of Ca2+ [Ca2+], in serially passed skin fibroblasts from normotensive black and white males. Depending on the experimental conditions, 45Ca2+ washout in these cells was described by either two or three exponential functions, whereas 45Ca2+ uptake was described only by a two-exponent function. There were no racial differences in 45Ca2+ uptake and washout of unstimulated fibroblasts. However, stimulation by human serum resulted in an increase in the 45Ca2+ washout that was higher in fibroblasts from blacks than from whites. The racial differences were expressed primarily by higher values of the apparent washout rate constant (k1) of 45Ca2+ from the largest and most rapidly exchangeable cellular pool. The effect of human serum was not related to its origin (blacks vs. whites). In 2 mM Ca2+ medium and 10% serum from blacks, the respective k1 (mean ± SEM; × 10-2/min) values for fibroblasts from blacks and whites were 89.68 ± 5.23 and 73.29 ± 4.0; in the presence of 10% serum from whites, the k1 values for cells from blacks and whites were 84.14 ± 2.80 and 76.36 ± 3.23 (overall significance of P .01). In Ca2+-deficient medium in the presence of 10% human serum, the k1 for fibroblasts from blacks and whites were 115.57 ± 3.76 and 102.15 ± 3.30 (P 〈 .05). Serum substantially increased the 45Ca2+ uptake in fibroblasts from both blacks and whites; however, racial differences were not observed. Basal levels of [Ca2+], were not different in fibroblasts of blacks vs. whites (46.8 ± 6.8 and 43.2 ± 7.1 nM for blacks and whites, respectively). However, the peak response of Ca2+ transients for cell stimulated by 5% human serum was significantly higher in blacks than whites (blacks = 963 ± 213, whites = 481 ± 162 nM; P = .0286). We conclude that Ca2+ regulation is different in serum-stimulated fibroblasts from blacks and whites and that, at least in part, this difference may relate to a greater agonist-induced mobilization of Ca2+ in fibroblasts from blacks.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041380220
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  • 2
    Electronic Resource
    Electronic Resource
    Reappraisal of neurofibrillary tangles (1989)
    Springer
    Acta neuropathologica 77 (1989), S. 258-266 
    Details
    ISSN: 1432-0533
    Keywords: Neurofibrillary tangles ; Alzheimer's disease ; Pick bodies ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the immunohistochemical reactivity and ultrastructure of both neurofibrillary tangles (NFTs) occurring with severe neurofibrillary diseases, and Pick bodies (PBs) associated with Pick's disease. The NFTs and PBs did not react immunohistochemically with the anti-nonphosphorylated neurofilament monoclonal antibody irrespective of whether they were pretreated with alkaline phosphatase. In granular neurons of the dentate fascia of Ammon's horn in cases of dementia of the Alzheimer type (DAT), NFTs either resembled PB-like inclusion bodies (Horoupian's inclusion bodies) in form, or had a perinuclear structure. Immunohistochemically and ultrastructurally, the NFTs in the dentate fascia in cases of DAT, including Horoupian's inclusion bodies, were similar to the NFTs in the pyramidal neurons of Ammon's horn, which are found most frequently in association with severe neurofibrillary diseases. Under a light microscope, Horoupian's inclusion bodies and PBs could not be differentiated and appeared to be argyrophilic round cytoplasmic inclusions in granular neurons of the dentate fascia. There were, however, ultrastructural differences. Horoupian's inclusion bodies consisted of bundles made up of straight tubules (STs), each about 15 nm in diameter. These bundles were intermixed with a few paired helical filaments which occurred at intervals of about 80 nm. On the other hand, PBs were composed of randomly distributed 15-nm-wide STs, intermixed with a very few fibrillary structures. These fibrils had a periodicity of about 160 nm, and ranged in width from about 15 nm to 30 nm. Horoupian's inclusion bodies associated with DAT and PBs associated with Pick's disease are different in this neuropathological aspect. The NFTs, including Horoupian's inclusion bodies in the dentate fascia in cases of DAT, are considered to be a manifestation of neurofibrillary degeneration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00687577
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  • 3
    Electronic Resource
    Electronic Resource
    Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: immunohistochemical and ultrastructural studies (1990)
    Springer
    Acta neuropathologica 79 (1990), S. 584-594 
    Details
    ISSN: 1432-0533
