Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to assess the role of the gonads and anterior pituitary gland in the production of poor quality semen of males with homozygous sickle cell disease (SCD) serum gonadotrophins, namely follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin and serum testosterone, were assayed radioimmunologically in 33 men with sickle cell disease and in 29 age-matched normal control subjects. Our results show a significantly lower mean serum testosterone, a higher mean FSH and prolactin in SCD subjects than in normal controls. No single SCD subject had significantly low serum testosterone associated with low FSH, LH or prolactin. The tendency for higher gonadotrophins associated with lower testosterone in subjects with SCD suggests that the hypothalamic/pituitary function in these patients is intact and that the primary fault leading to poor sperm production lies in the testes.
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PMID:Testicular dysfunction in men with sickle cell disease. 311 48

The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal disease, certain diuretics, the use of chelating agents such as penicillamine for Wilson's disease, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during the growing age period. The clinical manifestations in severe cases of zinc deficiency included bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males and it is fatal if untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss and hyperammonaemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and in man. Inasmuch as zinc is needed for protein and DNA synthesis and cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level and the hypothalamic--pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in a cell division, its deficiency may adversely affect testicular size and thus its function. In mice, the incidence of degenerate oocytes, and hypohaploidy and hyperhaploidy in metaphase II oocytes were increased due to zinc deficiency. Zinc at physiological concentrations reduced prolactin secretion from the pituitary in vitro and it has been suggested that this trace element may have a role in the in vivo regulation of prolactin release. Thymopoietin, a hormone needed for T-cell maturation, has also been shown to be zinc dependent. It is clear that zinc may have several roles in biochemical and hormonal functions of various endocrine organs. Future research in this area is very much needed.
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PMID:Clinical, endocrinological and biochemical effects of zinc deficiency. 390 80

The requirement of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, and chronic renal diseases; use of certain drugs such as penicillamine and, in some cases, diuretics; and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during growth. The clinical manifestations of severe zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, and hypogonadism in males; zinc deficiency can be fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and humans, probably because zinc is needed for protein and DNA synthesis and cell division. The effects of zinc and growth hormone on growth appear to be independent of each other in experimental animals. Whether zinc is required for the metabolism of somatomedin needs further investigation. Thyroid and adrenal functions do not appear to change as a result of zinc deficiency. Glucocorticoids may have an effect on zinc metabolism, although the clinical relevance of this effect is not known at present. In contrast, testicular function is affected adversely as a result of zinc deficiency in both humans and experimental animals. The effect appears to be a direct one since the hypothalamic-pituitary axis is intact, and may relate to the reduction in testicular size as a result of the need for zinc in cell division. In addition, zinc is required for the function of several testicular enzymes, although a specific role in steroidogenesis has not been identified. Zinc appears to have a role in the modulation of prolactin secretion, in the secretion and action of insulin, and in the production and biologic effects of thymic hormones. It is clear that the endocrine consequences of zinc deficiency are multiple, and that continued investigation should provide additional pathophysiologic and therapeutic insights.
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PMID:Clinical, endocrinologic, and biochemical effects of zinc deficiency. 391 98

In two patients with sickle cell disease who presented with headache pituitary adenoma and high levels of serum prolactin were found. Treatment with bromocriptine has controlled the headache. We believe that prolactin level determination should be part of the work-up of patients with sickle cell disease who complain of headache.
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PMID:Increased prolactin level and pituitary adenoma as a cause of headache in two patients with sickle cell disease. 871 8

