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PubMedDate not supplied

No alterations of serum levels of adrenal and gonadal hormones in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease with a marked preponderance of affected males compared to females of approximately 6 to 1. During the last two decades, this circumstance stimulated several research groups to investigate serum levels of gonadal and adrenal sex hormones. From available results of cross-sectional studies, there seems to be no particular defect in secretion or production of adrenal, gonadal, and pituitary hormones. This is in striking contrast to diseases such as rheumatoid arthritis and other chronic inflammatory diseases. In the latter diseases, low serum levels of dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), and testosterone have been described in an advanced chronic disease stage, whereas estrogen serum levels remain normal. Although AS is an inflammatory disease with signs of systemic inflammation such as elevated erythrocyte sedimentation rate or increased circulating proinflammatory cytokines, serum levels of adrenal and gonadal androgens are normal. It is unclear whether this can be considered as unexpected. It may be that inflammation does not reach the pituitary, adrenal, and gonadal glands or does not alter the aromatase complex in peripheral tissue. Furthermore, the inflammation-induced changes may be subtle so that only specific endocrine examination of these axes may reveal signs of alterations. In conclusion, current data on sex steroid hormones provide no straightforward explanation for the male predominance in AS. At the moment, there is no rationale to treat AS patients with sex steroid hormones.

Adrenal Cortex Hormones↗
PubMed2004

Spectrum of HNF1A and GCK mutations in Canadian families with maturity-onset diabetes of the young (MODY).

PURPOSE: Maturity-onset diabetes of the young (MODY) is a subtype of type 2 diabetes characterized by autosomal-dominant inheritance and early onset. The pathophysiology of MODY is primarily defective insulin secretion resulting from mutations in at least 6 different genes. Most affected patients harbour mutations in either GCK (encoding glucokinase, also called MODY2) and HNF1A (encoding hepatic nuclear factor-1alpha, also called MODY3). We studied Canadian probands to determine if they had mutations in MODY2 or MODY3 genes. METHOD: We used genomic DNA sequencing of probands from 9 previously unreported Canadian MODY families. RESULTS: Five MODY probands had mutations in HNF1A, of which 4 were novel (namely IVS5-1delTAG, E275fsdelGAAG, F268S and L44fsdelC) and 4 had mutations in GCK, of which 2 were novel (E237K and L324P). These mutations expand the spectrum of MODY mutations and bring the total number of Canadian MODY families that have been molecularly defined in our laboratory to 15 (8 MODY3 and 7 MODY2). CONCLUSION: Because of the growing evidence that molecular diagnosis may affect prognosis and treatment, this information may be important in future for Canadian MODY families and their physicians.

Adolescent↗
PubMed1977

[Male pseudohermaphroditism. Etiologic diagnosis. 2].

The cause of male pseudohermaphroditism : polydystrophy, gonadal dysplasia, agenesis or precocious abiotrophy of Leydig cells, defect of testicular stimulation by foetal hypophysis, testosterone, biosynthesis abnormalities 5 varieties of which are identified, 5 alpha reductase defect, testosterone or dihydrotestosterone insenstivity complete and incomplete forms, defect of secretion or action of Mullerian ducts inhibitor can be found in the majority of cases by clinical and para-clinical analysis. Practical management results from this diagnosis.

Adolescent↗
PubMed1990

Effects of magnesium on skeletal metabolism.

