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  • 1995-1999  (11)
  • 1985-1989  (12)
  • Life and Medical Sciences  (21)
  • Pharmacokinetics
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 473-476 
    ISSN: 1432-0843
    Keywords: Doxorubicin ; Pharmacokinetics ; Gender
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the variability in doxorubicin pharmacokinetics in 27 patients, all of whom had normal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography (HPLC). The relationship of doxorubicin clearance (dose/AUC) with biochemical tests (AST, bilirubin, alkaline phosphatase, albumin, creatinine) and physical characteristics (age, gender, height, weight, tumour type) was investigated. The 6 men had a significantly higher doxorubicin clearance than did the 21 women (median values, 59 and 27 lh−1 m−2, respectively;P=0.002). Doxorubicin clearance was significantly lower in patients with breast cancer than in those with other tumours (median values, 26 and 53 lh−1 m−2, respectively;P=0.0008). The other biochemical and physical parameters did not correlate with doxorubicin clearance. However, in multivariate analysis, gender was the only factor predicting doxorubicin clearance (r 2=40%). The ratio of the AUCs for doxorubicinol and doxorubicin (R) was higher in the men than in the women (median values, 0.62 and 0.36, respectively;P=0.03). We conclude that gender may be an important determinant of doxorubicin clearance in patients with normal liver biochemistry.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 473-476 
    ISSN: 1432-0843
    Keywords: Key words Doxorubicin ; Pharmacokinetics ; Gender
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied the variability in doxorubicin pharmacokinetics in 27 patients, all of whom had normal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography (HPLC). The relationship of doxorubicin clearance (dose/AUC) with biochemical tests (AST, bilirubin, alkaline phosphatase, albumin, creatinine) and physical characteristics (age, gender, height, weight, tumour type) was investigated. The 6 men had a significantly higher doxorubicin clearance than did the 21 women (median values, 59 and 27 lh-1 m-2, respectively; P=0.002). Doxorubicin clearance was significantly lower in patients with breast cancer than in those with other tumours (median values, 26 and 53 l h-1 m-2, respectively; P=0.0008). The other biochemical and physical parameters did not correlate with doxorubicin clearance. However, in multivariate analysis, gender was the only factor predicting doxorubicin clearance (r 2=40%). The ratio of the AUCs for doxorubicinol and doxorubicin (R) was higher in the men than in the women (median values, 0.62 and 0.36, respectively; P=0.03). We conclude that gender may be an important determinant of doxorubicin clearance in patients with normal liver biochemistry.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0730-2312
    Keywords: anticoagulants ; blood coagulation enzymes ; elastase ; emphysema ; isocoumarins ; molecular modeling ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Isocoumarins are potent mechanism-based heterocyclic irreversible inhibitors for a variety of serine proteases. Most serine proteases are inhibited by the general serine protease inhibitor 3,4-dichloroisocoumarin, whereas isocoumarins containing hydrophobic 7-acylamino groups are potent inhibitors for human leukocyte elastase and those containing 7-alkylureidogroups are inhibitors for porcine pancreatic elastase. Isocoumarins containing basic side chains that resemble arginine are potent inhibitors for trypsin-like enzymes. A number of 3-alkoxy-4-chloro-7-guanidinoisocoumarins are potent inhibitors of bovine thrombin, human factor Xa, human factor XIa, human factor XIIa, human plasma kallikrein, porcine pancreatic kallikrein, and bovine trypsin. Another cathionic derivative, 4-chloro-3-(2-isothiureidoethoxy) isocoumarin, is less reactive toward many of these enzymes but is an extremely potent inhibitor of human plasma kallikrein. Several guanidinoisocoumarins have been tested as anticoagulants in human plasma and are effective at prolonging the prothrombin time. The mechanism of inhibition by this class of heterocyclic inactivators involves formation of an acyl enzyme by reaction of the active site serine with the isocoumarin carbonyl group. Isocoumarins with 7-amino or 7-guanidino groups will then decompose further to quinone imine methide intermediates, which react further with an active site residue (probably His-57) to form stable inhibited enzyme derivatives. Isocoumarins should be useful in further investigations of the physiological function of serine proteases and may have future therapeutic utility for the treatment of emphysema and coagulation disorders.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 213 (1985), S. 464-472 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: White Leghorn chicken eggs, specific pathogen free, were treated with the organophosphate insecticide dicrotophos and the early defects thus induced were characterized histologically. Eggs were incubated for 24, 48, 72, or 96 hr, injected with doses of dicrotophos ranging from 250 μg to 2.0 mg per egg, and observed after an additional 48 hr of incubation. Treated embryos displayed general developmental retardation as well as unilateral retardation of the cranial sense organs, the youngest embryos being most severely affected. Many embryos injected with insecticide at 24 hr, and all but one injected at 48 or 72 hr, displayed notochordal folding, usually restricted to the cervical region; most of these also showed deformities of the adjacent spinal cord. Other defects, seen on a less consistent basis, included branching of the neural canal in the lumbar region, bifurcation of the neural epiphysis, deformation of the lens vesicle, and distention of the major blood vessels. The incidence and severity of epiphyseal, lens, and vascular defects were greatest among embryos treated at 24 hr, whereas notochordal and both types of neural defects were greatest among those treated at 48 hr. The incidence and severity of the abnormalities diminished with increasing age such that by 96 hr the only defect noted was a weak notochordal folding in one embryo. To a lesser extent, incidence and severity were dose-related also. Histological similarities between embryos displaying vascular distention and recently dead treated embryos suggested that this abnormality is a precursor to death. All defects were associated with the presence of the insecticide at the time the affected structures were undergoing initial or early morphogenesis or else the deposition of a supportive sheath, suggesting these activities as targets of the teratogen.
