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Biomedical subjects

G Kuiper

Publications and source records attributed to G Kuiper.

10 recordsLinked to original sources
PubMed2005

Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation.

During illness, changes in thyroid hormone metabolism occur, so-called nonthyroidal illness (NTI). NTI has been characterized by a fall of serum T(3) due to decreased extrathyroidal conversion of T(4) into T(3) by liver type 1 deiodinase (D1), without an increase in serum TSH. Type 3 deiodinase (D3) was thought not to play an important role during NTI, but recently it has been shown that D3 activity is up-regulated in liver and skeletal muscle of critically ill patients related to hypoxia. We studied D3 gene expression and activity in liver and muscle/subcutis of mice during illness, which was induced by two different stimuli: bacterial endotoxin (lipopolysaccharide) administration, resulting in an acute systemic response, and a turpentine injection in each hindlimb, resulting in a local sc abscess. Lipopolysaccharide induced a rapid decrease in liver D1 and D3 activity but not skeletal muscle of hindlimb. In contrast, local inflammation induced by turpentine did not decrease liver D1 and D3 activity but increased markedly D3 activity in the muscle/subcutis sample containing the abscess, associated with strongly increased IL-1beta and IL-6 mRNA expression. Inflammatory cells, surrounding the abscess showed D3 and T(3)-transporter monocarboxylate transporter-8 immunoreactivity, whereas muscle cells did not show any immunoreactivity. In conclusion, local inflammation strongly induces D3 activity in inflammatory cells, especially in invading polymorphonuclear granulocytes, suggesting enhanced local degradation of T(3).

Abscess↗
PubMed2000

Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract.

Estrogens induce pronounced structural and functional changes in male accessory sex glands and the lower urinary tract in both sexes, but the exact mechanisms of estrogen action are not fully understood. This study was undertaken to localise the tissue cell types that express estrogen receptor in adult rats, and to determine the receptor subtype (ERalpha and ERbeta) in order to identify sites that may respond directly to estrogens. In the male accessory sex glands (seminal vesicles, prostatic lobes and ampullary glands), ERbeta mRNA and protein were strongly expressed in the epithelium but not in the stroma, while ERalpha mRNA was present only in the fibromuscular tissue surrounding the prostatic collecting ducts in the posterior periurethral region and in ampullary gland stroma. In the epithelium of the urinary bladder and urethra of both sexes, high level of ERbeta mRNA and protein, but no ERalpha mRNA, was detected. The connective tissue in urinary bladder of both males and females, as well as that in prostatic urethra in males expressed ERalpha mRNA. The neural cells in the autonomic ganglia of the prostatic plexus were strongly positive for ERbeta mRNA, but were completely devoid of ERalpha. We conclude that ERbeta is the predominant ER subtype in the epithelium of adult male rat accessory sex glands and the lower urinary tract of both males and females, as well as in the prostatic neural plexus regulating the function of the lower urinary tract in males, while ERalpha is present only in the stromal compartment of distinct sites. These results indicate that in these tissues in intact adults there are multiple targets for direct estrogen action. Furthermore, the differential or complementary expression of the two ER subtypes suggests that they may have specific functions, and may explain the complex structural and functional changes induced by estrogens.

Animals↗
PubMed2000

Ligand-, cell-, and estrogen receptor subtype (alpha/beta)-dependent activation at GC-rich (Sp1) promoter elements.

17beta-Estradiol (E2) induces expression of several genes via estrogen receptor (ER)-Sp1 protein interactions with GC-rich promoter elements in which Sp1 but not ER binds DNA. This study reports the ligand- and cell context-dependent ER(alpha)/Sp1 and ER(beta)/Sp1 action using an E2-responsive construct (pSp1) containing a GC-rich promoter. Both ER(alpha) and ER(beta) proteins physically interact with Sp1 (coimmunoprecipitation) and preferentially bind to the C-terminal region of this protein in pull-down assays. E2- and antiestrogen-dependent transcriptional activation of ER(alpha)/Sp1 was observed in MCF-7, MDA-MB-231, and LnCaP cells, but not in HeLa cells. E2 did not affect or significantly decrease ER(beta)/Sp1 action, and antiestrogens had minimal effects in the same 4 cell lines. Exchange of activation function-1 (AF-1) domains of ER subtypes gave chimeric ER(alpha/beta) (AF-1alpha/AF-2beta) and ER(beta/alpha) (AF-1beta/AF-2alpha) proteins that resembled wild-type ER (alpha or beta) in terms of physical association with Sp1 protein. Transcriptional activation studies with chimeric ER(beta/alpha) and ER(alpha/beta) showed that only ER(alpha/beta) can activate transcription from an Sp1 element, not ER(beta/alpha). This indicates that the AF-1 domain from ER(alpha) is responsible for activation at an Sp1 element, independent of ER subtype context. In order to further characterize this observation, deletion constructs in the AF-1 domain of both ER(alpha) and ER(alpha/beta) were made, and transactivation studies indicated that the region between amino acids 79 and 117 of this domain is important for activation at an Sp1 element.