Magnesium (Mg) makes up 0.5-1% of bone ash and is therefore not a trace element in the skeleton. Mg influences both mineral and matrix metabolism in bone by a combination of effects on hormones and other factors that regulate skeletal and mineral metabolism, and by direct effects on bone itself. The skeletal content of Mg is very variable both between and within species, and reported values range between 150 and 440 mmol/kg ash weight (AW). Dietary Mg has a direct influence and age an inverse influence on skeletal Mg content. It is unclear whether skeletal Mg content varies from region to region. In humans, reported values cluster around the 200 mmol/kg AW level, 30-40% lower than most rat data. Human iliac crest cortical bone has 10-20% less Mg per unit weight than iliac crest trabecular bone. Mg depletion adversely affects all phases of skeletal metabolism. In the rat, cessation of bone growth is noted with a decrease in both osteoblast and osteoblast activity, decreased bone formation, osteopenia, increased fragility and development of a form of 'aplastic bone disease'. The epiphyseal growth plate is thinned and the percent ash weight of the growth plate is increased, possibly due to enhanced crystallization of bone salt under conditions of Mg depletion. In contrast, in chicks and in rats with severe Mg deficiency, these 'antianabolic' effects are not observed but instead, predominant inhibition of bone resorption occurs with increased cortical thickness rather than osteopenia, and the occasional development of subperiosteal hyperplasia or of fibrous tumors of the periosteum. It is probable that this unusual response under conditions of severe Mg deficiency is in part an indirect effect secondary to a defect in secretion and/or skeletal responsiveness to parathyroid hormone (PTH) and vitamin D metabolites. Mg excess also has adverse biologic effects on bone. Crystallization of bone salt is severely impaired and an osteomalacia-like picture may be produced with decreased osteoblastic activity, widened growth plates, excessive osteoid seams and short, thickened bones. In some studies, especially in mice, Mg excess stimulates bone resorption, independently of PTH. The role of Mg deficiency and excess in human skeletal conditions requires more extensive investigation. Bone Mg is uniformly increased in renal insufficiency and may play a role in renal osteodystrophy since improvement has been noted in the osteomalacic component by normalizing the serum Mg. Decreased bone Mg has been reported in alcoholic patients, diabetes and in osteoporosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

The clinical use of oral sulfonylureas in the management of non-insulin dependent diabetes mellitus (NIDDM).

Eighty percent of Americans afflicted with diabetes mellitus have Type II or non-insulin dependent diabetes mellitus (NIDDM). Impaired or defective insulin secretion and insulin resistance are universal pathophysiologic findings. Management involves attention to diet, exercise, and commonly the use of insulin and/or oral sulfonylureas. Currently there are six marketed first and second generation agents available for use in the United States. Although the newer agents are more potent, they all share a similar mechanism of action. These agents can only be effective if the patient has retained beta cell secretory function. Pharmacokinetic and pharmacodynamic differences may make the newer agents, glyburide and glipizide, preferred in the management of Type II diabetes mellitus. The combined use of insulin and oral sulfonylureas may be useful for the patient exhibiting persistent fasting hyperglycemia despite maximal oral drug therapy. The precise role for combination therapy and optimal patient characteristics awaits further study.

Administration, Oral↗
PubMed1989

[Treatment of functional infertility, caused by luteal deficiency, with pulsatile perfusion of gonadotropin releasing hormone].

The prehistory of cyclical development of corpus luteum goes back to early follicular phase. Reduced secretion or defective rhythm of gonadotropin releasing hormone (GnRH) can later cause unperfect ovulation or corpus luteum insufficiency. The authors carried out a low-dose pulsatory GnRH-treatment on eight patients with luteal insufficiency, who were earlier treated unsuccessfully with other ovulation-inductive methods (clomiphene, hCG, bromocryptin). As a result of GnRH administration hypertherm period expanded, plasma progesteron level increased and three pregnancies occurred. In their opinion exogenic administration of GnRH results in an improvement of luteal function.

Corpus Luteum Hormones↗
PubMed1988

Defective dopaminergic regulation of prolactin secretion in patients with hyperprolactinemia.

