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At least 883 records · Page 49Linked to original sources
PubMed1998

Rat prostaglandin D2 synthetase: its tissue distribution, changes during maturation, and regulation in the testis and epididymis.

The changes in glutathione-independent prostaglandin D2 synthetase (PGD-S) during maturation in the rat were determined in selected organs by an RIA using PGD-S purified from rat cerebrospinal fluid and a monospecific anti-rat PGD-S polyclonal antibody. In a survey of its tissue distribution in various organ extracts and biological fluids, it was found that the concentration of PGD-S was highest in the epididymis-about 6- and 80-fold greater than that in the brain and testis, respectively. During maturation, PGD-S concentration increased steadily in the testis and epididymis; this is in contrast to the pattern of changes in the brain and liver, which showed a general trend of decline. Reverse transcription-polymerase chain reaction and Southern blotting were used to demonstrate the presence of PGD-S mRNA transcript in the testis and in Sertoli and germ cells. In the epididymis, the steady-state PGD-S mRNA level was highest in the caput, followed by the cauda and corpus. Orchiectomy induced a drastic reduction of PGD-S concentration in all three epididymal compartments. Administration of dihydrotestosterone (DHT) failed to restore the reduced epididymal PGD-S level except in the caput epididymis, where 4 days after DHT treatment the level of PGD-S was restored to about 50% of the pre-orchiectomized level; this suggests that the epididymal PGD-S level is not entirely regulated by androgen and that another yet to be identified testicular factor(s) is likely to be involved in its regulation. Germ cell-conditioned medium was also shown to stimulate PGD-S expression in the Sertoli cell. These results illustrate that PGD-S is an important molecule in testicular and epididymal function and that it is likely involved in spermatogenesis and sperm maturation.

Animals↗
PubMed1999

[Tissue penetration properties of macrolide antibiotics--comparative tissue distribution of erythromycin-stearate, clarithromycin, roxithromycin and azithromycin in rats].

The ability of antibiotics to penetrate the target organs is an important factor for the clinical effects and side effects in the treatment of infection. In the present study, the comparative tissue distribution of 4 kinds of macrolide antibiotics was determined in rats. After oral administration of 20 mg/kg, roxithromycin (RXM) had the highest plasma concentration, and clarithromycin (CAM) has the second highest. The Cmax of RXM and CAM were 2.7 and 1.0 micrograms/ml, respectively. On the other hand, both levels of erythromycin-stearate (EM-S) and azithromycin (AZM) were extremely low, with a Cmax of 0.1 microgram/ml. Concentration of the 4 compounds were measurable in the liver, kidney, spleen, lung and heart. The concentration in all tissues for each compound were significantly higher than those in the plasma. AZM had the most sustained and the highest tissue levels. The distribution patterns of RXM and AZM were almost similar to the case of EM-S, in that the highest tissue concentration was observed in the liver, followed in descending order by concentration in the kidney, spleen, lung and heart. On the other hand, CAM had the highest concentration in the lung, and was moderated in the liver. Major clinical indications are infections of the respiratory tracts, and commonly reported side-effects are hepatotoxity. Therefore, it is worth noting that the lung levels of CAM were significantly higher than in the liver, as the separation of clinical effects and side-effects.

Animals↗
PubMed2001

Distinctive tissue distribution and phosphorylation of IRSp53 isoforms.

An insulin-receptor substrate of 53-kDa protein (IRSp53) is an adapter protein, which interacts with the Rho-family of GTPases and mediates neurite outgrowth. It also binds to DRPLA protein, a product of the gene responsible for a polyglutamine disease, dentatorubral-pallidoluysian atrophy (DRPLA). Isoforms of human IRSp53 have been reported, each with a unique amino acid sequence at the C-terminal end. Here we report the distinctive tissue distribution and phosphorylation of three isoforms (L, S, and T-forms). Western blotting analyses with isoform-specific antibodies demonstrated that the L and S-forms were expressed in the brain, whereas the T-form was not present in any tissues examined, but was found in a cancer cell line. The L and S-forms were phosphorylated upon stimulation with insulin, and the T-form with IGF-I. Since phospho-acceptor sites were localized to the common portion, the difference in phosphorylation seems to be due to the unique C-terminal sequence.

