[Present state of endocrinology in the Czech Republic].
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Czech Republic↗
Biomedical subjects
V Schreiber
Publications and source records attributed to V Schreiber.
[Laparoscopic Janeway gastrostomy: an advantageous solution for self-sufficient enteral feeding].
INTRODUCTION: Laparoscopic gastrostomy according to Janeway (LGJ) is an alternative to percutaneous gastrostomy techniques. METHODS: A series of 10 LGJ is reported. The laparoscopic technique involves an isoperistaltic tube of 6-7 cm of length and 10-12 mm of diameter is created by 2 applications of linear stapling and cutting device. The tube is led out, opened and fixed to the fascial and cutaneous planes and a Foley catheter is inserted. RESULTS: Mean operation time was 35 minutes. There was no complication. The LGJ was indicated in 9 patients with tumour of the pharynx and 1 patient with encephalopathy. CONCLUSION: The main drawback of the LGJ is the need of general anaesthesia. The main advantage is the creation by minimal invasive surgery of a permanent gastrostomy equipped with a removable catheter easily changeable by non specialized health professionals, and even by the patient himself.
Adolescent↗
[Two 150 years anniversaries: Claude Bernard's internal environment and Addison disease].
In 2005 two 150 years anniversaries, which essentially influenced the development of modern medicine will be celebrated. French physiologist Claude Bernard from College de France published his work "Lectures on Experimental Physiology, applied to medicine" and British medical doctor T. Addison described insufficiency of adrenal cortex, today known as Addison disease.
Addison Disease↗
Cytoreductive surgery and intraperitoneal chemohyperthermia for peritoneal carcinomatosis arising from gastric cancer.
HYPOTHESIS: The most common cause of palliative resection and recurrence in gastric cancer is peritoneal seeding. This study evaluates the efficacy of intraperitoneal chemohyperthermia after cytoreductive surgery in patients with peritoneal carcinomatosis arising from gastric cancer. DESIGN: Prospective clinical trial. SETTING: Surgical department at a university academic hospital. PATIENTS: Forty-nine consecutive patients with peritoneal carcinomatosis treated between January 1, 1989, and February 29, 2000. INTERVENTIONS: All patients underwent intraperitoneal chemohyperthermia with mitomycin C (40-60 mg); 21 patients had previously undergone extensive cytoreductive surgery. MAIN OUTCOME MEASURES: Clinicopathologic factors that affect overall survival rates. RESULTS: With median follow-up of 99 months, overall median survival was 10.3 months. Two factors were significant independent predictors of survival by multivariate analysis: preoperative ascites (P =.04) and completeness of cancer resection (CCR) by cytoreductive surgery (P<.001). Median survival was 21.3 months for patients with CCR-0 (macroscopic complete resection) or CCR-1 (diameter of residual nodules <5 mm) and 6.1 months for patients with CCR-2 (diameter of residual nodules >5 mm) (P<.001). Four patients survived longer than 5 years. CONCLUSIONS: An aggressive management strategy combining intraperitoneal chemohyperthermia with cytoreductive surgery is effective for patients with peritoneal carcinomatosis arising from gastric cancer. In highly selected patients (good general status, resectable primary tumor, resectable peritoneal carcinomatosis), this therapy may result in long-term survival.
Adult↗
Intraperitoneal chemohyperthermia and attempted cytoreductive surgery in patients with peritoneal carcinomatosis of colorectal origin.
BACKGROUND: Colorectal cancer with peritoneal carcinomatosis is usually considered incurable. The purpose of this study was to evaluate the efficacy of intraperitoneal chemohyperthermia (IPCH) following cytoreductive surgery in patients with colorectal carcinomatosis. METHODS: Between January 1989 and August 2002, 53 patients (mean age 48.6 years) were treated by IPCH with mitomycin C. IPCH was performed in 34 patients following extensive cytoreductive surgery (more than two peritonectomy procedures). Five patients underwent two operations and one patient three operations. RESULTS: Operative morbidity and mortality rates were 23 and 4 per cent respectively. At a median follow-up of 59.5 months, the overall median survival was 12.8 months. The extent of carcinomatosis, completeness of cytoreduction and histological differentiation were significant prognostic indicators by univariate analysis. The median survival was 32.9 months for patients whose resection was classified as completeness of cancer resection (CCR) 0 (complete cytoreduction), 12.5 months for those whose operation was CCR-1 (diameter of residual nodules 5 mm or less) and 8.1 months for patients who had a CCR-2 resection (diameter of residual nodules more than 5 mm) (P < 0.001). Completeness of cytoreduction was the only significant independent predictor of survival by multivariate analysis. CONCLUSION: IPCH combined with cytoreductive surgery seems to be an effective therapy for carefully selected patients with carcinomatosis from colorectal cancer. This strategy was most effective in patients with carcinomatosis of limited tumour volume or when cytoreductive surgery allowed sufficient downstaging (residual tumour nodules smaller than 5 mm).