In order to evaluate the dopaminergic control of the lactotroph, we examined the plasma prolactin response to metoclopramide (a dopamine receptor blocker, 10 mg iv bolus) and to dopamine (1 microgram/Kg/min iv infusion for 120 min) in 52 hyperprolactinemic female patients and 19 healthy volunteer women. Three diagnostic categories were included: "idiopathic" hyperprolactinemia (21), microadenoma (24), and macroadenoma (7). Patients from all groups showed a marked blunting of the prolactin response to metoclopramide as compared to the prolactin rise in normal women (p less than 0.001). However, normal responses were observed in 8 patients with idiopathic hyperprolactinemia and in one patient with adenoma. The magnitude of the prolactin response to metoclopramide (percent of baseline level) correlated negatively with the level of basal prolactin in each group except for macroadenoma patients. Dopamine infusion significantly (p = 0.015) reduced the mean plasma prolactin levels in hyperprolactinemic patients and normal women. However, patients with idiopathic hyperprolactinemia were hyposensitive to dopamine (p less than 0.05). Furthermore, microadenoma patients were less responsive to dopamine suppression than were the patients with macroadenoma (p less than 0.05). The results indicate the presence of a relative resistance to dopamine in patients with idiopathic hyperprolactinemia and in patients with microadenoma. They also suggest that in these patients, the decrease in prolactin response to metoclopramide may be explained by the relative refractoriness to endogenous dopamine.

Adenoma↗
PubMed1988

Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome.

The HIE syndrome is a rare disorder characterized by extremely high serum IgE levels; recurrent serious infections, primarily involving the skin and sinopulmonary tract; and chronic eczematoid dermatitis dating from early infancy. The most common organisms that infect these patients are S. aureus and C. albicans. In addition, they have increased susceptibility to infection with H. influenzae, S. pneumoniae, enteric gram-negative rods, herpesviruses, and a variety of fungal organisms. The infections are frequently deep-seated, with abscess formation in the case of skin infection and pneumatocele formation in the case of pneumonias. Osteomyelitis, septic arthritis, and visceral abscesses are also seen but less frequently. Associated features of this syndrome are coarse facies, growth retardation, osteoporosis, keratoconjunctivitis, and eosinophilia. The immunologic basis of the HIE syndrome is still speculative. It is believed that the elevated IgE levels reflect a T-cell imbalance characterized by T-cell activation and a deficiency of suppressor T cells to inhibit IgE production. The propensity for recurrent infection may be related to a unique abnormality in the humoral immune system: excessive production of IgE directed to S. aureus and other infectious organisms with a concurrent deficit in their ability to synthesize protective IgG antibody against the same organisms. The fluctuating neutrophil chemotactic abnormality found in these patients may be secondary to the underlying T-cell defect with secretion of chemotactic inhibitor substances from mononuclear cells. Alternatively, the interaction of infectious agents with IgE on the surface of Fc epsilon R-bearing immune effector cells results in the release of inflammatory mediators that impair local host immune response. Activation of the immune system may also contribute to the associated features in this syndrome via the secretion of mediators that regulate connective tissue production and bone mineralization. Further studies will be needed before we completely understand the pathogenesis of HIE syndrome. Therapy primarily involves use of prophylactic anti-S. aureus antibiotics and the use of intravenous antibiotics, antifungal agents, or antiviral agents during acute infections. Surgical drainage or resection of deep-seated infections are frequently indicated. In patients who do not respond to conservative management, there may be a role for intravenous gammaglobulin and/or plasmapheresis.

Antibody Formation↗
PubMed1971

Mechanisms of gene action in disorders of the endocrine glands.

Hereditary endocrinopathies may result from a wide variety of distinct pathogenetic mechanisms, including: abnormalities in hormonal structure, synthesis or secretion; neurostimulatory defects; biosynthetic enzyme deficiencies; developmental malformations; degenerative disorders; hormonal antagonists; peripheral unresponsiveness to hormonal action; and glandular hyperplasia and neoplasia. The majority of these defects can result in the same phenotype: ie, an endocrine deficiency state. Hormonal deficiency states are usually recessively inherited, whereas those involving glandular hyperplasia or neoplasia are usually dominantly inherited.