    Additional Material: 17 Ill.
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 241 (1995), S. 439-450 
    ISSN: 0003-276X
    Keywords: Golgi ; TGN ; Inflammation ; Acute phase response ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Background: During the acute phase response to inflammation, the Golgi apparatus of rat hepatocytes processes an increased quantity of glycoproteins, in the form of acute phase reactants.Methods: The compartmental organization of the hepatocyte Golgi of control and 24 hour inflamed rats was studied, using transmission electron microscopic techniques, including cytochemistry, to detect nicotinamide adenine dinucleotide phosphatase (NADPase), thiamine pyrophosphatase (TPPase), and cytidine monophosphatase (CMPase) activity.Results: In inflamed rats, individual Golgi stacks were enlarged, but retained their organization into four compartments:1) a phosphatase negative, perforated cis-element, 2) two mid-saccules which sometimes were positive for NADPase, 3) one or occasionally two NADPase and TPPase positive trans-saccules, and 4) a tubulovesicular trans-Golgi network (TGN) which was NADPase reactive and contained a spotty TPPase reaction product. Two of these compartments were noticably altered in response to inflammation. The two mid-saccules were consistently and uniformly dilated. The TGN was altered to the point of being difficult to recognize and had acquired CMPase reactivity. In control rats the TGN consisted of anastomosing tubules forming cage-like structures; secretory granules containing lipoprotein particles pinched off from these. In inflamed rats, most of the cage-like TGN structures had been replaced with an extensive vesicular syncytium which produced secretory granules with a granulofilamentous content.Conclusions: In hepatocytes from inflamed rats an apparent switch had occured in the type of secretory material processed by the Golgi apparatus. Furthermore, the inflammation-induced increase in the size of individual Golgi stacks apparently was not due to a parallel increase in size of all Golgi saccules. Rather, saccules within given Golgi compartments responded in a characteristic and specific manner to the increase in glycoprotein processing that occurs during inflammation. © 1995 Wiley-Liss, Inc.
    Additional Material: 17 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 241 (1995), S. 563-578 
    ISSN: 0003-276X
    Keywords: Substantia nigra ; Basal ganglia ; Cytoarchitecture ; Light microscopy ; Electron microscopy ; Opossum ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Background: The substantia nigra has been divided into three subdivisions. However, the cytoarchitecture of one of these subdivisions, the pars lateralis (SNI), has not been previously examined in detail at the light and electron microscopic levels in any species. In the adult opossum, the three nigral subdivisions can be easily distinguished as distinct, rostrocaudally oriented cell groups separated by neuron-free zones. Thus it was possible to determine the boundaries of the SNI unambiguously. This report covers the results of an examination of the morphology and organization of the SNI in the opossum.Methods: Material from 13 opossums was used for this study. Eight of the animals had been previously stained for Nissl substance (n=4) or impregnated by the Golgi technique (n=4). The remaining five animals were prepared for electron microscopic studies using standard procedures.Results: Two cell types were identified on the basis of morphological differences, small and medium-large neurons. Small neurons (10-18 μm long axis) have large nuclei with moderate amounts of heterochromatin and a thin rim of cytoplasm. They have long (up to 500 μm), spine-free dendrites. Medium-large neurons (18-54 μm long axis) have rounded nuclei with electron-lucent nucleoplasm. Few indentations of the nuclear envelope were observed. The surrounding cytoplasm has dense arrays of organelles. Nissl bodies are particularly prominent in the form of pyramids with their bases at juxtanuclear positions and their apices directed toward emerging dendrites. Dendrites of medium-large neurons are long (some〉1 mm in length), are primarily oriented in the frontal plane, and extend along the dorsal surface of or into the cerebral peduncle. Some cells have dendrites that are moderately spinous, whereas other neurons possess sparsely spinous dendrites. Relatively few synaptic profiles are observed to contact somata and proximal dendrites.Conclusion: This report provides added morphological support for the idea that the SNI is a distinct subdivision of the substantia nigra, a distinction previously made on the basis of the physiologically characterized relationship between the lateral substantia nigra and orienting behaviors and seizure-related function. © 1995 Wiley-Liss, Inc.