Cloning, Molecular↗
PubMed2000

Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract.

Estrogens induce pronounced structural and functional changes in male accessory sex glands and the lower urinary tract in both sexes, but the exact mechanisms of estrogen action are not fully understood. This study was undertaken to localise the tissue cell types that express estrogen receptor in adult rats, and to determine the receptor subtype (ER alpha and ER beta) in order to identify sites that may respond directly to estrogens. In the male accessory sex glands (seminal vesicles, prostatic lobes and ampullary glands), ER beta mRNA and protein were strongly expressed in the epithelium but not in the stroma, while ER alpha mRNA was present only in the fibromuscular tissue surrounding the prostatic collecting ducts in the posterior periurethral region and in ampullary gland stroma. In the epithelium of the urinary bladder and urethra of both sexes, high level of ER beta mRNA and protein, but no ER alpha mRNA, was detected. The connective tissue in urinary bladder of both males and females, as well as that in prostatic urethra in males expressed ER alpha mRNA. The neural cells in the autonomic ganglia of the prostatic plexus were strongly positive for ER beta mRNA, but were completely devoid of ER alpha. We conclude that ER beta is the predominant ER subtype in the epithelium of adult male rat accessory sex glands and the lower urinary tract of both males and females, as well as in the prostatic neural plexus regulating the function of the lower urinary tract in males, while ER alpha is present only in the stromal compartment of distinct sites. These results indicate that in these tissues in intact adults there are multiple targets for direct estrogen action. Furthermore, the differential or complementary expression of the two ER subtypes suggests that they may have specific functions, and may explain the complex structural and functional changes induced by estrogens.

Adolescent↗
PubMed1998

Estrogen receptor-beta messenger ribonucleic acid ontogeny in the prostate of normal and neonatally estrogenized rats.

Neonatal exposure to estrogens permanently alters rat prostate growth and epithelial differentiation leading to prostatic dysplasia on aging. The effects are lobe-specific, with the greatest response observed in the ventral lobe. Recently, a novel estrogen receptor (ER) complementary DNA was cloned from the rat prostate and termed ER-beta (ER beta) due to its high homology with the classical ER alpha. The protein possesses high affinity for 17beta-estradiol, indicating that ER beta is an alternate molecule for mediating estrogenic effects. Importantly, ER beta messenger RNA (mRNA) was localized to rat prostatic epithelial cells, which contrasts with the stromal localization of ER alpha in the rat prostate. The present study was undertaken to determine the ontogeny of ER beta mRNA expression in the rat prostate lobes and to examine the effects of early estrogen exposure on prostatic ER beta expression. Male rat pups were given 25 microg estradiol or oil on days 1, 3, and 5; were killed on day 1, 3 (oils only), 6, 10, 30, or 90; and prostate lobes were frozen. Longitudinal sections were processed for in situ hybridization using an 35S-labeled antisense mRNA probe corresponding to a 400-bp EcoRI-AccI fragment in the 5' untranslated region of rat ER beta complementary DNA. Image analysis was used to quantitate silver grains. In addition, total RNA was isolated from the ventral prostate (VP) and used for semiquantitative RT-PCR. Results from in situ hybridization revealed that at birth, ER beta was equivalently expressed at low levels in both mesenchymal and epithelial cells in oil-treated rats. From day 1 onwards, expression in all stromal cells slowly and significantly declined, so that in the control adult prostate, stromal ER beta mRNA was slightly above background. In the oil-treated control rats, epithelial ER beta mRNA increased to moderate levels between days 6-10 in the VP and days 10-15 in the dorsal and lateral lobes as cells began differentiation and ducts lumenized. A further significant increase in ER beta message was observed at day 30, which indicates that full epithelial ER beta expression may require the completion of functional differentiation. By day 90, expression levels were maximal and similar between the lobes. RT-PCR substantiated this developmental increase in ER beta between days 1-90. Neonatal exposure to estrogens did not have an immediate effect on prostatic ER beta mRNA levels as determined by in situ hybridization and RT-PCR. However, the marked increase in epithelial cell expression at day 30 observed in the control VP was dampened in the VP of animals exposed neonatally to estrogens. By day 90, the VP of estrogenized rats possessed low ER beta message levels compared with the high expression in oil controls. In contrast, the dorsal and lateral lobes of neonatally estrogenized rats possessed high levels of ER beta mRNA at day 90, equivalent to controls. The present data demonstrate that ER beta mRNA expression in the rat prostate is developmentally regulated, and that neonatal estrogen can affect this expression in the adult VP. Because the effect of neonatal estrogens was not immediate, the data imply that early estrogen exposure may not directly autoregulate ER beta expression, and suggests that the adult effects on ER beta mRNA expression may be indirect. The differences in ER beta mRNA imprinting in the separate lobes may account for or reflect the lobe-specific neonatal estrogen imprints previously observed in the rat prostate.