Adult↗
Ghrelin -- a new endogenous growth hormone secretagogue.
Ghrelin is a new endogenous peptide, discovered in 1999 by Kojima et al., as the result of a search for an endogenous ligand for an orphan receptor of known structure and function. Ghrelin is composed of 28 amino acids and is produced mostly by cells of the stomach, hypothalamus, and hypophysis, but it has also been detected in other tissues. Its discovery is related to the development of a new hypothesis regarding the regulation of growth hormone secretion. It is an antagonist of somatostatin. Ghrelin activates the release of growth hormone from the somatotrophic cells of the hypophysis. It participates in the regulation of energy homeostasis, increases food intake, decreases energy output and exerts a lipogenetic effect. Its metabolic effects do not depend on the GH/IGF-I system, but are mediated by the NPY/Y1 and AGRP receptor system. Ghrelin influences the secretion and motility of the gastrointestinal tract, especially the stomach. The presence of ghrelin and its receptors has also been demonstrated in many other tissues. Its function in these tissues has not yet been studied, thus providing many possibilities for further research.
Animals↗
The role of dopamine in methylene blue-mediated inhibition of estradiol benzoate-induced anterior pituitary hyperplasia in rats.
Recently, we demonstrated that methylene blue partially inhibited estradiol-benzoate-induced anterior pituitary hyperplasia in rats. Since central dopaminergic systems participate in the regulation of estrogen-induced anterior pituitary growth and tumor transformation, this study examined whether a 3-week treatment with methylene blue could affect anterior pituitary levels of dopamine (DA), dihydroxyphenylalanine (DOPA), and dihydroxyphenylacetic acid and dopamine (D-2) receptors in male rats. Compared to controls, methylene blue significantly decreased anterior pituitary weight, increased basal anterior pituitary DA levels, and inhibited estradiol benzoate-induced decreases in anterior pituitary DA concentrations. Furthermore, we found that methylene blue alone decreased anterior pituitary D-2 receptor number. Methylene blue given in combination with estradiol benzoate partially inhibited estradiol benzoate-induced anterior pituitary growth and estradiol benzoate-induced increases in D-2 receptor number. Estradiol benzoate-treated rats had significantly lower anterior pituitary DOPA accumulation after intraperitoneal administration of 3,4-hydroxybenzyl-hydrazine dihydrochloride (NSD-1015), an irreversible inhibitor of L-aromatic amino acid decarboxylase whereas methylene blue did not affect anterior pituitary DOPA accumulation when compared to controls. Methylene blue decreased anterior pituitary prolactin levels and inhibited increases in anterior pituitary prolactin after estradiol benzoate administration. The present results suggest that anterior pituitary DA may play an important role in estrogen-induced anterior pituitary hyperplasia and tumor formation and that antioxidant drugs such as methylene blue may attenuate estrogen-induced pituitary growth. This may occur via increases in anterior pituitary DA levels associated with down-regulation of anterior pituitary D-2 receptors.
3,4-Dihydroxyphenylacetic Acid↗
[Endocrinology 1999-2000].