Amino Acid Sequence↗
PubMed1985

Metabolism and tissue distribution of tobacco-specific N-nitrosamines in the marmoset monkey (Callithrix jacchus).

Three male marmoset monkeys (Callithrix jacchus) were injected i.v. with the tobacco-specific carcinogen [2'-14C]N'-nitrosonornicotine (NNN) (20.3 mumol/kg body weight) or [carbonyl-14C]4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (18.8 or 420 mumol/kg body weight). They were sacrificed 4 h later. Tissue distribution was studied in two monkeys by whole-body autoradiography and by computer-assisted densitometric analysis of the autoradiograms. The autoradiograms showed a high level of radioactivity in the liver, nasal mucosa, kidneys, melanin of the eyes, hair-follicles of the skin and in the ceruminous ear glands of the monkeys. Total level of radioactivity was 5.7 times higher in the liver of the [carbonyl-14C]NNK-injected monkey than in that of [2'-14C]-NNN-injected monkey. Washing the sections with trichloroacetic acid and organic solvents selectively removed free metabolites leaving metabolites bound to cellular macromolecules. Level of bound metabolites was 1.5 times higher in the nasal mucosa than in the liver of the [2'-14C]NNN monkey. Levels of bound metabolites were similar in the liver of NNN- and NNK-treated monkeys. The results indicate that the liver and nasal mucosa of C. jacchus can activate NNN and NNK to alkylating species. Unbound metabolites present in the liver, lung, kidneys, eye, blood and urine were extracted and separated by h.p.l.c. Hydroxylation of the carbons alpha to the N-nitroso group of NNN were the major metabolic pathways. Unmetabolized NNN was the major radioactive component in the liver, lung, eye and blood. Reduction of the carbonyl of NNK yields 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol (NNAl). NNAl was present in all tissues analyzed and was the major radioactive component in the eye and stomach lumen. It was also excreted in the urine. NNK and NNAl were metabolized by alpha-carbon hydroxylation. These results suggest that in C. jacchus, NNN, NNK and NNAl are activated to alkylating species by alpha-carbon hydroxylation. In the third monkey injected with NNK, DNA methylation was observed in the liver and nasal mucosa but not in the lung and kidneys. Pulmonary tissues of C. jacchus, unlike those of F344 rats, do not have the enzymic capacities to activate NNK to methylating species.

Animals↗
PubMed1981

Tissue distribution of unentrapped or liposome-entrapped 131I-labeled beta-galactosidase injected into rats.

Either unentrapped (free) or liposome-entrapped 131I-labeled beta-galactosidase was injected into rats from tail veins. Tissue distribution and intracellular localization of the radioactivity of both sources were compared. The half-life of liposome-entrapped enzyme in the circulation was much longer than that of the free enzyme. The radioactivity removed from the circulation was recovered primarily in the liver, and to a lesser extent in almost all tissues studied. A small but significant uptake of liposome-entrapped enzyme by the brain was also observed. Uptake of liposome-entrapped enzyme was greater thant that of free enzyme in the spleen, heart, lungs and brain, excepting the liver and kidneys. Subcellular fractionation showed distribution of the radioactivity of liposome-entrapped enzyme favoring the mitochondrial-lysosomal fraction from these tissues except the heart. There was a difference in the pattern of intracellular distribution of the radioactivity in the brain of rats between the administration of free enzyme and that of liposome-entrapped enzyme. These findings suggest that when liposomes containing beta-galactosidase were injected into rats from the tail veins, they would penetrate the blood-brain barrier and would reach the lysosomes in the central nervous system tissue more effectively than the free enzyme itself. Beta-galactosidase; liposome; enzyme replacement therapy; rat tissues, 131I.