Endocrine System Diseases↗
PubMed1995

Transdermal nicotine and gastroesophageal reflux.

OBJECTIVES: Studies have shown that cigarette smoking acutely increases gastroesophageal reflux (GER). Patients prescribed transdermal nicotine often complain of pyrosis. The purpose of this study was to ascertain the effect of transdermal nicotine on GER. METHODS: Twenty volunteers (12 smokers and eight nonsmokers) were studied with a 24-h pH/motility apparatus while wearing a placebo patch for 24 h and a nicotine patch for a subsequent 24-h period. Each subject completed the entire 48-h monitoring session. RESULTS: A significant increase in the total acid score (p = 0.005), duration of acid exposure (p = 0.010), and supine duration of acid exposure (p = 0.004) were noted with transdermal nicotine versus placebo. There were no significant differences in esophageal motility after transdermal nicotine. CONCLUSIONS: Whether enhanced supine reflux is related to lower esophageal sphincter dysfunction, increased acid secretion, or defective acid clearance is not clear. Nonetheless, it may be prudent to recommend removal of the transdermal nicotine patch at night in the patient with symptomatic nocturnal GERD.

Administration, Cutaneous↗
PubMed1994

[Anemia and erythropoietin level in some hematology malignancies].

UNLABELLED: Pathogenesis of anemia in patients with myeloma, low grade lymphoma and acute leukaemia was the aim of the study. Erythropoietin (Epo) serum level was detected according to ELISA test. Significant increase of Epo serum level in 13 myeloma and 30 low grade lymphoma patients was found. In 21 acute leukemia cases the Epo serum level was significantly increased (disproportional to Hb concentration). CONCLUSION: in the studied myeloma and low grade lymphoma patients anemia did not depend on defective Epo secretion. Significant increase of Epo serum level in acute leukaemia, strongly suggested additional stimulation mechanism for hormone synthesis. Further studies of this mechanism are needed.

Adult↗
PubMed1994

[A pedigree with maternally transmitted diabetes mellitus, deafness and cardiomyopathy].

A pedigree with maternally transmitted diabetes mellitus, deafness, and cardiomyopathy is described. A A-->G mutation at nucleotide pair 3243 in mitochondrial gene was detected by Apa I digestion of PCR amplified genomic DNA from 3 brothers and their mother. The proband, suffering from CHF, showed unique fine granular pattern of hyperechogenic cardiomyopathy as his brother and their mother did. Although he is recently treated with insulin, he was initially NIDDM treated by sulfonylurea. His urinary CPR excretion decreased gradually to as low as less than 10 micrograms/day in these 3 years. The insulin response to oral glucose was decreased in all other family members with the mutation. It is suggested that the defective insulin secretion exists in this family with the mutation and the progressive decrease in insulin secretion might resulted in IDDM in the proband.

Adult↗
PubMed1994

Analysis of Sec 19-1 mutant of Saccharomyces cerevisiae.

Saccharomyces cerevisiae Sec 19-1 cells are secretion mutants defective at 37 degrees C. The cells were analysed in order to ascertain the effect of mutation temperature on cell wall formation. At the restrictive temperature of 37 degrees C, the Sec 19-1 mutants had 37 micrograms/mg N-acetylglucosamine in the wall cells, while the wild type S. cerevisiae showed 84 micrograms/mg hexosamine. The mutants Sec 19-1 showed a maximum activity of chitin synthetase of 0.113 nmoles/min/ml, and the activity increased to 0.33 nmoles/min/ml in the wild type cells. On the other hand, variations of chitin distribution in the wall cells occurred at the restrictive temperature, but changes in actin organization were not evident. The results indicated that the mutation caused variations in the levels of N-acetylglucosamine and chitin synthetase, as well as in cell wall chitin distribution.

Actins↗
PubMed1993

[Passive immunotherapy for treatment of endobronchitis in cystic fibrosis].