Long-lasting problem on the differentiation of adenohypophyseal cell, which prepares them for their specific tasks (somatotropic, lactotropic ect.), becomes elucidated after recognition of the differentiational effect of transcription factor Pit-1. Expression of that factor in somatotrops results in STH secretion, contrary to lactotrops producing prolactin. Subclinical hypothyreosis (increased TSH with normal T3 and T4) endangers vessel not because of hypercholesterolemia, but because of changes in the dynamics of the blood flow. The idea of cardiotropic effect of thyroidal hormones is supported by the finding that administration of trijodthyronine to children after the surgical correction of heart malformations (cardiopulmonary bypass) improves myocardial function--it elevates cardiac output and decreases requirements on the intensive care. Receptors for hormones in tissues are flexible, they can be "heterooligomers" for dopamine and somatostatin. Mutations of mineralocorticoid receptor may cause hypertension in pregnancy and progesterone receptors have several isoforms. Receptors can be also activated by short exposition to a hormone. Glucocorticoids have probably also membrane receptors. Diabetes mellitus "type I" needn't to be immunogenic and DM type II not only results from down-regulation of receptors and subsequent insulin resistance, but it can be also caused by defects in insulin secretion. Insulin has receptors in the brain and participates in the appetite regulation. The attempt to use "desensibilisation" by peroraly administered insulin in patients with immunogenic DM had no effect. Stress affects memory mechanisms, heavy emotional stress during gravidity can bring congenital malformations. The decrease of mental functions in aged women depends on the level of free estradiol (the fraction, which is not bound to plasma proteins). Activation of dopaminergic neurons can be achieved by neurotropic growth factors. Nesiritide is a recombinant brain natriuretic hormone successfully tested in heart failure. The role of leptin in the appetite regulation in man is still not clear, other signalling molecules may have also an effect, e.g., ghrelin, which primarily stimulates STH secretion and brings about weight gain. Sildenafil influences nitrergic neurons elsewhere than in penis, for example it has positive effects in patients with oesophageal achalasia.
Endocrine System Diseases↗
A bidirectional promoter connects the poly(ADP-ribose) polymerase 2 (PARP-2) gene to the gene for RNase P RNA. structure and expression of the mouse PARP-2 gene.
Poly(ADP-ribose) polymerase 2 (PARP-2) is a DNA damage-dependent enzyme that belongs to a growing family of enzymes seemingly involved in genome protection. To gain insight into the physiological role of PARP-2 and to investigate mechanisms of PARP-2 gene regulation, we cloned and characterized the murine PARP-2 gene. The PARP-2 gene consists of 16 exons and 15 introns spanning about 13 kilobase pairs. Interestingly, the PARP-2 gene lies head to head with the gene encoding the mouse RNase P RNA subunit. The distance between the transcription start sites of the PARP-2 and RNase P RNA genes is 114 base pairs. This suggested that regulation of the expression of both genes may be coordinated through a bi-directional promoter. The PARP-2/RNase P RNA gene organization is conserved in the human. To our knowledge, this is the first report of a RNA polymerase II gene and an RNA polymerase III gene sharing the same promoter region and potentially the same transcriptional control elements. Reporter gene constructs showed that the 113-base pair intergenic region was indeed sufficient for the expression of both genes and revealed the importance of both the TATA and the DSE/Oct-1 expression control elements for the PARP-2 gene transcription. The expression of both genes is clearly independently regulated. PARP-2 is expressed only in certain tissues, and RNase P RNA is expressed in all tissues. This suggests that both genes may be subjected to multiple levels of control and may be regulated by different factors in different cellular contexts.
Animals↗
[Jugular lymph node metastasis of papillary thyroid gland carcinoma 10 years later].
We present a patient with occult papillary thyroid carcinoma, in whom a single nodal metastasis had been excised. Ten years later a nodal recurrence was diagnosed by ultrasound and fine needle aspiration cytology. The diagnosis of recurrence was erroneous, and we discuss the differential diagnostic problems, the natural course, and the adequate treatment of occult papillary microcarcinoma.
Carcinoma, Papillary↗
Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1.