Animals↗
PubMed1995

Tissue distribution of zinc-mesoporphyrin in rats: relationship to inhibition of heme oxygenase.

Metalloporphyrins, including heme and others that inhibit heme oxygenase, are agents with expanding therapeutic potential. Recent results from our laboratory showed that a combination of heme and zinc-mesoporphyrin was remarkably effective in ameliorating biochemical features of acute porphyria. The aim of this study was to assess plasma clearance, tissue distribution and persistence, stability, toxicology and metabolic effects of zinc-mesoporphyrin, after its i.v. administration to rats. After administration of 15 mumol/kg b.wt. of zinc-mesoporphyrin (bound to serum albumin in a 1:1 molar ratio) the metalloporphyrin was rapidly cleared from plasma (half-life 3.6 h) with uptake primarily into liver and spleen, considerably less into the kidney and none detectable into the heart or brain. Hepatic heme oxygenase activity was undetectable for 4 days and less than 50% of control 1 week later. Inhibition of splenic heme oxygenase activity was also substantial but less marked than in the liver. No mortality was observed in any of the treated animals, and there was no detectable effect on gross or microscopic appearance of the liver, spleen, kidneys, heart, lungs or brain. Blood counts and chemistries remained within normal limits. We conclude that single doses of ZnMP-serum albumin are nontoxic, rapidly cleared from the plasma and persist primarily in the liver and spleen where heme oxygenase is inhibited for prolonged periods.

Animals↗
PubMed1994

Tissue distribution of TAG-72 in malignant mixed müllerian tumors of the uterus.

Malignant mixed müllerian tumors are the most frequent sarcomas arising from the uterus. Since these tumors are traditionally associated with a poor prognosis, tumor-associated antigens may be useful in the evaluation and follow-up of affected patients. The purpose of this study was to determine the frequency and tissue distribution of TAG-72, an antigen frequently expressed in endometrial carcinomas, and to compare it to CA 125 and CA 19-9 expression in malignant mixed müllerian tumors of the uterus. Consecutive, paraffin-embedded sections from 35 tumors were immunohistochemically evaluated using primary antibodies directed against the tumor-associated antigens. These antigens were demonstrated in the neoplastic glandular epithelium and not in the sarcomatous portion of the tumor. The degree of antigen expression was unrelated to the nature of the sarcomatous element present (homologous vs heterologous). Positive staining (> or = 5% of the glandular epithelium) for TAG-72 was present in 66% of the tumors; another 6% of the tumors contained focal staining (< 5% of the glandular epithelium) for TAG-72. Although cytoplasmic and intraluminal staining were present, cell surface staining was the most prominent feature of TAG-72 expression. Tumors were more likely to be positive for TAG-72 than either CA 125 (P = 0.046) or CA 19.9 (P = 0.004). The extent of TAG-72 expression was unrelated to the extent of disease (intrauterine vs extrauterine) and overall patient survival. However, antigen expression was correlated with the differentiation of the glandular component present.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Specific antibodies and the selective inhibitor ICI 118233 demonstrate that the hormonally stimulated 'dense-vesicle' and peripheral-plasma-membrane cyclic AMP phosphodiesterases display distinct tissue distributions in the rat.