    Keywords: Olivopontocerbellar atrophy ; Argyrophilic inclusion ; Pontine nucleus ; Ubiquitin ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Patients with olivopontocerebellar atrophy (OPCA) were studied, and cytoplasmic inclusions were observed in some of the remaining neurons of the pontine nuclei, nuclei reticularis tegmenti pontis and arcuate nuclei. The cytoplasmic argyrophilic inclusions were demonstrated by silver impregnation techniques such as Bielschowsky and Bodian staining. With hematoxylin and eosin stain, the inclusions were sharply demarcated and appeared pale. The inclusions were not stained by the following routine histological methods: Klüver-Barrera, phosphotungstic acid hematoxylin, Holzer, periodic acid-Schiff, Mallory azan, alcian blue, nile blue, Masson trichrome, Congo red, thioflavine S, oil red O and Sudan black B stains. Immunohistochemistry with anti-ubiquitin antiserum showed that these inclusions were ubiquitinated. However, the inclusions did not react with any of the following antibodies (Abs) or antisera: anti-phosphorylated neurofilament (NF) Ab, anti-nonphosphorylated NF Abs (160 and 200 kDa), anti-paired helical filament antiserum, anti-tau antiserum, anti-tubulin Abs (alpha and beta), anti-microtubule-associated proteins antiserum, anti-glial fibrillary acidic protein antiserum, anti-vimentin Ab, anti-desmin Ab, anti-cytokeratin Abs (low and high molecular weights), anti-actin antiserum, anti-skeletal myosin antiserum and anti-myelin basic protein Ab. Ultrastructurally, the inclusion bodies noted in OPCA were composed primarily of fibrils having a width ranging from about 24 to 40 nm, which were entirely coated with osmiophilic granular material along their whole length. They were occasionally intermingled with a few filaments about 10 nm in width. Electron microscopical examination on silver-impregnated specimens revealed that each granule-coated fibril had a great affinity for silver particles. In elucidating the pathogenesis of OPCA, it was considered to be an important neuropathological finding that some of the remaining pontine neurons affected by OPCA developed characteristic cytoplasmic argyrophilic inclusions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00294235
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  • 4
    Electronic Resource
    Electronic Resource
    Bunina bodies in amyotrophic lateral sclerosis on Guam: a histochemical, immunohistochemical and ultrastructural investigation (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 150-156 
    Details
    ISSN: 1432-0533
    Keywords: Key words Amyotrophic lateral sclerosis ; Bunina body ; Guam ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An investigation of Bunina bodies is important when studying the pathoetiology and pathomechanisms involved in amyotrophic lateral sclerosis (ALS). It may serve as a clue essential for the study of the pathogenesis of Guamanian amyotrophic lateral sclerosis (ALS-G), and it may provide a means of answering the question of whether ALS-G is the same disease as classical ALS or a different entity. In ALS-G, however, no precise histochemical, immunohistochemical, or detailed ultrastructural examination has been published to date. To elucidate the pathological differences/similarities of Bunina bodies between classical ALS and ALS-G, we performed histochemical, immunohistochemical, topographic and ultrastructural examinations. Histochemically, hematoxylin and eosin, Masson’s trichrome, methylgreen-pyronin, phosphotungstic acid-hematoxylin, Klüver-Barrera, Bodian and periodic acid-Schiff staining were utilized. Immunohistochemical examination was performed using antibodies for cystatin C, ubiquitin, Tau-2, Cu/Zn superoxide dismutase, phosphorylated neurofilament and glial fibrillary acidic protein. Histochemical findings were consistent with those previously described for classical ALS. The immunohistochemical study showed that in ALS-G Bunina bodies were intensely labeled by an anti-cystatin C antibody. Topographic examination demonstrated that Bunina bodies were distributed in the spinal anterior horns and Clarke’s column in the spinal cord. Ultrastructurally, Bunina bodies were composed of electron-dense amorphous/ granular material accompanied by vesicular structures and neurofilaments. The results of the present study have revealed that the pathological features of Bunina bodies in ALS-G are identical to those seen in classical ALS. These findings strongly suggest that a similar degenerative process occurs in the spinal anterior horn cells in both ALS-G and classical ALS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051063
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  • 5
    Electronic Resource
    Electronic Resource
    Studies on a diabetic (KK) strain of the mouse (1967)
    Springer
    Diabetologia 3 (1967), S. 212-221 
    Details
    ISSN: 1432-0428
    Keywords: Spontaneous Diabetes ; KK mice ; Japanese mice ; Obesity ; Growth hormone ; Pituitary ; Islets of Langerhans ; Pancreas ; Ultrastructure ; Beta cells ; Insulin in pancreas ; Sex and diabetes ; Adrenal cortex ; Zinc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé 1. Un état diabétique est démontré chez des souris d'une souche japonaise, la souche KK, mis en évidence par une élévation du sucre sanguin et par une diminution de la tolérance au glucose. 2. Le poids corporel des souris KK dépasse la normale; il s'agit d'une obésité modérée. 3. L'activité insulinique du pancréas et le contenu en hormone de croissance de l'hypophyse de souris KK dépassent ceux observés chez des souris C57BL. 4. Histologiquement, on trouve chez les souris KK une hypertrophie et une hyperplasie des îlots de Langerhans, une hypertrophie et une dégranulation des cellules B, une abondance de ribosomes et de réticulum endoplasmique des cellules B, un développement marqué de la région de Golgi des mêmes cellules, et une diminution du contenu en zinc des cellules insulaires. D'autres anomalies ont également été observées dans d'autres organes des souris KK, plus particulièrement pour l'hypophyse, le foie, les surrénales et la parathyroïde.