In mammalian cells, damaged bases in DNA are corrected by the base excision repair pathway which is divided into two distinct pathways depending on the length of the resynthesized patch, replacement of one nucleotide for short-patch repair, and resynthesis of several nucleotides for long-patch repair. The involvement of poly(ADP-ribose) polymerase-1 (PARP-1) in both pathways has been investigated by using PARP-1-deficient cell extracts to repair single abasic sites derived from uracil or 8-oxoguanine located in a double-stranded circular plasmid. For both lesions, PARP-1-deficient cell extracts were about half as efficient as wild-type cells at the polymerization step of the short-patch repair synthesis, but were highly inefficient at the long-patch repair. We provided evidence that PARP-1 constitutively interacts with DNA polymerase beta. Using cell-free extracts from mouse embryonic cells deficient in DNA polymerase beta, we demonstrated that DNA polymerase beta is involved in the repair of uracil-derived AP sites via both the short and the long-patch repair pathways. When both PARP-1 and DNA polymerase beta were absent, the two repair pathways were dramatically affected, indicating that base excision repair was highly inefficient. These results show that PARP-1 is an active player in DNA base excision repair.
3T3 Cells↗
[Endocrinology 1998-1999].
In the cascade hormone--second messenger--cellular G-proteins (GTP binding proteins), impairment can occur also at the last step: Mutant G-proteins may amplify the response (e.g. hypophyseal and thyroid adenomas) or reduce it (pseudohypoparathyreosis, testitoxicosis). Other new group of diseases appears to be anexinopathy: Among anexins belong also lippocortins and impairments occur in the hemocoagulation. "Reverse endocrinology" is a process description when the recognition of receptor (called an "orphan receptor") comes earlier than that of the hormone: Such receptors are known for several steroid hormones, retinoids and eicosanoids and it appears they are important also in the metabolism of cholesterol. A single antigen--glutamic acid decarboxylase (GAD), can cause autoimmune disease as the immuno-dependent diabetes (IDDM). Treatment of the skin T-cell lymphoma by some retinoids can result in hypothyroidism. Retrotransposones are example of the human genome modification with yet unknown clinical manifestations. Hepatocytal growth factor reveals to be the hope for treatment of cirrhosis. Search for effective peroral insulin substitutes is at present based on testing of various metabolites of fungi. Antibodies against TNF (tumor necrosis factor) become tested as "anti-cytokine therapy" in patients with rheumatoid arthritis. Some other suggestions for new ways of treatment is also listed, including the intranasal administration of estradiol.
Endocrine System Diseases↗
A new mechanism for the control of a prokaryotic transcriptional regulator: antagonistic binding of positive and negative effectors.
MalT, the transcriptional activator of the Escherichia coli maltose regulon, self-associates, binds promoter DNA and activates initiation of transcription only in the presence of ATP and maltotriose, the inducer. In vivo studies have revealed that MalT action is negatively controlled by the MalY protein. Using a biochemical approach, we analyse here the mechanism whereby MalY represses MalT activity. We show that MalY inhibits transcription activation by MalT in a purified transcription system. In vitro, a constitutive MalT variant (which is partially active in the absence of maltotriose) is less sensitive than wild-type MalT to repression by MalY, as observed in vivo. We demonstrate that MalY forms a complex with MalT only in the absence of maltotriose and that, conversely, MalY inhibits maltotriose binding by MalT. Together, these results establish that MalY acts directly upon MalT without the help of any factor, and that MalY is a negative effector of MalT competing with the inducer for MalT binding.
Bacterial Proteins↗
Interaction between serum leptin levels and hypothalamo-hypophyseal-thyroid axis in patients with anorexia nervosa.
The main objective of the study was to evaluate the endocrinological picture of anorexia. Serum leptin levels are low in untreated anorexia nervosa (AN), but studies of the exact relationship between leptin, body weight and hormones of hypothalamo-hypophyseal-thyroid axis and the impact of refeeding in anorectics are limited. The sample consistent of 15 patients with anorexia nervosa before and 1 month after partial weight recovery, and 15 age-matched control subjects. The body mass index (BMI), leptin, plasma neuropeptide Y (NPY), serotonin, thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) in serum were evaluated for each subject. The mean serum levels of leptin, T4, and T3 were significantly lower before weight recovery in 15 patients with AN than they were in control subjects. After partial weight recovery, basal T3 levels were unchanged and significantly lower than in controls. Basal T4 was even still more reduced, but we observed significantly elevated ratio of T3/T4 and reduced ratio rT3/T4 of in AN patients after gain recovery, indicating increased conversion of T4 to T3 than to rT3. The levels of serum leptin were low in AN, but after partial weight recovery slightly increased, and correlated with BMI. No differences were observed in serum NPY. Serum levels of IGF-1 and serotonin were lower in AN than in controls before and after partial weight gain. IGF-1 was slightly increased after partial weight gain. We did not find correlation between serum levels of leptin and serum T4. The low serum levels of T3 associated with chronic starvation were thought to be the result of impaired peripheral conversion of T4 to T3. However, decreased levels of T3 were still apparent even after a partial weight gain, and the concentration of T4 was even lower. The diminished serum level of TSH in AN, however, appeared to return to the level of controls. On the basis of these results, we assume that low serum levels of thyroid hormones in AN reflect a dysfunction of the HPT axis in AN patients. It is known that in man serum serotonin levels correlate positively with T3 levels. It is possible that the low serum levels of thyroid hormones in AN subjects result in low serum serotonin and its product, melatonin. While IGF-1 reflects the energy intake of the previous few weeks, the serum leptin concentration reflects the true status of the adipose stores, a fact that has useful clinical implications.