Polyclonal-antibody preparations DV1 and PM1, raised against purified preparations of rat liver insulin-stimulated 'dense-vesicle' and peripheral-plasma-membrane cyclic AMP phosphodiesterases, were used to analyse rat liver homogenates by Western-blotting techniques. The antibody DV1 identified only the 63 kDa native subunit of the 'dense-vesicle' enzyme, and the antibody PM1 only the 52 kDa subunit of the plasma-membrane enzyme. These antibodies also detected the subunits of these two enzymes in homogenates of kidney, heart and white adipose tissue from rat. Quantitative immunoblotting demonstrated that the amount of these enzymes (by wt.) varied in these different tissues, as did the expression of these two enzymes, relative to each other, by a factor of as much as 7-fold. The ratio of the dense-vesicle enzyme to the peripheral-plasma-membrane enzyme was lowest in liver and kidney and highest in heart and white adipose tissue. ICI 118233 was shown to inhibit selectively the 'dense-vesicle' cyclic AMP phosphodiesterase in liver. It did this in a competitive fashion, with a Ki value of 3.5 microM. Inhibition of tissue-homogenate cyclic AMP phosphodiesterase activity by ICI 118233 was used as an index of the contribution to activity by the 'dense-vesicle' enzyme. By this method, a tissue distribution of the 'dense-vesicle' enzyme was obtained which was similar to that found by using the immunoblotting technique. The differential expression of isoenzymes of cyclic AMP phosphodiesterase activity in various tissues might reflect a functional adaptation, and may provide the basis for the different physiological actions of compounds which act as selective inhibitors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Cell surface localization and tissue distribution of a hepatocyte cell-cell adhesion glycoprotein (cell-CAM 105).

We recently identified a 105,000-dalton plasma membrane glycoprotein, denoted cell-CAM 105 (CAM, cell adhesion molecule), that is involved in intercellular adhesion of reaggregating rat hepatocytes (Ocklind, C., and B. Obrink, 1982, J. Biol. Chem., 257:6788-6795). In this communication we used a monospecific rabbit antiserum against cell-CAM 105 to localize the antigen by indirect immunofluorescence on isolated rat cells and on frozen rat tissue sections. This antiserum stained the surface of freshly isolated hepatocytes. In liver sections, however, the fluorescence seemed to be located exclusively along the bile canaliculi. In addition, cell-CAM 105 showed a very specific tissue distribution. Thus a specific fluorescence was seen only in the epithelia of the stomach, the small intestine, the large intestine, the glandular epithelium of the parotid gland, and the tubules of the kidney. No specific fluorescence was found in variety of other tissues, including cartilage, interstitial connective tissue, smooth muscle, skeletal muscle, heart muscle, eye, brain, skin, the epithelia of oesophagus, bladder, uterin mucosa, thyroid follicles, prostate gland, or collecting ducts of the kidney. In the simple epithelia of the intestine and the kidney tubules the fluorescence was confined to the apical, luminal portion. Thus, both in these epithelia and in liver, cell-CAM 105 was confined to the apical, luminal portion. Thus, both in these epithelia and in liver, cell-CAM 105 was located where the typical junctional complexes between cells are found. These findings taken together with the fact that cell-CAM 105 is involved in intercellular adhesion between hepatocytes suggest with the fac that cell-CAM 105 is involved in intercellular adhesion between hepatocytes suggest that cell-CAM 105 is a member of the junctional complexes of hepatocytes and some simple epithelia.

Adenosine Triphosphatases↗
PubMed2004

Gene expression and tissue distribution of the major human allergen Bla g 1 in the German cockroach, Blattella germanica L. (Dictyoptera: Blattellidae).

Exposure and sensitization to cockroach allergens is an important risk factor for allergic disease in humans. Despite a recent burgeoning of clinical and socioeconomic studies regarding environmental pervasiveness and human exposure to cockroach allergens, little is known about the basic biology of these proteins. The purpose of this study was to ascertain gene expression patterns and the tissue distribution of Blattella germanica allergen 1 (Bla g 1), a perennial indoor environmental allergen, thought to be involved in digestion in cockroaches. We also investigated the relative potential contribution of different life stages of the German cockroach to environmental Bla g 1. Enzyme-linked immunosorbent assay was used to quantify the Bla g 1 contents of feces and various anatomical tissues, and Northern blot analysis was used to elucidate tissue-specific expression of Bla g 1. Results showed that the Bla g 1 protein is most prevalent in the midgut, and the Bla g 1 gene is exclusively expressed by midgut cells. Although Bla g 1 is produced by both sexes and all life stages of the German cockroach, adult females produce and excrete significantly more Bla g 1 in their feces than males or nymphs, even when corrected for body mass or mass of voided feces. Our results show that the concentration of Bla g 1 in feces of adult females is 6- to 7- and 30-fold higher than in adult males and nymphs, respectively, probably because females process more food than other life stages of the German cockroach.