Chronic endobronchial infection with Pseudomonas aeruginosa is a major clinical problem in cystic fibrosis, a genetic disorder of epithelial ion transport and mucus secretion. Functional defects in the opsonic antibody response to critical surface antigens of P. aeruginosa, including lipopolysaccharide and mucoid exopolysaccharide (alginate), have been implicated in the initial colonization and/or persistence of infection of the respiratory tract of cystic fibrosis patients with this bacterium. These defects are correctable in vitro with functional opsonic antibodies against P. aeruginosa present in intravenously administered immunoglobulins (ivIg). Moreover, functional opsonic polyclonal and monoclonal antibodies against P. aeruginosa are protective in animal models of chronic pseudomonal endobronchitis. Two pilot studies on passive immunotherapy with ivIg--one with standard ivIg and one with hyperimmune globulin enriched with anti-Pseudomonas lipopolysaccharide antibodies (Psomaglobin N)--have demonstrated safety and short-term efficacy in terms of improved pulmonary function. Multicenter placebo-controlled trials of passive immunotherapy with conventional ivIg and hyperimmune globulin enriched with antibodies against P. aeruginosa alginate are planned in the United States.

Antibodies, Bacterial↗
PubMed1995

The key role of islet dysfunction in type II diabetes mellitus.

Fasting plasma glucose levels are constant from day to day in normal individuals. This constancy is due to a close co-ordination between glucose production by the liver and glucose uptake in peripheral tissues. This review focusses on the key role of the endocrine pancreas alpha- and beta-cells to provide this co-ordination. Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by fasting hyperglycemia. The degree of fasting hyperglycemia, in turn, is correlated with the basal rate of hepatic glucose production. This increased rate of glucose release by the liver results in part from impaired hepatic sensitivity to insulin, but is largely due to reduced insulin secretion and increased glucagon secretion. Though basal immunoreactive insulin and glucagon levels in patients with NIDDM may appear normal when compared to those of healthy individuals, islet function testing at matched glucose levels reveals impairments of basal, steady-state, and stimulated insulin and glucagon secretion due to a reduction in beta-cell secretory capacity and a reduced ability of glucose to suppress glucagon release. The degree of impaired beta-cell responsiveness to glucose is closely related to the degree of fasting hyperglycemia, but in a curvilinear fashion. Thus, islet alpha- and beta-cell function is reduced by more than 50% in NIDDM by the time that clinical fasting hyperglycemia develops (140 mg/dL). The efficiency of glucose uptake by the peripheral tissues is also impaired due to a combination of decreased insulin secretion and defective cellular insulin action.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1996

Two GTPase isoforms, Ypt31p and Ypt32p, are essential for Golgi function in yeast.

In eukaryotic cells, monomeric GTPases of the Ypt/Rab family function as regulators at defined steps of vesicular transport in exo- and endocytosis. Here we report on the isolation and characterization of two genes (YPT31 and YPT32) of the yeast Saccharomyces cerevisiae which encode members of the Ypt family exhibiting >80% sequence identity. Whereas the disruption of one of the two genes was phenotypically neutral, the disruption of both YPT31 and YPT32 led to lethality. Depletion of wild-type Ypt31p or of a short-lived ubiquitin-Ypt31p in a ypt32 null background led to a massive accumulation of Golgi-like membranes, an inhibition of invertase secretion and defects in vacuolar protein maturation. Similar alterations were observed in a conditional-lethal ypt31-1 mutant at 30 min after shift to the non-permissive temperature. According to subcellular fractionation, a significant part of Ypt31p appeared to be located in Golgi-enriched membrane fractions. In accordance with this, indirect immunofluorescence using affinity-purified anti-Ypt31p antibodies gave a punctate staining similar to that observed with Golgi-located proteins. From the phenotypic alterations observed in ypt31 and ypt32 mutants, it seems likely that the two GTPases are involved in intra-Golgi transport or in the formation of transport vesicles at the most distal Golgi compartment.

Amino Acid Sequence↗