The cytotoxicity of hydroxyurea (HU), currently used to combat various cancers, sickle cell anemia and human immunodeficiency infection, was assessed by exposing decidualized and pregnant uteri of Sprague-Dawley rats to this drug. Consecutive daily doses of HU (500 mg/kg(-1)) for 4 days were injected subcutaneously during decidualization when proliferation of the deciduoma was biochemically analyzed on pseudopregnancy day 9, or injected intraperitoneally during pregnancy when uterine developmental processes were evaluated on gestation day 16. Hydroxyurea displayed prominent antiproliferative effects on decidual growth. These actions were comparable to significantly impaired (P<0.001) developmental responses (increases in post-implantation losses, in resorbed fetuses and in reduced fetal and placental weights) during pregnancy. The cellular components inhibited by HU were DNA, protein, nitric oxide synthase, a matrix metalloproteinase and decidual prolactin-related protein mRNA (P<0.05). Steroid-related endocrine events (serum progesterone concentrations, estrogen receptor and mRNA levels) were unaffected by HU, implying direct cellular action by the drug. Interestingly, endometrial alkaline phosphatase bioactivity was enhanced by HU (P<0.05). Subsequently, the reproductive toxicity of HU was apparently related to mitogenic and differentiation-induced endometrial cellular activities.
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PMID:Hydroxyurea inhibition of cellular and developmental activities in the decidualized and pregnant uteri of rats. 1113 71

Pituitary gland dysfunction and its contribution to menarcheal delay in sickle cell anaemia patients was investigated. Ten SS patients mean age 17.5 years who had not achieved menarche were recruited and 10 each of AS and AA controls, mean ages 17.4 and 17.7 years were used as controls to study the effect of the heterozygous state. Dynamic studies with LHRH and TRH were performed for 60 minutes and LH, FSH, PRL and TSH assays were done. Median basal values were significantly lower in the SS patients compared with the AS and AA controls for LH, FSH and PRL. LH: 3.0; 7.1; 7.7 U/L, FSH: 2.1: 4.3: 5.1 U/L. PRL: 94.5; 590; 390 U/L, respectively. The median basal TSH values did not show any significant difference between the SS subjects (7.3 U/L) and the AS and AA controls (5.4 U/L) and 5.6 U/L, respectively. The readily releasable pool also showed the same pattern for LH, FSH and PRL as the basal values while the SS subjects had higher median TSH releasable pool values that were significantly different from those of the AA controls. From the prolactin responses three subjects demonstrated maturational delay in menarcheal achievement while seven demonstrated isolated gonadotrophin deficiency. It is concluded that SS patients with delayed menarche have a hypothalamopituitary axis dysfunction that gives rise to delay in menarcheal achievement and metabolic adaptations to stress of illness. The heterozygous state did not delay menarcheal onset.
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PMID:Anterior pituitary gland assessment in sickle cell anaemia patients with delayed menarche. 1295 90

Although research on dairy goat mammary gland have referred extensively to molecular mechanisms, research on lines of dairy goat mammary epithelial cells (MECs) are still rare. This paper sought to establish an immortal MEC line by stable transfection of human telomerase. MECs from a lactating (45 days post-parturition) Xinong Saanen dairy goat were cultured purely and subsequently transfected with a plasmid carrying the sequence of human telomerase. Immortalized MECs by human telomerase (hT-MECs) exhibited a typical cobblestone morphology and activity and expression levels of telomerase resembled that of MCF-7 cells. hT-MECs on passage 42 grew vigorously and 'S' sigmoid curves of growth were observed. Moreover, hT-MECs maintained a normal chromosome modal number of 2n=60, keratin 8 and epithelial membrane antigen (EMA) were evidently expressed, and beta-casein protein was synthesized and secreted. Beta-casein expression was enhanced by prolactin (P<0.05). Lipid droplets were found in hT-MECs, and messenger RNA levels of PPARG, SREBP, FASN, ACC and SCD in hT-MECs (passage 40) were similar to MECs (passage 7). In conclusion, the obtained hT-MEC line retained a normal morphology, growth characteristics, cytogenetics and secretory characteristics as primary MECs. Hence, it can be a representative model cell line, for molecular and functional analysis, of dairy goat MECs for an extended period of time.
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PMID:Establishment and characterization of a dairy goat mammary epithelial cell line with human telomerase (hT-MECs). 2488 18