    Abstract: Zusammenfassung 1. Bei Mäusen des KK-Stammes (japanische Zucht) ist mit Bestimmung von Glucosetoleranz und Blutzuckerwerten ein diabetischer Zustand nachweisbar. 2. Das Körpergewicht von KK-Mäusen liegt über der Norm, und es besteht eine leichte Fettsucht. 3. Die Insulinaktivität des Pankreas und der Gehalt der Hypophyse an Wachstumshormon sind bei KK-Mäusen höher als bei C57BL-Mäusen. 4. Das Pankreas der KK-Mäuse zeigt auffallende Veränderungen, wie Hypertrophie und Degranulierung derβ-Zellen, reichlich Ribosomen und endoplasmatisches Reticulum in denβ-Zellen, sowie starke Ausbildung des Golgiapparates und Verminderung des Zinkgehaltes der Inselzellen. 5. Auch andere Organe (z.B. Adenohypophyse, Leber, Nebenniere und Nebenschilddrüse) der KK-Mäuse weisen Veränderungen auf.
    Notes: Summary This review demonstrates the following points:1. By glucose tolerance test and the determination of non-fasting blood sugar values, mice of KK strain (a Japanese strain) have been shown to be in a diabetic state. 2. KK mice have greater than normal body weights, and moderate obesity. 3. Pancreatic insulin activity and adenohypophyseal growth hormone content of KK mice are greater than those of C75BL mice. 4. The pancreas of KK mice presents many striking changes, such as the hypertrophy and hyperplasia of the islets, the hypertrophy and degranulation of B cells, the abundance of B cell ribosomes and endoplasmic reticulum, the enlargement of the Golgi areas of B cells, and the diminution of the zinc content of insular cells. 5. In other organs (eg. adenohypophysis, liver, adrenal and parathyroid) of KK mice, many changes are also observed. The above features of KK mice are discussed in relation to the presumed metabolic disorder in the mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01222198
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  • 6
    Electronic Resource
    Electronic Resource
    A comparison of the bioavailability and potency of dexamethasone phosphate and sulphate in man (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 277-282 
    Details
    ISSN: 1432-1041
    Keywords: dexamethasone phosphate ; dexamethasone sulphate ; intravenous injection ; bioavailability ; pituitary-adreno-cortical suppression ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic fate and ACTH-supressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20 mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within 5 min. About 9% of the administered dose appeared in the urine as free dexamethasone. By contrast, virtually no free dexamethasone was found in plasma and urine after injection of dexamethasone sulphate. Pharmacokinetic analysis showed that dexamethasone sulphate had a shorter plasma half-life and a higher metabolic clearance rate than free dexamethasone. A larger fraction (60%) of dexamethasone sulphate was rapidly excreted unmetabolized in urine. The plasma cortisol level was significantly suppressed for more than 24 h after dexamethasone phosphate, while the plasma cortisol profile after dexamethasone sulphate merely showed physiological circadian variations. When the steroid esters were injected after pretreatment with metyrapone, a definite suppression of plasma ACTH was noted after dexamethasone phosphate, but again, dexamethasone sulphate was ineffective. These results cast serious doubt on the clinical value of dexamethasone sulphate as an injectable glucocorticoid, and critical reevaluation of this preparation is needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00618778
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of famotidine, a new H2-receptor antagonist, in relation to renal function (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 327-331 
    Details
    ISSN: 1432-1041