Age Factors↗
PubMed1989

Chronic nonspecific duodenitis. A multiple biopsy study of the duodenal bulb in health and disease.

A clinical, endoscopic and histopathologic study on chronic nonspecific duodenitis was performed in 174 subjects, 124 patients (control patients, patients with gastric or duodenal ulcer and nonulcer dyspepsia) and 50 healthy volunteers without clinical history of gastro-intestinal disease. Chronic nonspecific duodenitis was found in 6 healthy volunteers (12%), 5 control patients (7%), one gastric ulcer patient (7%), all duodenal ulcer patients and in 15 patients with nonulcer dyspepsia (83%). Chronic non-specific duodenitis is a focal process affecting the duodenal bulb. It can be missed when only one biopsy is studied. Superficial gastric metaplasia was directly correlated to gastric acid secretion and was found in 32 healthy volunteers (64%), 23 control patients (34%), six gastric ulcer patients (43%), 20 duodenal ulcer patients (20%) and in 17 patients with nonulcer dyspepsia (94%). This study suggests that chronic nonspecific duodenitis is a stage of duodenal ulcer disease.

Adult↗
PubMed1980

HLA antigen distribution and HLA haplotype segregation in Crohn's disease.

A study of the HLA-A, -B, -C, and -DR antigens in patients with Crohn's disease and controls did not reveal a significant strong association with a particular HLA antigens. A segregation analysis of parental HLA haplotypes in nine families with at least two children suffering from Crohn's disease did not show a significant deviation from the expected Mendelian segregation.

Crohn Disease↗
PubMed1978

Gastric and duodenal mucosa in 'healthy' individuals. An endoscopic and histopathological study of 50 volunteers.

The results of histological and immunohistochemical examination of gastric and duodenal biopsy specimens from 50 volunteers without a clinical history of gastrointestinal disease are reported. Multiple specimens of tissue from standard sites in the stomach and duodenum were carefully orientated, and serially sectioned for examination by light microscopy and for immunohistochemical characterisation of plasma cells within the lamina propria. The antrum and fundus were normal in 32 of the 50 subjects but the other 18 showed histopathological evidence of gastritis in either the antrum or fundus. The latter appeared to be age-related. There was considerable variation in the appearance of the surface epithelium of the duodenum within as well as among individual subjects. Superficial gastric metaplasia in one or more biopsy specimens from the duodenal bulb was found in 64% of individuals. Histopathological examination of the duodenum revealed signs of chronic inflammation in 12% of the subjects. In two individuals there was active inflammation but in only one of these was the diagnosis made on endoscopic appearances. Histological criteria important for the diagnosis of duodenitis are discussed. The number of plasma cells in different biopsy specimens from subjects not showing histological signs of inflammation was variable. The ratio IgA:IgG:IgM producing plasma cells was remarkably constant from subject to subject as well as from specimen to specimen.

Adult↗
PubMed1977

The influence of fixation on immunoperoxidase staining of plasmacells in paraffin sections of intestinal biopsy specimens.

The influence of different fixation methods on the results of immunoperoxydase staining of immunoglobulin and gastrin producing cells in gastric and duodenal mucosa was investigated. An indirect method was used on paraffin sections. It appeared that that fixatives containing sublimate gave the most consistent results, a sublimate-formaldehyde mixture being the best.

Fixatives↗