Allergens↗
PubMed2003

Molecular cloning, characterisation, and tissue distribution of oestrogen receptor alpha in eelpout (Zoarces viviparus).

A cDNA encoding the eelpout (Zoarces viviparus) oestrogen receptor alpha (eERalpha) has been isolated from eelpout liver, cloned and sequenced. The cDNA contains a complete open reading frame encoding 570 amino acid residues (mw: 63.0 kDa). The amino acid sequence of eERalpha showed a high degree of identity to ERalpha of other teleost species. The tissue distribution of eERalpha mRNA was examined using Northern blotting, RT-PCR and in situ hybridisation (ISH). All three methods identified a pronounced expression of eERalpha in liver, pituitary, testis and ovary. In the brain ISH experiments showed that ERalpha mRNA was highly expressed in distinct regions of the preoptic area and the mediobasal hypothalamus. We have provided evidence that the receptor is auto-regulated by 17beta-oestradiol (E(2)) not only in liver but also in the testis, indicating an important role for E(2) during spermatogenesis in male eelpout. RT-PCR analysis showed a broader expression pattern including significant expression in the brain, kidney, heart, and gut of adult eelpout. In eelpout embryos eERalpha expression has also been identified, indicating a possible role for the receptor in early development. This study contributes to the accumulating evidence that in fish E(2) is not only involved in the regulation of liver specific proteins, but has a much broader range of targets.

Animals↗
PubMed1989

Sequence, tissue distribution, and differential expression of mRNA for a putative insulin-responsive glucose transporter in mouse 3T3-L1 adipocytes.

The cDNAs for two putative glucose transporters from mouse 3T3-L1 adipocytes were isolated and sequenced. One of these cDNAs encodes the murine homolog of the human hepG2/erythrocyte glucose transporter, termed GT1. GT1 mRNA is most abundant in mouse brain and is expressed in both 3T3-L1 preadipocytes and adipocytes. The other cDNA encodes a glucose transporter-like protein, termed GT2, that has a unique amino acid sequence and tissue distribution. GT2 cDNA encodes a protein with 63% amino acid sequence identity and a similar structural organization to GT1. GT2 mRNA is found at high levels in mouse skeletal muscle, heart, and adipose tissue, all of which exhibit insulin-stimulated glucose uptake. GT2 mRNA is absent from 3T3-L1 preadipocytes but is induced dramatically during differentiation into adipocytes. This increase in mRNA content correlates closely with the acquisition of insulin-stimulated glucose uptake. We propose that GT2 is an insulin-regulated glucose transporter.

Adipose Tissue↗
PubMed1997

The A and B variants of the alpha 3 integrin subunit: tissue distribution and functional characterization.

The alpha subunits of the laminin-binding integrins alpha 3 beta 1, alpha 6 beta 1, and alpha 7 beta 1 have homologous sequences and are similar in structure. Two cytoplasmic variants, A and B, have been identified for each of these alpha subunits, although the alpha 3B splice variant has been detected only at the mRNA level. We prepared a panel of mouse monoclonal antibodies specific for the A and B variants of the alpha 3 subunit to study their tissue distribution. Four monoclonal antibodies react with alpha 3A, one of which recognizes only the nonphosphorylated form; of the three anti-alpha 3B antibodies, one cross-reacts with alpha 6B. Reverse transcriptase-PCR analysis of various human tissues revealed the presence of alpha 3B mRNA in brain, heart, and skeletal muscle. Moreover, the alpha 3B protein was detected by immunoblotting in brain and heart tissue but not in skeletal muscle. In contrast, alpha 3A mRNA and protein were present in all tissues studied. Thus, the expression of alpha 3B in adult tissues is more restricted than that of alpha 3A. Immunohistochemical studies showed that in brain tissue, both variants are exclusively expressed on small blood-vessel endothelium, whereas in heart tissue their distribution patterns differ markedly. Although alpha 3A is strongly expressed on vascular smooth muscle cells, alpha 3B is detected only on endothelial cells of veins. Expression of the two variant forms of alpha 3 in K562 cells revealed that the ligand-binding specificities of alpha 3A beta 1 and alpha 3B beta 1 are identical: both bind human laminin-2 and -4, laminin-5, and laminins isolated from bovine kidney, but not bovine laminin-2 and -4, mouse laminin-1, or human fibronectin. In addition, adhesion mediated by both integrins is induced to the same extent by phorbol 12-myristate 13-acetate. The alpha 3A, but not the alpha 3B subunit, is phosphorylated; and phosphorylation of alpha 3A increases after phorbol 12-myristate 13-acetate stimulation. Thus, we found no differences between the adhesion functions of the A and B variants of alpha 3.