Anorexia Nervosa↗
[Pharmacologic control of hypophyseal tumors: interactions of estrogens, thyroid hormones, growth and anti-growth factors].
Estrogens are involved in anterior pituitary (AP) growth and tumor transformation of AP. Central dopaminergic and noradrenergic systems are probably most important systems in regulation of AP growth. Estrogen-induced AP growth is associated with decreased metabolism of central catecholamines and increased dopaminergic DA-2 receptors. Application of thyroid hormones or methylene blue prevents both estrogen-induced catecholaminergic inhibition and dopamine DA-2 receptors increment in the AP. The alone given methylene blue increases the dopaminergic activity and the binding sites for dopamine. The study of interaction of natural regulators or synthetic compounds with estrogen-induced pituitary growth will be of value to understand better mechanisms of pituitary tumor formation and possibly find new approaches towards treating patients with these tumors.
Animals↗
Self-association of the Escherichia coli transcription activator MalT in the presence of maltotriose and ATP.
MalT, the transcriptional activator of the Escherichia coli maltose regulon, binds the MalT-dependent promoters and activates transcription initiation only in the presence of maltotriose and ATP (or adenylyl imidodiphosphate (AMP-PNP)). Cooperative binding of MalT to the array of cognate sites present in the MalT-dependent promoters suggests that promoter binding involves MalT oligomerization. Gel filtration and sedimentation experiments were used to analyze the quaternary structure of MalT in solution in the absence or presence of maltotriose and/or AMP-PNP, ATP, or ADP. The protein is monomeric in the absence of ligands and in the presence of ADP. In the presence of maltotriose, AMP-PNP, or ATP only, the protein self-associates, but a large fraction of the protein remains monomeric. In the presence of both maltotriose and AMP-PNP (ATP or ADP), the protein is essentially oligomeric, with the difference being that the oligomerization is less favored in the presence of ADP + maltotriose than in the presence of AMP-PNP + maltotriose. We present evidence that the association pathway comprises the following steps: monomers --> dimers --> (MalT)(n) --> aggregates, where 3 </= n </= 6. From these data, we conclude that the role of maltotriose and ATP as positive effectors is to induce the multimerization of MalT, and hence its cooperative binding to the mal promoters.
Adenosine Diphosphate↗
PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase.
Poly(ADP-ribosylation) is a post-translational modification of nuclear proteins in response to DNA damage that activates the base excision repair machinery. Poly(ADP-ribose) polymerase which we will now call PARP-1, has been the only known enzyme of this type for over 30 years. Here, we describe a cDNA encoding a 62-kDa protein that shares considerable homology with the catalytic domain of PARP-1 and also contains a basic DNA-binding domain. We propose to call this enzyme poly(ADP-ribose) polymerase 2 (PARP-2). The PARP-2 gene maps to chromosome 14C1 and 14q11.2 in mouse and human, respectively. Purified recombinant mouse PARP-2 is a damaged DNA-binding protein in vitro and catalyzes the formation of poly(ADP-ribose) polymers in a DNA-dependent manner. PARP-2 displays automodification properties similar to PARP-1. The protein is localized in the nucleus in vivo and may account for the residual poly(ADP-ribose) synthesis observed in PARP-1-deficient cells, treated with alkylating agents or hydrogen peroxide.
3T3 Cells↗