    Additional Material: 9 Ill.
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 216 (1986), S. 528-533 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Gravimetric determination of total bone water space was used as an index of available bone marrow space in mice following various specific stressors, i.e., splenectomy, hypoxia, bone fracture, and estrone-induced osteosclerosis. Data was corrected for bone weight and was reported as specific bone marrow volume (total bone water space/mg dry bone × 100).A direct relationship was observed between specific bone marrow volume and medullary hemopoietic activity induced by stress. Absolute and/or relative marrow space increased following splenectomy, hypoxia, and fracture. Osteosclerotic animals shift most hemopoietic activity from marrow to spleen, and splenectomized osteosclerotic animals become anemic. Both intact and splenectomized hypoxic animals develop increased specific bone marrow volume and successfully compensate for hypoxia with enhanced erythropoiesis. Animals sustaining a fracture callus increase both specific bone marrow volume and hemopoietic activity at the callus without an increase in hemopoietic demand.Increased specific bone marrow volume extends the marrow bone interface, where primitive stem cells accumulate, while expanding marrow stromal space, where stem cells lodge, proliferate and differentiate. Therefore, it would appear that availability of competent marrow space may play an integral part in passively permitting hematopoiesis and in determining hemopoietic reserve capacity.Stem cell migration increases during intensified hemopoietic demand, which also may be related to available marrow space. Mice have a low medullary hemopoietic reserve capacity; subsequently, when available medullary hematopoietic stroma becomes occupied, stem cells are more likely to migrate from the marrow to extra-medullary sites where they mature before entering the circulating pool.
    Additional Material: 2 Tab.
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  • 8
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Lactoferrin (Lf) in blood and/or marrow neutrophils was semiquantified using indirect immunofluorescence technique in nine mammalian species. Neutrophil iron-binding reactivity (NFeBR), which corresponds primarily to Lf, was also visualized and semiquantified using functional cytochemical (FeNTA-AF) technique at the light microscopic level in these nine and in an additional fifteen mammalian species, and in selected species at the ultrastructural level. Neutrophil immunoreactive Lf was positively correlated with total cellular and granule content of NFeBR among these nine species, and with previously reported concentrations of neutrophil Lf quantified by radioimmunoassay. Relative levels of Lf in neutrophil extracts from rat, hamster, and human were confirmed using SDS-polyacrylamide gel electrophoresis and immunoblotting. Relatively high levels of immunoreactive neutrophil Lf and/or NFeBR were observed in carnivores (ten species) and primates (six species). Among rodents (five species), the levels were variable, and the artiodactyls (four species) studied had low levels. These results demonstrate that neutrophil Lf levels vary widely among mammalian species. In addition, FeNTA-AF technique provides a rapid means of evaluating animals for relative quantities of neutrophil Lf.
    Additional Material: 4 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 212 (1985), S. 161-166 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Discovery of components of the renin-angiotensin system (RAS) in the adenohypophysis of several species has prompted speculation concerning the location and possible function of a pituitary RAS. Although both renin and angiotensin II have been localized within the rat adenohypophysis, their colocalization has not been previously demonstrated within the same cells. In the present study, immunohistochemical staining by the avidin-biotin-peroxidase complex technique was used to demonstrate the coexistence of renin and angiotensin II in adenohypophyseal cells identified morphologically and immunocytochemically as gonadotrophs. These results support the existence of an adenohypophyseal RAS, at least part of which is under intracellular control. The influence of this system on control of fluid balance, blood pressure, and the secretion of other hypophyseal hormones is discussed.
    Additional Material: 4 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 349-357 
    ISSN: 0730-2312
    Keywords: hypercholesterolemia ; nuclear membrane ; NTPase ; hyperlipidemia ; obesity ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: A nuclear pore complex-associated nucleoside triphosphatase (NTPase) activity is believed to provide energy for nuclear export of poly(A)+ mRNA. This study was initiated to determine if nuclear membrane lipid composition is altered during chronic hyperlipidemia, and what effect this has on NTPase activity. The JCR:LA-cp corpulent rat model is characterized by severe hypertriglyceridemia and moderate hypercholesterolemia, and thus represents an ideal animal model in which to study nuclear cholesterol and NTPase activity. NTPase activity was markedly increased in purified hepatic nuclei from corpulent female JCR:LA-cp rats in comparison to lean control rats as a function of assay time, [GTP], [ATP], and [Mg2+]. Nuclear membrane cholesterol and phospholipid content were significantly elevated in the corpulent animals. Nuclei of corpulent animals were less resistant to salt-induced lysis than nuclei of lean animals, suggesting a change in relative membrane integrity. Together, these results indicate that altered lipid metabolism in a genetic corpulent animal model can lead to changes in nuclear membrane lipid composition, which in turn may alter nuclear membrane NTPase activity and integrity. © 1996 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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