    Keywords: famotidine ; renal failure ; H2-receptor antagonist ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new, potent H2-receptor antagonist, famotidine, 20 mg i.v. was studied in 7 subjects with normal renal function and in 24 patients with varying degrees of renal impairment. The volume of distribution at steady state was 1.14 l/kg in normal subjects and was not altered in renal failure. The half-life of elimination was 2.59 h in normal subjects and was unchanged in mild renal failure (creatinine clearance, CLCR 90–60 ml/min/1.48 m2) but was increased to 4.72 h in moderate renal failure (CLCR 60–30 ml/min/1.48 m2), and to 12.07 h in severe renal failure (CLCR below 30 ml/min/1.48 m2). The cumulative urinary excretion and renal clearance of famotidine were correspondingly reduced in patients with impaired kidney function. In normal subjects and in patients with mild to moderate renal failure, about 70% of famotidine was excreted through the kidney, mainly by tubular secretion. In patients with a CLCR above 60 ml/min/1.48 m2 the normal daily dose of famotidine can be employed, but in those with a CLCR between 60 and 30 ml/min/1.48 m2 the dose should be reduced by half, and in patients with a CLCR below 30 ml/min/1.48 m2 a reduction by three quarters of the normal dose is recommended.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543332
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  • 8
    Electronic Resource
    Electronic Resource
    Stereoselective analysis of the disposition of tosufloxacin enantiomers in man (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 489-491 
    Details
    ISSN: 1432-1041
    Keywords: Tosufloxacin ; Enantiomer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of tosufloxacin enantiomers after oral administration of racemic tosufloxacin were examined in healthy volunteers. Only small differences were observed in time to peak concentration (2.6±0.3 [mean ± SEM] h for (+)-tosufloxacin vs 2.4±0.2 h for (−)-tosufloxacin), elimination half-life (3.61±0.24 h vs 3.49±0.23 h), and area under the curve (2.78±0.19 h·μg/ml vs 2.87±0.19 h·μg/ml); however, peak concentration (0.40±0.03 μg/ml vs 0.44±0.03 μg/ml), renal clearance (226±10 ml/min vs 202±10 ml/min), and urinary recovery (35.4±2.2% vs 32.4±1.9%) differed significantly between enantiomers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315523
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  • 9
    Electronic Resource
    Electronic Resource
    Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese subjects (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 391-396 
    Details
    ISSN: 1432-1041
    Keywords: Key words Lansoprazole ; CYP2C19; genotype ; hydroxy lation ; polymorphism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We investigated whether interindividual differences in the pharmacokinetic disposition of lansoprazole are attributed to the genetic polymorphism of CYP2C19 which occurred by two mutations, CYP2C19m1 and CYP2C19m2, in 20 Japanese subjects. Methods: Polymerase chain reaction (PCR) restriction fragment length polymorphism procedures were used to detect the CYP2C19m1 mutation in exon 5 and the CYP2C19m2 mutation in exon 4 using SmaI and BamHI, respectively. Results: Ten subjects were homozygous (wt/wt subjects) for the wt allele in both exon 5 and exon 4, four subjects were heterozygous (wt/m1) for the CYP2C19m1 mutation, and two subjects were heterozygous (wt/m2) for the CYP2C19m2. The remaining four subjects had both mutated alleles in CYP2C19 genes, i.e., two were homozygous (m1/m1) for the defect in exon 5 and two were heterozygous (m1/m2) for the two defects in exons 5 and 4. The subjects in group 1 (wt/wt, wt/m1 and wt/m2) were the extensive metabolizers (EMs) for 5-hydroxylation of lansoprazole and were in the range of hydroxylation indexes from 3.83 to 19.8, whereas the subjects in group 2 (m1/m1 and m1/m2) were the poor metabolizers (PMs) and the indexes were in the range of 38.5 to 47.6. In group 2, AUC, t1/2 and CL/f of lansoprazole were significantly greater, longer, and lower, respectively, than those in group 1. Conclusion: The hydroxylation of lansoprazole to 5-hydroxylansoprazole was apparently impaired in the subjects with the genetic defects of CYP2C19 (m1/m1 or m1/m2).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050307
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 411-414 
    Details
    ISSN: 1432-1041
    Keywords: SUN 1165 ; renal failure ; antiarrhythmic agent ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 1 · kg−1, the absorption rate constant was 2.2 h−1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml · min−1 · 1.48 m−2). Dosage adjustment of SUN 1165 is necessary in renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265853
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