Amino Acid Sequence↗
PubMed2001

The lacZ gene transfer into L929 cells and [14C]-DNA tissue distribution following intraperitoneal administration of new pH-sensitive lipoplexes in mice.

The efficacy of lacZ gene transfer into the L929 cell line and a local [l4C]-DNA delivery in male NMRI mice (10-12 weeks old), were studied using new pH-sensitive liposomes, containing phosphatidylcholine/glycyrrhizin (PC/GL) or alpha-tocopherol ester of succinic acid (PC/TSA). The reporter gene (pQE-LacZ plasmid) was transferred into L929 cells using corresponding lipoplexes, 0.5% of cells being transfected. Tissue distribution of Gasserian ganglion neurinoma cell [14C]-DNA fragments and corresponding PC/GL and PC/TSA lipoplexes, were examined following intraperitoneal administration of a 24 h postdose. The [14C]-DNA itself was not detected in any organs at a 1.5 h postdose. The use of PC/GL or PC/TSA lipoplexes considerably changed the biodistribution of [14C]-DNA in mice tissues. The maximal content of [14C]-DNA for both types of lipoplexes was observed in the intestine (50% dose equiv./g) and the spleen (30% dose equiv./g). The content of [14C]-DNA in liver and kidneys was equal to 4 and 10% for liver and kidneys in the case of PC/GL-lipoplexes, and 15 and 6%, for PC/TSA, respectively. Thus, the tropicity for PC/GL-lipoplexes to liver was not detected under i.p. administration.

Animals↗
PubMed1987

Clearance and tissue distribution of functionalized polymeric liposomes from the blood stream of rats.

Polymeric liposomes containing a synthetic porphinato-iron-imidazole complex (hemoglobin or red blood cell model) were labeled by introducing 1,2-di[1-14C]palmitoyl-sn-glycero-3-phosphocholine into their polymerized bilayers. After intravenous injection into rats, their clearance from a blood stream was measured. The apparent half-life time (50% disappearance time) was about 14 +/- 2 h. Their tissue distribution was determined with time by whole autoradiographic measurement.

Animals↗
PubMed1983

The pharmacology of verapamil. V. Tissue distribution of verapamil and norverapamil in rat and dog.

The relative distribution of verapamil and its demethylated metabolite, norverapamil, was studied in rats at intervals after intraperitoneal injection of the parent drug (30 mg/kg). This route of drug administration simulated oral drug dosing, and the highest concentrations of both unchanged drug and metabolite were found in the liver, with lung and kidney containing most of the remainder. The rates of disappearance of verapamil from various organs followed first-order kinetics, and the most rapid elimination occurred from brain and liver. In contrast, verapamil was given intravenously to 3 dogs by a bolus-infusion method to produce sustained steady state plasma concentrations (80, 140, 250 ng/ml) for 1, 2, and 3 h. After systemic administration, the lungs contained almost half the tissue verapamil and, 20% was found in kidney, with the liver accounting for only 17%. Norverapamil was not found in plasma or brain. These studies contrast the pattern of tissue distribution of verapamil after different routes of drug administration. The variable rates of drug elimination from specific tissues may explain the differing durations of the drug's observed effects.

Animals↗